Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A multicentre study of IL2 and IFN alpha has been performed in 58 patients with metastatic melanoma. The scheme consisted of IL2 3.0 BRMP MU/m2/d as a continuous infusion for 4 d combined with subcutaneous administration of IFN alpha 6 MU/m2/d, day 1 + 4. The cycle was repeated every 2 weeks for a maximum duration of 26 weeks. 54 patients were evaluable for response. One (2%) achieved a complete and 10 (19%) a partial response. 19 (35%) patients were stable and 24 (44%) showed progressive disease. Common side-effects included fever, chills, fatigue, skin rash, anorexia, nausea and diarrhoea. Hypothyroidism was noted in 10% of the patients. These results show that this regimen of IL2 and IFN alpha is active but, in contrast to what could be expected, not superior to IL2 alone possibly due to suboptimal dosing. In an ongoing study in Rotterdam and Nijmegen, a more intense schedule was chosen, consisting of three daily i.v. doses of IL2 4.5 BRMP MU/m2 and IFN alpha 3.0 MU/m2 for 5 d. This regimen is repeated at intervals of 3 weeks for a total of three cycles. Presently, nine patients have been entered. One patient achieved a complete response, four a partial response (overall 56%), three had stable disease and one progressed. Toxicity was severe and treatment was prematurely stopped in five patients: myocardial infarction (one patient), atrial fibrillation (one patient), negative T waves and myocardial hypokinesia (one patient) and psychosis (two patients). This regimen can only be justified if the therapeutic results are superb, which has yet to be awaited.
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PMID:Clinical experience with the combined use of recombinant interleukin-2 (IL2) and interferon alfa-2a (IFN alpha) in metastatic melanoma. 193 17

We investigated whether clinical and laboratory variables can predict perfusion status after t-PA administration, by using the data from 138 patients who received t-PA during the Thrombolysis in Myocardial Infarction (TIMI) I study. All clinical and laboratory variables that were collected at baseline or during perfusion for TIMI I were evaluated by the current study. Via stepwise discriminant analysis, 7 variables were closely associated with perfusion status at 90 minutes (listed in the order of their discriminant effect): baseline grade of stenosis in the infarct-related coronary artery, whether nausea was present during the infusion, baseline aspartate aminotransferase (SGOT) concentration, whether arrhythmias were present during the infusion, baseline fibrinogen concentration, baseline partial thromboplastin time, and baseline diastolic blood pressure. Baseline severity of stenosis and the likelihood of there being reperfusion were inversely related. Eighty-four percent of patients with adequate perfusion after 90 minutes of t-PA infusion were classified correctly, but only 50% of those without perfusion at 90 minutes were classified correctly. In addition, since 70% of the TIMI I patients, on average, did achieve perfusion, the use of these 7 variables added little predictive information. Our findings suggest that 1) there is as yet no practical way to predict reperfusion after t-PA therapy and 2) the severity of coronary stenoses, if known ahead of time, should be considered when selecting patients for thrombolytic therapy.
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PMID:Prediction of coronary artery reperfusion after tissue plasminogen activator infusion. 211 85

