tbuckley/cabot-search huggingface dataset:
Carcinoma of Colon in Youth of 17 causing Acute Intestinal Obstruction
Authors: J. Scholefield
Journal: BMJ (1946)

This medical humanities paper describes our qualitative research into pathways to care and informed consent for 10 children who had cardiac surgery in the Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Our multidisciplinary team consists of cardiologists, anthropologists, a social scientist and a general practitioner in two sites, South Africa and Australia. This paper builds on our first publication in a specialist cardiology journal on a ‘qualitative snapshot’ of these children’s life stories from 2011 to 2016 but turns to the medical humanities to explore a concept of ‘uncertainty’. Data analysis revealed that for the children’s parents and doctors, ‘uncertainty’ underscored procedures. Indeed, the literature review showed that ‘uncertainty’ is intrinsic to heart surgery and was integral to Barnard’s first heart transplant in Cape Town in 1967. We demonstrate that in meeting the challenges inherent in the ‘uncertainty dimension’, doctors established greater ‘medical certainty’about each operation. This happened as they encountered the difficult clinical and biopsychosocial factors that were fundamental to the diagnosis of children’s cardiac defects. It was doctors’ translation of these decision-making processes that informed parental decisions and described why, despite feelings of uncertainty, parents signed consent. To visually describe heart surgery in this locality we asked the South African photographer, Guy Neveling to record some children undergoing echocardiograms and surgery. These photographs qualitatively demonstrate what medical certainty entails, and parents’ trust in doctors and surgeons, whom they knew had ‘reasonable certainty’ that their child’s <i>‘heart is worth saving’</i>.
Mitochondrial Ca2+ and ROS take center stage to orchestrate TNF-α–mediated inflammatory responses
Authors: Laura A. Dada, Jacob I. Sznajder
Journal: Journal of Clinical Investigation (2011)

Proinflammatory stimuli induce inflammation that may progress to sepsis or chronic inflammatory disease. The cytokine TNF-α is an important endotoxin-induced inflammatory glycoprotein produced predominantly by macrophages and lymphocytes. TNF-α plays a major role in initiating signaling pathways and pathophysiological responses after engaging TNF receptors. In this issue of JCI, Rowlands et al. demonstrate that in lung microvessels, soluble TNF-α (sTNF-α) promotes the shedding of the TNF-α receptor 1 ectodomain via increased mitochondrial Ca²+ that leads to release of mitochondrial ROS. Shedding mediated by TNF-α-converting enzyme (TACE) results in an unattached TNF receptor, which participates in the scavenging of sTNF-α, thus limiting the propagation of the inflammatory response. These findings suggest that mitochondrial Ca²+, ROS, and TACE might be therapeutically targeted for treating pulmonary endothelial inflammation.
Prognostic implications of basophil differentiation in chronic myeloid leukemia
Authors: Judah A. Denburg, George Browman
Journal: American Journal of Hematology (1988)

Abstract Basophilia has been reported to indicate an accelerated phase of chronic myeloid leukemia (CML), heralding a poor prognosis. We have studied 47 patients with chronic‐phase CML by basophil growth and differentiation assays in vitro, demonstrating an association between basophil growth index (BGI) and clinical time to blast crisis as well as overall survival. In addition to confirming an association between positive BGI and phase of CML in a larger group of patients, a positive BGI predicted death or blast crisis within 2 years' study of chronic phase CML (p&lt;0.01), with a sensitivity of 78%, specificity, 81%; the positive predictive value of a positive test, 64%; and a negative predictive value of a negative test, 89%. The survival experience of the 22 evaluable patients with chronic‐phase CML and a positive BGI was significantly worse than the survival of the 19 patients with a negative BGI (p&lt;0.0001). At 1, 2, and 3 years the proportion of surviving patients with a positive BGI was 0.64, 0.32, and 0.23, respectively, compared with 1.00, 0.90, and 0.79 for those with a negative BGI. The median survival of chronic phase CML patients with a positive test at diagnosis (n = 14) was 27 months versus 54 months for those with a negative diagnosis (n = 14) (p&lt;0.05). These findings emphasize the prognostic utility of basophil growth assays in CML and suggest a molecular relationship between leukemic transformation and basophil lineage expression.
Primary Prevention of Ovarian Cancer
Authors: David A. Grimes
Journal: JAMA (1993)

