Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiation-induced esophagitis often results in treatment interruption, which may severely affect the probability of control of the local disease in patients undergoing chest radiotherapy (RT). No effective regimen that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of oral mucosal healing using topical recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) has been reported, the mechanism of such an interaction remains obscure. Effective topical application of rhGM-CSF for the treatment of radiation-induced esophagitis has never been reported in the past. In pharmacological studies, we observed that glycerol exerts a remarkable stabilizing effect on rhGM-CSF immunoreactivity. After studying the kinetics of esophageal emptying with nuclear imaging, we proposed a rhGM-CSF regimen that could be applied for topical treatment of esophagitis during RT. The regimen was applied for 5 consecutive days in a cohort of 36 patients undergoing chest RT, immediately after the documentation of grade 3 esophagitis. RT was not interrupted. Mucosal biopsies were performed endoscopically and examined immunohistochemically. Regression of dysphagia to grade 0/1 was observed in 19 of 36 (52%) patients, whereas grade 2 dysphagia persisted in 12 of 36 (33%) patients. Progression of dysphagia was seen in 5 of 36 (14%) patients. Recurrence of severe esophagitis within 5-8 days after rhGM-CSF therapy was observed in 7 of 31 (22%) patients with initial response to rhGM-CSF. Four of these patients presented significant improvement of symptomatology after additional rhGM-CSF medication. In immunohistochemical studies, active intraepithelial neovascularization and thymidine phosphorylase and vascular endothelial growth factor overexpression were observed in the damaged epithelium, which was not accompanied by macrophage or neutrophil infiltration. We conclude that rhGM-CSF topical therapy (p.o. administration) exerts a significant therapeutic effect against RT-induced esophagitis. The rhGM-CSF mucosa healing effect is probably due to its direct angiogenic activity and/or to the potentiation of the activity of other angiogenic factors released by the damaged epithelium.
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PMID:Oral administration of recombinant human granulocyte macrophage colony-stimulating factor in the management of radiotherapy-induced esophagitis. 1063 27

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is caused by deficiency in thymidine phosphorylase (TP), that regulates thymidine (dThd) and deoxyuridine (dUrd). Toxic levels of dThd and dUrd can lead to mitochondrial dysfunction by impairing mitochondrial DNA replication, causing GI and neurologic deterioration. We studied the impact of bone marrow transplant (BMT) and platelets, as a source of TP on the clinical outcome of MNGIE. We report a case of MNGIE, who presented with severe vomiting. Over time, he was non-ambulatory and his GI symptoms got progressively worse with severe dysphagia, abdominal pain episodes, persistent vomiting and diarrhea. Being unfit for intense conditioning regimen, he received a mini BMT, with mild conditioning regimen. Bone marrow was obtained from his HLA fully matched brother. One month after transplantation, donor chimerism in peripheral blood was 33%. Excellent clinical responses were achieved 3 months after transplantation and circulating donor cell chimerism decreased to 24% with a significant increase in platelet TP activity. Ten months post transplant the patient's symptoms recurred and fresh single donor platelets were infused, with a significant increase in platelet TP activity. Mini BMT and platelet transfusion can transiently increase circulating TP activity and might prevent progress of this fatal disease.
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PMID:Non-myeloablative bone marrow transplant and platelet infusion can transiently improve the clinical outcome of mitochondrial neurogastrointestinal encephalopathy: a case report. 2341 Sep 18

Mitochondrial neurogastrointestinal encephalopathy (MNGIE), usually an autosomal-recessive inherited condition, causes gastrointestinal dysmotility, ophthalmoplegia, ptosis, leukoencephalopathy and neuropathy. The chromosome 22 disorder, due to mutations in the nuclear gene TYMP encoding thymidine phosphorylase (TP), leads to the accumulation of thymidine and deoxyuridine, with mitochondrial dysfunction.This report describes a patient with an MNGIE-like syndrome with a heterozygous TYMP mutation who showed marked, but transient improvement postallogeneic haematopoietic stem cell transplantation (HSCT).The patient, showing ptosis and ophthalmoplegia, was initially managed for myasthenia gravis. She developed gastrointestinal symptoms, dysarthria, dysphagia and weakness, and MNGIE was considered due to its low TP levels and improvement after platelet transfusions. She underwent HSCT, with dramatic improvement, but regressed 18 months later despite normal TP levels, platelet counts and full chimerism.MNGIE may encompass a spectrum of disorders. TP deficiency alone is unlikely to explain all clinical signs, and other factors, including the possible development of anti-TP antibodies, which may play a role in the pathophysiology.
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PMID:Transient clinical improvement of a mitochondrial neurogastrointestinal encephalomyopathy-like syndrome after allogeneic haematopoietic stem cell transplantation. 2876 76