Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have demonstrated that maneuvers capable of reducing Ca influx into cells have beneficial effects in dystrophic hamsters and Duchenne muscular dystrophy. Since dantrolene inhibits Ca release from the sarcoplasmic reticulum, its effects on DMD was studied in 7 patients of 6 to 13 years of age (mean 10.8 years). Patients were studied for 4 years with tri-monthly evaluations of manual muscle testing (MMT), functional activity, and serum CK and aldolase. During the first 2-year period, no medicines were given and served as control. In the second 2-year period, dantrolene 8 mg/kg/d was administered. No side effects were observed. In 1 patient, mild weakness occurred that disappeared when the dose was reduced to 6 mg/kg/d. The 95% confidence limit for the difference in slopes of regression lines from tri-monthly MMT was asymmetric in favor of dantrolene in 5 of 7 patients. Serum CK did not differ between the first and second year of the control and treatment periods, respectively. However, it fell significantly from the second year of control to the first year of treatment (P = 0.003). The fall during the first year of treatment was significantly greater (P less than 0.01) than in age-matched natural history controls during the same length of observation. There was a 3-fold reduction in CK when the pooled values of the first and second year control vs. treatment periods were analyzed. No changes were observed in functional activity and serum aldolase. The data suggest that dantrolene reduces serum CK in DMD associated with a lessening trend in MMT deterioration.
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PMID:Effect of dantrolene in Duchenne muscular dystrophy. 185 56

Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.
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PMID:The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. 186 8

A two-year-old symptomatic carrier of Duchenne muscular dystrophy (DMD) confirmed by dystrophin immunohistochemical study was reported. She had mild proximal muscular weakness and elevated serum creatine kinase (CK) level. There were no family members of DMD. CT examination revealed low density areas in the muscles similar to that seen in the early stage of DMD. Biopsied specimen of muscle showed myopathic changes with necrotic and regenerating fibers. The immunohistochemical study using an antiserum against dystrophin showed the mosaic expression of the surface membrane, with positive and negative patches. Accordingly, she was strongly suggested to be a DMD carrier. This case shows that dystrophin immunohistochemistry is useful for diagnosis of a DMD carrier without affected family members.
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PMID:[A two-year-old clinically manifesting carrier of Duchenne muscular dystrophy]. 187 56

Two long-living brothers of dystrophin-related muscular dystrophy with an in-frame deletion of exon 3 of the dystrophin gene were described. Weakness of the lower extremities and pseudohypertrophy of calf muscles began at the age of 2 years in the elder brother and 4 years in the younger brother, respectively. Clinical symptoms progressed rapidly and both of them lost ambulation and became wheelchair bound at the age of 11-12 years. However, the progression of the disease process slowed in late teens, and now at the age of 36 and 33 years, respectively, they do not have respiratory or cardiac insufficiency, although they are disabled severely. Southern blotting with the entire dystrophin cDNAs, cDNA 1-2a, 2b-3, 4-5a, 5b-7, 8, and 9-14, revealed a single deletion of exon 3 in the 2 brothers. The mother was shown to be a heterozygote for this mutation. The unique clinical features of these brothers were presumed due to the following 2 factors: (1) a single deletion of exon 3 is an in-frame deletion of the dystrophin gene, and (2) exon 3 corresponds to a unique domain of the dystrophin molecule; the amino-terminal region which is highly homologous to the actin-binding-region of alpha-actinin. We consider that these 2 brothers are compatible with the so-called frame-shift hypothesis of Duchenne/Becker muscular dystrophy (DMD/BMD) phenotype, although they are diagnosed DMD by the classification method based on the patients' age of becoming permanently wheelchair bound.
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PMID:[Two long-living brothers of dystrophin-related muscular dystrophy with an in-frame deletion of exon 3 of the dystrophin gene--clinical features and diagnosis]. 189 67

Emery-Dreifuss muscular dystrophy (EDMD) is a rare X-linked muscular dystrophy characterized by early contractures, progressive muscle weakness, and atrial arrhythmias. Recent reports suggest that there may be additional cardiac problems in affected males and that carrier females may also show ECG abnormalities. We restudied two large families with EDMD in order to determine the extent of these problems. We examined 10 affected males and interviewed 2 others. The 3 affected males less than 20 years old had no ECG changes. All affected men of 35 years or older had arrhythmias. One had more severe arrhythmias when asleep, indicating the usefulness of continuous 24-h ECG monitoring in the evaluation of males affected with EDMD. Two required pacemakers, 4 had already had a pacemaker placed, and 4 other affected men with pacemakers had died prior to this study. One affected man with a pacemaker developed ventricular bigeminy and another developed congestive heart failure. Thus of 10 affected males with pacemakers, 6 had additional cardiac symptoms and 4 have died. Males with EDMD may survive longer with a ventricular pacemaker, but this may increase the likelihood that they will develop cardiomyopathy and ventricular arrhythmias. Of 34 carrier females examined, 6 had arrhythmias typical of EDMD. Two required a pacemaker. The risk of arrhythmia increased with age. Results from one family should be extrapolated to another with caution, as there appears to be significant interfamilial variation. We suggest careful cardiologic follow-up of EDMD patients and regular cardiac evaluations for older carrier females.
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PMID:Progression of cardiac disease in Emery-Dreifuss muscular dystrophy. 204 91

