tbuckley/cabot-search huggingface dataset:
Content of sex steroids and prolactin in tumor tissue in breast cancer.
Authors: Elena Frantsiyants, Valeriya Bandovkina, Ekaterina Komarova, Yuliana Shatova, Marina Vereskunova, Ludmila Kuchkina, Valeriya Karnaukhova
Journal: Journal of Clinical Oncology (2014)

e22238 Background: The relations of hormones in tissue of breasts has not been studied sufficiently, hence the objective was to study the saturation of tumor and perifocal area of a malignant neoplasm with estrogens, progesterone, and prolactin depending on the duration of menopause. Methods: The content of estrone (E1), progesterone (P4) and prolactin (Prl) was studied by the IFA method: in samples of tissues of solitary malignant breast tumors T2N0-1M0 in women during premenopause and postmenopausal ones. As the control samples, mammary gland tissue samples were used (n=16) that had been obtained during breast reduction operations. Results: The study has shown a growth of the level of Prl – in 1.6-3.4 times in the tumor tissue, and in 2.7-4.6 times in the perifocal area (PA) of the tumor in all patients. The PA (as compared to the tumor) was validly more saturated with Prl: 1.5 times more in premenopausal women, and 1.7 times more in postmenopausal ones. In all premenopausal patients and in 33% of postmenopausal ones, the level of E1 in the tumor tissue was above the norm in 4.8 times, while in 67% of the menopausal patients – 1.5 times. With regard to this, PA were also distinguished by their saturation with E1: the values exceeded the norm in 1.4 times with premenopausal women, as for postmenopausal ones, it was in 33% only that the concentration of the hormone was 2.7 times higher, with the remaining 67% of women, the concentration did not differ from the intact skin. Against the background of total high estrogenization of the tumor and PA with patients of both groups, the saturation of P4 was extremely low – in 2.2-2.5 times in the tumor tissue, and in 2.7 times in the PA. Conclusions: The study has found hyperestrogenism with progesterone deficiency, as well as excessive formation of prolactin in both the tumor node tissue and in its PA.
Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes
Authors: Maxwell C.K. Leung, Jimmy Phuong, Nancy C. Baker, Nisha S. Sipes, Gary R. Klinefelter, Matthew T. Martin, Keith W. McLaurin, R. Woodrow Setzer, Sally Perreault Darney, Richard S. Judson, Thomas B. Knudsen
Journal: Environmental Health Perspectives (2015)

Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies.In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system.We used U.S. EPA's animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA's in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features.A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network.Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s.Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male reproductive development: profiling 774 chemicals for molecular targets and adverse outcomes. Environ Health Perspect 124:1050-1061; http://dx.doi.org/10.1289/ehp.1510385.
European Immunization Week 2008 - time for reflection
Authors: P Kreidl, H Gomes, P L Lopalco, K Hagmaier, L Pastore Celentano, P Vasconcelos, C Yilmaz
Journal: Eurosurveillance (2008)

This week’s edition of Eurosurveillance is dedicated to European Immunization Week 2008, which will take place from 21 to 27 April. In 2005, the World Health Organization (WHO) organised the first European Immunization Week (http://www.euro.who.int/vaccine/eiw/20050608_1) to increase vaccination coverage by raising awareness about the importance of immunisation, with a special focus on reaching vulnerable and hard-to-reach population groups. During the week, each participating country implements activities to inform and engage key target groups using the slogan “prevent-protect-immunise” and focuses on critical challenges regarding immunisation in their country.
Responses of Granulocyte Colony-Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells to Alloantigen Stimulation
Authors: Yuichiro Nawa, Takanori Teshima, Kazutaka Sunami, Yasushi Hiramatsu, Tomofumi Yano, Katsuji Shinagawa, Eijiro Omoto, Mine Harada
Journal: Blood (1997)
Undulations in the Time-Response Curve for Tumor Immunity after Primary Immunization with Washed Erythrocytes
Authors: Barrett, Morris K., Hansen, Walter H.
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Undulations in the Time-Response Curve for Tumor Immunity after Primary Immunization with Washed Erythrocytes Get access Morris K. Barrett, Morris K. Barrett National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter H. Hansen Walter H. Hansen National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 1, January 1957, Pages 57–63, https://doi.org/10.1093/jnci/18.1.57 Published: 01 January 1957 Article history Received: 27 July 1956 Published: 01 January 1957
Neonatal Outcomes in Women With Untreated Antenatal Depression Compared With Women Without Depression
Authors: Alexander Jarde, Michelle Morais, Dawn Kingston, Rebecca Giallo, Glenda M. MacQueen, Lucy Giglia, Joseph Beyene, Yi Wang, Sarah D. McDonald
Journal: JAMA Psychiatry (2016)

