Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diencephalic syndrome (DS) is a complex of signs and symptoms related to hypothalamic dysfunction. Its main features are emaciation despite normal energy intake and an alert appearance. This syndrome has been described in association with space-occupying lesions of the hypothalamic-optic chiasm region, mainly low-grade glioma, and less often with tumors in the proximity of the IV ventricle. Two patients with DS are reported. The first patient was an 8-month old boy with classical features of DS. Extensive investigation of malabsorption revealed no abnormalities and the first neurologic sign was a rotatory nystagmus. Magnetic resonance imaging (MRI) showed evidence of a hypothalamic tumor, which was identified after surgical resection as a pilocytic astrocytoma. The second patient was an adolescent boy who presented a 20-kg weight loss over a 6-month period and psychological disturbances. Gastrointestinal disease was ruled out as a cause of malnutrition. Because of a polydipsia-polyuria syndrome, manifest while the patient was hospitalized with a suspected diagnosis of anorexia nervosa, MRI of the brain was performed. Multiple intracranial lesions were revealed, mainly in the hypothalamus, and were identified as a disseminated disgerminoma. No neurologic signs or symptoms were present. The patients died 2 years and 1 year after diagnosis, respectively. Although DS is rare, it should be considered in severe failure to thrive or emaciation despite adequate food intake and normal absorptive function of the small bowel.
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PMID:[Diencephalic syndrome: An uncommon cause of malnutrition]. 1204 23

A 12-year-old girl with cystic fibrosis was diagnosed with a high-grade glioma after radiographic and biopsy results confirmed the primary intracranial lesion. She was treated with single-agent erlotinib during and after daily localized radiation therapy. Pharmacokinetic studies were conducted to assess the effect of pancreatic enzyme deficiency and intestinal malabsorption secondary to cystic fibrosis on the bioavailability of orally administered erlotinib, a lipophilic drug. Pharmacokinetic analysis of plasma samples from days 1 and 8 demonstrated that absorption of oral erlotinib was not affected by the patient's cystic fibrosis when the drug was given concomitantly with pancreatic enzyme replacement. When pediatric patients with cystic fibrosis are receiving erlotinib or other lipophilic oral drugs, continued supplementation of pancreatic enzymes is recommended, with therapeutic drug monitoring of plasma drug concentrations when feasible, and close observation for therapeutic responses and adverse effects.
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PMID:Pharmacokinetics of erlotinib for the treatment of high-grade glioma in a pediatric patient with cystic fibrosis: case report and review of the literature. 1955 60

Normal tissue toxicity reduces the therapeutic index of radiotherapy and decreases the quality of life for cancer survivors. Apoptosis is a key element of the radiation response in normal tissues like the hippocampus and small intestine, resulting in neurocognitive disorders and intestinal malabsorption. The Early Growth Response 1 (Egr1) transcription factor mediates radiation-induced apoptosis by activating the transcription of proapoptosis genes in response to ionizing radiation (IR). Therefore, we hypothesized that the genetic abrogation of Egr1 and the pharmacologic inhibition of its transcriptional activity could attenuate radiation-induced apoptosis in normal tissues. We demonstrated that Egr1-null mice had less apoptosis in the hippocampus and intestine following irradiation as compared with their wild-type littermates. A similar result was achieved using Mithramycin A (MMA) to prevent binding of Egr1 to target promoters in the mouse intestine. Abolishing Egr1 expression using shRNA dampened apoptosis and enhanced the clonogenic survival of irradiated HT22 hippocampal neuronal cells and IEC6 intestinal epithelial cells. Mechanistically, these events involved an abrogation of p53 induction by IR and an increase in the ratio of Bcl-2/Bax expression. In contrast, targeted silencing of Egr1 in two cancer cell lines (GL261 glioma cells and HCT116 colorectal cancer cells) was not radioprotective, since it reduced their growth while also sensitizing them to radiation-induced death. Further, Egr1 depletion delayed the growth of heterotopically implanted GL261 and HCT116 tumors. These results support the potential of silencing Egr1 in order to minimize the normal tissue complications associated with radiotherapy while enhancing tumor control.
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PMID:Silencing Egr1 Attenuates Radiation-Induced Apoptosis in Normal Tissues while Killing Cancer Cells and Delaying Tumor Growth. 2620 32