tbuckley/cabot-search huggingface dataset:
Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk
Authors: Emma Jaeger, Emily Webb, Kimberley Howarth, Luis Carvajal-Carmona, Andrew Rowan, Peter Broderick, Axel Walther, Sarah Spain, Alan Pittman, Zoe Kemp, Kate Sullivan, Karl Heinimann, Steven Lubbe, Enric Domingo, Ella Barclay, Lynn Martin, Maggie Gorman, Ian Chandler, Jayaram Vijayakrishnan, Wendy Wood, Elli Papaemmanuil, Steven Penegar, Mobshra Qureshi, Susan Farrington, Albert Tenesa, Jean-Baptiste Cazier, David Kerr, Richard Gray, Julian Peto, Malcolm Dunlop, Harry Campbell, Huw Thomas, Richard Houlston, Ian Tomlinson
Journal: Nature Genetics (2007)
Book: Acute Medical Emergencies: The Practical Approach
Authors: D. Fatovich
Journal: BMJ (2001)

Advanced Life Support Group BMJ Books, £40, pp 512 ISBN 0 7279 1464 2 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Acute hospital medicine is widely practised around the world but is not often recognised as requiring special expertise. The authors of this text have done a splendid job of crafting an approach that is rooted in the real world. They have obviously dealt with real patients … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
HIV clinics are halting enrolment of new patients as funding stalls, MSF warns
Authors: B. Roehr
Journal: BMJ (2009)

The international medical charity Medecins Sans Frontieres (MSF) is calling for better and cheaper first line and second line treatments for HIV in the developing world, in a new report released on 20 July at the opening of the International AIDS Society meeting in Cape Town.

MSF says that a first line treatment regimen should be based on tenofovir rather than stavudine, an older, less potent drug that is more susceptible to the emergence of viral resistance and carries potential side effects of lipodystrophy and peripheral neuropathy. The World Health Organization has recommended use of tenofovir since 2006.

A generic tenofovir based regimen costs two to three times more than one based on stavudine, but that price should fall as the volume of purchases rises. Also, the more potent regimen would delay development of viral resistance, thus deferring a switch to …
Incidence and hospitalisation rates of Lyme borreliosis, France, 2004 to 2012
Authors: A Vandenesch, C Turbelin, E Couturier, C Arena, B Jaulhac, E Ferquel, V Choumet, C Saugeon, E Coffinieres, T Blanchon, V Vaillant, T Hanslik
Journal: Eurosurveillance (2014)

Binary file ES_Abstracts_Final_ECDC.txt matches
SYSTOLIC AORTIC REGURGITATION: AN UNDERESTIMATED PHENOMENON RELATED TO HEART FAILURE PROGNOSIS?
Authors: Alejandro Sanchez Espino, Juan Bonaque González, German Merchan Ortega, Ichiro Ikuta, Juan Jose Macancela Quinonez, Natalia Bolivar Herrera
Journal: Journal of the American College of Cardiology (2014)
Clotting and Hemorrhage in the Placenta — A Delicate Balance
Authors: Drucilla Roberts, Robert S. Schwartz
Journal: New England Journal of Medicine (2002)

Increased susceptibility to deep-vein thrombosis is a well-known facet of pregnancy and the puerperium, with the greatest risk occurring during the puerperium. It remains unclear, however, whether a genetically determined tendency toward clot formation in the mother can affect the fetus or cause obstetrical complications. It is important to clarify this issue because mutations and polymorphisms that contribute to a susceptibility to thrombosis — the inherited thrombophilias — occur in up to 20 percent of persons of European descent.In 1999, the Journal published a report on a case–control study by Kupferminc et al., which showed that a hypercoagulable state . . .
Allergic Sensitization, High Local IL-5 and IgE Predict Surgical Outcome 12 Years after Endoscopic Sinus Surgery for Chronic Rhinosinusitis with Nasal Polyposis
Authors: Philippe Gevaert, Lien Calus, Nicholas van Bruaene, Thibaut Van Zele, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2015)
Reduction in density of transverse tubules and L-type Ca2+ channels in canine tachycardia-induced heart failure
Authors: J He
Journal: Cardiovascular Research (2001)

