tbuckley/cabot-search huggingface dataset:
Acetaminophen and Asthma
Authors: V. W. Persky
Journal: Thorax (2010)

The article by Perzanowski et al in this issue of Thorax ( see page 118 ) adds one more piece of evidence supporting a possible role for acetaminophen in the development of asthma in children.1 Five previous studies, including three prenatal prospective cohorts,2–5 have suggested that in utero ingestion of acetaminophen may increase the risk of asthma and respiratory symptoms in children.2–7 Increased risk of asthma from postnatal use of acetaminophen is also suggested by reports of children8–12 and adults.8 13–17 The possibility that acetaminophen may contribute to the development of asthma is supported by parallel time trends in dramatic increases in use of the medication in response to reports of associations of aspirin use with Reye syndrome18–20 and increases in asthma prevalence between the mid 1970s and mid 1990s.21

There is also biological plausibility. Acetaminophen,22–24 as well as one of its metabolites, the highly reactive N -acetyl- p -benzoquinoneimine,23 has been associated with decreased glutathione. There is substantial literature documenting the antioxidant capacity of glutathione25 as well as the role of reactive oxygen species in asthma morbidity.26 In addition, decreased glutathione may affect the development of asthma by altering antigen recognition towards favouring T helper 2 (Th2) over Th1 cytokines.23 27 Other, less likely, possibilities relate to decreased suppression of cyclo-oxygenase or direct antigenicity of acetaminophen.23

The study by Perzanowski et al notes that associations of prenatal acetaminophen use …
Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas
Authors: Hirofumi Hirano, M. Beatriz S. Lopes, Edward R. Laws, Tetsuhiko Asakura, Masamichi Goto, Joan E. Carpenter, Larry R. Karns, Scott R. VandenBerg
Journal: Neuro-Oncology (1999)

Studies of experimental tumorigenesis have strongly implicated signaling of the insulin-like growth factor 1 (IGF-1) as a key component in astrocytic neoplasia; however, its role in the growth of low-grade and malignant human tumors is not well understood. Correlative analyses of IGF-1, p53, and Ki-67 (MIB-1) immunohistochemistry and IGF-1 receptor (IGF-1R) mRNA expression were performed to examine the cellular pattern of IGF-1 signaling in 39 cases of astrocytoma (World Health Organization grades II-IV). Tumor cells expressing IGF-1 and IGF-1R were present in all tumor grades. The proportion of tumor cells that expressed IGF-1 correlated with both histopathologic grade and Ki-67 labeling indices, while expression of IGF-1R mRNA correlated with Ki-67 indices. In cases where stereotactic tissue sampling could be identified with a specific tumor area by neuroimaging features, the numbers of IGF-1 immunoreactive cells correlated with the tumor zones of highest cellularity and Ki-67 labeling. In glioblastomas, the localization of IGF-1 immunoreactivity was notable for several features: frequent accentuation in the perivascular tumor cells surrounding microvascular hyperplasia; increased levels in reactive astrocytes at the margins of tumor infiltration; and selective expression in microvascular cells exhibiting endothelial/pericytic hyperplasia. IGF-1R expression was particularly prominent in tumor cells adjacent to both microvascular hyperplasia and palisading necrosis. These data suggest that IGF-1 signaling occurs early in astroglial tumorigenesis in the setting of cell proliferation. The distinctive correlative patterns of IGF-1 and IGF-1R expression in glioblastomas also suggest that IGF-1 signaling has an association with the development of malignant phenotypes related to aberrant angiogenesis and invasive tumor interactions with reactive brain.
Resistant Hypertension
Authors: Wanpen Vongpatanasin
Journal: JAMA (2014)

Resistant hypertension-uncontrolled hypertension with 3 or more antihypertensive agents-is increasingly common in clinical practice. Clinicians should exclude pseudoresistant hypertension, which results from nonadherence to medications or from elevated blood pressure related to the white coat syndrome. In patients with truly resistant hypertension, thiazide diuretics, particularly chlorthalidone, should be considered as one of the initial agents. The other 2 agents should include calcium channel blockers and angiotensin-converting enzyme inhibitors for cardiovascular protection. An increasing body of evidence has suggested benefits of mineralocorticoid receptor antagonists, such as eplerenone and spironolactone, in improving blood pressure control in patients with resistant hypertension, regardless of circulating aldosterone levels. Thus, this class of drugs should be considered for patients whose blood pressure remains elevated after treatment with a 3-drug regimen to maximal or near maximal doses. Resistant hypertension may be associated with secondary causes of hypertension including obstructive sleep apnea or primary aldosteronism. Treating these disorders can significantly improve blood pressure beyond medical therapy alone. The role of device therapy for treating the typical patient with resistant hypertension remains unclear.
Surgical morbidity of cervical lymphadenectomy for thyroid cancer: A retrospective cohort study over 25 years
Authors: Andrea Polistena, Massimo Monacelli, Roberta Lucchini, Roberta Triola, Claudia Conti, Stefano Avenia, Ivan Barillaro, Alessandro Sanguinetti, Nicola Avenia
Journal: International Journal of Surgery (2015)
Specific bronchial reactivity to toluene diisocyanate: relationship with baseline clinical findings.
Authors: P L Paggiaro, A Innocenti, E Bacci, O Rossi, D Talini
Journal: Thorax (1986)

