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 cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis are reported. A 12-year-old girl and a 10-year-old boy presented with polyarthritis, anaemia, haematuria, proteinuria, impaired renal function, anorexia, nausea, marked loss of weight and lethargy. The boy also had a vasculitic rash and anterior uveitis. Both children had diffuse cytoplasmic ANCA identified by indirect immunofluorescence and confirmed by specific enzyme-linked immunosorbent assay. Renal biopsies showed severe focal and segmental necrotizing glomerulonephritis with 100% crescents. They were treated with plasma exchange, prednisolone, cyclophosphamide and heparin. Within 1 month of commencing treatment, both had normal serum creatinine concentrations and ANCA was not detectable. Renal biopsies 6 weeks following commencement of treatment revealed quiescent disease, although up to 40% of glomeruli were sclerosed or had fibrous crescents. Following cessation of cyclophosphamide and heparin after 7 months and reduction in steroid dose, a biopsy at 10 months in the boy revealed quiescent disease, but the girl had recurrent disease associated with reappearance of a low titre of ANCA and small cellular crescents in 20% of the glomeruli. These cases reflect the potential usefulness of ANCA determination for categorizing paediatric patients, helping in the selection of therapy and as a possible marker of disease activity, similar to the experience in adults.
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PMID:Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in children. 843 72

Stiripentol (STP) was added to the antiepileptic drug (AED) regimen of 10 patients with uncontrolled atypical absence seizures (more than one seizure a day). Seven boys and three girls aged 6-16 years participated in the study. Concomitant AEDs included various combinations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). Parents counted daily seizures over a 4-week baseline period before institution of STP, and in a 20-week period during STP therapy. To compensate for drug interactions, doses of other AEDs were adjusted during STP administration to keep serum levels close to levels of the baseline period. Maintenance doses of STP were 1,000-3,000 mg/day, giving serum levels of 4-22 micrograms/mL. All patients experienced a decrease in atypical absence seizures. Average decrease was 70% (range 5-95%). Side effects experienced by some patients were dose related and included anorexia, nausea, vomiting, and lethargy. In only 1 patient did an adverse effect (vomiting) require discontinuation of STP. We conclude that STP shows promise in treatment of atypical absence seizures in children, and further trials are warranted.
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PMID:Stiripentol in atypical absence seizures in children: an open trial. 845 42

The efficacy of valproic acid in the treatment of intractable chronic daily headache, unresponsive to traditional prophylactic medications, was examined prospectively in 16 patients. Dosage of the medication was adjusted to maintain serum valproic acid levels between 50 and 100 micrograms/mL, provided there were no significant side effects at that level. Valproic acid prophylaxis was of some benefit in only 2 of 16 patients. One of these two patients discontinued therapy due to side effects. Eight of the 16 patients reported side effects which included nausea, diarrhea, anorexia, lethargy, sleepiness, confusion, blurred vision, and decreased libido. In conclusion, valproic acid was not effective in controlling chronic daily headache in the majority of patients in whom conventional therapy had failed, and 50% of patients reported side effects. There is a significant disparity in the reported efficacy of this drug in treating chronic daily headache. This disparity is most likely due to the poorly-defined nature of this variety of headache. It is, therefore, recommended that more stringent definition of this disorder be developed before therapeutic regimens are evaluated.
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PMID:Valproic acid treatment of chronic daily headache. 853 Feb 78

Desmopressin is a commonly used, well-tolerated agent for the treatment of primary nocturnal enuresis and central diabetes insipidus. Intranasal desmopressin provides symptomatic relief with few serious complications. A 29-year-old woman with a long history of primary nocturnal enuresis began treatment with intranasal desmopressin. Although the enuresis ceased, she developed throbbing headaches, nausea, vomiting, paresthesia, lethargy, fatigue, and altered mental status over the next 7 days. When she came to the emergency room her sodium concentration was 127 mmol/L. The history of desmopressin use was not obtained at that time. She was treated with intravenous fluids and discharged. The symptoms returned and worsened over the next 4 days, and she returned to the emergency room stuporous. A repeat sodium was 124 mmol/L, and she was admitted. The history of desmopressin use was still not available. Medical evaluations included computerized tomography, lumbar puncture, complete blood counts, serum chemistries, and serologies. The next morning the woman was improved and informed clinicians of her desmopressin use. Without other causes for the hyponatremia, she was diagnosed with the syndrome of inappropriate antidiuretic hormone, presumably caused by desmopressin. Within 24 hours of fluid restriction and cessation of desmopressin, her symptoms and hyponatremia resolved. A review of the literature found 11 children and 2 adults in whom intranasal desmopressin was associated with hyponatremia, all of whom experienced seizures or altered mental status. Our patient illustrates the importance of early recognition and treatment of hyponatremia before the onset of seizures. When vague symptoms develop during desmopressin therapy, hyponatremia must be considered as part of the differential diagnosis. It may also be prudent to screen for electrolyte abnormalities in patients taking this agent to prevent serious iatrogenic complications.
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PMID:Intranasal desmopressin-induced hyponatremia. 888 98

