tbuckley/cabot-search huggingface dataset:
2 ligand: a new, smart pill for visceral pain in patients with hypersensitive irritable bowel syndrome?
Authors: M. Camilleri
Journal: Gut (2007)

The heteromultimeric voltage-sensitive calcium (Ca2+) channel is involved in the function of excitable tissues including sensory nerves. It comprises a primary α1 subunit and auxiliary α2δ, β and γ subunits, and the associated α2δ ligand-binding site (see fig 1). The α1 subunit forms the ion-conducting pore and serves as voltage sensor. The α2δ subunit consists of the highly N-glycosylated extracellular α2 protein attached to the membrane-spanning δ protein that binds divalent metal cations and interacts directly with the α1 subunit. The β subunit is an intracellular protein that mediates modulation of Ca2+ channel function by intracellular kinases. The γ subunit is a glycoprotein with four transmembrane segments.1



 Figure 1  
 Three dimensional reconstruction of the L-type calcium channel showing α2δ ligand-binding site. This figure was published in Trends in Pharmacological Sciences , volume 28; Dooley, Taylor, Donevan et al ; Ca2+ channel α2δ ligands: novel modulators of neurotransmission, 75–82; copyright Elsevier, 2007.8



Pregabalin is a second-generation α2δ ligand that is approved in Europe for the treatment of neuropathic pain and epilepsy, and in the US for the management of neuropathic pain associated with diabetic peripheral neuropathy, post-herpetic neuralgia and as an adjunctive treatment for adults with partial onset seizures. It is 2–10 times more potent and has more predictable pharmacological effects than the prototype α2δ ligand, gabapentin. Although it is structurally related to γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system, it is functionally unrelated and inactive at GABAA, GABAB or benzodiazapine receptors and is not converted metabolically into GABA or a GABA agonist. Furthermore, clinically effective concentrations of pregabalin have been shown to have no effect on GABA uptake or degradation.2,3

Pregabalin binds potently to the α2δ auxiliary protein associated with voltage-gated calcium channels, …
Fibronectin and alpha5 integrin regulate keratinocyte cell cycling. A mechanism for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte hyperproliferation in psoriasis.
Authors: Z Bata-Csorgo, K D Cooper, K M Ting, J J Voorhees, C Hammerberg
Journal: Journal of Clinical Investigation (1998)

In addition to being T lymphocyte-driven, psoriasis may be due in part to abnormal integrin expression. Normal-appearing (uninvolved) skin from psoriatic patients was examined to determine whether altered fibronectin or its receptor expression is detectable before development of psoriatic lesions. In contrast to skin from normal subjects, we detect by immunofluorescence the abnormal presence of plasma fibronectin in the basal cell layer of the epidermis of psoriatic uninvolved skin. Furthermore, increased fibronectin exposure superinduces the in vitro cell cycle induction and expansion of psoriatic nonlesional keratinocytes in response to a cocktail of T cell lymphokines. Fibronectin alone also appeared to increase cell cycle entry among uninvolved but not normal keratinocytes. Concordantly, the alpha5 integrin fibronectin receptor, but not alpha2 or alpha3, is overexpressed in the in vivo nonlesional psoriatic epidermis. The involvement of alpha5beta1 in the early outgrowth of clonogenic keratinocytes in the ex vivo culture was demonstrated by the ability of anti-alpha5 mAb to inhibit keratinocyte growth on fibronectin. Thus, the fibronectin receptor appears to be one of the components required for the development of the hyperresponsiveness of psoriatic keratinocytes to signals for proliferation provided by lymphokines produced by intralesional T lymphocytes in psoriasis.
Inotropic Effects of Glyceryl Trinitrate and Spontaneous NO Donors in the Dog Heart
Authors: Benedikt Preckel, Georg Kojda, Wolfgang Schlack, Dirk Ebel, Karin Kottenberg, Eike Noack, Volker Thämer
Journal: Circulation (1997)

