Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-2 is a glycoprotein physiologically produced by human lymphocytes which is capable of mediating some still unknown immunologic reactions. In vitro, interleukin-2 was seen to induce a lytic reaction against tumor cells through the activation of a cytolytic system of natural killer cells. If administered to man in heavy doses, it causes a clinical response in the treatment of metastases from melanoma and renal cell carcinoma in 20-40% of cases. However, the clinical use of the drug, in therapeutic doses, is prevented by the occurrence of several side-effects, the major one being increased permeability of alveolar vessels with capillary leak and interstitial pulmonary edema (Vascular Leak Syndrome in the English literature). Thus, this work was aimed at evaluating chest radiographs during interleukin-2 treatment to detect, in the pulmonary district, the early stages of the vascular leak syndrome--i.e., pulmonary edema, pleural and pericardial effusions. Forty-three patients had been treated for metastases from renal cell carcinoma and melanoma November 1989 through September 1991: standard chest radiographs demonstrated 26 cases (60%) of pulmonary edema, 14 cases (32%) of bilateral pleural effusions and 12 cases (27%) of pericardial effusions. Daily chest films of the patients undergoing interleukin-2 therapy allowed the early stage of the vascular leak syndrome to be depicted, thus enabling the physician to use the highest tolerated doses and eventually to stop infusion before marked respiratory distress develops.
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PMID:[Radiologic characteristics of the thorax during therapy with interleukin-2]. 145 17

A new approach to cancer treatment has been developed based on the adoptive transfer of activated lymphocytes into cancer patients. Lymphocytes harvested from patients by leukapheresis are converted into lymphokine-activated killer (LAK) cells by incubation with recombinant interleukin-2 (rIL-2). These LAK cells are then infused back into the patients in combination with intravenous IL-2. Among 25 patients treated with this form of adoptive immunotherapy there were 11 patients with measurable tumor reductions, including 1 complete responder. The majority of responses occurred in patients with metastatic renal cell carcinoma, melanoma and colorectal carcinoma. The toxicities of IL-2, including fluid retention and pulmonary edema, limit therapy, and laboratory investigation is now aimed toward understanding the mechanism of IL-2 toxicity. The use of LAK cells and IL-2 in cancer therapy is still in a developmental stage and needs to be refined before its role can be definitely established.
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PMID:Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2. 312 51

Interleukin 2 (IL-2) exhibits anti-tumour activity. High-dose IL-2 regimens are limited by side-effects such as pulmonary oedema and a systemic vascular leak. The mechanisms by which IL-2 mediates transvascular fluid and protein losses in humans are largely unknown. We have, therefore, measured the transcapillary escape rate (TER) of albumin as a reflection of the vascular permeability by injecting [125I]albumin (5 microCi i.v.). In ten melanoma patients pretreated with interferon alpha (IFN-alpha) TER of albumin was measured before and after IL-2 injections (1.5 x 10(6) Cetus-U. s.c. daily for 4 days). The TER of albumin increased from 9.4 +/- 2.7% h-1 before to 14.9 +/- 3.3% h-1 (P < 0.001) after IL-2 injections and the absolute outflux of albumin (Jalb) from 159 +/- 28 mg kg-1 h-1 to 261 +/- 44 mg kg-1 h-1 (P < 0.001), whereas the intravascular albumin pool remained stable (136 +/- 19 g vs 136 +/- 18 g). IL-2 and IL-6 were not detectable in the plasma prior to IL-2 injections and increased to 549 +/- 315 U ml-1 (P < 0.001) and 7 +/- 6 pg ml-1 (P < 0.01), respectively, after IL-2 administration. In conclusion, IL-2 increases the vascular permeability in humans, without affecting the intravascular albumin pool. This suggests that mechanisms such as the lymphatic return can compensate for the severe transendothelial fluid/albumin losses.
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PMID:Interleukin 2-induced increase of vascular permeability without decrease of the intravascular albumin pool. 781 54

