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"text": "\n3237\nPositive nickel patch tests do not intensify positive reactions to adjacent patch tests with dichromate. Results from a double-blind multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).\n\nBrasch, J\n\nKreilgård, B\n\nHenseler, T\n\nAberer, W\n\nFuchs, T\n\nPflüger, R\n\nHoeck, U\n\nGefeller, O\n\nBeiträge in Fachzeitschriften\nISI:000088981800004\n10985630.0\n10.1034%2Fj.1600-0536.2000.043003144.x\nNone\nThe possible interference of neighbouring allergic patch-test reactions is still an open question. In this study, we investigated whether there is a distance-related mutual modification of neighbouring allergic patch-test reactions to nickel sulfate and potassium dichromate. We used a double-blind multicentre study design with randomized attachment of special TRUE Tests with 1, 3 and 7 cm distance between nickel sulfate and potassium dichromate patches. 589 patients with a history of nickel allergy (523 female, 66 male) were tested, with a mean age of 35 years. A log-linear modelling approach was used for statistical assessment of the relation between the distance separating neighbouring patch tests with nickel and dichromate and the reactions to the allergens. Non-reproducibility coefficients were compared by the generalized version of Fisher's exact test for arbitrary 2-dimensional contingency tables. For the left side of the back, virtually no differences (p=0.70) were found in the reaction patterns obtained for the 3 distances separating nickel and dichromate patch tests. On the right side of the back, the number of reactions to dichromate patches with only 1 cm distance from moderate/strong nickel reactions was lower than the number of positive dichromate tests at larger distances from nickel tests (on the border of statistical significance: p= 0.05). Corresponding side-related results were obtained for subgroups of patients with and without a history of atopic dermatitis. The non-reproducibility of reactions to dichromate was not significantly related to the distance between neighbouring tests. Our data argue against a "spillover" effect of strong/moderate nickel reactions, but indicate that such reactions may, under certain conditions, attenuate adjacent reactions to an unrelated allergen. In the case of future verification, this will have implications for the interpretation of patch tests.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n4859\nCutaneous myoepithelial neoplasms: clinicopathologic and immunohistochemical study of 20 cases suggesting a continuous spectrum ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and myoepithelial carcinoma.\n\nMentzel, T\n\nRequena, L\n\nKaddu, S\n\nSoares de Aleida, LM\n\nSangueza, OP\n\nKutzner, H\n\nBeiträge in Fachzeitschriften\nISI:000183010300002\n12753168.0\n10.1034%2Fj.1600-0560.2003.00063.x\nNone\nBACKGROUND: Myoepithelial neoplasms, both benign and malignant, are rare but well-established clinicopathologic entities in the salivary glands, the breast, and the lung. Despite similarities between cutaneous sweat glands and glandular structures in the above-mentioned organs as well as the presence of regular myoepithelial cells around cutaneous eccrine/apocrine glands, the concept of cutaneous myoepithelial neoplasms is still debatable and not commonly accepted. METHODS: Twenty cutaneous myoepithelial neoplasms have been studied histologically and immunohistochemically. RESULTS: Nine neoplasms showed features of benign mixed tumor of the skin (chondroid syringoma) (five females and four males, age range 19-65 years, all cases arose in the head and neck region). Two cases represented the eccrine and seven the apocrine subtype. Interestingly, in three cases of the apocrine subtype, solid areas composed predominantly of myoepithelial cells were detected; these neoplasms were designated as benign mixed tumors with prominent myoepithelial cells. Nine cutaneous neoplasms were composed of spindled, epithelioid, and plasmocytoid cells without ductal differentiation and immunohistochemically stained variably positive for vimentin, epithelial and myogenic markers, S-100 protein, calponin, and glial fibrillary acidic protein (four females and five males, age range 3-71 years, four cases arose in the head and neck region and one case each on the finger, the thigh, the lower leg, the foot, and the breast, respectively); these neoplasms were designated as cutaneous myoepitheliomas. Two morphologically malignant neoplasms with cytologic and immunohistochemical features of myoepithelial cells arose on the face of a 70-year-old female and a 79-year-old male patient; these neoplasms were designated as malignant cutaneous myoepitheliomas (cutaneous myoepithelial carcinomas). CONCLUSIONS: The study suggests a continuous spectrum of cutaneous myoepithelial neoplasms ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and cutaneous myoepithelial carcinoma. Further studies with extended follow-up information are necessary to establish prognostic factors.\n\nKaddu, Steven\n\n\n"
},
{
