tbuckley/cabot-search huggingface dataset:
Combining a Peptide Vaccine With High-Dose Interleukin-2
Authors: Paul B. Chapman
Journal: Journal of Clinical Oncology (2008)

High-dose interleukin-2 (IL-2) is a US Food and Drug Administration-approved treatment for metastatic melanoma.It was originally developed at the National Cancer Institute (NCI) Surgery Branch and represents one of the few examples in which antitumor effects seen in mice correctly predicted antitumor effects in patients.The initial clinical report, which used recombinant IL-2 plus lymphokine-activated killer cells (now known to be mostly natural killer cells), reported a 44% response rate. 1 This caught everybody's attention.Subsequently, over the next 9 years, as more patients were treated with IL-2 alone, the NCI Surgery Branch reported progressively lower response rates from 31% 2 to 24% 3 and finally to 17%. 4 Consistent with this, a pooled analysis of seven NCI-sponsored trials, representing 270 patients, reported a response rate of 16% with IL-2. 5 It is this number, 16%, that is most commonly cited as the response rate for high-dose IL-2.However, the substage of metastatic melanoma is an important predictor of response to IL-2.Durable responses are more common in patients with either M1a disease (subcutaneous sites only) or M1b disease (lung metastases) and much less common in patients with M1c disease. 5,6The importance of this will be discussed further in this editorial.Subsequent efforts by the NCI Surgery Branch to improve the response rate to high-dose IL-2 led to combining IL-2 with either lymphokine-activated killer cells or tumor-infiltrating lymphocytes. 7nitial studies in small cohorts of patients reported response rates of 44% and 60%, respectively, which seemed to represent an improvement over IL-2 alone.However, subsequent reports in larger numbers of patients did not reproduce these high response rates. 2,3,8,9The most likely explanation is that the patient populations were different and that the addition of lymphokine-activated killer or tumor-infiltrating lymphocyte cells did not have a significant effect on response.Another strategy to improve the response rate to high-dose IL-2 was to combine it with a vaccine.The NCI group used a heteroclitic peptide vaccine against gp100, which, although relatively inactive by itself, was associated with a 42% response rate in 31 patients when administered with high-dose IL-2. 10 Again, this was higher then the historical experience with high-dose IL-2 alone.The authors were careful to point out that a randomized trial would be needed to determine whether the addition of gp100 vaccine really did improve the response proportion to high-dose IL-2.It was this observation that a group of experienced investigators from the Cytokine Working Group sought to clarify in the article published in this issue. 11They carried out parallel phase II trials combining the gp100 peptide vaccine with high-dose IL-2 using three different treatment schedules.
Neonatal End-of-Life Decision Making
Authors: Marisa Rebagliato, Marina Cuttini, Lara Broggin, István Berbik, Umberto de Vonderweid, Gesine Hansen, Monique Kaminski, Louis A. A. Kollée, Audrũnas Kucinskas, Sylvie Lenoir, Adik Levin, Jan Persson, Margaret Reid, Rodolfo Saracci, None for the EURONIC Study Group
Journal: JAMA (2000)

The ethical issues surrounding end-of-life decision making for infants with adverse prognoses are controversial. Little empirical evidence is available on the attitudes and values that underlie such decisions in different countries and cultures.To explore the variability of neonatal physicians' attitudes among 10 European countries and the relationship between such attitudes and self-reported practice of end-of-life decisions.Survey conducted during 1996-1997 in 10 European countries (France, Germany, Italy, the Netherlands, Spain, Sweden, the United Kingdom, Estonia, Hungary, and Lithuania).A total of 1391 physicians (response rate, 89%) regularly employed in 142 neonatal intensive care units (NICUs).Scores on an attitude scale, which measured views regarding absolute value of life (score of 0) vs value of quality of life (score of 10); self-report of having ever set limits to intensive neonatal interventions in cases of poor neurological prognosis.Physicians more likely to agree with statements consistent with preserving life at any cost were from Hungary (mean attitude scores, 5.2 [95% confidence interval ¿CI¿, 4.9-5.5]), Estonia (4.9 [95% CI, 4.3-5.5]), Lithuania (5.5 [95% CI, 4.8-6.1]), and Italy (5.7 [95% CI, 5.3-6.0]), while physicians more likely to agree with the idea that quality of life must be taken into account were from the United Kingdom (attitude scores, 7.4 [95% CI, 7.1-7.7]), the Netherlands (7. 3 [95% CI, 7.1-7.5]), and Sweden (6.8 [95% CI, 6.4-7.3]). Other factors associated with having a pro-quality-of-life view were being female, having had no children, being Protestant or having no religious background, considering religion as not important, and working in an NICU with a high number of very low-birth-weight newborns. Physicians with scores reflecting a more quality-of-life view were more likely to report that in their practice, they had set limits to intensive interventions in cases of poor neurological prognosis, with an adjusted odds ratio of 1.5 (95% CI, 1.3-1.7) per unit change in attitude score.In our study, physicians' likelihood of reporting setting limits to intensive neonatal interventions in cases of poor neurological prognosis is related to their attitudes. After adjusting for potential confounders, country remained the most important predictor of physicians' attitudes and practices. JAMA. 2000;284:2451-2459.
Gastric antral vascular ectasia: a problem of recognition and diagnosis.
Authors: D R Gouldesbrough, A C Pell
Journal: Gut (1991)

