tbuckley/cabot-search huggingface dataset:
Vasopressin in Pediatric Vasodilatory Shock
Authors: Karen Choong, Desmond Bohn, Douglas D Fraser, Isabelle Gaboury, James S Hutchison, Ari R Joffe, Catherine Litalien, Kusum Menon, Patrick McNamara, Roxanne E Ward
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Vasopressin has been proposed as a potent vasoactive agent in the treatment of vasodilatory shock in adults and children. The objective of this trial was to evaluate the efficacy and safety of vasopressin as an adjunctive agent in pediatric vasodilatory shock.Methods: In this multicenter, double-blind trial, children with vasodilatory shock were randomized to receive low-dose vasopressin (0.0005–0.002 U/kg/min) or placebo in addition to open-label vasoactive agents. Vasoactive infusions were titrated to clinical endpoints of adequate perfusion. The primary outcome was time to vasoactive-free hemodynamic stability. Secondary outcomes included mortality, organ-failure–free days, length of critical care unit stay, and adverse events.Measurements and Main Results: Sixty-five of 69 children (94%) who were randomized received the study drug (33 vasopressin, 32 placebo) and were included in the analysis. There was no significant difference in the primary outcome between the vasopressin and placebo groups (49.7 vs. 47.1 hours; P = 0.85). There were 10 deaths (30%) in the vasopressin group and five (15.6%) in the placebo group (relative risk, 1.94; 95% confidence interval, 0.75–5.05; P = 0.24). There were no significant differences with respect to organ failure–free days (22 vs. 25.5 days; P = 0.11), ventilator-free days (16.5 23 days; P = 0.15), length of stay (8 vs. 8.5 days; P = 0.93), or adverse event rate ratios (12.0%; 95% confidence interval, −2.6 to 26.7; P = 0.15).Conclusions: Low-dose vasopressin did not demonstrate any beneficial effects in this pediatric trial. Although not statistically significant, there was a concerning trend toward increased mortality.Clinical trial registered with www.controlled-trials.com (ISRCTN11597444).
Noninvasive Evaluation of the Carotid Bruit
Authors: R W Barnes
Journal: Annual Review of Medicine (1980)

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
Increased Pulse Pressure Independently Predicts Incident Atrial Fibrillation in Patients With Type 2 Diabetes
Authors: Filippo Valbusa, Stefano Bonapace, Lorenzo Bertolini, Luciano Zenari, Guido Arcaro, Giovanni Targher
Journal: Diabetes Care (2012)

To examine whether baseline pulse pressure (PP), a marker of arterial stiffness, is associated with subsequent development of atrial fibrillation (AF) in type 2 diabetes.A total of 350 type 2 diabetic patients, who were free from AF at baseline, were followed for 10 years. A standard electrocardiogram was performed annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist.During the follow-up, 32 patients (9.1% of total) developed incident AF. After adjustments for age, sex, BMI, diabetes duration, presence of left ventricular hypertrophy, hypertension treatment, kidney dysfunction, and pre-existing history of coronary heart disease, heart failure, and mild valvular disease, baseline PP was associated with an increased incidence of AF (adjusted odds ratio 1.76 for each SD increment [95% CI 1.1-2.8]; P < 0.01).Our findings suggest that increased PP independently predicts incident AF in patients with type 2 diabetes.
Effect of 9-(1,3-Dihydroxy-2-Propoxymethyl) Guanine on Serious Cytomegalovirus Disease in Eight Immunosuppressed Homosexual Men
Authors: HENRY MASUR
Journal: Annals of Internal Medicine (1986)

Eight immunosuppressed homosexual men with cytomegalovirus viremia--seven with serious bilateral retinitis, one with colitis in addition to retinitis, and one with pneumonitis only--were treated with a new acyclovir derivative, 9-(1,3-dihydroxy-2-propoxymethyl) guanine, which has excellent in-vitro activity against cytomegalovirus. All patients had virologic and clinical improvement, but substantial leukopenia developed in three patients. Both clinical relapses and viral relapses occurred frequently, usually within 30 days after cessation of treatment. 9-(1,3-Dihydroxy-2-propoxymethyl) guanine represents the first clinically and virologically effective agent for the treatment of cytomegalovirus disease, but more effective and less toxic therapeutic regimens for both acute and chronic use must be developed.
Red tattoo reactions: X-ray microanalysis and patch-test studies
Authors: J. M. SOWDEN, J. P. H. BYRNE, A.G. SMITH, C. HILEY, V. SUAREZ, B. WAGNER, D. N. SLATER
Journal: British Journal of Dermatology (1991)

