tbuckley/cabot-search huggingface dataset:
Use of Tumor-Infiltrating Lymphocytes and Interleukin-2 in the Immunotherapy of Patients with Metastatic Melanoma
Authors: Steven A. Rosenberg, Beverly S. Packard, Paul M. Aebersold, Diane Solomon, Suzanne L. Topalian, Stephen T. Toy, Paul Simon, Michael T. Lotze, James C. Yang, Claudia A. Seipp, Colleen Simpson, Charles Carter, Steven Bock, Douglas Schwartzentruber, John P. Wei, Donald E. White
Journal: New England Journal of Medicine (1988)

Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.
THU0581 Spousal Protective Buffering is Related to a Lower Physical and Mental Quality of Life in Patients with Sjögren’s Syndrome
Authors: E. Bossema, N. van Leeuwen, A. A. Kruize, H. Bootsma, J. W. Bijlsma, R. Geenen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with Sjögren’s syndrome are hampered by dryness and fatigue, which impact on quality of life.<sup>1,2</sup> Social support –such as the help and understanding of spouses– is assumed to have a beneficial effect on quality of life, either directly (’direct effects hypothesis’) or indirectly by reducing the negative effect of symptoms on quality of life (’buffering hypothesis’).<sup>3</sup> <h3>Objectives</h3> To examine in patients with Sjögren’s syndrome 1) the direct effect of spousal response styles on quality of life, and 2) the moderating effect of spousal response styles on the relation between perceived dryness and fatigue on the one hand and quality of life on the other. <h3>Methods</h3> Research participants were 217 female partnered patients with primary Sjögren’s syndrome (mean age 55 years). Three spousal response styles were assessed with the Active Engagement, Protective Buffering and Overprotection Questionnaire<sup>4</sup> (Table 1), physical and mental quality of life with the RAND 36-item Health Survey,<sup>5</sup> and perceived dryness (the mean of ocular and oral dryness) and fatigue with Visual Analogue Scales. Stepwise hierarchical regression analysis (’enter’ method) was applied, including age in the first step. <h3>Results</h3> Of the three spousal response styles, only protective buffering was associated with a lower physical and mental quality of life (<i>β</i> = -0.20, <i>p</i> =.01 and <i>β</i> = -0.28, <i>p</i> &lt;.001, repectively). There was no moderating effect of any spousal response style on the existing negative relations between symptoms on the one hand and physical or mental quality of life on the other (<i>β</i> ≤ 0.10, <i>p</i> ≥.19). <h3>Conclusions</h3> The results suggest that the hiding of concerns by the spouse of a female patient with Sjögren’s syndrome could be harmful for quality of life. However, this protective buffering or other spousal response styles do not buffer or aggravate the impact of symptoms on quality of life. If future longitudinal research verifies the causality between spousal protective buffering and quality of life, then improving this spousal response style may lead to a better quality of life, irrespective of the severity of dryness or fatigue. <h3>References</h3> Vitali et al. Ann Rheum Dis 2002;61:554-8. Meijer et al. Rheumatol (Oxford) 2009;48:1077-82. Cohen et al. Psychol Bull 1985;98:310-57. Buunk et al. Gedrag Gezondheid 1996;24:304–13. Van der Zee et al. Int J Behav Med 1996;3:104-22. Kool et al. J Sex Marital Ther 2006;32:409-23. <h3>Disclosure of Interest</h3> None Declared
FRI0068 Diagnostic value of third generation anti-citrullinated peptides antibodies in rheumatoid artritis
Authors: D. Grados, A. Riveros, M. Martinez-Morillo, B. Tejera, S. Holgado, L. Mateo, A. Olivé, X. Tena, A. Teniente-Serra, V. García-Lόpez, E. Ruíz, E. Martínez-Cáceres
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Assays that detect anti-citrullinated peptides antibodies (ACPA) are considered to be more specific than rheumatoid factor in the diagnosis of rheumatoid arthritis (RA). Several tests have been developed using different antigens: first, second and third-generation cyclic-ACPA (CCP1, CCP2, CCP3) and modified citrullinated vimentin (MCV). <h3>Objectives</h3> To investigate anti-CCP3 in a group of patients positive citrullinated vimentin antibodies (MCVA). <h3>Methods</h3> The retrospective study was done at the university hospital with a reference population of 800,000. Atotal of 259 patients positive for IgG MCV antibodies (by ELISA) attending the