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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscular dystrophies are a heterogeneous group of disorders linked to defects in 20-30 different genes. Mutations in the genes encoding a pair of nuclear envelope proteins, emerin and lamin A/C, have been shown to cause the X-linked and autosomal forms respectively of Emery-Dreifuss muscular dystrophy. A third form of muscular dystrophy, limb girdle muscular dystrophy 1b, has also been linked to mutations in the lamin A/C gene. Given that these two genes are ubiquitously expressed, a major goal is to determine how they can be associated with tissue specific diseases. Recent results suggest that lamin A/C and emerin contribute to the maintenance of nuclear envelope structure and at the same time may modulate the expression patterns of certain mechanosensitive and stress induced genes. Both emerin and lamin A/C may play an important role in the response of cells to mechanical stress and in this way may help to maintain muscle cell integrity.
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PMID:Nuclear envelope defects in muscular dystrophy. 1690 76

To identify trends and patterns associated with muscular dystrophy (MD)-associated deaths, we analyzed population-based data from death certificates in the Multiple Cause Mortality Files compiled by the National Center for Health Statistics. From 1983 to 1998, 14,499 deaths in the United States were associated with ICD-9 codes for MD. The mortality rate for MD in the general U.S. population over this time period was 0.365 per 100,000 persons per year. Stratification by age at death revealed a trimodal distribution with peaks at 0, 17, and 62 years. The male-to-female ratio varied with age at death, a pattern consistent with a mixture of autosomal and X-linked MDs with different prognoses. Deaths related to MD appeared to be equally divided between presumed autosomal and X-linked MDs. The mortality rate was higher in Whites than in Blacks, for both autosomal and X-linked MDs. The median age at death was lower in Blacks than Whites for both males and females. Cardiac complications were more commonly noted among MD-associated deaths in Blacks (38.9%) than Whites (28.6%). Respiratory infections were noted in about 20% of MD-associated deaths and were more common in winter than summer months. Potential reasons for the racial differences include differences in prevalence rates, rates of diagnosis, and reporting on death certificates. Additional studies are needed to resolve these issues. Challenges in the interpretation of these data include the lack of ICD-9 codes specific for individual MDs and potential recording biases in underlying cause of death and contributing factors. We also present a method for estimating autosomal and X-linked contributions to the overall mortality rate of a genetically heterogeneous condition such as MD.
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PMID:Trends and racial disparities in muscular dystrophy deaths in the United States, 1983-1998: an analysis of multiple cause mortality data. 1702 78

Duchenne muscular dystrophy is a lethal X-linked muscle disease resulting from a defect in the muscle membrane protein dystrophin. The absence of dystrophin leads to muscle membrane fragility, muscle death (necrosis) and eventual replacement of skeletal muscle by fat and fibrous connective tissue. Extensive muscle wasting and respiratory failure results in premature death often by the early 20s. This short review evaluates drug and nutritional interventions designed to reduce the severity of muscular dystrophy, while awaiting the outcome of research into therapies to correct the fundamental gene defect. Combinations of dietary supplementation with amino-acids such as creatine, specific anti-inflammatory drugs and perhaps drugs that target ion channels might have immediate realistic clinical benefits although rigorous research is required to determine optimal combinations of such interventions.
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PMID:Duchenne muscular dystrophy: focus on pharmaceutical and nutritional interventions. 1713 28

Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP(+) cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient-X-linked, mouse muscular dystrophy (scid-mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.
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PMID:Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. 1733 Jan 16

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humero-peroneal muscular dystrophy associated with contractures and cardiomyopathy. In a 90 member family, we found 11 affected male individuals, three of whom displayed areflexia and neurogenic electromyographic changes. Muscle biopsy performed in one case demonstrated type grouping suggestive of a neurogenic disorder. These three individuals and another family member, who suffers from mild, static limb weakness but is clinically and genetically unaffected by EDMD showed an abnormal incremental response of over 100% to tetanic stimulation. In contrast, one affected family member showed myopathic features on needle electromyography and no definite pathology in repetitive stimulation studies. The diagnosis of EDMD was established by demonstrating a 1712_1713insTGGGC mutation in the emerin gene. This family apparently expresses co-morbidity of EDMD with an exceptionally mild form of pre-synaptic congenital myasthenic syndrome resembling the Lambert-Eaton myasthenic syndrome (LEMS). The superimposed pre-synaptic disorder may have contributed to the development of the neurogenic features demonstrated in these patients.
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PMID:Co-morbidity of Emery-Dreifuss muscular dystrophy and a congenital myasthenic syndrome possibly affecting the phenotype in a large Bedouin kindred. 1735 52

