tbuckley/cabot-search huggingface dataset:
Access to diphtheria antitoxin for therapy and diagnostics
Authors: L Both, J White, S Mandal, A Efstratiou
Journal: Eurosurveillance (2014)

The most effective treatment for diphtheria is swift administration of diphtheria antitoxin (DAT) with conjunct antibiotic therapy. DAT is an equine immunoglobulin preparation and listed among the World Health Organization Essential Medicines. Essential Medicines should be available in functioning health systems at all times in adequate amounts, in appropriate dosage forms, with assured quality, and at prices individuals and the community can afford. However, DAT is in scarce supply and frequently unavailable to patients because of discontinued production in several countries, low economic viability, and high regulatory requirements for the safe manufacture of blood-derived products. DAT is also a cornerstone of diphtheria diagnostics but several diagnostic reference laboratories across the European Union (EU) and elsewhere routinely face problems in sourcing DAT for toxigenicity testing. Overall, global access to DAT for both therapeutic and diagnostic applications seems inadequate. Therefore ? besides efforts to improve the current supply of DAT ? accelerated research and development of alternatives including monoclonal antibodies for therapy and molecular-based methods for diagnostics are required. Given the rarity of the disease, it would be useful to organise a small stockpile centrally for all EU countries and to maintain an inventory of DAT availability within and between countries.
Treatment of Symptomatic Hyponatremia and Its Relation to Brain Damage
Authors: J C Ayus, R K Krothapalli, A I Arieff
Journal: New England Journal of Medicine (1987)

We studied the effects of replacement therapy in two groups of patients with symptomatic hyponatremia. Thirty-three patients, who were studied prospectively, had no evidence of cerebral demyelinating lesions. Their hyponatremia (mean serum sodium concentration [+/- SE], 108 +/- 1 mmol per liter) was increased to 126 +/- 1 mmol per liter with hypertonic saline (856 mM) delivered at a rate of 1.3 +/- 0.2 mmol per liter per hour. The serum sodium concentration did not rise to normal or hypernatremic levels in the first 48 hours of therapy, and none of these patients had a respiratory arrest or other hypoxic episode. Twelve patients, evaluated retrospectively, had evidence of cerebral demyelinating lesions at autopsy or on computerized axial tomography. The rate of correction of hyponatremia (1 +/- 0.2 mmol per liter per hour) was similar to the rate in the patients in Group I. However, at least one of four characteristics was present: an increase in serum sodium to normal or hypernatremic levels in the first 48 hours, a change in the serum sodium concentration of more than 25 mmol per liter in the first 48 hours, a hypoxic-anoxic episode, and an elevation of serum sodium to hypernatremic levels in patients with hepatic encephalopathy. Although these four features were associated with demyelination, our observations suggest that this complication does not depend on the rate of correction of hyponatremia.
SAT0222 Evaluating Mri-Detected Tenosynovitis in Early Arthritis
Authors: W.P. Nieuwenhuis, A. Krabben, W. Stomp, J.L. Bloem, T.W.J. Huizinga, M. Reijnierse, A.H.M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> MRI is a sensitive method to detect local inflammation in Rheumatoid Arthritis (RA). In addition to synovitis and osteitis it also visualizes tenosynovitis. The prevalence of MRI-detected tenosynovitis and its diagnostic and prognostic value in early arthritis are unclear. <h3>Objectives</h3> This study aimed to identify the frequency of MRI-detected tenosynovitis at the metacarpophalangeal (MCP) and wrist joints in early arthritis, the diagnostic value for RA and the association with severity features within RA. <h3>Methods</h3> 178 early arthritis patients included in the Leiden EAC underwent unilateral 1.5T extremity-MRI at baseline. MRI-scans were made and scored using the RAMRIS-protocol. Tenosynovitis was scored at the wrist and MCP joints by two readers using the method as described by Haavardsholm et al.[1]During the first year 69 patients fulfilled the 2010-classification criteria for RA; patients with and without RA were compared. Within RA-patients comparisons were made for anti-citrullinated-peptide-antibody (ACPA)-positivity and for radiographic progression (increase in Sharp van der Heijde score) during the first year. <h3>Results</h3> 65% of the 178 early arthritis patients had MRI-detected tenosynovitis at any of the studied locations. The flexor tendon at MCP-3 and the tendon of the extensor carpi ulnaris were most frequently affected (22% and 34%). Furthermore, tenosynovitis was more often present in RA than non-RA patients (75% versus 59% p 0.023). More commonly affected locations in RA than in non-RA were the tendons of the flexors at MCP-5 (odds ratio (OR) 2.8 95% CI 1.2-7.0), the extensor at MCP-2 (OR 9.1 95% CI 1.9-42.8) and MCP-4 (OR 14.2 95% CI 1.7-115.9) and extensor compartment I at the wrist 4.0 (95% CI 1.4-11.1). The specificity for these locations ranged between 92-99% and the positive predictive value between 61-89%. The associations between tenosynovitis at these locations and RA were independent of the presence of local synovitis. Within RA-patients, the tenosynovitis scores were not associated with the presence of ACPA or radiographic progression during the first year. <h3>Conclusions</h3> MRI-detected tenosynovitis is common in early arthritis and is more common in RA patients than in early arthritis patients with other diagnoses. Locations with a high specificity for RA are the tendons of the flexor at MCP-5, the extensor at MCP-2 and MCP-4 and the first extensor compartment of the wrist. <h3>References</h3> Haavardsholm EA, Ostergaard M, Ejbjerg BJ, et al. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Ann Rheum Dis 2007;66:1216–20. doi:10.1136/ard.2006.068361 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2851
Abstract 728: Molecular mechanisms of resistance to anti-IGF-1R therapies in Ewing's sarcoma
Authors: Cecilia Garofalo, Maria Cristina Manara, Maria Teresa Marino, Pier Luigi Lollini, Piero Picci, Katia Scotlandi
Journal: Cancer Research (2011)

