tbuckley/cabot-search huggingface dataset:
Characterizing triple-negative breast cancer tumors
Authors: Sam Aparicio
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
We cannot afford an AIDS epidemic.
Authors: A Fiander
Journal: BMJ (1991)

Diagnostic utility of flumazenil in coma with suspected poisoning SIR, -There have been a number of worrying case reports when flumazenil treatment has been used in mixed poisoning with tricyclic antidepressants. 2 Dr Jonas Hojer and colleagues3 quite correctly state that a normal electrocardiogram recorded before giving flumazenil to an unconscious patient will imply a minimal risk of adverse reactions.The specific criteria used to define normal in this situation must, however, be clarified: a rate less than 100 beats/min, a QRS width less than 0-I s, and a corrected QT interval less than 0-418 s.4It is also important to point out that only 10% of unconscious pauients in the study of Hojer and colleagues had taken a large amount of tricyclic antidepressants.In another study this figure was as high as 48%,' and the risk of adverse reactions may be higher in this group.We therefore suggest that readers consider the local prevalence of overdosage with tricyclic antidepressants before accepting the widespread use of flumazenil in comatose patients.
Abstract 2130: Genomic profiling identifies CDX2 as a lineage-dependent oncogene amplified in colorectal cancer
Authors: Keyan Salari, Justin Cuff, Craig P. Giacomini, Albert Lin, Matt van de Rijn, Jonathan R. Pollack
Journal: Cancer Research (2010)

Abstract Somatic DNA alteration underlies tumor development and progression, and gives rise to tumors with diverse genetic contexts. Characterizing these contexts helps identify driving genetic lesions and potential therapeutic vulnerabilities. Here, we surveyed a collection of 29 colorectal cancer cell lines for DNA copy number alterations and identified in a subset of samples gain/amplification on chromosome 13, which was well represented among the genomic profiles of 344 primary colorectal tumors examined, but not in other tumor types. A minimal region of high-level amplification on 13q12.2, containing the caudal type homeobox transcription factor CDX2, was identified in one cell line and 7 of 123 (6%) primary colorectal tumors. A tissue microarray consisting of an independent set of 83 colorectal tumors confirmed the presence of a subset of tumors harboring copy number gain/amplification of 13q with increased CDX2 protein expression. In the context of genomic amplification, RNA interference experiments showed CDX2 is required for proliferation of colorectal cancer cells and promotes cell cycle progression without an effect on apoptosis. CDX2 is a known transcriptional regulator of normal gut development and intestinal epithelial cell differentiation and maintenance. Here we have shown that for a subset of lineage-derived colorectal tumors, cell proliferation is dependent on the abnormal amplification and overexpression of CDX2. Thus, we nominate CDX2 as a novel lineage-dependent oncogene deregulated in colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2130.
Does symptomatic primary HIV-1 infection accelerate progression to CDC stage IV disease, CD4 count below 200 x 106/l, AIDS, and death from AIDS?
Authors: S. Lindback, C. Brostrom, A. Karlsson, H. Gaines
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To investigate the prognostic significance of symptomatic primary HIV-1 infection. <b>Design</b>: Prospective study of homosexual men seroconverting to HIV in 1985 and 1986. Patients were followed up at least three times yearly with clinical examinations and T cell subset determinations for an average of 7.2 years. <b>Setting</b>: Research project centred on attenders for treatment and screening for HIV at the Karolinska Institute, Stockholm. Subjects—19 patients presenting with a glandularfever-like illness associated with seroconversion to HIV and 29 asymptomatic seroconverters. <b>Main outcome measures</b>: Progression to Centers for Disease Control and Prevention stage IV disease, CD4 cell count below 200 × 10<sup>6</sup>/l, AIDS, and death from AIDS. <b>Results</b>: Symptomatic seroconverters were significantly more likely to develop Centers for Disease Control and Prevention stage IV disease (95% (upsilon) 66%), CD4 cell counts below 200 × 10<sup>6</sup>/l (84% (upsilon) 55%), and AIDS (58% (upsilon) 28%) and die of AIDS (53% (upsilon) 7%). <b>Conclusion</b>: A glandular-fever-like illness associated with seroconversion to HIV-1 predicts accelerated progression to AIDS and other HIV related diseases.
Smarter Screening for Cancer
Authors: Sameer D. Saini, Frank van Hees, Sandeep Vijan
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Alexander Rattray Dow
Authors: L. Bartlet, R. Donald
Journal: BMJ (2010)

