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DMD
Terms modified by DMD Selected AbstractsVisuospatial attention disturbance in Duchenne muscular dystrophyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2010MARIA CLARA DRUMMOND SOARES DE MOURA 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 investigate attentional function in individuals with DMD. Method, Twenty-five males (mean age 12y; SD 2y 2mo) with DMD and 25 healthy males (mean age 12y; SD 2y) were tested in a visuospatial task (Posner computerized test). They were instructed to respond as quickly as possible to a lateralized visual target stimulus with the ipsilateral hand. Their attention was automatically orientated by a peripheral prime stimulus or, alternatively, voluntarily orientated by a central spatially informative cue. Results, The main result obtained was that the attentional effect (sum of the benefit and the cost of attention) did not differ between the two groups in the case of automatic attention (p=0.846) but was much larger for individuals with DMD than for comparison individuals in the case of voluntary attention (p<0.001). Interpretation, The large voluntary attentional effect exhibited by the participants with DMD seems similar to that of younger children, suggesting that the disease is associated with delayed maturation of voluntary attention mechanisms. [source] Management of scoliosis in Duchenne muscular dystrophy: a large 10-year retrospective studyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2006M Kinali MD Scoliosis affects 75 to 90% of patients with non-ambulant Duchenne muscular dystrophy (DMD). Spinal surgery is the treatment of choice but the indication varies among centres. Some offer surgery to all non-ambulant patients, irrespective of scoliosis severity. Early surgery has the advantage of targeting DMD when cardiorespiratory function is preserved, but not all patients develop scoliosis. We report our 10-year experience of scoliosis management in 123 patients with DMD who were at least 17 years old at the time of the study. Scoliosis was absent in 10%, and mild, non-progressive (at least 30°) in 13% of patients. Another 13% had moderate scoliosis (31,50°) and were managed conservatively. Surgery was considered in 57% (70/123) of patients with scoliosis greater than 50° and eventually performed in 35%. The remaining patients either refused surgery (9%) or were unfit because of cardiorespiratory compromise (13%). In a further 7%, scoliosis (greater than 50°), first noted after 14 years of age, was progressing slowly and surgery was not performed. At 17 years there was no difference in survival, respiratory impairment, or sitting comfort among patients managed conservatively or with surgery. One-third (44/123) of our patients were managed satisfactorily without receiving spinal surgery. We provide insight into the natural history of scoliosis in DMD that should help families and clinicians with decision-making when surgery is considered. [source] Charcot-Marie-Tooth neuropathy type 1A combined with Duchenne muscular dystrophyEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2007P. Vondracek We report a 24-year-old male with an unusual combination of two inherited neuromuscular disorders , Charcot-Marie-Tooth (CMT) disease type 1A and Duchenne muscular dystrophy (DMD). A phenotypic presentation of this patient included features of both these disorders. Nerve conduction studies revealed demyelinating peripheral neuropathy. Electromyography showed a profound myogenic pattern. The serum creatine kinase level was highly elevated. Muscle biopsy revealed a dystrophic picture with deficient dystrophin immunostaining. CMT1A duplication on chromosome 17p11.2 was found. The frame-shift mutation c.3609,3612delTAAAinsCTT (p.K1204LfsX11) was detected in the dystrophin gene by analysing mRNA isolated from the muscle tissue. The patient inherited both these mutations from his mother. The combination of CMT1A and DMD has not been reported as yet. [source] Diastereoselective Reactions of the Tiglic Acid Functionality Mediated by Oxazolidine Chiral Auxiliaries: A Mechanistic Comparison of DMD andm -CPBA Epoxidations versus Singlet Oxygen and PTAD Ene ReactionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 14 2005Aurelia Pastor Abstract 2,2-Dimethyloxazolidines have been utilized as chiral auxiliaries for the diastereoselective functionalization of the optically active tiglic acid derivatives (S)- 1 by means of epoxidation with DMD or m -CPBA and ene reactions with 1O2 or PTAD. In the DMD and m -CPBA epoxidations, high diastereoselectivities but opposite senses of diastereomer selection were observed. In contrast, the stereochemistry of the 1O2 and PTAD ene reactions depended on the size of the attacking enophile: whereas essentially perfect diastereoselectivity was obtained with PTAD, much lower stereoselection was observed with 1O2. The stereochemical results for the DMD and m -CPBA epoxidations and the PTAD ene reaction are explained in terms of the energy differences for the corresponding diastereomeric transition states, dictated by steric and electronic effects. The PTAD ene reaction for these tiglic acids (S)- 1 provides, after removal of the chiral auxiliaries, an attractive synthetic route for optically active ,-amino acid derivatives.