Gastric antral vascular ectasia (9water melon stomach9) is a poorly documented cause of occult upper gastrointestinal blood loss. We describe a case which emphasises the clinical and pathological difficulties that can be encountered in making this elusive diagnosis.
Cutaneous and muscular rasodilation in the canine hindlimb evoked by central stimulation.
Authors: W J Lang, C Bell, E L Conway, R Padanyi
Journal: Circulation Research (1976)

Using stereotaxic procedures, we electrically stimulated specific sites in the hypothalamus and midbrain of anesthetized dogs pretreated with guanethidine and atropine methonitrate. A tract in which stimulation caused noncholinergic dilator responses in the hindlimbs was identified. The course of this trace was different from that subserving cholinergic vasodilation in the hindlimb musculature. In a number of experiments we studied the proportional distribution of blood flow to leg and paw. Responses restricted to the paw were regarded as occurring mainly in cutaneous vessels; those restricted to the leg were regarded as occurring mainly in the skeletal muscle vessels. Some dilator responses in both beds were abolished by intra-arterial administration of antihistamines: other dilator responses were abolished by intra-arterial injections of dopamine antagonists. Centrally evoked dilation of leg and paw vessels by noncholinergic pathways suggests physiological roles for these fibers in the regulation of cardiovascular function.
Cardiovascular autonomic alterations and severity of the disease in community-acquired pneumonia
Authors: Eleonora Tobaldini, Stefano Aliberti, Vanessa Nunziata, Giulia Suigo, Alice D'Adda, Fabio Giuliani, Giulia Bonaiti, Andrea Roveda, Alberto Pesci, Nicola Montano, Francesco Blasi
Journal: European Respiratory Journal (2013)

No data evaluated cardiovascular autonomic control (CAC) in community-acquired pneumonia (CAP). Aim was to describe CAC according to the severity of CAP. Patients hospitalized in two university hospitals from Sept. 2011 to Jan. 2013 for CAP underwent 159 registration of ECG and respiration within 24 hours after admission. CURB65, gas exchange and the presence of severe CAP (sCAP ATS 2007) were recorded on admission. CAC was assessed using spectral (SP) and symbolic (SY) analysis of heart rate variability (HRV). SP evaluates rhythmical components of HRV identifying two oscillations: low (LF) and high (HF) frequency components, markers of sympathetic and vagal modulation, respectively. SY identifies two indices, 0V% and 2UV%, indices of sympathetic and vagal modulation, respectively. 58 patients (33 males; median age: 74 yrs) were enrolled. sCAP patients showed a higher HR (p=0.036), lower 0V% and higher 2UV% compared to patients without sCAP. Patients with CURB65 score≥3 were characterized by lower LFnu compared to patients with CURB65  CAP patients with a severe disease on admission show a relatively predominant vagal modulation associated with an altered sympathetic modulation, possibly due to the loss of rhythmical properties of sympathetic outflow.
Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study
Authors: Federico Rojo, Elías Gracias, Nadia Villena, Teresa Cruz, Josep Maria Corominas, Irene Corradino, Mercedes Cedeño, Clara Campas, Marta Osorio, Normando Iznaga, Beatriz Bellosillo, Ana Rovira, Silvia Marsoni, Pere Gascon, Sergio Serrano, Cristiana Sessa, Tania Crombet, Joan Albanell
Journal: Clinical Cancer Research (2010)

