tbuckley/cabot-search huggingface dataset:
Morphological and Virological Investigations on Cultured Burkitt Tumor Lymphoblasts (Strain Raji)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. A. Epstein, B. G. Achong, Y. M. Barr, B. Zajac, G. Henle, W. Henle
Journal: JNCI Journal of the National Cancer Institute (1966)

Cells of the Raji strain, established in vitro in Nigeria from a Burkitt lymphoma, were maintained and studied between the 16th and 28th months of culture. As judged by their mode of growth in suspension, appearance when stained, and fine structural organization, the cells were undifferentiated lymphoblasts similar to those of other tissue culture strains from Burkitt tumors. Characteristics suggesting a lack of differentiation were the formation of large aggregations containing many hundreds of individuals, a relatively large diameter, irregularly indented nuclei, and a fairly extensive cytoplasm with free ribosomes tending to clump. No virus particles could be found in the cells by electron microscopy, despite intensive searching of 16 separate samples. Although the cells were resistant to vesicular stomatitis virus, this resistance could not be transferred to other normally susceptible test cultures and an interferon-like inhibitor could not be found. The Raji cells could, however, produce interferon when stimulated by Newcastle disease virus. Unlike other cultured Burkitt tumor cells, Raji cells did not respond positively in immunofluorescence tests. The failure to detect virus particles or indirect evidence of virus infection in Raji cells is discussed.
Treatment Outcomes and Cost-Effectiveness of Shifting Management of Stable ART Patients to Nurses in South Africa: An Observational Cohort
Authors: Lawrence Long, Alana Brennan, Matthew P. Fox, Buyiswa Ndibongo, Imogen Jaffray, Ian Sanne, Sydney Rosen
Journal: PLoS Medicine (2011)

Lawrence Long and colleagues report that "down-referring" stable HIV patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health facility provides good health outcomes and cost-effective treatment for patients.
Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer
Authors: Herbert Hurwitz, Louis Fehrenbacher, William Novotny, Thomas Cartwright, John Hainsworth, William Heim, Jordan Berlin, Ari Baron, Susan Griffing, Eric Holmgren, Napoleone Ferrara, Gwen Fyfe, Beth Rogers, Robert Ross, Fairooz Kabbinavar
Journal: New England Journal of Medicine (2004)

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy.
Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor?
Authors: E. Hjardem, M. Ostergaard, J. Podenphant, U. Tarp, L. S. Andersen, J. Bing, E. Peen, H. M. Lindegaard, V. S. Ringsdal, A. Rodgaard, J. Skot, A. Hansen, H. H. Mogensen, J. Unkerskov, M. L. Hetland
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To investigate the efficacy of switching to a second biological drug in rheumatoid arthritis (RA) patients. <b>Methods:</b> Since 2000, Danish RA patients (n = 1021) receiving biological therapy have been registered in the nationwide DANBIO database. The first and second treatment series of patients, who switched therapy before 2005 (n = 235), were analysed for their reasons for switching, Disease Activity Score 28 (DAS28), DAS28 improvement, European League against Rheumatology (EULAR) response and drug survival. Most patients switched from infliximab to etanercept or adalimumab. <b>Results:</b> Median survivals for switchers' first/second treatment were 37/92 weeks (all patients' first treatment 119 weeks). Reasons for switching were lack of efficacy (LOE; 109 patients), adverse events (AE; 72), other reasons (54). If patients experienced AE to the first drug, 15% had AE to the second. Median DAS28 improvements in first/second treatment at 3 months were: LOE switchers 1.1/1.6; AE switchers 1.5/0.8. In LOE switchers, a good/moderate EULAR response was more prevalent during the second treatment course than during the first (63% versus 54%, p = 0.02). AE switchers achieved similar EULAR responses to both treatments (59% versus 50%, p = 0.38). <b>Conclusion:</b> LOE switchers had a better clinical response to the second treatment. AE switchers responded equally well to both treatments, with a low risk of discontinuing the second drug as a result of AE. Drug survival of the switchers' second biological therapy was higher than of the first, but lower than that of non-switchers. No difference between various sequences of drugs were found. Danish post-marketing data thus support that RA patients may benefit from switching biological therapy.
Imaging the Norepinephrine Transporter in Neuroblastoma: A Comparison of [18F]-MFBG and 123I-MIBG
Authors: Hanwen Zhang, Ruimin Huang, Nai-Kong V. Cheung, Hongfen Guo, Pat B. Zanzonico, Howard T. Thaler, Jason S. Lewis, Ronald G. Blasberg
Journal: Clinical Cancer Research (2014)

