tbuckley/cabot-search huggingface dataset:
PTH-005 Verifying Patient Reported Family History in the Colorectal Family History Screening Clinic (CFHSC)
Authors: M Pettman, J H Scholefield
Journal: Gut (2013)

<h3>Introduction</h3> National Colorectal Family History Screening guidelines categorise risk based on incidence of familial cancer, type of cancer, age and genetic proximity. High and Medium risk patients are recommended regular or one off screening colonoscopies. Appropriate assessment of risk involves obtaining detailed, relevant and accurate family history information. Incorrect assessment of risk can result in High/Medium risk patients not receiving tests or Low risk patients being subjected to unnecessary invasive and costly colonoscopies. The majority of asymptomatic referrals to the Nurse led CFHSC are from primary care. The family history information supporting referral provided by GP’s is non-standardised. Data provided can often be inaccurate for such reasons as; patients quote the wrong types of cancer, do not relate non bowel associated cancers, mistaking other benign bowel disorders for malignant disorders, and include distant family or family beyond age thresholds. The CFHSC expends significant resource in improving the accuracy and relevance, with respect to guidelines, of the family history information. This is done via a patient questionnaire then verification against medical records and cancer registry. This study aims to quantify the benefits of this verification process. <h3>Methods</h3> All consecutive GP referrals from Jan 2012 to end of Dec 2012 to the Nottingham Nurse led CFHSC were included in this study. Risk based on the family history data was assessed at three sources; based purely on GP information, based on patient questionnaire and finally following verification with the cancer registry and medical notes. Performance of GP referral and patient reported information was compared with the verified history using Chi Squared test. <h3>Results</h3> 54 patients were included in the study. Using GP referral information alone categorised 12 high, 12 upper moderate, 30 lower moderate and no low risk of familial colorectal cancer. Using the patient reported family history screening questionnaire data resulted in 10 high, 11 upper moderate and 29 lower moderate and 4 low risk patients. Final verification with medical records resulted in 8 high, 9 upper moderate, 27 lower moderate and 10 low risk patients. Thus there was a significant reduction in number of colonoscopies required following verification of the family history with 10 (18.5%, Chi Squared 11.4, p &lt; 0.01) patients no longer requiring a colonoscopy based on their confirmed family history data compared with the GP history. <h3>Conclusion</h3> The verification process adds significant value in reducing patient risk and preventing unnecessary screening procedures with an overall 18.5% reduction in colonoscopies requested compared to relying solely on the GP history. <h3>Disclosure of Interest</h3> None Declared.
Placebo-Controlled Fracture Trials in Osteoporosis — Comment on the Article by Stein and Ray
Authors: Clifford J. Rosen, Sundeep Khosla
Journal: New England Journal of Medicine (2010)

We agree with some of the points made by Stein and Ray but disagree about their conclusions. As clinicians, we recognize that fractures reduce the quality of life of patients with osteoporosis and increase the risk of coexisting conditions. Hence, we believe it is not ethical to randomly assign high-risk patients to receive placebo in a trial, nor do we believe that approval by an institutional review board or informed consent from the patient automatically makes a trial ethical. We also agree that physicians should not recruit their own patients into trials. However, we disagree on several points. First, although . . .
Abstract 620: Addition of silibinin to EGFR-TKIs overcomes T790M-mediated drug resistance
Authors: Jin Kyung Rho, Yun Jung Choi, Su Jin Choi, Gi Jeong Cheon, Hye-Ryoun Kim, Cheol Hyeon Kim, Chang-Min Choi, Jae Cheol Lee
Journal: Cancer Research (2010)

