Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with myotonic muscular dystrophy (MD) were examined by auditory event-related potentials (P300 ERPs), spirometric and blood gas analyses: arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2) and arterial oxygen saturation (SaO2). The aim of the study was to analyse the frequency of ERP abnormalities in this disease and to determine whether the neurophysiological evidence of cognitive impairment might be related to the ventilatory function abnormalities frequently described in MD. The mean P300 latency was significantly altered in MD patients compared with controls; P300 latencies did not correlate with spirometric parameters, blood gas values or with age, age at onset, duration or clinical status of the disease. This study provides neurophysiological evidence of cognitive impairment in MD patients. The cognitive deficits are not related to alveolar hypoventilation and appear to be a non progressive feature of the disease.
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PMID:P300 and respiratory findings in myotonic muscular dystrophy. 1056 15

Biochemical abnormalities have been reported in dystrophin-deficient muscle of boys with Duchenne (severe Xp21) muscular dystrophy or in the murine (mdx) model of the disease. These abnormalities include altered energy metabolism and responses to osmotic shock. In contrast, the situation in brain is less well understood and it is probable that dystrophin is playing a different role (or roles) in this organ. In this study we conclude that the elevation in choline-containing compounds reported in mdx brain is confined to cerebellum and hippocampus in older (> 6 months) mice. We report alterations in glucose metabolism in mdx brain under normal, awake conditions, and a reduced response of brain metabolism to the gamma-aminobutyric acid(A) receptor agonist muscimol. Using brain cortical slices we found no difference in the response of dystrophic tissue to hypoosmotic shock, but increased, substrate-dependent oxygen consumption rates at low oxygen partial pressures.
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PMID:Abnormalities in brain biochemistry associated with lack of dystrophin: studies of the mdx mouse. 1173 53

Rhabdomyolysis is one of the perioperative complications in patients with Duchenne's muscular dystrophy (DMD). It has been suggested that sevoflurane can be used safely for anesthesia in patients with DMD. In this report, we describe a case with DMD who received anesthesia with sevoflurane, in which rhabdomyolysis developed postoperatively. A 6-year-old boy diagnosed as DMD was scheduled for tonsillectomy under general anesthesia. Preoperative laboratory examination revealed a high level of creatine kinase (CK) (16,000-32,000 IU.l-1). An abnormality of the dystrophin gene was detected by DNA analysis. Anesthesia was induced with sevoflurane without muscle relaxant, and maintained with sevoflurane in nitrous oxide and oxygen under controlled ventilation. The course of anesthesia was uneventful and the patient recovered smoothly. Three hours postoperatively, dark red urine with a high concentration of myoglobin (1,390,000 ng.ml-1) was recognized with a high level of CK (63,500 IU.l-1). Body temperature was 37.6 degrees C, and electrocardiogram and serum potassium were within normal ranges. After the diuresis with mannitol and furosemide, the urine became clear. On the 4th postoperative day, he was discharged without any complication. This case suggested that rhabdomyolysis can develop after sevoflurane anesthesia in patients with DMD.
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PMID:[Sevoflurane can induce rhabdomyolysis in Duchenne's muscular dystrophy]. 1188 91

Dystrophin, a product of a gene located at the chromosome Xp21 locus, is a cytoskeletal protein expressed in skeletal, cardiac and smooth muscles, and in the brain, and is located on the inner site of the plasma membrane. Dystrophin in the skeletal muscles is absent or appears only in traces in Duchenne dystrophy, it is reduced with normal/changed molecular weight in Becker dystrophy and it is absent/reduced in mdx mice. It is supposed that dystrophin acts either as a structural scaffold that supports mechanical stress in sarcolemma, or participates in regulating intracellular Ca2+ level. There are also data indicating that dystrophin takes part in force and signal transduction processes, in the aggregation of neurotransmitter receptors, and prevents an excessive generation of reactive oxygen free radical species. The main hypotheses indicate that lack of structural support, an excessive influx of Ca2+ ions into the muscle cell, or a combination of both these mechanisms in dystrophin-deficient muscle fibres, is responsible for muscle pathology in progressive muscular dystrophy. There are arguments supporting these hypotheses. There are, however, also data indicating that the presented arguments are doubtful. Despite recent advances in the knowledge of the pathogenesis of muscular dystrophies and the advent of modern techniques, we are still very far away from understanding what is the real function of dystrophin in muscle.
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PMID:Controversies about the function of dystrophin in muscle. 1192 96