One hundred and fourteen subjects with asthma induced by toluene diisocyanate were identified and the pattern of their bronchial responses to challenge with toluene diisocyanate was studied. An occupational type specific bronchial provocation test with toluene diisocyanate (10-25 parts per thousand million for 10-15 minutes) elicited an immediate response in 24, a late response in 50, and a dual response in 40 patients. Subjects with a dual response showed at diagnosis a longer duration of symptoms and a greater prevalence of airway obstruction; in these subjects FEV1 (percentage of predicted value) was lower than in subjects with immediate or late reactions to toluene diisocyanate. The percentage of current smokers and ex-smokers was significantly lower in subjects with a late response (26%) than in subjects with immediate or dual responses (56% and 57% respectively). In 27 of the 114 subjects a non-specific challenge test with methacholine was performed and subjects with dual responses showed greater non-specific bronchial hyperresponsiveness than the other groups. These results suggest that a dual response to specific challenge in bronchial asthma related to toluene diisocyanate may be associated with more severe disease than other types of response, as assessed by duration of symptoms, baseline airway obstruction, and non-specific bronchial hyperresponsiveness. The high prevalence of non-smokers and low prevalence of smokers in the group with a late response to specific challenge is so far unexplained.
THE TREATMENT OF "TENNIS ELBOW."
Authors: G. P. Mills
Journal: BMJ (1928)

EDICAJOURA second attack of mental depression associated with lactation.The husband had been warned against further pregnancies.Present Illness.-Nowpregnant about six weeks.Became de- pressed again, spoke of " frightful forgetfulness " and of having a blank spot in her memory.In view of the two previous attacks of melancholia, the compli- cation at former confinement, and the apparent beginning of another attack of depression, it was decided that the pregnancy should be terminated.CASE 10.Mrs. P., aged 36; seen November 17th, 1924.Family Htstory.-Twosisters had-been under care for mental illness but recovered.Previous History.-Has had two children.Had been much concerned about.husband's money difficulties.Had been depressed since June.Recently had tried to poison herself by gas mn a bedroom, but promised not to make further attempts.Had been, however, allowed to sleep in a room alone in a friend's house, and one morning had precipitated hermelf from the bedroom window, sustaining fracture dislocation of the right ankle, dislocation of the left elbow, a scalp wound, and concussion.She was treated in a nursing home for the surgical troubles, concurrently with which she passed through a severe attack of mental disorder, part of the time being confused and delirious with rise of teniperature, and part of the time deeply melancholic with thoughts of suicide.Late in December, when she had sufficiently recovered surgically,
Tracing the Evolutionary History of Inositol, 1, 4, 5-Trisphosphate Receptor: Insights from Analyses of<i>Capsaspora owczarzaki</i>Ca<sup>2+</sup>Release Channel Orthologs
Authors: Kamil J. Alzayady, Arnau Sebé-Pedrós, Rahul Chandrasekhar, Liwei Wang, Iñaki Ruiz-Trillo, David I. Yule
Journal: Molecular Biology and Evolution (2015)