The norepinephrine transporter (NET) is a critical regulator of catecholamine uptake in normal physiology and is expressed in neuroendocrine tumors like neuroblastoma. Although the norepinephrine analog, meta-iodobenzylguanidine (MIBG), is an established substrate for NET, (123)I/(131)I-MIBG has several clinical limitations for diagnostic imaging. In the current studies, we evaluated meta-[(18)F]-fluorobenzylguanidine ([(18)F]-MFBG) and compared it with (123)I-MIBG for imaging NET-expressing neuroblastomas.NET expression levels in neuroblastoma cell lines were determined by Western blot and (123)I-MIBG uptake assays. Five neuroblastoma cell lines and two xenografts (SK-N-BE(2)C and LAN1) expressing different levels of NET were used for comparative in vitro and in vivo uptake studies.The uptake of [(18)F]-MFBG in cells was specific and proportional to the expression level of NET. Although [(18)F]-MFBG had a 3-fold lower affinity for NET and an approximately 2-fold lower cell uptake in vitro compared with that of (123)I-MIBG, the in vivo imaging and tissue radioactivity concentration measurements demonstrated higher [(18)F]-MFBG xenograft uptake and tumor-to-normal organ ratios at 1 and 4 hours after injection. A comparison of 4 hours [(18)F]-MFBG PET (positron emission tomography) imaging with 24 hours (123)I-MIBG SPECT (single-photon emission computed tomography) imaging showed an approximately 3-fold higher tumor uptake of [(18)F]-MFBG, but slightly lower tumor-to-background ratios in mice.[(18)F]-MFBG is a promising radiopharmaceutical for specifically imaging NET-expressing neuroblastomas, with fast pharmacokinetics and whole-body clearance. [(18)F]-MFBG PET imaging shows higher sensitivity, better detection of small lesions with low NET expression, allows same day scintigraphy with a shorter image acquisition time, and has the potential for lower patient radiation exposure compared with (131)I/(123)I-MIBG.
The Effects of Sevelamer Hydrochloride and Calcium Carbonate on Kidney Calcification in Uremic Rats
Authors: Mario Cozzolino, Adriana S. Dusso, Helen Liapis, Jane Finch, Yan Lu, Steven K. Burke, Eduardo Slatopolsky
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The control of serum phosphorus (P) and calcium-phosphate (Ca × P) product is critical to the prevention of ectopic calcification in chronic renal failure (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders, markedly increase serum Ca and positive Ca balance, the new calcium- and aluminum-free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without altering serum Ca in hemodialysis patients. Using an experimental model of CRF, these studies compare sevelamer and calcium carbonate (CaCO3) in the control of serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6 nephrectomized rats underwent one of the following treatments for 3 mo: uremic + high-P diet (U-HP); UHP + 3% CaCO3 (U-HP+C); UHP + 3% sevelamer (U-HP+S). Sevelamer treatment controlled serum P independent of increases in serum Ca, thus reducing serum Ca × P product and further deterioration of renal function, as indicated by the highest creatinine clearances. Sevelamer was as effective as CaCO3 in the control of high-P–induced SH, as shown by similar serum PTH levels, parathyroid (PT) gland weight, and markers of PT hyperplasia. Also, both P binders elicited similar efficacy in reducing the myocardial and hepatic calcifications induced by uremia. However, sevelamer caused a dramatic reduction of renal Ca deposition (29.8 ± 8.6 μg/g wet tissue) compared with both U-HP (175.5 ± 45.7 μg/g wet tissue, P < 0.01) and the U-HP+C (58.9 ± 13.7 μg/g wet tissue, P < 0.04). Histochemical analyses using Von Kossa and Alizarin red S staining of kidney sections confirmed these findings. The high number of foci of calcification in the kidney of uremic controls (108 ± 25) was reduced to 33.0 ± 11.3 by CaCO3 and decreased even further with sevelamer (16.4 ± 8.9, P < 0.02 versus CaCO3). Importantly, the degree of tubulointerstitial fibrosis was also markedly lower in U-HP+S (5%) compared with either U-HP+C (30%) or U-HP (50%). It is concluded that in experimental CRF in rats, despite a similar control of serum P and SH, sevelamer is more effective than CaCO3 in preventing renal Ca deposition and tubulointerstitial fibrosis, including better preservation of renal function. These findings cannot be extrapolated to human disease, and further studies in patients are necessary to determine the benefits of either P binder.
Pain in hand osteoarthritis is associated with inflammation: the value of ultrasound
Authors: M. C. Kortekaas, W.-Y. Kwok, M. Reijnierse, I. Watt, T. W. J. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2010)

