tbuckley/cabot-search huggingface dataset:
Penicillin Therapy and Haemolytic Anaemia
Authors: W. Weiner
Journal: BMJ (1966)

BRffisH associated with R.A. was observed in this small group.This suggests that the gradings for E.A. do not describe a continuous distribution, as their numerical sequence would suggest, but that there may be important qualitative differ- ences that have not been recognized-in other words, that E.A. is heterogeneous and con- sists of more than one different condition.In this context it is noteworthy that the majority of differences in the prevalence of E.A. between surveys conducted in different parts of the world have been found in those with mild rather than with severe changes.'The gradings of I.P. may be subject to analogous shortcomings.It is tempting to suggest that the group in the population with E.A. coincident in hands and feet and corre- lative I.P. and rheumatoid factor correspond to the disease R.A. in hospital patients, but the point cannot be established with certainty without fresh surveys specifically designed to examine this idea.Those with milder degrees of I.P. and E.A. are challenging problems, but their relation to R.A., if any, can be established only by further prospective studies.None of this affects the fundamental suggestions about the possible basis for disease complications made by Drs.Burch and Rowell, although the applicability of these ideas to R.A. would thus appear to be premature at the present time.It is right and proper to study both ends of the disease spectrum simultaneously, the established case in hospital and the person in the population with mild abnormalities, and Dr. Burch deserves our gratitude for reminding us that our function is not just to gather data but also to seek imaginatively for the fundamental significance of what we do find.Neverthe- less, I for one am reluctant to construct a model that joins together the two ends of the spectrum until we have improved the quality of the evidence that is to be applied in this manner.
CHOLECYSTOGRAPHY: AN ANALYSIS OF 137 CASES SHOWING THE RELIABILITY OF THE ORAL METHOD
Authors: T. G. Hardman
Journal: BMJ (1929)

CONCLUSION.In conclusion we may urge two points, the recognition of which seems to uis to be of paramount importance in the consideration of the treatmenet of malignant disease Mwith lead at the present time.First, no one in his senses would care to suggest that tlle possession of a knife alnd a few instruments is all that is r eqiuired for the surgical cure of cancer of the stomach.Yet some seem to think that for lead therapy in this disease all that is required is that lead shall be pumped into the veins of the sufferer.We now realize that it was not the fault of radium that it was of so little clinical use twenty years ago.Second, the scientifically minded inquirer will not, demand thlat a new method of treatment for cancer operating on the worst and most advanced types of cases shall give far better initial statistical results than those obtainable with other long-established and standardized forms of treatmen't acting on early and selected cases; but, if it should do so, those capable of appraising evidential values will appreciate the vast possibilities that await full and proper development of the method tested.I have to thank my colleagues Dr. Leslie Cunningham, Mr. J. B. Oldham, Dr. S. B. Herd, and Dr
Gene Expression Profiling in Multiple Myeloma—Reporting of Entities, Risk, and Targets in Clinical Routine
Authors: Tobias Meißner, Anja Seckinger, Thierry Rème, Thomas Hielscher, Thomas Möhler, Kai Neben, Hartmut Goldschmidt, Bernard Klein, Dirk Hose
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single “meta” risk stratification. Experimental Design: The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). Results: The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression–based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. Conclusion: GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. Clin Cancer Res; 17(23); 7240–7. ©2011 AACR.
The telecardiology revolution: improving the management of cardiac disease in primary care
Authors: Warren Backman, Daniel Bendel, Roby Rakhit
Journal: Journal of the Royal Society of Medicine (2010)

Summary Telecardiology allows for the remote specialist interpretation of electrocardiographic recordings via telephone transmission. It has the potential to change the way cardiac care is being delivered in the primary care setting. This review discusses the current status of cardiac care in the community, and highlights how telecardiology can help support general practitioners in the diagnosis and management of acute and chronic cardiac disease, as well as provide the potential for screening opportunities in particular patients at risk. Also reviewed is the success of recent trials of a telecardiology service in the north west of England. Thanks to developments in technology and ever decreasing costs, telecardiology has the potential to save time, money and lives. Telecardiology, it would seem, is set to revolutionize cardiac care in the community, making savings and bridging the gap between primary and secondary care.
PRECISION IN PSYCHOANALYSIS
Authors: N. S. LEHRMAN
Journal: American Journal of Psychiatry (1960)