Fifty-one patients with histologically confirmed epithelial stage III or IV ovarian cancer were entered into a study in which gemcitabine 800 mg/m2 was given as a 30 min intravenous infusion in a cycle once a week for 3 weeks followed by a week of rest. Patients were aged 58 years (range 23-70 years) with WHO performance status 0-2, and had received up to two different chemotherapy regimens. Thirty-eight patients had received only one prior platinum-containing chemotherapy regimen whereas 9 had received a first-line regimen on more than one occasion. A further 3 patients had received two different regimens. Of 42 patients evaluable for response, 8 (19%; 95% CI: 9%-34%) were partial responders. Seven of the 8 responders were resistant to first-line platinum-based therapy. Median duration of response was 8.1 months (range 4.4-12.5 months). Median progression-free survival was 2.8 months (range 0.2-12.5 months). Haematological toxicity with gemcitabine was modest, with grade 3 leukopenia (11 patients) and grades 3 and 4 thrombocytopenia (6 patients). Grade 3 non-haematological toxicity included nausea/vomiting (6 patients) and elevated AST/ALT (1 patient), while dose-limiting non-haematologic toxicity consisted of flu-like symptoms (2 patients), peripheral oedema (1 patient) and lethargy (1 patient). The activity and modest haematological and non-haematological toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of patients with ovarian cancer and in combination chemotherapy regimens, primarily in combination with platinum.
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PMID:Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients. 871 27

Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activity in vitro and in vivo. Maximum efficacy in preclinical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a syndrome of lethargy, diminished performance status, and mild hepatotoxicity was dose-limiting at 550 mg/m2. To avoid the higher drug concentrations associated with a brief infusion, a Phase I study of a weekly 24 hour infusional schedule was undertaken in an attempt to maximize dose-intensity. Doses were escalated from 550 to 800 mg/m2. Toxicities included nausea, anorexia, fatigue, and minor elevations of liver function tests. The dose limiting toxicity at 800 mg/m2 was a syndrome of severe abdominal pain. No neutropenia or thrombocytopenia was observed except in one patient who was found to have a myelodysplastic syndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increase in the tolerable dose.
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PMID:Phase I trial of ilmofosine as a 24 hour infusion weekly. 872 47

In normal erythrocytes, small quantities of methaemoglobin are formed constantly and are continuously reduced, almost entirely by the reduced nicotine adenine dinucleotide (NADH) diaphorase system, rather than the reduced nicotine adenine dinucleotide phosphate (NADPH) diaphorase system. Methaemoglobinaemias are usually the result of xenobiotics, either those that may directly oxidise haemoglobin or those that require metabolic activation to an oxidising species. The most clinically relevant direct methaemoglobin formers include local anaesthetics (such as benzocaine and, to a much lesser extent, prilocaine) as well as amyl nitrite and isobutyl nitrite, which have become drugs of abuse. Indirect, or metabolically activated, methaemoglobin formation by dapsone and primaquine may cause adverse reactions. The clinical consequences of methaemoglobinaemia are related to the blood level of methaemoglobin; dyspnoea, nausea and tachycardia occur at methaemoglobin levels of > or = 30%, while lethargy, stupor and deteriorating consciousness occur as methaemoglobin levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure and neurological depression, while levels of 70% are usually fatal. Cyanosis accompanied by a lack of responsiveness to 100% oxygen indicates a diagnosis of methaemoglobinaemia, which should be confirmed using a CO-oximeter. Pulse oximeters do not detect methaemoglobin and may give a misleading impression of patient oxygenation. Methaemoglobinaemia is treated with intravenous methylene blue (methyl-thioninium chloride; ;1 to 2 mg/kg of a 1% solution). If the patient does not respond, perhaps because of glucose-6-phosphate dehydrogenase (G6PD) deficiency or continued presence of toxin, admission to an intensive care unit and exchange transfusion may be required. Dapsone-mediated chronic methaemoglobin formation can be reduced by coadministration of cimetidine to aid patient tolerance. Increasing knowledge and awareness of drug-mediated acute methaemoglobinaemia among physicians should lead to prompt diagnosis and treatment of this potentially life-threatening condition.
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PMID:Drug-induced methaemoglobinaemia. Treatment issues. 882 17

We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.
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PMID:Serotonin reuptake inhibitor withdrawal. 888 7

Data on discontinuation phenomena associated with serotonin selective reuptake inhibitors (SSRIs) are derived primarily from (1) published case reports, (2) data bases of adverse drug reactions that have been spontaneously reported to national monitoring bureaus, and (3) clinical studies of drug discontinuation. Some of the symptoms seen on SSRI discontinuation, such as nausea, lethargy, insomnia, and headache, are similar to those reported with tricyclic discontinuation. However, SSRI discontinuation is also associated with novel symptom clusters, including problems with balance, sensory abnormalities, and possibly aggressive and impulsive behavior. Although generally mild and short-lived, discontinuation symptoms can be severe and chronic and have a major impact on the patient's lifestyle. The incidence of discontinuation symptoms varies widely among the different SSRIs; the highest rate is seen with paroxetine. The variation in incidence might be explained by the different pharmacokinetic and pharmacodynamic profiles of the SSRIs.
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PMID:Newer antidepressants and the discontinuation syndrome. 921 89

The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients, randomized to dog-leg RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. In group A (n = 10), nausea, vomiting, diarrhoea and abdominal discomfort were experienced in 90%, 80%, 70% and 90% respectively. Antiemetic and antidiarrhoeal agents were required in 70% and 10% respectively, with good response. For group B (n = 20), the overall incidences of nausea, vomiting diarrhoea and abdominal discomfort were 80%, 45%, 60% and 80% respectively. The ondansetron group experienced less nausea (P = 0.02) and less vomiting (P = 0.06). Both reduced field size and ondansetron groups appeared to have less diarrhoea (P = 0.06). The use of antiemetics in the expectant therapy groups resulted in at least a two-level reduction of toxicity grade in 86% of patients. A high incidence of lethargy, anorexia and headaches was noted for all groups. The incidence of headaches was not increased with ondansetron. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized trial of field sizes (TE10).
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PMID:The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in stage I seminoma of the testis: a randomized pilot study. 931 92


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