tbuckley/cabot-search huggingface dataset:
BITE OF A POISONOUS SPIDER, LATRODECTUS MACTANS.
Authors: ALEXANDER L. HODGDON
Journal: JAMA (1907)

The toxic qualities of the spider that is known as<i>Latrodectus mactans</i>are not, I believe, generally known. An appropriate name for the spider would be the "T and dot" spider, as the specimen I have seen was coal black with a red T and red dot. Some weeks ago I was called to see a man who, pulling on his boot, had pressed on one of these spiders with the side of his foot. The spider's bite at the time caused him but little pain or inconvenience. About twenty-five minutes after being bitten, however, acute and agonizing pains occurred all over the body, being particularly severe in the region of the chest. Aqua ammoniæ was applied locally and also administered, well diluted, internally, and previous to my arrival the patient had taken considerable whisky. Morphin sulphate, strychnin sulphate and nitroglycerin were administered hypodermically, and while the latter two drugs
A Decision Support Framework for Genomically Informed Investigational Cancer Therapy
Authors: Funda Meric-Bernstam, Amber Johnson, Vijaykumar Holla, Ann Marie Bailey, Lauren Brusco, Ken Chen, Mark Routbort, Keyur P Patel, Jia Zeng, Scott Kopetz, Michael A Davies, Sarina A Piha-Paul, David S Hong, Agda Karina Eterovic, Apostolia M Tsimberidou, Russell Broaddus, Elmer V Bernstam, Kenna R Shaw, John Mendelsohn, Gordon B Mills
Journal: JNCI Journal of the National Cancer Institute (2015)

Rapidly improving understanding of molecular oncology, emerging novel therapeutics, and increasingly available and affordable next-generation sequencing have created an opportunity for delivering genomically informed personalized cancer therapy. However, to implement genomically informed therapy requires that a clinician interpret the patient’s molecular profile, including molecular characterization of the tumor and the patient’s germline DNA. In this Commentary, we review existing data and tools for precision oncology and present a framework for reviewing the available biomedical literature on therapeutic implications of genomic alterations. Genomic alterations, including mutations, insertions/deletions, fusions, and copy number changes, need to be curated in terms of the likelihood that they alter the function of a “cancer gene” at the level of a specific variant in order to discriminate so-called “drivers” from “passengers.” Alterations that are targetable either directly or indirectly with approved or investigational therapies are potentially “actionable.” At this time, evidence linking predictive biomarkers to therapies is strong for only a few genomic markers in the context of specific cancer types. For these genomic alterations in other diseases and for other genomic alterations, the clinical data are either absent or insufficient to support routine clinical implementation of biomarker-based therapy. However, there is great interest in optimally matching patients to early-phase clinical trials. Thus, we need accessible, comprehensive, and frequently updated knowledge bases that describe genomic changes and their clinical implications, as well as continued education of clinicians and patients.
Behçet's syndrome: Immune regulation, circulating immune complexes, neutrophil migration, and colchicine therapy
Authors: Joseph L. Jorizzo, R. Donald Hudson, Frank C. Schmalstieg, Jerry C. Daniels, Prapand Apisarnthanarax, John C. Henry, Emilio B. Gonzalez, Yukinobu Ichikawa, Tito Cavallo
Journal: Journal of the American Academy of Dermatology (1984)
The neural representation of spatial predicate-argument structures in sign language
Authors: Bencie Woll
Journal: Behavioral and Brain Sciences (2003)

Evidence from studies of the processing of topographic and classifier constructions in sign language sentences provides a model of how a mental scene description can be represented linguistically, but it also raises questions about how this can be related to spatial linguistic descriptions in spoken languages and their processing. This in turn provides insights into models of the evolution of language.
Effects of interleukin (IL)‐3 and IL‐5 on human eosinophil degranulation induced by complement components C3a and C5a*
Authors: S. Takafuji, K. Tadokoro, K. Ito
Journal: Allergy (1996)

