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

Twenty-one patients developed acute renal failure in association with nontraumatic rhabdomyolysis and myoglobinuria. The illness followed an overdose of ethanol, heroin, or other depressant drug in 18 patients. Lethargy or coma was present in 17 patients and muscle swelling in 11. Evidence of rhabdomyolysis included markedly elevated creatine phosphokinase, myoglobinuria, and aldolase in blood. Initial biochemical findings were similar to those of acute renal failure due to other causes, but the abnormalities were exaggerated. There was a disproportionate rise in serum creatinine concentration in relation to serum urea nitrogen concentration. Profound hyperuricemia was present in most patients. Transient hypercalcemia developed during the diuretic phase in 5 patients. One patient died. We conclude that nontraumatic myoglobinuria with acute renal failure is not infrequent and may occur after an overdose of ethanol or heroin. The disease has good prognosis despite severe hypercatbolism and untreated profound hyperuricemia.
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PMID:Acute renal failure due to nontraumatic rhabdomyolysis. 93 19

Suberylglycine (HOOC(CH2)6CONHCH2COOH) was found in the urine from a patient with C6-C10-omega-dicarboxylic aciduria and unexplained episodes of lethargy and unconsciousness. The total excretion of adipic, suberic and sebacic acid ranged from 0.77 to 1.3 mg/mg creatinine after episodes of acute attack of the disease. Suberylglycine, identified by gas chromatography/mass spectrometry, was repeatedly found in the urine samples. The amount of this conjugate ranged from 0.2 to 0.5 mg/mg creatinine. The precursors of the dicarboxylic acids are suggested to be long chain monocarboxylic acids, oxidized through omega- and beta-oxidation to adipic, suberic and sebacic acid. Suberylglycine is subsequently formed by glycine-N-acylase catalyzed conjugation.
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PMID:Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria. 94 35

Intravesical alum irrigation is the safest and most effective method of treatment for intractable hematuria. Systemic absorption is reported to be minimal and there have been no reported deaths following its use. We describe an elderly man with compromised renal function (serum creatinine 420 mumol./l.) who was treated with 1% alum irrigation for 48 hours for hematuria due to inoperable bladder cancer. He received a total of 9.6 l. during 48 hours, which controlled the bleeding. After cessation of the alum he became lethargic, suffered respiratory depression and died the next day. Laboratory data showed mild metabolic acidosis and increasing daily aluminum levels that peaked at 7,014 nmol./l. (toxic greater than 2,000) beginning on the day after treatment was commenced. The efficacy and safety profile of alum irrigation is discussed.
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PMID:Aluminum toxicity and death following intravesical alum irrigation in a patient with renal impairment. 153 63

Cyclosporin-A-treated renal allograft recipients have demonstrated an improved graft survival rate, when compared to that of patients treated with conventional azathioprine and steroid therapy. Cyclosporin-A has been used for immunosuppressive therapy after renal transplantation at the National Taiwan University Hospital since November 1985. Since then, the one-year graft survival rate has been 78%, and the patient survival rate is 91%. At our service, acute rejection is confirmed mainly by an increase in the serum creatinine level of 0.5 mg% per day and a subsequent return of kidney function to normal after pulse steroid therapy. Twenty patients receiving cyclosporin-A and suffering from acute rejection episodes were chosen for comparison with 18 patients receiving conventional azathioprine and steroid therapy. Compared to conventional therapy, the classical systemic manifestations of rejection, such as malaise, lethargy, apathy, general weakness, vague discomfort, increase in body weight, swelling of graft with tenderness, were all more mild and less frequent in the cyclosporin-A-treated group. Episodes of rejection appeared earlier and the duration of rejection was shorter than in those of the conventional group. The urinary sodium concentration and the ratio of urine urea nitrogen to blood urea nitrogen were reliable references during the acute rejection episode in the conventional group, but it cannot be used as indices in the cyclosporine group. These findings can help us understand the changes which occurred in acute rejection in patients who receive renal transplantation during the cyclosporine era.
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PMID:Clinical manifestations of acute rejection in renal allograft recipients receiving cyclosporin-A therapy. 168 Sep 67