Persistent supraventricular tachycardia leads to the development of a dilated cardiomyopathy with impairment of excitation-contraction (EC) coupling. Since the initial trigger for EC coupling in ventricular muscle is the influx of Ca(2+) through L-type Ca(2+) channels (I(Ca)) in the transverse tubules (T-tubules), we determined if the density of the T-tubule system and L-type Ca(2+) channels change in canine tachycardia pacing-induced cardiomyopathy.Confocal imaging of isolated ventricular myocytes stained with the membrane dye Di-8-ANEPPS was used to image the T-tubule system, and standard whole-cell patch clamp techniques were used to measure I(Ca) and intramembrane charge movement.A complex staining pattern of interconnected tubules including prominent transverse components spaced every approximately 1.6 microm was present in control ventricular myocytes, but failing cells demonstrated a far less regular T-tubule system with a relative loss of T-tubules. In confocal optical slices, the average % of the total cell area staining for T-tubules decreased from 11.5+/-0.4 in control to 8.7+/-0.4% in failing cells (P<0.001). Whole-cell patch clamp studies revealed that I(Ca) density was unchanged. Since whole-cell I(Ca) is due to both the number of channels as well as the functional properties of those channels, we measured intramembrane charge movement as an assay for changes in channel number. The saturating amount of charge that moves due to gating of L-type Ca(2+) channels, Q(on,max), was decreased from 6.5+/-0.6 in control to 2.8+/-0.3 fC/pF in failing myocytes (P<0.001).Cellular remodeling in heart failure results in decreased density of T-tubules and L-type Ca(2+) channels, which contribute to abnormal EC coupling.
The Effect of Prolonged Administration of Ethanol on Cardiac Metabolism and Performance in the Dog
Authors: Otmar M. Pachinger, Harald Tillmanns, James C. Mao, Jean-Marie Fauvel, Richard J. Bing
Journal: Journal of Clinical Investigation (1973)

The effect of prolonged administration of alcohol on mitochondrial function and high-energy phosphate (ATP) of heart muscle was investigated in dogs. Animals were divided into two groups, a control group and a group that received alcohol. In the experimental series, dogs received 400 ml of a 25% solution of alcohol added to the food and drinking water. Measurements were carried out after ethanol had been withheld for 2 days. Total myocardial blood flow, cardiac output, and myocardial O(2) consumption remained at control levels. Measurement of cardiac contractility using the maximal rate of left ventricular pressure rise (dP/dt(max)) showed no change in animals exposed to alcohol. When the afterload of the heart was increased with angiotensin, a slight but not significant decline in cardiac contractility was observed. Activities of various intramitochondrial and extramitochondrial enzymes were measured in both groups. After alcohol administration, the primarily intramitochondrial isocitrate dehydrogenase diminished. ATP in heart muscle of dogs exposed to alcohol declined, and mitochondrial oxygen consumption and respiratory control indices diminished. These observations suggest that the primary lesion leading to alteration of myocardial performance is a biochemical malfunction of the mitochondria, which at this early stage is not reflected in changes in myocardial contractility.
Abstract 628: A novel SND1-BRAF fusion confers resistance to the cMet inhibitor PF-04217903 in GTL16 cells
Authors: Nathan V. Lee, Keith Ching, Maruja Lira, Adam Pavlicek, Roslyn Dillon, Sreesha P. Srinivasa, Carol Nilsson, Michael Greig, Michael North, Paul Rejto, James G. Christensen
Journal: Cancer Research (2010)

Abstract The hepatocyte growth factor receptor (HGFR/cMET) signaling pathway is a driver of tumorigenesis in a variety of tumor types, and a number of agents targeting cMet, including PF-04217903, are under investigation in clinical trials. Tumor types exhibiting an amplified MET gene locus such as gastric, NSCLC, or esophageal cancers are of particular interest for clinical development of c-Met inhibitors. While inhibition of other receptor tyrosine kinases (RTKs) such as ErbB2, EGFR, or KIT have proven to be effective treatments for cancer patients, most tumors become refractory to respective targeted therapies due to the emergence of resistance mechanisms associated with drug targets or upregulation of compensatory pathways. To identify potential mechanisms of resistance to c-Met inhibitors, a gastric carcinoma line (GTL16) was placed under selective pressure by culturing cells in increasing concentrations of PF-0421703 in vitro and resistant clones were isolated. Resistant clones were characterized for changes in signaling, gene expression, and DNA copy number variation as compared to parental GTL16 cells. These studies resulted in the identification of genomic rearrangements at the 7q32 and 7q34 loci which produce a novel SND1-BRAF fusion protein in resistant cells. The fusion protein includes the BRAF kinase domain and is both constitutively active and overexpressed relative to parent cells as determined by gene expression array, immunoblot, and mass spectrometry. In addition, phosphoproteomic analyses demonstrated enrichment of phosphopeptides associated with the MAPK pathway signaling proteins relative to wildtype cells. Cells expressing the fusion protein exhibited resistance to multiple c-Met inhibitors whereas treatment of resistant cells with a combination of c-Met and BRAF inhibitors or a MEK inhibitor (PD325901) reversed the resistance phenotype by reestablishing inhibition of MAPK signaling and restoring growth inhibition. Together, these data provide an unique example of a mechanism where MAPK activation, through BRAF amplification/rearrangement, confers resistance to a RTK/cMET inhibitor. Furthermore, the results suggest the importance of MEK/ERK signaling downstream of c-Met and that a potential combination strategy for c-Met inhibitors with BRAF or MEK inhibitors could be employed to delay onset or circumvent potential resistance mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 628.
Cortical Brain Lesions in Acute Intermittent Porphyria
Authors: Hugo Kupferschmidt
Journal: Annals of Internal Medicine (1996)

Letters1 September 1996Cortical Brain Lesions in Acute Intermittent PorphyriaHugo Kupferschmidt, MD, Peter J. Meier, MD, and Hans Schnorf, MDHugo Kupferschmidt, MDUniversity Hospital, Zurich, SwitzerlandHospital Cantoral de Gueve, Geneva, SwitzerlandSearch for more papers by this author, Peter J. Meier, MDUniversity Hospital, Zurich, SwitzerlandHospital Cantoral de Gueve, Geneva, SwitzerlandSearch for more papers by this author, and Hans Schnorf, MDUniversity Hospital, Zurich, SwitzerlandHospital Cantoral de Gueve, Geneva, SwitzerlandSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-5-199609010-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Sze suggests that the magnetic resonance imaging findings noted in our two patients with transient cortical blindness during an attack of acute intermittent porphyria were caused by hypertensive encephalopathy rather than by unopposed cerebral vasoconstriction resulting from a suggested deficiency of the theme protein nitric oxide synthase.Although hypertensive encephalopathy cannot be excluded in some patients with acute porphyric attacks, we do not believe that this condition could fully explain our observations. First, papilledema and cerebral edema—both of which are common manifestations of hypertensive encephalopathy—were conspicuously absent in our patients and in those with similar clinical abnormalities ...References1. Lai CW, Hung TP, Lin WS. Blindness of cerebral origin in acute intermittent porphyria. Arch Neurol. 1977; 34:310-2. Google Scholar2. King PH, Bragdon AC. MRI reveals multiple reversible lesions in an attack of acute intermittent porphyria. Neurology. 1991; 41:1300-2. Google Scholar3. Lindberg RL, Porcher C, Grandchamp B, Ledermann B, Burki K, Brandner S, et al. Porphobilinogen deaminase deficiency in mice causes the neuropathy of human hepatic porphyria. Nature Genetics. [In press]. Google Scholar Author, Article, and Disclosure InformationAuthors: Hugo Kupferschmidt, MD; Peter J. Meier, MD; Hans Schnorf, MDAffiliations: University Hospital, Zurich, SwitzerlandHospital Cantoral de Gueve, Geneva, Switzerland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHuman hereditary hepatic porphyrias 1 September 1996Volume 125, Issue 5Page: 423KeywordsBlindnessBlood pressureBrain diseasesHemorrhageMagnetic resonance imagingNitric oxidePorphyriaThrombosisVasoconstrictionVision ePublished: 15 August 2000 Issue Published: 1 September 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THE VALUE OF DOPPLER-BASED RENAL ARTERIAL RESISTIVE INDEX TO PREDICT ACUTE KIDNEY INJURY AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Jan-Malte Sinning, Viktoria Adenauer, Hannah Steinhäuser, Alexander Ghanem, Christoph Hammerstingl, Georg Nickenig, Nikos Werner, Medizinische Klinik
Journal: Journal of the American College of Cardiology (2011)
Regular review: HIV infection in children
Authors: H. Saloojee, A. Violari
Journal: BMJ (2001)

HIV has transformed paediatric practice in developing countries. A specialty that once dealt mainly with acute illnesses is now consumed, in many settings, with managing chronically ill and dying children. Last year, 600 000 children were newly infected with HIV, over 90% in sub-Saharan Africa and almost all having acquired the virus by vertical transmission, from mother to child.1 The statistics do not adequately portray the suffering and disrupted lives of the most vulnerable of the world's population.

The HIV pandemic has eroded many of the hard earned gains made in reducing infant and child mortality. The United Nations Program on HIV and AIDS (UNAIDS) recently reported that, by 2010, a doubling in child mortality is expected in regions with a high prevalence of infection. Globally, the number of orphans from AIDS will increase from the current 13.2 million to 44 million by 2010.2 Already, one child in 10 is an orphan in some countries. Finding appropriate responses to this crisis must rank as the single most important global challenge to child health in the next decade.

This article reviews advances in preventing vertical transmission, antiretroviral treatment, and vaccine development, and we attempt to predict future developments.

#### Summary points

HIV infection and AIDS have severely disrupted child health services in many developing countries

Efforts to prevent viral transmission form mother to child are inadequate in resource poor settings

The choice between breast feeding and feeding with formula milk remains controversial

An effective AIDS vaccine can be expected in the next 10 years

New antiretroviral treatments and innovative treatment strategies continue to be developed

A focus beyond education and promoting the use of condoms is required in poor countries

The review is based on a Medline search of original papers and reviews, unpublished material, presentations and abstracts from recent scientific meetings, …
Review by a local medical research ethics committee of the conduct of approved research projects, by examination of patients' case notes, consent forms, and research records and by interview
Authors: T. Smith, E. J H Moore, H. Tunstall-Pedoe
Journal: BMJ (1997)

To monitor the conduct of medical research projects that have already been approved by the local medical research ethics committee.Follow up study of ethically approved studies (randomly selected from all the studies approved in the previous year) by examination of patients' case notes, consent forms, and research records and by interview of the researchers at their workplace.Tayside, Scotland (mixed rural and urban population).30 research projects approved by Tayside local medical research ethics committee.Adherence to the agreed protocol, particularly for recruitment (obtaining and recording informed consent) and for specific requirements of the ethics committee, including notification of changes to the protocol and of adverse events.In one project only oral consent had been obtained, and in a quarter of the studies one or more consent forms were incorrectly completed. Inadequate filing of case notes in five studies and of consent forms in six made them unavailable for scrutiny. Adverse events were reported, but there was a general failure to report the abandoning or non-starting of projects in two studies the investigators failed to notify a change in the responsible researcher.Monitoring of medical research by local medical research ethics committees promotes and preserves ethical standards, protects subjects and researchers, discourages fraud, and has the support of investigators. We recommend that 10% of projects should undergo on-site review, with all others monitored by questionnaire. This would require about six person hours of time and a salary bill of 120 pounds per study monitored.
Partial cloning of rat CD34 cDNA and expression during stem cell- dependent liver regeneration in the adult rat
Authors: N Omori, M Omori, R P Evarts, T Teramoto, M J Miller, T N Hoang, S S Thorgeirsson
Journal: Hepatology (1997)

The sialomucin CD34 is expressed on human and mouse hematopoietic stem cells and is used as an important marker for isolating the hematopoietic stem/progenitor cells. The involvement of hepatic stem cells in liver regeneration under certain conditions in adult rats is now well supported. The objective of the present research was to explore the idea that CD34 might also be expressed on hepatic stem cell progeny. Polymerase chain reaction (PCR)-based cloning of rat CD34 was partially accomplished. During the hepatic stem cell activation (2- acetylaminofluorene/partial hepatectomy [AAF/PH] model), the CD34 transcripts were increased and reached the peak level between 9 and 12 days after partial hepatectomy when the progenitor cells (e.g., oval cells, early hepatocytes in basophilic foci, and intestinal type of cells) are most abundant. Both in situ hybridization and immunohistochemistry, using anti-mouse CD34 antibody, which recognizes the cytoplasmic domain, clearly showed the expression of CD34 on oval cells as well as on endothelial cells of large hepatic vessels. In addition, bile ductular epithelial (BDE) cells both in the AAF/PH model and in normal liver expressed CD34, suggesting a close relationship between BDE cells and the hepatic stem-cell compartment. Taken together, the data indicate that CD34 would, similar to its role in the hematopoietic system, be an important probe for characterizing the cellular biology of the hepatic stem-cell compartment.
USE OF COLLOIDAL LEAD IN THE TREATMENT OF CANCER
Authors: FRANCIS CARTER WOOD
Journal: JAMA (1926)

While the use of colloidal metals in the treatment of malignant diseases was first recommended by Torres in 1904 and carried out in a desultory way for a number of years, active interest in the subject was stimulated in 1911 by investigations of Wassermann and Keysser.<sup>1</sup>They pointed out that, in order to be effective, such agents must attack the tumor cells primarily; must reach the growth through the blood stream, and if possible attack the nucleus in order to exert the full lethal effect on the cell, as this is the most sensitive portion. It was already known that salts of tellurium and selenium were highly toxic, but tumors in animals were not found to be influenced by intravenous injections of selenium, though remarkable effects were obtained by the direct injection into the tumor itself. Wassermann therefore concluded that it was necessary to combine the selenium with some
Association between Screening for Osteoporosis and the Incidence of Hip Fracture
Authors: Lisa M. Kern, Neil R. Powe, Michael A. Levine, Annette L. Fitzpatrick, Tamara B. Harris, John Robbins, Linda P. Fried
Journal: Annals of Internal Medicine (2005)

Because direct evidence for the effectiveness of screening is lacking, guidelines disagree on whether people should be screened for osteoporosis.To determine whether population-based screening for osteoporosis in older adults is associated with fewer incident hip fractures than usual medical care.Nonconcurrent cohort study.Population-based cohort enrolled in the Cardiovascular Health Study (CHS) from 4 states (California, Pennsylvania, Maryland, and North Carolina).3107 adults 65 years of age and older who attended their CHS study visits in 1994-1995.31 participant characteristics (including demographic characteristics, medical histories, medications, and physical examination findings) and incident hip fractures over 6 years of follow-up.Bone density scans (dual-energy x-ray absorptiometry [DEXA] at the hip) for participants in California and Pennsylvania (n = 1422) and usual care for participants in Maryland and North Carolina (n = 1685).The incidence of hip fractures per 1000 person-years was 4.8 in the screened group and 8.2 in the usual care group. Screening was associated with a statistically significant lower hazard of hip fracture than usual care after adjustment for sex and propensity to be screened (Cox proportional hazard ratio, 0.64 [95% CI, 0.41 to 0.99]).The mechanism of the association was unclear. A small unmeasured confounder that decreased the hazard of hip fracture could diminish or erase the observed association.Use of hip DEXA scans to screen for osteoporosis in older adults was associated with 36% fewer incident hip fractures over 6 years compared with usual medical care. Further research is needed to explore the mechanism of this association.