tbuckley/cabot-search huggingface dataset:
SRD5B1 (AKR1D1) gene analysis in Δ4-3-oxosteroid 5β-reductase deficiency: evidence for primary genetic defect
Authors: Emmanuel Gonzales, Danièle Cresteil, Christiane Baussan, Alain Dabadie, Marie-Françoise Gerhardt, Emmanuel Jacquemin
Journal: Journal of Hepatology (2004)
Evidence does not support guidelines on saturated fat, researchers say
Authors: J. Wise
Journal: BMJ (2014)

Current guidelines that promote high consumption of polyunsaturated fatty acids and low consumption of total saturated fats to reduce the risk of cardiovascular disease are based on inadequate evidence, a new analysis concludes.1

Nutritional guidelines generally encourage eating a relatively low amount of saturated fats such as butter in favour of polyunsaturated fat such as olive oil and sunflower oil. However, …
Exercise-induced Bronchoconstriction Does Not Cause Eosinophilic Airway Inflammation or Airway Hyperresponsiveness in Subjects with Asthma
Authors: GAIL M. GAUVREAU, GISELLE M. RONNEN, RICK M. WATSON, PAUL M. O'BYRNE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The cysteinyl leukotrienes (LT) C4, D4, and E4 may partially mediate eosinophilic airway inflammation in patients with asthma. High- intensity exercise by patients with asthma can result in exercise- induced bronchoconstriction, partly due to leukotriene production, but it is still debated whether this causes airway inflammation. Ten subjects completed a randomized, controlled study to examine the effects of exercise-induced bronchoconstriction on airway inflammatory cells. Subjects completed exercise challenge and methacholine challenge in random order separated by 1 wk. Spirometry was measured for 2 h after challenges, and airway responsiveness was measured the day before and 24 h after each challenge. Blood and sputum samples were obtained before, and 2, 4, 7, and 24 h after each challenge for measurement of inflammatory cells. Nine of the subjects inhaled allergen at least 3 wk before or 1 wk after the study. Sputum samples were collected before, 7 h, and 24 h after challenge. The maximum percentage fall in FEV1 was 21.3 ± 1.5% after exercise, 29.9 ± 1.5% after methacholine, and 28.9 ± 2.7% after allergen. Exercise had no effect on airway responsiveness or inflammatory cells measured in blood or sputum, unlike allergen inhalation, which resulted in significant airway hyperresponsiveness and increases in sputum eosinophils (p < 0.05). This study demonstrates that exercise-induced bronchoconstriction does not cause eosinophilic airway inflammation in subjects with asthma who develop airway inflammation with the same degree of allergen-induced bronchoconstriction. We conclude that exercise-induced bronchoconstriction does not cause airway inflammation or airway hyperresponsiveness.
Ultrasonography Screening for Abdominal Aortic Aneurysms: A Systematic Evidence Review for the U.S. Preventive Services Task Force
Authors: Janelle M. Guirguis-Blake, Tracy L. Beil, Caitlyn A. Senger, Evelyn P. Whitlock
Journal: Annals of Internal Medicine (2014)

