tbuckley/cabot-search huggingface dataset:
BMJ archive: the videos
Authors: D. Payne
Journal: BMJ (2009)

Late last year the journal’s full archive was uploaded on to bmj.com, enabling readers to trawl 169 years of articles, letters, and research papers direct from the website. Suddenly, luminaries such as John Snow, David Livingstone, Arthur Conan Doyle, and Florence Nightingale can be found through a simple search.

But we wanted to do more to bring such figures and their contributions to life. Given the success of a short video we commissioned last Christmas to accompany a paper on Oliver Twist’s workhouse diet, we approached the science producer Martin Freeth.

He enlisted the neurobiologist Colin Blakemore, former head of …
Molecular Radiobiology: The State of the Art
Authors: Amato J. Giaccia
Journal: Journal of Clinical Oncology (2014)

Traditional cytotoxic agents used in cancer therapy were initially discovered based on their ability to kill rapidly dividing cells. The targets of these early-generation agents were typically one or more aspects of DNA synthesis or mitosis. Thus, dose-limiting toxicities commonly associated with these agents include GI dysfunction, immunosuppression, and other consequences of injury to normal tissues in which cells are replicating under normal physiologic conditions. Although many of these agents still play an important role in cancer therapy when given concurrently with radiation therapy, the major thrust of radiobiology research in the last two decades has focused on discovering tumor-specific traits that might be exploited for more selective targeting that would enhance the efficacy of radiotherapy with less normal tissue toxicity. These newer generation molecular targeted therapies interfere with the growth of tumor cells by inhibiting genes and their protein products that are needed specifically by the tumor for survival and expansion. These agents can be complementary to radiotherapy, a spatially targeted agent. Although there have been extraordinary technical advances in radiotherapy in recent years, we are reaching the limits of improvements that radiotherapy delivery technology can bring and need different approaches. This review will highlight promising new tumor biology-based targets and other novel strategies to reduce normal tissue injury, increase tumor control, and expand the use of radiotherapy to treat widespread metastatic disease.
Esther Stacey (nee Fonseca)
Authors: S. Curson
Journal: BMJ (2002)

Former general practitioner southeast London (b India 1942; q Cambridge/Westminster Hospital, London, 1969; DCH, DTM&H), died from peritoneal mesothelioma on 26 March 2002.

Esther worked as a community paediatrician before becoming a general practitioner in one of the most deprived parts of London. She was an innovative GP, introducing regular clinical audit in the 1980s and always embracing the challenges presented by continuing change. She was an inspirational trainer, particularly supporting those trainees who were not part of a formal vocational training programme. Her interests ranged from singing madrigals to collecting antique china. She leaves a husband, David; and two children.
Doing as well as thinking
Authors: Geoff Watts
Journal: BMJ (2004)

Does a broadcaster have the gravitas to run a health policy organisation? Niall Dickson , the new head of the King's Fund, tells Geoff Watts why he's the man for the job 

Sitting in his office reflecting on the condition of the King's Fund, Niall Dickson, the fund's new chief executive, recalls a conversation he's had earlier in the morning. The woman he'd spoken to is the director of a trust. “She said that her life had been transformed, her career transformed, by a King's Fund course… Well, we produce 1500 alumni every year. These are our ambassadors.”

Niall Dickson, lately of the BBC's social affairs department, took over at the fund in early January. As he is aware, the fund needs that reservoir of goodwill—and he may have to draw more heavily on that than some of his predecessors. The organisation may still be the brightest star in the health policy firmament, but it will have to burn more brightly to continue out-shining the competition in quantity and quality.

“Some individuals within the fund remain influential because they do good work,” says Klim McPherson, professor of public health epidemiology at the University of Bristol, “but I'm not sure it has much …
Native South American Genetic Structure and Prehistory Inferred from Hierarchical Modeling of mtDNA
Authors: C. M. Lewis, J. C. Long
Journal: Molecular Biology and Evolution (2008)

