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 role of prostaglandin E1 (PgE1) and prostacyclin in enhancing the ischemic tolerance of single-lung grafts was investigated. Fifteen donor dogs underwent pulmonary artery flushing with 60 mL/kg of 4 degrees C modified Euro-Collins solution; 5 dogs each received a 15-minute infusion of PgE1, prostacyclin, or saline solution before flushing. After 12 hours of storage at 4 degrees C, left lung transplantation was performed in 15 recipient dogs. Measurements were performed after 10 minutes of right pulmonary artery snaring before transplantation, after transplantation, and after 2, 4, and 6 hours of reperfusion. At 6 hours, the oxygen tensions (on 100% O2) were 478 +/- 64, 296 +/- 75, 79 +/- 12, and 71 +/- 23 mm Hg in control (nontransplanted), prostacyclin-, PgE1-, and saline-treated dogs, respectively (p less than 0.05, prostacyclin or control versus saline and PgE1 dogs). Mean pulmonary artery pressures increased within each group during reperfusion, but were not significantly different among groups. Similarly, peak inspiratory pressures and wet weight to dry weight ratios were not significantly different among groups after 6 hours of reperfusion. We conclude that donor pretreatment with prostacyclin is associated with superior oxygen transfer in canine lung allografts after 12 hours of cold storage, transplantation, and 6 hours of reperfusion. In this model, donor pretreatment with PgE1 conferred no benefit to prolonged lung allograft preservation.
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PMID:Prolonged preservation of canine lung allografts: the role of prostaglandins. 202 3

Platelet activating factor (PAF, 1-alkyl-2(R)-acetyl-glycero-3- phosphorylcholine) is a phospholipid that is released by a variety of cells. The similarity between the pathophysiological effects of PAF and posttransplant pulmonary dysfunction led to an evaluation of a PAF antagonist as an adjunct to lung preservation. The ginkgolide B, BN 52021, was selected as the PAF antagonist to be studied because of the large data base available on this compound. BN 52021 was given to the donor and recipient (10 mg/kg i.v.) prior to harvest and transplantation and was included in 1 L of preservation solution (10 mg/kg) used for flushing the pulmonary artery and for storage. Left single-lung transplantation was performed following a 22-hr preservation period at 10 degrees C. Arterial oxygen tension (pO2), pulmonary vascular resistance (PVR), alveolar arterial oxygen difference (A-aDO2), and dynamic lung compliance (DLC) were recorded for 6 hours following ligation of the native pulmonary artery. At the end of 6 hr pO2 was 243.5 +/- 61.5 vs. 71.7 +/- 10.2 mmHg (P less than 0.02) for the controls. A-aDO2 was less in the BN 52021 groups: 431.8 +/- 58.3 vs. 606.0 +/- 9.8 mmHg in the control groups (P less than 0.001), and PVR was significantly less in the BN 52021 group: 346 +/- 70.8 vs. 663 +/- 64.3 dynes/sec/cm-5 (P less than 0.035). We conclude that PAF antagonists like BN 52021 may be useful adjuncts for lung preservation. The effects of BN 52021 are easily explained by PAF antagonist activity in ischemic and reperfusion-induced pulmonary dysfunction. However this study does not exclude that BN 52021 may have direct effects.
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PMID:Long-term lung preservation with the PAF antagonist BN 52021. 204 90

An in vivo canine model was used to assess the ability of an oxygen free radical scavenger to decrease reperfusion injury in lung transplantation. In 12 dogs, the left lungs were transplanted after they had been preserved for 24 hours at 4 degrees C after pulmonary artery flushing with modified Eurocollins solution. In 6 dogs, dimethylthiourea, a potent oxygen free radical scavenger, was added to the flush solution and was also given to the recipients just before reperfusion. In all animals, the contralateral pulmonary artery and bronchus were ligated and lung function was assessed for 12 hours or until death. Three dogs died prematurely in the control group, whereas only 1 dog died prematurely in the dimethylthiourea group. This resulted in a statistically significant difference in the average length of survival (p less than 0.05). Pulmonary artery and right atrial pressures were significantly lower in the dimethylthiourea group during the first 6 hours (p less than 0.05). Treatment with dimethylthiourea resulted in a significantly higher arterial oxygen tension at 4 hours, and intrapulmonary shunt tended to be lower. Thus, it would appear that dimethylthiourea has a protective effect on lungs preserved for 24 hours before transplantation in dogs.
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PMID:Oxygen free radical scavengers decrease reperfusion injury in lung transplantation. 211 77

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

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

Using newborn rat calvaria, we determined the effects of oxygen tension on bone cell metabolism in vitro. Halved calvaria were incubated in medium either in air or after flushing nitrogen or oxygen and studied for collagen synthesis, calcium uptake, and DNA content. The percentages of DNA content, radioactive proline count in mg of bone tissue, and radioactive proline count combined with counts of medium and bone tissue in the nitrogen-exposed group were less than those of their pair-matched controls. Percent calcium counts per DNA and calcium uptake per mg of tissue were greater in the nitrogen-exposed group than in the pair-matched controls. In contrast, no difference was found in any measurements in the oxygen-exposed group compared with controls. It is concluded that collagen synthesis, in contrast to proline uptake, is not affected by low oxygen, whereas calcium uptake is greatly enhanced. Furthermore, low oxygen tension exerts a greater effect on bone cell metabolism than does the hyperoxic condition.
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PMID:The effect of oxygen tension on collagen synthesis and calcium uptake in newborn rats' calvaria in vitro. 231 96