Despite the prevalence of antenatal depression and the fact that only one-third of pregnant women with depression consider it acceptable to take antidepressants, the effect of untreated depression on neonatal outcomes remains to be addressed thoroughly.To undertake a systematic review and meta-analysis to understand the effect of untreated depression on neonatal outcomes.We executed our search strategy, with emphasis on its exhaustiveness, in MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials, and Web of Science. The search was conducted in July, 2015.We included randomized and nonrandomized studies that examined neonatal outcomes in women with depression receiving neither pharmacological nor nonpharmacological treatment compared with women without depression.Two reviewers independently screened titles and abstracts, assessed full-text articles, extracted data, and assessed their quality using a modified version of the Newcastle-Ottawa Scale. We pooled data using random-effects meta-analyses, quantified heterogeneity using the I2 statistic, and explored it with subgroup analyses by type of assessment of depression, severity, reported conflicts of interest, and study quality.Primary outcomes were preterm birth before 37 weeks and before 32 weeks, small and large for gestational age, low birth weight, and neonatal intensive care unit admission.Of the 6646 titles initially identified, 23 studies met inclusion criteria, all observational, with a total of 25 663 women. Untreated depression was associated with significantly increased risks of preterm birth (odds ratio [OR], 1.56; 95% CI, 1.25-1.94; 14 studies; I2, 39%) and low birth weight (OR, 1.96; 95% CI, 1.24-3.10; 8 studies; I2, 48%), with a trend toward higher risks for exposure to more severe depression. While the odds of preterm birth more than doubled in studies reporting conflicts of interest (OR, 2.50; 95% CI, 1.70-3.67; 5 studies; I2, 0%), studies not reporting such conflicts showed more moderate results (OR, 1.34; 95% CI, 1.08-1.66; 9 studies; I2, 30%).Our results contrast with what is, to our knowledge, the only previous systematic review that examined the question of untreated depression because we found significant risks of 2 key perinatal outcomes, preterm birth and low birth weight. These are important results for pregnant women and clinicians to take into account in the decision-making process around depression treatment.
Bretylium
Authors: Jan Koch-Weser
Journal: New England Journal of Medicine (1979)

BRETYLIUM tosylate (Bretylol) is a bromobenzyl quaternary ammonium compound (Fig. 1). In the fifties bretylium was shown to inhibit release of norepinephrine from adrenergic nerve endings1 and found its first clinical use in the treatment of hypertension.2 It soon fell out of favor, because absorption after oral administration is incomplete and variable and because tolerance to its antihypertensive effect develops rapidly. Interest in bretylium revived in the middle sixties, when it was found to exert antiarrhythmic actions.3 , 4 During the last decade these actions have been extensively studied both in laboratory animals and in patients with dysrhythmias. Recently, bretylium tosylate was . . .
PTU-018 Use of hemospray for non variceal upper gastrointestinal bleed in a district general hospital
Authors: A Malik, P Duane, P Eadala, U Dave
Journal: Gut (2015)