Background In vitro, NO has a biphasic effect on myocardial inotropy. To determine the inotropic effect of NO in vivo, we investigated the activity of glyceryl trinitrate (GTN) and the NO donors S -nitroso- N -acetyl- d,l -penicillamine (SNAP) and sodium-(2)-1-( N , N -diethyl-amino)-diazen-1-ium-1,2-diolat (DEA/NO) in dogs. Methods and Results Eight anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressures (tip manometers) and coronary flow (ultrasonic flow probes). Regional myocardial function was assessed by sonomicrometry as systolic wall thickening (sWT), mean systolic thickening velocity (V s ), and regional myocardial stroke work index (RSW). GTN, SNAP, and DEA/NO were infused into the left anterior descending coronary artery (LAD) to achieve defined coronary plasma concentrations of GTN, SNAP (both 10 to 100 μmol/L), and DEA/NO (2 to 20 μmol/L). All drugs increased LAD flow and myocardial contractile function in the LAD-dependent myocardium within the first 120 seconds. The greatest inotropic effect was noted after infusion of DEA/NO (20 μmol/L), which increased sWT by 9.7±3.1% from 28.5±2.2%, V s by 10.3±3.4% from 9.1±1.1 mm/s, and RSW by 7.1±2.1% from 200.0±22.1 mm Hg×mm ( P &lt;.05). At the same time, systemic hemodynamics remained unchanged. Prevention of the flow response to GTN by external narrowing of the LAD did not influence the inotropic effect of GTN. Conclusions Organic nitrates and NO donors evoke a small but constant positive inotropic effect in vivo that is not caused by coronary vasodilation.
TCT-695 Single Versus Double Stenting for the Left Main Coronary Bifurcation: A Systematic Review and Meta-Analysis
Authors: Wassef Karrowni, Nader Makki, Amandeep Dhaliwal, Saadeddine Dughman, Amy Blevins, Peter Cram, Phillip Horwitz
Journal: Journal of the American College of Cardiology (2012)
Pitfalls of tuberculosis programmes in prisons
Authors: H. Reyes, R. Coninx
Journal: BMJ (1997)

Gerhard Rose, one of Germany's most respected physicians, stood in the prisoner's dock at the Palace of Justice in Nuremberg, Germany, awaiting his sentence for "murders, tortures, and other atrocities committed in the name of medical science."Dr Rose, the department head for tropical medicine of the Robert Koch Institute, was on trial along with 22 of his medical colleagues, for perpetrating "ghastly" and "hideous" experiments on concentration camp prisoners during the war. 1 At one point in the trial when the chief prosecution witness, Dr Andrew C Ivy of the medical school of the University of Illinois, underscored the basic principle "that human experimental subjects must be volunteers," Dr Rose and his defence counsel vigorously objected, arguing that the United States was guilty of similar medical practices and giving several examples to support this contention.
Ischiorectal Abscess From Small Bone Penetration
Authors: S. D. Sarkar
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Foreign bodies in the alimentary canal may perforate the bowel at anatomical areas of fixation and sometimes point in a Meckel's diverticulum or the vermiform appendix; they may perforate the rectum and result in the formation of a perirectal abscess. Goligher<sup>1</sup>mentioned the possibility of laceration of the anorectal mucosa by sharp articles in the feces, for example, fish bones, rabbit bones, fragments of eggshell, enamel, or glass. Branning<sup>2</sup>described perforation of the colon by a fish bone, and a patient who had swallowed a turkey bone the day before his symptoms began suffered perforation of a diverticulum of the sigmoid colon with sinus formation (<i>New Eng J Med</i><b>265</b>:194, 1961). <h3>Report of a Case:—</h3> A 74-year-old woman was admitted on Feb 15, 1965, with complaints of a painful swelling on the left side of her anus during the previous ten days. On examination
Role of Infection in Asthma.
Authors: Murray Dworetzky
Journal: Annals of Internal Medicine (1967)

s1 May 1967Role of Infection in Asthma.Murray Dworetzky, M.D., F.A.C.P.Murray Dworetzky, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1026_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe mechanism by which infection in the bronchial tree aggravates asthma is still unclear. The irritating effects of the bacterial products and the mechanical obstruction produced by the infected secretion may cause bronchospasm, edema of the mucosa, and obstruction to the point of rendering the patient intractable. In addition, there may be an underlying allergic reaction to the bacterial proteins, which, like other proteins, are capable of antibody response and are therefore potentially allergenic.Whatever the mechanism, the most common factor responsible for intractability of asthma is the presence of infection in the paranasal sinuses and respiratory tract. Production of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1026-1026KeywordsAllergensAllergy and immunologyAntibody productionAsthmaEdemaMucous membranesProteinsRespiratory systemUpper respiratory tract infections Issue Published: 1 May 1967 PDF DownloadLoading ...
Pathogenesis of Farmer's Lung.
Authors: John Rankin
Journal: Annals of Internal Medicine (1964)