Abstract Although epidermal growth factor receptor EGFR tyrosine kinase inhibitors (EGFR-TKIs) produce an initially exhibit an initial dramatic response in lung cancer patients harboring a mutation in the EGFR gene, development of acquired resistanceis almost inevitable. The secondary mutation of T790M is associated with approximately one- half of the cases of acquired resistance. In this study, we investigated whether addition of silibinin to gefitinib or erlotinib could overcome T790M-mediated drug resistance considering that silibinin has various anti-tumor effects including EGFR modulation. Silibinin selectively reduced the activity of the EGFR family (EGFR, HER2 and ErbB3) in lung cancer cells with EGFR mutations, but not in those harboring wild type. In primary and acquired resistant cells with T790M, addition of silibinin enhanced the ability of EGFR-TKIs to down-regulate EGFR signals and to inhibit cell growth. Similarly, the combination of silibinin and erlotinib effectively suppressed the tumor growth in erlotinib resistance-bearing PC-9 xenografts. The results indicate that In conclusion, the addition of silibinin to EGFR-TKIs is can be a promising strategy to overcome T790M-mediated drug resistance. 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 620.
A Large Pheochromocytoma seen on Dynamic Bone Scintigraphy
Authors: NARESH VERMA, SURJIT SINGH-WADHWA, OTILIO M. ARVELA, BARRY S. ELISON
Journal: Clinical Nuclear Medicine (2002)

VERMA, NARESH M.B.B.S.; SINGH-WADHWA, SURJIT F.R.A.C.P.; ARVELA, OTILIO M. F.R.A.C.P.; ELISON, BARRY S. F.R.A.C.P. Author Information
Impaired Action of Thyroid Hormone Associated with Smoking in Women with Hypothyroidism
Authors: Beat Müller, Henryk Zulewski, Peter Huber, John G. Ratcliffe, Jean-Jacques Staub
Journal: New England Journal of Medicine (1995)

The effect of smoking on thyroid function is controversial, and its effect on thyroid hormone action is unknown. We investigated the effects of cigarette smoking in women with various grades of hypothyroidism and in normal women.
Tc-99m Ethyl Cysteinate Dimer Brain Perfusion SPECT in Presurgical Evaluation for Intractable Partial Epilepsy in a Young Infant
Authors: JOHAN FRIBERG, PHILIPPE CHOQUET, ANNE DE SAINT-MARTIN, DOMINIQUE CHRISTMANN, OLIVIER JOANNY-FLINNOIS, CHRISTIAN SAINTE-ROSE, EDOUARD HIRSCH, MICHEL FISCHBACH, IZZIE NAMER, ANDRE CONSTANTINESCO
Journal: Clinical Nuclear Medicine (2001)

FRIBERG, JOHAN M.D.; CHOQUET, PHILIPPE Ph.D.; DE SAINT-MARTIN, ANNE M.D.; CHRISTMANN, DOMINIQUE M.D.; JOANNY-FLINNOIS, OLIVIER M.D.; SAINTE-ROSE, CHRISTIAN M.D.; HIRSCH, EDOUARD M.D.; FISCHBACH, MICHEL M.D.; NAMER, IZZIE M.D.; CONSTANTINESCO, ANDRE M.D., Ph.D. Author Information
Economic evaluation of DVd versus VAd in the treatment of multiple myeloma: Results from a phase III multicenter randomized clinical trial
Authors: R. M. Rifkin, M. Hussein, R. Iskandar, A. O’Sullivan, D. Thompson, J. Forlenza, S. Fruchtman, M. Wildgust, L. McGarry
Journal: Journal of Clinical Oncology (2006)

6050 Background: A randomized Phase III clinical trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone (DVd) versus conventional doxorubicin, vincristine, and reduced-dose dexamethasone (VAd) found similar efficacy in the treatment of newly-diagnosed multiple myeloma (Cancer, in press). However, observed clinical advantages of DVd included less toxicity and supportive care. (Cancer In press). Methods: This economic evaluation was conducted as a piggyback to the clinical trial. Utilization data were collected prospectively for enrolled patients (DVd = 97; VAd = 95). Costs were estimated by applying standard US unit costs in 2004 to observed utilization. We compared resource utilization and costs for study drug administration, other care (hospitalizations due to AEs, tests, transfusions, and concomitant medications), and total costs during follow-up for patients receiving DVd versus VAd using 2-sided t-tests. Results: DVd patients required significantly fewer hospital (1.5 vs 8.5; p &lt; 0.01) and clinic days (4.8 vs 14.4; p &lt; 0.01) for study drug administration. Costs of study drug were significantly higher for DVd patients ($16,181 vs $788; p &lt; 0.01), but lower hospitalization costs ($3,311 vs $18,492; p &lt; 0.01) and clinic costs ($797 vs $2,412; p &lt; 0.01) for drug administration more than offset these costs, resulting in nominally lower overall study drug administration costs for DVd versus VAd ($20,289 vs $21,692; p = 0.64). No other component of care differed significantly between the two groups (costs of other care: $14,152 for DVd vs $14,154 for VAd; p = 0.99) and overall treatment costs ($34,442 for DVd vs $35,846 for VAd; p = 0.76) were similar in the two groups. DVd patients had approximately 10 additional days of follow-up over the trial period (149.4 vs 139.2) versus VAd patients. Conclusions: Despite higher drug acquisition costs, use of DVd did not increase the overall cost of treatment compared to VAd. [Table: see text]
Abstract 3971: Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas: Loss of microRNA-101 promotes overexpression of histone methyltransferase EZH2
Authors: Osamu Nakahara, Hiroshi Takamori, Yasuo Sakamoto, Hiroshi Tanaka, Akira Chikamoto, Kei Horino, Toru Beppu, Yumi Honda, Ken-ichi Iyama, Hideo Baba
Journal: Cancer Research (2011)