Abstract IGF-1R represents a promising therapeutic target, particularly in sarcomas. Identification of patient selection criteria and understanding the potential mechanisms involved in development of resistance will be crucial for an appropriate and successful design of clinical trials. Here we evaluated efficacy of the anti-IGF-IR monoclonal antibody (HAb) AVE1642, in a panel of sarcoma cell lines and we developed a model of resistance to the anti-IGF-1R human antibody AVE1642 or to the small tyrosine kinase inhibitor (TKI) NVP-AEW541 starting from two highly sensitive Ewing's sarcoma cell lines to identify indicators of intrinsic and adaptive resistance to anti-IGF1R therapies. Cells made resistant to AVE1642 showed same growth ability either in monolayer and in anchorage-independent condition respect to sensitive cells. Notably, resistant cells retained the same level of sensitivity to doxorubicin, vincristine, and ifosfamide as the parental cell lines. Annotation analysis highlighted that the insulin pathway seems to be significant in resistant cells. In fact, these cells showed higher proliferative response to insulin, in keeping with a switch towards insulin pathways sustaining proliferation and malignancy, rather than metabolism. Molecular characterization demonstrate that enhanced IR-A formation and IGF-II production are heavily involved in native and acquired resistance to IGF targeted therapies. This finding was extended to cells resistant to the small tyrosine kinase inhibitor NVP-AEW541. We also show that tumors with low IGF-1R:IR-A ratio are unlikely to greatly benefit from anti-IGF-1R therapies and that the efficacy of anti-IGF-1R therapies should be evaluated in relationship to the IR-A:IGF-1R ratio in cancer cells. Our findings demonstrate a role for IR-A in eliciting intrinsic and adaptive resistance to anti-IGF1R therapies and provide evidences supporting IR-A as an important target in sarcoma therapy. Future trials with these highly selective drugs should involve preselection of patients with tumors that express low levels of IR-A and IGF-2. Studies are supported by grants from the Italian Association for Cancer Research, the Italian Ministry of Health, the Italian Ministry of Research and Instruction and the EU project Eurobonet. 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 728. doi:10.1158/1538-7445.AM2011-728
WHOLE EXOME SEQUENCING IDENTIFIES RECESSIVE FORM OF FAMILIAL HYPOALPHALIPOPROTEINEMIA WITH COMPOUND HETEROZYGOUS MUTATIONS IN ATP-BINDING CASSETTE TRANSPORTER 1 GENE
Authors: Hayato Tada, Atsushi Nohara, Masa-aki Kawashiri, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2015)
Recommendations Endoscopy in inflammatory bowel disease: recommendations from the IBD Committee of the French Society of Digestive Endoscopy (SFED)
Authors: Laurent Peyrin-Biroulet, Guillaume Bonnaud, Arnaud Bourreille, Jean-Baptiste Chevaux, Patrick Faure, Jérôme Filippi, David Laharie, Lucine Vuitton, Philippe Bulois, Florent Gonzalez, Caroline Trang, Stéphane Koch, David Bernardini, Christophe Cellier
Journal: Endoscopy (2013)
Metabolic Effects of Metformin in Non-Insulin-Dependent Diabetes Mellitus
Authors: Michael Stumvoll, Nurjahan Nurjhan, Gabriele Perriello, George Dailey, John E. Gerich
Journal: New England Journal of Medicine (1995)