"text": "\n52552\nReduced access to insulin-sensitive tissues in dogs with obesity secondary to increased fat intake.\n\nEllmerer, M\n\nHamilton-Wessler, M\n\nKim, SP\n\nHuecking, K\n\nKirkman, E\n\nChiu, J\n\nRichey, J\n\nBergman, RN\n\nBeiträge in Fachzeitschriften\nISI:000238053400027\n16731841.0\n10.2337/db05-1509\nNone\nPhysiological hyperinsulinemia provokes hemodynamic actions and augments access of macromolecules to insulin-sensitive tissues. We investigated whether induction of insulin resistance by a hypercaloric high-fat diet has an effect on the extracellular distribution of macromolecules to insulin-sensitive tissues. Male mongrel dogs were randomly selected into two groups: seven dogs were fed an isocaloric control diet ( approximately 3, 00 kcal, 35% from fat), and six dogs were fed a hypercaloric high-fat diet ( approximately 5, 00 kcal, 54% from fat) for a period of 12 weeks. During hyperinsulinemic-euglycemic clamps, we determined transport parameters and distribution volumes of [(14)C]inulin by applying a three-compartment model to the plasma clearance data of intravenously injected [(14)C]inulin (0.8 microCi/kg). In another study with direct cannulation of the hindlimb skeletal muscle lymphatics, we investigated the effect of physiological hyperinsulinemia on the appearance of intravenously injected [(14)C]inulin in skeletal muscle interstitial fluid and compared the effect of insulin between control and high-fat diet groups. The hypercaloric high-fat diet resulted in significant weight gain (18%; P<0.001) associated with marked increases of subcutaneous (140%; P<0.001) and omental (83%; P<0.001) fat depots, as well as peripheral insulin resistance, measured as a significant reduction of insulin-stimulated glucose uptake during clamps (-35%; P<0.05). Concomitantly, we observed a significant reduction of the peripheral distribution volume of [(14)C]inulin (-26%; P<0.05), whereas the vascular distribution volume and transport and clearance parameters did not change as a cause of the diet. The second study directly confirmed our findings, suggesting a marked reduction of insulin action to stimulate access of macromolecules to insulin-sensitive tissues (control diet 32%, P<0.01; high-fat diet 18%, NS). The present results indicate that access of macromolecules to insulin-sensitive tissues is impaired during diet-induced insulin resistance and suggest that the ability of insulin itself to stimulate tissue access is diminished. We speculate that the observed diet-induced defects in stimulation of tissue perfusion contribute to the development of peripheral insulin resistance.\n\n\n"
},
{
"text": "\n64553\nDoes the presence of postmenopausal symptoms influence susceptibility to vertebral deformity? European Vertebral Osteoporosis Study (EVOS) Group.\n\nScoutellas, V\n\nO'Neill, TW\n\nLunt, M\n\nReeve, J\n\nSilman, AJ\n\nand and the European Vertebral Osteoporosis Study (EVOS) Group\n\nBeiträge in Fachzeitschriften\nISI:000082598000008\n10515675.0\n10.1016/S0378-5122(99)00025-0\nNone\nBACKGROUND: Previous reports suggest a possible increased risk of osteoporosis in those with postmenopausal symptoms. There are, however, no data from population samples, exploring the relationship between postmenopausal symptoms and vertebral osteoporosis. AIM: To determine if there is an association between self-reported postmenopausal symptoms and radiographic vertebral deformity. METHODS: Women aged 50 years and over were recruited from population registers in 30 European centres and invited to attend for an interviewer administered questionnaire and lateral thoracic and lumbar spine radiographs. The questionnaire sought information about aspects of lifestyle, personal, medical and gynaecological history, including postmenopausal symptoms: flushing, sleep disturbance and 'other' symptoms. Radiographs were taken according to a standard protocol and evaluated morphometrically. Vertebral deformity was defined according to the McCloskey-Kanis method. Bone mineral density data were obtained in a subsample of women at both the spine and femoral neck. RESULTS: A total of 4023 postmenopausal women, aged 50-64 years, were studied: 73% reported a history of flushing, 45% sleep disturbance and 23% 'other' symptoms, at or around their menopause. The prevalence of vertebral deformity was 8.2%. Those with postmenopausal symptoms were slightly younger and more likely to have ever taken hormone replacement therapy (HRT) than those without symptoms. After adjusting for potential confounders (age, centre, body mass index, cigarette smoking and HRT) there was no association between deformity and any of the postmenopausal symptoms: flushing (odds ratio (OR) 1.0; 95% confidence intervals (CI) 0.8, 1.3), sleep disturbance (OR 1.0; 95% CI 0.8, 1.2), 'other' symptoms (OR 0.9; 95% CI 0.7, 1.3). Amongst women who had ever taken HRT, however, those with vertebral deformity were more likely to report a history of flushing (OR 2.1; 95% CI 0.9, .8). CONCLUSION: A history of postmenopausal symptoms per se does not appear to be associated with increased susceptibility to vertebral osteoporosis. However, women with more severe symptoms (as suggested by their use of HRT) may be at increased risk.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n110687\nImpaired physical quality of life in patients with diastolic dysfunction associates more strongly with neurohumoral activation than with echocardiographic parameters: Quality of life in diastolic dysfunction\n\nEdelmann, F\n\nStahrenberg, R\n\nPolzin, F\n\nKockskamper, A\n\nDungen, HD\n\nDuvinage, A\n\nBinder, L\n\nKunde, J\n\nScherer, M\n\nGelbrich, G\n\nHasenfuss, G\n\nPieske, B\n\nWachter, R\n\nHerrmann-Lingen, C\n\nBeiträge in Fachzeitschriften\nISI:000289190500025\n21473981.0\n10.1016/j.ahj.2011.01.003\nNone\nBackground Quality of life (QoL) is impaired in diastolic heart failure. Little is known about QoL in diastolic dysfunction (DD) without heart failure. Methods In the DIAST-CHF observational study, outpatients with risk factors for or a history of heart failure were included. In a cross-sectional analysis, we classified patients with preserved systolic function as having normal diastolic function (N, n = 264) or DD without (DD-, n = 957) or with (DD+, n = 321) elevated filling pressures according to echocardiography. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. Results Short Form 36 physical function (SF-36-PF) was worse in DD+ (mean +/- SD 67.2 +/- 25.6) than in DD- (76.2 +/- 22.7, P < .05) than in N (mean +/- SD 81.1 +/- 23.5, P < .01). Other physical dimensions and the physical component score were also lower in DD, whereas the mental component score did not differ. The SF-36-PF correlated weakly with echocardiographic indicators of diastolic function. In multivariate linear regression controlling for age, sex, body mass index, depressiveness as assessed by Patient Health Questionnaire 9, N-terminal probrain-type natriuretic peptide, and midregional proadrenomedullin (MR-proADM), individual echocardiographic parameters or grade of DD was not independently associated with SF-36-PF, whereas the presence of DD+ was. Both N-terminal probrain-type natriuretic peptide and MR-proADM were independently associated with SF-36-PF, with MR-proADM showing the stronger association. Conclusions Physical dimensions of QoL are reduced in DD. Impaired SF-36-PF is only weakly associated with DD per se but rather seems to be contingent on the presence of elevated filling pressures. Biomarkers are more strongly and independently associated with SF-36-PF and may be more adequate surrogate markers of QoL in DD than echocardiographic measurements. (Am Heart J 2011; 161: 797-804.)\n\n\n"
},
{
"text": "\n118111\nHistological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests.\n\nKutzner, H\n\nMetzler, G\n\nArgenyi, Z\n\nRequena, L\n\nPalmedo, G\n\nMentzel, T\n\nRütten, A\n\nHantschke, M\n\nParedes, BE\n\nSchärer, L\n\nHesse, B\n\nEl-Shabrawi-Caelen, L\n\nShabrawi-Caelen, LE\n\nFried, I\n\nKerl, H\n\nLorenzo, C\n\nMurali, R\n\nWiesner, T\n\nBeiträge in Fachzeitschriften\nISI:000304839300007\n22388759.0\n10.1038/modpathol.2012.35\nNone\nCutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis.\n\nCerroni, Lorenzo\n\nEl-Shabrawi-Caelen, Laila\n\nFried, Isabella\n\nKerl, Helmut\n\n\n"
},
{
"text": "\n119867\nTraumatic epiphysiolysis of the proximal femur.\n\nEgkher, A\n\nSchlenz, I\n\nSeitz, H\n\nBeiträge in Fachzeitschriften\nISI:000303288900003\n22538100.0\nNone\nNone\nPURPOSE OF THE STUDY Several former studies show the treatment of slipped epiphysis of the femoral head (SEFH). Its reason is rather unknown. On the other hand the rare traumatic SEFH takes place due to a real accident. According to the literature these injuries are treated like chronic SEFHs. The aim of this study is to show the differences in pathology and treatment of an acute traumatic SEFH in relationship to the chronic SEFH. PATIENTS AND METHODS In 8 patients dislocated traumatic SEFHs were reduced anatomically and stabilized by the means of 3 to 4 Kirschner- (K-) wires or two cancellous screws. Each patient got a plaster-cast fixation for about 6 weeks of the ipsilateral hip and leg and was mobilized with two crutches and partial weight bearing for 12 weeks. The implants were removed 24 weeks after surgery. Four patients with not dislocated SEFHs were immobilized or mobilized with two crutches without weight bearing according to their pain sensation. The final examination of both groups took place 2 1/2 to 15 years after the initial treatment. RESULTS Four patients primarily under 10 years of age showed no or minimal radiological signs of a dislocated femoral head and were without any further inconvenience - the suspected SEFHs revealed as hip contusions. 8 children aged 10 years or older at the time of trauma were treated by closed reduction and internal fixation. Complications occurred in three cases - one necrosis of the femoral head because of a perforating K-wire, one subtrochanteric femur fracture after implant removal of a prophylactically stabilized contralateral femoral head and one minimally dislocated femoral head after postoperative too early full weight bearing. DISCUSSION The traumatic SEFH is very different to the chronic one regarding the pathology and acute treatment. Technical challenges must be solved. Unilateral K-wiring or screwing for 24 weeks and reduced weight bearing for the first 12 weeks after surgery is a sufficient way of treatment of the traumatic SEFH. CONCLUSIONS In the case of a traumatic SEFH it needs to be reduced anatomically and stabilized by surgical means in the acute phase. A prophylactic stabilization of the opposite intact side is usually not required.\n\n\n"
},
{
"text": "\n127118\nAdoptive Transfer of Epstein-Barr Virus (EBV) Nuclear Antigen 1-Specific T Cells As Treatment for EBV Reactivation and Lymphoproliferative Disorders After Allogeneic Stem-Cell Transplantation.