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)

The skin response in guinea pigs at various times after immunization with epididymal sperm in Freund's complete adjuvant is reported. Findings were correlated with the progression of the autoimmune orchitis. Also, possible skin reactivity to sperm extract at 8 months after bilateral vasectomies in which both ends of the vasa had been ligated was investigated. The histological changes in the testes at 5 months postvasectomy were studied. Epididymal sperm was obtained by flushing out the vas and epididymis of mature guinea pigs. The dried epididymal sperm was used for immunization, dissolved or suspended in PBS. For skin testing, a heat-treated extract of the sperm (BES) was used. The methods of preparing reagents is described. The skin reactions to BES and to a purified protein derivative (PPD) in females were similar to those of any standard protein antigen. In males, this reaction resembled that in females at 1 week after immunization but later was different. Induration and erythema were greater in females (p less than .001) from 2 weeks on. The response of males to PPD was less than in females at 1 week but at 2 weeks was the same. Males immunized with purified ovalbumin responded to PPD similarly to females. After 8 months, following vasectomy, the response to BES at 24 hours was similar to that of controls. Testes weighed at 1 week after immunization were increased, possibly due to edema, but after the 3rd week weight was decreased. Histology of the testes after immunization showed cellular infiltration after 2 weeks and disappearance of spermatogenic elements from the seminiferous tubules. Evidence of delayed hypersensitivity to sperm was not shown.
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PMID:Comparison of allergic aspermatogenesis with that induced by vasectomy. I. In vivo studies in the guinea-pig. 94 75

Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum cholesterol levels induces intense flushing in humans. We have recently shown that the vasodilation following ingestion of niacin is due to the release of prostaglandin (PG) D2. However, the site from which PGD2 is released is not known. It has previously been shown that topical application of methylnicotinate causes local cutaneous erythema. Thus, we investigated whether topical methylnicotinate causes a release of PGD2 locally from skin and the possibility that skin may be a major contributor to the release of PGD2 when niacin is administered by mouth. Topical administration of methylnicotinate (10(-1) M) to the forearms of human volunteers resulted in 58- to 122-times increases in levels of PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. Increased levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating that the PGD2 was released from the site of methylnicotinate application. The release of PGD2 in response to topically applied methylnicotinate occurred in a dose-dependent manner over the concentration range of 10(-3) to 10(-1) M. The release of PGD2 was not accompanied by a release of histamine, suggesting that the release of PGD2 was not from the mast cell. Following oral ingestion of niacin, levels of PGD2 in superficial venous blood draining the skin were 14 to 1200 times higher than the level in arterial blood supplying the skin of the same arm. This finding indicates that the skin is a major site from which PGD2 is released following oral ingestion of niacin. These studies thus indicate that the cutaneous vasodilation that occurs following oral administration of niacin is primarily due to a release of PGD2 from a niacin responsive cell that resides in the skin.
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PMID:Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. 137 50

Twenty-five febrile patients with a history of intravenous drug use who were receiving either vancomycin (15 patients) or teicoplanin (10 patients) as part of a multicenter, double-blind, randomized, clinical efficacy trial were enrolled, upon receipt of their first dose of antibiotic, into a study to evaluate the effect of 1 g of vancomycin and high-dose teicoplanin (30 mg/kg of body weight) on histamine release and the occurrence of "red man syndrome" (RMS). In addition, 10 healthy volunteer subjects (HVS) were randomized to receive either 1 g of vancomycin intravenously or a saline infusion in a double-blind, crossover design study. Patients and HVS were observed for the presence of erythema, flushing, pruritus, and hypotension during and for up to 1 h postinfusion by a blinded investigator. Histamine concentrations in plasma were measured at baseline and during and after drug infusion. No significant differences were noted in baseline temperature between patients (vancomycin recipients, 102.3 degrees F [39.1 degrees C]; teicoplanin recipients, 102.4 degrees F [39.1 degrees C]) or incidence of bacteremia (7 of 15 vancomycin recipients; 5 of 10 teicoplanin recipients). There were no significant differences in peak vancomycin concentrations in the sera of patients (40.8 micrograms/ml) and HVS (49.9 micrograms/ml). There were no reactions consistent with RMS in any patient who received teicoplanin (0 of 10); there was a significant difference in the occurrence of RMS in patients in comparison with that in HVS (0 of 15 patients, 9 of 10 HVS; P less than 0.001) who received vancomycin. The predominant reaction was erythema and pruritus. Histamine concentrations in plasma and the area under the histamine plasma concentration-time curve were highly variable within groups and were not statistically different between patients and HVS. The incidence of RMS secondary to vancomycin or teicoplanin in our patient population appears to be low and consistent with clinical observations. Similar to previous investigations, RMS secondary to vancomycin in HVS was high (90%). However, we found no relationship between the histamine concentration in plasma or the area under the plasma histamine concentration-time curve and the severity of RMS in HVS. The reason for the discrepancy of RMS in patients versus that in HVS in unknown, but it may be related to a blunted effect of glycopeptides to produce the reaction in the presence of infection or it may be specific to our patient population.
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PMID:Absence of "red man syndrome" in patients being treated with vancomycin or high-dose teicoplanin. 138 23