outpatient rheumatology clinic were tested for anti-CCP3 (by ELISA). From the total, 182 (70.3%) of them had a rheumatic disease: RA in 121 (66.5%) and other: elderly-onset arthritis, non-filiated arthritis, connective, vasculitis, Still's disease, espondiloarthritis, microcrystalline arthritis, polymyalgia rheumatica and sarcoidosis, in 61 (33.5%). There are 77 (29.7%) patients with other conditions (non rheumatic disease) positive for MCVA were also tested for anti-CCP3. <h3>Results</h3> From the 121 RA patients, 106 (87.6%) were positive for anti-CCP3. In contrast, only 15 (24.6%) of the 61 patients without RA and only 4 (5.2%) of the 77 MCVA positive patients with no rheumatic disease associated were CCP3 positive. Interestingly, within the group no RA, of the 13 patients with anti-CCP3 values &gt;60 U/ml, 6 (46.2%) were patients with palindromic rheumatism and two of them had developed RA. Specificity of anti-CCP3 for RA as compared to other rheumatic disease was 76.7%, that raised to 86.9% when comparing RA versus to non-RA (with or without another rheumatic disease). Positive and negative predictive values of anti-CCP3 for RA were 85.5% and 88.8%, respectively whereas positive predictive values for anti-MCV was 39.1%. <h3>Conclusions</h3> Anti-CCP3 antibodies show a higher specificity for RA when compared to MCVA with a better positive predictive values, a crucial feature for a test in use for clinical practice. <h3>Disclosure of Interest</h3> None Declared
SAT0143 Tumor necrosis factor-blocker use in us managed care: Utilization and dosing patterns among rheumatoid arthritis patients:
Authors: M. Fisher, C. Watson, K.M. Fox, Y.-W. Chen, S.R. Gandra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The 3 most common tumor necrosis factor (TNF)-blocker therapies for the treatment of moderate to severe rheumatoid arthritis (RA) are etanercept (ETN), adalimumab (ADA), and infliximab (INF). Treatment patterns (discontinuation, switch, or restart) after TNF-blocker initiation have not been well characterized. RA patients may require dose escalation of TNF-blockers, which may impact costs. <h3>Objectives</h3> To describe the real-world utilization and dosing patterns of ETN, ADA, and INF in RA patients in a US managed care population. <h3>Methods</h3> In this retrospective analysis, the HealthCore Integrated Research Database was used to identify biologic-naïve, adult (18-64 years) RA patients with ≥1 claim for ETN, ADA, or INF between 1 July 2007 and 31 January 2010 (first claim is index claim). Patients having 6 months pre-index eligibility and 12 months post-index claim were included (study end date 31 January 2011). Patients were excluded if they had any other conditions for which RA biologic therapies were indicated or contraindicated. Therapy persistence, discontinuation, dose escalation, and biologic switch patterns were evaluated. Patients who remained on index TNF-blocker therapy for 1 year without ≥60-day gap were included in the dose escalation analysis, where dose escalation was defined as follows: 50mg to 75mg or 100mg weekly of ETN; 40mg every other week to 40mg weekly of ADA; or increase in vial or decrease in infusion interval to &lt;6 weeks for INF after the fourth infusion (maintenance only). <h3>Results</h3> Data from 2426 patients were analyzed (1595 ETN; 417 ADA; 414 INF); mean age was 48.8 yrs, 77% were women. Rates of persistence, discontinuation, switching, and dose escalation are shown (Table). Rates of persistence, switching, and discontinuation were similar between groups (<i>P</i>&gt;0.1 for all 2-way comparisons). <h3>Conclusions</h3> Discontinuation and switching patterns within the first year of initiating TNF-blocker therapy were similar among patients receiving ETN, ADA, and INF in a US managed care population. The percentage of patients with a dose escalation was similar to previous studies with lower percentages in patients on ETN than on ADA or INF. <i>This study sponsored by Immunex, a wholly owned subsidiary of Amgen Inc. and by Wyeth, which was acquired by Pfizer Inc. in October 2009.</i> <h3>Disclosure of Interest</h3> M. Fisher Grant/Research support from: Amgen Inc., C. Watson Shareholder of: Amgen Inc., Employee of: Amgen Inc., K. Fox Consultant for: Amgen Inc., Y.-W. Chen Grant/Research support from: Amgen Inc., S. Gandra Shareholder of: Amgen Inc., Employee of: Amgen Inc.