\n\nIcheva, V\n\nKayser, S\n\nWolff, D\n\nTuve, S\n\nKyzirakos, C\n\nBethge, W\n\nGreil, J\n\nAlbert, MH\n\nSchwinger, W\n\nNathrath, M\n\nSchumm, M\n\nStevanovic, S\n\nHandgretinger, R\n\nLang, P\n\nFeuchtinger, T\n\n\n\nBeiträge in Fachzeitschriften\nISI:000312911900015\n23169501.0\n10.1200/JCO.2011.39.8495\nNone\nPurpose Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promising treatment option. However, generation of antigen-specific T-cell populations has been difficult within a short time frame. Patients and Methods To improve availability in urgent clinical conditions, we developed a rapid protocol for isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) -specific T cells by using an interferon gamma (IFN-gamma) capture technique. Results We report on the use of adoptive transfer of EBNA-1-specific T cells in 10 pediatric and adult patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft-versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive T-cell transfer. In vivo expansion of transferred EBNA-1-specific T cells was observed in eight of 10 patients after a median of 16 days following adoptive transfer that was associated with clinical and virologic response in seven of them (70%). None of the responders had EBV-associated mortality. Within clinical responders, three patients were disease free by the day of last follow-up (2 to 36 months), three patients died of other infectious complications, and one patient died as a result of relapse of malignancy. EBV-related mortality was observed in two of 10 patients, and another patient had ongoing viremia without clinical symptoms at last follow-up. Conclusion Adoptive ex vivo transfer of EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option, representing a fast and efficient procedure to achieve reconstitution of antiviral T-cell immunity after SCT. J Clin Oncol 31:39-48. (c) 2012 by American Society of Clinical Oncology\n\nSchwinger, Wolfgang\n\n\n"
},
{
"text": "\n127954\nPhase synchronization of hemodynamic variables at rest and after deep breathing measured during the course of pregnancy.\n\nMoertl, MG\n\nLackner, HK\n\nPapousek, I\n\nRoessler, A\n\nHinghofer-Szalkay, H\n\nLang, U\n\nKolovetsiou-Kreiner, V\n\nSchlembach, D\n\nBeiträge in Fachzeitschriften\nISI:000319109800085\n23577144.0\n10.1371/journal.pone.0060675\nPMC3618276\nThe autonomic nervous system plays a central role in the functioning of systems critical for the homeostasis maintenance. However, its role in the cardiovascular adaptation to pregnancy-related demands is poorly understood. We explored the maternal cardiovascular systems throughout pregnancy to quantify pregnancy-related autonomic nervous system adaptations.\n Continuous monitoring of heart rate (R-R interval; derived from the 3-lead electrocardiography), blood pressure, and thoracic impedance was carried out in thirty-six women at six time-points throughout pregnancy. In order to quantify in addition to the longitudinal effects on baseline levels throughout gestation the immediate adaptive heart rate and blood pressure changes at each time point, a simple reflex test, deep breathing, was applied. Consequently, heart rate variability and blood pressure variability in the low (LF) and high (HF) frequency range, respiration and baroreceptor sensitivity were analyzed in resting conditions and after deep breathing. The adjustment of the rhythms of the R-R interval, blood pressure and respiration partitioned for the sympathetic and the parasympathetic branch of the autonomic nervous system were quantified by the phase synchronization index γ, which has been adopted from the analysis of weakly coupled chaotic oscillators.\n Heart rate and LF/HF ratio increased throughout pregnancy and these effects were accompanied by a continuous loss of baroreceptor sensitivity. The increases in heart rate and LF/HF ratio levels were associated with an increasing decline in the ability to flexibly respond to additional demands (i.e., diminished adaptive responses to deep breathing). The phase synchronization index γ showed that the observed effects could be explained by a decreased coupling of respiration and the cardiovascular system (HF components of heart rate and blood pressure).\n The findings suggest that during the course of pregnancy the individual systems become increasingly independent to meet the increasing demands placed on the maternal cardiovascular and respiratory system.\n\nHinghofer-Szalkay, Helmut\n\nKolovetsiou-Kreiner, Vassiliki\n\nLackner, Helmut Karl\n\nMörtl, Manfred Georg\n\nRössler, Andreas\n\n\n"
},
{
"text": "\n152307\nEvaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.\n\nLal, D\n\nReinthaler, EM\n\nDejanovic, B\n\nMay, P\n\nThiele, H\n\nLehesjoki, AE\n\nSchwarz, G\n\nRiesch, E\n\nIkram, MA\n\nvan Duijn, CM\n\nUitterlinden, AG\n\nHofman, A\n\nSteinböck, H\n\nGruber-Sedlmayr, U\n\nNeophytou, B\n\nZara, F\n\nHahn, A\n\nGenetic Commission of the Italian League against Epilepsy\n\nEuroEPINOMICS CoGIE Consortium\n\nGormley, P\n\nBecker, F\n\nWeber, YG\n\nCilio, MR\n\nKunz, WS\n\nKrause, R\n\nZimprich, F\n\nLemke, JR\n\nNürnberg, P\n\nSander, T\n\nLerche, H\n\nNeubauer, BA\n\nBeiträge in Fachzeitschriften\nISI:000372582800030\n26990884.0\n10.1371/journal.pone.0150426\nPMC4798642\nThe SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic.\n We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients.\n We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.\n\n\n"
},
{
"text": "\n155862\nOccult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile.\n\nGotthardt, DN\n\nSenft, J\n\nSauer, P\n\nWeiss, KH\n\nFlechtenmacher, C\n\nEckerle, I\n\nSchaefer, Y\n\nSchirmacher, P\n\nStremmel, W\n\nSchemmer, P\n\nSchnitzler, P\n\nBeiträge in Fachzeitschriften\nISI:000325009200012\n23894112.0\n10.1002/lt.23713\nNone\nCholestatic complications, important causes of morbidity and mortality after orthotopic liver transplantation (OLT), often have an unclear etiology. Human cytomegalovirus (CMV) infections occur in immunosuppressed patients and can be detected in blood samples. However, CMV analyses of body fluids and biopsies are more sensitive. Here we evaluated whether a CMV analysis of bile could reveal occult CMV cholangitis. We evaluated OLT patients undergoing endoscopic retrograde cholangiography (ERC) for suspected biliary complications after OLT at a tertiary care center. Biliary CMV DNA levels were measured with real-time polymerase chain reaction. A nonanastomotic biliary lesion (NABL) group consisted of patients with nonanastomotic strictures (NASs) at the time of ERC (n = 59) and patients with normal ERC findings but microscopic biliary lesions in biopsy samples (n = 12). The anastomotic stricture (AS) group comprised patients with ASs only (n = 53). In all, 124 OLT patients underwent 240 ERC procedures. Biliary CMV DNA was detected in 14 of the 124 patients and was more frequently found in the NABL group (12/71 for the NABL group versus 2/53 for the AS group, P = 0.02). Concurrent sampling of CMV DNA in blood yielded negative results. Biliary CMV was more frequently detected in patients with a positive recipient status (13/73 or 17.8% versus 1/44 or 2.3%, P < 0.05). There was no significant difference in the incidence of biliary CMV between patients with a high-risk CMV status and patients with a low-risk CMV status. The median interval between OLT and biliary CMV detection was 8.4 months (range = 0.4-212.8 months). In conclusion, biliary CMV was detected in a substantial number of patients after OLT and was significantly associated with NASs or microscopic biliary lesions. A potential occult CMV infection could, therefore, be considered as a contributory etiological factor in the development of biliary complications.\n Copyright © 2013 American Association for the Study of Liver Diseases.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n159056\nBest practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group.\n\nStacchiotti, S\n\nGronchi, A\n\nFossati, P\n\nAkiyama, T\n\nAlapetite, C\n\nBaumann, M\n\nBlay, JY\n\nBolle, S\n\nBoriani, S\n\nBruzzi, P\n\nCapanna, R\n\nCaraceni, A\n\nCasadei, R\n\nColia, V\n\nDebus, J\n\nDelaney, T\n\nDesai, A\n\nDileo, P\n\nDijkstra, S\n\nDoglietto, F\n\nFlanagan, A\n\nFroelich, S\n\nGardner, PA\n\nGelderblom, H\n\nGokaslan, ZL\n\nHaas, R\n\nHeery, C\n\nHindi, N\n\nHohenberger, P\n\nHornicek, F\n\nImai, R\n\nJeys, L\n\nJones, RL\n\nKasper, B\n\nKawai, A\n\nKrengli, M\n\nLeithner, A\n\nLogowska, I\n\nMartin Broto, J\n\nMazzatenta, D\n\nMorosi, C\n\nNicolai, P\n\nNorum, OJ\n\nPatel, S\n\nPenel, N\n\nPicci, P\n\nPilotti, S\n\nRadaelli, S\n\nRicchini, F\n\nRutkowski, P\n\nScheipl, S\n\nSen, C\n\nTamborini, E\n\nThornton, KA\n\nTimmermann, B\n\nTorri, V\n\nTunn, PU\n\nUhl, M\n\nYamada, Y\n\nWeber, DC\n\nVanel, D\n\nVarga, PP\n\nVleggeert-Lankamp, CLA\n\nCasali, PG\n\nSommer, J\n\nBeiträge in Fachzeitschriften\nISI:000402861900009\n28184416.0\n10.1093/annonc/mdx054\nPMC5452071\nChordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.\n © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.\n\nLeithner, Andreas\n\nScheipl, Susanne\n\n\n"
},
{
"text": "\n165033\nSolarium Use and Risk for Malignant Melanoma: Meta-analysis and Evidence-based Medicine Systematic Review.\n\nBurgard, B\n\nSchöpe, J\n\nHolzschuh, I\n\nSchiekofer, C\n\nReichrath, S\n\nStefan, W\n\nPilz, S\n\nOrdonez-Mena, J\n\nMärz, W\n\nVogt, T\n\nReichrath, J\n\nBeiträge in Fachzeitschriften\nISI:000423315300078\n29374757.0\n10.21873/anticanres.12339\nNone\nThere is an ongoing debate whether solarium use (indoor tanning/artificial UV) may increase the risk for primary cutaneous malignant melanoma.\n A systematic literature search was conducted using MEDLINE and ISI Web of Science. Included studies were critically assessed regarding their risk of bias, and methodological shortcomings. Levels of evidence and grades of recommendation were determined according to guidelines of the Oxford Centre for Evidence-Based Medicine. Summary risk estimates and 95% confidence intervals for four different outcomes (ever exposure, exposure at younger age, high/low exposure vs. non-exposure) were derived from random-effects meta-analyses to account for possible heterogeneity across studies.\n Two cohort and twenty-nine case-control studies were eligible. Overall, quality of included studies was poor as a result of severe limitations, including possible recall and selection bias, and due to lack of interventional trials. Summary risk estimates suggested a weak association (odds ratio (OR)=1.19, 95% confidence interval (CI)=1.04-1.35, p=0.009) for ever-exposure to UV radiation from a solarium with melanoma risk. However, sensitivity analyses did not show an association for studies from Europe (OR=1.10; 95%CI=0.95-1.27, p=0.218), studies with low risk of bias (OR=1.15; 95%CI=0.94-1.41, p=0.179), and studies conducted after 1990 (OR 1.09; 95%CI=0.93-1.29, p=0.295). Moreover, moderate associations were found for first exposure to UV radiation from a solarium at younger age (<25 years) and high exposure (>10 sessions in lifetime) with melanoma risk. However, for all outcomes analyzed, overall study quality and resulting levels of evidence (3a-) and grades of recommendation (D) were low due to lack of interventional studies and severe limitations including unobserved or unrecorded confounding.\n Current scientific knowledge is mainly based on observational studies with poor quality data, which report associations but do not prove causality. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk.\n Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.\n\nMärz, Winfried\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n168206\nA novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family.