In this phase I study, 16 adult cancer patients were treated with concurrent 4-day continuous infusions of ifosfamide at 12 g/m2 and escalating doses of carboplatin (400-1600 mg/m2) to determine the major non-haematological dose-limiting toxicity of the combination. Mesna was given by continuous infusion over 5 days for uroprotection (total dose per course = 15 g/m2). Autologous bone marrow support, which was mandated for subsequent dose levels once granulocytes remained below 500/microliters for more than 14 days in at least 2 patients entered at a given dose level, was used at dose levels above 400 mg/m2 carboplatin. Renal toxicity became dose-limiting at the maximum tolerated dose level of 1600 mg/m2 carboplatin. Temporary creatinine elevations above 2 mg/dl (median peak 2.6 mg/dl) were observed in 3 and irreversible renal toxicity occurred in 1 (peak creatinine 6.9 mg/dl, chronic creatinine 5-6 mg/dl) of the 5 patients entered at this dose level. Severe confusion and lethargy associated with rising creatinine developed in 2 patients. Two complete and four partial responses were documented in 14 heavily pretreated evaluable patients. The complete responses continue at 14+ and 20+ months in a patient with germ cell carcinoma and Ewing's sarcoma, respectively. Carboplatin appears to contribute to the renal toxicity of ifosfamide. Nevertheless, the combination of carboplatin and ifosfamide at 80% and 75% of the single-agent maximal tolerated doses respectively produced acceptable non-haematological toxicity. Further studies in the treatment of sarcoma, germ cell, ovarian and lung carcinomas with this combination are warranted.
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PMID:Escalating doses of carboplatin with high-dose ifosfamide using autologous bone marrow as support: a phase I study. 179 9

Bilateral renal dysplasia and nephron hypoplasia was diagnosed in a Quarter Horse foal with clinical signs of lethargy, convulsions, and diarrhea. Laboratory evaluation revealed anemia, hypoproteinemia, leukopenia, hyponatremia, hypochloremia, and hyposmolality. The foal also had high concentrations of serum creatinine, BUN, and phosphorus. Evaluation of urinary indices revealed a high ratio of urinary gamma-glutamyl-transferase activity to concentration of creatinine, as well as a high fractional clearance ratio of sodium and potassium. Intravenous treatment with saline solution (0.9% NaCl) and antimicrobials provided only temporary resolution of some of the abnormalities. Diagnosis was partly established by histologic evaluation of renal tissue obtained via an ultrasonographically guided biopsy and was confirmed at necropsy. Pathologic changes in the kidney were unique in that the size of the kidneys, along with the appearance and number of glomeruli, were essentially normal despite marked hypoplasia of nephron tubules in the medulla.
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PMID:Bilateral renal dysplasia with nephron hypoplasia in a foal. 236 27

A phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NCS 286193, tiazofurin) was conducted using a 5-day i.v. bolus schedule, every 21 days. Thirty one patients with advanced cancer were entered on the trial. A total of 106 cycles were administered with doses ranging from 550 to 2750 mg/m2. Concomitant administration of Allopurinol was necessary to prevent hyperuricemia. Tiazofurin was difficult to evaluate and many side effects were variable and sporadic. The dose limiting toxicities were nonhematologic consisting particularly of myalgias, headaches and general malaise. Other toxicities included nausea, vomiting, stomatitis, lethargy, sleeping difficulty, sinus bradycardia, skin rash, desquamation of the palms and soles, photophobias and burning of the eyes. Hematologic toxicity was mild and not dose related though it led to a neutropenic septic death in one patient at 2750 mg/m2. Anemia was documented in 60% of cycles. Biochemical abnormalities consisted of mild hyperglycemia, hyperuricemia and elevated skeletal creatinine phosphokinase levels which did not correlate with the incidence or degree of myalgias. Though some patients were able to tolerate higher doses, the recommended dose for phase 2 study is 1650 mg/m2. Further studies will be required to achieve a better understanding of this interesting drug.
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PMID:Phase I study of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). 238 15

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


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