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.

Q: Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants.', 'Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1.', 'Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14-0.26 mumol/l) whereas ezetimibe was 30-100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112+/-66 ngxh/ml vs. *1a/*1b, N=8, 88+/-39 ngxh/ml vs. *1b/*1b, N=5, 55+/-18 ngxh/ml; Jonkheere-Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704+/-296 vs. 878+/-369 vs. 1059+/-363 ngxh/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms.

A: Is disposition of ezetimibe influenced by polymorphisms of the hepatic uptake carrier OATP1B1?
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Q: The objective in lung transplantation is to prolong life, but the survival effect in patients with chronic obstructive pulmonary disease (COPD) or alpha1-anti-trypsin deficiency emphysema is still unresolved. This study assesses the impact of diagnosis, single-lung transplantation (SLT) vs bilateral lung transplantation (BLT) and timing of transplantation on survival in a national cohort.', 'In 219 consecutive patients accepted onto the lung transplantation waiting list in Norway, 1990 to 2003, we assessed predictors of death: (1) on the waiting list; (2) <or=90 days after transplantation; and (3) >90 days after transplantation. For each period we used Cox regression, including age, gender, diagnosis, baseline pulmonary function tests, cardiac catheterization data, exercise capacity and transplant type, as potential predictors. Survival benefit was assessed graphically by combining adjusted survival curves after transplantation with the curve for those waiting, modeling transplantation after 6, 12 or 24 months.', 'Mean patient age was 49 years (SD 10), with 55% women. High forced expiratory volume in 1 second (FEV(1)) percentage predicted death on the waiting list. Diagnoses other than COPD/emphysema and receiving SLT were associated with death <or=90 days after transplantation. Only low forced vital capacity (FVC) percentage predicted death >90 days after transplantation. In COPD/emphysema, there was no clear survival benefit from BLT or SLT. For patients in the "Other" group, the data suggest a survival benefit from BLT.

A: Is lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort without obvious survival benefit?
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Q: The significance of bile duct injury and ductular reaction in biopsies from autoimmune hepatitis patients is not clear. We aim to establish the prevalence and clinical relevance of both phenomena in autoimmune hepatitis.', 'Cases of newly diagnosed, untreated autoimmune hepatitis without overlap syndrome were selected. Pretreatment and follow up biopsies were scored for inflammation, fibrosis, bile ductal injury and ductular reaction.', 'Thirty-five cases were studied of whom 14 cases had follow up biopsies. Bile duct injury was present in 29 cases (83%), mostly in a PBC-like pattern and was not correlated with demographical or laboratory findings. Ductular reaction, observed in 25 of 35 cases (71%) using conventional histology and in 30 of 32 cases (94%) using immunohistochemistry, was correlated with portal and lobular inflammation, interface hepatitis and centrilobular necrosis as well as bile duct injury and fibrosis. In 11 of 14 cases (79%) ductular reaction remained present on post-treatment biopsy whereas bile duct injury persisted in six of 14 (43%) of cases.

A:
Are bile ductal injury and ductular reaction frequent phenomena with different significance in autoimmune hepatitis?
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