Ovarian cancer remains the deadliest gynecologic malignancy in the United States, killing more women each year than cervical and endometrial cancers combined. Despite aggressive operations and intensive chemotherapy, the 5-year survival rate is less than 40%.<sup>1</sup>Complications such as bowel obstruction, inanition, ascites, and pleural effusions can make this a wretched way to die. Hence, the finding of Hankinson et al<sup>2</sup>in this issue of<i>JAMA</i>is heartening: tubal sterilization may protect against this malignancy. See also p 2813. The Nurses' Health Study is not the first to observe this protection.<sup>3-5</sup>The importance of this research, however, stems from its design: a large, prospective cohort study. Cohort studies avoid some of the vexing problems of case-control studies, such as selection of an appropriate control group. Ascertainment bias is unlikely to have accounted for these results. The respondents were knowledgeable health professionals, and medical records confirmed reported illness. While
A Reasonable Suggestion
Authors: C. Johnson
Journal: BMJ (1865)

<h3>OBJECTIVE</h3> To investigate the hypothesis that the time to washout of radiographic contrast medium trapped distal to an occluded collateral receiving vessel is inversely related to collateral flow, and that this provides an accurate method for characterising coronary collaterals. <h3>METHODS</h3> An intracoronary pressure derived collateral flow index was determined in 54 patients undergoing percutaneous transluminal coronary balloon angioplasty (PTCA). The study group was subdivided according to whether the collateral vessels were sufficient (n = 17) or insufficient (n = 37) to prevent ECG signs of myocardial ischaemia during PTCA. Washout collaterometry—an angiographic washout method—was carried out simultaneously; after injection of radiographic contrast medium into the collateral receiving vessel followed immediately by vascular occlusion, the number of heart beats was counted until approximately half the length of the epicardial vessel was cleared of contrast. <h3>RESULTS</h3> The collateral flow index was higher (0.28 (0.09) <i>v</i> 0.12 (0.07); p &lt; 0.0001) and the contrast washout time shorter (8.0 (2.9)<i>v</i> 17.5 (6.7) heart beats; p &lt; 0.0001) in patients with sufficient versus insufficient collaterals. There was an inverse correlation between contrast washout time and collateral flow index (<i>r</i> = 0.72, p &lt; 0.0001). Washout of contrast distal to the occluded vessel within 11 heart beats correctly determined sufficient and insufficient collaterals with 88% sensitivity and 81% specificity. <h3>CONCLUSIONS</h3> Washout collaterometry is a new radiographic contrast washout method based on the inverse relation between collateral flow and the time to clearance of radiographic dye injected into the ipsilateral vessel during PTCA. It appears to be an accurate method of characterising coronary collateral vessels.
Low Exhaled Nitric Oxide and a Polymorphism in the NOS I Gene Is Associated with Acute Chest Syndrome
Authors: KEVIN J. SULLIVAN, NIRANJAN KISSOON, LAURIE J. DUCKWORTH, ERIC SANDLER, BRIDGET FREEMAN, EDWARD BAYNE, JAMES E. SYLVESTER, JOHN J. LIMA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Abnormalities of nitric oxide metabolism have been implicated in the pathogenesis of acute chest syndrome in subjects with sickle cell anemia. It is not known whether exhaled nitric oxide levels (Feno ) are abnormal in children with a history of the acute chest syndrome (ACS). We compared Feno , plasma nitric oxide metabolites (NO x ), serum arginine and citrulline levels, and the number of AAT repeats in intron 20 of NOS I in subjects with sickle cell disease (SCD) and a history of at least one episode of ACS (ACS+, n = 13), subjects with SCD and no prior history of ACS (ACS−, n = 7), and healthy children (HC, n = 6). Mean ± SD Feno (ppb) was lower in ACS+ than in ACS− and HC: (10.4 ± 4.3 versus 23.4 ± 6.1 p = 0.002] and 30.4 ± 15.8 [p = 0.0001], respectively). Plasma NO x ( μ M) were similar in all three groups (37.3 ± 19.4, 33.0 ± 13.2, 44.7 ± 7.8, respectively). Arginine and citrulline levels ( μ M) did not differ between ACS+ and ACS− groups. Spirometric data revealed a mildly diminished FEV1 and FVC in ACS+ that was statistically different from HC but not ACS−: (FEV1 as % of predicted for ACS+, ACS−, and HC; 83 ± 17 versus 87 ± 16 versus 102 ± 16, respectively, p < 0.05 between ACS+ and HC). The level of Feno was significantly associated with the sum of AAT repeats in intron 20 of NOS I gene alleles. The correlation coefficient (r) was 0.62 (p < 0.005). We conclude that Feno levels are significantly reduced in subjects who have a history of ACS and that the Feno levels are significantly correlated with the number of NOS I AAT repeats. Feno is a sensitive marker and may be a predictor of ACS prone children.
Implantation of Cardioverter Defibrillators Without Induction of Ventricular Fibrillation
Authors: Charles D. Swerdlow
Journal: Circulation (2001)