It is suggested that eosinophils (Eos) play an important role in the pathogenesis of bronchial asthma by releasing cytotoxic cationic eosinophil granule proteins and damaging bronchial epithelial cells. However, the exact nature of the actual inducer of eosinophil degranulation in vivo is unclear. We examined eosinophil cationic protein (ECP) release from human Eos in response to soluble agonists such as C5a, C3a, platelet-activating factor, and FMLP with or without interleukin (IL)-3 or IL-5 priming. Eosinophil degranulation induced by these soluble agonists required the pretreatment of Eos by cytochalasin B even in IL-3 priming. Among four agonists, C5a was the most effective stimulus of ECP release either with or without IL-5 priming. IL-3 and IL-5 remarkably enhanced ECP release in Eos triggered by C3a and C5a. The enhancement of ECP release by IL-3 and IL-5 occurred at 0.1-0.3 ng/ml and became maximal at 10-30 ng/ml, concentration-dependently. The enhancement of ECP release by cytokines became optimal at an interval of 10 min. Our data support the importance of complement components and cytokines in eosinophil degranulation in vivo.
Incidence and Prognosis of Different Types of Functional Renal Failure in Cirrhotic Patients With Ascites
Authors: Silvia Montoliu, Belén Ballesté, Ramon Planas, Marco Antonio Álvarez, Mònica Rivera, Mireia Miquel, Helena Masnou, Isabel Cirera, Rosa Maria Morillas, Susanna Coll, Margarita Sala, Montserrat García–Retortillo, Nuria Cañete, Ricard Solà
Journal: Clinical Gastroenterology and Hepatology (2010)
Doctors reject call for a ban on advertisements of reformulated drugs
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

NHS Employers, the organisation responsible for employment procedures in the NHS, defended its vetting practices this week after seven doctors and medical students-six in the United Kingdom and one in Australia-were held by police in connection with the failed car bombings in London and Glasgow.One doctor, Iraqi born Bilal Abdullah, who worked as a locum doctor at the Royal Alexandra Hospital, in Paisley, near Glasgow, was arrested at the scene of Saturday's attempt to blow up a jeep packed with gas cylinders at Glasgow airport.Another man detained at the scene with 90% burns is thought to be a junior hospital doctor.He is in the Royal Alexandra Hospital.Later that day, the 26 year old Jordanian born doctor Mohammed Asha and a 27 year old woman, thought to be his wife, were arrested in Sandbach, Cheshire, northwest England.Dr Asha, whose family comes originally from Palestine, had worked as a junior doctor at the Royal Shrewsbury Hospital and the Princess Royal Hospital, in Telford.In a statement NHS Employers said that all NHS hospitals "carry out rigorous checks before they appoint any member of staff, including verification of identity, qualifications, registration, and eligibility to work in the UK."The nature of their work means that staff are dealing with people who are vulnerable, and we need to be confident that patients are safe."It added, "While doing all they can to prevent unsuitable people taking up employment in the NHS, employers also have a duty to look after the rights of their staff, and this includes not discriminating against employees in any way on the grounds of their religion or belief." NHS defends vetting after doctors held for bombing bidsUK NEWS Economist says NICE should approve fewer costly drugs, p11 World NEWS �ost US surgeons in training get needlestic�� in�uries, few report them, p1� �ost US surgeons in training get needlestic�� in�uries, few report them, p1� , p1� bm�.comEgypt tightens ban on female genital mutilation after 1�� year old girl dies Egypt tightens ban on female genital mutilation after 1�� year old girl dies
Circulating Antibodies to Cow's Milk Proteins and Gluten in the Newborn
Authors: R. Wright, K. B. Taylor, S. C. Truelove, R. Aschaffenburg
Journal: BMJ (1962)

Recent studies have shown that in certain diseases of the alimentary tract abnormally high concentrations of circulating antibodies to cow's milk proteins may occur.Thus Taylor and Truelove (1961) found that such anti- bodies were more likely to be present in high titres in patients with ulcerative colitis than in healthy subjects, and this has been confirmed by other workers (Gray, 1961 ; Davidson, 1961).Similarly, patients with coeliac disease and idiopathic steatorrhoea are much more likely to have circulating antibodies in high titres to cow's milk proteins and to partly proteolysed wheat gluten (Taylor et al., 1961).These high antibody titres might be an expression of pre-existing states of hypersensitivity to common dietary proteins, which may serve as aetiological factors in these diseases, or they might indicate that in certain alimentary diseases abnormal absorption of such proteins occurs, with enhanced antibody formation.Acheson and Truelove (1961) have found that patients with ulcerative colitis are more likely to have been bottle-fed during the first few weeks of life than healthy matched controls.This suggests that there may be a relationship between early exposure to potentially anti- genic material and later development of a disease which could possibly be caused wholly or in part by a distur- bance of normal immunological response.That milk proteins may be involved in such a way is strongly supported by clinical observations which have shown that some patients with ulcerative colitis become symptom-free when put on a milk-free diet and relapse in a few days or weeks after reintroduction of cow's
GP in jail for child rape is struck off
Authors: C. Dyer
Journal: BMJ (2014)