Oral contraceptives (OCs, long-acting progestins (LAPs), and IUDS are reviewed in terms of new information on safety and efficacy. OC formulations are described and their mechanism of action and efficacy indicated. Reports are provided for thromboembolism, hemorrhagic and thrombotic stroke, ischemic heart diseases, alterations in lipid and hypoprotein and carbohydrate metabolism, hypertension, coagulation changes, breast and cervical cancers, and such minor side effects as menstrual irregularities, nausea, headaches, weight gain, premenstrual syndrome effects, and mood and libido changes. Noncontraceptive health benefits and clinical considerations are discussed. Norplant, as the only long acting progestin available in the US is described in terms of its formulations, mechanism of action, sequelae and metabolic effects, menstrual irregularities, metabolic effects, nuisance side effects, candidates for insertion, method of insertion and removal, and continuation rates. 2 IUD types are identified as the only ones available in the US, Progestasert T and T-Cu-380A (Paragard). Mechanism of action, efficacy, candidates, major sequelae such as salpingitis, infertility, and uterine perforation, minor sequelae such as metrorrhagia and dysmenorrhea, and other considerations are indicated. OCs in the US contain an average of 35 mg of ethinyl estradiol and assorted progestins e.g.s, ethynodiol diacetate, norethindrone acetate, nortestosterone derivatives with a complex mechanism of action. The failure rate for use effectiveness is 6 pregnancies/100 woman years. Modern formulations have combined rates of no more than 50 to 100 adverse events/100,000 users. Some of the effects are indicated as follows: Thromboembolism accounts for 60% of adverse effects and appears to be declining along with hemorrhagic and thrombotic stroke, however, modern use studies are only partially available. Myocardial infarction related to OC use may be embolic, and has a low risk at 7/100,000 users. Low-dose contraceptives substantially reduce the associated risks. Those with risk factors need close monitoring. Norplant is useful for those not wanting to take a daily regimen and is commonly accompanied by menstrual irregularity and sometimes headaches. Continuation is 80% after the 1st year and 40% after 5 years. Candidates for IUDs are parous women in monogamous relationships, who are not at risk for salpingitis, which is related to IUD use, or sexually transmitted diseases. Continuation is 70% after 1 year compared with 50% of OC users.
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PMID:Modern trends in contraception. 212 11

We tested the hypothesis that the administration of nitrous oxide (N2O) causes major (e.g., myocardial infarction, neuronal injury, hypoxemia, infection, death) or minor (e.g., nausea, vomiting, headache, earache) untoward effects in patients requiring anesthesia for 1.5-4 h. Given the higher morbidity and mortality associated with aging, we also tested whether aging increased any untoward effect of N2O. Finally, we investigated whether the substitution of N2O for a fraction of the anesthesia supplied by isoflurane altered the latter's pharmacologic effects. We studied 270 patients scheduled for elective total hip arthroplasty (n = 100), carotid endarterectomy (n = 70), or transsphenoidal hypophysectomy (n = 100) who were randomly assigned within each surgical group to receive isoflurane with or without 60% N2O. Regardless of patient age, we found no difference in major or minor untoward outcomes between anesthetic groups, nor a trend to suggest that a larger data cohort would reveal a significant adverse effect of N2O. The addition of N2O administration decreased the isoflurane requirement for clinical anesthesia but did not alter most of the clinical variables measured in practice, including blood pressure, heart rate, rate of recovery from anesthesia, development of postoperative pain, patient satisfaction with anesthesia, or duration of anesthesia or of hospitalization. Patients given N2O were no more likely to dream during anesthesia, remember events during anesthesia, or be frightened by those events. Our results support the continued use of N2O to anesthetize patients for elective surgery.
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PMID:Clinical pharmacology of nitrous oxide: an argument for its continued use. 224 Jun 27

Clinical trials in Europe have found that a single oral dose of RU-486, followed by prostaglandin administration, effectively and safely terminates early pregnancy in about 95% of women. In a multicenter study carried out in France, 1 600-mg dose of RU-486, followed 36-48 hours later by intramuscular sulprostone or intravaginal gemeprost, induced complete abortion in 96% of 2000 women with up to 49 days of amenorrhea. In a British multicenter study, the combination of RU-486 and intravaginal gemeprost induced abortion in 95% of 600 women with up to 63 days of amenorrhea. RU-486 is not effective in aborting ectopic pregnancies. Bleeding usually starts 1-2 days after treatment and lasts for 1-2 weeks. About 1% of patients have required curettage since the amount of blood loss exceeds that in a normal menstrual period. The other side effects recorded with any frequency--abdominal cramping, nausea, vomiting, diarrhea, and headache--are all transitory and mild. Only 1 case of myocardial infarction has been reported in the more than 20,000 RU-486 acceptors studied. Endometritis and salpingitis are extremely rare complications. There have been no maternal deaths, and no fetal abnormalities have been observed in women who took RU-486 alone early in pregnancy and failed to abort.
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PMID:Mifepristone (RU 486). 224 20

