tbuckley/cabot-search huggingface dataset:
Recombinant <scp>IGFBP</scp>‐3 inhibits allergic lung inflammation, <scp>VEGF</scp> production, and vascular leak in a mouse model of asthma
Authors: S. R. Kim, K. S. Lee, K. B. Lee, Y. C. Lee
Journal: Allergy (2012)

Abstract Background Vascular endothelial growth factor ( VEGF ) plays a pro‐inflammatory mediator as well as a vascular permeability factor in bronchial asthma. Insulin‐like growth factor ( IGF )‐ I is also involved in the inflammatory process associated with bronchial asthma and stimulates VEGF expression. The IGF ‐binding proteins ( IGFBP s), especially IGFBP ‐3, display distinctive properties and can interfere with various biological processes. Methods In this study, an ovalbumin ( OVA )‐induced murine model of allergic airway disease was used to investigate which mechanism is implicated in the preventive and therapeutic actions of IGFBP ‐3 administered exogenously on allergen‐induced bronchial inflammation and airway hyper‐responsiveness, in particular focusing on the regulation of VEGF expression. Results Administration of recombinant human IGFBP ‐3 to OVA ‐inhaled mice substantially attenuated the increases in hypoxia‐inducible factor ( HIF )‐α activity, IGF ‐I production, and VEGF protein levels in the lung. In addition, the blockade of IGF ‐I action decreased the OVA ‐induced VEGF expression, airway inflammation, and bronchial hyper‐responsiveness. The administration of recombinant human IGFBP ‐3 or CBO ‐P11 also reduced significantly increases in inflammatory cells, airway hyper‐responsiveness, levels of IL ‐4, IL ‐5, IL ‐13, and vascular permeability in the lung of OVA ‐inhaled mice. Moreover, when recombinant human IGFBP ‐3 was administered after the completion of OVA inhalation, these therapeutic effects of IGFBP ‐3 were also observed. Conclusions These results indicate that IGFBP ‐3 administered exogenously may attenuate antigen‐induced airway inflammation and hyper‐responsiveness through the modulation of vascular leakage and VEGF expression mediated by HIF ‐1α/ HIF ‐2α signaling as well as IGF ‐I action in allergic airway disease of mice.
Clomipramine and neuroleptic malignant syndrome
Authors: Alison Haddow, Martin Wilson
Journal: BMJ (2005)

Editor—Clomipramine is not a neuroleptic and is classed as an “antidepressant.” However, as mentioned in our article, this drug has an appreciable blocking effect at dopamine receptor sites, the traditional domain of the neuroleptic drug. This is a weak effect, but it is more potent than several other antidepressant agents.1 This action is recognised in the current edition of the BNF, which says that neuroleptic malignant syndrome may, very rarely, arise in the course of antidepressant treatment.2

We also made reference to 50 worldwide reports received regarding clomipramine and neuroleptic malignant syndrome or suspected neuroleptic malignant syndrome, in addition to four reports received by the Committee on Safety of Medicines and two published case reports.

We agree that we should have made clear that this patient's muscle rigidity was of the lead pipe variety, although some widely accepted diagnostic criteria require only severe muscle rigidity.3 The diagnostic criteria that we tabulated were based on Levinson and Sternabach and referenced in our article.4,5

We described in this patient an earlier diagnosed episode of serotonin syndrome, and no clinical evidence of rigidity was found on that occasion.

In view of the action at dopamine sites of clomipramine, and the statement in the BNF from the BMA and the Royal Pharmaceutical Society of Great Britain, we would continue to support our diagnosis of neuroleptic malignant syndrome in this informative case.
Linking genotypes with phenotypes in human retinal degenerations: Implications for future research and treatment
Authors: Michael W. Kaplan
Journal: Behavioral and Brain Sciences (1995)

Abstract Although undoubtedly it will be incomplete by the time it is published, the target article by Daiger et al. organizes mutations in genes that produce retinal degenerations in humans into categories of clinically relevant phenotypes. Such classifications should help us understand the link between altered photoreceptor cell proteins and subsequent cell death, and they may yield insight into methods for preventing consequent blindness.
Mushroom Poisoning
Authors: John P. Hanrahan
Journal: JAMA (1984)

