Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new series of disubstituted tetrahydrocarbazoles were synthesized. They are tested for antidepressive activity by the Porsolt's forced swimming test (one of the acute stress methods) and by the prevention of reserpine induced hypothermia and ptosis in mice. 3-Morpholino-1-[N-(6-methoxy-1,2,3,4- tetrahydrocarbozolyl)2-propanol, fumarate (XI) was demonstrated to be the most promising compound of this series. Besides, this series did not present the most common adverse effects of the conventional tricyclic-antidepressants (loss of locomotor coordination, ataxia and anticholinergic activity).
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PMID:Synthesis of disubstituted tetrahydrocarbazoles with potential antidepressive activity. 278 27

The clinical, pathological and toxicological findings in a cat poisoned with Pinesol, a household cleaning agent, are reported. Clinically severe depression, with unresponsive pupils and extreme ataxia were observed prior to death. Pathologic changes consisted of severe acute centrilobular hepatic necrosis and renal cortical necrosis. Pinesol specific fatty acids and isopropanol were found using gas chromatographic analysis of kidney and fat. It was concluded that the cat died of Pinesol intoxication.
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PMID:Acute Pinesol toxicity in a domestic cat. 375 Aug 13

We evaluated blood concentrations and clinical findings in 17 cases of isopropanol (IPROH) ingestion seen over a 8.5 year period at our institution. Eight ingestions involved IPROH alone ("pure") while the remainder involved at least ethanol in addition to IPROH ("mixed"). Fourteen patients had a history of alcoholism. Admission blood IPROH concentrations ranged from 5 to 70 mg/dL while the concentration of the acetone metabolite ranged from nondetectable to 220 mg/dL. The mean acetone concentration was significantly higher for "pure" ingestions than for "mixed" ingestions (p less than 0.05); however, the mean IPROH concentrations showed no significant difference. The mean anion gap was significantly higher for "mixed" ingestions than for "pure" ones (p less than 0.01). Fifteen patients were either alert or lethargic while two, who had ingested no compounds other than IPROH, were comatose. The most common other physical findings were tachycardia (10 cases), decreased deep tendon reflexes (5), dysarthria (4), and ataxia, hypotension, fever, and mydriasis (3 cases each). None of the findings including level of consciousness showed statistically significant correlation with the IPROH concentrations. Twelve patients were hospitalized; eleven of these recovered with supportive care alone. One patient expired from trauma suffered in a motor vehicle accident.
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PMID:Isopropanol ingestion: interpretation of blood concentrations and clinical findings. 666 30

Five groups of 25 Fischer 344 rats of each sex were exposed for 6 h to isopropanol vapor at 0, 500, 1500, 5000 or 10,000 ppm. Behavioral observations for 10 rats of each sex were made prior to and 1, 6, and 24 h after exposure. Motor activity was evaluated for 15 rats of each sex prior to and immediately following exposure. Exposure to isopropanol caused a spectrum of transient effects indicative of narcosis at 10,000 ppm and sedation at 5000 ppm. Prostration or severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular function, hypothermia and loss of reflex function were observed 1 and 6 h after exposure to 10,000 ppm isopropanol vapor. Similar, but less severe, alterations were observed in animals in the 5000 ppm exposure group 1 h after exposure. Exposure concentration-related decreases in motor activity were observed in males and females in the 5000 and 10,000 ppm groups and slight decreases in motor activity were observed in males in the 1500 ppm group. Animals in the 1500 and 5000 ppm exposure groups recovered from these motor activity effects within 5 h. Based on this study, exposure of male and female rats to isopropanol vapor produces transient, concentration-related narcosis and/or sedation at concentrations of 5000 and 10,000 ppm and minor decreases in motor activity in males at a concentration of 1500 ppm. The no-observed-effect level (NOEL) for this was 500 ppm isopropanol.
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PMID:Isopropanol: acute vapor inhalation neurotoxicity study in rats. 778 62

This study was conducted to evaluate the possible subchronic toxicity as well as neurobehavioral effects of isopropanol, a widely used industrial and commercial solvent. Five groups, each containing 10 Fischer 344 rats/sex and 10 CD-1 mice/sex, were exposed for 6 hr/day, 5 days/week, for 13 weeks to isopropanol vapor at concentrations of 0 (control), 100, 500, 1500, or 5000 ppm. An additional 15 rats/sex were assigned to the 0, 500, 1500, and 5000 ppm groups for assessment of neurobehavioral function. No exposure-related mortalities occurred during the study. The narcotic effects of isopropanol were noted only during exposures at 1500 and 5000 ppm. These signs, noted during exposures, were typically absent following exposures. The only clinical signs observed following exposures included swollen periocular tissue, perinasal encrustation, and ataxia for rats of the 5000 ppm group. Neurobehavioral evaluations indicated no changes in any of the parameters of the functional observational battery; however, increased motor activity for female rats in the 5000 ppm group was noted at Weeks 9 and 13. Decreases in body weight and body weight gain were observed for rats of the 5000 ppm group at the end of the first week of exposure. During the remaining weeks, increases in body weight and/or body weight gain were observed for rats of the 1500 and 5000 ppm groups. No exposure-related effects on body weight were noted for male mice; however, increased body weight and body weight gain were observed for female mice of the 5000 ppm group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isopropanol 13-week vapor inhalation study in rats and mice with neurotoxicity evaluation in rats. 783 43

