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)

Mastocytosis is a rare disease of mast-cell proliferation with involvement of the reticuloendothelial systems including skin, bone, gastrointestinal tract, liver, lungs, spleen, and lymph nodes. Systemic mastocytosis is characterized by a combination of symptoms that relate to the mast cells' release of vasoactive substances, such as histamine. These symptoms include urticaria pigmentosa, flushing, syncope with hypotension, headaches, nausea, vomiting, diarrhea, and occasional bronchospasm. The diagnosis of mastocytosis is typically based on the presence of the characteristic extraosseus manifestations. A well recognized roentgenographic feature seen in 70-75% of patients with mastocytosis is diffuse osteolysis and osteosclerosis, affecting primarily the axial skeleton and the ends of the long bones. Rarely, the bony involvement consists of generalized osteoporosis, which may lead to pathologic fracture, or solitary lesions (mastocytomas) which may cause symptoms of localized pain. Four patients with previously diagnosed systemic mastocytosis had unusual skeletal lesions. Clinical and laboratory evaluation of these patients eventually led to the correct diagnosis of systemic mastocytosis. We report these four cases to emphasize the need for thorough evaluation of unusual musculoskeletal findings in association with extraosseus symptoms that are characteristic of mastocytosis. Knowledge of a wide differential diagnosis of unusual skeletal lesions should include systemic mastosytosis.
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PMID:Mastocytosis presenting as a skeletal disorder. 912 84

Episodic vasomotor instability with flushing is an uncommon presentation that is suggestive of an endocrine etiology. This report is the case of a 42-year-old woman who presented to the ED 5 times in a 2-week period for recurrent, self-limited episodes of light-headedness associated with tachycardia, hypertension, and flushing. The patient's diagnosis eluded detection in both the outpatient and the inpatient settings for several months. The clinical diagnosis was ultimately confirmed by biochemical test samples obtained in the ED during a subsequent symptomatic event. The differential diagnosis of this patient's presentation includes pheochromocytoma, carcinoid syndrome, medullary thyroid carcinoma, systemic mastocytosis, and other endocrine and toxicologic diseases. ED management of the patient with transient yet significant vasomotor changes includes a workup for syncope, initiation of focused biochemical investigations, referral to the appropriate consultant, and consideration for admission.
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PMID:Recurrent near-syncope with flushing. 922 98

A 37-year-old woman with a 5-year history of multiple sclerosis is reported. She began having recurrent syncope even in the sitting position; other neurological features included hiccup, faciooro-lingual flushing and clumsiness of the hands. She had alternating Horner's syndrome, mild hypoalgesia of the right face, exaggerated deep tendon reflexes of the upper extremities, decreased deep sensation and ataxia of the upper extremities, and incomplete transverse myelopathy with a T4 sensory level. Head-up tilt testing confirmed orthostatic hypotension with relative preservation of the heart rate increase. Magnetic resonance imaging indicated abnormal intensities in the paramedian tegmentum and base of the medulla, which may have been additionally responsible for orthostatic hypotension. Steroid pulse therapy and L-threo-3,4-dihydroxyphenylserine caused regression of brainstem signs and reduced syncopal attacks.
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PMID:Orthostatic hypotension in a case with multiple sclerosis. 923 62

Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO-cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were <2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (beta blockers, alpha blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the same for patients treated with sildenafil or placebo. Concurrent disease states, such as renal or hepatic impairment, or concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could increase systemic exposure to sildenafil. Since the US market launch in April 1998, monitoring of spontaneous adverse event reports in association with sildenafil has demonstrated a pattern that is generally consistent with the experience observed during clinical development, with the exception of infrequent reports of priapism. In conclusion, extensive clinical testing has shown that overall treatment with sildenafil for up to 1 year is well tolerated and is associated with a low incidence of adverse events that result in discontinuation of treatment in <3% of patients.
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PMID:Overall cardiovascular profile of sildenafil citrate. 1007 41