Malignant Hyperthermia (MH) has been a recognized complication of general anesthesia after the first case reports in the 1940's. Since then a great deal has been discovered about the genetics, pathophysiology and treatment of this once fatal syndrome. MH is the only clinical entity specifically related to and caused by anesthetic agents. MH once triggered during anesthesia results in a profound hyper metabolic state with rise in the core temperature, increased carbon dioxide production and oxygen consumption. Death will ensue if specific treatment is not started. The incidence of fulminant MH ranges from 1:62,000 to 1: 84,000 of general anesthesia cases if succinylcholine and inhalation agents are used. Massseter muscle spasm on induction of anesthesia, with an incidence of between 1:16,000 and 1:4,000, may be a predromal indication of the development of MH. Anesthetic agents, which may trigger MH in susceptible individuals, are the depolarizing muscle relaxant, succinyl choline and all the volatile anesthetic gasses. Nitrous oxide, intravenous induction agents, benzodiazepines, opioids, and the non-depolarizing relaxants do not trigger MH. MH susceptibility is associated with certain disorders, such as Duchene muscular dystrophy, and triggering agent should not be used in these patients. Inheritance is an autosomal dominant trait with variable penetrance. The pathogenesis of MH involves the loss of control of intracellular calcium ions in skeletal muscle with resultant protracted spasm and hyper metabolism. Clinically this will progress to hypercarbia, hypoxia, hyperthermia, hyperkalemia and death will result if specific treatment is not started. Management involves immediate discontinuation of the triggering anesthetics, hyperventilation with 100% oxygen and most importantly the definitive treatment with intravenous dantrolene.The importance of instigating the use of dantrolene in cases of MH cannot be overemphasized. MH is now treatable when once it would be fatal before the availability of dantrolene. Unless of an emergent nature, surgery should be canceled following the acute phase of MH. The patient should be admitted to intensive care for at least 24 hours and dantrolene continued as recurrence has been described. It is imperative that the patient and their family are counseled, Medalert bracelets provided and registration with the Malignant Hyperthermia Association of the United States (MHAUS), encouraged. The caffeine/halothane testing of muscle biopsies is currently the most definitive test for malignant hyperthermia susceptibility. The routine use in suspected cases or the immediate family of known cases remains a matter of contention.
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PMID:Malignant hyperthermia. 1450 52

Progressive muscular dystrophy may produce abnormal reactions to several drugs. There is no consensus of opinion regarding the continuous infusion of propofol in patients with progressive muscular dystrophy. We successfully treated 2 patients with progressive muscular dystrophy who were anesthetized with a continuous infusion of propofol. In case 1, a 19-year-old, 59-kg man with Becker muscular dystrophy and mental retardation was scheduled for dental treatment under general anesthesia. General anesthesia was maintained by a continuous infusion of 6-10 mg/kg propofol per hour and an inhalational mixture of 67% nitrous oxide and 33% oxygen. No complications were observed during or after the operation. In case 2, a 5-year-old, 11-kg boy with Fukuyama type congenital muscular dystrophy and slight mental retardation was scheduled for dental treatment under general anesthesia. General anesthesia was maintained with a continuous infusion of 6-12 mg/kg propofol per hour and an inhalational mixture of 0.5-1.5% sevoflurane in 67% nitrous oxide and 33% oxygen. No complications were observed during or after the operation. It is speculated that a continuous infusion of propofol in progressive muscular dystrophy does not cause malignant hyperthermia because serum levels of creatine phosphokinase and myoglobin decreased after our anesthetic management. Furthermore, our observations suggest that sevoflurane may have some advantages in patients with progressive type muscular dystrophies other than Duchenne muscular dystrophy and Becker muscular dystrophy. In conclusion, our cases suggest that a continuous infusion of propofol for the patients with progressive muscular dystrophy is a safe component of our anesthetic strategy.
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PMID:Continuous infusion propofol general anesthesia for dental treatment in patients with progressive muscular dystrophy. 1585 43

The aim of the present study was to investigate the direct effects of a reactive oxygen species, H(2)O(2), on the contractile function and sarcoplasmic reticulum properties of dystrophin-deficient diaphragm using chemically skinned fibers and sarcoplasmic reticulum vesicle preparations. The results obtained using Triton X-100-skinned fibers demonstrate that exposure to 1 mM H(2)O(2) had similar effects on the maximal Ca(2+)-activated tension and on the Ca(2+) sensitivity of the contractile apparatus of diaphragm fibers in Bl10 and mdx mice. The effects of H(2)O(2) were also assessed on sarcoplasmic reticulum function using saponin-skinned fibers and sarcoplasmic reticulum vesicle preparations. We found that H(2)O(2) induced changes in sarcoplasmic reticulum properties, particularly in the Ca(2+) pump function. The most important finding was that diaphragm muscle from mdx mice displayed increased sensitivity to the oxidant. Furthermore, in isolated superfused diaphragm muscle from mdx mice, the data demonstrate that the amount of superoxide anion produced under fatiguing conditions was increased. Our study shows that the sarcoplasmic reticulum, and the Ca(2+) pump in particular, in dystrophin-deficient muscles display increased susceptibility to H(2)O(2) injuries. This suggests that free radicals might, therefore, be involved in the pathophysiological pathway and dysregulation of Ca(2+) homeostasis of muscular dystrophy.
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PMID:Greater susceptibility of the sarcoplasmic reticulum to H2O2 injuries in diaphragm muscle from mdx mice. 1680 56