Abstract BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) include various degree of dysplasia, and are supposed to be one of the precursors of pancreatic ductal adenocarcinoma (PDCA), however, IPMN carcinogenesis has not yet been established. MicroRNAs (miRNA) may be directly implicated in some carcinogenic process. These miRNAs can function as tumor suppressors or oncogenes. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target genes, and plays a pivotal role in the etiology of tumorigenisity in several cancers. PURPOSE: This study aimed to (1) evaluate whether expression of EZH2 promotes neoplastic progression of IPMN and PDCA, and (2) elucidate regulation of EZH2 expression by miR-101. METHODS: EZH2 mRNA and protein expression was investigated in eight human pancreatic cancer cell lines (PANC-1, PK8, PK9, PK-59, KLM-1, MIA PaCa2, Hs-700T, PK-45P) by PCR and western blotting. Pre-miR-101, and anti-miR-101 was transfected into pancreatic cancer cells to elucidate regulation of EZH2 by miR-101. To evaluate whether EZH2 modulates malignant progression of IPMN, EZH2 expression in both benign and malignant IPMN was examined in 54 patients by immunohistochemistry. Next, we collected malignant and benign cells from formalin-fixed paraffin-embedded samples of IPMNs using laser capture microdissection, and extracted RNA. MiR-101 expression in IPMN was assessed using real-time PCR. RESULTS: All pancreatic cancer cell lines expressed EZH2 mRNA and protein. The induction of miR-101 by transfection of pre-miR-101 in MIA PaCa-2 was closely related to a reduction in EZH2 protein production compared with control, whereas there was little difference in the expression of EZH2 mRNA. Anti-miR-101 transfected pancreatic cancer cells showed increase in EZH2 protein, while EZH2 mRNA level was not elevated. Immunohistochemistry revealed that the expression of EZH2 was significantly higher in malignant than benign IPMN. Expression of MiR-101 was significantly lower in malignant than benign IPMN. CONCLUSIONS: MiR-101 targets EZH2 at the posttranscriptional level, and loss of miR-101 could be a trigger for the adenoma-carcinoma sequence of IPMN by up-regulation of EZH2. This study suggests miR-101- EZH2 blockade as a potential therapeutic target in IPMN carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3971. doi:10.1158/1538-7445.AM2011-3971
Abstract 2846: SNPs in apoptosis and cell cycle control related genes and brain tumor risk among children in Korea
Authors: Sujee Jeon, Sohee Han, Kyoung-Mu Lee, Ae Kyung Park, Hyo Seop Ahn, Hee Young Shin, Hyoung Jin Kang, Hong Hoe Koo, Jong Jin Seo, Ji Eun Choi, Ho Kim, Daehee Kang
Journal: Cancer Research (2010)

