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)

We reviewed the natural history and differential diagnosis of ornithine transcarbamylase deficiency (an X-linked inborn error of urea synthesis) in 13 symptomatic female heterozygotes. The patients presented as early as the first week of life or as late as the sixth year. The most common symptoms before diagnosis were nonspecific: episodic extreme irritability (100 percent), episodic vomiting and lethargy (100 percent), protein avoidance (92 percent), ataxia (77 percent), Stage II coma (46 percent), delayed physical growth (38 percent), developmental delay (38 percent), and seizures (23 percent). Including the proband, 42 percent of the female members of the 13 families studied had symptoms. The median interval between the onset of major symptoms (vomiting and lethargy, seizures, and coma) and diagnosis was 16 months (range, 1 to 142). Five patients had IQ scores below 70 at the time of diagnosis. We suggest that careful evaluation of the family history, the dietary history, the episodic nature of the nonspecific symptoms, the response of these symptoms to the withdrawal of protein, and their frequent onset at the time of weaning from breast milk will permit early diagnosis and might thereby reduce the risk of death or neurologic impairment in female patients with partial ornithine transcarbamylase deficiency.
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PMID:Natural history of symptomatic partial ornithine transcarbamylase deficiency. 394 92

Two subchronic studies were conducted to assess the potential toxicity of N-D-ornithyl amphotericin B methyl ester (OAME). In both studies the comparative control substance was amphotericin B (AMB). Dogs (5/sex/group) were given OAME (82% pure, based on high-pressure liquid chromatographic (HPLC) analysis) at 0.6, 2.5, and 10 mg/kg or AMB at 0.6 mg/kg intravenously once daily for 3 months. Two dogs per sex per group were retained for a 7-week postdose observation period. Rats (15/sex/group) were given daily doses of OAME at 4, 12, 24, and 36 mg/kg or AMB at 5 and 12 mg/kg intraperitoneally for 3 months. The principal organs of toxicity in both species were the liver, kidneys, and circulating erythrocytes. Hepatic changes in dogs consisted of periportal and centrilobular inflammation in animals of all dosed groups and were equivalent in dogs given 0.6 mg/kg OAME or AMB. In rats, acute hepatic necrosis with periportal, centrilobular, or panlobular distribution in animals of all OAME (except 4 mg/kg) and AMB-dosed groups was observed. These changes were equivalent in the 36-mg/kg OAME- and 12-mg/kg AMB-dosed animals. Renal changes, evidenced by increases in serum urea nitrogen water consumption, urine volume, decreased urine osmolality, and renal tubular changes (ranging from degeneration and regeneration to necrosis), were observed in both species. In dogs, these changes in the OAME-dosed animals were less severe at all doses than those observed in the AMB-dosed dogs. Renal changes in rats, which were mild in comparison to the dogs, were equivalent at doses of 5 and 12 mg/kg AMB and 36 mg/kg OAME. Decreased erythrocyte counts, hematocrit, and hemoglobin values were observed in both species. Unique to the dog study, however, were irreversible behavioral (somnolence, ataxia, tremors, and compulsive searching) and/or morphologic brain changes (gliosis with astrocytic hypertrophy and hyperplasia) at doses of 2.5 and 10 mg/kg OAME. Similar changes were observed in two dogs given 10 mg/kg OAME (100% pure, based on HPLC analysis) in a 6-week pilot study, indicating that the neurological changes were induced by OAME rather than by an impurity. These changes appear related to prolonged exposure to high plasma concentrations of OAME.
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PMID:Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats. 404 96

Dementia, a syndrome of acquired intellectual deterioration, is an etiologically nonspecific condition that can be permanent or reversible. When evaluating demented patients, a careful exposure history will determine the possible role of drugs, metals, or toxins. Physical examination may reveal focal deficits in cases of intracranial mass lesions and spasticity or ataxia of the lower limbs if hydrocephalus is present. Coexistence of dementia and a peripheral neuropathy usually indicates the existence of a toxic or metabolic disorder. Depressed mood, sleep disturbance, anorexia, impotence, constipation, and psychomotor retardation indicate the presence of a depressive syndrome. Asterixis, myoclonus, and postural tremor are common in toxic-metabolic dementias, whereas resting tremor, choreoathetosis, or rigidity occur in progressive extrapyramidal disorder. EEG is focally abnormal in cases of cerebral mass lesions and shows generalized slowing in toxic-metabolic encephalopathies. CT will aid in the identification of hydrocephalus, subdural hematomas, and intracranial mass lesions. A thorough laboratory evaluation including complete blood count, erythrocyte sedimentation rate, electrolytes, blood urea nitrogen and blood sugar, liver and thyroid function tests, serum calcium and phosphorus levels, B12 and folate levels, serum copper and ceruloplasmin, VDRL, chest X-ray, electrocardiogram, and lumbar puncture may demonstrate treatable disorders that are adversely affecting intellectual function. Elderly individuals are particularly susceptible to the effects of toxic or metabolic disorders, and a mild dementia may be exaggerated by relatively minor fluctuations in metabolic status. Treatable causes of dementia should be sought in all demented patients.
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PMID:Treatable dementias. 635 58