Eighteen patients who developed cutaneous reactions to red tattoos were studied to identify the chemicals responsible for the reactions to modern red tattoo pigments. Biopsies from the tattoos were examined histologically and the chemical composition of the red pigments was analysed by X-ray microanalysis. A variety of metallic elements including aluminium, iron, calcium, titanium, silicon, mercury and cadmium were detected. Patch tests were performed to the relevant chemicals in nine cases, and only one patient reacted to mercury. This study demonstrates that although reactions to mercury still occur, other red dyes containing a variety of inorganic pigments may provoke a cutaneous inflammatory response.
Role of interleukin 8 on leucocyte-endothelial cell adhesion in intestinal inflammation.
Authors: H Arndt, M A Bolanowski, D N Granger
Journal: Gut (1996)

An important action of interleukin 8 (IL8) is stimulation of granulocytes. The object of this study was to assess the contribution of IL8 to the leucocyte-endothelial cell interactions associated with intestinal inflammation in the rat.Two indomethacin injections (48 and 24 hours prior to the experiments) induced a longlasting ileitis in rats. The number of adherent and emigrated leucocytes, leucocyte rolling velocity, and shear rate were monitored in normal and inflamed mesenteric postcapillary venules. Some animals received a monoclonal antibody (MAb) against IL8 or CD11b/CD18 at 24 and 12 hours prior to the experiment.Indomethacin elicited a seven-fold increase in leucocyte adherence and a 5.4-fold increase in leucocyte emigration, while leucocyte rolling velocity was reduced by nearly 80%. The indomethacin induced increases in leucocyte adherence and emigration were significantly reduced (by 57% and 67%, respectively) while leucocyte rolling velocity was increased (to 63% of control) by the IL8-specific MAb. The level of inhibition seen with the IL8 MAb was similar to that associated with administration of a MAb directed against the leucocyte adhesion molecule CD11b/CD18.IL8 contributes to the leucocyte-endothelial cell interactions elicited in mesenteric venules by indomethacin.
Targeting Fibroblast Growth Factor Receptors Blocks PI3K/AKT Signaling, Induces Apoptosis, and Impairs Mammary Tumor Outgrowth and Metastasis
Authors: Julien H. Dey, Fabrizio Bianchi, Johannes Voshol, Debora Bonenfant, Edward J. Oakeley, Nancy E. Hynes
Journal: Cancer Research (2010)

Abstract Members of the fibroblast growth factor receptor (FGFR) family have essential roles in normal physiology and in cancer where they control diverse processes. FGFRs have been associated with breast cancer development. Thus, models to study the role of FGFR in breast cancer and their targeting potential are important. We present an in vitro and in vivo analysis of FGFRs in the breast cancer model cell lines 67NR and 4T1. We show that both tumor cell lines coexpress FGFRs and ligands and display autocrine FGFR signaling activity. Fibroblast growth factor receptor substrate 2 (FRS2), a downstream mediator of FGFR, is constitutively tyrosine phosphorylated and multiple signaling pathways are active. Treatment of 67NR and 4T1 cultures with TKI258, an FGFR tyrosine kinase inhibitor (TKI), caused a rapid decrease in FRS2 phosphorylation; decreased the activity of extracellular signal–regulated kinase 1/2 (ERK1/2), AKT, and phospholipase Cγ; and blocked proliferation of both tumor lines. Furthermore, TKI258 induced 4T1 apoptotic cell death via blockade of the phosphoinositide 3-kinase/AKT pathway. In vivo, one dose of TKI258 rapidly lowered FRS2 phosphorylation and ERK1/2 and AKT activity in mammary tumors. Long-term TKI258 treatment of 4T1 tumor– and 67NR tumor–bearing mice had a significant effect on primary tumor outgrowth and 4T1 tumor–induced lung metastases. A microarray analysis was carried out to identify targets with roles in TKI258 antitumor activity and potential prognostic markers in human breast tumors. Of interest are the downregulated matrix metalloproteases (MMP), in particular MMP9, which is essential for metastatic spread of 4T1 tumors. Cancer Res; 70(10); 4151–62. ©2010 AACR.
Screening for activating EGFR mutations in surgically resected nonsmall cell lung cancer
Authors: K.B. Sriram, M.E. Tan, S.M. Savarimuthu, C.M. Wright, V. Relan, R.E. Stockwell, B.E. Clarke, E.E. Duhig, I.A. Yang, R.V. Bowman, K.M. Fong
Journal: European Respiratory Journal (2011)