Genetic diversity in Native South Americans forms a complex pattern at both the continental and local levels. In comparing the West to the East, there is more variation within groups and smaller genetic distances between groups. From this pattern, researchers have proposed that there is more variation in the West and that a larger, more genetically diverse, founding population entered the West than the East. Here, we question this characterization of South American genetic variation and its interpretation. Our concern arises because others have inferred regional variation from the mean variation within local populations without taking into account the variation among local populations within the same region. This failure produces a biased view of the actual variation in the East. In this study, we analyze the mitochondrial DNA sequence between positions 16040 and 16322 of the Cambridge reference sequence. Our sample represents a total of 886 people from 27 indigenous populations from South (22), Central (3), and North America (2). The basic unit of our analyses is nucleotide identity by descent, which is easily modeled and proportional to nucleotide diversity. We use a forward modeling strategy to fit a series of nested models to identity by descent within and between all pairs of local populations. This method provides estimates of identity by descent at different levels of population hierarchy without assuming homogeneity within populations, regions, or continents. Our main discovery is that Eastern South America harbors more genetic variation than has been recognized. We find no evidence that there is increased identity by descent in the East relative to the total for South America. By contrast, we discovered that populations in the Western region, as a group, harbor more identity by descent than has been previously recognized, despite the fact that average identity by descent within groups is lower. In this light, there is no need to postulate separate founding populations for the East and the West because the variability in the East could serve as a source for the Western gene pools.
THE EVOLUTION OF OBSTETRIC MEDICINE: WITH ILLUSTRATIONS FROM SOME OLD MIDWIFERY BOOKS
Authors: J. Byers
Journal: BMJ (1912)

somiie most interesting notes on two old voltumles wlichl lhe showed, and wlichll le subsequiently very kindly placed in my lhancls, dealing witi obstetric medicine.At the next meeting, February 15tlh, 1912, I was able to exlhibit twvo additional aincient books on the same subject.Some dletails abotut these works may be wortlh recording-apart fromn their own individual interest-for the light they tllhow uipon the early history of obstetrics, and its gradual development into a science and an art. I." THE BYRTH OF MANKYNDE."In the year 1909 there was found in the library of the Ulster Medical Society, in the midst of a number of otlher old publications, a beautifully preserved copv of the 1545 (second) edition of The Blyrth of Maicnkywle (the first
First Dorsal Interosseous Muscle Atrophy: A Clinical Sign of Impaired Glucose Metabolism.
Authors: Harry Bienenstock
Journal: Annals of Internal Medicine (1967)

s1 May 1967First Dorsal Interosseous Muscle Atrophy: A Clinical Sign of Impaired Glucose Metabolism.Harry Bienenstock, M.D. (Associate), Sheldon J. Davidson, M.D., Thomas J. Forschner, M.D.Harry Bienenstock, M.D. (Associate)Search for more papers by this author, Sheldon J. Davidson, M.D.Search for more papers by this author, Thomas J. Forschner, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1057_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOver a 16-month period, four patients were referred to the Rheumatology Division because of bilateral first dorsal interosseous muscle atrophy, diagnosed as "arthritis." Two of these patients were known to have diabetes mellitus, and two had abnormal oral glucose tolerance tests upon further study.In order to test whether first dorsal interosseous atrophy was an indicator of impaired glucose metabolism, medical and surgical inpatients, exclusive of those with arthritis and neuromuscular disease, were asked to show their hands to two independent examiners. No history was elicited until after the hands were inspected and evaluated. Thirty-two patients (group I) exhibited bilateral... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Harry Bienenstock, M.D. (Associate); Sheldon J. Davidson, M.D.; Thomas J. Forschner, M.D.Affiliations: Brooklyn, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byReliability of force per unit cross-sectional area measurements of the first dorsal interosseus muscle 1 May 1967Volume 66, Issue 5Page: 1057-1057KeywordsArthritisAtrophyDiabetes mellitusGlucose metabolismInpatientsMusclesNeuromuscular diseasesOral glucose tolerance testRheumatology ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Gastric Cancer Growth Control by BEZ235<i>In Vivo</i>Does Not Correlate with PI3K/mTOR Target Inhibition but with [18F]FLT Uptake
Authors: Thorsten Fuereder, Thomas Wanek, Pamina Pflegerl, Agnes Jaeger-Lansky, Doris Hoeflmayer, Sabine Strommer, Claudia Kuntner, Friedrich Wrba, Johannes Werzowa, Michael Hejna, Markus Müller, Oliver Langer, Volker Wacheck
Journal: Clinical Cancer Research (2011)

