WorldWideScience

Sample records for duchenne type controversies

  1. Progressive muscular dystrophy: Duchenne type. Controversies of the kinesitherapy treatment

    Directory of Open Access Journals (Sweden)

    Ana Valéria de Araujo Leitão

    Full Text Available The authors carried out a study of children with progressive muscular dystrophy of Duchenne type (DMD, giving special attention to physiatrical follow-up, having in mind that the practice of exercises has been debated very much in the specialized literature. The goal of this study is to try to settle the limits for the utilization of kinesitherapy which should be applied only in specific situations, such as: after skeletal muscular trauma or when the respiratory system is at risk. In this situation the physiatrical procedure would be to restrict physical activity, with early use of wheelchairs and the exclusion of the use of orthoses for orthostatism. DMD, at present, has been considered a result of duplication (60%, deletion (5 to 6% or point mutations at gen Xp21 (Zatz, 1994, that codifies a protein called Dystrophin ( Hoffman et al., 1987. Dystrophin is a cytoskeletal sarcolemmic protein that constitutes about .002% of the total protein of the muscle, present in skeletal fibers concentrated in muscle tendinous joints, which supplies mechanical reinforcement to the surface of the membrane during stretching and shortening physical activity. This protein is absent in DMD cases, wherefore, the sarcolemma undergoes a segmentary necrosis losing its contractile property during eccentric and concentric physical activity. The importance of physiatrical follow-up for DMD patients is to avoid deformities and tendon shortening, to ameliorate the patient's quality of life, to provide respiratory assistance and general couseling to members of the patient's family. The objective of this study is to try to clarify the risks and possibilities of kinesitherapy applied to DMD cases.

  2. Duchenne's/Becker's muscular dystrophy: Analysis of genotype-feno-type correlation in 28 patients

    Directory of Open Access Journals (Sweden)

    Keckarević Milica

    2002-01-01

    Full Text Available Duchenne's and Becker's muscular dystrophy (DMD & BMD is a X linked disease caused by mutations in the dystrophic gene. DMD is the malign form of the disease, which significantly shortens the lifetime of the patient, while BMD has late onset with slow progression. Sixty five percent of DMD and BMD cases are caused by deletion of one or more exons in the dystrophic gene, while duplications cause these diseases in 6 to 7% of the cases. There are two hot spots for deletions and duplications. These are exons in the proximal part of the gene (3rd to 18th and exons of a distal part of the gene (45th to 52nd. The remaining 30% of DMD and BMD cases are caused by point mutations, small deletions or inversions in the dystrophic gene. The correlation between School of Medicine, University of Belgrade, Belgrade the severity of the disease and the position of deletion shows that most of the out of frame deletions cause DMD phenotype, while in frame deletions result in BMD pheno-type. We report on the results of 28 non-related DMD and BMD patients. In 57% of cases deletions were detected and all were found in the distal hot spot of the gene. These results suggest that in most of the cases, out of frame deletions produce DMD phenotype while in frame deletions result in BMD phenotype. This is in compliance with data from literature.

  3. CT evaluation of the damaged upper limb muscle in patients with Duchenne type progressive muscular dystrophy (DMD)

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Hiroshi (Anan Central Hospital, Tokushima (Japan)); Matsuke, Yutaka

    1992-04-01

    In order to evaluate the changes of CT numbers and cross sectional areas of the muscles, we determined CT scores of the muscle. In twelve patients with Duchenne type progressive muscular dystrophy (DMD), we assessed the difference of CT scores of the muscle and the correlation between CT score of the muscle and 9-stage classification of upper extremities. CT scores of the subscapularis muscle and infraspinatus muscle were significantly lower than deltoideus muscle at the level of the shoulder, and flexor muscles showed also significantly lower than extensor muscles at the level of the upper extremity. Good correlations between CT score of the muscle and 9-stage classification of upper extremities were observed in the muscles of shoulder and upper arm. (author).

  4. Wild-type mouse models to screen antisense oligonucleotides for exon-skipping efficacy in Duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Limin Cao

    Full Text Available A readily available animal model is essential for rapidly identifying effective treatments for Duchenne muscular dystrophy (DMD, a devastating neuromuscular disorder caused by the lack of dystrophin protein, which results from frame-disrupting mutations in the DMD gene. Currently, the mdx mouse is the most commonly used model for antisense oligonucleotide (AO-mediated exon skipping pre-clinical studies, with a mild phenotype. However, the accessibility of mdx mouse colonies particularly in developing countries can constrain research. Therefore in this study we explore the feasibility of using wild-type mice as models to establish exon-skipping efficiency of various DMD AO chemistries and their conjugates. Four different strains of wild-type mice and six different AO chemistries were investigated intramuscularly and the results indicated that the same exon-skipping efficiency was achieved for all tested AOs as that from mdx mice. Notably, levels of exon-skipping obtained in C57BL6 and C3H and mdx mice were most closely matched, followed by ICR and BALB/C mice. Systemic validation revealed that wild-type mice are less responsive to AO-mediated exon skipping than mdx mice. Our study provides evidence for the first time that wild-type mice can be appropriate models for assessing DMD AO exon-skipping efficiency with similar sensitivity to that of mdx mice and this finding can further accelerate the development of effective DMD AOs.

  5. Signs of Duchenne

    Science.gov (United States)

    ... Duchenne How We Help Care for Him Care Guidelines Explore by Area Explore by Stage Surgery & Anesthesia Emergency Care Resource Materials For Professionals Advance Research Research Therapeutic Pipeline What We Are Funding Clinical Trials For ...

  6. Therapeutics in duchenne muscular dystrophy.

    Science.gov (United States)

    Strober, Jonathan B

    2006-04-01

    Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3,500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

  7. [Duchenne muscular dystrophy pathophysiology].

    Science.gov (United States)

    Péréon, Y; Mercier, S; Magot, A

    2015-12-01

    Dystrophin is a large cytoskeletal protein located at the plasma membrane in both muscle and non-muscle tissues, which mediates interactions between the cytoskeleton, cell membrane, and extracellular matrix. Dystrophin is a key component of multiprotein complexes (dystrophin- associated glycoprotein complex, or DGC). It is also involved in many intracellular cascades affecting membrane proteins such as calcium channels, or various signalisation pathways. In Duchenne Muscular Dystrophy, both dystrophin and DGC proteins are missing. This induces excessive membrane fragility and permeability, dysregulation of calcium homeostasis, oxidative damage, which in turn favour muscle cell necrosis. The latter is initially followed by regeneration. With age, the regenerative capacity of the muscles appears to be exhausted and muscle fibres are gradually replaced by connective and adipose tissue. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Management of obesity, insulin resistance and type 2 diabetes in children: consensus and controversy

    Directory of Open Access Journals (Sweden)

    Amy Fleischman

    2009-11-01

    Full Text Available Amy Fleischman, Erinn T RhodesDivision of Endocrinology, Children’s Hospital Boston, Boston, MA, United StatesAbstract: Childhood obesity has become a national and international epidemic. The prevalence and incidence of type 2 diabetes in youth have been increasing, and type 2 diabetes is one of the most challenging complications of obesity in childhood. Comprehensive lifestyle interventions that include attention to dietary change, increased physical activity and behavior change appear to be required for the successful treatment of pediatric obesity. In particular, aspects of behavioral interventions that have been identified as contributing to effectiveness have included intensity, parent/family participation, addressing healthy dietary change, promoting physical activity, and involving behavioral management principles such as goal setting. A multidisciplinary team approach is required for successful management of type 2 diabetes in youth as well. As with many therapies in pediatrics, clinical trials and support for treatments of obesity and type 2 diabetes in youth lag behind adult data. Pediatric recommendations may be extrapolated from adult data and are often based on consensus guidelines. Type 2 diabetes in children is most commonly managed with lifestyle modification and medications, metformin and/or insulin, the only medications currently approved for use in children. However, many opportunities exist for ongoing research to clarify optimal management for obesity and type 2 diabetes in youth.Keywords: children, obesity, type 2 diabetes, metformin, insulin, bariatric surgery

  9. Management of obesity, insulin resistance and type 2 diabetes in children: consensus and controversy.

    Science.gov (United States)

    Fleischman, Amy; Rhodes, Erinn T

    2009-11-27

    Childhood obesity has become a national and international epidemic. The prevalence and incidence of type 2 diabetes in youth have been increasing, and type 2 diabetes is one of the most challenging complications of obesity in childhood. Comprehensive lifestyle interventions that include attention to dietary change, increased physical activity and behavior change appear to be required for the successful treatment of pediatric obesity. In particular, aspects of behavioral interventions that have been identified as contributing to effectiveness have included intensity, parent/family participation, addressing healthy dietary change, promoting physical activity, and involving behavioral management principles such as goal setting. A multidisciplinary team approach is required for successful management of type 2 diabetes in youth as well. As with many therapies in pediatrics, clinical trials and support for treatments of obesity and type 2 diabetes in youth lag behind adult data. Pediatric recommendations may be extrapolated from adult data and are often based on consensus guidelines. Type 2 diabetes in children is most commonly managed with lifestyle modification and medications, metformin and/or insulin, the only medications currently approved for use in children. However, many opportunities exist for ongoing research to clarify optimal management for obesity and type 2 diabetes in youth.

  10. EMBOLISMO GRASO EN UN NIÑO CON DISTROFIA MUSCULAR DE DUCHENNE Y FRACTURA BILATERAL DE FÉMUR. UNA RARA ASOCIACIÓN. Fat embolism syndrome in a child with muscular dystrophy of Duchenne type bilateral femur fracture. A rare association.

    Directory of Open Access Journals (Sweden)

    Enrique Vergara Amador

    2007-03-01

    Full Text Available Las fracturas de fémur en pacientes que sufren de distrofia muscular de Duchenne (DMD son frecuentes, con una incidencia entre 15-44 por ciento. El embolismo graso se presenta en fracturas de huesos largos generalmente asociado a trauma de alta energía o a lesiones extensas de tejidos blandos. El diagnóstico de embolismo graso no es tan frecuente en niños posiblemente porque cursa con presentaciones subclínicas. No existen reportes de embolismo graso asociado a distrofia muscular de Duchenne. Informamos el caso de un niño con distrofia muscular Duchenne que sufrió fractura bilateral de fémur y embolismo graso.It is high the frequency of femur fracture in children with Duchenne Muscular Dystrophy (DMD, with an incidence between 15 and 44%. The fatty embolism is presented in fractures of long bones generally associated to trauma of high energy or to extensive lesions of soft tissues. The diagnosis is not frequent in children probably because they can be presentations subclínicas. We could not find reports of fatty embolism associated to Duchenne muscular dystrophy. We present the case of a boy with Duchenne muscular dystrophy that suffered bilateral fracture of femur and fatty embolism.

  11. Plutonium controversy

    Energy Technology Data Exchange (ETDEWEB)

    Richmond, C.R.

    1980-01-01

    The toxicity of plutonium is discussed, particularly in relation to controversies surrounding the setting of radiation protection standards. The sources, amounts of, and exposure pathways of plutonium are given and the public risk estimated. (ACR)

  12. [A benign variant of the course of Duchenne muscular dystrophy in a child with short stature].

    Science.gov (United States)

    Badalian, L O; Temin, P A; Kamennykh, L N; Zavadenko, N N; Nikanorova, M Iu; Arkhipov, B A; Malygina, N A

    1991-01-01

    The authors describe a case of a benign variety of progressive Duchenne type muscular dystrophy in a 8-year-old short-stature boy. Provide the electromyographic and electroneuromyographic data, measurements of the growth hormone in blood serum and osseous age. Make suggestions about coupled inheritance of progressive Duchenne type muscular dystrophy and short stature . The latter one is likely to be attended by a decrease of anabolic processes, which may determine a more benign course of the myodystrophic process.

  13. Prednisone Therapy for Duchenne Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available The effects of prednisone on muscle function and the extent of steroid-related adverse effects were studied in 17 ambulant children with Duchenne muscular dystrophy (DMD at University Hospital, Groningen; Rehabilitation Centre, Utrecht; and Leiden University Medical Centre, the Netherlands.

  14. Glucocorticoids for Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-07-01

    Full Text Available Investigators at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, and other centers in the UK, conducted a prospective longitudinal study across 17 neuromuscular centers in the UK of 360 boys aged 3-15 years with Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off prednisolone for a mean duration of 4 years.

  15. Proximity Begins with a Smile, But Which One? Associating Non-duchenne Smiles with Higher Psychological Distance.

    Science.gov (United States)

    Bogodistov, Yevgen; Dost, Florian

    2017-01-01

    This study reveals that Duchenne (genuine) and non-Duchenne (non-genuine, polite) smiles are implicitly associated with psychological proximity and distance, respectively. These findings link two extensive research streams from human communication and psychology. Interestingly, extant construal-level theory research suggests the link may work as smiles signaling either a benign situation or politeness, resulting in conflicting predictions for the association between smile type and psychological distance. The current study uses implicit association tests to reveal theoretically and empirically consistent non-Duchenne-smile-distance and Duchenne-smile-proximity associations for all four types of psychological distance: temporal, spatial, social, and hypothetical. Practically, the results suggest several useful applications of non-Duchenne smiles in human communication contexts.

  16. EMBOLISMO GRASO EN UN NIÑO CON DISTROFIA MUSCULAR DE DUCHENNE Y FRACTURA BILATERAL DE FÉMUR. UNA RARA ASOCIACIÓN. Fat embolism syndrome in a child with muscular dystrophy of Duchenne type bilateral femur fracture. A rare association.

    OpenAIRE

    Enrique Vergara Amador; Fernando Galván Villamarín; Marcela Piña Quintero

    2007-01-01

    Las fracturas de fémur en pacientes que sufren de distrofia muscular de Duchenne (DMD) son frecuentes, con una incidencia entre 15-44 por ciento. El embolismo graso se presenta en fracturas de huesos largos generalmente asociado a trauma de alta energía o a lesiones extensas de tejidos blandos. El diagnóstico de embolismo graso no es tan frecuente en niños posiblemente porque cursa con presentaciones subclínicas. No existen reportes de embolismo graso asociado a distrofia muscular de Duchenne...

  17. Duchenne muscular dystrophy - a molecular service

    African Journals Online (AJOL)

    Duchenne muscular dystrophy using molecular technology was instituted at the ..... utilising non-fat dry milk for analysis of proteins and nucleic acids transferred ... acid to high specific activity in vitro by nick translation with DNA polymerase.

  18. Duchenne muscular dystrophy: the management of scoliosis

    Science.gov (United States)

    Gardner, Adrian C.; Roper, Helen P.; Chikermane, Ashish A.; Tatman, Andrew J.

    2016-01-01

    This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group.

  19. Managing Controversies in the Fuzzy Front End

    DEFF Research Database (Denmark)

    Christiansen, John K.; Gasparin, Marta

    2016-01-01

    . The analysis investigates the microprocesses around the controversies that emerge during the fuzzy front end of four products. Five different types of controversies are identified: profit, production, design, brand and customers/market. Each controversy represents a threat, but also an opportunity to search...

  20. Duchenne muscular dystrophy and epilepsy.

    Science.gov (United States)

    Pane, M; Messina, S; Bruno, C; D'Amico, A; Villanova, M; Brancalion, B; Sivo, S; Bianco, F; Striano, P; Battaglia, D; Lettori, D; Vita, G L; Bertini, E; Gualandi, F; Ricotti, V; Ferlini, A; Mercuri, E

    2013-04-01

    Cognitive and behavioral difficulties occur in approximately a third of patients with Duchenne muscular dystrophy. The aim of our study was to assess the prevalence of epilepsy in a cohort of 222 DMD patients. Epileptic seizures were found in 14 of the 222 DMD patients (6.3%). The age of onset ranged from 3 months to 16 years (mean 7.8). Seizures were more often focal epilepsy (n=6), generalized tonic-clonic seizures (n=4) or absences (n=4). They were present in 12 of the 149 boys with normal IQ (8.1%) and in two of the 73 with mental retardation (2.7%). In two cases the parents did not report any past or present history of seizures but only 'staring episodes' interpreted as a sign of 'poor attention'. In both patients EEG showed the typical pattern observed in childhood absence epilepsy. Our results suggest that the prevalence of epilepsy in our study (6.3%) is higher than in the general pediatric population (0.5-1%). The risk of epilepsy does not appear to increase in patients with mental retardation.

  1. Metabolic effects of human growth hormone and of estrogens in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Rudman, D; Chyatte, S B; Patterson, J H; Gerron, G G; O'Beirne, I; Barlow, J; Jordan, A; Shavin, J S

    1972-05-01

    Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)((3/4)) per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested. The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW((3/4)) per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N, P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW((3/4)) per day) produced positive N, P, Na, and K balances in all three Duchenne cases tested with this agent. The data show that exogenous HGH causes a catabolic effect in boys with Duchenne dystrophy. These patients are hyperresponsive to the anabolic effect of diethylstilbestrol. The latter phenomenon may reflect the inhibitory effect of estrogen upon the peripheral actions of these boys' endogenous HGH.

  2. A CONTROVERSIAL ON THE DIAGNOSIS OF CHRONIC BULLOUS TYPE MUCOCUTANEOUS DISEASE INVOLVING ORAL MUCOSA (A CASE REPORT)

    OpenAIRE

    Isadora Gracia; Harum Sasanti

    2006-01-01

    A case of chronic bullous type mucocutaneous disease involving oral mucosa was reported from a 56 years old man with never healing oral ulcers and wound on the perianal skin for three years. There were also red and black spots on the limb and back skin and a lesion on nail. Painful oral lesion consisted of mucous erosion, desquamative gingivitis, and sloughing area on palate and tongue. The patient is diabetic. The first perianal skin diagnosis was granulomatous candidasis with differential d...

  3. A Drosophila model for Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Plas, Mariska Cathelijne van der

    2008-01-01

    Duchenne Muscular Dystrophy (DMD) is a severe X-linked disease characterized by progressive muscle wasting and sometimes mild mental retardation. The disease is caused by mutations in the dystrophin gene. DMD is correlated with the absence of Dp427, which is located along the sarcolemma in skeletal

  4. Infrastructure for Clinical Trials in Duchenne Dystrophy

    Science.gov (United States)

    2010-09-13

    following are key research accomplishments for the Year 1 funding period: Manuscripts in process • DM Escolar, C Tesi -Rocha, E Henricson, J Florence, J...in steroid treated Duchenne Muscular Dystrophy. In revision for journal submission. • A. Zimmerman, C. Tesi -Rocha, P.R. Clemens, A. Connolly, S.T

  5. Nutrition Considerations in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Davis, Jillian; Samuels, Emily; Mullins, Lucille

    2015-08-01

    Duchenne muscular dystrophy (DMD) is a serious degenerative muscular disease affecting males. Diagnosis usually occurs in childhood and is confirmed through genetic testing and/or muscle biopsy. Accompanying the disease are several nutrition-related concerns: growth, body composition, energy and protein requirements, constipation, swallowing difficulties, bone health, and complementary medicine. This review article addresses the nutrition aspects of DMD.

  6. Brain Function in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available The role of dystrophin disorders in the CNS function of boys with Duchenne muscular dystrophy (DMD and the dystrophin-deficient mdx mouse, an animal model of DMD, is reviewed at the University of New South Wales, University of Sydney, Australia.

  7. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    Science.gov (United States)

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  8. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    Science.gov (United States)

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  9. A CONTROVERSIAL ON THE DIAGNOSIS OF CHRONIC BULLOUS TYPE MUCOCUTANEOUS DISEASE INVOLVING ORAL MUCOSA (A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Isadora Gracia

    2006-04-01

    Full Text Available A case of chronic bullous type mucocutaneous disease involving oral mucosa was reported from a 56 years old man with never healing oral ulcers and wound on the perianal skin for three years. There were also red and black spots on the limb and back skin and a lesion on nail. Painful oral lesion consisted of mucous erosion, desquamative gingivitis, and sloughing area on palate and tongue. The patient is diabetic. The first perianal skin diagnosis was granulomatous candidasis with differential diagnosis pemphigus vegetates and acuminarum condiloma. However the histopathologic examination did not support these diagnosis. After several histopathologic examinations, the latest perianal skin diagnosis was lichen planus with differential diagnosis granulomatous vasculitis, bowenoid papulosis and pyodema gangrenosum. Other skin diagnosis was erythema multiforme. Oral diagnosis was mucous membrane pemphigoid with differential diagnosis lichen planus, Behçet's syndrome and erythema multiforme. Oral histopathologic examinations showed a sub-epithelial blister, which supported mucous membrane pemphigoid. A lip balm, prednisone 5 mg oral rinse and multivitamins were given but oral improvement started after blood sugar level was controlled. Conclusion: It is not yet known whether skin and oral mucous lesions are from the same disease or not.

  10. Urological manifestations of Duchenne muscular dystrophy.

    Science.gov (United States)

    Askeland, Eric J; Arlen, Angela M; Erickson, Bradley A; Mathews, Katherine D; Cooper, Christopher S

    2013-10-01

    Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

    Science.gov (United States)

    2017-07-11

    Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Disease; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  12. Circulating Biomarkers for Duchenne Muscular Dystrophy

    Science.gov (United States)

    Aartsma-Rus, Annemieke; Spitali, Pietro

    2015-01-01

    Abstract Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput – omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products. PMID:27858763

  13. Growth hormone evaluation in Duchenne muscular dystrophy.

    Science.gov (United States)

    Merlini, L; Granata, C; Ballestrazzi, A; Cornelio, F; Tassoni, P; Tugnoli, S; Cacciari, E

    1988-10-01

    Growth hormone (GH) release with pharmacological tests and sleep test, somatomedin C and auxological features were studied in 10 patients affected by Duchenne Muscular Dystrophy. GH release in these patients seems to be lower than normal; moreover some of them are of short stature without an evident relationship with GH deficit. The possible significance of the data obtained is discussed, particularly in relation to the clinical course of the disease, and to current therapeutic trials with a GH release inhibitor (mazindol).

  14. Fatty liver disease and hypertransaminasemia hiding the association of clinically silent Duchenne muscular dystrophy and hereditary fructose intolerance.

    Science.gov (United States)

    Paolella, Giulia; Pisano, Pasquale; Albano, Raffaele; Cannaviello, Lucio; Mauro, Carolina; Esposito, Gabriella; Vajro, Pietro

    2012-10-31

    We report a case with the association of well self-compensated hereditary fructose intolerance and still poorly symptomatic Duchenne type muscular dystrophy. This case illustrates the problems of a correct diagnosis in sub-clinical patients presenting with "cryptogenic" hypertransaminasemia.

  15. Fatty liver disease and hypertransaminasemia hiding the association of clinically silent Duchenne muscular dystrophy and hereditary fructose intolerance

    Directory of Open Access Journals (Sweden)

    Paolella Giulia

    2012-10-01

    Full Text Available Abstract We report a case with the association of well self-compensated hereditary fructose intolerance and still poorly symptomatic Duchenne type muscular dystrophy. This case illustrates the problems of a correct diagnosis in sub-clinical patients presenting with “cryptogenic” hypertransaminasemia.

  16. An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Hamada, M; Okuda, H; Oka, K; Watanabe, T; Ueda, K; Nojima, M; Kuby, S A; Manship, M; Tyler, F H; Ziter, F A

    1981-08-13

    The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further

  17. Cardiac assessment of patients with late stage Duchenne muscular dystrophy

    NARCIS (Netherlands)

    van Bockel, E. A. P.; Lind, J. S.; Zijlstra, J. G.; Wijkstra, P. J.; Meijer, P. M.; van den Berg, M. P.; Slart, R. H. J. A.; Aarts, L. P. H. J.; Tulleken, J. E.

    2009-01-01

    Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, b

  18. Non-deletion mutations in Egyptian patients with Duchenne ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-04-19

    Apr 19, 2014 ... most common form of all muscular dystrophies caused by mutations within the ..... Previous studies reported a correlation for IQ values in affected siblings with ... molecular testing of Duchenne muscular dystrophy. J Mol Diagn.

  19. FDA OKs 1st Drug to Treat Duchenne Muscular Dystrophy

    Science.gov (United States)

    ... html FDA OKs 1st Drug to Treat Duchenne Muscular Dystrophy Exondys 51 seems to fill unmet need ... the first drug for a rare form of muscular dystrophy. Exondys 51 (eteplirsen) was granted accelerated approval ...

  20. Obstetric controversies in thyroidology

    Directory of Open Access Journals (Sweden)

    Ambika Gopalakrishnan Unnikrishnan

    2013-01-01

    Full Text Available It is well known that thyroid disorders commonly affect women. The care of pregnant women affected by thyroid disease is an important clinical challenge for endocrinologists. Hypothyroidism is the commonest problem, and maternal hypothyroxinemia has been linked to adverse feto-maternal outcomes. This article would discuss the controversy regarding first-trimester thyroid hormone deficiency and fetal brain development. Certain obstetric controversies in the management of hyperthyroidism in pregnancy, including the indications of TSH receptor antibody measurements and fetal thyroid status monitoring would also be discussed.

  1. A Web of Controversies

    DEFF Research Database (Denmark)

    Baron, Christian

    2011-01-01

    Using the Burgess Shale controversies as a case-study, this paper argues that controversies within different domains may interact as to create a situation of “com- plicated intricacies,” where the practicing scientist has to navigate through a context of multiple thought collectives. To some extent...... of academic science have had a tendency to treat the practicing scientist as members of a single (enclosed) thought collective that stands intellectually isolated from other similar entities unless the discipline was in a state of crisis of paradigmatic proportions. The richness and complexity of Burgess...... Shale debate shows that this encapsulated kind of analysis is not enough....

  2. Relationship between muscle strength and motor function in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Milene F. Nunes

    2016-07-01

    Full Text Available ABSTRACT Measuring muscle strength and motor function is part of Duchenne muscular dystrophy (DMD assessment. However, the relationship between these variables is controversial. Objective To investigate the relationship between muscle strength and motor function and between these variables and age. Method Muscle strength was measured by Medical Research Council (MRC scale and motor function, by Motor Function Measure (MFM, in 40 non-ambulatory patients. Spearman tests investigated the relationships between muscle strength, motor function and age. Results Total MRC and MFM scores were strongly related to each other (r = 0.94; p 0.05. Strong and moderate relationships between partial muscle strength and motor function scores were found. Higher correlation coefficients were found between total scores and Dimensions 2 (axial/ proximal control and 3 (distal control of MFM. Conclusion Muscle strength and motor function are strongly correlated and seem to decrease proportionally in DMD.

  3. Clinical controversies in lipid management.

    Science.gov (United States)

    Tziomalos, K

    2015-06-01

    Even though it is firmly established that statins are the cornerstone of management of dyslipidemias, several controversies still exist in this area. In the present review, the most pertinent controversies in lipid management are discussed and the current evidence is summarized. Treatment with statins increases the risk for type 2 diabetes mellitus (T2DM) but this increase appears to be small and outweighed by the benefits of statins on cardiovascular disease prevention. Accordingly, statin treatment-associated T2DM should not affect management decisions. In patients who cannot achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximum tolerated dose of a potent statin, adding ezetimibe appears to be the treatment of choice. Finally, patients who achieved LDL-C targets with a statin but have elevated triglyceride levels appear to have increased cardiovascular risk and adding fenofibrate appears to reduce this risk. Even though additional large randomized controlled trials are unlikely to be performed with the existing lipid-lowering agents, mechanistic, genetic and epidemiological studies, as well as careful analyses of the existing trials will provide further insights in these controversial issues and will allow the optimization of the management of dyslipidemia aiming at further reductions in cardiovascular morbidity.

  4. Controversies in Nigeria

    African Journals Online (AJOL)

    This article examines, based on recent ethnographic data, one of the lesser known ... As one analyst has noted, 'a majority of the last remaining oil .... National Petroleum Corporation (NNPC e established in 1977) bears 55-60 percent of the ..... gives an insight into the controversies surrounding compensation and petro-.

  5. The Ebonics Controversy.

    Science.gov (United States)

    Williams, Robert L.

    1997-01-01

    Discusses the controversy over the use of Ebonics in the Oakland (California) schools and presents two schools of thought about the origin of Ebonics, the pidgin/Creole and the African retention theories. Three research studies are described that support the use of Ebonics in the classroom as a bridge to standard English. (SLD)

  6. Students' Conceptions of Controversial Knowledge.

    Science.gov (United States)

    Nicholls, John G.; Nelson, J. Ron

    1992-01-01

    Five boys and five girls each in grades one through six (n=60 students) asked controversial questions in interviews, recognized the lack of social consensus on the controversial topics and made subtle distinctions between controversial and noncontroversial topics. Implications for discussion of controversial issues in the classroom are discussed.…

  7. Natural history of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Qing KE

    2015-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is X-linked recessive hereditary disease. DMD gene mutations result in dystrophin deficiency, which causes not only muscle movement disorders but also scoliosis, cognitive dysfunction, urinary tract diseases, respiratory diseases and heart diseases. Most patients die in early adult for respiratory and circulatory failure. Early multidisciplinary therapies will significantly delay disease progression and improve patients' quality of life. However, DMD diagnosis and treatment exist significantly time delay now. In this study, we review the natural history of DMD, including motor, cognitive, respiratory and heart function, for improving DMD early recognition, diagnosis and treatment, so as to benefit DMD patients. DOI: 10.3969/j.issn.1672-6731.2015.05.004

  8. Importância do camundongo mdx na fisiopatologia da distrofia muscular de Duchenne The importance of mdx mouse in the pathophysiology of Duchenne's muscular distrophy

    Directory of Open Access Journals (Sweden)

    Sandra Lopes Seixas

    1997-09-01

    Full Text Available O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X (locus Xp21.1 e não expressa distrofina. Embora não apresente intensa fibrose do tecido muscular e acúmulo de tecido adiposo, é considerado o modelo animal mais adequado da distrofia muscular de Duchenne. As alterações estruturais no tecido muscular associadas à mionecrose e presença do infiltrado inflamatório com predomínio de linfócitos e monócitos/macrófagos sugerem uma participação do sistema imunológico nesta miopatia. Além disso a modulação na expressão dos componentes da matriz extracelular no microambiente muscular nas várias fases da doença (início, mionecrose, regeneração indicam um papel importante do conjuntivo no direcionamento das células inflamatórias para o foco da lesão muscular. O camundongo mdx coloca-se como um excelente modelo para o estudo dos mecanismos patogenéticos da mionecrose e regeneração na distrofia muscular de Duchenne, possibilitando inclusive o desenvolvimento de estratégias terapêuticas mais adequadas.The mdx mouse develop an X-linked recessive muscular dystrophy (locus Xp21.1 and lack dystrophin expression. Despite showing less intense myofibrosis and scarce deposition of fatty tissue, mdx mice are considered an adequate animal model for studies on the pathogenesis of Duchenne-type muscular dystrophy. Marked histological alterations in the muscular tissues associated to myonecrosis and inflammatory mononuclear cell infiltrate (lymphocytes, monocytes/macrophages suggest a participation of the immune system in this myopathy. Modulation of the extracellular matrix (ECM components in the muscular tissue during all phases (onset, myonecrosis and regeneration of disease, indicate an important role for the ECM driving inflammatory cells to the foci of lesion. Therefore mdx mice should be regarded as an important tool for studies on pathogenetic mechanisms of Duchenne-type muscular dystrophy. Such

  9. Evidence, lack of evidence, controversy, and debate in the provision and performance of the surgery of acute type A aortic dissection

    DEFF Research Database (Denmark)

    Bonser, Robert S; Ranasinghe, Aaron M; Loubani, Mahmoud;

    2011-01-01

    for malperfusion complications are necessary. The goals of surgery are to save life by prevention of pericardial tamponade or intra-pericardial aortic rupture, to resect the primary entry tear, to correct or prevent any malperfusion and aortic valve regurgitation, and if possible to prevent late dissection......-related complications in the proximal and downstream aorta. No randomized trials of treatment or techniques have ever been performed, and novel therapies-particularly with regard to extent of surgery-are being devised and implemented, but their role needs to be defined. Overall, except in highly specialized centers......, surgical outcomes might be static, and there is abundant room for improvement. By highlighting difficulties and controversies in diagnosis, patient selection, and surgical therapy, our over-arching goal should be to enfranchise more patients for treatment and improve surgical outcomes....

  10. Controversies in vaccine mandates.

    Science.gov (United States)

    Lantos, John D; Jackson, Mary Anne; Opel, Douglas J; Marcuse, Edgar K; Myers, Angela L; Connelly, Beverly L

    2010-03-01

    Policies that mandate immunization have always been controversial. The controversies take different forms in different contexts. For routine childhood immunizations, many parents have fears about both short- and long-term side effects. Parental worries change as the rate of vaccination in the community changes. When most children are vaccinated, parents worry more about side effects than they do about disease. Because of these worries, immunization rates go down. As immunization rates go down, disease rates go up, and parents worry less about side effects of vaccination and more about the complications of the diseases. Immunization rates then go up. For teenagers, controversies arise about the criteria that should guide policies that mandate, rather than merely recommend and encourage, certain immunizations. In particular, policy makers have questioned whether immunizations for human papillomavirus, or other diseases that are not contagious, should be required. For healthcare workers, debates have focused on the strength of institutional mandates. For years, experts have recommended that all healthcare workers be immunized against influenza. Immunizations for other infections including pertussis, measles, mumps, and hepatitis are encouraged but few hospitals have mandated such immunizations-instead, they rely on incentives and education. Pandemics present a different set of problems as people demand vaccines that are in short supply. These issues erupt into controversy on a regular basis. Physicians and policy makers must respond both in their individual practices and as advisory experts to national and state agencies. The articles in this volume will discuss the evolution of national immunization programs in these various settings. We will critically examine the role of vaccine mandates. We will discuss ways that practitioners and public health officials should deal with vaccine refusal. We will contrast responses of the population as a whole, within the

  11. Duchenne De Boulogne: a pioneer in neurology and medical photography.

    Science.gov (United States)

    Parent, André

    2005-08-01

    Guillaume-Benjamin-Amand Duchenne was born 200 years ago in Boulogne-sur-Mer (Pas-de-Calais, France). He studied medicine in Paris and became a physician in 1831. He practiced general medicine in his native town for about 11 years and then returned to Paris to initiate pioneering studies on electrical stimulation of muscles. Duchenne used electricity not only as a therapeutic agent, as it was commonly the case earlier in the 19th century, but chiefly as a physiological investigation tool to study the anatomy of the living body. Without formal appointment he visited hospital wards across Paris searching for rare cases of neuromuscular disorders. He built a portable electrical device that he used to functionally map all bodily muscles and to study their coordinating action in health and disease. He gave accurate descriptions of many neuromuscular disorders, including pseudohypertrophic muscular dystrophy to which his name is still attached (Duchenne muscular dystrophy). He also invented a needle system (Duchenne's histological harpoon) for percutaneous sampling of muscular tissue without anesthesia, a forerunner of today's biopsy. Duchenne summarized his work in two major treatises entitled De l'électrisation localisée (1855) and Physiologie des mouvements (1867). Duchenne's iconographic work stands at the crossroads of three major discoveries of the 19th century: electricity, physiology and photography. This is best exemplified by his investigation of the mechanisms of human physiognomy in which he used localized faradic stimulation to reproduce various forms of human facial expression. The album that complements his book on this issue is considered a true incunabulum of photography. Duchenne de Boulogne, a shy but hard-working, acute and ingenious observer, became one of most original clinicians of the 19th century. He died in Paris in 1875.

  12. Controversies in Obesity Treatment

    Directory of Open Access Journals (Sweden)

    Majid Karandish

    2015-06-01

    Full Text Available The markedly high prevalence of obesity contributes to the increased incidence of chronic diseases, such as diabetes, hypertension, sleep apnea, and heart disease. Because of high prevalence of obesity in almost all countries, it has been the focus of many researches throughout the world during the recent decades. Along with increasing researches, new concepts and controversies have been emerged. The existing controversies on the topic are so deep that some researches argue on absolutely philosophical questions such as “Is obesity a disease?” or “Is it correct to treat obesity?” These questions are based on a few theories and real data that explain obesity as a biological adaptation and also the final results of weight loss programs. Many people attempt to lose weight by diet therapy, physical activity and lifestyle modifications. Importantly, weight loss strategies in the long term are ineffective and may have unintended consequences including decreasing energy expenditure, complicated appetite control, eating disorders, reducing self-esteem, increasing the plasma and tissue levels of persistent organic pollutants that promote metabolic complications, and consequently, higher risk of repeated cycles of weight loss and weight regain. In this review, major paradoxes and controversies on obesity including classic obesity paradox, pre-obesity; fat-but-fit theory, and healthy obesity are explained. In addition, the relevant strategies like “Health at Every Size” that emphasize on promotion of global health behaviors rather than weight loss programs are explained.

  13. Diagnosi molecolare della Distrofia Muscolare di Duchenne e della Neurofibromatosi tipo 1 con la tecnologia di sequenziamento Next Generation

    OpenAIRE

    Chessa, Roberta

    2014-01-01

    Duchenne/Becker muscular dystrophies (DMD/BMD) are the most frequent inherited neuromuscular diseases caused by mutations in the dystrophin gene (DMD). Neurofibromatosis type 1 (NF1), caused by mutations in the neurofibromin gene (NF1), is a multisystem genetic disorder that commonly is associated with cutaneous, neurologic, and orthopedic manifestations. Full characterisation of the mutational spectrum is necessary for genetic counselling, prenatal diagnosis and selecting the patients eligib...

  14. Mapping Wind Energy Controversies

    DEFF Research Database (Denmark)

    Munk, Anders Kristian

    As part the Wind2050 project funded by the Danish Council for Strategic Research we have mapped controversies on wind energy as they unfold online. Specifically we have collected two purpose built datasets, a web corpus containing information from 758 wind energy websites in 6 different countries......, and a smaller social media corpus containing information from 14 Danish wind energy pages on Facebook. These datasets have been analyzed to answer questions like: How do wind proponents and opponents organize online? Who are the central actors? And what are their matters of concern? The purpose of this report...

  15. Controversy at Love Canal.

    Science.gov (United States)

    Paigen, B

    1982-06-01

    A cancer researcher reviews the events surrounding the toxic waste contamination at Love Canal with emphasis on the political nature of the controversy about its health impact. Antagonism between the community and the New York State Department of Health was fueled by several factors: the state's awareness that it gained from delay in investigation, disagreement on health problems to be studied, control over the information gathering process, silencing of opposition opinion, and the violation of norms of scientific behavior. The author calls for the establishment of standards of ethical behavior for scientists in such situations, standards for conflict resolution, and means of appeal for those injured.

  16. Mapping Wind Energy Controversies

    DEFF Research Database (Denmark)

    Munk, Anders Kristian

    As part the Wind2050 project funded by the Danish Council for Strategic Research we have mapped controversies on wind energy as they unfold online. Specifically we have collected two purpose built datasets, a web corpus containing information from 758 wind energy websites in 6 different countries......, and a smaller social media corpus containing information from 14 Danish wind energy pages on Facebook. These datasets have been analyzed to answer questions like: How do wind proponents and opponents organize online? Who are the central actors? And what are their matters of concern? The purpose of this report...

  17. Controversies on clitoroplasty

    Science.gov (United States)

    2011-01-01

    A review of the literature regarding the current state of knowledge of the anatomic and physiologic features of the female clitoris was conducted. Based on this evaluation, operations on the clitoris were reviewed. The anatomic and physiologic reconstruction problems of surgical techniques for female pseudohermaphroditism that have previously been reported were reviewed. The author suggests that clitoroplasty is essential for patients with ambiguous genitalia, but the decision regarding the correct procedure, taking into account anatomic and physiologic success, can be controversial. This may be because of unclear anatomic and physiologic definitions, even for healthy people. As a temporary solution, more conservative procedures for maximally effective treatment are suggested. PMID:22164197

  18. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  19. Molecular diagnosis of Duchenne muscular dystrophy.

    Science.gov (United States)

    Nallamilli, Babi Ramesh Reddy; Ankala, Arunkanth; Hegde, Madhuri

    2014-10-01

    Duchenne Muscular Dystrophy (DMD) is an X-linked inherited neuromuscular disorder caused by mutations in the dystrophin gene (DMD; locus Xp21.2). The mutation spectrum of DMD is unique in that 65% of causative mutations are intragenic deletions, with intragenic duplications and point mutations (along with other sequence variants) accounting for 6% to 10% and 30% to 35%, respectively. The strategy for molecular diagnostic testing for DMD involves initial screening for deletions/duplications using microarray-based comparative genomic hybridization (array-CGH) followed by full-sequence analysis of DMD for sequence variants. Recently, next-generation sequencing (NGS)-based targeted gene analysis has become clinically available for detection of point mutations and other sequence variants (small insertions, deletions, and indels). This unit initially discusses the strategic algorithm for establishing a molecular diagnosis of DMD and later provides detailed protocols of current molecular diagnostic methods for DMD, including array-CGH, PCR-based Sanger sequencing, and NGS-based sequencing assay.

  20. Idiopathic intracranial hypertension in a child with Duchenne muscular dystrophy.

    Science.gov (United States)

    Weig, Spencer G; Zinn, Matthias M; Howard, James F

    2011-12-01

    Duchenne muscular dystrophy is an X-linked, recessively inherited disorder characterized by progressive weakness attributable to the absence of dystrophin expression in muscle. In multiple studies, the chronic administration of corticosteroids slowed the loss of ambulation that develops in mid to late childhood. Corticosteroids, however, frequently produce unacceptable side effects, including Cushingoid appearance and weight gain. Deflazacort, an oxazoline analogue of prednisolone, produces equivalent benefits on muscle with fewer reported Cushingoid side effects. We present a 9-year-old boy with Duchenne muscular dystrophy who developed morbid obesity and subsequent idiopathic intracranial hypertension after 2 years of receiving deflazacort. Although deflazacort is typically thought to produce less obesity than prednisone, severe Cushingoid side effects may occur in some individuals. To our knowledge, this description is the first of idiopathic intracranial hypertension complicating chronic corticosteroid treatment of Duchenne muscular dystrophy.

  1. The evolution of controversial issues.

    Science.gov (United States)

    King, P

    1994-04-01

    The controversial issues concerning the differences of opinion about the validity of Melanie Klein's theory and technique did not arise suddenly when members of the Viennese Society joined the British Psycho-Analytical Society, before the outbreak of the Second World War. In this paper, I describe briefly the socio-historical, administrative and institutional background out of which these scientific divergences evolved alongside other issues concerned with how long members should hold office in the British Psycho-Analytical Society and therefore be in a position to influence the scientific disagreements and training policy in the Society. These causes for concern among members, which were discussed at five business meetings, are then summarised: they relate to differences of opinion with regard to Melanie Klein's contributions to psychoanalysis, the need for revision of the rules of the Society and the type of training in psychoanalysis that should be offered to candidates. Finally, proposals for different ways of exploring and perhaps dealing with these issues are discussed, including the decision to hold formal scientific discussions of Klein's point of view, once a month. These meetings are now referred to as the 'Controversial Discussions'.

  2. O retardo mental na distrofia muscular de Duchenne

    OpenAIRE

    Flávia Nardes; Alexandra P.Q.C. Araújo; Márcia Gonçalves Ribeiro

    2012-01-01

    OBJETIVO: Fazer um levantamento da literatura médica destinada ao estudo das disfunções cognitivas nos pacientes com distrofia muscular de Duchenne, através da descrição dos marcos do desenvolvimento neuropsicomotor e dos testes psicométricos para quantificação da inteligência. FONTES DOS DADOS: Revisão não sistemática sobre os aspectos da cognição na distrofia muscular de Duchenne nas principais bases médicas científicas: MEDLINE, LILACS, Biblioteca Cochrane e SciELO. SÍNTESE DOS DADOS: Os p...

  3. O retardo mental na distrofia muscular de Duchenne

    OpenAIRE

    Flávia Nardes; Araújo,Alexandra P. Q. C.; Márcia Gonçalves Ribeiro

    2012-01-01

    OBJETIVO: Fazer um levantamento da literatura médica destinada ao estudo das disfunções cognitivas nos pacientes com distrofia muscular de Duchenne, através da descrição dos marcos do desenvolvimento neuropsicomotor e dos testes psicométricos para quantificação da inteligência. FONTES DOS DADOS: Revisão não sistemática sobre os aspectos da cognição na distrofia muscular de Duchenne nas principais bases médicas científicas: MEDLINE, LILACS, Biblioteca Cochrane e SciELO. SÍNTESE DOS DADOS: Os p...

  4. Controversies in fat perception.

    Science.gov (United States)

    Heinze, Jaana M; Preissl, Hubert; Fritsche, Andreas; Frank, Sabine

    2015-12-01

    Nutritional fat is one of the most controversial topics in nutritional research, particularly against the background of obesity. Studies investigating fat taste perception have revealed several associations with sensory, genetic, and personal factors (e.g. BMI). However, neuronal activation patterns, which are known to be highly sensitive to different tastes as well as to BMI differences, have not yet been included in the scheme of fat taste perception. We will therefore provide a comprehensive survey of the sensory, genetic, and personal factors associated with fat taste perception and highlight the benefits of applying neuroimaging research. We will also give a critical overview of studies investigating sensory fat perception and the challenges resulting from multifaceted methodological approaches. In conclusion, we will discuss a multifactorial approach to fat perception to gain a better understanding of the underlying mechanisms that cause varying fat sensitivity which could be responsible for overeating. Such knowledge might be beneficial in new treatment strategies for obesity and overweight.

  5. Sabbath controversy in Matthew

    Directory of Open Access Journals (Sweden)

    Francois P. Viljoen

    2011-03-01

    Full Text Available Jesus� attitude towards the Sabbath plays a crucial part in Matthew�s argument. Some scholars argue that Jesus provocatively broke the Sabbath law; however, an attentive reading of the Sabbath controversies revealed a different reality. Matthew strategically places the Sabbath stories after he has firmly stated Jesus� teaching on the continuing validity of the law and the requirement of greater righteousness. The law and the prophets are fulfilled in the Person of Jesus, who demonstrated a fresh approach to Sabbath observance. God�s intention with the Sabbath must also be recognised. Matthew argues not if the Sabbath should be observed, but how it should be done to experience true rest according to the will of God.

  6. Cartography of architectural controversies

    DEFF Research Database (Denmark)

    Lotz, Katrine

    2009-01-01

    How can buildings be perceived not only for their properties as stable objects and spatial organisation, but also and at the same time as series of transformations, as socio-material orderings, as movements? Coming from a background in architecture and architectural theory I propose that spatial...... on the visual materials and documents produced during the process, and interviews with architects, clients and engineers, I describe the continuous efforts to establish and strengthen architectural motives, and how they eventually gain the ability to align other motives and other actors. I suggest...... that employing the visualising methods of the recent development of Actor-Network-Theory called ‘Cartography of Controversies' might contribute to trans-disciplinary efforts to develop analytic understanding of the conflicting human purposes and power-struggles at stake in the be-coming of architecture....

  7. Neuropsychological profile of duchenne muscular dystrophy.

    Science.gov (United States)

    Perumal, Anna Roshini; Rajeswaran, Jamuna; Nalini, Atchayaram

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder characterized by progressive muscle wasting. DMD is a fatal X-linked recessive disorder with an estimated prevalence of 1 in 3,500 male live births. This disease has long been associated with intellectual impairment. Research has shown that boys with DMD have variable intellectual performance, indicating the presence of specific cognitive deficits. The aim of the study was to use a battery of intelligence, learning, and memory tests to identify a neuropsychological profile in boys with DMD. A total of 22 boys diagnosed with DMD in the age range of 6 to 10 years old were evaluated using the Wechsler Intelligence Scale for Children-Third Edition, Rey's Auditory Verbal Learning Test, and the Memory for Designs Test. The data were interpreted using means, standard deviations, percentages, and percentiles. Normative data were also used for further interpretation. The results showed that boys with DMD had a significantly lower IQ (88.5). Verbal IQ (86.59) was found to be lower than Performance IQ (92.64). There was evidence of impaired performance on the Processing Speed, Freedom From Distractibility, and Verbal Comprehension Indexes. Specific deficits in information processing, complex attention, immediate verbal memory span, verbal working memory, verbal comprehension, vocabulary, visuoconstruction ability, and verbal learning and encoding were observed. However, perceptional organization, general fund of information, abstract reasoning, visual discrimination and acuity, visual learning and memory, and verbal memory were adequate. The neuropsychological findings support the hypothesis that these children have specific cognitive deficits as opposed to a global intellectual deficit.

  8. Recent advances in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Perkins KJ

    2012-10-01

    Full Text Available Kelly J Perkins,1,2 Kay E Davies21Sir William Dunn School of Pathology, 2MRC Functional Genomics Unit, University of Oxford, Oxford, UKAbstract: Duchenne muscular dystrophy (DMD, an allelic X-linked progressive muscle-wasting disease, is one of the most common single-gene disorders in the developed world. Despite knowledge of the underlying genetic causation and resultant pathophysiology from lack of dystrophin protein at the muscle sarcolemma, clinical intervention is currently restricted to symptom management. In recent years, however, unprecedented advances in strategies devised to correct the primary defect through gene- and cell-based therapeutics hold particular promise for treating dystrophic muscle. Conventional gene replacement and endogenous modification strategies have greatly benefited from continued improvements in encapsidation capacity, transduction efficiency, and systemic delivery. In particular, RNA-based modifying approaches such as exon skipping enable expression of a shorter but functional dystrophin protein and rapid progress toward clinical application. Emerging combined gene- and cell-therapy strategies also illustrate particular promise in enabling ex vivo genetic correction and autologous transplantation to circumvent a number of immune challenges. These approaches are complemented by a vast array of pharmacological approaches, in particular the successful identification of molecules that enable functional replacement or ameliorate secondary DMD pathology. Animal models have been instrumental in providing proof of principle for many of these strategies, leading to several recent trials that have investigated their efficacy in DMD patients. Although none has reached the point of clinical use, rapid improvements in experimental technology and design draw this goal ever closer. Here, we review therapeutic approaches to DMD, with particular emphasis on recent progress in strategic development, preclinical evaluation and

  9. Oral muscles are progressively affected in Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Bert de Swart; W. Klein; S. Pillen; L. Sie; I. de Groot; C. Erasmus; J. Hendriks; Alexander Geurts; L. van den Engel-Hoek

    2012-01-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based

  10. Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

    2007-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

  11. Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD)

    DEFF Research Database (Denmark)

    Brolin, Camilla; Shiraishi, Takehiko

    2011-01-01

    Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most pr...... oligonucleotides (2'-O-methyl phosphorothioate (2OME-PS), phosphorodiamidate morpholino oligomer (PMO)) and peptide nucleic acid (PNA)....

  12. Occupational Potential in a Population with Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Schkade, Janette K.; And Others

    1987-01-01

    Twenty-five males with Duchenne muscular dystrophy were tested to assess their potential for occupational activity. Tests measured possible sensory deficits, strength, endurance, and fatigue in response to sustained fine motor activity. Results indicate that, within limitations, persons with this diagnosis can engage in activity leading to skill…

  13. Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

    2007-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

  14. Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

    Science.gov (United States)

    Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-01-01

    Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

  15. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, EM; van der Wouw, PA; Wilde, AAM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; van Essen, AJ; Leschot, NJ; de Visser, M

    1999-01-01

    A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers

  16. Phonological Awareness Skills in Young Boys with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Waring, Phoebe; Woodyatt, Gail

    2011-01-01

    Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

  17. Dasatinib as a treatment for Duchenne muscular dystrophy.

    Science.gov (United States)

    Lipscomb, Leanne; Piggott, Robert W; Emmerson, Tracy; Winder, Steve J

    2016-01-15

    Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy.

  18. Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

    Science.gov (United States)

    Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-01-01

    Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

  19. Controversial identification in a historical case is illustrative of the complexity of DNA typing in forensic research. Response to Charlier et al.

    Science.gov (United States)

    Larmuseau, Maarten H D; Cassiman, Jean-Jacques; Decorte, Ronny

    2014-03-01

    The previously published genetic identification of presumptive samples attributed to two French kings, Henri IV and Louis XVI, by Charlier et al., was recently refuted by a genetic genealogic approach. This (provisional) refutation illustrates the difficulties in confirming the identification of historical DNA samples using limited genetic data. Therefore, we want to stress the necessity of including the genetic genealogic approach--which relies on DNA typing of living relatives of the presumptive donor as a confirmed reference--to validate genetic results in historical cases. Moreover, the popularity and broad media coverage of such studies are useful in bringing awareness to the general public, non-DNA forensic experts and lawyers about the complexity of DNA typing in forensic cases.

  20. [Current controversies in glycemic control targets. What do the results of the latest clinical trials tell us about the approach to type 2 diabetes mellitus?].

    Science.gov (United States)

    Mauricio, Dídac; Rius, Ferran

    2010-09-01

    The aim of this article is to discuss the implications of the results obtained in the latest large-scale clinical trials designed to evaluate the effect of intensive glycemic control on the vascular complications associated with type 2 diabetes mellitus. The current scientific evidence is reviewed and the implications of the ACCORD (The Action to Control Cardiovascular Risk in Diabetes study group), ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Control Evaluation) and VADT (Veterans Affairs Diabetes Trial) clinical trials are discussed. General concerns of the studies and their implications for clinical practice and the management of type 2 diabetes, as well as the questions which still need to be answered by future clinical research are discussed.

  1. Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes.

    Science.gov (United States)

    Radio, Francesca Clementina; Majore, Silvia; Aurizi, Caterina; Sorge, Fiammetta; Biolcati, Gianfranco; Bernabini, Sara; Giotti, Irene; Torricelli, Francesca; Giannarelli, Diana; De Bernardo, Carmelilia; Grammatico, Paola

    2015-06-01

    Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G>A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results. We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.

  2. Immunoproteasome in animal models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Chen, Chiao-Nan Joyce; Graber, Ted G; Bratten, Wendy M; Ferrington, Deborah A; Thompson, LaDora V

    2014-04-01

    Increased proteasome activity has been implicated in the atrophy and deterioration associated with dystrophic muscles of Duchenne muscular dystrophy (DMD). While proteasome inhibitors show promise in the attenuation of muscle degeneration, proteasome inhibition-induced toxicity was a major drawback of this therapeutic strategy. Inhibitors that selectively target the proteasome subtype that is responsible for the loss in muscle mass and quality would reduce side effects and be less toxic. This study examined proteasome activity and subtype populations, along with muscle function, morphology and damage in wild-type (WT) mice and two murine models of DMD, dystrophin-deficient (MDX) and dystrophin- and utrophin-double-knockout (DKO) mice. We found that immunoproteasome content was increased in dystrophic muscles while the total proteasome content was unchanged among the three genotypes of mice. Proteasome proteolytic activity was elevated in dystrophic muscles, especially in DKO mice. These mice also exhibited more severe muscle atrophy than either WT or MDX mice. Muscle damage and regeneration, characterized by the activity of muscle creatine kinase in the blood and the percentage of central nuclei were equally increased in dystrophic mice. Accordingly, the overall muscle function was similarly reduced in both dystrophic mice compared with WT. These data demonstrated that there was transformation of standard proteasomes to immunoproteasomes in dystrophic muscles. In addition, DKO that showed greatest increase in proteasome activities also demonstrated more severe atrophy compared with MDX and WT. These results suggest a putative role for the immunoproteasome in muscle deterioration associated with DMD and provide a potential target for therapeutic intervention.

