tbuckley/cabot-search huggingface dataset:
Changes to the GP contract threaten general practice in the UK
Authors: L. Buckman
Journal: BMJ (2012)

Because of failure to grasp the funding and capacity problems facing the NHS 

Last week, the UK government disregarded five months of painstaking negotiations between the BMA and NHS employers to announce a series of wide ranging changes to the general practitioner contract that could potentially damage general practice in the United Kingdom. Some of the changes had never been mentioned before. Extensive and detailed discussions, which had almost led to agreement on a potential package of changes to the GP contract that recognised the need to do as much as possible for patients despite financially austere times, were ignored. The government had been fully informed about negotiations all along, so what happened last week was surprising and distressing. 

There is considerable anger among GPs and within the BMA at how this decision was promulgated. Many other sectors of the medical profession are equally taken aback by the government’s autocratic approach. Furthermore, many of the new indicators that the government has decided to implement are simply unworkable.

GPs are under substantial pressure both financially and as a result of high workload. GP practice incomes have been frozen for several years, …
DRUJ instability after distal radius fracture: A comparison between cases with and without ulnar styloid fracture
Authors: Gholam Hossein Kazemian, Hooman Bakhshi, Matt Lilley, Mohammad Emami Tehrani Moghaddam, Mohammad M. Omidian, Farshad Safdari, Iman Mohammadpour
Journal: International Journal of Surgery (2011)
650. AU-rich 3′ UTR Elements for Increasing the Specificity of Promoter Regulated Adenoviral Gene Therapy
Authors: Merja Sarkioja, Minna Eriksson, Ristimaki Ari, Kanerva Anna, Hakkarainen Tanja, Hemminki Akseli
Journal: Molecular Therapy (2006)

Backround: Selective expression of genes in cancer cells would improve the safety and efficacy of many cancer gene therapy approaches. Adenoviruses can be targeted on a transductional level with capsid modification, or on a transcriptional level using tumor specific promoters (TSPs) and other regulatory elements. The control of mRNA stability and translation could be useful for restricted gene expression. There are a number of TSPs used in adenoviral gene therapy including the cyclooxygenase 2 (Cox2) promoter. Cox2 is expressed in various cancer tissues but also at inflammatory sites, while it is undetectable in normal healthy tissues. Therefore, it is potentially attractive for cancer gene therapy. However, it is currently unknown if Cox2 expression is induced by adenoviral infection per se, given its role as an inflammatory mediator, which might compromise specificity. The Cox2 promoter is partly regulated post-transcriptionally either by stimulation or inhibition of mRNA degregation by AU-rich elements (AREs) which are situated within 3′-untranslated regions (3′UTR) of mRNA. We sought to determine if adenovirus infection of tumor or normal cells results in Cox2 expression. Further, our hypothesis was that if infection induces Cox2, we might regain selectivity by utilization of AREs. Moreover, as the ARE of interest is controlled by the RAS pathway, which is frequently dysregulated in cancer cells, this control moiety might provide an additional level of tumor selectivity. Methods: 293, FHS173WE (non-malignant) and A549 (cancer) cells were transfected with plasmids containing either the Cox2 or CMV promoter driving luciferase, with or without additional post- transcriptional ARE control. Then, the transfected cells were infected with conditionally replicating adenoviruses (CRAds) Ad5-Δ24E3, Ad5/3-Δ24, Ad5-Δ24RGD or Ad5300wt and Ad5LacZ as control viruses. Selectivity and activity of the promoters and 3′UTR elements in vitro were analysed by lusiferase assay. Analysis will also be done in vivo. Results: Our data indicates that adenoviral infection induces the Cox2 promoter in normal and tumor cells, which might compromise utility of the promoter for tumor specific gene therapy. On the other hand, AREs in the 3′ UTR downregulated the expression of Cox2 and CMV driven luciferase in 293-and FHS173WE-cells and upregulated or maintained the luciferase expression in A549 cells. This was able to rescue the tumor selectivity of the Cox2 promoter and provided additional tumor selectivity per se.
Cancer Care, Money, and the Value of Life: Whose Justice? Which Rationality?
Authors: Daniel P. Sulmasy
Journal: Journal of Clinical Oncology (2007)

