tbuckley/cabot-search huggingface dataset:
Analysis of Liver Transplantation
Authors: Thomas E. Starzl, Shunzaburo Iwatsuki, Byers W. Shaw, David H. Van Thiel, J.Carlton Gartner, Basil J. Zitelli, Jeffrey J. Malatack, Robert R. Schade
Journal: Hepatology (1984)

To be a service, a new surgical procedure must be within the capability of more than the occasional surgeon.In addition, the indications for its use should be clear, and the results should be good enough to justify the effort and expense.In this communication, we will indicate that orthotopic liver transplantation has met all three of these criteria. MATERIALS AND METHODSTwo hundred and ninety-six patients were treated from March, 1963 through April, 1983.Until the end of 1979, "conventional" immunosuppression was used with azathioprine and prednisone to which antilymphocytic globulin was usually added (1, 2).In 16 patients treated in 1971 and 1972, cyclophosphamide was substituted for azathioprine.From early 1980 onward, immunosuppression was with cyclosporine and steroids.The surgical and medical techniques have been described elsewhere (1,2).The results were analyzed before and after the introduction of cyclosporine-steroid therapy.In the post-1980 era, we studied a greatly expanded volume of cases, the use of veno-venous bypasses with and without heparin, and the systematic training of younger surgeons whose objective could be to set up new centers.In all of the case material, the influence of original disease upon the results also was examined. RESULTS SURVIVAL WITH CONVENTIONALIMMUNOSUPPRESSION (1963)(1964)(1965)(1966)(1967)(1968)(1969)(1970)(1971)(1972)(1973)(1974)(1975)(1976)(1977)(1978)(1979) From 1963 to the end of 1979, 170 consecutive patients were treated; which is an average case load of less than 12 per year.Fifty-six (32.9%) recipients lived for at least 1 year, and 32 (18.8%) are still alive with follow-up of 31f2 to 13 1 12 years.Six of the residual group are more than
C-Reactive Protein in Heart Failure
Authors: Inder S. Anand, Roberto Latini, Viorel G. Florea, Michael A. Kuskowski, Thomas Rector, Serge Masson, Stefano Signorini, Paolo Mocarelli, Allen Hester, Robert Glazer, Jay N. Cohn
Journal: Circulation (2005)

