tbuckley/cabot-search huggingface dataset:
IOM Report a Blueprint for Elimination of TB
Authors: Joan Stephenson
Journal: JAMA (2000)

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Opisthorchiasis mimicking primary biliary cirrhosis as an indication for liver transplantation
Authors: Nathaniel Melling, Werner Hohenberger, Süleyman Yedibela
Journal: Journal of Hepatology (2009)

Background/AimsOpisthorchiasis, a helminthic infection occurring endemically in certain areas of Europe and Asia is caused by parasites of the class trematoda. Failure to treat or a significant delay in the institution of an adequate therapy can lead to considerable complications in the further course of the disease.CaseA 56-year-old patient diagnosed with primary biliary cirrhosis (PBC) with Child-Pugh stage B was referred to our surgical department from a peripheral hospital for liver transplantation. She had spent 50 years of her life in Kazakhstan.ResultsAs the treatment of choice, orthotopic liver transplantation was carried out. The routine postoperative pathological analysis of the explanted liver showed the histological picture of opisthorchiasis. Further work-up in an effort to confirm the histological diagnosis was repeatedly negative.ConclusionsOpisthorchiasis should always be a diagnostic consideration in an unclear case of chronic liver disease especially in patients living in endemic areas. Opisthorchiasis, a helminthic infection occurring endemically in certain areas of Europe and Asia is caused by parasites of the class trematoda. Failure to treat or a significant delay in the institution of an adequate therapy can lead to considerable complications in the further course of the disease. A 56-year-old patient diagnosed with primary biliary cirrhosis (PBC) with Child-Pugh stage B was referred to our surgical department from a peripheral hospital for liver transplantation. She had spent 50 years of her life in Kazakhstan. As the treatment of choice, orthotopic liver transplantation was carried out. The routine postoperative pathological analysis of the explanted liver showed the histological picture of opisthorchiasis. Further work-up in an effort to confirm the histological diagnosis was repeatedly negative. Opisthorchiasis should always be a diagnostic consideration in an unclear case of chronic liver disease especially in patients living in endemic areas.
Abstract P1-15-03: Eight-Year Update of a Prospective Study of Wide Excision Alone for Ductal Carcinoma In Situ (DCIS) of the Breast
Authors: JS Wong, BL Smith, SL Troyan, MA Gadd, R Gelman, SC Lester, SJ Schnitt, DC Sgroi, Y-H Chen, BJ Silver, JR. Harris
Journal: Cancer Research (2010)

Abstract Background: The need for radiation therapy (RT) in conservatively managed DCIS is a source of ongoing debate. This is an updated analysis of a phase II prospective study of wide excision alone for DCIS. The study was activated in May 1995 and closed in July 2002 following accrual of 158 patients because the number of local recurrences (LR) met the predetermined stopping rules. The objective of the analysis is to update the distribution and cumulative incidence of events (LR, contralateral breast cancer [CBC], second malignancy and death from other causes). Materials and Methods: A total of 158 patients had DCIS with predominant nuclear grade 1 or 2, a mammographic extent of ≥2.5 cm, and excision with final microscopic margins of ≥1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The results presented are from the 8-year analysis (8-year minimum potential follow-up time). Twenty-six patients without recurrence who were followed less than 8 years were excluded from the analysis as were 7 first events (4 LR) that occurred beyond 8 years of follow-up; the analysis thus includes 132 patients and 36 first events. Cumulative incidence curves were generated to assess the rates of LR or other events. Median follow up time was 10 years. Results: Overall, 36/132 patients (27%) had a first event as of April 2010. Of these 36 events, 19 were LR, 13 were CBC, 1 was a second malignancy, and 3 were deaths from other causes. Of the 19 LR, 13 (68%) were DCIS only and 6 (32%) were invasive. Fourteen occurred in the same quadrant and 5 were elsewhere in the ipsilateral breast. The 8-year estimated cumulative incidence of LR was 14.4% (95% CI: 8.4-20.4%). For all other events, the 8-year estimated cumulative incidence was 12.9% (95% CI: 3.6-13.1%). The estimated annual percentage rates of LR, CBC, and other events were 2.1%, 1.5% and 0.4%, respectively. Discussion: The results of this prospective study demonstrate a substantial and ongoing risk of LR and CBC in patients with small, nuclear grade 1 or 2 DCIS treated with wide excision with margins of ≥1cm in the absence of RT. Most LRs occurred in the same quadrant, rather than elsewhere in the breast, suggesting that excision alone is inadequate even for this highly selected population. Further study is warranted to determine if there is a subgroup of DCIS patients with nuclear grade 1 or 2 disease who are at low enough risk of LR following wide excision that RT can be omitted safely. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-15-03.
Differences in Quality of Care for Hospitalized Elderly Men and Women
Authors: Marjorie L. Pearson
Journal: JAMA (1992)

