The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
Lisbeth E Knudsen - One of the best experts on this subject based on the ideXlab platform.
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Transplacental Transfer of Monomethyl Phthalate and Mono(2-ethylhexyl) Phthalate in a Human Placenta
2016Co-Authors: Perfusion System, Tina Mose, Morten Hedegaard, Lisbeth E Knudsen, Gerda K MortensenAbstract:The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental Perfusion model with simultaneous Perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after Perfusion were also analyzed. Placentas were obtained immediately after elective ce-sarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal Perfusion medium to obtain con-centrations at 10 and 25 µg/L, respectively. The placental trans-fer was followed analyzing samples from fetal and maternal per-fusion media by liquid chromatography–mass spectrometry–mass spectrometry (LC-MS-MS). Four Perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ra-tio) of 0.30 ± 0.03 after 150 min of Perfusion. Four Perfusions with mEHP indicated a very slow or nonexisting placental trans-fer. mEHP was only detected in fetal Perfusion media from two Perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of Perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after Perfusions with mMP compared to Perfusions with mEHP suggest an accumulation of mMP during Perfusion. No tendency for accumulation of mEHP was observed during per-fusions with mEHP compared to Perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma sam-ples. mMP and possibly other short-chained phthalate monoester
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transport of benzo α pyrene in the dually perfused human placenta Perfusion model effect of albumin in the Perfusion medium
Basic & Clinical Pharmacology & Toxicology, 2009Co-Authors: Line Mathiesen, Tina Mose, Erik Rytting, Lisbeth E KnudsenAbstract:Transport of benzo(a)pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta Perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta Perfusions showed minimal transport through the placenta. To increase the solubility of BaP in Perfusion medium and to increase physiological relevance, Perfusions were also performed with albumin added to the Perfusion medium (2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)). The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 € 0.10 after 3 hr and 0.78 € 0.11 after 6 hr, whereas the FM ratio in Perfusions without albumin was only 0.05 € 0.03 after 6 hr of Perfusion. Less BaP accumulated in placental tissue in Perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances. Benzo(a)pyrene (BaP) is a five-ring polycyclic aromatic hydrocarbon that is mutagenic and highly carcinogenic. A large number of experiments have demonstrated that BaP causes tumours at several sites by several routes of adminis- tration, in both sexes, and in several animal species. Based on the sufficient evidence in experimental studies and strong evidence that the mechanisms of carcinogenesis in animals also operate in human beings, International Agency for Research on Cancer (IARC) has classified BaP as carcinogenic to humans (IARC, group 1) (1). BaP is the most studied
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transplacental transfer of monomethyl phthalate and mono 2 ethylhexyl phthalate in a human placenta Perfusion system
International Journal of Toxicology, 2007Co-Authors: Tina Mose, Morten Hedegaard, Lisbeth E Knudsen, Gerda K MortensenAbstract:The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental Perfusion model with simultaneous Perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after Perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal Perfusion medium to obtain concentrations at 10 and 25 μg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal Perfusion media by liquid chromatography–mass spectrometry–mass spectrometry (LC-MS-MS). Four Perfusions with mMP indicated a slow transplacental transfer, with a fetomaternal ratio (FM ratio) of 0.30 ± 0.03 after 150 min of Perfusion. Four Perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal Perfusion media from two pe...
Takeshi Yoshikawa - One of the best experts on this subject based on the ideXlab platform.
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dynamic contrast enhanced Perfusion area detector ct assessed with various mathematical models its capability for therapeutic outcome prediction for non small cell lung cancer patients with chemoradiotherapy as compared with that of fdg pet ct
European Journal of Radiology, 2017Co-Authors: Yoshiharu Ohno, Yasuko Fujisawa, Hisanobu Koyama, Yuji Kishida, Shinichiro Seki, Naoki Sugihara, Takeshi YoshikawaAbstract:Abstract Purpose To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) Perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Materials and methods Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-Perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial Perfusions and total Perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor Perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. Results The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial Perfusion, total Perfusion, and SUV max . Mean overall survival showed a significant difference for total Perfusion (p=0.003) and systemic arterial Perfusion (p=0.04). Conclusion Dynamic first-pass CE-Perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.
Rebecca Brais - One of the best experts on this subject based on the ideXlab platform.
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observations on the ex situ Perfusion of livers for transplantation
American Journal of Transplantation, 2018Co-Authors: Christopher J E Watson, Vasilis Kosmoliaptsis, Caitlin Pley, Lucy V Randle, Corinna Fear, Keziah Crick, A E S Gimson, Michael Allison, Sara Upponi, Rebecca BraisAbstract:Normothermic ex situ liver Perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver Perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 Perfusions, and glucose rose initially during Perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25-50% necrosis had a maximum pH 7.46. Liver viability during normothermic Perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid-base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy.
Steven A. Rosenberg - One of the best experts on this subject based on the ideXlab platform.
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isolated lung Perfusion with tumor necrosis factor for pulmonary metastases
The Annals of Thoracic Surgery, 1996Co-Authors: Harvey I. Pass, Karen Kranda, Daphne J Y Mew, Barbara K Temeck, Jessica S Donington, Steven A. RosenbergAbstract:Background A phase I trial was initiated to define the feasibility and safety of single-lung isolation Perfusion with tumor necrosis factor- α , interferon- γ , and moderate hyperthermia for patients with unresectable pulmonary metastases. Methods Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation Perfusion with 0.3 to 6.0 mg of tumor necrosis factor- α and 0.2 mg interferon- γ , delivered through an oxygenated pump circuit. Sixteen Perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation Perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation Perfusion was aborted for mechanical reasons. Results There were no significant changes in systemic arterial blood pressure or cardiac output during Perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation Perfusion levels after clamp release. The maximum systemic tumor necrosis factor- α level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1). Conclusions Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function.
Yoshiharu Ohno - One of the best experts on this subject based on the ideXlab platform.
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dynamic contrast enhanced Perfusion area detector ct assessed with various mathematical models its capability for therapeutic outcome prediction for non small cell lung cancer patients with chemoradiotherapy as compared with that of fdg pet ct
European Journal of Radiology, 2017Co-Authors: Yoshiharu Ohno, Yasuko Fujisawa, Hisanobu Koyama, Yuji Kishida, Shinichiro Seki, Naoki Sugihara, Takeshi YoshikawaAbstract:Abstract Purpose To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) Perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Materials and methods Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-Perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial Perfusions and total Perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor Perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. Results The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial Perfusion, total Perfusion, and SUV max . Mean overall survival showed a significant difference for total Perfusion (p=0.003) and systemic arterial Perfusion (p=0.04). Conclusion Dynamic first-pass CE-Perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.
