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

A 47-year-old woman whose elder son had typical Duchenne's muscular dystrophy (DMD) was diagnosed as the manifesting carrier of the disease. She had developed congestive heart failure but had no evidence of skeletal muscular atrophy. Histological observation of the cardiac muscle revealed a mosaic pattern of dystrophin negative fibres detected by immunofluorescence analysis.
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PMID:Dystrophin negative skeletal and myocardial muscle cells in a carrier of Duchenne's muscular dystrophy. 837 25

Dystrophin serves a variety of roles at the cell membrane through its associations, and defects in the dystrophin gene can give rise to muscular dystrophy and genetic cardiomyopathy. We investigated localization of cardiac dystrophin to determine potential intracellular sites of association. Subcellular fractionation revealed that while the majority of dystrophin was associated with the sarcolemma, about 35% of the 427-kDa form of dystrophin was present in the myofibrils. The dystrophin homolog utrophin was detectable only in the sarcolemmal membrane and was absent from the myofibrils as were other sarcolemmal glycoproteins such as adhalin and the sodium-calcium exchanger. Extraction of myofibrils with KC1 and detergents could not solubilize dystrophin. Dystrophin could only be dissociated from the myofibrillar protein complex in 5 M urea followed by sucrose density gradient centrifugation where it co-fractionated with one of two distinctly sedimenting peaks of actin. Immunoelectron microscopy of intracellular regions of cardiac muscle revealed a selective labeling of Z-discs by hystrophin antibodies. In the genetically determined cardiomyopathic hamster, strain CHF 147, the time course of development of cardiac insufficiency correlated with an overall 75% loss of myofibrillar dystrophin. These findings collectively show that a significant pool of the 427-kDa form of cardiac dystrophin was specifically associated with the contractile apparatus at the Z-discs, and its loss correlated with progression to cardiac insufficiency in genetic cardiomyopathy. The loss of distinct cellular pools of dystrophin may contribute to the tissue-specific pathophysiology in muscular dystrophy.
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PMID:The association of cardiac dystrophin with myofibrils/Z-disc regions in cardiac muscle suggests a novel role in the contractile apparatus. 864 39

The muscular dystrophies are a clinically and genetically heterogeneous group of skeletal muscle-wasting diseases that differ widely in their frequency and pattern of cardiac involvement. Myocardial disease manifesting predominantly as cardiomyopathy and congestive heart failure is characteristic of Duchenne and Becker muscular dystrophies and X-linked dilated cardiomyopathy, whereas conduction system abnormalities that cause heart block, arrhythmias, and sudden death are more commonly seen in limb-girdle type 1B, myotonic, and Emery-Dreifuss muscular dystrophies. Primary defects in the mechanical stabilization of the plasma membrane and signal transduction may underlie these two groups of muscular dystrophies. The identification of several new disease genes has yielded additional insights into the pathophysiology of muscular dystrophy. Molecular genetic and biochemical analyses of patient samples now permit accurate diagnosis and genotype-phenotype correlations. Ultimately, this knowledge will provide the foundation for etiology-specific gene therapy.
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PMID:Dystrophies and heart disease. 924 91

Abnormalities in the dystrophic gene product, dystrophin, have been implicated in initiating the primary membrane defect and excessive intracellular calcium accumulation (EICA), which play fundamental pathogenic roles in hereditary muscular dystrophy (HMD). Two other cytoskeletal proteins, spectrin and utrophin, bear remarkable structural and functional homologies to dystrophin. CHF-146 strain dystrophic hamsters (DH), like patients with Duchenne muscular dystrophy (DMD), die prematurely from cardiopulmonary insufficiency, focal myonecrosis, and progressive degeneration of the cardiac and skeletal muscles with EICA. Although DH present a suitable model for HMD, there are controversies concerning their dystrophin and utrophin status. Using immunocytochemistry and Western blotting, we studied dystrophin, spectrin and utrophin anomalies in the cardiac and skeletal muscles of 6-mo-old male DH. Age- and sex-matched CHF-148 strain albino normal hamsters (NH) served as controls. Sarcolemmal dystrophin staining was much weaker and interruptive in the DH. The densitometric analysis of the immunoblots revealed that dystrophin is reduced in DH by 83% in cardiac muscle (p < 0.0001), and by 50% in skeletal muscle (p < 0.0001). We conclude that sarcolemmal dystrophin distribution is markedly reduced and discontinuous in the cardiac and skeletal muscles of DH, with simultaneous upregulation of utrophin and a varied degree of spectrin labelling. This observation suggests that reduced sarcolemmal dystrophin is associated with membrane hyperpermeability, which leads to progressive muscle degeneration via EICA and segmental necrosis in DH. As in DMD, utrophin appears to play an important compensatory role in hamster dystrophinopathy.
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PMID:Reduced sarcolemmal dystrophin distribution and upregulation of utrophin in the cardiac and skeletal muscles of CHF-146 dystrophic hamsters. 937 24

