tbuckley/cabot-search huggingface dataset:
Comparison of serum markers for allergic bronchopulmonary aspergillosis in cystic fibrosis
Authors: P. Latzin, D. Hartl, N. Regamey, U. Frey, M. H. Schoeni, C. Casaulta
Journal: European Respiratory Journal (2007)

The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is a challenge. Thymus- and activation-regulated chemokine (TARC) has recently been reported to play a role in ABPA. The aim of this study was to compare the diagnostic value of TARC with that of known serological markers for diagnosis of ABPA in CF patients. The present study longitudinally followed 48 CF patients, of whom 12 had a diagnosis of ABPA according to Nelson's criteria, for 1–8 yrs with repeated measurements of serum total immunoglobulin (Ig)E, specific Aspergillus fumigatus IgE and IgG, specific IgE against recombinant A. fumigatus allergens (rAsp f) 1, 3, 4 and 6, and TARC. Median (interquartile range) TARC levels were 589 (465–673) pg·mL −1 in ABPA patients and 232 (189–289) pg·mL −1 in non-ABPA patients. Receiver operating characteristic curves revealed that TARC was superior to the other markers for diagnosis of ABPA. Diagnostic accuracy was greater for TARC (93%) than for total IgE (74%), or rAsp f 4 (75%) or f 6 (79%). The present study indicates that thymus- and activation-regulated chemokine may be useful in the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis patients. However, larger studies are needed before thymus- and activation-regulated chemokine can routinely be used in diagnostic algorithms.
G-CSF Receptor Positive Neuroblastoma Subpopulations Are Enriched in Chemotherapy-Resistant or Relapsed Tumors and Are Highly Tumorigenic
Authors: Danielle M. Hsu, Saurabh Agarwal, Ashley Benham, Cristian Coarfa, Denae N. Trahan, Zaowen Chen, Paris N. Stowers, Amy N. Courtney, Anna Lakoma, Eveline Barbieri, Leonid S. Metelitsa, Preethi Gunaratne, Eugene S. Kim, Jason M. Shohet
Journal: Cancer Research (2013)

Neuroblastoma is a neural crest-derived embryonal malignancy, which accounts for 13% of all pediatric cancer mortality, primarily due to tumor recurrence. Therapy-resistant cancer stem cells are implicated in tumor relapse, but definitive phenotypic evidence of the existence of these cells has been lacking. In this study, we define a highly tumorigenic subpopulation in neuroblastoma with stem cell characteristics, based on the expression of CSF3R, which encodes the receptor for granulocyte colony-stimulating factor (G-CSF). G-CSF receptor positive (aka G-CSFr(+) or CD114(+)) cells isolated from a primary tumor and the NGP cell line by flow cytometry were highly tumorigenic and capable of both self-renewal and differentiation to progeny cells. CD114(+) cells closely resembled embryonic and induced pluripotent stem cells with respect to their profiles of cell cycle, miRNA, and gene expression. In addition, they reflect a primitive undifferentiated neuroectodermal/neural crest phenotype revealing a developmental hierarchy within neuroblastoma tumors. We detected this dedifferentiated neural crest subpopulation in all established neuroblastoma cell lines, xenograft tumors, and primary tumor specimens analyzed. Ligand activation of CD114 by the addition of exogenous G-CSF to CD114(+) cells confirmed intact STAT3 upregulation, characteristic of G-CSF receptor signaling. Together, our data describe a novel distinct subpopulation within neuroblastoma with enhanced tumorigenicity and a stem cell-like phenotype, further elucidating the complex heterogeneity of solid tumors such as neuroblastoma. We propose that this subpopulation may represent an additional target for novel therapeutic approaches to this aggressive pediatric malignancy.
ENDOGENOUS DIGITALIS-LIKE NATRIURETIC FACTORS
Authors: S W Graves, G H Williams
Journal: Annual Review of Medicine (1987)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Comparison against baseline in randomised control trials (again)
Authors: John D. Blakey
Journal: European Respiratory Journal (2014)