Cost-containment in oncology is a moral issue. While economists use the word “rationing” to describe all limitations on resource utilization that result from human choice, the ordinary language distinction between allocation and rationing is morally meaningful and can help oncologists to determine their proper moral role in cost-containment. It is argued that oncologists should not be required to ration at the bedside, nor should they be given financial incentives to practice frugally, nor should they be subjected to a variety of bureaucratic mechanisms to control costs indirectly. In addition, it is argued that the fact that treatments have a price does not logically imply that patients have a price. Cost-effectiveness analysis is often suggested as a means of deciding how best to allocate resources, but some of its many ethical limitations are discussed. The alternative is an open, public, participatory process about how to ration care, abandoning the formulaic pretenses of cost-effectiveness analysis, but with a commitment to reason, good will, and common sense. Oncologists would then be free to advocate for their patients within the constraints imposed by this public process.
Cancer at Insulin Injection Site
Authors: Wallace I. Sampson
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Regarding the report of a mesenchymoma in the subcutaneous tissue of the thigh of an insulin-dependent diabetic (233:985,1975), I believe the conclusions of the authors are overdrawn. I do not wish to demean the importance of good, thorough, case reporting in the advancement of the science of medicine, nor of the importance of observed serendipitous (or so they may seem) associations of two or more phenomena; however, the subject of the role of trauma in the induction of malignancy, as the authors point out, is long, and after decades of attempts at firming up the association, I am not convinced the validity of the proposition has been established. More specifically, the statement that "the patient developed cancer at the precise injection site of long-term insulin injection," is unwarranted. Most diabetics alternate sites of injections, and if she had been properly instructed on appropriate insulin administration, she would
NRF2 mitigates radiation-induced hematopoietic death
Authors: John P. Chute
Journal: Journal of Clinical Investigation (2014)

Fractionated, high-dose total body irradiation (TBI) is used therapeutically to myeloablate and immune suppress patients undergoing hematopoietic stem cell (HSC) transplantation. Acute exposure to ionizing radiation can have fatal effects on the hematopoietic and immune systems. Currently, therapies aimed at ameliorating ionizing radiation–associated toxicities are limited. In the February 2014 issue of the JCI, Kim and colleagues demonstrated that induction of nuclear factor erythroid 2–related factor 2 (NRF2) enhances HSC regeneration and increases survival following ionizing radiation exposure in mice. The results of this study suggest that NRF2 is a novel potential target for the development of therapeutics aimed at mitigating the toxicities of ionizing radiation exposure.
P992 FIRST-LINE TREATMENT OF 90 CONSECUTIVE HCC WITH DRUG ELUTING BEADS CHEMOEMBOLIZATION (DEB-TACE)
Authors: M. Triolo, A. Sangiovanni, A. Nicolini, M. Iavarone, S. Crespi, M.A. Manini, C. Della Corte, S. Vavassori, M. Colombo
Journal: Journal of Hepatology (2014)
p73 Is up-regulated in a subset of hepatocellular carcinomas
Authors: Nirmitha I. Herath, Michael C. Kew, Vicki L. Whitehall, Michael D. Walsh, Jeremy R. Jass, Kum Kum Khanna, Joanne Young, Lawrie W. Powell, Barbara A. Leggett, Graeme A. Macdonald
Journal: Hepatology (2000)

