tbuckley/cabot-search huggingface dataset:
Getting to Zero Transmission of ERCP Infections—Reply
Authors: Rajesh N. Keswani, Nathaniel J. Soper
Journal: JAMA Surgery (2015)

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Continuous fixed dose schedule for capecitabine
Authors: J. J. Lokich
Journal: Journal of Clinical Oncology (2004)

3633 Background: Capecitabine is an oral fluoropyrimidine commonly used in a cycling 21 day schedule with 14 days on and 7 days off with a daily dose of 2000 to 2500 mg/m2. The major limiting toxicities with this dose and schedule are diarrhea and hand/foot syndrome. A daily “fixed dose” not based on m2 and with a continuous uninterrupted non cycling schedule offers the potential for continuous exposure emulating the parenteral low dose protracted 5-fluorouracil infusion and the potential for less toxicity. Methods: Fifty consecutive patients receiving fixed dose (2000 mg/day) continuous (non cycling) dosing of capecitabine were retrospectively reviewed to determine feasibility, patterns of toxicity and tolerability of this dose schedule. Diagnosis included colon cancer, 26 patients; other GI cancers, 6 patients; GU tumors, 8 patients; and breast cancer, 7 patients. Nineteen of 50 patients received the fixed daily capecitabine dosing as a single agent and 31 patients received capecitabine as part of a multi-modality therapy with radiation or combination chemotherapy regimen. Results: Duration of continuous dosing therapy was 2 weeks to 6 months, median 3 months. None of the 19 patients receiving capecitabine alone developed gastrointestinal or cutaneous toxicity; median duration of therapy 4 months. Seven of the remaining 31 patients (22%) experienced a grade 2 or 3 toxicity; hand/foot syndrome in four, (all grade 2); diarrhea in three patients, grade 2 (2); grade 3 (1). The dose intensity of the continuous fixed dose schedule was 8750 mg/m2/week compared to 11,666 mg/m2/week for the standard dose and schedule. Conclusions: Capecitabine administered as a continuous daily fixed dose has a low toxicity profile in comparison to the cycling 14 days on, 7 days off dose schedule at 2500 or even 2000 mg/m2/day particularly with regard to gastrointestinal and cutaneous toxicity. The dose intensity of the non cycling continuous regimen provides up to 94% of the dose intensity of the intermittent cycling regimen. No significant financial relationships to disclose.
Sir John Maddox and the Ethics of Heresy
Authors: Paul Root Wolpe
Journal: The American Journal of Bioethics (2009)

On Sunday, April 12, 2009, Sir John Maddox died. Sir John, as the British obituaries called him, was the editor of Nature from 1966 to 1973 and again from 1980 to 1995. Over his 22 years as editor ...
Committee's action will undermine further research and development
Authors: V. Wynn, I. F Godsland, D. Crook, J. C Stevenson
Journal: BMJ (1995)

using the pill early because they had had a thrombo- embolic event).The users of products containing levonorgestrel and norethisterone might then comprise, in effect, a population of survivors who are less at risk of the condition under study.I understand that further analyses are in progress to test this hypothesis in various ways.The same model, however, has important implications for prescribers now.A first time user could
ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Authors: Sagar Lonial, Meletios A. Dimopoulos, Antonio Palumbo, Darrell White, Sebastian Grosicki, Ivan Spicka, Adam Walter-Croneck, Philippe Moreau, María-Victoria Mateos, Hila Magen-Nativ, Andrew Belch, Donna Ellen Reece, Meral Beksac, Masafumi Taniwaki, Christoph Röllig, Anil K. Singhal, Jessica Katz, Eric W. Bleickardt, Valerie Poulart, Paul G. Richardson
Journal: Journal of Clinical Oncology (2015)

