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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked dystrophinopathy is the most common cause of isolated cases of myopathy in males. To investigate dystrophin abnormalities as a cause of myopathy in girls and women, we used dystrophin immunocytochemistry to study muscle biopsies from 505 girls and women with neuromuscular disease. Forty-six muscle biopsies showed a combination of fibers containing or lacking dystrophin; this mosaic immunostaining pattern denoted a carrier status. Twenty-one of 46 (45.6%) had a family history of Duchenne muscular dystrophy in males. Twenty-five of 46 (54.3%) were isolated cases, with no previous family history of neuromuscular disorder. The laboratory findings of the isolated cases were consistent with the familial cases; all showed myopathic histopathology and abnormal elevations of serum CK. The clinical presentations of the isolated cases varied but were consistent with the familial cases: 40% (10/25) of isolated cases showed proximal limb weakness before age 10, 24% (6/25) presented with myalgias or cramps, 24% (6/25) presented with incidental findings of grossly elevated CK levels, 8% (2/25) noted easy fatigue, and 4% (1/25) had slowly progressive proximal limb weakness beginning at age 45. From our data, the clinical criteria for consideration of an underlying dystrophinopathy in isolated female cases of myopathy are CK levels greater than 1,000 IU/l and myopathic histopathology. About 10% of the isolated cases of hyperCKemic myopathy (25/210) were proven by dystrophin analysis to have a dystrophinopathy as the cause of their disease (manifesting carriers of Duchenne dystrophy). However, we feel that this may be an underestimate. The correct diagnosis in these patients is imperative for appropriate genetic counseling to the patients and their families.
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PMID:Dystrophinopathy in isolated cases of myopathy in females. 157 51

We studied 27 Duchenne muscular dystrophy patients having spinal fusion for scoliosis. One patient died intraoperatively of cardiac arrest; all others have done well with no instances of malignant hyperthermia, postoperative ventilatory system dependence, pneumothorax, persisting infection, neurologic damage, nonunion, or pain. The anesthetic management included primarily intravenous general anesthetics with minimal myocardial depressant effects, avoiding succinylcholine and inhalation agents. Preoperative cardiac studies aided anesthetic management intra-operatively. There was an almost universal sinus tachycardia. Holter monitoring defined 4 of 16 with ventricular premature beats, 4 of 16 with atrial premature beats, and no ventricular tachycardia or atrial flutter or fibrillation. Echocardiogram demonstrated mitral prolapse in 2 of 22, frequent abnormal systolic performance with abnormal shortening fraction less than 28% in 7 of 16, and reduced rate-corrected velocity of fiber shortening in 9 of 15. Afterload was elevated in 7 of 15. The mean forced vital capacity (FVC) preoperatively was 45.3 +/- 15.9% with continuing diminution to 28.7 +/- 14.9% at 3.3 +/- 2.2 years after surgery. The main benefit of surgical stabilization is the relative ease and comfort of wheelchair seating compared with those nonoperated patients who develop progressive deformity. We have not seen lasting improvement or stabilization in FVC following surgery as decreasing function is related primarily to muscle weakness.
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PMID:Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach. 158 53

We studied dystrophin in three young girls with a sporadic myopathy of early onset, manifested by mild to severe limb weakness, calf hypertrophy, high serum creatine kinase, normal karyotype, and morphologic features in muscle consistent with muscular dystrophy. DNA analysis did not reveal a deletion of the dystrophin gene. Immunohistochemical studies of dystrophin in muscle biopsies showed a mosaic of fibers with and without dystrophin, and immunoblot analysis showed partial dystrophin deficiency in all three patients, more severe in the patient with the highest proportion of dystrophin-deficient fibers. These observations suggest that the patients are Duchenne muscular dystrophy carriers. The data also support the concept that uneven lyonization in muscle is responsible for the clinical myopathy in these patients. We suggest that any girl with sporadic proximal limb weakness should be evaluated as a possible Duchenne carrier by dystrophin studies.
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PMID:Dystrophin deficiency in young girls with sporadic myopathy and normal karyotype. 171 59

Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.
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PMID:Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy. 174 83