Comparison against baseline in randomised control trials (again)To the Editor: I read with interest the article by DIAS-JU ´NIOR et al.[1] describing a randomised controlled trial of a weight loss programme for obese asthmatics.I was, however, disappointed to see that the results were published as comparisons against baseline.This approach is biased and potentially misleading, as has been eloquently outlined by BLAND and ALTMAN [2]: their discussion includes the instructive example of a study that appeared to support the use of an over-the-counter antiageing cream [3] and thus created a good deal of misleading publicity.I strongly encourage the European Respiratory Journal to insist that randomised trials report differences between groups rather than within groups in future.Randomised trials should report differences between groups rather than within groups http://ow.ly/zVHbv
Opiate Therapy in Chronic Cough
Authors: Alyn H Morice, Madhav S Menon, Siobhan A Mulrennan, Caroline F Everett, Caroline Wright, Jennifer Jackson, Rachel Thompson
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Cough is the most common complaint for which medical attention is sought, and chronic cough can be both physically and mentally debilitating. There is currently no evidence supporting the use of antitussives in chronic treatment-resistant cough.We tested the hypothesis that morphine sulfate in the dose of 5 mg twice daily would bring about a reduction in cough frequency and severity in patients failing to respond to specific measures.Patients recruited from the Hull Cough Clinic were enrolled into a randomized double-blind placebo-controlled study using 4 weeks of slow-release morphine sulfate and a corresponding period of matched placebo. An open-labeled extension of the core study allowed dose escalation to 10 mg twice daily. Cough was assessed using the Leicester Cough Questionnaire, daily symptom diary, and citric acid cough challenge.Twenty-seven patients completed the core study. A significant improvement of 3.2 points over baseline was noted on the Leicester Cough Questionnaire (p < 0.01). A rapid and highly significant reduction by 40% in daily cough scores was noted among patients on slow-release morphine sulfate (p < 0.01). Objective testing of the cough reflex using citric acid cough challenge tests did not show any significant changes. Eighteen patients continued into the extension study. Two-thirds of these patients opted to increase the morphine to 10 mg twice daily. At the end of 3 months, there was a similar improvement in cough between the 5- and 10-mg groups.Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily.
Combined Associations of Genetic and Environmental Risk Factors: Implications for Prevention of Breast Cancer
Authors: M. Garcia-Closas, N. B. Gunsoy, N. Chatterjee
Journal: JNCI Journal of the National Cancer Institute (2014)

Genome-wide association studies (GWAS) have identified hundreds of genetic susceptibility loci for cancers and other complex diseases. However, the public health and clinical relevance of these discoveries is unclear. Evaluating the combined associations of genetic and environmental risk factors, particularly those that can be modified, will be critical in assessing the utility of genetic information for risk stratified prevention. In this commentary, using breast cancer as a model, we show that genetic information in combination with other risk factors can provide levels of risk stratification that could be useful for individual decision-making or population-based prevention programs. Our projections are theoretical and rely on a number of assumptions, including multiplicative models for the combined associations of the different risk factors, which need confirmation. Thus, analyses of epidemiological studies with high-quality risk factor information, as well as prevention trials, are needed to empirically assess the impact of genetics in risk stratified prevention.
Why a Royal in JRSM
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2012)

Should the heir to the throne comment on medicine and health? Should those views appear in a medical journal? Prince Charles has angered some medical professionals with previous contributions to the healthcare debate. Perhaps he will do so again? But he is a prominent and influential voice. When he sets out his vision for health, something he clearly thinks deeply about, speaking directly to medical professionals is the best way of allowing a constructive debate to flourish. This is the first time Prince Charles has written for a medical journal. It is an important article and the Prince's vision for health is engaging.1

You might disagree, in which case let us know, but as the Prince argues for health professionals to rediscover ancient wisdom, Simon Wessely and colleagues review historic and recent accounts of people rejecting modernity. Ask yourself these questions: Do you have a problem living in modern society? Do you have a compulsion to flee? Do you have a sense of persecution? Is your head filled with ideas of fighting for an under-recognised cause, for example, protecting dolphins from nitrogen pollution in Florida?2 Answer yes to these questions and you might wish to take refuge from modernity and live your life as a 21st century hermit.3

Most people, especially the elderly, do not choose isolation. Our modern world, with reduced inter-generational living, greater social and geographical mobility, and a rise in single-person households, is an ideal environment for older adults to become socially isolated. Loneliness and isolation are increasingly part of the experience of growing old, say Nicole Valtorta and Barbara Hanratty, yet we remain uncertain about the extent of the public health challenge and the potential health gain from intervention.4

The way forward is a renewed research agenda, an approach that James Lind, whose story dominates this issue and rediscovered portrait adorns the cover, would surely have approved of. Lind's treatise on scurvy included a rudimentary systematic review, an account of his trial of interventions, including oranges and lemons, to treat scurvy among sailors on a sea voyage to blockade the English Channel in May 1747, and a somewhat muddled conclusion—thus pioneering the importance of fair tests to evaluate interventions and showing that even the sharpest brains struggle to communicate their research findings and make a difference.5,6 Forty-two years after publication of Lind's treatise, the British Admiralty ordered lemon juice to be issued to sailors. Lind's struggle is a sobering lesson for any commoner, knight, or prince seeking to influence the ancient wisdoms of the medical profession, and a lesson for hermits everywhere: realising any dream, obscure or popular, is within the grasp of any man, woman, or dolphin.
Myocardial interstitial purine metabolites and lactate with increased work in swine
Authors: J. L. Hall, D. G.L. Van Wylen, R. D. Pizzurro, C.D. Hamilton, C. M. Reiling, W. C. Stanley
Journal: Cardiovascular Research (1995)