  3. Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy.

    Science.gov (United States)

    Bianco, Bianca; Christofolini, Denise Maria; Conceição, Gabriel Seixas; Barbosa, Caio Parente

    2017-09-21

    Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy. RESUMO A distrofia muscular de Duchenne é a doença muscular mais comum observadas em crianças do sexo masculino. Atualmente, não há terapia eficaz disponível para distrofia muscular de Duchenne, portanto, é essencial o diagnóstico pré-natal e o aconselhamento genético para reduzir o nascimento desses meninos. Relatamos um caso de diagnóstico genético pré-implantação associado à distrofia muscular de Duchenne. O casal E.P.R., 38 anos, heterozigota, sintomática para uma mutação de deleção dos éxons 2 a 47 no gene

  4. Photoprotection: facts and controversies.

    Science.gov (United States)

    Skotarczak, K; Osmola-Mańkowska, A; Lodyga, M; Polańska, A; Mazur, M; Adamski, Z

    2015-01-01

    Excessive exposure of the skin to sunlight can lead to many negative effects, such as sunburn, photoaging and skin cancer development. Pollution and stratospheric ozone layer depletion are factors that increase exposure to ultraviolet radiation. This work is an accurate summary of the current state of knowledge on broad-spectrum photoprotection. Avoiding the sun, skin protection through the use of protective clothing and protective filters are currently the most effective methods of sunscreen provided that they are suitably used. In addition, discussed are controversial issues such as the toxicity of zinc used in sunscreen preparations and the potential for deficiency of vitamin D3 in relation with the application of strict photoprotection. The study has also addressed issues concerning the most recent lines of research in the exploration of modern methods of photoprotection both local and systemic, such as with the use of photolyase or examination of various enzymes repairing damage after sun exposure, as well as the promising future in photoprotection technology.

  5. Abortion: the continuing controversy.

    Science.gov (United States)

    Behrens, C E

    1972-08-01

    While most countries of the world practice abortion, government policy, medical opinion, private opinion and actual practice vary widely. Although mortality from legal abortions is quite low, complications rise sharply after 12 gestational weeks. No conclusive proof shows adverse postabortion psychological effects. Romania, Japan and the Soviet Union experienced declining birth rates when abortion was made available and New York City saw a decline in illegitimacy of approximately 12% from 1970 to 1971. Throughout the world abortion laws vary from restrictive to moderate to permissive. Where laws are restrictive, as in France and Latin America, illegal abortions are estimated in the millions. The controversy over abortion centers around the arguments of what constitutes a human life, and the rights of the fetus versus the right of a woman to control her reproductive life. A review of state abortion laws as of August 1972 shows pressure on state legislatures to change existing laws. The future of abortion depends upon technological advances in fertility control, development of substitutes like menstral extraction, prostaglandins and reversible sterilization. Development of these techniques will take time. At present only through education and improved delivery of contraceptives can dependence on abortion as a method of fertility control be eased. Citizen education in the United States, both sex education and education for responsbile parenthood, is in a poor state according to the Commission on Population Growth and the American Future. If recourse to abortion is to be moderated, it is the next generation of parents who will have to be educated.

  6. Cardiac resynchronization therapy in a young patient with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Kono T

    2015-08-01

    Full Text Available Tamami Kono,1 Akiyoshi Ogimoto,1 Kazuhisa Nishimura,1 Toshihiro Yorozuya,2 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, 2Department of Anesthesiology and Resuscitology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan Abstract: A 32-year-old man with Duchenne muscular dystrophy (DMD was admitted to the hospital because of worsening dyspnea and general fatigue. He had received medication therapy for cardiomyopathy with heart failure and home mechanical ventilation for respiratory failure. An electrocardiogram on admission showed intermittent third-degree atrioventricular block. Echocardiography showed global mild left ventricular systolic dysfunction with dyssynchrony (ejection fraction: 45%. He underwent implantation of a cardiac resynchronization therapy–defibrillator. His B-type natriuretic peptide level was improved after cardiac resynchronization therapy–defibrillator implantation, and he remains asymptomatic. The incidence of cardiomyopathy increases with age. By adulthood, 100% of patients have cardiac involvement. Keywords: cardiac resynchronization therapy, Duchenne muscular dystrophy, progression of cardiomyopathy, heart failure, arrhythmia

  7. 假性肥大型肌营养不良儿童血清脑利钠肽水平与心脏功能的相关性%Correlation Between Serum B-Type Natriuretic Peptide Levels and Cardiac Function in Duchenne'S Muscular Dystrophy Patients

    Institute of Scientific and Technical Information of China (English)

    田淑芬

    2011-01-01

    目的:研究假肥大型肌营养不良(DMD)患者血清脑利钠肽(BNP)与左心室功能的相关性.方法:采用电化学发光免疫方法以及心脏超声检查分别测量50名DMD儿童和25名正常儿童的血清BNP水平和左心室功能相关指标.分析DMD儿童血清BNP与不同心脏功能分级的相关性.结果:DMD儿童血清BNP水平与左心室功能与正常对照组有显著性差异(P<0.01).不同心脏功能分级的DMD儿童血清BNP水平和左心室功能显著不同(P<0.05或P<0.01).DMD儿童LVMI、LVEDD、LVPWT与血清BNP水平正相关,LVEF、IVST、FS、E/A与血清BNP水平负相关(r绝对值:0.53-0.75,P<0.05).结论:DMD儿童血清BNP水平与左心室功能显著相关,可作为诊断DMD儿童心脏功能的指标.%Objective: To research the correlation between serum B-type natriuretic peptide (BNP) levels and function of left ventricle in Duchenne's muscular dystrophy (DMD) children.Methods: The serum BNP levels and function of left ventricle in 50 DMD children and 25 control children were detected respectively by electro-chemistry immunity assay and echocardiography, and the correlation between serum BNP levels and function of left ventricle in DMD children was analyzed.Results: The serum BNP levels and function of left ventricle were significantly different in statistics between DMD children and control children (P<0.01).The serum BNP levels and function of left ventricle were significantly different in DMD children with different NYHA grades (P< 0.05 or P<0.01).Left ventricular indices measured by echocardiograpy such as LVMI, LVEDD and LVPWT were positively correlated to serum BNP levels, but LVEF, IVST, FS, and E/A were negatively correlated to serum BNP levels in DMD children (|r|=0.53-0.75, P<0.05).Conclusion: Serum BNP levels correlate to the function of left ventricle, and could be used as the indicators to detect the cardiac function in DMD children.

  8. Teen Addiction. Current Controversies Series.

    Science.gov (United States)

    Winters, Paul A., Ed.

    The Current Controversies series explores social, political, and economic controversies that dominate the national and international scenes today from a variety of perspectives. Recent surveys have shown that, after years of decline, drug use among teenagers has increased during the 1990s, and that alcohol and tobacco use have remained…

  9. Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy: A case Report.

    Science.gov (United States)

    Kim, Ji Eun; Chun, Hea Rim

    2017-03-01

    Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

  10. Translational Studies of GALGT2 Gene Therapy for Duchenne Muscular Dystrophy

    Science.gov (United States)

    2014-10-01

    Therapy for Duchenne Muscular Dystrophy PRINCIPAL INVESTIGATOR: Paul T. Martin, PhD CONTRACTING ORGANIZATION: The Research Institute...for Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0416 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Paul T. Martin...translational studies in support of developing GALGT2 gene therapy for use in Duchenne Muscular dystrophy patients. In year 2, we have completed

  11. Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

    Science.gov (United States)

    2017-05-30

    Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  12. Current and emerging treatment strategies for Duchenne muscular dystrophy

    OpenAIRE

    Mah JK

    2016-01-01

    Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the...

  13. Duchenne muscular dystrophy with associated growth hormone deficiency.

    Science.gov (United States)

    Ghafoor, Tariq; Mahmood, Arshad; Shams, Shahnaz

    2003-12-01

    A patient with Duchenne muscular dystrophy (DMD) and growth hormone (GH) deficiency is described who had no clinical evidence of muscular weakness before initiation of GH replacement therapy. Treatment with human GH resulted in appearance of symptoms of easy fatigability and proximal muscle weakness. Thorough investigations including serum creatinine phosphokinase (CK) levels is recommended in every patient with GH deficiency before starting GH replacement therapy.

  14. Deflazacort in Duchenne dystrophy: study of long-term effect.

    Science.gov (United States)

    Angelini, C; Pegoraro, E; Turella, E; Intino, M T; Pini, A; Costa, C

    1994-04-01

    A randomized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo. The deflazacort group showed significant improvement in climbing stairs (P loss of ambulation for the treated group after we started the trial was 33.2 +/- 9 months; for the placebo group it was 20.5 +/- 11 months (deflazacort vs. placebo group, P weight gain and slight behavioral changes.

  15. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2012-03-01

    Full Text Available How to Cite this Article: Karimzadeh P, Ghazavi A. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy. IranianJournal of Child Neurology 2012;6(1:5-12.ObjectiveDuchenne muscular dystrophy (DMD is a degenerative disease that usually becomes clinically detectable in childhood as progressive proximal weakness. No cure is yet available for DMD, but the use of steroids improves muscle strength and function. This study has been carried out to select the best steroid for the management of DMD.Materials & MethodsThis study is a single-blind, randomized clinical trial with a sample volume of 34 DMD patients. Half of these patients were treated with deflazacort (0.9 mg/kg daily and the other half with prednisone (0.75 mg/kg daily for a period of 18 months. The motor function score and excess body weight were registered one year after the start and also at the end of the study and compared between the two groups.ResultsDeflazacort was more effective in the improvement of motor function after one year, but there was no significant difference between the two drugs at the end of the study (18 months after start. Weight gain after one year and at the end of the study was higher in prednisone group and steroid treatment with deflazacort appears to cause fewer side effects than prednisone regarding weight gain.ConclusionDeflazacort seems to be more effective than prednisone in the improvement of motor function causing fewer side effects, particularly weight gain. This medication may be important for the improvement of motor function and could be used as the best steroidal treatment for Duchenne muscular dystrophy. References Lankester BJA, Whitehouse MR, Gargan MF. Duchenne muscular dystrophy. Current Orthopedics 2007;21:298- 300. Wenger DR, Rang M. The art and practice of children’s orthopedics. Philadelphia, PA: Lippincott; Baltimore: Williams and Wilkins; 1993. Sussman M. Duchenne muscular dystrophy. J Am Acad Orthop Surg 2002 Mar

  16. O retardo mental na distrofia muscular de Duchenne

    Directory of Open Access Journals (Sweden)

    Flávia Nardes

    2012-02-01

    Full Text Available OBJETIVO: Fazer um levantamento da literatura médica destinada ao estudo das disfunções cognitivas nos pacientes com distrofia muscular de Duchenne, através da descrição dos marcos do desenvolvimento neuropsicomotor e dos testes psicométricos para quantificação da inteligência. FONTES DOS DADOS: Revisão não sistemática sobre os aspectos da cognição na distrofia muscular de Duchenne nas principais bases médicas científicas: MEDLINE, LILACS, Biblioteca Cochrane e SciELO. SÍNTESE DOS DADOS: Os pacientes com distrofia muscular de Duchenne apresentaram atraso para marcha e desenvolvimento da linguagem, os quais se correlacionaram a menores pontuações nos testes de inteligência no futuro. Há marcante disfunção nos subtestes das habilidades verbais. CONCLUSÕES: A média do coeficiente de inteligência encontra-se com um desvio padrão abaixo da média populacional. Quanto maior a disfunção cognitiva, piores serão os aspectos relacionados à morbidade e mortalidade na doença.

  17. Therapeutic Potential of Immunoproteasome Inhibition in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Farini, Andrea; Sitzia, Clementina; Cassani, Barbara; Cassinelli, Letizia; Rigoni, Rosita; Colleoni, Federica; Fusco, Nicola; Gatti, Stefano; Bella, Pamela; Villa, Chiara; Napolitano, Filomena; Maiavacca, Rita; Bosari, Silvano; Villa, Anna; Torrente, Yvan

    2016-11-01

    Duchenne muscular dystrophy is an inherited fatal genetic disease characterized by mutations in dystrophin gene, causing membrane fragility leading to myofiber necrosis and inflammatory cell recruitment in dystrophic muscles. The resulting environment enriched in proinflammatory cytokines, like IFN-γ and TNF-α, determines the transformation of myofiber constitutive proteasome into the immunoproteasome, a multisubunit complex involved in the activation of cell-mediate immunity. This event has a fundamental role in producing peptides for antigen presentation by MHC class I, for the immune response and also for cytokine production and T-cell differentiation. Here, we characterized for the first time the presence of T-lymphocytes activated against revertant dystrophin epitopes, in the animal model of Duchenne muscular dystrophy, the mdx mice. Moreover, we specifically blocked i-proteasome subunit LMP7, which was up-regulated in dystrophic skeletal muscles, and we demonstrated the rescue of the dystrophin expression and the amelioration of the dystrophic phenotype. The i-proteasome blocking lowered myofiber MHC class I expression and self-antigen presentation to T cells, thus reducing the specific antidystrophin T cell response, the muscular cell infiltrate, and proinflammatory cytokine production, together with muscle force recovery. We suggest that i-proteasome inhibition should be considered as new promising therapeutic approach for Duchenne muscular dystrophy pathology.

  18. The Homo floresiensis Controversy

    Directory of Open Access Journals (Sweden)

    COLIN GROVES

    2007-12-01

    Full Text Available A completely new and unexpected quasi human species, Homo floresiensis, nicknamed the Hobbit, was described in 2004 from Liang Bua, a cave in Flores. Like many important new contributions to the human fossil record in the past, many commentators refused to believe that a new species had been discovered, and the type specimen was interpreted as a pathological modern human, usually as a microcephalic dwarf. There is no substance to these claims: close analysis shows that Homo floresiensis is not only a genuinely new species, but that its closest affinities lie with Plio-Pleistocene African species such as Homo habilis, so that it documents an earlier dispersal of hominins from Africa and had hitherto been suspected.

  19. Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

    2009-01-01

    Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

  20. Quality of life of adult men with Duchenne muscular dystrophy in the Netherlands : Implications for care

    NARCIS (Netherlands)

    Pangalila, Robert F.; Van Den Bos, Geertrudis A M; Bartels, Bart; Bergen, Michael P.; Kampelmacher, Mike J.; Stam, Henk J.; Roebroeck, Marij E.

    2015-01-01

    Objective: To assess quality of life of adults with Duchenne muscular dystrophy in the Netherlands and to identify domains and major problems influencing quality of life. Design: Cross-sectional. Subjects: Seventy-nine men aged ≥ 20 years with Duchenne muscular dystrophy. Methods: The Medical

  1. Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

    2009-01-01

    Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

  2. Controversies on affirmative action

    Directory of Open Access Journals (Sweden)

    Milan Mesić

    2005-09-01

    Full Text Available Affirmative action was launched by American presidents J.F. Kennedy and L.B. Johnson, yet by ironic historical accident it attained its greatest expansion and most radical form during R. Nixon’s conservative administration. Affirmative action was originally a government programme aimed at improving the social position of Afro-Americans, mostly in the sphere of employment and education, as a kind of compensation for racial discrimination, and also other forms of social injustice suffered by minority and underprivileged groups. Its goal was to increase the proportion of Afro-Americans, and later members of other minorities, as well as women, in higher education institutions and in various types of employment. It was supported by many social researchers and activists. Law courts, namely their verdicts and explanations in the case of precedents, had an especially important role in the debate on affirmative action. Political conservatives attacked various affirmative action programmes (especially preferential enrolment quotas for minority students, basing their criticism on the American constitutional principles on equal rights for every citizen. Market conservatives, furthermore, claimed that the government’s policy of racial preference brought into question the very basis of the capital system (competition and at the same time was not in the interest of the Afro-American working class. Namely, the social strata that profited most was the relatively affluent segment of the Afro-American community, which only increased economic and social differences within the latter. Recently the debate on affirmative action in the US has not been limited only to two opposing sides (liberals and conservatives. More and more scientists and other participants have recognised the negative aspects and also the failures of affirmative action, while at the same time refuting conservative opinions and goals.

  3. Understanding Controversies in Urban Climate Change Adaptation

    DEFF Research Database (Denmark)

    Baron, Nina; Petersen, Lars Kjerulf

    2015-01-01

    This article explores the controversies that exist in urban climate change adaptation and how these controversies influence the role of homeowners in urban adaptation planning. A concrete SUDS project in a housing cooperative in Copenhagen has been used as a case study thereby investigating...... on the actor-network inspired theory of “urban green assemblages” we argue that at least three different assemblages can be identified in urban climate change adaptation. Each assemblage frames problems and responses differently, and thereby assigns different types of roles to homeowners. As climate change...... is a problem of unknown character and outcome in the future, we argue that it can be problematic if one way of framing urban climate change adaptation overrules the others. Some understandings of climate problems and adaptation options may become less influential, even though they could contribute to creating...

  4. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  5. Febrile Seizures: Controversy and Consensus

    Science.gov (United States)

    Doiron, Omer A.

    1983-01-01

    Although febrile convulsions are a relatively common complaint, the approach to their management is far from uniform and highly controversial. This article reviews the consensus statement on febrile convulsions arrived at by the Consensus Development Conference held in 1980 by the National Institutes of Health, together with other literature of interest to family physicians. Guidelines are given for the assessment, diagnosis and emergency treatment of febrile seizures. Epilepsy and atypical febrile convulsions are distinguished from simple febrile seizures. Prognosis, prevention, and the importance of counselling parents are discussed, as well as the controversial issue of prophylactic treatment. PMID:21286583

  6. Controversy

    OpenAIRE

    Allabadi, Fadwa

    2008-01-01

    This article focuses on the multilayered changes in the lives of Palestinian women over the years of the first and second Intifadas. On the one hand, women have become far more actively involved in politics, with a Women's Charter being drafted and legislation concerning women's rights being put on the political agenda. At the same time, the political shift from a Fatah- to a Hamas-dominated government has shifted understandings of whether the state should be secular or Islamist. Paradoxical ...

  7. Darwinian Controversies: An Historiographical Recounting

    Science.gov (United States)

    Depew, David J.

    2010-01-01

    This essay reviews key controversies in the history of the Darwinian research tradition: the Wilberforce-Huxley debate in 1860, early twentieth-century debates about the heritability of acquired characteristics and the consistency of Mendelian genetics with natural selection; the 1925 Scopes trial about teaching evolution; tensions about race,…

  8. Current controversies, is there merit?

    DEFF Research Database (Denmark)

    Twetman, S

    2009-01-01

    Xylitol has become a debated measure in caries prevention. This paper aims to examine and comment on some possible controversies, with emphasis on the most recent literature. A search for clinical trials was conducted through 2007 in PubMed, and papers describing a controlled xylitol intervention...

  9. Teaching Controversial Issues of Bioethics.

    Science.gov (United States)

    Stronck, David R.

    Many teachers avoid controversial topics because they do not want to upset students or parents, do not know appropriate instructional strategies, and fail to recognize the importance of motivating students through placing science in its relevant context. An example is provided for use in a methods course for helping future high school teachers to…

  10. Cartography of Controversies about MOOCs

    DEFF Research Database (Denmark)

    Khalid, Md. Saifuddin; Sorensen, Elsebeth Korsgaard

    2015-01-01

    in current literature result in the production of systematic literature reviews, case studies, and theoretical or conceptual frameworks. This work-in-progress paper explores the controversies about MOOCs by adopting the recently developed method “cartography of controversies” from the science and technology...

  11. Progress study of the cardiac damage in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    ZHANG Yao

    2013-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is a fatal muscular disease with rapid progression in children. Most patients die of respiratory and circulatory failure before the age of 20 if there is no systematic treatment. Now the heart problem in this disease has become increasingly prominent, and is thought to be closely associated with certain dystrophin exon deletion. We would like to review the epidemiology, relevance of dystrophin, pathogenesis, clinical manifestations and pathological features, as well as early prevention and treatment of DMD.

  12. Diagnosis delay of Duchenne Muscular Dystrophy Demora no diagnóstico da Distrofia Muscular de Duchenne

    Directory of Open Access Journals (Sweden)

    Alexandra Prufer de Queiroz Campos Araújo

    2004-06-01

    Full Text Available OBJECTIVES: to study the clinical features of Duchenne Muscular Dystrophy with emphasis on diagnosis delay. METHODS: an observational descriptive retrospective study was performed using medical records of patients with diagnosis of Duchenne Muscular Dystrophy given in the period from 1989 to 2000 at the neuropediatric out-patient clinic of a University Hospital. RESULTS: immunohistochemical results or deletion on the dystrophin gene confirmed the diagnosis of the 78 boys included in this study. Parents had noticed the first symptoms since the median age of two years. The final diagnosis was reached at a median age of seven. CONCLUSIONS: diagnosis age is closer to the age of ambulation loss than that of the first symptoms. There is a marked delay for the diagnosis of this disease in our setting.OBJETIVOS: estudar as características clínicas da Distrofia Muscular de Duchenne, com especial enfoque no tempo decorrido para o diagnóstico. MÉTODOS: realizou-se um estudo observacional descritivo e retrospectivo de pacientes com diagnóstico de distrofia muscular atendidos nos ambulatórios de neuropediatria de um Hospital Universitário no período de 1989 a 2000. RESULTADOS: foram incluídos 78 meninos com confirmação diagnóstica por imunohistoquímica ou deleção no gene da distrofina. A idade mediana da percepção dos primeiros sintomas pela família foi de dois anos e a idade mediana do diagnóstico definitivo de sete anos. CONCLUSÕES: a época do diagnóstico se aproxima mais da idade da perda da marcha do que do início dos sintomas. É grande a demora para o diagnóstico desta doença em nosso meio.

  13. Telehomecare technology across sectors: claims of jurisdiction and emerging controversies

    Directory of Open Access Journals (Sweden)

    Birthe Dinesen

    2007-11-01

    Full Text Available Purpose: The purpose of this study was to explore and identify inter-organisational and inter-professional controversies that emerge when telehomecare technology is implemented across healthcare sectors. Theory: A combined inter-organisational and inter-professional perspective constitutes the conceptual framework for this study. Methods: The case study approach was applied as the overall methodology of the study. A triangulation of data collection techniques was used in order to provide multiple sources of evidence for exploring and identifying controversies (documents, participant observation, qualitative interviews, focus group interviews. Findings: During the design and implementation phases of a telehomecare system, several types of controversies emerged as part of the inter-organisational and inter-professional agenda. These controversies involved competing claims of jurisdiction, controversies over knowledge technologies, or differences in network visions and network architecture. Discussion and conclusions: The identification of such controversies and differences in the design and implementation process of the concept of home hospitalisation for heart patients by means of telehomecare technology can contribute to the uncovering of new knowledge. These issues should be taken into account when initiating a telehomecare project and implementing telehomecare technology. Technology in a network and across inter-professional relations poses a challenge to this new field. There is a particular need to precisely define the claims of jurisdiction, and the accompanying controversies that can arise related to knowledge technologies, network visions and network architecture.

  14. Anestesia em paciente com Distrofia Muscular de Duchenne: relato de caso

    OpenAIRE

    Tonelli Deoclécio; Pinho Iglair; Sacco Paula de Camargo Neves; Vianna Eduardo Piccinini; Vasconcellos José Correia de; Souza Raquel Vasconcelos de; Umakoshi Sidney

    2003-01-01

    JUSTIFICATIVA E OBJETIVOS: A distrofia muscular de Duchenne é uma afecção recessiva ligada ao cromossomo X, geralmente diagnosticada na infância, acentuando-se progressivamente até agravar a função respiratória. O objetivo deste relato é apresentar um caso de um paciente com distrofia muscular de Duchenne diagnosticada há 2 anos, submetido à postectomia, sob anestesia geral com cetamina S. RELATO DO CASO: Paciente com 9 anos de idade com Distrofia Muscular de Duchenne diagnosticada há 2 anos,...

  15. Cytokines and Chemokines as Regulators of Skeletal Muscle Inflammation: Presenting the Case of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Boel De Paepe

    2013-01-01

    Full Text Available Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1 in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is an important facet of disease pathophysiology and is strongly associated with disease severity in the individual patient. In the chronic inflammation that characterizes Duchenne muscle, cytokines and chemokines are considered essential activators and recruiters of inflammatory cells. In addition, they provide potential beneficiary effects on muscle fiber damage control and tissue regeneration. In this review, current knowledge of cytokine and chemokine expression in Duchenne muscular dystrophy and its relevant animal disease models is listed, and implications for future therapeutic avenues are discussed.

  16. Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Melinda F. Davis

    2010-10-01

    Full Text Available Medical investigations use a wide variety of outcome indicators that are often not comparable. It can be challenging to integrate results across multiple studies that do not share a common metric. Some conditions such as Duchenne and Becker muscular dystrophy have a predictable course of disease progression. Severity can be inferred from a patient's medical history. This paper describes the development of a disease severity measure using common markers of disease progression. Rasch modeling was used to estimate severity using dichotomous events that indicate disease progression. Caregivers of 34 young men with Duchenne or Becker muscular dystrophy completed structured interviews about their care and medical history. Interview questions included surgeries (tendon release, scoliosis, tracheostomy, respiratory equipment (assisted ventilation, cough assist devices, and the use of other medical equipment (e.g., braces, walkers, wheelchairs, transfer boards, hospital beds. The resulting measure had a reliability of .83. The correlation between the severity measure and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS was .68. Preliminary results and item calibrations are provided for the severity measure that can be estimated from caregiver reports or administrative data. DOI: 10.2458/azu_jmmss.v1i1.76

  17. Drugs in development and dietary approach for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Angelini C

    2015-08-01

    Full Text Available Corrado Angelini, Elisabetta Tasca Neuromuscular Laboratory, Fondazione San Camillo Hospital IRCCS, Venice, Italy Abstract: Therapeutic trials studying Duchenne muscular dystrophy (DMD in Europe and the USA have been done using a protocol that includes manual muscle testing and functional testing, and have shown the efficacy of steroid drugs in various doses and regimens. Further, drisapersen and eteplirsen (exon skipping drugs and ataluren (a drug to overcome stop codon mutations have achieved some clinical improvement. Cardioprotective drugs are efficacious in DMD, and eplerenone, an aldosterone inhibitor and diuretic, is now being used to treat the disease. The dietary approach should be used in wheelchair-bound DMD children in combination with respiratory assistance. The importance of some of the treatments proposed is that they might also be useful in other genetic disorders where stop codon mutations are present; moreover, it is possible that these new treatments will improve quality of life for many patients. Keywords: Duchenne muscular dystrophy, steroids, ataluren, drisapersen, eplerenone, eteplirsen

  18. Cardiac involvement in Duchenne and Becker muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Sophie; Mavrogeni; George; Markousis-Mavrogenis; Antigoni; Papavasiliou; Genovefa; Kolovou

    2015-01-01

    Duchenne and Becker muscular dystrophy(DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation,not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction,heart block or malignant arrhythmias. Not only DMD/BMD patients,but also female carriers may present cardiac involvement. Clinically overt heart failure in dystrophinopathies may be delayed or absent,due to relative physical inactivity. The commonest electrocardiographic findings include conduction defects,arrhythmias(supraventricular or ventricular),hypertrophy and evidence of myocardial necrosis. Echocardiography can assess a marked variability of left ventricular dysfunction,independently of age of onset or mutation groups. Cardiovascular magnetic resonance(CMR) has documented a pattern of epicardial fibrosis in both dystrophinopathies’ patients and carriers that can be observed even if overt muscular disease is absent. Recently,new CMR techniques,such as postcontrast myocardial T1 mapping,have been used in Duchenne muscular dystrophy to detect diffuse myocardial fibrosis. A combined approach using clinical assessment and CMR evaluation may motivate early cardioprotective treatment in both patients and asymptomatic carriers and delay the development of serious cardiac complications.

  19. Controversies in Pediatric Perioperative Airways

    Directory of Open Access Journals (Sweden)

    Jozef Klučka

    2015-01-01

    Full Text Available Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP, and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI, laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient.

  20. Controversial reversal of nuclear option

    OpenAIRE

    2002-01-01

    Nuclear option is in a unique position to restore its original role of the main source of energy with an increased attention paid to the security of electricity supply as well as regulatory changes affecting fossil fuels, particularly with due introduction of climate change prevention measures. Recent developments indicate the advantages of nuclear option over other possible options in terms of sustainable development. However, a large number of controversial issues on nuclear energy make its...

  1. Multiple sclerosis: evidence and controversies

    OpenAIRE

    Gutiérrez-Álvarez, Ángela-María

    2010-01-01

    Introduction: Multiple sclerosis is a chronic recurrent inflammatory disorder of the central nervous system. The pharmacological treatment of multiple sclerosis has been evaluated with multiple controlled clinical trials that allow the clinician to count with evidence based information to decide the more indicated treatment for each patient. Methodology: A review of the scientific literature was conducted to clarify controversial issues in a clinical relevant topic. Development: The diagnosti...

  2. Controversies in Fistula in Ano

    OpenAIRE

    2012-01-01

    Managing a complex fistula in ano can be a daunting task for most surgeons; largely due to the two major dreaded complications—recurrence & fecal incontinence. It is important to understand the anatomy of the anal sphincters & the aetiopathological process of the disease to provide better patient care. There are quite a few controversies associated with fistula in ano & its management, which compound the difficulty in treating fistula in ano. This article attempts to clear some of those major...

  3. Controversies in neurosciences critical care.

    Science.gov (United States)

    Chang, Tiffany R; Naval, Neeraj S; Carhuapoma, J Ricardo

    2012-06-01

    Neurocritical care is an evolving subspecialty with many controversial topics. The focus of this review is (1) transfusion thresholds in patients with acute intracranial bleeding, including packed red blood cell transfusion, platelet transfusion, and reversal of coagulopathy; (2) indications for seizure prophylaxis and choice of antiepileptic agent; and (3) the role of specialized neurocritical care units and specialists in the care of critically ill neurology and neurosurgery patients.

  4. Gaucher Disease and Cancer: Concept and Controversy

    Directory of Open Access Journals (Sweden)

    Francis Y. M. Choy

    2011-01-01

    Full Text Available Gaucher disease is an inherited disorder caused by a deficiency in the lysosomal hydrolase glucocerebrosidase. There is a wide spectrum of clinical presentations, with the most common features being hepatosplenomegaly, skeletal disease, and cytopenia. Gaucher disease has been classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (nonneuronopathic, Type 2 (acute neuronopathic, and Type 3 (subacute neuronopathic. The two main treatment options include enzyme replacement therapy and substrate reduction therapy. Recently, discussion has escalated around the association of Gaucher disease and cancer, with conflicting reports as to whether Gaucher patients have an increased risk of malignancy. In this review, we present both the concept and controversy surrounding the association of Gaucher disease with cancer.

  5. Analysing the disability- sexuality controversy

    Directory of Open Access Journals (Sweden)

    Patrick Sibanda

    2015-10-01

    Full Text Available Sexuality is one of the many phenomena which are least openly discussed particularly in the African culture. Sexuality is conceived variously in different cultures and disability is seen as a threat to sexuality in many of the cultures. Meanwhile, sexuality is regarded as a central theme in the development of self-esteem and self-identity since it has been conceived within the bodily perfection and bodily beauty complexes. Thus, the way sexuality is conceived for people with disabilities forms the central thrust of this paper. Views about the sexuality of people with disabilities have manifested in the construction of what we term the disability- sexuality controversy. The paper examines this controversy and explores ways of resolving it in the context of educational programming. The paper concludes that the disability- sexuality controversy is more of a social than a biological construct. This conclusion is premised on the hypothetical view that both disability and sexuality are intimately tied to the concept of self in which case sexuality is constructed within the social realm of the bodily beauty complexes. The way forward is a multi- sectorial approach towards the eradication of disability stereotypes. In addition, the paper recommends active parental involvement in the programming and implementation of sexuality education for their children with disabilities.

  6. A different spectrum of DMD gene mutations in local Chinese patients with Duchenne/Becker muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Ivan Fai-man Lo; Kent Keung-san Lai; Tony Ming-for Tong; Stephen Tak-sum Lam

    2006-01-01

    Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chinese patients with Duchenne or Becket muscular dystrophy (DMD/BMD), and to study genotype-phenotype correlation.Methods A retrospective review of 67 patients.Results Twenty-three (34.3%) patients had exon deletions; whereas 5 (7.5%) patients had exon duplications.Twenty-three (34.3%) patients had small mutations, including 17-point mutations and 6 small insertions or deletions. No correlation was found between the type of mutation and the muscle phenotype or mental retardation.Significantly fewer maternal carriers were found in patients with exon deletions, and a positive family history was more common in those with small mutations. DMD phenotype was significantly less common in patients with exon deletions/duplications at the 5' hotspot, whereas all 4 small mutations associated with mental retardation were located in the 3' end of the gene.Conclusions The percentage of DMD exon deletions in local Chinese patients was significantly lower than the commonly quoted 60%. This indicated an ethnic or regional difference in predisposition to DMD exon deletions.

  7. Intermittent prednisone therapy in Duchenne muscular dystrophy : A randomized controlled trial

    NARCIS (Netherlands)

    Beenakker, EAC; Fock, JM; Van Tol, M; Maurits, NM; Koopman, HM; Brouwer, OF; Van der Hoeven, JH

    Background: Prednisone treatment is used to prolong ambulation in patients with Duchenne muscular dystrophy (DMD). However, since severe adverse effects often accompany prednisone treatment, it is debatable whether the benefits of prednisone treatment outweigh its adverse effects. Objectives: To

  8. Glycosaminoglycan modifications in Duchenne muscular dystrophy: specific remodeling of chondroitin sulfate/dermatan sulfate

    NARCIS (Netherlands)

    Negroni, E.; Henault, E.; Chevalier, F.; Gilbert-Sirieix, M.; Kuppevelt, T.H. van; Papy-Garcia, D.; Uzan, G.; Albanese, P.

    2014-01-01

    Widespread skeletal muscle degeneration and impaired regeneration lead to progressive muscle weakness and premature death in patients with Duchenne muscular dystrophy (DMD). Dystrophic muscles are progressively replaced by nonfunctional tissue because of exhaustion of muscle precursor cells and exce

  9. Intermittent prednisone therapy in Duchenne muscular dystrophy : A randomized controlled trial

    NARCIS (Netherlands)

    Beenakker, EAC; Fock, JM; Van Tol, M; Maurits, NM; Koopman, HM; Brouwer, OF; Van der Hoeven, JH

    2005-01-01

    Background: Prednisone treatment is used to prolong ambulation in patients with Duchenne muscular dystrophy (DMD). However, since severe adverse effects often accompany prednisone treatment, it is debatable whether the benefits of prednisone treatment outweigh its adverse effects. Objectives: To stu

  10. Mouthpiece ventilation in Duchenne muscular dystrophy: a rescue strategy for noncompliant patients.

    Science.gov (United States)

    Fiorentino, Giuseppe; Annunziata, Anna; Cauteruccio, Rosa; Frega, Gianfranco Scotto di; Esquinas, Antonio

    2016-01-01

    To evaluate mouthpiece ventilation (MPV) in patients with Duchenne muscular dystrophy (DMD) who are noncompliant with noninvasive ventilation (NIV). We evaluated four young patients with DMD who had previously refused to undergo NIV. Each patient was reassessed and encouraged to try MPV. The four patients tolerated MPV well and were compliant with NIV at home. MPV proved to be preferable and more comfortable than NIV with any other type of interface. Two of the patients required overnight NIV and eventually agreed to use a nasal mask during the night. The advantages of MPV over other types of NIV include fewer speech problems, better appearance, and less impact on the patient, eliminating the risk of skin breakdown, gastric distension, conjunctivitis, and claustrophobia. The use of a mouthpiece interface should be always considered in patients with DMD who need to start NIV, in order to promote a positive approach and a rapid acceptance of NIV. Using MPV during the daytime makes patients feel safe and more likely to use NIV at night. In addition, MPV increases treatment compliance for those who refuse to use other types of interfaces. Avaliar a ventilação bucal (VB) em pacientes com distrofia muscular de Duchenne (DMD) não aderentes à ventilação não invasiva (VNI). Foram avaliados quatro pacientes jovens com DMD que anteriormente recusaram-se a se submeter à VNI. Cada paciente foi reavaliado e encorajado a tentar VB. Os quatro pacientes toleraram bem a VB e aderiram ao uso de VNI em casa. O uso de VB provou ser uma alternativa preferível e mais confortável que o uso de VNI com qualquer outro tipo de interface. Dois dos pacientes necessitaram de VNI noturna e eventualmente aceitaram utilizar uma máscara nasal durante a noite. As vantagens da VB sobre outros tipos de VNI incluem menores problemas na fala, melhor aparência e menor impacto no paciente, eliminando o risco de lesões na pele, distensão gástrica, conjuntivite e claustrofobia. O uso da

  11. Mouthpiece ventilation in Duchenne muscular dystrophy: a rescue strategy for noncompliant patients

    Directory of Open Access Journals (Sweden)

    Giuseppe Fiorentino

    Full Text Available ABSTRACT Objective: To evaluate mouthpiece ventilation (MPV in patients with Duchenne muscular dystrophy (DMD who are noncompliant with noninvasive ventilation (NIV. Methods: We evaluated four young patients with DMD who had previously refused to undergo NIV. Each patient was reassessed and encouraged to try MPV. Results: The four patients tolerated MPV well and were compliant with NIV at home. MPV proved to be preferable and more comfortable than NIV with any other type of interface. Two of the patients required overnight NIV and eventually agreed to use a nasal mask during the night. Conclusions: The advantages of MPV over other types of NIV include fewer speech problems, better appearance, and less impact on the patient, eliminating the risk of skin breakdown, gastric distension, conjunctivitis, and claustrophobia. The use of a mouthpiece interface should be always considered in patients with DMD who need to start NIV, in order to promote a positive approach and a rapid acceptance of NIV. Using MPV during the daytime makes patients feel safe and more likely to use NIV at night. In addition, MPV increases treatment compliance for those who refuse to use other types of interfaces.

  12. Mouthpiece ventilation in Duchenne muscular dystrophy: a rescue strategy for noncompliant patients

    Science.gov (United States)

    Fiorentino, Giuseppe; Annunziata, Anna; Cauteruccio, Rosa; Frega, Gianfranco Scotto di; Esquinas, Antonio

    2016-01-01

    ABSTRACT Objective: To evaluate mouthpiece ventilation (MPV) in patients with Duchenne muscular dystrophy (DMD) who are noncompliant with noninvasive ventilation (NIV). Methods: We evaluated four young patients with DMD who had previously refused to undergo NIV. Each patient was reassessed and encouraged to try MPV. Results: The four patients tolerated MPV well and were compliant with NIV at home. MPV proved to be preferable and more comfortable than NIV with any other type of interface. Two of the patients required overnight NIV and eventually agreed to use a nasal mask during the night. Conclusions: The advantages of MPV over other types of NIV include fewer speech problems, better appearance, and less impact on the patient, eliminating the risk of skin breakdown, gastric distension, conjunctivitis, and claustrophobia. The use of a mouthpiece interface should be always considered in patients with DMD who need to start NIV, in order to promote a positive approach and a rapid acceptance of NIV. Using MPV during the daytime makes patients feel safe and more likely to use NIV at night. In addition, MPV increases treatment compliance for those who refuse to use other types of interfaces. PMID:28117478

  13. Partisan Scholarship in Technoscientific Controversies

    DEFF Research Database (Denmark)

    Galis, Vasilis; Hansson, Anders

    2012-01-01

    Several academic traditions have addressed epistemological objectivity and/or partisanship in the study of technoscientific controversies. On the one hand, positivist and relativist scholars agree that the political commitments of the social researcher should not impinge on scientific enquiry......, while on the other hand, feminist and Marxist scholars not only take stands in diverse technoscientific debates, but even claim their agendas to be more credible than those of orthodox scientists. Such perspectives stress that all research is partisan in one way or another because it involves questions...

  14. Duchenne muscular dystrophy drugs face tough path to approval.

    Science.gov (United States)

    Hodgkinson, L; Sorbera, L; Graul, A I

    2016-03-01

    Highly anticipated as new disease-modifying treatments for Duchenne muscular dystrophy (DMD), therapeutics by BioMarin Pharmaceutical (Kyndrisa™; drisapersen) and Sarepta Therapeutics (eteplirsen; AVI-4658) both recently received negative FDA reviews and are now facing battles for approval in the U.S. At present, BioMarin is committed to working with the FDA to forge a pathway to approval following the failure of its NDA, while Sarepta awaits the formal decision on its NDA, which is expected by late May 2016. Despite the critical nature of both reviews, analysts consider that there is still a narrow possibility of approval of both drugs. According to Consensus forecasts from Thomson Reuters Cortellis for Competitive Intelligence, Kyndrisa is forecast to achieve sales of USD 533.71 million in 2021.

  15. Prenatal Diagnosis of the Duchenne Muscular Dystrophy. A Family Presentation

    Directory of Open Access Journals (Sweden)

    Humberto Perera Navarro

    2007-05-01

    Full Text Available The Duchenne muscular dystrophy is one of the most frequent hereditary myopathies that exist. It is characterized by degeneration of the muscle skeletal fibers which produce handicap in the first decade of life bringing about death due to cardiac or respiratory failure. The responsible gene of the disease is known as DMD and it is located in the X chromosome shorter arm. A family history is presented in which the pregnant woman who is the sick patient’s sister asks for a prenatal diagnosis. An indirect molecular study was performed with the STR-50 polymorphic marker. After the analysis of the results in which the lab methodology was applied, the fetus was found to be sick and the family decided to interrupt the pregnancy.

  16. Treatment of Duchenne muscular dystrophy with growth hormone inhibitors.

    Science.gov (United States)

    Zatz, M; Betti, R T; Frota-Pessoa, O

    1986-07-01

    A controlled, double-blind therapeutic trial with the drug mazindol, a growth hormone inhibitor, was performed in a pair of 7 1/2 year-old monozygotic twins, with Duchenne muscular dystrophy (DMD). The rationale for this trial was based on a patient (reported previously) affected simultaneously with DMD and growth hormone (GH) deficiency, who is showing a benign course of the dystrophic process and is still walking at 18 years. One of the twins received 2 mg of mazindol daily, while the other received a placebo. The assessment, repeated every 2 months, included weight and height measurements, functional and motor ability tests, ergometry and determinations of serum enzymes and GH levels. After one year of trial the code was broken and it was seen that the twin under placebo treatment was strikingly worse than his brother, the progression of whose condition was practically arrested. These results strongly suggest that treatment with a GH inhibitor is beneficial for DMD patients.

  17. Current controversies in childhood vaccination.

    Science.gov (United States)

    Carrillo-Marquez, Maria; White, Lisa

    2013-01-01

    As pediatric practitioners, one of the contemporary challenges in providing medical care for children is the increasing proportion of vaccination refusal. This occurs in spite of the demonstrated individual and collective benefit and cost effectiveness of vaccination. Controversies regarding vaccine components and side effects have misled parents to believe that vaccines might be harmful based on inaccurate data from the Internet, celebrities, as well as misinterpreted and frankly bad science. This belief of vaccines being harmful has led to fear and decreased immunization rates in spite of sound scientific evidence supporting the safety of vaccines and their lack of association with autism, developmental disabilities or other medical disorders. Some parents also believe in alternative ways to avoid disease, often adhering to practices that have little foundation in the best of empiric science. It is not a coincidence that recent outbreaks of vaccine-preventable diseases, including measles and pertussis (whooping cough), have occurred in areas where vaccination has declined largely due to exemptors. This article intends to review some of the common vaccine myths and controversies and to serve as a resource to provide accurate information and references for busy practitioners and the families that we serve.

  18. Dysphagia in Duchenne muscular dystrophy: practical recommendations to guide management.

    Science.gov (United States)

    Toussaint, Michel; Davidson, Zoe; Bouvoie, Veronique; Evenepoel, Nathalie; Haan, Jurn; Soudon, Philippe

    2016-10-01

    Duchenne muscular dystrophy (DMD) is a rapidly progressive neuromuscular disorder causing weakness of the skeletal, respiratory, cardiac and oropharyngeal muscles with up to one third of young men reporting difficulty swallowing (dysphagia). Recent studies on dysphagia in DMD clarify the pathophysiology of swallowing disorders and offer new tools for its assessment but little guidance is available for its management. This paper aims to provide a step-by-step algorithm to facilitate clinical decisions regarding dysphagia management in this patient population. This algorithm is based on 30 years of clinical experience with DMD in a specialised Centre for Neuromuscular Disorders (Inkendaal Rehabilitation Hospital, Belgium) and is supported by literature where available. Dysphagia can worsen the condition of ageing patients with DMD. Apart from the difficulties of chewing and oral fragmentation of the food bolus, dysphagia is rather a consequence of an impairment in the pharyngeal phase of swallowing. By contrast with central neurologic disorders, dysphagia in DMD accompanies solid rather than liquid intake. Symptoms of dysphagia may not be clinically evident; however laryngeal food penetration, accumulation of food residue in the pharynx and/or true laryngeal food aspiration may occur. The prevalence of these issues in DMD is likely underestimated. There is little guidance available for clinicians to manage dysphagia and improve feeding for young men with DMD. This report aims to provide a clinical algorithm to facilitate the diagnosis of dysphagia, to identify the symptoms and to propose practical recommendations to treat dysphagia in the adult DMD population. Implications for Rehabilitation Little guidance is available for the management of dysphagia in Duchenne dystrophy. Food can penetrate the vestibule, accumulate as residue or cause aspiration. We propose recommendations and an algorithm to guide management of dysphagia. Penetration/residue accumulation

  19. Inspiratory flow reserve in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    De Bruin, P F; Ueki, J; Bush, A; Y Manzur, A; Watson, A; Pride, N B

    2001-06-01

    Patients with advanced muscular dystrophy frequently develop ventilatory failure. Currently respiratory impairment usually is assessed by measuring vital capacity and the mouth pressure generated during a maximal inspiratory maneuver (PI,max), neither of which directly measures ventilatory capacity. We assessed inspiratory flow reserve in 26 boys [mean (SD) age 12.8 (3.8) years] with Duchenne muscular dystrophy (DMD) without ventilatory failure and in 28 normal boys [mean (SD) age 12.6 (1.9) years] by analyzing the ratio between the largest inspiratory flow during tidal breathing (V'I,max(t)) and during a forced vital capacity maneuver (V'I,max(FVC), (V'I,max(t)/V'I,maxFVC). We have compared this ratio with the forced vital capacity FVC and PI,max measured at functional residual capacity. Mean PI,max was -90(30)cmH2O, average 112% (range 57-179%) of predicted values in control boys and -31(11)cmH2O, average 40% predicted values in DMD boys (control vs DMD, P ratio was higher in DMD 0.22 (0.08) than in controls 0.12 (0.03) (P reserve in DMD. Inspiratory flow reserve was within the normal range in 8 of 19 DMD patients with PI,max less than 50% of predicted values. We conclude that measurement of inspiratory flow reserve (V'I,max(t)/V'I,maxFVC ratio) provides a simple and direct assessment of dynamic inspiratory muscle function which is not replicated by static measurement of PI,max or vital capacity and might be useful in assessment of respiratory impairment in boys with Duchenne muscular dystrophy. Follow-up studies are required to establish whether measures of inspiratory flow reserve are of clinical value in predicting subsequent ventilatory failure.

  20. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2012-03-01

    Full Text Available ObjectiveDuchenne muscular dystrophy (DMD is a degenerative disease that usually becomes clinically detectable in childhood as progressive proximal weakness. No cure is yet available for DMD, but the use of steroids improves muscle strength and function. This study has been carried out to select the best steroid for the management of DMD.Materials & MethodsThis study is a single-blind, randomized clinical trial with a sample volume of 34 DMD patients. Half of these patients were treated with deflazacort (0.9 mg/kg daily and the other half with prednisone (0.75 mg/kg daily for a period of 18 months. The motor function score and excess body weight were registered one year after the start and also at the end of the study and compared between the two groups.ResultsDeflazacort was more effective in the improvement of motor function after one year, but there was no significant difference between the two drugs at the end of the study (18 months after start. Weight gain after one year and at the end of the study was higher in prednisone group and steroid treatment with deflazacort appears to cause fewer side effects than prednisone regarding weight gain.ConclusionDeflazacort seems to be more effective than prednisone in the improvement of motor function causing fewer side effects, particularly weight gain. This medication may be important for the improvement of motor function and could be used as the best steroidal treatment for Duchenne muscular dystrophy.

  1. [Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy].

    Science.gov (United States)

    Silva, Helga Cristina Almeida da; Hiray, Marcia; Vainzof, Mariz; Schmidt, Beny; Oliveira, Acary Souza Bulle; Amaral, José Luiz Gomes do

    2017-05-31

    Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040IU.L(-1) (normal 174IU.L(-1)). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  2. Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Yingyin Liang

    2015-05-01

    Full Text Available The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD and Becker (BMD muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD, spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin – those that bind associated proteins of the dystrophin-glycoprotein complex (DGC. On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD.

  3. Muscle ERRγ mitigates Duchenne muscular dystrophy via metabolic and angiogenic reprogramming.

    Science.gov (United States)

    Matsakas, Antonios; Yadav, Vikas; Lorca, Sabina; Narkar, Vihang

    2013-10-01

    Treatment of Duchenne muscular dystrophy (DMD) by replacing mutant dystrophin or restoring dystrophin-associated glycoprotein complex (DAG) has been clinically challenging. Instead, identifying and targeting muscle pathways deregulated in DMD will provide new therapeutic avenues. We report that the expression of nuclear receptor estrogen-related receptor-γ (ERRγ), and its metabolic and angiogenic targets are down-regulated (50-85%) in skeletal muscles of mdx mice (DMD model) vs. wild-type mice. Corelatively, oxidative myofibers, muscle vasculature, and exercise tolerance (33%) are decreased in mdx vs. wild-type mice. Overexpressing ERRγ selectively in the dystrophic muscles of the mdx mice restored metabolic and angiogenic gene expression compared with control mdx mice. Further, ERRγ enhanced muscle oxidative myofibers, vasculature, and blood flow (by 33-66%) and improved exercise tolerance (by 75%) in the dystrophic mice. Restoring muscle ERRγ pathway ameliorated muscle damage and also prevented DMD hallmarks of postexercise muscle damage, hypoxia, and fatigue in mdx mice. Notably, ERRγ did not restore sarcolemmal DAG complex, which is thus dispensable for antidystrophic effects of ERRγ. In summary, ERRγ-dependent metabolic and angiogenic gene program is defective in DMD, and we demonstrate that its restoration is a potential strategy for treating muscular dystrophy.

  4. Subclinical hypothyroidism: Controversies to consensus

    Directory of Open Access Journals (Sweden)

    Syed Abbas Raza

    2013-01-01

    Full Text Available Diagnoses of subclinicaal hypothyroidism (SCH is biochemically made, when serum thyroid stimulating hormone (TSH levels is elevated while free thyroid hormone levels are within normal reference range. SCH is diagnosed after excluding all other causes of elevated TSH levels. Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms. The risk of progression to overt hypothyroidism is related to number of factors including initial serum TSH concentration, presence of auto antibodies, family history and presence goiter. Various screening recommendations for thyroid function assessment are in practice. There are still controversies surrounding SCH and associated risk of various cardiovascular diseases (CVDs, pregnancy outcomes, neuropsychiatric issues, metabolic syndrome, and dyslipidemia. Consensus will require more large randomized clinical studies involving various age groups and medical condition, especially in developing countries. All these efforts will definitely improve our understanding of disease and ultimately patient outcomes.

  5. Cholesterol confusion and statin controversy

    Institute of Scientific and Technical Information of China (English)

    Robert; Du; Broff; Michel; de; Lorgeril

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.

  6. Metabolic scaling: consensus or controversy?

    Directory of Open Access Journals (Sweden)

    Wheatley Denys N

    2004-11-01

    Full Text Available Abstract Background The relationship between body mass (M and standard metabolic rate (B among living organisms remains controversial, though it is widely accepted that in many cases B is approximately proportional to the three-quarters power of M. Results The biological significance of the straight-line plots obtained over wide ranges of species when B is plotted against log M remains a matter of debate. In this article we review the values ascribed to the gradients of such graphs (typically 0.75, according to the majority view, and we assess various attempts to explain the allometric power-law phenomenon, placing emphasis on the most recent publications. Conclusion Although many of the models that have been advanced have significant attractions, none can be accepted without serious reservations, and the possibility that no one model can fit all cases has to be more seriously entertained.

  7. Darwinian Controversies: An Historiographical Recounting

    Science.gov (United States)

    Depew, David J.

    2010-05-01

    This essay reviews key controversies in the history of the Darwinian research tradition: the Wilberforce-Huxley debate in 1860, early twentieth-century debates about the heritability of acquired characteristics and the consistency of Mendelian genetics with natural selection; the 1925 Scopes trial about teaching evolution; tensions about race, culture, and eugenics at the 1959 centenary celebration Darwin’s Origin of Species; adaptationism and its critics in the Sociobiology debate of 1970s and, more recently, Evolutionary Psychology; and current disputes about Intelligent Design. These controversies, I argue, are etched into public memory because they occur at the emotionally charged boundaries between public-political, technical-scientific, and personal-religious spheres of discourse. Over most of them falls the shadow of eugenics. The main lesson is that the history of Darwinism cannot be told except by showing the mutual influence of the different norms of discourse that obtain in the personal, technical, and public spheres. Nor can evolutionary biology successfully be taught to citizens and citizens-to-be until the fractious intersections between spheres of discourse have been made explicit. In the course of showing why, I take rival evolutionary approaches to be dynamical historical research traditions rather than static theories. Accordingly, I distinguish Darwin’s version of Darwinism from its later transformations. I pay special attention to the role Darwin assigned to development in evolution, which was marginalized by twentieth-century population genetical Darwinism, but has recently resurfaced in new forms. I also show how the disputed phrases “survival of the fittest” and “social Darwinism” have shaped personal anxieties about “Darwinism,” have provoked public opposition to teaching evolution in public schools, and have cast a shadow over efforts to effectively communicate to the public largely successful technical efforts to make

  8. The Controversies over Bioenergy in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Andersen, Bente Hessellund

    2012-01-01

    for processing of biomass for biofuels. The alignment with the private car regime is strong, because biofuel enables continuation of fuel-driven vehicles as dominating transportation mode. Danish farmers see manure as important source for biogas while arguing for reduction of climate impact and nuisances from...... a prominent role in several Danish climate and energy plans, alongside with wind and solar energy, and energy savings. There are major controversies about targets for bioenergy with respect to acceptable types, sources and amounts of biomass. Strong path dependency is identified. Energy companies in Denmark...... convert coal fired power plants to biomass in order to sustain the role of these power plants. Their increasing use of imported wood pellets is criticized for increasing greenhouse gas emissions because of fast logging of years of forest growth. A Danish biotech company is developing enzymes...