Background— The role of C-reactive protein (CRP) in heart failure is not well studied. We assessed the prognostic value of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CRP that were associated with valsartan. Methods and Results— Characteristics of patients with baseline CRP levels above and below the median value were compared. Univariable and multivariable Cox proportional hazards regression models were used to examine the relationship of CRP to mortality and morbidity. Interactions were tested to determine whether differences in CRP changes from baseline to 4 and 12 months between groups randomly assigned to valsartan or placebo depended on baseline ACE inhibitor use. Median plasma CRP was 3.23 mg/L (interquartile range 1.42 to 7.56 mg/L), which is higher than in the general population. Patients with CRP above the median had features of more severe heart failure than those with CRP levels below the median. The cumulative likelihood of death and first morbid event increased with increasing quartile of CRP. Relative to the lowest CRP quartile, the risk of mortality (hazard ratio 1.51, 95% CI 1.2 to 1.9) and first morbid event (hazard ratio 1.53, 95% CI 1.28 to 1.84) was increased in the highest CRP quartile in multivariable models. CRP added incremental prognostic information to that provided by brain natriuretic peptide alone. CRP did not change significantly over time in the placebo group; however, after 12 months, valsartan was associated with a decrease in CRP in patients not receiving ACE inhibitors but not in those receiving ACE inhibitors at 12 months. Conclusions— CRP is increased in heart failure. Higher levels are associated with features of more severe heart failure and are independently associated with mortality and morbidity. The ability of treatments to reduce CRP levels and the prognostic importance of reducing CRP require further study.
Association of Left-Heart Dysfunction with Severe Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Fekri Abroug, Lamia Ouanes-Besbes, Noureddine Nciri, Noura Sellami, Faouzi Addad, Khaldoun Ben Hamda, Adel Ben Amor, Mohamed F. Najjar, Jalel Knani
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Cardiac biomarkers are used to distinguish acute dyspnea due to left-heart dysfunction from that of pulmonary origin. However, they have not been assessed in the specific setting of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), where they might be released without left-heart impairment.To assess the accuracy of troponin T and of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD associated with left ventricular (LV) dysfunction.Both biomarkers were measured in 148 consecutive patients on intensive care unit admission for AECOPD. A panel of physicians adjudicated blindly the cause of AECOPD to be unlikely, possibly associated, or definitely associated with LV dysfunction.The final diagnosis was AECOPD definitely associated with acute left-heart dysfunction in 31.1%, possibly associated with LV dysfunction in 13.5%, and probably not associated with LV dysfunction in 55.4%. Both NT-proBNP and troponin T levels were significantly different among the three groups. The area under the receiver operating characteristic curve was greater for NT-proBNP (0.95 vs. 0.67). A cutoff of 1,000 pg/ml was accurate to rule out left-heart involvement in AECOPD (sensitivity, 94%; negative predictive value, 94%; negative likelihood ratio, 0.08). A cutoff of 2,500 pg/ml had the best operating characteristics to rule in the diagnosis (positive likelihood ratio, 5.16). Left-heart involvement in AECOPD was the only variable independently associated with increased secretion of NT-proBNP (odds ratio, 74; 95% confidence interval, 15-375; p = 0.0001).NT-proBNP and troponin T are useful in excluding AECOPD associated with left ventricular dysfunction. NT-proBNP was the more accurate of the two.
Effect of Exposure to Good vs Poor Medical Trainee Performance on Attending Physician Ratings of Subsequent Performances
Authors: Peter Yeates, Paul O’Neill, Karen Mann, Kevin W. Eva
Journal: JAMA (2012)

Competency-based models of education require assessments to be based on individuals' capacity to perform, yet the nature of human judgment may fundamentally limit the extent to which such assessment is accurately possible.To determine whether recent observations of the Mini Clinical Evaluation Exercise (Mini-CEX) performance of postgraduate year 1 physicians influence raters' scores of subsequent performances, consistent with either anchoring bias (scores biased similar to previous experience) or contrast bias (scores biased away from previous experience).Internet-based randomized, blinded experiment using videos of Mini-CEX assessments of postgraduate year 1 trainees interviewing new internal medicine patients. Participants were 41 attending physicians from England and Wales experienced with the Mini-CEX, with 20 watching and scoring 3 good trainee performances and 21 watching and scoring 3 poor performances. All then watched and scored the same 3 borderline video performances. The study was completed between July and November 2011.The primary outcome was scores assigned to the borderline videos, using a 6-point Likert scale (anchors included: 1, well below expectations; 3, borderline; 6, well above expectations). Associations were tested in a multivariable analysis that included participants' sex, years of practice, and the stringency index (within-group z score of initial 3 ratings).The mean rating scores assigned by physicians who viewed borderline video performances following exposure to good performances was 2.7 (95% CI, 2.4-3.0) vs 3.4 (95% CI, 3.1-3.7) following exposure to poor performances (difference of 0.67 [95% CI, 0.28-1.07]; P = .001). Borderline videos were categorized as consistent with failing scores in 33 of 60 assessments (55%) in those exposed to good performances and in 15 of 63 assessments (24%) in those exposed to poor performances (P < .001). They were categorized as consistent with passing scores in 5 of 60 assessments (8.3%) in those exposed to good performances compared with 25 of 63 assessments (39.5%) in those exposed to poor performances (P < .001). Sex and years of attending practice were not associated with scores. The priming condition (good vs poor performances) and the stringency index jointly accounted for 45% of the observed variation in raters' scores for the borderline videos (P < .001).In an experimental setting, attending physicians exposed to videos of good medical trainee performances rated subsequent borderline performances lower than those who had been exposed to poor performances, consistent with a contrast bias.
Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications
Authors: Wei Wang, Subhasree Nag, Xu Zhang, Ming‐Hai Wang, Hui Wang, Jianwei Zhou, Ruiwen Zhang
Journal: Medicinal Research Reviews (2014)