The aim of this study was to evaluate the systemic and haemodynamic postoperative effects of ILP with medium-low dose of TNF alpha in patients diagnosed with primary or recurrent limb melanoma or sarcoma, and to compare the resulting toxicity with Systemic Inflammatory Response Syndrome (SIRS). A prospective study on 17 consecutive patients with primary or recurrent limb tumor (melanoma or sarcoma) subjected to ILP with escalating doses of TNF alpha (0.5-2.0mg) was carried out. Seventeen patients with primary or recurrent limb melanoma or sarcoma were subjected to ILP with escalating doses of TNF alpha. ILP was carried out with the standard techniques, blood being warmed at 42 degrees C for an hour. Serial serum TNF alpha determinations were performed before, during and after limb perfusion in nine patients. Systemic and pulmonary haemodynamics, by a radial and pulmonary artery catheter inserted before the induction of anesthesia, were monitored at 5 different times: before the induction of anesthesia (T0), and 6, 12, 24 and 48 hours after treatment (T1-4). Complete isolation of the limb was not always achieved, therefore leakage of TNF alpha occurred frequently during the perfusion in all patients with maximum systemic TNF alpha concentrations ranging from 431 to 111000 pg/ml. After perfusion only two patients showed detectable TNF alpha levels in peripheral blood which returned to baseline values within nine hours. These two patients had serious systemic toxicity: shock and respiratory failure secondary to pulmonary edema. Acute pulmonary edema was also observed in another patient. All three cases required supportive therapy provided by means of mechanical ventilation. In the remaining 14 patients a sepsis-like syndrome was observed. The most significant haemodynamic changes were due to the CO, which rose by 35%, and the SVR, which remained consistently low throughout. A reduction in Hb was observed in all patients (with an average decrease of 4 g/dl), while DO2 and VO2 levels rose, though not to statistically significant levels. Hypoxia occurred in all 14 patients. In three of the remaining 14 cases bilateral pulmonary leaks were noted, however the use of mechanical ventilation was not required. No perioperative death occurred and the aforementioned side effects were all reversible resulting in a patient's mean postoperative ICU permanence of 4 days (range 3 to 7 days). In conclusion, ILP with TNF alpha induces cardiovascular, respiratory and hematological toxicity with haemodynamic parameters being similar to those noted in SIRS probably due to leakage of TNF alpha in the systemic circulation during the perfusion. Nevertheless, this systemic toxicity was short-lived resulting in an acute reaction following a single application.
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PMID:Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha. 1535 6

High-dose bolus or continuous infusion interleukin-2-based therapy can cause capillary leak syndrome. Significant cardiovascular/hemodynamic events, including myocardial infarction, hypotension, pulmonary edema, and cardiac arrhythmia, have been described with such therapy. Concern over the toxicity of highdose interleukin-2 (IL-2) therapy has led to some clinicians excluding patients 70 years of age or over. We have treated 15 patients 70 years of age or over having an Eastern Conference Oncology Group (ECOG) performance status of 0 or 1, with therapy based on continuous infusion IL-2 18 MIU/sq m/24 hours for 72 hours. All patients underwent a pretreatment evaluation of cardiac status with a low-level stress or adenosine stress test. Cycles were typically repeated every 3 weeks for 4 cycles, then every 3-4 weeks thereafter. Patients were treated by oncology nurses in either the stem cell transplant (intermediate unit) or the oncology inpatient unit. Patient characteristics were: median age, 72 years (range, 70-83 years); tumor types: melanoma (10), kidney cancer (5); most common sites of disease: lung (11), lymph nodes (6), subcutaneous (3), liver (2); prior therapy included: none (8), outpatient IL-2 (5), other immunotherapy (4). Median number of cycles received: 3 (1-10). Most common toxicities were: fever, rigors, nausea, emesis, hypophosphatemia, and hypomagnesemia. Three patients required the use of dopamine for blood pressure support. Two patients declined further therapy. There were no treatment-related deaths. No patients required endotracheal intubation or transfer to an intensive care unit. One complete and 8 partial responses (60% response rate) have been seen. Responding sites include the lung, lymph node, intact kidney primary, and liver. Median survival has not been reached at over 14 months (range 3+-26+ months). Patients who are 70 years of age and older with an ECOG performance status of 0 or 1 are able to tolerate high-dose continuous infusion IL-2-based therapy and may respond to such treatment.
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PMID:Administration of high-dose continuous infusion interleukin-2 to patients age 70 or over. 1577 74

The administration of high-dose continuous intravenous infusion interleukin-2 (IL-2) is able to induce the presence of lymphokine-activated killer (LAK) cells. LAK are able to nonspecifically lyse tumor cells. They are also able to lyse endothelial cells, which accounts for, at least in part, the capillary leak syndrome seen as one of the toxicities with this therapy. A pulmonary manifestation of capillary leak syndrome is the presence of pulmonary edema. We postulated that capillary leak may also be a mechanism by which LAK could conceivably reach pulmonary metastases or could be a reflection of damage of endothelial cells in vasculature supplying metastases and that capillary leak syndrome may actually correlate with the response of pulmonary metastases. We examined our database of patients with lung metastases treated with high-dose continuous infusion IL-2 (18 MIU/m(2)/day for 3 days) regimens. Eighteen patients had the following characteristics: melanoma (11), renal cancer (7), median age of 67 years (range, 28-79 years), and males (15). All patients were treated by oncology nurses on either the stem cell transplant unit or oncology ward. Pulmonary edema was defined as the presence of pleural fluid on a chest X-ray, computed tomography (CT) scan, and/or as noted on a physical examination by at least 2 observers. No patients required endotracheal intubation, mechanical ventilation, or an intensive care unit transfer. The median number of cycles received was 6 (range, 1-13). All 8 responding patients (6 patients with melanoma, 2 patients with kidney cancer) manifested pulmonary edema during interleukin-2 therapy. Four patients with pulmonary edema were nonresponders. The presence of pulmonary edema correlated with the response to therapy (p = 0.01). The median duration of response of pulmonary nodules was 5 months (range, 1-16 months). There is a correlation between the development of pulmonary edema and the response of pulmonary metastases in patients with melanoma and kidney cancer treated with high-dose continuous infusion interleukin-2.
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PMID:Correlation between development of pulmonary edema and response of pulmonary metastases of metastatic melanoma and kidney cancer to high-dose continuous-infusion interleukin-2. 1586 48