Here, we present the first study of a human neuromuscular disorder at transcriptional and proteomic level. Autosomal dominant facio-scapulo-humeral muscular dystrophy (FSHD) is caused by a deletion of an integral number of 3.3-kb KpnI repeats inside the telomeric region D4Z4 at the 4q35 locus. We combined a muscle-specific cDNA microarray platform with a proteomic investigation to analyse muscle biopsies of patients carrying a variable number of KpnI repeats. Unsupervised cluster analysis divides patients into three classes, according to their KpnI repeat number. Expression data reveal a transition from fast-glycolytic to slow-oxidative phenotype in FSHD muscle, which is accompanied by a deficit of proteins involved in response to oxidative stress. Besides, FSHD individuals show a disruption in the MyoD-dependent gene network suggesting a coregulation at transcriptional level during myogenesis. We also discuss the hypothesis that D4Z4 contraction may affect in trans the expression of a set of genes involved in myogenesis, as well as in the regeneration pathway of satellite cells in adult tissue. Muscular wasting could result from the inability of satellite cells to successfully differentiate into mature fibres and from the accumulation of structural damages caused by a reactive oxygen species (ROS) imbalance induced by an increased oxidative metabolism in fibres.
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PMID:Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes. 1701 91

Myotonic dystrophy (MD) is the commonest adult muscular dystrophy and is associated with respiratory muscle weakness. The role of screening sleep studies is unclear in MD. We prospectively evaluated polysomnography/overnight oximetry in a group of MD patients and related this to the daytime respiratory function in an attempt to evaluate the usefulness of screening sleep studies. Twenty-five patients with type I MD [15 males; mean age (SD) 40.0 (10.9) years] who had at least one symptom suggestive of nocturnal hypoventilation were included in the study. We performed spirometry, maximal inspiratory and expiratory mouth pressures, sniff nasal inspiratory pressure, arterial blood gases and polysomnography or overnight oximetry. Excessive tiredness and sleepiness were the most common presenting symptoms. Prevalence of sleep related breathing disorder (SRBD) was 36%. FVC was found to be normal in 33% of subjects with significant SRBD. Mouth pressures were reduced more than FVC, even in patients with normal overnight oxygen saturation. Of all the daytime measures, FVC correlated best with arterial carbon dioxide tension (r = -0.7). Sleep studies were useful to identify a small group of myotonic dystrophy patients (12%, three out of 25 in our series) with SRBD that would have been missed with routine daytime assessments. Targeted sleep monitoring in patients who are older, with multiple symptoms suggestive of SRBD, especially if they are overweight seems to be the best way to utilize the existing resources. Home unattended oximetry was well tolerated and offers a practical screening tool in this challenging patient group where excess daytime sleepiness is often due to causes other than SRBD.
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PMID:Assessment of sleep studies in myotonic dystrophy. 1741 48

Reactive oxygen species may contribute to the pathogenesis of muscular dystrophy. High intensity exercise clearly induces muscle damage in mdx mice; however, the effects of low intensity exercise training (LIT) on mdx muscle are less clear. We examined the effect of LIT on markers of oxidative stress (malondialdehyde and protein carbonyls), antioxidant (superoxide dismutase, catalase, and glutathione peroxidase), and mitochondrial (2-oxoglutarate dehydrogenase and cytochrome oxidase) enzymes in skeletal muscle of mdx and wild-type mice. Mdx and wild-type mice were allocated to LIT and sedentary groups. Malondialdehyde levels were higher in white muscle from sedentary mdx as compared to both sedentary and LIT wild-type mice (P<0.001). Protein carbonyl content was higher in white and red muscle of mdx versus wild-type mice (P<0.05). LIT was associated with lower levels of malondialdehyde and protein carbonyls in white muscle of mdx mice (decreased 38 and 44%, P<0.001 and P<0.01, respectively). Antioxidant and mitochondrial enzyme activities were higher in white muscle of mdx than in wild-type mice (P<0.05). LIT in mdx mice induced physiological adaptation resulting in lower levels of markers of oxidative stress that were not different than those from wild type. These results are of relevance for therapeutic exercise in patients with dystrophinopathy where exercise prescription remains controversial.
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PMID:Low intensity training decreases markers of oxidative stress in skeletal muscle of mdx mice. 1756 Nov 3


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