Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

The prevalence of impaired renal acidification in alcoholic liver disease and its relationship to clinical and biochemical features were evaluated during a one-year period in a 60-bed liver unit. No cases of overt renal tubular acidosis (RTA) were found; all of 12 patients with low serum bicarbonate values and normal anion gap proved to have chronic respiratory alkalosis. However, there was a 57% prevalence of incomplete distal RTA in 42 patients who were tested with an acid load. Subjects with RTA had higher serum bilirubin levels (5.3 +/- 6.1 v 2.1 +/- 2.7 mg/dL) and lower prothrombin times (45% +/- 22% v 64% +/- 20%). Urinary pH correlated directly with serum bilirubin levels (r = +.38) and inversely with prothrombin times (r = -.46). The frequency of ascites and encephalopathy did not differ notably between the two groups of patients. No pathogenetic relation was observed with avid sodium retention, decreased excretion of nonreabsorbable anions, and elevated urinary excretion of bile acids. Therefore, we conclude that impaired renal acidification in alcoholic liver disease may be a sign of liver cell failure since it is more frequently observed in patients with a greater degree of liver dysfunction.
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PMID:Impaired renal acidification in alcoholic liver disease. 671 10

A 15-year-old girl is described with encephalopathy associated with Hashimoto thyroiditis which subsequently developed into autoimmune thyrotoxicosis (hashitoxicosis) and distal renal tubular acidosis at age 5 years, pernicious anemia at age 9, and encephalopathy at age 12. Thyroid hormone levels were within the normal ranges at the time of neurologic presentation. Serum IgG concentration and oligoclonal IgG bands in cerebrospinal fluid closely correlated with the severity of neurologic symptoms. Treatment with glucocorticoids improved the level of consciousness but her mental state continued to deteriorate. Repeated cranial computed tomographic scans revealed progressive symmetric atrophy in the gray matter without infarction. These findings suggest that encephalopathy associated with Hashimoto thyroiditis is caused by an antineuronal antibody-mediated reaction.
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PMID:Hashimoto encephalopathy: etiologic considerations. 770 95

A case of a 12-year-old girl with a multiple auto-immune disorder is reported. She showed Hashimoto thyroiditis which subsequently developed to hashitoxicosis and distal renal tubular acidosis at 5 years of age, pernicious anaemia at the age of 9 and severe encephalopathy at the age of 12. Laboratory studies revealed very high titres of anti-microsomal and anti-thyroglobulin antibodies and positive gastric parietal cell antibody. As to the encephalopathy, positive oligoclonal IgG bands and high values of IgG index and IgG synthesis ratio in CSF were observed with aggravation of her neurological symptoms. High-dose steroid therapy was effective toward the encephalopathy. Paediatricians should pay careful attention to patients with Hashimoto thyroiditis for association with other autoimmune disorders.
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PMID:Hashimoto thyroiditis, distal renal tubular acidosis, pernicious anaemia and encephalopathy: a rare combination of auto-immune disorders in a 12-year-old girl. 815 29

Accumulation of D-lactate after gastrointestinal surgery, particularly jejuno-ileal bypass, is an uncommon and often misdiagnosed clinical disturbance. The syndrome may be complicated by dizziness, ataxia, confusion, headache, memory loss, and aggressive behavior. Serum chemistries are often deceptive because the anion gap is frequently normal in spite of severe metabolic acidosis. Moreover, the urine anion gap may be positive, incorrectly suggesting a defect in renal net acid excretion. Indeed, the combination of a normal anion gap metabolic acidosis and positive urine anion gap may erroneously suggest a diagnosis of renal tubular acidosis. Importantly, all reported cases of D-lactic acidosis secondary to bypass surgery have been encountered within 5 to 10 years following the surgery. Here we present an unusual case of D-lactic acidosis (complicated by encephalopathy) presenting 23 years after a jejuno-ileal bypass procedure. The patient was initially diagnosed with a drug intoxication secondary to benzodiazepines. Ultimately, the diagnosis of D-lactate encephalopathy was established after challenging the patient with a carbohydrate load. Thus, administration of 40 kcal/kg over 16 hours reproduced the clinical syndrome and was accompanied by a marked increment in serum and urine D-lactate concentration. The patient had sustained resolution of her symptoms after treatment with oral vancomycin.
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PMID:D-lactic acidosis 23 years after jejuno-ileal bypass. 1092 30