\n\nGlöcklhofer, CR\n\nSteinfurt, J\n\nFranke, G\n\nHoppmann, A\n\nGlantschnig, T\n\nPerez-Feliz, S\n\nAlter, S\n\nFischer, J\n\nBrunner, M\n\nRainer, PP\n\nKöttgen, A\n\nBode, C\n\nOdening, KE\n\nBeiträge in Fachzeitschriften\nISI:000457582800019\n29947763.0\n10.1093/europace/euy127\nNone\nCharacterization of the cardiac phenotype associated with the novel LMNA nonsense mutation c.544C>T, p.Q182*, which we have identified in a large five-generation family.\n A family tree was constructed. Clinical data [arrhythmia, syncope, sudden cardiac death (SCD), New York Heart Association (NYHA) class] were collected from living and deceased family members. DNA of 23 living family members was analysed for mutations in LMNA. Additionally, dilated cardiomyopathy multi-gene-panel testing and whole exome sequencing were performed in some family members to identify potential phenotype-modifiers. In this five-generation family (n = 65), 17 SCDs occurred at 49.3 ± 10.0 years. Furthermore, we identified eight additional mutation-carriers, seven symptomatic (44 ± 13 years), and one asymptomatic (44 years). First signs of disease [sinus bradycardia with atrioventricular (AV)-block I°] occurred at 36.5 ± 8.1 years. Paroxysmal atrial fibrillation (AF) (onset at 41.8 ± 5.7 years) rapidly progressed to permanent AF (46.2 ± 9.8 years). Subsequently, AV-conduction worsened, syncope, pacemaker-dependence, and non-sustained ventricular tachycardia (43.3 ± 8.2 years) followed. Ventricular arrhythmia caused SCD in patients without implantable cardioverter-defibrillator (ICD). Patients protected by ICD developed rapidly progressive heart failure (45.2 ± 10.6 years). A different phenotype was seen in a sub-family in three patients with early onset of rapidly decompensating heart failure and only minor prior arrhythmia-related symptoms. One patient received high-urgency heart transplantation (HTX) at 32 years, while two died prior to HTX. One of them developed lethal peripartum-associated heart failure. Possible disease-modifiers were identified in this 'heart failure sub-family'.\n The novel LMNA nonsense mutation c.544C>T causes a severe arrhythmogenic phenotype manifesting with high incidence of SCD in most patients; and in one sub-family, a distinct phenotype with fast progressing heart failure, indicating the need for early consideration of ICD-implantation and listing for heart-transplantation.\n\nGlantschnig, Theresa\n\nRainer, Peter\n\n\n"
},
{
"text": "\n168600\nGeolocation with respect to personal privacy for the Allergy Diary app - a MASK study.\n\nSamreth, D\n\nArnavielhe, S\n\nIngenrieth, F\n\nBedbrook, A\n\nOnorato, GL\n\nMurray, R\n\nAlmeida, R\n\nMizani, MA\n\nFonseca, J\n\nCosta, E\n\nMalva, J\n\nMorais-Almeida, M\n\nPereira, AM\n\nTodo-Bom, A\n\nMenditto, E\n\nStellato, C\n\nVentura, MT\n\nLarenas-Linnemann, D\n\nFuentes-Pérez, JM\n\nHuerta-Villalobos, YR\n\nCruz, AA\n\nStelmach, R\n\nda Silva, J\n\nEmuzyte, R\n\nKvedariene, V\n\nValiulis, A\n\nAnnesi-Maesano, I\n\nBosse, I\n\nDemoly, P\n\nDevillier, P\n\nFontaine, JF\n\nKuna, P\n\nSamolinski, B\n\nKlimek, L\n\nMösges, R\n\nPfaar, O\n\nShamai, S\n\nBewick, M\n\nRyan, D\n\nSheikh, A\n\nAnto, JM\n\nCardona, V\n\nMullol, J\n\nValero, A\n\nChavannes, NH\n\nFokkens, WJ\n\nReitsma, S\n\nRoller-Wirnsberger, RE\n\nTomazic, PV\n\nHaahtela, T\n\nToppila-Salmi, S\n\nValovirta, E\n\nMakris, M\n\nPapadopoulos, NG\n\nProkopakis, EP\n\nPsarros, F\n\nGemicioğlu, B\n\nYorgancioglu, A\n\nBindslev-Jensen, C\n\nEller, E\n\nKull, I\n\nWickman, M\n\nBachert, C\n\nHellings, PW\n\nPugin, B\n\nBosnic-Anticevich, S\n\nO'Hehir, RE\n\nKolek, V\n\nSova, M\n\nWehner, K\n\nDe Vries, G\n\nvan Eerd, M\n\nLaune, D\n\nWittmann, J\n\nBousquet, J\n\nPoncelet, P\n\nMASK study group\n\nBeiträge in Fachzeitschriften\nISI:000438717200001\n30061979.0\n10.1186/s40413-018-0194-3\nPMC6048852\nCollecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel networK: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data.To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method.\n Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization).\n Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54, 00 (58.5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy.\n k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.\n\nRoller-Wirnsberger, Regina\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n170797\nA Pilot Randomized Trial Assessing the Effect of a Psychoeducational Intervention on Psychoneuroimmunological Parameters Among Patients With Nonmetastatic Breast Cancer.\n\nStanzer, S\n\nAndritsch, E\n\nZloklikovits, S\n\nLadinek, V\n\nFarkas, C\n\nAugustin, T\n\nObermayer-Pietsch, B\n\nSamonigg, H\n\nBauernhofer, T\n\nBeiträge in Fachzeitschriften\nISI:000459591300007\n30489436.0\n10.1097/PSY.0000000000000656\nNone\nThe aim of this study was to determine a potential benefit of the specific psychoeducational intervention "Learning to Live with Cancer" (LTLWC) for patients with operated nonmetastatic breast cancer, with respect to psychological variables and endocrine and immune parameters.\n Fifty-two postmenopausal women with operated stage I to III breast cancer were randomized to either a breast cancer intervention group (BCIG, n = 30) who immediately began participating in the LTLWC intervention program or to a breast cancer control group (BCCG, n = 22). Matched healthy women were asked to participate as a noncancer comparison group (n = 26). All participants were evaluated at three different time points (t1-t3) using a set of standardized questionnaires and blood samples were taken to analyze immune cell subsets and stress hormone levels.\n A significant reduction in trait anxiety/State Trait Anxiety Inventory score was observed in the BCIG (t1: median = 35.0 [interquartile range = 28.0-38.0] versus t3: median = 26.0 [interquartile range = 18.5-37.0], p = .0001) compared with the BCCG (t1: median = 41.0 [interquartile range =32.75-49.0]; t3: median = 38.5 [interquartile range = 30.75-46.5], p = .01524; p interaction = .001). In parallel, a significant rise of serotonin levels (t1: median = 66.5 ng/ml [interquartile range = 11.50-106.00] versus t3: median = 80.5 ng/ml [interquartile range =59.00-118.00], p = .00008) as well as a significant reduction of the elevated number of Treg cells at baseline (t1: median = 4.45% [interquartile range = 4.00-5.33] versus t3: median = 2.80% [interquartile range = 2.68-3.13], p < .00001) were observed in the BCIG versus no change in the BCCG. A significant statistical association between reduced trait anxiety and decreased Treg cell number could be demonstrated in the BCIG (r = .62, p < .01).\n The observed results of this study provide preliminary support for the efficacy of the LTLWC program in significantly improving psychoneuroimmunological parameters in patients with nonmetastatic breast cancer.\n\nAndritsch, Elisabeth\n\nBauernhofer, Thomas\n\nFarkas, Clemens\n\nObermayer-Pietsch, Barbara\n\nSamonigg, Hellmut\n\nStanzer, Stefanie\n\n\n"
},
{
"text": "\n181413\nMulticenter Evaluation of Circulating Cell-Free DNA Extraction and Downstream Analyses for the Development of Standardized (Pre)analytical Work Flows\n\nLampignano, R\n\nNeumann, MHD\n\nWeber, S\n\nKloten, V\n\nHerdean, A\n\nVoss, T\n\nGroelz, D\n\nBabayan, A\n\nTibbesma, M\n\nSchlumpberger, M\n\nChemi, F\n\nRothwell, DG\n\nWikman, H\n\nGalizzi, J-P\n\nBergheim, IR\n\nRussnes, H\n\nMussolin, B\n\nBonin, S\n\nVoight, C\n\nMusa, H\n\nPinzani, P\n\nLianidou, E\n\nBrady, G\n\nSpeicher, MR\n\nPantel, K\n\nBetsou, F, Schuuring, E\n\nKubista, M\n\nAmmerlaan, W\n\nSprenger-Haussels, M\n\nSchlange, T\n\nHeitzer, E\n\nBeiträge in Fachzeitschriften\nISI:000514384200027\n31628139.0\n10.1373/clinchem.2019.306837\nNone\nIn cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived DNA (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, which challenges downstream applications. Therefore, established preanalytical work flows in combination with cost-efficient and reproducible reference materials for ccfDNA analyses are crucial for analytical validity and subsequently for clinical decision-making.\n We describe the efforts of the Innovative Medicines Initiative consortium CANCER-ID (http://www.cancer-id.eu) for comparing different technologies for ccfDNA purification, quantification, and characterization in a multicenter setting. To this end, in-house generated mononucleosomal DNA (mnDNA) from lung cancer cell lines carrying known TP53 mutations was spiked in pools of plasma from healthy donors generated from 2 different blood collection tubes (BCTs). ccfDNA extraction was performed at 15 partner sites according to their respective routine practice. Downstream analysis of ccfDNA with respect to recovery, integrity, and mutation analysis was performed centralized at 4 different sites.\n We demonstrate suitability of mnDNA as a surrogate for ccfDNA as a process quality control from nucleic acid extraction to mutation detection. Although automated extraction protocols and quantitative PCR-based quantification methods yielded the most consistent and precise results, some kits preferentially recovered spiked mnDNA over endogenous ccfDNA. Mutated TP53 fragments derived from mnDNA were consistently detected using both next-generation sequencing-based deep sequencing and droplet digital PCR independently of BCT.\n This comprehensive multicenter comparison of ccfDNA preanalytical and analytical work flows is an important contribution to establishing evidence-based guidelines for clinically feasible (pre)analytical work flows.\n © 2019 American Association for Clinical Chemistry.\n\nHeitzer, Ellen\n\nSpeicher, Michael\n\nWeber, Sabrina\n\n\n"
},
{
"text": "\n185385\nFate of the syndesmotic screw--Search for a prudent solution.\n\nKaftandziev, I\n\nSpasov, M\n\nTrpeski, S\n\nZafirova-Ivanovska, B\n\nBakota, B\n\nBeiträge in Fachzeitschriften\nNone\n26582218.0\n10.1016/j.injury.2015.10.062\nNone\nAnkle fractures are common injuries. Since the recognition of the importance of syndesmotic injury in ankle fractures, much of the scientific work has been focused on concomitant syndesmotic injury. Despite the invention of novel devices for restoration and maintenance of the congruent syndesmosis following syndesmotic injury, the metallic syndesmotic screw is still considered to be the "gold standard". The aim of this study was to compare the clinical results in patients who retained the syndesmosis screw with those in whom the screw was removed following open reduction and internal fixation of the malleolar fracture associated with syndesmosis disruption.\n This was a retrospective study of 82 patients. Minimum follow-up was 12 months. Clinical evaluation included American Orthopaedic Foot and Ankle Society (AOFAS) score and Visual Analogue Scale (VAS) for patient general satisfaction. The condition of the screw (removed, intact or broken), presence of radiolucency around the syndesmotic screw and the tibiofibular clear space were recorded using final follow-up radiographs.\n Three cortices were engaged in 66 patients (80%) and quadricortical fixation was performed in the remaining 16 patients (20%). The number of engaged cortices did not correlate with the clinical outcome and screw fracture. A single syndesmotic screw was used in 71 patients (86%. The mean AOFAS score in the group with intact screw (I) was 83; the scores in the group with broken screw (B) and removed screw (R) were 92.5 and 85.5, respectively. There was a statistically significant difference between the three groups: this was due to the difference between groups I and B; the difference between groups I and R and groups B and R were not statistically significant. There were no statistically significant differences in VAS results.