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 describe a 47 year old woman with a 30-year history of generalized myasthenia gravis whose condition had been stable and well controlled on a combination of pyridostigmine and ephedrine until she presented. At this time she gave a 2 month history of weakness, nausea, vomiting and more recently intermittent confusion. Investigations confirmed both primary hypothyroidism and primary adrenal failure (Schmidt syndrome). The autoimmune aetiology of these three conditions was confirmed by positive acetylcholine receptor, adrenal and thyroid microsomal antibodies.
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PMID:Myasthenia gravis and Schmidt syndrome. 325 19

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation has been complete removal of the thymus, but there has been controversy about the surgical technique and its relation to results. Surgical-anatomic studies have shown gross and microscopic thymus widely distributed in the neck and mediastinum. We believe that an en bloc transcervical-transsternal "maximal" thymectomy is required to remove all thymic tissue predictably. Ninety-five patients with generalized myasthenia gravis underwent "maximal" thymectomy consecutively between 1977 and 1985 and were evaluated 6 months to 89 months after operation. In Group A (N = 72), myasthenia gravis without thymoma, the uncorrected data revealed that 96% (69) had benefited from operation: 79% (57) had no symptoms; 46% (33) were in remission; 33% (24) were symptom free when receiving minimal doses of pyridostigmine; and none were worse. Life table analysis yielded a remission rate of 81% at 89 months. In group B (N = 8), myasthenia gravis without thymoma for which patients underwent reexploration for incapacitating weakness after earlier transcervical or transsternal operations, residual thymus was found in all. One patient was in remission, two were symptom free when receiving medication, one was unchanged, and none were worse. In group C (N 15), myasthenia gravis and thymoma, two patients were in remission and nine were symptom free when receiving medication. Two patients in this group died 2 and 4 years postoperatively in crisis. Response to thymectomy in group A was greater in patients with mild myasthenia gravis and may have been better in patients who had symptoms for less than 60 months preoperatively, but the response did not depend on age, sex, presence or absence of thymic hyperplasia or involution, or titers of acetylcholine receptor antibodies. The response to thymectomy in group B was striking but slower than in group A, perhaps because symptoms were more severe and of longer duration. The response in group C was also less good than in group A and proportionately fewer benefited. These results support the recommendation for thymectomy in the treatment of patients with generalized myasthenia gravis and indicate the desirability of a maximal procedure. For persistent or recurrent severe symptoms after previous transcervical or submaximal transsternal resections, reoperation by this technique is also recommended.
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PMID:"Maximal" thymectomy for myasthenia gravis. Results. 336 27

The diagnosis of myasthenia gravis (MG) can usually be made on the basis of the characteristic clinical history and signs, improvement by the use of anticholinesterase drugs, decremental responses in repetitive nerve stimulations, and assay of anti-acetylcholine receptor (AchR) antibody titers. We, however, have difficulty to make diagnosis of ocular MG patients with mild symptoms because muscular weakness is minimal and ancillary tests are negative. In the present communication, we report clinical usefulness of a hot test to provoke ptosis by warming the eyelid in ocular MG patients with minimal fatigability. Patient 1, a 27-year-old housewife, developed drooping of the right upper eyelid in May 1985. The ptosis was absent in the morning, but became apparent and worsened later. Neurological examination carried out 3 months after the onset revealed mild right ptosis, but fatigability of the levator palpebrae superioris could not be elicited by the provocative procedures such as sustained upward gaze or repeated opening and closing of eyelids. Both Tensilon and cold tests yielded negative responses. Repetitive nerve stimulations produced no decremental responses. Titers of anti-AChR antibody and antistriational antibody were within normal limits. In order to find a possible neuro-muscular blockade, we warmed the right upper eyelid by applying hot water of about 45 degrees C in a vinyl bag for 3 minutes. The hot test worsened the right ptosis and induced mild left ptosis. Tensilon administration reversed the eyelids to the previous position. Patient 2 was a 12-year-old boy with a typical history and clinical signs of ocular MG. His symptoms remitted spontaneously without any medication 3 weeks after the onset.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Diagnostic usefulness of a hot test in patients with mild ocular myasthenia gravis]. 342 58

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

The nicotinic acetylcholine receptor (AChR) is a large membrane protein found in muscle cells. It is involved in the transformation of acetylcholine packets into a membrane depolarization, which thereby leads to a muscle twitch. This large, complex molecule is the target of the autoimmune attack in myasthenia gravis, and much has been learned in the past decade about myasthenia by the induction of autoimmunity to AChR in experimental animals. Experimental autoimmune myasthenia gravis (EAMG) has been produced in a variety of animals by immunization with AChR or AChR-like material, or by the passive transfer of anti-AChR antibodies or lymphocytes from afflicted animals into normal animals. EAMG is a remarkably faithful model of human myasthenia and has provided much information about how the immune response to AChR progresses and how weakness and damage to the neuromuscular junction ensure. EAMG has also allowed the development of a number of revolutionary forms of treatment in which only the abnormal response to AChR is restrained, and other necessary immune functions are left intact. These advances in treatment are not far from being tested in human myasthenia gravis. The experience gained in applying these concepts in EAMG and human myasthenia will be helpful in developing similar forms of treatment for other autoimmune diseases.
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PMID:Experimental models of myasthenia gravis: lessons in autoimmunity and progress toward better forms of treatment. 349 75