Abstract Objective In a hospital-based case-control study in Korea, we evaluated the association between polymorphisms in genes involved in apoptosis and cell cycle control and brain tumor risk among children. Methods Incident brain tumor cases (n=70) and non-cancer controls (n=254) were recruited from three teaching hospitals in Seoul between May 2003 and August 2006. Information on the characteristics of children and their parents were collected by trained interviewers using structured questionnaire. Tagging single-nucleotide polymorphisms (SNPs) were selected using a pairwise linkage-disequilibrium (LD) based algorithm (n=304) were genotyped for 43 cases and 153 controls in this study. Odds ratios (ORs) and 95% confidence intervals (CIs) for SNP genotypes were estimated using unconditional logistic regression adjusted for age and birth weight. The false discovery rate (FDR) was estimated to evaluate the probability of false positive associations; we considered FDR &amp;lt;0.2 as noteworthy. Results Eleven tag SNPs in six genes, AICDA, LMO2, MYC, BCL2, BCL2A1, and CASP7 were significantly associated with childhood brain tumor (Ptrend&amp;lt;0.05). Two SNPs (rs12306110 and rs3794318) in AICDA gene, encoding activation-induced cytidine deaminase, remained significant after adjusting of multiple tests. These SNPs were in tight LD. The most significant association with childhood brain tumor risk was for the rs12306110 (OR, 0.24; 95% CI, 0.11-0.51). ConclusionOur results suggest that genetic polymorphisms in AICDA may be associated with the risk of brain tumor in childhood. 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 2846.
A10.25 Synovial Tissue Transcriptome and Synovial Fluid Proteome have Stronger Discriminatory Power than Serum in Dissecting Inflammation in RA
Authors: Biljana Smiljanovic, Bruno Stuhlmueller, Silvia Pade, Marina Backhaus, Gerd-R Burmester, Andreas Radbruch, Andreas Grützkau, Thomas Häupl
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is a chronic disease associated with polyarticular inflammation, cartilage and/or bone destruction. Current diagnosis of RA is based on clinical criteria and measurement of non-specific makers of inflammation in the blood. A main challenge in diagnosis of RA is to establish objective criteria able to provide a more detailed insight into joint pathobiology. In search for convenient biomarkers, gene-expression profiles from synovial tissues of RA and osteoarthritis (OA) patients were generated. These profiles were used for selection of candidate biomarkers that were measured at the protein level both in synovial fluid and matched serum samples from RA and OA patients. <h3>Materials and Methods</h3> Gene-expression profiles from synovial tissues of RA and OA patients were generated by Affymtetrix HG-U133A arrays. The BioRetis database was used for array analyses and selection of RA candidate genes. ELISA and multiplex immunoassays were used for validation of the candidate markers at the protein level. <h3>Results</h3> Transcriptome analyses of synovial tissues from RA and OA patients revealed more than 1000 differentially expressed genes. Genes involved in chemotaxis, inflammation, cell adhesion and activation were strongly up-regulated in patients with RA. In total, 20 genes out 1000 were used for validation at the protein level, including 1) cytokines: IL8, MIF, MIG, CXCL13, CCL18; 2) the shedded form of membrane molecules: sCD14, sCD163, sCD44, uPAR, sICAM1, sVCAM1, P- Selectin, E-Selectin; and 3) markers related to bone destruction and bone formation: NTxI and PINP. These molecules were measured both in SF and matched serum samples from RA and OA patients. Protein levels of all these markers were elevated in SF of RA patients, showing an obvious inflammatory profile that clearly discriminated RA from OA. Serum levels of these markers were elevated in RA patients, compared to OA and/or healthy donors (ND) as well. Among all serum markers CXCL13, sCD14, CCL18, PINP and NTxI disclosed the highest level of specificity and sensitivity. Nevertheless, the potential of serum markers in general to discriminate RA from OA and/or ND was far weaker compared to those in SF. <h3>Conclusions</h3> Disease-specific profiles were evident in the joint where both synovial tissue transcripts and related SF proteins revealed a clear differences between RA and OA. Despite blood is a favourable diagnostic material, the results from this study indicated that the capacity of blood to dilute and neutralise inflammation is robust enough to limit discrimination between RA and OA.
Norms, goals, and the study of thinking
Authors: Raymond S. Nickerson
Journal: Behavioral and Brain Sciences (2011)

