tbuckley/cabot-search huggingface dataset:
Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer's disease
Authors: E Mori, N Hirono, H Yamashita, T Imamura, Y Ikejiri, M Ikeda, H Kitagaki, T Shimomura, Y Yoneda
Journal: American Journal of Psychiatry (1997)

Both the magnitude of brain atrophy and premorbid brain size determine the volume of the brain affected by Alzheimer's disease. To examine the possibility that premorbid brain volume is a determinant of cognitive reserve in patients with Alzheimer's disease, the relation between diffuse brain atrophy and cognitive decline and the impact of premorbid brain size on cognitive decline were studied in patients with Alzheimer's disease.By measuring whole brain volume and intracranial volume in 60 patients with probable Alzheimer's disease, mild to moderate in severity, with the use of high-resolution magnetic resonance imaging and image processing, the authors studied the impact of premorbid brain volume and magnitude of diffuse brain atrophy on cognitive functions. On the basis of the normative brain-calvarium relationship derived from data an 28 healthy adults and the total intracranial volume measure of each patient, the magnitude of brain atrophy and premorbid brain volume were estimated.After control for the effects of age, sex, and education as confounding factors, it was found that the Alzheimer's disease patients' intelligence was correlated both positively with premorbid brain volume and negatively with magnitude of brain atrophy, while impairments in language and memory were correlated with magnitude of brain atrophy but not with premorbid brain volume.These findings partially support the hypothesis that premorbid brain volume is a determinant of reserves against intellectual decline in Alzheimer's disease.
OP0104 Hypouricemia due to high urate renal excretion in septic systemic inflammatory response syndrome
Authors: V. Pardo, M. Andres, J.M. Caturla, E. Pascual
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Uric Acid (UA) is filtered at the glomeruli and absorbed at the tubule, so only 7-12% of the filtered UA is finally excreted. It has been shown that Serum Uric Acid (SUA) can lower during an acute gout flare. These changes in SUA result from an increase in renal fractional excretion of UA (FE_UA) and correlate to the intensity of inflammation. SUA also drops during other acute inflammatory events such as surgical critically ill patients, though pathogenesis remains here unclear. <h3>Objectives</h3> Our aim is to determine whether during overwhelming septic systemic inflammatory response syndrome (SIRS) changes in SUA related to alterations in UA renal handling do occur and to gauge its possible significance. <h3>Methods</h3> We prospectively recruited patients meeting established criteria for severe sepsis or septic shock who were admitted in our Intensive Care Unit since May 2010. APACHE II score was used to evaluate clinical severity during the first 24 hours following ICU admission and SUA and FE_UA were measured in each patient. None of them was on UA-lowering medication. The study is ongoing. <h3>Results</h3> 17 consecutive patients (9 men:8 women) with diagnosis of severe sepsis (n=11) and septic shock (n=6) of different origins were included. Age: 73 years (IQR 54-78). Median APACHE II: 17 (IQR 13-24). FE_UA was above 12% in 15 patients (82%). FE_UA median was 22% (IQR 14-40) -normal 7-12%&gt;. SUA median was 2.9 mg/dl (IQR 1.3-5.7). Seven patients (41.2%) had hypouricemia (SUA &lt;2.5 mg/dl). There was an inverse correlation between SUA and FE_UA (p=-0.569 [p&lt;0.05]). Presence of shock associated with lower SUA and higher FE_UA (SUA: p=-0.503 [p&lt;0.05]; FE_UA: p=0.779 [p&lt;0.01]). Noteworthy, FE_UA exhibited a significant positive correlation with APACHE II score (p=0.539 [p&lt;0.05]). <h3>Conclusions</h3> A raised excretion of UA (measured as FE_UA) resulting in low SUA levels was noted in patients with septic SIRS; higher increases in FE_UA correlated with higher APACHE II scores. This strongly suggests that the drop of SUA might be a usual consequence related to acute inflammation that appears largely explained by a higher renal clearance of urate. The underlying urate renal handling mechanisms still need clarification. Whether the relation found with APACHE II may have clinical or prognostic implications requires further studies. <h3>References</h3> [1]Urano J, Rheumatol 2002;29:1950. [2]Giovannini C, Clin Chem Lab Med 2007;45:1207. [3]Chuang CC, Crit Care 2006;10:R36. <h3>Disclosure of Interest</h3> None Declared
THU0082 An evaluation of flare in patients with early rheumatoid arthritis using the omeract preliminary flare questionnaire:
Authors: V.P. Bykerk, S.J. Bartlett, E. Choy, G. Boire, C. Hitchon, J. Pope, C. Thorne, B. Haraoui, E. Keystone, C.O. Bingham
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Domains for assessment of Rheumatoid Arthritis (RA) flare identified by patients (pts) and health care professionals through OMERACT Delphi exercises have included pain, function, stiffness, participation, coping, patient global assessment (PtGAS), fatigue and self-management strategies<sup>1</sup>. <h3>Objectives</h3> To determine how these domains correspond to flare in pts with early RA. <h3>Methods</h3> Pts in the Canadian early ArThritis CoHort (CATCH) completed the OMERACT preliminary flare questionnaire (PFQ) at study visits between 11-2011 and 1- 2012. The PFQ asks pts to indicate if they are in a flare (F) or not (NF), the severity of Flare (0-10 NRS), PtGAS, levels of function, fatigue, pain, stiffness, coping, and participation (0-10 NRS), and to describe self-management strategies. At each visit rheumatologists rated whether their pt was in a flare (0-10 (VAS)). <h3>Results</h3> Of 263 pts answering the PFQ, 30% (79) reported being in a flare (F) and 70% were not in a flare (NF). Mean age (SD) in Flare group was 52.3 (16.6); 77% were female and 68.4% were RF+. RA symptom duration at time of flare ranged from &lt;4 to &gt;48 months. 15% of flares lasted 1-3 d, 20% 4-7 d, 12% 8-14 d, and 53% over14 d. Concordance between physicians and pts was low (kappa =0.4114) overall, but more likely with increasing severity of flare domains (Table). 5% of Flare pts sought help from a rheumatologist; 3% increased steroid doses; 58% used analgesics, and 48% reduced activities. Most used ≥1 self management strategy. <h3>Conclusions</h3> Flares are common in early RA and agreement between patients and rheumatologists as to whether they were in a flare was low overall. Concordance is highest and directly related to increasing severity of patient reported outcomes (PROs) (pain, function, stiffness, coping, participation, PtGAS, and fatigue). PROs across multiple domains during flares are consistent with focus group, Delphi and results of others identifying heterogeneity of symptoms reported by patients when defining flare. These real life data in an early RA cohort also suggest that multiple approaches to self-management are attempted by RA pts experiencing a flare before visiting their physician. <h3>References</h3> Bartlett SJ, et al.,Arthritis Rheum 2011;63(suppl):128. <h3>Disclosure of Interest</h3> V. Bykerk Grant/Research support from: CATCH Study is supported by unrestricted research grants from Amgen, Pfizer, Abbott, BMS, Janssen, Roche, UCB, S. Bartlett: None Declared, E. Choy: None Declared, G. Boire: None Declared, C. Hitchon: None Declared, J. Pope: None Declared, C. Thorne: None Declared, B. Haraoui: None Declared, E. Keystone: None Declared, C. Bingham III: None Declared
BEING ASYMPTOMATIC WITH ATRIAL FIBRILLATION: IS IT A GENETIC TRAIT?
Authors: Sanghamitra Mohanty, Amelia Hall, Prasant Mohanty, Chintan Trivedi, Carola Gianni, Amin Al-Ahmad, John Burkhardt, G. Joseph Gallinghouse, Rodney Horton, Javier Sanchez, Patrick Hranitzky, Luigi Di Biase, Vishwanath Iyer, Andrea Natale
Journal: Journal of the American College of Cardiology (2016)
Abstract 2397: Fat soluble vitamin B1 analogue, benfotiamine, prevents colon cancer cell growth and aberrant crypt foci formation in murine models of colon cancer
Authors: Kota V. Ramana, Ashish Saxena, Ravinder Tammali, Aramati BM Reddy, Satish K. Srivastava
Journal: Cancer Research (2011)

