tbuckley/cabot-search huggingface dataset:
THU0290 Peripheral mononuclear cells of systemic juvenile idiopathic arthritis patients have no intrinsic defect in interferon-gamma signaling
Authors: K. Put, A. Avau, T. Mitera, S. Put, B. Bader-Meunier, P. Quartier, C. Wouters, P. Matthys
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic juvenile idiopathic arthritis (sJIA) is one of the most severe pediatric systemic immune-inflammatory disorders, characterized by arthritis and systemic features including fever, rash, lymphadenopathy and leukocytosis. A frequent, potentially fatal complication of sJIA is macrophage activation syndrome (MAS). An excessive production of pro-inflammatory cytokines has been demonstrated in sJIA with or without MAS, yet the exact cause and pathogenesis are still unknown. Studies on gene expression profiles performed on freshly isolated peripheral blood mononuclear cells (PBMCs) from sJIA patients revealed a conspicuous absence of interferon-gamma (IFN-γ)-upregulated genes. This is a peculiar finding, given the highly inflammatory nature of sJIA and the concept that IFN-γ is a driver of MAS. <h3>Objectives</h3> In this study we explored whether PBMCs of sJIA patients have a defect in IFN-γ signaling by studying induced genes and proteins upon <i>in vitro</i> stimulation with IFN-γ. <h3>Methods</h3> 9 sJIA patients (7 under treatment and in remission, 1 with active disease despite treatment, 1 untreated) and 1 sJIA patient presenting with MAS were recruited from the University Hospital of Leuven after giving informed consent. PBMCs from patients and healthy controls were obtained by gradient centrifugation and were cultured for 24 hours in the presence or absence of IFN-γ. RNA was extracted from the harvested cells. cDNA was synthesized and qPCR was performed on different IFN-γ-induced genes. IFN-γ-induced proteins (interferon-induced protein (IP-10) and monocyte chemotactic factor-1 (MCP-1)) were analyzed in supernatant of cells, by ELISA. <h3>Results</h3> In PBMCs from healthy control patients, IFN-γ induced - as expected - upregulation of STAT 1 mRNA, an important IFN-γ-induced transcription factor, as well as other IFN-γ-induced genes such as indoleamine 2,3-dioxygenase (IDO) and IP-10. Some genes such as suppressor of cytokine signaling 3 (SOCS3), MCP-1 and interferon regulatory factor-1 (IRF-1) were not upregulated in healthy PBMCs. Most importantly, all of the IFN γ-associated genes that were significantly induced in healthy control PBMCs were at the least equally well induced in sJIA patients (in both treated, untreated and MAS conditions). Significant production of IP-10 protein was found in the supernatant of IFN-γ-stimulated PBMCs, and here again there was no difference between patients and controls. <h3>Conclusions</h3> We conclude that PBMCs from sJIA/MAS patients have no intrinsic defect in the IFN-γ machinery. Thus the absence of an IFN-γ signature in sJIA, as reported in gene expression studies, cannot be explained by decreased <i>in vitro</i> responsiveness of PBMCs to IFN-γ, and further research is required to explain this discrepancy. <h3>Disclosure of Interest</h3> None Declared
NCIC CTG MA.17: hormone receptor expression of in-breast recurrences and contralateral primary breast cancers arising on aromatase inhibitors.
Authors: B Moy, D Tu, LE Shepherd, MJ Palmer, JN Ingle, PE Goss
Journal: Cancer Research (2009)

