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At least 127 records · Page 7Linked to original sources
PubMed2002

The effect of malignant effusions on methotrexate disposition.

PURPOSE: The purpose of this study was to evaluate the effect of malignant effusions on the pharmacokinetics of methotrexate (MTX). METHODS: Simulated drug concentrations in blood, tissues and effusion fluid spaces were generated using a previously published physiologically based pharmacokinetic (PBPK) model for MTX in humans. The model was expanded to incorporate effusion spaces with permeability rate-limited drug transport. The model was used first to simulate MTX plasma concentrations in patients without effusions. Then the effects of cardiac, peritoneal and pleural effusions on MTX plasma concentrations were investigated followed by an examination of the influence of effusion volume, binding in the effusate, and effusion space permeability clearance (PA) on MTX plasma pharmacokinetics. In addition, the effect of the disposition characteristics (e.g. volume of distribution) of the anticancer drug on the overall influence of an effusate was evaluated. Finally, the simulations were compared with MTX concentrations observed in the plasma and pleural fluid of a patient with a pleural effusion treated with MTX. RESULTS: There was good agreement between the PBPK-simulated MTX plasma concentrations and observed values in patients without effusions. There was also a remarkable similarity between simulated and measured plasma and effusion MTX concentrations in a pediatric patient with a malignant pleural effusion. The physiological characteristics of an effusion, i.e. fluid volume, protein binding and membrane permeability clearance, modulate the influence of an effusion on the drug plasma concentration-time course. In general, effusions cause an increase in the steady-state volume of distribution but no change in the overall clearance of a drug. Malignant effusions were noticeable only in the disposition phase of MTX resulting in an apparent "third space." This was most prominent when the effusion fluid volume was large, the binding of MTX in the effusion fluid was greater than in plasma and the PA value was low. The percentage change in terminal half-life due to an effusion is significant for drugs with small volumes of distribution (332%) but not for those with large volumes of distribution (1.29%). In the case of MTX, and probably other anticancer drugs, the resulting increase in half-life may be associated with unanticipated toxicity.

Antimetabolites, Antineoplastic↗
PubMed1994

Relationship between pleural effusion and pericardial involvement after myocardial revascularization.

The explanation for the high incidence of pleural effusion after cardiac surgery is unclear. There is a high incidence of left pleural effusion with inflammatory pericardial disease. We hypothesized that after coronary artery bypass grafting (CABG) there would be a higher incidence of pleural effusions in patients with pericardial involvement. We prospectively studied 47 patients undergoing elective CABG; 17 had only saphenous vein grafts (SVG group) and 30 received at least one internal mammary artery graft (IMA group) in addition to SVG. Patients had a chest radiograph, chest ultrasound, and an echocardiogram on the 7th, 14th, and 30th postoperative days. Seven days after the surgery, 42 to 47 patients (89.4 percent) had a pleural effusion and 36 (76.6 76.6 percent) pericardial involvement. No relationship was found between the presence of a pleural effusion and a pericardial effusion (p > 0.05). On the 14th postoperative day, 36 patients (76.6 percent) had a pleural effusion while 33 patients (70.2 percent) had a pericardial effusion. There was a significant relationship between the presence of a pleural effusion and a pericardial effusion (p < 0.05). On the 30th postoperative day, 27 patients (57.4 percent) had a pleural effusion and 25 (53.2 percent) had a pericardial effusion. Again, there was a significant relationship between a pleural effusion and a pericardial effusion (p < 0.05). Finally, there was no relationship between the ejection fraction and the presence of pleural effusion at any time (p > 0.05). From this study, we conclude that there is a high prevalence of both pleural and pericardial effusion postoperatively in patients undergoing CABG. Both types of effusions tend to be asymptomatic, gradually disappear, and are more common in the IMA group. Patients who have a persistent pericardial effusion are more likely to have a persistent pleural effusion.

Coronary Artery Bypass↗
PubMed2001

Expression levels of the nerve growth factor receptors TrkA and p75 in effusions and solid tumors of serous ovarian carcinoma patients.

