tbuckley/cabot-search huggingface dataset:
Serum 1,25-Dihydroxyvitamin D Levels in Normal Subjects and in Patients with Hereditary Rickets or Bone Disease
Authors: Charles R. Scriver, Teresa M. Reade, Hector F. DeLuca, Alan J. Hamstra
Journal: New England Journal of Medicine (1978)

The serum concentration of 1,25-dihydroxylvitamin D (1,25-[OH]2D) in normal children and in children with inherited diseases of bone was compared by use of a competitive binding assay. Observed values were: in 12 normal children and adolescents, 37.1 +/- 1.9 pg per milliliter (mean +/- S.D.); in 14 patients with X-linked hypophosphatemic rickets treated with vitamin D2 and phosphate supplements, 15.6 +/- 7.8 (P less than 0.01 versus control); in six patients with autosomal recessive vitamin D dependency treated with vitamin D2, 9.5 +/- 2.9 (P less than 0.01 versus control); and in four untreated patients with autosomal dominant hypophosphatemic (non-rachitic) bone disease, 30.2 +/- 6.3 (not significantly different from the controls). The difference in bone disease between X-linked hypophosphatemia (severe) and hypophosphatemic bone disease (mild) at comparable low serum levels of phosphate implies that 1,25-(OH)2D and phosphate may have independent roles in the pathogenesis of defective bone mineralization.
Abstract 2265: Clinical significance of HER3 expression in curatively resected pancreatic cancer
Authors: Toshiki Hirakawa, Bunzo Nakata, Shinichiro Kashiwagi, Yukihiro Kato, Yuhiko Fuyuhiro, Takehiko Iwauchi, Junko Matsusoka, Gentaro Itoh, Naoki Aomatsu, Mami Yoshii, Tsuyoshi Hasegawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Nobuya Yamada, Masakazu Yashiro, Tetsuji Sawada, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2011)

Abstract Introduction: HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated.HER2/HER3 heterodimer is likely to be the most effective complex for activating downstream pathways.Because of special importance of HER2/HER3 heterodimer in tumorgenesis, the signaling pathways and downstream effectors of the HER family become key molecules in the strategy of cancer therapy.HER3 is overexpressed in diverse human cancers, and has been associated with poor prognosis in breast, lung, and ovarian cancer.The objective of this study was to evaluate the significance of HER3 expression in pancreatic cancer cells. Material and Methods: A total 86 patients were enrolled.The pancreatic cancers were stained with antibodies against HER3 by immunohistochemistry. HER3 expression was evaluated by intensity of staining.Intensity was given scores 0-3 (score 0:no staining, score1+:barely perceptible staining, score2+:moderate staining, score3+:strong staining). Scores of 0 and 1+ were considered to be negative for HER3 expression, while 2+ and 3+ were considered to be positive (overexpression).We examined the association between HER3 expression and other clinicopathologic variables. Results: HER3 expression was positive in 36 (41.9%) cases.There were no significant correlation between HER3 expression and other clinicopathological factors. The prognosis of HER3 positive patients was significantly poorer than that of HER3-negative patients (p=0.002). A univariate survival analysis revealed that HER3 overexpression, intrapancreatic nerve invasion and T category were significantly correlated with patient survival. A multivariate analysis showed HER3 overexpression was an independent predictor of worse prognosis in resectable pancreatic cancer. Conclusion: The expression of HER3 might be a novel predictive prognostic marker for patients with pancreatic cancers. 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 2265. doi:10.1158/1538-7445.AM2011-2265
PTH-073 Social Media use by Inflammatory Bowel Disease and Viral Hepatitis Patients and Potential Application for Healthcare
Authors: C Timms, D Chan, J-Y Kang, D Forton, A Poullis
Journal: Gut (2013)