Abstract Abstract #1134 Background: The selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene reduce the risk of ER+ (but not ER-) invasive breast cancers in healthy women at high risk for developing breast cancer. Aromatase inhibitors (AIs) given as adjuvant therapy to treatment-naïve or post-tamoxifen patients significantly reduce the risk of in-breast recurrences (IBRs) and contralateral breast cancers (CBCs) and are currently in clinical trials for breast cancer prevention (NCIC CTG MAP.3 and IBIS-II). It is hypothesized that SERMS inhibit promotion of ER+ breast cancer whereas AIs may reduce both ER+ and ER- breast cancer by inhibiting both tumor initiation and promotion. Little is known about the characteristics of IBRs and CBCs that arise on AI therapy. We present the ER/PR expression and clinicopathologic features of IBRs and CBCs that occurred on MA.17.&amp;#x2028; Methods: We examined ER/PR status of IBRs and CBCs that arose on letrozole vs. placebo among women enrolled in MA.17, a placebo-controlled (PLAC) trial of letrozole (LET) following 5 years of tamoxifen in postmenopausal women with early stage breast cancer.&amp;#x2028; Results: Seventy-one patients (pts) developed an IBR and 87 developed a CBC on trial. Consistent with results previously reported, fewer IBRs (LET 20 vs PLAC 51) and CBCs (LET 35 vs PLAC 52) were observed in the LET group. ER and PR status is currently available on 35 women with an IBR and 39 with a CBC. The majority of IBRs were ER+ in both the LET and PLAC groups (10/11 [91%] vs 18/24 [75%], respectively; p=NS) but numbers of both ER+ and – IBRs were less in LET group, suggesting that letrozole may decrease both ER+ and ER- IBRs. CBCs that arose on PLAC were more likely to be ER+ than on LET (16/22 [73%] vs 6/19 pts [32%], respectively; p=0.01), suggesting that letrozole predominantly prevents ER+ CBCs. Discordance in ER expression between primary breast cancer and IBRs among women randomized to LET vs. PLAC was observed in 1/11 [9%] and 6/24 [26%] women respectively (p=NS) and between primary breast cancer and CBCs in 12/18 pts [67%] vs. 6/21 [29%] women respectively (p=0.01). Other clinicopathologic characteristics such as grade, tumor size, PR, HER-2/neu, and nodal status of IBRs and CBCs will be presented at the meeting.&amp;#x2028; Conclusion: Extended adjuvant endocrine therapy with letrozole results in fewer IBRs and CBCs compared with placebo as previously reported. Our data suggests that letrozole may decrease both ER+ and ER- IBRs. Letrozole appears to prevent ER+ CBCs but has little or no apparent effect on the development of ER- CBCs. These results need confirmation in the primary prevention trials of AIs.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1134.
Esophageal and Tracheal Activity During Myocardial Scintigraphy with Tc-99m Sestamibi
Authors: W Araujo, M Kamran, M Mirzai, E G DePuey
Journal: Clinical Nuclear Medicine (2000)

A 78-year-old woman underwent a dipyridamole stress test with Tc-99m sestamibi after a myocardial infarction. Her course of hospitalization had been complicated by upper gastrointestinal bleeding, respiratory failure resulting from aspiration pneumonia that required tracheostomy and mechanical ventilation, and a cerebrovascular accident that required a gastrostomy tube for feeding. Myocardial perfusion SPECT showed apical ischemia. Marked intraluminal gastric activity, extending throughout the entire esophagus and into the trachea, was observed incidentally. This finding was observed on planar and SPECT images. The pattern observed was strongly suggestive of duodenogastric reflux, severe gastroesophageal reflux, and subsequent tracheal aspiration.
Commentary: Perspectives in Radiation and Health: Reflections on the International Conference in Beer Sheva
Authors: Keith F. Baverstock
Journal: Environmental Health Perspectives (1997)

Insofar as international conferences reflect the state of development of the subject under discussion, they provide an opportunity to question, at a rather fundamental level, the direction of and progress in the subject.With regard to the effects of radiation on health, many of the problems faced today, including uncertainties in the relationship between risk and dose and the origins of the psychosocial phenomena associated with many aspects of environmental radiation exposure, arise from a lack of adequate frameworks within which to understand the radiopathological impact of radiation exposure and the psychological and social implications of such exposures.It is concluded that in seeking an understanding of the relationship of health effects to exposure, through the underlying radiobiological processes, the perturbation of the dynamic interactions within the components of the organism should receive more emphasis.The public perception of risk from environmental radiation exposures appears to encompass factors in addition to the accrued health detriment.It is argued that the radiological protection of the public might be seen more beneficially in the context of other environmental risks.
The Role of the Emergency Department
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (1996)