A 23-year-old Japanese man was admitted to our hospital because of acute generalized muscle weakness and frequent vomiting. He had been diagnosed as having hypokalemic periodic paralysis, since he had recurrent episodes of transient generalized muscle weakness with a hypokalemia. Laboratory studies have revealed a severe hypokalemic hyperchloremic metabolic acidosis, elevated serum levels of creatine phosphokinase and ammonia. The urinary level of the hippuric acid, a metabolic product of toluene, was found to be extremely high, suggesting that he had been exposed to toluene. With intravenous supplement of potasium, his muscle strength improved. Chronic exposure to toluene induces various neurological disorders, such as encephalopathy, cerebellar and pyramidal signs, peripheral neuropathy. In addition, it should be kept in mind that hypokalemic muscle weakness can be induced by the renal tubular acidosis resulting from chronic toluene exposure, and that it is by no means easy to distinguish hypokalemic periodic paralysis if it occurs recurrently.
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PMID:[Generalized muscle weakness mimicking periodic paralysis in a patient with toluene abuse]. 1205 13

We report here unusual clinical manifestations in a case of kerosene poisoning. The patient presented with encephalopathy and in the course of stay in the hospital developed renal tubular acidosis, delayed first-degree burns and myocarditis. With supportivetherapy the patient recovered completely and was discharged without any sequelae.
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PMID:Kerosene poisoning--varied systemic manifestations. 1563 23

We present two new patients with the recently described mitochondrial m.3242G > A mutation. Although the mutation is situated next to the well known m.3243A > G mutation, the most common alteration associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, the clinical presentation is quite different, but characteristic. All three m.3242G > A patients presented in the neonatal period with hypertrophic and dilated cardiomyopathy, generalized muscle hypotonia and lactic acidosis. Two additionally had creatine kinase elevation, renal tubular acidosis/dysfunction and showed a mild clinical course with a favourable psychomotor development. The third patient had more neurological involvement and died in infancy. The mutation occurred de novo in the two patients where maternal investigations were performed. The combination of hypertrophic cardiomyopathy and renal tubular acidosis/renal tubular dysfunction is clinically distinctive and may represent a separate entity.
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PMID:Mitochondrial DNA m.3242G > A mutation, an under diagnosed cause of hypertrophic cardiomyopathy and renal tubular dysfunction? 2278 53

Encephalopathy and Myopathy in children of varying ages can be due to variety of causes including Mitochondrial diseases, metabolic diseases like renal tubular acidosis, storage diseases as well as fatty acid oxidation (FAO) disorders. FAO related disorders have variable clinical presentation and manifest in different ages. They may present with hypoglycemia, effort intolerance, multi organ involvement with or without ketonuria. High degree of suspicion and appropriate investigations are mandatory for diagnosis. Here we describe an 11 Year old boy, born to non - consanguineous parents. Presented with exertion induced muscle pain and fatigue of 1year duration, which slowly progressed to severe weakness and vomiting. His reflexes were retained. Therefore metabolic vs inflammatory muscle diseases were considered. Patient had ketonuria with elevated blood levels of medium chain acyl carnitine and long chain acyl carnitine suggestive of MADD. Urine organic acid assessment showed elevated excretion of 2-hydroxyglutarate (2HG), adipate and arabitol. Muscle biopsy showed multiple fine vacuoles on Eosin- hematoxylin stained preparation. Modified Gomori - trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stains showed vacuolated fibers with 'oil red O' positive material suggesting lipid storage. Above combination of features is consistent of MADD. Genetic evaluation is not done due to financial constraint. Patient was started on high dose riboflavin and carnitine, with which the child became near normal. Our patient is a case of MADD presenting as Reye's syndrome like features and showed excellent response to riboflavin, carnitine, dietary and life style changes. High degree of suspicion is lifesaving.
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PMID:Lipid Storage Myopathy with Ketonuria: A Case of Fatty Acid Oxidation-Related Myopathy and Encephalopathy due to Multiple Acyl-CoA Dehydrogenase Deficiency. 3027 77