Cellular Ca2+ homeostasis is tightly regulated and is pivotal to life. Inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) are the major ion channels that regulate Ca2+ release from intracellular stores. Although these channels have been extensively investigated in multicellular organisms, an appreciation of their evolution and the biology of orthologs in unicellular organisms is largely lacking. Extensive phylogenetic analyses reveal that the IP3R gene superfamily is ancient and diverged into two subfamilies, IP3R-A and IP3R-B/RyR, at the dawn of Opisthokonta. IP3R-B/RyR further diversified into IP3R-B and RyR at the stem of Filozoa. Subsequent evolution and speciation of Holozoa is associated with duplication of IP3R-A and RyR genes, and loss of IP3R-B in the vertebrate lineages. To gain insight into the properties of IP3R important for the challenges of multicellularity, the IP3R-A and IP3R-B family orthologs were cloned from Capsaspora owczarzaki, a close unicellular relative to Metazoa (designated as CO.IP3R-A and CO.IP3R-B). Both proteins were targeted to the endoplasmic reticulum. However, CO.IP3R-A, but strikingly not CO.IP3R-B, bound IP3, exhibited robust Ca2+ release activity and associated with mammalian IP3Rs. These data indicate strongly that CO.IP3R-A as an exemplar of ancestral IP3R-A orthologs forms bona fide IP3-gated channels. Notably, however, CO.IP3R-A appears not to be regulated by Ca2+, ATP or Protein kinase A-phosphorylation. Collectively, our findings explore the origin, conservation, and diversification of IP3R gene families and provide insight into the functionality of ancestral IP3Rs and the added specialization of these proteins in Metazoa.
In-utero transplantation of parental CD34 haematopoietic progenitor cells in a patient with X-linked severe combined immunodeficiency (SCIDX1)
Authors: Georg S Wengler, Arnalda Lanfranchi, Tiziana Frusca, Rosanna Verardi, Arabella Neva, Duilio Brugnoni, Silvia Giliani, Maurilia Fiorini, Patrizia Mella, Fabiola Guandalini, Evelina Mazzolari, LD Notarangelo, Sergio Pecorelli, Fulvio Porta, AG Ugazio
Journal: The Lancet (1996)
HBe antibody unrelated to ‘e minus’ hepatitis B virus variant infection in patients with chronic type D hepatitis
Authors: Giovanni Raimondo, Giuseppina Rodino', Santa Brancatelli, Maria Adriana Sardo, Salvatore Campo, Vincenzo Smedile, Daniela Villari, Maurizio Pernice, Giuseppe Longo, Giuseppe Squadrito
Journal: Journal of Hepatology (1991)
Phase III Study of Capecitabine Plus Oxaliplatin Compared With Continuous-Infusion Fluorouracil Plus Oxaliplatin As First-Line Therapy in Metastatic Colorectal Cancer: Final Report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial
Authors: Eduardo Díaz-Rubio, Jose Tabernero, Auxiliadora Gómez-España, Bartomeu Massutí, Javier Sastre, Manuel Chaves, Alberto Abad, Alfredo Carrato, Bernardo Queralt, Juan José Reina, Joan Maurel, Encarnación González-Flores, Jorge Aparicio, Fernando Rivera, Ferrán Losa, Enrique Aranda
Journal: Journal of Clinical Oncology (2007)

The aim of this phase III trial was to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion high-dose fluorouracil (FU) plus oxaliplatin (FUOX) regimens as first-line therapy for metastatic colorectal cancer (MCRC).A total of 348 patients were randomly assigned to receive XELOX (oral capecitabine 1,000 mg/m2 bid for 14 days plus oxaliplatin 130 mg/m2 on day 1 every 3 weeks) or FUOX (continuous-infusion FU 2,250 mg/m2 during 48 hours on days 1, 8, 15, 22, 29, and 36 plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 every 6 weeks).There were no significant differences in efficacy between XELOX and FUOX arms, which showed, respectively, median time to tumor progression (TTP; 8.9 v 9.5 months; P = .153); median overall survival (18.1 v 20.8 months; P = .145); and confirmed response rate (RR; 37% v 46%; P = .539). The safety profile of the two regimens was similar, although there were lower rates of grade 3/4 diarrhea (14% v 24%) and grade 1/2 stomatitis (28% v 43%), and higher rates of grade 1/2 hyperbilirubinemia (37% v 21%) and grade 1/2 hand-foot syndrome (14% v 5%) with XELOX versus FUOX, respectively.This randomized study shows a similar TTP of XELOX compared with FUOX in the first-line treatment of MCRC, although there was a trend for slightly lower RR and survival. XELOX can be considered as an alternative to FUOX.
Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease
Authors: J. M H Van den Brande, T. C Koehler, Z. Zelinkova, R. J Bennink, A. A te Velde, F. J W ten Cate, S. J H van Deventer, M. P Peppelenbosch, D. W Hommes
Journal: Gut (2006)

<b>Background:</b> The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro. <b>Aim:</b> To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease. <b>Methods:</b><sup>99m</sup>Technetium–annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohńs Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of &gt;100 points). <b>Results:</b> Colonic uptake of <sup>99m</sup>Tc-annexin V significantly increased in 2,4,6-trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of <sup>99m</sup>Tc–annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic <sup>99m</sup>Tc–annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41(0.07) (p&lt;0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of <sup>99m</sup>Tc–annexin V could be detected in 10 of the 14 responding patients (CDAI &gt;100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis. <b>Conclusions:</b> These in vivo observations support the notion that colonic uptake of <sup>99m</sup>Tc–annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.
Effects of Recombinant Human DNase and Hypertonic Saline on Airway Inflammation in Children with Cystic Fibrosis
Authors: Ranjan Suri, Lindsay J. Marshall, Colin Wallis, Christopher Metcalfe, Andrew Bush, Janis K. Shute
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.
Oncogene withdrawal engages the immune system to induce sustained cancer regression
Authors: Stephanie C Casey, Yulin Li, Alice C Fan, Dean W Felsher
Journal: Journal for ImmunoTherapy of Cancer (2014)

