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)

On the day of the disaster, 641 victims were seen at St. Luke's International Hospital. Among those, five victims arrived with cardiopulmonary or respiratory arrest with marked miosis and extremely low serum cholinesterase values; two died and three recovered completely. In addition to these five critical patients, 106 patients, including four pregnant women, were hospitalized with symptoms of mild to moderate exposure. Other victims had only mild symptoms and were released after 6 hours of observation. Major signs and symptoms in victims were miosis, headache, dyspnea, nausea, ocular pain, blurred vision, vomiting, coughing, muscle weakness, and agitation. Almost all patients showed miosis and related symptoms such as headache, blurred vision, or visual darkness. Although these physical signs and symptoms disappeared within a few weeks, psychologic problems associated with posttraumatic stress disorder persisted longer. Also, secondary contamination of the house staff occurred, with some sort of physical abnormality in more than 20%.
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PMID:Sarin poisoning on Tokyo subway. 919 33

We studied two families with five affected members suffering from ptosis and slowly progressive limb-girdle muscle weakness. All patients had abnormal decremental response on low-frequency nerve stimulation, but there were no repetitive responses to single stimuli. The patients improved on anti-acetylcholinesterase drugs. Intercostal muscle was obtained for special studies from one patient of each family. In vitro microelectrode studies were done in Patient 1. Miniature end-plate potentials were of low amplitude, and the quantal content of the evoked end-plate potentials was normal. Light microscopy revealed a marked type 1 fiber predominance. Acetylcholinesterase reactivity was dispersed over increased length of individual fibers in Patient 2. On morphometry of the end-plate ultrastructure, the number of secondary synaptic clefts per neuromuscular junction and the expansion of the postsynaptic area were markedly reduced. In Patient 1, but not in Patient 2, the envelopment of the nerve terminal by Schwann cell was increased. Acetylcholine-receptor (AChR) density was reduced as judged by the reduced immunoreactivity to antibodies against different receptor subunits. Immunohistochemical analysis of proteins known to be involved in orchestrating the end-plate structure showed deficiency of the AChR-associated protein utrophin. These patients appear to have a defect in the development or maintenance of the postsynaptic clefts; whether this defect results from or causes a reduced expression of utrophin or AChR is unclear.
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PMID:Congenital myasthenic syndromes in two kinships with end-plate acetylcholine receptor and utrophin deficiency. 944 57

1. Twenty-one cases out of 272 patients of acute organophosphates poisoning were diagnosed as intermediate syndrome (IMS) with a prevalence at 7.7%. The responsible OP insecticides included parathion, omethoate and some OP containing pesticide mixtures. IMS occurred mainly in severe OP poisoning patients who recovered from the acute cholinergic crisis at 7-75 h after the onset of acute poisoning. 2. Muscular weakness appeared in the following three categories of muscles: (1) neck flexors and proximal limb muscles; (2) muscles innervated by motor cranial nerves and/or (3) respiratory muscles. Blood acetylcholinesterase activity was persistently inhibited. Electroneuromyography (ENMG) with repetitive nerve stimulation (RNS) at frequencies of 20 Hz or 30 Hz in seven patients showed decrements of common muscle action potentials during the presence of myasthenia in five patients and became normal when their muscle strength recovered. 3. Mild IMS recovered within 2-7 days and had a favorable prognosis. Severe IMS patients with respiratory paralysis needed immediate endotracheal intubation and mechanical ventilation. Recovery of weakness of the respiratory muscles and proximal limb muscles took longer, the slowest being 30 days. Four of the patients died of respiratory paralysis and the fatality rate was 19%. 4. The mechanism of IMS remains to be further investigated. The RNS/ENMG changes indicate a post-synaptic block at the neuromuscular junctions. 5. In order to promote the recognition of this syndrome, we proposed to name the syndrome as Intermediate Myasthenia Syndrome (IMS).
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PMID:Intermediate myasthenia syndrome following acute organophosphates poisoning--an analysis of 21 cases. 949 37