ENCEPHALOPATHIA ALCOHOLICA
Authors: NORMAN JOLLIFFE, HERMAN WORTIS
Journal: American Journal of Psychiatry (1941)

An attempt has been made to evaluate critically the results of nutritional and, more particularly, vitamin studies, as they relate to the clinical syndromes of delirium tremens, the Korsakoff psychosis, Wernicke's syndrome and the various cerebral disorders that result from a deficiency of nicotinic acid. The manner in which chronic alcoholism may produce dietary insufficiency is briefly discussed. We emphasize the fact that while alcohol is apparently not immediately responsible for most of the observable damage, alcoholism is responsible for these changes. The effect of alcohol per se has still to be evaluated. We accentuate also the frequency with which these pictures merge one into the other, and the fact that vitamin therapy, to be effective, must be instituted before irreversible structural changes have occurred. As in vitamin deficiency diseases occurring elsewhere, those affecting the nervous system are usually the result of multiple rather than single deficiencies. A well balanced diet should therefore always supplement treatment with the specifically indicated vitamin or vitamins. It is our belief that future studies of the type here reviewed will yield much information of value to students of nervous economy.
Abstract 4697: Liquid chromatography-electrospray ionization tandem mass spectrometry analysis of 7-ethylguanine in human urine
Authors: Silvia Balbo, J. Bradley Hochalter, Peter W. Villalta, Steven G. Carmella, Stephen S. Hecht
Journal: Cancer Research (2010)

Abstract Considerable evidence in the literature demonstrates the exposure of humans to an unknown ethylating agent. Previous studies have demonstrated the presence of 3-ethyl-Ade in urine, 7-ethylguanine (7-ethyl-Gua) in urine and human liver DNA, 7-ethyldGuo and O4-ethyl-dThd in human lung DNA, and ethylvaline in hemoglobin. Some studies also report higher levels of ethyl adducts in smokers compared to nonsmokers, and there is convincing evidence for an uncharacterized ethylating agent in cigarette smoke. To further investigate this question and evaluate the potential role of ethylating agents in smoking-induced cancer we have developed a liquid chromatography-electrospray ionization tandem mass spectrometry-selected reaction monitoring (LC-ESI-MS/MS-SRM) method for analysis of 7-ethyl-Gua in human urine. A two-dimensional chromatography approach was used with [15N5]7-ethyl-Gua as the internal standard. Human urine was diluted with 15 mM ammonium acetate and partially purified by a solid-phase extraction cartridge (Strata-X 33 µm, 30 mg/1 mL, Phenomenex) and a mixed mode cation exchange reversed-phase extraction cartridge (Oasis MCX, 30 mg/cartridge, Waters). The fraction from this last purification step containing the analyte (30% MeOH, 5% NH4OH) was dried and redissolved in 80% acetonitrile, 0.1% formic acid and purified by HPLC on a YMC Polyamino II column (150 × 1.0 mm I.D. 5 μm). The fraction containing 7-ethyl-Gua was collected, dried, dissolved in H2O and analysed by LC-ESI-MS/MS-SRM using a Thermo Hypersil Gold PFP column (150 × 0.5 mm I.D. 3 μm). The analysis was carried out using the transition m/z 180 [M + H]+ → m/z 152 [Gua+ H]+ for 7-ethyl-Gua and m/z 185 → m/z 157 for the internal standard. Recovery was about 50%. The detection limit was approximately 10 fmol on column. The peaks attributed to 7-ethyl-Gua and the labeled internal standard had identical retention time and were observed in most of the human urine samples analyzed. The identity of the peak was confirmed by re-injecting the samples after spiking with a standard solution of 7-ethyl-Gua. Twenty-one human urine samples (1 mL) from 11 smokers and 10 nonsmokers were analyzed. 7-Ethyl-Gua was clearly detected in 8 out of 11 samples from smokers and 5 out of 10 samples from nonsmokers. These results strongly indicate that 7-ethyl-Gua is present in human urine and demonstrate that it can be detected and quantified. Further investigation is required to clarify its relationship to cigarette smoking. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4697.