The clinical applicability of screening surgically resected nonsmall cell lung cancer (NSCLC) tumour tissue and serum for activating epidermal growth factor receptor ( EGFR ) mutation is unknown. Furthermore, the comparative accuracy of inexpensive EGFR mutation tests, mutant-enriched (ME)-PCR and high-resolution melt (HRM) has not been determined. Lung tumour DNA from 522 surgically resected stage I–IV NSCLC and matched serum DNA from a subset of 64 subjects was analysed for EGFR mutations in exons 19 and 21 using ME-PCR and HRM. Additionally, 97 subjects had previous EGFR DNA sequencing data available for comparison. ME-PCR and HRM detected EGFR mutations in 5% (27 out of 522) of tumour samples. Compared to DNA sequencing, ME-PCR had a sensitivity of 100% and specificity of 99%, while HRM had 100% sensitivity and specificity. Six subjects with EGFR mutation tumours had matched serum, where ME-PCR detected mutations in three samples and HRM in two samples. In the cohort of never-smoker subjects, those with EGFR mutated tumours had worse survival compared with wild-type tumours (30 versus 49 months; p=0.017). ME-PCR and HRM have similar accuracy in detecting EGFR mutations but the prognostic implications of the mutations in resected NSCLC warrants further study.
Strong functional patterns in the evolution of eukaryotic genomes revealed by the reconstruction of ancestral protein domain repertoires
Authors: Christian M Zmasek, Adam Godzik
Journal: Genome biology (2011)

Abstract Background Genome size and complexity, as measured by the number of genes or protein domains, is remarkably similar in most extant eukaryotes and generally exhibits no correlation with their morphological complexity. Underlying trends in the evolution of the functional content and capabilities of different eukaryotic genomes might be hidden by simultaneous gains and losses of genes. Results We reconstructed the domain repertoires of putative ancestral species at major divergence points, including the last eukaryotic common ancestor (LECA). We show that, surprisingly, during eukaryotic evolution domain losses in general outnumber domain gains. Only at the base of the animal and the vertebrate sub-trees do domain gains outnumber domain losses. The observed gain/loss balance has a distinct functional bias, most strikingly seen during animal evolution, where most of the gains represent domains involved in regulation and most of the losses represent domains with metabolic functions. This trend is so consistent that clustering of genomes according to their functional profiles results in an organization similar to the tree of life. Furthermore, our results indicate that metabolic functions lost during animal evolution are likely being replaced by the metabolic capabilities of symbiotic organisms such as gut microbes. Conclusions While protein domain gains and losses are common throughout eukaryote evolution, losses oftentimes outweigh gains and lead to significant differences in functional profiles. Results presented here provide additional arguments for a complex last eukaryotic common ancestor, but also show a general trend of losses in metabolic capabilities and gain in regulatory complexity during the rise of animals.
Factors influencing the restoration of fluid and electrolyte balance after exercise in the heat.
Authors: R J Maughan, J B Leiper, S M Shirreffs
Journal: British Journal of Sports Medicine (1997)

Maintenance of fluid balance is a major concern for all athletes competing in events held in hot climates. This paper reviews recent work relating to optimisation of fluid replacement after sweat loss induced by exercising in the heat. Data are taken from studies undertaken in our laboratory. Issues investigated were drink composition, volume consumed, effects of consuming food with a drink, effects of alcohol in rehydration effectiveness, voluntary intake of fluid, and considerations for women related to the menstrual cycle. The results are presented as a series of summaries of experiments, followed by a discussion of the implications. The focus of this review is urine output after ingestion of a drink; fluid excreted in urine counteracts rehydration. Also included are data on the restoration of plasma volume losses. Ingestion of large volumes of plain water will inhibit thirst and will also promote a diuretic response. If effective rehydration is to be maintained for some hours after fluid ingestion, drinks should contain moderately high levels of sodium (perhaps as much as 50-60 mmol/l) and possibly also some potassium to replace losses in the sweat. To surmount ongoing obligatory urine losses, the volume consumed should be greater than the volume of sweat lost. Palatability of drinks is important in stimulating intake and ensuring adequate volume replacement. Where opportunities allow, the electrolytes required may be ingested as solid food consumed with a drink. There are no special concerns for women related to changes in hormone levels associated with the menstrual cycle. Ingestion of carbohydrate-electrolyte drinks in the post-exercise period restores exercise capacity more effectively than plain water. The effects on performance of an uncorrected fluid deficit should persuade all athletes to attempt to remain fully hydrated at all times, and the aim should be to start each bout of exercise in a fluid replete state. This will only be achieved if a volume of fluid in excess of the sweat loss is ingested together with sufficient electrolytes.
Induced CD4<sup>+</sup>Foxp3<sup>+</sup>Regulatory T Cells in Immune Tolerance
Authors: Angelina M. Bilate, Juan J. Lafaille
Journal: Annual Review of Immunology (2012)