8508 Background: Elo, a monoclonal antibody (mAb) targeting Signaling Lymphocytic Activation Molecule F7 (SLAMF7), kills myeloma cells with minimal effect on normal tissue. Elo showed encouraging activity with Len/dex (Ld) in a phase Ib/II study in pts with RRMM. This phase III study (NCT01239797) compared efficacy and safety of Elo/Len/dex (ELd) vs Ld. Methods: Pts with RRMM, 1–3 prior therapies (not Len-refractory), were randomized 1:1 to ELd or Ld in 28-day cycles to disease progression/unacceptable toxicity: Elo (10 mg/kg intravenously) weekly cycles 1+2 then biweekly; Len (25 mg) D1–21; dex weekly (40 mg or [Elo wks] 28 mg oral + 8 mg intravenous). Response/progression was assessed by independent review committee by EBMT criteria. Primary endpoints were progression-free survival (PFS) and overall response rate (ORR). Results of an interim analysis are reported. Results: Six hundred and forty-six pts were randomized (321 ELd, 325 Ld; median age 66; del(17p) 32%; t[4;14] 9%; refractory to last therapy 35%). Median (range) prior therapies: 2 (1–4), including bortezomib 70%, thalidomide 48%, Len 6%. At data cut-off (4 November 2014), 35% (ELd) and 21% (Ld) of pts remained on therapy; discontinuation was mainly for disease progression (42% ELd, 47% Ld). Median follow-up was 24 months; median (95% CI) PFS: ELd 19.4 (16.6, 22.2) months, Ld 14.9 (12.1, 17.2) months (HR [95% CI] 0.70 [0.57, 0.85]; p = 0.0004). 1-year PFS was 68% ELd, 57% Ld; 2-year PFS: 41% ELd, 27% Ld. PFS benefit with ELd was consistent across key subgroups. ORR (95% CI) was 79% (74, 83) ELd, 66% (60, 71) Ld (p = 0.0002). G3–4 adverse events ≥ 15% (ELd vs Ld) were neutropenia (25%, 33%); anemia (15%, 16%). Exposure-adjusted infection rate was the same in both arms (incidence rate/100 person-years of exposure, 197). Infusion reactions (IRs) occurred in 10% of pts with ELd (mostly G1–2). There were 210 deaths (94 ELd, 116 Ld). Conclusions: A clinically relevant 30% reduction in risk of progression or death was seen with ELd vs Ld. More pts remain on ELd vs Ld and follow-up for long-term outcomes, including survival, is ongoing. IRs were manageable. Elo, a mAb with a novel immunotherapeutic mechanism of action, showed improved PFS, with minimal added toxicity in combination with Ld vs Ld alone, in pts with multiple myeloma. Clinical trial information: NCT01239797.
High malignancy yield in core needle biopsy of BIRADS 3 breast lesions with calcification
Authors: A. Larke, A. O’Doherty, C. Quinn
Journal: Journal of Clinical Oncology (2006)

10568 Background: Breast cancer screening programmes reduce mortality but result in increased numbers of breast biopsies. Stereotactic and ultrasound-guided core needle biopsy yield similar results to each other and to open biopsy. Study: Analysis of prospectively-acquired data relating to 174,338 screening mammograms performed in BreastCheck between Jan 2001 to Oct 2004. Relative use of ultrasound and stereotactic guidance for core needle biopsy is ascertained, and malignancy yields analysed. Results: In this time period, 174,338 screening mammograms discovered a total of 2782 lesions requiring further assessment. Of 2760 complete records, 1066 were BiRads R3–5 (39%) and 1033 of these (97%) had CNB. Guidance was provided exclusively by ultrasound in 737 (71%), and by stereotaxis in 270 (26%) of cases. There were no differences in malignancy yield of ultrasound versus sterotactically-guided CNB of R4 and R5 lesions (approximately 50% and 90% respectively). The malignancy yield in R3 lesions was significantly higher when performed with stereotactic guidance (12%) than when performed with ultrasound-guidance (5%) and both were significantly higher than R3 biopsy malignancy yields reported in the literature. Conclusion: Almost all BIRADS 3, 4 and 5 lesions are biopsied. The relatively high malignancy yield in R3 biopsies, particularly those with calcification, supports current practice. No significant financial relationships to disclose.
ABT-737 increased intracellular ceramides through sphingomyelin hydrolysis in ALL cell lines
Authors: Zesheng Wan, Kyunghwa Hwang, C. Reynolds, Min H. Kang
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2819 