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Severe alterations of endothelial and glial cells in the blood-brain barrier of dystrophic mdx miceGLIA, Issue 3 2003Beatrice Nico Abstract In this study, we investigated the involvement of the blood-brain barrier (BBB) in the brain of the dystrophin-deficient mdx mouse, an experimental model of Duchenne muscular dystrophy (DMD). To this purpose, we used two tight junction markers, the Zonula occludens (ZO-1) and claudin-1 proteins, and a glial marker, the aquaporin-4 (AQP4) protein, whose expression is correlated with BBB differentiation and integrity. Results showed that most of the brain microvessels in mdx mice were lined by altered endothelial cells that showed open tight junctions and were surrounded by swollen glial processes. Moreover, 18% of the perivascular glial endfeet contained electron-dense cellular debris and were enveloped by degenerating microvessels. Western blot showed a 60% reduction in the ZO-1 protein content in mdx mice and a similar reduction in AQP4 content compared with the control brain. ZO-1 immunocytochemistry and claudin-1 immunofluorescence in mdx mice revealed a diffuse staining of microvessels as compared with the control ones, which displayed a banded staining pattern. ZO-1 immunogold electron microscopy showed unlabeled tight junctions and the presence of gold particles scattered in the endothelial cytoplasm in the mdx mice, whereas ZO-1 gold particles were exclusively located at the endothelial tight junctions in the controls. Dual immunofluorescence staining of ,-actin and ZO-1 revealed colocalization of these proteins. As in ZO-1 staining, the pattern of immunolabeling with anti,,-actin antibody was diffuse in the mdx vessels and pointed or banded in the controls. ,-actin immunogold electron microscopy showed gold particles in the cytoplasms of endothelial cells and pericytes in the mdx mice, whereas ,-actin gold particles were revealed on the endothelial tight junctions and the cytoskeletal microfilaments of pericytes in the controls. Perivascular glial processes of the mdx mice appeared faintly stained by anti-AQP4 antibody, while in the controls a strong AQP4 labeling of glial processes was detected at light and electron microscope level. The vascular permeability of the mdx brain microvessels was investigated by means of the horseradish peroxidase (HRP). After HRP injection, extensive perivascular areas of marker escape were observed in mdx mice, whereas HRP was exclusively intravascularly localized in the controls. Inflammatory cells, CD4-, CD8-, CD20-, and CD68-positive cells, were not revealed in the perivascular stroma of the mdx brain. These findings indicate that dystrophin deficiency in the mdx brain leads to severe injury of the endothelial and glial cells with disturbance in ,-actin cytoskeleton, ZO-1, claudin-1, and AQP4 assembly, as well as BBB breakdown. The BBB alterations suggest that changes in vascular permeability are involved in the pathogenesis of the neurological dysfunction associated with DMD. GLIA 42:235,251, 2003. © 2003 Wiley-Liss, Inc. [source] Nutritional quality of semi-arid grassland in western Spain over a 10-year period: changes in chemical composition of grasses, legumes and forbsGRASS & FORAGE SCIENCE, Issue 3 2000Vázquez-de-Aldana From 1987 to 1996, the nutritional quality of the main botanical components (grasses, legumes and forbs) in semi-arid grasslands in the dehesa ecosystem in western Spain was analysed. Herbage samples were collected at the end of spring, in 30 locations, at two different topographic positions (upper and lower slope zones). Herbage mass over 2 cm and proportion of botanical components were estimated and samples were analysed for crude protein, neutral-detergent fibre (NDF), hemicellulose, cellulose, lignin and in vitro dry matter digestibility (DMD). Analysis of variance revealed a significant effect of sampling year on the herbage mass, proportion of botanical components and their nutritional quality. The three botanical groups, grasses, legumes and forbs, followed similar year-to-year trends in their crude protein, cellulose and lignin contents and in vitro DMD. Herbage mass was not significantly related to any meteorological variables, suggesting that interannual variation in biomass production of botanically complex pastures cannot be explained by a single factor. However, annual precipitation was significantly related to the proportion of the botanical group that was dominant at each slope zone: grasses in the lower zone and forbs in the upper zone. In the upper zone, spring precipitation explained part of the interannual variation in the NDF, cellulose, lignin contents and in vitro DMD of the botanical components. [source] Epoxidation of Polyunsaturated Fatty Acid Double Bonds by Dioxirane Reagent: Regioselectivity and Lipid Supramolecular OrganizationHELVETICA CHIMICA ACTA, Issue 10 2006Stanislav Abstract The use of dimethyldioxirane (DMD) as the epoxidizing agent for polyunsaturated fatty acids was investigated. With fatty acid methyl esters, this is a convenient method for avoiding acidic conditions, using different solvents, and simplifying the isolation procedures, with less contamination due to by-products. The reagent was also tested with free fatty acids in water. In this case, the supramolecular organization of fatty acids influenced the reaction outcome, and the epoxidation showed interesting regioselective features. The CC bonds closest to the aqueous-micelle interface is the most favored for the interaction with dimethyldioxirane. The preferential epoxidation of linoleic acid (=,(9Z,12Z)-octadeca-9,12-dienoic acid) to the 9,10-monoepoxy derivative