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)

Two infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.Vitamin B(12) was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.The urine concentrations of methylmalonic acid in the four parents were normal.
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PMID:Methylmalonic acidemia: 6 years' clinical experience with two variants unresponsive to vitamin B12 therapy. 3 17

Streptozotocin (STZ) has shown antitumor activity against various tumors in man, but the clinical usefulness of this drug has been limited, mainly because of renal and gastrointestinal toxicity. Nineteen patients with advanced cancer of various types were given a mean dose of 3.4 g/m2 of STZ by continuous iv infusion over 5-6 days each month for one or two monthly cycles. Basic serum and urine studies were performed immediately before and after each treatment cycle. Following STZ treatment, no significant changes in BUN or creatinine were seen. Four patients in whom initial tests for proteinuria were negative developed grade 1 or 2+ proteinuria after completion of the treatment cycle. No myelosuppression or renal failure was observed. Six patients had no nausea or vomiting, seven patients had nausea only, three patients had nausea and vomiting which were well-controlled with antiemetics, and three patients had uncontrollable nausea and vomiting. Confusion, lethargy, and depression were noted in five patients who had no prior central nervous system abnormalities; these effects appeared during treatment or in the immediate posttreatment period. Two patients with diffuse non-Hodgkin's lymphoma had complete remission, while several other patients had documented improvement. Although central nervous system toxicity may be a limiting factor, prolonged STZ infusions may have significant clinical promise.
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PMID:Continuous streptozotocin infusion: a phase I study. 16 Aug 36

A 4-year Basset bitch with a 9-week history of depression, lethargy, inappetence and weight loss was found to have azotaemia, hypercalcaemia and hyperphosphataemia. Laparotomy and kidney biopsy revealed end-stage renal disease and the dog was killed. Hyperplasia of all 4 parathyroid glands was found at autopsy. The presumptive diagnosis was idiopathic renal failure with resulting tertiary hyperparathyroidism.
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PMID:Renal failure, hyperparathyroidism and hypercalcaemia in a dog. 46 39

The clinical and morphologic findings of three patients with metabolic acidosis, methylmalonic aciduria, and homocystinuria are presented. The clinical evolution of the patients was similar and was characterized in the first weeks of life by failure to thrive, hypotonia, and lethargy associated with pancytopenia and hepatic dysfunction, eventually progressing to severe respiratory insufficiency and renal failure consistent with a hemolytic-uremic syndrome. The patients died at 40, 45, and 75 days of age. Biochemical analyses and complementation studies revealed a congenital anomaly of vitamin B12 metabolism (cobalamin C disease). Postmortem morphologic findings in all three cases were dominated by a thrombotic microangiopathy of the kidneys and lungs, diffuse hepatic steatosis, and megaloblastic changes in the bone marrow. A severe gastritis with striking cystic dysplastic mucosal changes and total absence of parietal and chief cells was a consistent finding in all three cases, the rest of the gastrointestinal tract appearing essentially normal. Cobalamin C disease is an intracellular defect of cobalamin metabolism with possible recessive inheritance that can result in multiorgan failure early in life, with a thrombotic microangiopathy and unusual changes in the gastric mucosa.
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PMID:A congenital anomaly of vitamin B12 metabolism: a study of three cases. 156 46

This report describes clinical and histopathological findings of a case of a 43-year-old male with granulomatous interstitial nephritis. The patient developed renal failure following renal insufficiency of 4 months duration. The patient presented with lethargy and nocturia. The first renal biopsy revealed granulomatous interstitial nephritis. There was no apparent evidence of a systemic granulomatous disease or drug hypersensitivity. Therapy with reducing regime of prednisolone produced a marked improvement in symptoms and renal function. Relapse occurred 3 months later in association with early discontinuation of the corticosteroid therapy. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in both kidneys. The second renal biopsy did not show the obvious improvement. With the re-administration of the corticosteroid therapy, renal function rapidly improved again. Twelve months after the re-administration of the steroid therapy, Ga-scintigraphy showed no renal uptake. Corticosteroid therapy yielded a favorable outcome for renal function. The third renal biopsy showed disappearance of the granulomas lesion. Re-administration of the corticosteroid therapy continued for 22 months and the patient has not yet relapsed 9 months after the withdrawal of the steroid therapy.
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PMID:[A case of granulomatous interstitial nephritis presented reversible renal failure treated with the steroid therapy: repeated renal biopsy case]. 158 73

Renal amyloidosis was diagnosed in 14 young Chinese Shar Pei dogs, all of which were related. Clinical signs were those of renal failure and included vomiting, anorexia, lethargy, polydipsia, polyuria, weight loss, and dehydration. Some dogs had a history of intermittent fever and joint swelling. Laboratory findings also were compatible with renal failure and included azotemia, hyperphosphatemia, low total CO2 content in serum, isosthenuria, proteinuria, and hypercholesterolemia. All dogs had medullary deposition of amyloid, and 9 of 14 (64%) had glomerular involvement. The remaining renal lesions were typical of end-stage renal disease. In some dogs, amyloid deposits were found in other tissues (eg, liver, spleen, stomach, small intestine, myocardium, lymph node, prostate gland, thyroid gland, and pancreas). Amyloid deposits were sensitive to potassium permanganate oxidation, suggesting the presence of amyloid protein AA.
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PMID:Familial renal amyloidosis in Chinese Shar Pei dogs. 221 Dec 93

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
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PMID:Acromegaly in 14 cats. 240 66

Triphasic waves (TWs) are a distinctive, but nonspecific, EEG pattern found in metabolic encephalopathies and a variety of other neurologic conditions. The prognostic value of TWs was studied in 30 patients with altered state of consciousness. Patients were either comatose (18 patients) or very lethargic (12 patients). Triphasic waves were the dominant EEG pattern, present for at least 35% of the tracing. The etiology of their underlying encephalopathy was multiple metabolic derangements (12 patients), hepatorenal syndrome (5 patients), renal failure (4 patients), hypoxic encephalopathy (4 patients), hepatic failure (3 patients), hyponatremia (1 patient), and hypoglycemia (1 patient). Patients were followed up to 22 months. Fifty percent of the subjects died within 30 days of recording TWs. The overall mortality was 77%. Seven patients (23%) have survived, but only three patients (10%) are neurologically normal. In conclusion, TWs occur most often in patients with metabolic encephalopathies, cannot be used to distinguish different diagnostic entities, and indicate a poor prognosis for survival.
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PMID:Prognostic significance of EEG triphasic waves in patients with altered state of consciousness. 279 20

Mannitol is an osmotic diuretic widely used in the diagnosis and prevention of acute oliguric renal failure, acute cerebral edema and acute glaucoma. Mannitol, though ordinarily a benign substance, may accumulate in renal failure with potentially deleterious consequences. Mannitol intoxication is ordinarily characterized by confusion, lethargy, stupor, and if severe enough, coma. The use of mannitol in renal failure has rarely been associated with a worsening of the preexistent renal dysfunction. We report a case of acute oliguric renal failure solely attributable to mannitol administered in the course of therapy for acute glaucoma.
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PMID:Mannitol-induced acute renal failure. 310 45

Three horses less than or equal to 3 years old were evaluated because of stunted growth, weight loss, anorexia, depression, and lethargy of at least 1 month's duration. A neonatal foal was examined after its death. In each case, gross and microscopic renal lesions were compatible with bilateral renal hypoplasia (ie, cortical hypoplasia with severe medullary hypoplasia). In young horses with renal failure, bilateral renal hypoplasia should be considered in the differential diagnosis, and may represent a congenital lesion.
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PMID:Bilateral renal hypoplasia in four young horses. 374 81


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