  9. Race and Genetics: Controversies in Biomedical, Behavioral, and Forensic Sciences

    Science.gov (United States)

    Ossorio, Pilar; Duster, Troy

    2005-01-01

    Among biomedical scientists, there is a great deal of controversy over the nature of race, the relevance of racial categories for research, and the proper methods of using racial variables. This article argues that researchers and scholars should avoid a binary-type argument, in which the question is whether to use race always or never.…

  10. In vitro mouse model in Duchenne muscular dystrophy diagnosis using 50-MHz ultrasound waves.

    Science.gov (United States)

    Laux, D; Blasco, H; Ferrandis, J Y; Hugon, G; Despaux, G; Leydier, A; Mornet, D

    2010-08-01

    Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, the protein that plays a key mechanical role in maintaining muscle membrane integrity. One of the major consequences of dystrophin deficiency is the degeneration of muscle fibres, with a progressive loss in muscle strength. The objective of this research was to find an ultrasonic parameter sensitive to DMD, which could give relevant information related to microstructure if compared to traditional investigations such as morphometrical analysis. This "in vitro" study focused on the Mdx mouse model and investigated the potential differences between wild-type and dystrophin-deficient mice diaphragms. Using a 50MHz ultrasonic sensor built in our group, we recorded an increase in ultrasonic wave attenuation in the dystrophin-deficient samples in comparison with normal muscles. A correlation between attenuation, mouse age and the percentage of non-muscular proportion in muscle was observed. As Mdx mouse is the best animal model for DMD and reproduces the degenerative pattern observed in human DMD muscles, this approach could be a powerful tool for in vitro DMD investigation and, more generally, for the characterisation of muscle properties. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  11. Duchenne or Becker muscular dystrophy: A clinical, genetic and immunohistochemical study in China

    Directory of Open Access Journals (Sweden)

    Qian Wang

    2011-01-01

    Full Text Available Background and Objective: Duchenne and Becker muscular dystrophies are X-linked diseases caused by mutations in the dystrophin gene, which affect approximately 1 in 3,500 and 1 in 18,000 boys, respectively. The aim of this work was to develop a method to assist the diagnosis and classification of the disease. Materials and Methods: A large data set of dystrophin mutations was detected in 167 Chinese patients by multiplex ligation-dependent probe amplification and sequencing. Muscle biopsy, immunohistochemistry and STR analysis were also carried out in the patients and carriers. Results: One hundred and three deletions, 23 duplications and two-point mutations. The deletion of one or more exons was detected in 103 (61.7% patients. The region spanning exons 44-55 was the most frequent deletion. The duplication was identified in 23 (13.8% patients, which was more common than previously reported. Most duplications were found in exons 2-18. Six out of the 45 muscle biopsies analyzed showed the presence of other muscle diseases. Conclusions: This study may be important to enable comparisons of mutation type and the most appropriate analytical approach for samples from different geographical areas and ethnicities.

  12. Molecular Diagnosis of Duchenne/Becker Muscular Dystrophy: Analysis of Exons Deletion and Carrier Detection

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Akbari

    2010-01-01

    Full Text Available Objective: Duchenne and Becker Muscular Dystrophy (DMD and BMD are X-linked conditionsresulting from a defect in the dystrophin gene located at Xp21.2. DMD is the mostfrequent neuromuscular disease in humans (1/3500 male newborns. In approximately65% of DMD and BMD patients, deletions in the dystrophin gene have been identified asthe molecular determinant. The frequency and distribution of dystrophin gene deletions inDMD/BMD patients from different populations are different.The aim of this study was to delineate various types of deleted exons and their frequencyin affected male patients and identification of carrier females by linkage analysis.Materials and Methods: In this study 100 unrelated patients with DMD/BMD were studiedfor intragenic deletions in 28 exons and the promoter region of the dystrophin geneusing multiplex PCR. We also performed linkage analysis within the dystrophin gene utilizing8 short tandem repeat markers.Results: Fifty-two (52% patients showed intragenic deletions. A total of 81% of the deletionswere located at the distal hot spot region (44-55 exons and 19% of the deletionswere located at the proximal region (exon 2-19. The most frequent deleted exons were47(16%, 48 and 46 (11%.Most of the STR markers showed heterozygosity in the families studied. The linkageanalysis was useful for detecting carrier status.Conclusion: The present study suggests that intragenic dystrophin gene deletions occurwith the same frequency in Iranian patients compared with other ethnic groups.

  13. Specific cognitive deficits are common in children with Duchenne muscular dystrophy.

    Science.gov (United States)

    Wicksell, Rikard K; Kihlgren, Margareta; Melin, Lennart; Eeg-Olofsson, Orvar

    2004-03-01

    A neuropsychological assessment was conducted to study cognition, with emphasis on memory, information processing/learning ability, and executive functions in boys with Duchenne muscular dystrophy (DMD). A group of 20 boys with DMD, aged 7 to 14 years (mean age 9 years 5 months, SD 2 years 2 months), was contrasted with 17 normally developing age-matched comparison individuals, using specific neuropsychological tests (Block Span, Digit Span, Story Recall, Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Spatial Learning Test, Verbal Fluency, Trail Making Test, Tower of London, Memory for Faces, and Raven's Coloured Progressive Matrices). The DMD group performed significantly worse on all aspects of memory, learning, and executive functions. There was no significant difference in general intellectual ability between the two groups. Analyses of group differences indicate that problems in short-term memory are the most apparent, suggesting specific cognitive deficits. The differences between the groups were similar for both verbal-auditory and visuospatial tests, thus contradicting the idea that cognitive deficits are related to type of stimulus presented. It is concluded from this study that short-term memory deficits might play a critical role in the cognitive impairment and intellectual development seen in those with DMD.

  14. Exacerbation of pathology by oxidative stress in respiratory and locomotor muscles with Duchenne muscular dystrophy.

    Science.gov (United States)

    Lawler, John M

    2011-05-01

    Duchenne muscular dystrophy (DMD) is the most devastating type of muscular dystrophy, leading to progressive weakness of respiratory (e.g. diaphragm) and locomotor muscles (e.g. gastrocnemius). DMD is caused by X-linked defects in the gene that encodes for dystrophin, a key scaffolding protein of the dystroglycan complex (DCG) within the sarcolemmal cytoskeleton. As a result of a compromised dystroglycan complex, mechanical integrity is impaired and important signalling proteins (e.g. nNOS, caveolin-3) and pathways are disrupted. Disruption of the dystroglycan complex leads to high susceptibility to injury with repeated, eccentric contractions as well as inflammation, resulting in significant damage and necrosis. Chronic damage and repair cycling leads to fibrosis and weakness. While the link between inflammation with damage and weakness in the DMD diaphragm is unresolved, elevated oxidative stress may contribute to damage, weakness and possibly fibrosis. While utilization of non-specific antioxidant interventions has yielded inconsistent results, recent data suggest that NAD(P)H oxidase could play a pivotal role in elevating oxidative stress via integrated changes in caveolin-3 and stretch-activated channels (SACs). Oxidative stress may act as an amplifier, exacerbating disruption of the dystroglycan complex, upregulation of the inflammatory transcription factor NF-B, and thus functional impairment of force-generating capacity.

  15. Physical Activity in Boys With Duchenne Muscular Dystrophy Is Lower and Less Demanding Compared to Healthy Boys

    NARCIS (Netherlands)

    Heutinck, L.B.; Kampen, N. van; Jansen, M.; Groot, I.J.M. de

    2017-01-01

    This study describes the amount of physical activity and perception of physical activity in boys with Duchenne muscular dystrophy (DMD) compared to healthy boys. A questionnaire described 6 domains of physical activity. Four Duchenne muscular dystrophy subgroups were made: early and late ambulatory,

  16. Lightweight, modular knee-ankle-foot orthosis for Duchenne muscular dystrophy: design, development, and evaluation.

    Science.gov (United States)

    Taktak, D M; Bowker, P

    1995-12-01

    The study aimed to design and construct a modular system of knee-ankle-foot orthotics (KAFOs) that could be quickly and easily assembled and provided to children with Duchenne muscular dystrophy. A pilot study would then compare the modular orthotics with the childrens' existing devices. Measurements from the legs of a consecutive sample of 26 Duchenne boys were taken to determine the sizing of the modular system. Nine boys with Duchenne muscular dystrophy were randomly selected to take part in a pilot study that focused on a comparison between their original and modular KAFOs of supply time, weight, energy expenditure during gait, gait speed, and ease of don/doff. The supply and fitting of the KAFOs can be done either in the hospital, clinic, or school. Boys with Duchenne muscular dystrophy, referred by the clinician for provision of KAFOs. Nine boys were approached to take part in the pilot study; all accepted. Their age range was 5 to 13 years. It is possible, by use of a modular KAFO system, to provide long leg orthoses to boys with Duchenne muscular dystrophy in approximately 1 hour. The pilot study also showed that the modular KAFOs provided a 23% weight saving, resulting in a 10% energy saving during ambulation and an 8% increase in walking speed. They were easier to don/doff and were preferred by all involved.

  17. PrEP: controversy, agency and ownership

    OpenAIRE

    Cairns, Gus P; Kane Race; Pedro Goicochea

    2016-01-01

    Pre-exposure prophylaxis (PrEP) has been and continues to be an intervention that causes controversy and debate between stakeholders involved in providing or advocating for it, and within communities in need of it. These controversies extend beyond the intrinsically complex issues of making it available. In this commentary, some of the possible roots of the air of dissent and drama that accompanies PrEP are explored. The similarities between the controversies that dogged the earliest human tr...

  18. Current and emerging treatment strategies for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Mah JK

    2016-07-01

    Full Text Available Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments

  19. Computer task performance by subjects with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Malheiros SRP

    2015-12-01

    Full Text Available Silvia Regina Pinheiro Malheiros,1 Talita Dias da Silva,2 Francis Meire Favero,2 Luiz Carlos de Abreu,1 Felipe Fregni,3 Denise Cardoso Ribeiro,4 Carlos Bandeira de Mello Monteiro1,4,5 1School of Medicine of ABC, Santo Andre, Brazil; 2Department of Medicine, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil; 3Center for Neurosciences, University of São Paulo, São Paulo, Brazil; 4Post-graduate Program in Rehabilitation Sciences, Faculty of Medicine, University of São Paulo, São Paulo, Brazil; 5School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil Aims: Two specific objectives were established to quantify computer task performance among people with Duchenne muscular dystrophy (DMD. First, we compared simple computational task performance between subjects with DMD and age-matched typically developing (TD subjects. Second, we examined correlations between the ability of subjects with DMD to learn the computational task and their motor functionality, age, and initial task performance.Method: The study included 84 individuals (42 with DMD, mean age of 18±5.5 years, and 42 age-matched controls. They executed a computer maze task; all participants performed the acquisition (20 attempts and retention (five attempts phases, repeating the same maze. A different maze was used to verify transfer performance (five attempts. The Motor Function Measure Scale was applied, and the results were compared with maze task performance.Results: In the acquisition phase, a significant decrease was found in movement time (MT between the first and last acquisition block, but only for the DMD group. For the DMD group, MT during transfer was shorter than during the first acquisition block, indicating improvement from the first acquisition block to transfer. In addition, the TD group showed shorter MT than the DMD group across the study.Conclusion: DMD participants improved their performance after practicing

  20. The Parkfield Stress Drop Controversy

    Science.gov (United States)

    Abercrombie, R. E.; Nadeau, R. M.

    2003-12-01

    Nadeau et al. (1995) found that the seismicity on the San Andreas fault at Parkfield is highly clustered. Individual clusters consist of a sequence of near periodically repeating small earthquakes of similar seismic moment. Nadeau and Johnston (1998) compared the moments and timing of these repeating earthquakes (Mw 1000 MPa) for the small earthquakes (Mw patches of high Δ σ would be resolvable by standard seismic methods. However, to date nobody has used seismic methods to determine source parameters for these controversial small earthquakes at Parkfield. We use closely located earthquakes of different sizes (for example, the sub-clusters of cluster CL14, Nadeau et al., 1995, Mw-0.2 to 1), recorded on the HRSN borehole network to analyse the source parameters. The smaller earthquakes are used as empirical Green's functions to resolve source processes of the larger events. Preliminary results from the earthquakes in cluster CL14 result in a source dimension of about 25 m and Δ σ of about 1 MPa for the Mw1 earthquakes, assuming that rupture velocity is the same as that for large earthquakes. We also resolve source-time functions for these earthquakes at most stations and so we can investigate the directivity and velocity of the rupture. Finally we compare the source parameter estimates from the seismic modeling, with those from recurrence and creep rate, and assess the validity of the various proposed models.

  1. [Controversy on treatments for gliomas].

    Science.gov (United States)

    Nomura, K

    1998-09-01

    Gliomas are representative primary malignant brain tumors, and with such tumors it is difficult to define the advanced stage. If the advanced stage indicates no curability by surgery alone, most gliomas would belong to this criterion because of their poor prognosis without any completely effective treatment. In this sense, no one could show a standard therapy to treat these unfortunate patients, for example, patients with glioblastoma, they could permit only 1 year survived even they had any applicable treatments to the lesions, these days. Treatment for low-grade gliomas has been most controversial for a long time, and no standard treatments have been determined so far. In this paper, as the treatment of low-grade gliomas it was intended to report what must be done for this patient and the present results of opinion survey for the treatment of gliomas which was done to professors of 80 institutes, from schools of medicine at all universities and medical colleges in Japan. For high-grade gliomas, some effectiveness of radiation therapy was disclosed as well as chemotherapy from recent papers. Gene therapy was also discussed briefly, its present status and future.

  2. Lyme disease: why the controversy?

    Science.gov (United States)

    Beaman, M H

    2016-12-01

    Some Australians have become convinced of the existence of locally acquired Lyme disease (LD). The history of LD, since its recognition in the early 1970s, is reviewed as a model for investigative approaches to unknown syndromes. Australian Management Guidelines for LD include the requirement for diagnostic testing by National Association of Testing Authorities-accredited laboratories using Therapeutic Goods Administration-licensed tests, which result in the efficient diagnosis of LD in overseas travellers. Despite this, patients who have not left Australia pay many thousands of dollars for non-specialist consultations and testing at overseas laboratories. Unproven long-term therapy with multiple antibiotics has resulted in serious complications, including allergies, line sepsis, pancreatitis and pseudomembranous colitis. Studies have shown that LD vectors are not found in Australia, and Lyme Borrelia has not been found in Australian vectors, animals or patients with autochthonous illnesses. I propose that (i) A non-controversial name for the chronic syndrome should be adopted, 'Australian Multisystem Disorder'. (ii) Research funding should enable the development of a consensus case definition and studies of the epidemiology of this syndrome with laboratory investigations to identify an aetiology and surrogate markers of disease. Prospective, randomised treatment studies could then be undertaken using ethical protocols. © 2016 Royal Australasian College of Physicians.

  3. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  4. The Social Life of Data (Prototyping Controversies)

    DEFF Research Database (Denmark)

    Jørgensen, Tobias Bornakke; Birkbak, Andreas; Petersen, Morten Krogh

    are out, which leaves it to the public to stumble upon the webpages and explore the results. This unspecified public, however, often seems to have more similarities to a void of non-engagement than a receptive social room. In this paper we take two related steps to counter the lack of public engagement...... that we have produced a map of the controversy. Rather we attempt to make available a potentially controversial data set, followed by an invitation for actors to raise new issues with it. In sum, we try to move from mapping controversies to prototyping controversies. In order to do so, we build a website...

  5. Red-Green Color Vision Impairment in Duchenne Muscular Dystrophy

    Science.gov (United States)

    Costa, Marcelo Fernandes ; Oliveira, Andre Gustavo Fernandes ; Feitosa-Santana, Claudia ; Zatz, Mayana ; Ventura, Dora Fix 

    2007-01-01

    The present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 70 age-matched healthy male subjects with no ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red-green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with statistical agreement (P.05). Of the patients with deletion downstream of exon 30, 66% had a red-green color defect. No color defect was found in the patients with deletion upstream of exon 30. A negative correlation between the color thresholds and age was found for the controls and patients with DMD, suggesting a nonprogressive color defect. The percentage (66%) of patients with a red-green defect was significantly higher than the expected <10% for the normal male population (P<.001). In contrast, patients with DMD with deletion upstream of exon 30 had normal color vision. This color defect might be partially explained by a retina impairment related to dystrophin isoform Dp260. PMID:17503325

  6. Laminin-111: a potential therapeutic agent for Duchenne muscular dystrophy.

    Science.gov (United States)

    Goudenege, Sébastien; Lamarre, Yann; Dumont, Nicolas; Rousseau, Joël; Frenette, Jérôme; Skuk, Daniel; Tremblay, Jacques P

    2010-12-01

    Duchenne muscular dystrophy (DMD) still needs effective treatments, and myoblast transplantation (MT) is considered as an approach to repair damaged skeletal muscles. DMD is due to the complete loss of dystrophin from muscles. The lack of link between the contracting apparatus and the extracellular matrix leads to frequent damage to the sarcolemma triggering muscle fiber necrosis. Laminins are major proteins in the extracellular matrix. Laminin-111 is normally present in skeletal and cardiac muscles in mice and humans but only during embryonic development. In this study, we showed that intramuscular injection of laminin-111 increased muscle strength and resistance in mdx mice. We also used laminin-111 as a coadjuvant in MT, and we showed this protein decreased considerably the repetitive cycles of degeneration, inflammatory reaction, and regeneration. Moreover, MT is significantly improved. To explain the improvement, we confirmed with the same myoblast cell batch that laminin-111 improves proliferation and drastically increases migration in vitro. These results are extremely important because DMD could be treated only by the injection of a recombinant protein, a simple and safe therapy to prevent loss of muscle function. Moreover, the improvement in MT would be significant to treat the muscles of DMD patients who are already weak.

  7. Motor assessment in patients with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Gabriela Palhares Campolina Diniz

    2012-06-01

    Full Text Available OBJECTIVE: Evaluate muscle force and motor function in patients with Duchenne muscular dystrophy (DMD in a period of six months. METHOD: Twenty children and adolescents with diagnosis of DMD were evaluated trough: measurement of the strength of the flexors and extensors of the shoulder, elbow, wrist, knee and ankle through the Medical Research Council (MRC, and application of the Motor Function Measure (MFM. The patients were evaluated twice within a six-month interval. RESULTS: Loss of muscle strength was identified in the MRC score for upper proximal members (t=-2.17, p=0.04. In the MFM, it was noted significant loss in the dimension 1 (t=-3.06, p=0.006. Moderate and strong correlations were found between the scores for muscular strength and the MFM dimensions. CONCLUSION: The MFM scale was a useful instrument in the follow up of patients with DMD. Moreover, it is a more comprehensive scale to assess patients and very good for conducting trials to evaluate treatment.

  8. Functional muscle ischemia in Duchenne and Becker muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Gail D Thomas

    2013-12-01

    Full Text Available Duchenne and Becker muscular dystrophy (DMD/BMD comprise a spectrum of devastating X-linked muscle wasting disease for which there is no treatment. DMD/BMD is caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that stabilizes the muscle membrane and also targets other proteins to the sarcolemma. Among these is the muscle-specific isoform of neuronal nitric oxide synthase (nNOSµ which binds spectrin-like repeats within dystrophin’s rod domain and the adaptor protein α-syntrophin. Dystrophin deficiency causes loss of sarcolemmal nNOSµ and reduces paracrine signaling of muscle-derived nitric oxide (NO to the microvasculature, which renders the diseased muscle fibers susceptible to functional muscle ischemia during exercise. Repeated bouts of functional ischemia superimposed on muscle fibers already weakened by dystrophin deficiency result in use-dependent focal muscle injury. Genetic and pharmacologic strategies to boost nNOSµ-NO signaling in dystrophic muscle alleviate functional muscle ischemia and show promise as novel therapeutic interventions for the treatment of DMD/BMD.

  9. Octreotide enhances positive calcium balance in Duchenne muscular dystrophy.

    Science.gov (United States)

    Nutting, D F; Schriock, E A; Palmieri, G M; Bittle, J B; Elmendorf, B J; Horner, L H; Edwards, M C; Griffin, J W; Sacks, H S; Bertorini, T E

    1995-09-01

    Although receptors for somatostatin are found in bone cells, the effect of somatostatin analogs on calcium metabolism is unknown. The authors studied, in a metabolic ward, the effect of octreotide (a long-acting somatostatin analog) and a placebo in two 6-day calcium balance periods in 8 children with Duchenne muscular dystrophy. As expected, octreotide (2 micrograms/kg, subcutaneously, every 8 hours) reduced serum growth hormone and somatomedin (IGF-1) to levels found in growth hormone deficiency. Octreotide enhanced calcium retention by 30% (96 mg daily [P < 0.04]) in 7 boys for whom complete data (diet, urine, and fecal calcium) were available. In 6 children with urinary calcium excretion (Uca) greater than 50 mg daily, octreotide markedly lowered Uca, from 114 +/- 23 mg daily to 61 +/- 9 mg daily (P < 0.03). Calcium retention occurred in patients with or without initial hypercalciuria, but the higher the basal Uca, the greater was the inhibition by octreotide (r = 0.79; P < 0.03). Inactive, nonambulatory patients had a more pronounced response of Uca to octreotide (P < 0.02). Octreotide caused a mild, nonsignificant reduction in fecal calcium, with no major changes in serum calcium, phosphorus, parathyroid hormone, urinary excretion of sodium and potassium, or in creatinine clearance. Based on the current observations and the presence of receptors for somatostatin in bone cells, this hormone may have, at least on a short-term basis, an anabolic effect on calcium, perhaps favoring its deposition in bone.

  10. Muscle Activation during Gait in Children with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Vuillerot, Carole; Tiffreau, Vincent; Peudenier, Sylviane; Cuisset, Jean-Marie; Pereon, Yann; Leboeuf, Fabien; Delporte, Ludovic; Delpierre, Yannick; Gross, Raphaël

    2016-01-01

    The aim of this prospective study was to investigate changes in muscle activity during gait in children with Duchenne muscular Dystrophy (DMD). Dynamic surface electromyography recordings (EMGs) of 16 children with DMD and pathological gait were compared with those of 15 control children. The activity of the rectus femoris (RF), vastus lateralis (VL), medial hamstrings (HS), tibialis anterior (TA) and gastrocnemius soleus (GAS) muscles was recorded and analysed quantitatively and qualitatively. The overall muscle activity in the children with DMD was significantly different from that of the control group. Percentage activation amplitudes of RF, HS and TA were greater throughout the gait cycle in the children with DMD and the timing of GAS activity differed from the control children. Significantly greater muscle coactivation was found in the children with DMD. There were no significant differences between sides. Since the motor command is normal in DMD, the hyper-activity and co-contractions likely compensate for gait instability and muscle weakness, however may have negative consequences on the muscles and may increase the energy cost of gait. Simple rehabilitative strategies such as targeted physical therapies may improve stability and thus the pattern of muscle activity. PMID:27622734

  11. [Principles of multidisciplinary management of Duchenne muscular dystrophy].

    Science.gov (United States)

    Chabrol, B; Mayer, M

    2015-12-01

    Given the gradual progression observed in Duchenne muscular dystrophy, organization of care in multidisciplinary consultations is essential for optimal management of the different aspects of the disease. Drawing up a care plan is always preceded by a specific consultation for the announcement of the diagnosis with both the parents and the child. Explaining to the child the origin of his problems with simple words, telling him that why he experienced a particular symptom has been understood, is a fundamental step. The child needs to receive the information at different times of the disease following the rhythms of the disease stages, with an appropriate lead time. With the progress achieved in managing this disease, more than 90% of these children now live into adulthood. The switch from pediatric consultations to adult consultations, marking the transition from childhood management at adulthood, is a major challenge in the organization of care. Although today death occurs most often in adulthood, some children die in childhood. For the majority of teams who care for children, whatever the initial pathology may be, the notion of care continuity and accompaniment from the announcement of the disease to the terminal phase is essential. Increasing numbers of therapeutic trials have been developed over the past few years aiming to investigate children with DMD. However, they must not neglect the overall management of these patients and provide the best accompaniment possible.

  12. Neuropsychological and neurobehavioral functioning in Duchenne muscular dystrophy: a review.

    Science.gov (United States)

    Snow, Wanda M; Anderson, Judy E; Jakobson, Lorna S

    2013-06-01

    Duchenne muscular dystrophy (DMD) is a genetic condition affecting predominantly boys that is characterized by fatal muscle weakness. While there is no cure, recent therapeutic advances have extended the lifespan of those with DMD considerably. Although the physiological basis of muscle pathology is well-documented, less is known regarding the cognitive, behavioral, and psychosocial functioning of those afflicted. Several lines of evidence point to central nervous system involvement as an organic feature of DMD, challenging our view of the disorder as strictly neuromuscular. This report provides a review of the literature on neuropsychological and neurobehavioral functioning in DMD. Recent research identifying associations with DMD and neuropsychiatric disorders is also discussed. Lastly, the review presents implications of findings related to nonmotor aspects of DMD for improving the quality of life in those affected. While the literature is often contradictory in nature, this review highlights some key findings for consideration by clinicians, educators and parents when developing therapeutic interventions for this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Cardiac and pulmonary function variability in Duchenne/Becker muscular dystrophy: an initial report.

    Science.gov (United States)

    Birnkrant, David J; Ashwath, Mahi Lakshmi; Noritz, Garey H; Merrill, Michelle C; Shah, Tushar A; Crowe, Carol A; Bahler, Robert C

    2010-09-01

    The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks and then progressively declines. In this report, the authors quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. The authors concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in their clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for the use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy.

  14. [7 MHz real-time sonography of the skeletal musculature in Duchenne muscular dystrophy].

    Science.gov (United States)

    Forst, R; Casser, H R

    1985-12-01

    The lumbar paravertebral musculature, the M. quadriceps femoris and M. triceps surae of boys suffering from Duchenne's muscular dystrophy of different clinical progression, were examined via sonography. The sonographic incisions were made at fixed levels. The sonographic findings were compared with those of healthy boys. The sonographic findings showed - depending on the clinical stage of Duchenne's muscular dystrophy - typical reflex patterns of different intensity determined by lipomatosis and fibrosis of the skeletal musculature, correlating with the clinical stage, and hence musclesonography is an important diagnostic element in the observation of the course and in therapy planning in Duchenne's muscular dystrophy. The 7-MHz transducer has an advantage over the low-frequency transducers mostly in use, because the image quality is substantially superior.

  15. Nutraceuticals and Their Potential to Treat Duchenne Muscular Dystrophy: Separating the Credible from the Conjecture.

    Science.gov (United States)

    Woodman, Keryn G; Coles, Chantal A; Lamandé, Shireen R; White, Jason D

    2016-11-09

    In recent years, complementary and alternative medicine has become increasingly popular. This trend has not escaped the Duchenne Muscular Dystrophy community with one study showing that 80% of caregivers have provided their Duchenne patients with complementary and alternative medicine in conjunction with their traditional treatments. These statistics are concerning given that many supplements are taken based on purely "anecdotal" evidence. Many nutraceuticals are thought to have anti-inflammatory or anti-oxidant effects. Given that dystrophic pathology is exacerbated by inflammation and oxidative stress these nutraceuticals could have some therapeutic benefit for Duchenne Muscular Dystrophy (DMD). This review gathers and evaluates the peer-reviewed scientific studies that have used nutraceuticals in clinical or pre-clinical trials for DMD and thus separates the credible from the conjecture.

  16. Umbilical cord mesenchymal stem cell transplantation for the treatment of Duchenne muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng Yang; Yanxiang Wu; Xinping Liu; Yifeng Xu; Naiwu Lü; Yibin Zhang; Hongmei Wang; Xin Lü; Jiping Cui; Jinxu Zhou; Hong Shan

    2011-01-01

    Due to their relative abundance, stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy, which is a muscular atrophy disease. Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion, in combination with multi-point intramuscular injection. They were followed up for 12 months after cell transplantation. Results showed that clinical symptoms significantly improved, daily living activity and muscle strength were enhanced,the sero-enzyme, electromyogram, and MRI scans showed improvement, and dystrophin was expressed in the muscle cell membrane. Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged, fibrous degeneration was alleviated, and fat infiltration was improved. These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.

  17. Nutraceuticals and Their Potential to Treat Duchenne Muscular Dystrophy: Separating the Credible from the Conjecture

    Directory of Open Access Journals (Sweden)

    Keryn G. Woodman

    2016-11-01

    Full Text Available In recent years, complementary and alternative medicine has become increasingly popular. This trend has not escaped the Duchenne Muscular Dystrophy community with one study showing that 80% of caregivers have provided their Duchenne patients with complementary and alternative medicine in conjunction with their traditional treatments. These statistics are concerning given that many supplements are taken based on purely “anecdotal” evidence. Many nutraceuticals are thought to have anti-inflammatory or anti-oxidant effects. Given that dystrophic pathology is exacerbated by inflammation and oxidative stress these nutraceuticals could have some therapeutic benefit for Duchenne Muscular Dystrophy (DMD. This review gathers and evaluates the peer-reviewed scientific studies that have used nutraceuticals in clinical or pre-clinical trials for DMD and thus separates the credible from the conjecture.

  18. Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

    Science.gov (United States)

    Straathof, C S M; Doorenweerd, N; Wokke, B H A; Dumas, E M; van den Bergen, J C; van Buchem, M A; Hendriksen, J G M; Verschuuren, J J G M; Kan, H E

    2014-10-01

    Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship. © The Author(s) 2014.

  19. Teachers, Classroom Controversy, and the Media

    Science.gov (United States)

    Faulconer, Tracy; Freeman, Ayesha Coning

    2005-01-01

    This article discusses the relationship between teachers, classroom controversy and the media. It also features the story of Ayesha, who coincidentally is one of the authors of this article. Ayesha's story is a social studies teacher's bad dream featuring one of her worst fears: (1) public criticism; and (2) controversy over something that has…

  20. Teaching about NAFTA Using Academic Controversy.

    Science.gov (United States)

    Starr, Eileen M.

    1997-01-01

    Examines a teaching strategy called "constructive controversy" where students are required to argue both the pro and con positions concerning a controversial current topic. Describes students' response to a class using this method to examine the North American Free Trade Agreement (NAFTA). Student response was generally favorable. (MJP)

  1. Evolutionary Psychology: Controversies, Questions, Prospects, and Limitations

    Science.gov (United States)

    Confer, Jaime C.; Easton, Judith A.; Fleischman, Diana S.; Goetz, Cari D.; Lewis, David M. G.; Perilloux, Carin; Buss, David M.

    2010-01-01

    Evolutionary psychology has emerged over the past 15 years as a major theoretical perspective, generating an increasing volume of empirical studies and assuming a larger presence within psychological science. At the same time, it has generated critiques and remains controversial among some psychologists. Some of the controversy stems from…

  2. The evolving perception of controversial movies

    CERN Document Server

    Amendola, Luca; Quartin, Miguel

    2015-01-01

    Polarization of opinion is an important feature of public debate on political, social and cultural topics. The availability of large internet databases of users' ratings has permitted quantitative analysis of polarization trends-for instance, previous studies have included analyses of controversial topics on Wikipedia, as well as the relationship between online reviews and a product's perceived quality. Here, we study the dynamics of polarization in the movie ratings collected by the Internet Movie database (IMDb) website in relation to films produced over the period 1915-2015. We define two statistical indexes, dubbed hard and soft controversiality, which quantify polarized and uniform rating distributions, respectively. We find that controversy decreases with popularity and that hard controversy is relatively rare. Our findings also suggest that more recent movies are more controversial than older ones and we detect a trend of "convergence to the mainstream" with a time scale of roughly 40-50 years. This ph...

  3. Distrofia muscular de Duchenne em menina com translocação cromossômica

    OpenAIRE

    Lineu Cesar Werneck; Silvia M. L. Lemos; Neiva Magdalena

    1988-01-01

    Relato do caso de menina que apresentava clínica e laboratorialmente elementos para o diagnóstico de distrofia muscular progressiva pseudo-hipertrófica de Duchenne, cuja investigação genética revelou translocação cromos&ômica 46,X,t(Bp+, Xq-). Foi feita revisão da literatura, enfatizando a importância dos métodos diagnósticos e a explicação do aparecimento de casos de distrofia muscular pseudo-hipertrófica de Duchenne em pacientes do sexo feminino.

  4. Distrofia muscular de Duchenne em menina com translocação cromossômica

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1988-12-01

    Full Text Available Relato do caso de menina que apresentava clínica e laboratorialmente elementos para o diagnóstico de distrofia muscular progressiva pseudo-hipertrófica de Duchenne, cuja investigação genética revelou translocação cromos&ômica 46,X,t(Bp+, Xq-. Foi feita revisão da literatura, enfatizando a importância dos métodos diagnósticos e a explicação do aparecimento de casos de distrofia muscular pseudo-hipertrófica de Duchenne em pacientes do sexo feminino.

  5. Distrofia muscular de Duchenne em menina com translocação cromossômica

    OpenAIRE

    Lineu Cesar Werneck; Lemos,Silvia M. L.; Neiva Magdalena

    1988-01-01

    Relato do caso de menina que apresentava clínica e laboratorialmente elementos para o diagnóstico de distrofia muscular progressiva pseudo-hipertrófica de Duchenne, cuja investigação genética revelou translocação cromos&ômica 46,X,t(Bp+, Xq-). Foi feita revisão da literatura, enfatizando a importância dos métodos diagnósticos e a explicação do aparecimento de casos de distrofia muscular pseudo-hipertrófica de Duchenne em pacientes do sexo feminino.

  6. Deciding What Is a Controversial Issue: A Case Study of Social Studies Curriculum Controversy

    Science.gov (United States)

    Camicia, Steven P.

    2008-01-01

    Frame analysis was used to examine how competing stakeholders framed a sixth grade curriculum controversy over whether the WWII internment of Japanese Americans should be categorized as a controversial issue. Teachers and administrators in a northwestern U.S. school claimed that the internment was clearly wrong and not controversial, but these…

  7. Gene correction of a duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in.

    Science.gov (United States)

    Popplewell, Linda; Koo, Taeyoung; Leclerc, Xavier; Duclert, Aymeric; Mamchaoui, Kamel; Gouble, Agnés; Mouly, Vincent; Voit, Thomas; Pâques, Frédéric; Cédrone, Frédéric; Isman, Olga; Yáñez-Muñoz, Rafael J; Dickson, George

    2013-07-01

    Duchenne muscular dystrophy (DMD) is a severe inherited, muscle-wasting disorder caused by mutations in the DMD gene. Gene therapy development for DMD has concentrated on vector-based DMD minigene transfer, cell-based gene therapy using genetically modified adult muscle stem cells or healthy wild-type donor cells, and antisense oligonucleotide-induced exon-skipping therapy to restore the reading frame of the mutated DMD gene. This study is an investigation into DMD gene targeting-mediated correction of deletions in human patient myoblasts using a target-specific meganuclease (MN) and a homologous recombination repair matrix. The MN was designed to cleave within DMD intron 44, upstream of a deletion hotspot, and integration-competent lentiviral vectors expressing the nuclease (LVcMN) were generated. MN western blotting and deep gene sequencing for LVcMN-induced non-homologous end-joining InDels (microdeletions or microinsertions) confirmed efficient MN expression and activity in transduced DMD myoblasts. A homologous repair matrix carrying exons 45-52 (RM45-52) was designed and packaged into integration-deficient lentiviral vectors (IDLVs; LVdRM45-52). After cotransduction of DMD myoblasts harboring a deletion of exons 45 to 52 with LVcMN and LVdRM45-52 vectors, targeted knock-in of the RM45-52 region in the correct location in DMD intron 44, and expression of full-length, correctly spliced wild-type dystrophin mRNA containing exons 45-52 were observed. This work demonstrates that genome surgery on human DMD gene mutations can be achieved by MN-induced locus-specific genome cleavage and homologous recombination knock-in of deleted exons. The feasibility of human DMD gene repair in patient myoblasts has exciting therapeutic potential.

  8. Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    van Ommen Gert-Jan B

    2007-07-01

    Full Text Available Abstract Background Antisense-mediated exon skipping is currently one of the most promising therapeutic approaches for Duchenne muscular dystrophy (DMD. Using antisense oligonucleotides (AONs targeting specific exons the DMD reading frame is restored and partially functional dystrophins are produced. Following proof of concept in cultured muscle cells from patients with various deletions and point mutations, we now focus on single and multiple exon duplications. These mutations are in principle ideal targets for this approach since the specific skipping of duplicated exons would generate original, full-length transcripts. Methods Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed. Results For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62, by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons. Conclusion The correction of DMD duplications by exon skipping depends on the specific exons targeted. Its options vary from the ideal one, restoring for the first time the true, wild type dystrophin, to requiring more 'classical' skipping strategies, while the correction of multi-exon deletions may need the design of tailored approaches.

  9. Anestesia em paciente com Distrofia Muscular de Duchenne: relato de caso Anestesia en paciente con Distrofia Muscular de Duchenne: relato de caso Anesthesia in Duchenne’s Muscular Dystrophy patient: case report

    OpenAIRE

    Deoclécio Tonelli; Iglair Pinho; Paula de Camargo Neves Sacco; Eduardo Piccinini Vianna; José Correia de Vasconcellos; Raquel Vasconcelos de Souza; Sidney Umakoshi

    2003-01-01

    JUSTIFICATIVA E OBJETIVOS: A distrofia muscular de Duchenne é uma afecção recessiva ligada ao cromossomo X, geralmente diagnosticada na infância, acentuando-se progressivamente até agravar a função respiratória. O objetivo deste relato é apresentar um caso de um paciente com distrofia muscular de Duchenne diagnosticada há 2 anos, submetido à postectomia, sob anestesia geral com cetamina S. RELATO DO CASO: Paciente com 9 anos de idade com Distrofia Muscular de Duchenne diagnosticada há 2 anos,...

  10. Recent advance in therapy for Duchenne muscular dystrophy%Duchenne 型肌营养不良症的治疗进展

    Institute of Scientific and Technical Information of China (English)

    周洁; 张金; 郭军红

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive lethal disease and usually found at around the age of 6, patients was unable to walk in 9 to 14 years old. Mostly they are died of heart or pulmonary function failure at around 20 years of age. At present the treatment of DMD is deficiency, this paper reviewed the recent progress in the treatment of DMD.%Duchenne 型肌营养不良症(DMD)是一种 X 连锁隐性遗传的致死性肌病,一般6岁左右发病,9~14岁渐至不能行走,多于20岁左右死于心、肺功能衰竭。目前 DMD 的治疗方法匮乏,本文对 DMD 治疗进展进行综述。

  11. Dysphagia in Duchenne muscular dystrophy assessed objectively by surface electromyography.

    Science.gov (United States)

    Archer, Sally K; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-06-01

    Objective swallowing assessment is indicated in the management of patients with Duchenne muscular dystrophy (DMD). Surface electromyography (sEMG) provides a non-invasive, objective method of quantifying muscle activity. It was hypothesised that the measurement of sEMG activity during swallowing would distinguish between preserved and disordered swallow function in DMD. This comparative study investigated the peak, duration, and relative timing of muscle activity during swallowing of four muscle groups: orbicularis oris, masseter, submental, and infrahyoid. The study included three groups of participants: Nine DMD patients with dysphagia (mean age = 21.7 ± 4.2 years), six DMD patients with preserved swallow function (21.0 ± 3.0 years), and 12 healthy controls (24.8 ± 3.1 years). Dysphagic DMD participants produced significantly higher normalised peak amplitude measurements than the healthy control group for masseter (61.77 vs. 5.07; p ≤ 0.01) and orbicularis oris muscles (71.87 vs. 26.22; p ≤ 0.05). Intrasubject variability for masseter peak amplitude was significantly greater for dysphagic DMD participants than the other groups (16.01 vs. 5.86 vs. 2.18; p ≤ 0.05). There were no differences in timing measurements between groups. Different characteristic sEMG waveforms were observed for the three groups. sEMG provides useful physiological information for the evaluation of swallowing in DMD patients, justifying further study.

  12. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    McDonald, Craig M; Meier, Thomas; Voit, Thomas; Schara, Ulrike; Straathof, Chiara S M; D'Angelo, M Grazia; Bernert, Günther; Cuisset, Jean-Marie; Finkel, Richard S; Goemans, Nathalie; Rummey, Christian; Leinonen, Mika; Spagnolo, Paolo; Buyse, Gunnar M

    2016-08-01

    In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10-18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated "by patient" (HR 0.33, p = 0.0187) and for "all BAEs" (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics.

  13. Growth and psychomotor development of patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Sarrazin, Elisabeth; von der Hagen, Maja; Schara, Ulrike; von Au, Katja; Kaindl, Angela M

    2014-01-01

    Duchenne muscular dystrophy (DMD) is one of the most common hereditary degenerative neuromuscular diseases and caused by mutations in the dystrophin gene. The objective of the retrospective study was to describe growth and psychomotor development of patients with DMD and to detect a possible genotype-phenotype correlation. Data from 263 patients with DMD (mean age 7.1 years) treated at the Departments of Pediatric Neurology in three German University Hospitals was assessed with respect to body measurements (length, weight, body mass index BMI, head circumference OFC), motor and cognitive development as well as genotype (site of mutation). Anthropometric measures and developmental data were compared to those of a reference population and deviations were analyzed for their frequency in the cohort as well as in relation to the genotypes. Corticosteroid therapy was implemented in 29 from 263 patients. Overall 30% of the patients exhibit a short statue (length development at 2-5 years of age, and this is even more prevalent when steroid therapy is applied (45% of patients with steroid therapy). The BMI shows a rightwards shift (68% > 50th centile) and the OFC a leftwards shift (65% development is delayed in a third of the patients (mean age at walking 18.3 months, 30% > 18 months, 8% > 24 months). Almost half of the patients show cognitive impairment (26% learning disability, 17% intellectual disability). Although there is no strict genotype-phenotype correlation, particularly mutations in the distal part of the dystrophin gene are frequently associated with short stature and a high rate of microcephaly as well as cognitive impairment.

  14. Evaluation of neural damage in Duchenne muscular dystrophy patients.

    Science.gov (United States)

    Salam, Ekram Abdel; Abdel-Meguid, Iman Ehsan; Shatla, Rania; Korraa, Soheir

    2014-05-01

    The presence of non-progressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy (DMD). Concurrently, the amyloid beta peptide (Aβ42) protein has been associated with changes in memory and cognitive functions. Also, it has been shown that different subtypes of neural stem/progenitor cells (CD 34, CD 45, nestin) are involved in the innate repair of plasticity mechanisms by the injured brain, in which Nerve Growth Factor (NGF) acts as chemotactic agents to recruit such cells. Accordingly, the present study investigated levels of CD 34, CD 45, nestin and NGF in an attempt to investigate makers of neural regeneration in DMD. Neural damage was assayed in terms of Aβ42. Results showed that Aβ42 (21.9 ± 6.7 vs. 12.13 ± 4.5) was significantly increased among DMD patients compared to controls. NGF (165.8 ± 72 vs. 89.8 ± 35.9) and mononuclear cells expressing nestin (18.9 ± 6 vs. 9 ± 4), CD 45 (64 ± 5.4 vs. 53.3 ± 5.2) and CD34 (75 ± 6.2 vs. 60 ± 4.8) were significantly increased among DMD patients compared to controls. In conclusion cognitive function decline in DMD patients is associated with increased levels of Aβ42, which is suggested to be the cause of brain damage in such patients. The significant increase plasma NFG and in the number of mononuclear cells bearing CD34, CD45 and nestin indicates that regeneration is an ongoing process in these patients. However, this regeneration cannot counterbalance the damage induced by dystrophine mutation and increased Aβ42.

  15. Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Andrea Barp

    Full Text Available Dilated cardiomyopathy (DCM is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD. DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4 also modify DCM onset.A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior; DCM-free patients were censored at the age of last echocardiographic follow-up.Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027.We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts.

  16. Presence of mechanical dyssynchrony in duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Akula Nandakishore

    2011-02-01

    Full Text Available Abstract Background Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD is a leading cause of death. Cardiac resynchronization therapy (CRT has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR may predict CRT efficacy. Methods DMD patients (n = 236 were stratified into 4 groups based on age, diagnosis of DMD, left ventricular (LV ejection fraction (EF, and presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE compared to normal controls (n = 77. Dyssynchrony indices were calculated based on timing of CMR derived circumferential strain (ecc. The calculated indices included cross-correlation delay (XCD, uniformity of strain (US, regional vector of variance (RVV, time to maximum strain (TTMS and standard deviation (SD of TTMS. Abnormal XCD value was defined as > normal + 2SD. US, RVV, TTMS and SD were calculated for patients with abnormal XCD. Results There was overall low prevalence of circumferential dyssynchrony in the entire DMD population; it increased to 17.1% for patients with abnormal EF and to 31.2% in the most advanced stage (abnormal EF with fibrosis. All but one DMD patient with mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. The calculated US and RVV values (0.91 ± 0.09, 1.34 ± 0.48 indicate disperse rather than clustered dyssynchrony. Conclusion Mechanical dyssynchrony is frequent in boys with end stage DMD-associated cardiac dysfunction. It is associated with normal QRS complex as well as extensive lateral fibrosis. Based on these findings, it is unlikely that this patient population will benefit from CRT.

  17. Left ventricular T2 distribution in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Hagenbuch Sean

    2010-03-01

    Full Text Available Abstract Background Although previous studies have helped define the natural history of Duchenne Muscular Dystrophy (DMD-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known. The objective of this study was to assess the distribution of transverse relaxation time (T2 in the left ventricle (LV of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26 and normal control subjects (n = 13 were studied by Cardiovascular Magnetic Resonance (CMR. DMD subject data was stratified based on subject age and LV Ejection Fraction (EF into the following groups: A (12 years, n = 5. LV mid-slice circumferential myocardial strain (εcc was calculated using tagged CMR imaging. T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The Full Width at Half Maximum (FWHM was calculated from a histogram of LV T2 distribution constructed for each subject. Results In DMD subject groups, FWHM of the T2 histogram rose progressively with age and decreasing EF (Group A FWHM= 25.3 ± 3.8 ms; Group B FWHM= 30.9 ± 5.3 ms; Group C FWHM= 33.0 ± 6.4 ms. Further, FWHM was significantly higher in those with reduced circumferential strain (|εcc| ≤ 12% (Group B, and C than those with |εcc| > 12% (Group A. Group A FWHM was not different from the two normal groups (N1 FWHM = 25.3 ± 3.5 ms; N2 FWHM= 24.0 ± 7.3 ms. Conclusion Reduced EF and εcc correlates well with increased T2 heterogeneity quantified by FWHM, indicating that subclinical functional impairments could be associated with pre-existing abnormalities in tissue structure in young DMD patients.

  18. VIRTUAL CURRENCY "BITCOIN" – CHALLENGES AND CONTROVERSIES

    Directory of Open Access Journals (Sweden)

    ȘOAVĂ GEORGETA

    2016-06-01

    Full Text Available In the knowledge society, when there is a rapidly evolving information technology, the virtual markets, namely the online transactions, have created the premises emergence and development of new technologies of using of finances, namely virtual coin (Bitcoin. Use of this coin appears as an alternative to traditional currencies, but they are not under the control of no body, are devoid of inflation and maintain the anonymity of users. Following the evolution of this new type of coin, we proposed in this paper to present some general aspects of this coin focusing on global controversies on using Bitcoin. We have reviewed several myths that have arisen with the development and penetration of its on market and because it is a volatile coin can generate huge gains but and huge losses, we have studied fluctuation and implications for users and investors and the attraction of the drug dealers and criminals for using virtual currency, Bitcoin. At the end of the paper, based on the analysis we have tried to outline the future of this modern payment system. Thus, we found that lately, in that its value has fluctuated strongly, and increased buyer confidence, but appeared and increased cyber attacks, and the fear that if the state has no a role in protecting citizens from fraud, we can assist at the development of financial schemes extremely dangerous. The financial experts believe that if the world banks would jointly solve all the problems, the virtual money will have a real chance of life.

  19. Enterobius vermicularis: A Controversial Cause of Appendicitis

    Directory of Open Access Journals (Sweden)

    "Gh Mowlavi

    2004-08-01

    Full Text Available Enterobiasis is undoubtedly one of the most common human helminths infections through the world, with an estimate of 1000 million cases worldwide. Although adult worms and their eggs are frequently found in inflamed appendices, but the role of the parasite in producing appendicitis in humans still remains controversial. Although acute appendicitis may occur at any age, but it is relatively rare at the extremes of age. A histopathological study of infested appendices with Enterobius vermicularis was performed in Khuzestan province, south western Iran, during 2001 to 2003. All 40 samples had surgically been removed during the emergency operations and histopathological process with (H&E staining has been performed for each. One of the main objects of this work was to collect more data about the possible role of this highly prevalent human round worm as a causative agent of appendicitis in humans, leading to different types of appendicitis in this part of the country. In this occasion over the slide examinations of the tissue sections, fewer cases than expected, with worm infested appendices were seen exclusively affected with this parasite.

  20. Controversies in Surgical Staging of Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    R. Seracchioli

    2010-01-01

    Full Text Available Endometrial cancer is the most common gynaecological malignancy and its incidence is increasing. In 1998, international federation of gynaecologists and obstetricians (FIGO required a change from clinical to surgical staging in endometrial cancer, introducing pelvic and paraaortic lymphadenectomy. This staging requirement raised controversies around the importance of determining nodal status and impact of lymphadenectomy on outcomes. There is agreement about the prognostic value of lymphadenectomy, but its extent, therapeutic value, and benefits in terms of survival are still matter of debate, especially in early stages. Accurate preoperative risk stratification can guide to the appropriate type of surgery by selecting patients who benefit of lymphadenectomy. However, available preoperative and intraoperative investigations are not highly accurate methods to detect lymph nodes and a complete surgical staging remains the most precise method to evaluate extrauterine spread of the disease. Laparotomy has always been considered the standard approach for endometrial cancer surgical staging. Traditional and robotic-assisted laparoscopic techniques seem to provide equivalent results in terms of disease-free survival and overall survival compared to laparotomy. These minimally invasive approaches demonstrated additional benefits as shorter hospital stay, less use of pain killers, lower rate of complications and improved quality of life.

  1. Controversies in the management of pancreatic IPMN.

    Science.gov (United States)

    Tanaka, Masao

    2011-01-01

    Although considerable progress has been made in our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, some issues still remain to be resolved. Uncertainty exists regarding the classification of IPMNs. The necessity of the mixed-type category of IPMN and whether such lesions should be defined radiographically or histologically needs to be determined. The preoperative distinction of branch duct IPMNs from nonmucinous cysts should be further investigated so that potentially malignant lesions can be identified and management strategies guided effectively. The role and safety of cystic fluid analysis remains to be clarified in this context. With regard to the diagnosis of malignancy in branch duct IPMNs, criteria for identifying malignancy need to be re-evaluated. The presence of mural nodules is a very reliable predictor; however, controversy exists over the value of size as a reliable indicator. Criteria with increased specificity are needed, perhaps including histological subtype of lesion, to reduce the false-positive rate of the present criteria. Finally, the best modality and interval for surveillance of branch duct IPMNs requires determination because of its significance in terms of malignant transformation, development of distinct ductal adenocarcinoma and disease recurrence after resection.

  2. Studies on the adenylate kinase isozymes from the serum and erythrocyte of normal and Duchenne dystrophic patients. Isolation, physicochemical properties, and several comparisons with the Duchenne dystrophic aberrant enzyme.

    Science.gov (United States)

    Hamada, M; Sumida, M; Kurokawa, Y; Sunayashiki-Kusuzaki, K; Okuda, H; Watanabe, T; Kuby, S A

    1985-09-25

    Two species of adenylate kinase isozymes (ATP:AMP phosphotransferase, EC 2.7.4.3) from human Duchenne dystrophic serum were separated by Blue Sepharose CL-6B affinity column chromatography. One of these species was the "aberrant" adenylate kinase isozyme, found specifically in the Duchenne type of this disease (Hamada, M., Okuda, H., Oka, K., Watanabe, T., Ueda, K., Nojima, M., Kuby, S.A., Manship, M., Tyler, F., and Ziter, F. (1981) Biochim. Biophys. Acta 660, 227-237). The separated aberrant form possessed a molecular size of 98,000 (+/- 1,500), whereas the normal serum species of the enzyme was 87,000 (+/- 1,600) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, by gel filtration, and by sedimentation equilibrium. The sedimentation coefficient of each species was found to be 5.8 S for the aberrant form and 5.6 S for the normal form, respectively. The subunit size (Mr = 24,700) of the aberrant enzyme in 8 M urea proved to be very similar to that of the normal human liver enzyme (Hamada, M., Sumida, M., Okuda, H., Watanabe, T., Nojima, M., and Kuby, S.A. (1982) J. Biol. Chem. 257, 13120-13128), and the normal species subunit (Mr = 21,700) was found to be very similar to that of the normal human muscle enzyme (Kuby, S.A., Fleming, G., Frischat, A., Cress, M.C., and Hamada, M. (1983) J. Biol. Chem. 258, 1901-1907). Both species were tetrameric enzymes in the serum. The amino acid composition for the normal species was similar to that for the muscle-type enzyme, and that for the aberrant species was similar to the liver enzyme, but with some notable exceptions in both cases. Thus, the normal species had no tryptophan and two half-cystine residues/subunit; whereas, there was 1 tryptophan and 4 half-cystine residues/subunit of the aberrant molecule. The amino acid composition of both serum isozymes when compared to their respective muscle or liver-type enzyme differed mainly in the content of Glu, Asp, His, Leu, Ile, Gly. Kinetic properties of the two forms

  3. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    van Westrum, S. M. Schade; Hoogerwaard, E. M.; Dekker, L.; Standaar, T. S.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; van Essen, A. J.; Leschot, N. J.; Wilde, A. A. M.; de Haan, R. J.; de Visser, M.; van der Kooi, A. J.