<h3>Objective.</h3> —To analyze whether important gender differences exist in the quality of hospital care provided to patients with four major medical conditions. <h3>Design.</h3> —Bivariate and multivariate comparisons of clinically detailed sickness at admission, quality, utilization, and outcome measures. <h3>Setting.</h3> —Acute care hospitals located in five states. <h3>Patients or Other Participants.</h3> —A total of 11 242 patients 65 years or older who were hospitalized with one of four diseases: congestive heart failure, acute myocardial infarction, pneumonia, and cerebrovascular accident. We derived our data from the nationally representative sample used to study the quality of hospital care for Medicare patients before and after the implementation of the prospective payment system. A hierarchical (nested) cluster sampling design was used to draw disease-specific samples of patients hospitalized in 1981, 1982, 1985, or 1986 in one of 297 hospitals located in 30 areas within five states. <h3>Interventions.</h3> —This was an observational study. <h3>Main Outcome Measures.</h3> —Sickness at admission, process, use rates, length of stay, discharge status, discharge destination, and mortality. <h3>Results.</h3> —Sex differences in sickness at admission varied by disease. There was some evidence that women received worse process of care, but the difference was very small. We found many similarities in the process and outcomes of care for male and female patients. <h3>Conclusions.</h3> —After controlling for sickness at admission, age, and other important covariates, the in-hospital experiences of elderly men and women showed greater similarities than differences. The concern that sex bias enters into clinical decision making during hospitalization is eased, although not entirely eliminated. (<i>JAMA</i>. 1992;268:1883-1889)
Release of HMGB1 in Response to Proapoptotic Glioma Killing Strategies: Efficacy and Neurotoxicity
Authors: Marianela Candolfi, Kader Yagiz, David Foulad, Gabrielle E. Alzadeh, Matthew Tesarfreund, A.K.M. Ghulam Muhammad, Mariana Puntel, Kurt M. Kroeger, Chunyan Liu, Sharon Lee, James F. Curtin, Gwendalyn D. King, Jonathan Lerner, Katsuaki Sato, Yohei Mineharu, Weidong Xiong, Pedro R. Lowenstein, Maria G. Castro
Journal: Clinical Cancer Research (2009)

Abstract Purpose: In preparation for a phase I clinical trial using a combined cytotoxic/immunotherapeutic strategy with adenoviruses (Ad) expressing Flt3L (Ad-Flt3L) and thymidine kinase (Ad-TK) to treat glioblastoma (GBM), we tested the hypothesis that Ad-TK+GCV would be the optimal tumor-killing agent in relation to efficacy and safety when compared with other proapoptotic approaches. Experimental Design: The efficacy and neurotoxicity of Ad-TK+GCV was compared with Ads encoding the proapoptotic cytokines [tumor necrosis factor-α, tumor necrosis factor–related apoptosis-inducing factor (TRAIL), and Fas ligand (FasL)], alone or in combination with Ad-Flt3L. In rats bearing small GBMs (day 4), only Ad-TK+GCV or Ad-FasL improved survival. Results: In rats bearing large GBMs (day 9), the combination of Ad-Flt3L with Ad-FasL did not improve survival over FasL alone, whereas Ad-Flt3L combined with Ad-TK+GCV led to 70% long-term survival. Expression of FasL and TRAIL caused severe neuropathology, which was not encountered when we used Ad-TK+/−Ad-Flt3L. In vitro, all treatments elicited release of high mobility group box 1 protein (HMGB1) from dying tumor cells. In vivo, the highest levels of circulating HMGB1 were observed after treatment with Ad-TK+GCV+Ad-Flt3L; HMGB1 was necessary for the therapeutic efficacy of AdTK+GCV+Ad-Flt3L because its blockade with glycyrrhizin completely blocked tumor regression. We also showed the killing efficacy of Ad-TK+GCV in human GBM cell lines and GBM primary cultures, which also elicited release of HMGB1. Conclusions: Our results indicate that Ad-TK+GCV+Ad-Flt3L exhibit the highest efficacy and safety profile among the several proapoptotic approaches tested. The results reported further support the implementation of this combined approach in a phase I clinical trial for GBM.
A testing time for ethical standards
Authors: Woody Caan
Journal: BMJ (2005)