Inherited cardiomyopathies may arise from mutations in genes that are normally expressed in both heart and skeletal muscle and therefore may be accompanied by skeletal muscle weakness. Phenotypically, patients with familial dilated cardiomyopathy (FDC) show enlargement of all four chambers of the heart and develop symptoms of congestive heart failure. Inherited cardiomyopathies may also be accompanied by cardiac conduction-system defects that affect the atrioventricular node, resulting in bradycardia. Several different chromosomal regions have been linked with the development of autosomal dominant FDC, but the gene defects in these disorders remain unknown. We now characterize an autosomal dominant disorder involving dilated cardiomyopathy, cardiac conduction-system disease, and adult-onset limb-girdle muscular dystrophy (FDC, conduction disease, and myopathy [FDC-CDM]). Genetic linkage was used to exclude regions of the genome known to be linked to dilated cardiomyopathy and muscular dystrophy phenotypes and to confirm genetic heterogeneity of these disorders. A genomewide scan identified a region on the long arm of chromosome 6 that is significantly associated with the presence of myopathy (D6S262; maximum LOD score [Z(max)] 4.99 at maximum recombination fraction [theta(max)] .00), identifying FDC-CDM as a genetically distinct disease. Haplotype analysis refined the interval containing the genetic defect, to a 3-cM interval between D6S1705 and D6S1656. This haplotype analysis excludes a number of striated muscle-expressed genes present in this region, including laminin alpha2, laminin alpha4, triadin, and phospholamban.
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PMID:Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23. 938 2

Membrane-mediated excessive intracellular calcium accumulation (EICA) and diminished cellular energy production are the hallmarks of dystrophic pathobiology in Duchenne and Becker muscular dystrophies. We reported reversal of respiratory damage and Ca(2+)-overloading in the in vitro cardiac mitochondria from CHF-146 dystrophic hamsters (DH) with hereditary muscular dystrophy (Bhattacharya et al., 1993). Here we studied respiratory dysfunctions in the skeletal muscle mitochondria from young and old DH, and whether these abnormalities can be reversed by reducing [Ca2+] in the isolation medium, thereby lowering intramitochondrial Ca(2+)-overloading. Age- and sex-matched CHF-148 albino normal hamsters (NH) served as controls. As an index of EICA and cellular degeneration, Ca and Mg levels were assayed in the skeletal muscle and mitochondria. Mitochondria from young and old DH, isolated without EDTA (BE medium), revealed poor coupling of oxidative phosphorylation, diminished stimulated oxygen consumption rate, and lower respiratory control ratio and ADP/O ratios, compared to NH. Incorporation of 10 mM EDTA (Bo medium) in the isolation medium restored mitochondrial functions of the dystrophic organelles to a near-normal level, and reduced Ca(2+)-overloading. The mitochondrial Ca level in DH was significantly higher than in NH, irrespective of the medium. However, compared to Bo medium, the dystrophic organelles isolated in BE medium had lower Ca levels and markedly improved oxidative phosphorylation as seen in NH. Muscle Ca contents in the young and old DH were elevated relative to NH, showing a positive correlation with the increased mitochondrial Ca(2+)-sequestration. Dystrophic muscle also revealed Ca deposition with an abundance of Ca(2+)-positive and necrotic myofibers by light microscopy, and intramitochondrial Ca(2+)-overloading by electron microscopy, respectively. However, Mg levels in the muscle and mitochondria did not alter with age or dystrophy. These data parallel our observations in the heart, and suggest that functional impairments and Ca(2+)-overloading also occur in the skeletal muscle mitochondria of DH, and are indeed reversible if EICA is regulated by slow Ca(2+)-channel blocker therapy (Johnson and Bhattacharya, 1993).
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PMID:Reversal of impaired oxidative phosphorylation and calcium overloading in the skeletal muscle mitochondria of CHF-146 dystrophic hamsters. 977 46

