Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DACA, also known as XR5000, is an acridine derivative active against both topoisomerase I and II. In this phase I study, DACA was given as a 3-h intravenous infusion on 3 successive days, repeated every 3 weeks. A total of 41 patients were treated at 11 dose levels between 9 mg m(-2) d(-1) and the maximum tolerated dose of 800 mg m(-2) day(-1). The commonest, and dose-limiting, toxicity was pain in the infusion arm. One patient given DACA through a central venous catheter experienced chest pain with transient electrocardiogram changes, but no evidence of myocardial infarction. At the highest dose levels, several patients also experienced flushing, pain and paraesthesia around the mouth, eyes and nose and a feeling of agitation. Other side-effects, such as nausea and vomiting, myelosuppression, stomatitis and alopecia, were uncommon. There was one minor response but no objective responses. DACA pharmacokinetics were linear and did not differ between days 1 and 3. The pattern of toxicity seen with DACA is unusual and appears related to the mode of delivery. It is possible that higher doses of DACA could be administered using a different schedule of administration.
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PMID:Phase I and pharmacokinetic study of DACA (XR5000): a novel inhibitor of topoisomerase I and II. CRC Phase I/II Committee. 1046 97

The purpose of the present study was to examine whether its is possible to successfully replace ondansetron (OND) with metoclopramide (MCP) in patients exposed to moderately emetogenic chemotherapy who did not experience severe nausea and vomiting while undergoing OND treatment during their first chemotherapy cycle. After switching to MCP, patients continued with this drug for three cycles, provided that they had adequate control of nausea and vomiting. Otherwise, they were switched back to OND. There were 76 patients, 60 women and 16 men, whose median age was 56 (mean 58) years. Karnofsky performance status score was 100 in 18 patients, 90 in 23, and 80 in 11 patients. No patient had previous chemotherapy. Thirty-four patients had breast cancer and received fluorouracil 500 mg/m2, epirubicin 100 500 mg/m2, and cyclophosphamide 500 mg/m2. Twelve patients had small cell lung cancer and received carboplatin 400 mg/m2 + etoposide 120 mg/m2 x 3 days. Twenty patients with ovarian cancer received carboplatin 350 mg/m2 and cyclophosphamide 500 mg/m2. Ten patients had cancer of unknown primary and received carboplatin 400 mg/m2, epirubicin 60 mg/m2, and etoposide 120 mg/m2 x 3 days. The OND schedule consisted of methylprednisolone 40 mg intravenous bolus followed by OND 8 mg in a 15-min infusion before chemotherapy, followed by OND 4 mg orally x 3 on the same and the next 2 days. Patients who did not experience nausea and vomiting with OND continued with an MCP schedule consisting of methylprednisolone 40 mg bolus followed by MCP 2 mg/kg in a 15-min infusion before chemotherapy, followed by MCP (20 mg x 4 on the day of therapy and the next 2 days after). Patients who failed with MCP or OND continued with OND. Considering our results as a whole, the intensity of nausea does not appear to influence the results of Gralla's scale. The results of Gralla's scale do not appear to be affected by the analysis of the antiemetic results and nausea on the next 2 days following chemotherapy administration. Overall, patients received 145 cycles with OND and 159 cycles with MCP. Of the 76 patients receiving OND-based antiemetic regimen during the first cycle, 13 (21%) experienced severe vomiting (Grade 2, 3) and the remaining 63 (79%) had mild or no vomiting (Grade 0, 1). Patients with Grade 0, 1 vomiting (63, 83%) continued with MCP in the second cycle. The final number of patients who failed on MCP, after 4 cycles of chemotherapy increased to 33 (43%); 43 (57%) were able to complete chemotherapy with MCP. Headache occurred in 15 (10%) cycles with OND and 8 (5%) with MCP. Flushing was noted in 12 (8%), and constipation occurred in 43 (30%) of OND cycles, and extrapyramidal manifestations occurred in 3 (5%) of patients receiving MCP. Diarrhea was noted in 3 (2%) of cycles with OND and in 28 (18%) with MCP. The cost ratio between MCP and OND was 1:14. If we administered OND only in patients who needed it, the overall cost decreased to 44%. Following the strategy applied in the present study, the cost decreased to 47%.
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PMID:Antiemetic prophylaxis with ondansetron and methylprednisolone vs metoclopramide and methylprednisolone in mild and moderately emetogenic chemotherapy. 1051 44

Patients with systemic mastocytosis present symptoms related to the tissue response to the release of mediators from mast cells and to the local mast cell burden. Such patients often have a history of chronic and acute mediator-related symptoms. Most patients have indolent disease with a good prognosis and a normal life span. Symptoms can include pruritus, flushing, syncope, gastric distress, nausea and vomiting, diarrhea, bone pain and neuropsychiatric symptoms, most of which are controlled by medication. Because there is no current cure for mastocytosis, successful therapeutic interventions rely on the recognition of mediator-related symptoms and their treatment, and established intervention approaches for the relatively uncommon leukemic concomitants. Efforts to link a particular mast cell-derived mediator to some aspect of the symptom complex depend on the known actions of the mediator and the efficacy of target-based interventions.
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PMID:Mastocytosis: mediator-related signs and symptoms. 1191 27