To investigate the association of ultrasound (US) features-grey scale (GS) synovitis, synovial thickening, effusion and power Doppler signal (PDS)-with symptoms in hand osteoarthritis (HOA).Fifty-five consecutive patients (mean age 62 years, 87% women) with HOA, fulfilling the American College of Rheumatology criteria, were assessed for pain upon palpation and filled in Australian/Canadian Osteoarthritis Index (AUSCAN) scores, visual analogue scale pain and Short Form-36 (SF-36). US was performed in all metacarpophalangeal, proximal interphalangeal, distal interphalangeal, first interphalangeal and first carpometacarpal joints, and features were semiquantitatively scored (0-3). Generalised estimating equations were used to calculate OR (95% CI) for the association between US features and pain per joint adjusted for relevant confounders. The association between US features summated scores and self-reported outcomes was studied by linear regression analysis.GS synovitis, effusion, synovial thickening and PDS were shown in 96%, 91%, 73% and 86% of patients, respectively. US features were dose-dependently associated with pain upon palpation (OR 4.5 (95% CI 2.2 to 9.0), 4.4 (2.0 to 9.4), 4.9 (2.2 to 11.0) and 4.1 (2.2 to 7.9)). GS synovitis was associated with AUSCAN pain, stiffness and SF-36, and effusion with AUSCAN pain.GS synovitis, effusion, synovial thickening and PDS are associated with pain in HOA, suggesting a role for inflammation. Further follow-up studies are warranted.
Associations between the organisation of stroke services, process of care, and mortality in England: prospective cohort study
Authors: B. D. Bray, S. Ayis, J. Campbell, A. Hoffman, M. Roughton, P. J. Tyrrell, C. D. A. Wolfe, A. G. Rudd
Journal: BMJ (2013)

<b>Objective</b> To estimate the relations between the organisation of stroke services, process measures of care quality, and 30 day mortality in patients admitted with acute ischaemic stroke. <b>Design</b> Prospective cohort study. <b>Setting</b> Hospitals (n=106) admitting patients with acute stroke in England and participating in the Stroke Improvement National Audit Programme and 2010 Sentinel Stroke Audit. <b>Participants</b> 36 197 adults admitted with acute ischaemic stroke to a participating hospital from 1 April 2010 to 30 November 2011. <b>Main outcome measure</b> Associations between process of care (the assessments, interventions, and treatments that patients receive) and 30 day all cause mortality, adjusting for patient level characteristics. Process of care was measured using six individual measures of stroke care and summarised into an overall quality score. <b>Results</b> Of 36 197 patients admitted with acute ischaemic stroke, 25 904 (71.6%) were eligible to receive all six care processes. Patients admitted to stroke services with high organisational scores were more likely to receive most (5 or 6) of the six care processes. Three of the individual processes were associated with reduced mortality, including two care bundles: review by a stroke consultant within 24 hours of admission (adjusted odds ratio 0.86, 95%confidence interval 0.78 to 0.96), nutrition screening and formal swallow assessment within 72 hours (0.83, 0.72 to 0.96), and antiplatelet therapy and adequate fluid and nutrition for first the 72 hours (0.55, 0.49 to 0.61). Receipt of five or six care processes was associated with lower mortality compared with receipt of 0-4 in both multilevel (0.74, 0.66 to 0.83) and instrumental variable analyses (0.62, 0.46 to 0.83). <b>Conclusions</b> Patients admitted to stroke services with higher levels of organisation are more likely to receive high quality care as measured by audited process measures of acute stroke care. Those patients receiving high quality care have a reduced risk of death in the 30 days after stroke, adjusting for patient characteristics and controlling for selection bias.
Molecular Analysis of HER2 Signaling in Human Breast Cancer by Functional Protein Pathway Activation Mapping
Authors: Julia D. Wulfkuhle, Daniela Berg, Claudia Wolff, Rupert Langer, Kai Tran, Julie Illi, Virginia Espina, Mariaelena Pierobon, Jianghong Deng, Angela DeMichele, Axel Walch, Holger Bronger, Ingrid Becker, Christine Waldhör, Heinz Höfler, Laura Esserman, Lance A. Liotta, Karl-Friedrich Becker, Emanuel F. Petricoin
Journal: Clinical Cancer Research (2012)