The metabolic effects and mechanism of action of metformin are still poorly understood, despite the fact that it has been used to treat patients with non-insulin-dependent diabetes mellitus (NIDDM) for more than 30 years.
Data sharing in research: benefits and risks for clinicians
Authors: E. Antman
Journal: BMJ (2014)

The cycle of research begins with identification of an idea, design of the study to answer the scientific question that is posed, conducting and analyzing the findings, and publishing the results. Figure 1 shows the position of the open source, open data, and open access components of the open science concept superimposed on the cycle of research.⇓ One can readily advocate, in principle, for open data to provide doctors and their patients all the data needed for optimum decision-making (figure 2).⇓ 1 



Figure 1 Research cycle. JAHA— Journal of the American Heart Association is an example of an open access publication





Figure 2 Advantages of open data



To illustrate the issues involved, however, consider the flow of data when a clinical trial is completed (figure 3).⇓ A series of raw databases are created. They are populated from the case report forms, and contain patient level information on such topics as baseline demographics, concomitant medications, study drug compliance, suspected endpoint events, clinical laboratory data, and adverse events. Other raw databases might include the final adjudication by the blinded endpoint committee as to whether an endpoint occurred, genetic data, quality of life survey results, and core laboratory data. A data dictionary is developed to link the information from the raw databases to several derived databases that cover items such as endpoints, time to event, and allocation to treatment arm. The derived databases are the source from which data tables are generated for preparation of manuscripts that ultimately appear in the medical …
COMMUNICATION PREFERENCES FOR ADVANCE CARE PLANNING IN ADULTS WITH CONGENITAL HEART DISEASE
Authors: Lisa X. Deng, Lacey P. Gleason, Abigail May Khan, David Drajpuch, Stephanie Fuller, Leah A. Goldberg, Christopher E. Mascio, Sara L. Partington, Lynda Tobin, Yuli Y. Kim, Adrienne Kovacs
Journal: Journal of the American College of Cardiology (2015)
Resolution of Hyperparathyroidism, Renal Osteodystrophy and Metastatic Calcification after Renal Homotransplantation
Authors: A. C. Alfrey, D. Jenkins, C. G. Groth, W. S. Schorr, L. Gecelter, D. A. Ogden
Journal: New England Journal of Medicine (1968)