    2011-01-01

    Objectives: Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities during long-term follow-up is unknown. We describe the long-term follow-up of dilated cardio

  4. The clinical and molecular genetic approach to Duchenne and Becker muscular dystrophy : an updated protocol

    NARCIS (Netherlands)

    vanEssen, AJ; Kneppers, ALJ; vanderHout, AH; Scheffer, H; Ginjaar, IB; tenKate, LP; vanOmmen, GJB; Buys, CHCM; Bakker, E

    1997-01-01

    Detection of large rearrangements in the dystrophin gene in Duchenne and Becker muscular dystrophy is possible in about 65-70% of patients by Southern blotting or multiplex PCR. Subsequently, carrier detection is possible by assessing the intensity of relevant bands, but preferably by a non-quantita

  5. Reliability of the EK scale, a functional test for non-ambulatory persons with Duchenne dystrophy

    DEFF Research Database (Denmark)

    Steffensen, Birgit F.; Hyde, Sylvia A.; Attermann, Jørn

    2002-01-01

    The EK {Egen Klassifikation} scale was developed to assess overall functional ability in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The purpose of this study was to examine the reliability of the EK scale. Six subjects with DMD, selected as representative of the entire range o...

  6. Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment

    NARCIS (Netherlands)

    Engel-Hoek, L. van den; Erasmus, C.E.; Hendriks, J.C.M.; Geurts, A.C.H.; Klein, W.M.; Pillen, S.; Sie, L.T.L.; Swart, B.J.M. de; Groot, I.J.M. de

    2013-01-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based

  7. Aumento de transaminasas: una manifestación de distrofia muscular de Duchenne

    OpenAIRE

    Avaria, María de los Ángeles; Beytía, María de los Ángeles; Kleinsteuber, Karin; Rodillo, Eliana; Alegría, Sylvia

    2012-01-01

    Los autores de este artículo pretenden demostrar la correlación entre el alza de la creatinkinasa (cK) y transaminasas en pacientes con el diagnóstico de distrofia muscular de Duchenne (DMD), la enfermedad neuromuscular más frecuente en niños.

  8. Swallowing difficulties in Duchenne muscular dystrophy: indications for feeding assessment and outcome of videofluroscopic swallow studies

    DEFF Research Database (Denmark)

    Aloysius, A.; Born, P.; Kinali, M.

    2008-01-01

    Feeding difficulties are known to occur with advancing age in Duchenne muscular dystrophy (DMD). We evaluated the role of videofluoroscopy swallow study (VFSS) in a group of 30 DMD patients with feeding difficulties. Indications for feeding assessment were: respiratory infections potentially...

  9. Improving the Reading Skills of Young People with Duchenne Muscular Dystrophy in Preparation for Adulthood

    Science.gov (United States)

    Hoskin, Janet; Fawcett, Angela

    2014-01-01

    Duchenne muscular dystrophy (DMD) is a progressive genetic condition that affects both muscle and brain. Children with DMD are at risk of psycho-social difficulties such as poor academic achievement and behavioural and socio-emotional problems. This article by Janet Hoskin and Angela Fawcett, both from the University of Swansea, describes how 34…

  10. Refinement of antisense oligonucleotide mediated exon skipping as therapy for Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Heemskerk, Johannes Antonius

    2011-01-01

    In recent years, modulation of mRNA has emerged as a promising therapeutic tool. For instance, in the field of neuromuscular disorders therapeutic strategies are being developed for several diseases, including antisense oligonucleotide (AON) mediated exon skipping for Duchenne Muscular Dystrophy (DM

  11. Single skinned muscle fibers in Duchenne muscular dystrophy generate normal force.

    Science.gov (United States)

    Horowits, R; Dalakas, M C; Podolsky, R J

    1990-06-01

    We measured the intrinsic mechanical properties and protein content of single skinned muscle fibers obtained from patients who had Duchenne muscular dystrophy. To check for possible nonspecific changes caused by muscle disease per se, we also studied the properties of muscle fibers obtained from patients exhibiting severe muscle weakness due to polymyositis. Relative to control fibers obtained from 4 patients with normal or nonmyopathic muscle, we found no significant changes in the ability of muscle fibers from the patients with Duchenne muscular dystrophy or polymyositis to generate active tension in response to calcium or resting tension in response to stretch. In addition, we found no significant changes in the concentrations of the major contractile proteins myosin and actin, of the elastic protein titin, or of the structural proteins nebulin and alpha-actinin. In contrast, immunocytochemical studies showed that dystrophin was absent in the biopsy specimens from the patients with Duchenne muscular dystrophy, but localized at the cell membrane in all of the other muscle biopsy specimens used in this study. These results indicate that myofibrils assemble and function normally in Duchenne muscular dystrophy. Therefore, the absence of dystrophin, which is the primary biochemical defect in this disease, leads to clinical weakness by causing the breakdown of muscle fibers that were once capable of generating normal force, while the surviving fibers exhibit normal contractility.

  12. Refinement of antisense oligonucleotide mediated exon skipping as therapy for Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Heemskerk, Johannes Antonius

    2011-01-01

    In recent years, modulation of mRNA has emerged as a promising therapeutic tool. For instance, in the field of neuromuscular disorders therapeutic strategies are being developed for several diseases, including antisense oligonucleotide (AON) mediated exon skipping for Duchenne Muscular Dystrophy (DM

  13. Prevalence and psychosocial impact of lower urinary tract symptoms in patients with Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Wijk, H.A.R.; Messelink, B.J.; Heijnen, L.; Groot, I.J.M. de

    2009-01-01

    Patients with Duchenne muscular dystrophy (DMD) frequently report lower urinary tract symptoms at the outpatient rehabilitation clinic. The purpose of this study was to determine the prevalence of lower urinary tract symptoms in the Dutch male DMD population and their effect on quality of life. A po

  14. BIRTH AND POPULATION PREVALENCE OF DUCHENNE MUSCULAR-DYSTROPHY IN THE NETHERLANDS

    NARCIS (Netherlands)

    VANESSEN, AJ; BUSCH, HFM; TEMEERMAN, GJ; TENKATE, LP

    1992-01-01

    Mutations causing Duchenne muscular dystrophy (DMD) have a short survival. Therefore, birth and population prevalence are maintained by new mutations. The present inventory was made to estimate the birth and population prevalence rates of DMD in the Netherlands. Seven methods of case identification

  15. Prevalence and psychosocial impact of lower urinary tract symptoms in patients with Duchenne muscular dystrophy

    NARCIS (Netherlands)

    van Wijk, Evaline; Messelink, Bert J.; Heijnen, Lily; de Groot, Imelda J. M.

    2009-01-01

    Patients with Duchenne muscular dystrophy (DMD) frequently report lower urinary tract symptoms at the outpatient rehabilitation clinic. The purpose of this study was to determine the prevalence of lower urinary tract symptoms in the Dutch male DMD population and their effect on quality of life. A po

  16. Dystrophin gene mutation location and the risk of cognitive impairment in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Taylor, P.J.; Betts, G.A.; Maroulis, S.; Gilissen, C.F.H.A.; Pedersen, R.L.; Mowat, D.R.; Johnston, H.M.; Buckley, M.F.

    2010-01-01

    BACKGROUND: A significant component of the variation in cognitive disability that is observed in Duchenne muscular dystrophy (DMD) is known to be under genetic regulation. In this study we report correlations between standardised measures of intelligence and mutational class, mutation size, mutation

  17. Community-engaged approaches to explore research priorities in Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Peay, Holly Landrum

    2015-01-01

    This thesis presents a series of translational research studies to explore topics of importance to a patient stakeholder community--Duchenne and Becker muscular dystrophy. The overarching objective was to inform a patient/family foundation's interventions and policy and advocacy approaches. Results

  18. Clinical genetic aspects of Duchenne and Becker muscular dystrophy in the Netherlands

    NARCIS (Netherlands)

    Helderman-van den Enden, Apollonia Theodora Josina Maria

    2012-01-01

    Dystrophinopathies include the well known Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). This thesis is a collection of several clinical and genetic studies on dystrophinopathies with implications for genetic counselling of patients and their families and for future therapy (

  19. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  20. The influence of low dystrophin levels on disease pathology in mouse models for Duchenne Muscular Dystrophy

    NARCIS (Netherlands)

    Putten, Maaike van

    2013-01-01

    Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disorder, caused by mutations in the DMD gene that prevent synthesis of dystrophin. Fibers that lack dystrophin are sensitive to exercise-induced damage, resulting in progressive muscle wasting, loss of ambulation and premature de

  1. Prednisone 10 days on/10 days off in patients with Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Straathof, C.S.; Overweg-Plandsoen, W.C.; Burg, G.J. van den; Kooi, A.J. van der; Verschuuren, J.J.; Groot, I.J.M. de

    2009-01-01

    Corticosteroids are effective in improving motor function in Duchenne muscular dystrophy (DMD) patients within 6 months-2 years of treatment initiation, but there is as yet no consensus on which treatment scheme is the best. We retrospectively analyzed data of 35 DMD patients who were treated with p

  2. Accurate assessment of intragenic recombination frequency within the Duchenne muscular dystrophy gene.

    Science.gov (United States)

    Abbs, S; Roberts, R G; Mathew, C G; Bentley, D R; Bobrow, M

    1990-08-01

    Polymorphic loci that lie at the two extremities of the Duchenne/Becker muscular dystrophy (DMD/BMD) gene have been used to estimate intragenic recombination rates. Multipoint linkage analysis of the CEPH panel of families suggests a total intragenic recombination frequency of nearly 0.12 (confidence intervals 0.041-0.226) over the genomic length of approximately 2 Mb.

  3. Aumento de transaminasas: una manifestación de distrofia muscular de Duchenne

    OpenAIRE

    Avaria, María de los Ángeles; Beytía, María de los Ángeles; Kleinsteuber,Karin; Rodillo, Eliana; Alegría, Sylvia

    2012-01-01

    Los autores de este artículo pretenden demostrar la correlación entre el alza de la creatinkinasa (cK) y transaminasas en pacientes con el diagnóstico de distrofia muscular de Duchenne (DMD), la enfermedad neuromuscular más frecuente en niños.

  4. Investigation of Poor Academic Achievement in Children with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Hinton, V. J.; De Vivo, D. C.; Fee, R.; Goldstein, E.; Stern, Y.

    2004-01-01

    Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

  5. Dystropathology increases energy expenditure and protein turnover in the Mdx mouse model of Duchenne muscular dystrophy

    Science.gov (United States)

    The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the diet...

  6. PrEP: controversy, agency and ownership

    National Research Council Canada - National Science Library

    Cairns, Gus P; Race, Kane; Goicochea, Pedro

    2016-01-01

    Pre‐exposure prophylaxis (PrEP) has been and continues to be an intervention that causes controversy and debate between stakeholders involved in providing or advocating for it, and within communities in need...

  7. Antidote to Controversy? Responses to Carolyn Henly.

    Science.gov (United States)

    Randall, Mary Ella; And Others

    1993-01-01

    Provides four practicing teachers' written responses to Carolyn Henly's article entitled "Reader Response Theory as Antidote to Controversy: Teaching "The Bluest Eye," which appears in the same issue. (HB)

  8. Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells

    Directory of Open Access Journals (Sweden)

    Carmen eBertoni

    2014-04-01

    Full Text Available The progressive loss of muscle mass characteristic of many muscular dystrophies impairs the efficacy of most of the gene and molecular therapies currently being pursued for the treatment of those disorders. It is becoming increasingly evident that a therapeutic application, to be effective, needs to target not only mature myofibers, but also muscle progenitors cells or muscle stem cells able to form new muscle tissue and to restore myofibers lost as the result of the diseases or during normal homeostasis so as to guarantee effective and lost lasting effects. Correction of the genetic defect using oligodeoxynucleotides (ODNs or engineered nucleases holds great potential for the treatment of many of the musculoskeletal disorders. The encouraging results obtained by studying in vitro systems and model organisms have set the groundwork for what is likely to become an emerging field in the area of molecular and regenerative medicine. Furthermore, the ability to isolate and expand from patients various types of muscle progenitor cells capable of committing to the myogenic lineage provides the opportunity to establish cell lines that can be used for transplantation following ex vivo manipulation and expansion.The purpose of this article is to provide a perspective on approaches aimed at correcting the genetic defect using gene editing strategies and currently under development for the treatment of Duchenne muscular dystrophy (DMD, the most sever of the neuromuscular disorders. Emphasis will be placed on describing the potential of using the patient own stem cell as source of transplantation and the challenges that gene editing technologies face in the field of regenerative biology.

  9. Chronic hypoxia impairs muscle function in the Drosophila model of Duchenne's muscular dystrophy (DMD.

    Directory of Open Access Journals (Sweden)

    Matias Mosqueira

    Full Text Available Duchenne's muscular dystrophy (DMD is a severe progressive myopathy caused by mutations in the DMD gene leading to a deficiency of the dystrophin protein. Due to ongoing muscle necrosis in respiratory muscles late-stage DMD is associated with respiratory insufficiency and chronic hypoxia (CH. To understand the effects of CH on dystrophin-deficient muscle in vivo, we exposed the Drosophila model for DMD (dmDys to CH during a 16-day ascent to the summit of Mount Denali/McKinley (6194 meters above sea level. Additionally, dmDys and wild type (WT flies were also exposed to CH in laboratory simulations of high altitude hypoxia. Expression profiling was performed using Affymetrix GeneChips® and validated using qPCR. Hypoxic dmDys differentially expressed 1281 genes, whereas the hypoxic WT flies differentially expressed 56 genes. Interestingly, a number of genes (e.g. heat shock proteins were discordantly regulated in response to CH between dmDys and WT. We tested the possibility that the disparate molecular responses of dystrophin-deficient tissues to CH could adversely affect muscle by performing functional assays in vivo. Normoxic and CH WT and dmDys flies were challenged with acute hypoxia and time-to-recover determined as well as subjected to climbing tests. Impaired performance was noted for CH-dmDys compared to normoxic dmDys or WT flies (rank order: Normoxic-WT ≈ CH-WT> Normoxic-dmDys> CH-dmDys. These data suggest that dystrophin-deficiency is associated with a disparate, pathological hypoxic stress response(s and is more sensitive to hypoxia induced muscle dysfunction in vivo. We hypothesize that targeting/correcting the disparate molecular response(s to hypoxia may offer a novel therapeutic strategy in DMD.

  10. Night Activity Reduction is a Signature Physiological Biomarker for Duchenne Muscular Dystrophy Dogs

    Science.gov (United States)

    Hakim, Chady H.; Peters, Austin A.; Feng, Feng; Yao, Gang; Duan, Dongsheng

    2016-01-01

    Background Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease. Dystrophic dogs are excellent models to test novel therapies for DMD. However, the use of the dog model has been hindered by the lack of an effective method to evaluate whole-body mobility. We recently showed that night activity is a good indicator of dog mobility. However, our published method relies on frame-by-frame manual processing of a 12-hour video for each dog. This labor-intensive and time-consuming approach makes it unrealistic to use this assay as a routine outcome measurement. Objective To solve this problem, we developed an automatic video-capturing/imaging processing system. The new system reduces the data analysis time over 1,000 fold and also provides a more detailed activity profile of the dog. Methods Using the new system, we analyzed more than 120 twelve-hour recordings from 12 normal and 22 affected dogs. Results We observed similar activity profiles during repeated recording of the same dog. Throughout the night, normal dogs were in motion 10.4 ± 0.9% of the time while affected dogs were in motion 4.6 ± 0.2% of the time (p < 0.0001). Further, normal dogs made significantly more movements (p < 0.0001) while affected dogs rested significantly longer (p < 0.0001) during the period of recording (from 6 pm to 6 am next day). Importantly, statistical significance persisted irrespective of the coat color, gender and mutation type. Conclusions Our results suggest that night activity reduction is a robust, quantitative physiological biomarker for dystrophic dogs. The new system may be applicable to study mobility in other species.

  11. The ubiquitin ligase tripartite-motif-protein 32 is induced in Duchenne muscular dystrophy.

    Science.gov (United States)

    Assereto, Stefania; Piccirillo, Rosanna; Baratto, Serena; Scudieri, Paolo; Fiorillo, Chiara; Massacesi, Manuela; Traverso, Monica; Galietta, Luis J; Bruno, Claudio; Minetti, Carlo; Zara, Federico; Gazzerro, Elisabetta

    2016-08-01

    Activation of the proteasome pathway is one of the secondary processes of cell damage, which ultimately lead to muscle degeneration and necrosis in Duchenne muscular dystrophy (DMD). In mdx mice, the proteasome inhibitor bortezomib up-regulates the membrane expression of members of the dystrophin complex and reduces the inflammatory reaction. However, chronic inhibition of the 26S proteasome may be toxic, as indicated by the systemic side-effects caused by this drug. Therefore, we sought to determine the components of the ubiquitin-proteasome pathway that are specifically activated in human dystrophin-deficient muscles. The analysis of a cohort of patients with genetically determined DMD or Becker muscular dystrophy (BMD) unveiled a selective up-regulation of the ubiquitin ligase tripartite motif-containing protein 32 (TRIM32). The induction of TRIM32 was due to a transcriptional effect and it correlated with disease severity in BMD patients. In contrast, atrogin1 and muscle RING-finger protein-1 (MuRF-1), which are strongly increased in distinct types of muscular atrophy, were not affected by the DMD dystrophic process. Knock-out models showed that TRIM32 is involved in ubiquitination of muscle cytoskeletal proteins as well as of protein inhibitor of activated STAT protein gamma (Piasγ) and N-myc downstream-regulated gene, two inhibitors of satellite cell proliferation and differentiation. Accordingly, we showed that in DMD/BMD muscle tissue, TRIM32 induction was more pronounced in regenerating myofibers rather than in necrotic muscle cells, thus pointing out a role of this protein in the regulation of human myoblast cell fate. This finding highlights TRIM32 as a possible therapeutic target to favor skeletal muscle regeneration in DMD patients.

  12. Controversies in Persistent (Chronic) Lyme Disease

    Science.gov (United States)

    2016-01-01

    The Centers for Disease Control and Prevention estimates that more than 300 000 new cases of Lyme disease occur each year in the United States and that 10% to 20% of these patients will remain symptomatic despite receiving appropriate antibiotic therapy. Many elements of the disease are poorly understood and have generated considerable controversy. This paper discusses the medical controversies related to posttreatment manifestations and their potential impact on infusion nurses. PMID:27755213

  13. Hate Speech Revisited: The "Toon" Controversy

    OpenAIRE

    Rajeev Dhavan; Aparna Ray

    2010-01-01

    Examining the cartoon controversy which ignited violent protests and ban in various countries, this article examines the contours of "hate speech" in various legal systems. While broadly supporting the case of free speech the authors remind users of free speech to exercise self-restraint. Absolute bans should not be made, but time, person and place constraints may be essential. Ironically, the toon controversy also reveals the silence of the sympathetic majority. Similarly, there is a duty to...

  14. Clinical analysis of 155 patients with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Qi BING

    2015-05-01

    Full Text Available Objective To investigate the clinical manifestations and laboratory examinations of Duchenne muscular dystrophy (DMD patients and evaluate the principle of intermittent intravenous combined with oral glucocorticoid therapy.  Methods The clinical features, laboratory examinations andfollow-up data of 155 DMD patients were collected. These patients were given dexamethasone 5-10 mg/d by intravenous infusion for 10-15 d and oral prednisone acetate 0.50-0.75 mg/(kg·d for one month. After treatment, the motor ability of lower limbs, the level of serum creatine kinase (CK and 99mTc-MIBI gated myocardial perfusion imaging (GMPI findings were compared with those before glucocorticoid therapy by statistical analysis.  Results 1 The motor ability was improved in 70 follow-up cases of DMD patients with long-term oral prednisone (squat and rise: Z = 207.000, P = 0.034; climbing stairs: Z = 237.000, P =0.008. 2 The level of serum CK of 155 first diagnosed patients reached the peak at 3 years old, and declined after the age of 8 (P < 0.05, for all. The serum CK of 70 follow-up cases was significantly decreased after 10-15 d dexamethasone intravenous infusion (P = 0.000, and increased again after one-month oral administration of prednisone acetate (P = 0.000, but was still lower than that before treatment (P = 0.008. 3 The 99mTc-MIBI GMPI of 77 patients showed different degrees of myocardial involvement and significantly uneven left ventricular radionuclide distribution, especially in apex cordis (55 cases, inferior wall (45 cases and anterior wall (30 cases of apex. Conclusions There exists increased level of serum CK in the sub⁃clinical stage of DMD. The level of serum CK declined year by year after the age of 8. Intermittent intravenous combined with oral glucocorticoid therapy has an important effect on protecting motor and cardiac functions, extending walking time and reducing serum CK level and muscle cell damage. Early glucocorticoid therapy is

  15. Desirability of early identification of Duchenne Muscular Dystrophy (DMD): parent’s experiences of the period prior to diagnosis.

    NARCIS (Netherlands)

    Eilers, R.; Kleinveld, J.H.; Vroom, E.; Westerman, M.J.; Plass, A.M.C.

    2012-01-01

    Duchenne Muscular Dystrophy (DMD), X-linked recessively inherited, is the most common progressive muscular disorder in children. Early diagnosis could offer opportunities for timely initiation of treatment possibilities, genetic counselling, and prevent a long diagnostic quest. Despite the

  16. Desirability of early identification of Duchenne Muscular Dystrophy (DMD): parent’s experiences of the period prior to diagnosis.

    NARCIS (Netherlands)

    Eilers, R.; Kleinveld, J.H.; Vroom, E.; Westerman, M.J.; Plass, A.M.C.

    2012-01-01

    Duchenne Muscular Dystrophy (DMD), X-linked recessively inherited, is the most common progressive muscular disorder in children. Early diagnosis could offer opportunities for timely initiation of treatment possibilities, genetic counselling, and prevent a long diagnostic quest. Despite the availabil

  17. Non-operative treatment for perforated gastro-duodenal peptic ulcer in Duchenne Muscular Dystrophy: a case report

    Directory of Open Access Journals (Sweden)

    Wever Jan

    2004-01-01

    Full Text Available Abstract Background Clinical characteristics and complications of Duchenne muscular dystrophy caused by skeletal and cardiac muscle degeneration are well known. Gastro-intestinal involvement has also been recognised in these patients. However an acute perforated gastro-duodenal peptic ulcer has not been documented up to now. Case presentation A 26-year-old male with Duchenne muscular dystrophy with a clinical and radiographic diagnosis of acute perforated gastro-duodenal peptic ulcer is treated non-operatively with naso-gastric suction and intravenous medication. Gastrointestinal involvement in Duchenne muscular dystrophy and therapeutic considerations in a high risk patient are discussed. Conclusion Non-surgical treatment for perforated gastro-duodenal peptic ulcer should be considered in high risk patients, as is the case in patients with Duchenne muscular dystrophy. Patients must be carefully observed and operated on if non-operative treatment is unsuccessful.

  18. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy

    National Research Council Canada - National Science Library

    Finkel, Richard S; Flanigan, Kevin M; Wong, Brenda; Bönnemann, Carsten; Sampson, Jacinda; Sweeney, H Lee; Reha, Allen; Northcutt, Valerie J; Elfring, Gary; Barth, Jay; Peltz, Stuart W

    2013-01-01

    Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124...

  19. Contrasting Controversies: Fracking and Climate Change

    Science.gov (United States)

    Duggan-Haas, D.; Zabel, I. H. H.; Ross, R. M.

    2014-12-01

    Slickwater high-volume hydraulic fracturing (commonly known as "fracking") is highly controversial. So is global warming, and the two issues are closely related, but the natures of these two controversies have substantial and important differences. Building upon years of experience in teaching and developing resources and strategies for teaching about evolution and climate change, staff at the Paleontological Research Institution have engaged in public outreach and educator professional development to help nurture understanding of fracking and the broader energy system. How are these controversies similar to and different from one another, and how should understanding these similarities and differences inform educational programming (and about how you talk about these issues with your Uncle Fred at the family holiday dinner?). It is nearly universally agreed amongst scientists who study climate that changes now underway are real and human caused, and are posing or likely to pose very serious problems for humanity. Scientists who study slickwater high-volume hydraulic fracturing agree that it causes environmental damage, but there is no consensus as to whether fracking causes more or less harm (e.g., among different kinds of environment harm, across different temporal and spatial scales, and among different social contexts) than other ways of producing energy on a large scale. In other words, the basic tenets of climate change are not a matter of scientific controversy, though the implications for policy making obviously remain politically controversial, while fracking is an issue of both scientific and political controversy. Without advocating for or against fracking, we help audiences disentangle scientific and political issues, better understand the energy resources used in their own communities, and consider issues of scale, systems, and complexity. We will compare and contrast the overlapping controversies surrounding climate change and fracking and highlight

  20. Metabolic syndrome: definitions and controversies

    Directory of Open Access Journals (Sweden)

    Kaltsas Gregory

    2011-05-01

    Full Text Available Abstract Metabolic syndrome (MetS is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS.

  1. Anestesia em paciente portador de distrofia muscular de Duchenne: relato de casos Anestesia en un paciente portador de distrofia muscular de Duchenne: relato de casos Anesthesia for Duchenne muscular dystrophy patients: case reports

    OpenAIRE

    Rodrigo Machado Saldanha; Juliano Rodrigues Gasparini; Letícia Sales Silva; Roberto Rigueti de Carli; Victor Ugo Dorigo de Castilhos; Mariana Moraes Pereira das Neves; Fernando Paiva Araújo; Paulo César de Abreu Sales; José Francisco Nunes Pereira das Neves

    2005-01-01

    JUSTIFICATIVA E OBJETIVOS: Este estudo objetiva relatar dois casos de anestesia em pacientes portadores de Distrofia Muscular de Duchenne (DMD), uma doença rara, progressiva e incapacitante, e discutir sobre a conduta anestésica. O comprometimento das funções pulmonar e cardíaca, a possibilidade de ocorrência de hipertermia maligna, a maior sensibilidade aos bloqueadores neuromusculares e o aumento da morbidade pós-operatória são alguns dos desafios enfrentados pelo anestesiologista. RELATO D...

  2. Distrofia muscular de Duchenne: análise eletrocardiográfica de 131 pacientes Distrofia muscular de duchenne: análisis electrocardiográfica de 131 pacientes Duchenne muscular dystrophy: electrocardiographic analysis of 131 patients

    OpenAIRE

    Maria Auxiliadora Bonfim Santos; Francisco de Assis Costa; Aline Ferreira Travessa; Maria Teresa Nogueira Bombig; Francisco Helfenstein Fonseca; Bráulio Luna Filho; Aurélia Mussi; Dilma de Souza; Acary de Oliveira; Rui Povoa

    2010-01-01

    FUNDAMENTO: É conhecido o envolvimento cardíaco em pacientes com distrofia muscular de Duchenne (DMD). O eletrocardiograma (ECG) apresenta algumas alterações típicas na DMD, fato que o torna um exame útil no diagnóstico da lesão cardíaca nessa patologia. OBJETIVO: Avaliar as alterações eletrocardiográficas em pacientes portadores de DMD, correlacionando-as com a idade da população estudada. MÉTODOS: Foram analisados os ECG de 131 pacientes com diagnóstico de DMD. Avaliaram-se diversas variáve...

  3. Balancing Opposing Views to Reduce Controversy

    CERN Document Server

    Garimella, Kiran; Gionis, Aristides; Mathioudakis, Michael

    2016-01-01

    Society is often polarized by controversial issues, that split the population into groups of opposing views. When such issues emerge on social media, we often observe the creation of 'echo chambers', i.e., situations where like-minded people reinforce each other's opinion, but do not get exposed to the views of the opposing side. In this paper we study algorithmic techniques for bridging these chambers, and thus, reducing controversy. Specifically, we represent the discussion on a controversial issue with an endorsement graph, and cast our problem as an edge-recommendation problem on this graph. The goal of the recommendation is to reduce the controversy score of the graph, which is measured by a recently-developed metric based on random walks. At the same time, we take into account the acceptance probability of the recommended edge, which represents how likely the edge is to materialize in the endorsement graph. We propose a simple model based on a recently-developed user-level controversy score, that is com...

  4. 胃肠减重手术治疗2型糖尿病的前景和争议%Bariatric surgery for type 2 diabetes meilitus:Prospect and controversy

    Institute of Scientific and Technical Information of China (English)

    石建霞; 邹大进

    2012-01-01

    肥胖是T2DM的一个主要的独立危险因素,随着肥胖人群的增加,T2DM的发病率也随之增加.肥胖的T2DM除了内科治疗之外,胃肠减重的外科手术治疗也取得了良好的效果,外科手术治疗改善T2DM的机制也得到了广泛的研究,但手术所带来一些副作用以及手术的适应人群仍是需要关注的问题.%Obesity is a major independent risk factor for the development of type 2 diabetes. As a consequence, the currently increasing prevalence of obesity is associated with a growing incidence of T2DM. Apart from medical treatment, bariatric surgery has also acquired favorable effect, and the mechanism which improve type 2 diabetes has been extensively studied. At the same time the side effects and the indications of bariatric surgery should be paid a great attention.

  5. Newspaper coverage of the breast implant controversy.

    Science.gov (United States)

    Powers, A

    1999-01-01

    Newspaper coverage of the silicone breast implant controversy from 1992 through 1996 was analyzed to determine whether women in the United States were provided with a fair and balanced account. The paper also addressed whether or not Dow Corning's public relations campaign impacted newspaper coverage. All stories from the New York Times, the Chicago Tribune and the Wall Street Journal were analyzed. Findings suggested that early coverage of the controversy focused on the health risks of silicone breast implants while later coverage focused on the financial situations of the implant manufacturers. The most-interviewed sources were spokespersons for the implant manufacturers, while the least-interviewed sources were women with implants. The findings suggested that reporting patterns were influenced by the public relations efforts of the implant manufacturer, raising questions concerning the coverage of health care controversies involving large corporations seeking refuge from litigation.

  6. The controversy of cranial bone motion.

    Science.gov (United States)

    Rogers, J S; Witt, P L

    1997-08-01

    Cranial bone motion continues to stimulate controversy. This controversy affects the general acceptance of some intervention methods used by physical therapists, namely, cranial osteopathic and craniosacral therapy techniques. Core to these intervention techniques is the belief that cranial bone mobility provides a compliant system where somatic dysfunction can occur and therapeutic techniques can be applied. Diversity of opinion over the truth of this concept characterizes differing viewpoints on the anatomy and physiology of the cranial complex. Literature on cranial bone motion was reviewed for the purpose of better understanding this topic. Published research overall was scant and inconclusive. Animal and human studies demonstrate a potential for small magnitude motion. Physical therapists should carefully scrutinize the literature presented as evidence for cranial bone motion. Further research is needed to resolve this controversy. Outcomes research, however, is needed to validate cranial bone mobilization as an effective treatment.

  7. Green tea extract and its major polyphenol (−)-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy

    National Research Council Canada - National Science Library

    Olivier M. Dorchies; Stéphanie Wagner; Ophélie Vuadens; Katri Waldhauser; Timo M. Buetler; Pavel Kucera; Urs T. Ruegg

    Duchenne muscular dystrophy is a frequent muscular disorder caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that contributes to the stabilization of muscle fiber membrane...

  8. Hate Speech Revisited: The "Toon" Controversy

    Directory of Open Access Journals (Sweden)

    Rajeev Dhavan

    2010-01-01

    Full Text Available Examining the cartoon controversy which ignited violent protests and ban in various countries, this article examines the contours of "hate speech" in various legal systems. While broadly supporting the case of free speech the authors remind users of free speech to exercise self-restraint. Absolute bans should not be made, but time, person and place constraints may be essential. Ironically, the toon controversy also reveals the silence of the sympathetic majority. Similarly, there is a duty to speak. Even though not enforceable, it remains a duty to democracy.

  9. What price politics? Scientists and political controversy.

    Science.gov (United States)

    Nye, M J

    1999-01-01

    There is a long tradition within scientific communities that encourages governments, patrons and citizens to enlist scientific expertise in the service of the public good. However, since the 17th century, scientists who have engaged in public political controversy have often been judged harshly by scientific colleagues, as well as by political adversaries. Some prominent scientists were politically active in Germany, France and England during the 1920s and 1930s; controversial stands were taken by the British physicist P.M.S. Blackett and the American chemist Linus C. Pauling against their countries' nuclear weapons policy following the Second World War.

  10. Controversies in the management of primary sclerosingcholangitis

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Primary sclerosing cholangitis (PSC) remains a rare butsignificant disease, which affects mainly young malesin association with inflammatory bowel disease. Therehave been few advances in the understanding of thepathogenesis of the condition and no therapeutics withproven mortality benefit aside from liver transplantation.There remain areas of controversy in the managementof PSC which include the differentiation from othercholangiopathies, in particular immunoglobulin G4related sclerosing cholangitis, the management ofdominant biliary strictures, and the role of ursodeoxycholicacid. In addition, the timing of liver transplantationin PSC remains difficult to predict withstandard liver severity scores. In this review, we addressthese controversies and highlight the latest evidencebase in the management of PSC.

  11. Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach Distrofia muscular de Duchenne e Becker: abordagem molecular e imuno-histoquímica

    OpenAIRE

    Aline Andrade Freund; Rosana Herminia Scola; Raquel Cristina Arndt; Paulo José Lorenzoni; Claudia Kamoy Kay; Lineu Cesar Werneck

    2007-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of t...

  12. Importância do camundongo mdx na fisiopatologia da distrofia muscular de Duchenne The importance of mdx mouse in the pathophysiology of Duchenne's muscular distrophy

    OpenAIRE

    Sandra Lopes Seixas; Jussara Lagrota-Cândido; Wilson Savino; Thereza Quirico-Santos

    1997-01-01

    O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X (locus Xp21.1) e não expressa distrofina. Embora não apresente intensa fibrose do tecido muscular e acúmulo de tecido adiposo, é considerado o modelo animal mais adequado da distrofia muscular de Duchenne. As alterações estruturais no tecido muscular associadas à mionecrose e presença do infiltrado inflamatório com predomínio de linfócitos e monócitos/macrófagos sugerem uma participação do sistema imunológico nest...

  13. The experiences of patients with Duchenne muscular dystrophy in facing and learning about their clinical conditions

    Directory of Open Access Journals (Sweden)

    Haruo Fujino

    2016-10-01

    Full Text Available Patients experience extreme difficulty when facing an intractable genetic disease. Herein, we examine the experiences of patients with Duchenne muscular dystrophy in facing and learning about their disease. A total of seven patients with Duchenne muscular dystrophy (age range: 20–48 participated. We conducted in-depth interviews with them about how they learned of their disease and how their feelings regarding the disease changed over time. Transcribed data were analysed using thematic analysis. The following themes emerged from this analysis: “experiences before receiving the diagnosis,” “experiences when they learned of their condition and progression of the disease,” “supports,” and “desired explanations.” Anxiety and worry were most pronounced when they had to transition to using wheelchairs or respirators due to disease progression; indeed, such transitions affect the patients psychological adjustment. In such times, support from significant others in their lives helped patients adjust.

  14. Psychological aspects in children affected by Duchenne de Boulogne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Michele Roccella

    2012-01-01

    Full Text Available Impairment of intelligence in Duchenne muscular dystrophy (DMD patients was described by Duchenne de Boulogne himself in 1868. Further studies report intelligence disorders with mayor impairment of memory. The aim of the present study was to assess the presence of affective and personality disorders in a group of children affected by DMD. Twenty six male DMD patients, mean age eleven and four months years old, were assessed for their affective and personality disorder. Only eight subjects had a total IQ below average with major difficulties in verbal and visual-spatial memory, comprehension, arithmetic and vocabulary. All the subjects presented some disorders: tendency to marginalization and isolation, self-depreciation, sense of insecurity, hypochondriac thoughts and marked state of anxiety. These disorders are often a dynamic prolongation of a psychological process which starts when the diagnosis is made and continues, in a slow and latent fashion, throughout the evolution of the disease.

  15. Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain

    Science.gov (United States)

    Chamberlain, Jeffrey S.; Pearlman, Joel A.; Muzny, Donna M.; Gibbs, Richard A.; Ranier, Joel E.; Reeves, Alice A.; Caskey, C. Thomas

    1988-03-01

    Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

  16. Duchenne and Becker muscular dystrophies: An Indian update on genetics and rehabilitation

    Directory of Open Access Journals (Sweden)

    Nadkarni Jayshree

    2008-01-01

    Full Text Available The application of molecular diagnostic techniques has greatly improved the diagnosis, carrier detection, prenatal testing and genetic counseling for families with Duchenne and Becker muscular dystrophy (D/BMD in India. The prediction of Duchenne muscular dystrophy (DMD patients to have out-framed deletions and Becker′s muscular dystrophy (BMD patients to have in-frame deletions of dystrophin gene holds well in the vast majority of cases. Mutation detection is obviously critical for diagnosis but it may also be important for future therapeutic purposes. These factors underscore the need for earlier referral, genetic counseling and provision of support and rehabilitation services which are the main priorities for psychosocial assessment and intervention at medical and social levels.

  17. Teaching Controversial Issues in Social Studies.

    Science.gov (United States)

    Guyton, Edith M.; Hoffman, Alan J.

    The design of a methods course offered at Georgia State University to prepare social studies teachers for dealing with controversial issues in the middle school or secondary social studies classroom is presented. The course focuses on identification, selection, an analysis of an issue as well as the requirement that the student develop some method…

  18. A Decision Model for Locating Controversial Facilities

    Science.gov (United States)

    Mumphrey, Anthony J.; And Others

    1971-01-01

    Locating controversial public facilities, such as highways or airports, that generate significant public opposition requires a more sophisticated methodology than the traditional least cost" procedures for minimizing physical costs. Two models--a short-run political placation" model and a long-run welfare distribution" model--evaluate the…

  19. LCA – Unique and Controversial Case Studies

    Science.gov (United States)

    This session will focus on case studies and applications that have a unique or controversial aspect. Some of the most recent topics that seem to have significant interest include: LCA-based product declarations, LCA-based standards, LCA-based labels, alternative energy, agricul...

  20. Federal Judge Orders Showing of Controversial Film.

    Science.gov (United States)

    Flygare, Thomas J.

    1987-01-01

    Reviews a recent court decision in Nebraska regarding the cancellation of a controversial film on the University of Nebraska campus. The film was cancelled after a state senator threatened to close the theater if the movie was shown. The lawsuit alleged the university violated the First Amendment in cancelling the film; the judge ruled for the…

  1. Parental Voices and Controversies in Autism

    Science.gov (United States)

    Langan, Mary

    2011-01-01

    Parents of children with autism have played a prominent role in controversies surrounding this condition. Parental voices were critical in challenging the "refrigerator mother" theory and more recently have attracted public attention for claims that autism may be caused by childhood vaccinations and that "unorthodox biomedical" treatments may…

  2. Anticipation and Controversy Surround "Superman" Release

    Science.gov (United States)

    Aarons, Dakarai I.

    2010-01-01

    Well in advance of its official release, the education film "Waiting For Superman" has attracted a level of attention that could make it one of the year's most-watched documentaries--and one of the most controversial among educators, some of whom question its depictions of the American school system and how to improve it. Made by…

  3. Debating Diversity: Ethics and Controversial Public Issues

    Science.gov (United States)

    Darr, Christopher R.

    2016-01-01

    Courses: Ethics, Organizational Communication, Political Communication. Objectives: After completing this unit activity, students should be able to (1) apply multiple ethical perspectives to real-world diversity issues in a debate format, and (2) explain the role of informational and social category diversity in current controversies.

  4. Controversies in watermanagement: Frames and mental models

    NARCIS (Netherlands)

    Kolkman, Rien; van der Veen, A.; Geurts, Petrus A.T.M.

    2007-01-01

    Controversies in decision and policy-making processes can be analysed using frame reflection and mental model mapping techniques. The purpose of the method presented in this paper is to improve the quality of the information and interpretations available to decision makers, by surfacing and

  5. Controversial Novels and Censorship in the Schools.

    Science.gov (United States)

    Katz, John Stuart

    The legal history of censorship in general in the United States as well as the legal context in particular of the censorship of novels from schools is discussed. This thesis deals with four novels which have aroused substantial controversy when taught in the schools. The novels are: "The Catcher in the Rye," by J. D. Salinger, "The Adventures of…

  6. Teaching Controversial Issues in Social Studies.

    Science.gov (United States)

    Guyton, Edith M.; Hoffman, Alan J.

    The design of a methods course offered at Georgia State University to prepare social studies teachers for dealing with controversial issues in the middle school or secondary social studies classroom is presented. The course focuses on identification, selection, an analysis of an issue as well as the requirement that the student develop some method…

  7. Breast cancer radiotherapy: controversies and prospectives

    Institute of Scientific and Technical Information of China (English)

    YU Jin-ming; WANG Yong-sheng

    2008-01-01

    @@ Despite consensus on breast cancer radiotherapy, there are still some controversies over post-mastectomy radiotherapy (PMRT) in patients with 1-3 positive lymph nodes, accelerated partial breast irradiation (APBI), appropriate sequence of radiotherapy, chemotherapy and hormonal treatment, and radiotherapy after preoperative systemic therapy.

  8. Cardiac and Pulmonary Function Variability in Duchenne/Becker Muscular Dystrophy: An Initial Report

    OpenAIRE

    Birnkrant, David J.; Ashwath, Mahi Lakshmi; Noritz, Garey H.; Merrill, Michelle C.; Shah, Tushar A.; Crowe, Carol A.; Bahler, Robert C.

    2010-01-01

    The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks, then progressively declines. In this report, we quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pul...

  9. Complementary and alternative medicine for Duchenne and Becker muscular dystrophies: characteristics of users and caregivers.

    Science.gov (United States)

    Zhu, Yong; Romitti, Paul A; Conway, Kristin M; Andrews, Jennifer; Liu, Ke; Meaney, F John; Street, Natalie; Puzhankara, Soman; Druschel, Charlotte M; Matthews, Dennis J

    2014-07-01

    Complementary and alternative medicine is frequently used in the management of chronic pediatric diseases, but little is known about its use by those with Duchenne or Becker muscular dystrophy. Complementary and alternative medicine use by male patients with Duchenne or Becker muscular dystrophy and associations with characteristics of male patients and their caregivers were examined through interviews with 362 primary caregivers identified from the Muscular Dystrophy Surveillance, Tracking, and Research Network. Overall, 272 of the 362 (75.1%) primary caregivers reported that they had used any complementary and alternative medicine for the oldest Muscular Dystrophy Surveillance, Tracking, and Research Network male in their family. The most commonly reported therapies were from the mind-body medicine domain (61.0%) followed by those from the biologically based practice (39.2%), manipulative and body-based practice (29.3%), and whole medical system (6.9%) domains. Aquatherapy, prayer and/or blessing, special diet, and massage were the most frequently used therapies. Compared with nonusers, male patients who used any therapy were more likely to have an early onset of symptoms and use a wheel chair; their caregivers were more likely to be non-Hispanic white. Among domains, associations were observed with caregiver education and family income (mind-body medicines [excluding prayer and/or blessing only] and whole medical systems) and Muscular Dystrophy Surveillance, Tracking, and Research Network site (biologically based practices and mind-body medicines [excluding prayer and/or blessing only]). Complementary and alternative medicine use was common in the management of Duchenne and Becker muscular dystrophies among Muscular Dystrophy Surveillance, Tracking, and Research Network males. This widespread use suggests further study to evaluate the efficacy of integrating complementary and alternative medicine into treatment regimens for Duchenne and Becker muscular

  10. Anestesia em paciente com Distrofia Muscular de Duchenne: relato de caso

    Directory of Open Access Journals (Sweden)

    Tonelli Deoclécio

    2003-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A distrofia muscular de Duchenne é uma afecção recessiva ligada ao cromossomo X, geralmente diagnosticada na infância, acentuando-se progressivamente até agravar a função respiratória. O objetivo deste relato é apresentar um caso de um paciente com distrofia muscular de Duchenne diagnosticada há 2 anos, submetido à postectomia, sob anestesia geral com cetamina S. RELATO DO CASO: Paciente com 9 anos de idade com Distrofia Muscular de Duchenne diagnosticada há 2 anos, submetido à anestesia geral com levo-cetamina (1,5 mg.kg-1, por via venosa, sob ventilação espontânea assistida manualmente por sistema de Baraka (Mapleson A e bloqueio peniano com bupivacaína a 0,5% (25 mg. Foram usados monitores de pressão arterial não invasiva, oximetria de pulso, cardioscopia e temperatura esofagiana. No decorrer da cirurgia, o caso evoluiu sem intercorrências, sendo que no período pós-operatório o paciente apresentou alguns episódios de vômitos sem outras alterações significativas. Permaneceu internado por 24 horas, tendo alta hospitalar assintomático. CONCLUSÕES: A avaliação pré-anestésica cuidadosa, o uso de monitorização adequada e medicações que não predisponham o aparecimento de complicações tornam seguro o procedimento em pacientes portadores de Distrofia Muscular de Duchenne e seu pós-operatório.

  11. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Coakley, J H; Moorcraft, J; Hipkin, L J; Smith, C S; Griffiths, R D; Edwards, R H

    1988-12-01

    Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

  12. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

    OpenAIRE

    Coakley, J. H.; Moorcraft, J; Hipkin, L J; Smith, C. S.; R.D. Griffiths; Edwards, R H

    1988-01-01

    Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

  13. Diagnosis and cell-based therapy for Duchenne muscular dystrophy in humans, mice, and zebrafish

    OpenAIRE

    2006-01-01

    The muscular dystrophies are a heterogeneous group of genetically caused muscle degenerative disorders. The Kunkel laboratory has had a longstanding research program into the pathogenesis and treatment of these diseases. Starting with our identification of dystrophin as the defective protein in Duchenne muscular dystrophy (DMD), we have continued our work on normal dystrophin function and how it is altered in muscular dystrophy. Our work has led to the identification of the defective genes in...

  14. Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

    Science.gov (United States)

    Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

    1988-03-01

    A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

  15. Expression of dystrophin-glycoprotein complex at the skeletal muscle sarcolemma in Duchenne muscular dystrophy

    OpenAIRE

    Zhao, Lei; Chao-ping HU; Wang, Yi; Shui-zhen ZHOU; Shi, Yi-Yun; Xi-hua LI

    2015-01-01

    Background  Eccentric exercise or high tension exercise could cause damage to skeletal muscle structure, resulting in deficiency of dystrophin and secondary loss of dystrophin-glycoprotein complex (DGC) from the sarcolemma, which indicated that down-regulation of dystrophin was one of the key points of skeletal muscle injury from eccentric exercise. Duchenne muscular dystrophy (DMD) is caused by mutations of DMD gene, resulting in the absence of dystrophin, which means that skeletal muscles o...

  16. Distrofia muscular de Duchenne: análise eletrocardiográfica de 131 pacientes

    OpenAIRE

    Santos, Maria Auxiliadora Bonfim [UNIFESP; COSTA, Francisco de Assis; Travessa,Aline Ferreira; Bombig, Maria Teresa Nogueira [UNIFESP; Fonseca, Francisco Antonio Helfenstein [UNIFESP; Luna Filho, Bráulio [UNIFESP; Mussi,Aurélia; Souza,Dilma de; Oliveira, Acary Souza Bulle; Póvoa, Rui Manuel dos Santos [UNIFESP

    2010-01-01

    BACKGROUND: Cardiac involvement is known to occur in patients with Duchenne muscular dystrophy (DMD). The electrocardiogram (ECG) shows some typical changes in DMD, which makes it a useful test for the diagnosis of cardiac lesion in this disease. OBJECTIVE: To evaluate the electrocardiographic changes in patients with DMD and to correlate these changes with the age of the population studied. METHODS: ECG of 131 patients diagnosed with DMD were examined. Several electrocardiographic variables ...

  17. Sleep-Disordered Breathing in Duchenne Muscular Dystrophy: An Assessment of the Literature

    Science.gov (United States)

    Hoque, Romy

    2016-01-01

    Study Objectives: The aim of this review is to review the literature on sleep-disordered breathing in Duchenne muscular dystrophy (DMD). Methods: PubMed was searched with an array of search terms, including “OSA,” “obstructive sleep apnea,” “sleep-disordered breathing,” “muscular dystrophy,” “neuromuscular,” “Duchenne muscular dystrophy,” “polysomnography,” and “portable monitoring.” All relevant articles were discussed. Results: Eighteen research articles and 1 consensus statement were reviewed, and assessed with relevant data presented. Three early studies prior to 1990 assessed DMD associated obstructive sleep apnea. Five studies assessed positive airway pressure (PAP) ventilation and/or sleep in varying neuromuscular disorders, including a cohort with DMD. Six studies since 2000 include PSG data in exclusively DMD cohorts. Three studies involved portable monitoring (PM). Conclusions: PSG with transcutaneous CO2 capnography is an important part of the clinical care for those with DMD. The utility of PM in DMD is unclear with only 1 study to date comparing PSG to PM data. Initiation of PAP therapy using bilevel modality may prevent the need for device switching as the disease progresses. Citation: Hoque R. Sleep-disordered breathing in Duchenne muscular dystrophy: an assessment of the literature. J Clin Sleep Med 2016;12(6):905–911. PMID:27070248

  18. A comprehensive database of Duchenne and Becker muscular dystrophy patients in Children's Hospital of Fudan University

    Directory of Open Access Journals (Sweden)

    Xi-hua LI

    2015-05-01

    Full Text Available Background China is one of the countries that have the largest number of patients suffering from Duchenne and Becker muscular dystrophy (DMD/BMD. Although the building of international DMD/BMD databases has laid a foundation for clinical drug development and clinical trials, it has not yet been carried out in China. In this study, a modified registry form of Remudy was applied to 229 DMD/BMD patients in order to establish a comprehensive database, which will lay the groundwork for international cooperation.  Methods A total of 229 DMD/BMD patients diagnosed by genetic testing or muscle biopsy admitted in Children's Hospital of Fudan University (CHFU during the period of August 2011 to December 2013 were enrolled in this study. The data included sex, age, age at diagnosis, geographic distribution of patients, DMD gene mutation types, family history, walking capability, cardiac and respiratory function, steroid treatment and rehabilitation intervention.  Results There were 194 DMD and 35 BMD male patients who were diagnosed at the age of 0-18 years, and among them, most patients were diagnosed at the age of > 3-4 (16.59%, 38/229 and > 7-8 (14.85%, 34/229 years. Exon deletion was the most frequent genetic mutations for DMD/BMD [65.46% (127/194 and 74.29% (26/35], respectively. Patients with a family history accounted for 23.14% (53/229. The rate of DMD registrants losing walking capability was 17.53% (34/194, and all the BMD registrants were able to walk. Cardiac functions were examined in 46.29% (106/229 DMD/BMD boys and respiratory functions were examined in 17.90% (41/229 DMD/BMD boys. The proportion of DMD patients receiving prednisone with dosage of 0.75 mg/(kg·d was 26.29% (51/194.  Conclusions This database describes in detail the genotype, clinical manifestation, diagnosis and treatment and rehabilitation status of 229 DMD/BMD patients in China. The database not only provides comprehensive information for DMD/BMD patient management

  19. Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

    Directory of Open Access Journals (Sweden)

    Luz Berenice López-Hernández

    2015-03-01

    Full Text Available Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD, a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162 with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001. To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.

  20. Comparison of mutation profiles in the Duchenne muscular dystrophy gene among populations: implications for potential molecular therapies.

    Science.gov (United States)

    López-Hernández, Luz Berenice; Gómez-Díaz, Benjamín; Luna-Angulo, Alexandra Berenice; Anaya-Segura, Mónica; Bunyan, David John; Zúñiga-Guzman, Carolina; Escobar-Cedillo, Rosa Elena; Roque-Ramírez, Bladimir; Ruano-Calderón, Luis Angel; Rangel-Villalobos, Héctor; López-Hernández, Julia Angélica; Estrada-Mena, Francisco Javier; García, Silvia; Coral-Vázquez, Ramón Mauricio

    2015-03-09

    Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.

  1. The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations

    Science.gov (United States)

    Bladen, Catherine L; Salgado, David; Monges, Soledad; Foncuberta, Maria E; Kekou, Kyriaki; Kosma, Konstantina; Dawkins, Hugh; Lamont, Leanne; Roy, Anna J; Chamova, Teodora; Guergueltcheva, Velina; Chan, Sophelia; Korngut, Lawrence; Campbell, Craig; Dai, Yi; Wang, Jen; Barišić, Nina; Brabec, Petr; Lahdetie, Jaana; Walter, Maggie C; Schreiber-Katz, Olivia; Karcagi, Veronika; Garami, Marta; Viswanathan, Venkatarman; Bayat, Farhad; Buccella, Filippo; Kimura, En; Koeks, Zaïda; van den Bergen, Janneke C; Rodrigues, Miriam; Roxburgh, Richard; Lusakowska, Anna; Kostera-Pruszczyk, Anna; Zimowski, Janusz; Santos, Rosário; Neagu, Elena; Artemieva, Svetlana; Rasic, Vedrana Milic; Vojinovic, Dina; Posada, Manuel; Bloetzer, Clemens; Jeannet, Pierre-Yves; Joncourt, Franziska; Díaz-Manera, Jordi; Gallardo, Eduard; Karaduman, A Ayşe; Topaloğlu, Haluk; El Sherif, Rasha; Stringer, Angela; Shatillo, Andriy V; Martin, Ann S; Peay, Holly L; Bellgard, Matthew I; Kirschner, Jan; Flanigan, Kevin M; Straub, Volker; Bushby, Kate; Verschuuren, Jan; Aartsma-Rus, Annemieke; Béroud, Christophe; Lochmüller, Hanns

    2015-01-01

    Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations). PMID:25604253

  2. Normal height and weight in a series of ambulant Duchenne muscular dystrophy patients using the 10 day on/10 day off prednisone regimen.

    NARCIS (Netherlands)

    Dam, K. ten; Groot, I.J.M. de; Noordam, C.; Alfen, N. van; Hendriks, J.C.M.; Sie, L.T.L.

    2012-01-01

    Prednisone treatment delays the progressive course of Duchenne muscular dystrophy. The aim of this study was to determine the influence of the 10 day on/10 day off treatment on height and weight. We retrospectively reviewed the growth and weight charts of Duchenne patients born between 1988 and 2006

  3. Disturbing pasts: Memories, controversies and creativity

    Directory of Open Access Journals (Sweden)

    Leon Wainwright

    2014-10-01

    Full Text Available This themed issue of the Open Arts Journal, ‘Disturbing pasts: Memories, controversies and creativity’, brings together a range of artists, curators, policy-makers and academics from around the world, who explore creative engagements with controversial and traumatic pasts in art practice, curating and museums. The material is presented in three parts: ‘Difficult Pasts and Public Space’ (writings on historical issues and museums, ‘Visual Investigations’ (artists’ statements and criticism, and ‘Collaborations’ (visual analysis and artist-scholar pairings of writings and original artworks. This collection was developed through a two-year international research project led by Leon Wainwright, which involved three consortia of researchers from universities throughout Europe, and focused on a major public event at the Museum of Ethnology Vienna/ Weltmuseum, Wien (November 2011. The project is funded by HERA (Humanities in the European Research Area, the European Science Foundation.