Four incidents of mushroom poisoning, representing four of the seven established groups of toxic mushrooms, are presented. These case reports illustrate the range of gastrointestinal and neurological symptoms caused by mushroom poisoning and reflect a nationwide increase in reports of serious poisonings in recent years. Severity of poisonings often parallels the time span between consumption and onset of symptoms, with serious poisonings having longer incubation periods. New therapies for amatoxin poisoning may reduce mortality caused by these poisonings. (<i>JAMA</i>1984;251:1057-1061)
Application of integrated genetic monitoring: the optimal approach for detecting environmental carcinogens.
Authors: M S Legator, W W Au
Journal: Environmental Health Perspectives (1994)

Short-term in vitro genetic toxicity assays have not fulfilled their anticipated role in predicting the carcinogenicity of environmental agents reliably and economically. A reduction in emphasis from nonanimal systems to relevant animal assays and population monitoring will help to reestablish the credibility of this field. An analysis of the various steps in the carcinogenic process indicates the biological responses occurring during these stages can be utilized for early detection of environmental carcinogens. Emphasis should be placed on using the earliest significant response that indicates genetic damage (e.g., gene mutations and chromosome alterations). Assays that detect pregenomic damage (e.g., adduct formation), without evidence of subsequent heritable genetic alterations, may produce misleading results for risk assessment and should not be considered as stand-alone monitoring procedures. Late biological responses may occur in tissues or organs where genetic damage may be difficult to measure, and the opportunity for intervention diminishes as we approach the clinical outcome. For example, analyzing localized cells that contain activated protooncogenes and inactivated tumor suppressor genes, although they further document adverse response from exposure to carcinogens, may be of greater value for indicating clinical outcome than for genetic monitoring. With few notable exceptions, the window of opportunity for genetic monitoring is the period after exposure where genetic damage is evident and where circulating lymphocytes can faithfully record this damage. An ongoing study of butadiene-exposed workers illustrates an optimum protocol, where multiple assays can be carried out and correlated with both external and internal measurements of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor
Authors: Roger Prades, Simón Guerrero, Eyleen Araya, Claudia Molina, Edison Salas, Esther Zurita, Javier Selva, Gustavo Egea, Carmen López-Iglesias, Meritxell Teixidó, Marcelo J. Kogan, Ernest Giralt
Journal: Biomaterials (2012)
Poor coding by health boards has masked true length of Scotland's waiting lists
Authors: C. White
Journal: BMJ (2013)

Many patients in Scotland may have waited considerably longer for hospital treatment than official figures suggest because of poor management and scrutiny of NHS waiting lists, according to an investigation by the country’s public spending watchdog, Audit Scotland.1

Limited data, inadequate controls, and poor audit trails make it impossible to pinpoint the exact numbers of patients affected and whether human error, inconsistent interpretation of national guidance, or deliberate manipulation of the figures are to blame, says the watchdog.

Audit Scotland analysed all health boards’ applications of waiting list codes in electronic patient records between April and December 2011, after it emerged that NHS Lothian had deliberately manipulated its data for patient waiting times during this period. …
Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.
Authors: P A Lorkin, A D Stephens, M E Beard, P F Wrigley, L Adams, H Lehmann
Journal: BMJ (1975)

A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident.
When saliva meets acid: chemical warfare at the oesophagogastric junction
Authors: K E L McColl
Journal: Gut (2004)

In the Western world at least, most upper gastrointestinal cancers now arise from the mucosa near to the oesophagogastric junction. Research into the mechanism of the development of adenocarcinoma at the oesophagogastric junction has mainly focused on the noxious effects of acid and bile. There is however an alternative concept for explaining the location of adenocarcinomas: the cancers are occurring at the anatomical site where saliva encounters acidic gastric juice and their interaction generates reactive nitrogen species which are potentially mutagenic and carcinogenic. At present, it is unclear whether the active nitrite chemistry is exerting detrimental effects on the surrounding tissue but it is important to investigate this possibility as it could reveal new ways of preventing and treating the high prevalence of disease occurring at this anatomical site
Tripping on the HIPAA Hurdle
Authors: Robert F. Schilling
Journal: Annals of Internal Medicine (2011)