In this study, we tested the antitumor activity of the dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitor BEZ235 against gastric cancer in vitro and in vivo.Gastric cancer cell lines (N87, MKN45, and MKN28) were incubated with BEZ235 and assessed for cell viability, cell cycle, and PI3K/mTOR target inhibition. In vivo, athymic nude mice were inoculated with N87, MKN28, or MKN45 cells and treated daily with BEZ235. 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake was measured via small animal positron emission tomography (PET).In vitro, BEZ235 dose dependently decreased the cell viability of gastric cancer cell lines. The antiproliferative activity of BEZ235 was linked to a G(1) cell-cycle arrest. In vivo, BEZ235 treatment resulted in PI3K/mTOR target inhibition as shown by dephosphorylation of AKT and S6 protein in all xenograft models. However, BEZ235 treatment only inhibited tumor growth of N87 xenografts, whereas no antitumor effect was observed in the MKN28 and MKN45 xenograft models. Sensitivity to BEZ235 in vivo correlated with downregulation of the proliferation marker thymidine kinase 1. Accordingly, [(18)F]FLT uptake was only significantly reduced in the BEZ235-sensitive N87 xenograft model as measured by PET.In conclusion, in vivo sensitivity of gastric cancer xenografts to BEZ235 did not correlate with in vitro antiproliferative activity or in vivo PI3K/mTOR target inhibition by BEZ235. In contrast, [(18)F]FLT uptake was linked to BEZ235 in vivo sensitivity. Noninvasive [(18)F]FLT PET imaging might qualify as a novel marker for optimizing future clinical testing of dual PI3K/mTOR inhibitors.
Mortality Trends in Type 1 Diabetes
Authors: Rimei Nishimura, Ronald E. LaPorte, Janice S. Dorman, Naoko Tajima, Dorothy Becker, Trevor J. Orchard
Journal: Diabetes Care (2001)

OBJECTIVES—To investigate long-term mortality and its temporal trends as of 1 January 1999 among the 1,075 patients with type 1 diabetes (onset age &amp;lt;18 years, diagnosed between 1965 and 1979) who comprise the Allegheny County population-based registry. RESEARCH DESIGN AND METHODS—Overall, sex- and race-specific mortality rates per person-year of follow-up were determined. Standardized mortality ratios were also calculated. Survival analyses and Cox proportional hazard model were also used. Temporal trends were examined by dividing the cohort into three groups by year of diagnosis (1965–1969, 1970–1974, and 1975–1979). RESULTS—Living status of 972 cases was ascertained as of January 1, 1999 (ascertainment rate 90.4%). The mean duration of diabetes was 25.2 ± 5.8 (SD) years. Overall, 170 deaths were observed. The crude mortality rate was 627 per 100,000 person-years (95% CI 532–728) and standardized mortality ratio was 519 (440–602). Life-analyses by the Kaplan-Meier method indicated cumulative survival rates of 98.0% at 10 years, 92.1% at 20 years, and 79.6% at 30 years duration of diabetes. There was a significant improvement in the survival rate between the cohort diagnosed during 1965–1969 and that diagnosed during 1975–1979 by the log-rank test (P = 0.03). Mortality was higher in African-Americans than in Caucasians, but there were no differences seen by sex. The improvement in recent years was seen in both ethnic groups and sexes. CONCLUSIONS—An improvement in long-term survival was observed in the more recently diagnosed cohort. This improvement is consistent with the introduction of HbA1 testing, home blood glucose monitoring, and improved blood pressure therapy in the 1980s.
Abstract 1754: Dormant cancer cells are resistant to conventional therapies and induce tumor vessels after chemotherapy.
Authors: Shuya Yano, Sumiyuki Mii, Yasunori Tome, Yukihiko Hiroshima, Fuminari Uehara, Shinji Miwa, Toshiyoshi Fujiwara, Robert M. Hoffman
Journal: Cancer Research (2013)

Abstract Dormant cancer cells were visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). FUCCI-expressing xenografts were established from MKN45 gastric cancer cells. Within 7 days after inoculation, FUCCI-expressing nascent tumors contained a mixture of cancer cells in G0/G1 phase and in S/G2/M phases. Nascent tumors treated with cyto-toxic agents showed that cancer cells in G0/G1 phase can survive and become dormant. As tumors grew, the proliferating area was only at the surface and the dormant area predominated. Chemotherapy killed only the minority population of proliferating cancer cells at the surface and had little effect on the majority of dormant cancer cells in the tumor center. Furthermore, we investigated tumor chemoresistance using nestin-driven GFP transgenic mice that have GFP-expressing nascent tumor vessels. Chemotherapy-treated tumors had much more and deeper tumor vessels than control tumors, suggesting that dormant cancer cells may protect themselves by inducing tumor vessels. This report suggests that dormant cancer cells play a large role in drug resistance. Citation Format: Shuya Yano, Sumiyuki Mii, Yasunori Tome, Yukihiko Hiroshima, Fuminari Uehara, Shinji Miwa, Toshiyoshi Fujiwara, Robert M. Hoffman. Dormant cancer cells are resistant to conventional therapies and induce tumor vessels after chemotherapy. [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 1754. doi:10.1158/1538-7445.AM2013-1754
Long-term Suppression of Genital Herpes
Authors: Jeffrey P. Engel
Journal: JAMA (1998)