was achieved, with a high yield and 65% regioselectivity. In case of arachidonic acid (=,(5Z,8Z,11Z,14Z)-eicosa-5,8,11,14-tetraenoic acid) micelles, the regioselective outcome with formation of the four possible monoepoxy isomers was studied under different conditions. It resulted to be a convenient synthesis of ,cis -5,6-epoxyeicosatrienoic acid' (=,3-[(2Z,5Z,8Z)-tetradeca-2,5,8-trienyl]oxiran-2-butanoic acid), whereas in reverse micelles, epoxidation mostly gave ,cis -14,15-epoxyeicosatrienoic acid (=,(5Z,8Z,11Z)-13-(3-pentyloxiran-2-yl)trideca-5,8,11-trienoic acid). [source] Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort,HUMAN MUTATION, Issue 12 2009Kevin M. Flanigan Abstract Mutations in the DMD gene, encoding the dystrophin protein, are responsible for the dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC). Mutation analysis has traditionally been challenging, due to the large gene size (79 exons over 2.2,Mb of genomic DNA). We report a very large aggregate data set comprised of DMD mutations detected in samples from patients enrolled in the United Dystrophinopathy Project, a multicenter research consortium, and in referral samples submitted for mutation analysis with a diagnosis of dystrophinopathy. We report 1,111 mutations in the DMD gene, including 891 mutations with associated phenotypes. These results encompass 506 point mutations (including 294 nonsense mutations) and significantly expand the number of mutations associated with the dystrophinopathies, highlighting the utility of modern diagnostic techniques. Our data supports the uniform hypermutability of CGA>TGA mutations, establishes the frequency of polymorphic muscle (Dp427m) protein isoforms and reveals unique genomic haplotypes associated with "private" mutations. We note that 60% of these patients would be predicted to benefit from skipping of a single DMD exon using antisense oligonucleotide therapy, and 62% would be predicted to benefit from an inclusive multiexonskipping approach directed toward exons 45 through 55. Hum Mutat 30:1657,1666, 2009. © 2009 Wiley-Liss, Inc. [source] Mutation-specific database and bioinformatics resource for DMDHUMAN MUTATION, Issue 6 2009Kevin M. Flanigan No abstract is available for this article. [source] DMD exon 1 truncating point mutations: Amelioration of phenotype by alternative translation initiation in exon 6,HUMAN MUTATION, Issue 4 2009Olga L. Gurvich Abstract Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD). We have previously identified a nonsense mutation (c.9G>A; p.Trp3X) within the first exon of the DMD gene, encoding the unique N-terminus of the 427-kDa muscle isoform of the dystrophin protein. Although this mutation would be expected to result in severe disease, the clinical phenotype is very mild BMD, with ambulation preserved into the seventh decade. We identify the molecular mechanism responsible for the amelioration of disease severity to be initiation of translation at two proximate AUG codons within exon 6. Analysis of large mutational data sets suggests that this may be a general mechanism of phenotypic rescue for point mutations within at least the first two exons of the DMD gene. Our results directly demonstrate, for the first time, the use of alternate translational initiation codons within the DMD gene, and suggest that dystrophin protein lacking amino acids encoded by the first five exons retains significant function. Hum Mutat 0:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] Array-MLPA: comprehensive detection of deletions and duplications and its application to DMD patients,HUMAN MUTATION, Issue 1 2008Fanyi Zeng Abstract Multiplex ligation-dependent probe amplification (MLPA) is widely used to screen genes of interest for deletions and duplications. Since MLPA is usually based on size-separation of the amplification products, the maximum number of target sequences that can be screened in parallel is usually limited to ,40. We report the design of a robust array-based MLPA format that uses amplification products of essentially uniform size (100,120,bp) and distinguishes between them by virtue of incorporated tag sequences. We were thus able to increase probe complexity to 124, with very uniform product yields and signals that have a low coefficient of variance. The assay designed was used to screen the largest set studied so far (249 patients) of unrelated Duchenne muscular dystrophy (DMD) cases from the Chinese population. In a blind study we correctly assigned 98% of the genotypes and detected rearrangements in 181 cases (73%); i.e., 163 deletions (65%), 13 duplications (5%), and five complex rearrangements (2%). Although this value is significantly higher for Chinese patients than previously reported, it is similar to that found for other populations. The location of the rearrangements (76% in the major deletion hotspot) is also in agreement with other findings. The 96-well flow-through microarray system used in this research provides high-throughput and speed; hybridization can be completed in 5 to 30,minutes. Since array processing and data analysis are fully automated, array-MLPA should be easy to implement in a standard diagnostic laboratory. The universal array can be used to analyze any tag-modified MLPA probe set. Hum Mutat 29(1), 190,197, 2008. © 2007 Wiley-Liss, Inc. [source] Effective detection of corrected dystrophin loci in mdx mouse myogenic precursors,HUMAN MUTATION, Issue 8 2007Marian Todaro Abstract Targeted corrective gene conversion (TCGC) holds much