On Being a Doctor18 January 2011Tripping on the HIPAA HurdleRobert F. Schilling, MDRobert F. Schilling, MDFrom University of Wisconsin School of Medicine and Public Health, Madison, WI 53706.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-2-201101180-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In 1954, a boy aged 16 years was referred to our institution for evaluation of hemolytic anemia. Spherocytes were seen on his blood film. Five of his 6 siblings also had evidence of hemolytic spherocytosis. Although neither parent had clinical or laboratory evidence of hemolysis or spherocytosis, the condition was obviously inherited because a paternal aunt had been cured of hemolytic anemia by splenectomy. I was intrigued by the variable manifestations of disease in the family and made hereditary spherocytosis a continuing area of investigation. Over the next half-century, my colleagues and I collected clinical data from approximately 700 affected ... Author, Article, and Disclosure InformationAffiliations: From University of Wisconsin School of Medicine and Public Health, Madison, WI 53706.Note: A list of references may be obtained from the author.Corresponding Author: Robert F. Schilling, MD, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Room 4285, Madison, WI 53706; e-mail, [email protected]wisc.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTripping Over the HIPAA Hurdle John A. Hermos and Avron Spiro III Metrics Cited byTripping Over the HIPAA HurdleJohn A. Hermos, MD and Avron Spiro III, PhD 18 January 2011Volume 154, Issue 2Page: 133-134KeywordsChartsDatabasesEpidemiologyHemolytic anemiaMyocardial infarctionSpleenSplenectomyVeins ePublished: 18 January 2011 Issue Published: 18 January 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Mental health projects in developing countries share $19m investment
Authors: A. Gulland
Journal: BMJ (2012)

<h3>Background</h3> HIV pre-exposure prophylaxis (PrEP) and chemsex present both opportunities and challenges for sexual health improvement among gay and bisexual men (GBM). However, there is scant evidence to inform responses in New Zealand (NZ), notably prevalence, uptake and cessation of behaviours over time. We sought a better understanding by recruiting a diverse national cohort of GBM. <h3>Methods</h3> Flux NZ is a national online prospective observational study investigating wellbeing among GBM in NZ. The protocol, questionnaire and data management system were based on a concurrent Australian study. Recruitment was predominantly via social media and community partners. Eligible participants were GBM living in NZ. We present baseline descriptions of PrEP, STI and illicit drug-related data among the cohort to date. <h3>Results</h3> The 315 participants are broadly reflective of the target population (10.8% identified as indigenous Maori, 59% lived outside Auckland the largest city, mean age 33.6 years (SD 15.6), 8.3% diagnosed HIV-positive). Among HIV-negative participants, 50% had heard “a lot” and 44% “a little” about PrEP; 18.2% were currently using PrEP. 57% of all participants had tested for STIs in the past 6 months; 7%, 5.7% and 3.2% were diagnosed with gonorrhoea, chlamydia and syphilis respectively. Drug use in the past 6 months was 37.5% cannabis, 35.6% amyl, 17.5% MDMA, 5.1% methamphetamine, 4.8% LSD, 4.4% cocaine, 3.2% GHB, 2.5% amphetamine, 1.0% ketamine, 0.3% synthetic cannabis, 0% mephedrone, 0% heroin, and 1.9% other hallucinogens/psychedelics. “Any” drug use was 57.8% in the past 6 months and 78.7% ever. Of those using “party drugs” (MDMA, amphetamine, cocaine, methamphetamine, GHB, ketamine, LSD) recently, 29.2% had done so to enhance sex, the majority “once” (4.7%) or “a few times” (15.1%). <h3>Conclusion</h3> The Flux online cohort design effectively recruits GBM in NZ. This will enable comparative research of the impact of HIV, STI and drug harm reduction policies in the two countries. <h3>Disclosure</h3> No significant relationships.
OC-002 Predicting Outcome In Acute Ulcerative Colitis: Comparison Of The Travis And Ho Scores Using Uk Ibd Audit Data
Authors: AM Churchhouse, RW Lynch, A Protheroe, ID Arnott
Journal: Gut (2014)

