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)

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c) AMP is known to act as a second messenger for inhibition of platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side-effects, primarily, nausea, emesis, flushing, diaphoresis, and restlessness. In hypertensive patients blood-pressure responses are complex and are influenced to some extent by renin secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and it also has an indirect effect by activating the sympathetic nervous system. Thus, it is useless as an antihypertensive agent even apart from its debilitating side-effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize large amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be greatly reduced. Some drugs (thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to reduce their antihypertensive effects. The effects of low- and high-dose aspirin on prostacyclin and thromboxane synthesis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prostacyclin in hypertension]. 149 51

Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible.
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PMID:Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study. 150 55

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.
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PMID:Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. 151 36

Electrophysiologic studies have shown that intravenous magnesium sulfate prolongs atrioventricular (AV) nodal conduction and refractoriness and thus could play a role in the management of patients with paroxysmal AV reentrant supraventricular tachycardia (SVT). The present study evaluates the clinical and electrophysiologic effects of intravenous magnesium sulfate in patients with SVT and compares them with those of adenosine triphosphate (ATP), one of the most potent drugs in the treatment of this arrhythmia. Patients with inducible sustained SVT were treated with ATP (10 or 20 mg) and magnesium sulfate (2 g over 15 seconds) during electrophysiologic study. If the tachycardia failed to terminate by the sixth minute, an additional 2 g dose of magnesium was given. ATP (10 or 20 mg) was significantly better than magnesium for terminating induced tachycardias (14 of 14 vs 6 of 14, p less than 0.0001). Arrhythmia termination with ATP was due to anterograde AV nodal blockade in all but 1 patient who developed retrograde block over an accessory pathway with decremental conduction. Arrhythmia termination by magnesium was due to retrograde block over an accessory pathway in 3 patients (including the patient with accessory pathway exhibiting decremental conduction), anterograde AV nodal conduction block in 2 patients and premature ventricular complexes in 1 patient. During induced tachycardias, only AH intervals were prolonged by ATP, whereas magnesium significantly prolonged AH and QRS intervals. Short-lasting side effects (chest pain, flushing, nausea) occurred after both drugs were administered but were more severe after magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and electrophysiologic effects of magnesium sulfate on paroxysmal supraventricular tachycardia and comparison with adenosine triphosphate. 152 41

The purpose of this study was to evaluate the significance of increased Tl-201 uptake by the lungs after oral dipyridamole testing. In conjunction with myocardial perfusion scintigraphy, intravenous dipyridamole has been recently approved as an alternative to exercise for the evaluation of coronary artery disease in patients who cannot adequately exercise, and it will largely replace oral dipyridamole testing. This study contributes to the understanding of the significance of increased lung thallium uptake during pharmacologic stress testing. Oral dipyridamole, 400 mg, was administered to 192 patients undergoing Tl-201 imaging for clinical indications. Mild adverse effects occurred in 31% of patients (chest pain, nausea, headache, or flushing). Dipyridamole had minimal hemodynamic effects. The lung/heart thallium activity ratio was determined in 152 patients. These were subdivided into four groups according to the presence or absence of ischemia, transient myocardial perfusion defect, or scar as indicated by a fixed myocardial perfusion defect. In 61 patients without transient myocardial perfusion defect or fixed myocardial perfusion defect (group 1), the lung/heart thallium activity ratio was 0.39 +/- 0.01 (mean +/- SEM). In 31 patients without transient myocardial perfusion defect but with fixed myocardial perfusion defect (group 2), the lung/heart thallium activity ratio was higher, 0.44 +/- 0.02 (P less than 0.05). In 27 patients with transient myocardial perfusion defect but no fixed myocardial perfusion defect (group 3) and in 33 patients with both transient myocardial perfusion defect and fixed myocardial perfusion defect (group 4), the lung/heart thallium activity ratio was 0.51 +/- 0.03 and 0.52 +/- 0.03, respectively, both significantly higher than either group 1 or group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of increased Tl-201 uptake by the lungs in patients undergoing oral dipyridamole-thallium myocardial imaging. 161 45

Intravenous dipyridamole planar thallium-201 imaging is a safe and effective test for detection and prognosis of coronary artery disease (CAD) in the general population. The relative diagnostic accuracy and side-effect profile of dipyridamole thallium-201 stress imaging in women is not defined. Forty-three consecutive female and 71 male patients who underwent dipyridamole thallium-201 imaging (0.56 mg/kg) within 3 months of cardiac catheterization were studied. Scans were considered abnormal if fixed or reversible perfusion defects were detected. Stenosis severity of greater than or equal to 50% luminal diameter reduction of any artery defined CAD. Overall sensitivity for detection of CAD was 0.87 in women and 0.94 in men; specificity was 0.58 in women and 0.63 in men (p = not significant). Sensitivity for detection of 1-vessel CAD was 0.60 in women and 0.94 in men (p = 0.001). The sensitivity for detection of multivessel CAD (with or without surgical revascularization) was 1.0 and 0.94 in women and men, respectively. Adverse effects were reported in 62% of women and in 38% of men (p = 0.01). There was no significant difference in the incidences of chest pain, headache, nausea, flushing or electrocardiographic changes. The incidences of severe ischemia and dizziness were higher in women. Possible explanations for this difference in adverse effects include gender differences in the volume of distribution of dipyridamole due to varied fat-to-muscle ratios and different subjective nocioceptive sensitivities to the effects of dipyridamole. Overall sensitivity and specificity are comparable between the sexes.
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PMID:Comparison of accuracy for detecting coronary artery disease and side-effect profile of dipyridamole thallium-201 myocardial perfusion imaging in women versus men. 162 2