The effects of lung traction on arterial blood pressure and plasma prostacyclin concentrations were studied in five patients undergoing partial pneumonectomy or lobectomy. After manual traction of a lung segment, mean arterial blood pressure decreased from 77 +/- 5 mm Hg (mean +/- SEM, before lung traction) to 59 +/- 5 mm Hg. The concentrations of 6-keto prostaglandin F1 alpha (a stable breakdown product of prostacyclin) increased significantly from 46 +/- 6 pg/mL (mean +/- SEM, before thoracotomy) to 593 +/- 91 pg/mL. Four of five patients showed facial flushing and palmar erythema. Arterial blood pressure returned to pretraction value, and both the facial flushing and palmar erythema disappeared within 30 min after lung traction. These results suggest that traction of the lung stimulates release and/or production of prostacyclin, which results in facial flushing, palmar erythema, and decrease in arterial blood pressure.
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PMID:Lung traction causes an increase in plasma prostacyclin concentration and decrease in mean arterial blood pressure. 141 33

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

Leukopenia or pancytopenia as a result of bone marrow dysfunction are manifestations of various diseases or complications of therapeutic regimens. The spectrum of diseases associated with leukopenia is wide and includes congenital as well as acquired neutropenias secondary to conditions such as myelodysplastic syndromes, AIDS, malignant tumors with or without chemotherapy-enhanced neutropenia, bone marrow transplantation or therapeutic or accidental radiation. The morbidity and mortality of infectious diseases is greatly enhanced during neutropenic phases. Over the last few years attempts have been made to shorten the duration and lessen the severity of neutropenia in patients with the above conditions by administration of Granulocyte Macrophage Colony Stimulating Factor (G-CSF). Both cytokines were successfully tested in phase I and II trials. Treatment with GM-CSF or G-CSF results in a dose-dependent increase of the neutrophil count. GM-CSF also increases the number of eosinophils and monocytes in peripheral blood. The effect of both cytokines on the neutrophil count is transient as long as the underlying disease persists. This prompted the institution of maintenance therapy, which has been successfully used with either cytokine. Long-term treatment is usually well tolerated and results in a reduction in the frequency of infections as well as in the duration of antibiotic treatments. Side effects of GM-CSF or G-CSF are usually mild and include fever, myalgia, bone pain, and erythema. A number of patients developed dyspnea, hypotension, sweating, flushing and erythema after the first dose of GM-CSF in each treatment cycle. This first-dose reaction occurs more frequently after intravenous than reactions were reported with G-CSF. Some patients with myelodysplastic syndrome progressed to acute myeloic leukemia during or after treatment with GM-CSF or G-CSF. Most of these patients presented with an increased fraction of blasts in the bone marrow, which preceded the treatment with the colony stimulating factors. Since GM-CSF and possibly G-CSF may increase the risk of developing acute leukemia in patients with myelodysplastic syndrome, it appears prudent to limit the use of these cytokines in patients with this disease. The subcutaneous route of administration appears to be preferable to intravenous administration, since the incidence and severity of side effects are reduced. While many questions concerning dosage, long-term therapy and combination therapy still remain unanswered, the information presented in this review concerning the clinical use of these cytokines warrants an optimistic outlook.
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PMID:[GM-CSF and G-CSF: cytokines in clinical application]. 170 94

After Phase I studies of benzisoquinolinedione (amonafide) in solid tumors identified myelosuppression as the dose-limiting toxicity, we conducted a Phase I study in patients with relapsed or refractory acute leukemia to define the optimal dose. Amonafide was given i.v. over 2-4 h daily for 5 days. The starting dose was 600 mg/m2/day with subsequent escalation to 750, 900, 1100, 1400, and 1800 mg/m2/day. Thirty-eight courses were administered to 24 patients, of whom 12 participated in concomitant pharmacological studies. Nausea and vomiting, transient orange discoloration of the skin, and tinnitus occurred at all dose levels. The latter symptom, along with lightheadedness and flushing, was related to infusion duration; this was increased to 4 h with doses greater than or equal to 900 mg/m2. The dose-limiting toxicities were mucositis and painful skin erythema which occurred in all 4 patients treated with 1800 mg/m2. No remissions occurred. Clearing of peripheral blood blasts occurred in 67% of patients treated with 1100 mg/m2 and in all patients treated with greater than or equal to 1100 mg/m2/day. A decrease in marrow leukemic infiltrate (% blasts x % cellularity) to less than 10% occurred in 15 and 50% of patients treated at these levels, respectively. There were 10 deaths (42%), which were unrelated to dosage. The harmonic mean terminal plasma half-life was 4.6 h (range, 2.5-35.5 h). Three patients had long drug half-lives of 9.7, 16.4, and 35.5 h and each had initial bilirubin levels greater than 1.0 mg/dl. The average urinary excretion of amonafide over 5 days was 3.5% of the total dose. This establishes 1100-1400 mg/m2/day for 5 days as the maximally tolerated dose of amonafide for studies in acute leukemia.
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PMID:Phase I clinical investigation of benzisoquinolinedione (amonafide) in adults with refractory or relapsed acute leukemia. 198 34