<h3>Abstract</h3> <h3>Background</h3> Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL) but also for discriminating general from cell-type-specific effects. <h3>Results</h3> Here, we present a two-step computational framework <i>MAGAR</i>, which fully supports identification of methQTLs from matched genotyping and DNA methylation data, and additionally the identification of quantitative cell-type-specific methQTL effects. In a pilot analysis, we apply <i>MAGAR</i> on data in four tissues (ileum, rectum, T-cells, B-cells) from healthy individuals and demonstrate the discrimination of common from cell-type-specific methQTLs. We experimentally validate both types of methQTLs in an independent dataset comprising additional cell types and tissues. Finally, we validate selected methQTLs (<i>PON1</i>, <i>ZNF155</i>, <i>NRG2</i>) by ultra-deep local sequencing. In line with previous reports, we find cell-type-specific methQTLs to be preferentially located in enhancer elements. <h3>Conclusions</h3> Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell-type-specific epigenomic variation.
FDG-PET/CT in Evaluation and Prognostication of Primary Prostate Lymphoma
Authors: Richard Hodgson, Yi- Tung Huang, Karin Steinke, Aravind S. Ravi Kumar
Journal: Clinical Nuclear Medicine (2010)

A 76-year-old man was incidentally diagnosed with prostate lymphoma following transurethral resection of the prostate for prostatism. Staging F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed markedly increased FDG uptake in the prostate, with no evidence of other disease. Following combination chemotherapy, restaging FDG-PET/CT demonstrated a complete metabolic response. The patient subsequently achieved prolonged remission on follow-up. Because of its rarity, FDG-PET in predicting outcome after therapy has not been validated for primary prostate lymphoma. This case highlights the potential of FDG-PET/CT in not only evaluation of disease extent but also prognostication of primary lymphoma of the prostate.
Super-normal retention in hibernating myocardium: an ex-vivo study using the failing human heart
Authors: Oberdan Parodi, Renata De Maria, Roberto Testa, Ettore Vitali, Livia Ruffini, Giovanna Paleari, Edoardo Gronda, Jonica Campolo, Alessandro Pellegrini
Journal: Cardiovascular Research (1998)

Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated.In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis.Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flows < or = 0.60 ml.min-1.g-1 and 20 segments with flows > 0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion.This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.
Hospital vocational training Local audits are helpful
Authors: M Rickenbach, R Hicks, S Hargreaves
Journal: BMJ (1994)