Scientific precision has far too often been consciously excluded from classical psychoanalysis, because Freud rejected it. In consequence, classical psychoanalysis has assumed many of the trappings of a religion, and lost many of the essential characteristics of a science. Two anti-scientific trends in the field, defensive secrecy and arrogant "elitism," seem to have occurred in part as a result of perpetuation of this lack of precision.
ATRIAL-BASED PACING ALGORITHMS ARE NOT HEMODYNAMICALLY OPTIMAL FOR PATIENTS WITH FIRST DEGREE ATRIOVENTRICULAR BLOCK RECEIVING DUAL CHAMBER PACEMAKERS FOR SYMPTOMATIC BRADYCARDIA
Authors: Isabel Josephine Boero, Varuna Gadiyaram, Hiro Kawata, Ajit Raisinghani, Gregory Feld, Ulrika Green, Navinder Sawhney
Journal: Journal of the American College of Cardiology (2013)
Early T Cell Activation: Integrating Biochemical, Structural, and Biophysical Cues
Authors: Bernard Malissen, Pierre Bongrand
Journal: Annual Review of Immunology (2015)

T cells carry out the formidable task of identifying small numbers of foreign antigenic peptides rapidly and specifically against a very noisy environmental background of endogenous self-peptides. Early steps in T cell activation have thus fascinated biologists and are among the best-studied models of cell stimulation. This remarkable process, critical in adaptive immune responses, approaches and even seems to exceed the limitations set by the physical laws ruling molecular behavior. Despite the enormous amount of information concerning the nature of molecules involved in the T cell antigen receptor (TCR) signal transduction network, and the description of the nanoscale organization and real-time analysis of T cell responses, the general principles of information gathering and processing remain incompletely understood. Here we review currently accepted key data on TCR function, discuss the limitations of current research strategies, and suggest a novel model of TCR triggering and a few promising ways of going further into the integration of available data.
New Approaches to Controlling Health Care Costs
Authors: David Lieberman, John Allen
Journal: JAMA Internal Medicine (2015)

26. Wooldridge J. Econometric Analysis of Cross Section and Panel Data. 2nd ed. Cambridge,MA:MIT Press; 2010. 27. Tu H, Felland L, Ginsburg PB, Liebhaber A, Cohen G, Kemper N. Sacramento: Powerful Hospital SystemsDominate a StableMarket. California Healthcare Foundation; July 2009. http://www.chcf .org/~/media/MEDIA%20LIBRARY%20Files/PDF/A /PDF%20AlmanacRegMktBriefSacramento09.pdf. Accessed July 24, 2015.
Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization
Authors: Michael J. Randles, Adrian S. Woolf, Jennifer L. Huang, Adam Byron, Jonathan D. Humphries, Karen L. Price, Maria Kolatsi-Joannou, Sophie Collinson, Thomas Denny, David Knight, Aleksandr Mironov, Toby Starborg, Ron Korstanje, Martin J. Humphries, David A. Long, Rachel Lennon
Journal: Journal of the American Society of Nephrology (2015)

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.
A gene-expression signature can quantify the degree of hepatic fibrosis in the rat
Authors: Tohru Utsunomiya, Masahiro Okamoto, Masaji Hashimoto, Keiji Yoshinaga, Takeshi Shiraishi, Fumiaki Tanaka, Koshi Mimori, Hiroshi Inoue, Goro Watanabe, Graham F. Barnard, Masaki Mori
Journal: Journal of Hepatology (2004)
Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt/β-catenin signaling in human hepatocellular carcinoma
Authors: Xian-Cheng Zeng, Fo-Qiu Liu, Rong Yan, Hui-Min Yi, Tong Zhang, Guo-Ying Wang, Yang Li, Nan Jiang
Journal: Molecular Cancer (2014)