A single-agent dose-escalating Phase I and pharmacological study of the polyamine synthesis inhibitor SAM 486A was performed. A dosing regimen of four weekly infusions followed by 2 weeks off therapy was studied. Fifty patients were entered into the study. Dose levels studied were 1.25, 2.5, 5, 8, 16, 32, 48, 70, 110, 170, 270, and 325 mg/m2/week. Pharmacokinetic sampling was done on day 1, and trough samples were taken weekly during the first treatment cycle. Pharmacodynamic sampling was done on days 1 and 22. At 325 mg/m2/week, dose-limiting toxicity was seen (one patient each with grade 4 febrile neutropenia, grade 3 neurotoxicity, and grade 3 hypotension with syncope and T-wave inversions on electrocardiogram). The recommended dose for further testing was set at 270 mg/m2/week. Infusion time was increased from 10 to 180 min due to facial paresthesias and flushing and somnolence. Drug exposure increased linearly with dose. Mean +/- SD t1,2 at 70-325 mg/m2 doses was 61.4+/-26.2 h, with a large volume of distribution at steady state. In peripheral blood leukocytes, a clear relationship between dose and inhibitory effect on S-adenosylmethionine decarboxylase or changes in intracellular polyamine pools was not recorded. SAM 486A can be administered safely using a dosing regimen of four weekly infusions followed by 2 weeks off therapy. The recommended dose for Phase II studies using this regimen is 270 mg/m2/week.
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PMID:Phase I and pharmacological study of weekly administration of the polyamine synthesis inhibitor SAM 486A (CGP 48 664) in patients with solid tumors. European Organization for Research and Treatment of Cancer Early Clinical Studies Group. 1081 92

Administration of the myeloid growth factor G-CSF after allogeneic hematopoietic stem cell transplantation is usually well tolerated, and associated with rapid hematopoietic engraftment. We report a high incidence (50%) of side-effects associated with post-transplant G-CSF in patients with chronic phase chronic myeloid leukemia undergoing allogeneic HLA-identical sibling peripheral blood stem cell transplantation. One or more of the following signs and symptoms were observed shortly after the subcutaneous injection of G-CSF: dyspnea, chest pain, nausea, hypoxemia, diaphoresis, anaphylaxis, syncope and flushing. These reactions led to discontinuation of G-CSF in the majority of patients. Predictive factors could not be identified, and the underlying mechanism leading to these reactions is unknown.
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PMID:Adverse side-effects associated with G-CSF in patients with chronic myeloid leukemia undergoing allogeneic peripheral blood stem cell transplantation. 1084 33

Beginning in the late 18th century, facial flushing and bounding carotid artery pulses during seizures were seen as evidence that seizures resulted from "venous hyperaemia" of the CNS. Consequently, physicians used digital compression of the carotid artery, and later carotid ligation, to abort seizures. In the early 1880s, New York neurologist James Leonard Corning (1855--1923) developed several instruments for carotid artery compression in the treatment of seizures. These devices included a two-pronged, fork-like instrument (the "carotid fork") for temporary compression as an abortive treatment and an adjustable belt-like instrument to encircle the neck (the "carotid truss") for chronic compression as a prophylactic treatment. Corning's uncontrolled observations suggested that the abortive treatment decreased the duration of seizures and that the prophylactic treatment decreased the frequency of seizures. Corning later combined instrumented carotid artery compression with other devices to decrease cerebral blood flow, including transcutaneous electrical vagal nerve and cervical sympathetic stimulation. Observed side effects of treatment included bradycardia, dizziness, and syncope. Corning's use of instrumented carotid compression and his precocious application of transcutaneous electrical vagal nerve stimulation were not widely adopted by neurologists, and these techniques and devices ultimately were abandoned in the late 19th century.
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PMID:J.L. Corning and vagal nerve stimulation for seizures in the 1880s. 1183 48

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

Bosentan is a nonpeptide, specific, competitive, dual antagonist at both endothelin receptor subtypes (ET(A) and ET(B)). Orally administered bosentan effectively prevents endothelin 1-induced vasoconstriction in pulmonary vessels in patients with pulmonary arterial hypertension. Improvement in exercise capacity from baseline was significantly greater with bosentan than with placebo in two phase III trials in patients with WHO functional class III or IV pulmonary arterial hypertension (primary or associated with connective tissue disease) despite treatment with vasodilators, diuretics, anticoagulants, cardiac glycosides, or supplemental oxygen. The beneficial effects of bosentan on exercise capacity were maintained for at least 20 weeks. Compared with placebo, bosentan led to a significantly greater improvement from pretreatment values in secondary efficacy endpoints such as the Borg dyspnea index, WHO functional class, and cardiopulmonary hemodynamic parameters (cardiac index, pulmonary vascular resistance, pulmonary artery pressure, pulmonary capillary wedge pressure, mean right atrial pressure). Bosentan significantly reduced the incidence, and delayed the onset, of clinical worsening of pulmonary arterial hypertension compared with placebo. In published clinical trials, adverse events that occurred with similar or greater frequency with bosentan 125 mg twice daily than with placebo included headache, syncope, flushing and abnormal hepatic function. Those that occurred less frequently with bosentan 125 mg twice daily than with placebo included dizziness, worsening of symptoms of pulmonary arterial hypertension, cough and dyspnea.
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PMID:Bosentan. 1472 63

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


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