consultations per hour in the afternoon).By contrast, the potential consultation time for one of the doctors who held walk in surgeries was eight minutes per patient.3The nurses' fee for service work earned about one third of the salary costs borne by the practice.2Most of the tasks that the nurses carried out were simple, such as changing dressings, taking blood pressure, and testing urine; some of them could be delegated to staff who were not nurses, freeing resources for more difficult work such as giving advice on health.Mark R Williamson has argued that venepuncture should be delegated to receptionists.4In the study by Fallon et al 9-2% of tasks were venepuncture.Delegating this task would free substantial time.Fallon et al's study supports the argument for rethinking skill mix in primary care, offers the hypothesis that nurses are popular with patients because they have more time than doctors to spend with patients, and provides further data on the relative costs in relation to consultations under- taken.Policymakers cannot assume that changing skill mix will save money as the advent of practice nurses has shown.With a massive iceberg of unmet need in the population,5 changing the skill mix is a way of providing a broader and more appropriate range of services, of freeing highly trained staff for the most demanding tasks, and of enriching the work experience of those who accept the delegated work.
Erlotinib Monotherapy for Stage IIIB/IV Non-small Cell Lung Cancer: A Multicenter Trial by the Korean Cancer Study Group
Authors: Ji Eun Uhm, Byeong-Bae Park, Myung-Ju Ahn, Jeeyun Lee, Jin Seok Ahn, Sang We Kim, Heung-Tae Kim, Jong Seog Lee, Jin Hyung Kang, Jae Yong Cho, Hong Suk Song, Se Hoon Park, Chang Hak Sohn, Sang Won Shin, Jin Hyuck Choi, Keunchil Park
Journal: Journal of Thoracic Oncology (2009)
S130 Outcomes of pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis
Authors: L. White, G. Mirrani, M. Grover, J. Rollason, A. Malin, J. Suntharalingam
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> In patients with non-cystic fibrosis (CF) bronchiectasis, <i>Pseudomonas aeruginosa</i> infection is associated with increased hospital admissions, poorer quality of life and accelerated lung function decline. The BTS guidelines recommend early <i>Pseudomonas</i> eradication therapy. However, despite clear evidence in CF, there is little evidence in non-CF bronchiectasis. Since 2004, we have initiated eradication therapy following initial <i>Pseudomonas</i> infection in non-CF bronchiectasis patients. This retrospective study assessed clinical and microbiological outcomes. <h3>Methods</h3> All patients undergoing <i>Pseudomonas</i> eradication therapy from 2004 to 2010 were identified from our electronic database. Therapy included intravenous, oral and nebulised antibiotics. Patients were assessed for microbiological eradication, exacerbation frequency (measured by number of antibiotic courses), hospital admissions, clinical symptoms and lung function. <h3>Results</h3> 30 patients were identified. 21 (67.7%) were females and mean age was 62.2 years. Median follow-up time was 26.4 months. Eradication therapy involved 2 weeks of intravenous antibiotics (12 patients), intravenous antibiotics followed by oral ciprofloxacin (13 patients) or oral ciprofloxacin alone (five patients), combined with 1–4 months of nebulised colomycin in 26 patients. <i>Pseudomonas</i> was initially eradicated from sputum in 24 patients (80.0%). 13 patients (43.3%) remained <i>Pseudomonas</i>-free at latest follow-up. 11 patients (36.7%) were subsequently reinfected with median time to reinfection of 6.2 months (Abstract S130 Figure 1). 17 patients with chronic infection were maintained on regular nebulised antibiotics. Exacerbation frequency was significantly reduced, with mean number of antibiotic courses per year 3.93 pre-eradication, and 2.09 post-eradication (p=0.002). Mean number of hospital admissions per year were similar, at 0.39 pre-eradication and 0.29 post-eradication (p=NS). At first follow-up, 20 patients (66.7%) reported overall clinical improvement, with reduced cough in 12 (40.0%), reduced sputum volume in 14 (46.7%) and reduced sputum purulence in 11 (36.7%). Of the 21 patients followed up to 1 year, 6 (28.6%) had further overall improvement and 13 (61.9 %) remained stable. Lung function was not affected by eradication therapy, with mean percentage predicted FEV<sub>1</sub> 62.1% pre and 64.1% post-eradication (p=NS). <h3>Conclusion</h3> This study demonstrated that <i>Pseudomonas</i> eradication therapy can lead to prolonged clearance of this organism and highly significantly reduces exacerbation rate. This important outcome requires confirmation in a prospective study.
Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice
Authors: Olivier Le Moine, Hubert Louis, Anne Demols, Fabrice Desalle, François Demoor, Eric Quertinmont, Michel Goldman, Jacques Devière
Journal: Hepatology (2000)

Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-γ) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-γ were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-γ release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-γ release (−66% or −41%, −95% or −94%, and −70% or −70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell- and macrophage-dependent cytokines.
Acute Pancreatitis and Steroid Therapy
Authors: Joseph H. Isenstead
Journal: JAMA (1962)

ABSTRACT To the Editor:— The letters of Drs. Irvin S. Eskwith and Wil B. Nelp on Acute Pancreatitis and Steroid Therapy (JAMA179:916 [March 17] 1962) call for further discussion of the proper therapeutic administration of steroids. Having used them for more than a decade, I offer the following remarks.Steroids are either administered orally or hypodermically. When given by mouth, the problem of absorption enters the picture and is bound to complicate it. Dr. Nelp reports in his letter 3 cases which offer proof for the fact that it is impossible to predict how much of a drug will be absorbed from the intestinal tract.One patient received 840 mg. of prednisolone in 14 days, another had 510 mg. in 17 days, and the third, 280 mg. in 7 days. In these 3 cases symptoms of severe pancreatitis developed. It is obvious that each of these patients absorbed prednisolone to
Catheter Ablation Therapy for Supraventricular Arrhythmias
Authors: Joseph E. Marine
Journal: JAMA (2007)

