Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancopride ((+-)N-(1-azabicyclo-[2,2,2]-oct-3-yl)-2-cyclopropylmethoxy-4-ami no-5-chlorobenzamide) is a new potent and selective 5-HT3 receptor antagonist, orally and parenterally effective against cytotoxic drug-induced emesis. In vitro, pancopride displayed high affinity (Ki = 0.40 nM) for [3H]GR65630-labelled 5-HT3 recognition sites in membranes from the cortex of rat brains. In vivo, pancopride antagonized 5-HT-induced bradycardia in anaesthetized rats when administered i.v. 5 min (ID50 = 0.56 microgram/kg) or p.o. 60 min (ID50 = 8.7 micrograms/kg) before 5-HT challenge. A single oral dose (10 micrograms/kg) of pancopride produced a significant inhibition of the bradycardic reflex over an 8-h period. Pancopride dose dependently inhibited the number of vomiting episodes and delayed the onset of vomiting induced by cisplatin in dogs (ID50 = 3.6 micrograms/kg i.v. and 7.1 micrograms/kg p.o.). Pancopride was also effective in blocking mechlorethamine- and dacarbazine-induced emesis. Unlike metoclopramide, pancopride was shown to lack any measurable antidopaminergic activity both in vitro and in vivo. These results support clinical data, indicating that pancopride will be a useful drug for treating cytostatic-induced emesis in humans.
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PMID:Pancopride, a potent and long-acting 5-HT3 receptor antagonist, is orally effective against anticancer drug-evoked emesis. 145 37

We report a 17-year-old female case of ornithine transcarbamylase (OTC) deficiency who died of brain edema due to hyperammonemic attack. The patient had a brother with OTC deficiency who had died of hyperammonemia at 17 years of age. She firstly had a symptom of headache, nausea, vomiting and myalgia at 14 years old and twice thereafter. On admission she had a severe disorientation and vomiting. The plasma ammonia level was 89 micrograms/dl, then increased to 400 micrograms/dl in five hours. In addition to plasma exchange, hemodialysis and then peritoneal dialysis for next 5 days, parenteral sodium benzoate and arginine were administered. Although the plasma ammonia level improved gradually, her consciousness never returned and she died of severe brain edema with uncontrollable hypotension on day 8. Histology of a necropsy liver sample showed fatty metamorphosis of hepatocytes mainly with fine lipid droplets. Electron micrograph of hepatocytes showed crystalloid inclusions in mitochondria. Significance of the clinical course and the treatment during hyperammonemic crisis was discussed.
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PMID:[Abrupt onset and rapid deterioration in the course of congenital ornithine transcarbamylase deficiency: a case report]. 221 May 91

We report on 21 male patients who presented after 28 days of age with ornithine transcarbamylase (OTC) deficiency, which we define as late-onset OTC deficiency. These patients appeared normal at birth, but irritability, vomiting, and lethargy, which were often episodic, later developed. The age at presentation ranged from 2 months to 44 years. Biochemical testing revealed hyperammonemia, hyperglutaminemia, hypocitrullinemia, increased urinary orotate excretion, and decreased liver OTC activity measured in vitro, which ranged from 0% to 15% of normal. Male patients who were older at presentation had a somewhat different pattern of presenting symptoms and were more likely to die. These data illustrate the phenotypic variability of OTC deficiency. Unexplained episodes of repetitive or protracted vomiting in association with progressive alterations in behavior or neurologic findings should suggest the diagnosis of a urea cycle defect (or another symptomatic inborn error of metabolism), regardless of the age or medical history of the patient.
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PMID:Late-onset ornithine transcarbamylase deficiency in male patients. 224 87

The patient, 2 years and 9 months of age, was referred to our hospital with complaints of frequent vomiting, left hemiconvulsion and deep coma. The serum ammonia level was 251 micrograms/dl. Urine had a high orotate level (3,900 mumol/g creatinine). There was 7% residual of ornithine transcarbamylase (OTC) activity in the liver. Activities of other enzymes of the urea cycle were within normal limits. CT scanning on admission showed diffuse low density of both frontal lobes and of the right temporo-parietal lobe, narrowing of the right lateral ventricle and a shift of the mid-line to the left. The diffuse low density area was not enhanced after contrast medium injection. Follow-up CT scanning showed progressive bilateral ventricular dilatation and cerebral and cerebellar atrophy.
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PMID:A female case of ornithine transcarbamylase deficiency with marked computed tomographic abnormalities of the brain. 673 21

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

The anti-emetic activity of oral and intravenously-administered BRL 46470 (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3yl)-2,3-dihydro-3,3- dimethyl-indole-1-carboxamide HCl) has been assessed in conscious ferrets. BRL 46470 (0.05-0.5 mg kg-1, p.o.) dose-dependently prevented emesis evoked over a 2 h period by total body X-irradiation. This anti-emetic activity occurred with oral or intravenously-administered BRL 46470 even when dosed 3-4 h before radiation. In conjunction with data obtained in other species, we conclude that BRL 46470 has a potent and long-lasting ability to antagonize actions that are mediated by the 5-HT3 receptor in-vivo.
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PMID:Prolonged anti-emetic activity and 5-HT3-receptor antagonism by BRL 46470 in conscious ferrets. 793 54