<h3>Introduction</h3> Non-variceal upper GI bleeding (NVUGIB) is a common problem with significant morbidity and 30-day mortality. Hemospray (HS) is a recently introdued endoscopic treatment for NVUGIB. It is a proprietary hemostatic spray propelled by carbon dioxide under pressure, which can achieve rapid hemostasis when it comes in contact with blood. The drying effect of the spray and activation of clotting, in addition to pure tamponade, underlies its mechanism of action. <h3>Method</h3> A retrospective single centre study was conducted of patients in whom HS was used as monotherapy or part of dual therapy for control of NVUGIB by different endoscopists. The aim of the study was to evaluate efficacy of HS for treatment of NVUGIB. <h3>Results</h3> A total of 19 patients; mean age 68 years (range 42 to 89 years), 16 males; with NVUGIB were treated with HS between Oct 13 to Oct 14. Clinical presentation included hematemesis and/or melena in 18 (95%) and anaemia in 1 (5%). The mean Rockall score (post endoscopic) was 6.5 and mean Blatchford score was 11.6. Medication review found use of aspirin in 3, NSAID’s in 3 and warfarin in 1 patient. Investigations prior to endoscopy revealed a mean haemoglobin of 79.4 gm/L (range 51 to 136), thrombocytopenia (platelets &lt;150) in 6 (32%) and coagulopathy (INR ≥ 1.3) in 4 (21%) patients. Endoscopic findings included bleeding from oesophageal banding induced ulceration in 2 (10.5%), peptic ulcers in 10 (53%); Forrest class Ib 6, IIa 3 and IIb 1; bleeding tumours in 4 (21%), post-sphincterotomy bleed in 2 (10.5%) and hemobilia in 1 (5%). HS was administered as monotherapy in 8 (42%) patients, 8/8 achieved immediate haemostasis, however 2/8 had recurrent bleed (1 was treated with adrenaline injection and 1 patient was too unwell for further intervention). HS was used as second modality (post adrenaline injection) in 11 (58%) patients where thermal modalities or clips could not be applied for technical reasons or were not considered at the discretion of the endoscopists. 2/11 failed to achieve immediate hemostasis (1 needed immediate laprotomy and 1 died next day) while 3/11 had recurrent bleed (2 needed laprotomy and 1 was treated with OGD and further HS). Average length of stay was 34.5 days (range 5 to 152) and 30 day mortality was 21%. <h3>Conclusion</h3> The data shows that when HS was used as monotherapy immediate hemostasis was achieved in 100% while re-bleeding occurred in 25% cases. As part of dual therapy HS achieved immediate hemostasis in 82% of cases while re-bleeding was seen in 27% of cases. This can be compared to the conventional endoscopic hemostatic methods which achieve overall success rates of 85–95% for immediate hemostasis with re-bleeding in 5–10% cases. The high re-bleeding could be accounted for by the more complex pathologies (tumours, banding induced ulcers) treated with HS. <h3>Disclosure of interest</h3> None Declared.
462P A clinical nomogram and recursive partitioning analysis to determine five-year disease-free survival in patients with thoracic esophageal carcinoma after radical surgery
Authors: S. Yu, Z. Xiao, W. Deng, W. Ni, J. Yang, L. Tan, W. Zhang, Q. Wang, Z. Zhou, H. Zhang, J. Liang, T. Zhang
Journal: Annals of Oncology (2015)
The system works
Authors: A W Macara, I Bogle
Journal: BMJ (1996)

and community controls we published both sets of results.The component of the study that looked at acute myocardial infarction was not powerful enough for analysis of subgroups (except perhaps the community controls).In the British dataset for the component that looked at venous thromboembolic disease there were no differences in the estimates of risk between the hospital and community controls.Table 1-Use of oral contraceptives by controls in component oftransnational study looking at venous thromboembolic disease No Third Second current generation generation use pills pills Hospital controls 470 103 180 Community controls
PTH-287 7-year experience with perineal reconstruction following abdominoperineal or multivisceral resection using inferior gluteal artery perforator flaps
Authors: M-G Pramateftakis, H Creasy, P Roblin, P-N Mohanna, D Ross, A Schizas, M George
Journal: Gut (2015)

