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)

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

A 15-year-old male was admitted to the hospital because of a disturbance of consciousness. He was in good mental and physical condition until the previous day, when he vomited and experienced a reduction of consciousness. He was brought to the hospital the day following the onset of symptoms. On admission the patient was stuporous. Neurological focal signs were not demonstrated. Computed tomographic (CT) scanning on admission showed no definite abnormality. Cerebrosprinal fluid had no pleocytosis. At this time, Reye's syndrome was suspected because of the acute change of consciousness and the presence of hyperammonemia. The disturbance of consciousness progressed and he became comatose on the day following admission. CT scanning showed that the suprasellar, ambient and quadrigeminal cisterns could almost not be detected and the bilateral ventricles were narrowed. The plasma aminogram demonstrated an elevation of alanine, lysine, glutamine, glutamic acid, aspartate and proline. Ketonuria was negative, but the urinary excretion of orotic acid was markedly increased. This data was indicative of the existence of an ornithine transcarbamylase (OTC) deficiency. The patient was died on the third day after hospitalization. The OTC activity in the liver was 10% of normal. Activities of other enzymes in the urea cycle were within normal limits. It is unusual that the symptoms of the enzyme deficiency occurred, both acutely and late at an adult age, as in this case. This case demonstrates that OTC deficiency should be considered in the differential diagnosis of hyperammonemia of adult onset.
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PMID:A case of ornithine transcarbamylase deficiency with acute and late onset simulating Reye's syndrome in an adult male. 225 72

The clinical and haematological changes which occurred in 18 Bali cattle (Bos javanicus) experimentally infected with Jembrana disease are described. The major clinical signs were an elevated rectal body temperature persisting for 7 days (range 5 to 12 days), lethargy, anorexia, enlargement of the superficial lymph nodes, a mild ocular and nasal discharge, diarrhoea with blood in the faeces and pallor of the mucous membranes. Not all of these changes occurred in all affected cattle. The major haematological changes included leucopenia, lymphopenia, eosinopenia and a slight neutropenia, a mild thrombocytopenia, a normocytic normochromic anaemia, elevated blood urea concentrations and reduced total plasma protein. The mortality rate in the experimentally infected cattle was 17 per cent. The similarity of Jembrana disease to malignant catarrhal fever and to diseases of cattle associated with Ehrlichia is discussed.
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PMID:Studies on experimental Jembrana disease in Bali cattle. II. Clinical signs and haematological changes. 239 47

102 children with acute gastroenteritis were thought by the admitting junior doctors to be 5% or more dehydrated. As judged by subsequent weight recovery in hospital, the main indicators of mild to moderate dehydration were decreased peripheral perfusion, deep breathing, decreased skin turgor, high urea, low pH, and a large base deficit; a history of increased thirst was just short of statistical significance. Dehydration was not indicated by a history of oliguria, by the presence of restlessness or lethargy, sunken eyes, dry mouth, or a sunken fontanelle or by the absence of tears. Clinical signs of dehydration became apparent at 3-4% rather than 5% dehydration. The degree of dehydration was overestimated by a mean of 3.2%; this caused unnecessary hospital admissions and overtreatment with intravenous fluid.
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PMID:Clinical signs of dehydration in children. 257 63

An 8-year-old sexually intact male llama was euthanatized because of obstruction of the penile portion of the urethra and rupture of the urinary bladder. Clinical signs of obstruction included anorexia, lethargy, teeth grinding, straining to defecate, inability to urinate, and tense abdomen. Laboratory findings included anemia, leukocytosis with left shift, high serum urea nitrogen, creatinine, and phosphorus concentrations, and low serum chloride concentration. Necropsy revealed ruptured urinary bladder and acute fibrinous peritonitis. A firm, gray, nonmineralized urethral plug occluded the penile portion of the urethra for a distance of 14 cm in the midpenile region, distal to the sigmoid flexure of the penis. The urinary bladder mucosa and the urethra had microscopic evidence of chronic inflammation. Escherichia coli, Klebsiella sp, and alpha-streptococci were isolated from the urethral plug.
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PMID:Urethral obstruction in a male llama. 259 47