Abstract Chronic inflammatory diseases and oxidative stress are major risk factors of colorectal cancer (CRC), the third most common cause of death among cancer patients. Although several agents such as antioxidants, plant products and nutritional supplements have been shown to have some chemopreventive effects on colon cancer, none are very effective to completely. Recent studies indicate that a fat soluble analogue of vitamin B1, benfotiamine is an excellent antioxidant and anti-inflammatory. However, the chemo-preventive or -therapeutic efficacy of benfotiamine in preventing CRC is not known. Our hypothesis is that benfotiamine through its anti-oxidant and anti-inflammatory properties could be very effective in preventing CRC. We therefore investigated the role of benfotiamine in the prevention of carcinogenic signals leading to CRC in cell culture as well as murine models of CRC. Our results show that treatment of human colon cancer cells (HT-29 and Caco-2) in culture with benfotiamine prevented the cancer cell proliferation. Further, benfotiamine also prevented the growth of human adenocarcinoma cells (SW480) -induced tumor growth in nude mice xenografts. Our studies also indicate that benfotiamine prevented NF-kB-dependent survival signals and activated caspase-3 dependent apoptotic signals in colon cancer cells. Further, benfotiamine supplementation also suppressed azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation in mice and AOM-induced inflammatory changes such as activation of Cox-2 and iNOS, and carcinogenic changes such as expression of cyclin D1 and β-catenin in mice colons. In conclusion, our results indicate that benfotiamine prevents colon cancer cell growth in culture and nude mice xenografts as well as formation of ACF in AOM-treated mice. Thus benfotiamine supplementation could be used as an excellent chemopreventive agent for the treatment of CRC. 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 2397. doi:10.1158/1538-7445.AM2011-2397
Digitalis purpurea (Foxglove)
Authors: J L Naiman
Journal: New England Journal of Medicine (1994)