Loss of heterozygosity (LOH) at 1p36 occurs in a number of solid tumors including hepatocellular carcinoma (HCC). Recently, a novel gene, p73, has been identified at 1p36.33. p73 is structurally and functionally related to p53 located at 17p13.1, which is a target for inactivation in HCCs. p73 produces at least two splicing variants, p73α and β, and a polymorphism in exon 2 results in two alleles, GC or AT. Initially, only the AT allele and p73α transcripts were identified in malignant cell lines, suggesting a role for these in the malignant phenotype. The aims of this study were to determine the extent of LOH at 1p36 and 17p13.1 in HCCs from Australia and South Africa, and to identify patterns of p73 mRNA and p73 and p53 protein expression. LOH at 1p36 was found in 8 of 25 Australian and 6 of 10 South African cases. p73 mRNA expression occurred in 8 HCCs, but not in nonmalignant liver tissue. Two of these 8 HCCs had LOH of 1p36. Both α and β transcripts were observed in GC/GC homozygotes and GC/AT heterozygotes. No p73 protein expression was observed by immunohistochemistry in nonmalignant liver tissue or in HCC. p53 inactivation appeared to be associated with up-regulation of p73 expression, suggesting a compensatory role for p73 in this situation. The LOH at 1p36 implies a liver-specific tumor suppressor gene is in this region. However, the up-regulation of p73 mRNA suggests p73 is not the target of this loss.
Flushing Reactions: Consequences and Mechanisms
Authors: JONATHAN K. WILKIN
Journal: Annals of Internal Medicine (1981)

The mechanisms of flushing reactions are pharmacologically and physiologically heterogeneous. Flushing may result from agents acting directly on the vascular smooth muscle or may be mediated by vasomotor nerves. Vasomotor nerves may lead to flushing as a result of events at both peripheral and central sites. In susceptible persons, frequent, intense flushing leads to a cluster of physical signs (rosacea). Flushing provoked by alcohol has been associated with ethnic sensitivity, a possible predisposition to alcoholism, various disulfiramlike agents, one type of diabetes mellitus, and the carcinoid syndrome and other types of neoplasia. Flushing reactions also occur during the menopause, after glutamate ingestion, and in response to oral thermal challenges.
Improving the Accuracy of Death Certificates
Authors: Randy Hanzlick
Journal: JAMA (1995)

To the Editor.  —Because of death certificate inaccuracies and other reasons, including the trend toward electronic document filing, the National Center for Health Statistics has called meetings of a steering committee to reengineer the death registration process. 1,2 The suggestion was made that the Uniform Hospital Discharge Data Set (UHDDS) might contain information that could improve or augment the death certificate because the UHDDS is often available quickly after death, it contains a list of diagnoses used for coding a patient's conditions, and it is a telegraphic distillation of the medical record. On the surface the idea sounds good, but an important problem needs to be addressed.  The UHDDS captures the admitting diagnoses, principal diagnoses, and other diagnoses in the medical record. However, it is possible that major diagnoses that would serve as the underlying cause of death (for the death certificate) might escape capture in the UHDDS. For example,
Human Blood and Cardiac Stem Cells Synergize to Enhance Cardiac Repair When Cotransplanted Into Ischemic Myocardium
Authors: Nicholas Latham, Bin Ye, Robyn Jackson, Bu-Khanh Lam, Drew Kuraitis, Marc Ruel, Erik J. Suuronen, Duncan J. Stewart, Darryl R. Davis
Journal: Circulation (2013)

Background— Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction. The superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the effect of human CACs and CSCs, alone or in combination, on myocardial function in an immunodeficient mouse model of myocardial infarction. Methods and Results— CACs and CSCs were cultured from left atrial appendages and blood samples obtained from patients undergoing clinically indicated heart surgery. CACs expressed a broader cytokine profile than CSCs, with 3 cytokines in common. Coculture of CACs and CSCs further enhanced the production of stromal cell–derived factor-1α and vascular endothelial growth factor ( P ≤0.05). Conditioned media promoted equivalent vascular networks and CAC recruitment with superior effects using cocultured conditioned media. Intramyocardial injection of CACs or CSCs alone improved myocardial function and reduced scar burdens when injected 1 week after myocardial infarction ( P ≤0.05 versus negative controls). Cotransplantation of CACs and CSCs together improved myocardial function and reduced scar burdens to a greater extent than either stem cell therapy alone ( P ≤0.05 versus CAC or CSC injection alone). Conclusions— CACs and CSCs provide unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration, and myocardial repair. Combination therapy with both cell types synergistically improves postinfarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complimentary paracrine signatures that promote revascularization and the growth of new myocardium.
Molecular Pathways: Exploiting Tumor-Specific Molecular Defects in DNA Repair Pathways for Precision Cancer Therapy
Authors: Felix Dietlein, H. Christian Reinhardt
Journal: Clinical Cancer Research (2014)

