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)

Autonomic hyperreflexia occurs in up to 85 percent of individuals with spinal cord injuries above the major splanchnic sympathetic outflow. In such cases, paroxysmal reflex sympathetic activity develops in response to noxious stimuli below the level of the neurologic lesion. The clinical features of autonomic hyperreflexia are due largely to reflex sympathetic adrenergic and cholinergic discharges with dysfunctional supraspinal regulatory control. Cephalgia, diaphoresis, flushing, tachycardia or bradycardia, and paroxysmal hypertension are most commonly observed. Although a variety of stimuli can provoke autonomic responses of variable magnitudes, bladder and bowel distention continue to account for most episodes. Removal of the offending stimulus is important to restoring the autonomic nervous system to its baseline activity. Current understanding of the pathophysiology, clinical features, and medical management of this fascinating but potentially serious complication of spinal cord injury are reviewed.
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PMID:Autonomic hyperreflexia with spinal cord injury. 150 Sep 43

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

The Royal Army Medical Corps (RAMC) of the UK is considering offering women in the Army the option of inducing amenorrhea especially those in war. Logistics problems of supplying sufficient sanitary protection makes inducing amenorrhea in these women an advantage. It is important that the Royal Army not force servicewomen ready for war to agree to chemical induction of amenorrhea, however. A survey of civilian women shows that 80% liked the notion of eliminating menstruation. continuous combined oral contraceptive (COC) therapy induces amenorrhea, but it poses some side effects including bleeding and spotting, 2 kg weight gain, breast tenderness, depression, and headaches. 12 weeks of COC therapy costs range form 2 to 6 pounds. The synthetic androgen used to treat endometriosis, danazol, may also induce amenorrhea at daily doses of 800 mg. It causes various side effects including reduced breast size, flushing, sweating, loss of libido, acne, weight gain, edema, hirsutism, and voice change. 12-week danazol therapy costs about 200 pounds. Another drug with androgenic, antigonadotrophic, antiestrogenic, and antiprogestogenic properties which is also used to treat endometriosis, gestrinone, in another possible amenorrhea inducer at 2 doses of 2.5-5 mg/week. Side effects are similar to those of danazol. In 1 study, all 20 patients developed acne and seborrhea. Its 12 week costs are considerably more than danazol and COC therapy (450 pounds). Intermittent administration of 2 gonadotropin releasing hormone (GnRH) analogues, buserelin and goserelin, suppresses production of gonadotropins. Health workers need to inject 3.6 mg goserelin every 28 days while they administer buserelin subcutaneously or intranasally. the leading side effect on both GnRH analogues is not flushes. 12-week therapy is about 375 pounds. Fertility is restored after discontinuation of all the aforementioned therapies. The GnRH analogue goserelin is the most effective therapy, but the cost factor causes the Royal Army to favor COCs.
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PMID:The induction of amenorrhoea. 153 75

Amlodipine and nitrendipine are calcium antagonists of the 1,4-dihydropyridine group which differ in their pharmacokinetic and pharmacodynamic properties. The clinical relevance of these differences was investigated in a study designed to compare the efficacy and safety of once-daily amlodipine (5 mg) and nitrendipine (20 mg) in patients with mild-to-moderate essential hypertension. Ambulatory blood pressure monitoring and conventional measurements showed that amlodipine and nitrendipine produced comparable reductions in blood pressure after 4 weeks of treatment. However, the onset of the antihypertensive effect was gradual for amlodipine, while most of the reduction achieved at the end of treatment with nitrendipine was seen after the first dose. There were no significant changes in heart rate with amlodipine, but significant increases occurred during the first 6 h of nitrendipine treatment. Amlodipine was associated with a significantly lower incidence of vasodilator-related adverse effects at initiation of therapy (headache, flushing, tachycardia) compared with nitrendipine, which may reflect its slower onset of action. The different pharmacodynamic and toleration profiles of amlodipine and nitrendipine at therapeutically equivalent doses suggest that amlodipine may have advantages in the treatment of hypertension, especially in terms of the low incidence of acute side effects, which may ultimately translate into improved patient compliance.
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PMID:Amlodipine compared to nitrendipine in hypertensive patients: the effects on toleration in relationship to the onset of action. 153 15

The frequency and severity of adverse effects during the first 14 days of treatment with amlodipine (5 mg once daily), nifedipine retard (20 mg twice daily) or placebo were compared in a multicentre, three-way, cross-over study involving 97 patients with mild-to-moderate hypertension. All three groups of patients were well matched for age, sex and baseline blood pressure. Amlodipine and nifedipine retard produced highly significant and comparable reductions in blood pressure, indicating that the doses were therapeutically equivalent. The incidence of adverse effects considered to be definitely or probably related to nifedipine retard treatment (41%) was significantly higher than for placebo (16%, p less than 0.01) or amlodipine (27%, p less than 0.05). There were no significant differences in the incidence of vasodilator-related adverse effects between amlodipine and placebo. In contrast, headache, flushing and dizziness were reported more frequently by patients while on nifedipine retard than on placebo or amlodipine. The convenience of once-daily dosing, together with a lower incidence of adverse effects, with consequently fewer withdrawals from therapy, suggests that amlodipine has clinical advantages over nifedipine retard in the treatment of hypertension.
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PMID:Comparison of early side effects with amlodipine and nifedipine retard in hypertension. 153 16