EDITOR—The General Medical Council's recognition that “fitness to practise” is a lifelong issue is welcome.1 In the recent GMC conference Medical Education: From Here to Where? Janet Smith reflected on the homicidal general practitioner Alan Shipman. According to one summary she said: “Medical students who fail to demonstrate ethical sense should not be allowed to qualify.” She proposed the GMC intervene more in …
SIMULTANEOUS MEASUREMENT OF EFFECTIVE RENAL BLOOD FLOW AND CARDIAC OUTPUT IN RESTING NORMAL SUBJECTS AND PATIENTS WITH ESSENTIAL HYPERTENSION 1
Authors: Alfred A. Bolomey, Alexander J. Michie, Catharine Michie, Ernest S. Breed, George E. Schreiner, Henry D. Lauson
Journal: Journal of Clinical Investigation (1949)

Unpublished data of Bradley and associates (1) indicate that about 25 to 30 per cent of the cardiac output, as measured by the ballistocardio- graph (2), perfuses the kidney of healthy adults at rest.This figure has been reported in a review on renal physiology (3).Levy and Blalock (4) obtained an average value of 18.5 per cent in un- anesthetized dogs, using the catheterization tech- nique or heart puncture and the direct Fick principle for the determination of the cardiac output.When normal human values for the resting car- diac output obtained by the direct Fick procedure (5, 6) are divided into the normal human values for effective renal blood flow (7), the resulting effective renal fraction is about 19 to 20 per cent.The present investigation was undertaken to make these measurements simultaneously in a series of normal subjects and in patients with es- sential hypertension, using the cardiac catheteri- zation technique (8, 9) and the direct Fick principle for the measurements of the cardiac output. METHODSAll studies were made during the morning at least 12 hours after the previous meal.Effective renal blood flow was determined from the renal plasma clearance of p-aminohippurate or diodrast and from the hematocrit (10).At the same time, the glomerular filtration rate was measured by the renal plasma clearance of mannitol, inulin (10), or sodium
Emerging Role of Infectious Etiologies in the Pathogenesis of Marginal Zone B-cell Lymphomas
Authors: Emanuele Zucca, Francesco Bertoni, Barbara Vannata, Franco Cavalli
Journal: Clinical Cancer Research (2014)

Abstract Extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The most frequently affected organ is the stomach, where MALT lymphoma is incontrovertibly associated with a chronic gastritis induced by a microbial pathogen, Helicobacter pylori. Gastric MALT lymphoma therefore represents a paradigm for evaluating inflammation-associated lymphomagenesis, which may lead to a deeper understanding of a possible etiologic association between other microorganisms and nongastric marginal zone lymphomas. Besides infectious etiology, chronic inflammation caused by autoimmune diseases, such as Sjögren syndrome or Hashimoto thyroiditis, can also carry a significant risk factor for the development of marginal zone lymphoma. In addition to the continuous antigenic drive, additional oncogenic events play a relevant role in lymphoma growth and progression to the point at which the lymphoproliferative process may eventually become independent of antigenic stimulation. Recent studies on MALT lymphomas have in fact demonstrated genetic alterations affecting the NF-κB) pathway, a major signaling pathway involved in many cancers. This review aims to present marginal zone lymphoma as an example of the close pathogenetic link between chronic inflammation and tumor development, with particular attention to the role of infectious agents and the integration of these observations into everyday clinical practice. See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.” Clin Cancer Res; 20(20); 5207–16. ©2014 AACR.
Chemokines show potential against HIV
Authors: S. Mayor
Journal: BMJ (1997)

Researchers are making progress in new approaches to protect cells against the AIDS virus, with the discovery of molecules that are able to prevent HIV-1 entering and infecting T cells.