P258 A case-control study of associations between hereditary haemorrhagic telangiectasia and common respiratory conditions
Authors: FN Abdulla, I Awan, BM Silva, HL Devlin, AE Hosman, CL Shovlin
Journal: Thorax (2013)

<h3>Background</h3> Hereditary haemorrhagic telangiectasia (HHT) is an inherited disease of the vasculature presenting with nosebleeds, telangiectasia and arteriovenous malformations (AVMs). HHT is caused by gene mutations affecting the transforming growth factor beta (TGF-β) superfamily signalling pathway. As TGF-β signalling is crucial for embryonic lung maturation, respiratory homeostasis and plays a pivotal role in the pathogenesis of several respiratory diseases, we hypothesised that HHT could alter the respiratory environment and respiratory disease susceptibility. As a first step, we aimed to examine associations between HHT and other respiratory conditions common in the British population. <h3>Methods</h3> An online questionnaire at www.imperial.ac.uk/medicine/HHTsurvey2012 was used to collect data. Questions regarding HHT were used to assign HHT status. Participants were categorised based on self-reported status, positive/negative family history and presence of Curaçao criteria (nosebleeds, telangiectasia in specific patterns, and AVMs) Participants’ demographics and coexisting respiratory conditions were analysed with Spearman’s, Mann-Whitney, and logistic regression analyses using STATA (version 12, Texas USA). <h3>Results</h3> By data download on 5 April 2013, 1,465 participants had completed the questionnaire. 1,080 were classified as HHT patients and 179 as controls. Ages ranged from 17–92 (53)years. A history of smoking was provided by 31.5% of the HHT population and 33.1% of the controls. In univariate analyses, COPD, venous thromboemboli, pulmonary hypertension and sleep apnoea were more common in the HHT population in comparison to the controls (respectively, p = 0.038; p = 0.019; p = 0.004; p = 0.015). When multiple regression analyses were used to correct for age and smoking, the association with COPD was lost. However, the positive associations with pulmonary hypertension (p = 0.034), venous thromboemboli (p = 0.036) and sleep apnoea (p = 0.033) remained. Sleep apnoea demonstrated a 2.6 fold higher prevalence in the study HHT population (69/100,000) in comparison to published figures for the general population (27/100,000 from the Hospital Episodes System (HES). <h3>Conclusions</h3> The study identified two known associations (HHT and pulmonary hypertension; HHT and venous thromboemboli), supporting the validity of the study methodology. Further investigation is needed to validate and understand the rationale for a possible novel association between HHT and sleep apnoea. <h3>References</h3> Lung and Asthma Information Agency. Obstructive Sleep Apnoea. Available at http://www.laia.ac.uk/pdfs/osa.pdf
Measurement of Norepinephrine and 3,4-Dihydroxyphenylglycol in Urine and Plasma for the Diagnosis of Pheochromocytoma
Authors: Mark W. Duncan, Paul Compton, Leslie Lazarus, George A. Smythe
Journal: New England Journal of Medicine (1988)

We compared the value of plasma samples with that of 24-hour urine samples in identifying patients with pheochromocytoma among those with hypertension. We employed specific gas chromatographic–mass spectrometric analysis of both urine and plasma for simultaneous assay of norepinephrine and its neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG). The study population consisted of 1086 patients with hypertension, among them 25 patients with proved pheochromocytoma. Reference ranges for free norepinephrine and DHPG in plasma and urine were established. Measurement of free norepinephrine in 24-hour urine samples provided the best index of a pheochromocytoma. This technique had 100 percent sensitivity and 98 percent specificity among 1192 urine samples, as compared with 82 percent sensitivity and 95 percent specificity among 358 plasma samples. Simultaneous measurement of norepinephrine and DHPG in urine further improved specificity (to 99 percent), but the use of the ratio of norepinephrine to DHPG reduced sensitivity (to 95 percent), since some patients with pheochromocytoma secrete large amounts of DHPG. We therefore recommend measurement of 24-hour urinary levels of free norepinephrine for the diagnosis of pheochromocytoma and suggest that simultaneous analysis for DHPG may sometimes prove useful in reducing the rate of false positive results. (N Engl J Med 1988; 319:136–42.)