Fourteen patients with blastic phase chronic myelogenous leukemia received combination chemotherapy with mitoxantrone 5 mg/m2 intravenously daily for 3 days, cytosine arabinoside 100 mg/m2 intravenously over 2 hours bid for 7 days and high dose methylprednisolone 1000 mg/day intravenously for 5 days. The patients' mean age was 52 +/- 10 (range 34-64) and Philadelphia chromosome was positive in all. Five patients (35%) achieved complete remission and four patients (28%) had a partial remission. Overall remission rate was 64%. The mean survival was 11.1 +/- 8.6 months (median 13) for all patients, 19.4 +/- 4.0 months (median 19) for those achieving a complete remission, 12.50 +/- 5.7 months (median 14) for patients with partial remission and 1.8 +/- 1.8 months (median 2) for the unresponsive patients. Two of 5 unresponsive patients died early after the second course of remission induction. The treatment regimen was generally well tolerated. Marrow hypoplasia was observed in 9 (64%) patients and 7 (50%) had febrile episodes. Non-myelosupressive toxicity of the regimen was acceptable. Nausea and vomiting were observed in 8 (57%) patients and 3 (21%) patients developed flushing due to cytosine arabinoside. These results suggest that the regimen with mitoxantrone, cytosine arabinoside and high dose methylprednisolone in remission-induction of blastic phase chronic myelogenous leukemia may be a valid option that may also improve overall prognosis.
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PMID:Treatment of blastic phase chronic myeloid leukemia with mitoxantrone, cytosine arabinoside and high dose methylprednisolone. 1224 55

A fluoride overfeed occurred at a well site near an elementary school in Portage, Michigan. The incident resulted in a high concentration of fluoride (92 milligrams per liter) in drinking water at the school. Seven students who drank water from the school fountain reportedly suffered nausea and vomiting. Toxicological evaluations were made by conducting a risk assessment. On the basis of the symptoms experienced by the students, it was concluded that the fluoride had irritated the stomach causing nausea and vomiting. This mild oral exposure to fluoride was, however, deemed too low to cause any long-term appreciable adverse health effects. Despite subsequent flushing, the concentration of the fluoride in the drinking water remained variable during the first nine days after the incident. With several flushings over the 48 days after the incident, the concentration of fluoride was brought down to optimal levels. The electrical circuit that energized the fluoride system was modified to prevent another overfeed. In addition, operational changes were made to further minimize the impact of such an overfeed.
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PMID:Fluoride overfeed at a well site near an elementary school in Michigan. 1236 44

Mastocytosis comprises several diseases characterized by an abnormal increase in tissue mast cells. Cutaneous mastocytosis (CM) is the most common form of mastocytosis, affects predominantly children, and presents as a mast cell hyperplasia limited to the skin. Systemic mastocytosis (SM) comprises multiple distinct entities in which mast cells in filtrate the skin and/or other organs. The diagnosis of SM is based on the presence of one major criterion and one minor criterion or three minor criteria. Major criteria include the presence of multifocal dense infiltrates of > 15 mast cells in bone marrow and/or other extracutaneous organs. Four minor criteria include the presence of elevated serum alpha-tryptase levels > 20 ng/mL, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, the presence of a c-kit mutations on bone marrow and/or other tissues mast cells, and the presence of > 25% abnormal spindle-shaped mast cells in bone marrow and/or tissues. Symptoms of CM include pruritus, flushing urticaria, and dermatographism. Symptoms of SM include cutaneous symptoms in association with syncope, gastric distress, nausea and vomiting, diarrhea, bone pain, and neuropsychiatric symptoms. Activating and nonactivating mutations of c-kit (Asp816Val) are seen in adult SM and in some pediatric CM (Gly839Lys), indicating a clonal dysregulation. There is no cure for mastocytosis but the majority of pediatric CM regress at puberty. Women with mastocytosis are fertile and pregnancy and delivery have been successful by blocking mast cell-mediated symptoms. Symptomatic treatment aimed at reducing the effect of mediators is effective with antihistamines and mast cell-stabilizing agents such as sodium cromolyn. To reduce mast cell burden, interferon alpha, steroids, and purine analogs have been used with varying results. Future directions include tyrosine kinase inhibitors and bone marrow transplant.
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PMID:Mastocytosis: classification, diagnosis, and clinical presentation. 1505 60