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.
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PMID:Long-term benefit from prednisone therapy in Duchenne muscular dystrophy. 174 40

Recent advances concerning the genetic and biochemical basis of Duchenne and Becker muscular dystrophies have resulted in a good understanding of the etiology of these common dystrophies. An important secondary consequence of the genetic and biochemical research has been the generation of gene-based and protein-based diagnostic tools which enable a 'molecular diagnosis' for patients and their families. This review summarizes our current understanding of the genetics, biochemistry, and pathophysiology of Duchenne dystrophy, and gives an overview of the molecular diagnostic tools and their applications. Recent correlations of clinical, genetic and biochemical data have indicated that dystrophinopathies can present with a wide range of neuromuscular symptoms, and that neither male sex nor proximal weakness are diagnostic prerequisites for consideration of an underlying dystrophin abnormality.
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PMID:Dystrophin and disease. 177 Aug 36

Animal models have proven very useful in furthering insight into a number of muscle diseases. Studies of ethanol-fed rats are being used to understand the pathogenetic mechanisms underlying acute and chronic myopathy induced by ethanol. Several animal species, including mice, dogs, and cats, develop X-linked muscular dystrophies, which have genetic defects identical to those of Duchenne muscular dystrophy. As in the human disease, these animals lack dystrophin. They are being used to investigate the mechanisms by which lack of dystrophin results in weakness and to examine myoblast transfer as a treatment modality. A model of eosinophilia-myalgia syndrome has recently been induced in Lewis rats by the feeding of L-tryptophan samples that were implicated in the clinical syndrome in humans, making possible studies of the pathogenesis of this interesting new entity. A dermatomyositis-like syndrome occurs spontaneously in dogs, and polymyositis-like illnesses can be induced in mice by immunization with muscle or following infection with selected viruses, especially enteroviruses. Study of the latter is helping us understand mechanisms in the etiology and pathogenesis of inflammatory myositis and virus-induced autoimmunity.
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PMID:Animal models of myopathy. 177 47

Duchenne muscular dystrophy (DMD) is a genetically transmitted disease characterized by progressive muscle weakness and usually leads to death. DMD results from the absence, deficiency or dysfunction of the protein dystrophin. Analysis of protein data bases, including homology alignments and domain recognition patterns, have located highly significant correlations between dystrophin and other calcium regulating proteins. In particular, a major portion of the dystrophin sequence has been found to contain repeating units of approximately 100 amino acid residues. These repeating units were found to exhibit significant homology to troponin I. Troponin I has been found to bind to the calcium binding proteins calmodulin and troponin C. The regions of highest homology were characterized by patterns of high localization of charged amino acids and thus could represent a possible calmodulin or troponin C surface accessible binding site. Since subcellular localization studies have indicated that dystrophin is associated with the triadic junction, these findings imply that dystrophin could be involved in controlling intracellular calcium homeostasis.
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PMID:Duchenne muscular dystrophy and dystrophin: sequence homology observations. 179 14

Five cases of Emery-Dreifuss muscular dystrophy in four generations of a family was reported. It is a rare form X-linked recessive muscular dystrophy. The distinctive features of this disease are: Firstly, early contractures of elbows and achilles tendons and posterior cervical muscles are revealed. Secondly, muscle weakness is more proximal (scapulo-humeral) in the upper limbs and distal (anterior tibial and peroneal muscle) in the lower limbs. Thirdly, there is no calf pseudohypertrophy. Fourthly, myocardial involvement with cardiac conduction defects is frequent and important features. The CPK level is usually slightly raised. In our report, the EMG and muscle biopsies showed a mixed pattern of neurogenic and myogenic changes.
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PMID:[Emery-Dreifuss muscular dystrophy--reported a family with 5 cases]. 180 56

Evidence suggesting that dystrophin is a component of the membrane cytoskeleton of excitable cells continues to accumulate. Whereas the specific mechanisms leading to muscle pathology in Duchenne muscular dystrophy are still being debated it is apparent that the progressive weakness that occurs in this disease is the result of a chronic process that is initiated by dystrophin deficiency.
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PMID:Recent advances in dystrophin research. 182 86


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