A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March 20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache and weakness of the lower limbs and oropharyngeal muscles. Despite these symptoms, he visited a hot spring on the same day with his family. On March 25 th, his muscle weakness progressed, and a low grade fever appeared. His muscle weakness disappeared 8 days after exposure to sarin, but respiratory failure rapidly developed, necessitating artificial ventilation within four day after hospitalization on March 28th. Chemotherapy with erythromycin, imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of sputum collected by bronchofiberscopy were positive for Legionella pneumophila, serogroup I. His respiratory state improved, but subsequent infection with Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata caused his death 71 days after admission. Oropharyngeal muscle weakness caused by sarin-mediated cholinesterase inhibition was strongly suspected as the cause of hot spring water aspiration. Transbronchial lung biopsy revealed organizing pneumonia with fibrosis. Bronchoscopic findings included redness, edema and fragility of all visible areas of the airway, which was thought to be due to bronchitis caused by Legionellosis.
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PMID:[Legionella pneumonia caused by aspiration of hot spring water after sarin exposure]. 965 77

Congenital myasthenic syndrome (CMS) with end-plate acetylcholinesterase (AChE) deficiency is a rare autosomal recessive disease, recently classified as CMS type Ic (CMS-Ic). It is characterized by onset in childhood, generalized weakness increased by exertion, refractoriness to anticholinesterase drugs, and morphological abnormalities of the neuromuscular junctions (NMJs). The collagen-tailed form of AChE, which is normally concentrated at NMJs, is composed of catalytic tetramers associated with a specific collagen, COLQ. In CMS-Ic patients, these collagen-tailed forms are often absent. We studied a large family comprising 11 siblings, 6 of whom are affected by a mild form of CMS-Ic. The muscles of the patients contained collagen-tailed AChE. We first excluded the ACHE gene (7q22) as potential culprit, by linkage analysis; then we mapped COLQ to chromosome 3p24.2. By analyzing 3p24.2 markers located close to the gene, we found that the six affected patients were homozygous for an interval of 14 cM between D3S1597 and D3S2338. We determined the COLQ coding sequence and found that the patients present a homozygous missense mutation, Y431S, in the conserved C-terminal domain of COLQ. This mutation is thought to disturb the attachment of collagen-tailed AChE to the NMJ, thus constituting the first genetic defect causing CMS-Ic.
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PMID:Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic). 975 17

We have performed C7 spinal nerve transfer to treat root injury of the brachial plexus since 1989. Out of a total of 43 patients, 21 have been followed up for at least 2 years. Evaluation of the effect of C7 transection included clinical examination, intraoperative C7 stimulation, LIDO Workset machine and electrophysiological studies to test C7 innervated muscles, and histochemical analysis of the anterior and posterior division of the upper trunk using acetylcholinesterase stain. Nearly half of the study group (48%) reported no significant sensory changes and most patients (81%) did not notice any weakness of the limb following C7 transection. Some patients did experience sensory and motor abnormalities which were most frequent during the first postoperative month, improved during the 2nd month and in most cases resolved in the 3rd postoperative month. The only longer persistent abnormality was the triceps reflex, which becomes weak or absent. We also found that intraoperative C7 stimulation was a useful predictor of possible post-transection morbidity. Subclinical deficits, detected by the LIDO workset machine and by electro-physiological studies, were quite common. Histochemical analysis revealed that the posterior division of C7 had more motor fibres than the anterior division.
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PMID:Clinical evaluation of C7 spinal nerve transection: 21 patients with at least 2 years' follow-up. 977 46

Short and long-term health effects from exposure to organophosphorus (OP) military and insecticidal nerve agents are evaluated based on the abundant scientific literature published over five decades on health effects in humans (from human experimentation and occupational exposures) and in laboratory animals. Four distinct health effects are identified: acute cholinergic toxicity; organophosphate-induced delayed neuropathy (OPIDN); subtle long-term neuropsychological and neurophysiological effects; and a reversible muscular weakness called 'intermediate syndrome'. Some effects are subtle and difficult to differentiate from health effects caused by other diseases or occupational exposures. Each effect has data suggesting threshold exposure levels below which it is unlikely to be clinically detectable. Therefore, meaningful interpretation of human and animal studies requires rigid exposure characterization. Because precise exposure levels are often difficult to reconstruct, a system for characterizing exposure is proposed based upon observed initial acute signs and symptoms, as high-level (definitive cholinergic poisoning); intermediate-level (threshold cholinergic effects including miosis, rhinorrhea or clinically measurable depression of cholinesterase); and low-level (no immediate clinical signs or symptoms) exposure. Threshold exposure levels for known long-term effects from OP nerve agent are at or above intermediate-level exposure. Long-term health effects seen at intermediate-level exposures or in many survivors of high-level exposure are subtle, detectable in exposed populations but not individuals, and not reported in individuals experiencing low-level exposure alone. Co-exposure to other pharmaceutical agents may promote or protect against health effects from OP nerve agents, but qualitatively they are the same effects seen with OP nerve agents alone. Thus, the system for characterizing exposure based on initial acute effects is also useful for evaluating health outcomes from co-exposure to OP nerve and other agents.
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PMID:Review of health consequences from high-, intermediate- and low-level exposure to organophosphorus nerve agents. 984 Jul 47