The upper limit of vulnerability (ULV) is the weakest shock at which ventricular fibrillation (VF) is not induced by a T-wave shock. This study tested the hypothesis that a vulnerability safety margin based on the ULV can be used as an implantable cardioverter-defibrillator implantation criterion.Implantable cardioverter-defibrillators were implanted in 80 patients if T-wave shocks did not induce VF and the baseline-rhythm R wave was >/=7 mV. The T-wave shock was 10 J in the first 45 patients (group A) and 15 J in the last 35 patients (group B). After inductionless implantations, the first VF shock was programmed to the T-wave shock plus 5 J. If T-wave shocks induced VF, the ULV was measured and the first shock was programmed to the ULV+5 J. Inductionless implantations were performed in 58 patients (72%), 28 in group A (62%) and 30 in group B (86%; P=0.04). If T-wave scanning had been done at 15 J in group A patients, inductionless implantations could have been performed in 84% of them. At 3 months, VF was induced twice during electrophysiological study in 75 patients (94%). All VFs were detected in </=4.7 s and were terminated by the first shock. During follow-up, 197 of 198 appropriate first shocks for rapid ventricular tachycardia or VF (99%) were successful in patients who had inductionless implantations (95% confidence intervals, 97% to 100%).Inductionless implantations can be performed in >80% of implantable cardioverter-defibrillator recipients using a vulnerability safety margin based on a T-wave scan at 15.
THE HEMODYNAMIC EFFECTS OF HYPOTENSIVE DRUGS IN MAN. II. DIHYDROERGOCORNINE 1
Authors: Edward D. Freis, Joseph R. Stanton, Julius Litter, James W. Culbertson, Meyer H. Halperin, F. Corbin Moister, Robert W. Wilkins
Journal: Journal of Clinical Investigation (1949)

Dale in 1906 recognized the sympatholytic ac- tivity of crude extracts of ergot as well as their property of direct stimulation of smooth muscle, including that of the blood vessels (1).Despite their sympatholytic effects their direct vasocon- strictor action prevented significant lowering of arterial pressure.Later chemical purification of the crude drug resulted in the isolation of five alkaloids: ergot- amine (2), ergobasine (3), ergokryptine, ergocornine and ergocristine (4).The basic chemical structure of these compounds was clarified by Jacobs and Craig (5) who demonstrated the presence of lysergic acid in all of the alkaloids (6).By hydrogenating the reducible double bond of the lysergic acid component of four of these alkaloids, Stoll and Hofmann (7) in 1943 produced a new series of compounds, dihydroergotamine, di- hydroergocristine, dihydroergocornine (DHO-180) 5 and dihydroergokryptine (DHK-135).5Pharmacological studies in animals (8) indicated that these modified compounds have enhanced sympatholytic and adrenolytic properties but little or no direct constrictor action on smooth muscle.In addition, they are hypotensive, this effect being mediated at least in part via the central nervous system (9).In man DHO and DHK in non-toxic doses have sympatholytic and hypotensive prop-
Early Fetal Growth and Development
Authors: D V Walters
Journal: BMJ (1994)

Ed R H T Ward, S K Smith, D Donnai RCOG Press, £35, pp 456 ISBN 0-902331-64-7

It is surprising in this day and age to come across a biological subject which is so poorly understood and so comparatively little researched that it hardly impinges on our consciousness. Furthermore, it is equally refreshing to discover that it is one in which genetic mechanisms are not all powerful. Indeed, the underlying theme of Early Fetal Growth and Development is that it is environmental factors which have a …
Small molecule Toll-like receptor 7 agonists localize to the MHC class II loading compartment of human plasmacytoid dendritic cells
Authors: Carla Russo, Ivan Cornella-Taracido, Luisa Galli-Stampino, Rishi Jain, Edmund Harrington, Yuko Isome, Simona Tavarini, Chiara Sammicheli, Sandra Nuti, M. Lamine Mbow, Nicholas M. Valiante, John Tallarico, Ennio De Gregorio, Elisabetta Soldaini
Journal: Blood (2011)
Protection from ischaemic-reperfusion injury with adenosine pretreatment is reversed by inhibition of ATP sensitive potassium channels
Authors: C. F Toombs, D S. McGee, W. E Johnston, J. Vinten-Johansen
Journal: Cardiovascular Research (1993)