To assess the pharmacodynamic effects of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody with intermediate affinity for the receptor, in skin and tumor tissues from head and neck cancer patients.Pharmacodynamic study in patients with advanced squamous cell carcinoma of the head and neck, unsuitable for chemoradiotherapy, enrolled in a single-center trial. Patients received 8 weekly infusions of nimotuzumab. The first nimotuzumab infusion was administered 1 week before starting radiation, whereas the remaining doses were administered concomitantly with irradiation. Paired biopsies were taken from skin and primary tumors, before (pretherapy) and 1 week (on single-agent therapy) after first infusion. Immunohistochemistry was conducted to assay the effects of nimotuzumab on total and phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), p-AKT, and proliferation (Ki-67).Nimotuzumab was well tolerated and there was no evidence of skin rash. Objective response was achieved in 9 of 10 patients. The pharmacodynamic assays showed inhibition of p-EGFR in both skin and tumor (P = 0.042 in skin and P = 0.034 in tumor). No significant changes in p-ERK1/2, p-AKT, or Ki-67 were detected in skin. In addition, lymphocytic infiltrates, folliculitis, or perifolliculitis were not observed. In tumor samples, there was an upregulation of p-AKT (P = 0.043), a reduction in proliferation index (P = 0.012), and a nonsignificant trend toward a decrease of p-ERK1/2 (P = 0.091).The pharmacodynamic data confirmed the ability of nimotuzumab to decrease EGFR phosphorylation. Downstream effects were observed in tumor cells but not in skin, a finding that may help to explain the lack of skin rash in patients treated with nimotuzumab.
Targeting Tomoregulin for Radioimmunotherapy of Prostate Cancer
Authors: Xiao-Yan Zhao, Doug Schneider, Sandra L. Biroc, Renate Parry, Bruno Alicke, Pamela Toy, Jian-Ai Xuan, Choitsu Sakamoto, Ken Wada, Michael Schulze, Beate Müller-Tiemann, Gordon Parry, Harald Dinter
Journal: Cancer Research (2005)

Abstract Radiotherapy is an effective approach for the treatment of local prostate cancer. However, once prostate cancer metastasizes, radiotherapy cannot be used due to the distribution of multiple metastases to lymph nodes and bones. In contrast, radioimmunotherapy should still be efficacious in metastatic prostate cancer as radioisotopes are brought to tumor cells by targeting antibodies. Here we identify and validate a prostate-expressed molecule, tomoregulin, as a target for radioimmunotherapy of prostate cancer. Tomoregulin is a transmembrane protein selectively expressed in the brain, prostate, and prostate cancer, but not expressed in other normal tissues. Immunohistochemical studies of tomoregulin protein in clinical samples show its location in the luminal epithelium of normal prostate, benign prostatic hyperplasia, and prostatic intraepithelial neoplasia. More importantly, the tomoregulin protein is expressed in primary prostate tumors and in their lymph node and bone metastases. The nature of tomoregulin as a transmembrane protein and its tissue-specific expression make tomoregulin an attractive target for radioimmunotherapy, in which tomoregulin-specific antibodies will deliver a radioisotope to prostate tumor cells and metastases. Indeed, biodistribution studies using a prostate tumor xenograft model showed that the 111In-labeled anti-tomoregulin antibody 2H8 specifically recognizes tomoregulin protein in vivo, leading to a strong tumor-specific accumulation of the antibody. In efficacy studies, a single i.p. dose of 150 μCi (163 μg) 90Y-labeled 2H8 substantially inhibits the growth rate of established LNCaP human prostate tumor xenograft in nude mice but produces no overt toxicity despite cross-reactivity of 2H8 with mouse tomoregulin. Our data clearly validate tomoregulin as a target for radioimmunotherapy of prostate cancer.
Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF
Authors: M.T. Henry, K. McMahon, A.J. Mackarel, K. Prikk, T. Sorsa, P. Maisi, R. Sepper, M.X. FitzGerald, C.M. O'Connor
Journal: European Respiratory Journal (2002)

The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis. The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MMP-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement. Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9. Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.
Food Advice for the Waiting Out-patient
Authors: W. C. W. Nixon
Journal: BMJ (1941)

Objective: To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection.  Methods: Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection.  Results: After interview and blinded chart review, 51 patients with dissection (mean age 41 ± 10 years; 59% female) and 100 control patients (44 ± 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p   Conclusions: This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.
NHS doctors in England face audit and annual appraisals
Authors: L. Beecham
Journal: BMJ (1999)

NHS doctors working in England will have to take part in an external clinical audit and face annual appraisals in a package of measures introduced to tackle the problem of poor performance.

The proposals, which have been drawn up by the chief medical officer for England, Professor Liam Donaldson, overhaul some aspects of the NHS that have not changed since 1948.

They are aimed at ensuring that doctors' practice is monitored to pick up problems early, that poor performance is tackled swiftly, and that tough action is taken in response to poor performance.