Abstract Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins (RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs–MDM2 interactions, resulting in p53‐dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53‐independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.
The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts
Authors: Tatsuya Yoshizawa, Eiichi Hinoi, Dae Young Jung, Daisuke Kajimura, Mathieu Ferron, Jin Seo, Jonathan M. Graff, Jason K. Kim, Gerard Karsenty
Journal: Journal of Clinical Investigation (2009)

The recent demonstration that osteoblasts have a role in controlling energy metabolism suggests that they express cell-specific regulatory genes involved in this process. Activating transcription factor 4 (ATF4) is a transcription factor that accumulates predominantly in osteoblasts, where it regulates virtually all functions linked to the maintenance of bone mass. Since Atf4-/- mice have smaller fat pads than littermate controls, we investigated whether ATF4 also influences energy metabolism. Here, we have shown, through analysis of Atf4-/- mice, that ATF4 inhibits insulin secretion and decreases insulin sensitivity in liver, fat, and muscle. Several lines of evidence indicated that this function of ATF4 occurred through its osteoblastic expression. First, insulin sensitivity is enhanced in the liver of Atf4-/- mice, but not in cultured hepatocytes from these mice. Second, mice overexpressing ATF4 in osteoblasts only [termed here alpha1(I)Collagen-Atf4 mice] displayed a decrease in insulin secretion and were insulin insensitive. Third, the alpha1(I)Collagen-Atf4 transgene corrected the energy metabolism phenotype of Atf4-/- mice. Fourth, and more definitely, mice lacking ATF4 only in osteoblasts presented the same metabolic abnormalities as Atf4-/- mice. Molecularly, ATF4 favored expression in osteoblasts of Esp, which encodes a product that decreases the bioactivity of osteocalcin, an osteoblast-specific secreted molecule that enhances secretion of and sensitivity to insulin. These results provide a transcriptional basis to the observation that osteoblasts fulfill endocrine functions and identify ATF4 as a regulator of most functions of osteoblasts.
Oxygenation Index Predicts Outcome in Children with Acute Hypoxemic Respiratory Failure
Authors: Daniel Trachsel, Brian W. McCrindle, Satoshi Nakagawa, Desmond Bohn
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

To define outcome and time dependence of predictors of outcome in pediatric acute hypoxemic respiratory failure, 131 patients (age range, 1 month to 18 years) were prospectively followed. Parametric models were used to describe time-related events, and competing risks analysis was performed for mortality estimates. Multiple logistic analysis was applied to describe time-related predictors of ventilation time and mortality. Overall mortality was 27%. Peak oxygenation index (OI) measured at any time point (p < 0.001, 91% reliability in bootstrapping, after inverse transformation) and Pediatric Risk of Mortality, or PRISM, score within the first 12 hours of mechanical ventilation (p < 0.001, 63% reliability in bootstrapping, after square transformation) were identified as independent predictors of mortality. Peak OI, younger age, and need for renal replacement therapy were significantly associated with a longer time to extubation. Although OI was less reliable as outcome predictor within the first 12 hours of intubation, it still predicted duration of mechanical ventilation. No clear-cut threshold of OI was identified that could accurately predict mortality. Survival was characterized by a peak rate of extubations at approximately 1 week, with a more gradual decline thereafter, whereas death appeared as a constant risk over time, which exceeded chances of survival at approximately 4 weeks. Severity of oxygenation failure at any point in time during acute hypoxemic respiratory failure correlates with duration of mechanical ventilation and mortality. This is best reflected by the OI, which shows a direct correlation to outcome in a time-independent manner.
Clinical and economic consequences of dyspepsia in the community
Authors: P Moayyedi, J Mason
Journal: Gut (2002)