<h3>Introduction</h3> Currently, inflammatory bowel disease (IBD) and viral hepatitis management involve regular visits to hospital clinics. This requires frequent time taken out of work and family life to attend. This study investigates patients’ current social media use and attitude toward the potential role social media could have in reducing their hospital visits. <h3>Methods</h3> Over a one month period (November 2012), IBD and hepatitis B and C patients attending the Gastroenterology and Hepatology Outpatient Departments of St. George’s Hospital were identified. Convenience sampling was used; all IBD and hepatitis B and C patients encountered in these clinics were asked to participate. Patients were asked to complete a questionnaire, gathering information about their disease, current use of social media and their views about social media in the management of their disease <h3>Results</h3> 180 patients participated in the study: 95 patients were male and 85 were female. The combined mean age was 38.9 years (range of 15–85 years). 112 patients had IBD and 68 had viral hepatitis. The mean age for the IBD patients was 39 years (range 16–85 years) and the mean age for the hepatitis patients was 38.6 years (range 15–63 years). 46 (43.75%) of the IBD patients and 49 (72%) of the hepatitis patients were male. In our study, 82.1% of the IBD and 72.1% of the viral hepatitis patients used one or more social networking site. Facebook was the most popular site. 29.5% of the IBD and 33.8% of the viral hepatitis patients used social media for support with their illness. 80.4% of the IBD patients and 72.9% of the viral hepatitis patients said they would be happy with some form of social media interaction by healthcare professionals. 84.8% of the IBD patients and 72.1% of the viral hepatitis patients were in favour of a specific social media website for their disease. <h3>Conclusion</h3> A large proportion of patients with IBD and viral hepatitis already use social networking sites. This study suggests that the majority of both IBD and viral hepatitis patients would welcome the use of social media as part of their illness management. There are already some social media sites that have been setup for these patient groups. Increasing the awareness of these sites and further research investigating the integration of social media into the current management of both these patient groups is needed. <h3>Disclosure of Interest</h3> None Declared.
Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair–Proficient Stage II Colon Cancer
Authors: Pradipta Ghosh, Jeanne Tie, Andrea Muranyi, Shalini Singh, Patrick Brunhoeber, Katherine Leith, Rebecca Bowermaster, Zhiming Liao, Yifei Zhu, Bonnie LaFleur, Ben Tran, Jayesh Desai, Ian Jones, Matthew Croxford, Rodrigo Jover, Ajay Goel, Paul Waring, Song Hu, Volker Teichgraber, Ulrich-Peter Rohr, Ruediger Ridder, Kandavel Shanmugam, Peter Gibbs
Journal: Clinical Cancer Research (2016)

Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients.Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated.For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12].GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms. Clin Cancer Res; 22(14); 3488-98. ©2016 AACR.
PTH-036 End Of Life Care In Liver Disease
Authors: F Chiplen, S Lawton, G Linklater, S Salunke, L Cogdell, A Fraser, B Vijayan
Journal: Gut (2014)