About 50% of patients with progressive muscular dystrophy have a cardiomyopathy, manifested commonly by tachycardia, but also by arrythmias, refractory congestive heart failure and sudden death. Studies from the literature report manifold but nonspecific electrocardiographic changes in 41% to 85% of patients with progressive muscular dystrophy. The principal lesion is a diffuse myocardial fibrosis with minor degenerative changes in myocardial fibres unaccompanied by significant inflammation. The heart is enlarged and has a prominent deposit of epicardial fat. The myocardium is pale, coarse, flabby and friable, often showing gross evidence of scarring. The dilated chambers often contain mural thrombus.
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PMID:THE CARDIOMYOPATHY OF MUSCULAR DYSTROPHY: REPORT OF TWO CASES WITH A REVIEW OF THE LITERATURE. 1413 25

Patients with Duchenne muscular dystrophy (DMD) and severe congestive heart failure (CHF) frequently feel mental anguish due to severe mental and physical restriction. Since therapy is not efficacious enough, their quality of life is often disturbed during the terminal stage. We retrospectively evaluated the treatment and care for 11 cases of DMD with severe CHF in our hospital. All cases had unrest and anxiety, which were successfully treated with benzodiazepines and haloperidol. In many cases, patients' families craved for patients' comfort without mental and physical pain. Nine cases resulted in death and 2 cases survived. We also sent a questionnaire to doctors of muscular dystrophy wards of 27 Japanese national hospital, inquiring about therapy protocol, monitoring system, intravenous nutrition, limitation of feeding/recreation/visitors, management of pain/anxiety/sedation, and cardiopulmonary resuscitation (CPR). Sixty-eight doctors answered the questionnaire. Forty-seven doctors (69%) had the experience to treat DMD patients with severe CHF. The majority of them monitored electrocardiography, SpO2 and blood pressure. About a half adopted intravenous nutrition. If recovery was expected, limitation of feeding/recreation/visitors was based mainly on discussion with the patients and their families. If recovery was impossible, the limitation was decided according to their wishes. Nonsteroidal anti-inflammatory drugs were properly used for pain, and minor and major tranquilizers for sedation. Morphine was also used. Only one doctor adopted positive CPR, while the others answered "do not CPR" or "do CPR according to the wish of patients' families". The burden to patients and their families during treatment is unavoidable but should be reduced as much as possible. Medical staffs should ask themselves about the problems to support the families as well as patients repetitively.
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PMID:[How we have treated and cared patients with Duchenne muscular dystrophy and severe congestive heart failure]. 1602 89

Bridge to transplant is a well-known strategy to enable patients with congestive heart failure to live until transplant. A 15-year-old boy with Beckers' muscular dystrophy and cardiomyopathy was accepted for heart transplantation. He suffered a cardiac arrest and was placed on extracorporeal membrane oxygenator. A paracorporeal biventricular assist device and a total artificial heart were considered for bridge to transplant. A CardioWest total artificial heart was chosen because of the patient's size. Multiple left ventricular thrombi were identified at the time of the ventriculectomy. The patient did well with the total artificial heart was transplanted and discharged home. The unknown presence of significant left ventricular thrombi raises the question of outcome with a paracorporeal ventricular assist device.
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PMID:CardioWest total artificial heart in a moribund adolescent with left ventricular thrombi. 1618 97

Atrial standstill is a rare form of bradyarrhythmia and consists of a transitory or permanent loss of the electrical and mechanical activity of the atria. It has been described in a few cases of long-standing valvular disease, amyloidosis, myocarditis, and muscular dystrophy. We report on a young female with noncompaction cardiomyopathy that progressed to congestive heart failure. Electrocardiogram showed persistence atrial standstill that was confirmed clinically and by electrocardiomyopathy, Doppler two-dimensional echocardiogram, and tissue Doppler imaging. We assume that worsening of asymptomatic noncompaction and progression to the congestive form of cardiomyopathy could be presaged by the presence of persistent atrial standstill. Thus, persistence of atrial standstill in asymptomatic cardiomyopathy is a sign of poor prognosis.
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PMID:Persistent atrial standstill in noncompaction cardiomyopathy. 1656 5


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