Regulatory T lymphocytes are essential to maintain homeostasis of the immune system, limiting the magnitude of effector responses and allowing the establishment of immunological tolerance. Two main types of regulatory T cells have been identified—natural and induced (or adaptive)—and both play significant roles in tuning down effector immune responses. Adaptive CD4 + Foxp3 + regulatory T (iTreg) cells develop outside the thymus under a variety of conditions. These include not only antigen presentation under subimmunogenic or noninflammatory conditions, but also chronic inflammation and infections. We speculate that the different origin of iTreg cells (noninflammatory versus inflammatory) results in distinct properties, including their stability. iTreg cells are also generated during homeostasis of the gut and in cancer, although some cancers also favor expansion of natural regulatory T (nTreg) cells. Here we review how iTreg cells develop and how they participate in immunological tolerance, contrasting, when possible, iTreg cells with nTreg cells.
Inhibition of arterial lesion progression in CD16-deficient mice: evidence for altered immunity and the role of IL-10
Authors: John A. Kelly, Mary E. Griffin, Roy A. Fava, Sheryl G. Wood, Katherine A. Bessette, Elizabeth R. Miller, Sally A. Huber, Christoph J. Binder, Joseph L. Witztum, Peter M. Morganelli
Journal: Cardiovascular Research (2009)

Given the importance of IgG Fc receptors in immune regulation, we hypothesized that Fcg receptor type III (FcgRIII, CD16) plays an important role in atherogenesis. We therefore analysed the formation of arterial lesions in LDL receptor-deficient (LDLR−/−) and FcgRIII−/−×LDLR−/− double knockout mice at three different points up to 24 weeks of exposure to a high-fat diet. Analysis of Oil Red-O-stained sections revealed no difference in lesion formation between strains after 6 weeks of a high-fat diet, and a modest decrease after 14 weeks in double knockouts relative to LDLR−/− controls. After 24 weeks, lesion formation was decreased in the aortic root (30%) and innominate artery (50%) in FcgRIII double knockouts relative to LDLR−/− controls. Analysis of peripheral CD4+ T-cells by intracellular flow cytometry from double knockouts after 24 weeks of a high-fat diet revealed statistically significant increases in the percentages of cells producing interferon-γ, interleukin (IL)-10, and IL-4 relative to controls, differences that were also observed by analyses of whole aortas for cytokine mRNA levels. As determined by flow cytometry, FcgRIII deficiency resulted in an expansion of CD4+ cells and an increase in the CD4 to CD8 ratio. Analysis of plasma anti-oxidized LDL (OxLDL) antibodies by chemiluminescent assay revealed that IgG1 and IgG2c titers to OxLDL were increased in FcgRIII −/−×LDLR−/− double knockouts relative to LDLR−/− controls, while total IgG levels were similar. These results reveal altered immunity in FcgRIII−/−×LDLR−/− mice and a reduction in lesion formation associated with increased production of IL-10 by an expansion of CD4+ T-cells. The reduction in lesion formation was manifest well after evidence of an immune response to OxLDL, suggesting that FcgRIII contributes to lesion progression in murine atherosclerosis.
ABSORPTION OF ARSENIC FOLLOWING INTRA-MUSCULAR INJECTIONS OF SALVARSAN AND NEOSALVARSAN
Authors: Homer F. Swift
Journal: The Journal of Experimental Medicine (1913)

Intramuscular injection of salvarsan and neosalvarsan in rabbits always produces necrosis of the muscles. A much more intense reaction is produced by salvarsan than by neosalvarsan. The rate of absorption of arsenic following intramuscular injections of salvarsan is very slow, while following intramuscular injections of neosalvarsan between 75 and 85 per cent of the arsenic is absorbed during the first week. The subsequent absorption is quite slow.
Embracing social media: Table 1
Authors: Nicholas S Hopkinson, Nicholas Hart, Gisli Jenkins, Alan Smyth
Journal: Thorax (2015)