The clinical and clinicopathologic effects of excess oral pyridoxine hydrochloride (150 mg/kg body weight/day) and clioquinol (200 mg/kg body weight/day) alone and in combination were evaluated in adult Beagle dogs over an experimental period of approximately 100 days. Anorexia and loss of body weight occurred in the first weeks of the trial period in each treatment group, but was most severe in dogs given both compounds. Dogs in each treatment group (10 of 10 pyridoxine-treated dogs, 6 of 13 clioquinol-treated dogs and 12 of 13 pyridoxine plus clioquinol-treated dogs) developed neurologic disease, manifested principally by ataxia. Pyridoxine-treated dogs had proprioceptive loss involving both fore- and hindquarters, characterized by stiff, spastic, dysmetric leg movements. In clioquinol-treated dogs, dysmetric leg movements were accompanied by failure to support body weight in the hindquarters, but similar forelimb involvement occurred in severely affected dogs. The neurologic disease in dogs given both compounds varied; signs in some dogs resembled those of affected dogs of the pyridoxine-treated group, and in others, those in clioquinol-treated group. Erythrocyte counts, hemoglobin concentrations and packed cell volumes were reduced in dogs in each treatment group and were lowest in dogs given both compounds. Plasma protein was mildly reduced in dogs given pyridoxine or pyridoxine plus clioquinol. Few or no differences were present in the leukocyte counts, blood urea nitrogen concentrations, in activities of serum alanine aminotransferase and aspartate aminotransferase, and in concentrations of sodium, chloride or potassium in treated dogs as compared to control dogs.
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PMID:The subacute neurotoxicity of excess pyridoxine HCl and clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs. I. Clinical disease. 645 37

Hydroxygentamicin, an aminoglycoside antibiotic, was administered subcutaneously to cats in doses up to 160 mg base/kg daily for 10 to 13 weeks. Gentamicin and a vehicle solution were tested as positive and negative control, respectively; in one test netilmicin was also included for comparative purposes. Several parameters, including serum urea nitrogen, serum creatinine, organ/body weight ratios, serum and tissue concentrations of the antibiotics, and renal pathology, were determined to ascertain the nephrotoxic potential of the three aminoglycosides. In addition, observations for the onset of ataxia and impairment of righting reflex were made during the course of the studies to compare the vestibular ototoxic effects of the three antibiotics. Although serum urea nitrogen and serum creatinine values increased markedly in those cats which eventually died or were sacrificed moribund, these parameters in survivors were slightly but not significantly higher than controls. Serum concentrations of the drugs were proportional to the doses administered, but renal concentrations were approximately two and five times as high for netilmicin and gentamicin, respectively, as they were for equivalent doses of hydroxygentamicin. The morphological changes observed in the kidney of cats given 60 mg base/kg of hydroxygentamicin were slightly less than those seen in cats administered 10 mg base/kg of gentamicin; similarly, kidney changes in cats given netilmicin were observed approximately twice as frequently as they were in those receiving equivalent doses of hydroxygentamicin. The nephrotoxic effects of aminoglycoside antibiotics were directly related to renal drug concentration and not to serum concentration, which was a function of dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nephrotoxic and ototoxic effects of hydroxygentamicin in cats. 647 2

Strychnine toxicosis is characterized by inducible tetanic seizures and metaldehyde poisoning by fine fasciculations progressing to generalized tremors and seizures. Intoxication with 1080 causes seizures, random running movements, vomiting, defecation, urination, acidosis and hyperglycemia. Intoxication with rodenticides causing coagulopathy is characterized by hemorrhage into body cavities but not necessarily external hemorrhage. Anticholinesterase insecticides cause salivation, urination and defecation, while chlorinated hydrocarbon insecticides cause CNS disturbances. Ethylene glycol intoxication results in ataxia, depression, coma, vomiting and tachypnea, followed by acute renal failure. Urea poisoning causes bloat and CNS signs in cattle. Monensin intoxication in horses lasts several days and causes stiffness, colic, uneasiness and recumbency. Salt poisoning results in depression, seizures and hypernatremia. Lead poisoning is associated with central and peripheral nervous system signs, as well as increased numbers of nucleated RBC and basophilic stippling of RBC. Arsenic poisoning results in GI pain, diarrhea, weakness and death. Copper toxicosis in sheep is manifested by hemolytic anemia, hemoglobinemia and hemoglobinuria. Plants that may intoxicate domestic animals include sorghum, greasewood, halogeton, water hemlock, Japanese yew, larkspur, lupine, milk-weed, philodendron, oleander, castor bean and precatory bean.
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PMID:Practical toxicologic diagnosis. 649 3

