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)

The effectiveness of aminoglutethimide as an adrenal inhibitor has been well-documented by decreases in plasma testosterone and delta 4 levels, which fall significantly following the drug in previously orchiectomized patients. The use of cortisone or cortisol along with aminoglutethimide complicates the interpretation of the role of aminoglutethimide in effecting clinical responses. However, since physiologic replacement doses were used in most cases, a significant role for cortisone in effecting a clinical response is unlikely. Aminoglutethimide does have side-effects including rash and lethargy. It requires administration of replacement doses of cortisone and sometimes mineralocorticoid as well since it inhibits adrenal steroid synthesis in all pathways. Peripheral adrenal androgen inhibitors, such as flutamide, Megace, cyproterone acetate or 5 alpha-reductase inhibitors, in the future may be equally effective and simpler to administer than aminoglutethimide but objective and adequate numbers of studies using acceptable objective criteria must be done in order to adequately compare these drugs to aminoglutethimide. There appears to be approximately a 33% response rate (partial objective regression and objectively stable) following blockade of adrenal androgens in patients in relapse after castration. Blockade of adrenal androgen is certainly more tolerable and has many fewer side-effects than the alternative of chemotherapy which does not give response rates in most cases that are significantly different from those noted with aminoglutethimide. Murray's paper, combined with prior studies by Drago et al., goes a long way in establishing adrenal androgen blockade with that drug as the next step to be taken in patients following relapse from prior castration (medical or surgical). The most important question revolves around the timing of adrenal androgen blockade. As stated by Murray, will adrenal androgen blockade provide better survival if given earlier following relapse? The answer is not known yet. The answer may come from the work of Labrie [1], Geller and Albert [2] and others, who suggest that total survival in prostate cancer may be improved with blockade of adrenal androgens not after relapse following castration, but with panandrogen blockade at the time of initial therapy for prostate cancer.
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PMID:Adrenal androgen blockade in relapsed prostate cancer. 293 57

The case of a 3-week-old male infant is described. After receiving an iatrogenic overdose of metoclopramide (1.0 mg/kg every six hours) throughout a 36-hour period for the treatment of suspected gastroesophageal reflux, he became cyanotic, lethargic, and irritable, he fed poorly, and he had diarrhea and respiratory distress. Methemoglobinemia (20.5%) and reduced oxyhemoglobin saturation (79%) were identified. The patient had an excellent clinical response following a single IV dose of methylene blue. Subsequently, methemoglobin reductase activity was normal and there was no measurable hemoglobin M. The diagnosis of methemoglobinemia should be considered in any infant receiving large doses of metoclopramide who has clinical findings of cyanosis, ashen color, or a history of lethargy and/or motor restlessness.
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PMID:Metoclopramide-induced methemoglobinemia. 340 65

1. GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1 day-1 were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg-1 day-1 for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2. Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes. There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1 day-1 and above. 3. Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4. Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity. 5. Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function. 6. HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.
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PMID:Toxicity of a novel HMG-CoA reductase inhibitor in the common marmoset (Callithrix jacchus). 804 18

Although disorders of thyroid function may cause a wide range of muscle disturbances, an overt myopathy has been rarely reported as an isolated clinical presentation of hypothyroidism. We observed 10 patients (5 males and 5 females) who had been referred to the department of neurology because of muscular fatigability, myalgia, cramps, or proximal weakness. Laboratory investigation showed that all patients had hypothyroidism due to Hashimoto's thyroiditis (atrophic variant in 9/10). Classic symptoms/signs of hypothyroidism such as lethargy, constipation, cold intolerance, myxedematous facies, and/or bradycardia were absent, as assessed independently by the three coauthoring thyroidologists. Muscular complaints improved greatly and then disappeared after substitutive levothyroxine treatment. Muscle biopsy revealed nonspecific changes. Nicotinamide adenine dinucleotide reductase (NADH-TR)-hyporeactive cores were present in two patients (10% and 90% of type 1 fibers). On electron microscopy, the core areas showed disorganized myofibrils, Z-band streaming, rod formation, and paucity of mitochondria and glycogen granules. Desmin intermediate filaments were overexpressed only in some cores. The similarity of the pattern of desmin expression between hypothyroid cores and target lesions of denervated fibers supports the hypothesis that, at least in some of our patients, myopathy was the result of an impaired nerve-mediated action of thyroid hormones on skeletal muscle. Our observations suggest that an isolated myopathy as the sole manifestation of hypothyroidism is not a rare event. We postulate that our cases may constitute a peculiar subgroup of Hashimoto's thyroiditis patients: (1) the strikingly abnormal F/M ratio of 1:1; (2) the relatively younger age; (3) the rarity of the goitrous variant; (4) the unusual finding of antithyroglobulin (Tg-Ab) > antithyroid peroxidase (TPO-Ab). Thorough evaluation of thyroid function is appropriate in patients with myopathy of uncertain origin.
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PMID:Myopathy as the persistently isolated symptomatology of primary autoimmune hypothyroidism. 984 19

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
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PMID:Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. 1569 61