Emergency department care for patients whose problems are not true emergencies has become a fashionable scapegoat for the ills of the health care system in the United States. Such care is considered wasteful and expensive and is therefore a prime target for cost-cutting efforts by health maintenance organizations (HMOs) and other insurers.1,2 In 1992, there were 89.8 million visits to the emergency departments of nonfederal, short-stay hospitals in the United States, or 35.7 visits per 100 persons.3 The majority (55.4 percent) were classified as nonurgent. Patients with nonurgent conditions often face long waits at emergency departments; they contribute to . . .
Endoscopic Ultrasound guided Celiac Ganglion Irradiation with Iodine-125 Seeds in Patients with Unresectable Pancreatic Cancer: Results of a Pilot Trial
Authors: Wang Kai-Xuan, Jin Zhen-Dong, Liu Yan, Wang Dong, Zhan Xian-bao, Chen Jie, Li Zhao-Shen
Journal: Endoscopy (2011)

Aims: Celiac plexus neurolysis and block are considered safe but provide limited pain relief. The recent recognition that celiac ganglia can be visualized by endoscopic ultrasound (EUS)now allows direct injection into celiac ganglia for neurolysis (CGN). Radioactive rays have a definite injurious effect on neural tissues.
Hemigastrectomy Combined with Resection of the Vagus Nerves
Authors: Douglas A. Farmer, Reginald H. Smithwick
Journal: New England Journal of Medicine (1952)

MANY surgeons have come to consider subtotal gastrectomy the procedure of choice for duodenal ulcers demanding elective operative therapy. The results of this maneuver are gratifying in most cases. There are, however, two primary causes of dissatisfaction, which although relatively infrequent are sufficiently serious to justify continued efforts to reduce their incidence. One is the development of gastrojejunal ulceration, which is reported to occur in approximately 2 to 5 per cent of cases in most large series.1 , 2 The other is the appearance of certain postoperative sequelae such as intolerance for certain foods, the dumping syndrome, the need for eating frequent . . .
Cytokine gene polymorphism: Influence in the response of bladder superficial carcinoma to the immunotherapeutic with BCG
Authors: M. V. Silva, F. Calais da Silva, D. Ligeiro, H. Trindade
Journal: Journal of Clinical Oncology (2007)