<h3>Introduction</h3> Living and Dying Well: a national action plan for palliative and end of life care for Scotland calls for the identification, assessment, monitoring and care planning for palliative patients, irrespective of diagnosis or location. The primary aim of this project was to audit the assessment, care planning and recording of palliative status in the Gastroenterology Department in Aberdeen. <h3>Methods</h3> Patients who died of chronic liver disease between July 2011 and May 2012 were identified using a retrospective notes review approach. A data capture sheet was devised in consultation with Senior Medical staff from the Gastroenterology and Palliative Medicine Departments. <h3>Results</h3> Twenty patients were identified. The audit standard of 90% was met in the following: dying recognised and recorded in the medical notes; dying recognised and recorded in the nursing notes; DNACPR in place; record of discussion with the family and agreed plan with family; anticipatory prescribing. The 90% standard was not met for medication review, discontinuing unnecessary medication or non-essential monitoring/ interventions. None of the prognostic tools examined (MELD, Child Pugh, MI, GAHS) showed high sensitivity for recognising poor prognosis in this patient group. Almost all the patients who died in the acute sector had been admitted as unscheduled emergencies. None had any evidence of pre-admission advance care planning. <h3>Conclusion</h3> This audit demonstrated a high standard of end-of-life care in the GI unit despite the difficulties identified in prognosticating in this patient group. There is a need to further explore whether advance care planning is possible and practicable for patients with chronic liver disease. <h3>Reference</h3> Scottish Government <i>Living and Dying Well: A National Audit Plan for Palliative and End-of-Life Care in Scotland </i>The Scottish Government Edinburgh September 2008 <h3>Disclosure of Interest</h3> F. Chiplen: None Declared, S. Lawton: None Declared, G. Linklater: None Declared, S. Salunke Grant/research support from: Shire Innovation award for registrars, L. Cogdell: None Declared, A. Fraser: None Declared, B. Vijayan: None Declared.
100 BASELINE MODELS HELP IN IDENTIFYING RESPONDERS TO CORTICOSTEROIDS IN SEVERE ALCOHOLIC HEPATITIS: A MULTICENTER STUDY ON MORE THAN 600 PATIENTS
Authors: A. Louvet, F. Artru, M. Colin, G. Lassailly, E. Diaz, J.G. O'Grady, J. Boursier, R.L. Carithers, S. Naveau, P. Deltenre, V. Canva-Delcambre, S. Dharancy, T.R. Morgan, P. Mathurin
Journal: Journal of Hepatology (2012)
AB0972 Pain in knee osteoarthritis seems to be not associated with ultrasonographic joint effusion
Authors: H. Rkain, I. Ben Slama, L. Traki, I. Bouaddi, L. Bouazzaoui, F. Allali, N. Hajjaj Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In this study, we have included 29 patients with knee osteoarthritis. We analyzed whether the presence and/or intensity of pain were associated with the presence of US joint effusion. <h3>Objectives</h3> The aim of this study was to search eventual association between ultrasonographic (US) knee effusion and pain in patients with knee osteoarthritis (OA). <h3>Methods</h3> 29 patients (mean age 59.5 [50-76] ± 8.7 years) with bilateral knee OA according to ACR criteria (median 24 months of evolution (11.48)) were included. Pain was measured by the visual analog scale from 0 to 10 cm. A knee US examination was performed in all patients by a blinded rheumatologist with good experience in ultrasonography. The effusion was searched in three regions: the sub-quadriceps cul-de-sac, the medial and lateral patellar retinacula. We analyzed whether the presence and/or intensity of pain were associated with the presence of US joint effusion. <h3>Results</h3> 58 osteoarthritic knees were studied. Pain on clinical examination was found on 44 knees (75.9%). The intensity of pain assessed by VAS of pain was 54.5 [10-80] ± 20.4. The joint effusion was present on ultrasound in 23 knees (39.7%) and was located in the sub-quadriceps cul-de-sac, the medial and lateral patellar retinacula respectively in 27.6%, 25.9% and 8.6% of knees evaluated. We found no association between pain presence and US effusion (p: NS). The pain intensity was also comparable in both groups with and without US joint effusion (49.1% ± 19.5% vs 58±20.5; p: NS). <h3>Conclusions</h3> This study suggests that US joint effusion in patients with knee osteoarthritis is not associated neither with presence nor with intensity of pain. It would be interesting to verify these results with larger studies. <h3>Disclosure of Interest</h3> None Declared
Coexistence of Intussusception and Henoch's Purpura
Authors: I. D. Steinhardt, August F. Jonas
Journal: New England Journal of Medicine (1957)

INTUSSUSCEPTION may closely simulate Henoch's purpura with bleeding into the intestine; accurate diagnosis is of great importance, for the treatment of the first condition is surgical or by barium enema, whereas in the second, operation may prove harmful. Yet the two conditions may coexist, and failure to realize this and act promptly may cost the patient's life. Since Vierhuff1 reported the coincident occurrence of anaphylactoid purpura and intussusception in 1893, 24 cases have been recorded in the literature. An additional case is here presented, with a review of the subject.Case ReportL.H. (K.F.H. 414947), a 5-year-old girl, was admitted . . .
Dissemination of<i>Neisseria meningitidis</i>
Authors: Vincent Quagliarello
Journal: New England Journal of Medicine (2011)

Infection of the mucosal epithelium of the nasopharynx by Neisseria meningitidis can lead to systemic invasion, resulting in fulminant sepsis and meningitis. A recent study divulges a molecular event relevant to the dissemination of the bacterium.
Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients
Authors: S Szymanski, J A Lieberman, J M Alvir, D Mayerhoff, A Loebel, S Geisler, M Chakos, A Koreen, D Jody, J Kane
Journal: American Journal of Psychiatry (1995)