promise as a future therapy for many hereditary diseases in humans. Mutation correction frequencies varying between 0.0001% and 40% have been reported using chimeraplasty, oligoplasty, triplex-forming oligonucleotides, and small corrective PCR amplicons (CPA). However, PCR technologies used to detect correction events risk either falsely indicating or greatly exaggerating the presence of corrected loci. This is a problem that is considerably exacerbated by attempted improvement of the TCGC system using high corrective nucleic acid (CNA) to nuclear ratios. Small fragment homologous replacement (SFHR)-mediated correction of the exon 23 dystrophin (DMD) gene mutation in the mdx mouse model of DMD has been used in this study to evaluate the effect of increasing CPA amounts. In these experiments, we detected extremely high levels of apparently corrected loci and determined that at higher CNA to nuclear ratios the extent of locus correction was highly exaggerated by residual CNA species in the nucleic acids extracted from the treated cells. This study describes a generic locus-specific detection protocol designed to eradicate residual CNA species and avoid the artifactual or exaggerated detection of gene correction. Hum Mutat 28(8), 816,823, 2007. © 2007 Wiley-Liss, Inc. [source] Protein- and mRNA-based phenotype,genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene,HUMAN MUTATION, Issue 2 2007Nathalie Deburgrave Abstract Straightforward detectable Duchenne muscular dystrophy (DMD) gene rearrangements, such as deletions or duplications involving an entire exon or more, are involved in about 70% of dystrophinopathies. In the remaining 30% a variety of point mutations or "small" mutations are suspected. Due to their diversity and to the large size and complexity of the DMD gene, these point mutations are difficult to detect. To overcome this diagnostic issue, we developed and optimized a routine muscle biopsy,based diagnostic strategy. The mutation detection rate is almost as high as 100% and mutations were identified in all patients for whom the diagnosis of DMD and Becker muscular dystrophy (BMD) was clinically suspected and further supported by the detection on Western blot of quantitative and/or qualitative dystrophin protein abnormalities. Here we report a total of 124 small mutations including 11 nonsense and frameshift mutations detected in BMD patients. In addition to a comprehensive assessment of muscular phenotypes that takes into account consequences of mutations on the expression of the dystrophin mRNA and protein, we provide and discuss genomic, mRNA, and protein data that pinpoint molecular mechanisms underlying BMD phenotypes associated with nonsense and frameshift mutations. Hum Mutat 28(2), 183,195, 2007. © 2006 Wiley-Liss, Inc. [source] Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy,HUMAN MUTATION, Issue 2 2007Christophe Béroud Abstract Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD phenotype into a BMD phenotype appeared as a new treatment strategy with the development of antisense oligonucleotides technology, which is able to induce an exon skipping at the pre-mRNA level in order to restore an open reading frame. Because the DMD gene contains 79 exons, thousands of potential transcripts could be produced by exon skipping and should be investigated. The conventional approach considers skipping of a single exon. Here we report the comparison of single- and multiple-exon skipping strategies based on bioinformatic analysis. By using the Universal Mutation Database (UMD)-DMD, we predict that an optimal multiexon skipping leading to the del45-55 artificial dystrophin (c.6439_8217del) could transform the DMD phenotype into the asymptomatic or mild BMD phenotype. This multiple-exon skipping could theoretically rescue up to 63% of DMD patients with a deletion, while the optimal monoskipping of exon 51 would rescue only 16% of patients. Hum Mutat 28(2), 196,202, 2007. © 2006 Wiley-Liss, Inc. [source] Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategiesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2003C.A. Collins Summary., Duchenne's muscular dystrophy (DMD) is a lethal childhood disease caused by mutations of the dystrophin gene, the protein product of which, dystrophin, has a vital role in maintaining muscle structure and function. Homologues of DMD have been identified in several animals including dogs, cats, mice, fish and invertebrates. The most notable of these are the extensively studied mdx mouse, a genetic and biochemical model of the human disease, and the muscular dystrophic Golden Retriever dog, which is the nearest pathological counterpart of DMD. These models have been used to explore potential therapeutic approaches along a number of avenues including gene replacement and cell transplantation strategies. High-throughput screening of pharmacological and genetic therapies could potentially be carried out in recently available smaller models such as zebrafish and Caenorhabditis elegans. It is possible that a successful treatment will eventually be identified through the integration of studies in multiple species differentially suited to addressing particular questions. [source] Productivity of Bahiagrass Pastures in South-western Japan: Synthesis of Data from Grazing TrialsJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2006M. Hirata Abstract This study examined the rate of herbage production and herbage quality of bahiagrass (Paspalum notatum Flügge) using data from five grazing