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder associated with dystrophin deficiency that results in chronic inflammation and severe skeletal muscle degeneration. In DMD mouse models and patients, we find that IkappaB kinase/NF-kappaB (IKK/NF-kappaB) signaling is persistently elevated in immune cells and regenerative muscle fibers. Ablation of 1 allele of the p65 subunit of NF-kappaB was sufficient to improve pathology in mdx mice, a model of DMD. In addition, conditional deletion of IKKbeta in mdx mice elucidated that NF-kappaB functions in activated macrophages to promote inflammation and muscle necrosis and in skeletal muscle fibers to limit regeneration through the inhibition of muscle progenitor cells. Furthermore, specific pharmacological inhibition of IKK resulted in improved pathology and muscle function in mdx mice. Collectively, these results underscore the critical role of NF-kappaB in the progression of muscular dystrophy and suggest the IKK/NF-kappaB signaling pathway as a potential therapeutic target for DMD.
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PMID:Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. 1738 Feb 5

Much progress has been made over the last few years in understanding and classifying neuromuscular diseases. The heart is frequently affected but often in a dissociated manner with respect to the neuromuscular signs although it has a significant impact on the prognosis. In children and adolescents, the dystrophinopathies, especially Duchenne's muscular dystrophy, are the principal problems but the mild arrhythmic events observed seem to be related to left ventricular dysfunction. On the other hand, in myotonic dystrophies (Steinert's disease), ventricular arrhythmias or conduction defects may appear at an early stage of the disease with serious consequences justifying appropriate follow-up and invasive preventive measures. Emery Dreifuss X-linked dystrophy and other laminopathies are rare conditions but are associated with sudden death and cardiomyopathies of the young adult. Specialised cardiological follow-up is justified in childhood from the time of diagnosis. Medication or implantable electric devices may be justified before the end of the second decade of life. Progressive infra-hisian conduction defects have also been reported in Kearns-Sayre oculo-pharyngeal myopathy. Prospective studies are required at this age to determine the natural history of these pathologies that are probably under diagnosed. The present recommendations, which are based mainly on data from adult series, could then be adapted for younger patients.
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PMID:[Arrhythmia follow-up of children and adolescents with neuromuscular diseases]. 1764 81

Duchenne muscular dystrophy (DMD) is a recessive X-linked lethal condition which affects a boy in every 3300 births. It is caused by the absence of dystrophin, a protein occurring especially within the musculoskeletal system and in neurons in specific regions of the central nervous system (CNS). Growth hormone (GH) inhibition is believed to decrease the severity of DMD and could perhaps be used in its treatment. However, the underlying pathological mechanism is not known. The golden retriever muscular dystrophy dog (GRMD) represents an animal model in the study of DMD. In this paper we investigated the morphological aspects of the adenohypophysis as well as the total number and size of GH-granulated cells using design-based stereological methods in a limited number of dystrophic and healthy golden retrievers. GH-cells were larger (32.4%) in dystrophic dogs than in healthy animals (p=0.01) and they occupied a larger portion (62.5%) of the adenohypophysis volume (p=0.01) without changes in either adenohypophysis volume (p=0.893) or total number of GH-granulated cells (p=0.869). With regard to ultrastructure, granulated cells possessed double-layer electron-dense granules which were evenly distributed in the cytosol. Furthermore, these granules in dystrophic animals occupied a larger proportion of GH-granulated cell volume (66.9%; p=0.008) as well as of all GH-cells in the whole pars distalis of adenohypophysis (77.3%; p=0.035), albeit IGF-1 serum concentration was lower in severe cases. This suggests difficulties in the GH secretion that might possibly be associated to dystrophin absence. In contrast to earlier reports, our data suggest that a lower IGF-1 concentration may be more related to a severe, as opposed to a benign, clinical form of muscular dystrophy.
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PMID:Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers. 1766 78

Recessive X-linked amyotrophic spinobulbar muscular atrophy (SBMA) or Kennedy disease is a neuroendocrine disorder with a slowly progressive phenotype, caused by an expansion of a polymorphic tandem CAG repeat of the androgen receptor gene. Classical clinical hallmarks include onset in the third decade of life, weakness and wasting predominantly in proximal extremity muscles, variable weakness of bulbar muscles, abundant muscle fasciculations, sensory nerve action potential abnormalities and signs of androgen insensitivity such as gynecomastia and testicular atrophy. The diagnosis has been recently made easier by the availability of genetic testing but Kennedy disease is probably still underdiagnosed because of phenotypic variability. We report 11 new cases, of which seven had atypical initial manifestations presenting respectively with myasthenia, cramps and fasciculation syndrome, polyneuropathy, post-trauma monomelic neuronopathy, effort-dependent muscle intolerance and/or muscular dystrophy, with the aim to enlarge the phenotypic spectrum of the published series.
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PMID:[Multiple phenotypic manifestations of X-linked spinobulbar muscular atrophy]. 1866 19

Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most common muscular dystrophy in children, presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys. Patients usually become wheelchair-bound by the age of 12 years, and die of cardiorespiratory complications in their late teens to early twenties. Advances in the management of DMD, including treatment with corticosteroids and the use of intermittent positive pressure ventilation have provided improvements in function, ambulation, quality of life and life expectancy, although novel therapies still aim to provide a cure for this devastating disorder. The clinical features, investigations, and management of DMD are reviewed, as well as the latest in some of the novel therapies.
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PMID:Duchenne muscular dystrophy. 1897 49


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