Nitroglycerin was administered to eight healthy volunteers in the form of sublingual tablets, oral sustained-release tablets, and an oral solution. Blood samples were collected for measurement of nitroglycerin and its two isomeric glyceryl dinitrate metabolites. Blood pressure and pulse rate were monitored; subjective evaluations of headache, dizziness, facial flushing, skin irritation, and gastrointestinal upset were made. Nitroglycerin itself was virtually undetectable after the solution and tablet preparations; the metabolites were consistently detectable from a few minutes after dosing to 24 h later. Mean total (nitroglycerin plus metabolite) concentrations were comparable in the 15 min following sublingual administration, and the 8 h following tablet administration. The relative bioavailability of the tablets in comparison with the oral solution was 70 per cent based on metabolite concentrations. Nitroglycerin sustained-release tablets appear to exert their beneficial effects in the prolonged prophylaxis of angina through active metabolites.
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PMID:Pharmacokinetics of nitroglycerin and its metabolites after administration of sustained-release tablets. 155 Sep 9

A patient is described with a 17-year history of intractable left-sided facial pain. The pain occurred daily in 5 sec spasms to a maximum of one every 2-3 min and was restricted to the left upper face. It was associated with rhinorrhoea on the left and often with ipsilateral facial flushing. Conventional therapy, including carbamazepine, baclofen and three posterior fossa explorations, had not provided lasting relief. Local facial stimulation by tapping a painful trigger point led to both pain and flushing of the face ipsilaterally. During this flushing, blood was collected and assayed using sensitive radioimmunoassays for several neuropeptides (neuropeptide Y, substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide). A marked (119%) increase in calcitonin gene-related peptide was noted in the external jugular vein blood ipsilaterally during the flushing with no change in the other peptides measured. To quantitate the effect of calcitonin gene-related peptide on human extracranial vessels, standard pharmacological procedures were used to examine the potency of the peptide as a vasodilator of human facial artery. The IC50 of calcitonin gene-related peptide for the prostaglandin F2 alpha-precontracted human facial artery was 10(-9) mol/l. The relevance of these observations to the clinical problem of migraine is considered.
Cephalalgia 1992 Feb
PMID:Cutaneous sensory stimulation leading to facial flushing and release of calcitonin gene-related peptide. 155 59

In a phase I study, the sequentially administered combination of recombinant human interleukin-3 (rhIL-3) and rhGM-CSF was compared with treatment with rhIL-3 alone in 15 patients with advanced tumors but normal hematopoiesis. Patients were initially treated with rhIL-3 for 15 days. After a treatment-free interval, the patients received a second 5-day cycle of rhIL-3 at an identical dosage, immediately followed by a 10-day course of rhGM-CSF, to assess the toxicity and biologic effects of this sequential rhIL-3/rhGM-CSF combination. rhIL-3 doses tested were 125, and 250 micrograms/m2, whereas rhGM-CSF was administered at a daily dosage of 250 micrograms/m2. Both cytokines were administered by subcutaneous (SC) bolus injection. rhIL-3/rhGM-CSF treatment was more effective than rhIL-3 but equally effective to each other in increasing peripheral leukocyte counts, especially neutrophilic and eosinophilic granulocyte counts. In contrast, both modes of cytokine therapy raised the platelet counts to the same degree. rhIL-3/GM-CSF treatment was more effective than rhIL-3 in increasing the number of circulating hematopoietic progenitor cells BFU-E and CFU-GM. High-dose rhIL-3, but not low-dose rhIL-3, was as effective as the rhIL-3/rhGM-CSF combinations in increasing the number of circulating CFU-GEMM. The increase in absolute neutrophil counts correlated with the increase in the number of circulating CFU-GM. Side effects, mainly fever, headache, flushing, and sweating, were generally mild, but in two patients the occurrence of chills, rigor, and dyspnea after initiation of GM-CSF treatment necessitated dose reduction and discontinuation, respectively. These results indicate that sequential treatment with rhIL-3 and rhGM-CSF is as effective as single-factor treatment with rhIL-3 in stimulating platelet counts, whereas the effect of combination therapy on neutrophil counts and circulating progenitor cells is superior.
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PMID:Sequential in vivo treatment with two recombinant human hematopoietic growth factors (interleukin-3 and granulocyte-macrophage colony-stimulating factor) as a new therapeutic modality to stimulate hematopoiesis: results of a phase I study. 158 11

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


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