Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.
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PMID:Nervous system degeneration produced by acrylamide monomer. 17 76

Doxifluridine, a new fluorouracil analog with a low myelosuppressive effect, has recently been subject to various disease-oriented, Phase II trials. For the present evaluation of drug tolerance, the Phase II data of 114 patients having received 376 doxifluridine cycles has been used. The treatment cycles consisted of 5 daily intravenous injections of 4,000 mg/m2 non-pretreated patients, and 3,000 mg/m2 in pretreated patients. Previous observations showing that doxifluridine is less myelotoxic than fluorouracil have been confirmed. 54% of the patients had no leucopenia (maintaining WBC counts over 3,000/mm3 and 90% had no thrombopenia (platelets not lower than 100,000/mm3) throughout treatment. However, a WHO grade 4 hematologic toxicity was observed in 9 patients, and 2 toxic deaths were related to severe granulocytopenia and sepsis. Digestive tract toxicity was similar and equally frequent as the one observed with fluorouracil: mucositis with oral ulcerations (19%), nausea and vomiting requiring specific treatment (8%) and severe but never hemorrhagic diarrhoea (5%). Neurologic toxicity was frequent, with 20% of patients complaining of somnolence and/or peripheral neuropathy, 7% of impaired consciousness and 1% of WHO grade 4 cerebellar ataxia. Among the 10% of patients with cardiac symptoms, 6% were benign and transient arrhythmias, and 4% were severe, including 1 myocardial infarction, 1 spontaneously reversible cardiac arrest and 2 ventricular fibrillations successfully treated with cardioversion. In spite of its encouraging antitumor activity and its good hematologic tolerance, intravenous doxifluridine, as used in this study, cannot be recommended because of the observed neurologic and cardiac toxicity. Oral doxifluridine is presently under investigation with preliminary results suggesting a lack of neuro- or cardiotoxicity.
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PMID:[Doxifluridine toxicity, a fluorouracil analog with low myelosuppressive effect]. 214 Feb 80

The three best-described genetic polymorphisms of drug metabolism--the debrisoquin/sparteine type of oxidative polymorphism (hereafter referred to as the debrisoquin polymorphism), the polymorphism of N-acetylation, and the mephenytoin type of oxidative polymorphism--are reviewed. For all three polymorphisms, the poor-metabolizer phenotype is inherited as an autosomal recessive trait. The debrisoquin and mephenytoin oxidative polymorphisms involve defects in two separate cytochrome P450 enzymes. The prevalence of the poor-metabolizer phenotype for debrisoquin ranges between 2% and 10% for groups of various ethnic origins. The poor-metabolizer phenotype for mephenytoin comprises about 5% of the Caucasian population and about 20% of the Japanese population. N-acetyltransferase is a cytosolic enzyme whose clinical polymorphism was discovered using isoniazid as the substrate probe. The prevalence of the slow-acetylator phenotype among American and European Caucasian and American black groups is about 50%; among the Japanese it is about 10%. More than 20 agents are substrates for debrisoquin hydroxylase, about 15 for N-acetyltransferase, and 3-5 for mephenytoin. In poor metabolizers, debrisoquin can cause hypotension, and sparteine can cause blurred vision, headache, and dizziness. Clinical consequences of the slow-acetylator phenotype include increased susceptibility to systemic lupus erythematosus induced by procainamide and hydralazine, peripheral neuropathy induced by isoniazid, hydralazine, and dapsone, and sulfasalazine-induced dose-related leukopenia, nausea, vomiting, headache, and vertigo. After administration of mephenytoin, poor metabolizers have increased somnolence and intellectual impairment. Awareness of genetic polymorphisms of drug metabolism should improve understanding of interindividual variability in drug disposition and response.
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PMID:Polymorphic drug metabolism. 268 60

Sensitizing and neurotoxic effect of ornidazole, was tested in a double-blind randomized study in patients with carcinoma of the cervix and larynx. Ornidazole or placebo were given orally, two times weekly, for 3 weeks. Dose was 2.5 g/m2 for each administration. Total dose given was 15 g/m2. Radiation therapy was given 3 h after the drug administration. Ornidazole was well tolerated in the majority of the patients. No neurotoxic side effects, such as peripheral neuropathy or convulsion, were observed with a total dose of up to 30 g. Dizziness, somnolence and nausea were the prominent acute side effects, seen mostly (70%) in women. In the placebo group this rate was 17% (p less than 0.01). No important side effect was observed in men receiving ornidazole. Serum concentration of ornidazole reached the maximum level in 2-4 h after oral administration and ranged (23 patients) from 65.1 to 139.8 micrograms/ml. Mean half-life was 15.6 +/- 2.8 h. Peak concentration in tumour tissue was achieved 1-3 h after the administration, ranging from 13.0 to 78.0 micrograms/g. Tumour concentration of ornidazole ranged from 14 to 93% of the serum concentration at the time of irradiation.
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PMID:Use of ornidazole in fractionated radiotherapy: dose tolerance, serum and tumour tissue concentration. 352 36

We studied sleep disordered breathing (SDB) in 12 patients with group A xeroderma pigmentosum (XP) by means of respiratory inductive plethysmography (Respisomnograph:Nims) during polysomnographical examination. The subjects were 6 male and 6 female patients aged from 10 months to 25 years. Four out of the subjects had SDB:3 showed sleep apnea (apnea index ranged from 5.2 to 44.2/h) and 1 presented desaturation during sleep (desaturation time per total sleep time was 4.3%). All these patients were over 12 years. The patients below 14 years had mainly the central type of SDB, and the others aged over 16 years had both the central and obstructive types of SDB. Three of the 4 patients had daytime sleepiness or restless sleep, which seemed to be due to SDB. We discussed the pathophysiology of SDB with XP in relation with brain stem function and peripheral neuropathy. We must pay attention to SDB in patients with XP aged over 12 years.
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PMID:[Sleep disordered breathing in group A xeroderma pigmentosum]. 807 94