trials in the low-altitude region of Kyushu, south-western Japan, in an effort to (a) evaluate productivity of bahiagrass pastures, (b) analyse its relationship to meteorological, vegetational and managerial variables, and (c) obtain implications for better management of bahiagrass pastures. The rate of herbage production, ranging from ,56 to 213 kg DM ha,1 day,1, tended to increase from spring (April,May) to mid-summer (July) and decrease thereafter. The rate was expressed by a multiple regression equation where nitrogen fertilizer rate, air temperature, rainfall and herbage mass had positive effects. Dry matter digestibility (DMD) and crude protein (CP) concentration of herbage were in the range of 471,727 and 84,161 g kg,1 DM respectively. DMD was expressed by a regression equation where the day number from 1 April and herbage mass had negative effects, and the sampling height and nitrogen rate had positive effects. CP concentration was expressed by an equation showing a positive effect of nitrogen rate and a negative effect of herbage mass. The results indicate that management of bahiagrass pastures should aim at maintaining herbage mass closely above the critical level below which intake by grazing animals is restricted, in order to increase quality and ensure quantity. This is particularly important when nitrogen fertilizer is applied. [source] DNA methylation patterns at the IGF2-H19 locus in sperm of Swiss Landrace and Swiss Large White boarsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 6 2009Petra Giannini Summary DNA methylation patterns at the IGF2-H19 locus were investigated in sperm DNA from Swiss Landrace (SL) and Swiss Large White (LW) boars. The putative IGF2 differentially methylated regions (DMR) 0, 1 and 2, a quantitative trait nucleotide (QTN) region in the intron 3 and a CpG island in the intron 4 of the IGF2 gene as well as three regions around porcine CTCF binding sites within the H19 differentially methylated domain (DMD) were selected for the DNA methylation analysis. In both breeds putative IGF2 DMR0, 1, 2 and H19 DMD were hypermethylated. Significant differences in DNA methylation content were found between the two breeds in the two DMD regions proximal to the H19 gene. The IGF2 QTN region and the CpG island in the IGF2 intron 4 were hypomethylated in sperm DNA of both breeds. The methylation analysis revealed significantly more methylated CpG sites in the intron 4 of sperm from the LW breed than in that from SL. No difference was found in global DNA methylation between the two breeds. These results indicate differences in DNA methylation patterns between breeds and it remains to be established whether variation in DNA methylation patterns impacts on phenotypic traits. [source] In situ rumen degradation and in vitro gas production of some selected grains from TurkeyJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 9-10 2002H. D. Umucalilar Summary An investigation of the dry matter degradability (DMD) and effective dry matter degradability (EDDM) was performed for barley, wheat, rye, corn, triticale and oat samples, using the Nylon-bag technique. Gas production (GP), metabolizable energy (ME) and in vitro organic matter digestibility (IVOMD) were also studied by using Hohenheim gas test. The DM from barley, wheat, rye and triticale was digested rapidly in the rumen, and, at the 48 h of incubation, degradability was found to be approximately about 80%. The higher degradability observed for these grains than for oats and corn was attributable to the structure of these grains. In contrast, DM of corn and oats was degraded very slowly and reached 66.7 and 66.5 at 48 h, respectively. Effective degradability values of barley, wheat, rye, corn, triticale and oats were determined to be 61.4, 69.0, 64.0, 41.7, 66.7 and 58.6% in 5% rumen outflow rate, respectively. At the end of the 48 h incubation, total gas productions in barley, wheat, rye, corn, triticale and oats were estimated to be 83.6, 87.2, 87.5, 83.5, 85.8 and 63.9 ml/200 mg DM, respectively. The mean ME values of these grains calculated from cumulative gas amount at 24 h incubation were 11.8, 12.1, 12.3, 10.9, 12.4 and 10.2 MJ/kg DM, respectively. In vitro digestible organic matter of barley, wheat, rye, corn, triticale and oats were estimated to be 85.0, 87.3, 88.2, 79.5, 89.0 and 72.6%. Percentage overall EDDM (k=5%) of barley, wheat, rye, triticale and oats was positively correlated with in vitro GP at 6 h, cumulative GP at 24 h and total GP at 48 h (p<0.05). As a result, in situ dry matter degradation of grains showed great differences depending on the chemical compositions. In situ EDDM of grains may be predicted from in vitro gas production parameters. [source] A review of nutrition in Duchenne muscular dystrophyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 5 2009Z. E. Davidson Abstract Duchenne muscular dystrophy (DMD) is a recessive X linked genetic disorder characterised by progressive muscle weakness and reduced muscle tone. Affecting only boys, it limits life expectancy to approximately 20 years. A literature review was conducted using MEDLINE and the Cochrane Library, employing the term ,Duchenne muscular dystrophy'. A total of 1491 articles in English were recovered. These papers were searched thematically under the headings: body composition (n = 10), energy expenditure (n = 10), nutrition (n = 6), corticosteroid therapy (n = 55) and gene therapy (n = 199). Key dietetic practice points were identified relevant to