Dyspepsia is a common problem where many sufferers do not seek healthcare. The clinical impact of the condition in the community and the economic costs were assessed using data from a large cross sectional survey. Dyspepsia may be costing society £1 billion each year in the UK. Thus dyspepsia is a huge clinical and economic burden and cost effective management strategies and treatments are urgently required.
Efficacy and safety of ipilimumab in patients with pre-treated, uveal melanoma
Authors: M. Maio, R. Danielli, V. Chiarion-Sileni, J. Pigozzo, G. Parmiani, R. Ridolfi, F. De Rosa, M. Del Vecchio, L. Di Guardo, P. Queirolo, V. Picasso, P. Marchetti, F. De Galitiis, M. Mandalà, M. Guida, E. Simeone, P.A. Ascierto
Journal: Annals of Oncology (2013)
Adenosine-Supplemented Blood Cardioplegia Attenuates Postischemic Dysfunction After Severe Regional Ischemia
Authors: V. H. Thourani, R. S. Ronson, D. G.L. Van Wylen, S. T. Shearer, S. L. Katzmark, Z.-Q. Zhao, D. C. Han, R. A. Guyton, J. Vinten-Johansen
Journal: Circulation (1999)

Various studies have reported that the administration of adenosine (ADO) in cardioplegia reduces myocardial ischemic injury, but this timing may not utilize ADO's potential against myocardial reperfusion injury. This study tested the hypothesis that ADO-supplemented blood cardioplegia (BCP) or ADO administered during reperfusion reduces postischemic dysfunction after severe regional ischemia.After 75 minutes of left anterior descending coronary artery occlusion, total cardiopulmonary bypass was initiated; cold (4 degrees C) antegrade BCP (8:1 blood:crystalloid) was delivered every 20 minutes for the first 3 doses, and 27 degrees C BCP was delivered for the terminal infusion. Dogs (n=6 per group) received unsupplemented BCP, ADO (100 micromol/L/L) supplemented in all infusions of BCP (ADO-CP), or ADO (100 micromol x L(-1) x L(-1)) supplemented only in the terminal infusion of BCP followed by intravenous ADO (140 microg x kg(-1) x min(-1)) infusion for the first 30 minutes of reperfusion (ADO-R). Postischemic regional systolic shortening was significantly greater in the ADO-R group (5+/-2.0%) than in the BCP group (-3+/-1.0%), but not in the ADO-CP group (2+/-0.2%). Postischemic regional diastolic stiffness in the area at risk during end reperfusion was lower with ADO-R (1.8+/-0.3%) than with ADO-CP (2.7+/-0.3%) or BCP (4.4+/-0.5%). Infarct size was reduced in the ADO-CP (29+/-2%) and ADO-R (21+/-2%) groups compared with the BCP group (42+/-4%). Edema in the myocardial area at risk was decreased in the ADO-CP (82+/-0.2%) and ADO-R (80+/-0.4%) groups compared with the BCP group (86+/-0.7%). Adherence of fluorescently labeled neutrophils (PMNs) to postischemic coronary artery endothelium was attenuated by ADO-R (55+/-2 PMNs/mm(2)), but not by ADO-CP (114+/-5 PMNs/mm(2)), compared with BCP (118+/-3 PMNs/mm(2)).The results show that BCP supplemented with ADO reduces infarct size, preserves postischemic systolic and diastolic regional function but does not attenuate coronary artery endothelial dysfunction unless administered during reperfusion.
Protein kinases in human leukemic cells
Authors: F. Phan‐Dinh‐Tuy, J. Henry, C. Boucheix, J. Y. Perrot, C. Rosenfeld, A. Kahn
Journal: American Journal of Hematology (1985)