The toxic effects of PR toxin were observed in mice, rats, anesthetized cats and isolated rat auricle preparations. In mice and rats the toxic effects included abdominal writhing, decrease of motor activity and respiratory rate, weakness of hindleg and ataxia. In mice, the i.p. LD50 was 5.8 mg/kg. In mice, rats and cats PR toxin given i.p. caused ascites fluid an edema in the scrotum and lungs, and i.v. injection caused edema in the lungs, giving rise to a large volume of pleural and pericardial fluid. In rats, at the LD50 dose level (11.6 mg/kg, i.p. and 8.2 mg/kg, i.v.), the water content in the lungs was increased, but in the skin it was decreased. Blood K+, hematocrit, red blood cell, white blood cell, hemoglobin, uric acid, cholesterol, blood urea nitrogen and alkaline phosphatase concentrations were all increased, while the total protein and albumin contents were decreased after i.p. injection of PR toxin. High content of protein was found in the pleural fluid and fluid due to ascites. In anesthetized cats the blood pressure and respiratory rate were progressively decreased and the heart rate was reflexly increased after i.p. injection. The i.v. injection produced a multiple response on the arterial blood pressure, but with a progressively decreasing heart rate. Arrhythmias were observed in the late shock stage in the case of i.p. or i.v. injection. In the isolated rat auricle preparations contractile force was more affected that heart rate. We conclude that PR toxin produced acute toxic effects in animals via an increase of capillary permeability and a direct damage to the lungs, heart, liver and kidney.
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PMID:Acute toxicity of PR toxin, a mycotoxin from Penicillium roqueforti. 708 52

The toxic effects of oral administration of Cassia occidentalis to goats was evaluated. The prominent signs of Cassia poisoning were diarrhea, inappetence, dyspnea, staggering, ataxia and recumbency. Lesions consisted of hemorrhages and congestion in the heart, lungs, abomasum and spleen, catarrhal enteritis, hepatic fatty change and necrosis, splenic hemosiderosis, pulmonary emphysema, necrosis and/or degeneration of the epithelial cells of the renal convoluted tubule, and packing of the glomeruli with endothelial and small round cells. These changes were accompanied by increases in GOT activity and in the serum concentrations of ammonia and urea, as well as by decreases in the total protein and calcium in serum. There were decreases in Hb, PCV and RCB, and increased leucocyte counts. Total lipids were higher in the liver, kidneys and heart of the Cassia-poisoned goats.
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PMID:The toxicity of Cassia occidentalis to goats. 713 98

Argininosuccinic aciduria (ASA-uria) is a rare inborn error of the urea cycle, in which there is massive excretion of argininosuccinic acid (ASA) in the urine together with elevated concentrations of ASA in the plasma and the CSF. The characteristic symptoms are either those of overwhelming metabolic disease in the newborn period, or variable psychomotor retardation. The present patient, the first Finnish one to be reported, was a 49-year-old woman. She was hospitalized at the age of 26 with a diagnosis schizophrenia and mental retardation. Her clinical symptoms consisted of ataxia, disturbance of coordination, clumsiness, intention treMor and a positive Romberg's sign. The laboratory findings were consistent with the mild, late-onset type of ASA-uria.
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PMID:Argininosuccinic aciduria in a Finnish woman presenting with psychosis and mental retardation. 713 86

Ornithine transcarbamylase deficiency is an X-linked recessive disorder of urea biosynthesis characterized by recurrent, often fatal, hyperammonemic encephalopathy in affected males; carrier females are usually asymptomatic. We report here the clinical and laboratory findings in five symptomatic heterozygous females with ornithine transcarbamylase deficiency. In each case, the onset of symptoms occurred in the 1st year of life, but diagnosis was delayed by up to 15 years. Symptoms included recurrent vomiting with lethargy (five patients), dietary protein intolerance (five), irritability (four), severe acute encephalopathy (three), ataxia (three), and acute hemiparesis (two). All eventually showed evidence of developmental delay or learning difficulties. Two of the three who experienced severe, acute, hyperammonemic encephalopathy suffered serious, permanent neurologic sequelae. Three of the patients showed decreased ornithine transcarbamylase activity in liver obtained by needle biopsy, and the other two had marked orotic aciduria associated with hyperammonemia. Neuroimaging studies demonstrated persistent abnormal lobar attenuation and abnormal signal on computed tomographic scan and magnetic resonance imaging. All patients showed marked symptomatic improvement on treatment with dietary protein restriction supplemented by pharmacologic measures to increase nonprotein nitrogen excretion. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of acute or chronic encephalopathy in females at any age.
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PMID:Ornithine transcarbamylase deficiency in females: an often overlooked cause of treatable encephalopathy. 749 56


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