During a recent outbreak of Rhodesian sleeping sickness in the Lambwe Valley no asymptomatic Rhodesian sleeping sickness patients were found although 54% of the primary patients had mild symptoms and 9% were stuporous or comatose at presentation. The duration of symptoms was three months or less in 90% of the patients. Headache, weakness, joint and back pains and weight loss were claimed by at least 75% of the patients, while 82% of the females reported amenorrhoea and 70% of the males claimed impotency. Physical examination revealed lymphadenopathy in 86% but fever in only 36% of the patients, while chancres were found in only 16%. Patients had significantly lower levels of haemoglobin and thrombocytes than controls and their erythrocyte sedimentation rates were elevated. A comparison of both blood group and haemoglobin type between patients and controls yielded no significant differences. Fifty-seven per cent of the primary patients reporting mild symptoms had abnormal levels of leucocytes in their CSF. All relapse patients had abnormal CSF parameters. Levels of serum urea nitrogen were significantly elevated in patients, but SGOT, SGPT and total bilirubin were not. Levels of albumin and beta-globulin in patients were significantly lower than controls while gamma-globulin was elevated. Mean serum IgM levels in patients were elevated to nearly three-fold those of controls, but 35% of the individual patient values fell within the 95% range of control values. Some patients had extended prothrombin and thrombin times while fibrinogen levels were significantly elevated. No patients reported haemorrhage, and none was seen.
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PMID:Presenting features of Rhodesian sleeping sickness patients in the Lambwe Valley, Kenya. 261 98

We have developed a rabbit model of toxic shock syndrome that uses a subcutaneous infusion pump to administer toxic shock syndrome toxin 1 (TSST-1). A dose of 150 micrograms, infused at a constant rate over a period of 7 days, resulted in a characteristic illness highlighted by fever, conjunctival hyperemia, cachexia, and lethargy. The illness was uniformly fatal, with a mean interval until death of 3.2 +/- 0.4 days. Serial determinations of serum chemistries confirmed the multisystem nature of this illness. Rabbits developed profound hypocalcemia, with levels falling from 15.5 +/- 0.2 to 7.6 +/- 0.4 mg/dl under the influence of TSST-1. Blood urea nitrogen and creatinine rose dramatically, in the setting of oliguria or anuria. Serum glutamicpyruvic transaminase was the most reliable indicator of hepatic dysfunction, with the mean rising from 48 U/liter before administration of TSST-1 to 546 U/liter among rabbits surviving 2 days of the infusion. Creatine phosphokinase also rose dramatically in 10 of 16 rabbits. Rabbits demonstrated relative neutrophilia and lymphopenia as well as an increase in the partial thromboplastin time. Histopathologic examination demonstrated disease of multiple organs, particularly the liver, spleen, and lymph nodes, all of which demonstrated inflammation, thrombosis, hemorrhage, and erythrophagocytosis. The concurrent administration of prednisolone with TSST-1 prevented death in four of four rabbits and greatly lessened the morbidity. Rabbits were not protected from morbidity or mortality by the concurrent administration of polymyxin B. We believe that a constant, subcutaneous infusion of TSST-1 in rabbits provides a reproducible model for studying the pathogenesis of TSS.
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PMID:A rabbit model of toxic shock syndrome that uses a constant, subcutaneous infusion of toxic shock syndrome toxin 1. 357 Apr 55

A phase I clinical trial of the intravenous administration of a novel pyridyl imidazoline ethyl carboxy phenyl urea was carried out in 42 patients with advanced solid tumors. Five schedules were evaluated: I, daily X 5; II, daily X 10; III, daily X 15; IV, continuous infusion for 5 days; V, continuous infusion for 7 days. Toxicity was not seen in schedule I (maximum dose 3 g/m2/day) and was minimal in schedule IV (6 g/m2/day). In schedule II it was seen at 2 and 3 g/m2/day, in schedule III at 2 g/m2/day and in schedule V at 6 g/m2/day. Dose-limiting toxicity consisted of a syndrome of lethargy and fatigue. There were no definitely drug-related changes in hematologic or serum chemistry parameters. No responses were seen, but relief of pain in three patients with prostate cancer was noted. Pharmacokinetics indicate a short half-life, limited volume of distribution, and rapid renal clearance. The recommended dose for phase II studies is 3 g/m2/day X 10 or 2 g/m2/day X 15 days.
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PMID:Phase I clinical trial of 1-(2-[2-(4-pyridyl)-2-imidazoline-1-yl]-ethyl)-3-(4-carboxy-phenyl) urea (CGP 15720A). 366 34

Two siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria are reported. The clinical picture included protein intolerance, mental retardation, seizures, and stuporous episodes. One patient had cerebellar ataxia, myoclonus, convulsive seizure, and muscular weakness in both legs. Isolated liver mitochondria in the patient revealed that ornithine transport and citrulline synthesis were decreased, but urea cycle enzymes and ornithine aminotransferase were normal. Ornithine metabolism was decreased in cultured skin fibroblasts.
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PMID:Hyperornithinemia, hyperammonemia, and homocitrullinuria: case report and biochemical study. 367 Jun 19

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


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