Background: Long-term follow-up of population-based randomized, controlled trials (RCTs) has demonstrated that screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates in men aged 65 years or older. Purpose: To systematically review evidence about the benefits and harms of ultrasonography screening for AAAs in asymptomatic primary care patients. Data Sources: MEDLINE, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials (January 2004 through January 2013), clinical trial registries, reference lists, experts, and a targeted bridge search for population-based screening RCTs through September 2013. Study Selection: English-language, population-based, fair- to good-quality RCTs and large cohort studies for AAA screening benefits as well as RCTs and cohort and registry studies for harms in adults with AAA. Data Extraction: Dual quality assessment and abstraction of study details and results. Data Synthesis: Reviews of 4 RCTs involving 137 214 participants demonstrated that 1-time invitation for AAA screening in men aged 65 years or older reduced AAA rupture and AAA-related mortality rates for up to 10 and 15 years, respectively, but had no statistically significant effect on all-cause mortality rates up to 15 years. Screening was associated with more overall and elective surgeries but fewer emergency operations and lower 30-day operative mortality rates at up to 10- to 15-year follow-up. One RCT involving 9342 women showed that screening had no benefit on AAA-related or all-cause mortality rates. Limitations: Trials included mostly white men outside of the United States. Information for subgroups and about rescreening was limited. Conclusion: One-time invitation for AAA screening in men aged 65 years or older was associated with decreased AAA rupture and AAA-related mortality rates but had little or no effect on all-cause mortality rates. Primary Funding Source: Agency for Healthcare Research and Quality.
Long-term safety of adefovir dipivoxil (ADV) 10 MG once daily for chronic hepatitis B (CHB): An integrated analysis of two phase III studies
Authors: T.T. Chang, S.G. Lim, S. Hadziyannis, N. Tassopoulos, M. Tong, W. Sievert, R. Fallis, M. Wollman, C. James, J. Fry, S.S. Chen, C. Brosgart
Journal: Journal of Hepatology (2003)
The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses
Authors: Nathalie Arhel, Martin Lehmann, Karen Clauß, G. Ulrich Nienhaus, Vincent Piguet, Frank Kirchhoff
Journal: Journal of Clinical Investigation (2009)

Viruses that infect T cells, including those of the lentivirus genus, such as HIV-1, modulate the responsiveness of infected T cells to stimulation by interacting APCs in a manner that renders the T cells more permissive for viral replication. HIV-1 and other primate lentiviruses use their Nef proteins to manipulate the T cell/APC contact zone, the immunological synapse (IS). It is known that primate lentiviral Nef proteins differ substantially in their ability to modulate cell surface expression of the TCR-CD3 and CD28 receptors critical for the formation and function of the IS. However, the impact of these differences in Nef function on the interaction and communication between virally infected T cells and primary APCs has not been investigated. Here we have used primary human cells to show that Nef proteins encoded by HIV-2 and most SIVs, which downmodulate cell surface expression of TCR-CD3, disrupt formation of the IS between infected T cells and Ag-presenting macrophages or DCs. In contrast, nef alleles from HIV-1 and its simian precursor SIVcpz failed to suppress synapse formation and events downstream of TCR signaling. Our data suggest that most primate lentiviruses disrupt communication between virally infected CD4+ Th cells and APCs, whereas HIV-1 and its SIV precursor have largely lost this capability. The resulting differences in the levels of T cell activation and apoptosis may play a role in the pathogenesis of AIDS.
Multisystem Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees
Authors: Scott C. Fears, Susan K. Service, Barbara Kremeyer, Carmen Araya, Xinia Araya, Julio Bejarano, Margarita Ramirez, Gabriel Castrillón, Juliana Gomez-Franco, Maria C. Lopez, Gabriel Montoya, Patricia Montoya, Ileana Aldana, Terri M. Teshiba, Zvart Abaryan, Noor B. Al-Sharif, Marissa Ericson, Maria Jalbrzikowski, Jurjen J. Luykx, Linda Navarro, Todd A. Tishler, Lori Altshuler, George Bartzokis, Javier Escobar, David C. Glahn, Jorge Ospina-Duque, Neil Risch, Andrés Ruiz-Linares, Paul M. Thompson, Rita M. Cantor, Carlos Lopez-Jaramillo, Gabriel Macaya, Julio Molina, Victor I. Reus, Chiara Sabatti, Nelson B. Freimer, Carrie E. Bearden
Journal: JAMA Psychiatry (2014)

Genetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes.
Abstract 4696: Expression of the DNA repair protein UNG predicts lung cancer sensitivity to pemetrexed
Authors: Lachelle D. Weeks, Stanton L. Gerson, Lili Liu
Journal: Cancer Research (2012)