In 17 patients followed for an average of 18 months after renal homotransplantation, mean phosphate clearance was 18 ml per minute, tubular reabsorption of phosphate 60 per cent, and creatinine clearance 58 ml per minute. Calcium infusion tests performed in six were abnormal in all but one. Bone disease present in five patients improved or resolved in the post-transplant period. Hypercalcemia developed one and a half to six months after transplantation in nine patients, probably because of hyperparathyroidism present since operation but unmasked when phosphorus depletion was induced by aluminum hydroxide, with consequent increased hypercalcemia, hypercalciuria and negative calcium balance. In seven patients the hypercalcemia was mild and resolved when the antacid was changed to aluminum phosphate. One patient was given long-term phosphorus supplementation, and one required parathyroidectomy for control of hypercalcemia.
A5.18 Impact of Rituximab on Synovial Gene Expression
Authors: Yasser M El-Sherbiny, Sarah Churchman, Paul Emery, Edward M Vital, Frederique Ponchel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> Quality and duration of rituximab therapy response in rheumatoid arthritis have not been totally explained. In the synovium, three studies have indicated a relationship between higher plasma cell numbers at baseline and worse, or shorter lasting responses [1–3]. In this study we measured synovial expression of genes involved in B-cell biology, cell survival, cell trafficking and inflammation. <h3>Methodology</h3> Synovial arthroscopic biopsies were collected and snap frozen from patients at baseline and 26 weeks after rituximab. Immunohistochemistry was performed for CD3, CD19, CD20cy, CD138 and CD68 and scored for positive cells/mm<sup>2</sup> using digital image analysis. The remainder of the tissue was used for RNA extraction. A 48 gene custom Taqman array was designed, including genes for cell lineage markers (CD19, CD20, CD3, CD138 &amp; CD68), BAFF-APRIL system, immunoglobulins, cytokines, chemokines and adhesion molecules or cell trafficking. Informative data are available from 32 biopsies pre-Rituximab treatment and 23 post-treatment. Unsupervised clustering was performed to all gene expression to all patients pre and post rituximab. <h3>Results</h3> Clustering of gene expressions revealed 3 main groups pre-rituxmab synovial biopsies, a definite cluster of B cell/survival factors signature associated low expression other genes synovial biopsies was associated with a higher disease activity (DAS28) at baseline and after treatment compared to the other two groups pooled together. This resulted in a lower rate of EULAR Good response. Comparing EULAR responders and non-responders, there were trends to higher baseline CD20 gene expression in non-responders (p = 0.079) and greater reduction in CXCL13 (p = 0.066) and MMP (p = 0.024) in responders. Lower expression of ICAM (p = 0.021), FGF (p = 0.044), CD20 (p = 0.055) and p53 (p = 0.025) and higher expression of APRIL (p = 0.029) at baseline was associated with normalisation of CRP after therapy. Furthermore, these patients also showed a significantly greater reduction in expression of CD4, CD55, CD68, CXCL12, EGF, FGF, ICAM, PECAM, STAT5, TGF-beta, APRIL and BAFF (all p &lt; 0.05). <h3>Conclusions</h3> Results point to key differences in synovial gene expression in patients with clinical response to rituximab, obviously in relation with genes involved in cell trafficking and survival. <h3>References</h3> 1. Teng <i>et al</i>, <i>A&amp;R</i> (2008) 56(12). 2. Thurlings <i>et al</i>, <i>ARD</i> (2008) 67. 3. Vital <i>et al</i>, <i>EULAR</i> 2012.
Prospective Evaluation of the Eyeball Test for Assessing Frailty in Patients With Valvular Heart Disease
Authors: Aisha Ahmed, Paul Sorajja, Akila Pai, Nicholas Plimpton, Richard Bae, Wesley A. Pedersen, Lisa Tindell, R. Saeid Farivar, Kevin Harris, Mario Gössl
Journal: Journal of the American College of Cardiology (2016)
PTU-290 What’s on offer for patients presenting to a giant (gi and nutrition team) clinic in a specialist cancer centre?
Authors: A Muls, A Lalji, H Andreyev
Journal: Gut (2015)