Audit and appraisals will apply to hospital doctors and GPs. Several …
Colorectal Cancer Screening, Version 1.2015
Authors: Dawn Provenzale, Kory Jasperson, Dennis J. Ahnen, Harry Aslanian, Travis Bray, Jamie A. Cannon, Donald S. David, Dayna S. Early, Deborah Erwin, James M. Ford, Francis M. Giardiello, Samir Gupta, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, M. Sambasiva Rao, Scott E. Regenbogen, Moshe Shike, Gideon Steinbach, David Weinberg, Mary A. Dwyer, Deborah A. Freedman-Cass, Susan Darlow
Journal: Journal of the National Comprehensive Cancer Network (2015)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer.
Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy
Authors: Minbiao Ji, Daniel A. Orringer, Christian W. Freudiger, Shakti Ramkissoon, Xiaohui Liu, Darryl Lau, Alexandra J. Golby, Isaiah Norton, Marika Hayashi, Nathalie Y. R. Agar, Geoffrey S. Young, Cathie Spino, Sandro Santagata, Sandra Camelo-Piragua, Keith L. Ligon, Oren Sagher, X. Sunney Xie
Journal: Science Translational Medicine (2013)

Stimulated Raman scattering microscopy provides a rapid, label-free means of detecting tumor infiltration of brain tissue ex vivo and in vivo.
IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain—containing protein tyrosine phosphatase 1
Authors: Alison Taylor, Mübeccel Akdis, Andrea Joss, Tunç Akkoç, Renate Wenig, Marco Colonna, Isabelle Daigle, Egbert Flory, Kurt Blaser, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2007)
The pan phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) blocks survival, adhesion and proliferation of primary chronic lymphocytic leukemia cells
Authors: R Thijssen, J ter Burg, G G W van Bochove, M F M de Rooij, A Kuil, M H Jansen, T W Kuijpers, J W Baars, A Virone-Oddos, M Spaargaren, C Egile, M H J van Oers, E Eldering, M J Kersten, A P Kater
Journal: Leukemia (2015)
Inhibitory <i>KIR3DL1</i> alleles are associated with psoriasis
Authors: R.S. Ahn, H. Moslehi, M.P. Martin, M. Abad-Santos, A.M. Bowcock, M. Carrington, W. Liao
Journal: British Journal of Dermatology (2015)

Journal Article Inhibitory KIR3DL1 alleles are associated with psoriasis Get access R.S. Ahn, R.S. Ahn Department of Dermatology University of California San Francisco 2340 Sutter Street, Box 0808 San Francisco CA 94143‐0808 U.S.A Search for other works by this author on: Oxford Academic Google Scholar H. Moslehi, H. Moslehi Department of Dermatology University of California San Francisco 2340 Sutter Street, Box 0808 San Francisco CA 94143‐0808 U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.P. Martin, M.P. Martin Cancer and Inflammation Program Laboratory of Experimental Immunology Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick MD U.S.ARagon Institute of Massachusetts General Hospital Massachusetts Institute of Technology, and Harvard University Cambridge MA U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Abad‐Santos, M. Abad‐Santos Department of Dermatology University of California San Francisco 2340 Sutter Street, Box 0808 San Francisco CA 94143‐0808 U.S.A Search for other works by this author on: Oxford Academic Google Scholar A.M. Bowcock, A.M. Bowcock National Heart and Lung Institute Imperial College London London U.K Search for other works by this author on: Oxford Academic Google Scholar M. Carrington, M. Carrington Cancer and Inflammation Program Laboratory of Experimental Immunology Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick MD U.S.ARagon Institute of Massachusetts General Hospital Massachusetts Institute of Technology, and Harvard University Cambridge MA U.S.A Search for other works by this author on: Oxford Academic Google Scholar W. Liao W. Liao Department of Dermatology University of California San Francisco 2340 Sutter Street, Box 0808 San Francisco CA 94143‐0808 U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Pages 449–451, https://doi.org/10.1111/bjd.14081 Published: 01 February 2016
Development and evaluation of in vivo tissue engineered blood vessels in a porcine model
Authors: Tonia C. Rothuizen, Febriyani F.R. Damanik, Tom Lavrijsen, Michel J.T. Visser, Jaap F. Hamming, Reshma A. Lalai, Jacques M.G.J. Duijs, Anton Jan van Zonneveld, Imo E. Hoefer, Clemens A. van Blitterswijk, T.J. Rabelink, Lorenzo Moroni, Joris I. Rotmans
Journal: Biomaterials (2015)