We have treated with intravenous iloprost twelve patients suffering from cardiac insufficiency compensated under oral digoxin (NYHA class II) associated with severe limb ischaemia due to arterial insufficiency. Our aim was to study its possible interaction on digoxin levels and to evaluate the long-term efficacy of iloprost. Although iloprost slowed the digoxin absorption by approximately one hour, we found no clinically significant difference between the digoxin pharmacokinetic data before and during treatment by iloprost. Moreover, 11 out of the 12 patients had a good clinical fate after the treatment, which persisted at 6 months. The pain disappeared in 4 and diminished in 7; and all skin ulcers healed. This improvement has lasted up to two and a half years in two patients. The clinical tolerance of iloprost was acceptable despite frequent headache and flushing associated with hypotension and nausea. We conclude that iloprost seems to be a very promising treatment of severe limb ischaemia when no intervention on the proximal arteries is possible. The patients on digoxin can continue their treatment without dose alteration while starting on iloprost.
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PMID:[Treatment with iloprost of critical ischemia of the lower limbs associated with cardiac insufficiency. Study of interaction with the pharmacokinetics of digoxin]. 172 27

Intravenous fluorescein angiography is a commonly performed and extraordinarily valuable diagnostic procedure. The frequency of adverse reactions after angiography has varied considerably in previous reports. In a prospective study of 2789 angiographic procedures in 2025 patients, the authors found that the percentage of adverse reactions depended strongly on the patient's angiographic history. Overall, adverse reactions followed 4.8% of the angiographic procedures. These reactions included nausea (2.9%), vomiting (1.2%), flushing/itching/hives (0.5%), and other reactions (dyspnea, syncope, excessive sneezing) (0.2%). No cases of anaphylaxis, myocardial infarction, pulmonary edema, or seizures occurred. The percentage of reactions was 1.8% for patients who had had previous angiography without ever having had an adverse reaction. In contrast, the percentage of reactions was 48.6% for patients who had had an adverse reaction to angiography previously.
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PMID:Frequency of adverse systemic reactions after fluorescein angiography. Results of a prospective study. 189 Dec 25

The major use of N-acetylcysteine in clinical toxicology is in the treatment of acetaminophen (paracetamol) overdosage. The hepatorenal toxicity of acetaminophen is mediated by a reactive metabolite normally detoxified by reduced glutathione. If glutathione is depleted, covalent binding to macromolecules and/or oxidation of thiol enzymes can lead to cell death. Oral or intravenous N-acetylcysteine or oral D,L-methionine mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides; L-methionine also forms cysteine, thus giving rise to glutathione and other products. Oral therapy with N-acetylcysteine or methionine for acetaminophen poisoning is contraindicated in the presence of coma or vomiting, or if activated charcoal has been given by mouth. Nausea, vomiting, and diarrhea may also occur as a result of oral N-acetylcysteine administration. Anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into N-acetylcysteine infusion (20 hours intravenous regimen) in up to 10% of patients. Following accidental intravenous overdosage, the adverse reactions of N-acetylcysteine are similar but more severe; fatalities have occurred. A reduction in the loading dose of N-acetylcysteine may reduce the risk of adverse reactions while maintaining efficacy. Administration of N-acetylcysteine for a longer period might provide enhanced protection for patients in whom acetaminophen absorption or elimination is delayed. N-acetylcysteine may also have a role in the treatment of toxicity from carbon tetrachloride, chloroform, 1,2-dichloropropane, and other compounds. The possible use of N-acetylcysteine and other agents in the prevention of the neuropsychiatric sequelae of acute carbon monoxide poisoning is an important area for future research.
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PMID:Use of N-acetylcysteine in clinical toxicology. 192 4

Clinical interest in salmon calcitonin began in 1972 when this peptide was shown to be effective in the treatment of Paget's disease. Salmon calcitonin is more potent than porcine calcitonin, with human calcitonin intermediate in potency. Salmon calcitonin is a highly effective therapeutic agent in the treatment of Paget's disease. During chronic treatment with salmon calcitonin, alkaline phosphatase activity and urinary hydroxyproline excretion decrease on an average of 50% in patients with Paget's disease. Patients may experience a variety of clinical benefits during chronic treatment, including relief of bone pain, a reversal of neurological deficits, stabilization or improvement of hearing loss, and improvement of vascularity of bone. Radiologic healing of osteolytic lesions in particularly striking with calcitonin treatment. Paget's disease patients prefer treatment with salmon calcitonin administered by means of a nasal spray. Salmon calcitonin has an excellent safety profile and produces mild side effects in a small percentage of patients. The most common side effects associated with salmon calcitonin administration are nausea and facial flushing. It is unusual to observe severe side effects. In about 20% of patients, production of antibodies may neutralize the effects of the exogenously administered calcitonin; these patients respond to human calcitonin. At this time salmon calcitonin should still be considered a valuable therapeutic agent in the treatment of Paget's disease, particularly in patients with osteolytic lesions.
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PMID:Clinical efficacy of salmon calcitonin in Paget's disease of bone. 193 17


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