The supraventricular arrhythmias include a wide spectrum of disorders including, in descending order of frequency, atrial fibrillation, atrial flutter, atrioventricular nodal reentry, Wolff-Parkinson-White syndrome, and atrial tachycardia. While not life-threatening in most cases, they may cause important symptoms, such as palpitations, chest discomfort, breathlessness, anxiety, and syncope, which significantly impair quality of life. Medical therapy has variable efficacy, and most patients are not rendered free of symptoms. Research over the past several decades has revealed fundamental mechanisms involved in the initiation and maintenance of all of these arrhythmias. Knowledge of mechanisms has in turn led to highly effective surgical and catheter-based treatments. Atrial fibrillation remains a therapeutic challenge but is also yielding to investigation and therapeutic efforts. The supraventricular arrhythmias and their treatment are described in this report.
Silent Mitral Insufficiency in Acute Myocardial Infarction
Authors: JAMES S. FORRESTER, GEORGE DIAMOND, SHELDON FREEDMAN, HOWARD N. ALLEN, WILLIAM W. PARMLEY, JACK MATLOFF, H. J. C. SWAN
Journal: Circulation (1971)

Severe mitral insufficiency in the absence of an audible murmur was diagnosed by left ventricular angiography in three patients with power failure secondary to acute myocardial infarction during evaluation for mechanical circulatory assist and surgery. Mitral valve prolapse was present in two patients. Postmortem examination did not reveal an anatomic basis for the mitral insufficiency: the valve, papillary muscles, and supporting structures were all grossly normal. A single papillary muscle removed at surgery revealed a marked decrease in force development (0.22 g/mm 2 vs 0.62 ± 0.22 g/mm 2 in eight normal papillary muscles from patients with rheumatic heart disease). During isoproterenol stimulation, force development in this muscle decreased 20%, whereas in the normal muscles force development increased 73 ± 31%. Microscopically, all papillary muscles revealed evidence of extensive necrosis. Silent mitral insufficiency in acute myocardial infarction, therefore, was probably related to diminished flow velocity across the mitral valve secondary to diminished myocardial contractility. Failure to recognize and treat this entity may contribute significantly to the genesis of power failure and ultimate mortality.
Chilean Medicine under Social Revolution
Authors: Ernesto Medina, Ricardo Cruz-Coke
Journal: New England Journal of Medicine (1976)

Abstract During the last decade Chile has experienced a series of social changes under Christian Socialist (1964–1970), Marxist Socialist (1970–1973) and military (1973–1975) governments. These changes grossly affected the evolution of medicine and public health in Chile. Nevertheless, vital statistics show an overall improvement in health indexes, with a short interruption during the Marxist government. During this period medical standards and the quality of medical services declined when revolutionaries disrupted the organization of traditional socialized Chilean medicine founded 50 years ago. The vital statistics of 1974 suggest an overall recovery, but physical and human resources for health, eroded by revolution and the present acute economic crisis, have not yet begun to improve. Nevertheless, Chilean medicine has reassumed the technical character that should never have been abandoned. (N Engl J Med 295:193–197, 1976)
What is hazardous? What is safe?
Authors: J W Healy
Journal: Environmental Health Perspectives (1978)

The definition of an acceptable risk involves many facets most of which are outside the control of the decision maker, but they must be recognized if a proper definition is to be made. Six of the principal factors are stated and discussed. (1) nothing is absolutely safe; (2) each individual or group of individuals has his own standards by which he judges risk; (3) perceptions of risk vary with the conditions at any one time in history; (4) there must be a compensatory benefit for taking any risk; (5) societal perception of a risk may be different from the actual risk; and (6) safety is only one of the many factors that must be considered in the design of a product or service.