Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 10-year-old boy with the hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome is described. With dietary restriction of protein intake and supplementary administration of L-ornithine and L-arginine, the high concentration of ammonia decreased and the clinical signs of truncal ataxia and lethargy improved. A deficiency of ornithine transport into liver mitochondria was demonstrated biochemically, and glycogen granules and smooth surface endoplasmic reticulum were increased, but mitochondria showed normal construction ultrastructurally. Cranial computed tomography (CT) showed diffuse white matter low density and cerebellar vermis atrophy. The impairment of ornithine transport and energy production in the central nervous system may be related to the cranial CT findings and neurological signs.
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PMID:Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. 340 56

Disproportionate enlargement or isolation of the fourth ventricle are rare complications of ventriculo-peritoneal shunt for post-haemorrhagic hydrocephalus. Obvious features such as ataxia may indicate raised intracranial pressure in the posterior fossa. The child may, however, present with less specific signs of vomiting, anorexia, and lethargy and these symptoms may be misinterpreted as secondary to dilation of the lateral ventricular system due to malfunction of the ventriculo-peritoneal shunt. Two children with disproportionate enlargement of the fourth ventricle and two children with isolation of the fourth ventricle are described to illustrate the wide variations in clinical presentation. These rare complications can be diagnosed by real time ultrasound examination of the brain or computed tomography of the head. They should be considered in the differential diagnosis of a child who deteriorates after lateral ventriculo-peritoneal shunting for post-haemorrhagic hydrocephalus, and dealt with specifically to avoid the risk of upward herniation of the enlarged fourth ventricle.
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PMID:Specific enlargement of the fourth ventricle after ventriculo-peritoneal shunt for post-haemorrhagic hydrocephalus. 349 66

Recent treatment strategies have been directed toward blockade of estrogen action or inhibition of estrogen biosynthesis as a means of inducing regression of hormone-dependent breast cancer. The major source of estrogen in postmenopausal women is the peripheral conversion of androstenedione to estrone through the enzyme aromatase. It is known that aromatase activity increases proportionately with degree of obesity in women. To test the importance of this modulatory factor, we correlated body weight with estrogen excretion in our population of patients with breast cancer and found significant relationships. In situ production of estradiol from plasma precursors within breast cancer tissue may provide another source of estrogen. Major enzymes mediating estrogen biosynthesis were found to be present in tumor biopsy specimens. Aromatase activity was found to be present in 48/61 human tumors, sulfatase in 35/35, and 17 beta -hydroxysteroid dehydrogenase in 41/41. One inhibitor of aromatase, aminoglutethimide, has been extensively studied in patients with breast cancer. The additional effects of this drug on cholesterol side-chain cleavage and on 11-hydroxylase activity require coadministration of replacement glucocorticoid in treatment regimens. In pilot trials, 37% of patients experienced objective tumor regression with a combination of 1000 mg aminoglutethimide and 40 mg hydrocortisone daily. In randomized clinical trials with this regimen, aromatase inhibition with aminoglutethimide produced tumor regression with similar frequency as did surgical hypophysectomy, surgical adrenalectomy, or tamoxifen administration. The side effects of aminoglutethimide, including lethargy, skin rash, and ataxia complicate its use even though these problems are generally transient. Regimens of low-dose aminoglutethimide are being developed to reduce these side effects. Low-dose aminoglutethimide appears to block aromatase effectively and to have limited side effects, and is undergoing extensive clinical trial. A more specific aromatase inhibitor, 4-hydroxyandrostenedione, is now also being tested clinically, whereas MDL 18962, another new selective inhibitor, is undergoing study in animals.
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PMID:Inhibition of aromatase as treatment of breast carcinoma in postmenopausal women. 354 61

A three-year-old boy with a progressive history of headache, vomiting and ataxia in the course of 2 months, was admitted on August 1983, when he was lethargic. Neurological examination revealed dysphagia, scanning speech and tremor in the bilateral hand. CT scan showed a very large enhanced mass in the center of posterior fossa with central necrosis in it and the dilatation of whole ventricular system. Suboccipital craniectomy was immediately performed and the tumor that occupied the vermis and invaded into both cerebellar hemisphere was subtotally removed. Postoperative irradiation was well performed: 4140 rads to the whole brain and 3162 rads to the spinal cord. However, 5 months later, facial palsy in the left side and progressive ataxia became prominent. CT scan showed multiple enhanced masses in the left trigonum and right anterior horn of the lateral ventricles and in the left cerebellopontine angle. In spite of chemotherapy, the patient had a down-hill course, especially after the ventricular hemorrhage, and died on June 9th, 1984. Histologically, the tumor had a lobulated appearance with an aggregation of tumor cells encircled by vascular septae. The cells within lobules generally had vesicular nuclei, which were arranged in parallel row. Occasionally smaller hyperchromatic cells with scant cytoplasm were present along the vascular septae. Reticulin was present within the septa, but was not observed within the lobules. Scattered astrocytic cells and processes were identified within the lobules by the immunoperoxidase technique for GFAP. The fibrillary cytoplasmic processes within the lobules were stained by immunoperoxidase technique for neurofilament (68K).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of cerebellar neuroblastoma]. 361 40