s1 February 1964Pathogenesis of Farmer's Lung.John Rankin, M.D.John Rankin, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-336_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFrequent exposure to moldy organic dusts may result in serious acute or chronic lung disease. The characteristic syndrome seen in more than 80 farmers exposed to a variety of moldy forages consisted of chills, fever, cough, and dyspnea within a few hours of exposure, and the subsequent development of an acute diffuse granulomatous interstitial pneumonitis which slowly cleared over a period of weeks to months. Chest roentgenograms varied with the severity and duration of the illness, but the usual finding was a very fine reticular pattern of granular or mottled densities, linear striations and patchy areas of conglomeration.The physiologic... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Madison, Wisconsin PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 336-336KeywordsDustDyspneaFeversInterstitial lung diseasesLungsPathogenesisThorax Issue Published: 1 February 1964 PDF DownloadLoading ...
Doctors and Nurses
Authors: G. Bognolo
Journal: BMJ (2004)

BBC 1, Tuesdays at 10 35 pm, from 13 January Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Can you set a comedy in an NHS department and generate a good laugh while still dealing with serious issues? Scriptwriters Nigel Smith and Phil Hammond have had a good try, with reasonably good results. Their six-episode series is located at the fictional St Anne's Hospital, on the Isle of Wight, and centres around the love-hate relationship between two orthopaedic consultants, Roy Glover (played by Adrian Edmondson) and George Banatwala (Madhav Sharma). Roy is totally committed to the NHS, trying hard to save and cure as many patients as he can, regardless of the personal consequences. He is even prepared to risk suspension to carry out the operation that he promised to a … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
DNA-based prenatal exclusion of bullous congenital ichthyosiform erythroderma at the early stage, 10 to 11 weeks' of pregnancy, in two consequent siblings
Authors: Yukiko Tsuji-Abe, Masashi Akiyama, Hideki Nakamura, Yasuko Takizawa, Daisuke Sawamura, Kayoko Matsunaga, Kaoru Suzumori, Hiroshi Shimizu
Journal: Journal of the American Academy of Dermatology (2004)
Understanding other's emotions: From affective resonance to empathic action
Authors: Lisa A. Parr
Journal: Behavioral and Brain Sciences (2002)

Empathy is a developmental process whereby individuals come to understand the emotional states of others. While the exact nature of this process remains unknown, PAM's utility is that it establishes empathy along a continuum of behavior ranging from emotional contagion to cognitive forms, a very useful distinction for understanding the phylogeny and ontogeny of this important process. The model will undoubtedly fuel future research, especially from comparative domains where data are most problematic.
726 ADD-ON OF PEG-INTERFERON TO A STABLE NUCLEOS(T)IDE REGIMEN LEADS TO LOSS OF HBS-AG IN PATIENTS WITH CHRONIC HEPATITIS B
Authors: J.M. Kittner, M.F. Sprinzl, A. Grambihler, A. Weinmann, R.R. Galle, M. Schuchmann
Journal: Journal of Hepatology (2011)
Comparison of five practice schedules located along the contextual interference continuum on the learning of novel motor skills
Authors: J P G Cheong, B Lay, R Grove, N Medic, R Razman
Journal: British Journal of Sports Medicine (2010)

A majority of contextual interference (CI) studies have focused on block and random practice conditions which are located at the extreme ends of the CI continuum. There is an increasing need to investigate other practice schedules with different combinations of interference within applied settings. This study was designed to investigate the effect of five practice schedules located along the CI continuum on the learning of three basic field hockey skills. Fifty-five pre-university students (males: age=18, SD=0) with no prior experience in field hockey were assigned into low interference (block), moderate (serial, randomised blocks, block random) or high interference (random) treatment groups. Participants practiced the Indian dribble, push pass and hit in six acquisition sessions, with 15 trials of each skill executed in each session. All participants completed a pre-test, two acquisition tests and a retention test 1 week after the final practice session. Indian dribble ball control, speed and accuracy of the push pass and hit were assessed. A significant time effect was found (p&lt;0.05) for Indian dribble ball control as well as push pass and hit speed. Follow-up analysis revealed that the pre-test scores were lower than the acquisition and retention scores indicating that collectively, the five practice conditions led to improvements in both the acquisition and learning of novel motor skills. However, significant differences were not found between the five experimental groups in either the acquisition or retention phase. As the CI effect was not present in this study, it is suggested that low, moderate or high interference practice schedules can be used effectively when learning a novel skill.
Trimethoprim-Induced Aseptic Meningitis
Authors: Stephen J. Derbes
Journal: JAMA (1984)