5081 Background: Gene polymorphisms in key immunoregulatory molecules may contribute to the heterogeneity in outcome between individuals with bladder superficial carcinome receiving the immunotherapeutic treatment with BCG. This study aims to verify and identify cytokine gene polymorphisms that could influence the immune response to BCG and antitumoural action in those patients. Methods: We studied 90 patients, after turb and BCG intravesical, there where 72 responders (80 %), 18 non-responders (20%) all patients are multiple or recurrent except T1 G3 or Cis, the median follow up is 4,5 years The cytokines single nucleotide polymorphisms (SNP’s) (IL-1a (-889T/C), IL-1β (-511C/T), IL-1β (3962T/C), IL-1R (970 C/T), IL-1Ra (11100 T/C), IL-4 (-590 C/T), IL4-Ra (+576 G/A), IL-6 (-174 G/C), IL-10 (-1082GA/-819CT/-592CA), IL-12p35 (-916C/T), TGF-β (Codon 10 C/T), TNF-a (488GA/-238GA/-308GA), TNF-β (252 G/A), IFN-γ (+874 T/A)) genotypes were assessed by PCR with Sequence Specific Primers (PCR-SSP). Genotypes and allele frequencies of responders and non-responders (with tumour recidive) to the treatment were compared and evaluated by the two-sided Fisher’s exact test or Chi square and odds ratios (OR) were calculated as an estimate of relative risk. Results: It was found a correlation of cytokine gene polymorphisms to outcome of patients for both the genotype and haplotype TNF-a 488G/-238G/-308G frequencies, which are significantly higher in patients with tumour recidive after BCG treatment (non-responders 72,2% vs responders 42% OR=3,6; 95%CI 1.15 to 11.17 p=0.033). From the other genes studied, we could depict a weak association of the IL-1R 970 T/T genotype, with a higher frequency in non-responder patients (27,8% vs 4.2% in responders, p&lt;0.05) and with IL-10 -1082 A allele also more frequent in non-responders to BCG (75% vs 54,8%; p&lt;0.05). Conclusions: These results suggest that host genetics of immune regulatory molecules may play a role in predicting the antitumoural response after BCG treatment of bladder cancer. Confirmation of these findings in other populations is required. No significant financial relationships to disclose.
A8.23 Carrier-mediated transport systems for specific targeting of tyrosine kinase signalling pathways in rheumatoid arthritis
Authors: S Harrach, B Edemir, E Schlatter, T Pap, G Ciarimboli, J Bertrand
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> Tyrosine kinase inhibitors (TKI) are effective in treating malignant disorders and were suggested to have also an impact on non-malignant diseases such as rheumatoid arthritis (RA). To exert their effect, hydrophilic TKI have to be actively accumulated in target cells by membrane transporters, a process which is known to govern drug efficiency. This study aims to evaluate the importance of transport processes for TKI delivery in inflammatory diseases and their pathology-induced regulation at the example of the RA-treatment with the c-Abl and Src kinase inhibitor Saracatinib (AZD0530). Since Saracatinib is an organic cation and fibroblasts are major players in RA-development, we focused on its interaction with transporters for organic cations (OCTs) in synovial fibroblasts (SFs). <h3>Methods</h3> Saracatinib transport was investigated in OCT-transfected HEK293 cells, in SF from from RA patients (RASF) and from hTNFtg mice (hTNFtg SF) using a HPLC method to quantify intracellular Saracatinib levels. The Saracatinib-transporter was identified in RASF by inhibition with specific competitors and by its siRNA-downregulation. Moreover, the impact of the transport process on the target c-Abl was determined by western blot analysis. Saracatinib transport under disease-relevant conditions like stimulation with TNFa was also assessed. Expression of OCTs in SF after TNFa stimulation was analysed using qRT-PCR. <h3>Results</h3> Transport inhibition experiments in RASF and hTNFtg SF identified OCTN1 (organic cation transporter, novel, type 1) as mediator of the uptake process. OCTN1 transporter function governs effectiveness of saracatinib on tyrosine kinase c-Abl in RASF. The stimulation with TNFa enhanced Saracatinib uptake in RASF by increasing OCTN1 expression. Similarily, Saracatinib uptake was significantly increased in hTNFtg SF compared to wt SF. <h3>Conclusion</h3> The uptake of Saracatinib in SF is mediated by OCTN1, whose activity is up-regulated by RA associated pro-inflammatory cytokines, such as TNFa. For these reasons, Saracatinib seems to be a suitable TKI for treatment of RA. Furthermore, our results show that investigating transporter mediated drug processing is important for developing intracellularly acting drugs used in inflammatory diseases.
Effect of Removal of Planned Parenthood from the Texas Women’s Health Program
Authors: Amanda J. Stevenson, Imelda M. Flores-Vazquez, Richard L. Allgeyer, Pete Schenkkan, Joseph E. Potter
Journal: New England Journal of Medicine (2016)

Texas is one of several states that have barred Planned Parenthood affiliates from providing health care services with the use of public funds. After the federal government refused to allow (and courts blocked) the exclusion of Planned Parenthood affiliates from the Texas Medicaid fee-for-service family-planning program, Texas excluded them from a state-funded replacement program, effective January 1, 2013. We assessed rates of contraceptive-method provision, method continuation through the program, and childbirth covered by Medicaid before and after the Planned Parenthood exclusion.
Abstract 2896: Effects of Calcium and Vitamin D Supplementation on the Inflammation Marker Cyclooxygenase-2 (COX-2) in Normal Colon Mucosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Vincent Chen, Roberd M. Bostick
Journal: Cancer Research (2010)