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
Influence of Sex and Hormone Status on Circulating Natriuretic Peptides
Authors: Carolyn S.P. Lam, Susan Cheng, Karen Choong, Martin G. Larson, Joanne M. Murabito, Christopher Newton-Cheh, Shalender Bhasin, Elizabeth L. McCabe, Karen K. Miller, Margaret M. Redfield, Ramachandran S. Vasan, Andrea D. Coviello, Thomas J. Wang
Journal: Journal of the American College of Cardiology (2011)
comparative Approaches to Risk Reduction of Coronary Heart Disease in Tecumseh Non-Insulin-Dependent Diabetic Population
Authors: D A Smith
Journal: Diabetes Care (1986)

Analysis of 182 Tecumseh residents with non-insulin-dependent diabetes mellitus (NIDDM) and 364 controls matched for age and sex demonstrates increased levels of relative weight, blood pressure, and cholesterol in the diabetic group but similar smoking habits for the two groups. Consequently, the risk for acquiring coronary heart disease (CHD) in the next 8 yr calculated by the Framingham logistic regression equation shows a marked increase in risk for both men and women with diabetes (relative risk = 1.3 and 1.9, respectively). This calculated risk for CHD incidence predicts actual deaths from CHD, cardiovascular disease, and all causes in diabetic individuals in the succeeding 15 yr. Baseline levels of cholesterol, blood pressure, and smoking in the NIDDM population were hypothetically reduced according to results achieved in recent coronary-risk intervention trials. Average population risk for CHD incidence was recalculated and compared with new risk estimates calculated by hypothetically eliminating diabetes in various proportions of the population. Crude estimates suggest that realistic attempts to lower one, two, or three coronary risk factors in the population would reduce calculated CHD risk equivalent to eliminating diabetes in 20, 40, and 60% of the population, respectively.
Evidence for mitochondrial KATP channels as effectors of human myocardial preconditioning
Authors: S Ghosh
Journal: Cardiovascular Research (2000)

Background: Sublethal periods of ischemia preceding a prolonged interval of ischaemia protect the myocardium. This myocardial preconditioning (PC) appears to be effected by KATP channels. These channels occur both in the sarcolemma and the mitochondrial membrane. We investigated whether mitochondrial KATP channels are the end-effector of PC in the human myocardium. Methods: Right atrium specimens obtained from patients undergoing cardiac surgery were prepared and incubated in buffer solution at 37°C. After 30-min stabilisation, the muscles were made ischemic for 90 min and then reperfused for 120 min. The preparations were randomised into eight experimental groups (n=6/group): (1) Aerobic control — incubated in oxygenated buffer for 210 min, (2) ischemia alone — 90 min ischemia followed by 120 min reperfusion, (3) PC — preconditioned with 5 min ischemia/5 min reperfusion, (4) Glibenclamide (10 μM) in the incubation media for 10 min before PC, (5) 5-hydroxydecanoate (5-HD, MitoKATP blocker, 1 mM) in the incubation media for 10 min before PC, (6) HMR 1883 (SarcKATP blocker, 10 μM) in the incubation media for 10 min before PC, (7) Pinacidil (0.5 mM) in the incubation media for 10 min before ischemia, and (8) Diazoxide (MitoKATP opener, 0.1 mM) in the incubation media for 10 min before ischemia. Creatinine kinase leakage into the medium (CK, IU/g wet wt) and MTT reduction (OD/mg wet wt.), an index of cell viability, were assessed at the end of the experiment. Results: Ischemia alone resulted in a significant increase in CK leakage (8.01±0.35) and decrease in MTT (0.15±0.01) from the values seen in the aerobic control (2.24±0.52 and 0.78±0.10 respectively, P<0.05 in both instances). PC fully reversed the effect of ischemia (CK=2.97±0.31 and MTT=0.61±0.05; P<0.05 vs. ischemia alone group but P=NS vs. aerobic control group). Both Glibenclamide and 5-HD abolished the protection induced by PC (CK=6.23±0.5 and 7.84±0.64; MTT=0.18±0.03 and 0.13±0.02, respectively, P<0.05 vs. PC), but interestingly, the protective effect of PC was not abolished by HMR 1883 (CK=2.85±0.24 and MTT=0.58±0.05, P=NS vs. PC). Diazoxide mimicked the protective effect of PC (CK=3.56±0.32 and MTT=0.58±0.02, P=NS vs. PC), however pinacidil exhibited less protection than PC (CK=4.02±0.16 and MTT=0.30±0.02, P<0.05 vs. PC). Conclusions: These studies demonstrate that KATP channels are the end-effectors of ischemic preconditioning and that protection is mediated by mitochondrial KATP channels in human right atrial myocardium.
Preconditioning does not attenuate myocardial stunning.
Authors: M Ovize, K Przyklenk, S L Hale, R A Kloner
Journal: Circulation (1992)

BACKGROUND Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown. METHODS AND RESULTS We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning. CONCLUSIONS Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.