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)

This study examines the efficacy and side effects of 15-methyl-prostaglandins F2alpha (PGF2a) free acid administered intramuscularly for midtrimester abortion. 50 healthy women aged 14 to 37 years and between 12 to 18 weeks gestation were randomly selected from the abortion clinic at the Los Angeles County/USC Medical Center, Women's Hospital to participate in the study. The prostaglandin preparation was supplied in ampules containing 1.1 mg. in 2.2 ml. of aqueous solution. The injection was given every 2 hours until the fetus was expelled or for a maximum of 12 injections. Vital signs of the patients were closely monitored. 46% (23) of the subjects aborted within 12 hours and 90% within 27 hours. Mean injection-abortion time was 13.5 hours (range, 5 3/4 to 27 hours). The effectiveness and rapidity of abortion was related with gestational age: the lower the gestational age, the shorter the abortion time. Women with more than 17 weeks gestation had a higher failure rate. Mean number of injections was 7.5. 5 patients failed to abort with prostaglandin alone, all of them primigravidas and weighing in excess of 150 lbs; supplemental therapy was provided. Side effects and complications associated with 15-methyl-PGF2a included: emesis (66%); diarrhea (76%); flushing (12%); chills (4%); fever of 100 degrees Fahrenheit (12%); pain requiring medication (16%); and blood loss (6%). The success of this method appears to be related to dosage; parity; gestational age; weight of patient; and frequency of administration. Although there were side effects, these were outweighed by rapid abortion time, mild contractions, and ease of administration. Asthma is the only medical contraindication to prostaglandin therapy.
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PMID:Midtrimester abortion with intramuscular injection of 15-methyl-prostaglandin F2alpha. 113 40

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

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

Seventeen patients with malignant carcinoid tumour, ten of whom had the malignant carcinoid syndrome, were treated with recombinant alpha-2b interferon by subcutaneous injection (3 MU per dose) three times per week for a median of 12 weeks (range 4-48). No objective tumour responses were observed; however, there was a greater than 50% reduction in 24-hour urinary 5-hydroxyindolacetic acid (5-HIAA) excretion in four of ten patients (40%) with elevated pretreatment levels. Five of ten patients (50%) with flushing, five of seven patients (71%) with diarrhoea and both patients with wheezing experienced relief of symptoms. Three of four patients (75%) with weight loss as their only problem experienced weight gain. Responses occurred within the first eight weeks of treatment, but were generally of short duration. Toxicity occurred in all patients, and consisted mainly of fever, chills, anorexia, fatigue and weight loss. Four patients ceased therapy due to toxic reactions. Although interferon has activity against carcinoid tumours, its benefits are short-lived and toxicity limits its use with increasing dose. Patients with carcinoid syndrome appear to achieve the best therapeutic response, and it is likely that low doses (9-20 million IU weekly) are as effective as higher doses (36-72 million IU weekly).
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PMID:Recombinant alpha-2b interferon in patients with malignant carcinoid tumour. 172 59

Fluosol, a perfluorcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, Fluosol has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non small cell carcinoma of the luing. Fifty patients were enrolled in the study which was closed for accrual in November 1987. Five patients were withdrawn prior to the institution of radiation: one patient diagnosed with bone metastasis and four patients withdrawn due to mild to moderate reactions to Fluosol. Of the 49 patients administered Fluosol, 34 mild to moderate adverse reactions were noted in 22 patients to either the test dose/infusion (16 reactions including withdrawn patients) or post infusion (18). Flushing, dyspnea and hypertension (test dose/infusion) and chills and/or fever (postinfusion) were the typical symptoms. Transient elevation of blood chemistries (SGOT, SGPT, alkaline phosphatase, BUN) were noted in some patients. Six patients had transient depression of WBC counts (toxicity scores of 1 or 2) and two patients had transient depression of platelets (toxicity score of 1). None of these altered treatment. Forty-five patients received Fluosol of which 34 completed the planned therapy. Six patients were diangosed with metastatic disease during therapy and three patients died of their disease during treatment. One patient was withdrawn due to ineligibility and one patient withdrawn due to moderate reactions to Fluosol during the 3rd and 4th infusions. The total dose of Fluosol was escalated from 42 mL/Kg to 49 mL/Kg in 5, 6, or 7 weekly infusions. Patients breathed 100% oxygen for a minimum of one-half hr prior to and during radiation treatment. Radiation therapy was administered at a daily fraction of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy. Seventeen of 34 patients (50%) achieved a complete response to treatment and 11 patients (32%) had a partial response. Thirteen patients remain alive (range of 12 to 20 months) including 10 of 17 complete responders, 2 of 11 partial responders, and 1 treated with chemotherapy postradiation. The median absolute survival time of the patients completing therapy was 15.5 months and the 12 and 18 month absolute survival rates were 81% and 74%, respectively. The 45 patients starting protocol therapy had a median absolute survival of 9.2 months with a 12-month and 18-month survival of 45% and 35%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fluosol and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: results of a phase I/II study. 216 21

Low-density lipoprotein apheresis (LDL-apheresis) is an extracorporeal procedure that preferentially removes LDL cholesterol from the blood. One of the primary techniques for performing this procedure uses immunoadsorption columns containing monospecific polyclonal sheep antibodies to human LDL covalently coupled to a gel filtration medium. LDL-apheresis has generally been well-tolerated, with chills, fever, or flushing occurring rarely. The possibility of an immune reaction was investigated as a basis for these reactions observed in 12 of the 1312 procedures performed. Antibodies to sheep IgG developed in 12 of the 15 patients treated with LDL-apheresis as a result of the shedding of small quantities of the sheep immunoglobulin from the columns. A column acid-washing procedure minimized the quantity of shed antibody but did not prevent immunization of the patient. The clinical reactions were probably unrelated to shedding and immunization, as the reactions occurred even in patients who were not immunized to the sheep IgG. Immunization to ethylene oxide was not the cause, as determined by a radioallergosorbent test. The reactions were more likely related to the activation of complement, as indicated by the generation of C3a des Arg by the columns and an increase in C3a des Arg levels systemically.
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PMID:Humoral immune response following extracorporeal immunoadsorption therapy of patients with hypercholesterolemia. 219 Mar 66

Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.
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PMID:Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon. 273 23

Didemnin B (NSC-325319), a cyclic depsipeptide isolated from a marine tunicate, has been evaluated in a Phase I trial. The drug was administered in a single intravenous infusion in 150 cm3 of normal saline every 30 min given every 28 days. Forty-three patients received 80 courses of the drug at doses ranging from 0.14 to 4.51 mg/m2. The dose-limiting toxicity was nausea and vomiting which began during or shortly after the infusion and was of variable duration. This toxicity was somewhat ameliorated by pretreatment with an aggressive antiemetic regimen. Mild hepatic toxicity also occurred with mild elevations of transaminases and bilirubin. One patient experienced an allergic reaction during his second infusion, characterized by chills, diaphoresis, flushing and hypotension. No objective anti-tumor response was seen during this trial. The recommended dose for Phase II studies on a single-dose schedule is 2.67 mg/m2 without prophylactic antiemetics and 3.47 mg/m2 if an antiemetic regimen is used. Preliminary pharmacokinetics suggest that didemnin B is sequestered or rapidly converted to a metabolite not identified by the antibody used in the radioimmunoassay. Further evaluation will be performed during Phase II studies.
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PMID:Phase I clinical and pharmacokinetic investigation of didemnin B, a cyclic depsipeptide. 320 14

33 patients with advanced malignant melanoma were studied after intravenous administration of 131I-labeled Fab fragments specific for p97, an oncofetal glycoprotein of human melanoma. In all, 47 gamma camera imaging studies were performed for the purpose of localization of metastatic deposits. In addition to tumor, 131I-Fab uptake was also seen in liver and kidney. 20 of these studies included simultaneous administration of both an 131I-labeled Fab specific for p97, and an 125I-labeled Fab not specific for p97. Blood clearance of p97-specific Fab was significantly more rapid than for nonspecific Fab. Eight of these patients had biopsies of subcutaneous nodules at 48 and 72 h postinjection in order to assess whether localization of radioactivity was antigen specific. Antigen-specific localization was observed with average ratios of specific/nonspecific uptake of 3.7 (48 h) and 3.4 (72 h); uptake was strongly correlated with tumor p97 concentration (r = 0.81, P less than 0.01). Also, imaging studies of the bio-distribution of 131I-labeled anti-p97 Fab in patients selected for high p97 tumor concentration showed avid tumor uptake and more prolonged retention of labeled Fab in tumor than in normal tissues. Based on these studies, we estimated that total 131I doses of 500 mCi could be safely given to patients before dose-limiting toxicity would be observed. Accordingly, in seven selected patients, phase I radiotherapeutic trials were begun. For improved radiation safety, we developed automated methods to label Fab fragments with up to 200 mCi of 131I. So far, a total of 12 individual therapeutic doses, ranging from 34 to 197 mCi of 131I-labeled to 5 to 10 mg of Fab, have been administered with excellent tumor localization and without major target organ toxicity. Cumulative doses ranged from 132 to 529 mCi 131I. Side effects attributable to the radiation were mild, with a transient drop slightly greater than 50% in platelet and absolute neutrophil counts being observed in the two patients who received cumulative doses greater than 500 mCi. In the combined series of 47 diagnostic and 12 therapeutic studies, four acute reactions were observed: one episode each of transient chills and fever; flushing and hypotension; and two skin rashes. All of these reactions responded promptly to symptomatic therapy. After multiple administrations of 131I-(anti-p97) Fab (IgG1), isotype-specific immunity was observed in three patients. In two of these patients it was possible to successfully reinfuse after immunity had developed with 131I-(anti-p97) Fab of a different isotype (IgG2a). Dosimetry estimates were performed based on the biodistribution of (131)I-Fab in these patients,and for every 100 mCi of (131)I-Fab given, tumor receives 1,040 rads; liver. 325 rads; and bone marrow, 30 rads. Marrow would be expected to be the critical organ, if doses >500 mCi (131)I-Fab are given. These studies demonstrated that, with proper precautions, large doses (of an (131)I-labeled murine Fab fragments immunologically specific for a human melanoma-associated antigen) could be safely given to humans by using repetitive intravenous injections.
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PMID:Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy. 619 80

The infusion of high-dose (275 mg/kg body weight) immune globulin intravenous (IGIV) after 466 plasma exchanges in 64 patients with autoimmune disease was studied. Side effects occurred during 15% of IGIV infusions. For the most part they were transient and mild, and could be controlled by slowing the infusion rate. Two percent of infusions had to be terminated because of more persistent or severe side effects. Chills were the most common side effect, followed by nausea, flushing, anxiety, and nausea. Serum IgG levels were immediately restored into the normal range by IGIV infusions, and they were much more effective in restoring IgG levels after plasma exchange than intramuscular injection of 9.9 g of immune serum globulin (ISG). Up to 15 weekly high-dose IGIV infusions were well tolerated without unusual side effects. These patients did not have any major bacterial infections, but were not protected from developing Herpes zoster at the dosages used. In patients with myasthenia gravis, a short term impact of a single IGIV infusion on titers of antibody to acetylcholine receptor could not be demonstrated. This study showed IGIV to be a safe and effective preparation for the replacement of normal IgG removed during plasma exchange.
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PMID:Immune globulin intravenous replacement after plasma exchange. 668 80


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