nutritional management. Papers supporting these key themes were assigned a level of evidence and grade of recommendation. There is limited high-quality evidence to guide the nutritional management of boys with DMD. Currently, the majority of evidence is based on expert opinion and clinical expertise. Delayed growth, short stature, muscle wasting and increased fat mass are characteristics of DMD and impact on nutritional status and energy requirements. The early introduction of steroids has altered the natural history of the disease, but can exacerbate weight gain in a population already susceptible to obesity. Prior to commencing steroids, anticipatory guidance for weight management should be provided. Malnutrition is a feature of end stage disease requiring a multidisciplinary approach, such as texture modification and supplemental feeding. Micronutrient requirements are yet to be determined but, as a result of corticosteroid treatment, vitamin D and calcium should be supplemented. Some evidence exists supporting supplementation with creatine monohydrate to improve muscle strength. More research is needed to provide a higher quality of evidence for dietitians working within this area. [source] CMTX: heterozygosity for a GJB1/CX32 mutation in a XXY male results in a mild phenotypeJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004M Milani Mutations in the GJB1/Cx32 gene (Xq13.1) cause the most common X-linked form of CMT (CMTX1) and are the most frequent cause of CMT disease after the CMT1A duplication. The disorder is characterized by a moderate-to-severe neuropathy in affected males and mild-to-no symptoms in carrier females. We report here a CMT1A-negative family in which 4 females and 2 males were affected, exhibiting different disease severity. Molecular analysis of the GJB1/Cx32 gene uncovered a nonsense mutation (Arg22stop) in exon 2. The mutation, which had been previously described by others and observed by us in numerous other families, occurred in heterozygous form in the 4 females. However, while one of the two male patients was severely affected and shown to be hemizygous, as expected, the other was mildly affected and found to carry the mutation in heterozygous form. Genotyping at the SRY (Yp11.3) and DMD (Xp21) loci suggested the occurrence of the XXY genotype associated with Klinefelter syndrome. Microsatellite analysis indicated that the nondysjunctional error was of paternal origin, as it is usually observed in about half the cases. The patient had no children. At clinical examination, he exhibited a very mild neurologic phenotype and showed signs of hypogonadism (mild gynecomastia and small testes) as well as moderate cognitive impairment. Electrophysiologic, cytogenetic and endocrinologic investigations are in progress in order to define the unusual phenotype in this patient. [source] The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophyMUSCLE AND NERVE, Issue 4 2010Craig M. McDonald MD Abstract Walking abnormalities are prominent in Duchenne muscular dystrophy (DMD). We modified the 6-minute walk test (6MWT) for use as an outcome measure in patients with DMD and evaluated its performance in 21 ambulatory boys with DMD and 34 healthy boys, ages 4 to 12 years. Boys with DMD were tested twice, ,1 week apart; controls were tested once. The groups had similar age, height, and weight. All tests were completed. Boys who fell recovered rapidly from falls without injury. Mean ± SD [range] 6-minute walk distance (6MWD) was lower in boys with DMD than in controls (366 ± 83 [125,481] m vs. 621 ± 68 [479,754] m; P < 0.0001; unpaired t -test). Test-retest correlation for boys with DMD was high (r = 0.91). Stride length (R2 = 0.89; P < 0.0001) was the major determinant of 6MWD for both boys with DMD and controls. A modified 6MWT is feasible and safe, documents disease-related limitations on ambulation, is reproducible, and offers a new outcome measure for DMD natural history and therapeutic trials. Muscle Nerve, 2010 [source] Assessment of regional body composition with dual-energy X-ray absorptiometry in Duchenne muscular dystrophy: Correlation of regional lean mass and quantitative strengthMUSCLE AND NERVE, Issue 5 2009Andrew J. Skalsky MD Abstract The purpose of this study was to assess regional body composition and its correlation with regional strength in Duchenne muscular dystrophy (DMD) subjects and able-bodied controls. Regional dual-energy X-ray absorptiometry (DEXA) measurements and isometric strength were obtained for 23 DMD subjects and 23 control subjects. DMD subjects showed a decreased regional lean mass (P < 0.001). The correlation between regional strength and regional lean mass was stronger for controls than for DMD subjects. DMD subjects had decreased regional lean mass, increased regional fat mass, and decreased strength. Muscle Nerve 39: 647,651, 2009 [source] Annexin expression in inflammatory myopathiesMUSCLE AND NERVE, Issue 1 2004Stefan Probst-Cousin MD Abstract The pathogenesis of the inflammatory myopathies is still unclear, making their treatment largely empirical. Improved understanding of the molecular mechanisms of inflammatory muscle injury may, however, lead to the development of more specific immunotherapies. To elucidate a possible pathogenic contribution of calcium-binding proteins such as the annexins, we immunohistochemically investigated muscle biopsy specimens from patients with dermatomyositis (10 cases), polymyositis (9 cases), and inclusion-body myositis (4 cases), compared to