  4. Erythropoietin in bone - Controversies and consensus.

    Science.gov (United States)

    Hiram-Bab, Sahar; Neumann, Drorit; Gabet, Yankel

    2017-01-01

    Erythropoietin (Epo) is the main hormone that regulates the production of red blood cells (hematopoiesis), by stimulating their progenitors. Beyond this vital function, several emerging roles have been noted for Epo in other tissues, including neurons, heart and retina. The skeletal system is also affected by Epo, however, its actions on bone are, as yet, controversial. Here, we review the seemingly contradicting evidence regarding Epo effects on bone remodeling. We also discuss the evidence pointing to a direct versus indirect effect of Epo on the osteoblastic and osteoclastic cell lineages. The current controversy may derive from a context-dependent mode of action of Epo, namely opposite skeletal actions during bone regeneration and steady-state bone remodeling. Differences in conclusions from the published in-vitro studies may thus relate to the different experimental conditions. Taken together, these studies indicate a complexity of Epo functions in bone cells.

  5. The first Pico-Ficino Controversy

    DEFF Research Database (Denmark)

    Aasdalen, Unn Irene

    2011-01-01

    In the first controversy between Marsilio Ficino (1433-1499) and Giovanni Pico della Mirandola (1463-1494), the Florentine Duecento poet Guido Cavalcanti is central to the argument. The dispute between Ficino and Pico over Cavalcanti’s canzone Donna me prega is therefore in this article used...... in an attempt to throw light upon their further disagreement about the Platonic philosophy of love. The first Pico-Ficino controversy is in part played out over Florentine poetry, but does not have poetry as its prime concern. In essence, the miniature dispute about the Donna me prega encapsulates a grand...... mainly through the seventh book of his Symposium commentary, and Pico’s counter-position from his detailed commentary on a canzone by Girolamo Benivieni’s, the Amor dalle cui, in his Commento....

  6. Controversies Concerning Theological Language: Cognitivity and Revelation

    Directory of Open Access Journals (Sweden)

    Mindaugas Briedis

    2011-04-01

    Full Text Available Theological language as a problem under research is especially a controversial one. The question of language enerpsrise is crucial if we are willing to concider theology as a rational and/or critical discipline despite its „object“ or „religious substance“ which can be defined as irrational in the sense of divine mistery. The reflection of a specific referential system which is constituted by theological propositions uncovers peculiar logic of theological language which in turn is always in correlation with basic shifts in philosophy. The paper questions this mutuality as well as presents several characteristic controversies in contemporary theology, particularly in the protestant one. After these goals are achieved, it is possible to formulate concluding  ideas about the problem of cognitive value of revelation, and, on the other hand, about the influence of concrete forms of knowledge (modern ontology for the structures of faith. 

  7. Persistent Confusion and Controversy Surrounding Gene Patents

    Science.gov (United States)

    Guerrini, Christi J.; Majumder, Mary A.; McGuire, Amy L.

    2016-01-01

    There is persistent confusion and controversy surrounding basic issues of patent law relevant to the genomics industry. Uncertainty and conflict can lead to the adoption of inefficient practices and exposure to liability. The development of patent-specific educational resources for industry members, as well as the prompt resolution of patentability rules unsettled by recent U.S. Supreme Court decisions, are therefore urgently needed. PMID:26849516

  8. Comment: An Apparent Controversy in Auroral Physics

    Science.gov (United States)

    Haerendel, Gerhard

    2007-03-01

    In his article ``A turning point in auroral physics,'' Bryant argued against what he called the `standard' theory of auroral acceleration, according to which the electrons ``gain their energy from static electric fields,'' and offered wave acceleration as an alternative. Because of the importance of the process, not only for the aurora borealis but also for other cosmic plasmas, a clarification of this apparent controversy seems to be in place.

  9. Sugar substitutes: Health controversy over perceived benefits

    OpenAIRE

    Tandel, Kirtida R.

    2011-01-01

    Sugar is an inseparable part of the food we consume. But too much sugar is not ideal for our teeth and waistline. There have been some controversial suggestions that excessive sugar may play an important role in certain degenerative diseases. So artificial sweeteners or artificially sweetened products continue to attract consumers. A sugar substitute (artificial sweetener) is a food additive that duplicates the effect of sugar in taste, but usually has less food energy. Besides its benefits, ...

  10. Eighth Joint National Committee: Other Controversial Issues

    Directory of Open Access Journals (Sweden)

    Alberto Morales Salinas

    2014-05-01

    Full Text Available The Eighth Joint National Committee has generated extensive discussion. We recently analyzed the unfair exclusion of beta-blockers as first-line therapy for uncomplicated hypertension in this journal. Now, we will briefly present some considerations on other controversial issues of the Eighth Joint National Committee, such as the methodology used and the increased therapeutic goal in patients over 60 years old.

  11. Skeletal muscle fibrosis in the mdx/utrn+/- mouse validates its suitability as a murine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Gutpell, Kelly M; Hrinivich, William T; Hoffman, Lisa M

    2015-01-01

    Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and myofiber damage in the mdx, mdx/utrn+/- and double knockout (dko) mouse models. We used Masson's trichrome stain and percentage of centrally-nucleated myofibers as indicators of fibrosis and myofiber regeneration, respectively, to assess disease progression in diaphragm and gastrocnemius muscles harvested from young and aged wild-type, mdx, mdx/utrn+/- and dko mice. Our results indicated that eight week-old gastrocnemius muscles of both mdx/utrn+/- and dko hind limb developed fibrosis whereas age-matched mdx gastrocnemius muscle did not (p = 0.002). The amount of collagen found in the mdx/utrn+/- diaphragm was significantly higher than that found in the corresponding diaphragm muscles of wild-type animals, but not of mdx animals (p = 0.0003). Aged mdx/utrn+/- mice developed fibrosis in both diaphragm and gastrocnemius muscles compared to wild-type controls (p = 0.003). Mdx diaphragm was fibrotic in aged mice as well (p = 0.0235), whereas the gastrocnemius muscle in these animals was not fibrotic. We did not measure a significant difference in collagen staining between wild-type and mdx gastrocnemius muscles. The results of this study support previous reports that the moderately-affected mdx/utrn+/- mouse is a better model of DMD, and we show here that this difference is apparent by 2 months of age.

  12. [Addressing the controversy regarding the association between thimerosal-containing vaccines and autism].

    Science.gov (United States)

    García-Fernández, Lisset; Hernández, Adrián V; Suárez Moreno, Víctor; Fiestas, Fabián

    2013-04-01

    Vaccination is one of the most important public health interventions in the reduction childhood morbidity and mortality. Thimerosal is an organic mercury compound used as preservante in multi-dose vials. Often in Peru, there are waves of controversy about the safety of this type of vaccines, mainly arguing that there is an association between them and autism. As a result of these controversies, there have been some voices asking for laws banning thimerosal-containing vaccines, which would have a large impact in costs and the logistic aspects of the public vaccination programs. The aim of this article is to review the literature for the main controversies about thimerosal in vaccines and its supposed association to autism. We made an historical review about these controversies given the available scientific evidence and the statements from important international organizations. We concluded that the current available evidence do not support an association between thimerosal and childhood neurodevelopmental disorders, such as autism.

  13. RESULTS OF MEDICO-GENETIC STUDY OF PATIENTS WITH DUCHENNE/BECKER PROGRESSIVE MUSCULAR DYSTROPHIES IN UZBEKISTAN

    Directory of Open Access Journals (Sweden)

    Umida Tulkinovna Omonova

    2014-11-01

    Full Text Available The purpose of study was to analyze clinical and genetic polymorphism of Duchenne/Becker progressive muscular dystrophies among patients with neuromuscular diseases in Uzbekistan. 106 male patients with progressive pseudohypertrophic forms of muscular dystrophy were retrospectively and prospectively analyzed in the period from 2004 till 2014: 93 patients with Duchenne PMD aged from 3 years to 18 years and 13 patients with Becker PMD aged from 10 years to 25 years, who had been examined in the medico-genetic consulting department of the Republican Center “Mother and Child Screening” of Tashkent city. Comprehensive clinical, neurophysiological, biochemical and genetic study of patients as the integral part in the differential diagnosis of Duchenne/Becker progressive muscular dystrophies allows creating the national database on D/B PMD to prevent the birth of children in families burdened by this disease.

  14. A Two-amino Acid Mutation Encountered in Duchenne Muscular Dystrophy Decreases Stability of the Rod Domain 23 (R23) Spectrin-like Repeat of Dystrophin.

    Science.gov (United States)

    Legardinier, Sébastien; Legrand, Baptiste; Raguénès-Nicol, Céline; Bondon, Arnaud; Hardy, Serge; Tascon, Christophe; Le Rumeur, Elisabeth; Hubert, Jean-François

    2009-03-27

    Lack of functional dystrophin causes severe Duchenne muscular dystrophy. The subsarcolemmal location of dystrophin, as well as its association with both cytoskeleton and membrane, suggests a role in the mechanical regulation of muscular membrane stress. In particular, phenotype rescue in a Duchenne muscular dystrophy mice model has shown that some parts of the central rod domain of dystrophin, constituted by 24 spectrin-like repeats, are essential. In this study, we made use of rare missense pathogenic mutations in the dystrophin gene and analyzed the biochemical properties of the isolated repeat 23 bearing single or double mutations E2910V and N2912D found in muscle dystrophy with severity grading. No dramatic effect on secondary and tertiary structure of the repeat was found in mutants compared with wild type as revealed by circular dichroism and NMR. Thermal and chemical unfolding data from circular dichroism and tryptophan fluorescence show significant decrease of stability for the mutants, and stopped-flow spectroscopy shows decreased refolding rates. The most deleterious single mutation is the N2912D replacement, although we observe additive effects of the two mutations on repeat stability. Based on three-dimensional structures built by homology molecular modeling, we discuss the modifications of the mutation-induced repeat stability. We conclude that the main forces involved in repeat stability are electrostatic inter-helix interactions that are disrupted following mutations. This study represents the first analysis at the protein level of the consequences of missense mutations in the human dystrophin rod domain. Our results suggest that it may participate in mechanical weakening of dystrophin-deficient muscle.

  15. The Controversies over Bioenergy in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Andersen, Bente Hessellund

    2012-01-01

    for processing of biomass for biofuels. The alignment with the private car regime is strong, because biofuel enables continuation of fuel-driven vehicles as dominating transportation mode. Danish farmers see manure as important source for biogas while arguing for reduction of climate impact and nuisances from...... digested manure. Such biogas is questioned by some NGOs who fear manure-based biogas is used as argument for increased animal husbandry. The bioenergy controversies concern also methodologies for environmental assessments, including for indirect land use changes (ILUC), and reliability of certification...

  16. Panels and Lectures Address China Controversies

    Directory of Open Access Journals (Sweden)

    Video Resources

    2010-04-01

    Full Text Available Editors note: Over the past several months, colleagues have brought to our attention three public panel discussions and lectures that address contemporary controversies in Chinese studies. These discussions have been video-recorded and are available to view on the internet. These presentations may be useful either for scholarly pursuits or may be excerpted for classroom viewing. We wish to thank those who contacted us about these resources, and we encourage readers who know of other such video resources to let us know about them so that we can inform our ASIANetwork colleagues of their existence and availability.

  17. Prenatal Diagnosis of the Duchenne Muscular Dystrophy. A Family Presentation Diagnóstico prenatal de la distrofia muscular de Duchenne. Presentación de una familia

    Directory of Open Access Journals (Sweden)

    Mariesky Zayas Guillot

    2007-05-01

    Full Text Available The Duchenne muscular dystrophy is one of the most frequent hereditary myopathies that exist. It is characterized by degeneration of the muscle skeletal fibers which produce handicap in the first decade of life bringing about death due to cardiac or respiratory failure. The responsible gene of the disease is known as DMD and it is located in the X chromosome shorter arm. A family history is presented in which the pregnant woman who is the sick patient’s sister asks for a prenatal diagnosis. An indirect molecular study was performed with the STR-50 polymorphic marker. After the analysis of the results in which the lab methodology was applied, the fetus was found to be sick and the family decided to interrupt the pregnancy.
    La distrofia muscular de Duchenne es una de las miopatías hereditarias más frecuentes que existe. Se caracteriza por la degeneración de las fibras musculares esqueléticas, que provocan la invalidez en la primera década de vida y, luego, la muerte por fallos respiratorios o cardíacos El gen responsable de la enfermedad se conoce como DMD y se localiza en el brazo corto del cromosoma X. Se presenta la historia de una familia en que, con un embarazo de 15 semanas, la hermana del enfermo solicita diagnóstico prenatal. Se realizó el estudio molecular indirecto con el marcador polimórfico STR- 50. Tras el análisis de los resultados obtenidos después de aplicada la metodología de laboratorio el feto resultó estar enfermo, y la familia optó por la interrupción del embarazo.

  18. The Reviewing of Controversial Juvenile Books: A Study.

    Science.gov (United States)

    Crow, Sherry R.

    1986-01-01

    Describes a study which examined reviewers' treatment of controversial juvenile books in Booklist, Bulletin of Center for Children's Books, Horn Book, and School Library Journal. The total number of controversial books reviewed by each journal, promptness of reviews, and extent of discussion of controversial features are discussed. (MBR)

  19. Tratamiento fisioterápico en la distrofia muscular de Duchenne

    OpenAIRE

    Burgos González, Sara

    2014-01-01

    la Distrofia Muscular de Duchenne es una enfermedad neuromuscular hereditaria de carácter recesivo ligada al cromosoma X. Afecta aproximadamente a 1 de cada 3500 niños varones nacidos vivos. Se caracteriza por cursar con una debilidad progresiva como resultado de una degeneración de los músculos, iniciando en piernas y pelvis y posteriormente abarcando todo el cuerpo. Este trastorno se debe a una mutación que es culpable de la ausencia de una proteína muscular, la distrofina...

  20. Histone deacetylase inhibitors: a potential epigenetic treatment for Duchenne muscular dystrophy.

    Science.gov (United States)

    Consalvi, Silvia; Saccone, Valentina; Mozzetta, Chiara

    2014-01-01

    Duchenne muscular dystrophy (DMD) is a life-threatening genetic disease that currently has no available cure. A number of pharmacological strategies that aim to target events downstream of the genetic defect are currently under clinical investigation, and some of these are outlined in this report. In particular, we focus on the ability of histone deacetylase inhibitors to promote muscle regeneration and prevent the fibro-adipogenic degeneration of dystrophic mice. We describe the rationale behind the translation of histone deacetylase inhibitors into a clinical approach, which inspired the first clinical trial with an epigenetic drug as a potential therapeutic option for DMD patients.

  1. Características do Portador de Distrofia Muscular de Duchenne (DMD) - Revisão

    OpenAIRE

    Caromano, Fátima Aparecida

    2008-01-01

    A Distrofia Muscular de Duchenne (DMD) é um distúrbio genético que se caracteriza por uma degeneração progressiva e irreversível da musculatura esquelética. A atuação da Fisioterapia altera as perspectivas de qualidade e expectativa de vida. Assim, conhecer a doença favorece a elaboração de objetivos e intervenção de forma mais objetiva e eficiente. Nosso objetivo com este artigo foi fornecer con...

  2. Importância do camundongo mdx na fisiopatologia da distrofia muscular de Duchenne

    OpenAIRE

    Seixas,Sandra Lopes; Lagrota-Cândido,Jussara; Savino, Wilson; Quirico-Santos,Thereza

    1997-01-01

    O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X (locus Xp21.1) e não expressa distrofina. Embora não apresente intensa fibrose do tecido muscular e acúmulo de tecido adiposo, é considerado o modelo animal mais adequado da distrofia muscular de Duchenne. As alterações estruturais no tecido muscular associadas à mionecrose e presença do infiltrado inflamatório com predomínio de linfócitos e monócitos/macrófagos sugerem uma participação do sistema imunológico nest...

  3. Neuronal modelling with Duchenne muscular dystrophy patients using pluripotent stem cells

    OpenAIRE

    Isabella Rodrigues Fernandes

    2015-01-01

    A Distrofia Muscular de Duchenne (DMD) é uma patologia neuromuscular causada pela mutação ou deleção do gene da distrofina, localizado no cromossomo X, levando a degeneração muscular ao longo da vida do paciente. A doença também tem sido associada a déficit cognitivo e falta de habilidade comportamental. Pesquisas com células neurais de pacientes com DMD poderiam ajudar a elucidar os sintomas neurológicos associados. Neste trabalho, através de células-tronco pluripotentes induzidas (iPSC) der...

  4. Detection of the mutation may guide treatment of heart and muscle in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Finsterer J

    2016-03-01

    Full Text Available Josef Finsterer,1 Sinda Zarrouk-Mahjoub21Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia We read with great interest the article, by Kono et al, about a 32-year-old male with Duchenne muscular dystrophy (DMD, who was admitted for dilated cardiomyopathy manifesting as heart failure, left bundle branch block, Mobitz-II block, bradycardia, and arterial hypotension. He profited from implantation of a cardiac resynchronization therapy-D system with a defibrillator and beta-blocker treatment. View original article by Kono et al.  

  5. Rapid carrier and prenatal diagnosis of Duchenne and Becker muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, R.G.; Cole, C.G.; Hart, K.A.; Bobrow, M.; Bentley, D.R. (Guy' s Hospital, London (England))

    1989-01-25

    Carrier and prenatal diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD) by DNA methods uses Southern blotting to detect either the informative segregation of restriction fragment length polymorphisms (RFLPs) or the absence of restriction fragments in affected males. Recently, the use of the polymerase chain reaction (PCR) for rapid detection of deletions in some affected males was reported eliminating the need for Southern blotting of 37% of all samples. This approach is not applicable, however, to non-deletion cases or for carrier diagnosis. The authors have used PCR for rapid analysis of intragenic RFLPs to permit both carrier and prenatal diagnosis in the majority of familial cases.

  6. Cirugía funcionalizadora en la distrofia muscular progresiva (Enfermedad de Duchenne)

    OpenAIRE

    Arendar, G.; Canelo, B.; Paladino, D.; Zacarias, A. J.

    1995-01-01

    Presentamos una serie de 55 pacientes afectados de Distrofia Muscular Progresiva (Enfermedad de Duchenne) de los cuales 22 fueron operados de los miembros inferiores con tecnoplastias de Aquiles principalmente, biopedestados en el término de 24 hs. y equipados ortodésicamente en la primera semana y que por término medio prolongaron su independencia de marcha por 20 meses. El criterio utilizado, mejoró notablemente la calidad de vida de estos niños postergando la aparición de co...

  7. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy

    OpenAIRE

    Nelson, Christopher E.; Hakim, Chady H.; Ousterout, David G.; Thakore, Pratiksha I.; Moreb, Eirik A.; Rivera, Ruth M. Castellanos; Madhavan, Sarina; Pan, Xiufang; Ran, F. Ann; Yan, Winston X.; Asokan, Aravind; Zhang, Feng; Duan, Dongsheng; Gersbach, Charles A.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the CRISPR/Cas9 system to the mdx mouse model of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery...

  8. Management of scoliosis in patients with Duchenne muscular dystrophy and spinal muscular atrophy: A literature review.

    Science.gov (United States)

    Garg, Sumeet

    2016-01-01

    Scoliosis occurs in nearly all non-ambulatory children with spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD). Non-operative treatments have not been shown to be effective at preventing progression of scoliosis. Progressive scoliosis can impact the ability of patients to sit comfortably, be cosmetically unappealing, and in severe cases exacerbate pulmonary disease. The main goal of operative treatment is to improve sitting balance and prevent progression of scoliosis. Complication rates are high and there is little data on effect of operative treatment on quality of life in children with SMA and DMD. Comprehensive multi-disciplinary pre-operative evaluations are vital to reduce the risks of operative treatment.

  9. Tratamiento con oligonucleótidos antisentido en la enfermedad de Duchenne

    OpenAIRE

    Pascual Pascual, Samuel Ignacio

    2012-01-01

    Se revisa el estado actual de los tratamientos de modificación del ARN de distrofina, que persiguen convertir la forma grave de la distrofia muscular de Duchenne a una forma leve (Becker), especialmente con la omisión del exón 51 mediante oligonucleótidos en antisentido y la terapia de restauración de la lectura de la distrofina, suprimiendo un codón de terminación prematura mediante PTC124. Constituyen un avance notable en el tratamiento. Consiguen una producción significativa de...

  10. Importância do camundongo mdx na fisiopatologia da distrofia muscular de Duchenne

    OpenAIRE

    Sandra Lopes Seixas; Jussara Lagrota-Cândido; Wilson Savino; Thereza Quirico-Santos

    1997-01-01

    O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X (locus Xp21.1) e não expressa distrofina. Embora não apresente intensa fibrose do tecido muscular e acúmulo de tecido adiposo, é considerado o modelo animal mais adequado da distrofia muscular de Duchenne. As alterações estruturais no tecido muscular associadas à mionecrose e presença do infiltrado inflamatório com predomínio de linfócitos e monócitos/macrófagos sugerem uma participação do sistema imunológico nest...

  11. Tratamiento fisioterápico en la distrofia muscular de Duchenne

    OpenAIRE

    Burgos González, Sara

    2014-01-01

    la Distrofia Muscular de Duchenne es una enfermedad neuromuscular hereditaria de carácter recesivo ligada al cromosoma X. Afecta aproximadamente a 1 de cada 3500 niños varones nacidos vivos. Se caracteriza por cursar con una debilidad progresiva como resultado de una degeneración de los músculos, iniciando en piernas y pelvis y posteriormente abarcando todo el cuerpo. Este trastorno se debe a una mutación que es culpable de la ausencia de una proteína muscular, la distrofina...

  12. Phenotypic contrasts of Duchenne Muscular Dystrophy in women: Two case reports

    Directory of Open Access Journals (Sweden)

    Karen T. Nozoe

    2016-07-01

    Full Text Available We discussed two cases of symptomatic female carriers to Duchenne Muscular Dystrophy. The first case is a 20 year-old girl with classical phenotypic manifestation of the disease, similar to the condition in boys. The case 2 is a 62 year-old woman with progressive muscular weakness. The disease is much less common in woman than men so both cases described here are considered rare forms of the disease, with several clinical implications. In both cases, a progressive muscle weakness, impairment in walking and sleeping was observed, in addition to obstructive sleep apnea syndrome and alveolar hypoventilation, that required noninvasive ventilatory support.

  13. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy

    OpenAIRE

    Nelson, Christopher E.; Hakim, Chady H.; Ousterout, David G.; Thakore, Pratiksha I; Moreb, Eirik A.; Rivera, Ruth M. Castellanos; Madhavan, Sarina; Pan, Xiufang; Ran, F. Ann; Yan, Winston X.; Asokan, Aravind; Zhang, Feng; Duan, Dongsheng; Gersbach, Charles A.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the CRISPR/Cas9 system to the mdx mouse model of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery...

  14. Controversies in the Etiologies of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ali Safdar Khan

    2010-11-01

    Full Text Available Acute pancreatitis is a potentially life threatening acute inflammatory condition of the pancreas with an annual incidence in the United States estimated to be 40 cases per 100,000 adults [1] which is one of the highest in the world [2]. There is also a rising trend in the incidence of acute pancreatitis in the United States which has been observed over the past several decades [3]. Though most cases are mild with mortality below 1%, there is a subset classified as severe pancreatitis in which the mortality can reach as high as 30% [4]. The direct medical cost of hospitalization for acute pancreatitis is estimated to be $2.2 billion at a mean cost per hospital day of $1,670 [5] which is likely an underestimation. To determine the etiology of the acute pancreatitis is crucial to the management of this potentially fatal condition. Even though a wide variety of etiologies have been proposed, the exact role of the some of these still remains controversial and in some cases ill-defined. A cause is not clinically determined in up to 30% of cases which are labeled idiopathic pancreatitis [6]. This review attempts to re-visit some of the controversies surrounding these etiologies, discuss the current understanding of the mechanisms that underlie them and to identify areas requiring further research.

  15. Pediatric urinary tract infections: current controversies.

    Science.gov (United States)

    MacNeily, A E

    2001-06-01

    Few topics in pediatric urology engender such vigorous debate as the who, when, how, and why related to the investigation of pediatric urinary tract infections (UTIs). Further controversy stems from management of the underlying pathology. This article first discusses the patient characteristics that are important in the evaluation of pediatric patients with UTIs, and the indications for screening tests (such as voiding cystourethrograms, ultrasound, dimercaptosuccinic acid renal scintigraphy, and intravenous pyelography). Following this, the author reviews what is known about three controversial aspects about the management of these patients. First, although the role of the prepuce in pediatric UTI is well established, the role of routine circumcision is not. Second, the natural history and etiology of antenatally detected vesicoureteral reflux (VUR) has provoked us to view the concept of "primary reflux" in a new light. Third, although the way to diagnose vesicoureteral reflux is generally agreed upon, the utility of our surgical management in view of long-term follow-up is less clear.

  16. Sugar substitutes: Health controversy over perceived benefits

    Directory of Open Access Journals (Sweden)

    Kirtida R Tandel

    2011-01-01

    Full Text Available Sugar is an inseparable part of the food we consume. But too much sugar is not ideal for our teeth and waistline. There have been some controversial suggestions that excessive sugar may play an important role in certain degenerative diseases. So artificial sweeteners or artificially sweetened products continue to attract consumers. A sugar substitute (artificial sweetener is a food additive that duplicates the effect of sugar in taste, but usually has less food energy. Besides its benefits, animal studies have convincingly proven that artificial sweeteners cause weight gain, brain tumors, bladder cancer and many other health hazards. Some kind of health related side effects including carcinogenicity are also noted in humans. A large number of studies have been carried out on these substances with conclusions ranging from "safe under all conditions" to "unsafe at any dose". Scientists are divided in their views on the issue of artificial sweetener safety. In scientific as well as in lay publications, supporting studies are often widely referenced while the opposing results are de-emphasized or dismissed. So this review aims to explore the health controversy over perceived benefits of sugar substitutes.

  17. Automixis in Artemia: solving a century-old controversy.

    Science.gov (United States)

    Nougué, O; Rode, N O; Jabbour-Zahab, R; Ségard, A; Chevin, L-M; Haag, C R; Lenormand, T

    2015-12-01

    Parthenogenesis (reproduction through unfertilized eggs) encompasses a variety of reproduction modes with (automixis) or without (apomixis) meiosis. Different modes of automixis have very different genetic and evolutionary consequences but can be particularly difficult to tease apart. In this study, we propose a new method to discriminate different types of automixis from population-level genetic data. We apply this method to diploid Artemia parthenogenetica, a crustacean whose reproductive mode remains controversial despite a century of intensive cytogenetic observations. We focus on A. parthenogenetica from two western Mediterranean populations. We show that they are diploid and that markers remain heterozygous in cultures maintained up to ~36 generations in the laboratory. Moreover, parallel patterns of population-wide heterozygosity levels between the two natural populations strongly support the conclusion that diploid A. parthenogenetica reproduce by automictic parthenogenesis with central fusion and low, but nonzero recombination. This settles a century-old controversy on Artemia, and, more generally, suggests that many automictic organisms harbour steep within-chromosome gradients of heterozygosity due to a transition from clonal transmission in centromere-proximal regions to a form of inbreeding similar to self-fertilization in centromere-distal regions. Such systems therefore offer a new avenue for contrasting the genomic consequences of asexuality and inbreeding.

  18. Epistemological depth in a GM crops controversy.

    Science.gov (United States)

    Hicks, Daniel J

    2015-04-01

    This paper examines the scientific controversy over the yields of genetically modified [GM] crops as a case study in epistemologically deep disagreements. Appeals to "the evidence" are inadequate to resolve such disagreements; not because the interlocutors have radically different metaphysical views (as in cases of incommensurability), but instead because they assume rival epistemological frameworks and so have incompatible views about what kinds of research methods and claims count as evidence. Specifically, I show that, in the yield debate, proponents and opponents of GM crops cite two different sets of claims as evidence, which correspond to two rival epistemological frameworks, classical experimental epistemology and Nancy Cartwright's evidence for use. I go on to argue that, even if both sides of the debate accepted Cartwright's view, they might still disagree over what counts as evidence, because evidence for use ties standards of evidence to what is sometimes called the "context of application."

  19. Cold dark matter: controversies on small scales

    CERN Document Server

    Weinberg, David H; Governato, Fabio; de Naray, Rachel Kuzio; Peter, Annika H G

    2013-01-01

    The cold dark matter (CDM) cosmological model has been remarkably successful in explaining cosmic structure over an enormous span of redshift, but it has faced persistent challenges from observations that probe the innermost regions of dark matter halos and the properties of the Milky Way's dwarf galaxy satellites. We review the current observational and theoretical status of these "small scale controversies." Cosmological simulations that incorporate only gravity and collisionless CDM predict halos with abundant substructure and central densities that are too high to match constraints from galaxy dynamics. The solution could lie in baryonic physics: recent numerical simulations and analytic models suggest that gravitational potential fluctuations tied to efficient supernova feedback can flatten the central cusps of halos in massive galaxies, and a combination of feedback and low star-formation efficiency could explain why most of the dark matter subhalos orbiting the Milky Way do not host visible galaxies. H...

  20. Controversies in the Management of Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    V. Masciullo

    2010-01-01

    Full Text Available Endometrial cancer (EC remains the most common malignancy of the female genital tract. The median age at diagnosis is the sixth decade, with abnormal uterine bleeding at the presentation in 90% of the patients. Surgical treatment, including complete hysterectomy, removal of remaining adnexal structures, and an appropriate surgical staging, represents the milestone of curative therapy for patients with EC. Adjuvant therapy is necessary in patients at high risk of recurrence. Conservative treatment approaches should be used in selected cases for women with a desire of fertility preservation. This review summarizes the management of EC and discusses current controversies regarding the role of lymphadenectomy and radiotherapy in patients with intermediate-risk tumors confined to the uterus.

  1. The Casimir effect: Recent controversies and progress

    CERN Document Server

    Milton, K A

    2004-01-01

    The phenomena implied by the existence of quantum vacuum fluctuations, grouped under the title of the Casimir effect, are reviewed, with emphasis on new results discovered in the past four years. The Casimir force between parallel plates is rederived as the strong-coupling limit of $\\delta$-function potential planes. The role of surface divergences is clarified. A summary of effects relevant to measurements of the Casimir force between real materials is given, starting from a geometrical optics derivation of the Lifshitz formula, and including a rederivation of the Casimir-Polder forces. A great deal of attention is given to the recent controversy concerning temperature corrections to the Casimir force between real metal surfaces. A summary of new improvements to the proximity force approximation is given, followed by a synopsis of the current experimental situation. New results on Casimir self-stress are reported, again based on $\\delta$- function potentials. Progress in understanding divergences in the self...

  2. The Cartoon Controversy: Offence, Identity, Oppression?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2007-01-01

    If the publication of twelve drawings of the Prophet Mohammad in the Danish newspaper Jyllands-Posten, which sparked the ‘cartoon controversy', was wrong, why might this be the case? The article considers four arguments advanced in relation to the quite similar Rushdie affair for judging...... such publications to be wrong, and asks whether they provide plausible moral reasons against such publications, and whether they justify legal restrictions on freedom of speech. The arguments concern: (a) the consistent extension of group defamation legislation to cover Muslims; (b) offence to religious...... for judging the kind of publications under consideration to be morally wrong or suitable objects for legal restrictions. The argument from oppression is different, however, in pointing to different kinds of factors, but its applicability is limited both by a number of conditions for when oppression provides...

  3. Controversies in diagnosis of pulmonary embolism.

    Science.gov (United States)

    Stein, Paul D; Sostman, H Dirk; Dalen, James E; Bailey, Dale L; Bajc, Marika; Goldhaber, Samuel Z; Goodman, Lawrence R; Gottschalk, Alexander; Hull, Russell D; Matta, Fadi; Pistolesi, Massimo; Tapson, Victor F; Weg, John G; Wells, Philip S; Woodard, Pamela K

    2011-04-01

    The approach to the diagnosis of acute pulmonary embolism (PE) is under constant revision with advances in technology, noninvasive approaches, and increasing awareness of the risks of ionizing radiation. Optimal approaches in some categories of patients are controversial. Data are insufficient for evidence-based recommendations. Therefore, this survey of investigators in the field was undertaken. Even among experts there were marked differences of opinion regarding the approach to the diagnosis of acute PE. Although CT pulmonary angiography was usually the imaging test of choice, the respondents were keenly aware of the dangers of ionizing radiation. In view of advances in scintigraphic diagnosis since the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trial, ventilation/perfusion (V/Q) lung scans or perfusion scans alone and single photon emission computed tomography (SPECT) V/Q lung scans are often recommended. The choice depends on the patient's age, gender, and complexity of the findings on the plain chest radiograph.

  4. Do hormones influence melanoma? Facts and controversies.

    Science.gov (United States)

    Gupta, Amie; Driscoll, Marcia S

    2010-01-01

    The issue of whether hormones influence malignant melanoma (MM) has been controversial for many years. Although early case reports demonstrated a negative effect of hormones, recent evidence has not supported a potential role for hormones in MM. We address whether exogenous and endogenous hormones influence a woman's risk for MM or affect her prognosis if diagnosed with MM. Multiple epidemiologic studies show the use of oral contraceptives or hormone replacement therapy does not appear to increase a woman's risk for MM. Pregnancy does not appear to influence a woman's risk of MM, nor does pregnancy appear to affect prognosis in the woman diagnosed with MM. When counseling the woman who is diagnosed with MM during pregnancy or during the childbearing years, future use of oral contraceptives or hormone replacement therapy is not contraindicated; counseling concerning future pregnancies should be done on a case-by-case basis, with emphasis placed on established prognostic factors for MM.

  5. Controversies in pharmacotherapy of pain management.

    Science.gov (United States)

    Davis, Mellar P; Walsh, Declan; Lagman, Ruth; LeGrand, Susan B

    2005-09-01

    Since the establishment of the WHO three-step ladder for management of cancer pain, several controversies have arisen, which are partly due to new drug development, reformulations of older analgesics, and technological advancements. As a result, clinicians need clarification of several questions. Is morphine the opioid of choice for moderate to severe pain in cancer? Should combinations of opioids be used? When should spinal opioids be used to treat pain in cancer? What are the appropriate opioid doses for breakthrough pain? Should selective cyclo-oxygenase (COX) 2 inhibitors be used? What is the best tactic to treat neuropathic pain, and what first-line adjuvant analgesic should be used? And do bisphosphonates relieve bone pain in cancers other than breast cancer and myeloma? This review addresses these questions.

  6. Element 74, the Wolfram Versus Tungsten Controversy

    Energy Technology Data Exchange (ETDEWEB)

    Holden,N.E.

    2008-08-11

    Two and a quarter centuries ago, a heavy mineral ore was found which was thought to contain a new chemical element called heavy stone (or tungsten in Swedish). A few years later, the metal was separated from its oxide and the new element (Z=74) was called wolfram. Over the years since that time, both the names wolfram and tungsten were attached to this element in various countries. Sixty years ago, IUPAC chose wolfram as the official name for the element. A few years later, under pressure from the press in the USA, the alternative name tungsten was also allowed by IUPAC. Now the original, official name 'wolfram' has been deleted by IUPAC as one of the two alternate names for the element. The history of this controversy is described here.

  7. Evolution of the Two Cultures controversy

    Science.gov (United States)

    Bieniek, Ronald J.

    1981-05-01

    The Two Cultures schism is a persistent problem in our society. For over a century, scientific spokesmen and literary critics, from T. H. Huxley and M. Arnold to C. P. Snow and F. R. Leavis, have been involved in the Two Cultures issue. This article examines the evolution of the controversy between the ''scientific'' and ''humanistic'' elements of Western culture and its relation to educational policies. The division and antagonism between these two cultures appears to have arisen from differences in the human attitudes that they are preceived to engender. ''Scientific'' professionalism has been associated with a progressive optimism and self-assurance that nurture a broad humanitarianism, while the ''literary'' tradition is characterized by restraint, acceptance, and a more selective humanism.

  8. [On controversies around the Oedipus Complex].

    Science.gov (United States)

    Drwiega, Marek

    2002-01-01

    In the article the author would like to draw the readers' attention to one of the central issues of psychoanalysis, i.e. Oedipus complex. In the development of the psychoanalysis the classical conception of Oedipus complex presented by Freud gave rise to a severe criticism both on the part of some psychoanalysts, especially women such as e.g. Melanie Klein, and on the part of ethnographers such as B. Malinowski. In the paper the author presents the main controversies concerning this interesting discussion. The fact of the matter is that the Oedipus complex is a hotly debated subject, not only from the cultural point of view but also within the psychoanalytical movement.

  9. Imposed risk controversies: a critical analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, G.L.

    The author focuses on risk controversies where someone in one locale is concerned about being seriously injured as a result of human activities carried on elsewhere. Discussion is limited to unintentional risks, such as, nuclear power plants, dams, toxic pollutants and biological laboratories containing virulent organisms. He attempts to fashion a new judicial institution for settling disputes where liability is not well defined. The proposed system is a two-step process. The first is arbitration where defendant participation is voluntary. If judgment at first stage is against the defendant the system progresses to the second stage; otherwise the process is completed. The second stage is a full-scale hearing where burden of proof shifts to defendant. (PSB)

  10. DGGE based whole-gene mutation scanning of the dystrophlin gene in Duchenne and Becker muscular dystrophy patients

    NARCIS (Netherlands)

    Hofstra, RMW; Mulder, IM; Vossen, R; de Koning-Gans, PAM; Kraak, M; Ginjaar, IB; van der Hout, AH; Bakker, E; Buys, CHCM; van Essen, AJ; den Dunnen, JT

    2004-01-01

    Duchenne and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene. Large rearrangements in the gene are found in about two,thirds of DMD patients, with similar to60% carrying deletions and 5-10% carrying duplications. Most of the remaining 30-35% of patients are exp

  11. Physical training in boys with Duchenne Muscular Dystrophy : the protocol of the No Use is Disuse study

    NARCIS (Netherlands)

    Jansen, M.; Groot, I.J.M. de; Alfen, N. van; Geurts, A.C.H.

    2010-01-01

    BACKGROUND: "Use it or lose it" is a well known saying which is applicable to boys with Duchenne Muscular Dystrophy (DMD). Besides the direct effects of the muscular dystrophy, the increasing effort to perform activities, the fear of falling and the use of personal aids indirectly impair leg and arm

  12. Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients.

    NARCIS (Netherlands)

    Helderman-van den Enden, A.T.; Straathof, C.S.; Aartsma-Rus, A.; Dunnen, J.T. den; Verbist, B.M.; Bakker, E.; Verschuuren, J.J.; Ginjaar, H.B.

    2010-01-01

    Theoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated skipping of exon 51 to restore the reading frame, which results in the production of a shortened dystrophin protein. We give a detailed description with longitudinal follow up of three patients with B

  13. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands : a cohort study

    NARCIS (Netherlands)

    Hoogerwaard, EM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; Leschot, NJ; Van Essen, AJ; Brunner, HG; van der Wouw, PA; Wilde, AAM; de Visser, M

    1999-01-01

    Background Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of definit

  14. Slender Spring Systems, for a close-to-body dynamic arm support for people with Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Dunning, A.G.

    2016-01-01

    The goal of this dissertation is to develop a wearable, passive, dynamic arm support that provides users with Duchenne muscular dystrophy (DMD) with support to perform activities of daily living. The arm support needs to be inconspicuous and not stigmatizing, to encourage the users to participate in

  15. Slender Spring Systems, for a close-to-body dynamic arm support for people with Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Dunning, A.G.

    2016-01-01

    The goal of this dissertation is to develop a wearable, passive, dynamic arm support that provides users with Duchenne muscular dystrophy (DMD) with support to perform activities of daily living. The arm support needs to be inconspicuous and not stigmatizing, to encourage the users to participate in

  16. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands : a cohort study

    NARCIS (Netherlands)

    Hoogerwaard, EM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; Leschot, NJ; Van Essen, AJ; Brunner, HG; van der Wouw, PA; Wilde, AAM; de Visser, Marianne

    1999-01-01

    Background Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of

  17. Efficient and fast functional screening of microdystrophin constructs in vivo and in vitro for therapy of duchenne muscular dystrophy

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Larochelle, Nancy; Orlopp, Kristian

    2009-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked, lethal genetic disorder affecting the skeletal muscle compartment, and is caused by mutation(s) in the dystrophin gene. Gene delivery of microdystrophin constructs using adeno-associated virus (AAV) and antisense-mediated exon skipping restoring...

  18. Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents

    Directory of Open Access Journals (Sweden)

    Steve D Wilton

    2011-03-01

    Full Text Available Steve D Wilton, Sue FletcherCentre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, Perth, WA, AustraliaAbstract: The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD was expected to lead to timely development of effective therapies. Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals. Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments. Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms.Keywords: Duchenne muscular dystrophy, molecular therapeutics, small molecules

  19. Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure.

    Science.gov (United States)

    Rutter, Meilan M; Collins, James; Rose, Susan R; Woo, Jessica G; Sucharew, Heidi; Sawnani, Hemant; Hor, Kan N; Cripe, Linda H; Wong, Brenda L

    2012-12-01

    This study evaluated efficacy and safety of growth hormone treatment in Duchenne muscular dystrophy boys with glucocorticoid-induced growth failure. We reviewed 39 consecutive boys (average age 11.5 years; 32 ambulatory) treated with growth hormone for 1 year during a four-year period. Boys were on long-term daily deflazacort or prednisone (mean duration 5 ± 2.2 years; dosing regimen prednisone 0.75 mg/kg/day equivalent). Primary outcomes were growth velocity and height-for-age z-scores (height SD) at 1 year. Height velocity increased from 1.3 ± 0.2 to 5.2 ± 0.4 cm/year on growth hormone (pgrowth hormone decline in height SD (-0.5 ± 0.2SD/year) stabilized at height SD -2.9 ± 0.2 on growth hormone (pgrowth hormone and 2.6 ± 0.7 kg/year at 1 year. Motor function decline was similar pre-growth hormone and at 1 year. Cardiopulmonary function was unchanged. Three experienced side effects. In this first comprehensive report of growth hormone in Duchenne muscular dystrophy, growth hormone improved growth at 1 year, without detrimental effects observed on neuromuscular and cardiopulmonary function.

  20. Dystrophic changes in masticatory muscles related chewing problems and malocclusions in Duchenne muscular dystrophy.

    Science.gov (United States)

    van den Engel-Hoek, L; de Groot, I J M; Sie, L T; van Bruggen, H W; de Groot, S A F; Erasmus, C E; van Alfen, N

    2016-06-01

    Dysphagia in Duchenne muscular dystrophy (DMD) worsens with age, with increasingly effortful mastication. The aims of this study were to describe mastication problems in consecutive stages in a group of patients with DMD and to determine related pathophysiological aspects of masticatory muscle structure, tongue thickness, bite force and dental characteristics. Data from 72 patients with DMD (4.3 to 28.0 years), divided into four clinical stages, were collected in a cross sectional study. Problems with mastication and the need for food adaptations, in combination with increased echogenicity of the masseter muscle, were already found in the early stages of the disease. A high percentage of open bites and cross bites were found, especially in the later stages. Tongue hypertrophy also increased over time. Increased dysfunction, reflected by increasingly abnormal echogenicity, of the masseter muscle and reduced occlusal contacts (anterior and posterior open bites) were mainly responsible for the hampered chewing. In all, this study shows the increasing involvement of various elements of the masticatory system in progressive Duchenne muscular dystrophy. To prevent choking and also nutritional deficiency, early detection of chewing problems by asking about feeding and mastication problems, as well as asking about food adaptations made, is essential and can lead to timely intervention.

  1. Autologous bone marrow mononuclear cell transplantation in Duchenne muscular dystrophy - a case report.

    Science.gov (United States)

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

    2014-01-01

    Male, 9 FINAL DIAGNOSIS: Duchenne muscular dystrophy Symptoms: Hyporeflexia • hypotonia • weaknes of lower limbs - Clinical Procedure: - Specialty: Neurology. Congenital defects/diseases. Duchenne muscular dystrophy (DMD) is a fatal, genetic, progressive, degenerating muscle disorder. Current treatment options are palliative. Newer options of cellular therapy promise to alter the disease process. Preclinical studies have successfully tested myogenic, neurogenic potential and dystrophin expression of bone marrow mononuclear cells. We treated a 9-year-old boy suffering from DMD with serial autologous bone marrow mononuclear cell transplantations followed by multidisciplinary rehabilitation. Brooke-Vignos score was 10 and he was wheelchair-bound. Over 36 months, gradual progressive improvement was noticed in muscle strength, ambulation with assistive devices, fine motor movements, Brooke-Vignos score, and functional independence measure score. Nine months after the transplantation, electromyography findings showed development of new normal motor unit potentials of the vastus medialis muscle. Magnetic resonance imaging scan of musculoskeletal systems showed no increase in fatty infiltration. This case report provides early investigative findings or the restorative effects of cellular therapy in DMD.

  2. Controversies in laparoscopic repair of incisional hernia

    Directory of Open Access Journals (Sweden)

    Sarela Abeezar

    2006-01-01

    Full Text Available Background: Incisional hernias can be a significant problem after open abdominal surgery. Laparoscopic incisional hernia repair (LIHR is conceptually appealing: a large, abdominal wall re-incision with potential wound-related ill effects is avoided and an intra-peritoneal onlay mesh is expected to provide security that is equivalent to open, retro-muscular mesh repair. As such, LIHR has gained substantial popularity despite sparse, randomised clinical data to compare with conventional, open repair. Aim: To enumerate and discuss important, controversial issues in patient-selection, technique and early post-operative care for LIHR. Materials and Methods: Pragmatic summary of comprehensive review of English language literature, discussion with experts and personal experience. Outcomes: Six important areas of some dispute were identified: 1. Size of abdominal-wall defect that is suitable for LIHR: Generally, defect-diameter > 10 cm is better served by open retromuscular repair with tension-free re-approximation of the edges of the defect. 2. Extent of adhesiolysis: Complete division of adhesions to the anterior abdominal wall may identify sub-clinical "Swiss-cheese" defects but incurs some risk of additional complications. 3. Intra-operative recognition of enterotomy: Possible options are either laparoscopic suture of bowel injury and simultaneous completion of LIHR, or staged LIHR or conversion to open suture-repair. 4. Choice of mesh: "Composite" meshes are regarded as the current standard of care but there is paucity of data regarding potential dangers of intra-peritoneal polypropylene mesh. 5. Technique of mesh-fixation: Trans-parietal sutures are more secure than tacks, with limited data to correlate with post-operative pain. 6. Alarm over post-operative pain: Unlike other advanced laparoscopic operations, the specificity of pain as a marker of intra-abdominal sepsis after LIHR remains unclear. Conclusion : Recognition of and attention to

  3. The controversy on chronic cerebrospinal venous insufficiency

    Directory of Open Access Journals (Sweden)

    Paolo Zamboni

    2013-08-01

    Full Text Available The objective of this review is to analyze the actual scientific controversy on chronic cerebrospinal venous insufficiency (CCSVI and its association with both neurodegenerative disorders and multiple sclerosis (MS. We revised all published studies on prevalence of CCSVI in MS patients, including ultrasound and catheter venography series. Furthermore, we take into consideration other publications dealing with the pathophysiologic consequences of CCSVI in the brain, as well as ecent data characterizing the pathology of the venous wall in course of CCSVI. Finally, safety and pilot data on effectiveness of endovascular CCSVI treatment were further updated. Studies of prevalence show a big variability in prevalence of CCSVI in MS patients assessed by established ultrasonographic criteria. This could be related to high operator dependency of ultrasound. However, 12 studies, by the means of more objective catheter venography, show a prevalence >90% of CCSVI in MS. Global hypo-hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Postmortem studies and histology corroborate the 2009 International Union of Phlebology (UIP Consensus decision to insert CCSVI among venous malformations. Finally, safety of balloon angioplasty of the extracranial veins was certainly demonstrated, while prospective data on the potential effectiveness of endovascular treatment of CCSVI support to increase the level of evidence by proceeding with a randomized control trial (RCT. Taking into account the current epidemiological data, including studies on catheter venography, the autoptic findings, and the relationship between CCSVI and both hypo-perfusion and cerebro-spinal fluid flow, we conclude that CCSVI can be definitively inserted among the medical entities. Research is still inconclusive in elucidating the CCSVI role in the pathogenesis of neurological disorders. The controversy between the vascular and the

  4. [Abortion and misoprostol: health practices and scientific controversy].

    Science.gov (United States)

    Corrêa, Marilena Cordeiro Dias Villela; Mastrella, Miryam

    2012-07-01

    This article puts into perspective the controversy between the association of the use of misoprostol for abortion and teratogenicity studies of the type found in a case report. The use of herbal medicinal drugs and the medical-obstetric and national and international norms governing the registration and circulation of pharmaceutical products were examined. Official documents of ANVISA, the Ministry of Health and the World Health Organization on the use of misoprostol, as well as 68 articles such as case reports published in national journals, linking abortion, misoprostol and teratogenicity were reviewed, systematically filed and analyzed using the monographic method. The legal prohibition of abortion prevents the proper prescription and use of a drug such as misoprostol that is both safe and effective. Thus, the danger for the health of women is linked not to the intrinsic characteristics of the drug, but to the moral arguments that constitute negligence and disregard for the fundamental rights of women.

  5. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Richard S Finkel

    Full Text Available BACKGROUND: Approximately 13% of boys with Duchenne muscular dystrophy (DMD have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124 enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins. METHODS: This Phase 2a open-label, sequential dose-ranging trial recruited 38 boys with nonsense mutation DMD. The first cohort (n = 6 received ataluren three times per day at morning, midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20 was dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12 was dosed at 20, 20, 40 mg/kg. Treatment duration was 28 days. Change in full-length dystrophin expression, as assessed by immunostaining in pre- and post-treatment muscle biopsy specimens, was the primary endpoint. FINDINGS: Twenty three of 38 (61% subjects demonstrated increases in post-treatment dystrophin expression in a quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative analysis also showed positive changes in dystrophin expression. Expression was not associated with nonsense mutation type or exon location. Ataluren trough plasma concentrations active in the mdx mouse model were consistently achieved at the mid- and high- dose levels in participants. Ataluren was generally well tolerated. INTERPRETATION: Ataluren showed activity and safety in this short-term study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in a Phase 2b, double-blind, long-term study in nonsense mutation DMD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00264888.

  6. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.

    Science.gov (United States)

    Finkel, Richard S; Flanigan, Kevin M; Wong, Brenda; Bönnemann, Carsten; Sampson, Jacinda; Sweeney, H Lee; Reha, Allen; Northcutt, Valerie J; Elfring, Gary; Barth, Jay; Peltz, Stuart W

    2013-01-01

    Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124) enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins. This Phase 2a open-label, sequential dose-ranging trial recruited 38 boys with nonsense mutation DMD. The first cohort (n = 6) received ataluren three times per day at morning, midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20) was dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12) was dosed at 20, 20, 40 mg/kg. Treatment duration was 28 days. Change in full-length dystrophin expression, as assessed by immunostaining in pre- and post-treatment muscle biopsy specimens, was the primary endpoint. Twenty three of 38 (61%) subjects demonstrated increases in post-treatment dystrophin expression in a quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative analysis also showed positive changes in dystrophin expression. Expression was not associated with nonsense mutation type or exon location. Ataluren trough plasma concentrations active in the mdx mouse model were consistently achieved at the mid- and high- dose levels in participants. Ataluren was generally well tolerated. Ataluren showed activity and safety in this short-term study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in a Phase 2b, double-blind, long-term study in nonsense mutation DMD. ClinicalTrials.gov NCT00264888.

  7. Controversies in the treatment of gastroesophageal reflux and achalasia

    Institute of Scientific and Technical Information of China (English)

    Kurt E Roberts; Andrew J Duffy; Robert L Bell

    2006-01-01

    The immense success of laparoscopic surgery as an effective treatment of gastroesophageal reflux disease (GERD) and achalasia has established minimal invasive surgery as the gold standard for these two conditions with lower morbidity and mortality, shorter hospital stay,faster convalescence, and less postoperative pain. One controversy in the treatment of GERD evolves around laparoscopic antireflux surgery (LAR S) as the preferred treatment for Barrett's esophagus and the procedure's potential to reduce the risk of adenocarcinoma of the esophagus.GERD has also been associated with respiratory symptoms, asthma and laryngeal injury, and a second controversy prompts discussions about whether total or partial fundoplication is the more appropriate treatment for GERD. A new and promising alternative in the treatment of GERD is endoluminal therapy. Three types of this new treatment option will be discussed: radiofrequency energy delivered to the lower esophageal sphincter, the creation of a mechanical barrier at the gastroesophageal junction, and the direct endoscopic tightening of the lower esophageal sphincter.Laparoscopic surgery is discussed not only as a very effective treatment for GERD but also as permanent cure for achalasia. This review analyzes the three most important treatment options for achalasia: medications,pneumatic dilatation, and surgical therapy. Medications as the only true non-invasive option in the treatment of achalasia are not as effective as LARS because of their short half-life and variable absorption due to the poor esophageal emptying. The second treatment option,pneumatic dilatation, involves the stretching of the lower esophagus and is still considered the most effective non-surgical treatment for achalasia. Finally, surgical therapy for achalasia and the two major controversies concerning this laparoscopic treatment are discussed. The first involves the extent to which the myotomy is extended onto the stomach, and the second concerns the

  8. Controversies in diabetes in 2013 - a brief update.

    Science.gov (United States)

    Gajos, Grzegorz; Piłaciński, Stanisław; Zozulińska-Ziółkiewicz, Dorota

    2013-01-01

    Incidence of diabetes is increasing worldwide at an alarming rate. Therefore, a proper understanding of the mechanisms and efficient treatment of the disease is becoming increasingly important. The article briefly describes controversies in type 1 diabetes (T1DM) pathogenesis and diagnosis (genetic background, accelerator hypothesis, new autoantibodies, new information on LADA - latent autoimmune diabetes in adults, and the role of TRAIL - tumor necrosis factor-related apoptosis-inducing ligand) and treatment (how to deal with fluctuations of blood glucose concentrations and the occurrence of hypoglycemia, the role of healthy lifestyle, especially physical exercise, and a proper diet, treatment of insulin resistance and the challenges in detecting diabetic neuropathy). Moreover, issues in the pathogenesis of macrovascular complications in type 2 diabetes (T2DM) are considered (novel risk factors - vascular hyperglycemic memory, hypoglycemia, altered profile of microRNAs expression, impaired function of vascular progenitor cells, altered fibrin clot properties and iron-induced blood coagulation). Modern treatment of T2DM, based on lifestyle intervention and antidiabetic drugs, is full of controversies and it seems that over time the number of uncertainties is constantly increasing. Recent trials have reported disappointing results in lifestyle intervention (LOOK-AHEAD) and antihyperglycemic treatment (ACCORD, SAVOR-TIMI 53, EXAMINE, concerns about sulfonylureas safety). Moreover, there are considerable deviations from treatment targets that are recommended by the guidelines (blood glucose, hypertension, blood lipids) in real-life clinical practice in patients at different stages of the disease development. It seems that beneficial modification of the natural history of diabetes is unlikely in the foreseeable future unless we are able to obtain a more in-depth understanding of the pathomechanisms of the disease.