Abstract Elqayam &amp; Evans (E&amp;E) argue that the major objective of research on human thinking should be the development of descriptive theories, and they challenge normativism – “the belief that people ought to conform to a normative standard” (target article, sect. 1, para. 10). I contend that although their argument for the importance of developing descriptive theories is compelling, normative theories are also important, not only for improving thinking but for investigating and understanding it as well.
Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical-Cord Blood from Unrelated Donors
Authors: Mary J. Laughlin, Juliet Barker, Barbara Bambach, Omer N. Koc, David A. Rizzieri, John E. Wagner, Stanton L. Gerson, Hillard M. Lazarus, Mitchell Cairo, Cladd E. Stevens, Pablo Rubinstein, Joanne Kurtzberg
Journal: New England Journal of Medicine (2001)

Umbilical-cord blood from unrelated donors who are not HLA-identical with the recipients can restore hematopoiesis after myeloablative therapy in children. We studied the use of transplantation of umbilical-cord blood to restore hematopoiesis in adults.
AB0872 Inflammatory bowel disease associated arthropathy: A single center cohort report
Authors: C. Ponte, E. Vieira-Sousa, C. Miranda Rosa, J.A. Pereira da Silva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Arthritis is the most common extraintestinal manifestation of inflammatory bowel disease (IBD) and occurs in 9 to 53% of the patients with this disease. IBD associated arthropathy is considered a subtype of seronegative spondyloarthropathy, with axial, peripheral, or a combination of both joint manifestations. <h3>Objectives</h3> To evaluate the different types of joint involvement in patients with the diagnosis of Enteropathic arthritis at a single institution during five years. <h3>Methods</h3> Chart review, from 2006 to 2011, of all patients diagnosed as having Enteropathic arthritis at the Rheumatology outpatient clinic of Santa Maria Hospital, Lisbon. <h3>Results</h3> Sixty five patients, 26 men (40,0%) and 39 women (60,0%), were identified as having IBD: 45 with Crohn's disease (CD) and 25 with ulcerative colitis (UC). The mean age was 48,4 years [range 20-81 years]. The gastroenterological initial disease manifestations occurred at a mean age of 31,2 years [range 11-60 years] and the joints involvement started at a mean age of 35,2 years [range 14-62 years]. In most patients (63.1%) the bowel involvement preceded the arthritic manifestations, especially in UC (85,0%). Peripheral arthritis was found in 64,6% of the patients (polyarthritis 52.3%, oligoarthritis 45,2% and monoarthritis 2,3%) affecting preferentially the knees (76.2%), ankles (52.4%) and hand small joints (42,9%). Radiographic erosions of de peripheral joints were only seen in 2 patients (hand and feet small joints). Almost half the patients (49,2%) had low inflammatory back pain, started at a mean age of 30.3 years [range 16-50 years]. Radiographic sacroiliitis was found in 36.9% of the patients (27.7% unilateral) and spine involvement in 21,5% (mostly vertebral squaring and syndesmophytes). Results of histocompatibility typing (HLA-B27) were found in 42 patients and only 7 showed HLA-B27 positivity (16,7%): 5 with CD and 2 with UC. Six of them had radiographic sacroiliitis (85,7%) and five (71,4%) had asymmetrical peripheral arthritis. <h3>Conclusions</h3> In our small cohort of patients it was possible to identify a higher prevalence of joint manifestations in patients with CD, when comparing with UC. Peripheral arthritis, especially polyarthitis, was the most frequent type of joint involvement observed. Surprisingly, there were only 16.7% of positive HLA-B27 patients, similar to the prevalence found in the general population. <h3>References</h3> Arvikar SL et al.Inflammatory bowel disease associated arthropathy. Curr Rev Musculoskelet Med. 2011 Jun 28 Holden W et al. Enteropathic arthritis. Rheum Dis Clin North Am 2003; 29:513-530. <h3>Disclosure of Interest</h3> None Declared
Case 24-2011
Authors: Don C. Bienfang, Michael J. McKenna, George N. Papaliodis, R. Gilberto Gonzalez, Anat Stemmer-Rachamimov
Journal: New England Journal of Medicine (2011)

A 36-year-old man was seen because of headaches, confusion, and memory loss, followed by visual and hearing loss. MRI showed hyperintense lesions in the white matter and corpus callosum. Funduscopic examination showed vascular narrowing and beading.