Fertility Studies in the Human Male with Traumatic Injuries of the Spinal Cord and Cauda Equina
Authors: Herbert W. Horne, David P. Paull, Donald Munro
Journal: New England Journal of Medicine (1948)

HUMAN males who have suffered traumatic injuries of the spinal cord and cauda equina have long been considered sterile. This study was performed to determine whether or not this assumption is true. A previous paper1 discussed the incidence of erection and ejaculation in the human male with traumatic injuries of the spinal cord and cauda equina.The 18 cases studied in the present series were patients at Cushing Veterans Administration Hospital who had suffered traumatic injuries of the spinal cord and cauda equina. Their ages ranged from twenty-one to thirty-five years, with an average age of twenty-seven years. The length . . .
Interleukin-22 receptor is overexpressed in nonsmall cell lung cancer and portends a poor prognosis
Authors: Antoine Guillon, Fabien Gueugnon, Konstantinos Mavridis, Emilie Dalloneau, Youenn Jouan, Patrice Diot, Nathalie Heuzé-Vourc'h, Yves Courty, Mustapha Si-Tahar
Journal: European Respiratory Journal (2016)

The recent decade has witnessed a change of view about cancer mechanisms. Considerable evidence now suggests that the tumour microenvironment status is well correlated with disease outcome. The presence of particular immune cell types or molecules determines whether a pro- or antitumour immune response predominates within the microenvironment [1]. Accordingly, improved understanding of the factors that modulate the tumour microenvironment will be critical for the development of effective future strategies for cancer management. High expression of IL-22R1 in nonsmall cell lung cancer is an independent indicator of poor overall survival <http://ow.ly/WZxKh>
ET-35 * PACRITINIB: A NOVEL JAK/STAT INHIBITOR WITH TRANSLATIONAL RELEVANCE FOR GBM
Authors: A. Luchman, A. Aman, R. Al-Awar, S. Weiss
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity. GBM-derived brain tumor initiating cells (BTICs) closely model this molecular heterogeneity and may have a key role in tumor recurrence and therapeutic resistance. Recent evidence, from our lab and others, indicates that the Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway is an important mediator of tumor cell survival, growth, and invasion in a large group of GBMs. Thus, inhibition of the JAK/STAT3 pathway may hold great promise as a therapeutic strategy for GBM. However, to date, drugs targeting activated STAT3 in clinically relevant models have not been successfully transitioned into clinical studies. Here we investigated the efficacy of a novel JAK/STAT inhibitor, Pacritinib, in BTIC lines cultured from GBM patients. Pacritinib is currently in a multicenter, randomized, Phase 3 trial comparing its efficacy and safety with that of best available therapy in patients with primary myelofibrosis. In GBM BTICs, Pacritinib administration resulted in on-target JAK2/STAT3 inhibition at 1-2 µΜ that dramatically reduced cell survival in a large number of lines, regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. Pacritinib was also found to cross the blood-brain barrier in NOD-SCID mice, by liquid chromatography-mass spectrophometry, with no toxicity observed on repeated administration of up to 200mg/kg per day by oral gavage. Previous studies on different JAK/STAT3 inhibitors, by others and us, demonstrated toxicity at doses required to shut-off STAT3 signaling and achieve tumour cell death in vivo. We are currently investigating the actions of Pacritinib in orthotopic BTIC xenograft animal survival studies. Given its previously established human safety profile and demonstrated activity in the clinically relevant BTIC model, Pacritinib may hold considerable promise for clinical translation in GBM.
Phenobarbital for Febrile Seizures — Effects on Intelligence and on Seizure Recurrence
Authors: Jacqueline R. Farwell, Young Jack Lee, Deborah G. Hirtz, Stephen I. Sulzbacher, Jonas H. Ellenberg, Karin B. Nelson
Journal: New England Journal of Medicine (1990)

Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo.
620 DIAGNOSIS OF ADRENAL INSUFFICIENCY USING SERUM TOTAL CORTISOL AND PLASMA FREE CORTISOL RESPONSE AFTER LOW DOSE SHORT SYNACTHEN TEST: DISCREPANCY EXISTS IN ADVANCED LIVER DISEASE
Authors: G. Fede, L. Spadaro, T. Tomaselli, G. Privitera, R. Scicali, P. Vasianopoulou, N. Martin, M. Thomas, F. Purrello, A.K. Burroughs
Journal: Journal of Hepatology (2012)