Figure 1. Digitalis purpurea (Foxglove). In 1775 William Withering demonstrated that the leaves of the foxglove plant alleviated certain forms of dropsy (edema), and in 1799 John Ferriar ascribed their beneficial effects to a primary action on the heart. All physicians have learned about digitalis, but few recognize its plant source. Digoxin, the preparation most commonly used in the United States, is derived from related plants, Digitalis lanata and D. orientalis.
Venous Bypass After Deep Venous Thrombosis Visible on an Early-Phase Bone Scan
Authors: Martin Gotthardt, Désirée Brandt, Horst Kuni, Klaus Joseph
Journal: Clinical Nuclear Medicine (2000)

Bone scintigraphy was performed on a 66-year-old woman because of pain in the left hip 5 years after prosthetic replacement of the joint. Loosening of the prosthesis was suspected. Changes secondary to a prior deep vein thrombosis and superficial vein prominence were seen.
O048 : First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway
Authors: K. Hoeflich, M. Hagel, C. Miduturu, M. Sheets, N. Rubin, W. Weng, N. Stransky, N. Bifulco, J. Kim, B. Hodous, N. Brooijmans, A. Shutes, C. Winter, C. Lengauer, N. Kohl, T. Guzi
Journal: Journal of Hepatology (2015)
Abstract 228: A comprehensive study to functionally classify the BRCA2 missense mutations found in Fanconi anemia patients
Authors: Kajal Biswas, Ranabir Das, Blanche P. Alter, Sergey Kuznetsov, Susan L. North, Stacey Stauffer, Sandra Burkett, Lawrence C. Brody, Stefan Meyer, Andrew R. Byrd, Shyam K. Sharan
Journal: Cancer Research (2011)