control cases comprising sarcoid myopathy (3 cases), Duchenne muscular dystrophy (DMD; 4 cases), and normal muscle (3 cases). We found expression of annexins A1, A2, A4, and A6 in the vascular endothelium of all cases. Myofibers expressed annexins A5, A6, and A7 diffusely and weakly in the cytosol, whereas annexins A5 and A7 were also particularly localized to the sarcolemma. In the inflammatory myopathies, in areas of myonecrosis in DMD, and in granulomatous lesions of sarcoid myopathy, reactivity of annexins A1, A2, A4, A5, and A6 was observed in macrophages and T-lymphocytes. Whereas the latter annexins appear to be nonspecific indicators of activation, annexin A1 upregulation may represent endogenous anti-inflammatory mechanisms that merit further investigation. Muscle Nerve 30: 102,110, 2004 [source] Gentamicin fails to increase dystrophin expression in dystrophin-deficient muscleMUSCLE AND NERVE, Issue 5 2003Patrick Dunant PhD Abstract A recent report that aminoglycoside antibiotics restored the expression of functional dystrophin to skeletal muscles of mdx mice, a model of Duchenne muscular dystrophy (DMD), raised hopes that DMD may be treatable by a conventional drug. Subsequently, several human trials were initiated for evaluating gentamicin therapy in selected DMD patients. An increase of dystrophin expression was not detected in one human trial that was fully reported. Here, we report that we were unable to replicate previously published beneficial results by gentamicin treatment in the mdx mouse. Therefore, we believe that additional animal experimentation is required to further evaluate the possibility of in vivo aminoglycoside therapy of DMD. Muscle Nerve 27: 624,627, 2003 [source] Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletionsNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2004S. Torelli Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is localized to the sarcolemma. In rare cases, however, this labelling is equivocal and similar to that observed in controls making diagnosis difficult. We report here that in such instances immunolabelling with antibodies to the neuronal form of nitric oxide synthase (nNOS) can be useful in suspecting a dystrophinopathy with a mutation in the ,hot-spot' rod domain and help to direct molecular analysis. nNOS localizes to the sarcolemma of mature muscle fibres via several components of the dystrophin-associated protein complex (DAPC) including dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very low or absent because of deletions in critical regions of the rod domain. We report three cases who presented with only mild or no muscle weakness but had elevated serum creatine kinase activity and dystrophin immunolabelling indistinguishable from normal, making a pathological diagnosis difficult. All three cases had a complete absence of sarcolemmal nNOS and were subsequently found to have an in-frame deletion in the common rod domain exons (in these cases 48, 45,51, 47,53) compatible with a BMD. In addition, we observed that nNOS appears to be developmentally regulated with the antibody used and was often absent from the sarcolemma of immature fibres. These findings demonstrate the value of including antibodies to nNOS in routine immunohistochemical studies and that absence of nNOS can be a more sensitive marker than up-regulation of utrophin for diagnosis of BMD. Immaturity of fibres, however, needs to be taken into account, especially in neonates. [source] Reversal of rocuronium-induced neuromuscular blockade by pyridostigmine in patients with Duchenne muscular dystrophyPEDIATRIC ANESTHESIA, Issue 3 2008TINO MUENSTER MD Summary Background:, The aim of this study was to investigate the effect and safety of pyridostigmine for the reversal of a neuromuscular block (NMB) in patients with Duchenne muscular dystrophy (DMD). In patients with DMD recovery from a rocuronium-induced NMB is markedly delayed. Methods:, Fourteen DMD patients (aged between 11 and 19 years) scheduled for elective scoliosis repair were studied. Following tracheal intubation without muscle relaxant, all patients received a single dose of rocuronium 0.6 mg·kg,1. NMB was monitored by acceleromyography at the adductor pollicis muscle. When the first twitch height (T1) of the train-of-four (TOF) had recovered to 25% seven patients received either pyridostigmine 0.1 mg·kg,1 (the anticholinergic drug with a long duration of action) or saline in a blinded manner. The times to attain TOF ratio of 0.9 were recorded. For comparison the Mann,Whitney U -test was used. Results:, Recovery to TOF ratio of 0.9 was significantly (P < 0.05) accelerated by pyridostigmine [84 (median), 57,141(range)] compared with controls (148, 84,243 min). The recovery time (time between T1 of 25% and TOF of 90%) was also significantly (P < 0.01) shortened by pyridostigmine (15, 8,49 vs 76, 43,144 min, respectively). Time to recovery of T1 to 90% was not different between the groups (108, 63,134 vs 169. 