  9. Tasers and Community Controversy: Investigating Training Officer Perceptions of Public Concern over Conducted Energy Weapons

    Science.gov (United States)

    De Angelis, Joseph; Wolf, Brian

    2013-01-01

    Over the last several decades, "Tasers," "stun guns" and other conducted energy devices (CEDs) have become a widely adopted, though publicly controversial, form of police restraint technology. While there is a growing body of research on the physiological effects of these types of weapons, less attention has been devoted to the…

  10. Daring to Debate: Strategies for Teaching Controversial Issues in the Classroom

    Science.gov (United States)

    Fournier-Sylvester, Nicole

    2013-01-01

    Have you ever avoided discussing controversial issues in the classroom? Teachers report often avoiding these types of discussions due to concerns about the unpredictability of student reactions, accusations of trying to push a political agenda, and insufficient knowledge or skills to work through complex issues. Debates, however, have been shown…

  11. Alteraciones en el electrorretinograma de los pacientes con distrofia muscular de duchenne y su relación con las deleciones del gen responsable de la enfermedad Alterations in electroretinography of patients with Duchenne muscular dystrophy and their relationship with deletions of gene of the disease

    Directory of Open Access Journals (Sweden)

    Mayra Rodríguez Hernández

    1999-12-01

    Full Text Available La distrofia muscular tipo Duchenne es la más común y grave de las distrofias musculares, que afecta a uno de cada 3,500 varones nacidos vivos. La alta frecuencia con que han sido reportadas alteraciones en el electrorretinograma (ERG en pacientes con distrofia muscular de Duchenne (DMD, demuestra una posible relación entre la actividad eléctrica de la retina y las mutaciones presentes en el gen DMD que codifica para la proteína distrofina, responsable del fenotipo DMD. La mutación más común del gen DMD son las deleciones del 70 % de los pacientes, y se presentan con una gran heterogeneidad al igual que el ERG, por lo que nos propusimos comparar estas variables para conocer si están o no relacionadas. Se estudiaron 22 pacientes con manifestaciones clínicas de DMD desde el punto de vista molecular y electrorretinográfico para lo cual se utilizó las técnicas de reacción en cadena de la polimerasa para chequear 18 regiones del gen, y el registro electrorretinográfico mesópico. El 69 % de los casos presentaron deleciones, las cuales varían en extensión y ubicación de las cuales el 80 % se encontraba en el extremo 3' del gen. Predominó el ERG de tipo negativo con marcada disminución de la onda B y A en límite inferior normal o también disminuida, con relación b/a menor de uno. Este tipo de ERG, estuvo relacionado con la presencia de deleción (p= 0,027 y su ubicación en el extremo 3' del gen (p= 0,03, con un nivel de significación de 0,05, por lo que se recomienda el estudio electrorretinográfico como un elemento para reforzar el diagnóstico y sospechar el sitio de la deleción.Duchenne muscular dystrophy is the most common and serious of all muscular distropies affecting one in 3 500 males born live. The high frequency of reported alterations in electroretinographies of patients with Duchenne muscular dystrophy (DMD proves that there is a possible relationship between the electrical activity of retina and the DMD gen

  12. Confusion and controversy in the stress field.

    Science.gov (United States)

    Selye, H

    1975-06-01

    An attempt is made to further clarify present areas of controversy in the stress field, in response to a two-part article by Dr. John W. Mason which concludes in this issue of the Journal of Human Stress. The author tries to elucidate each source of confusion enumerated by Dr. Mason. The continued use of the word "stress" for the nonspecific response to any demand is deemed most desirable. The once vague term can now be applied in a well-defined sense and is accepted in all foreign languages as well, including those in which no such word existed previously in any sense. Subdivision of the stress concept has become necessary as more recent work has led to such notions as "eustress," "distress," "systemic stress" and "local stress." Confusion between stress as both an agent and a result can be avoided only by the distinction between "stress" and "stressor". It is explained that the stress syndrome is--by definition--nonspecific in its causation. However, depending upon conditioning factors, which can selectively influence the reactivity of certain organs, the same stressor can elicit different manifestations in different individuals.

  13. Current Controversies in Lupus Anticoagulant Detection

    Directory of Open Access Journals (Sweden)

    Gary W. Moore

    2016-12-01

    Full Text Available Antiphospholipid syndrome is an autoimmune, acquired thrombophilia diagnosed when vascular thrombosis or pregnancy morbidity are accompanied by persistent antiphospholipid antibodies. Lupus anticoagulants (LA are one of the criteria antibodies but calibration plasmas are unavailable and they are detected by inference based on antibody behaviour in a medley of coagulation-based assays. Elevated screening tests suggest the presence of a LA, which is confirmed with mixing tests to evidence inhibition and confirmatory tests to demonstrate phospholipid-dependence. At least two screening tests of different principle must be used to account for antibody heterogeneity and controversy exists on whether assays, in addition to dilute Russell’s viper venom time and activated partial thromboplastin time, should be employed. A variety of approaches to raw data manipulation and interpretation attract debate, as does inclusion or exclusion of mixing studies in circumstances where the presence of a LA is already evident from other results. Therapeutic anticoagulation compromises coagulation-based assays but careful data interpretation and use of alternative reagents can detect or exclude LA in specific circumstances, and this aspect of LA detection continues to evolve. This review focuses on the main areas of debate in LA detection.

  14. The Controversy over the Buddhas of Bamiyan

    Directory of Open Access Journals (Sweden)

    Pierre Centlivres

    2008-12-01

    Full Text Available The author analyses a rare case of mirror-outrage that followed the destruction of the Buddhas of Bamiyan. This event brought the Taliban and the international community into opposition in 2001. The article first stresses the intriguing paradigmatic similarities between the destruction of the Buddhas and the destruction of Artemis Temple in 356 BC, when the eradication of a monument, sacred as well as emblematic of a cultural heritage, was perceived as an outrage against piety and beauty. This analogy helps the author emphasize the uncertainty regarding the identification of the victims: were they ‘the people’ in general, abstract deities, or specific communities? The article then elaborates on the argumentation and self-justification presented by the Taliban, and underlies their sense of indignation at a protest coming from ‘Christian’ countries, which they saw as exclusively concerned with saving ‘idols’ but ignorant of the ordeal endured by the Afghans. It finally argues that conflicting visions over the very meaning of ‘cultural heritage’ were at the core of the controversy.

  15. Phytosynthesis of nanoparticles: concept, controversy and application

    Science.gov (United States)

    Husen, Azamal; Siddiqi, Khwaja Salahuddin

    2014-05-01

    Nanotechnology is an exciting and powerful discipline of science; the altered properties of which have offered many new and profitable products and applications. Agriculture, food and medicine sector industries have been investing more in nanotechnology research. Plants or their extracts provide a biological synthesis route of several metallic nanoparticles which is more eco-friendly and allows a controlled synthesis with well-defined size and shape. The rapid drug delivery in the presence of a carrier is a recent development to treat patients with nanoparticles of certain metals. The engineered nanoparticles are more useful in increasing the crop production, although this issue is still in infancy. This is simply due to the unprecedented and unforeseen health hazard and environmental concern. The well-known metal ions such as zinc, iron and copper are essential constituents of several enzymes found in the human system even though the indiscriminate use of similar other metal nanoparticle in food and medicine without clinical trial is not advisable. This review is intended to describe the novel phytosynthesis of metal and metal oxide nanoparticles with regard to their shape, size, structure and diverse application in almost all fields of medicine, agriculture and technology. We have also emphasized the concept and controversial mechanism of green synthesis of nanoparticles.

  16. Lyme disease: diagnostic issues and controversies.

    Science.gov (United States)

    Aguero-Rosenfeld, Maria E; Wormser, Gary P

    2015-01-01

    The diagnosis of Lyme disease is a controversial topic. Most practitioners and scientists recognize that Lyme disease is associated with certain objective clinical manifestations supported by laboratory evidence of infection with Borrelia burgdorferi sensu lato (the etiologic agent). There are others, however, who believe that patients with Lyme disease may have a wide variety of entirely nonspecific symptoms without any objective clinical manifestation and that laboratory evidence of infection by B. burgdorferi is not required to support the diagnosis. In reality, this perspective is not evidence based and would inevitably lead to innumerable misdiagnoses, given the high frequency of medically unexplained symptoms, such as fatigue and musculoskeletal pains, in the general population. Although those espousing this viewpoint do not believe that a positive laboratory test is required, nevertheless, they often seek out and promote alternative, unapproved testing methods that frequently provide false-positive results to justify their diagnosis. Herein, we provide a brief overview of Lyme disease testing, emphasizing current usage and limitations. We also discuss the use of nonvalidated procedures and the prospects for a reduction in such testing practices in the future.

  17. Gliomatosis Cerebri: Current Understanding and Controversies

    Directory of Open Access Journals (Sweden)

    Surabhi Ranjan

    2017-08-01

    Full Text Available Gliomatosis cerebri (GC is a rare, extensively infiltrating glioma involving multiple contiguous lobes of the brain. This lethal disease affects all age groups, and the majority of patients have a poor outcome despite aggressive treatment. Despite its initial recognition in 1938, GC remains a controversial entity with little consensus in its definition, histology, or treatment. The majority of GC tumors are astrocytic, although mixed phenotypes have been identified. Treatment of GC is challenging as surgery is generally not an option due to the extensive areas of brain involved, the benefit of radiation therapy is unclear, and no chemotherapy has proven efficacy. Due to the rarity of the disease and its heterogeneity, both at histopathological and molecular levels, it is difficult to conduct clinical trials tailored for this diagnosis. This review summarizes our current knowledge, examines clinical studies focusing on the treatment of GC, highlights ongoing challenges, and discusses the recent molecular insights into adult and pediatric GC. We conclude that, although no longer recognized as a distinct pathological entity, GC represents a unique disease phenotype. Given the histologic and molecular overlap with other diffuse gliomas, the research emphasis should be on investigating its unique invasive biology.

  18. Cellulite: advances in treatment: facts and controversies.

    Science.gov (United States)

    Emanuele, Enzo

    2013-01-01

    Cellulite is traditionally considered a highly prevalent aesthetic condition in women. From a clinical standpoint, it is characterized by a cottage-cheese-like appearance of the skin, which can be most commonly found in certain areas of the body (eg, thighs, buttocks, and legs). Although cellulite is generally asymptomatic, the more severe stages can be accompanied by the appearance of painful nodules and increased local temperature, which are suggestive of an inflammatory reaction occurring in the dermis and in the underlying subcutaneous adipose tissue. Whether cellulite is a real disease or only a disturbing aesthetic issue is still a matter of controversy. This debate notwithstanding, it seems clear from market trends that there is considerable commercial interest in developing effective strategies aimed at reducing the cottage-cheese-like appearance of cellulite areas. Quite disturbingly, the majority of treatment attempts to date have been conducted in an empirical manner and without the application of rigorous scientific methodology. This is likely due--at least in part--to the lack of major, evidence-based pathophysiological insights into the nature of this condition. More stringent regulatory control is needed over commercial products aiming at improving the appearance of cellulite. © 2013 Elsevier Inc. All rights reserved.

  19. Treatment and Controversies in Paraesophageal Hernia Repair

    Directory of Open Access Journals (Sweden)

    P. Marco eFisichella

    2015-04-01

    Full Text Available Background: Historically all paraesophageal hernias were repaired surgically, today intervention is reserved for symptomatic paraesophageal hernias. In this review, we describe the indications for repair and explore the controversies in paraesophageal hernia repair, which include a comparison of open to laparoscopic paraesophageal hernia repair, the necessity of complete sac excision, the routine performance of fundoplication, and the use of mesh for hernia repair.Methods: We searched Pubmed for papers published between 1980 and 2015 using the following keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia, gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH monitoring, proton pump inhibitors, anemia, iron deficiency anemia, Nissen fundoplication, sac excision, mesh, mesh repair. Results: Indications for paraesophageal hernia repair have changed, and currently symptomatic paraesophageal hernias are recommended for repair. In addition, it is important not to overlook iron-deficiency anemia and pulmonary complaints, which tend to improve with repair. Current practice favors a laparoscopic approach, complete sac excision, primary crural repair with or without use of mesh, and a routine fundoplication.

  20. The catatonia conundrum: controversies and contradictions.

    Science.gov (United States)

    Padhy, Susanta Kumar; Parakh, Preeti; Sridhar, M

    2014-02-01

    Although catatonia is known to psychiatrists for more than a century, it is still poorly understood, often under recognized, have inspired debate and criticism about nosological status of the catatonic syndrome in recent times without reaching its conclusion. It can present with a number of psychiatric and medical illnesses and is easily treatable, though treatment response varies depending upon the underlying condition and can lead on to a multitude of complications, if not treated. Some issues are more than forty catatonic signs are available to scientific audience for diagnosis; threshold number for labelling varies according to the nosological system followed and the underlying condition; and mood stabilizers like carbamazepine and lithium are helpful in some cases of idiopathic periodic catatonia. Researchers have been asking for a separate diagnostic category for catatonia since long and the debate has gained pace over the last few years, with new editions of both DSM and ICD coming up. Therefore, this paper looks at the controversies associated with the diagnosis and classification of catatonia, the arguments and counter-arguments and future directions, in crisp.

  1. Resolution of the Abraham-Minkowski Controversy

    CERN Document Server

    Mansuripur, Masud

    2012-01-01

    The momentum of light inside ponderable media has an electromagnetic part and a mechanical part. The local and instantaneous density of the electromagnetic part of the momentum is given by the Poynting vector divided by the square of the speed of light in vacuum, irrespective of the nature of the electromagnetic fields or the local or global properties of the material media. The mechanical part of the momentum is associated with the action of the electromagnetic field on the atomic constituents of the media, as specified by the Lorentz law of force. Proper interpretation and application of the Maxwell-Lorentz equations within the material bodies as well as at their surfaces and interfaces is all that is needed to obtain a complete picture of the momentum of light, including detailed numerical values at each and every point in space and time. That the Abraham-Minkowski controversy surrounding the momentum of light inside material media has persisted for nearly a century is due perhaps to an insufficient apprec...

  2. Mendelian controversies: a botanical and historical review.

    Science.gov (United States)

    Fairbanks, D J; Rytting, B

    2001-05-01

    Gregor Mendel was a 19(th) century priest and botanist who developed the fundamental laws of inheritance. The year 2000 marked a century since the rediscovery of those laws and the beginning of genetics. Although Mendel is now recognized as the founder of genetics, significant controversy ensued about his work throughout the 20(th) century. In this paper, we review five of the most contentious issues by looking at the historical record through the lens of current botanical science: (1) Are Mendel's data too good to be true? (2) Is Mendel's description of his experiments fictitious? (3) Did Mendel articulate the laws of inheritance attributed to him? (4) Did Mendel detect but not mention linkage? (5) Did Mendel support or oppose Darwin?A synthesis of botanical and historical evidence supports our conclusions: Mendel did not fabricate his data, his description of his experiments is literal, he articulated the laws of inheritance attributed to him insofar as was possible given the information he had, he did not detect linkage, and he neither strongly supported nor opposed Darwin.

  3. LDL cholesterol: controversies and future therapeutic directions.

    Science.gov (United States)

    Ridker, Paul M

    2014-08-16

    Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

  4. Controversial Embodiment: Sport, Masculinity, Dis/Ability

    Directory of Open Access Journals (Sweden)

    Marilena Parlati

    2015-11-01

    Full Text Available This essay is an attempt at investigating visible forms of complex, indeed controversial embodiment, with the specific intention of concentrating on the ways they interrogate delicate issues such as disability, masculinity and prosthetic sport performance. I intend to sound the shifting boundaries between dis-ability and super-ability as manifested in iconic figures such as Stelarc and, in other fields, Oscar Pistorius, whose unsteady position as privileged/disabled bladerunner seems to require – and indeed to gather – particularly intense scrutiny. I shall introduce a few contemporary discourses on corporeality and embodiment, which focus on the ‘troubling’ nature of auxiliary organs Freud refers to in the much contended paragraph I adopt as epigraph and guiding procedural light; I shall move from Butler and Giddens to Jean-Luc Nancy’s work on transplants and/as prostheses to include theoretical debates on disintegrating embodiment and disability studies, in order to proceed towards an analysis of the short-circuiting of allegedly secure practices of (masculine embodiment in sport culture and theory.

  5. Exon exchange approach to repair Duchenne dystrophin transcripts.

    Directory of Open Access Journals (Sweden)

    Stéphanie Lorain

    Full Text Available BACKGROUND: Trans-splicing strategies for mRNA repair involve engineered transcripts designed to anneal target mRNAs in order to interfere with their natural splicing, giving rise to mRNA chimeras where endogenous mutated exons have been replaced by exogenous replacement sequences. A number of trans-splicing molecules have already been proposed for replacing either the 5' or the 3' part of transcripts to be repaired. Here, we show the feasibility of RNA surgery by using a double trans-splicing approach allowing the specific substitution of a given mutated exon. METHODOLOGY/PRINCIPAL FINDINGS: As a target we used a minigene encoding a fragment of the mdx dystrophin gene enclosing the mutated exon (exon 23. This minigene was cotransfected with a variety of exon exchange constructions, differing in their annealing domains. We obtained accurate and efficient replacement of exon 23 in the mRNA target. Adding up a downstream intronic splice enhancer DISE in the exon exchange molecule enhanced drastically its efficiency up to 25-45% of repair depending on the construction in use. CONCLUSIONS/SIGNIFICANCE: These results demonstrate the possibility to fix up mutated exons, refurbish deleted exons and introduce protein motifs, while keeping natural untranslated sequences, which are essential for mRNA stability and translation regulation. Conversely to the well-known exon skipping, exon exchange has the advantage to be compatible with almost any type of mutations and more generally to a wide range of genetic conditions. In particular, it allows addressing disorders caused by dominant mutations.

  6. Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation.

    Science.gov (United States)

    Pradhan, Sunil; Ghosh, Debabrata; Srivastava, Niraj Kumar; Kumar, Ashok; Mittal, Balraj; Pandey, Chandra Mani; Singh, Uttam

    2006-10-01

    An open controlled trial of 0.75 mg/Kg/day prednisolone was conducted at a stage when the patients had started falling several times in a day and stopped on their attaining a chair bound stage, thus minimising the total period of steroid therapy. Out of the 67 DMD patients enrolled in this study, 44 were put on prednisolone therapy and 23 served as controls. All patients were followed-up at two-monthly intervals for two years and thereafter they continued to take their respective medications till their chair-bound stage; then the drug was gradually withdrawn. In the treatment group 24 patients could not continue the trial because of adverse effects - 14 due to excessive obesity, 3 due to measles, 4 due to pulmonary tuberculosis, 2 due to recurrent throat and chest infection and 1 due to an unexplained high leukocyte count. Of the remaining 20 patients in the treatment group, steroid therapy was stopped in 5 patients as there was no improvement in power in six months. Fifteen patients in the treatment group and 19 patients in the control group could be followed regularly for 2 years and then up to chair-bound stage. Outcome parameters included fall frequency, peak expiratory flow rate, limb muscle power, ability to lift weights, time taken in getting up from squatting position, walking 9 metres and climbing 13 stairs. Maximum improvement was noted between 2 and 4 months while mild improvement in some parameters continued up to six months. All parameters remained stabilised for 1 year or so, after which there was slight deterioration. Deterioration at 2 years was, however, less than the natural course of events noted in control patients. Prednisolone treated patients and controls became chair bound at the mean age of 169 +/- 9 and 132 +/- 8 months respectively. Till the ideal stage of the disease and the type or dosage of starting steroid therapy is defined by specially designed studies, 0.75 mg/Kg/day prednisolone therapy may be started in DMD patients at the stage

  7. Peripartum cardiomyopathy in a previously asymptomatic carrier of Duchenne muscular dystrophy.

    Science.gov (United States)

    Cheng, Victoria E; Prior, David L

    2013-08-01

    A 40 year-old woman presented to hospital with 12h of progressive shortness of breath. She was 11 days postpartum, having delivered a full-term male infant. She was discharged on antibiotics for presumed pneumonia, but represented two days later with NYHA class IV symptoms and in acute decompensated heart failure confirmed on clinical examination and chest X-ray. Echocardiography showed a left ventricular ejection fraction (LVEF) of 20%. She was treated for peripartum cardiomyopathy (PPCM) with angiotensin converting enzyme inhibitors (ACEi), beta-blockers and diuretics with normalisation of her cardiac function within six months. Four years later, her son was diagnosed with Duchenne muscular dystrophy (DMD) and she tested positive as a carrier of the mutant gene. It is unclear whether the DMD carrier state alone is associated with increased susceptibility to PPCM or if this is merely the first expression of cardiomyopathy in a previously asymptomatic carrier.

  8. Avaliação miométrica de pacientes com distrofia muscular de Duchenne

    Directory of Open Access Journals (Sweden)

    Alexandra P.Q.C. Araújo

    1995-06-01

    Full Text Available Os autores relatam sua experiência com a avaliação da força muscular pela utilização do miômetro manual em 16 pacientes com distrofia muscular de Duchenne (DMD. Observaram rápida diminuição da força de extensão da perna entre 6 e 8 anos de idade, analisando pacientes de diferentes faixas etárias. Paralelamente, ocorreu perda da deambulação. Verificaram aumentos de força em dois pacientes avaliados evolutivamente num período de 6 meses, sem explicação até o momento. Revêem a literatura e concluem no sentido da importância da difusão do método.

  9. Force-controlled ultrasound to measure passive mechanical properties of muscle in Duchenne muscular dystrophy.

    Science.gov (United States)

    Pigula, Anne J; Wu, Jim S; Gilbertson, Matthew W; Darras, Basil T; Rutkove, Seward B; Anthony, Brian W

    2016-08-01

    The purpose of this study is to assess differences in skeletal muscle compressibility between patients with Duchenne muscular dystrophy (DMD) and normal subjects. The transverse passive mechanical properties of muscle, particularly those related to stiffness and elasticity, can be measured using force-controlled ultrasound. We acquired ultrasound videos of muscle compression under known pressures in the biceps and quadriceps in 23 boys with DMD and 20 age-matched healthy controls. We calculated the bulk linear spring constant, nonlinear stress-strain response, and average Young's modulus for each. Young's modulus was found to be significantly higher in the DMD population in both the biceps (normal: 33 ± 6 kPa, DMD: 45 ± 14, p Muscle compressibility measured by force-controlled ultrasound is an objective and robust technique to quantitatively monitor the effects of DMD and distinguish from normal subjects.

  10. Brazilian consensus on Duchenne muscular dystrophy. Part 1: diagnosis, steroid therapy and perspectives.

    Science.gov (United States)

    Araujo, Alexandra P Q C; Carvalho, Alzira A S de; Cavalcanti, Eduardo B U; Saute, Jonas Alex M; Carvalho, Elmano; França, Marcondes C; Martinez, Alberto R M; Navarro, Monica de M M; Nucci, Anamarli; Resende, Maria Bernadete D de; Gonçalves, Marcus Vinicius M; Gurgel-Giannetti, Juliana; Scola, Rosana H; Sobreira, Cláudia F da R; Reed, Umbertina C; Zanoteli, Edmar

    2017-08-01

    Significant advances in the understanding and management of Duchenne muscular dystrophy (DMD) took place since international guidelines were published in 2010. Our objective was to provide an evidence-based national consensus statement for multidisciplinary care of DMD in Brazil. A combination of the Delphi technique with a systematic review of studies from 2010 to 2016 was employed to classify evidence levels and grade of recommendations. Our recommendations were divided in two parts. We present Part 1 here, where we describe the guideline methodology and overall disease concepts, and also provide recommendations on diagnosis, steroid therapy and new drug treatment perspectives for DMD. The main recommendations: 1) genetic testing in diagnostic suspicious cases should be the first line for diagnostic confirmation; 2) patients diagnosed with DMD should have steroids prescribed; 3) lack of published results for phase 3 clinical trials hinders, for now, the recommendation to use exon skipping or read-through agents.

  11. Brazilian consensus on Duchenne muscular dystrophy. Part 1: diagnosis, steroid therapy and perspectives

    Directory of Open Access Journals (Sweden)

    Alexandra P. Q. C. Araujo

    Full Text Available ABSTRACT Significant advances in the understanding and management of Duchenne muscular dystrophy (DMD took place since international guidelines were published in 2010. Our objective was to provide an evidence-based national consensus statement for multidisciplinary care of DMD in Brazil. A combination of the Delphi technique with a systematic review of studies from 2010 to 2016 was employed to classify evidence levels and grade of recommendations. Our recommendations were divided in two parts. We present Part 1 here, where we describe the guideline methodology and overall disease concepts, and also provide recommendations on diagnosis, steroid therapy and new drug treatment perspectives for DMD. The main recommendations: 1 genetic testing in diagnostic suspicious cases should be the first line for diagnostic confirmation; 2 patients diagnosed with DMD should have steroids prescribed; 3 lack of published results for phase 3 clinical trials hinders, for now, the recommendation to use exon skipping or read-through agents.

  12. Research progress of motor function assessments and their clinical applications in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Wei SHI

    2015-07-01

    Full Text Available Duchenne muscular dystrophy (DMD, clinically featured as progressive skeletal muscle atrophy with gradual loss of muscle strength and activity abilities, is the most common genetic muscular disease in children throughout the world. The core and continuous characteristic of DMD is motor dysfunction. Motor function assessments of DMD are now focusing on muscle strength, walking ability, range of motion and ability of activities, still without unified standards. Confirming the comprehensive, scientific, reasonable and accurate evaluation tools for DMD assessment is the premise of research in motor developmental rules of DMD, which will help to better understand the motor progress of DMD and to supply evidences for choosing treatment methods, confirming timing of intervention, assessing effect of treatments and designing rehabilitation plans. DOI: 10.3969/j.issn.1672-6731.2015.06.002

  13. Treatable renal failure found in non-ambulatory Duchenne muscular dystrophy patients.

    Science.gov (United States)

    Motoki, Takahiro; Shimizu-Motohashi, Yuko; Komaki, Hirofumi; Mori-Yoshimura, Madoka; Oya, Yasushi; Takeshita, Eri; Ishiyama, Akihiko; Saito, Takashi; Nakagawa, Eiji; Sugai, Kenji; Murata, Miho; Sasaki, Masayuki

    2015-10-01

    Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and heart failures are the main causes of death. Intensive intervention in respiratory and cardiac function has dramatically improved the prognosis; however, dysfunction in other multiple organs may emerge in the later stages of the disease. We report the case of four non-ambulatory DMD patients who presented with renal failure. Common findings included decreased fluid intake, use of diuretics, and presence of chronic heart failure. The levels of serum cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass, were elevated in all four patients. In two patients, renal failure improved by increasing fluid intake, and discontinuing or reducing the dose of diuretics. The findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney perfusion, which potentially leads to prerenal failure. Therefore, in DMD patients, dehydration signs and CysC levels should be monitored.

  14. Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco

    Directory of Open Access Journals (Sweden)

    Hanane Bellayou

    2009-01-01

    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis.

  15. Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y. [Tel Aviv Univ. (Israel)

    1994-02-15

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

  16. Effect of mazindol on growth hormone levels in patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Zatz, M; Rapaport, D; Vainzof, M; Pavanello, R de C; Rocha, J M; Betti, R T; Otto, P A

    1988-12-01

    Human growth hormone (HGH) inhibition may be beneficial in Duchenne muscular dystrophy (DMD) and slow down the rate of progression of the disease. The purposes of the present investigation were: 1) to assess, through pharmacological stimuli (L-dopa test), the HGH response in untreated DMD patients, and 2) to evaluate the inhibitory effect of mazindol on HGH levels as a potential treatment for DMD. In 55 DMD patients, HGH levels were measured through the L-dopa test, and 40 received mazindol. After 1 year, there was wide variability in the individual response to mazindol. An apparent diminution in the mean HGH level was observed in the whole group of patients; this was statistically significant after 3 and 6 months but not after 9 and 12 months of treatment. The results suggest that this drug is not effective for arresting growth or inhibiting HGH secretion for a prolonged period of time.

  17. Short stature in Duchenne muscular dystrophy: a study of 34 patients.

    Science.gov (United States)

    Nagel, B H; Mortier, W; Elmlinger, M; Wollmann, H A; Schmitt, K; Ranke, M B

    1999-01-01

    In Duchenne muscular dystrophy (DMD), short stature is a feature of unknown cause. This cross-sectional study of 34 male patients (mean age 8.0 y, age range 1.2-13.7 y) was conducted to examine the relationship between auxological parameters, markers of growth and the extent of muscular weakness. Weight and length at birth (SDS +/- SD; 0.0 +/- 1.2; 0.2 +/- 1.5) and target height SDS (-0.2 +/- 0.7) were normal. Height (HT) SDS (-1.0 +/- 1.1) was lower than the normal population (p Growth hormone deficiency does not seem to be the cause of short stature in DMD. Significantly low BAP levels are probably the result of the reduced muscle mass, which leads to a lower biomechanical load on the bone and thus a reduction in bone turnover. The short stature observed in our study is unlikely to be the result of muscular weakness.

  18. Rapid DNA haplotyping using a multiplex heteroduplex approach: application to Duchenne muscular dystrophy carrier testing.

    Science.gov (United States)

    Prior, T W; Wenger, G D; Papp, A C; Snyder, P J; Sedra, M S; Bartolo, C; Moore, J W; Highsmith, W E

    1995-01-01

    A new strategy has been developed for rapid haplotype analysis based on an initial multiplex amplification of several polymorphic sites, followed by heteroduplex detection. Heteroduplexes formed between two different alleles are detected because they migrate differently than the corresponding homoduplexes in Hydrolink-MDE gel. This simple, rapid method does not depend on specific sequences such as restriction enzyme sites or CA boxes and does not require the use of isotope. This approach has been tested using commonly occurring polymorphisms spanning the dystrophin gene as a model. We describe the use of the method to assign the carrier status of females in Duchenne muscular dystrophy (DMD) pedigrees. The method may be used for other genetic diseases when mutations are unknown or there are few dinucleotide markers in the gene proximity, and for the identification of haplotype backgrounds of mutant alleles.

  19. Dystrophin expression in a Duchenne muscular dystrophy patient with a frame shift deletion.

    Science.gov (United States)

    Prior, T W; Bartolo, C; Papp, A C; Snyder, P J; Sedra, M S; Burghes, A H; Kissel, J T; Luquette, M H; Tsao, C Y; Mendell, J R

    1997-02-01

    The exon 45 deletion is a common dystrophin gene deletion. Although this is an out-of-frame deletion, which should not allow for protein synthesis, it has been observed in mildly affected patients. We describe a patient with an exon 45 deletion who produced protein, but still had a severe Duchenne muscular dystrophy phenotype. RT-PCR analysis and cDNA sequencing from the muscle biopsy sample revealed that the exon 45 deletion induced exon skipping of exon 44, which resulted in an in-frame deletion and the production of dystrophin. A conformational change in dystrophin induced by the deletion is proposed as being responsible for the severe phenotype in the patient. We feel that the variable clinical phenotype observed in patients with the exon 45 deletion is not due to exon splicing but may be the result of other environmental or genetic factors, or both.

  20. A missense mutation in the dystrophin gene in a Duchenne muscular dystrophy patient.

    Science.gov (United States)

    Prior, T W; Papp, A C; Snyder, P J; Burghes, A H; Bartolo, C; Sedra, M S; Western, L M; Mendell, J R

    1993-08-01

    About two thirds of Duchenne muscular dystrophy (DMD) patients have either gene deletions or duplications. The other DMD cases are most likely the result of point mutations that cannot be easily identified by current strategies. Utilizing a heteroduplex technique and direct sequencing of amplified products, we screened our nondeletion/duplication DMD population for point mutations. We now describe what we believe to be the first dystrophin missense mutation in a DMD patient. The mutation results in the substitution of an evolutionarily conserved leucine to arginine in the actin-binding domain. The patient makes a dystrophin protein which is properly localized and is present at a higher level than is observed in DMD patients. This suggests that an intact actin-binding domain is necessary for protein stability and essential for function.

  1. Avaliação miométrica de pacientes com distrofia muscular de Duchenne

    OpenAIRE

    Araújo,Alexandra P. Q. C.; Luiz A. Duro; Abelardo Q.C. Araújo; Penque,Glória M.C.A.

    1995-01-01

    Os autores relatam sua experiência com a avaliação da força muscular pela utilização do miômetro manual em 16 pacientes com distrofia muscular de Duchenne (DMD). Observaram rápida diminuição da força de extensão da perna entre 6 e 8 anos de idade, analisando pacientes de diferentes faixas etárias. Paralelamente, ocorreu perda da deambulação. Verificaram aumentos de força em dois pacientes avaliados evolutivamente num período de 6 meses, sem explicação até o momento. Revêem a literatura e conc...

  2. Deletion Analysis Of The Duchenne/Becker Muscular Dystrophy Gene Using Multiplex Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Dastur R

    2003-01-01

    Full Text Available The diagnosis of Duchenne Muscular Dystrophy (DMD and Becker Muscular Dystrophy (BMD is mainly based on clinical profile, serum CPK values, muscle biopsy and immunostaining for dystrophin. Most recent and accurate method for diagnosing DMD/BMD is by detection of mutations in the DMD gene. This was done in 100 unrelated patients using 19 exons including the promoter region in two sets of multiplex polymerase chain reaction (PCR. These primers amplify most of the exons in the deletion prone ′hotspot′ regions allowing determination of deletion end point. Intragenic deletions were detected in 74 patients indicating that the use of PCR-based assays will allow deletion detection help in prenatal diagnosis for most of the DMD/BMD patients. The frequency of deletions observed in the present study was 74%.

  3. Air stacking and chest compression increase peak cough flow in patients with Duchenne muscular dystrophy

    OpenAIRE

    Magneide Fernandes Brito; Gustavo Antonio Moreira; Márcia Pradella-Hallinan; Sergio Tufik

    2009-01-01

    OBJETIVO: Avaliar a eficiência da tosse através do uso de duas manobras manuais de auxílio à tosse. MÉTODOS: Foram selecionados 28 pacientes portadores de distrofia muscular de Duchenne em uso de ventilação mecânica não-invasiva noturna e CVF < 60% do previsto. O pico de fluxo da tosse (PFT) foi medido, com o paciente sentado, em quatro momentos: com esforço expiratório máximo (EEM) de forma espontânea (basal), EEM associado à compressão torácica, EEM após empilhamento de ar com bolsa de vent...

  4. Musculoskeletal simulation can help explain selective muscle degeneration in Duchenne muscular dystrophy.

    Science.gov (United States)

    Hu, Xiao; Blemker, Silvia S

    2015-08-01

    Duchenne muscular dystrophy (DMD) is a genetic disease that occurs due to the deficiency of the dystrophin protein. Although dystrophin is deficient in all muscles, it is unclear why degeneration progresses differently across muscles in DMD. We hypothesized that each muscle undergoes a different degree of eccentric contraction during gait, which could contribute to the selective degeneration in lower limb muscle, as indicated by various amounts of fatty infiltration. By comparing eccentric contractions quantified from a previous multibody dynamic musculoskeletal gait simulation and fat fractions quantified in a recent imaging study, our preliminary analyses show a strong correlation between eccentric contractions during gait and lower limb muscle fat fractions, supporting our hypothesis. This knowledge is critical for developing safe exercise regimens for the DMD population. This study also provides supportive evidence for using multiscale modeling and simulation of the musculoskeletal system in future DMD research.

  5. Lichen planus pigmentosus: The controversial consensus

    Directory of Open Access Journals (Sweden)

    Aparajita Ghosh

    2016-01-01

    Full Text Available A pigmented variant of lichen planus (LP was first reported from India in 1974 by Bhutani et al. who coined the term LP pigmentosus (LPP to give a descriptive nomenclature to it. LP has a number of variants, one of which is LPP. This disease has also later been reported from the Middle East, Latin America, Korea, and Japan, especially in people with darker skin. It has an insidious onset. Initially, small, black or brown macules appear on sun-exposed areas. They later merge to form large hyperpigmented patches. The disease principally affects the sun-exposed areas of the body such as the face, trunk, and upper extremities. The oral mucosa may rarely be involved. However, the palms, soles, and nails are not affected. Histologically, the epidermis is atrophic along with vacuolar degeneration of basal cell layer. The dermis exhibits incontinence of pigment with scattered melanophages and a sparse follicular or perivascular infiltrate. There is a considerable similarity in histopathological findings between LPP and erythema dyschromicum perstans. However, there are immunologic and clinical differences between the two. These observations have led to a controversy regarding the identity of the two entities. While some dermatologists consider them to be the same, others have opined that the two should be considered as distinctly different diseases. A number of associations such as hepatitis C virus infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic syndrome have been reported with LPP. A rare variant, LPP inversus, with similar clinical and histopathological findings was reported in 2001. As opposed to LPP, this variant occurs in covered intertriginous locations such as groins and axillae and mostly affects white-skinned persons.

  6. The (178m2)Hf Controversy

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J A; Gemmell, D S; Schiffer, J P; Wilhelmy, J B

    2003-07-24

    Since its discovery in the 1960's the {sup 178m2}Hf isomer has garnered high attention from both the basic and applied communities in nuclear science. It's combination of high spin (16+), long half life (31 yrs), and high excitation energy (2.446 MeV) offer unique possibilities as an energy storage medium. Interest in the isomer was rekindled beginning in 1999 when a series of publications began to appear from a group (referred to here as the ''Texas collaboration'') primarily based at the University of Texas, Dallas [1]. They reported observations that some of the stored energy could be released (''triggered'') when the isomer was exposed to a fluence of photons in the energy range {approx}10 to {approx}60 keV. The implications of this observation are profound. Even though the claimed cross section for the process was {approx}7 orders of magnitude greater than would be predicted from the known systematics of photon absorption by nuclei in this mass range [2], such a highly efficient method for triggering the isomeric deexcitation immediately suggested applications utilizing the explosive or the controlled gradual energy release from a very compact source. The prospect of such applications has focused considerable interest on realizing the promise that is implicit in the reported observations. However, two experiments performed by a group from ANL/LANL/LLNL at the Advanced Photon Source at Argonne (the ''APS collaboration'') reported negative results for the observation of any photon-triggered deexcitation of the {sup 178m2}Hf isomer [3]. This has led to a continued controversy, where both sides have adamantly defended their observations. At this point an outsider has difficulty determining whether there is indeed a triggering effect that should be pursued energetically with substantial resources, or whether the phenomenon consists of overly optimistic interpretation of data.

  7. Infections in cancer patients: some controversial issues.

    Science.gov (United States)

    Schimpff, S C; Scott, D A; Wade, J C

    1994-03-01

    Despite more than two decades of clinical research into the management of infections in the neutropenic cancer patient, many patients still develop serious morbidity from infection and all too many still die. A number of controversies surround (a) the use of combination versus monotherapy for initial empiric administration; (b) the use of vancomycin as part of the initial regimen; (c) the origin of Staphylococcus epidermidis infections (i.e., mostly from vascular catheters or mostly from the alimentary canal); (d) the use of acyclovir for herpes simplex prophylaxis during remission induction for acute leukemia patients not undergoing bone marrow transplantation; (e) the use of alimentary canal microbial suppression or reverse isolation in a room with laminar air flow, or both, as infection prevention techniques. Current recommendations and observations include the following. (a) Monotherapy with ceftazidime or imipenem is effective and appropriate for patients with moderate granulocytopenia at limited risk for infection with a resistant organism. Combination therapy is recommended for patients with profound, persistent granulocytopenia who are at high risk for gram-negative bacteremia; such bacteremic patients have a better prognosis with combined-modality therapy. (b) Vancomycin need not be included in the initial regimen although some centers may choose to do so because of the high prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of indwelling vascular catheters, most S. epidermidis infections among neutropenic patients originate from along the alimentary canal. (d) Herpes simplex infection is much more common following standard remission induction chemotherapy than previously recognized. Acyclovir will reduce these infections and concurrently probably reduce the likelihood of resultant bacterial/fungal co-infections and superinfections. (e) Selective microbial suppression is appropriate for patients expected to experience prolonged

  8. Risky, early, controversial. Puberty in medical discourses.

    Science.gov (United States)

    Cozzi, Donatella; Vinel, Virginie

    2015-10-01

    This article comes within the compass of a research program (entitled CorAge. Bodily Experiences and AgePassages among 9-13 year-olds (ANR-09-ENFT-017) conducted between 2009 and 2013 about the emergence of a "new" age in life--"preadolescence"--as instanced in France (Alsace, Lorraine) and Italy (Venetia). The impressive amount of references to "early puberty" and "precocious puberty", in a context of feeling of a premature end of childhood, led us to make an in-depth study of this issue: first, through an analysis of international and French and Italian medical journals; second, through interviews with health professionals. Following the thesis of Foucault, we assume that the discourses on puberty timing participate of classifications of the child body drenched with moral representations of childhood, especially on gender and age issue. Our results: the question of whether a secular trend in puberty timing even exists continues to be debated between American and European scientists. Second, the terms "puberty", "precocious puberty", "early puberty" have been used to indicate a variety of puberty markers, increasing confusion. A controversy has focused on early breast development in girls, because this attribute is questioning the order of ages and gender. Moreover, psychosocial factors presented as accelerating early puberty, do not demonstrate the relation between earliness and risk behavior. The literature, as it is moved by the female precocity, creates a medical category to objectify the complex and flexible process of puberty and invent female child precocity. These differences between American and European scholars and the interviews with French and Italian health professional show a gap between the international literature and practitioners, clinicians and nurses who regularly work with children: they neither find pubertal advancement, nor increase of "true precocious puberty", although they share concerns about premature feminization of girls (France) or

  9. Carotid endarterectomy: current consensus and controversies.

    Science.gov (United States)

    Meerwaldt, Robbert; Hermus, Linda; Reijnen, Michel M P J; Zeebregts, Clark J

    2010-10-01

    Stroke is the third most common cause of mortality, and carotid artery stenosis causes 8% to 29% of all ischemic strokes. Best medical treatment forms the basis of carotid stenosis treatment, and carotid endarterectomy (CEA) has an additional beneficial effect in high-grade stenosis. Carotid angioplasty and stenting (CAS) has challenged CEA as a primary carotid intervention. At present, CEA remains the gold standard, but in the future, CAS techniques will evolve and might become beneficial for subgroups of patients with carotid stenosis. This chapter briefly describes the history of carotid interventions and current consensus and controversies in CEA. In the last two years, several meta-analyses were published on a variety of aspects of best medical treatment, CEA, and CAS. It is still a matter of debate as to whether asymptomatic patients with carotid stenosis should undergo a carotid intervention. Especially because medical treatment has dramatically evolved since the early carotid trials. On the other hand, it is clear that carotid interventions in symptomatic patients with a high-grade stenosis should be performed as early as possible after the initial neurological event in order to achieve optimal stroke risk reduction. In CEA, the use of patching is advocated above primary closure, while the role of selective patching is still unclear. No differences in stroke and mortality rates are observed for routine versus selective shunting, for conventional versus eversion CEA, or for local versus general anesthesia. It is anticipated that in the future, there will be several interesting developments in carotid interventions such as plaque morphology analysis, acute interventions during stroke in progress, and further evolvement of CAS techniques.

  10. Cold dark matter: Controversies on small scales.

    Science.gov (United States)

    Weinberg, David H; Bullock, James S; Governato, Fabio; Kuzio de Naray, Rachel; Peter, Annika H G

    2015-10-06

    The cold dark matter (CDM) cosmological model has been remarkably successful in explaining cosmic structure over an enormous span of redshift, but it has faced persistent challenges from observations that probe the innermost regions of dark matter halos and the properties of the Milky Way's dwarf galaxy satellites. We review the current observational and theoretical status of these "small-scale controversies." Cosmological simulations that incorporate only gravity and collisionless CDM predict halos with abundant substructure and central densities that are too high to match constraints from galaxy dynamics. The solution could lie in baryonic physics: Recent numerical simulations and analytical models suggest that gravitational potential fluctuations tied to efficient supernova feedback can flatten the central cusps of halos in massive galaxies, and a combination of feedback and low star formation efficiency could explain why most of the dark matter subhalos orbiting the Milky Way do not host visible galaxies. However, it is not clear that this solution can work in the lowest mass galaxies, where discrepancies are observed. Alternatively, the small-scale conflicts could be evidence of more complex physics in the dark sector itself. For example, elastic scattering from strong dark matter self-interactions can alter predicted halo mass profiles, leading to good agreement with observations across a wide range of galaxy mass. Gravitational lensing and dynamical perturbations of tidal streams in the stellar halo provide evidence for an abundant population of low-mass subhalos in accord with CDM predictions. These observational approaches will get more powerful over the next few years.

  11. Comparison of left ventricular function assessment between echocardiography and MRI in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Buddhe, Sujatha; Lewin, Mark; Olson, Aaron; Soriano, Brian D. [University of Washington School of Medicine and Seattle Children' s Hospital, Division of Cardiology, Department of Pediatrics, Seattle, WA (United States); Ferguson, Mark [University of Washington School of Medicine and Seattle Children' s Hospital, Department of Radiology, Seattle, WA (United States)

    2016-09-15

    Cardiomyopathy in Duchenne muscular dystrophy (DMD) is associated with death in approximately 40% of patients. Echocardiography is routinely used to assess left ventricular (LV) function; however, it has limitations in these patients. We compared echocardiographic measures of cardiac function assessment to cardiac MRI. We included children and young adults with DMD who had MRI performed between January 2010 and July 2015. We measured echocardiographic and MRI parameters of function assessment, including strain. Presence of late gadolinium enhancement (LGE) was assessed by MRI. Subjects were divided into two groups based on MRI left ventricular ejection fraction (LVEF): group I, LVEF ≥55% and group II, LVEF <55%. We included 41 studies in 33 subjects, with 25 in group I and 16 in group II. Mean age of subjects was 13.6 ± 2.8 years and mean duration between echocardiogram and MRI was 7.6 ± 4.1 months. Only 8 of 16 (50%) patients in group II had diminished function on echocardiogram. Echocardiographic images were suboptimal in 16 subjects (39%). Overall, echocardiographic parameters had weak correlation with MRI-derived ejection fraction percentage. MRI-derived myocardial strain assessment has better correlation with MRI ejection fraction as compared to echocardiography-derived strain parameters. Echocardiography-based ventricular functional assessment has weak correlation with MRI parameters in children and young adults with Duchenne muscular dystrophy. While this correlation improves in the subset of subjects with adequate echocardiographic image quality, it remains modest and potentially suboptimal for clinical management. Accordingly, we conclude that MRI should be performed routinely and early in children with DMD, not only for LGE imaging but also for functional assessment. (orig.)

  12. Quality of life of patients with Duchenne muscular dystrophy: from adolescence to young men.

    Science.gov (United States)

    Lue, Yi-Jing; Chen, Shun-Sheng; Lu, Yen-Mou

    2017-07-01

    This study investigated quality of life (QOL) in adolescent and young men with Duchenne muscular dystrophy (DMD). Health-related QOL and global QOL were assessed with the Short Form 36 (SF-36) and World Health Organization Quality of Life-BREF (WHOQOL-BREF). Associations between functional status and QOL were assessed. All domains of the SF-36 were below Taiwan norms (effect size: -14.2 to -0.5), especially Physical Function, Role Physical, and Social Function. Three of the four domains of the WHOQOL-BREF were below Taiwan norms (effect size: -2.0 to -0.7). The Physical Function of the SF-36 was moderately correlated with functional status (mobility, basic activities of daily living, and arm function). The Social Function of the SF-36 and Social Relationships of the WHOQOL-BREF were also moderately correlated with functional status (impairment, basic activities of daily living, and arm function). The adolescent and young men with DMD had poor health-related and global QOL. Poor QOL was related to both physical condition and social health. We suggest that rehabilitation programs focus on using assistive devices to facilitate arm function and encouraging participation in social activities to improve the QOL of patients with DMD. Implications for rehabilitation Duchenne muscular dystrophy (DMD) is a progressive muscle weakness disease that not only impacts physical health but also leads to poor quality of life in many domains. A valuable rehabilitation goal for patients with DMD is to encourage participation in social activities. Medical care and educational programs should plan a formal transition processes for patients with DMD from pediatric to adult care to maximum their quality of life. Arm function is associated with many domains of global quality of life, so a key element in improving quality of life may be to improve arm function.

  13. Integrating Art Education Models: Contemporary Controversies in Spain

    Science.gov (United States)

    Belver, Manuel; Ulln, Ana; Acaso, Mara

    2005-01-01

    In this article, a basic controversy for art education in Spain is analysed, and its antecedents in thought and social and artistic practices are reviewed. The controversy refers to the question whether school art education should be oriented towards the fine arts or towards the manual arts. Consequently, which should be the cultural model of…

  14. Culture Shock: Using Art and Art Controversy To Teach History.

    Science.gov (United States)

    McBride, Robert, Jr.

    1999-01-01

    Endorses the television series entitled "Culture Shock" that views controversial art as an artifact suggesting that the arts, and controversies surrounding them, can help viewers think critically about the issues of past and present societies. Focuses on "The Adventures of Huckleberry Finn," the painting "Olympia,"…

  15. Current controversies and future perspectives in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Agustí, Alvar; Vestbo, Jørgen

    2011-01-01

    Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work. This review discusses these controversies and anticipates...... some of the changes that may occur in the near future in the field of COPD....

  16. Improving Learning by Discussing Controversies in 20th Century Physics.

    Science.gov (United States)

    Niaz, Mansoor; Rodriguez, Maria A.

    2002-01-01

    Textbooks rarely emphasize how controversial some physics theories were at the time of their proposal. Makes the case that useful classroom debate can be generated by considering the controversy that arose over models of the atom such as Rutherford's and Bohr's, and ideas about fractional charges put forward by Millikan and arising from quark…

  17. Tennessee to Texas: Tracing the Evolution Controversy in Public Education

    Science.gov (United States)

    Armenta, Tony; Lane, Kenneth E.

    2010-01-01

    Darwin's Theory of Evolution has stirred controversy since its inception. Public schools in the United States, pressed by special interest groups on both sides of the controversy, have struggled with how best to teach the theory, if at all. Court cases have dealt with whether states can ban the teaching of evolutionary theory, whether Creationism…

  18. Visualizing Social Justice: Using Controversial Images in Social Studies Classrooms

    Science.gov (United States)

    Hawley, Todd S.; Crowe, Alicia R.; Mooney, Evan

    2016-01-01

    In this article, we promote the use of controversial images to enhance the discussion of social justice issues in schools. Controversial images provide rich opportunities for students to question what is occurring currently in society as well as what has occurred in the past. We provide an example set of activities to be used in teacher education…

  19. Conducting Discussions on Controversial Issues in College Classrooms

    Institute of Scientific and Technical Information of China (English)

    谢力帆

    2014-01-01

    Student identity, their dichotomous logical framework, and teachers’beliefs constitute the major obstacles in conduct-ing classroom discussion on controversial issues. This essay analyzes these obstacles and provides suggestions for teachers in tackling the problems, so that classroom discussions on controversial issues may exert beneficial outcomes.

  20. Current controversies and future perspectives in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Agustí, Alvar; Vestbo, Jørgen

    2011-01-01

    Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work. This review discusses these controversies and anticipates...

  1. Thoracic cirtometry in children with Duchenne muscular dystrophy: expansion of the method Toracometria em crianças com Distrofia Muscular de Duchenne: expansão do método

    OpenAIRE

    Agenor Garcia Júnior; Fátima A. Caromano; Contesini,Adriana M.; Renata Escorcio; Lilian A. Y. Fernandes; Sílvia M. A. João

    2013-01-01

    BACKGROUND: Thoracic cirtometry is a simple and accessible technique to evaluate chest mobility during forced breathing. However, it does not allow for the assessment of compensatory movements commonly used by people with chronic diseases, such Duchenne muscular dystrophy (DMD). DMD is a condition characterized by progressive and irreversible degeneration of the musculoskeletal system. OBJECTIVES: To expand the method of thoracic cirtometry to allow for the assessment of compensatory movement...

  2. Event-related potentials (P300) and neuropsychological assessment in boys exhibiting Duchenne muscular dystrophy Potencial evocado cognitivo (P300) e testagem neuropsicológica em pacientes com distrofia muscular de Duchenne

    OpenAIRE

    Marcus Vinicius Della Coletta; Rosana Herminia Scola; Gislaine Richter Minhoto Wiemes; Cláudia Nasser Fonseca; Maria Joana Mäder; Aline Andrade Freund; Lineu César Werneck

    2007-01-01

    OBJECTIVE: To examine auditory cognitive evoked potentials (P300 potentials) and neuropsychological dysfunction in patients with Duchenne muscular dystrophy (DMD). METHOD: P300 potentials and neuropsychological test results were obtained from 16 healthy control boys and 20 DMD patients. Full Intelligence Quotients (IQ) were estimated for patients and control group. Mean age was 9.5 years in the DMD patient group, and 10 years in the control group (p>0.05). RESULTS: The mean IQ values were 64....

  3. Is functional dependence of Duchenne muscular dystrophy patients determinant of the quality of life and burden of their caregivers?

    Directory of Open Access Journals (Sweden)

    Maria Clara Drummond Soares de Moura

    2015-01-01

    Full Text Available Objective The relationship between functional dependence and quality of life (QOL in Duchenne muscular dystrophy (DMD patients and burden and QOL in caregivers is not clear. This study investigated possible relationships between functional dependence/QOL of DMD patients and QOL/burden of caregivers. Method This study included 35 boys (6-17 years and respective caregivers (above 21 years. Caregivers answered to World Health Organization Quality of Life and Zarit Burden Interview questionnaires. Patients were assessed with the Motor Function Measure and the Autoquestionnaire Qualité de vie Enfant Imagé. Spearman correlations and linear regressions were run to investigate relationships between the variables. Results The occurrence of lower QOL and higher burden among the caregivers of patients with Duchenne muscular dystrophy was evidenced. The functional dependence of patients was not considered a determinant factor. Higher caregivers’ burden was related to lower caregivers’ QOL and to higher patients’ ages.