Abstract Biallelic mutations in breast cancer susceptibility gene 2 (BRCA2) cause a severe Fanconi Anemia (FA) phenotype that is a rare recessive disorder and reflects the cellular and phenotypic consequences of genetic instability. A number of mutations found in FA patients are missense mutations in BRCA2 and classified as variants of unknown clinical significance. This study is aimed towards the evaluation of functional significance of a few BRCA2 unclassified variants. In this study, six of the human mutations (L2510P, R2336H, I2490T, W2626C, K2729N and IVS7+2T&amp;gt;G) were generated in human BRCA2 gene cloned in a bacterial artificial chromosome vector. The effect of these variants on BRCA2 function was examined by using a mouse embryonic stem (ES) cell-based assay. We have shown the ability of wild-type human BRCA2 and neutral BRCA2 variants to rescue the lethality of Brca2-null mouse ES cells and functionally complement the loss of endogenous mouse Brca2. W2626C and IVS 7+2T&amp;gt;G mutations failed to restore the viability of ES cell colonies after deletion of the endogenous mouse Brca2. The K2729N BRCA2 rescued the ES cell lethality and appeared similar to wild-type BRCA2 in various functional assays. In contrast, L2510P and R2336H BRCA2 exhibited reduced ES cell viability. In addition, ES cells expressing L2510P BRCA2 are sensitive to DNA damaging agents. Furthermore, L2510P BRCA2 mutant ES cells are slow growing, have increased genomic instability, defective in G1-S checkpoint control and show upregulation of p53 and p21. These mutant cells are defective in homologous recombination mediated DNA repair. IVS7+2T&amp;gt;G and R2336H mutations result in exon-skipping leading to premature protein truncation. Alterations in L2510P, I2490T, W2626C and K2729N map to a highly conserved region of BRCA2 and the homology based molecular modeling of the mutant proteins supports our ES-cell results. L2510P and W2626C mutations disrupt the BRCA2 structure and the interaction of BRCA2 with a highly conserved protein DSS1, whereas I2490T and K2729N mutations do not affect the BRCA2 structure and are neutral in nature. It is possible that the patients with the variant alleles that are neutral in this assay have other undetected mutation in that allele or have mutations in some other FA genes. In conclusion, this study provides functional classification of a few variants of unknown clinical significance that should help in counseling individuals carrying these alleles. . 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 228. doi:10.1158/1538-7445.AM2011-228
Preoperative Diagnosis of Pyoadenomyosis With 67Ga SPECT/CT
Authors: En-Tzu Wu, Mei-Fang Cheng, Jie-Yang Jhuang, Jehn-Hsiahn Yang
Journal: Clinical Nuclear Medicine (2013)

Abscess formation inside adenomyosis rarely occurred. A 49-year-old woman had adenomyosis for several years with the symptoms of menorrhagia and dysmenorrhea. She presented with fever of unknown etiology for 3 weeks. 67Ga SPECT/CT demonstrated increased tracer accumulation inside the uterus, which was confirmed as pyoadenomyosis after hysterectomy, and her fever subsided dramatically thereafter. For women with adenomyosis and fever of unknown origin, pyoadenomyosis is a rare but possible cause. 67Ga SPECT/CT is a valuable tool for accurate diagnosis.
Abstract ES3-1: Evaluation of Breast Cancer Predisposition in Different Clinical Venues
Authors: SEE Plon
Journal: Cancer Research (2010)

Abstract DNA sequence-based cancer susceptibility testing of the BRCA1/2 genes is now one of the most commonly ordered genetic tests in the United States. Increasingly sophisticated computer models help to inform the clinician as to the probability of identify a cancer-associated mutation based on both the nature of the tumor, e.g. estrogen receptor status, the age of onset of cancer, presence of ovarian cancer and the family history of the patient. However, even in clearly high-risk families there are additional levels of complexity which impact the cost of the testing, test choice and the usefulness of the results. Whenever possible it is preferable to initiate testing with an individual with cancer first, in order to clarify whether a BRCA1/2 mutation is responsible for the cancer susceptibility. Results of comprehensive sequence analysis can include either negative, deleterious mutation or variant of uncertain significance (VUS). Currently, the potential cancer risk associated with a VUS result is very broad which leads to confusion among providers and patients. Recommendations for further classifying these VUS results into risk stratified categories to aid clinical decision making have been proposed and efforts to implement these recommendations are being initiated by international groups. A key reason to pursue genetic testing is to identify which healthy relatives are at increased of cancer. Thus, to maximize the cost effectiveness of genetic testing, research on how testing is being performed on these downstream relatives is needed. In particular, the most efficient and least expensive testing requires that physicians caring for the relatives have available the detailed test results of the cancer patient. If the cancer patient carries a VUS, then testing of the healthy relative is typically not indicated. If the cancer patient carries a deleterious mutation, then testing of the relative should be for that specific mutation known as single site testing (or familial mutation testing). Our group queried physicians across five different medical specialties (family medicine, internal medicine, obstetrics/gynecology, general surgery and hematology/oncology) for test recommendations of at-risk relatives. The majority of physicians recommended full BRCA1/2 sequencing of a healthy at-risk relative whether provided information that the relative with cancer carried a deleterious mutation or VUS. These findings were not impacted by the physician's own experience with BRCA1/2 testing and potentially result in tenfold higher testing costs compared with national recommendations. Thus, utilization of genetic professionals and improved education of diverse physician specialties about family-centered genetic test decision making may improve efficacy of risk prediction and substantially reduce costs associated with genetic testing for cancer susceptibility. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES3-1.
Abstract 711: The expression of human equilibrative nucleoside transporter 1 (hENT1) is associated with overall survival in advanced biliary tract carcinoma (BTC) treated with gemcitabine
Authors: Akihiro Murata, Ryousuke Amano, Kenjiro Kimura, Nobuya Yamada, Bunzo Nakata, Hisashi Nagahara, Eiji Noda, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Tetsurou Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2012)