Neuromuscular disorders can impose significant disability in patients by virtue of weakness, pain, and sensory and autonomic symptoms and deficits. For all of these disorders, supportive measures, appropriate physical therapy, and respiratory support are beneficial. Pain management can be accomplished by the use of antiepileptic medications, such as carbamazepine, phenytoin, valproic, and gabapentin. Tricyclic antidepressants can also be helpful for pain management and depression. Benzodiazepines and baclofen are helpful for management of spasticity. No specific treatment exists yet for the motor neuron disorders. In peripheral neuropathies, identifying and treating the cause is most important. In other neuropathies, such as in acute or chronic inflammatory demyelinating neuropathies, immunosuppression is indicated. Myasthenia gravis can be treated with cholinesterase inhibitors and immunosuppression. A specific treatment does not exist yet for muscular dystrophies. Immunosuppression is helpful in patients with inflammatory myopathies. Toxic myopathies can be treated by removing the causative agent and by supportive measures. Endocrine myopathies will respond to treatment of the primary endocrinopathy.
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PMID:Diagnostic algorithms for neuromuscular diseases. 992 72

The expression of sarcoplasmic esterases, lipases as well as the lipid content in the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos was studied. Lipid accumulation was documented at light, electron microsopic and by morphometric studies. The distribution of these lipid droplets was irregular and abundant in myofibers with numerous mitochondria (predominantly oxidative fibers). Histochemical inhibition of sarcoplasmic esterases and lipases was observed in the intoxicated animals. This sarcoplasmic inhibition of esterases occurs roughly in parallel to the inhibition of plasma cholinesterase activity. The inhibition of sarcoplasmic lipases may explain, at least partially, the accumulation of lipids. This inhibition probably makes difficult the use of lipids as fuel, especially in the oxidative fibers. In contrast to the small amount of muscle necrosis, (1.30+/-0.745), metabolic muscle impairment was intense and extensive, i.e., decreased activities of esterases and lipases in the sarcoplasm, that should contribute to muscle weakness. Therefore, because segmental necrosis was most prominent in oxidative fibers (and these fibers use lipids as the principal fuel and contain the greater amount of lipases in the sarcoplasm), it is possible that inhibition of activity of lipases is responsible for the segmental necrosis. Although the exact role of these metabolic changes is not known, it is possible that they contribute not only to the induction and evolution of muscle cell necrosis but also to the muscle weakness and clinical impairment of animals and humans in the acute intoxication by these compounds.
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PMID:Sarcoplasmic lipase and non-specific esterase inhibition in myofibers of rats intoxicated with the organophosphate isofenphos. 1004 10

This paper investigates the acute effects of carbofuran in workers of two pesticide-formulating plants. Mean airborne carbofuran concentrations ranged from 0.025 to 1.115 mg/m3 in plant A and from 0.018 to 0.067 mg/m3 in plant B, respectively. In workers of plant A the post-shift blood cholinesterase activity was significantly reduced, compared to pre-shift values. No difference in blood cholinesterase activity was found between pre- and post-shift values in workers of plant B. During the investigation, 25 cases of acute carbofuran poisoning were diagnosed by their clinical picture and depressed cholinesterase activity in blood. Usual symptoms included dizziness, weakness, blurred vision, nausea and sweating. Pallor, epigastric pain, vomiting and chest tightness occurred only in a few cases. Myosis was recorded in 24 cases. Fasciculation of muscle gastrocnemius induced by percussion was found in 6 cases, and four of them had also fasciculation of muscle orbicularis oculi. Inhibition of cholinesterase activity in the blood was related with the clinical features; however, the inhibition was rapidly reversible. In most cases, recovery was complete within 2-3 hours, with or without atropine treatment, after the subjects were removed from exposure. Rapid onset, mild illness and quick recovery are typical characteristics of occupational acute carbofuran poisoning.
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PMID:Acute effects of carbofuran in workers of two pesticide plants. 1021 31


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