Y-90-DOTA-Phe1-Tyr3-Octreotide (90Y-SMT 487, OctreoTher) has shown potential for effectively treating patients with neuroendocrine tumors. The dose-limiting organ for this agent is the kidney. The purpose of this work is to assess the effectiveness of a commercially available amino acid solution on reducing renal uptake of 90Y-SMT 487 and determine the safety profile of this solution. Subjects with In-111 pentetreotide positive tumors and normal creatinine levels were treated with 3 cycles of 90Y-SMT 487, 120 mCi/cycle, at 6-9 week intervals. During each treatment two liters of an amino acid solution containing arginine and lysine (Aminosyn II 7%, Abbott Laboratories, Abbott Park, IL) were infused IV over 4 hours. Adverse events were recorded. To assess the effect of Aminosyn II on renal uptake of 90Y-SMT 487, a subgroup of subjects underwent bremsstrahlung imaging 24 hours following infusion. Kidney to liver (K/L) count density ratios were generated from the baseline In-111 pentetreotide images (performed without amino acid infusion) and the 90Y bremsstrahlung images. Follow-up creatinine levels were obtained. Thirty-seven subjects received a total of 89 90Y-SMT 487 treatments. The number of amino-acid infusions associated with one or more episodes of emesis was 53 (62%). During 13 (15%) of these infusions, the Aminosyn II rate had to be reduced because of severe nausea and vomiting. Symptomatic flushing occurred during 16 (18%) of the infusions. One subject experienced a near syncopal event shortly after completing the infusion. Creatinine levels remained normal in 34 of 36 subjects during a mean follow-up period of 9.8 months. Fourteen subjects underwent bremsstrahlung imaging following infusion of 90Y-SMT 487. Kidney uptake appeared to decrease with administration of the amino acid solution in 13 of 14 subjects. For the 28 individual kidneys, the mean percent decrease in the Kidney/Liver uptake ratio with the amino acid solution was found to be 32%. We conclude that 2 L of Aminosyn II 7% infused over 4 hours appears to notably reduce renal uptake of 90Y-SMT 487. Aminosyn is generally well tolerated, particularly at lower infusion rates with occasional moderate to severe nausea and vomiting at higher rates.
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PMID:Effects of intravenous amino acid administration with Y-90 DOTA-Phe1-Tyr3-Octreotide (SMT487[OctreoTher) treatment. 1506 9

(1) The reference first-line drug therapy for migraine attacks in adolescents is a non specific analgesic such as paracetamol or a nonsteroidal antiinflammatory drug like ibuprofen. Two specific analgesics are authorised for use in this setting in France, namely ergotamine and dihydroergotamine. (2) Nasal sumatriptan is the first triptan to be licensed for this age group in France. (3) Evaluation data includes three flawed placebo-controlled trials. (4) Effects were modest at best. Only one of the three trials showed that sumatriptan was more likely than placebo to give complete pain relief within two hours. The three trials fail to show that sumatriptan is effective against symptoms such as nausea and vomiting, photophobia and phonophobia. (5) The principal known adverse effects of sumatriptan are chest tightness, flushing, and increased blood pressure. (6) In the only trial report containing relevant information, unpleasant taste was the only adverse effect more commonly associated with sumatriptan than with placebo. (7) Postmarketing follow-up revealed a number of serious adverse effects, including stroke, myocardial infarction and loss of vision. (8) The packs containing 6 or 12 spray vials carry a risk of overuse and self-induced headache. (9) In practice, sumatriptan must not be used to treat migraine attacks in adolescents.
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PMID:Nasal sumatriptan: new dosage. For adolescents with migraine: too little benefit. 1587 37

Patients with mastocytosis have symptoms related to the tissue response to the release of mediators from mast cells (MC), local mast cell burden or associated non-mast cell hematological disorders. MC contain an array of biologically active mediators in their granules, which are preformed and stored. MC are also able to produce newly generated membrane-derived lipid mediators and are a source of multifunctional cytokines. Mediator-related symptoms can include pruritus, flushing, syncope, gastric distress, nausea and vomiting, diarrhea, bone pain and neuropsychiatric disturbances; these symptoms are variably controlled by adequate medications. Management of patients within all categories of mastocytosis includes: a) a careful counseling of patients (parents in pediatric cases) and care providers, b) avoidance of factors triggering acute mediator release, c) treatment of acute and chronic MC-mediator symptoms and, if indicated, d) an attempt for cytoreduction and treatment of organ infiltration by mast cells.
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PMID:Current options in the treatment of mast cell mediator-related symptoms in mastocytosis. 1661 65

Niacin has beneficial effects on plasma lipoproteins and has demonstrated clinical benefits in reducing cardiovascular events and atherosclerosis progression. The side effects of niacin, however, have limited its use in general clinical practice. An understanding of cutaneous flushing based on the best available evidence should enhance patient education efforts and improve adherence. Although serious hepatic toxicity from niacin administration has been reported, it is largely confined to the use of slow-release formulations given as unregulated nutritional supplements. Niacin has been shown to induce insulin resistance in short-term trials, but the glycemic response in subjects with and without diabetes is usually minor. Niacin can be used safely in patients with diabetes. Despite a few case reports of myopathy associated with niacin-statin (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) combination therapy, 2 decades of clinical evidence since the introduction of statins do not support a general myopathic effect of niacin either alone or in combination with statins. Rare, less well-defined side effects of niacin include blurred vision due to cystoid macular edema, nausea and vomiting, and the exacerbation of peptic ulcers. Laboratory abnormalities that are usually small (< or =10%) and clinically unimportant include increased prothrombin time, increased uric acid, and decreases in platelet count and serum phosphorus. Overall, the perception of niacin side effects is often greater than the reality. As a result, a valuable medication for cardiovascular risk is underused.
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PMID:Safety considerations with niacin therapy. 1736 76


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