<h3>Background</h3> The English NHS Bowel Cancer Screening Programme has offered biennial faecal occult blood testing to people aged 60–69 years since 2006, and to those aged 60–74 years since 2010. Analysis of the first 2.6 million screening invitations found that 54% of eligible people took up the invitation. The reasons for this low uptake are unclear. We investigated whether participation in screening varies according to cognitive ability and personality. <h3>Methods</h3> Participants were members of The English Longitudinal Study of Ageing. In 2010–2011, respondents were asked about participation in bowel cancer screening, and cognitive ability and the ‘Big Five’ personality traits were assessed. Logistic regression was used to examine the cross-sectional relationships between cognitive ability and personality and screening participation in 2681 people aged 60–75 years who were eligible to have been invited to take part in the UK national screening programme for bowel cancer. <h3>Results</h3> In age-adjusted and sex-adjusted analyses, better cognition and higher conscientiousness were associated with increased participation in cancer screening. ORs (95% CIs) per SD increase were 1.10 (1.03 to 1.18) for cognitive ability and 1.10 (1.01 to 1.19) for conscientiousness. After further adjustment for household wealth and health literacy—shown previously to be associated with participation—these associations were attenuated (ORs were 1.07 (1.00 to 1.15) and 1.07 (0.97 to 1.18), respectively). <h3>Conclusions</h3> We found some indication that better cognitive function and greater conscientiousness may be linked with a slightly increased likelihood of participation in bowel cancer screening. These relationships need investigation in other cohorts of older people.
613 NEBIVOLOL DETERIORATES PORTAL HEMODYNAMICS IN CIRRHOTIC RATS BY INCREASING SPLANCHNIC BLOOD FLOW
Authors: T. Reiberger, B.A. Payer, B. Angermayr, V. Fuhrmann, P. Schwabl, B. Jäger, T. Hummel, T. Horvatits, M. Mitterhauser, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2011)
Abstract 4052: Highlighting intratumoral heterogeneity and peritumoral areas in human melanoma biopsies by infrared spectral microimaging
Authors: David Sebiskveradze, Cyril Gobinet, Nathalie CARDOT-LECCIA, Jean-Paul ORTONNE, Michel MANFAIT, Pierre JEANNESSON, Olivier PIOT
Journal: Cancer Research (2012)

Abstract Infrared (IR) spectral microimaging is an efficient label-free optical method to analyze biological samples and to provide information about their intrinsic biochemical composition. Recent studies have shown its potential to detect and characterize cancerous tissues in their early stages, independently of visual morphology. IR microimaging appears more informative than conventional histology and could thus be developed as a sensitive, non-destructive and objective diagnostic tool in clinical oncology. The discrimination between tumoral and surrounding tissues relies on highlighting subtle IR spectral differences. An innovative fuzzy clustering based algorithm was thus developed in order to introduce the notion of nuance into the clustering of IR image pixels and to automatically determine the optimal clustering parameters, particularly the number of clusters. IR spectral imaging has been directly acquired on formalin-fixed paraffin-embedded tissue sections of human cutaneous melanomas with different degrees of invasiveness (n=10 patients). After the application of the fuzzy algorithm, the reconstructed color-coded clustering images allow recovering different histological structures automatically, particularly to precisely localize tumoral areas and their normal counterparts. However, more than reproducing classical histology, our algorithm can give access to additional information about the tissular structures. The notion of nuance introduced by fuzzy clustering is valuable for the pixels located at the interface between tumoral tissue and its microenvironment. Heterogeneous transitional areas between tumor and marginal normal tissue are identified, what is not possible on hematoxylin-eosin stained section or by conventional clustering. In addition, this automatic approach of IR data processing permits to highlight the interconnectivity between heterogeneous intratumoral areas and between tumoral and peritumoral structures. These preliminary results show significant potential for probing tumor progression and for early determination of tumor aggressiveness in cutaneous melanomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4052. doi:1538-7445.AM2012-4052
Inhibitory effect of 9-amino- 1,2,3,4-tetrahydroacridine (THA) on the potassium current of rabbit sinoatrial node
Authors: H. Kotake, I. Hisatome, S. Matsuoka, H. Miyakoda, J. Hasegawa, H. Mashiba
Journal: Cardiovascular Research (1990)