  4. Adequate managment of patients with dystrophinopathies (muscular dystrophy Duchenne/Becker: objective scales and additional diagnostic methods

    Directory of Open Access Journals (Sweden)

    A. S. Nosko

    2014-01-01

    Full Text Available There are still no guidlines on managment of Duchenne/Becker myodystrophy in domestic medical practice. It leads to decrease of quality of life and, what is more important, lifespan of patients. In this article we have described our Western coleagues lаst decade experience, including consensus guidelines published in 2010 on mаnаgment of Duchenne myodystrophy, supplemented with our practicle experience. We have described standardized motor development scale and muscle tone score for patients with MDD/MDB, and algorithm of multidiscipline care with focus on prevention, diagnosis and treatment of main disease and steroid therapy complications: cardiovascular, orthopedics, respirator etc. These recommendations not only improve quality of live and extend lifespan of MDD/MDB patients, but allow to take part in multicentre trials on searching of pathognomonic and symptomatic treatment.

  5. Non-surgical prevention and management of scoliosis for children with Duchenne muscular dystrophy: what is the evidence?

    Science.gov (United States)

    Harvey, Adrienne; Baker, Louise; Williams, Katrina

    2014-10-01

    A review was performed to examine the evidence for non-surgical interventions for preventing scoliosis and the need for scoliosis surgery in children with Duchenne muscular dystrophy. Medline and Embase databases and reference lists from key articles were searched. After the inclusion and exclusion criteria were applied, 13 studies were critically appraised independently by two reviewers. The included studies examined spinal orthoses and steroid therapy. There were no studies with high levels of evidence (randomised or other controlled trials). The studies with the highest level of evidence were non-randomised experimental trials. There is some evidence that children with Duchenne muscular dystrophy who receive steroid therapy might have delayed onset of scoliosis, but more evidence is required about the long-term risks versus benefits of this intervention. There is weak evidence that spinal orthoses do not prevent and only minimally delay the onset of scoliosis.

  6. Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach Distrofia muscular de Duchenne e Becker: abordagem molecular e imuno-histoquímica

    Directory of Open Access Journals (Sweden)

    Aline Andrade Freund

    2007-03-01

    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains. The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.As distrofias musculares de Duchenne (DMD e de Becker (DMB são doenças causadas por mutação no gene da distrofina. Foram estudados 106 casos com a suspeita diagnóstica de DMD/BMD com a analise de 20 exons do gene da distrofina no sangue e biópsia muscular com imuno-histoquímica para distrofina em alguns casos. Em 71,7% dos casos foi encontrada deleção em pelo menos um dos exons, sendo que 68% das deleções localizam-se na região 3' hot spot. Foram encontradas deleções em 81,5% dos DMD e em todos os BMD, sendo que os sem deleção tinham deficiência de distrofina, incluindo a mulher com DMD. As portadoras sintomáticas não tinham deleções mas anormalidades na distribuição da distrofina no sarcolema. Os outros casos sem deleção, com auxilio da

  7. Successful Surgery for Scoliosis Supported by Pulmonary Rehabilitation in a Duchenne Muscular Dystrophy Patient With Forced Vital Capacity Below 10%

    OpenAIRE

    Lee, Jang Woo; Won, Yu Hui; Choi, Won Ah; Lee, Soon Kyu; Kang, Seong Woong

    2013-01-01

    Low vital capacity is a risk factor for scoliosis correction operation in Duchenne muscular dystrophy (DMD) patients, but pulmonary rehabilitation, including noninvasive intermittent positive pressure ventilator application, air stacking exercise, and assisted coughing technique, reduces the pulmonary complications and perioperative mortality risk. In this case, the patient's preoperative forced vital capacity (FVC) was 8.6% of normal predicted value in sitting position and 9.4% in supine pos...

  8. The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Karen T. Nozoe

    2014-08-01

    Conclusions: This study indicates that caregiving mothers of sons with DMD show major risk for sexual dysfunction and a reduction in their quality of sleep mediated in part by the hormonal changes related to stress. Nozoe KT, Hachul H, Hirotsu C, Polesel DN, Moreira GA, Tufik S, and Andersen ML. The relationship between sexual function and quality of sleep in caregiving mothers of sons with Duchenne muscular dystrophy. Sex Med 2014;2:133–140.

  9. Independent living with Duchenne muscular dystrophy and home mechanical ventilation in areas of Japan with insufficient national welfare services.

    OpenAIRE

    2013-01-01

    In Japan, there is no national 24-hour home care system for people with severe impairments. Despite this fact, a small number of people with Duchenne muscular dystrophy on home mechanical ventilation pursue independent living. Therefore, our aim was to better understand the process by which these individuals arrived at this goal for independence (i.e., choosing to live at home in Japan instead of in special sanatoriums that provide sufficient support and care). Twenty-one participants were in...

  10. Growth hormone inhibition causes increased selenium levels in Duchenne muscular dystrophy: a possible new approach to therapy.

    OpenAIRE

    Collipp, P. J.; Kelemen, J.; Chen, S. Y.; Castro-Magana, M; Angulo, M.; Derenoncourt, A

    1984-01-01

    Nine children with Duchenne muscular dystrophy were given Sanorex (mazindol), a growth hormone inhibitor, daily for 6 months. There was no significant change in their muscle function, but there was a significant reduction in weight gain and in levels of growth hormone, somatomedin C, hair zinc, serum zinc, and serum LDH. Selenium and glutathione peroxidase in the serum increased significantly. Thirteen other children with growth hormone deficiency had a significant reduction in hair selenium ...

  11. Restoring Dystrophin Expression in Duchenne Muscular Dystrophy Muscle: Progress in Exon Skipping and Stop Codon Read Through

    OpenAIRE

    Hoffman, Eric P.; Bronson, Abby; Levin, Arthur A.; Takeda, Shin'ichi; Yokota, Toshifumi; Baudy, Andreas R.; Connor, Edward M.

    2011-01-01

    The identification of the Duchenne muscular dystrophy gene and protein in the late 1980s led to high hopes of rapid translation to molecular therapeutics. These hopes were fueled by early reports of delivering new functional genes to dystrophic muscle in mouse models using gene therapy and stem cell transplantation. However, significant barriers have thwarted translation of these approaches to true therapies, including insufficient therapeutic material (eg, cells and viral vectors), challenge...

  12. The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

    OpenAIRE

    Nozoe, Karen T.; Helena Hachul, MD, PhD; Camila Hirotsu, PhD; Daniel N. Polesel, MSc; Gustavo A. Moreira, MD, PhD; Sergio Tufik, MD, PhD; Monica L. Andersen, PhD

    2014-01-01

    Introduction: The task of the caregiver, especially a caregiving mother of a son with a chronic and fatal disease, may interfere with their quality of sleep, sexuality, and some hormone levels. Aim: The aim of this study was to evaluate the sexual function and the quality of sleep of caregiving mothers of sons with Duchenne muscular dystrophy (DMD). Methods: We evaluated 20 caregiving mothers of sons with DMD and 20 caregiving mothers of sons without any neuromuscular or chronic disease...

  13. Duchenne display responses towards sixteen enjoyable emotions: Individual differences between no and fear of being laughed at

    OpenAIRE

    Platt, Tracey; Hofmann, Jennifer; Ruch, Willibald; Proyer, Rene T.

    2013-01-01

    The present study aims to identify whether individuals’ with a fear of being laughed at (gelotophobia), respond with less facially displayed joy (Duchenne display) generally towards enjoyable emotions or only those eliciting laughter. Forty participants (no vs. gelotophobia) described their feelings to scenarios prototypical for the 16 enjoyable emotions proposed by Ekman (Emotions revealed: recognizing faces and feelings to improve communication and emotional life. Times Books, New York, 200...

  14. The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States.

    Science.gov (United States)

    Thayer, Sarah; Bell, Christopher; McDonald, Craig M

    2017-06-01

    A Duchenne muscular dystrophy (DMD) cohort was identified using a claims-based algorithm to estimate health care utilization and costs for commercially insured DMD patients in the United States. Previous analyses have used broad diagnosis codes that include a range of muscular dystrophy types as a proxy to estimate the burden of DMD. To estimate DMD-associated resource utilization and costs in a sample of patients identified via a claims-based algorithm using diagnosis codes, pharmacy prescriptions, and procedure codes unique to DMD management based on DMD clinical milestones. DMD patients were selected from a commercially insured claims database (2000-2009). Patients with claims suggestive of a non-DMD diagnosis or who were aged 30 years or older were excluded. Each DMD patient was matched by age, gender, and region to controls without DMD in a 1:10 ratio (DMD patients n = 75; controls n = 750). All-cause health care resource utilization, including emergency department, inpatient, outpatient, and physician office visits, and all-cause health care costs were examined over a minimum 1-year period. Costs were computed as total health-plan and patient-paid amounts of adjudicated medical claims (in annualized U.S. dollars). The average age of the DMD cohort was 13 years. Patients in the DMD cohort had a 10-fold increase in health care costs compared with controls ($23,005 vs. $2,277, P costs were significantly higher for the DMD cohort across age strata and, in particular, for DMD patients aged 14-29 years ($40,132 vs. $2,746, P costs of DMD are substantial and increase with age. Funding for this study (GHO-10-4441) was provided by GlaxoSmithKline (GSK). Optum was contracted by GSK to conduct the study. Thayer was an employee of Optum Health Economics and Outcomes Research at the time of this study and was not compensated for her participation as an author of this manuscript. Bell is an employee and shareholder of GSK. McDonald has been a consultant for GSK, Sarepta

  15. Progression and variation of fatty infiltration of the thigh muscles in Duchenne muscular dystrophy, a muscle magnetic resonance imaging study.

    Science.gov (United States)

    Li, Wenzhu; Zheng, Yiming; Zhang, Wei; Wang, Zhaoxia; Xiao, Jiangxi; Yuan, Yun

    2015-05-01

    The purpose of this study was to assess the progression and variation of fatty infiltration of the thigh muscles of Duchenne muscular dystrophy patients. Muscle magnetic resonance imaging was used to measure the degree of fatty infiltration of the thigh muscles of 171 boys with Duchenne muscular dystrophy (mean age, 6.09 ± 2.30 years). Fatty infiltration was assigned using a modified Mercuri's scale 0-5 (normal-severe). The gluteus maximus and adductor magnus were affected in patients less than two years old, followed by the biceps femoris. Quadriceps and semimembranosus were first affected at the age of five to six years; the sartorius, gracilis and adductor longus remained apparently unaffected until seven years of age. Fatty infiltration of all the thigh muscles developed rapidly after seven years of age. The standard deviation of the fatty infiltration scores ranged from 2.41 to 4.87 before five years old, and from 6.84 to 11.66 between six and ten years old. This study provides evidence of highly variable degrees of fatty infiltration in children of different ages with Duchenne muscular dystrophy, and indicates that fatty infiltration progresses more quickly after seven years of age. These findings may be beneficial for the selection of therapeutic regimens and the analysis of future clinical trials. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Distrofia muscular de Duchenne: análise eletrocardiográfica de 131 pacientes Distrofia muscular de duchenne: análisis electrocardiográfica de 131 pacientes Duchenne muscular dystrophy: electrocardiographic analysis of 131 patients

    Directory of Open Access Journals (Sweden)

    Maria Auxiliadora Bonfim Santos

    2010-05-01

    Full Text Available FUNDAMENTO: É conhecido o envolvimento cardíaco em pacientes com distrofia muscular de Duchenne (DMD. O eletrocardiograma (ECG apresenta algumas alterações típicas na DMD, fato que o torna um exame útil no diagnóstico da lesão cardíaca nessa patologia. OBJETIVO: Avaliar as alterações eletrocardiográficas em pacientes portadores de DMD, correlacionando-as com a idade da população estudada. MÉTODOS: Foram analisados os ECG de 131 pacientes com diagnóstico de DMD. Avaliaram-se diversas variáveis eletrocardiográficas, sendo os pacientes separados em dois grupos: aqueles com e sem alterações, por variável estudada. Fez-se a correlação desses dois grupos com a idade dos pacientes. Foram utilizados os critérios de Garson para estabelecer os parâmetros eletrocardiográficos de normalidade. RESULTADOS: O ECG estava anormal em 78,6% dos pacientes. Todos apresentavam ritmo sinusal. Foram os seguintes os percentuais encontrados para as principais variáveis estudadas: PR curto = 18,3%, ondas R anormais em V1 = 29,7%, ondas Q anormais em V6 = 21,3%, alterações da repolarização ventricular = 54,9%, ondas QS anormais em paredes inferior e/ou lateral alta = 37,4%, distúrbios de condução pelo ramo direito = 55,7%, intervalo QT C prolongado = 35,8% e alargamento do QRS = 23,6%. O teste t não pareado foi utilizado para se estabelecer a correlação da idade com as variáveis eletrocardiográficas estudadas nos dois grupos e, apenas a variável alteração da repolarização mostrou diferença estatisticamente significante. CONCLUSÃO: As alterações eletrocardiográficas na DMD são frequentes, revelando comprometimento cardíaco precoce. Apenas a variável alteração da repolarização ventricular foi mais frequente, porém em faixa etária menor (p FUNDAMENTO: Se sabe de la afectación cardíaca en pacientes con distrofia muscular de Duchenne (DMD. El electrocardiograma (ECG presenta algunas alteraciones típicas en la DMD

  17. Anestesia em paciente portador de distrofia muscular de Duchenne: relato de casos Anestesia en un paciente portador de distrofia muscular de Duchenne: relato de casos Anesthesia for Duchenne muscular dystrophy patients: case reports

    Directory of Open Access Journals (Sweden)

    Rodrigo Machado Saldanha

    2005-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Este estudo objetiva relatar dois casos de anestesia em pacientes portadores de Distrofia Muscular de Duchenne (DMD, uma doença rara, progressiva e incapacitante, e discutir sobre a conduta anestésica. O comprometimento das funções pulmonar e cardíaca, a possibilidade de ocorrência de hipertermia maligna, a maior sensibilidade aos bloqueadores neuromusculares e o aumento da morbidade pós-operatória são alguns dos desafios enfrentados pelo anestesiologista. RELATO DOS CASOS: O primeiro caso foi o de um paciente pediátrico com diagnóstico de DMD e rabdomiossarcoma, agendado para exérese da lesão e esvaziamento cervical ampliado. Na avaliação pré-anestésica (anamnese, exame clínico e exames complementares não foram detectadas alterações, exceto pela tumoração cervical. Optou-se pela técnica venosa total, com remifentanil em infusão contínua e propofol em infusão alvo-controlada, sem a utilização de bloqueadores neuromusculares. O procedimento cirúrgico teve duração de 180 minutos, sem intercorrências. O segundo caso foi de um paciente do sexo masculino, 24 anos, com diagnóstico de DMD e colelitíase com indicação cirúrgica, cuja avaliação pré-operatória revelou pneumopatia restritiva grave, com diminuições da capacidade e da reserva respiratórias, sendo necessário o uso de BIPAP nasal noturno. Neste paciente, optou-se pela intubação traqueal com sedação mínima e anestesia tópica, seguida pela técnica venosa total com remifentanil em infusão contínua e propofol em infusão alvo-controlada, sem a utilização de bloqueadores neuromusculares. Ao término, o paciente foi extubado ainda na sala de operações e imediatamente colocado no BIPAP nasal. Encaminhado à UTI, com alta no 2º PO e alta hospitalar no 3º PO. CONCLUSÕES: A anestesia venosa total com infusão contínua de propofol e remifentanil sem bloqueadores neuromusculares constitui-se em opção segura e

  18. Physical training in boys with Duchenne Muscular Dystrophy: the protocol of the No Use is Disuse study

    Directory of Open Access Journals (Sweden)

    Jansen Merel

    2010-08-01

    Full Text Available Abstract Background "Use it or lose it" is a well known saying which is applicable to boys with Duchenne Muscular Dystrophy (DMD. Besides the direct effects of the muscular dystrophy, the increasing effort to perform activities, the fear of falling and the use of personal aids indirectly impair leg and arm functions as a result of disuse. Physical training could oppose this secondary physical deterioration. The No Use is Disuse (NUD study is the first study in human subjects with DMD that will examine whether a low-intensity physical training is beneficial in terms of preservation of muscle endurance and functional abilities. The study consists of two training intervention studies: study 1 "Dynamic leg and arm training for ambulant and recently wheelchair-dependent boys with DMD and, study 2 "Functional training with arm support for boys with DMD who have been confined to a wheelchair for several years". This paper describes the hypotheses and methods of the NUD study. Methods Study 1 is an explorative randomized controlled trial with multiple baseline measurements. Thirty boys with a DNA-established diagnosis of DMD will be included. The intervention consists of a six-months physical training during which boys train their legs and arms with active and/or assisted cycling training equipment. The primary study outcomes are muscle endurance and functional abilities, assessed with a Six-Minute Bicycle Test and the Motor Function Measure. Study 2 has a within-group repeated measurements design and will include ten boys with DMD who have already been confined to a wheelchair for several years. The six-months physical training program consists of 1 a computer-assisted training and 2 a functional training with an arm support. The primary study outcome is functional abilities of the upper extremity, assessed with the Action Research Arm Test. Discussion The NUD study will fill part of the gap in the current knowledge about the possible effects of

  19. Physical training in boys with Duchenne Muscular Dystrophy: the protocol of the No Use is Disuse study

    Science.gov (United States)

    2010-01-01

    Background "Use it or lose it" is a well known saying which is applicable to boys with Duchenne Muscular Dystrophy (DMD). Besides the direct effects of the muscular dystrophy, the increasing effort to perform activities, the fear of falling and the use of personal aids indirectly impair leg and arm functions as a result of disuse. Physical training could oppose this secondary physical deterioration. The No Use is Disuse (NUD) study is the first study in human subjects with DMD that will examine whether a low-intensity physical training is beneficial in terms of preservation of muscle endurance and functional abilities. The study consists of two training intervention studies: study 1 "Dynamic leg and arm training for ambulant and recently wheelchair-dependent boys with DMD and, study 2 "Functional training with arm support for boys with DMD who have been confined to a wheelchair for several years". This paper describes the hypotheses and methods of the NUD study. Methods Study 1 is an explorative randomized controlled trial with multiple baseline measurements. Thirty boys with a DNA-established diagnosis of DMD will be included. The intervention consists of a six-months physical training during which boys train their legs and arms with active and/or assisted cycling training equipment. The primary study outcomes are muscle endurance and functional abilities, assessed with a Six-Minute Bicycle Test and the Motor Function Measure. Study 2 has a within-group repeated measurements design and will include ten boys with DMD who have already been confined to a wheelchair for several years. The six-months physical training program consists of 1) a computer-assisted training and 2) a functional training with an arm support. The primary study outcome is functional abilities of the upper extremity, assessed with the Action Research Arm Test. Discussion The NUD study will fill part of the gap in the current knowledge about the possible effects of training in boys with DMD and

  20. Controversial Issues in Kyphoplasty and Vertebroplasty in Osteoporotic Vertebral Fractures

    Directory of Open Access Journals (Sweden)

    Ioannis D. Papanastassiou

    2014-01-01

    Full Text Available Kyphoplasty (KP and vertebroplasty (VP have been successfully employed for many years for the treatment of osteoporotic vertebral fractures. The purpose of this review is to resolve the controversial issues raised by the two randomized trials that claimed no difference between VP and SHAM procedure. In particular we compare nonsurgical management (NSM and KP and VP, in terms of clinical parameters (pain, disability, quality of life, and new fractures, cost-effectiveness, radiological variables (kyphosis correction and vertebral height restoration, and VP versus KP for cement extravasation and complications profile. Cement types and optimal filling are analyzed and technological innovations are presented. Finally unipedicular/bipedicular techniques are compared. Conclusion. VP and KP are superior to NSM in clinical and radiological parameters and probably more cost-effective. KP is superior to VP in sagittal balance improvement and cement leaking. Complications are rare but serious adverse events have been described, so caution should be exerted. Unilateral procedures should be pursued whenever feasible. Upcoming randomized trials (CEEP, OSTEO-6, STIC-2, and VERTOS IV will provide the missing link.

  1. Increased sarcolipin expression and decreased sarco(endo)plasmic reticulum Ca2+ uptake in skeletal muscles of mouse models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Schneider, Joel S; Shanmugam, Mayilvahanan; Gonzalez, James Patrick; Lopez, Henderson; Gordan, Richard; Fraidenraich, Diego; Babu, Gopal J

    2013-12-01

    Abnormal intracellular Ca(2+) handling is an important factor in the progressive functional decline of dystrophic muscle. In the present study, we investigated the function of sarco(endo)plasmic reticulum (SR) Ca(2+) ATPase (SERCA) in various dystrophic muscles of mouse models of Duchenne muscular dystrophy. Our studies show that the protein expression of sarcolipin, a key regulator of the SERCA pump is abnormally high and correlates with decreased maximum velocity of SR Ca(2+) uptake in the soleus, diaphragm and quadriceps of mild (mdx) and severe (mdx:utr-/-) dystrophic mice. These changes are more pronounced in the muscles of mdx:utr-/- mice. We also found increased expression of SERCA2a and calsequestrin specifically in the dystrophic quadriceps. Immunostaining analysis further showed that SERCA2a expression is associated both with fibers expressing slow-type myosin and regenerating fibers expressing embryonic myosin. Together, our data suggest that sarcolipin upregulation is a common secondary alteration in all dystrophic muscles and contributes to the abnormal elevation of intracellular Ca(2+) concentration via SERCA inhibition.

  2. Tooth-bleaching procedures and their controversial effects: A literature review

    OpenAIRE

    Alqahtani, Mohammed Q.

    2014-01-01

    Aim: This review article will help clinicians improve their understanding of the history of bleaching procedures, bleaching types, components, mechanisms, and their effects on soft tissue, tooth structures, resin composite, and bonding. Methods: The controversial issues about bleaching procedures and their effects are reviewed. Additionally, the consequences of pre- and post-bleaching on the bonding potential of composite resin restorations to tooth structure are discussed. Conclusion: ...

  3. State of the art: therapeutic controversies in severe acute asthma.

    Science.gov (United States)

    Gibbs, M A; Camargo, C A; Rowe, B H; Silverman, R A

    2000-07-01

    This is a transcript of the 1999 SAEM State-of-the-Art session on "Therapeutic Controversies in Severe Acute Asthma," presented at the 1999 SAEM annual meeting in Boston. The aim of this session was to address some of the current controversies in the management of acute asthma exacerbations, a major issue in emergency medicine. Despite many recent advances in asthma management, morbidity and mortality remain high. While many of us have strong feelings on how asthma patients should be treated, many of our assertions are not based on good science, and there are numerous areas of controversy. This discussion focuses on the controversy over beta agonist treatment for acute asthma, the physiology of corticosteroids in asthma, and the emergency use of leukotriene-modifying agents.

  4. Practising infanticide, observing narrative: controversial texts in a field science.

    Science.gov (United States)

    Rees, A

    2001-08-01

    In recent recent years, social studies of science have developed a deep interest in the conduct of science in the field. However, studies of controversial field science remain relatively rare. This paper presents an analysis of a controversy about the origin of primate infanticide that began in the 1970s, and discusses the ways in which controversies in the field differ from those in the laboratory. Particularly important here is the inability of researchers to control the behaviour of their research subjects; to an important extent, the conduct of their research is dependent on the agency of their research subjects. Finally, it also points to the rôle played by the sciences of animal behaviour in the constructions of stories about the biological basis of human culture, a rôle that means that the investigation of controversy in these sciences is of paramount public importance.

  5. Assessment of controversial pediatric asthma management options using GRADE

    NARCIS (Netherlands)

    N. Boluyt (Nicole); B.L. Rottier (Bart); J.C. de Jongste (Johan); R. Riemsma; E.J.L.E. Vrijlandt; P.L.P. Brand (Paul L.P.)

    2012-01-01

    textabstractOBJECTIVES: To develop explicit and transparent recommendations on controversial asthma management issues in children and to illustrate the usefulness of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in rating the quality of evidence and strength

  6. Assessment of Controversial Pediatric Asthma Management Options Using GRADE

    NARCIS (Netherlands)

    Boluyt, Nicole; Rottier, Bart L.; de Jongste, Johan C.; Riemsma, Rob; Vrijlandt, Elianne J.L.E.; Brand, Paul L. P.

    2012-01-01

    OBJECTIVES: To develop explicit and transparent recommendations on controversial asthma management issues in children and to illustrate the usefulness of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in rating the quality of evidence and strength of recommend

  7. Controversies around official poverty measurements and methods in contemporary Argentina

    Directory of Open Access Journals (Sweden)

    Soledad A. Pérez

    2013-01-01

    Full Text Available Theoretical as well as methodological controversies often have a fundamental role in epistemic development. This paper addresses the controversies regarding the methods and the official poverty measurements in Argentina between 2003 and 2011. Results point to three different phases: the first one, between 2003 and 2005, when controversies were about methodology and starred the National Macroeconomic Policy Coordinating body and the National Institute for Statistics and Census (INDEC. The second, during 2006, when the dispute was led between the INDEC and the Ministry of Domestic Trade and methodological discussions on poverty lost dominance. The final period began in 2007, when new players joined the controversies and the legitimacy of the measurement results became the focus of discussions.

  8. Effects of Normal and Perturbed Social Play on the Duration and Amplitude of Different Types of Infant Smiles

    Science.gov (United States)

    Fogel, Alan; Hsu, Hui-Chin; Shapiro, Alyson F.; Nelson-Goens, G. Christina; Secrist, Cory

    2006-01-01

    Different types of smiling varying in amplitude of lip corner retraction were investigated during 2 mother-infant games--peekaboo and tickle--at 6 and 12 months and during normally occurring and perturbed games. Using Facial Action Coding System (FACS), infant smiles were coded as simple (lip corner retraction only), Duchenne (simple plus cheek…

  9. Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report

    Directory of Open Access Journals (Sweden)

    Kaur Jasmeet

    2011-06-01

    Full Text Available Abstract Introduction Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental. Case presentation We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin. Conclusion Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.

  10. Motor physical therapy affects muscle collagen type I and decreases gait speed in dystrophin-deficient dogs.

    Directory of Open Access Journals (Sweden)

    Thaís P Gaiad

    Full Text Available Golden Retriever Muscular Dystrophy (GRMD is a dystrophin-deficient canine model genetically homologous to Duchenne Muscular Dystrophy (DMD in humans. Muscular fibrosis secondary to cycles of degeneration/regeneration of dystrophic muscle tissue and muscular weakness leads to biomechanical adaptation that impairs the quality of gait. Physical therapy (PT is one of the supportive therapies available for DMD, however, motor PT approaches have controversial recommendations and there is no consensus regarding the type and intensity of physical therapy. In this study we investigated the effect of physical therapy on gait biomechanics and muscular collagen deposition types I and III in dystrophin-deficient dogs. Two dystrophic dogs (treated dogs-TD underwent a PT protocol of active walking exercise, 3×/week, 40 minutes/day, 12 weeks. Two dystrophic control dogs (CD maintained their routine of activities of daily living. At t0 (pre and t1 (post-physical therapy, collagen type I and III were assessed by immunohistochemistry and gait biomechanics were analyzed. Angular displacement of shoulder, elbow, carpal, hip, stifle and tarsal joint and vertical (Fy, mediolateral (Fz and craniocaudal (Fx ground reaction forces (GRF were assessed. Wilcoxon test was used to verify the difference of biomechanical variables between t0 and t1, considering p<.05. Type I collagen of endomysium suffered the influence of PT, as well as gait speed that had decreased from t0 to t1 (p<.000. The PT protocol employed accelerates morphological alterations on dystrophic muscle and promotes a slower velocity of gait. Control dogs which maintained their routine of activities of daily living seem to have found a better balance between movement and preservation of motor function.

  11. Controversy of the year. Biomedical ethics on the front burner.

    Science.gov (United States)

    2000-12-22

    CONTROVERSY OF THE YEAR: Biomedical Ethics on the Front Burner It was a hot year for debates over research ethics. Controversy erupted in late 1999 after the death of 18-year-old Jesse Gelsinger in a gene-therapy clinical trial at the University of Pennsylvania. Because Penn and one of its clinicians had a financial stake in a gene-therapy company, questions about potential conflicts of interest arose at once.

  12. Mapping Controversies with Social Media: The Case for Symmetry

    Directory of Open Access Journals (Sweden)

    Noortje Marres

    2015-09-01

    Full Text Available This article assesses the usefulness for social media research of controversy analysis, an approach developed in Science and Technology Studies (STS and related fields. We propose that this approach can help to address an important methodological problem in social media research, namely, the tension between social media as resource for social research and as an empirical object in its own right. Initially developed for analyzing interactions between science, technology, and society, controversy analysis has in recent decades been implemented digitally to study public debates and issues dynamics online. A key feature of controversy analysis as a digital method, we argue, is that it enables a symmetrical approach to the study of media-technological dynamics and issue dynamics. It allows us to pay equal attention to the ways in which a digital platform like Twitter mediates public issues, and to how controversies mediate “social media” as an object of public attention. To sketch the contours of such a symmetrical approach, the article discusses examples from a recent social media research project in which we mapped issues of “privacy” and “surveillance” in the wake of the National Security Agency (NSA data leak by Edward Snowden in June 2013. Through a discussion of social media research practice, we then outline a symmetrical approach to analyzing controversy with social media. We conclude that the digital implementation of such an approach requires further exchanges between social media researchers and controversy analysts.

  13. Maintenance Therapy for NSCLC: Consensus and Controversy

    Institute of Scientific and Technical Information of China (English)

    Shun Lu; Yong-feng Yu

    2011-01-01

    Nowadays,advanced non-small cell lung cancer (NSCLC) is still an incurable disease.However,recent researches on maintenance therapy have led to considerable progress.Recently,pemetrexed and erlotinib have been approved for maintenance chemotherapy by both the U.S.Food and Drug Administration and European Medicines Agency.However,there are not adequate data to support the maintenance therapy as the standard treatment for advanced NSCLC and there has been no conclusive predictor of who will get benefit from maintenance chemotherapy and what type of maintenance,continuation or switch,is preferred.This article reviews the main studies on maintenance therapy of advanced NSCLC and discusses the results available to date.

  14. Surgical treatment of dislocated acromioclavicular syndesmolysis remains controversial

    Directory of Open Access Journals (Sweden)

    Slaviša Mihaljevič

    2007-12-01

    Full Text Available Background: Operative treatment of acromioclavicular (AC joint dislocations Allman-Tossy III type is controversial. There are more than 30 types of operative treatments described. At the Department of Traumatology of Celje General and Teaching Hospital (CGTH we operate the AC joint dislocation by the AC joint opened reduction and fixation using two Kirschner wires and additional figure of eight wire loop over the AC joint. The purpose of the analysis is to evaluate the results of acromioclavicular joint complete dislocation Allman-Tossy III type operative treatment.Patients and methods: In the 2-year period from July 1st 1997, to June 31st, 1999, at the Department of Traumatology of CGTH we operatively treated 59 injured persons with the AC joint dislocation. There were 55 men (93 % and 4 women (7 %. The average age was 40 years (from 20 to 72 years. 56 (95 % injured persons had the AC joint injury of Allman-Tossy III type. In first three weeks (early reconstruction we operated 45 injured persons (76.3 %. The applied material was removed after 8 weeks. 47 (79.7 % injured persons were re-examined at least one year after the injury (27 months in average; 14–39 months. The results were evaluated according to University of California at Los Angeles (UCLA scale for the shoulder function evaluation. The impact of factors on a good treatment result was presented by the odds ratio and uni-variant analysis calculation.Results: Out of 47 injured persons re-examined according to the UCLA scale at least one year after the injury there were 17 injured persons (36.2 % rated with an excellent result (UCLA 34– 35, 22 good (46.8 % (UCLA 28–33, 5 satisfactory (10.6 % (UCLA 21–27 and 3 bad (6.4 % (UCLA 0–20. In total we achieved 83 % of excellent and good results. The injured persons age did not significantly affect the treatment result. Complications occurred in 14 (29.8 % injured patients. If no complications were occurred the odds ratio for good

  15. Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Sanchez, Raúl; Escobar, Rosa E.; Cruz-Guzmán, Oriana del Rocío; López-Alarcón, Mardia; Bernabe García, Mariela; Coral-Vázquez, Ramón; Matute, Guadalupe; Velázquez Wong, Ana Claudia

    2015-01-01

    Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR. PMID:26089900

  16. Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment.

    Science.gov (United States)

    van den Engel-Hoek, Lenie; Erasmus, Corrie E; Hendriks, Jan C M; Geurts, Alexander C H; Klein, Willemijn M; Pillen, Sigrid; Sie, Lilian T; de Swart, Bert J M; de Groot, Imelda J M

    2013-05-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based recommendations for safe swallowing. In this cross-sectional study, participants were divided into: early and late ambulatory stage (AS, n = 6), early non-ambulatory stage (ENAS, n = 7), and late non-ambulatory stage (LNAS, n = 11). Quantitative oral muscle ultrasound was performed to quantify echo intensity. Swallowing was assessed with a video fluoroscopic swallow study, surface electromyography (sEMG) of the submental muscle group and tongue pressure. Differences in outcome parameters among the three DMD stages were tested with analysis of variance. Oral muscles related to swallowing were progressively affected, starting in the AS with the geniohyoid muscle. Tongue (pseudo) hypertrophy was found in 70 % of patients in the ENAS and LNAS. Oral phase problems and post-swallow residue were observed, mostly in the LNAS with solid food. sEMG and tongue pressure data of swallowing solid food revealed the lowest sEMG amplitude, the longest duration and lowest tongue pressure in the LNAS. In case of swallowing problems in DMD, based on the disturbed mechanisms of swallowing, it is suggested to (1) adjust meals in terms of less solid food, and (2) drink water after meals to clear the oropharyngeal area.

  17. Whole-body vibration training in children with Duchenne muscular dystrophy and spinal muscular atrophy.

    Science.gov (United States)

    Vry, Julia; Schubert, Isabel J; Semler, Oliver; Haug, Verena; Schönau, Eckhard; Kirschner, Janbernd

    2014-03-01

    Whole-body-vibration training is used to improve muscle strength and function and might therefore constitute a potential supportive therapy for neuromuscular diseases. To evaluate safety of whole-body vibration training in ambulatory children with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). 14 children with DMD and 8 with SMA underwent an 8-week vibration training programme on a Galileo MedM at home (3 × 3 min twice a day, 5 days a week). Primary outcome was safety of the training, assessed clinically and by measuring serum creatine kinase levels. Secondary outcome was efficacy as measured by changes in time function tests, muscle strength and angular degree of dorsiflexion of the ankles. All children showed good clinical tolerance. In boys with DMD, creatine kinase increased by 56% after the first day of training and returned to baseline after 8 weeks of continuous whole-body vibration training. No changes in laboratory parameters were observed in children with SMA. Secondary outcomes showed mild, but not significant, improvements with the exception of the distance walked in the 6-min walking test in children with SMA, which rose from 371.3 m to 402.8 m (p training is clinically well tolerated in children with DMD and SMA. The relevance of the temporary increase in creatine kinase in DMD during the first days of training is unclear, but it is not related to clinical symptoms or deterioration. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  18. Laparoscopic suture repair of idiopathic gastric perforation in Duchenne muscular dystrophy.

    Science.gov (United States)

    Miyano, Go; Nouso, Hiroshi; Morita, Keiichi; Nakajima, Hideaki; Koyama, Mariko; Kaneshiro, Masakatsu; Miyake, Hiromu; Yamoto, Masaya; Fukumoto, Koji; Urushihara, Naoto

    2015-01-01

    We report herein an adolescent case of Duchenne muscular dystrophy (DMD) with idiopathic gastric perforation, in which emergency surgical repair was performed laparoscopically. A 14-year-old nonambulatory boy with DMD was brought to our emergency department with sudden onset of severe abdominal pain and distention. Plain radiograph and computed tomography confirmed the presence of free intraperitoneal air and intrapelvic effusion. The patient elected to undergo laparoscopic inspection with 4 trocars, revealing a focal perforation, 3-4 cm in diameter, on the upper gastric body near the diaphragm. The stomach was also found to have a thin wall without evidence of peptic ulcer disease or other abnormalities. An interrupted suture was placed using 4-0 PDS. The abdomen was extensively irrigated, and multiple J-Vac drains were left in situ. Total operation time was 90 min, and no intraoperative complications were encountered. Enteral feeding through a nasogastric tube was started on postoperative day 7. The postoperative course has been uneventful as of the 12-month follow-up. Pediatric surgeons should be aware of the increased risk of gastric perforation associated with DMD, and that laparoscopic repair can be safely performed even in emergency settings.

  19. Laparoscopic suture repair of idiopathic gastric perforation in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Go Miyano

    2015-01-01

    Full Text Available We report herein an adolescent case of Duchenne muscular dystrophy (DMD with idiopathic gastric perforation, in which emergency surgical repair was performed laparoscopically. A 14-year-old nonambulatory boy with DMD was brought to our emergency department with sudden onset of severe abdominal pain and distention. Plain radiograph and computed tomography confirmed the presence of free intraperitoneal air and intrapelvic effusion. The patient elected to undergo laparoscopic inspection with 4 trocars, revealing a focal perforation, 3-4 cm in diameter, on the upper gastric body near the diaphragm. The stomach was also found to have a thin wall without evidence of peptic ulcer disease or other abnormalities. An interrupted suture was placed using 4-0 PDS. The abdomen was extensively irrigated, and multiple J-Vac drains were left in situ. Total operation time was 90 min, and no intraoperative complications were encountered. Enteral feeding through a nasogastric tube was started on postoperative day 7. The postoperative course has been uneventful as of the 12-month follow-up. Pediatric surgeons should be aware of the increased risk of gastric perforation associated with DMD, and that laparoscopic repair can be safely performed even in emergency settings.

  20. Revised North Star Ambulatory Assessment for Young Boys with Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Mercuri, Eugenio; Coratti, Giorgia; Messina, Sonia; Ricotti, Valeria; Baranello, Giovanni; D'Amico, Adele; Pera, Maria Carmela; Albamonte, Emilio; Sivo, Serena; Mazzone, Elena Stacy; Arnoldi, Maria Teresa; Fanelli, Lavinia; De Sanctis, Roberto; Romeo, Domenico M; Vita, Gian Luca; Battini, Roberta; Bertini, Enrico; Muntoni, Francesco; Pane, Marika

    2016-01-01

    The advent of therapeutic approaches for Duchenne muscular dystrophy (DMD) has highlighted the need to identify reliable outcome measures for young boys with DMD. The aim of this study was to develop a revised version of the North Star Ambulatory Assessment (NSAA) suitable for boys between the age of 3 and 5 years by identifying age appropriate items and revising the scoring system accordingly. Using the scale in 171 controls between the age of 2.9 and 4.8 years, we identified items that were appropriate at different age points. An item was defined as age appropriate if it was completed, achieving a full score, by at least 85% of the typically developing boys at that age. At 3 years (±3months) there were only 8 items that were age appropriate, at 3 years and 6 months there were 13 items while by the age of 4 years all 17 items were appropriate. A revised version of the scale was developed with items ordered according to the age when they could be reliably performed. The application of the revised version of the scale to data collected in young DMD boys showed that very few of the DMD boys were able to complete with a full score all the age appropriate items. In conclusion, our study suggests that a revised version of the NSAA can be used in boys from the age of 3 years to obtain information on how young DMD boys acquire new abilities and how this correlates with their peers.

  1. Motor function measure scale, steroid therapy and patients with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Elaine C. da Silva

    2012-03-01

    Full Text Available OBJECTIVE: To assess the evolution of motor function in patients with Duchenne muscular dystrophy (DMD treated with steroids (prednisolone or deflazacort through the Motor Function Measure (MFM, which evaluates three dimensions of motor performance (D1, D2, D3. METHODS: Thirty-three patients with DMD (22 ambulant, 6 non-ambulant and 5 who lost the capacity to walk during the period of the study were assessed using the MFM scale six times over a period of 18 months. RESULTS: All the motor functions remained stable for 14 months in all patients, except D1 for those who lost their walking ability. In ambulant patients, D2 (axial and proximal motor capacities motor functions improved during six months; an improvement in D3 (distal motor capacity was noted during the total follow-up. D1 (standing posture and transfers and total score were useful to predict the loss of the ability to walk. CONCLUSIONS: The use of the MFM in DMD patients confirms the benefits of the steroid treatment for slowing the progression of the disease.

  2. Compensatory movements during functional activities in ambulatory children with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Joyce Martini

    2014-01-01

    Full Text Available Objective: During the transitional phase (ambulatory to non-ambulatory, synergies characterize the evolution of Duchenne muscular dystrophy (DMD. This study was performed to describe and quantify compensatory movements while sitting down on/rising from the floor and climbing up/down steps. Method: Eighty videos (5 children × 4 assessments × 4 tasks were recorded quarterly in the year prior to gait loss. Compensatory movements from the videos were registered based on the Functional Evaluation Scale for DMD. Results: The most frequently observed compensatory movements were upper limb support on lower limbs/floor/handrail during all the tasks and lumbar hyperlordosis, trunk support on handrail, equinus foot, increased base of support, non-alternated descent, and pauses while climbing up/down steps. Conclusion: Climbing up/down steps showed a higher number of compensatory movements than sitting down on/rising from the floor, which seemed to be lost before climbing up/down steps in ambulatory children with DMD.

  3. Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Maricela Rodríguez-Cruz

    2015-01-01

    Full Text Available Aim. Our aim was (1 to determine the frequency of insulin resistance (IR in patients with Duchenne/Becker muscular dystrophy (DMD/BMD, (2 to identify deleted exons of DMD gene associated with obesity and IR, and (3 to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3% exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69 and 50 (OR = 8.73; 95% CI = 1.17–65.10 from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.

  4. Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status

    Directory of Open Access Journals (Sweden)

    Oriana del Rocío Cruz-Guzmán

    2015-01-01

    Full Text Available Inflammation described in patients with Duchenne muscular dystrophy (DMD may be related to loss of muscle function or to obesity. It is unknown if circulating proinflammatory cytokines (IL-6, IL-1, and TNF-α levels are associated with muscle function. The purpose was to evaluate whether an association exists between systemic inflammation with muscle function and nutritional status in DMD patients. In 66 DMD patients without corticosteroid treatment, the following were evaluated in serum: cytokines (IL-1, IL-6, and TNF-α, C-reactive protein (CRP, leptin, adiponectin, and creatine kinase (CK. Muscle function was evaluated using Vignos Scale. Patients with better muscle function had the highest concentration of CK, IL-1, and TNF-α compared with less muscle function. No differences in IL-6 and adiponectin concentration were identified among groups with different levels of muscle function. Also, no differences were observed in the concentration of cytokines among groups with different nutritional status levels (underweight, normal weight, and overweight/obese. However, CRP and leptin were increased in the obese group compared with normal and underweight subjects. Systemic inflammation is increased in patients with better muscle function and decreases in DMD patients with poorer muscle function; nevertheless, systemic inflammation is similar among different levels of nutritional status in DMD patients.

  5. Noninvasive evaluation of respiratory muscles in pre-clinical model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Daniela M. Oliveira

    2016-04-01

    Full Text Available Abstract Since respiratory insufficiency is the main cause of death in patients affected by Duchenne Muscular Dystrophy (DMD, the present study aims at establishing a new non-invasive method to evaluate the clinical parameters of respiratory conditions of experimental models affected by DMD. With this purpose in mind, we evaluated the cardiorespiratory clinical conditions, the changes in the intercostal muscles, the diaphragmatic mobility, and the respiratory cycles in Golden Retriever Muscular Dystrophy (GRMD employing ultrasonography (US. A control group consisting of dogs of the same race, but not affected by muscular dystrophy, were used in this study. The results showed that inspiration, expiration and plateau movements (diaphragm mobility were lower in the affected group. Plateau phase in the affected group was practically non-existent and showed that the diaphragm remained in constant motion. Respiratory rate reached 15.5 per minute for affected group and 26.93 per minute for the control group. Expiration and inspiration movements of intercostal muscles reached 8.99mm and 8.79mm, respectively, for control group and 7.42mm and 7.40mm, respectively, for affected group. Methodology used in the present analysis proved to be viable for the follow-up and evaluation of the respiratory model in GRMD and may be adapted to other muscular dystrophy experimental models.

  6. The therapeutic potential of skeletal muscle plasticity in Duchenne muscular dystrophy: phenotypic modifiers as pharmacologic targets.

    Science.gov (United States)

    Ljubicic, Vladimir; Burt, Matthew; Jasmin, Bernard J

    2014-02-01

    Duchenne muscular dystrophy (DMD) is a life-limiting, neuromuscular disorder that causes progressive, severe muscle wasting in boys and young men. Although there is no cure, scientists and clinicians can leverage the fact that slower, more oxidative skeletal muscle fibers possess an enhanced degree of resistance to the dystrophic pathology relative to their faster, more glycolytic counterparts, and can thus use this knowledge when investigating novel therapeutic avenues. Several factors have been identified as powerful regulators of muscle plasticity. Some proteins, such as calcineurin, peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α), PPARβ/δ, and AMP-activated protein kinase (AMPK), when chronically stimulated in animal models, remodel skeletal muscle toward the slow, oxidative myogenic program, whereas others, such as receptor-interacting protein 140 (RIP140) and E2F transcription factor 1 (E2F1), repress this phenotype. Recent studies demonstrating that pharmacologic and physiological activation of targets that shift dystrophic muscle toward the slow, oxidative myogenic program provide appreciable molecular and functional benefits. This review surveys the rationale behind, and evidence for, the study of skeletal muscle plasticity in preclinical models of DMD and highlights the potential therapeutic opportunities in advancing a strategy focused on remodeling skeletal muscle in patients with DMD toward the slow, oxidative phenotype.

  7. Co-administration of deflazacort and doxycycline: a potential pharmacotherapy for Duchenne muscular dystrophy.

    Science.gov (United States)

    Pereira, Juliano Alves; Marques, Maria Julia; Santo Neto, Humberto

    2015-07-01

    The standard therapy used in the treatment of Duchenne muscle dystrophy (DMD) is corticoids, such as deflazacort and prednisone. However, they have limited therapeutic value, and their combination with drugs already in use to treat other human diseases could potentially increase corticoid outcomes in DMD. In the present study, we evaluated whether a combined therapy of the corticoid deflazacort with doxycycline could result in greater improvement in mdx dystrophy than deflazacort alone. Deflazacort alone or deflazacort/doxycycline were administered for 36 days (starting on postnatal day 0) in drinking water. Histopathological, biochemical (creatine kinase), functional (forelimb muscle grip strength and fatigue) parameters and inflammatory markers (MMP-9, TNF-α, NF-kB) were evaluated in biceps brachii and diaphragm muscles of the mdx mice. The combined therapy was superior in improving the dystrophic phenotype compared to monotherapy. The primary results were observed in attenuating muscle fatigue, decreasing muscle total calcium and inflammatory markers and increasing β-dystroglycan, a main component of the dystrophin-protein complex. Furthermore, the combined therapy was effective in preventing the loss of body mass observed with deflazacort alone at this very early stage of therapy. The present study offers preclinical data to support further studies with deflazacort/doxycycline combined therapy in DMD clinical trials.

  8. Utility of skinfold thickness measurement in non-ambulatory patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Ishizaki, Masatoshi; Kedoin, Chika; Ueyama, Hidetsugu; Maeda, Yasushi; Yamashita, Satoshi; Ando, Yukio

    2017-01-01

    Nutritional disorders in Duchenne muscular dystrophy (DMD) worsen the medical condition. In particular, obesity is a serious problem that increases the risk of cardiomyopathy and affects nursing care. However, it is often difficult to evaluate body fatness in the advanced stages of DMD. Skinfold thickness measurement is a classical method to evaluate body fatness and is easily performed, even for bed-bound patients at home. We aimed to investigate the utility of skinfold thickness measurement in non-ambulatory DMD patients. Twenty-two patients with non-ambulatory, steroid-naive DMD ranging in age of 12-47 years were evaluated by body mass index (BMI), blood tests, measurement of triceps skinfold thickness (TSF), and abdominal computed tomography (CT) measurement of the areas of both subcutaneous and visceral fat. TSF showed good correlation with BMI (r = 0.80; p skinfold thickness measurement may be applicable as a screening tool in clinical practice where CT and magnetic resonance imaging assessment is often difficult in patients with advanced DMD. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. PRO-051, an antisense oligonucleotide for the potential treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Hammond, Suzan M; Wood, Matthew Ja

    2010-08-01

    PRO-051 (GSK-2402968), being developed by GlaxoSmithKline plc, under license from Leiden University Medical Center and Prosensa Therapeutics BV, is a 2'-O-methyl phosphorothioate antisense oligonucleotide for the potential treatment of Duchenne muscular dystrophy (DMD). The PRO-051 oligonucleotide sequence induces skipping of exon 51 of the dystrophin gene by binding to a sequence within the dystrophin pre-mRNA and masking the exon inclusion signals that are used for splicing. Removal of exon 51 from an exon 45 to 50, 47 to 50, 48 to 50, 49 to 50, 50, 52 or 52 to 63 deleted transcript allows restoration of the open reading frame and synthesis of an internally truncated, semi-functional dystrophin protein. By targeting exon 51, approximately 13% of patients with DMD could be treated, the largest proportion of patients that could benefit from targeting a single dystrophin exon. A proof-of-concept clinical trial of PRO-051 in patients with DMD demonstrated that a single intramuscular administration of PRO-051 induced exon skipping within muscle fibers adjacent to the injection site, while biopsies revealed dystrophin expression in treated but not control muscle fibers. At the time of publication, a phase I/IIa trial to evaluate subcutaneous delivery of PRO-051 had been completed, although full results were yet to be published.

  10. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

    Science.gov (United States)

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

  11. Duchenne Muscular Dystrophy: a Survey of Perspectives on Carrier Testing and Communication Within the Family.

    Science.gov (United States)

    Hayes, Brenna; Hassed, Susan; Chaloner, Jae Lindsay; Aston, Christopher E; Guy, Carrie

    2016-06-01

    Carrier testing is widely available for multiple genetic conditions, and several professional organizations have created practice guidelines regarding appropriate clinical application and the testing of minors. Previous research has focused on carrier screening, predictive testing, and testing for X-linked conditions. However, family perspectives on carrier testing for X-linked lethal diseases have yet to be described. In this study, we explored communication within the family about carrier testing and the perspectives of mothers of sons with an X-linked lethal disease, Duchenne muscular dystrophy (DMD). Twenty-five mothers of sons with DMD participated in an anonymous online survey. Survey questions included multiple choice, Likert scale, and open ended, short answer questions. Analysis of the multiple choice and Likert scale questions revealed that most mothers preferred a gradual style of communication with their daughters regarding risk status. In addition, most participants reported having consulted with a genetic counselor and found it helpful. Comparisons between groups, analyzed using Fisher's exact tests, found no differences in preferred style due to mother's carrier status or having a daughter. Thematic analysis was conducted on responses to open ended questions. Themes identified included the impact of family implications, age and maturity, and a desire for autonomy regarding the decision to discuss and undergo carrier testing with at-risk daughters, particularly timing of these discussions. Implications for genetic counseling practice are discussed.

  12. Left Ventricular Tonic Contraction as a Novel Biomarker of Cardiomyopathy in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Su, Jennifer A; Ramos-Platt, Leigh; Menteer, JonDavid

    2016-04-01

    Dilated cardiomyopathy (DCM) inevitably afflicts patients with Duchenne muscular dystrophy (DMD) as a consequence of cell death induced by unguarded calcium influx into cardiomyocytes. This mechanism may also inhibit muscle relaxation in early stages of cardiomyopathy. ACE inhibition (ACEi) is known to delay the onset and slow the progression of DCM in DMD. The objective of this study is to use echocardiography to assess for preclinical cardiac changes consistent with intracellular calcium dysregulation before the onset of overt ventricular dysfunction, and to evaluate how prophylactic ACEi may alter these pre-cardiomyopathic changes in the pediatric DMD population. We examined 263 echocardiograms from 70 pediatric patients with DMD. We defined abnormal tonic contraction (TC) as left ventricular internal dimension in diastole (LVIDd) Z-score < -1.5. In our cohort, we found that TC is detectable as early as 8 years of age, and most commonly affects patients between 11 and 15 years. This effect was independent of LV mass and systolic function. Prophylactic ACEi decreased the incidence of TC (p = 0.007) and preserved cardiac function (p < 0.0001). Left ventricular TC often precedes DCM in DMD, most commonly affecting the 11- to 15-year-old age range. TC is not related to ventricular hypertrophy, but rather may be a clinical correlate of the "calcium hypothesis" of DMD pathophysiology. LV TC is thus a promising biomarker for early detection of cardiomyopathy in DMD. ACEi prophylaxis suppresses LV TC and delays the development of DCM in DMD.

  13. The role of branched fibres in the pathogenesis of Duchenne muscular dystrophy.

    Science.gov (United States)

    Chan, S; Head, S I

    2011-06-01

    Branched fibres are a well-documented phenomenon of regenerating skeletal muscle. They are found in the muscles of boys with Duchenne muscular dystrophy (DMD), a severe condition of progressive muscle wasting caused by an absence of the sarcolemmal protein dystrophin, and in the muscles of the mdx mouse, an animal model of DMD. However, only a handful of studies have investigated how the physiological properties of these morphologically deformed fibres differ from those of normal fibres. These studies have found an association between the extent of fibre branching in mdx muscles and the susceptibility of these muscles to damage from eccentric contractions. They have also found that branched mdx muscle fibres cannot sustain maximal contractions in buffered Ca(2+) solutions, that branch points are sites of increased mechanical stress and that myofibrillar structure is greatly disturbed at branch points. These findings have important implications for understanding the function of dystrophin. It is commonly thought that the role of dystrophin is mechanical stabilization of the sarcolemma, as numerous studies have shown that eccentric contractions damage mdx muscle more than normal muscle. However, the finding that branched mdx fibres are mechanically weakened raises the question, is it the lack of dystrophin or is it the fibre branching that leads to the vulnerability of mdx muscle to contractile damage? The importance of this question to our understanding of the function of dystrophin warrants further research into the physiological properties of branched fibres and how they differ from morphologically normal fibres.

