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)

Reduction in dead space through conventional tracheostomy has been used to treat patients with chronic CO2 retention. The insufflation of air directly into the trachea by transtracheal catheter (airway insufflation, AI) provides reductions in dead space as great or greater than those of tracheostomy. The physiologic effects of AI on gas exchange have not been adequately studied because instillation of gases into the trachea contaminates minute ventilation (VL), dead space volume (VD), tidal volume (VT), and other indices of gas exchange, as measured by usual technics. We overcame this problem by devising special methods of measuring inspired and expired ventilation, alveolar and dead space ventilation, and VT and VD by using pneumotachographic timing of inspiration and expiration so that true inspired and expired ventilation were calculated. We studied 5 patients with chronic CO2 retention from either COPD, scoliosis, or muscular dystrophy (annual average PaCO2 = 45 to 75 mm Hg) during 75 min of AI with serial gas exchange and arterial blood gas measurements. AI at about 5 L/min of room air through the trachea in 5 patients reduced VL by 18% (from 7.91 to 6.48 L/min), VT by 25% (from 450 to 338 ml), and VD by 37% (from 223 to 141 ml), while not affecting PaCO2 (from 51.8 to 48.2 mm Hg) or PaO2 (from 65.1 to 63.4 mm Hg). In 2 patients, AI administered continuously for 4 to 12 months (as 30 to 50% O2) maintained PaCO2 as well as or better than breathing enriched O2 from a tracheal collar via an open tracheostomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Airway insufflation: physiologic effects on acute and chronic gas exchange in humans. 250 22

Prior studies have shown that nasal intermittent positive pressure ventilation (NIPPV) can improve arterial blood gas values, prevent symptoms resulting from alveolar hypoventilation, and decrease hospitalization in patients with chronic respiratory failure. Most studies have involved small samples of patients followed up for a limited time. This study reviews our experience during 5 years use of NIPPV in 276 patients with kyphoscoliosis, posttuberculosis sequelae, Duchenne-type muscular dystrophy, COPD, and bronchiectasis followed up for > or = 3 years while receiving NIPPV. Outcomes were compared for patients who survived short term eg, died or converted to management with a tracheostomy and intermittent positive ventilation (TIPPV) during year 1 or year 2 on a regimen of NIPPV and long term, eg, survived more > or = 2 years on a regimen of NIPPV. The most favorable outcome was achieved by patients with kyphoscoliosis and posttuberculosis sequelae with improvement in PaO2 and PaCO2 (p < 0.0001) and a reduction in days of hospitalization for respiratory illness (p < 0.0001) for > or = 2 years while receiving NIPPV. Patients with Duchenne-type muscular dystrophy also had fewer hospital days during NIPPV (p < 0.003) but only 9 of 16 patients (56 percent) continued using NIPPV for the duration of followup. Benefit was also more short term for patients with COPD and bronchiectasis. NIPPV can sustain improvement in gas exchange, while reducing hospitalization for substantial periods of time. NIPPV can be an attractive and effective alternative to other methods of assisted ventilation such as TIPPV.
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PMID:Nasal intermittent positive pressure ventilation. Long-term follow-up in patients with severe chronic respiratory insufficiency. 784 13

The development of positive pressure ventilation delivered through a nasal or face mask has greatly expanded the use of non-invasive ventilation in patients with chronic respiratory insufficiency, particularly during sleep. Disorders ranging from neurologic and neuromuscular, such as polio and muscular dystrophy, central alveolar hypoventilation, thoracic cage disorders such as kyphoscoliosis, and pulmonary disorders such as COPD, particularly of the blue-bloater type. The relative hypoventilation that is common to each condition is due to varying combinations of an inadequate respiratory drive and an increase in the work of breathing. Previous studies have shown sustained reversal of awake hypercapnia in patients with alveolar hypoventilation syndrome using nocturnal NIPPV. We analysed 10 consecutive patients with chronic respiratory insufficiency due to diverse aetiologies over a period of time using long-term domiciliary nocturnal NIPPV. Awake hypercapnia and hypoxaemia improved in nine patients over time and deteriorated in one patient. There was no significant change in pulmonary function apart from one patient with progressive muscular dystrophy who deteriorated. A considerable reduction in the need for subsequent hospital admission was noted in the group as a whole following institution of NIPPV. We conclude that nocturnal NIPPV improves awake gas exchange in patients with chronic respiratory failure.
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PMID:Nocturnal nasal intermittent positive pressure ventilation (NIPPV) therapy for chronic respiratory failure: long-term effects. 1059 22

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
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PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.
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PMID:Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. 1282 51

The natural course of progressive neuromuscular diseases can be complicated by respiratory muscle involvement. In muscular dystrophies such as Duchenne muscular dystrophy and myotonic dystrophy, respiratory muscle involvement is common. In others such as Becker, limb-girdle, and facioscapulo-humeral dystrophies, respiratory muscle involvement is infrequent and generally occurs in the more severe cases. Recently, it was reported that a mutation in the dysferlin gene and/or dysferlin deficiency causes proximal and distal forms of muscular dystrophy, which are known by the term dysferlinopathy. We describe a case of severe weakness of both limb-girdle and respiratory muscles in a patient who was carrier of the dysferlin gene mutation and who also had COPD. We suggest that the systemic inflammatory response of COPD and the dysferlin deficit interact and are responsible for both the skeletal and respiratory muscle impairment.
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PMID:Severe respiratory and skeletal muscles involvement in a carrier of dysferlinopathy with chronic obstructive pulmonary disease. 2066 57

Specific respiratory muscle training (IMT) improves the function of the inspiratory muscles. According to literature and clinical experience, there are 3 established methods: 1.) resistive load 2.) threshold load and 3.) normocapnic hyperpnea. Each training method and the associated devices have specific characteristics. Setting up an IMT should start with specific diagnostics of respiratory muscle function and be followed by detailed individual introduction to training. The aim of this review is to take a closer look at the different training methods for the most relevant indications and to discuss these results in the context of current literature. The group of neuromuscular diseases includes muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, paralysis of the phrenic nerve, and injuries to the spinal cord. Furthermore, interstitial lung diseases, sarcoidosis, left ventricular heart failure, pulmonary arterial hypertension (PAH), kyphoscoliosis and obesity are also discussed in this context. COPD, asthma, cystic fibrosis (CF) and non-CF-bronchiectasis are among the group of obstructive lung diseases. Last but not least, we summarize current knowledge on weaning from respirator in the context of physical activity.
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PMID:[Respiratory Muscle Training: State of the Art]. 2678 31

Adenine nucleotides (AdNs: ATP, ADP, AMP) are essential biological compounds that facilitate many necessary cellular processes by providing chemical energy, mediating intracellular signaling, and regulating protein metabolism and solubilization. A dramatic reduction in total AdNs is observed in atrophic skeletal muscle across numerous disease states and conditions, such as cancer, diabetes, chronic kidney disease, heart failure, COPD, sepsis, muscular dystrophy, denervation, disuse, and sarcopenia. The reduced AdNs in atrophic skeletal muscle are accompanied by increased expression/activities of AdN degrading enzymes and the accumulation of degradation products (IMP, hypoxanthine, xanthine, uric acid), suggesting that the lower AdN content is largely the result of increased nucleotide degradation. Furthermore, this characteristic decrease of AdNs suggests that increased nucleotide degradation contributes to the general pathophysiology of skeletal muscle atrophy. In view of the numerous energetic, and non-energetic, roles of AdNs in skeletal muscle, investigations into the physiological consequences of AdN degradation may provide valuable insight into the mechanisms of muscle atrophy.
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PMID:Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy. 3187 12