Gender differences in onset of illness, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. Patients with first-episode schizophrenia were examined to determine whether gender differences also occur in these patients.Fifty-four neuroleptic-naive schizophrenic patients (29 men and 25 women) were studied beginning in an initial stage of the first hospitalization for psychosis while undergoing treatment with a standardized medication regimen. Before antipsychotic drug treatment and during 1 year of follow-up each patient was rated on the Schedule for Affective Disorders and Schizophrenia--Change Version (psychosis and disorganization items), Scale for the Assessment of Negative Symptoms, Clinical Global Impression, modified Simpson Tardive Dyskinesia Scale, and Simpson-Angus Rating Scale for extrapyramidal side effects. Methylphenidate challenge testing was done at study entry. Plasma neuroleptic, homovanillic acid (HVA), and prolactin levels were determined weekly for the first 6 weeks.The female schizophrenic patients had a later onset and better treatment response than the men. Plasma HVA levels at baseline and week 1 and changes in prolactin levels from baseline to weeks 1 through 6 were greater among the women.Gender differences in onset and degree of treatment response in first-episode schizophrenic patients are similar to those of chronic patients and are apparent at early stages of the illness. The greater pharmacologic responsivity of the female patients, as indicated by the neuroendocrine results, is consistent with the gender difference in degree of symptom improvement with medication.
Tumor Lysis Syndrome Following Treatment with 2-Chlorodeoxyadenosine for Refractory Chronic Lymphocytic Leukemia
Authors: Eldad J. Dann, Shmuel Gillis, Aaron Polliack, Elimelech Okon, Deborah Rund, Eliezer A. Rachmilewitz
Journal: New England Journal of Medicine (1993)

The deoxyadenosine analogue 2-chlorodeoxyadenosine is an effective and relatively nontoxic treatment for hairy-cell leukemia1 and other B-cell neoplasms, including chronic lymphocytic leukemia (CLL)2,3. In a recent study of 90 patients with CLL, including 62 with advanced disease, the overall rate of response was 44 percent, the most severe toxic effect being myelosuppression4. Excellent responses were recently reported in four patients who did not respond to fludarabine therapy, with myelosuppression as the only untoward side effect5. We report the occurrence of tumor lysis syndrome after the infusion of 2-chlorodeoxyadenosine in a patient with CLL and bulky lymphadenopathy. . . .
Abstract 584: Identification of mutations in HSV-1 envelope glycoprotein B that enhance retargeted infection
Authors: Hiroaki Uchida, Janet Chan, William F. Goins, Paola Grandi, Izumi Kumagai, Justus B. Cohen, Joseph C. Glorioso
Journal: Cancer Research (2010)

Abstract Conditionally-replicating herpes simplex virus type 1 (HSV-1) vectors, including mutants deleted for the neurovirulence factor ICP34.5 currently in clinical trials, are promising agents for oncolytic virotherapy. As an alternative strategy to accomplish cytocidal HSV replication exclusively in cancer cells, we have designed modified viral envelope glycoproteins to limit virus entry uniquely to EGF receptor (EGFR)-bearing cells. HSV-1 entry is initiated by the interaction of glycoprotein D (gD) with one of its receptors, herpesvirus entry mediator (HVEM) or nectin-1. Receptor binding results in a conformational change in gD triggering activation of gB and gH as the effectors of fusion between the viral envelope and cell membranes. To target virus entry solely to EGFR-expressing cells, we mutated or deleted gD residues essential for binding to the natural entry receptors and inserted an EGFR-specific single-chain antibody (scFv). Although ablation of virus entry through HVEM and nectin-1 was successful, entry through the EGFR was detectable but inefficient. To address this flaw, we carried out in vitro evolution experiments to isolate gain-of-function mutations that could compensate for defective gD-receptor interactions. We passaged a nectin-1-binding impaired HSV-1 mutant repeatedly through cells expressing a gD-binding impaired nectin-1 until visible plaques appeared. Plaque purification and sequence analysis revealed that each isolate contained the same double mutation in gB. We transferred the gB double mutation into wild-type virus and observed entry into cells that are normally resistant to HSV infection due to the absence of authentic gD receptors. In addition, we found that the mutant-gB virus was capable of entering cells through nectins other than nectin-1, and that entry into nectin-1-bearing cells was markedly accelerated compared to wild-type virus. We combined the gB double mutation with the EGFR-retargeted gD allele and found that this combination yielded increased entry into target cells without raising off-target infection. We are currently expanding this strategy to target other cancer-specific cell-surface markers. By enhancing the efficiency of retargeted infection, the gB double mutation is likely to reduce the need for strong mutations in current oncolytic vectors that not only prevent virus replication in normal cells, but also diminish replication in tumor cells. 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 584.
P683The role of nitric oxide synthase (NOS) and its essential cofactor tetrahydrobiopterin (BH4) in diabetic cardiomyopathy
Authors: D Duglan, R Carnicer, JN Simon, S Chuaiphichai, A Hale, KM Channon, B Casadei
Journal: Cardiovascular Research (2014)

