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)

Chronic depletion of body chloride developed in a group of infants ingesting a diet consisting almost exclusively of chloride deficient Neo-Mull-Soy. Ten of the 12 infants were on this diet three to five months before loss of appetite, failure to thrive, muscle weakness, and lethargy led to a diagnostic evaluation. The outstanding laboratory features were severe hypokalemic metabolic alkalosis, low urinary chloride concentrations (< 10 mEq/liter), and erythrocyturia. There was marked decrease in weight for age in all 12 infants. Head circumference for age had decreased in five of six and length for age in five of ten infants for whom earlier measurements were available. The biochemical abnormalities reverted to normal following dietary supplementation with either sodium or potassium chloride. Appetite, affect, and muscle strength improved, and weight gain resumed. Head circumference for age has moved toward the percentile level present prior to starting Neo-Mull-Soy in all instances. With one exception, length measurements show a similar pattern. The erythrocyturia has decreased or vanished. Chloride deficiency led to contraction of the extracellular volume and the substitution of poorly reabsorbable anions for readily reabsorbable chloride. These alterations caused development of the negative hydrogen ion and potassium balances which led to the hypokalemic metabolic alkalosis.
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PMID:The dietary chloride deficiency syndrome. 693 41

Thirteen infants, 2 to 10 months of age, developed hypochloremic alkalosis (serum chloride 59 to 92 mEq/l) while taking Neo-Mull-Soy (Syntex), a soy-based formula low in chloride (measured to be 0 to 2 mEq/l) but with considerable potassium citrate. Range of symptoms included lethargy, anorexia, mild spitting up, diarrhea, hematuria, and growth failure. Urine chloride excretion was less than 3 mEq/l. Plasma renin activity or aldosterone, measured in six infants, was elevated. All responded promptly to supplemental salt. One infant receiving Neo-Mull-Soy redeveloped alkalosis when supplemental salt was discontinued. Two of nine apparently normal infants receiving Neo-Mull-Soy also had hypochloremia (85, 86 mEq/l). Three of four receiving Prosobee (Mead Johnson; Cl content 7 mEq/l) had urine chloride concentration less than 20 mEq/l. The chloride content of some infant formulas is insufficient to offset salt losses following mild stress.
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PMID:Hypochloremic alkalosis in infants associated with soy protein formula. 718 58

To grow and metastasize, solid tumours must develop their own blood supply by neo-angiogenesis. Thalidomide inhibits the processing of mRNA encoding peptide molecules including tumour necrosis factor-alpha (TNF-alpha) and the angiogenic factor vascular endothelial growth factor (VEGF). This study investigated the use of continuous low dose Thalidomide in patients with a variety of advanced malignancies. Sixty-six patients (37 women and 29 men; median age, 48 years; range 33-62 years) with advanced measurable cancer (19 ovarian, 18 renal, 17 melanoma, 12 breast cancer) received Thalidomide 100 mg orally every night until disease progression or unacceptable toxicity was encountered. Three of 18 patients with renal cancer showed partial responses and a further three patients experienced stabilization of their disease for up to 6 months. Although no objective responses were seen in the other tumour types, there were significant improvements in patients' sleeping (P < 0.05) and maintained appetite (P < 0.05). Serum and urine concentrations of basic fibroblast growth factor (bFGF), TNF-alpha and VEGF were measured during treatment and higher levels were associated with progressive disease. Thalidomide was well tolerated: Two patients developed WHO Grade 2 peripheral neuropathy and eight patients developed WHO grade 2 lethargy. No patients developed WHO grade 3 or 4 toxicity. Further studies evaluating the use of Thalidomide at higher doses as a single agent for advanced renal cancer and in combination with biochemotherapy regimens are warranted.
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PMID:Continuous low dose Thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. 1073 51

Thalidomide is reported to suppress levels of several cytokines, angiogenic and growth factors including TNF-alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects form the rationale for investigating thalidomide in the treatment of malignancies. We have evaluated the use of high-dose oral thalidomide (600 mg daily) in patients with renal carcinoma. 25 patients (all men; median age, 51 years; range 34-76 years) with advanced measurable renal carcinoma, who had either progressed on or were not suitable for immunotherapy, received thalidomide in an escalating schedule up to a maximum dose of 600 mg daily. Treatment continued until disease progression or unacceptable toxicity were encountered. 22 patients were assessable for response. 2 patients showed partial responses (9%; 95% CI: 1-29), 7 (32%; 95% CI: 14-55) had stable disease for more than 6 months and a further 5 (23%; 95% CI: 8-45) had stable disease for between 3 and 6 months. We also measured levels of TNF-alpha, bFGF, VEGF, IL-6 and IL-12 before and during treatment. In patients with SD > or = 3 months or an objective response, a statistically significant decrease in serum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (> or = grade II, 10 patients), constipation (> or = grade II, 11 patients) and neuropathy (> or = grade II, 5 patients). Toxicities were of sufficient clinical significance for use of a lower and well tolerated dose of 400 mg in currently accruing studies.
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PMID:The treatment of advanced renal cell cancer with high-dose oral thalidomide. 1159 64

Thalidomide is highly effective against multiple myeloma, but some patients must discontinue this medication due to adverse effects. We present herein an instructive case report on thalidomide-associated hypothyroidism in a patient with multiple myeloma. Thyroid hormone replacement therapy allowed us to restart administration of thalidomide, a potentially life-saving therapy. Known adverse effects of thalidomide, such as lethargy, constipation, and bradycardia, are potential symptoms of hypothyroidism, but we tend to overlook drug-associated hypothyroidism. Our case highlights the importance of routinely testing thyroid function in patients receiving thalidomide therapy.
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PMID:[Thalidomide-associated hypothyroidism in a patient with multiple myeloma]. 2574 67