Dobutamine stimulates the beta-receptors in the heart and increases myocardial blood flow and oxygen consumption 2-3-fold, similar to effects seen with exercise. The purpose of this study was to assess temporal changes in myocardial interstitial purine metabolites, adenosine monophosphate (AMP) and lactate during and following 30 min of dobutamine infusion.Dobutamine (15 micrograms/kg/min) was infused via the jugular vein into 9 anesthetized, open-chest, domestic swine. Interstitial fluid was sampled with microdialysis probes placed in the midmyocardium. The effluent from the probes, referred to as the dialysate, was used to estimate myocardial interstitial purine metabolites, AMP, and lactate levels before, during, and following a dobutamine-induced increased work state.Dobutamine infusion resulted in a 77% increase in heart rate, a 258% increase in left ventricular dP/dt, a 208% increase in myocardial oxygen consumption, and a 155% increase in rate x pressure product. Myocardial blood flow was increased in the subepicardium, midmyocardium, and subendocardium by 207, 268, and 268%, respectively, compared to the control period. Neither coronary venous nor dialysate lactate concentrations changed throughout the protocol. Dialysate adenosine and AMP levels were both significantly elevated (P < 0.05) during the dobutamine period and fell back to control values during the recovery period.The dobutamine-induced increases in myocardial oxygen consumption, rate x pressure product, and blood flow, without an increase in coronary venous or interstitial lactate suggest that energy balance is maintained during dobutamine infusion. Thus an increase in myocardial work, in the absence of demand-induced ischemia, resulted in accumulation of adenosine and AMP in the interstitium.
Clearance of Hbsag in Seven Patients With Chronic Hepatitis B
Authors: Hiroshi Adachi, Shuichi Kaneko, Eiki Matsushita, Yutaka Inagaki, Masashi Unoura, Kenichi Kobayashi
Journal: Hepatology (1992)

The natural history of chronic hepatitis B patients who spontaneously cleared serum HBsAg was investigated. A total of 351 patients with chronic hepatitis B were observed in our hospital for at least 3 yr. Seven of these patients became HBsAg negative during the follow–up period. HBsAg disappeared within 6 mo (range = 11 to 169 days, mean = 70 days) after acute elevation of ALT. ALT levels as high as 500 IU were found in three patients, whereas such elevation was not demonstrated in the other four patients. After the disappearance of HBsAg, ALT levels returned to normal in all patients. With one exception, all patients seroconverted to antibody to HBsAg; however, hepatitis B virus DNA remained detectable in serum using the polymerase chain reaction in five patients. The titer of percent inhibition of antibody to HBcAg gradually decreased to less than 70% when a 1:200 dilution of the serum of six patients was used. Four of the patients had active liver disease develop: two had chronic active hepatitis and two had cirrhosis. Three of these four patients subsequently had hepatocellular carcinoma develop. These findings suggest that patients may suffer complications of chronic hepatitis even after normalization of transaminase activities and after the clearance of HBsAg. Thus hepatitis B virus should be considered as a possible factor associated with hepatocellular carcinoma even in the absence of HBsAg, particularly if serum hepatitis B virus DNA persists.
Juvenile Mental Health Histories of Adults With Anxiety Disorders
Authors: Alice M. Gregory, Avshalom Caspi, Terrie E. Moffitt, Karestan Koenen, Thalia C. Eley, Richie Poulton
Journal: American Journal of Psychiatry (2007)