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of the Class I antiarrhythmic agent moricizine hydrochloride are reviewed. Moricizine is chemically similar to the phenothiazines but does not appear to block dopaminergic receptors. Its major electrophysiologic actions are a concentration-dependent decrease in maximum rate of phase 0 depolarization; increased rates of phase 2 and 3 repolarization, decreased action potential duration, and decreased effective refractory period. Moricizine causes a dose-related prolongation of the PR interval and of AV nodal, infranodal, and intraventricular conduction times but has little effect on ventricular repolarization. The antiarrhythmic and electrophysiologic effects are not correlated with plasma concentrations of the drug or its metabolites. Moricizine reduces the occurrence of ventricular premature contractions (VPCs), couplets, and nonsustained ventricular tachycardia. It appears to suppress symptomatic nonsustained ventricular tachycardia, sustained ventricular tachycardia, and ventricular fibrillation or flutter. Moricizine appears to be as effective as quinidine and more effective than disopyramide, propranolol, and imipramine but less effective than flecainide and encainide at reducing VPCs. Moricizine continues to be evaluated in the Cardiac Arrhythmia Suppression Trial, which was designed to assess the long-term benefit of arrhythmia suppression in patients with left ventricular dysfunction after myocardial infarction. Moricizine seems to be better tolerated than quinidine, disopyramide, and imipramine and to have less proarrhythmic potential than flecainide or encainide. Noncardiac adverse effects include dizziness, nausea, and headache. Cimetidine appears to decrease moricizine clearance, and decreased theophylline clearance has been reported in subjects given moricizine. The usual adult dosage of moricizine hydrochloride is 600-900 mg/day given in three divided doses; an every-12-hour regimen may be used in some patients. Because of the risk of proarrhythmic effects, indications are limited to treatment of documented life-threatening arrhythmias. Moricizine will compete with other agents as first-line therapy for life-threatening arrhythmias.
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PMID:Moricizine: a new class I antiarrhythmic. 227 51

A phase II trial of intermittent high-dose recombinant interleukin-2 (rIL-2) was initiated to evaluate the response rate, remission duration, and toxic effects in patients with measurable metastatic renal cell carcinoma. The rIL-2 was administered as a bolus intravenous infusion at a dose level of 10.0 x 10(6) U/m2 three times weekly, preceded by indomethacin (50 mg orally). Dose reductions of rIL-2 for hypotension and other grade 3 or 4 toxic effects were permitted. Forty-four patients were entered and 41 were eligible. Previous treatment included nephrectomy (23 patients), radiation therapy (seven), and hormone therapy (three). Most toxic effects observed were moderate and included nausea, vomiting, anorexia (85%); hypotension (85%); fever, chills (78%); central nervous system changes (24%); myelosuppression (27%); and creatinine elevation (15%). Four instances of grade 4 toxicity were observed and included nausea, vomiting with dehydration; hypotension; and myocardial infarction. Thirty patients (73%) required dose adjustments because of toxicity. Five responses (12%) were seen, which included one complete and four partial. Sites of response included lung, liver, and soft tissue; the duration of response ranged from 2 to 20+ months. These results demonstrate that this schedule of rIL-2 can be administered in an outpatient setting, and can produce tumor regression in patients with metastatic renal cell carcinoma, including durable complete responses.
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PMID:Phase II trial of high-dose intermittent interleukin-2 in metastatic renal cell carcinoma: a Southwest Oncology Group study. 229 24

We report a case of nearly fatal cardiovascular collapse attributable to an idiopathic anaphylactic reaction in a 76-year-old man. The event began with gastrointestinal symptoms of abdominal cramps, diarrhea, nausea, and vomiting as manifestations of IA. The patient subsequently progressed to develop urticaria, flushing, cardiovascular symptoms of chest pain, hypotension, and eventually cardiovascular collapse and myocardial infarction over a five-hour interval. This case emphasizes that the potential for life-threatening cardiovascular events from IA exists in patients without previously defined cardiac risk factors.
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PMID:Nearly fatal idiopathic anaphylactic reaction resulting in cardiovascular collapse and myocardial infarction. 237 90