Abstract Uracil misincorporation is a direct consequence of TS inhibition by the multi-target antifolate, pemetrexed. The DNA base excision repair (BER) enzyme Uracil DNA glycosylase (UNG) is the major glycosylase responsible for the removal of misincorporated genomic uracil. We have previously illustrated that human colon cancer cells (DLD1) with engineered stable somatic knockout of UNG expression are hypersensitive to pemetrexed owing to the cytotoxicity of genomic uracil accumulation. Here, we examined the relationship between the expression of UNG and the pemetrexed sensitivity in a small panel of lung cancer cell lines (n∼10). The levels of UNG were measured by western blot (for protein) and RT-PCR (for mRNA). Results revealed that UNG mRNA expression is well correlated with protein expression in all cell lines. Moreover, there was a wide range of distribution of UNG levels in the lung cancer cell lines evaluated. UNG cutting assay and AP site measurements confirm that these differences in UNG expression result in varied potential for BER activation and subsequent AP site formation. To determine the role of this variation in UNG expression in pemetrexed cytotoxicity, colony survival studies were performed. In general, cell lines with higher UNG expression were more resistant to pemetrexed. H460 cells having 7-fold lower expression of UNG mRNA than H1975 cells are &amp;gt;5 fold more sensitive to pemetrexed than H1975 cells (H460 IC50 = 200nM; H1975 IC50 = &amp;gt;1000nM). Analysis of tissue microarray data in Oncomine confirms variations in UNG expression in primary human lung cancer samples. Moreover, small cell lung cancer and squamous cell lung cancer, both notoriously resistant to pemetrexed, have significantly increased median UNG expression compared to all other lung cancer subtypes (1.5-fold greater UNG expression p&amp;lt;0.005). These data motivate future evaluation of UNG as a clinical predictor of pemetrexed response using lung cancer biopsy specimens. Together, our results clearly indicate that the BER protein, UNG is differentially expressed in lung cancer cells. The inherent variation in UNG expression may have particular impact on our ability to predict the therapeutic efficacy of pemetrexed in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4696. doi:1538-7445.AM2012-4696
Echocardiographic Criteria in the Diagnosis of Idiopathic Hypertrophic Subaortic Stenosis
Authors: RONALD M. ROSSEN, DANIEL J. GOODMAN, ROBERT E. INGHAM, RICHARD L. POPP
Journal: Circulation (1974)

Echocardiography has proven to be a useful technique in the diagnosis and assessment of therapy in idiopathic hypertrophic subaortic stenosis (IHSS). Asymmetric septal hypertrophy has been described as the pathognomonic anatomic marker of the disease. A characteristic systolic anterior motion of the anterior mitral valve leaflet has been detected in the presence of hemodynamically significant subaortic left ventricular outflow obstruction. An echocardiographic quantification of the outflow gradient (the obstruction index) has been derived previously. Four patients were studied by ultrasound at the time of cardiac catheterization. All four demonstrated systolic anterior motion of the anterior mitral leaflet in the absence of a resting gradient. In three of the four, the calculated obstruction index predicted hemodynamically significant resting gradients. All four patients were shown to have labile gradients with provocative maneuvers. A fifth patient with abnormal systolic anterior motion demonstrated a close correlation between the obstruction index and resting gradient; however, symmetric hypertrophy of the septum and left ventricular posterior wall was detected by ultrasound. Therefore, the abnormal mitral valve pattern may be seen in the absence of a resting gradient and symmetric left ventricular hypertrophy may exist in the presence of IHSS.
Studies on Measles Vaccination in Nigerian Children
Authors: R. G. Hendrickse, D. Montefiore, P. M. Sherman, H. M. Van Der Wall
Journal: BMJ (1964)

Children given measles vaccine.t Children given poliomyelitis vaccine.the number of children participating in the trials, including the defaulters and those known to be immune.Reports have been obtained from the mothers of all except 15 of the defaulters.The reasons for failure to attend were generally a misunderstanding about the dates for reporting, or, because the child was well, the mother did not consider it necessary to come back.There is no reason to suppose that the children who failed to
Etiology of Malformations
Authors: Ian Leck
Journal: New England Journal of Medicine (1965)

HUMAN malformations have always been obobjects of speculation. In prescientific days they were regarded either as copies of things seen by the pregnant woman or as marks of bestial parentage or supernatural intervention. With the rise of biology these theories were abandoned, and the discovery of recessive inheritance encouraged the idea that the majority of malformations were genetically determined. More recently the opposite view —that most defects are caused by events after conception — has been gaining ground, as a result of experience with rubella and thalidomide in man and with various other teratogens in laboratory animals.The assumption underlying . . .
Immune Globulin to Prevent Nosocomial Infections
Authors: George R. Siber
Journal: New England Journal of Medicine (1992)