<h3>Introduction</h3> Aim of this study is to present our long-term experience of the use of inferior gluteal artery perforator (IGAP) flaps for the immediate reconstruction of the perineum following excisional surgery. To our knowledge, this is the largest series of immediate perineal reconstruction using IGAP flaps published to date. <h3>Method</h3> We performed a retrospective analysis of a group of 142 patients who over a period of 7 years (from April 2007 to April 2014) underwent abdominoperineal resection (57 patients, 40%), multivisceral resection (49 patients, 34.5%), local perineal excision (14 patients, 9.8%), panproctocolectomy (3 patients, 2.1%) and perineal hernia repair (2 patients, 1.4%). The remaining 17 patients of our group (11.9%) underwent various perineal procedures such as fistula resections, pilonidal sinus resections or postoperative perineal sinus resections. We used IGAP flaps to immediately reconstruct the perineal defect of all these patients. 74 patients (52%) were male and 68 female (48%), with a mean age of 60 years (range 19–88). The indication for the excision was rectal cancer in 53 patients (37.3%), recurrent rectal cancer in 27 patients (19%), anal cancer in 12 patients (8.4%), recurrent anal cancer in 11 patients (7.7%), gynaecological malignancy in 8 patients (5.6%), inflammatory bowel disease in 12 patients (8.4%), postoperative wound dehiscence in 3 patients (2.1%) and postoperative perineal sinus formation in 9 patients (6.3%). The remaining 7 patients (4.9%) underwent excision and reconstruction for persistent perineal sinuses or pilonidal sinuses. 111 patients (78%) underwent neoadjuvant chemoradiotherapy. <h3>Results</h3> The average length of inpatient stay was 17.6 days (range 3–100). Most patients are still being followed up in our outpatient clinic and are being assessed with regards to pain, discomfort and herniation. The commonest complication observed was a dehiscence of the IGAP flaps, which was observed in 53 patients (37.3%). 44 dehiscence cases were observed following surgery for malignant disease and 9 following surgery for benign disease. 81% of these cases were managed conservatively in the form of simple wound care (dressings), negative-pressure wound dressings (VAC) or primary suturing of the defect. Only 10 of the patients had to be re-operated for debridement, washout and closure or flap revision. A total of 2 patients formed a chronic perineal sinus following dehiscence. <h3>Conclusion</h3> Our experience has shown that the IGAP flaps are a safe, robust and reliable option for the reconstruction of the perineum following major excisions, with an acceptable rate of complications when compared to other reconstruction options. <h3>Disclosure of interest</h3> None Declared.
PWE-385 Transperineal rectocoele repair: a systematic review
Authors: EF Zimmermann, AM Warwick, IR Daniels, NJ Smart
Journal: Gut (2015)