  14. Non-invasive assessment of muscle stiffness in patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Lacourpaille, Lilian; Hug, François; Guével, Arnaud; Péréon, Yann; Magot, Armelle; Hogrel, Jean-Yves; Nordez, Antoine

    2015-02-01

    Assessment of muscle mechanical properties may provide clinically valuable information for follow-up of patients with Duchenne muscular dystrophy (DMD) through the course of their disease. In this study we aimed to assess the effect of DMD on stiffness of relaxed muscles using elastography (supersonic shear imaging). Fourteen DMD patients and 13 control subjects were studied. Six muscles were measured at 2 muscle lengths (shortened and stretched): gastrocnemius medialis (GM); tibialis anterior (TA); vastus lateralis (VL); biceps brachii (BB); triceps brachii (TB); and abductor digiti minimi (ADM). Stiffness was significantly higher in DMD patients compared with controls for all the muscles (main effect for population, P < 0.033 in all cases), except for ADM. The effect size was small (d = 0.33 for ADM at both muscle lengths) to large (d = 0.86 for BB/stretched). Supersonic shear imaging is a sensitive non-invasive technique to assess the increase in muscle stiffness associated with DMD. © 2014 Wiley Periodicals, Inc.

  15. Glycosaminoglycan modifications in Duchenne muscular dystrophy: specific remodeling of chondroitin sulfate/dermatan sulfate.

    Science.gov (United States)

    Negroni, Elisa; Henault, Emilie; Chevalier, Fabien; Gilbert-Sirieix, Marie; Van Kuppevelt, Toin H; Papy-Garcia, Dulce; Uzan, Georges; Albanese, Patricia

    2014-08-01

    Widespread skeletal muscle degeneration and impaired regeneration lead to progressive muscle weakness and premature death in patients with Duchenne muscular dystrophy (DMD). Dystrophic muscles are progressively replaced by nonfunctional tissue because of exhaustion of muscle precursor cells and excessive accumulation of extracellular matrix (ECM). Sulfated glycosaminoglycans (GAGs) are components of the ECM and are increasingly implicated in the regulation of biologic processes, but their possible role in the progression of DMD pathology is not understood. In the present study, we performed immunohistochemical and biochemical analyses of endogenous GAGs in skeletal muscle biopsies of 10 DMD patients and 11 healthy individuals (controls). Immunostaining targeted to specific GAG species showed greater deposition of chondroitin sulfate (CS)/dermatan (DS) sulfate in DMD patient biopsies versus control biopsies. The selective accumulation of CS/DS in DMD biopsies was confirmed by biochemical quantification assay. In addition, high-performance liquid chromatography analysis demonstrated a modification of the sulfation pattern of CS/DS disaccharide units in DMD muscles. In conclusion, our data open up a new path of investigation and suggest that GAGs could represent a new and original therapeutic target for improving the success of gene or cell therapy for the treatment of muscular dystrophies.

  16. Melanocytes--a novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy.

    Science.gov (United States)

    Pellegrini, Camilla; Zulian, Alessandra; Gualandi, Francesca; Manzati, Elisa; Merlini, Luciano; Michelini, Maria E; Benassi, Luisa; Marmiroli, Sandra; Ferlini, Alessandra; Sabatelli, Patrizia; Bernardi, Paolo; Maraldi, Nadir M

    2013-06-01

    Dystrophin is a subsarcolemmal protein that, by linking the actin cytoskeleton to the extracellular matrix via dystroglycans, is critical for the integrity of muscle fibers. Here, we report that epidermal melanocytes, obtained from conventional skin biopsy, express dystrophin with a restricted localization to the plasma membrane facing the dermal-epidermal junction. In addition the full-length muscle isoform mDp427 was clearly detectable in melanocyte cultures as assessed by immunohistochemistry, RNA, and Western blot analysis. Melanocytes of Duchenne muscular dystrophy (DMD) patients did not express dystrophin, and the ultrastructural analysis revealed typical mitochondrial alterations similar to those occurring in myoblasts from the same patients. Mitochondria of melanocytes from DMD patients readily accumulated tetramethylrhodamine methyl ester, indicating that they are energized irrespective of the presence of dystrophin but, at variance from mitochondria of control donors, depolarized upon the addition of oligomycin, suggesting that they are affected by a latent dysfunction unmasked by inhibition of the ATP synthase. Pure melanocyte cultures can be readily obtained by conventional skin biopsies and may be a feasible and reliable tool alternative to muscle biopsy for functional studies in dystrophinopathies. The mitochondrial dysfunction occurring in DMD melanocytes could represent a promising cellular biomarker for monitoring dystrophinopathies also in response to pharmacological treatments.

  17. Quality of life and wishes in Duchenne Muscular Dystrophy: the perception of children and their parents

    Directory of Open Access Journals (Sweden)

    Benito Arias Martínez

    2009-12-01

    Full Text Available Objective: To assess the agreement between children with Duchenne Muscular Dystrophy (DMD and their parents regarding the perception of quality of life (QOL and the wishes expressed by children. Methods: The study involved 14 patients (median age = 9.9 yearsold followed up in Sarah Rehabilitation Center – Fortaleza, Brazil and their parents. The following instruments were used: AUQEI questionnaire (Autoquestionnaire Qualité de Vie Enfant Imagé and Three Wishes Projective Technique, this being analyzed by Nereo & Hinton’s system of categories (2003. Results: The analysis of AUQEI showed a good agreement with ICC (intraclass correlation coefficient = 0,699 and a positive and significant correlation between scores of both children and their parents (rho = 0.54, p < 0.05. The Three Wishes also showed a good agreement, mainly in the categories of Material Goods and Activities. Conclusions: Despite children with DMD and their parents exhibited similar perceptions of the QOL and wishes, we suggest that both be heard in respect to aspects of the rehabilitation program. This study provides additional data concerning the need for child QOL assessment instruments that include parallel versions directed to the children and their parents.

  18. Utility of MLPA in mutation analysis and carrier detection for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Prashant K Verma

    2012-01-01

    Full Text Available Context: Multiplex ligation probe amplification (MLPA is a new technique to identify deletions and duplications and can evaluate all 79 exons in dystrophin gene in patients with Duchenne muscular dystrophy (DMD. Being semi-quantitative, MLPA is also effective in detecting duplications and carrier testing of females; both of which cannot be done using multiplex PCR. It has found applications in diagnostics of many genetic disorders. Aim: To study the utility of MLPA in diagnosis and carrier detection for DMD. Materials and Methods: Mutation analysis and carrier detection was done by multiplex PCR and MLPA and the results were compared. Results and Conclusions: We present data showing utility of MLPA in identifying mutations in cases with DMD/BMD. In the present study using MLPA, we identified mutations in additional 5.6% cases of DMD in whom multiplex PCR was not able to detect intragenic deletions. In addition, MLPA also correctly confirmed carrier status of two obligate carriers and revealed carrier status in 6 of 8 mothers of sporadic cases.

  19. Serum Creatinine Level: A Supplemental Index to Distinguish Duchenne Muscular Dystrophy from Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Huili Zhang

    2015-01-01

    Full Text Available Background. To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn level reflects disease severity. Methods. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Results. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r=-0.793 and partial correlation analysis after adjustment for age, height, and weight (r=-0.791; both P<0.01. Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations (Z=-4.716, P<0.01 and in Becker muscular dystrophy (BMD patients than Duchenne muscular dystrophy (DMD patients at ages 4, 5, 7, and 9 yr (all P<0.0125. After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β=7.140, t=6.277, P<0.01. Conclusions. Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

  20. "Molecular Analysis of Iranian Patients with Duchenne/Becker Muscular Dystrophies"

    Directory of Open Access Journals (Sweden)

    S Kheradmand kia

    2003-09-01

    Full Text Available Duchenne Muscular Dystrophy (DMD and the milder allelic Becker Muscular Dystrophy (BMD are X-linked disorders. Both DMD & BMD result from heterogenous mutation in the dystrophin gene and in about 65% of the cases one or more exons of the gene are deleted or duplicated. One third of cases arise from new mutation and the rest are familial. To analyze the prevalence of deletion in Iranian patients, a deletion screening was performed on group 18 exons of dystrophin gene. Deletions were detected in 56.8% of patients. Seventy four percent of deleted exons were located in the major hot spot region, whereas 26% were in the minor hot spot one. The most frequently deleted exons were exons 50, 48 & 47 16.2%, 16.2% & 12% respectively. No deletion was detected in exon 43. The intragenic RFLP analysis (pERT87-15/BamHI & pERT87-8/Taql were carried out on DNA samples obtained from 22 Iranian unrelated families (196 males & females showing DMD & BMD clinical symptoms, that 45% of them had informative patterns. The percentage of heterozygosity was 22.75% for BamHl intragenic RFLP, and 22.75% for Taql intragenic RFLP.

  1. Loss of heterozygosity and carrier identification in Duchenne muscular dystrophy: a familiar case with recombination event

    Directory of Open Access Journals (Sweden)

    Fonseca-Mendoza Dora Janeth

    2012-04-01

    Full Text Available Duchenne/Becker Muscular Dystrophy (DMD/BMD is an X-linked recessive disease characterizedby muscular weakness. It is caused by mutations on the dystrophin gen. Loss of heterozygosityallows us to identify female carriers of deletions on the dystrophin gen. Objective: identifyfemale carriers in a family with a patient affected by DMD. Material and methods: nine familymembers and the affected child were analyzed using DNA extraction and posterior amplificationof ten STRs on the dystrophin gen. Haplotypes were constructed and the carrier status determinedin two of the six women analyzed due to loss of heterozygosity in three STRs. Additionally, weobserved a recombination event. Conclusions: loss of heterozygosity allows us to establish witha certainty of 100% the carrier status of females with deletions on the dystrophin gen. By theconstruction of haplotypes we were able to identify the X chromosome with the deletion in twoof the six women analyzed. We also determined a recombination event in one of the sisters of theaffected child. These are described with a high frequency (12%. A possible origin for the mutationis a gonadal mosaicism in the maternal grandfather or in the mother of the affected childin a very early stage in embryogensis. This can be concluded using the analysis of haplotypes.

  2. Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, L.S.; Hoffman, E.P. (Univ. of Pittsburgh Schoool of Medicine, Pittsburgh, PA (United States)); Tarleton, J. (Self Memorial Hospital, Greenwood, SC (United States)); Popovich, B. (Children' s Hosptial and Health Center, San Diego, CA (United States)); Seltzer, W.K. (Univ. of Colorado Health Sciences Center, Denver, CO (United States))

    1992-10-01

    The authors have developed a fast and accurate PCR-based linkage and carrier detection protocol for families of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients with or without detectable deletions of the dystrophin gene, using fluorescent PCR products analyzed on an automated sequencer. When a deletion is found in the affected male DMD/BMD patient by standard multiplex PCR, fluorescently labeled primers specific for the deleted and nondeleted exon(s) are used to amplify the DNA of at-risk female relatives by using multiplex PCR at low cycle number (20 cycles). The products are then quantitatively analyzed on an automatic sequencer to determine whether they are heterozygous for the deletion and thus are carriers. As a confirmation of the deletion data, and in cases in which a deletion is not found in the proband, fluorescent multiplex PCR linkage is done by using four previously described polymorphic dinucleotide sequences. The four (CA)[sub n] repeats are located throughout the dystrophin gene, making the analysis highly informative and accurate. The authors present the successful application of this protocol in families who proved refractory to more traditional analyses. 22 refs., 3 figs.

  3. Exon skipping and Duchenne muscular dystrophy: Hope, hype and how feasible?

    Directory of Open Access Journals (Sweden)

    Wilton Steve

    2008-01-01

    Full Text Available Duchenne muscular dystrophy (DMD, the most common and serious form of childhood muscle wasting is generally caused by protein-truncating mutations in the large DMD gene. Specific removal of an exon from a defective DMD gene transcript has the potential to allow synthesis of a semi-functional dystrophin, thereby reducing the severity and presumably progression of muscle wasting. The efficacy of this treatment will vary greatly between the different mutations that preclude the synthesis of a functional dystrophin. Restoration of the reading frame from a large multi-exon genomic deletion, typically greater than 36 exons, may lead to synthesis of a protein with only partial function and limited clinical benefit, whereas excising a nonsense mutation in a redundant exon should generate a near normal dystrophin. A clinical trial has recently confirmed proof-of-principle that exclusion of Exon 51 from human dystrophin mRNAs, carrying frame-shifting deletions adjacent to this exon, results in dystrophin expression. No major side-effects after local administration of the antisense oligomer were reported. Additional trials are underway, targeting the same exon but using an oligomer of different backbone chemistry. If functional dystrophin synthesis is demonstrated, and safety issues are addressed, subsequent trials will involve systemic delivery. Great challenges are ahead, some technical; establishing an effective delivery regimen, some ethical; choosing subsequent targets for therapy, and others of an administrative and regulatory nature.

  4. Genetic polymorphism in muscle biopsies of Duchenne and Becker muscular dystrophy patients.

    Directory of Open Access Journals (Sweden)

    Anand A

    1999-07-01

    Full Text Available Duchenne muscular dystrophy (DMD, with an incidence of one in 3500 male new borns, and its milder variant, Becker muscular dystrophy (BMD, are allelic X-linked recessive disorders, caused by mutations in the gene coding for dystrophin, a 427 kD cytoskeleton protein. There are no available molecular markers to differentiate these two. The purpose of this study was to study genetic polymorphism in muscular dystrophy and explore its potential in discriminating these two allelic forms of the disease. The results revealed unambiguously the presence of three transcripts : 598bp, 849bp and 1583bp long which are selectively expressed in the muscles afflicted with muscular dystrophy as compared to the normal muscle. 1583bp gene transcript was conspicuously present in the muscle tissues of both DMD and BMD patients whereas 598bp and 849bp long transcripts were exclusively present in DMD but not in BMD patients or normal human subjects. These gene transcripts had no sequence homology with dystrophin gene and these were also present in the families belonging to DMD and BMD patients. These results point to the fact that based upon the selective expression of these three gene transcripts, one could not only differentiate between DMD and BMD diseases at the molecular level, but also between normal and dystrophic muscle. Further, these findings also reveal that apart from dystrophin gene, these gene transcripts may also be responsible for the differential progression of DMD/BMD phenotype.

  5. Dystrophin and the two related genetic diseases, Duchenne and Becker muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Elisabeth Le Rumeur

    2015-07-01

    Full Text Available Mutations of the dystrophin DMD gene, essentially deletions of one or several exons, are the cause of two devastating and to date incurable diseases, Duchenne (DMD and Becker (BMD muscular dystrophies. Depending upon the preservation or not of the reading frame, dystrophin is completely absent in DMD, or present in either a mutated or a truncated form in BMD. DMD is a severe disease which leads to a premature death of the patients. Therapy approaches are evolving with the aim to transform the severe DMD in the BMD form of the disease by restoring the expression of a mutated or truncated dystrophin. These therapies are based on the assumption that BMD is a mild disease. However, this is not completely true as BMD patients are more or less severely affected and no molecular basis of this heterogeneity of the BMD form of the disease is yet understood. The aim of this review is to report for the correlation between dystrophin structures in BMD deletions in view of this heterogeneity and to emphasize that examining BMD patients in details is highly relevant to anticipate for DMD therapy effects.

  6. Arquitetura comparativa dos pulmões de camundongos normais e afetados pela Distrofia Muscular de Duchenne

    Directory of Open Access Journals (Sweden)

    Thais B. Lessa

    2015-12-01

    Full Text Available Resumo: A Distrofia Muscular de Duchenne (DMD é uma doença genética de caráter recessivo que caracterizada por fraqueza muscular progressiva de cintura pélvica e escapular evoluindo para insuficiência respiratória e, ou cardíaca. O camundongo mdx é um modelo amplamente utilizado para estudos da DMD. Apesar do fenótipo destes animais serem mais suave, estes apresentam o principal músculo respiratório, o diafragma com morfologia e bioquímica semelhante à DMD humana, fato este que pode comprometer a função respiratória e consequentemente os pulmões. Foi realizado um estudo anatômico descritivo do parênquima pulmonar dos pulmões de 5 animais modelo mdx comparando estes com os pulmões de 5 camundongos BALB/C57 (Mus musculus. Os pulmões foram analisados macroscopicamente e através de microscopia de luz e eletrônica de varredura. Os achados sugerem que o modelo mdx apresenta morfologia pulmonar semelhante aos camundongos BALB/C57 e que seu uso deve ser cauteloso e criterioso em ensaios clínicos que aborde este órgão.

  7. Gene therapies that restore dystrophin expression for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Robinson-Hamm, Jacqueline N; Gersbach, Charles A

    2016-09-01

    Duchenne muscular dystrophy is one of the most common inherited genetic diseases and is caused by mutations to the DMD gene that encodes the dystrophin protein. Recent advances in genome editing and gene therapy offer hope for the development of potential therapeutics. Truncated versions of the DMD gene can be delivered to the affected tissues with viral vectors and show promising results in a variety of animal models. Genome editing with the CRISPR/Cas9 system has recently been used to restore dystrophin expression by deleting one or more exons of the DMD gene in patient cells and in a mouse model that led to functional improvement of muscle strength. Exon skipping with oligonucleotides has been successful in several animal models and evaluated in multiple clinical trials. Next-generation oligonucleotide formulations offer significant promise to build on these results. All these approaches to restoring dystrophin expression are encouraging, but many hurdles remain. This review summarizes the current state of these technologies and summarizes considerations for their future development.

  8. Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model

    Directory of Open Access Journals (Sweden)

    Karima Relizani

    2017-09-01

    Full Text Available Antisense oligonucleotides (AONs hold promise for therapeutic splice-switching correction in many genetic diseases. However, despite advances in AON chemistry and design, systemic use of AONs is limited due to poor tissue uptake and sufficient therapeutic efficacy is still difficult to achieve. A novel class of AONs made of tricyclo-DNA (tcDNA is considered very promising for the treatment of Duchenne muscular dystrophy (DMD, a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment. Herein, we report the efficacy and toxicology profile of a 13-mer tcDNA in mdx mice. We show that systemic delivery of 13-mer tcDNA allows restoration of dystrophin in skeletal muscles and to a lower extent in the brain, leading to muscle function improvement and correction of behavioral features linked to the emotional/cognitive deficiency. More importantly, tcDNA treatment was generally limited to minimal glomerular changes and few cell necroses in proximal tubules, with only slight variation in serum and urinary kidney toxicity biomarker levels. These results demonstrate an encouraging safety profile for tcDNA, albeit typical of phosphorothiate AONs, and confirm its therapeutic potential for the systemic treatment of DMD patients.

  9. Valley sign in Becker muscular dystrophy and outliers of Duchenne and Becker muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Pradhan Sunil

    2004-04-01

    Full Text Available Valley sign has been described in patients with Duchenne muscular dystrophy (DMD. As there are genetic and clinical similarities between DMD and Becker muscular dystrophy (BMD, this clinical sign is evaluated in this study in BMD and DMD/BMD outliers. To evaluate the sign, 28 patients with Becker muscular dystrophy (BMD, 8 DMD/BMD outliers and 44 age-matched male controls with other neuromuscular diseases were studied. The sign was examined after asking patients to abduct their arms to about 90ºwith hands directed upwards; the muscle bulk over the back of the shoulders was observed. The sign was considered positive if the infraspinatus and deltoid muscles were enlarged and between these two muscles, the muscles forming the posterior axillary fold were wasted as if there were a valley between the two mounts. Twenty-five BMD patients and 7 DMD/BMD outliers had positive valley sign. However, it was less remarkable in comparison to DMD. It was absent in all the 44 controls. It was concluded that the presence of valley sign may help in differentiating BMD from other progressive neuromuscular disorders of that age group.

  10. Contribution of oxidative stress to pathology in diaphragm and limb muscles with Duchenne muscular dystrophy.

    Science.gov (United States)

    Kim, Jong-Hee; Kwak, Hyo-Bum; Thompson, LaDora V; Lawler, John M

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease that makes walking and breathing difficult. DMD is caused by an X-linked (Xp21) mutation in the dystrophin gene. Dystrophin is a scaffolding protein located in the sarcolemmal cytoskeleton, important in maintaining structural integrity and regulating muscle cell (muscle fiber) growth and repair. Dystrophin deficiency in mouse models (e.g., mdx mouse) destabilizes the interface between muscle fibers and the extracellular matrix, resulting in profound damage, inflammation, and weakness in diaphragm and limb muscles. While the link between dystrophin deficiency with inflammation and pathology is multi-factorial, elevated oxidative stress has been proposed as a central mediator. Unfortunately, the use of non-specific antioxidant scavengers in mouse and human studies has led to inconsistent results, obscuring our understanding of the importance of redox signaling in pathology of muscular dystrophy. However, recent studies with more mechanistic approaches in mdx mice suggest that NAD(P)H oxidase and nuclear factor-kappaB are important in amplifying dystrophin-deficient muscle pathology. Therefore, more targeted antioxidant therapeutics may ameliorate damage and weakness in human population, thus promoting better muscle function and quality of life. This review will focus upon the pathobiology of dystrophin deficiency in diaphragm and limb muscle primarily in mouse models, with a rationale for development of targeted therapeutic antioxidants in DMD patients.

  11. Intrinsic laryngeal muscles are spared from myonecrosis in the mdx mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Marques, Maria Julia; Ferretti, Renato; Vomero, Viviane Urbini; Minatel, Elaine; Neto, Humberto Santo

    2007-03-01

    Intrinsic laryngeal muscles share many anatomical and physiological properties with extraocular muscles, which are unaffected in both Duchenne muscular dystrophy and mdx mice. We hypothesized that intrinsic laryngeal muscles are spared from myonecrosis in mdx mice and may serve as an additional tool to understand the mechanisms of muscle sparing in dystrophinopathy. Intrinsic laryngeal muscles and tibialis anterior (TA) muscle of adult and aged mdx and control C57Bl/10 mice were investigated. The percentage of central nucleated fibers, as a sign of muscle fibers that had undergone injury and regeneration, and myofiber labeling with Evans blue dye, as a marker of myofiber damage, were studied. Except for the cricothyroid muscle, none of the intrinsic laryngeal muscles from adult and old mdx mice showed signs of myofiber damage or Evans blue dye labeling, and all appeared to be normal. Central nucleation was readily visible in the TA of the same mdx mice. A significant increase in the percentage of central nucleated fibers was observed in adult cricothyroid muscle compared to the other intrinsic laryngeal muscles, which worsened with age. Thus, we have shown that the intrinsic laryngeal muscles are spared from the lack of dystrophin and may serve as a useful model to study the mechanisms of muscle sparing in dystrophinopathy.

  12. Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Tirsa L. E. van Westering

    2015-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death. The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced damage. Moreover, it pathologically alters intracellular calcium (Ca2+ concentration, neuronal nitric oxide synthase (nNOS localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy. Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense. Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping. Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction. However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function. This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca2+, nNOS and mitochondrial dysregulation. It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart.

  13. Xp21/A translocation: a rarely considered genetic cause for manifesting carriers of duchenne muscular dystrophy.

    Science.gov (United States)

    Trippe, Heike; Wieczorek, Stefan; Kötting, Judith; Kress, Wolfram; Schara, Ulrike

    2014-10-01

    Clinically manifesting carriers of Duchenne muscular dystrophy (DMD) are rare among the pediatric population. A standardized diagnostic procedure in supposed DMD carriers entails performing a Multiplex Ligation-dependent Probe Amplification analysis of the DMD gene first, then taking a muscle biopsy to confirm reduced dystrophin levels and/or finally a complete sequencing of the DMD gene. We describe a girl with high-elevated creatine kinase, myalgia, and cardiomyopathy. Muscle biopsy showed a dystrophic pattern and nearly absent expression of dystrophin. Diagnosis could not be confirmed by molecular genetic procedures. Because of a mild mental retardation, a chromosome analysis and molecular karyotyping were performed, revealing a balanced translocation t(X;4)(p21;q31).arr(1-22,X)x2 dn with breakpoint on the X-chromosome within an intron of the DMD gene. The inactivation of the nonderivative X-chromosome was found to be in a nonrandom pattern, resulting in a functionally balanced karyotype and thus leading to a manifesting DMD carrier in this case. Chromosome analysis should be recommended in cases of genetically unsolved DMD carriers as a part of the standard genetic procedures.

  14. Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy

    Science.gov (United States)

    Hogarth, Marshall W.; Houweling, Peter J.; Thomas, Kristen C.; Gordish-Dressman, Heather; Bello, Luca; Vishwanathan, V.; Chidambaranathan, S.; Douglas Biggar, W.; McAdam, Laura C.; Mah, Jean K.; Tulinius, Mar; Cnaan, Avital; Morgenroth, Lauren P.; Leshner, Robert; Tesi-Rocha, Carolina; Thangarajh, Mathula; Duong, Tina; Kornberg, Andrew; Ryan, Monique; Nevo, Yoram; Dubrovsky, Alberto; Clemens, Paula R.; Abdel-Hamid, Hoda; Connolly, Anne M.; Pestronk, Alan; Teasley, Jean; Bertorini, Tulio E.; Webster, Richard; Kolski, Hanna; Kuntz, Nancy; Driscoll, Sherilyn; Bodensteiner, John B.; Carlo, Jose; Gorni, Ksenija; Lotze, Timothy; Day, John W.; Karachunski, Peter; Henricson, Erik K.; Abresch, Richard T.; McDonald, Craig M.; Pegoraro, Elena; Hoffman, Eric P.; Head, Stewart I.; North, Kathryn N.

    2017-01-01

    Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10 m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that α-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients. PMID:28139640

  15. Tongue pressure during swallowing is decreased in patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Hamanaka-Kondoh, Sato; Kondoh, Jugo; Tamine, Ken-Ichi; Hori, Kazuhiro; Fujiwara, Shigehiro; Maeda, Yoshinobu; Matsumura, Tsuyoshi; Yasui, Kumiko; Fujimura, Harutoshi; Sakoda, Saburo; Ono, Takahiro

    2014-06-01

    Although dysphagia is a life-threatening problem in patients with Duchenne muscular dystrophy (DMD), the pathophysiology of oral stage dysphagia is yet to be understood. The present study investigated the tongue motor deficit during swallowing in patients with DMD and its relationship with disease-specific palatal morphology. Tongue pressure during swallowing water was recorded in 11 male patients with DMD and 11 age- and sex-matched healthy subjects using an intra-oral sensor with five measuring points, and the state of tongue pressure production was compared between the groups. Palatal morphology was assessed by a non-contact three-dimensional scanner on maxillary plaster models. In patients with DMD, the normal sequential order of tongue-palate contact was lost and the maximal magnitude and integrated value of tongue pressure on the mid-anterior part of palate were smaller than those in healthy subjects. The width of the palate in patients was greater than that in healthy subjects and the depth of the palate in patients had a negative correlation with tongue pressure magnitude on the median palate. Our results suggested that the deteriorated tongue motor kinetics prevented tongue movement during swallowing that was appropriate for the depth of the palate and affects the state of tongue pressure production during swallowing.

  16. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Thibaut Larcher

    Full Text Available A few animal models of Duchenne muscular dystrophy (DMD are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

  17. The effects of myotonic dystrophy and Duchenne muscular dystrophy on the orofacial muscles and dentofacial morphology.

    Science.gov (United States)

    Kiliaridis, S; Katsaros, C

    1998-12-01

    This article takes a closer view of two of the less rare myopathies, myotonic dystrophy (MyD) and Duchenne muscular dystrophy (DMD). A high prevalence of malocclusions was found among the patients affected by these diseases. The development of the malocclusions in MyD patients seems to be strongly related to the vertical aberration of their craniofacial growth due to the involvement of the masticator, muscles in association with the possibly less affected suprahyoid musculature. Thus, a new situation is established around the teeth transversely. The lowered tongue is not in a position to counterbalance the forces developed during the lowering of the mandible by the stretched facial musculature. This may affect the teeth transversely, decreasing the width of the palate and causing posterior crossbite. The lowered position of the mandible, in combination with the decreased biting forces, may permit an overeruption of the posterior teeth, with increased palatal vault height and development of anterior open bite. The development of the malocclusions in DMD patients also seems to be strongly related to the involvement of the orofacial muscles by the disease. However, the posterior crossbite is not developed owing to the narrow maxillary arch, as is the case in MyD patients. On the contrary, the posterior crossbite in DMD is due to the transversal expansion of the mandibular arch, possibly because of the decreased tonus of the masseter muscle near the molars, in combination with the enlarged hypotonic tongue and the predominance of the less affected orbicularis oris muscle.

  18. Variables associated with upper extremity function in patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Janssen, Mariska M H P; Hendriks, Jan C M; Geurts, Alexander C H; de Groot, Imelda J M

    2016-09-01

    Preserving upper extremity (UE) function in patients with Duchenne muscular dystrophy (DMD) is extremely important as it is related to independence and quality of life. For clinical decision making, knowledge of variables associated with UE function is necessary. This knowledge is, however, limited. Therefore, this study aims to gain more insight into the variables associated with UE function in DMD. Data from an international web-based questionnaire on UE function, obtained from 213 DMD patients, were used. Six dependent variables regarding UE function were used in multivariable linear regression analyses. In addition, 26 independent variables regarding patient characteristics, medication, therapy, supportive aids, pain, stiffness and participation were used. Twelve independent variables showed a significant relation to UE function. Variables with a negative relation to UE function were: later disease stage, occurrence of scoliosis, higher age, use of UE splints, more frequent stiffness complaints, more limitations due to stiffness, more frequent elbow pain, and having physical therapy. A positive relation with UE function was seen for going to school or work, use of corticosteroids, higher BMI, and higher age at diagnosis. These variables explained 56-81 % of the variation of the different measures of UE function. Knowledge of variables associated with UE function is very important in the clinical management of DMD patients. The results of this study suggest that corticosteroid use and participation in school and work related activities are positively related to UE function in DMD patients, as well as reducing pain and stiffness and preventing scoliosis.

  19. Mutational spectrum of Duchenne muscular dystrophy in Spain: Study of 284 cases.

    Science.gov (United States)

    Vieitez, I; Gallano, P; González-Quereda, L; Borrego, S; Marcos, I; Millán, J M; Jairo, T; Prior, C; Molano, J; Trujillo-Tiebas, M J; Gallego-Merlo, J; García-Barcina, M; Fenollar, M; Navarro, C

    Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Evaluation of plantar flexion contracture contribution during the gait of children with Duchenne muscular dystrophy.

    Science.gov (United States)

    Gaudreault, Nathaly; Gravel, Denis; Nadeau, Sylvie

    2009-06-01

    Because of extensor weakness, children with Duchenne muscular dystrophy (DMD) maintain internal flexion moments at the joints of the lower extremities when they walk. We believe that at the ankle, the plantar flexion moments caused by contractures may contribute significantly to the production of the net ankle flexion moment during the gait in these children. The goal of the present study is to quantify ankle plantar flexion passive moments that may be associated with the presence of flexion contractures and to estimate their contribution to the net moment during the gait of children with DMD. Kinematic and kinetic parameters were collected during gait of eleven subjects with DMD. Ankle plantar flexion passive moments were also measured experimentally during the same session. Fourteen control children participated in the study in order to have normal reference values. The presence of ankle plantar flexion contractures in children with DMD was reflected by a rigidity coefficient obtained at a common moment of -7 Nm that was higher for these children (0.75 Nm/degrees vs. 0.48 Nm/degrees; p<0.05). The relative passive moment contribution to the net plantar flexion moments was higher for the children with DMD at the end of the lengthening phase of the plantar flexors (25% vs. 18%; p<0.05). We believe that the passive moments can compensate for the presence of progressive muscle weakness in the children with DMD and help these children with gait.

  1. A method to evaluate contractures effects during the gait of children with Duchenne dystrophy.

    Science.gov (United States)

    Gaudreault, Nathaly; Gravel, Denis; Nadeau, Sylvie; Desjardins, Pierre; Brière, Anabèle

    2007-03-01

    Joint contractures are the second major impairment affecting the locomotor system of children with Duchenne muscular dystrophy (DMD). While the negative influence of joint contractures has been documented, the passive moments produced by joint contractures could benefit the gait of patients with muscle weakness. We describe a biomechanical model that quantifies the mechanical contribution of ankle and hip flexion contractures to the gait of DMD children. Kinematic and kinetic parameters were measured under the same experimental conditions during the gait and passive resistance assessment of two subjects: one healthy child as a control, and one child with DMD. The child with DMD had a plantar flexion contracture and a greater ankle stiffness coefficient than the control child. During gait, the contribution of the ankle passive moment to the net moment was more important for the child with DMD than for the control child. At the hip, passive joint moments and passive moment contribution were more important for the control child but this was not related to the presence of hip flexion contracture. These preliminary results suggest the model might be used to evaluate contractures effect on a larger cohort of subjects.

  2. The first exon duplication mouse model of Duchenne muscular dystrophy: A tool for therapeutic development.

    Science.gov (United States)

    Vulin, Adeline; Wein, Nicolas; Simmons, Tabatha R; Rutherford, Andrea M; Findlay, Andrew R; Yurkoski, Jacqueline A; Kaminoh, Yuuki; Flanigan, Kevin M

    2015-11-01

    Exon duplication mutations account for up to 11% of all cases of Duchenne muscular dystrophy (DMD), and a duplication of exon 2 is the most common duplication in patients. For use as a platform for testing of duplication-specific therapies, we developed a mouse model that carries a Dmd exon 2 duplication. By using homologous recombination we duplicated exon 2 within intron 2 at a location consistent with a human duplication hotspot. mRNA analysis confirms the inclusion of a duplicated exon 2 in mouse muscle. Dystrophin expression is essentially absent by immunofluorescent and immunoblot analysis, although some muscle specimens show very low-level trace dystrophin expression. Phenotypically, the mouse shows similarities to mdx, the standard laboratory model of DMD. In skeletal muscle, areas of necrosis and phagocytosis are seen at 3 weeks, with central nucleation prominent by four weeks, recapitulating the "crisis" period in mdx. Marked diaphragm fibrosis is noted by 6 months, and remains unchanged at 12 months. Our results show that the Dup2 mouse is both pathologically (in degree and distribution) and physiologically similar to mdx. As it recapitulates the most common single exon duplication found in DMD patients, this new model will be a useful tool to assess the potential of duplicated exon skipping.

  3. Duchenne muscular dystrophy drug discovery - the application of utrophin promoter activation screening.

    Science.gov (United States)

    Moorwood, Catherine; Khurana, Tejvir S

    2013-05-01

    Duchenne muscular dystrophy (DMD) is a devastating genetic muscle wasting disease caused by mutations in the DMD gene that in turn lead to an absence of dystrophin. Currently, there is no definitive therapy for DMD. Gene- and cell-based therapies designed to replace dystrophin have met some degree of success, as have strategies that seek to improve the dystrophic pathology independent of dystrophin. In this review the authors focus on utrophin promoter activation-based strategies and their implications on potential therapeutics for DMD. These strategies in common are designed to identify drugs/small molecules that can activate the utrophin promoter and would allow the functional substitution of dystrophin by upregulating utrophin expression in dystrophic muscle. The authors provide an overview of utrophin biology with a focus on regulation of the utrophin promoter and discuss current attempts in identifying utrophin promoter-activating molecules using high-throughput screening (HTS). The characterisation of utrophin promoter regulatory mechanisms coupled with advances in HTS have allowed researchers to undertake screens and identify a number of promising lead compounds that may prove useful for DMD. In principle, these pharmacological compounds offer significant advantages from a translational viewpoint for developing DMD therapeutics.

  4. Living with severe physical impairment, Duchenne's muscular dystrophy and home mechanical ventilation.

    Science.gov (United States)

    Dreyer, Pia S; Steffensen, Birgit F; Pedersen, Birthe D

    2010-08-02

    To study life-experiences of people living with Duchenne's muscular dystrophy (DMD), home mechanical ventilation (HMV) and physical impairment. Since the introduction of invasive HMV in the late 1980s people with DMD in Denmark live longer and have the experience of adulthood and a high degree of physical dependency. Nineteen patients with DMD and invasive HMV were interviewed in 2007. The interviews were recorded, transcribed verbatim and analysed according to a method inspired by Ricoeur's theory of interpretation. HMV not only extended the participants lifespan, it also gave them the capacity to live an active life. They were totally dependent in everyday living, but in spite of this, they did not see themselves as physically impaired. They realised that there were activities that were physically impossible, but they considered themselves to be just the same person they had always been. This dependency was described as "independent dependency". The lived-experience of physical impairment is found to be "independent dependency" in an active life. To solve problems with loneliness, society needs to work with prejudice and misunderstanding and for better physical accessibility to enable full participation.

  5. Quantitative MR evaluation of body composition in patients with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Pichiecchio, Anna; Uggetti, Carla; Egitto, Maria Grazia [Department of Neuroradiology, Istituto Neurologico ' ' Fondazione C.Mondino' ' I.R.C.C.S, Via Palestro, 3, 27100 Pavia (Italy); Berardinelli, Angela; Orcesi, Simona; Gorni, Ksenija Olga Tatiana [Department of Neuropsychiatry, Istituto Neurologico ' ' Fondazione C.Mondino' ' I.R.C.C.S, Via Palestro, 3, 27100 Pavia (Italy); Zanardi, Cristina; Tagliabue, Anna [Department of Human Nutrition, Cascina Cravino, Via Bassi, 23, 27100 Pavia (Italy)

    2002-11-01

    The aim of this study was to propose a quantitative MR protocol with very short acquisition time and good reliability in volume construction, for the evaluation of body composition in patients affected by Duchenne muscular dystrophy (DMD). This MR protocol was compared with common anthropometric evaluations of the same patients. Nine boys affected by DMD, ranging in age from 6 to 12 years, were selected to undergo MR examination. Transversal T1-weighted spin-echo sequences (0.5T; TR 300 ms, TE 10 ms, slice thickness 10 mm, slice gap 1 mm) were used for all acquisitions, each consisting of 8 slices and lasting just 54 s. Whole-body examination needed an average of nine acquisitions. Afterwards, images were downloaded to an independent workstation and, through their electronic segmentation with a reference filter, total volume and adipose tissue volumes were calculated manually. This process took up to 2 h for each patient. The MR data were compared with anthropometric evaluations. Affected children have a marked increase in adipose tissue and a decrease in lean tissue compared with reference healthy controls. Mean fat mass calculated by MR is significantly higher than mean fat mass obtained using anthropometric measurements (p<0.001). Our MR study proved to be accurate and easy to apply, although it was time-consuming. We recommend it in monitoring the progression of the disease and planning DMD patients' diet. (orig.)

  6. Carrier detection of Duchenne muscular dystrophy in Colombian families by microsatellite analysis.

    Directory of Open Access Journals (Sweden)

    Dora Fonseca

    2009-11-01

    Full Text Available Introducción: Las distrofias musculares de Duchenne y Becker son enfermedades recesivas ligadas al cromosoma X; la identificación de portadoras se puede hacer por métodos directos cuando se ha identificado la mutación, o por indirectos como el análisis de haplotipos. Objetivo: Se busca establecer mediante análisis de STRs y construcción de haplotipos el estado de portadora o no portadora en 37 familias con afectados por DMD/DMB. Metodología: Se estudiaron 174 personas mediante el análisis de 10 STRs intra y extragénicos del gen de la distrofina y la construcción de haplotipos para la identificación del ligado a la mutación. Resultados: Con la metodología mencionada se logró determinar el estado de portadora en 89.2% de las mujeres participantes, de las cuales 65.7% eran portadoras y 23.5% no portadoras. Conclusiones: El análisis indirecto mediante construcción de haplotipos permitió establecer el estado de portadora en una gran proporción de la población analizada de mujeres y permitió brindar un adecuado asesoramiento genético.

  7. Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study.

    Science.gov (United States)

    Rae, C; Scott, R B; Thompson, C H; Dixon, R M; Dumughn, I; Kemp, G J; Male, A; Pike, M; Styles, P; Radda, G K

    1998-10-08

    Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. We obtained localised 1H magnetic resonance spectra from the left frontal lobe and left cerebellum of 15 boys with DMD (mean age 106 months+/-32) and 15 similarly aged control boys (mean age 115 months+/-31); all boys underwent a battery of neuropsychological tests. We found a significant (PAnalogies Test (MAT). The MAT is a test of visuo-spatial ability and non-verbal reasoning which requires neither manual dexterity nor a verbal response for an adequate performance. A comparison of DMD boys whose cerebellar Cho/NA fell within 2 standard deviations of the control norm (0.56+/-0.24) with DMD boys whose cerebellar Cho/NA was outside this range (i.e. >0.80) revealed a significant difference in ability on the MAT (P<0.05). DMD boys whose Cho/NA ratio is more than two standard deviations higher than controls perform significantly better on the MAT than DMD boys whose Cho/NA ratio is within the normal range. This finding suggests that the observed elevation in Cho/NA and Cho/creatine is not associated with intellectual deficit (as sampled by the MAT), and may represent a compensatory mechanism. The possible interpretations of these metabolic changes are discussed.

  8. [Relationship between gene mutations and intelligence in children with Duchenne muscular dystrophy].

    Science.gov (United States)

    Wang, Li-Bo; Ma, Hong-Wei; Wang, Lin; Tian, Xiao-Bo; Hu, Man; Ren, Shuang; Tan, Ying-Hua

    2011-10-01

    To study the level of intelligence in children with Duchenne muscular dystrophy (DMD), and the relationship between the level of intelligence and gene mutations. One hundred and two children with DMD between January 2009 and March 2011 were enrolled. DMD gene detection was performed through the multiplex ligation-dependent probe amplification (MLPA) in 84 cases. The level and the structure of intelligence were evaluated by Chinese Wechsler Intelligence Scale for Children (C-WISC) in 50 children with DMD (≥6 years old; DMD group) and in 50 age-and gender-matched healthy children (control group). The average intelligence quotient (IQ) was 84±21 in 102 children with DMD. Thirty patients (29.4%) had the full intelligence quotient (FIQ) less than 70. The FIQ, verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ) and the scores of 11 sub-tests of intelligence in the DMD group were significantly lower than those in the control group (Pchildren with DMD are lower than those in healthy children. There is association between mental retardation and gene mutations.

  9. Drug discovery for Duchenne muscular dystrophy via utrophin promoter activation screening.

    Directory of Open Access Journals (Sweden)

    Catherine Moorwood

    Full Text Available BACKGROUND: Duchenne muscular dystrophy (DMD is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. METHODOLOGY/PRINCIPAL FINDINGS: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. CONCLUSIONS/SIGNIFICANCE: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics and safety in humans are already well described, and which represents a lead compound for utrophin upregulation as a therapy for DMD.

  10. Quantitative MR evaluation of body composition in patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Pichiecchio, Anna; Uggetti, Carla; Egitto, Maria Grazia; Berardinelli, Angela; Orcesi, Simona; Gorni, Ksenija Olga Tatiana; Zanardi, Cristina; Tagliabue, Anna

    2002-11-01

    The aim of this study was to propose a quantitative MR protocol with very short acquisition time and good reliability in volume construction, for the evaluation of body composition in patients affected by Duchenne muscular dystrophy (DMD). This MR protocol was compared with common anthropometric evaluations of the same patients. Nine boys affected by DMD, ranging in age from 6 to 12 years, were selected to undergo MR examination. Transversal T1-weighted spin-echo sequences (0.5T; TR 300 ms, TE 10 ms, slice thickness 10 mm, slice gap 1 mm) were used for all acquisitions, each consisting of 8 slices and lasting just 54 s. Whole-body examination needed an average of nine acquisitions. Afterwards, images were downloaded to an independent workstation and, through their electronic segmentation with a reference filter, total volume and adipose tissue volumes were calculated manually. This process took up to 2 h for each patient. The MR data were compared with anthropometric evaluations. Affected children have a marked increase in adipose tissue and a decrease in lean tissue compared with reference healthy controls. Mean fat mass calculated by MR is significantly higher than mean fat mass obtained using anthropometric measurements ( p<0.001). Our MR study proved to be accurate and easy to apply, although it was time-consuming. We recommend it in monitoring the progression of the disease and planning DMD patients' diet.

  11. Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status

    Science.gov (United States)

    Cruz-Guzmán, Oriana del Rocío; Rodríguez-Cruz, Maricela; Escobar Cedillo, Rosa Elena

    2015-01-01

    Inflammation described in patients with Duchenne muscular dystrophy (DMD) may be related to loss of muscle function or to obesity. It is unknown if circulating proinflammatory cytokines (IL-6, IL-1, and TNF-α) levels are associated with muscle function. The purpose was to evaluate whether an association exists between systemic inflammation with muscle function and nutritional status in DMD patients. In 66 DMD patients without corticosteroid treatment, the following were evaluated in serum: cytokines (IL-1, IL-6, and TNF-α), C-reactive protein (CRP), leptin, adiponectin, and creatine kinase (CK). Muscle function was evaluated using Vignos Scale. Patients with better muscle function had the highest concentration of CK, IL-1, and TNF-α compared with less muscle function. No differences in IL-6 and adiponectin concentration were identified among groups with different levels of muscle function. Also, no differences were observed in the concentration of cytokines among groups with different nutritional status levels (underweight, normal weight, and overweight/obese). However, CRP and leptin were increased in the obese group compared with normal and underweight subjects. Systemic inflammation is increased in patients with better muscle function and decreases in DMD patients with poorer muscle function; nevertheless, systemic inflammation is similar among different levels of nutritional status in DMD patients. PMID:26380303

  12. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Nelson, Christopher E; Hakim, Chady H; Ousterout, David G; Thakore, Pratiksha I; Moreb, Eirik A; Castellanos Rivera, Ruth M; Madhavan, Sarina; Pan, Xiufang; Ran, F Ann; Yan, Winston X; Asokan, Aravind; Zhang, Feng; Duan, Dongsheng; Gersbach, Charles A

    2016-01-22

    Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to the mdx mouse model of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery to adult mice and systemic delivery to neonatal mice. Exon 23 deletion by CRISPR-Cas9 resulted in expression of the modified dystrophin gene, partial recovery of functional dystrophin protein in skeletal myofibers and cardiac muscle, improvement of muscle biochemistry, and significant enhancement of muscle force. This work establishes CRISPR-Cas9-based genome editing as a potential therapy to treat DMD. Copyright © 2016, American Association for the Advancement of Science.

  13. Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    van Ommen Gert Jan B

    2011-04-01

    Full Text Available Abstract Background Myostatin is a potent muscle growth inhibitor that belongs to the Transforming Growth Factor-β (TGF-β family. Mutations leading to non functional myostatin have been associated with hypermuscularity in several organisms. By contrast, Duchenne muscular dystrophy (DMD is characterized by a loss of muscle fibers and impaired regeneration. In this study, we aim to knockdown myostatin by means of exon skipping, a technique which has been successfully applied to reframe the genetic defect of dystrophin gene in DMD patients. Methods We targeted myostatin exon 2 using antisense oligonucleotides (AON in healthy and DMD-derived myotubes cultures. We assessed the exon skipping level, transcriptional expression of myostatin and its target genes, and combined myostatin and several dystrophin AONs. These AONs were also applied in the mdx mice models via intramuscular injections. Results Myostatin AON induced exon 2 skipping in cell cultures and to a lower extent in the mdx mice. It was accompanied by decrease in myostatin mRNA and enhanced MYOG and MYF5 expression. Furthermore, combination of myostatin and dystrophin AONs induced simultaneous skipping of both genes. Conclusions We conclude that two AONs can be used to target two different genes, MSTN and DMD, in a straightforward manner. Targeting multiple ligands of TGF-beta family will be more promising as adjuvant therapies for DMD.

  14. Compositional analysis of muscle in boys with Duchenne muscular dystrophy using MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Marden, Franklin A.; Siegel, Marilyn J.; Rubin, David A. [Mallinckrodt Institute of Radiology at Washington University Medical Center, St. Louis (United States); Barnes-Jewish Hospital, Department of Radiology, St. Louis (United States); Connolly, Anne M. [St. Louis Children' s Hospital, Department of Pediatrics, St. Louis (United States); Barnes-Jewish Hospital, Washington University School of Medicine, Department of Neurology, 660 S. Euclid, Box 8111, St. Louis (United States)

    2005-03-01

    Boys with Duchenne muscular dystrophy (DMD) present by age 5 years with weakness and, untreated, stop walking unaided by age 10 or 11 years. We used magnetic resonance (MR) imaging to study age-related changes in the composition and distribution of diseased muscles. Eleven boys (mean 7.1{+-}1.6 years) with DMD underwent clinical and MR examinations. Quantitative muscle strength and timed functional testing was performed. Thigh muscles were scanned at three levels (hip, mid-thigh, and knee) using T1-weighted spin echo and short-tau inversion recovery (STIR) sequences. Outcome measures included intramuscular fatty infiltration, intermuscle fat deposition, edema, and muscle size. Ten boys completed the study. Older boys demonstrated more prominent fatty infiltration of muscles. Fatty infiltration occurred in a characteristic pattern with the gluteus and adductor magnus muscles most commonly involved and the gracilis most commonly spared. Similarly, patchy increases in free water content suggested a pattern of intramuscular edema or inflammation. Atrophy occurred in muscles heavily infiltrated with fat, and true hypertrophy selectively occurred in those that were spared. While fibrofatty changes have been described in DMD, this study further defines differential involvement and additionally suggests widespread edema or inflammation. Improved imaging techniques to quantify the degree and distribution of these changes may provide a basis for exploring mechanisms of action of medications and perhaps another means for selecting treatment regimens and monitoring their effects. (orig.)

  15. The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

    Science.gov (United States)

    Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

  16. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Larcher, Thibaut; Lafoux, Aude; Tesson, Laurent; Remy, Séverine; Thepenier, Virginie; François, Virginie; Le Guiner, Caroline; Goubin, Helicia; Dutilleul, Maéva; Guigand, Lydie; Toumaniantz, Gilles; De Cian, Anne; Boix, Charlotte; Renaud, Jean-Baptiste; Cherel, Yan; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio; Huchet, Corinne

    2014-01-01

    A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

  17. Controversies in contraception for women with epilepsy

    Directory of Open Access Journals (Sweden)

    Sanjeev V Thomas

    2015-01-01

    Full Text Available Contraception is an important choice that offers autonomy to women with regard to prevention of unintended pregnancies. There is wide variation in the contraceptive practices between continents, countries, and societies. The medical eligibility for contraception for sexually active women with epilepsy (WWE is determined by the type of anti-epileptic drugs (AEDs that they use. Enzyme inducing AEDs such as phenobarbitone, phenytoin, carbamazepine, and oxcarbazepine increase the metabolism of orally administered estrogen (and progesterone to a lesser extent. Estrogen can increase the metabolism of certain AEDs, such as lamotrigine, leading to cyclical variation in its blood level with resultant adverse effect profile or seizure dyscontrol. AEDs and sex hormones can increase the risk of osteoporosis and fracture in WWE. The potential interactions between AEDs and hormonal contraception need to be discussed with all women in reproductive age-group. The alternate options of oral contraception such as intrauterine copper device, intrauterine levonorgestrel release system, and supplementary protection with barriers need to be presented to them. World Health Organization has recommended to avoid combination contraceptive pills containing estrogen and progesteron in women who desire contraception and in breastfeeding mothers. Care providers need to consider the option of non-enzyme-inducing AEDs while initiating long-term treatment in adolescent and young WWE.

  18. [Genetically modified food--unnecessary controversy?].

    Science.gov (United States)

    Tchórz, Michał; Radoniewicz-Chagowska, Anna; Lewandowska-Stanek, Hanna; Szponar, Elzbieta; Szponar, Jarosław

    2012-01-01

    Fast development of genetic engineering and biotechnology allows use of genetically modified organisms (GMO) more and more in different branches of science and economy. Every year we can see an increase of food amount produced with the use of modification of genetic material. In our supermarkets we can find brand new types of plants, products including genetically modified ingredients or meat from animals fed with food containing GMO. This article presents general information about genetically modified organisms, it also explains the range of genetic manipulation, use of newly developed products and current field area for GMO in the world. Based on scientific data the article presents benefits from development of biotechnology in reference to modified food. It also presents the voice of skeptics who are extremely concerned about the impact of those organisms on human health and natural environment. Problems that appear or can appear as a result of an increase of GMO are very important not only from a toxicologist's or a doctor's point of view but first of all from the point of view of ordinary consumers--all of us.

  19. Ediacaran in Uruguay: Facts and controversies

    Science.gov (United States)

    Aubet, Natalie R.; Pecoits, Ernesto; Heaman, Larry M.; Veroslavsky, Gerardo; Gingras, Murray K.; Konhauser, Kurt O.

    2014-11-01

    The Ediacaran of Uruguay has been regarded as containing a significant geological and paleontological record, which would make these successions critical to unraveling diverse aspects regarding the assembly of southwestern Gondwana and to understanding the conditions surrounding the rise of animal life in a period punctuated by drastic paleoenvironmental changes. However, a review of currently available data leads to the conclusion that, although variable, the stratigraphy, distribution and age of these units remain ambiguous. The same is true for existing basin models and tectonic evolution, which show different and sometimes contradicting supporting evidence. Here, we propose that the Ediacaran record consists of the Maldonado Group (Playa Hermosa, Las Ventanas and San Carlos formations), and the Tacuarí, Barriga Negra, Rocha and Sierra de Aguirre formations. The Arroyo del Soldado Group (Yerbal, Polanco Limestones and Cerro Espuelitas formations) and the Arroyo de la Pedrera Group (Piedras de Afilar and Cerro Victoria formations) were likely deposited between 700 and 1000 Ma. The best available radiometric age constraints indicate intense magmatic-tectonic activity occurred between 600 and 560 Ma, incompatible with previous models suggesting a stable, Atlantic-type passive margin on this portion of southwestern Gondwana. Further research is needed in order to firmly establish a consistent litho- and chronostratigraphic framework; particularly, before attempting any regional or global correlation, and inferences on global paleoenvironmental and paleobiological events.

  20. Controversies in contraception for women with epilepsy.

    Science.gov (United States)

    Thomas, Sanjeev V

    2015-01-01

    Contraception is an important choice that offers autonomy to women with regard to prevention of unintended pregnancies. There is wide variation in the contraceptive practices between continents, countries, and societies. The medical eligibility for contraception for sexually active women with epilepsy (WWE) is determined by the type of anti-epileptic drugs (AEDs) that they use. Enzyme inducing AEDs such as phenobarbitone, phenytoin, carbamazepine, and oxcarbazepine increase the metabolism of orally administered estrogen (and progesterone to a lesser extent). Estrogen can increase the metabolism of certain AEDs, such as lamotrigine, leading to cyclical variation in its blood level with resultant adverse effect profile or seizure dyscontrol. AEDs and sex hormones can increase the risk of osteoporosis and fracture in WWE. The potential interactions between AEDs and hormonal contraception need to be discussed with all women in reproductive age-group. The alternate options of oral contraception such as intrauterine copper device, intrauterine levonorgestrel release system, and supplementary protection with barriers need to be presented to them. World Health Organization has recommended to avoid combination contraceptive pills containing estrogen and progesteron in women who desire contraception and in breastfeeding mothers. Care providers need to consider the option of non-enzyme-inducing AEDs while initiating long-term treatment in adolescent and young WWE.