Intravenous immunoglobulin, 400 mg/kg, was administered daily for five days to 12 patients with exacerbation of generalized myasthenia gravis. Degree of weakness, duration of illness, use of prednisone, and history of thymectomy or thymoma did not affect the response to intravenous immunoglobulin. Eleven patients improved, beginning 3.6 +/- 2.7 (mean +/- SD) days after the start of treatment and becoming maximal in 8.6 +/- 4.6 days, with sustained improvement lasting 52 +/- 37 days. Vital capacity increased from 1748 +/- 510 to 2700 +/- 614 mL at peak effect. Decreases in strength occurred in four patients beginning on day 3.2 +/- 2.5, lasted 1.5 +/- 0.6 days, and were mild in three patients. Other effects were minimal. There was no significant change in acetylcholine receptor antibody titers, which were elevated in all patients. Immunoglobulin seemed to produce a more rapid improvement than corticosteroids and is recommended as an adjunct in the management of myasthenia gravis exacerbations.
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PMID:High-dose intravenous immunoglobulin in the management of myasthenia gravis. 371 34

To examine the differing susceptibility of C57BL/6J and C3H/HeJ mice to experimental autoallergic myasthenia gravis (EAMG), we have compared the pathogenicity of sera from the two strains. Mice were immunized with acetylcholine receptor from T. californica and muscle weakness assessed as the time mice were capable of running on an exercise drum following the administration of a sub-lethal dose of D-tubocurarine. 16 of 20 C57BL/6J and only 4 of 19 C3H/HeJ mice developed muscle weakness. However, anti-AChR antibody titres were similar in both strains. The effect of transfer of pooled immune sera from each strain to naive recipients was therefore compared. Transfer of pooled C57BL/6J sera to naive C3H/HeJ and C57BL/6J mice produced significant muscle weakness (P less than 0.001 & P less than 0.001 respectively). Transfer of pooled C3H/HeJ sera did not produce statistically significant muscle weakness in either strain. It is concluded that differences in disease susceptibility result from differences in antibody specificities of the major antibody populations, rather than differences in total antibody amounts or other factors.
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PMID:Susceptibility to murine experimental autoallergic myasthenia gravis: the role of antibody specificity. 373 22

Fifteen patients with ocular myasthenia gravis were examined in detail for 21 different signs, and tested for acetylcholine receptor antibodies. The major signs of ocular myasthenia gravis included ptosis, disorders of ocular rotations, weakness of eyelid closure, "pseudosupranuclear" signs and the lid twitch sign. Acetylcholine receptor antibodies were found in eight of the 15 patients. One hundred and four normal, non-myasthenic patients were also examined for the lid twitch response, and the relationship between the lid twitch of ocular myasthenia gravis and that found in normal subjects is discussed.
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PMID:An evaluation of signs in ocular myasthenia gravis and correlation with acetylcholine receptor antibodies. 383 99

Purified acetylcholine receptor (AChR) covalently coupled to the catalytically toxic A chain of ricin has been used to selectively eliminate rat lymph node cells involved in in vitro anti-AChR antibody responses. The resulting inhibition was specific in view of the lack of such inhibition of anti-Keyhole limpet hemocyanin antibody responses. Furthermore, when fractionated B cell or T cell populations were treated with AChR-A chain, both populations were found to be sensitive to the specific cytotoxicity. However, T cell cytotoxicity required higher concentrations of the immunotoxin. Furthermore, when AChR-immune lymphocytes were treated with AChR-A chain in vitro, they became unable to mediate secondary adoptive transfer responses in vivo. The abrogation of the anti-AChR adoptive response correlated with the lack of muscle weakness characteristic of experimental autoimmune myasthenia gravis. Thus, it is possible, in principle, to eliminate clones of antigen-reactive lymphocytes with antigen-ricin A chain immunotoxins. This lets open the possibility of using such agents in immunotherapeutic approaches to autoimmune disease.
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PMID:Selective in vitro inhibition of an antibody response to purified acetylcholine receptor by using antigen-ricin A chain immunotoxin. 387 74

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Associate Professor of Medicine. Current findings indicate that autoimmune myasthenia gravis is an acquired immune complex disorder of neuromuscular transmission in voluntary striated muscle. There is a break in immunologic tolerance leading to blocking and degradation of acetylcholine receptors, together with widening of the synaptic cleft associated with partial destruction, simplification and shortening of the postjunctional membrane. Thymic hyperplasia and thymoma may be present. A decremental response to nerve-muscle stimulation, blocking and jitter on single-fiber electromyography and circulating antibodies to acetylcholine receptor are detectable in most patients with generalized weakness. Although the cause of this abnormal immunologic mechanism remains to be discovered, anticholinesterases, corticosteroids, immunosuppressants, plasmapheresis or thymectomy (individually or in combination) provide control and better prognosis in most patients.
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PMID:Myasthenia gravis--current concepts. 389 51


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