Abstract Disabling mutations in genome maintenance and DNA repair pathways are frequently observed in cancer. These DNA repair defects represent genetic aberrations that are specific to cancer cells and not present in healthy tissues. It is thought that these molecular defects produce a “mutator phenotype,” which allows incipient cancer cells to accumulate additional cancer-promoting mutations. In recent years, our molecular understanding of DNA double-strand break (DSB) repair mechanisms has led to the development of targeted therapeutic approaches to selectively eradicate cancer cells that display defects in homologous recombination–mediated DNA DSB repair. These regimens for the treatment of homologous recombination–defective tumors predominantly aim at pharmacologically repressing the activity of PARP1, which is crucial for base excision repair, or to inhibit the nonhomologous end joining kinase DNA-PKcs (DNA-dependent protein kinase, catalytic subunit). Normal tissue can bypass PARP1- or DNA-PKcs inhibitor–induced genotoxic lesions via homologous recombination–mediated DNA DSB repair. In contrast, homologous recombination–defective cancer cells are unable to properly repair DNA DSBs, in the presence of PARP1 or DNA-PKcs inhibitors, ultimately leading to apoptotic cancer cell death. Clin Cancer Res; 20(23); 5882–7. ©2014 AACR.
GW25-e0278 Coronary Flow Reserve in the Remote Myocardium Predict Left Ventricular Remodeling Following Acute Myocardial Infarction
Authors: Cheng Rongchao, Wei Guoqian, Yu Longhao, Wei Li, Tian Jiawei, Li Xueqi
Journal: Journal of the American College of Cardiology (2014)
Trends in incidence of AIDS associated with transfusion of blood and blood products in Europe and the United States, 1985-93
Authors: S Franceschi, L D. Maso, C La Vecchia
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To quantify patterns and trends in incidence of AIDS associated with transfusion of blood and its products in 14 European countries and the United States. <b>Design</b>: Data were derived from the World Health Organisation9s European non-aggregate AIDS dataset and, for the United States, from the Centers for Disease Control AIDS public information dataset. Rates were standardised by using the world standard populations and adjusted for reporting delays in each country. <b>Subjects</b>: Cases of AIDS in patients with haemophilia and recipients of transfusions. <b>Results</b>: Overall, between 1985 and 1993 almost 6000 cases of AIDS associated with transfusions were registered in the 14 European countries considered and over 8000 in the United States between 1985 and 1992. Most European countries had annual age adjusted rates lower than 0.5 per million children aged 12 or less and between 1 and 2 per million adults. The United States had rates around 1 per million children and 5 per million adults in the most recent period. For children, the highest rates were generally reached in 1985-7, whereas in adults the highest rates were in the late 1980s. France had the highest overall incidence of AIDS related to transfusion in Europe (3.3 per million). Romania had a major epidemic in children (over 30 cases per million children in 1988-90). Incidence rates of AIDS associated with transfusion were still increasing in some southern European countries in the early 1990s. <b>Conclusions</b>: Apart from in France and Romania it is clear that rates of bloodborne AIDS in European countries are lower than those registered in the United States.
Evolution and Animal Models—Reply
Authors: Bruce A. Carlson
Journal: JAMA Neurology (2013)

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Abnormal Illness Behaviour (Dysnosognosia)
Authors: Issy Pilowsky
Journal: Psychotherapy and Psychosomatics (1986)