Bilirubin inhibits in vitro oxidative phosphorylation and glycolysis. This study investigated the in vivo effect of bilirubin on cerebral oxygen, glucose, and lactate uptake in newborn piglets. Seventeen 2- to 4-day-old piglets were divided into three groups and examined as follows: group 1 = control (C); group 2 = control with sulfisoxazole; and group 3 = experimental, given bilirubin with sulfisoxazole. In the experimental group, bilirubin was infused for 4 h. The cerebral bilirubin content in the bilirubin-infused group was 11.0 +/- 1.4 nmol/g of cerebral cortex (mean +/- SEM), consistent with levels found in infants with kernicterus. However, this level of brain bilirubin had no major, acute effects on cerebral uptake of oxygen, glucose, or lactate despite producing lethargy and ataxia which were consistent with bilirubin intoxication. This suggests that mitochondrial changes may not be involved in vivo in acute bilirubin encephalopathy.
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PMID:The in vivo effect of bilirubin and sulfisoxazole on cerebral oxygen, glucose, and lactate metabolism in newborn piglets. 365 36

The GABAergic agonist, muscimol, and antagonists, picrotoxin and bicuculline, have been studied in rats with chronic portacaval shunts and in rats developing hepatic encephalopathy after massive ischemic necrosis due to hepatic artery ligation within 48 hr of a portacaval shunt. After the chronic portacaval shunt and to a lesser extent in normal rats intraventricular muscimol resulted in chewing and eating behavior, ataxia and loss of balance that lasted 2 to 3 hr. Lethargy, stupor and coma did not occur. Intraventricular saline had no effect. Bicuculline i.p. lessened the effects of the muscimol. In rats developing hepatic encephalopathy, intraventricular muscimol shortened the time to precoma and coma by approximately 40%. Bicuculline i.p. counteracted this effect of muscimol significantly. However, neither bicuculline nor picrotoxin given alone altered the times to precoma (Stage III), coma (Stage IV) or death. While hepatic encephalopathy in this experimental model is susceptible to GABAergic effects, its natural progression does not appear to be due to GABA.
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PMID:In vivo studies of GABAergic effects in experimental hepatic encephalopathy. 375 44

The authors report a case of erythromycin-induced carbamazepine toxicity in a 6-year-old child following use of erythromycin ethylsuccinate (50 mg/kg/day). Within 5 days of erythromycin use, vomiting, weakness, lethargy, ataxia, nystagmus, and cogwheeling movements developed. A serum carbamazepine concentration had increased from 11.9 mg/L (measured 1 week prior to antibiotic use) to 25.8 mg/L. Following erythromycin withdrawal, serum concentrations returned toward baseline, and symptoms resolved. Erythromycin has known effects on hepatic enzyme function, with altered cytochrome P-450 function. The dramatic reduction in carbamazepine clearance observed in this patient is similar to that reported when erythromycin is used concurrently with other drugs. A brief review of potentially significant erythromycin drug interactions is presented.
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PMID:Erythromycin-induced drug interactions. An illustrative case and review of the literature. 381 8

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

A case of D-lactic acidosis in a 2 1/2-year-old child followed for 11 months is reported. The infant had previously undergone extensive small intestinal resection for midgut volvulus. Diagnosis was confirmed by measurement of plasma D-lactate. Metabolic acidosis, increased anion gap, ataxia, and lethargy in patients with small intestinal resection warrant investigation for D-lactic acidosis. The presumed etiology is absorption of D-lactic acid produced by bacterial fermentation of carbohydrate in the colon. Antibiotic treatment resulted in prompt resolution of symptoms in this case. Prospective and prolonged monitoring of acidosis in patients with small bowel resection is encouraged.
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PMID:Long-term monitoring of D-lactic acidosis in a child. 403 82

A 49-year-old woman treated with cimetidine 300 mg tid for more than 18 months for Zollinger-Ellison syndrome experienced lethargy, dizziness, ataxia, and auditory and visual hallucinations after receiving triazolam 0.375 mg hs for sleep. Triazolam plasma concentrations were measured, and a triazolam elimination half-life was calculated to be approximately 8 hours (reported range 1.7-3 h). Cimetidine has been reported to decrease the apparent oral clearance of triazolam, resulting in increased triazolam plasma concentrations with the potential for exaggerated triazolam pharmacologic effects. Cimetidine may have been responsible for the unusually large elimination half-life in this patient. Until the mechanisms and clinical significance of this potential drug interaction are determined, clinicians should use the combination of triazolam and cimetidine with caution.
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PMID:Central nervous system toxicity associated with concurrent use of triazolam and cimetidine. 404 60


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