ASEPTIC meningitis has been described in association with the administration of anti-inflammatory drugs, including ibuprofen, sulindac and tolmetin sodium, and azathioprine.<sup>1-4</sup>Most, but not all, of the patients reported have had either systemic lupus erythematosus (SLE) or mixed connective-tissue disease.<sup>5,6</sup>Sulfamethizole-induced meningitis and pancreatitis have been described in a patient who was ostensibly free of underlying chronic disease.<sup>7</sup>More recently, aseptic meningitis has been associated with the use of trimethoprim-sulfamethoxazole.<sup>8</sup>This report describes a patient with Sjögren's syndrome who had four episodes of aseptic meningitis temporally related to the use of trimethoprim-sulfamethoxazole, and a single episode of aseptic meningitis following the use of trimethoprim alone. <h3>Report of a Case</h3><h3>First Admission.—</h3> A 61-year-old diabetic woman was hospitalized in June 1979 with a two-day history of fever, headache, nausea, and myalgias. Three years previously, she had complained of hair loss, arthralgias, and dryness of the eyes and
Acute infective gastroenteritis.
Authors: J F Galpine
Journal: BMJ (1972)

piss pills"-most commonly frusemide without potassium supplements.The diuretics may be taken only before the weigh-in, or ingested regularly.Those who do the latter complain of the decrease in efficacy which is a natural consequence of potassium depletion.Purgation is often practised on the morning of the race with potassium depletion consequent upon its effects.Although hyperkalaemia is more dan- gerous any change in the potassium status of the individual may change his E.C.G. and those doctors who have jockeys as patients should be aware of the incidence of self-medication.-Iam, etc.,
Characterization of the CD4 TH1 and CD8 responses against hepatitis C virus and HIV in peripheral blood of HCV-HIV coinfected patients
Authors: N. Alatrakchi, V. Dimartino, Y. Benhamou, M. Bochet, C. Katlama, T. Poynard, B. Autran, A. Alt
Journal: Journal of Hepatology (2001)
Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass: a population-based prospective cohort study
Authors: L S Lohmander, M Gerhardsson de Verdier, J Rollof, P M Nilsson, G Engström
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To determine in a prospective population-based cohort study relationships between different measures of body mass and the incidence of severe knee and hip osteoarthritis defined as arthroplasty of knee or hip due to osteoarthritis. Materials and methods: Body mass index (BMI), waist circumference, waist–hip ratio (WHR), weight and percentage of body fat (BF%) were measured at baseline in 11 026 men and 16 934 women from the general population. The incidence of osteoarthritis over 11 years was monitored by linkage with the Swedish hospital discharge register. Results: 471 individuals had knee osteoarthritis and 551 had hip osteoarthritis. After adjustment for age, sex, smoking and physical activity, the relative risks (RR) of knee osteoarthritis (fourth vs first quartile) were 8.1 (95% CI 5.3 to 12.4) for BMI, 6.7 (4.5 to 9.9) for waist circumference, 6.5 (4.6 to 9.43) for weight, 3.6 (2.6 to 5.0) for BF% and 2.2 (1.7 to 3.0) for WHR. Corresponding RR for hip osteoarthritis were 2.6 (2.0 to 3.4) for BMI, 3.0 (2.3 to 4.0) for weight, 2.5 (1.9 to 3.3) for waist, 1.3 (0.99 to 1.6) for WHR and 1.5 (1.2 to 2.0) for BF%. Conclusion: All measures of overweight were associated with the incidence of knee osteoarthritis, with the strongest relative risk gradient observed for BMI. The incidence of hip osteoarthritis showed smaller but significant differences between normal weight and obesity. Our results support a major link between overweight and biomechanics in increasing the risk of knee and hip osteoarthritis in men and women.
Occupational allergy to weeping fig in plant keepers
Authors: I. G. K. Axelsson, S. G. O. Johansson, O. Zettertö
Journal: Allergy (1987)