With the introduction of intravenous formulations, the use of immune globulins, once limited to IgG replacement in severe humoral immunodeficiencies, has been extended to include the prevention or treatment of a wide variety of infections and immunologic disorders.1 , 2 Though the role of immune globulin in the prevention of systemic and sinopulmonary bacterial infections in agammaglobulinemia is well established, its role in the management of more subtle humoral immunodeficiencies associated with B-cell neoplasms, bone marrow transplantation, and IgG-subclass deficiencies remains controversial.1 , 2 In premature babies, a physiologic hypogammaglobulinemia due to reduced transplacental transfer and endogenous synthesis of IgG provides a strong rationale . . .
Gender of Companions
Authors: Franklin Drucker
Journal: JAMA (1984)

<h3>To the Editor.—</h3> I am struck by the letter of Richard F. Herndon, MD,<sup>1</sup>concerning companions. Except for a passing reference to a grown daughter<i>or</i>son, all examples of companions given are female. This corresponds to my own observations. I agree with Dr Herndon that the companion is almost always relevant, has an influence on care, and should be catered to. However, I do not understand how Dr Herndon asks the companion "why<i>he</i>came."
Risk Stratification in the Long-QT Syndrome
Authors: Silvia G. Priori, Peter J. Schwartz, Carlo Napolitano, Raffaella Bloise, Elena Ronchetti, Massimiliano Grillo, Alessandro Vicentini, Carla Spazzolini, Janni Nastoli, Georgia Bottelli, Roberta Folli, Donata Cappelletti
Journal: New England Journal of Medicine (2003)

Mutations in potassium-channel genes KCNQ1 (LQT1 locus) and KCNH2 (LQT2 locus) and the sodium-channel gene SCN5A (LQT3 locus) are the most common causes of the long-QT syndrome. We stratified risk according to the genotype, in conjunction with other clinical variables such as sex and the length of the QT interval.We evaluated 647 patients (386 with a mutation at the LQT1 locus, 206 with a mutation at the LQT2 locus, and 55 with a mutation at the LQT3 locus) from 193 consecutively genotyped families with the long-QT syndrome. The cumulative probability of a first cardiac event, defined as the occurrence of syncope, cardiac arrest, or sudden death before the age of 40 years and before the initiation of therapy, was determined according to genotype, sex, and the QT interval corrected for heart rate (QTc). Within each genotype we also assessed risk in the four categories derived from the combination of sex and QTc (<500 msec or > or =500 msec).The incidence of a first cardiac event before the age of 40 years and before the initiation of therapy was lower among patients with a mutation at the LQT1 locus (30 percent) than among those with a mutation at the LQT2 locus (46 percent) or those with a mutation at the LQT3 locus (42 percent) (P<0.001 by Fisher's exact test). Multivariate analysis showed that the genetic locus and the QTc, but not sex, were independent predictors of risk. The QTc was an independent predictor of risk among patients with a mutation at the LQT1 locus and those with a mutation at the LQT2 locus but not among those with a mutation at the LQT3 locus, whereas sex was an independent predictor of events only among those with a mutation at the LQT3 locus.The locus of the causative mutation affects the clinical course of the long-QT syndrome and modulates the effects of the QTc and sex on clinical manifestations. We propose an approach to risk stratification based on these variables.
Effect of cobalt and chromium ions on MMP-1, TIMP-1, and TNF-α gene expression in human U937 macrophages: A role for tyrosine kinases
Authors: Li Luo, Alain Petit, John Antoniou, David J. Zukor, Olga L. Huk, Roger C.W. Liu, Françoise M. Winnik, Fackson Mwale
Journal: Biomaterials (2005)
The Autoimmune Diseases
Authors: Robert H. Carter
Journal: JAMA (2007)

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Hypnotics and anxiolytics
Authors: P G Nutley
Journal: BMJ (1983)