Progress in medicine and science depends on the dissemination of accurate information about health, disease and therapy. Social media are key tools to facilitate this, bringing research findings to people's attention more rapidly than ever before and also to a wider and more diverse population than previously. For information to be useful, it must be presented and interpreted in context. This is the difference between information and knowledge. We are keen to help our authors participate in this beyond the simple publication of papers to improve the quality of online debate, engaging researchers and clinicians as well as patients1 and others with a stake in healthcare. From now on, we …
Amniotic fluid interleukin 6 in preterm labor. Association with infection.
Authors: R Romero, C Avila, U Santhanam, P B Sehgal
Journal: Journal of Clinical Investigation (1990)

To evaluate whether IL-6 participates in the host response to intrauterine infection, we studied IL-6 bioactivity and isoforms in amniotic fluid (AF). Two different assays for IL-6 were used: the hepatocyte stimulating factor assay (in Hep3B2 cells) and the SDS-PAGE/immunoblot assay. IL-6 determinations were performed in 205 AF samples. Samples were obtained from patients in the midtrimester of pregnancy (n = 25), at term with no labor (n = 31), at term in active labor (n = 40), and from patients in preterm labor (n = 109). Higher AF IL-6 levels were observed in women in preterm labor with intraamniotic infection than in women in preterm labor without intraamniotic infection (median = 375 ng/ml, range = 30-5000 ng/ml vs. median = 1.5 ng/ml, range = 0-500, respectively, P less than 0.0001). The 23-25- and 28-30-kD IL-6 species could be readily detected in SDS-PAGE immunoblots performed directly on 10-microliters aliquots of AF from patients with intraamniotic infection. Among women in preterm labor with culture-negative AF, those who failed to respond to subsequent tocolytic treatment had higher AF IL-6 concentrations than those who responded to therapy (median = 50 ng/ml vs. median = 1.2 ng/ml, respectively, P less than 0.05). Only low levels of IL-6 were detected in AF obtained from normal women in the midtrimester and third trimester of pregnancy. Decidual tissue explants obtained from the placentas of women undergoing elective cesarean section at term without labor (n = 11) produced IL-6 in response to bacterial endotoxin. In a pilot study, AF IL-6 was determined in 56 consecutive women admitted with preterm labor. All patients (n = 10) with elevated AF IL-6 (cutoff = 46 ng/ml) delivered a premature neonate. 4 of these 10 patients had positive AF cultures for microorganisms. These studies implicate IL-6 in the host response to intrauterine infection and suggest that evaluation of AF IL-6 levels may have diagnostic and prognostic value in the management of women in preterm labor.
Use of Antidiabetic Drugs in the U.S., 2003–2012
Authors: Christian Hampp, Vicky Borders-Hemphill, David G. Moeny, Diane K. Wysowski
Journal: Diabetes Care (2014)

To describe market trends for antidiabetic drugs, focusing on newly approved drugs, concomitant use of antidiabetic drugs, and effects of safety concerns and access restrictions on thiazolidinedione use.Nationally projected data on antidiabetic prescriptions for adults dispensed from U.S. retail pharmacies were extracted from IMS Health Vector One National and Total Patient Tracker for 2003-2012 and from Encuity Research Treatment Answers and Symphony Health Solutions PHAST Prescription Monthly for 2012.Since 2003, the number of adult antidiabetic drug users increased by 42.9% to 18.8 million in 2012. Metformin use increased by 97.0% to 60.4 million prescriptions dispensed in retail pharmacies in 2012. Among antidiabetic drugs newly approved for marketing between 2003 and 2012, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin had the largest share with 10.5 million prescriptions in 2012. Rosiglitazone use plummeted to <13,000 prescriptions dispensed in retail or mail-order pharmacies in 2012. Concomitancy analyses showed that 44.9% of metformin use was for monotherapy. Between 33.4 and 48.1% of sulfonylurea, DPP-4 inhibitor, thiazolidinedione, and glucagon-like peptide 1 analog use was not accompanied by metformin.The antidiabetic drug market is characterized by steady increases in volume, and newly approved drugs experienced substantial uptake, especially DPP-4 inhibitors. The use of rosiglitazone has been negligible since restrictions were put in place in 2011. Further study is needed to understand why one-third to one-half of other noninsulin antidiabetic drug use was not concomitant with metformin use despite guidelines recommending that metformin be continued when other agents are added to treatment.