A 42-year-old so-called manifesting carrier of Duchenne muscular dystrophy (DMD), whose first complaints were severe myocardial symptoms, is described. Immunohistochemical study using anti-dystrophin anti-serum and analysis of cloned segments of X chromosome DNA were performed. Her two sons and one of her brothers appear to have had the same disease. She was admitted to the hospital complaining of dyspnoea, back pain and palpitations and was first diagnosed as having myocardial infarction. However, this diagnosis was excluded. The echocardiogram showed diffuse abnormalities of myocardial function. Serum enzymes were increased. Minimal weakness and decreased deep tendon reflexes were detected in her left lower extremity. Muscle biopsy revealed a small number of necrotic fibres. Immunohistochemical study using anti-dystrophin antiserum showed a mosaic pattern of the surface membrane. Analysis of cloned segments of X chromosome DNA from the patient and her son showed the XmnI(Asp) alleles of pERT 87-15 and the TaqI alleles of pERT 87-8 in both patients.
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PMID:A manifesting carrier of Duchenne muscular dystrophy with severe myocardial symptoms. 207 51

The gait parameters (speed, stride length and cadence) of nine boys with Duchenne muscular dystrophy were compared with those of 21 normal boys in the same age range. Differences found were due to the altered ability to control their dynamic state and, to a lesser extent, physical limitations of joint range. This simple method of quantifying gait is proposed as a way in which progression or response to treatment in muscular dystrophy might be monitored. The information obtained may alert the clinician to the fact that the progressive muscle weakness and joint contractures have begun to cause compensatory mechanisms during walking to fail. It is also useful to obtain information on gait in clinical treatment trials as there are very few reliable methods for testing function in muscular dystrophy.
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PMID:Variations of gait parameters in Duchenne muscular dystrophy. 209 Jan 27

A 25-year-old female patient with an approximate 10-year-history of slowly progressive muscle weakness was diagnosed as a manifesting carrier of Duchenne muscular dystrophy (DMD) because her muscle biopsy showed scattered fibers with no dystrophin on immunohistochemical staining. She had no family history of neuromuscular disorders. She was in good health until about 14 years of age, when she developed muscle weakness and atrophy of the extremities with slow aggravation. On admission at the age of 25 years, she had asymmetrical muscle atrophy in the lower extremities; the left femur, right femur, left crus, and right crus measured 36.0, 40.5, 31.5, and 35.5 cm in circumference, respectively. However, the muscle weakness of the extremities was symmetrical with no laterality, and the proximal muscles in the lower extremities were predominantly affected to 3+/5 MMT test. She walked with a mild wadding manner and stood up with Gower' maneuver. Deep tendon reflexes of the extremities were almost normoactive with no pathologic reflexes. As to laboratory findings, serum enzymes of muscular origin were elevated; GOT was 44 IU/l, GPT 60 IU/l, LDH 829 IU/l, CK 4238 IU/l, and aldolase 31 SL units. The electromyogram showed myopathic changes mixed with some neurogenic components. Peripheral nerve conduction velocity was normal. A computed tomography of the skeletal muscles showed more marked atrophy and lower density in the left lower extremity than in the right. The biopsied left gastrocnemius muscle demonstrated a marked variation in fiber size with some necrotic and regenerating fibers. On immunohistochemical stain with anti-dystrophin antibody, the dystrophin negative fibers were scattered among positive fibers in a mosaic distribution.
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PMID:[A manifesting carrier of Duchenne muscular dystrophy presenting mosaic distribution of dystrophin negative and positive muscle fibers]. 218 62

We studied monozygous twin women, age 63. One, asymptomatic, had a serum creatine kinase (CK) level of 191 units (normal, 1 to 50); her son died of typical Duchenne muscular dystrophy (DMD) at age 18. Her twin sister had symptomatic limb weakness from about age 40. Her serum CK was 495 units. EMG and muscle biopsy were compatible with myopathy. In the asymptomatic twin, the peripheral blood lymphocyte karyotype was 46,XX. In the affected twin, 18% of cells were 45,X, and the others 46,XX, without X/autosome translocation. DNA analysis did not reveal a deletion at the DMD locus. Immunologic studies of dystrophin showed a partial deficiency of the protein that was more severe in the symptomatic twin. The clinical discordance and the different severity of dystrophin deficiency may have resulted from the effects of lyonization.
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PMID:Partial dystrophin deficiency in monozygous twin carriers of the Duchenne gene discordant for clinical myopathy. 219 49

We examined serum cardiac myosin light chain I (LCI), serum creatine kinase (CK) levels and left ventricular function in patients with muscular dystrophy and secondary cardiac involvement. LCI levels were determined by a two-site immunoradiometric assay method in 25 patients with muscular dystrophy and 10 normal subjects. This study included 15 patients with Duchenne muscular dystrophy (DMD), 8 patients with Fukuyama type congenital muscular dystrophy (FCMD) and 2 sisters with non-Fukuyama type congenital muscular dystrophy (nFCMD). We measured the value of left ventricular fractional shortening (FS) using echocardiography. All patients with DMD and FCMD showed moderate or severe skeletal muscle weakness. The mean values of LCI were significantly higher in patients with DMD (11.0 +/- 8.3 ng/ml, p less than 0.01) and in patients with FCMD (1.6 +/- 1.4 ng/ml, p less than 0.05) than in normal subjects (0.3 +/- 0.2 ng/ml). In patients with DMD, LCI level correlated closely with CK level (r = 0.81, p less than 0.01) but not with FS (r = 0.35, n.s.). In patients with FCMD, LCI level correlated significantly with CK level (r = 0.75, p less than 0.05) but not with FS (r = 0.44, n.s.). Close correlation between LCI and CK levels was thought to result from the cross reaction between cardiac LCI and myosin light chains of skeletal muscle in the assay method we used. Two siblings with nFCMD showed mild skeletal muscle weakness. A 22-year-old sister with mild left ventricular dysfunction (FS = 0.41) showed high level of CK (4794/U/L) and mild elevation of LCI (7.3 ngml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical significance of serum cardiac myosin light chain I in patients with muscular dystrophy]. 225 17


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