Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle dysfunction and associated mobility impairment, common among the frail elderly, increase the risk of falls, fractures, and functional dependency. We sought to characterize the muscle weakness of the very old and its reversibility through strength training. Ten frail, institutionalized volunteers aged 90 +/- 1 years undertook 8 weeks of high-intensity resistance training. Initially, quadriceps strength was correlated negatively with walking time (r = -.745). Fat-free mass (r = .732) and regional muscle mass (r = .752) were correlated positively with muscle strength. Strength gains averaged 174% +/- 31% (mean +/- SEM) in the 9 subjects who completed training. Midthigh muscle area increased 9.0% +/- 4.5%. Mean tandem gait speed improved 48% after training. We conclude that high-resistance weight training leads to significant gains in muscle strength, size, and functional mobility among frail residents of nursing homes up to 96 years of age.
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PMID:High-intensity strength training in nonagenarians. Effects on skeletal muscle. 234 14

Cabergoline (CAB) is a new oral dopaminergic compound showing a very long-lasting PRL-lowering activity and reported to be well tolerated. The efficacy and tolerability of chronic treatment with CAB in 30 female hyperprolactinemic patients, aged 18-52 yr (6 microadenomas, 3 macroadenomas, and 21 functional hyperprolactinemias), were studied. In a group of 10 patients who received CAB (0.8 mg once weekly or 0.4 mg twice weekly) for 8 weeks PRL levels normalized while on treatment and remained normal (8 patients) or greatly reduced (1 patient) for 1-2 months after discontinuation of the drug. Twenty-six patients underwent chronic treatment (6-12 months) with an initial dose of 0.5 mg once weekly, subsequently increased to 1-2 mg in 10 patients and decreased in the other 2. Due to severe side-effects CAB was discontinued in 3 patients, in 1, 8, and 12 weeks. A significant reduction of PRL levels was already observed after the first week of treatment (mean +/- SEM basal values, 90.1 +/- 13.3 vs. 29.5 +/- 6.3 micrograms/L; P less than 0.001). Twenty-two patients had normal PRL levels in 1-36 weeks (mean, 6 weeks) with 0.5-2 mg CAB. Twenty-two patients resumed regular menses; 2 patients became pregnant after 3-11 months of treatment. Thirteen patients complained of side-effects (nausea, hypotension, headache, gastric pain, dizziness, and weakness) that disappeared with time in 10 of them. The comparison with a previous bromocriptine treatment regimen in 20 patients had shown that the number of patients requiring discontinuation of the latter drug was significantly higher (7 vs. 3 patients; P less than 0.001). However, 2 patients who needed to discontinue CAB were able to tolerate bromocriptine therapy. A computed tomographic scan performed after 12 months of therapy in 7 patients showed a significant reduction (50%) of the adenoma in 5. In conclusion, our results show that CAB is a well tolerated new dopamine agonist with long-lasting activity that represents an advance in chronic medical treatment of hyperprolactinemic conditions.
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PMID:Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hyperprolactinemic patients. 257 Jul 90

We have made use of isogeneic anti-idiotopic (anti-Id) monoclonal antibodies (mAb to modify experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. High-avidity anti-Id mAb HC-4A (Kd = 0.1 nM) and HC-29 (Kd = 0.1 nM) were produced against an anti-acetylcholine receptor (anti-AChR) Lewis-rat mAb 132A (Kd = 0.34 nM) that is capable of inducing passive-transfer EAMG. mAb HC-4A and HC-29 define separate framework Id cross-reactive with anti-AChR mAb recognizing different AChR epitopes. Animals were preinjected i.p. with either anti-Id mAb or with control mAb and then were actively immunized 2 wk later with purified AChR. All animals had elevated total serum anti-AChR antibody titers, despite the absence of weakness or decremental electromyographic findings. Animals preinjected with control mAb developed serum anti-AChR titers of 1.34 +/- 0.29 microM (mean +/- SEM) and reduced muscle AChR content to 30 percent of normal. Animals injected with 0.5 mg/kg of either anti-Id had significantly lower serum anti-AChR titers, 0.55 +/- 0.1, p less than 0.05, and normal muscle AChR content. Both the 132A Id and the anti-Id complementary to 132A were detected in the serum of all of the animals preinjected with this dose of either anti-Id HC-29 or HC-4A, whereas both were detected in a much smaller percentage of the animals receiving control mAb. These results show that pretreatment with anti-Id not only perturbs this Id-anti-Id network, but also suppresses the overall polyclonal anti-AChR response with resultant protection of actively immunized animals from EAMG.
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PMID:Suppression of development of experimental autoimmune myasthenia gravis with isogeneic monoclonal anti-idiotopic antibody. 348 57