61,208 min, respectively). Conclusions:, Pyridostigmine 0.1 mg·kg,1 effectively reversed a rocuronium-induced NMB in DMD patients. [source] C Histomorphology of neuromuscular junction in Duchenne muscular dystrophyPEDIATRIC ANESTHESIA, Issue 3 2008MARY C THEROUX MD Summary Background:, Our objective was to better understand neuromuscular junction (NMJ) morphology in children with Duchenne muscular dystrophy (DMD). Methods:, We examined the NMJs of four children, age 6,13 years, who were diagnosed with DMD. Using our previously established staining technique, we examined the gross appearance of the NMJs in patients with DMD and evaluated the spread of acetylcholine receptors (AChRs) in relationship to the NMJs. We used a computerized algorithm to measure the area of staining corresponding to AChRs and NMJ. Results:, Abnormal shape and morphological appearance of some of the NMJs was clearly evident. The spread of AChRs in DMD patients is comparable with the spread of AChRs in nonDMD patients. Conclusions:, The distribution of AChRs in relationship to the boundaries of NMJs in DMD children is similar to the distribution of NMJs in the erector spinae muscles of idiopathic scoliosis patients. [source] The respiratory management of patients with duchenne muscular dystrophy: A DMD care considerations working group specialty article,PEDIATRIC PULMONOLOGY, Issue 8 2010David J. Birnkrant MD Abstract In 2001, the Muscular Dystrophy Community Assistance, Research and Education Amendments (MD-CARE Act) was enacted, which directed federal agencies to coordinate the development of treatments and cures for muscular dystrophy. As part of the mandate, the Centers for Disease Control and Prevention (CDC) initiated surveillance and educational activities, which included supporting development of care considerations for Duchenne muscular dystrophy (DMD) utilizing the RAND/UCLA Appropriateness Method (RAM). This document represents the consensus recommendations of the project's 10-member Respiratory Panel and includes advice on necessary equipment, procedures and diagnostics; and a structured approach to the assessment and management of the respiratory complications of DMD via assessment of symptoms of hypoventilation and identification of specific thresholds of forced vital capacity, peak cough flow and maximum expiratory pressure. The document includes a set of Figures adaptable as "pocket guides" to aid clinicians. This article is an expansion of the respiratory component of the multi-specialty article originally appearing in Lancet Neurology, comprising respiratory recommendations from the CDC Care Considerations project. Pediatr. Pulmonol. 2010; 45:739,748. © 2010 Wiley-Liss, Inc. [source] New challenges in the management of prolonged survivors of pediatric neuromuscular diseases: A pulmonologist's perspectivePEDIATRIC PULMONOLOGY, Issue 12 2006David J. Birnkrant MD Abstract Many patients with pediatric neuromuscular diseases (NMDs) are now achieving prolonged survival through advances in management of the cardiopulmonary complications of their illnesses. Because respiratory complications are among the main causes of mortality and morbidity in these diseases, pulmonologists are in a unique position to observe and describe the largely unanticipated medical, social, and ethical problems generated when patients with progressive NMDs achieve prolonged survival. For example, prolonged survivors of pediatric NMDs are now experiencing previously rare or unknown medical complications, an unprecedented severity of burden of disease and the potential for prolonged impairment of quality of life. As the patients age, their families must cope with a high level of burden of care. Society's acceptance of the eligibility of these patients to utilize critical care resources, and issues related to the transition of prolonged survivors from pediatric to adult medical providers and venues have resulted in complex practical and ethical issues. In this article, the author, a pediatric pulmonologist closely involved in the care of patients with NMDs, will identify and discuss some of the major medical, social, and ethical implications of prolonged survival among these patients, with an emphasis on Duchenne muscular dystrophy (DMD), the most common of the pediatric NMDs. Pediatr Pulmonol. 2006; 41:1113,1117. © 2006 Wiley-Liss, Inc. [source] Validity of the EK scale: a functional assessment of non-ambulatory individuals with Duchenne muscular dystrophy or spinal muscular atrophyPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 3 2001Birgit Steffensen Abstract Background and Purpose The EK scale comprises ten categories (EK 1,10), each contributing to an overall picture of function in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The purpose of the present study was to investigate content and construct validity of the EK scale as a tool to discriminate between levels of functional ability in individuals with DMD or spinal muscular atrophy (SMA) who were non-ambulatory. Method Data from a sample of 56 subjects with DMD and 38 with SMA, who were non-ambulatory, were obtained from four separate studies. The relationship of functional ability by use of the EK scale and (1) muscle strength, (2) contractures, (3) forced vital capacity and (4) years of wheelchair dependency were assessed. All items of the EK scale were used except the one representing severe hypoventilation. Results Regression analyses showed that the EK sum was the most significant explanatory variable (p<0.05) of all variables measured to explain muscle strength in both DMD and SMA subjects. The individual categories of EK (1,10) all contributed as significant explanatory variables (p<0.05) to the other variables measured. Conclusions The categories and items of the EK scale were relevant and valid as means of discriminating between levels of functional performance in the population studied which was evidence of content and construct validity. Copyright © 2001 Whurr Publishers Ltd. [source] | ||||||||||||||||||||||||||||||||||