The aim was to test the hypothesis that the cardioprotective effects against ischaemic-reperfusion injury of pretreatment with adenosine are mediated in part by activation of ATP sensitive potassium channels (K+ATP channels).42 anaesthetised New Zealand White rabbits underwent 30 min coronary occlusion, followed by 2 h reperfusion. Half the animals received a 5 min infusion of 140 micrograms.kg-1.min-1 of adenosine as pretreatment. The remainder of the animals received a 5 min infusion of saline alone as pretreatment. Animals pretreated with adenosine received either a low dose of the K+ATP channel blocker glibenclamide (0.3 mg.kg-1), high dose glibenclamide (3.0 mg.kg-1), or vehicle immediately prior to ischaemia to test whether glibenclamide can reverse the protective effects of adenosine, thus allowing the adenosine effect but antagonising K(+)ATP channel activation during ischaemia. Animals which received saline pretreatment also received low dose glibenclamide, high dose glibenclamide, or vehicle (controls) to evaluate the effect of glibenclamide alone. Infarct size was determined with tetrazolium and Unisperse Blue stains, and transmural blood flow was measured using radioactive microspheres.Although there were no differences in collateral myocardial blood flow during ischaemia or in risk area among the groups, infarct size was reduced by adenosine pretreatment to 8 (SEM 3)% v 36(4)% in controls (p < 0.05). K(+)ATP channel blockade with low dose glibenclamide in saline pretreated animals did not by itself extend the degree of necrosis [33(4)%], whereas low dose glibenclamide prevented the protective effects of adenosine pretreatment [38(3)%]. High dose glibenclamide reversed adenosine protection as well [54(3)%], but at a dose which increased infarct size in saline pretreated animals [52(3)%].While adenosine pretreatment protects against necrosis in the rabbit, (1) the expression of this protection depends at least in part upon the actions of K(+)ATP channels during ischaemia, and (2) glibenclamide at higher doses increases infarct size, suggesting either that the K(+)ATP channel is endogenously protective during ischaemia, or that the higher dose has other infarct extending effects.
Biliverdin inhibits hepatitis C virus nonstructural 3/4A protease activity: Mechanism for the antiviral effects of heme oxygenase?
Authors: Zhaowen Zhu, Anne T. Wilson, Bruce A. Luxon, Kyle E. Brown, M. Meleah Mathahs, Sarmistha Bandyopadhyay, Anton P. McCaffrey, Warren N. Schmidt
Journal: Hepatology (2010)

Induction of heme oxygenase-1 (HO-1) inhibits hepatitis C virus (HCV) replication. Of the products of the reaction catalyzed by HO-1, iron has been shown to inhibit HCV ribonucleic acid (RNA) polymerase, but little is known about the antiviral activity of biliverdin (BV). Herein, we report that BV inhibits viral replication and viral protein expression in a dose-dependent manner in replicons and cells harboring the infectious J6/JFH construct. Using the SensoLyte 620 HCV Protease Assay with a wide wavelength excitation/emission (591 nm/622 nm) fluorescence energy transfer peptide, we found that both recombinant and endogenous nonstructural 3/4A (NS3/4A) protease from replicon microsomes are potently inhibited by BV. Of the tetrapyrroles tested, BV was the strongest inhibitor of NS3/4A activity, with a median inhibitory concentration (IC(50)) of 9 μM, similar to that of the commercial inhibitor, AnaSpec (Fremont, CA) #25346 (IC(50) 5 μM). Lineweaver-Burk plots indicated mixed competitive and noncompetitive inhibition of the protease by BV. In contrast, the effects of bilirubin (BR) on HCV replication and NS3/4A were much less potent. Because BV is rapidly converted to BR by biliverdin reductase (BVR) intracellularly, the effect of BVR knockdown on BV antiviral activity was assessed. After greater than 80% silencing of BVR, inhibition of viral replication by BV was enhanced. BV also increased the antiviral activity of α-interferon in replicons.BV is a potent inhibitor of HCV NS3/4A protease, which likely contributes to the antiviral activity of HO-1. These findings suggest that BV or its derivatives may be useful in future drug therapies targeting the NS3/4A protease.
Hypertension Subtype and Risk of Cardiovascular Disease in Chinese Adults
Authors: Tanika N. Kelly, Dongfeng Gu, Jing Chen, Jian-feng Huang, Ji-chun Chen, Xiufang Duan, Xigui Wu, C. Lillian Yau, Paul K. Whelton, Jiang He
Journal: Circulation (2008)