The targeted inactivation of a single oncogene can induce dramatic tumor regression, suggesting that cancers are "oncogene addicted." Tumor regression following oncogene inactivation has been thought to be a consequence of restoration of normal physiological programs that induce proliferative arrest, apoptosis, differentiation, and cellular senescence. However, recent observations illustrate that oncogene addiction is highly dependent upon the host immune cells. In particular, CD4<sup>+</sup> helper T cells were shown to be essential to the mechanism by which MYC or BCR-ABL inactivation elicits "oncogene withdrawal." Hence, immune mediators contribute in multiple ways to the pathogenesis, prevention, and treatment of cancer, including mechanisms of tumor initiation, progression, and surveillance, but also oncogene inactivation-mediated tumor regression. Data from both the bench and the bedside illustrates that the inactivation of a driver oncogene can induce activation of the immune system that appears to be essential for sustained tumor regression.
New approaches to the diagnosis of psychopathy and personality disorder
Authors: P. Tyrer
Journal: Journal of the Royal Society of Medicine (2004)

No-one doing research on personality disorder is satisfied with the current diagnostic systems. Like a baker without a rolling pin, the clinician has a rough idea of what personality disorder is and how it should be described, but with the diagnostic implements at his disposal he can only produce a lumpy imitation of what he really wants. The many deficiencies of the current ICD and DSM diagnostic systems seem to derive from the simple error of assuming that personality disorders could be classified in the same way as mental state disorders, by use of well-defined symptoms or characteristics that are (ideally) pathognomonic. Nearly a quarter of a century after the introduction of such operational criteria by the American Psychiatric Association in DSM-III 1 we realize why the diagnostic experiment for personality disorders has failed.
The potential gradient field created by epicardial defibrillation electrodes in dogs.
Authors: P S Chen, P D Wolf, F J Claydon, E G Dixon, H J Vidaillet, N D Danieley, T C Pilkington, R E Ideker
Journal: Circulation (1986)

Knowledge of the potential gradient field created by defibrillation electrodes is important for the understanding and improvement of defibrillation. To obtain this knowledge by direct measurements, potentials were recorded from 60 epicardial, eight septal, and 36 right ventricular transmural electrodes in six open-chest dogs while 1 to 2 V shocks were given through defibrillation electrodes on the right atrium and left ventricular apex (RA. V) and on the right and left ventricles (RV .LV). The potential gradient field across the ventricles was calculated for these low voltages. Ventricular fibrillation was electrically induced, and ventricular activation patterns were recorded after delivering high-voltage shocks just below the defibrillation threshold. With the low-voltage shocks, the potential gradient field was very uneven, with the highest gradient near the epicardial defibrillation electrodes and the weakest gradient distant from the defibrillation electrodes for both RA. V and RV .LV combinations. The mean ratio of the highest to the lowest measured gradient over the entire ventricular epicardium was 19.4 +/- 8.1 SD for the RA. V combination and 14.4 +/- 3.4 for the RV .LV combination. For both defibrillation electrode combinations, the earliest sites of activation after unsuccessful shocks just below the defibrillation threshold were located in areas where the potential gradient was weak for the low-voltage shocks. We conclude that there is a markedly uneven distribution of potential gradients for epicardial defibrillation electrodes with most of the voltage drop occurring near the electrodes, the potential gradient field is significant because it determines where shocks fail to halt fibrillation, and determination of the potential gradient field should lead to the development of improved electrode locations for defibrillation.
Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial
Authors: Charles L Loprinzi, John W Kugler, Jeff A Sloan, James A Mailliard, Beth I LaVasseur, Debra L Barton, Paul J Novotny, Shaker R Dakhil, Kate Rodger, Teresa A Rummans, Bradley J Christensen
Journal: The Lancet (2000)
The Diagnosis of the Commoner Causes of Chronic Jaundice
Authors: P. J. Cammidge
Journal: BMJ (1911)

SINCE jaundice is due to obstruction of the free flow of bile into the intestine, it is only a symptom, and, if a saccessful line of treatment is to be followed, it is neces- sary that the nature and situation of the obstruction head of the pancreas and growths of the common bile duct or ampulla of Vater.But in many cases of chronic jaundice (MARCH 4, I9II- CHRONIC JAUNDICE.