Among 37 patients who underwent total gastrectomy for nonmalignant disease, operative mortality was 4 per cent after 27 elective operations and 10 per cent after 10 emergency operations. Three other patients died 1 to 6 months after operation. Major postoperative complications occurred in 24 per cent. Long-term follow-up of 26 patients (81 per cent of survivors) after a mean +/- SEM of 8.4 +/- 1.1 years showed that 73 per cent of patients had no or only occasional, easily controlled, mild abdominal symptoms and good enough health to enable them to work or carry out normal activities for their age. The patients lost a mean of 15 per cent of their body weight, however, and about one third of them had weakness and diarrhea. A quarter of them had anemia despite iron and vitamin B12 therapy. Our conclusion was that total gastrectomy is a reasonable operation for benign diseases. Nonetheless, in view of the substantial postoperative mortality and morbidity, the operation should be used only when less extensive operations will not suffice.
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PMID:Total gastrectomy for benign disease. 358 2

Pulmonary functions at rest and cardiorespiratory responses to low speed treadmill walking were investigated in 24 patients (P), (mean age, 38 years; range, 20 to 56 yr) with multiple sclerosis and compared with a control group (C). The following parameters were significantly (p less than 0.01) different in P from those in C. At rest in P, the residual volume to TLC ratio was 21% greater, respiratory muscle strength index was 28% lower, and heart rate (HR) was 11 beats/min-1 higher. During treadmill walking at a given speed, HR, minute ventilation (VE), and O2 consumption (VO2) were all elevated (37 to 119%). In addition, the energy cost of walking, per unit distance, above resting, was 2 to 3 times greater, with mean +/- SEM values for P of 0.299 +/- 0.019 and C of 0.147 +/- 0.006 at 2 km/h and 0.275 +/- 0.042 and 0.110 +/- 0.005 (for P and C, respectively) ml O2 kg-1 m-1 at 4 km/h; the HR and VE/VO2, also when referred to a given VO2, were higher. We conclude that a high energy cost of walking may be an important contributing factor to breathlessness and leg fatigue in patients with multiple sclerosis. Poor conditioning, altered cardiovascular control, and respiratory muscle weakness may play additional roles.
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PMID:Energy cost of walking and exertional dyspnea in multiple sclerosis. 377 62

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disease characterized by progressive weakness and severe muscle wasting. Alterations in carbohydrate metabolism are often associated with neuromuscular disorders. We performed oral glucose tolerance tests and insulin binding studies on erythrocytes from 17 DMD and 8 normal males. Furthermore, we measured insulin binding to erythrocytes from 12 normal males and from 11 mothers and 10 sisters of affected males. As a group, DMD patients had mild glucose intolerance and both fasting and postabsorptive marked hyperinsulinemia (insulin resistance). Levels of glucose and insulin, expressed as incremental areas under their respective curves, were significantly elevated in the wheelchair-ridden patients. Incremental areas of glucose (0-2 h) and insulin (0-5 h) were 42 +/- 5 mg/dl X h (mean +/- SEM) and 96 +/- 18 microU/ml X h, respectively, in normal subjects and 71 +/- 6 (P less than 0.05) and 206 +/- 30 (P less than 0.05), respectively, in the wheelchair-confined DMD patients. All of the ambulatory DMD males had normal oral glucose tolerance tests. Insulin binding to erythrocytes was 20-30% lower (P less than 0.01) in all DMD patients than in normal males appropriately matched for age and degree of sexual development. This difference in binding was a result of lower affinity of the insulin receptor in DMD erythrocytes. On the other hand, insulin binding to fibroblasts was the same in normal males and DMD patients, suggesting that the abnormality of erythrocyte binding in DMD is probably not genetically induced. Insulin binding to erythrocytes and monocytes was the same in all females studied, regardless of whether they were carriers of the DMD gene. Our results suggest that abnormal insulin binding in DMD erythrocytes is an acquired rather than genetic abnormality, but insulin binding is not helpful in the identification of carrier females. The defect in insulin binding in DMD is present before the development of insulin resistance, which occurs only in severely immobilized patients. Thus, the cause of the insulin resistance in DMD may reside at steps beyond the binding of insulin to its receptor.
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PMID:Dissociation of insulin resistance and decreased insulin receptor binding in Duchenne muscular dystrophy. 396 91