Drs Hockings and Ballinger, cause daytime dopiness and impaired judgment.Very short acting hypnotics should now be distinguished and their potential problems recognised.If the doctor feels impelled to prescribe a hypnotic then he must strike a balance, and at present the best choice would appear to be a benzodiazepine with an elimination half life of around 10 hours (it may take longer in the elderly): long enough to sustain sleep without leading to appreciable daytime dopiness, yet leaving sufficient in the tissues to prevent withdrawal phenomena pending any next dose, or at least to moderate withdrawal features by avoiding a precipitous fall in tissue con- centrations.
Steroidal Influences on Catecholamines
Authors: Timothy S. Harrison, Ramesh C. Chawla, Raymond S. Wojtalik
Journal: New England Journal of Medicine (1968)

FEW treatments in medicine are based on more tenuous evidence than that used to justify paralysis of the adrenergic nervous system in the contemporary clinical management of "shock." To a large degree such efforts have resulted from preoccupation with one aspect of adrenergic activity, vasoconstriction, and other fundamental aspects of adrenergic responsiveness have been largely ignored. Although alpha-adrenergic receptor blockade with phenoxybenzamine, frequently coupled with high doses of hydrocortisone, has been used to combat vasoconstriction no convincing experimental data exist to justify it; whereas data do support the use of glucocorticoid hormones in shock, there is little information on how . . .
Use of an Automated Decision Support Tool Optimizes Clinicians’ Ability to Interpret and Appropriately Respond to Structured Self-Monitoring of Blood Glucose Data
Authors: Helena W. Rodbard, Oliver Schnell, Jeffrey Unger, Christen Rees, Linda Amstutz, Christopher G. Parkin, Zhihong Jelsovsky, Nathan Wegmann, Matthias Axel-Schweitzer, Robin S. Wagner
Journal: Diabetes Care (2012)

We evaluated the impact of an automated decision support tool (DST) on clinicians' ability to identify glycemic abnormalities in structured self-monitoring of blood glucose (SMBG) data and then make appropriate therapeutic changes based on the glycemic patterns observed.In this prospective, randomized, controlled, multicenter study, 288 clinicians (39.6% family practice physicians, 37.9% general internal medicine physicians, and 22.6% nurse practitioners) were randomized to structured SMBG alone (STG; n = 72); structured SMBG with DST (DST; n = 72); structured SMBG with an educational DVD (DVD; n = 72); and structured SMBG with DST and the educational DVD (DST+DVD; n = 72). Clinicians analyzed 30 patient cases (type 2 diabetes), identified the primary abnormality, and selected the most appropriate therapy.A total of 222 clinicians completed all 30 patient cases with no major protocol deviations. Significantly more DST, DVD, and DST+DVD clinicians correctly identified the glycemic abnormality and selected the most appropriate therapeutic option compared with STG clinicians: 49, 51, and 55%, respectively, vs. 33% (all P < 0.0001) with no significant differences among DST, DVD, and DST+DVD clinicians.Use of structured SMBG, combined with the DST, the educational DVD, or both, enhances clinicians' ability to correctly identify significant glycemic patterns and make appropriate therapeutic decisions to address those patterns. Structured testing interventions using either the educational DVD or the DST are equally effective in improving data interpretation and utilization. The DST provides a viable alternative when comprehensive education is not feasible, and it may be integrated into medical practices with minimal training.
Balloon Dilation of the Abdominal Aorta
Authors: Charles J. Tegtmeyer
Journal: JAMA (1980)

PERCUTANEOUS transluminal angioplasty was developed by Dotter and Judkins<sup>1</sup>in 1964 for the treatment of atherosclerotic peripheral vascular disease. Grüntzig and Hopff<sup>2</sup>revolutionized the technique when they developed the flexible balloon catheter. This versatility permitted successful dilation of the branches of the aorta, including the renal<sup>1</sup>and coronary<sup>4</sup>arteries. The present report describes the successful transluminal dilation of a lesion in the distal abdominal aorta. <h3>Report of a Case</h3> A 47-year-old woman was referred to the University of Virginia Medical Center with bilateral hip and lower extremity claudication. Over the past four months she had experienced progressive pain while walking. At the time of admission she described pain after walking a distance of only one block. Physical examination showed a bruit in the upper abdomen. Bruits were also heard over the iliac and femoral vessels bilaterally. The right femoral pulse was 2+, and the left femoral pulse