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)

The membranes of mammalian cells are composed of an ordered array of lipids and proteins, the latter containing carbohydrate residues directed towards the exterior and important in the interaction of cells with each other and with external proteins. This external (plasma) membrane and other more simple membranes within the cell are damaged in all diseases which compromise the integrity of the cell. However, in many cases, chemical or functional changes in these membranes are central to the pathogenesis of the disease. These processes are illustrated, and a classification of membrane-related diseases is proposed. This includes: receptor-related diseases such as type II familial hypercholesterolaemia, Grave's disease, some lysosomal storage diseases and some forms of diabetes and obesity; structural instability as manifested by red cell abnormalities and multiple sclerosis; changes in lipid state as in muscular dystrophy and multiple sclerosis; altered permeability or transport as in cystic fibrosis, diseases associated with specific transport defects, and the action of many bacterial toxins, and abnormality of the cytoskeleton-membrane interface as in Chediak-Higashi disease and some diseases associated with red cell abnormalities. Different mechanisms can contribute to the membrane disorder in a single disease state and many of these are described to illustrate this diversity.
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PMID:Role of membranes in disease. 302 80

Midthigh muscle and subcutaneous tissue thickness were measured using a real-time linear array ultrasound scanner in 50 patients attending our Muscle Clinic; 28 had muscular dystrophy and 21 spinal muscular atrophy. In muscular dystrophy the muscle thickness was found to be normal or increased, whereas in spinal muscular atrophy it was reduced, with an associated increase in subcutaneous tissue thickness that did not relate to obesity. Measurement of muscle and subcutaneous tissue thickness provides a more accurate way of assessing muscle atrophy and hypertrophy than clinical assessment, and is a useful guide in the discrimination between muscular dystrophy and spinal muscular atrophy.
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PMID:Assessment of quadriceps femoris muscle atrophy and hypertrophy in neuromuscular disease in children. 315 Mar 99

While deficient exercise performance of sick children results from hypoactivity and detraining, it can also be caused by specific pathophysiological factors. These can affect one or more components of physical fitness. A low maximal aerobic power will result from a low maximal stroke volume, as in aortic stenosis or cardiomyopathy; a low maximal heart rate, as in congenital complete heart block or intake of beta-blockers; a low O2 content of the arterial blood, as in anemia or advanced cystic fibrosis; and a high O2 content of mixed-venous blood, as in muscle atrophy or severe malnutrition. A high O2 cost of locomotion, as in advanced obesity or cerebral palsy, will cause the patient to exert at a high percentage of his maximal aerobic power and thus fatigue easily. A subnormal muscle strength, as in progressive muscular dystrophy or juvenile rheumatoid arthritis, is sometimes the primary factor that limits the walking ability or other daily functions. Recent data suggest that local muscle endurance, as assessed by the Wingate anaerobic test, is particularly deficient in some neuromuscular diseases. Examples are muscular dystrophies and spastic cerebral palsy. The ratio of peak anaerobic power to peak aerobic power seems lower in such patients than in able-bodied controls.
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PMID:Pathophysiological factors which limit the exercise capacity of the sick child. 372 7

Charts of nine patients with Duchenne and one with Becker's muscular dystrophy who had undergone spinal fusion and Harrington rod insertion for scoliosis were reviewed retrospectively. The mean age was 15 years and mean angle of scoliosis was 69 degrees. Preoperative pulmonary function studies showed a restrictive defect with a mean vital capacity of 1.3 +/- 0.69 litres, 35 +/- 20 per cent of predicted value, 33 +/- 20 ml . kg-1 and a mean inspiratory capacity of 0.99 +/- 0.5 litres, 23 +/- 13 ml . kg-1. There were no anaesthetic complications during operation and obstructive cardiomyopathy, hyperpyrexia, hyperkalaemia and rhabdomyolysis were not problems. Succinylcholine was avoided. One patient developed an arrhythmia postoperatively and one patient whose postoperative problems included tracheostomy, pneumonia and sepsis could not be weaned from the ventilator and died 11 weeks after operation. As assessing risk and survival of the operation depends on objective pulmonary function, a vital capacity of at least 20 ml . kg-1 in the range of 30 per cent of predicted volume with an inspiratory capacity of at least 15 ml . kg-1 would appear to be adequate in patients with muscular dystrophy requiring Harrington rod insertion. Other factors including the rapidity of progression of the muscular disease, other respiratory and cardiovascular problems, and disease such as obesity should also be considered.
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PMID:Anaesthetic considerations in patients with muscular dystrophy undergoing spinal fusion and Harrington rod insertion. 707 3