PURPOSE: The purpose of this study was to analyze the expression of the high- and low-affinity nerve growth factor (NGF) receptors TrkA and p75 in effusions and in primary and metastatic tumors of serous ovarian carcinoma patients, as well as to evaluate their association with clinicopathological parameters and disease outcome. EXPERIMENTAL DESIGN: Sections from 77 malignant effusions and 78 primary and metastatic lesions were evaluated for protein expression of TrkA and p75 using immunohistochemistry (IHC). Expression of the phosphorylated form of TrkA (p-TrkA) was evaluated in 75 effusions using IHC. TrkA and p75 mRNA expression was studied in 44 effusions using reverse transcription-PCR (RT-PCR). RESULTS: TrkA protein membrane expression was detected in carcinoma cells in 30 of 77 (39%) effusions and 64 of 78 (82%) solid tumors. The decrease in TrkA expression in effusions approached, but did not reach, statistical significance when only corresponding lesions were analyzed (P = 0.06 in the comparison of effusions and primary tumors, P = 0.09 for effusions and metastases). Conversely, p75 protein membrane expression was more common in effusions, which was detected in 16 of 77 (21%) effusions as compared with 6 of 78 (8%) solid tumors (P > 0.05 in analysis of corresponding lesions). Expression of p-TrkA in carcinoma cells was limited to 5 of 75 effusions. Interestingly, 11 of 16 p75-positive effusions were also immunoreactive for the antibody against TrkA (P = 0.001), suggesting NGF activation using two signaling pathways. TrkA and p75 protein expression in tumor cells was similar in pleural and peritoneal effusions (P > 0.05). Using reverse transcription-PCR, TrkA mRNA was detected in 2 of 45 effusions, whereas p75 mRNA was present in 3 of 45 specimens. TrkA and p75 showed no association with tumor grade, Fédération Internationale des Gynaecologistes et Obstetristes stage, chemotherapy status, the extent of residual disease, or survival (P > 0.05). CONCLUSIONS: TrkA and p75 are both expressed in advanced-stage ovarian carcinoma, but whereas p75 expression is elevated in effusions, TrkA shows an opposite trend. The different expression of NGF receptors in effusions may relate to the different microenvironment and growth factor availability in body cavities, as also supported by the infrequent activation of TrkA in effusions. The similar expression of TrkA and p75 in carcinoma cells in pleural and peritoneal effusions provides further evidence for our hypothesis that there are few, if any, phenotypic differences between ovarian carcinoma cells at these two sites. TrkA and p75 expression in effusions does not appear to be a predictor of disease outcome in advanced-stage serous ovarian carcinoma.

Animals↗
PubMed2001

An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer.

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.

Aged↗
PubMed1996

Pleural effusion and ventilation/perfusion scan interpretation for acute pulmonary embolus.

UNLABELLED: This study was conducted to determine if pleural effusion size affects ventilation/perfusion (V/Q) scan interpretation algorithms for acute pulmonary embolus (PE). METHODS: Retrospective analysis identified 163 consecutive patients undergoing angiography for PE with radiographic evidence for pleural effusion. V/Q scanning was performed in 94 (58%) of cases and reported using original Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria. Effusions were classified as small, large and/or bilateral. Radiographic and scintigraphic results were compared with regard to size and location of abnormalities. RESULTS: Of the 163 patients, 57 (35%) had angiographically-proven PE, 77 (47%) had at least one large pleural effusion and 86 (53%) had a small effusion; 33 (43%) with large effusions and 24 (28%) with small effusions had emboli at angiography. Thirty-six of 119 patients (30%) with clear chest radiographs (a control group) had PE. Thus, large effusions were associated with a higher incidence of PE than those with small effusions or clear lungs (p < 0.05). Of those with V/Q scanning, 26 of 94 (28%) had a solitary large effusion, with 12 (46%) positive for emboli. V/Q-matched abnormalities limited to effusion size were found in 16 with a solitary large effusion and 10 with a solitary small effusion. In both groups, 50% were angiographically positive for emboli. Twenty-three (66%) of 35 with bilateral effusions had corresponding V/Q-matched defects at one (n = 11) or both (n = 12) lung bases, and 9 (39%) were positive for emboli. In total, 45% with a V/Q-matched defect of equivalent size to the effusion were angiographically positive for PE. CONCLUSION: Pulmonary emboli are associated with pleural effusions of all sizes. Matched V/Q defects corresponding to radiographically-evident pleural effusions are of intermediate probability for PE. Thus, revision of the traditional lung scan interpretive criteria based upon pleural effusion size is not warranted.

Acute Disease↗