<h3>Introduction</h3> GI toxicity experienced by patients related to cancer therapy has been largely ignored by gastroenterologists. <h3>Method</h3> A prospective evaluation was conducted of patients referred with chronic changes in GI function after cancer therapy after discharge from our clinic. All patients complete a Gastrointestinal Symptom Rating Scale recording 30 symptoms and a Bristol Stool Chart at every clinic visit. Patient characteristics, symptom incidence, severity, investigations and diagnoses were recorded. <h3>Results</h3> From April 2013 to March 2014, there were 1266 clinic appointments, 398 new patients and 868 follow-ups, 326 patients were discharged. 62% referred by in-house oncology teams, 24% tertiary and 14% GP referrals. Median age was 68 years (20–90), the majority were male (56%). Time from cancer diagnosis to referral was 3.3 years (median, range 0–42). The majority were treated for urology (43%) or gynaecological malignancy (21%), 12% for colorectal, 10% for GI and 14% for other cancers. 94% had more than one troublesome symptom. The most commonly reported GI symptoms (diarrhoea, urgency, flatulence, tenesmus, bloating, abdominal pain, faecal incontinence, borborygmi, nocturnal defaecation, perianal pain and steatorrhoea) all improved by discharge. Only 4% had symptoms that required only endoscopic investigation. 84% reported ongoing fatigue, 45% urinary and 36% sexual concerns. Following an algorithm proven to be effective, 86% required blood tests, 58% OGD+ duodenal aspirate, 53% breath tests, 51% SeHCAT scanning, 48% flexible sigmoidoscopy, 20% colonoscopy, 45% stool faecal elastase and 3% other radiological imaging. Six investigations (median 0–10) were requested. 62% had 3 or more diagnoses made which included 46% small bowel bacterial overgrowth, 38% vitamin D deficiency, bile acid malabsorption 28%, gastritis 22%, radiation-induced bleeding 20%, vitamin B12 deficiency 17%, weak pelvic floor 17%, 13% had polyp requiring removal, 5% pancreatic insufficiency. 3 visits were required (median, 1–16) before discharge. Those requiring more than 1 visit (n = 256) were followed up for 6 months (median, 0.4–142 months). 36% were referred for dietetic assessment and targeted dietary interventions as part of management. Referrals to other teams included: psychological support (4%), urology (2%), psychosexual counselling (1%), physiotherapy (1%) and endocrinology (1%). <h3>Conclusion</h3> Many GI causes contribute to chronic change in bowel function after cancer treatment, endoscopic evaluation without addressing other GI symptoms is only appropriate in a small minority. Most can be discharged after a small number of consultations with significant improvement or resolution of symptoms if a systematic investigational and treatment approach is adopted. <h3>Disclosure of interest</h3> None Declared.
Effects of Human Growth Hormone in Men over 60 Years Old
Authors: Daniel Rudman, Axel G. Feller, Hoskote S. Nagraj, Gregory A. Gergans, Pardee Y. Lalitha, Allen F. Goldberg, Robert A. Schlenker, Lester Cohn, Inge W. Rudman, Dale E. Mattson
Journal: New England Journal of Medicine (1990)

The declining activity of the growth hormone-insulin-like growth factor I (IGF-I) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging.
Directions for Bipartisan Medicare Reform
Authors: Gail R. Wilensky
Journal: New England Journal of Medicine (2012)

Interview with Gail Wilensky on possible directions for bipartisan Medicare reform. (16:08)Download Although meaningful Medicare reform is not likely to occur until after the 2012 elections, some Republicans and Democrats appear to be in substantial agreement about some changes that might make Medicare more efficient, effective, and fiscally sustainable.
Diagnosis of Normal-Pressure Hydrocephalus
Authors: D. Frank Benson, Marjorie LeMay, David H. Patten, Alan B. Rubens
Journal: New England Journal of Medicine (1970)

When normal-pressure hydrocephalus is suspected on the basis of clinical findings, the diagnosis can be confirmed by use of intrathecal radioisotope scans and pneumoencephalographic findings. The pneumoencephalographic studies clearly outline the ventricular space and provide evidence of the presence or absence of obstructive hydrocephalus. The isotope scan, done over a period of three or four days, offers a dynamic picture of cerebrospinal-fluid circulation. From the combination of tests, cases with obstructive-communicating hydrocephalus can be defined for consideration for ventricular-shunt procedures.
The use of cell proliferation data in modeling of skin carcinogenesis.
Authors: A Kopp-Schneider
Journal: Environmental Health Perspectives (1993)

A simple model for papilloma formation is used to analyze data from a mouse skin-painting experiment performed with NMRI mice. The results suggest that one of two conclusions may be drawn: Either the model fails to properly describe the growth behavior of papilloma cells or the model suggests that papilloma cells do not have growth advantage over normal cells, even during promotion.