The induction of ovulation by hormone treatment, preparation of fertilized eggs by in vitro fertilization and recovery of offspring by embryo transfer were studied in five strains of mutant mice: C57BL/6-dy/dy progressive muscular dystrophy model, C57BL/6-ob/ob obesity model, and BALB/c-rl/rl, BALB/c- shi/shi and C57BL/6-mld/mld motor ataxia models. The homozygotes of these mutant mice are all affected with the disease about 2 weeks after birth, followed by reproductive disturbances. Ovulation could be induced by injection with PMSG-hCG in the females. Sperm was obtained from the cauda epididymis of males and used for in vitro fertilization. The success rate of the in vitro fertilization was as low as 71.6% in C57BL/6-dy/dy mice, but was over 85% in the other strains. When 2-cell embryos obtained by in vitro fertilization were transferred to the oviducts of pseudopregnant recipients, offspring were obtained from 39.2-57.7% of the transferred embryos. These offspring developed the expected diseases about 2 weeks after birth, and it was confirmed that the disease characters were reliably reproduced. These results demonstrate that the experimental system of in vitro fertilization and embryo transfer enables production of the offspring homozygous for a mutant gene and use of them for experiments before the onset of the disease which has been impossible.
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PMID:The creation of mouse models for human diseases associated with reproductive disturbances by in vitro fertilization and embryo transfer. 760 Dec 23

Effectiveness of treatment with domiciliary nocturnal noninvasive positive pressure ventilation is analyzed in a group of patients with chronic alveolar hypoventilation of different etiologies. It was applied with two levels of pressure (BiPAP) via nasal mask. Criteria for evaluation were symptomatology and improvement in gas exchange. Data were analyzed by Student t tests. A total of 13 patients were included, mean age 55.7 range 20 to 76 years (5 male 8 female). Main diagnosis was tuberculosis in 6, four of them having had surgical procedure (thoracoplasty 2, frenicectomy 1 and neumonectomy 1), myopathy 3 (myasthenia gravis 1, muscular dystrophy 1 and diaphragmatic paralysis 1), obesity-hypoventilation syndrome 1, escoliosis 1, bronchiectasis 1 and cystic fibrosis 1. These last two patients were on waiting list for lung transplantation. At the moment of consultation, the symptoms were: dysnea 13/13 (100%), astenia 13/13 (100%), hypersomnolency 10/13 (77%), cephalea 9/13 (69%), leg edema 6/13 (46%), loss of memory 6/13 (46%). Regarding gas exchange, they showed hypoxemia and hypercapnia. Mean follow up was of 2.2 years (range 6 months to 4 years). Within the year, all 13 patients became less dyspneic. Astenia, hypersomnolency, cephalea, leg edema and memory loss disappeared. Improvement in gas exchange was: PaO2/FiO2 from 269 +/- 65.4 (basal) to 336.7 +/- 75.3 post-treatment (p = 0.0018). PaCO2 from 70.77 +/- 25.48 mmHg (basal) to 46.77 +/- 8.14 mmHg (p = 0.0013). Ventilatory support was discontinued en 5 patients: three because of pneumonia requiring intubation and conventional mechanical ventilation, two of them died and one is still with tracheostomy; One patient with bronchiectasis and one with cystic fibrosis were transplanted. The remaining eight patients are stable. In conclusion, chronic alveolar hypoventilation can be effectively treated with domiciliary nocturnal noninvasive ventilation. Long term improvement in symptomatology and arterial blood gases can be obtained without significant complications.
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PMID:[Domiciliary noninvasive positive pressure ventilation in chronic alveolar hypoventilation]. 1118 89

Adeno-associated viral (AAV) vectors are derived from a nonpathogenic, replication-deficient virus with a small (~4.7-kb) single-stranded DNA genome. AAV vectors are devoid of viral-coding sequences and may efficiently transfer genes to nondividing cells such as muscle fibers or hepatocytes following in vivo transduction. Recombinant AAV can be administered to skeletal muscle of experimental animals and, as recently documented in a Phase I clinical trial, to humans at high vector doses without local or systemic toxicity (8,9). The potential of the vector to activate cytotoxic T lymphocytes is greatly reduced compared with some other viral vectors, thereby reducing the risk of inflammation at the site of gene transfer (7,10,11). Sustained expression of therapeutic transgenes such as coagulation factor IX (F.IX), erythropoietin, leptin, insulin-like growth factor (IGF), sarcoglycans, mini-dystrophin genes, alpha1-antitrypsin, and others have been demonstrated (2,12-18). Efficient gene transfer to myofibers by intramuscular (im) injection has been shown in several species including mice, hamsters, dogs, and nonhuman primates (6-8,13,19). These studies resulted in various levels of correction of the disease phenoypes in small and large animal models of hemophilia B (F.IX deficiency), muscular dystrophy, obesity, age-related atrophy, and beta-thalassemia (8,12,13,15,17,18,20-25).
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PMID:AAV-mediated gene transfer to skeletal muscle. 1497 May 92