The main objective of this study was to evaluate the safety and efficacy of a perfluorochemical emulsion, Fluosol, with short-term high inspired oxygen tension as an adjuvant to radiation therapy in the treatment of high-grade tumors of the brain. Radiation was delivered to the whole brain at 1.8 Gy per daily treatment for 5 weeks to a total dose of 45 Gy. The radiation portals were then reduced in size to encompass the known volume of tumor, as determined by the presurgical contrast-enhancing ring on computed tomography (CT), plus a 3-cm margin. An additional 10 treatments of 2 Gy each were given to the smaller volume, to bring the total tumor dose to 65 Gy in 7 weeks. This report describes the experience of the first 18 patients treated at the University of Kansas Medical Center on this study, whose median follow-up time from the date of surgery is 77 weeks (62-115 w). Immediately following Fluosol administration on a Monday, patients breathed 100% oxygen for at least 45 minutes prior to and throughout their radiation treatment. On each subsequent day of the weeks in which they received Fluosol, patients breathed 100% oxygen. Hematology and blood chemistries were also drawn prior to Fluosol treatment each Friday during treatment and at the 2-week, 3-month, and 6-month follow-up visits. The median age of the patients was 45 years (16-72); 13 patients were male and 15 carried the diagnosis of glioblastoma multiforme (3 had anaplastic astrocytoma). Two thirds of the patients had an initial allergic reaction to the Fluosol consisting of back pain, shortness of breath, and flushing, but all responded to 50-100 mg of Benadryl. During radiation therapy, all patients developed scalp erythema and complete alopecia by the end of 3 weeks, but no patient required a treatment rest. The serum levels of SGOT, SGPT, and alkaline phosphatase were examined before and throughout the Fluosol treatment and, by week 5, 11/18 of the patients had increased values of all three enzymes above the upper range of normal. These increases persisted through the end of treatment, but most values returned to essentially normal by the 3-month follow-up visit. We conclude that Fluosol, given in the manner described above, appears to be associated with minimal significant side effects and no changes could be detected in the white matter of any of the patients at the time of their magnetic resonance imaging study at 6 months follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A phase I/II study of the use of Fluosol as an adjuvant to radiation therapy in the treatment of primary high-grade brain tumors. 216 56

1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects.
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PMID:Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension. 218 68

1. In a double-blind, randomised, parallel group study, 128 patients with sitting diastolic blood pressure between 95 and 125 mm Hg (Phase V) after 2-4 weeks run-in on placebo, received enalapril 10-40 mg once daily (65 patients) or nifedipine retard 10-40 mg twice daily (63 patients), utilising a double dummy technique. Dual target blood pressures were less than 150 mm Hg systolic and less than 90 mm Hg sitting diastolic. Inadequate responders had hydrochlorothiazide 12.5-50 mg once daily added. 2. The 3 h post-dose sitting blood pressures were lowered by 18/14 mm Hg (enalapril) and 20/14 mm Hg (nifedipine), but nifedipine gave greater standing reductions (16/13 mm Hg enalapril, 22/17 mm Hg nifedipine). The dual target blood pressures were achieved by 45% of those taking enalapril monotherapy and 43% of those taking nifedipine monotherapy. At the end of the hydrochlorothiazide phase the dual target pressures were achieved by 63% of the enalapril group and 56% of the nifedipine group. 3. Overall, 17 patients reported adverse events during the placebo run-in. During the active treatment-periods, 42 patients in the enalapril group experienced adverse events, as did 49 of those on nifedipine. Orthostatic effects were confined to those taking enalapril, whereas flushing/erythema, oedema and palpitations were more common in the nifedipine group. 4. Five patients in the enalapril and 14 in the nifedipine groups were withdrawn because of adverse events. One of those withdrawn on enalapril had angioneurotic oedema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enalapril and nifedipine in the treatment of mild to moderate essential hypertension: a 6 month comparison. 220 83


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