We examined the relationship between hypertension subtype and cardiovascular disease incidence and mortality in Chinese adults.We conducted a prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged >or=40 years. Data on systolic (SBP) and diastolic blood pressure (DBP) and other variables were obtained at a baseline examination in 1991 with the use of standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Hypertension subtypes were defined as combined systolic and diastolic hypertension (SBP >or=140 and DBP >or=90 mm Hg), isolated systolic hypertension (SBP >or=140 and DBP <90 mm Hg), isolated diastolic hypertension (SBP <140 and DBP >or=90 mm Hg), and 2 categories of treated hypertension (SBP <140 and DBP <90 mm Hg or SBP >or=140 and/or DBP >or=90 mm Hg). After participants with missing BP values were excluded, 169 577 adults were included in the analyses. Compared with normotensives, relative risks (95% CIs) of cardiovascular disease incidence and mortality were 2.73 (2.60 to 2.86) and 2.53 (2.39 to 2.68) for combined systolic and diastolic hypertension, 1.78 (1.69 to 1.87) and 1.68 (1.58 to 1.78) for isolated systolic hypertension, 1.59 (1.43 to 1.76) and 1.45 (1.27 to 1.65) for isolated diastolic hypertension, 2.01 (1.64 to 2.48) and 1.61 (1.28 to 2.03) for treated hypertension with SBP <140 and DBP <90 mm Hg, and 3.37 (3.07 to 3.69) and 2.88 (2.60 to 3.19) for treated hypertension with SBP >or=140 and/or DBP >or=90 mm Hg, respectively, after adjustment for important covariables.Our results indicate that all hypertension subtypes are associated with significantly increased risk of cardiovascular disease in Chinese adults. Primary prevention of hypertension should be a public health priority in the Chinese population.
Development of molecularly targeted therapies in biliary tract cancers: Reassessing the challenges and opportunities
Authors: Andrew X. Zhu, Aram F. Hezel
Journal: Hepatology (2011)

Biliary tract cancers (BTCs), which encompass intra- and extrahepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic chemotherapy approaches are emerging, the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early-stage clinical trials with targeted therapies appear promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here we summarize the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC.
Health Care in the 21st Century
Authors: William H. Frist
Journal: New England Journal of Medicine (2005)

Dr. William H. Frist is the majority leader of the U.S. Senate and a cardiac-transplantation surgeon. He is the fifth cardiac surgeon and the first U.S. senator to deliver the Shattuck Lecture, the 114th in this series. Dr. Frist outlines his vision for the U.S. health care system in the year 2015.
The March of Unreason: Science, Democracy, and the New Fundamentalism
Authors: Geoff Watts
Journal: BMJ (2005)

Let me start with a brief quote, not from Dick Taverne's book, but from an essay unpromisingly titled “Constructivism in the works of Gibson” by (allegedly) Stephen McElwaine of Harvard and John Geoffrey of the Massachusetts Institute of Technology. A warning: you may find it hard going. But stay with me—it's only a paragraph.

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Dick Taverne

Oxford University Press, £18.99, pp 310

ISBN 0 19 280485 5

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“If one examines precultural narrative, one is faced with a choice: either accept postmaterialist textual theory or conclude that sexual identity has intrinsic meaning. But a number of deappropriations concerning the difference between class and sexuality exist. Baudrillard uses the term ‘precultural narrative’ to denote not theory per se , but subtheory. Therefore, Sontag's model of the postconceptual paradigm of context implies that the raison d'etre of the observer is deconstruction.”

Did you understand that? If you think you did, the understanding lies exclusively within your own brain because that passage—and the essay from which it came—was the 1 536 888th written by a computer. Each is unique and each was created, on demand …

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