Snoring and obstructive sleep apnea are a frequent problem not only in adults, but also in children and adolescents, as can be seen from current epidemiological data. The epidemiology, etiology, diagnosis, and management of obstructive sleep apnea syndrome (OSAS) in adults have been adequately established on the basis of evidential data. As a result of this, both physicians and the public are increasingly aware of OSAS in adults. Although there are numerous parallels between pediatric and adult OSAS, the situation in children differs that in adults. There is a greater variety of symptoms in children with OSAS, diagnosis is often more difficult with serious consequences for growth and development of children. Treatment of OSAS in children is also different from that of the adult patient. There are many possible causes for the development of obstructive sleep apnea in children. These include hypertrophy of the tonsils and syndromes such as Down syndrome, Pickwickian syndrome, Prader-Willi syndrome or Marfan syndrome. OSAS can, however, also be the result of obesity, midfacial dysplasia, retro- or micrognathia, allergic rhinitis or muscular dystrophy. Epidemiological data presented in the literature concerning the incidence of OSAS in children is extremely varied. This wide range is probably due to the fact that snoring may be misdiagnosed as OSAS. The diagnosis of OSAS in children may only be made by considering clinical history (such as rate of growth, tendency to fall asleep during the day, sleep disturbances, susceptibility to infection, etc.), polysomnography (if possible during several nights) and accompanying instrumental diagnosis including cephalometry or laryngoscopy. One of the problems of polysomnography in childhood is that performance and interpretation of the results have not yet been standardized or evaluated for different age groups. Treatment depends on the cause of OSAS and require multidisciplinary management involving the pediatrician, pediatric or adolescent psychiatrist, ear, nose, and throat specialist, maxillofacial surgeons, and neurosurgeons. Adenotonsillectomy (ATE) is the therapy generally chosen if the child has adenoidal vegetations and/or tonsillar hypertrophy. Corrective surgery is possible for rare malformation syndromes. Nocturnal masks for continuous positive airway nasal pressure or procedures for mask respiration are effective in children, but are only used in exceptional cases, such as when ATE is contraindicated or when symptoms of OSAS remain after surgery. The success of pharmacological treatment of OSAS in children has not been evaluated in controlled clinical trials.
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PMID:Obstructive sleep apnea syndrome in children: a state-of-the-art review. 1518 12

In the majority of potential applications gene therapy will require an effective transfer of a transgene in vivo resulting in high-level and long-term transgene expression, all in the absence of significant toxicity or inflammatory responses. The most efficient vehicles for delivery of foreign genes to the target tissues are modified adenoviruses. Adenoviral vectors of the first generation, despite the high infection efficacy, have an essential drawback: they induce strong immune response, which leads to short term expression of the transgene, and limits their usefulness in clinical trials. In contrast, helper-dependent adenoviral vectors (HdAd) lacking all viral coding sequences display only minimal immunogenicity and negligible side-effects, allowing for long-term transgene expression. Thus, HdAd vehicles have become the carrier of choice for adenoviral vector-mediated experimental gene therapy, effectively used in animal models for delivery of transgenes into the liver, skeletal muscle, myocardium or brain. Strong and long-lasting expression of therapeutic genes has allowed for successful treatment of dyslipidemias, muscular dystrophy, obesity, hemophilia, and diabetes. Additionally, the large cloning capacity of HdAd, up to 37 kb, facilitates the use of physiologically regulated, endogenous promoters, instead of artificial viral promoter sequences. This enables also generation of the single vectors expressing multiple genes, which can be potentially useful for treatment of polygenic diseases. In this review we characterize the basic features of HdAd vectors and describe some of their experimental and potential clinical applications.
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PMID:Helper-dependent adenoviral vectors in experimental gene therapy. 1608 8

The transforming growth factor-beta (TGF-beta) superfamily includes TGF-betas, activin, myostatin and bone morphogenetic proteins. Misregulation of the activity of TGF-beta family members is involved in pathogenesis of cancer, muscular dystrophy, obesity and bone and tooth remodeling. Natural inhibitors for the TGF-beta superfamily regulate fine-tuning of activity of TGF-beta family in vivo. In addition to natural inhibitors for the TGF-beta family, soluble forms of receptors for the TGF-beta family, blocking monoclonal antibodies and small chemical TGF-beta inhibitors have been developed. In this review, we summarize recent advances in our understanding of inhibitors for the TGF-beta superfamily and their medical applications.
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PMID:Inhibitors of the TGF-beta superfamily and their clinical applications. 1710 Jun 37


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