<h3>Introduction</h3> Surgical treatment of symptomatic rectocoele is considered for patients where conservative measures have failed. Surgical approaches can be described as transabdominal (TAb), transvaginal (TV), transanal (TA), and transperineal (TP). Transperineal repairs can be performed as an isolated fascial repair or in combination with synthetic or biologic mesh augmentation and are hypothesised to reduce the risk of complications compared with alternative approaches. <h3>Method</h3> A systematic review was performed with the aim of ascertaining long-term success and complication rates of transperineal rectocoele repairs. <h3>Results</h3> Fourteen studies, comprising seven case series, six comparative studies and one randomised controlled trial were included in this review. Of 566 patients, 333 underwent a transperineal rectocoele repair and 220 a transanal repair. Complications were identified postoperatively in 27/220 (12.3%) transanal repairs and in 41/333 (12.3%) transperineal repairs. Outcome reporting differed between studies precluding full meta-analysis. A significant effect on symptom resolution following TP rectocoele repair was noted in eight studies, one was non significant but showed improvement, and four showed improvement but did not comment on statistical significance of the effect. There is not enough data to make a reliable comparison between mesh and non-mesh transperineal repairs, or to compare biologic and synthetic mesh use. <h3>Conclusion</h3> Transperineal rectocoele repair offers an effective method of symptom improvement that appears to be superior to transanal repairs, and is associated with similar complication rates. Concomitant use of synthetic and biologic mesh to enhance the repair is becoming more common, however, high quality comparative data is lacking and further studies are required. <h3>Disclosure of interest</h3> None Declared.
OP0125 Replication of GWAS of Response to TNF Inhibitors in Patients with Rheumatoid Arthritis
Authors: A. Ferreiro-Iglesias, A. Montes, E. Pérez-Pampín, P. Carreira, B. Joven, R. Caliz, M.A. Ferrer, M.J. Moreno-Ramos, E. Raya, C. Magro, Y. Vasilopoulos, T. Sarafidou, A. Balsa, D. Pascual-Salcedo, A. Fernández-Nebro, M.C. Ordόñez, J.J. Alegre-Sancho, A. Márquez, F. Navarro, V. Moreira, F.J. Blanco, J. Narvaez, J.D. Cañete, J. Martin, J.J. Gόmez-Reino, A. Gonzalez
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Three large GWAs (1-3) examining the response to TNF inhibitors have provided evidence suggesting 16 SNP associations, but none of them reached the GWAS significance threshold. <h3>Objectives</h3> We aim to replicate association of the 16 SNPs with TNFi response in an independent sample collection. <h3>Methods</h3> A total of 755 European RA patients receiving TNFi (397 infliximab, 155 etanercept, and 203 adalimumab) were included. Response was evaluated either as change in the disease activity score using 28 joints (ΔDAS28) between baseline and 3, 6 and 12 months of treatment, or as classification according to the EULAR response criteria (good + moderate responders vs. non responders) at the same time points. The genotypes of the 16 SNPs were obtained with a single-base extension methodology. We considered the SNPs according to an additive model in linear and logistic regression analyses, for ΔDAS28 and EULAR criteria, respectively. Baseline DAS28, gender and treatment were considered as covariates. <h3>Results</h3> All the SNPs were successfully genotyped (call rate=99.5%; HWE&gt;0.05). None of them was associated with response to TNFi at any time of follow-up. However, NUBPL rs2378945 minor allele (A) showed the same trend as the reported by Mirkov et al. (B = -0.14, 95% CI -0.31-0.03, P=0.10 for ΔDAS28 at 3 months as reported). This trend became a significant association after stratifying by drug, in the subgroup treated with etanercept (B = -0.50, 95% CI (-0.82, -0.17), P=0.003), but no association or trend was identified with the other drugs. <h3>Conclusions</h3> We have found a specific association with response to etanercept of NUBPL rs2378945, which is an analysis not reported in the original GWAS and, therefore, not amounting to replication. None of the other 15 associations was replicated, indicating that none of the results from these GWAS could still be taken as validated. <h3>References</h3> Mirkov et al. Ann Rheum Dis. 2013 Aug;72(8):1375-81 Plant et al. Arthritis Rheum. 2011 Mar;63(3):645-53 Cui et al. Rheum Dis Clin North Am. 2009 Nov;35(4):745-57 <h3>Acknowledgements</h3> Instituto de Salud Carlos III (Spain), grants PI11/01048, PI12/01909 and RD12/0009/0008 that are partially financed by the European Regional Development Fund <h3>Disclosure of Interest</h3> None declared
The cat lipocalin Fel d 7 and its cross‐reactivity with the dog lipocalin Can f 1
Authors: D. Apostolovic, S. Sánchez‐Vidaurre, K. Waden, M. Curin, J. Grundström, G. Gafvelin, T. Cirkovic Velickovic, H. Grönlund, W. R. Thomas, R. Valenta, C. Hamsten, M. van Hage
Journal: Allergy (2016)

We investigated the prevalence of sensitization to the cat lipocalin Fel d 7 among 140 cat-sensitized Swedish patients and elucidated its allergenic activity and cross-reactivity with the dog lipocalin Can f 1. Sixty-five of 140 patients had IgE to rFel d 7 whereof 60 also had IgE to rCan f 1. A moderate correlation between IgE levels to rFel d 7 and rCan f 1 was found. rFel d 7 activated basophils in vitro and inhibited IgE binding to rCan f 1 in 4 of 13 patients, whereas rCan f 1 inhibited IgE binding to rFel d 7 in 7 of 13 patients. Fel d 7 and Can f 1 showed high similarities in protein structure and epitopes in common were found using cross-reactive antisera. Fel d 7 is a common allergen in a Swedish cat-sensitized population that cross-reacts with Can f 1, and may contribute to symptoms in cat- but also in dog-allergic patients.