Isopropanol (IPA) is a volatile solvent that is used in many industrial process. The major symptoms of acute isopropanol toxicity include dizziness, incoordination, headache, hypothermia, eye ataxia, irritation of upper respiratory tract and shortness of breath. Vomiting, hematemesis, diarrhoea and hypotension may occur following accidental ingestion of IPA. No data regarding subchronic or chronic toxicity of IPA were identified. The aim of this study was to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and of gamma-glutamyltransferase (gamma-GT) of the last five years in 40 printer workers after the removal of IPA from the industry. The serum levels of ALT, AST and gamma-GT were higher in the exposed workers than in non exposed. In conclusion, the results of this study show that the removal of IPA from the industry had a positive health effect improving the hepatic function of the workers.
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PMID:[Modifications of hepatic transaminases in workers exposed to low doses of isopropanol]. 1840 81

PRO: In the past decade, genotyping has started to help the neurologic practitioner treat patients with three types of epilepsy causing mutations, namely (1) SCN1A, a sodium channel gene mutated in Dravet's sporadic severe myoclonic epilepsy of infancy (SMEI and SMEB); (2) laforin (dual specificity protein phosphatase) and malin (ubiquitin E3 ligase) in Lafora progressive myoclonic epilepsy (PME); and (3) cystatin B in Unverricht-Lundborg type of PME. Laforin, malin, and cystatin B are non-ion channel gene mutations that cause PME. Genotyping ensures accurate diagnosis, helps treatment and genetic counseling, psychological and social help for patients and families, and directs families to organizations devoted to finding cures for specific epilepsy diseases. In SCN1A and cystatin B mutations, treatment with sodium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine) should be avoided. Because of early and correct diagnosis by genotyping of SCN1A mutations, the avoidance of sodium channel blockers, and aggressive treatment of prolonged convulsive status, there is hope that Dravet's syndrome may not be as severe as observed in all past reports. Genotyping also identifies nonsense mutations in Lafora PME. Nonsense mutations can be corrected by premature stop codon readthrough drugs such as gentamicin. The community practitioner together with epilepsy specialists in PME can work together and acquire gentamicin (Barton-Davis et al., 1999) for "compassionate use" in Lafora PME, a generalized lysosome multiorgan storage disorder that is invariably fatal. In Unverricht-Lundborg PME, new cohorts with genotyped cystatin B mutations have led to the chronic use of antioxidant N-acetylcysteine and combination valproate clobazam or clonazepam plus antimyoclonic drugs topiramate, zonisamide, piracetam, levetiracetam, or brivaracetam. These cohorts have minimal ataxia and no dementia, questioning whether the syndrome is truly progressive. In conclusion, not only is genotyping a prerequisite in the diagnosis of Dravet's syndrome and the progressive myoclonus epilepsies, but it also helps us choose the correct antiepileptic drugs to treat seizures in Dravet's syndrome and Unverricht-Lundborg PME. Genotyping also portends a brighter future, helping us to reassess the true course, severity, and progressive nature of Dravet's syndrome and Unverricht-Lundborg PME and helping us craft a future curative treatment for Dravet's syndrome and Lafora disease. Without the genotyping diagnosis of epilepsy causing mutations we are stuck with imprecise diagnosis and symptomatic treatment of seizures. CON: Genotyping of epilepsy may help to better understand the genetics of epilepsy, to establish an etiology in a patient with epilepsy, to provide genetic counseling, and to confirm a clinical diagnosis. However, critical analysis reveals that genotyping does not contribute to an improved treatment for the patients. In order to improve treatment, genotyping would have to (1) improve our ability to select the drug of choice for a given epilepsy or epileptic syndrome; (2) improve our ability to predict the individual risk of adverse reactions to certain drugs; (3) improve our ability to avoid unnecessary treatments or treatments that could aggravate seizures. Many example illustrate the lack of impact of genetic information on the treatment outcome: we do not treat Dravet syndrome more successfully since SCN1A testing became available; we do not treat Lafora disease more successfully since testing for laforin and malin became available; we do not need to know the genetic nature of Unverricht-Lundborg disease or test for the cystatin B mutation in order to select or avoid certain drugs; we do not treat Rett syndrome more successfully since MECP2 testing became available; we do not treat JME more successfully since we know its genetic origin; we do not treat autosomal dominant nocturnal frontal lobe epilepsy more successfully since we know its genetic origin and can test for its mutation. The clinical characteristics as well as the response to treatment of these epilepsy syndromes have been well established before genotyping became available. It can not be argued that genotyping is necessary for establishing a diagnosis or ensure accurate diagnosis. Since not all individuals with given syndromes have been shown to have the corresponding mutation, the clinical diagnosis must have been based on well-established clinical criteria. In addition, the presence or absence of the mutation in a given patient has never been shown to specifically predict the response to any form of treatment, positive or negative. Finally, the appropriate psychological and social help in a given patient will not depend on the identification of a mutation. This does not leave any role for genotyping in epilepsy for the sole reason of improving treatment of the patient. Claiming that the result of genotyping predicts optimal treatment in certain epilepsies is equivalent to stating that genotyping for diabetes has become available and that, based on this breakthrough, insulin can now be selected as the treatment of choice in those who test positive.
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PMID:Debate: Does genetic information in humans help us treat patients? PRO--genetic information in humans helps us treat patients. CON--genetic information does not help at all. 1908 13