Pyruvate dehydrogenase deficiency is one of the most common causes of encephalopathy associated with lactic acidosis and is known to account for congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome. Hitherto, however, peripheral neuropathy has not been regarded as a presenting symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon reflexes, and reduced motor nerve conduction velocities at 8 months of age. Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma were highly suggestive of a pyruvate dehydrogenase deficiency, and the determination of pyruvate dehydrogenase activity in circulating lymphocytes led to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband. Based on this observation, we suggest that pyruvate dehydrogenase deficiency should be considered in the diagnosis of peripheral neuropathy in infancy, especially when associated with persistent hyperpyruvicemia, normal lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and hypotonia of unknown origin.
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PMID:Leigh syndrome: pyruvate dehydrogenase defect. A case with peripheral neuropathy. 815 Oct 84

Legionella is a frequent etiologic agent in the development of both nosocomial and community acquired pneumonias. Involvement of the nervous system is common in Legionella infections. We present a case of Legionnaires' disease which illustrates distinctive neurologic findings including delirium and cerebellar dysfunction. Furthermore, this paper reviews the neurological and psychiatric features of 609 Legionella infected patients with involvement of the nervous system. The most common signs were disorientation (58%), headache (52.4%), and somnolence (39.7%). Less frequent or rare were: cerebellar dysfunction (11.2%), hallucinations (8.4%), agitation or stupor (4.1%), affective disorders (3.1%), peripheral neuropathy (2.8%), pyramidal disturbances (2.1%), memory loss (1.6%), seizures (1.5%), cranial nerve palsies (1.5%), incontinence (0.7%), and extrapyramidal disturbances (0.3%). Cranial CT scans, cerebrospinal fluid findings, and nerve and muscle biopsies were usually unremarkable. Neuropathologic examinations failed to demonstrate specific characteristics. Hyponatremia and serum CPK level elevation were present in up to 89% and 50% of patients, respectively. Prognosis of disturbances of the nervous system was mainly good. We conclude that in the presence of definite neurological findings, pulmonary infection, hyponatremia, and CPK elevation Legionella infection should be considered.
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PMID:[Neurologic and psychiatric symptoms of legionella infection. Case report and overview of the clinical spectrum]. 927 65

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogeneic bone marrow transplantation (BMT). Thalidomide was found to have immunosuppressive properties and it has been used in a limited number of children with cGVHD. We report our experience with refractory and/or high-risk cGVHD in 14 children. Six children showed complete clinical response to thalidomide in a median time of 2 months. Four children had partial responses and four failed. Side-effects were usually mild (somnolence, constipation) and only two patients developed sensory peripheral neuropathy. An increased incidence of infectious complications attributable to thalidomide was not observed. Nine out of 10 responding patients are alive 49-111 months post-BMT. Thalidomide can be effective particularly in children with prevailing mucocutaneous cGVHD. All patients should be carefully monitored to detect peripheral neuropathy early.
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PMID:The role of thalidomide in the treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children. 954 61

1. In animal studies, TPTA was found to be neurotoxic. In humans, variable CNS pictures have been described with or without significant EEG findings. Brain CT does not usually reveal any abnormalities. 2. Our patient presented with intermittent unique spontaneous involuntary movement of hands, facial twitching, silly smile and crying. Diplopia, drowsiness, giddiness, vertigo, bidirectional nystagmus, impairment of calculation ability, as well as disorientation to time, people and place also developed. EEG showed mild cortical dysfunction without seizures. MRI and Tc-99m HMPAO brain SPECT revealed no significant findings. TPTA may cause cellular dysfunction of brain without structural damage, which results in variable CNS clinical presentations. 3. Nadir of leucopenia was noted on the sixth day after consumption of TPTA. Liver impairment occurred on the ninth day. Borderline demyelinated neuropathy developed on the fifty-third day. CNS abnormalities, delayed peripheral neuropathy, hepatitis and leucopenia deserve monitoring for a prolonged period, even when the victim initially presents with GI upset only after consumption of TPTA.
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PMID:Unique cerebral dysfunction following triphenyltin acetate poisoning. 972 37

Disulfiram is known to cause hepatitis, which is sometimes fatal. The best estimate of the frequency of disulfiram-induced fatal hepatitis is 1 case in 30,000 patients treated/year. Its appears to be more common in patients given disulfiram for the treatment of nickel sensitivity. Frequent blood testing for liver function is probably not necessary, but patients taking disulfiram should be in regular contact with a physician. There are rare reports of psychosis and confusional states in conjunction with disulfiram treatment and peripheral neuropathy and optic neuritis have been reported; these effects are dose-related. Psychiatric complications appear to be more common with the use of disulfiram in India than in Western countries. Of the less serious adverse effects, tiredness, headache and sleepiness are the most common. Deaths from the disulfiram-alcohol (ethanol) interaction have not been reported in recent years, possibly because the dosages used are lower than those used 40 years ago, and patients with cardiac disease are now excluded from treatment. There is no evidence to suggest that disulfiram causes cancer. Of note, there are drug interactions with compounds that utilise the cytochrome P450 enzyme system. Disulfiram can be viewed as a drug with a moderate record of adverse effects. Alcohol dependence, for which it can be a helpful treatment, is associated with a high morbidity and mortality.
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PMID:Safety issues concerning the use of disulfiram in treating alcohol dependence. 1034 93


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