Wnt/β-catenin signaling pathway plays important roles in human cancer progression. Better understanding the mechanism underlying regulation of Wnt/β-catenin signaling pathway might provide novel therapeutic targets for cancer treatment. miR-610 expression levels in hepatocellular carcinoma (HCC) cell lines, HCC tissues and 76 archived HCC specimens were determined using real-time PCR. Cell viability was measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. The level of DNA synthesis was determined by BrdU incorporation assay. Flow cytometry analysis was used to analyze cell cycle progression. The cells proliferation and tumorigenesis were determined by colony formation and anchorage-independent growth assays in vitro, and by xenograft tumors in vivo. Luciferase assay and micro-ribonucleoprotein complex immunoprecipitation assay were used to confirm the association of the targeted mRNAs with miR-610. miR-610 was downregulated in human HCC cells and tissues, and correlated with HCC progression and patient survival. Inhibition of miR-610 promoted, but overexpression of miR-610 reduced, HCC cell proliferation and tumorigenicity both in vitro and in vivo. Furthermore, we found that inhibiting miR-610 activated, but overexpressing miR-610 decreased, the Wnt/β-catenin activity through directly suppressing lipoprotein receptor-related protein 6 (LRP6) and transducin β–like protein 1 (TBL1X). The in vitro analysis was consistent with the inverse correlation detected between miR-610 levels with expression of LRP6 and TBL1X in a cohort of human HCC samples. Our results indicate that miR-610 downregulation plays essential roles in HCC progression and reduced miR-610 is correlated with Wnt/β-catenin signaling pathway.
Profiling of Chemonaive Osteosarcoma and Paired-Normal Cells Identifies EBF2 as a Mediator of Osteoprotegerin Inhibition to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis
Authors: Ana Patiño-García, Marta Zalacain, Cecilia Folio, Carolina Zandueta, Luis Sierrasesúmaga, Mikel San Julián, Gemma Toledo, Javier De Las Rivas, Fernando Lecanda
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Osteosarcoma is the most prevalent bone tumor in children and adolescents. At present, the mechanisms of initiation, maintenance, and metastasis are poorly understood. The purpose of this study was to identify relevant molecular targets in the pathogenesis of osteosarcoma. Experimental Design: Tumor chemonaive osteoblastic populations and paired control normal osteoblasts were isolated and characterized phenotypically from seven osteosarcoma patients. Global transcriptomic profiling was analyzed by robust microarray analysis. Candidate genes were confirmed by real-time PCR and organized in molecular pathways. EBF2 and osteoprotegerin (OPG) levels were determined by real-time PCR and OPG protein levels were assessed by ELISA. Immunohistochemical analysis was done in a panel of 46 osteosarcoma samples. Silencing of EBF2 was achieved by lentiviral transduction of short hairpin RNA. Apoptosis was determined by caspase-3/7 activity. Results: A robust clustered transcriptomic signature was obtained in osteosarcoma. Transcription factor EBF2, a known functional bone regulator, was among the most significantly overexpressed genes. Immunohistochemical analysis showed that osteosarcoma is expressed in ∼70% of tumors analyzed. Because EBF2 was shown previously to act as a transcriptional activator of OPG, elevated levels of EBF2 were associated with high OPG protein levels in osteosarcoma samples compared with normal osteoblastic cells. Knockdown of EBF2 led to stunted abrogation of OPG levels and increased sensitivity to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis. Conclusions: These findings suggest that EBF2 represents a novel marker of osteosarcoma. EBF2 up-regulation may be one of the mechanisms involved in the high levels of OPG in osteosarcoma, contributing to decrease TRAIL-induced apoptosis and leading to TRAIL resistance. (Clin Cancer Res 2009;15(16):5082–91)
Association of Mortality and Hospitalization with Achievement of Adult Hemoglobin Targets in Adolescents Maintained on Hemodialysis
Authors: Sandra Amaral, Wenke Hwang, Barbara Fivush, Alicia Neu, Diane Frankenfield, Susan Furth
Journal: Journal of the American Society of Nephrology (2006)

With the use of data from the Centers for Medicare & Medicaid Services' ESRD Clinical Performance Measures Project (October through December 1999 and 2000) linked with US Renal Data System hospitalization and mortality records, whether achieving adult target hemoglobin (Hb) levels in adolescents who are on hemodialysis (HD) was associated with decreased risk for death or hospitalization was assessed. Of 677 adolescents, 238 were hospitalized and 54 died. In bivariate analysis, 11.7% with Hb <11 g/dl at study entry died versus 5% of those with initial Hb > or =11 g/dl (P = 0.001); 40.3% with baseline Hb <11 g/dl were hospitalized versus 31.1% with initial Hb > or =11 g/dl (P = 0.013). In multivariate analysis, Hb > or =11 g/dl was associated with decreased risk for death (hazard ratio [HR] 0.38; 95% confidence interval [CI] 0.20 to 0.72) but did not show a statistically significant association with decreased risk for hospitalization (HR 0.87; 95% CI 0.66 to 1.15). When Hb was recategorized as Hb <10, > or =10 and <11, > or =11 and < or =12, and >12 g/dl, risk of mortality declined as Hb level increased. At Hb 11 to 12 g/dl (versus Hb <10 g/dl), mortality risk decreased by 69% (HR 0.31; 95% CI 0.14 to 0.65). Risk for mortality was similar for Hb 11 to 12 and >12 g/dl. For hospitalization, no statistically significant difference in risk between Hb categories was found. This observational study of adolescents who are on HD is consistent with adult literature showing decreased mortality in patients who have ESRD and meet adult Hb targets. Further studies in the form of randomized, clinical trials are needed to assess optimal Hb levels for adolescents who are on HD.
The ethical junior: a typology of ethical problems faced by house officers
Authors: Rosalind McDougall, Daniel K Sokol
Journal: Journal of the Royal Society of Medicine (2008)