Abstract [Introduction] The outcome of patients with unresectable and postoperative recurrent biliary tract carcinoma (BTC) is mostly miserable and most patients are possible candidates for palliative chemotherapy. Gemcitabine is a pyrimidine nucleoside analogue that is commonly used chemotherapeutic agent for advanced BTC. Gemcitabine is transported into the cell mostly by human equilibrative nucleoside transporter 1(hENT1). The hENT1 expression has been demonstrated to play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of the present study was to investigate a predictive marker for good prognosis of gemcitabine chemotherapy for unresectable and postoperative recurrent BTC. [Materials and methods] The analysis was performed on samples from 25 patients with unresectable (6 patients) and postoperative recurrent (19 patients) BTC treated with gemcitabine at the host institute between January 1997 and January 2011. The hENT1 expression levels in tumors were evaluated by immunohistochemistry. The clinical and histopathological variables were analyzed to evaluate predictive values for survival. [Results] Of the 25 tumor specimens, 18 (72%) specimens had positive hNET1 immunostaing, while 7 (28%) specimens were classified as negative. No statistical significant differences were found between the expression of hENT1 and patient characteristics (gender, age, tumor stage, lymph node stage, lymph duct invasion, vascular invasion, perineural invasion). In the univariate analysis, hENT1 expression was significantly correlated with overall survival (OS). The median OS was 15.3 versus 4.2 months, respectively in patients with positive versus negative hENT1 staining (p=0.006). As a result of multivariate analysis, hENT1 expression was useful as a predictive marker for good prognosis with significant difference (p&amp;lt;0.001). [Conclusions] Patients with positive hENT1 expression in BTC have a significantly longer survival after gemcitabine chemotherapy than patients with negative hENT1 expression. Our results suggest that hENT1 expression in advanced BTC patients treated with gemcitabine is a prognostic predictive indicator and is useful to decide gemcitabine chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 711. doi:1538-7445.AM2012-711
VASCULOGENESIS IN VON HIPPEL-LINDAU DISEASE ASSOCIATED TUMORS
Authors: R. R. Lonser, J. Frerich, K. Huntoon, C. Yang, M. Merrill, Z. Abdullaev, S. Pack, S. Shively, G. Stamp, Z. Zhuang
Journal: Neuro-Oncology (2014)

BACKGROUND: Emerging data indicate that von Hippel-Lindau disease (VHL) associated tumors arise from embryologic hemangioblasts that can form vessels (endothelial cells) and blood cells. Nevertheless, the origin of VHL-associated vasculature is not known. To determine the origin of VHL-associated tumor vasculature, we investigated the neoplastic vasculature from VHL patients. METHODS: Microdissected VHL-associated tumor (compared to control non-VHL tissues) vascular features were examined using immunohistochemical staining for CA9, HIF-2a, HIF-1a, CD31 and Factor VIIIa. Origin of tumor vascular elements (tumor versus non-tumor) was assessed by LOH and FISH analysis. Intratumoral vasculogenesis was assessed in vivo using the VHL-deficient UMRC6 renal carcinoma murine xenograft model. RESULTS: We demonstrate that isolated vascular structures and blood vessels within VHL-associated neoplasms (including hemangioblastomas, renal cell carcinoma and pancreatic tumors) are a result of tumor-derived vasculogenesis. Further, similar to hemangioblastomas, other VHL-associated neoplasms possess vascular tissue of tumor origin. Similarly, tumor-derived endothelial cells emerge within implanted VHL deficient UMRC6 renal cell carcinoma murine xenografts. CONCLUSIONS: These findings further establish the embryologic, developmentally arrested, hemangioblast as the tumor cell of origin for VHL-associated hemangioblastomas and indicate that it is also the progenitor cell for other VHL-associated tumors. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.