<h3>Introduction</h3> Patients with severe Ulcerative Colitis (UC) are commonly identified using the Truelove and Witts<sup>1</sup> criteria on presentation. The Travis<sup>2</sup> and Ho<sup>3</sup> scores are subsequently used to identify patients with severe UC who are at high risk of failing medical therapy and needing second line therapy or colectomy. To date there has been no direct comparison between Travis and Ho scores to determine which is superior. <h3>Methods</h3> We analysed data from 3049 patients with UC collected during the 2010 round of the UK IBD audit. 984 patients had acute severe UC according to the Truelove and Witts criteria. Those that failed steroid therapy were scored using both Travis and Ho criteria and allocated into either a Travis “high” or “low” risk group <i>and </i>either a Ho “high”, “medium” or “low” risk group. We assessed whether further medical or surgical intervention varied between groups. <h3>Results</h3> Patients requiring surgery did not differ between the high risk groups (Travis 49%, n = 93 and Ho 51%, n = 84, respectively). However, only 35% (n = 53) in the medium risk Ho group, 26% (n = 17) in the low risk Ho group and 32% (n = 65) in the low risk Travis group underwent surgery. Similarly 41% (n = 78) and 38% (n = 63) of patients in the high risk Travis and Ho groups respectively were treated with ciclosporin, whereas only 34% (n = 51) were treated in the medium risk Ho group, 25% (n = 16) in the low risk Ho group and 27% (n = 55) in the low risk Travis group. Resistance to ciclosporin correlated with increasing risk stratification, although this failed to reach statistical significance for all groups. The use of anti-TNFs was the same across all three groups, although like ciclosporin, the tendency to TNF resistance also increased with increasing risk group. <h3>Conclusion</h3> The Travis and Ho scores are equally able to identify patients who are at high risk of failing medical therapy and needing colectomy or second line medical therapy. The Ho score may also be able to identify an intermediate risk group which also has an intermediate response to second line therapy. Both scores are useful tools to aid clinical decision making but do not replace timely multidisciplinary care for these patients. <h3>References</h3> 1 Truelove SC, Witts DJ. Cortisone in ulcerative colitis. <i>Br Med J</i> 1955;2(4947):1041–1048 2 Travis SPL, Farrant JM, Ricketts C, Nolan DJ, Mortensen NM, Kettlewell MGW, Jewell DP. Predicting outcome in severe ulcerative colitis. <i>Gut</i> 1996;38(6):905–910 3 Ho GT, Mowat C, Goddard CJR, Fennell JM, Shah NB, Prescott RJ, Satsangi J. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. <i>Aliment Pharmacol Ther</i> 2004;19(10):1079–87 <h3>Disclosure of Interest</h3> None Declared.
BENDAVIA (MTP-131), A NOVEL MITOCHONDRIA-TARGETING PEPTIDE, NORMALIZES EXPRESSION OF CARDIOLIPIN REMODELING GENES AND PROTEINS IN LEFT VENTRICULAR MYOCARDIUM OF DOGS WITH ADVANCED HEART FAILURE
Authors: Hani N. Sabbah, Ramesh C. Gupta, Sharad Rastogi, Mengjun Wang, Kefei Zhang, Paula Mohyi, Kristina J. Szekely
Journal: Journal of the American College of Cardiology (2014)
Alfred William Raffan
Authors: Alexander Adam, Iain Levack
Journal: BMJ (2006)

​FormerFormer consultant anaesthetist Aberdeen Hospitals (b 1912, q Aberdeen 1938; TD, DA, FFA RCS), d 16 January 2006.