Plant keepers take regular care of green plants in public buildings and offices. One of the most common green plants in Scandinavia is weeping fig (Ficus benjamina). We have previously reported on two plant keepers sensitized to this plant, one had asthma and the other allergic rhinitis. We now report a study of four plant-leasing firms employing 60 plant keepers and 24 less exposed. Positive RAST and skin tests in 16 of the plant keepers and two of the employees showed them to be sensitized. All sensitized subjects suffered from conjunctivitis and/or rhinitis and six had asthma. Handling of green plants is a new example of an occupation which may cause IgE-mediated allergy.
Dangerous Secrets: Maladaptive Responses to Stress
Authors: Arnold Goldberg
Journal: JAMA (1984)

Psychiatrists often divide the world of patients into those who suffer the pain of their illness in the form of symptoms such as depression or phobias, and those who inflict the struggle of their psyche on the world in the form of "acting out." The author of this book about some of the more wrenching kinds of the latter conditions tells us that much acting out is kept hidden and surfaces only in moments of severe stress and crisis. As a guide to these dark and secret parts of what we now call "behavior disorders," Dr Weissberg is an exemplary instructor in telling us just how to recognize the deviant behavior, how we may expect to react to it, and how we should handle it. It is the sort of book that excels so much in these essentials that I enthusiastically recommend it to my fellow psychiatrists as well as
Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands
Authors: Ilan Weinreb, Salvatore Piscuoglio, Luciano G Martelotto, Daryl Waggott, Charlotte K Y Ng, Bayardo Perez-Ordonez, Nicholas J Harding, Javier Alfaro, Kenneth C Chu, Agnes Viale, Nicola Fusco, Arnaud da Cruz Paula, Caterina Marchio, Rita A Sakr, Raymond Lim, Lester D R Thompson, Simion I Chiosea, Raja R Seethala, Alena Skalova, Edward B Stelow, Isabel Fonseca, Adel Assaad, Christine How, Jianxin Wang, Richard de Borja, Michelle Chan-Seng-Yue, Christopher J Howlett, Anthony C Nichols, Y Hannah Wen, Nora Katabi, Nicholas Buchner, Laura Mullen, Thomas Kislinger, Bradly G Wouters, Fei-Fei Liu, Larry Norton, John D McPherson, Brian P Rubin, Blaise A Clarke, Britta Weigelt, Paul C Boutros, Jorge S Reis-Filho
Journal: Nature Genetics (2014)
Antihypertensive Treatment and Secondary Prevention of Cardiovascular Disease Events Among Persons Without Hypertension
Authors: Angela M. Thompson, Tian Hu, Carrie L. Eshelbrenner, Kristi Reynolds, Jiang He, Lydia A. Bazzano
Journal: JAMA (2011)

Cardiovascular disease (CVD) risk increases beginning at systolic blood pressure levels of 115 mm Hg. Use of antihypertensive medications among patients with a history of CVD or diabetes and without hypertension has been debated.To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension.Meta-analysis with systematic search of MEDLINE (1950 to week 3 of January 2011), EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials and manual examination of references in selected articles and studies.From 874 potentially relevant publications, 25 trials that fulfilled the predetermined inclusion and exclusion criteria were included in the meta-analysis.Information on participant characteristics, trial design and duration, treatment drug, dose, control, and clinical events were extracted using a standardized protocol. Outcomes included stroke, myocardial infarction (MI), congestive heart failure (CHF), composite CVD outcomes, CVD mortality, and all-cause mortality.Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1000 persons were -7.7 (95% CI, -15.2 to -0.3) for stroke, -13.3 (95% CI, -28.4 to 1.7) for MI, -43.6 (95% CI, -65.2 to -22.0) for CHF events, -27.1 (95% CI, -40.3 to -13.9) for composite CVD events, -15.4 (95% CI, -32.5 to 1.7) for CVD mortality, and -13.7 (95% CI, -24.6 to -2.8) for all-cause mortality. Results did not differ according to trial characteristics or subgroups defined by clinical history.Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality. Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.