\n There were no statistically significant differences in clinical outcome between the group with the screw retained and the group in which the screw was removed; however, the group with broken screws had the best clinical outcome based on AOFAS score. Widening of the syndesmosis after screw removal was not evident. We do not recommend routine syndesmosis screw removal.\n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n6292\nLeft ventricular remodeling after infarction: sequential MR imaging with oral nicorandil therapy in rat model.\n\nSaeed, M\n\nWatzinger, N\n\nKrombach, GA\n\nLund, GK\n\nWendland, MF\n\nChujo, M\n\nHiggins, CB\n\nBeiträge in Fachzeitschriften\nISI:000177621700032\n12202722.0\n10.1148/radiol.2243011372\nNone\nPURPOSE: To use magnetic resonance (MR) imaging in quantification of the short- and long-term effects of therapy with orally administered nicorandil on left ventricular (LV) geometry and function independent of infarction size. MATERIALS AND METHODS: Forty-six rats were subjected to reperfused infarction and randomly divided into two groups. Group 1 rats (n = 21) were treated with nicorandil (3 mg/kg/day in drinking water) for 4 days before infarction and 8 weeks after infarction (hereafter, the nicorandil group). Group 2 rats (n = 25) received tap water for the same period and served as the control group. Mesoporphyrin- (as a necrosis-specific agent) enhanced MR imaging was used to define necrotic myocardium on day 2 after infarction in all 46 animals. Contrast material-enhanced MR images showed large but identical infarction size in 11 control and 11 nicorandil rats. Only these 22 rats underwent repeat MR imaging at 8 weeks after infarction. The following variables were measured: LV volumes, ejection fraction, mass, wall thickness, and infarction size. Student t test and analysis of variance for repeated measurements were used for statistical analysis. RESULTS: The size of the necrotic region on mesoporphyrin-enhanced MR images was 39% +/- 3 of the size of the left ventricle in the control group and 41% +/- 2 in the nicorandil group (difference not significant, unpaired Student t test). Pretreatment with nicorandil for 6 days before imaging did not reduce LV dilation or improve function compared with those in control animals with identical infarction size. Eight weeks after infarction, control animals showed deterioration in LV function, wall thinning, and gradient in regional dysfunction (analysis of variance test). Nicorandil produced significant salutary effects on LV ejection fraction (37% +/- 3 in the nicorandil group vs 24% +/- 3 in the control group), end-diastolic volume (0.53 mL +/- 0.03 vs 0.65 mL +/- 0.04), end-systolic volume (0.36 mL +/- 0.03 vs 0.49 mL +/- 0.05), LV wall thickening in remote noninfarcted myocardium (28% +/- 2 vs 19% +/- 1), and a rim of infarction (16% +/- 2 vs 8% +/- 1) (P \n\nWatzinger, Norbert\n\n\n"
},
{
"text": "\n50103\nCoordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids.\n\nZollner, G\n\nWagner, M\n\nMoustafa, T\n\nFickert, P\n\nSilbert, D\n\nGumhold, J\n\nFuchsbichler, A\n\nHalilbasic, E\n\nDenk, H\n\nMarschall, HU\n\nTrauner, M\n\nBeiträge in Fachzeitschriften\nISI:000236663300010\n16357057.0\n10.1152/ajpgi.00490.2005\nNone\nThe bile acid receptor farnesoid X receptor (FXR) is a key regulator of hepatic defense mechanisms against bile acids. A comprehensive study addressing the role of FXR in the coordinated regulation of adaptive mechanisms including biosynthesis, metabolism, and alternative export together with their functional significance is lacking. We therefore fed FXR knockout (FXR(-/-)) mice with cholic acid (CA) and ursodeoxycholic acid (UDCA). Bile acid synthesis and hydroxylation were assessed by real-time RT-PCR for cytochrome P-450 (Cyp)7a1, Cyp3a11, and Cyp2b10 and mass spectrometry-gas chromatography for determination of bile acid composition. Expression of the export systems multidrug resistance proteins (Mrp)4-6 in the liver and kidney and the recently identified basoalteral bile acid transporter, organic solute transporter (Ost-alpha/Ost-beta), in the liver, kidney, and intestine was also investigated. CA and UDCA repressed Cyp7a1 in FXR(+/+) mice and to lesser extents in FXR(-/-) mice and induced Cyp3a11 and Cyp2b10 independent of FXR. CA and UDCA were hydroxylated in both genotypes. CA induced Ost-alpha/Ost-beta in the liver, kidney, and ileum in FXR(+/+) but not FXR(-/-) mice, whereas UDCA had only minor effects. Mrp4 induction in the liver and kidney correlated with bile acid levels and was observed in UDCA-fed and CA-fed FXR(-/-) animals but not in CA-fed FXR(+/+) animals. Mrp5/6 remained unaffected by bile acid treatment. In conclusion, we identified Ost-alpha/Ost-beta as a novel FXR target. Absent Ost-alpha/Ost-beta induction in CA-fed FXR(-/-) animals may contribute to increased liver injury in these animals. The induction of bile acid hydroxylation and Mrp4 was independent of FXR but could not counteract liver toxicity sufficiently. Limited effects of UDCA on Ost-alpha/Ost-beta may jeopardize its therapeutic efficacy.\n\nDenk, Helmut\n\nFickert, Peter\n\nMoustafa, Tarek\n\nSilbert-Wagner, Dagmar\n\nSommer, Judith\n\nWagner, Martin\n\nZollner, Gernot\n\n\n"
}
]
}