Abstract Protein kinase activities and cyclic AMP binding capacity were investigated in human peripheral blood cells from leukemic patients and normal controls. Using [γ 32 P] ATP as phosphoryldonor, the phosphorylating activities were not found to be significantly different in either normal or leukemic cells when measured on both artificial basic and acidic substrates. In contrast, the GTP‐dependent casein kinase activity, CK2, which is almost undetectable in normal granulocytes, was markedly increased in highly proliferating myeloblastic cells from patients with acute myelogenous leukemia (AML) or with chronic myelogenous leukemia in blastic crisis (BC‐CML). Levels of endogenous phosphotyrosine were not higher in leukemic cells than in normal peripheral lymphocytes or granulocytes. Finally, cAMP binding capacity was found to be increased in several types of proliferating leukemic cells, due to a higher amount of the R1‐type regulatory subunit of the cAMP‐dependent protein kinases. Specific patterns of cAMP binding proteins observed in the different types of normal blood cells were rather blurred in leukemic cells. In conclusion, modifications observed in human leukemic cells seem to be more related to proliferation or blockage in normal differentiation than to their cellular origin.
A Reevaluation of CD22 Expression in Human Lung Cancer
Authors: Laurentiu M. Pop, Stephen Barman, Chunli Shao, Jonathan C. Poe, Guglielmo M. Venturi, John M. Shelton, Iliodora V. Pop, David E. Gerber, Luc Girard, Xiao-yun Liu, Carmen Behrens, Jaime Rodriguez-Canales, Hui Liu, Ignacio I. Wistuba, James A. Richardson, John D. Minna, Thomas F. Tedder, Ellen S. Vitetta
Journal: Cancer Research (2014)

Abstract CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22+ Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22+ Daudi cells expressed high levels of CD22 mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non–small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins. Cancer Res; 74(1); 263–71. ©2014 AACR.
Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma
Authors: Martina Sanlorenzo, Aditi Choudhry, Igor Vujic, Christian Posch, Kim Chong, Katia Johnston, Melissa Meier, Simona Osella-Abate, Pietro Quaglino, Adil Daud, Alain Algazi, Klemens Rappersberger, Susana Ortiz-Urda
Journal: Journal of the American Academy of Dermatology (2014)
Safety and Efficacy of Regorafenib in Japanese Patients with Metastatic Colorectal Cancer: A Subgroup Analysis of the Phase III Correct Trial
Authors: Y. Yamada, T. Yoshino, Y. Komatsu, K. Yamazaki, A. Tsuji, T. Ura, A. Grothey, E. Van Cutsem, A. Wagner, A. Ohtsu
Journal: Annals of Oncology (2013)
Protracted Pressor Response to Angiotensin After Bilateral Nephrectomy in Rats
Authors: Edward H. Gabelman, Paul A. Rondell
Journal: Circulation Research (1966)

The pressor response of nephrectomized rats to an injection of renin is marked by a prolonged stable plateau. A similar, prolonged response to angiotensin has been demonstrated and the following aspects of this pressor effect were evaluated. 1. The protracted response was shown not to be due to a persistence of angiotensin in the blood of nephrectomized animals. There are several indications from unrelated studies that angiotensin is destroyed rapidly. Cross-circulation experiments indicate that during the protracted pressor phase blood levels of constrictor materials have fallen to undetectably low levels. 2. No evidence could be obtained to indicate that the neurogenic buffer system is involved in the development of the protracted response. Ganglionic blockade was ineffective in preventing its development. 3. The hemodynamic basis for the response must be a persistent increase in total peripheral resistance (TPR) since there is no increase in cardiac output (CO) in response to the angiotensin infusion. Before infusion, the CO of nephrectomized animals is higher than that of sham-operated control animals. 4. The increase in TPR must be due to an increase in geometric hindrance for no changes in hematocrit or in viscosity result from angiotensin infusion. Blood viscosity is lower in nephrectomized than in sham-operated animals, but this can account for only part of the lower pre-injection control pressure seen in this group. It appears that in animals depleted of endogenous renin, a large infusion of angiotensin increases vascular resistance by some non-neurogenic, non-humoral mechanism which may represent another type of vascular tone.