Targeting of the HER2 protein in human breast cancer represents a major advance in oncology but relies on measurements of total HER2 protein and not HER2 signaling network activation. We used reverse-phase protein microarrays (RPMA) to measure total and phosphorylated HER2 in the context of HER family signaling to understand correlations between phosphorylated and total levels of HER2 and downstream signaling activity.Three independent study sets, comprising a total of 415 individual patient samples from flash-frozen core biopsy samples and formalin-fixed and paraffin-embedded (FFPE) surgical and core samples, were analyzed via RPMA. The phosphorylation and total levels of the HER receptor family proteins and downstream signaling molecules were measured in laser capture microdissected (LCM) enriched tumor epithelium from 127 frozen pretreatment core biopsy samples and whole-tissue lysates from 288 FFPE samples and these results were compared with FISH and immunohistochemistry (IHC).RPMA measurements of total HER2 were highly concordant (>90% all sets) with FISH and/or IHC data, as was phosphorylation of HER2 in the FISH/IHC(+) population. Phosphorylation analysis of HER family signaling identified HER2 activation in some FISH/IHC(-) tumors and, identical to that seen with FISH/IHC(+) tumors, the HER2 activation was concordant with EGF receptor (EGFR) and HER3 phosphorylation and downstream signaling endpoint activation.Molecular profiling of HER2 signaling of a large cohort of human breast cancer specimens using a quantitative and sensitive functional pathway activation mapping technique reveals IHC(-)/FISH(-)/pHER2(+) tumors with HER2 pathway activation independent of total HER2 levels and functional signaling through HER3 and EGFR.
Characteristics and Outcomes of Ventilated Patients According to Time to Liberation from Mechanical Ventilation
Authors: Oscar Peñuelas, Fernando Frutos-Vivar, Cristina Fernández, Antonio Anzueto, Scott K. Epstein, Carlos Apezteguía, Marco González, Nicolas Nin, Konstantinos Raymondos, Vinko Tomicic, Pablo Desmery, Yaseen Arabi, Paolo Pelosi, Michael Kuiper, Manuel Jibaja, Dimitros Matamis, Niall D. Ferguson, Andrés Esteban
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed.Objectives: To analyze outcomes based on the new weaning classification in a cohort of mechanically ventilated patients.Methods: Secondary analysis included 2,714 patients who were weaned and underwent scheduled extubation from a cohort of 4,968 adult patients mechanically ventilated for more than 12 hours.Measurements and Main Results: Patients were classified according to a new weaning classification: 1,502 patients (55%) as simple weaning, 1,058 patients (39%) as difficult weaning, and 154 (6%) as prolonged weaning. Variables associated with prolonged weaning (>7 d) were: severity at admission (odds ratio [OR] per unit of Simplified Acute Physiology Score II, 1.01; 95% confidence interval [CI], 1.001–1.02), duration of mechanical ventilation before first attempt of weaning (OR per day, 1.10; 95% CI, 1.06–1.13), chronic pulmonary disease other than chronic obstructive pulmonary disease (OR, 13.23; 95% CI, 3.44–51.05), pneumonia as the reason to start mechanical ventilation (OR, 1.82; 95% CI, 1.07–3.08), and level of positive end-expiratory pressure applied before weaning (OR per unit, 1.09; 95% CI, 1.04–1.14). The prolonged weaning group had a nonsignificant trend toward a higher rate of reintubation (P = 0.08), tracheostomy (P = 0.15), and significantly longer length of stay and higher mortality in the intensive care unit (OR for death, 1.97; 95% CI, 1.17–3.31). The adjusted probability of death remained constant until Day 7, at which point it increased to 12.1%.Conclusions: Only patients who need more than 7 days for weaning have an increased mortality.
Loss of polymeric immunoglobulin receptor expression is associated with lung tumourigenesis
Authors: Sebahat Ocak, Tetyana V. Pedchenko, Heidi Chen, Frederick T. Harris, Jun Qian, Vasiliy Polosukhin, Charles Pilette, Yves Sibille, Adriana L. Gonzalez, Pierre P. Massion
Journal: European Respiratory Journal (2011)