A team from the Institute of Cancer Research in London report that a modified chemokine–AOP-RANTES–potently inhibits infection of several cell types by certain HIV-1 strains ( Science 1997;276:276-9). Project …
IDH mutations and trisomy 8 in myelodysplastic syndromes and acute myeloid leukemia
Authors: D Caramazza, T L Lasho, C M Finke, N Gangat, D Dingli, R A Knudson, S Siragusa, C A Hanson, A Pardanani, R P Ketterling, A Tefferi
Journal: Leukemia (2010)
Abstract 2037: Establishment and characterization of paired mutant B-raf, vemurafenib-sensitive and -resistant patient-derived xenograft models.
Authors: Michael J. Wick, Teresa L. Vaught, Lizette Gamez, Justin Meade, Skylar Carden, Anthony W. Tolcher, Drew W. Rasco, Amita Patnaik, Alexander Miller, Ronald Drengler, Kyriakos P. Papadopoulos
Journal: Cancer Research (2013)

Abstract Background: Vemurafenib is a recently approved anticancer therapy for B-RafV600E metastatic melanoma. Treatment with this agent increases overall patient survival compared with dacarbazine; however, most patients receiving vemurafenib progress within a year and are left with limited treatment options. Few validated screening tools exist to evaluate potentially beneficial therapies for these resistant/refractory patients. To address this deficiency we have generated a panel of paired mutant B-Raf vemurafenib-sensitive and -resistant patient-derived xenograft (PDX) models of metastatic melanoma and colorectal cancer. Each parent model was screened for activating mutations and all evaluated in vivo against vemurafenib. In addition, select model pairs were subjected to whole genome sequencing and RNA analysis to identify differences in genetic and expression profiles. Methods: Establishment of parent models was previously described. Vemurafenib-resistant PDX models (PDX-VR) were generated by in vivo administration of clinical-grade vemurafenib at increasing concentrations over limited tumor passages. Parental vemurafenib-sensitive models were screened for activating mutations of fifty-two known cancer genes using a PCR-based assay with customized primers. DNA and RNA was extracted from select model pairs and profiled and compared for alterations. Results: To date we have generated six B-RafV600E PDX-VR models (3 melanoma + 3 colorectal) with additional B-RafV600E and B-RafV600K PDX-VR models in development. In vivo studies evaluating vemurafenib in parent models reported notable tumor growth inhibition in all but one colorectal model (ST428), including tumor regressions in melanoma. PDX-VR models reported tumor growth similar to untreated controls at vemurafenib concentrations up to 150 mg/kg/day. Comparative analysis of paired models revealed some differences in DNA and RNA profiles. Conclusion: We have generated a panel of paired mutant B-raf vemurafenib-sensitive and -resistant patient-derived xenograft (PDX) models representing metastatic melanoma and colorectal cancer available as validated screening tools to evaluate potentially beneficial therapies for vemurafenib-resistant/refractory patients. Citation Format: Michael J. Wick, Teresa L. Vaught, Lizette Gamez, Justin Meade, Skylar Carden, Anthony W. Tolcher, Drew W. Rasco, Amita Patnaik, Alexander Miller, Ronald Drengler, Kyriakos P. Papadopoulos. Establishment and characterization of paired mutant B-raf, vemurafenib-sensitive and -resistant patient-derived xenograft models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2037. doi:10.1158/1538-7445.AM2013-2037
Gelatinases in soft tissue biomaterials. Analysis of different crosslinking agents
Authors: P. Calero, E. Jorge-Herrero, J. Turnay, N. Olmo, I. López de Silanes, M.A. Lizarbe, M.Martı́n Maestro, B. Arenaz, J.L. Castillo-Olivares
Journal: Biomaterials (2002)
Generic Substitution: Trick or Treat?
Authors: Louis Lasagna
Journal: JAMA (1978)