Purpose: Diabetes can impact on cardiovascular health by causing a distinct condition termed "diabetic cardiomyopathy". Its characteristic left ventricular (LV) diastolic dysfunction has been associated with interstitial fibrosis, reduced NO availability, and abnormal calcium handling. However, the early triggers and the underlying cellular mechanisms remain unknown. Here, we investigate changes in vascular and myocardial reactive oxygen species (ROS) and NO availability in a murine model of type 1 diabetes, and evaluate potential beneficial effects of inducing a myocardial-specific increase in the NOS cofactor tetrahydrobiopterin (BH4) on the development of LV dysfunction. Methods: Diabetes was induced in male mice by daily intraperitoneal streptozotocin (STZ) injection (43mg/kg, 5 consecutive days). To augment myocardial BH4 and increase NOS activity, transgenic mice were generated with myocardial-specific overexpression of the rate-limiting enzyme for BH4 synthesis, GTP cyclohydrolase 1 (mGCH1 Tg). Vascular function in isolated aortas was evaluated by isometric tension studies (myograph), NOS activity and biopterins by HPLC, and superoxide production by lucigenin-enhanced chemiluminescence. High-resolution echocardiography was used to assess LV function. Results: After 12 weeks of diabetes, WT and mGCH1 Tg mice showed impaired aortic endothelium-dependent vasodilatation, in association with increased superoxide production and reduced BH4 bioavailability (n=6-10 per group). By contrast, diabetic LV homogenates showed no increase in superoxide generation or reduced BH4:BH2 ratio and no reduction in NOS activity (n=9-12 per group). Nevertheless, in vivo echocardiography revealed significant LV diastolic dysfunction in WT diabetic mice, which was prevented in mGCH1 Tg mice (E'/A' diabetic vs control: 1.52±0.08 vs 1.53±0.08 in mGCH1 Tg; 0.89±0.07 vs 1.35±0.06 in WT, n=9 per group, P<0.01 for the interaction between genotype and diabetes). In line with these results, isolated LV myocytes from WT diabetic mice displayed prolonged relaxation, which was prevented in diabetic mGCH1 Tg (t50 relaxation, diabetic vs control: 105.3±2.8 vs 95.6±2.4 in WT and 77.3±3 vs 73.3±2 in mGCH1 Tg; n=25 cells from 2-5 hearts per group, P<0.05 for the interaction between genotype and diabetes). Conclusions: Impaired LV diastolic function in diabetic mice can be prevented by myocardial GCH1 overexpression in the absence of NOS dysfunction or increased oxidative stress, suggesting that GCH1/BH4 protect the diabetic myocardium by mechanisms other than redressing the local nitroso-redox balance.
Résultat de l'enquête SFED 2011 sur la coloscopie: une semaine d'endoscopie en France
Authors: M Barret, C Boustière, JM Canard, JP Arpurt, D Bernardini, P Bulois, S Chaussade, D Heresbach, I Joly, J Lapuelle, R Laugier, G Lesur, P Pienkowski, T Ponchon, B Pujol, B Richard-Molard, M Robaszkiewicz, R Systchenko, C Cellier
Journal: Endoscopy (2013)

Cette nouvelle enquête prospective évalue la pratique de la coloscopie et ses performances diagnostiques en France.