TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: The biliary cast syndrome (BCS) is a frequent problem following liver transplantation. The pathogenesis of this complication is not well understood. Previous research has demonstrated that the soluble form of MICA (sMICA) is significantly higher in patients with chronic liver disease and hepatocellular carcinoma (HCC) than in healthy volunteers. The aim of this study is to investigate the possible involvement of sMICA in the formation of BCS after liver transplantation.', 'Serum soluble MICA was retrospectively evaluated in pre- and post-transplant sera from 133 consecutive primary liver transplant patients and in sera from 88 healthy volunteers using sandwich ELISA. Normal distribution of serum sMICA was described by the data obtained from healthy population and sMICA concentration that was greater than the upper bound 95% normal range was considered as high levels of sMICA. Patient records were reviewed to identify patients who developed BCS.', 'The results demonstrated that 37.6% of patients with end-stage liver diseases had significantly higher pre-transplant serum sMICA than in healthy population. 34.4% of recipients with post-transplant high levels of sMICA developed BCS. In contrast, 17.3% of patients with post-transplant normal levels of sMICA developed BCS. The risk of BCS development is significantly associated with the presence of post-transplant high levels of sMICA (P=0.0365). Further analysis disclosed that patients with decreased post-transplant sMICA following liver transplantation had a lower incidence rate of BCS than those with remained high levels of sMICA after transplantation (10.5% vs. 38.7%, P=0.0302). Furthermore, log-rank test showed that BCS occurrence was significantly associated with dynamic changes of sMICA among different groups (P=0.0188).

SOLUTION: Are high levels of soluble Major Histocompatibility Complex class I related chain A ( MICA ) associated with biliary cast syndrome after liver transplantation?

PROBLEM: A transgenic mouse model has revealed parameters of the angiogenic switch during multistep tumorigenesis of pancreatic islets, and demonstrated efficacy of antiangiogenic therapies. Pericytes have been revealed as functionally important for tumor neovasculature, using kinase inhibitors targeting their platelet-derived growth factor receptors (PDGFRs). Additionally, vascular endothelial growth factor receptor (VEGFR) inhibitors and metronomic chemotherapy show modest benefit against early- but not late-stage disease.', 'Seeking to improve efficacy against otherwise intractable end-stage pancreatic islet tumors, two receptor tyrosine kinase inhibitors, imatinib and SU11248, were used to disrupt PDGFR-mediated pericyte support of tumor endothelial cells in concert with maximum-tolerated dose (MTD) or metronomic chemotherapy and/or VEGFR inhibition.', 'Imatinib, despite equivocal efficacy as monotherapy, reduced pericyte coverage of tumor vessels and enhanced efficacy in combination with metronomic chemotherapy or VEGFR inhibition. A regimen involving all three was even better. MTD using cyclophosphamide caused transitory regression, but then rapid regrowth, in contrast to metronomic cyclophosphamide plus imatinib, which produced stable disease. The MTD regimen elicited apoptosis of tumor cells but not endothelial cells, whereas the other regimens increased endothelial cell apoptosis concordant with efficacy. A "chemo-switch" protocol, involving sequential MTD and then metronomic chemotherapy, overlaid with multitargeted inhibition of PDGFR and VEGFR, gave complete responses and unprecedented survival advantage in this model.

SOLUTION: Is a multitargeted , metronomic , and maximum-tolerated dose `` chemo-switch '' regimen antiangiogenic , producing objective responses and survival benefit in a mouse model of cancer?

PROBLEM: It has been contended that, during cardiopulmonary bypass at 27 degrees C, pH-stat management decreases cerebral metabolic rate for oxygen (CMRO2) more than alpha-stat management. In contrast, other studies have not found CMRO2 to differ between techniques. Using each animal as its own control, the authors assessed the effect of alpha-stat versus pH-stat management of CMRO2, cerebral blood flow (CBF), and brain oxygen extraction during cardiopulmonary bypass at 27 degrees C.', 'Fourteen New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent cardiopulmonary bypass at 27 degrees C (membrane oxygenator, centrifugal pump, and bifemoral arterial perfusion). Group 1 animals (n = 7) had alpha-stat management for the initial 65-70 min of bypass, and were then changed to pH-stat management for the remaining 30 min of bypass. Group 2 animals (n = 7) had pH-stat management for the initial 65-70 min of bypass, and were then changed to alpha-stat management for the remaining 30 min. Measurement of CBF (radiolabeled microspheres), CMRO2 (CBF x brain arterial-venous oxygen content difference), brain temperature, systemic hemodynamics, and arterial blood gases were made in each animal under both alpha-stat and pH-stat conditions.', 'CMRO2 did not differ between alpha-stat and pH-stat conditions (1.4 +/- 0.3 ml.100 g-1.min-1; median +/- quartile deviation), and was independent of order of determination. Changes in CBF between alpha-stat and pH-stat conditions were associated with proportional opposite changes in cerebral oxygen extraction. Cerebral blood flow was significantly greater with pH-stat management than with alpha-stat management (37 +/- 5 vs. 30 +/- 3 ml.100 g-1.min-1, respectively). The CBF response to changing PaCO2 was significantly greater when going from alpha-stat to pH-stat conditions (group 1) than in the reverse order (group 2).

SOLUTION:
Does hypothermic acid-base management affect cerebral metabolic rate for oxygen at 27 degrees C. A study during cardiopulmonary bypass in rabbits?