Late onset of symptoms in a 12 1/2-year-old male with ornithine transcarbamylase (OTC) deficiency were associated with unusual histological features in the liver. The patient presented with an acute onset of hyperammonemia and altered mental status after a 2-day prodrome of vomiting and lethargy. Physical examination showed a combative and disoriented male with icteric sclerae but with no fever or hepatomegaly. The plasma ammonia level was 282 microM. Enzyme assays of liver tissue obtained by percutaneous needle biopsy showed OTC activity of approximately 3% of normal; carbamyl phosphate synthetase was normal. Histopathological findings included severe microvesicular centrilobular steatosis. Hepatic architecture and reticulin framework were well preserved. Many hepatocyte nuclei were filled with glycogen. Electron microscopy showed mitochondria that were rounded and expanded with cristae at the edge of the mitochondrial membrane. In contrast to other reports, only slight variations in size and shape were seen. Megamitochondria and intramatrical paracrystalline inclusions were not identified. The cytoplasm contained scattered fat globules, peroxisomes, and dilated smooth endoplasmic reticulum. The prominent mitochondrial abnormalities commonly found in OTC deficiency were notably absent.
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PMID:Histopathological findings in a male with late-onset ornithine transcarbamylase deficiency. 800 87

Ornithine transcarbamylase (OTC) deficiency, the most common inborn error of the urea cycle, shows X-linked inheritance with frequent new mutations. Using polymerase chain reaction (PCR) amplification of the individual exons including adjacent intron sequences followed by direct sequencing of the amplimers we identified four new mutations affecting donor splice sites of introns 2, 5, 6, and 8. The mutation at the first position of intron 2 was a G to A exchange associated with acute neonatal hyperammonemia in a male patient at the age of 5 months. A G to C substitution in intron 5 was detected in a boy who developed 2 days after birth hypotonia, and respiratory distress, followed by severe hyperammonemia and terminal coma. The intron 6 mutation, a G to T substitution, was detected in a girl presenting with first episodes of vomiting and agitation at the age of 2 months. The mutation in intron 8, also a G to T transition, caused fatal hyperammonemia and early death at the age of 15 days in a male patient. We present four donor splice site mutations resulting in severe neonatal or very early onset of the disease in three boys and in one female patient. As the GT dinucleotide of the 5' donor splice site is invariant and required for correct splicing the described mutations may lead to improperly spliced mRNAs and aberrant gene products.
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PMID:Identification of four novel splice site mutations in the ornithine transcarbamylase gene. 856 55

A case of a 13-year-old boy with protracted vomiting, ataxia, and altered mental status, ultimately diagnosed with late-onset ornithine transcarbamylase (OTC) deficiency, is presented. OTC deficiency is the most common urea cycle defect and typically is diagnosed in male infants with irritability, poor feeding, vomiting, lethargy, and often death caused by the effects of hyperammonemia. Late-onset OTC deficiency has been described in patients of all ages. The presenting symptoms in these patients vary but the most common are vomiting and lethargy. The pathophysiology, clinical features, differential diagnosis, and treatment of this disorder are discussed. Because of the risks of serious consequences, early detection and treatment of OTC deficiency and hyperammonemic episodes are mandatory. Emergency physicians caring for children and adults need to be aware of the spectrum of clinical presentations of OTC deficiency, including late-onset disease.
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PMID:Vomiting, ataxia, and altered mental status in an adolescent: late-onset ornithine transcarbamylase deficiency. 885 3

Late-onset urea cycle disorder in a 20-month-old boy is unusually associated with Klinefelter syndrome with a 47XXY karyotype. We record the typical clinical and biochemical findings of ornithine transcarbamylase (OTC) deficiency in a young boy with a short history of recurrent vomiting, self mutilating behaviour, lethargy, ataxia and seizures. Laboratory studies showed hyperammonaemia and orotic aciduria, with normal citrulline and other urea cycle amino acids. Unfortunately, a liver biopsy for OTC activity measurement was refused by the parents. A rapid reversal of phenotype was seen on the introduction of a low-protein diet with accompanying benzoate and phenylbutyrate administration. Linkage studies suggested the inheritance of two X chromosomes, which was confirmed by karyotype analysis. Sequencing of all exons and immediate splice site regions revealed no sequence alterations in these sections of the OTC gene. A search for skewing of X-inactivation in the liver was not possible but we did show a random pattern of X-inactivation in leukocytes. The possibility of maternal X chromosome iso-disomy in our patient was discounted by microsatellite analysis, which revealed the inheritance of two independent X chromosomes. Mutation analysis in the OTC gene has shown that approximately 20% of patients with liver biopsy confirmed OTC deficiency do not have mutations in the coding or immediate splice-site sequences of this gene. Their classification as OTC phenocopies remains speculative, awaiting clarification of the underlying DNA alteration. We report on the novel association of OTC deficiency and Klinefelter syndrome with the additional interest of a probable unusual genetic defect underlying the OTC abnormality.
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PMID:An OTC deficiency 'phenocopy' in association with Klinefelter syndrome. 1718 14


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