Previous studies have shown that high-altitude hypoxic hypoxia is associated with reduced ventilatory capacity that may be related to skeletal muscle weakness. In the present investigation, ascent to high altitude (4,000 m) was simulated experimentally by exposure of male rats (Sprague-Dawley, 250-350 g), anesthetized with thiopental sodium (25 mg/kg, i.p.), to a breathing gas mixture of 12% oxygen diluted in 88% nitrogen (FiO2 = 0.12). Determinations of oxygen saturation on microsamples (250 ul) of arterial and central venous blood were made spectrophotometrically. Neuromuscular conduction latency was measured following electrostimulation of the sciatic nerve (1-5 V, 0.5 msec duration, 1-40 Hz) and recording of the electromyogram from the gastrocnemius muscle. Experimental hypoxia (FiO2 = 0.12) produced a highly significant increase in conduction latency from a control value (mean +/- SEM) of 3.06 +/- 0.16 msec to 4.02 +/- 0.31 msec (n = 10, P less than 0.001). Conduction latency increased with decreasing arterial oxygen saturation from a control value of 92.9% +/- 0.18% to 83.2% +/- 0.76% (P less than 0.001) in the absence of statistically significant changes in central venous oxygen saturation, central venous pressure, arterial and central venous pH, and heart rate. A significant decrement in the mean arterial blood pressure from a control value of 85 +/- 1.5 mm Hg to 69 +/- 1.5 mm Hg suggests that local ischemia may be a component of this model. These responses were accompanied by marked reduction in uptake of 3,3'-diaminobenzidine (DAB) by gastrocnemius muscle mitochondria, suggesting decreased intracellular activity of cytochrome oxidase. It was concluded that exposure of rodents to hypoxic gas mixtures may provide a suitable model for studying the mechanism of skeletal muscle weakness associated with ascent to high altitude and of other conditions wherein the supply of oxygen to tissues is limited.
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PMID:Relationship between intracellular oxygenation and neuromuscular conduction during hypoxic hypoxia. 609 57

To investigate individual components of the humoral immune response directed against the acetylcholine receptor in experimental myasthenia, we injected monoclonal antireceptor antibody into normal rats. These antibodies were produced by cloned hybridoma lines formed by fusion of immune spleen cells with the myeloma cell line P3-X63-Ag8. Antibodies from two of seven clones induced acute experimental myasthenia, manifested by clinical weakness, decremental electromyographic response to repetitive nerve stimulation, and diminished mean amplitudes of miniature end-plate potentials (mepps): 0.55 +/- 0.02 mv (SEM) versus 0.71 mv for controls (p less than 0.001). In clinically affected animals, mepp amplitudes from the diaphragm correlated with decremental responses in the gastronemius muscle (r = -0.91, p less than 0.01). The results suggest that binding of a single antibody species to a single determinant on the acetylcholine receptor molecule is sufficient to induce acute experimental myasthenia gravis.
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PMID:Myasthenia induced by monoclonal anti-acetylcholine receptor antibodies: clinical and electrophysiological aspects. 616 99

The clinical significance of serum aspartate aminotransferase (GOT) isozymes was studied in 18 patients with polymyositis. Abnormally high levels of mitochondrial GOT (mGOT) (6.2 +/- 1.2 IU/L, mean +/- SEM; normal, less than 2.0 IU/L) and cytosol GOT (sGOT) (95 +/- 21.6 IU/L; normal, less than 25 IU/L) were observed in sera. In polymyositic muscles, the sGOT level was significantly decreased but mGOT was not. The levels of serum sGOT and mGOT and the ratio of mGOT/tGOT before corticosteroid therapy correlated well with the severity of muscle weakness. Serial determination of CPK, sGOT, and mGOT during corticosteroid therapy revealed that mGOT most rapidly returned to normal. Exercise did not increase serum mGOT in polymyositis.
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PMID:Serum mitochondrial aspartate aminotransferase in patients with polymyositis. 683 Jan 52

Serum myoglobin levels were measured longitudinally in patients undergoing therapy because of various thyroid disorders. Elevated myoglobin values - 72.6 (58.7-89.7) micrograms/l (mean +/- SEM) were found in group of hypothyroid subjects. The degree of myoglobin increase seemed related to the severity of hypothyroidism. When rendered euthyroid the myoglobin levels of these patients were normalized - 41.0 (37.3-45.1) micrograms/l. In patients with hyperthyroidism, due to Graves' disease or subacute thyroiditis (de Quervain), only minor changes of myoglobin values within the reference range of health subjects, were measured. This suggests that mechanisms not affecting myoglobin release are responsible for the muscular weakness of thyrotoxic patients.
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PMID:Serum myoglobin in thyroid disease. 689 84


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