Objective: Information about the psychiatric histories of adults with anxiety disorders was examined to further inform nosology and etiological/ preventive efforts. Method: The authors used data from a prospective longitudinal study of a representative birth cohort (N=1,037) from ages 11 to 32 years, making psychiatric diagnoses according to DSM criteria. For adults with anxiety disorders at 32 years, follow-back analyses ascertained first diagnosis of anxiety and other juvenile disorders. Results: Of adults with each type of anxiety disorder, approximately half had been diagnosed with a psychiatric disorder (one-third with an anxiety disorder) by age 15. The juvenile histories of psychiatric problems for adults with different types of anxiety disorders were largely nonspecific, partially reflecting comorbidity at 32 years. Histories of anxiety and depression were most common. There was also specificity. For example, adults with panic disorder did not have histories of juvenile disorders, whereas those with other anxiety disorders did. Adults with posttraumatic stress disorder had histories of conduct disorder, whereas those with other anxiety disorders did not. Adults with specific phobia had histories of juvenile phobias but not other anxiety disorders. Conclusions: Strong comorbidity between different anxiety disorders and lack of specificity in developmental histories of adults with anxiety disorders supports a hierarchical approach to classification, with a broad class of anxiety disorders having individual disorders within it. The early first diagnosis of psychiatric difficulties in individuals with anxiety disorders suggests the need to target research examining the etiology of anxiety disorders and preventions early in life.
NK<sub>1</sub> Receptor Stimulation Causes Contraction and Inositol Phosphate Increase in Medium-size Human Isolated Bronchi
Authors: SILVIA AMADESI, JOELLE MOREAU, MICHELE TOGNETTO, JOCHEM SPRINGER, MARCELLO TREVISANI, EMMANUEL NALINE, CHARLES ADVENIER, AXEL FISHER, DAMIANO VINCI, CRISTINA MAPP, DEBORAH MIOTTO, GIORGIO CAVALLESCO, PIERANGELO GEPPETTI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size ( ∼ 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2–5 mm in diameter) human isolated bronchi. Specific staining was seen in bronchial sections with an antibody directed against the human NK1 receptor. The selective NK1 receptor agonist, [Sar9, Met(O2)11]SP, contracted about 60% of human isolated bronchial rings. This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar9, Met(O2)11]SP was independent of acetylcholine and histamine release and epithelium removal, and was not affected by nitric oxide synthase and cyclooxygenase (COX) inhibition. [Sar9, Met(O2)11]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size ( ∼ 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar9, Met(O2)11]SP in small-size, but not in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large proportion of medium-size human bronchi. Unlike small-size bronchi this effect is independent of prostanoid release, and the results are suggestive of a direct activation of smooth muscle receptors and IP release.
Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease
Authors: Christian Besler, Kathrin Heinrich, Lucia Rohrer, Carola Doerries, Meliana Riwanto, Diana M. Shih, Angeliki Chroni, Keiko Yonekawa, Sokrates Stein, Nicola Schaefer, Maja Mueller, Alexander Akhmedov, Georgios Daniil, Costantina Manes, Christian Templin, Christophe Wyss, Willibald Maier, Felix C. Tanner, Christian M. Matter, Roberto Corti, Clement Furlong, Aldons J. Lusis, Arnold von Eckardstein, Alan M. Fogelman, Thomas F. Lüscher, Ulf Landmesser
Journal: Journal of Clinical Investigation (2011)

Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1– and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair–stimulating effects of HDL.
Effects of growth factors and receptor blockade on gastrointestinal cancer
Authors: R J Playford
Journal: Gut (2004)

The advent of recombinant peptide technology offers the potential to use one or several peptides to treat a variety of gastrointestinal conditions. However, although cell culture and animal models have shown proof of concept, we are still at a relatively early stage in translating their use to standard clinical practice. Similarly, peptide and non-peptide antagonists of growth factor receptors show great potential as novel antichemotherapy agents. However, their actual place in clinical practice has yet to be established.
Screening Women Aged 40-49 Years: Where Are We Today?
Authors: R. A. Smith
Journal: JNCI Journal of the National Cancer Institute (1995)

The fact that mammographic screening can reduce deaths from breast cancer is well established and is unarguably true for women aged 50-69 years (12)- While the unique value of mammography in the early detection of breast cancer is also well established, it is less certain if early detection results in similar mortality reductions for women diagnosed with breast cancer between the ages of 40 and 49 years compared with women aged 50 years and older. This uncertainty is, at the outset, the result of an inadequate base of scientific data. Specifically, no trial to date, with the exception of the Canadian National Breast Screening Study (NBSS-1), was designed to have adequate statistical power to test the hypothesis of a benefit from mammography for women aged 40^9 years, and the results are not universally accepted due to concerns about study methodology. While the majority of these trials suggest a benefit for women aged 40-49 years, none of the observed mortality differences in individual studies has achieved conventional criteria for statistical significance (3). Periodic updates of trial data have been published, but small sample sizes in individual studies remain a limiting factor. However, there are other limiting factors that potentially influence trial results, and these factors may have been especially influential on outcomes for women aged 40-49 years. These factors include mammographic technique, one versus two views, and the interval between screenings. To address the limitations of small sample sizes and these quality-assurance
Regulatory T Cells Move in When Gliomas Say “I DO”
Authors: Bryan D. Choi, Peter E. Fecci, John H. Sampson
Journal: Clinical Cancer Research (2012)

Abstract Indoleamine 2,3-dioxygenase (IDO) is an enzyme with known immunosuppressive and tolerogenic effects in cancer. Mounting evidence has associated IDO expression with the induction of regulatory T cells (Treg) and malignant progression. IDO inhibition may therefore provide a promising therapeutic approach for glioblastoma, where the need for novel treatment is great. Clin Cancer Res; 18(22); 6086–8. ©2012 AACR.