Polymeric immunoglobulin receptor (pIgR) expression is downregulated in lung cancer, but its implications in lung tumourigenesis remain unknown. We hypothesised that loss of pIgR expression occurs early, and is associated with cell proliferation and poor prognosis. pIgR expression was evaluated by immunohistochemistry in airways of patients with normal mucosa, pre-invasive lesions and invasive lesions, and correlated with clinical outcomes. 16-HBE and A549 cells stably transfected with pIgR were tested for proliferation, apoptosis and cell cycle progression. Immunostaining was strong in normal epithelium, but severely reduced in pre-invasive lesions and most lung cancers. Persistent expression was associated with younger age and adenocarcinoma subtype but not survival. pIgR overexpression significantly reduced A549 and 16-HBE proliferation. Growth inhibition was not due to cell cycle arrest, increased apoptosis or endoplasmic reticulum stress, but we observed altered expression of genes encoding for membrane proteins, including NOTCH3. Interestingly, NOTCH3 expression was inversely correlated with pIgR expression in cell lines and tissues. pIgR expression was lost in most lung cancers and pre-invasive bronchial lesions, suggesting that pIgR downregulation is an early event in lung tumourigenesis. pIgR overexpression in A549 and 16-HBE cells inhibited proliferation. Future investigations are required to determine the mechanisms by which pIgR contributes to cell proliferation.
National Institutes of Health State-of-the-Science Conference Statement: Diagnosis and Management of Ductal Carcinoma In Situ September 22-24, 2009
Authors: C. J. Allegra, D. R. Aberle, P. Ganschow, S. M. Hahn, C. N. Lee, S. Millon-Underwood, M. C. Pike, S. D. Reed, A. F. Saftlas, S. A. Scarvalone, A. M. Schwartz, C. Slomski, G. Yothers, R. Zon
Journal: JNCI Journal of the National Cancer Institute (2010)

ForewordNational Institutes of Health consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality, 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the Federal Government.The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.
Pectoralis major tears: comparison of surgical and conservative treatment
Authors: C M Hanna, A B Glenny, S N Stanley, M A Caughey
Journal: British Journal of Sports Medicine (2001)

Objectives— To compare objective measures of strength and subjective functional outcomes in complete distal pectoralis major tears treated either surgically or non-surgically. Methods— Twenty two pectoralis major tears were included in 21 patients. Ten were surgically repaired and 12 were managed non-surgically. Patients completed a standard questionnaire, and clinical examination and isokinetic dynamometry were carried out. Results— In patients who had surgical repair, peak torque returned to 99% of that of the uninjured side and work performed returned to 97%. For those managed conservatively, peak torque and work performed returned to only 56% of that of the uninjured side (p = 0.003 for the difference in peak torque, and p = 0.01 for work performed). Findings were independent of the strength of the patient, whether or not the dominant arm was involved, the age of the patient, and the length of time from injury or surgery to testing. Patients were grouped into one of three subjective functional outcome groups, and those who had a surgical repair had a better functional outcome. Conclusions— Surgical repair results in greater recovery of peak torque and work performed than conservative management of patients with rupture of the pectoralis major.