Abstract To investigate whether calcium and vitamin D reduce the expression of the inflammation marker COX-2 in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n=92) of 2.0 g elemental calcium daily and vitamin D3 800 IU/day, alone and in combination, versus placebo over 6 months. COX-2 expression and colorectal crypt distribution in biopsies of normal-appearing colorectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. COX-2 expression along the entire crypt increased by 4% (p=0.73) in the calcium group and decreased by 3% (p=0.86) and 4% (p=0.73) in the vitamin D3 and joint calcium and vitamin D3 supplementation groups, respectively, relative to the placebo group. The distribution of COX-2 in the colorectal crypts overall or in various regions of the crypt (proliferative zone, differentiation zone, and area closest to contact with colon lumen contents) did not substantially change over follow-up. Our findings did not support the hypothesis that calcium and/or vitamin D3 supplementation can substantially decrease COX-2 expression in the normal appearing colorectal mucosa of sporadic adenoma patients. 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 2896.
THE PROGNOSTIC SIGNIFICANCE OF RENAL DISEASE ACCORDING TO INDICATION FOR PERCUTANEOUS CORONARY INTERVENTION: AN ANALYSIS OF 45,288 PATIENTS FROM THE BRITISH COLUMBIA CARDIAC REGISTRY
Authors: Bilal Iqbal, Imad Nadra, Michael Fryer, Lillian Ding, Anthony Fung, Eve Aymong, Albert Chan, Steven Hodge, Anthony Della Siega, Simon Robinson
Journal: Journal of the American College of Cardiology (2016)
A Sleeping Giant
Authors: Alanna Morris, Sarah Grudberg, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2011)

A 71-year-old woman presented with abdominal pain and night sweats. Four weeks earlier, headache, sinus pressure, and night sweats had developed, and amoxicillin was prescribed for presumed sinusitis. Her symptoms improved, but after 1 week, new abdominal pain developed.
Abstract 256: Distinct roles for gain and loss of function p53 mutations in medullary thyroid cancer
Authors: Nagako Akeno, Xiaolan Ma, Kathryn A. Wikenheiser-Brokamp
Journal: Cancer Research (2010)

Abstract Medullary thyroid carcinoma (MTC) accounts for 5-10% of all thyroid cancers and presents as metastatic diseases in ∼50% of patients. Patients with metastatic MTC are typically incurable because of the poor tumor response to current chemotherapeutics and radiation treatment. MTC occurs as sporadic tumors in ∼75% of cases. The remaining cases are familial and associated with either multiple neuroendocrine neoplasia syndromes or familial MTC syndrome. The Rearranged during Transfection (RET) proto-oncogene plays a key role in MTC development: however, the absence of RET mutations in ∼50% of sporadic cases and the variable clinical manifestations in patients with the same RET mutation provide compelling evidence that other genetic alterations are involved in MTC pathogenesis. Recent studies in human tumors and mouse models suggest that the Rb and p53 pathways cooperate to suppress MTC evolution. Although some p53 mutations cause a loss of function, most p53 mutations detected in human cancers result in expression of a mutant p53 protein which may exhibit gain of function properties. The objective of this study was to identify the function of p53 mutant proteins commonly expressed in human cancers in MTC pathogenesis. A conditional mouse model was generated in which MTC is initiated by Rb inactivation. Using this model, the consequences of p53 mutant protein expression on MTC initiation and progression were compared to p53 deletion. Loss of a single copy of p53 led to accelerated medullary thyroid tumor progression resulting in decreased survival. Loss of both p53 alleles resulted in a markedly more severe phenotype leading to a median survival of 4 months. Expression of the structural p53R172H mutant, but not the DNA contact p53R270H mutant, resulted in accelerated death compared with p53 deletion demonstrating that p53R172H has a gain of function property. Interestingly, mice heterozygous for p53R172H/+ and p53R270H/+ showed similar survival as mice with loss of a single p53 allele providing evidence that neither p53 mutant protein functions in a dominant negative fashion to promote MTC initiated by Rb loss. These results clearly demonstrate that p53 suppresses the progression of MTC initiated by Rb loss and indicate that gain of function p53 mutations confer poorer prognosis than p53 loss. Given the critical roles played by the Rb and p53 pathways in tumor response to therapy, identifying key Rb and p53 functions in MTC pathogenesis is important for future design of therapies to combat these currently treatment resistant malignancies. 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 256.