Study objective – To examine the effect of 9-amino-1,2,3,4-tetrahydroacridine (THA), a compound similar to the K+ blocker 4-aminopyridine, on potassium channels in the sinoatrial node. Design – The pace making portion of rabbit sinoatrial nodes was studied using the double microelectrode voltage clamp method in the presence of THA at various concentrations. Measurements and results – Above 1 μmol·litre−1, THA prolonged the spontaneous cycle length and the transmembrane action potential duration at 50% repolarisation. Above 10 μmol·litre−1, the compound also decreased the maximum rate of rise, the action potential amplitude, and the rate of diastolic depolarisation. Under voltage clamp conditions, THA reduced the time dependent K+ current (IK) in a dose dependent manner. Neither the decay process of IK nor its activation process were altered by THA. Conclusions – THA depresses sinoatrial node IK without changing its kinetics. Thus it may inhibit the open state of the potassium channels.
Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes
Authors: Giorgia De Berardis, Giuseppe Lucisano, Antonio D’Ettorre, Fabio Pellegrini, Vito Lepore, Gianni Tognoni, Antonio Nicolucci
Journal: JAMA (2012)

The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage.To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin.A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period.Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy.There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44).In a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.
Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion.
Authors: W J Dreyer, L H Michael, M S West, C W Smith, R Rothlein, R D Rossen, D C Anderson, M L Entman
Journal: Circulation (1991)

BACKGROUND We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism. METHODS AND RESULTS We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region. CONCLUSIONS These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.
The Learning Curve
Authors: Raphael P. Nenner
Journal: JAMA (1994)

<h3>To the Editor.</h3> —In his Editorial, Mr Hatlie states that complications occur infrequently with laparoscopic cholecystectomy.<sup>1</sup>This general conclusion is based on a number of published prospective and retrospective studies that have reported morbidity and mortality rates comparable with those associated with open cholecystectomy.<sup>2</sup>However, these excellent results with laparoscopic cholecystectomy must be viewed with caution because they reflect outcomes of experienced and skilled laparoscopists. In a retrospective study of 1520 Medicare patients who underwent laparoscopic cholecystectomy between January 1, 1990, and June 30, 1991, we found complications in 15.8%. Of these, 8.8% were surgical in character, reflecting deficits in surgical skills, judgment, and technique.<sup>3</sup>In a hospital-based case review study that we conducted in New York State on 2940 Medicare and 1108 Medicaid patients who underwent laparoscopic cholecystectomy in 1991, hospitals reported complications in 11.9% of the former and 9.7% of the latter.<sup>4</sup>These very
γ-Glutamyltranspeptidase–Deficient Knockout Mice as a Model to Study the Relationship Between Glutathione Status, Mitochondrial Function, and Cellular Function
Authors: Yvonne Will, Kay A. Fischer, Robert A. Horton, Rhonda S. Kaetzel, Marda K. Brown, Olaf Hedstrom, Michael W. Lieberman, Donald J. Reed
Journal: Hepatology (2000)

γ-Glutamyltranspeptidase (GGT)-deficient mice (GGT −/− ) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (&lt;20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by ≥50% in GGT −/− mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT −/− mice liver mitochondria were ≤60% those of wild-type mice primarily as a result of impaired state 3 respiration. Mitochondrial adenine nucleotide content was decreased by ≥40% in mitochondria obtained from GGT −/− mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (&lt;50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT −/− knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT −/− mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT −/− mice with N -acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT −/− mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice.