tbuckley/cabot-search huggingface dataset:
G-Protein–coupled Receptor Polymorphisms Are Associated with Asthma in a Large German Population
Authors: Michael S. D. Kormann, David Carr, Norman Klopp, Thomas Illig, Wolfgang Leupold, Christian Fritzsch, Stephan K. Weiland, Erika von Mutius, Michael Kabesch
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Recently, a new asthma susceptibility gene, GPRA (G-protein-related receptor for asthma), has been identified by positional cloning. Initial association studies in a Finnish and Canadian population suggested an association with asthma and elevated serum IgE levels.In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed.Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology, 1,872 German children aged 9 to 11 years (including 624 children with asthma and/or bronchial hyperresponsiveness) were genotyped for seven polymorphisms in the GPRA gene.Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed.SNP 546333 increased the risk for asthma (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04-1.88; p = 0.025) and concomitant asthma and bronchial hyperresponsiveness (BHR; OR, 2.38; 95% CI, 1.22-4.66; p = 0.009). Also, SNP 585883 was associated with asthma (OR, 1.34; 95% CI, 1.04-1.72; p = 0.022) and asthma in combination with BHR (OR, 2.71; 95% CI, 1.45-5.09; p = 0.001). Furthermore, SNP 585883 was associated with elevated serum IgE levels (OR, 1.63; 95% CI, 1.10-2.42; p = 0.015). Haplotype combinations of risk alleles increased the OR for asthma to 1.83 (95% CI, 1.08-3.08; p = 0.024) and for asthma and concomitant BHR to OR 3.51 (95% CI, 1.08-11.37; p = 0.036).These results indicate that GPRA polymorphisms increase the susceptibility for asthma and BHR, and to a lesser degree for the elevation of serum IgE, in a German population, confirming initial observations in other white populations.
378 SYNERGISTIC EFFECTS OF A1896, T1653 AND T1762/A1764 MUTATIONS IN GENOTYPE C2 HEPATITIS B VIRUS GENOME ON THE OCCURRENCE OF HEPATOCELLULAR CARCINOMA
Authors: H. Lyu, Y.-H. Chung, J.A. Kim, D. Lee, J.-H. Lee, P. Mathews, Y.-J. Jin, W. Park, E. Jaffee, L. Zheng, E. Yu, Y.J. Lee
Journal: Journal of Hepatology (2011)
NSAIDs--should every prescription carry a government health warning?
Authors: R Cockel
Journal: Gut (1987)

NSAIDsshould every prescription carry a Government Health Warning?Non-steroidal anti-inflammatory drugs (NSAIDs) excite quite different emotions on the one hand from pathologists, surgeons, and to a lesser extent gastroenterologists, and on the other from rheumatologists and general practitioners.The former group sees NSAIDs as dangerous and potentially lethal irritants of the gastrointestinal tract, while the latter insists that they are extremely valuable and generally well tolerated drugs for first line use in arthritis and musculoskeletal disorders.These seemingly irreconcilable opinions are readily explained by personal experience, rather than by careful consideration of statistics.The pathologist sees only the fatal end result if perforation or haemorrhage causes death, the surgeon sees only those with perforation or continued haemorrhage, whilst the rheumatologist and general practitioner issue immense numbers of prescriptions for NSAIDs with only infrequently observed major problems.The precise incidence of serious gastrointestinal adverse effects amongst NSAID users is not known, but estimates suggest a rate of one episode of bleeding for 6000 prescriptions issued.'Nevertheless, because of the large number of prescriptions written annually for these drugs (approximately 22 million in 1983') some thousands of patients will develop problems constituting a sizeable proportion of all cases with haemorrhage or perforation.Thus despite the faint impression made on the individual prescriber, the cumulative morbidity and mortality is unacceptably high.The report of two surgeons, C P Armstrong and A L Blower, on page 527 in this issue of Gut presents details of all patients during a three year period needing emergency surgery for bleeding or perforation of peptic ulcer, and of all patients dying from these conditions whether in hospital or at home in the South Cheshire Health District.This report clearly shows the magnitude of the problem -almost 80% of those dying from ulcer complications had received NSAIDs.The only other investigation which has tried to identify all cases of death from peptic ulcer and relate these to use of NSAIDs was the Confidential enquiry into deaths from peptic ulcer in Hampshire between 1981-3.' Information was sought by questionnaire about all those whose death certificates indicated peptic ulcer, but because of various organisational difficulties replies were incomplete.Nevertheless where information was available about those dying in hospital, approximately 50% had been on NSAIDs.The number of deaths associated with the ingestion of NSAIDs nationally is not known, but if the figures from South Cheshire are representative then extrapolation suggests that perhaps more than 4000 people die annually in the United Kingdom from these gastrointestinal complications.To put this into perspective, the annual death rate from self-poisoning, one of the epidemics of our time, amounts also to about 4000, of which less than one fifth occur in hospital.
Human trafficking and smuggling in sports: challenges and the way forward
Authors: Florence B Adeyanju
Journal: British Journal of Sports Medicine (2010)

Human trafficking and smuggling have become a big business worldwide. In the illegal trade, men and women are being defrauded, manipulated, kidnapped and lured into the situation, often regarded as modern day slavery, through various means, including sports events. The incidence of human trafficking and smuggling in sports events has raised serous concerns in Africa as criminal gangs now use sports events as cover up to carry out their activities, luring boys and girls to various countries with promises of better life for the victims. Unfortunately, in actual fact, these victims are subjected to conditions of hopelessness and situations that debase their humanity. In this paper, some case studies were presented. It also discussed the relationship and distinction between human trafficking and smuggling, the causes and mode of operation. The challenges to combating the menace, among which are paucity of reliable data and research document, strong organised criminal gang networks, lack of genuine political will, the paradox of action and conspiracy of silence among government officials, etc. Recommendations towards tackling the menace of human trafficking and smuggling in sports were put forward.
Long-QT Syndrome After Age 40
Authors: Ilan Goldenberg, Arthur J. Moss, James Bradley, Slava Polonsky, Derick R. Peterson, Scott McNitt, Wojciech Zareba, Mark L. Andrews, Jennifer L. Robinson, Michael J. Ackerman, Jesaia Benhorin, Elizabeth S. Kaufman, Emanuela H. Locati, Carlo Napolitano, Silvia G. Priori, Ming Qi, Peter J. Schwartz, Jeffrey A. Towbin, G. Michael Vincent, Li Zhang
Journal: Circulation (2008)

Previous studies that assessed the risk of life-threatening cardiac events in patients with congenital long-QT syndrome (LQTS) have focused mainly on the first 4 decades of life, whereas the clinical course of this inherited cardiac disorder in the older population has not been studied.The risk of aborted cardiac arrest or death from age 41 though 75 years was assessed in 2759 subjects from the International LQTS Registry, categorized into electrocardiographically affected (corrected QT interval [QTc] > or = 470 ms), borderline (QTc 440 to 469 ms), and unaffected (QTc < 440 ms) subgroups. The affected versus unaffected adjusted hazard ratio for aborted cardiac arrest or death was 2.65 (P<0.001) in the age range of 41 to 60 years and 1.23 (P=0.31) in the age range of 61 to 75 years. The clinical course of study subjects displayed gender differences: Affected LQTS women experienced a significantly higher cumulative event rate (26%) than borderline (16%) and unaffected (12%) women (P=0.001), whereas event rates were similar among the 3 respective subgroups of men (29%, 26%, and 27%; P=0.16). Recent syncope (< 2 years in the past) was the predominant risk factor in affected subjects (hazard ratio 9.92, P<0.001), and the LQT3 genotype was identified as the most powerful predictor of outcome in a subset of 871 study subjects who were genetically tested for a known LQTS mutation (hazard ratio 4.76, P=0.02).LQTS subjects maintain a high risk for life-threatening cardiac events after age 40 years. The phenotypic expression of affected subjects is influenced by age-specific factors related to gender, clinical history, and the LQTS genotype.
ABC of palliative care: Bereavement
Authors: F. Sheldon
Journal: BMJ (1998)

<h3>Abstract</h3> Cardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland’s population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere. In FinnGen, a large Finnish biobank study, we identified an inframe insertion rs534125149 in <i>MFGE8</i> to have protective effect against coronary atherosclerosis (OR = 0.75, p = 2.63×10<sup>-16</sup>) and related endpoints. This variant is highly enriched in Finland (70-fold compared to Non-Finnish Europeans) with allele frequency of 3% in Finland. The protective association was replicated in meta-analysis of biobanks of Japan and Estonian (OR = 0.75, p = 5.41×10<sup>-7</sup>). Additionally, we identified a splice acceptor variant rs201988637 in <i>MFGE8</i>, independent of the rs534125149 and similarly protective in relation to coronary atherosclerosis (OR = 0.72, p = 7.94×10<sup>-06</sup>) and related endpoints, with no significant risk-increasing associations. The protein-truncating variant was also associated with lower pulse pressure, pointing towards a function of <i>MFGE8</i> in arterial stiffness and aging also in humans in addition to previous evidence in mice. In conclusion, our results show that inhibiting the production of lactadherin could lower the risk for coronary heart disease substantially.
Case 43-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Eve E. Slater, John T. Fallon
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 28-year-old man was admitted to the hospital because of hypertension.He was well until seven years previously, when mild hypertension was found; no treatment was prescribed. He began to experience fatigue, exertional dyspnea and occasional dull occipital headaches. Two months before admission examination elsewhere disclosed a murmur over the posterior thoracic area. A pulmonary arteriographic examination was reported to show coarctation of the aorta. He was referred to this hospital.The patient was a Korean national who was studying in the United States. An uncle had hypertension. There was no personal history of epistaxis, claudication or . . .
Sinusoidal Obstructive Syndrome Diagnosed With Superparamagnetic Iron Oxide–Enhanced Magnetic Resonance Imaging in Patients With Chemotherapy-Treated Colorectal Liver Metastases
Authors: Janice Ward, James A. Guthrie, Maria B. Sheridan, Sheila Boyes, Jonathan T. Smith, Daniel Wilson, Judy I. Wyatt, Darren Treanor, Philip J. Robinson
Journal: Journal of Clinical Oncology (2008)

To assess the predictive value of superparamagnetic iron oxide (SPIO) -enhanced T2-weighted gradient echo (GRE) imaging to determine the presence and severity of sinusoidal obstructive syndrome (SOS).Sixty hepatic resection patients with colorectal metastases treated with chemotherapy underwent unenhanced magnetic resonance imaging (MRI) followed by T2-weighted GRE sequences obtained after SPIO. The images were reviewed in consensus by two experienced observers who determined the presence and severity of linear and reticular hyperintensities, indicating SOS-type liver injury, using a 4-point ordinal scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% CIs for the detection of SOS were calculated.Twenty-four of 60 patients had moderate to severe SOS on MRI. MRI achieved a sensitivity of 87% (95% CI, 66% to 97%), specificity of 89% (95% CI, 75% to 97%), PPV of 83% (95% CI, 63% to 95%), and NPV of 92% (95% CI, 77% to 98%). SOS was never found at surgery or histology in patients whose background liver parenchyma was normal on SPIO-enhanced MRI.SOS is present in a significant proportion of patients with treated colorectal metastases and is effectively detected on SPIO-enhanced T2-weighted GRE images.
Effects of bile acids and hydrogen ion on the fine structure of oesophageal epithelium.
Authors: D Hopwood, M C Bateson, G Milne, I A Bouchier
Journal: Gut (1981)

Oesophageal mucosal biopsies were incubated in 20, 0, and 0.2mM solutions of cholic, chenodeoxycholic, ursodeoxycholic, and deoxycholic bile acids. Both conjugated and unconjugated bile acids were studied at pH 1 and 7 singly and in combination. Observations were also made using 0.1 N hydrochloric acid and human gastric juice at pH 1-3 and 7-8. After incubation for up to 15 minutes the mucosa was examined under transmission electron microscopy. We concluded that high and moderate concentration of all the common bile acids damaged the oesophagus irrespective of the pH, that low concentrations of bile acids were damaging only at high acid levels, and that damage to the epithelium did not occur when the pH of the gastric juice had been raised.
What is a good death?: Humour may be important even at the end
Authors: D. F Bird
Journal: BMJ (2003)

Editor—I write to contribute to the discussion of what constitutes a good death.1 Some years ago my colleague Peter was dying from secondaries from a bowel carcinoma. Looked after devotedly by his wife and his medical carers, Peter gradually deteriorated. However, even near the end he was able to spend a day on his beloved West Somerset Railway, organised by friends.

A northerner, Peter shared a blunt, affectionate, sense of humour with my wife, Joan. Saying farewell, after what was to be our last visit to him, Peter commented that he was worn out and now just wanted to go with dignity. With her usual speedy repartee Joan replied: You've never done anything with dignity before, Peter. Why start now? Peter's chuckles remain with us as a memory of a very brave man and as a reminder of the importance of laughter in our lives, even at the end.
Alcohol and Other Substance Abuse and Impairment among Physicians in Residency Training
Authors: Richard D. Aach, Donald E. Girard, Holly Humphrey, Jack D. McCue, David B. Reuben, Jay W. Smith, Lisa Wallenstein, Jack Ginsburg
Journal: Annals of Internal Medicine (1992)

▪Substance abuse and impairment are serious societal problems. Physicians have historically had high rates of substance abuse, which has been viewed as an occupational hazard. Most authorities agree that the rate of alcoholism among practicing physicians is similar to that among control populations and that the rates of other substance abuse are greater, although some studies have shown no difference. Data about substance abuse among residents in training are limited but suggest that the use of benzodiazepines is greater than that among aged-matched peers, whereas the use of alcohol is similar between the two groups. Medical institutions, including those with teaching programs, have legal and ethical responsibilities concerning substance abuse among current and future physicians. Many training programs, however, do not provide educational programs on this subject, do not have faculty trained in substance abuse medicine, and do not have a formal system to address the problem of residents who are suspected or known to be substance abusers. This position paper examines the extent of substance abuse, including alcohol abuse, among physicians in residency training. It outlines approaches to the problem and delineates responsibilities of institutions and residency program directors. Recommendations are made to establish an informational program and a clearly defined, organized process to address the problems of substance abuse among residents. Careful and humane approaches can be used to identify and treat residents with substance abuse problems and thus allowing them to complete their training as competent and drug-free professionals.
1021-54 Multiplane Transesophageal Echo Has a Greater Impact on Clinical Care than Biplane: The VOTE Study
Authors: Martin E. Goldman, Steven Goldstein, Itzhak Kronzon, Benico Barzilai, Ravin Davidoff, Anthony DeMaria, Howard Dittrich, Shunichi Homma, Michael Motro, Natesa Pandian, Michael Picard, Stacey Rosen, Steven Schwartz, Paul A. Tunick, Zvi Vered, Gad Keren, David Vorchheimer, Larry Baruch, Oma David, Jacqueline Budd, Edward Fisher
Journal: Journal of the American College of Cardiology (1995)
Transcatheter Device Closure of Congenital and Postoperative Residual Ventricular Septal Defects
Authors: Alison L. Knauth, James E. Lock, Stanton B. Perry, Doff B. McElhinney, Kimberlee Gauvreau, Michael J. Landzberg, Jonathan J. Rome, William E. Hellenbrand, Carlos E. Ruiz, Kathy J. Jenkins
Journal: Circulation (2004)

Our purpose was to describe a 13-year experience with patients undergoing transcatheter device closure of unrepaired congenital or postoperative residual ventricular septal defects (VSDs).Since 1989, 170 patients (median age, 3.9 years) have undergone catheterization for closure of 1 or more congenital (n=92) or postoperative (n=78) residual VSDs using successive generations of STARFlex-type devices. Outcomes included echocardiographic assessment of residual flow and device position, assessment of VSD shunt/severity, and adverse events. Among 168 patients in whom device implantation was performed, between 1 and 7 devices were placed per patient (median, 1), with multiple devices placed in 40%. There was a significant decrease in left-to-right shunting after device implantation (P<0.001) and significant improvement in VSD size/severity, and device position proved stable. Of 332 adverse events, 39 were related to the device and 261 were related to the catheterization; all but 5 occurred in the periprocedural period. At a median follow-up of 24 months (0 to 154 months), 14 patients had died and 18 had device(s) explanted.Congenital and postoperative VSD closure using STARFlex-type devices resulted in stable improvement in clinical status and decreased interventricular shunting. Although periprocedural events occurred frequently, late events caused by the device were rare. Transcatheter device closure is an effective management option for patients with complex muscular VSDs that are difficult to approach surgically and for postoperative residual VSDs.
In situ expression of factor VII in the liver of patients withchronic hepatitis: Correlation with the severity of the liverdisease
Authors: E. Rodriguez-Iñigo, J. Bartolomé, J.A. Quiroga, U. Hedner, A. Suarez, J.F. Tomás, C. Arocena, M.L. Manzano, V. Carreño
Journal: Journal of Hepatology (2000)
Coughing and Aerosols
Authors: Julian W Tang, Gary S Settles
Journal: New England Journal of Medicine (2008)

hen a healthy volunteer coughs, he expels a turbulent jet of air with density changes that distort a projected schlieren light beam (Panel A).A velocity map early in the cough (Panel B) was obtained from image analysis.Sequential schlieren images during the cough (Panel C and video) were recorded at 3000 frames per second.A maximum airspeed of 8 m per second (18 mph) was observed, averaged during the half-second cough.Several phases of cough airflow are revealed in the figure.The cough plume may project infectious aerosols into the surrounding air.There is an increasing interest in visualizing such expelled airflows without the use of intrusive methods because of concern regarding the transmission of various airborne pathogens, such as viruses that cause influenza and the severe acute respiratory syndrome (SARS).
Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma.
Authors: W Palinski, S Hörkkö, E Miller, U P Steinbrecher, H C Powell, L K Curtiss, J L Witztum
Journal: Journal of Clinical Investigation (1996)

Many reactive products may be formed when LDL undergoes lipid peroxidation, which in turn can react with lipids, apoproteins, and proteins, generating immunogenic neoepitopes. Autoantibodies recognizing model epitopes of oxidized low density lipoprotein, such as malondialdehydelysine, occur in plasma and in atherosclerotic lesions of humans and animals. Because apo E-deficient mice develop particularly high titers of such autoantibodies, we used their spleens to clone 13 monoclonal antibodies to various epitopes of oxidized LDL ("E0 antibodies"). Binding and competitive RIAs demonstrated significant differences in fine specificity even between E0 antibodies initially selected for binding to the same screening antigen. For example, some E0 antibodies selected for binding to malondialdehyde-LDL also recognized copper oxidized LDL, acrolein-LDL, or LDL modified by arachidonic or linoleic acid oxidation products. Circulating IgG and IgM autoantibodies binding to copper-oxidized LDL, 4-hydroxynonenal-LDL, acrolein-LDL, and LDL modified with arachidonic or linoleic acid oxidation products were found in apo E-deficient mice, suggesting that the respective antigens are formed in vivo. Epitopes recognized by some of the E0 monoclonal antibodies were also found on human circulating LDL. Each of the E0 monoclonal antibodies immunostained rabbit and human atherosclerotic lesions, and some of them yielded distinct staining patterns in advanced lesions. Together, this suggests that the natural monoclonal antibodies recognize different epitopes of complex structures formed during oxidation of lipoproteins, or epitopes formed independently at different lesion sites. Our data demonstrate that a profound immunological response to a large number of different epitopes of oxidized lipoproteins occurs in vivo. The availability of "natural" monoclonal autoantibodies should facilitate the identification of specific epitopes inducing this response.