Politicians, consumers, and third-party payers are all interested in saving money on drugs, although drug costs represent only approximately 10% of the national health bill. Most people naturally object to paying more money for anything than they have to, but few would argue that inadequate cheap drugs are preferable to dependable but more expensive versions.  Passions run high about generic substitution. The debate has not been helped by two flimflams perpetrated on the public— the notion that generic prescribing invariably leads to savings for the consumer and the readiness with which everyone ignores the importance of the pharmacist in determining prescription prices.  Several studies testify to the fact that a person always encounters a substantial range in drug prices if he takes the same prescription to different drugstores in the same city, whether the prescription is for a brand name or a generic drug. Clearly, generic prescribing that has as
Clinical Trials and Medical Care: Defining the Therapeutic Misconception
Authors: Gail E Henderson, Larry R Churchill, Arlene M Davis, Michele M Easter, Christine Grady, Steven Joffe, Nancy Kass, Nancy M. P King, Charles W Lidz, Franklin G Miller, Daniel K Nelson, Jeffrey Peppercorn, Barbra Bluestone Rothschild, Pamela Sankar, Benjamin S Wilfond, Catherine R Zimmer
Journal: PLoS Medicine (2007)

A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment.
959-103 A Systematic Approach to the Evaluation of Chest Pain in the Emergency Department: A Prospective Risk Assessment and Treatment Protocol Based on Patient Presentation, ECG and Rest Technetium 99m-Sestamibi
Authors: Christopher S. Nicholson, Charlotte S. Roberts, James L. Tatum, Joseph P. Ornato, Robert L. Jesse
Journal: Journal of the American College of Cardiology (1995)
Intra-articular Injections for Arthritis
Authors: A. C. Elkin
Journal: BMJ (1958)

New Jersey (NJ) implemented the first-in-the-US Graduated Driver Licensing (GDL) decal provision in May 2010 for young drivers with learner9s permits or intermediate licenses. Previous analyses found an association between the provision and crash reduction among intermediate drivers. The aim of this study is to examine the association between NJ’s provision and GDL citation and crash rates among drivers aged &lt;21 years with learner9s permits. We estimated monthly per-driver rates from January 2006 through June 2012. Negative binomial modeling compared pre and post decal crash rates adjusted for gender, age, calendar month, and gas price. The monthly GDL citation rate was two per 10 000 drivers in the predecal and postdecal periods. Crashes were rare and rates declined similarly pre and post decal (adjusted rate ratio of postdecal vs predecal slope: 1.04 (0.97 to 1.12)). NJ9s GDL decal provision was not associated with a change in citation or crash rates among young NJ drivers with learner9s permits.
One-time general consent for research on biological samples: Autonomy and majority rules have been misunderstood
Authors: David Hunter
Journal: BMJ (2006)

One-time general consent for research on biological samples Opt out system for patients is optimal and endorsed in many countriesEditor-Wendler's valuable overview of empirical studies of patients' preferences about the use of residual (leftover) tissue for research is not complete. 1 The discussion has already been settled by legislation in many countries.In 2004 the Danish act on patient rights was amended with an opt out system for using residual tissue for research.In 2004 the US Office for Human Research Protections (OHRP) issued guidance that research on residual tissue which is anonymous to the researcher is not human subject research and therefore the tissue can be used without consent. 2Earlier the Dutch Federation of Medical Research Societies' code of conduct on research with residual tissue drafted with patients' organisations had an opt out system for research on samples anonymous to the researcher. 3 In the recent UK Human Tissue Act no form of consent is needed for the use of fully anonymous or coded (or linked) residual tissue that is anonymous to the researcher, provided that an ethical review board has permitted the study.The more restrictive provisions in the original bill were amended also because of pressure from patient groups afraid that research to their benefit would be hampered by the proposed consent system.Wendler emphasises autonomy and argues that one-time consent protects the autonomy of individuals and protects them from serious risks.There are two major arguments against this.Firstly, autonomy should be balanced against other values such as the interests of patients who might benefit from this research. 4 Secondly, autonomy as such cannot protect individuals from risks but only from risks they do want to carry.Research on residual tissue, whether anonymous or anonymously used and being coded, does not carry any risks to individuals.Ethical review boards should oversee that sufficient measures have been taken to ensure that the samples used in research remain anonymously used.It should be possible to enrich data from tissue research with patient data.Fully anonymising samples, as suggested by Wendler, is a waste of valuable information.