1. The present study was performed to examine and compare the effect of increasing doses of vasoactive intestinal polypeptide (VIP) on vaginal blood flow following vaginal subepithelial and intravenous injection in normal women. 2. Local vaginal blood flow was measured by a heated oxygen electrode. 3. Peripheral blood samples were collected throughout the experiments for VIP analysis by radioimmunoassay. 4. Both subepithelial and intravenous injections induced a significant and dose-dependent increase in vaginal blood flow (P less than 0.05), displaying the same efficacy, potency and sensitivity. 5. The vaginal flow values correlated with the corresponding plasma VIP concentrations after both routes of administration. 6. The systemic vascular side effects; that is, flushing, hypotension and tachycardia, were observed following both subepithelial and intravenous injection. 7. The findings indicate that the effect of VIP on vaginal blood flow irrespective of route of administration is part of a systemic vasodilatory effect rather than a local response.
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PMID:Vasoactive intestinal polypeptide and human vaginal blood flow: comparison between transvaginal and intravenous administration. 235 Sep 2

The physiologic effects of 12-hour lung preservation were assessed in six mongrel dogs studied for 20 hours after double-lung allograft implantation. Donor animals were pretreated with allopurinol (30 mg/kg) and methylprednisolone (500 mg) intravenously at anesthesia induction. Heart-lung blocks were harvested after cardioplegic arrest, and a simple pulmonary artery flush of 4 degrees C modified Collins' solution was administered at 15 ml/kg/min. The lungs were ventilated with 100% nitrogen during flushing and inflation. Recipient animals received an infusion of deferoxamine (20 mg/kg) during implantation and were pretreated with methylprednisolone (500 mg) intravenously. All six implantations were technically successful. Two animals died of cardiac standstill 12 and 24 hours postoperatively. Gas exchange deteriorated after implantation compared with donor levels but remained in a range compatible with survival, and at 20 hours arterial oxygen tension (FiO2 0.4) was 138 +/- 91 mm Hg. Similar changes were seen in alveolar-arterial oxygen gradients and arterial-alveolar oxygen tension fraction. Elimination of carbon dioxide was satisfactory. Pulmonary venous shunt fraction rose significantly at the end of the study. Hemodynamic changes consisted of a gradual increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated, with a gradual rise in airway resistance and a fall in compliance. The double-lung model allows detailed assessment of the early effects of preservation and may have certain advantages over heart-lung models of preservation. The preservation technique warrants further study.
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PMID:Acute physiologic changes after extended pulmonary preservation. 235 75

Pulmonary surfactant during lung transplantation was investigated in the control group of a canine single lung transplantation model by measuring dipalmitoyl-phosphatidylcholine, the main phosphocholine fraction of surfactant in bronchoalveolar lavage. In a second group of dogs, L-carnitine, an essential cofactor for transfer of long-chain fatty acids into the mitochondria, was applied. Organ function after pulmonary artery flushing with modified Euro-Collins solution and hypothermic storage for 4 hours was adequate in both groups, with significantly higher arterial oxygen pressure levels in the L-carnitine group after 12 (p less than 0.05) and 24 (p less than 0.025) hours, respectively. In the control group, a reduction of the dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholines was observed 4 and 12 hours after transplantation of the left lung (p less than 0.005 and p less than 0.01, respectively, both specified by Student's t test for dependent data, not significant by Bonferroni correction). In the simultaneously stored right lungs, a constant fall of the dipalmitoyl-phosphotidylcholine portion was demonstrated. In the L-carnitine group, significantly higher dipalmitoyl-phosphotidylcholine levels were observed in the transplanted left lungs after 4 hours (p less than 0.01) and in the continuously stored right lungs after 24 hours (p less than 0.005), when compared with the control group. These results suggest that dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholine decreases parallel to the extent of the ischemic damage. Furthermore, the application of L-carnitine improved pulmonary function after transplantation, possibly by reducing the impairing effect of ischemia on alveolar type II cell metabolism and thereby on pulmonary surfactant system.
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PMID:Pulmonary surfactant in bronchoalveolar lavage after canine lung transplantation: effect of L-carnitine application. 235 22

The contrast agent Iotrolan 300 has potential advantages for bronchography over previous agents in that it can be injected directly through the bronchoscope and it does not obscure bronchoscopic vision or interfere with further bronchoscopic procedures. It was used for selective bronchography in 20 patients with suspected bronchiectasis. Side effects and change in FEV1 and in arterial oxygen saturation were compared in these patients and in 14 patients undergoing bronchoscopy for suspected carcinoma. Thirteen of the 20 patients undergoing bronchography had side effects, mainly headache, nausea, and a feeling of heat or flushing. The fall in FEV1 at four hours (0.3 l) did not differ from the fall in the control group (0.1 l). The fall in arterial oxygen saturation (SaO2) during bronchography (9.4%) did not differ significantly from the fall during bronchoscopy in the control group (6.1%). Iotrolan gave good quality bronchograms, which in all cases provided a diagnosis. Iotrolan appears to be suitable for bronchography by fibreoptic bronchoscope and to be well tolerated.
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PMID:Suitability of and tolerance to Iotrolan 300 in bronchography via the fibreoptic bronchoscope. 240 28


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