Although many studies have explored the experiences of doctors in their first postgraduate year, few have focused on the ethical issues encountered by this group. Based on an extensive literature review of research involving house officers, we argue that these doctors encounter a broad range of‘ everyday’ ethical challenges, from truth-telling to working in non-ideal conditions. We propose a typology of house officers' ethical issues and advocate prioritizing these issues in undergraduate medical ethics and law curricula.
Uptake of Cardiovascular Drugs Into the Human Heart
Authors: Markus Grube, Henriette E.U. Meyer zu Schwabedissen, Damaris Präger;, Jeanette Haney, Klaus-Uwe Möritz, Konrad Meissner, Dieter Rosskopf, Lothar Eckel, Michael Böhm, Gabriele Jedlitschky, Heyo K. Kroemer
Journal: Circulation (2006)

Background— To date, the uptake of drugs into the human heart by transport proteins is poorly understood. A candidate protein is the organic cation transporter novel type 2 (OCTN2) (SLC22A5), physiologically acting as a sodium-dependent transport protein for carnitine. We investigated expression and localization of OCTN2 in the human heart, uptake of drugs by OCTN2, and functional coupling of OCTN2 with the eliminating ATP-binding cassette (ABC) transporter ABCB1 (P-glycoprotein). Methods and Results— Messenger RNA levels of OCTN2 and ABCB1 were analyzed in heart samples by quantitative polymerase chain reaction. OCTN2 was expressed in all auricular samples that showed a pronounced interindividual variability (35 to 1352 copies per 20 ng of RNA). Although a single-nucleotide polymorphism in OCTN2 (G/C at position −207 of the promoter) had no influence on expression, administration of β-blockers resulted in significantly increased expression. Localization of OCTN2 by in situ hybridization, laser microdissection, and immunofluorescence microscopy revealed expression of OCTN2 mainly in endothelial cells. For functional studies, OCTN2 was expressed in Madin-Darby canine kidney (MDCKII) cells. Using this system, verapamil, spironolactone, and mildronate were characterized both as inhibitors (EC 50 =25, 26, and 21 μmol/L, respectively) and as substrates. Like OCTN2, ABCB1 was expressed preferentially in endothelial cells. A significant correlation of OCTN2 and ABCB1 expression in the human heart was observed, which suggests functional coupling. Therefore, the interaction of OCTN2 with ABCB1 was tested with double transfectants. This approach resulted in a significantly higher transcellular transport of verapamil, a substrate for both OCTN2 and ABCB1. Conclusions— OCTN2 is expressed in the human heart and can be modulated by drug administration. Moreover, OCTN2 can contribute to the cardiac uptake of cardiovascular drugs.
Relevance of Linearizing Nasal Prongs for Assessing Hypopneas and Flow Limitation During Sleep
Authors: RAMON FARRÉ, JORDI RIGAU, JOSEP M. MONTSERRAT, EUGENI BALLESTER, DANIEL NAVAJAS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Respiratory disturbances in patients with the sleep apnea–hypopnea syndrome (SAHS) may be detected by means of nasal prongs (NP) pressure (Pnp). Nevertheless, Pnp is nonlinearly related to flow (V˙). Our aim was to demonstrate the relevance of linearizing P np for assessing hypopneas and flow limitation in SAHS. V˙ was measured with a pneumotachograph during the hypopneas and flow limitation events in a continuous positive airway pressure (CPAP) titration in six patients with severe SAHS. These flow patterns were reproduced by a flow generator through an analog of the nares and recorded by NP. Pnp was linearized [V˙ np = (Pnp)1/2] by a specially designed analog circuit. For each event we used V˙, P np, and V˙ np to compute the hypopnea flow amplitude (HFA) and a flow limitation index (FLI). Owing to NP nonlinearity, Pnp considerably misestimated HFA and FLI. By contrast, V˙ np provided HFA and FLI values that were very close to those obtained from V˙: HFA (V˙ np) = 1.098 · HFA(V˙) − 0.063 (r2 = 0.98) and FLI(V˙ np) = 1.044 · FLI(V˙) + 0.004 (r2 = 0.99). Square-root linearization of NP greatly increases the accuracy of quantifying hypopneas and flow limitation. This procedure, which could be readily carried out in routine practice by means of the analog circuit we developed, is of interest in optimizing the assessment of respiratory sleep disturbances in SAHS.