The basic proteinase inhibitor from bovine organs, aprotinin, was first identified in 1930 and its effect on enzyme and other biological systems has since been extensively studied. Aprotinin can only be administered intravenously and has a half-life of about 2 hours. Its administration at the start of cardiopulmonary bypass surgery appears to reduce blood loss and to protect against global myocardial ischaemia. Similarly, a smaller infarct size seems to result from early administration of aprotinin within the first hour after myocardial infarction, though further studies are needed to confirm this effect. A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used. Aprotinin is also effective as adjuvant treatment in traumatic haemorrhagic shock. The recommended loading dose is 15,000 to 20,000 KIU/kg bodyweight administered as a short intravenous infusion, followed by 50,000 KIU/hour by continuous infusion. Side effects of aprotinin are very rare. Epsilon-Aminocaproic acid (EACA), p-aminomethylbenzoic acid (PAMBA) and tranexamic acid are synthetic antifibrinolytic amino acids. Saturation of the lysine binding sites of plasminogen with these inhibitors displaces plasminogen from the fibrin surface. On a molar basis tranexamic acid is at least 7 times more potent that epsilon-aminocaproic acid and twice as potent as p-aminomethylbenzoic acid. All 3 compounds are readily absorbed from the gastrointestinal tract and excreted in active form in the urine. The plasma half-life of tranexamic acid is about 80 minutes. The main indications for tranexamic acid are the prevention of excessive bleeding after tonsillectomy, prostatic surgery, and cervical conisation, and primary and IUD-induced menorrhagia. It is possible that gastric and intestinal bleeding can also be reduced as well as recurrent epistaxis. Tranexamic acid could also be useful after ocular trauma. The value of fibrinolysis inhibitors in the prevention of bleeding after tooth extraction in patients with haemophilia is well documented, as is the treatment of hereditary angioneurotic oedema. The usual dose of tranexamic acid is 0.5 to 1g (10 to 15 mg/kg bodyweight) given intravenously 2 to 3 times daily, or 1 to 1.5 g orally 3 to 4 times daily. This dose needs to be reduced in patients with renal insufficiency. The main side effects of tranexamic acid are nausea or diarrhoea.
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PMID:Clinical application of inhibitors of fibrinolysis. 258 Jun 84

A phase I study of mitoxantrone given as a continuous infusion for 21 days using a venous access port and a portable pump was performed. The first dose step was 0.3 mg/m2/d for 21 days. Courses were repeated every 6 weeks. Dose increment per step was 0.1 mg/m2/d in the first three dose steps and 0.2 mg/m2/d in the latter dose steps. Twenty-five patients entered the study and received a total of 50 courses, with a median of two courses (range, one to five). Up to 0.5 mg/m2/d, no toxicity (according to the World Health Organization [WHO] criteria) occurred. At 0.7 mg/m2/d, one patient experienced grade 2 leukocytopenia and at the 0.9 mg/m2/d dose step, one patient experienced grade 2 leukocytopenia, grade 1 thrombocytopenia, and grade 1 hair loss. At 1.1 mg/m2/d, two of six patients had grade 3 leukocytopenia, and in one patient treatment was discontinued after two days because of myocardial infarction. In both patients receiving 1.3 mg/m2/d, treatment was discontinued after 2 weeks because of grade 3 leukocytopenia. Three patients at the 1.1 mg/m2/d, dose step and two patients at the 1.3 mg/m2/d dose step experienced some nausea in the last week of the infusion period. One patient developed subclavian vein thrombosis. No infectious complications occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Plasma steady-state was reached after 35 hours. During steady-state there was a linear relationship between the mitoxantrone dose administered and the level of mitoxantrone in plasma (r = .93, P less than .005). The mitoxantrone level in leukocytes increased significantly during the infusion period at the 0.9 mg/m2, the 1.1 mg/m2, and the 1.3 mg/m2 dose steps. The area under the curve (AUC) in leukocytes was higher with continuous infusion of 1.1 mg/m2/d for 21 days compared with bolus injection of 12 mg/m2. Mitoxantrone could be detected in plasma for at least five days after the end of the 21-day infusion period and in leukocytes for at least 14 days. Continuous infusion mitoxantrone may increase intracellular drug uptake as expressed by intracellular AUC. We recommend a dose of 1.1 mg/m2/d for 3 weeks for evaluation of antitumor efficacy in phase II studies.
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PMID:A phase I pharmacokinetic study of 21-day continuous infusion mitoxantrone. 271 7


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