The remarkable ability of TNF, especially in combination with Interferon-gamma or melphalan, to inhibit the growth of malignant tumor cells is so far unmatched. Unfortunately, its high systemic toxicity and hepatotoxicity prevent its systemic use in cancer patients. An elegant manner to circumvent this problem is the isolated limb and liver perfusion for the treatment of melanoma, soft tissue sarcoma and liver tumors, respectively, although the latter method can lead to a reversible hepatotoxicity. In order to allow also the treatment of other cancers with TNF, new strategies have to be developed that aim at sensitizing tumor cells to TNF and at reducing its systemic and liver toxicity, without losing its antitumor efficiency. Moreover, the lectin-like domain of TNF, which is spatially distinct from the receptor binding sites, could be useful in reducing cancer treatment-related pulmonary edema formation. This review will discuss some recent developments in these areas, which can lead to a renewed interest in TNF for the systemic treatment of cancer.
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PMID:TNF: a moonlighting protein at the interface between cancer and infection. 1850 93

Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrotoxicity. Research has focused on pharmaceuticals and enzyme/molecular alterations as alternatives to long-term diuresis. No agents have currently been identified that can protect from all toxicities. Cisplatin has shown activity against osteosarcoma, transitional cell carcinoma, squamous cell carcinoma (SCC), melanoma, mesothelioma, carcinomatosis and germinal cell tumours in the dog. In the cat, cisplatin cannot be utilized because of fulminant pulmonary oedema that occurs at standard doses. Intralesional cisplatin has been utilized in horses for the treatment of SCC and sarcoids.
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PMID:Cisplatin: a review of toxicities and therapeutic applications. 1917 59

IL-2 immunotherapy is an attractive treatment option for certain metastatic cancers. However, administration of IL-2 to patients can lead, by ill-defined mechanisms, to toxic adverse effects including severe pulmonary edema. Here, we show that IL-2-induced pulmonary edema is caused by direct interaction of IL-2 with functional IL-2 receptors (IL-2R) on lung endothelial cells in vivo. Treatment of mice with high-dose IL-2 led to efficient expansion of effector immune cells expressing high levels of IL-2Rbetagamma, including CD8(+) T cells and natural killer cells, which resulted in a considerable antitumor response against s.c. and pulmonary B16 melanoma nodules. However, high-dose IL-2 treatment also affected immune cell lineage marker-negative CD31(+) pulmonary endothelial cells via binding to functional alphabetagamma IL-2Rs, expressed at low to intermediate levels on these cells, thus causing pulmonary edema. Notably, IL-2-mediated pulmonary edema was abrogated by a blocking antibody to IL-2Ralpha (CD25), genetic disruption of CD25, or the use of IL-2Rbetagamma-directed IL-2/anti-IL-2 antibody complexes, thereby interfering with IL-2 binding to IL-2Ralphabetagamma(+) pulmonary endothelial cells. Moreover, IL-2/anti-IL-2 antibody complexes led to vigorous activation of IL-2Rbetagamma(+) effector immune cells, which generated a dramatic antitumor response. Thus, IL-2/anti-IL-2 antibody complexes might improve current strategies of IL-2-based tumor immunotherapy.
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PMID:Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. 2054 66

A diffuse interstitial infiltrative pattern of lung metastasis in a patient with malignant melanoma is rare and can be confused with benign conditions such as pulmonary edema or drug-induced pneumonitis. We experienced a case of diffuse interstitial infiltrative lung metastasis in malignant melanoma in a 37-year-old man. This case was confirmed by a transbronchial lung biopsy. We herein describe the findings on CT and positron emission tomography scan.
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PMID:Diffuse interstitial infiltrative lung metastasis of malignant melanoma: a case report. 2143 Sep 44


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