This paper reviews the concept of abnormal illness behaviour (dysnosognosia). The need for a multidisciplinary approach is emphasized, especially for patients who affirm the presence of somatic illness in an inappropriate way. Taking the multidisciplinary pain clinic as a model of this approach, the range of treatments available is discussed. It is suggested that 'thymologia' and 'somatologia' may be more value-free ways of describing patients' verbal behaviour than alexithymia, and that psychotherapeutic methods can be utilized if a flexible style is adopted.
Think Globally, Act Locally
Authors: Theodore S. Lawrence, Nicholas J. Petrelli, Benjamin D. Li, James M. Galvin
Journal: Journal of Clinical Oncology (2007)

ThisspecialissueoftheJournalofClinicalOncologyisdevoted not to the elimination of global warming, but to advances in the local therapy of cancer. There are a number of reasons for us to be concerned about local control. The simplest is surgical resection alone cures many thousands of patients with early-stage cancers each year. In addition, there is now strong evidence from randomized trials that demonstrate that other local therapies (especially when combined with chemotherapeutic agents used as sensitizers) can lead to long-term survival for patients with locally advanced cancers, including gliomas, head and neck, lung, cervix, and prostate (in the case of radiation therapy), and liver (in the case of chemoembolization or radiofrequency ablation). In other instances, improvements in local therapy permit healthy tissue to be spared, such as avoiding xerostomia in the treatment of head and neck cancer, breast conservation in the treatment of breast cancer, andsphinctersparingsurgeryforrectalcancer.Thus,althoughitis truethatmanypatientswillsuccumbtosystemicdisease,improvementsinlocaltherapyhavethepotentialtoimproveboththesurvival and quality of life of many patients who develop malignancies. This special issue begins with a series of articles on how state-ofthe-artradiationtherapyandinterventionalradiologyisadministered in 2007. Our goal in soliciting these articles was to describe the key principles of these approaches, so as to better appreciate the framework of these fields. The last set of articles focuses on specific disease sites so as to illustrate how these principles of local therapy have been applied to improve the outcome of treatment. TheissuebeginswithadiscussionbyDrsGalvinandDeNeve 1
An Outbreak of Ritter's Disease
Authors: William L. London, Fred S. Rosen
Journal: New England Journal of Medicine (1961)

EXFOLIATIVE dermatitis of the newborn infant was first described by Ritter von Rittershain1 in 1878, and has come to be known as Ritter's disease. Although the cause of the disease has been a matter of controversy for many years many have suggested an infectious etiology for this condition. Sporadic case reports have associated the presence of staphylococci on the skin with the lesions of this exfoliative dermatitis in the newborn period.2 , 3 Three cases of Ritter's disease, affecting all the infants admitted to a newly opened nursery, are the subject of this report.Case ReportsThese cases occurred in a new . . .
Five years of Laparoscopic Cholecystectomy: A reappraisal. Progress in Surgery
Authors: M. Wilson, R. McCloy
Journal: Gut (1996)

Letters to the editor, Book reviews cularis, and serosa receive their blood supply by secondary branches from the submucosal plexus of vessels.' 8 Vasa recta have clearly been demonstrated passing through the bowel wall and joining the submucosal plexus.' 6 Hence it seems probable that reduced serosal perfusion stems from either extramural vascular disease or obliterative lesions within the submocosal plexus.The colonic microcirculation represents the final common pathway for the delivery of oxygen and nutrients to the tissues of the bowel wall and we agree with Fawcett et al that its integrity is critical to successful anasto- motic healing.However, the importance of the serosal plexus, as emphasised by these authors remains open to question.It is note- worthy that the distal two thirds of the rectum is devoid of serosa and hence it is untenable that the vascularity of this layer plays any part in the healing of anastomoses below the peri- toneal reflection.Based on our own microradiographic and fluorescent x ray analysis studies,' 12-14 the submucosal region provides the cornerstone of perfusion of other layers of the bowel well.We believe that preservation of the submucosal plexus by careful extramucosal appositional anastomosis provides the most favourable set of circumstances for uneventful anastomotic healing.