Figure 1



Alfred Raffan (“Alfie”) went to war in 1939 with the 15th Scottish General Hospital Royal Army Medical Corps. Initially in Cairo, he followed the action across North Africa to Italy and then to France and Germany where he was anaesthetist in a maxillofacial field surgical team. Later he became a consultant. He was president of the Scottish Society of Anaesthetists and a founder of the Scottish Standing Committee of the Faculty of Anaesthetists. Predeceased by his first wife, he leaves a wife, Pat, and two children from his first marriage.
GROWTH HORMONE OF THE ANTERIOR LOBE OF THE PITUITARY GLAND
Authors: HERBERT M. EVANS
Journal: JAMA (1941)

<h3>INTRODUCTION</h3> Nutritional studies in the domain of the vitamins have long since shown the fallacy of designating any one of these factors as peculiarly growth promoting; as a matter of fact, growth cannot ensue with all of these factors present in a diet which is inadequate for proper nutrition. Just as normal growth is dependent on a multiplicity of these extrinsic factors, so also the same may be said as to intrinsic factors, for more than one of the glands of internal secretion can be shown to have very definite relations with growth. When the thyroid, for example, is removed from a young mammal, growth is always impaired; growth ceases abruptly after hypophysectomy. In the last-mentioned instance, the claim that the cessation of growth has resulted from the removal of a pituitary hormone essential for growth has only gradually gained validation. As regards the nutritive, or extrinsic, factors influencing growth,
Been There, Not Done That — Melanoma in the Age of Molecular Therapy
Authors: Marc S. Ernstoff
Journal: New England Journal of Medicine (2011)

In 1976, the detection of estrogen-receptor expression in melanomas ushered in the era of targeted therapy in melanoma, although we did not use that term back then.1 In 1992, Cocconi et al. found that dacarbazine plus tamoxifen provided a higher response rate and longer survival than dacarbazine, but only in women.2 Subsequently, whether melanoma cells express estrogen receptors was questioned, and the efficacy of tamoxifen could not be confirmed. Since then, the drug has not been used to treat melanoma. However, molecular analysis of tumors has revealed specific growth-promoting pathways in human cancers that have become targets for therapy.BRAF . . .
Hepatitis B virus transmission from a surgeon to his patients during high as well as low-risk procedures. Unnoticed transmissions over a four-year period
Authors: I.J.B. Spijkerman, L.J. van Doorn, M.H.W. Janssen, C.J. Wijkmans, M.A.J. Bilkert-Mooiman, R.A. Coutinho, G. Weers-Pothoff
Journal: Journal of Hepatology (2000)
Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes
Authors: Edmund J. Lewis, Lawrence G. Hunsicker, William R. Clarke, Tomas Berl, Marc A. Pohl, Julia B. Lewis, Eberhard Ritz, Robert C. Atkins, Richard Rohde, Itamar Raz
Journal: New England Journal of Medicine (2001)

It is unknown whether either the angiotensin-II–receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure.
Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC)
Authors: G Sanz, A Pajarón, E Alegría, I Coello, M Cardona, J A Fournier, M Gómez-Recio, J Ruano, R Hidalgo, A Medina
Journal: Circulation (1990)

To analyze the efficacy of low-dose aspirin in preventing early aortocoronary vein graft occlusion, 1,112 consecutive patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial comparing 50 mg t.i.d. aspirin, 50 mg aspirin plus 75 mg t.i.d. dipyridamole, and placebo. All patients received 100 mg q.i.d. dipyridamole for 48 hours before surgery, and assigned treatment was started 7 hours after surgery. Vein graft angiography was performed in 927 patients (83%) within 28 days of surgery (mean, 10 days). Aspirin plus dipyridamole significantly (p = 0.017) reduced the occlusion rate of distal anastomoses from 18% (placebo) to 12.9%. Occlusion rate in the aspirin group was 14%, which approached statistical significance (p = 0.058). Furthermore, only aspirin plus dipyridamole reduced (p = 0.01) the number of patients with occluded grafts (placebo, 33%; aspirin, 27.1%; aspirin plus dipyridamole, 24.3%). Mediastinal drainage was slightly higher (p = 0.04) in the aspirin plus dipyridamole group (713 +/- 456 ml) than in the other two groups (placebo, 670 +/- 437 ml; aspirin, 629 +/- 337 ml), but hospital mortality (average, 4.6%) and early reoperation (average, 3.9%) rates were similar among the three groups. Thus, low-dose aspirin plus dipyridamole safely improves early saphenous vein aortocoronary graft patency; this effect is an added benefit to a preoperative regimen of dipyridamole.