Ceramides are thought to act as lipid second messengers in cell death pathways. Some antineoplastaic drugs, such as daunorubicin, Ara-C, or vincristine increase ceramides through sphingomyelin (SM) hydrolysis, while others (doxorubicin, etoposide, fenretinide) stimulate de novo synthesis of ceramides. We reported that the combinatoin of ABT-737 (a Bcl-2 family inhibitor) and the cytotoxic retinoid fenretinide (4-HPR) caused a greater increase in ceramides in acute lymphoblastic leukemia (ALL) cells than either drug alone (Proc AACR 47:1336, 2006). We have examined the mechanism by which ABT-737 increased ceramides in the ALL cell lines RS4-11 (pre-B) and CEM (T cell). Ceramides were measured by thin-layer chromatography and [14C]-L-serine. Cytotoxicity was determined using a fluorescence-based DIMSCAN assay. RNA expression of sphingmyelinases was determined by Taqman RT-PCR. In CEM cells pre-labeled overnight with [14C]-L-serine, ABT-737 caused a time-dependent increase in ceramides relative to controls (8-fold at 6 hours). Myriocin, a serine palmitoyltransferase (SPT) inhibitor did not affect the increase in ceramides in response to ABT-737, but GW4869, a neutral sphingomyelinase (nSMase) inhibitor, significantly decreased the generation of ceramides by ABT-737 (p= 0.007). Similar results were obtained with RS4-11 cells. These data indicate that synthesis of ceramides by ABT-737 is mainly due to sphingomyelin hydrolysis. In addition, real-time RT-PCR showed that mRNA for both neutral-SMase (1.51 ± 0.06-fold; p=0.007 at 2h) and acid-SMase (2.25 ± 0.24; p=0.09 at 4h) were up-regulated by ABT-737 in RS4-11 cells. However, cytotoxicity of ABT-737 for ALL cells was minimally affected by the nSMase inhibitor GW4869 or by desipramine (an acid-SMase inhibitor). Thus, ABT-737 increased intracellular ceramides in ALL cells via the sphingomyelin hydrolysis pathway in a time-dependent manner, but the role of ceramides in ABT-737-induced cytotoxicity appeared to be minimal.
pH‐Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer
Authors: Xinyu He, Haijun Yu, Xiaoyue Bao, Haiqiang Cao, Qi Yin, Zhiwen Zhang, Yaping Li
Journal: Advanced Healthcare Materials (2015)

Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis.
REGULATION OF THE IMMUNE RESPONSE
Authors: John W. Kappler, Michael Hoffmann
Journal: The Journal of Experimental Medicine (1973)

The kinetics of the in vivo response to SRBC was studied in mouse spleen at both the B cell and T cell levels. The B cell response was assayed by following the appearance of antibody-secreting cells in the spleen using the hemolytic plaque assay. The T cell response was monitored by following the increase in or "priming" of helper activity in the spleen using a quantitative in vitro assay. The role of cellular proliferation in both responses was established with the inhibitor of mitosis, vinblastine. The results show that, although the development of T cell activity precedes that of anti-SRBC PFC by as much as 1 day, T cells lag at least 1 day behind B cells in the onset of cellular proliferation. The evidence suggests either that the helper T cell which proliferates in response to SRBC does so after helping in the initiation of the primary B cell response or that the proliferative T cell response and the initiation of the primary B cell response involve two different subpopulations of T cells.
Immunotherapy with patient-specific antigens selection reduced the metastasis of a cervical cancer patient
Authors: Yanyan Han, Jianting Long, Sheng Ye, Ran Tao, Dongyun Wu, Jin Li, Xiangjun Zhou
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Cervical cancer is the second most common gynecologic malignant tumor, and is frequently associated with human papilloma virus (HPV) infection. Patients with vascular invaded tumors are more likely to develop metastatic disease after radical resection of primary tumor. Current
Abstract P84: Pre-hospital Lactate Levels Are Better Predictors of Mortality and Hospital Admission Than Traditional Vital Signs
Authors: Kyle J Gunnerson, Seth Brant, Neal Greenfield, Penny S Reynolds, Tim Aro, Allen Yee, Joseph P Ornato, Kevin R Ward
Journal: Circulation (2009)

Intro: Traditional vital signs are routinely obtained in the pre-hospital environment. These vital signs are used to make triage and treatment decisions without showing strong relationships to illness severity. Conversely, elevated lactate levels are good predictors of outcome in the Emergency Department (ED) and inpatient areas. Recent advances in point of care (POC) testing have made the ability to accurately measure lactate readily available to EMS providers.  Hypothesis: We assessed the hypothesis that POC whole blood lactate, collected in the pre-hospital environment, will predict severity of illness measured by death and ED disposition.  Methods: Prospective, observational, blinded, cohort study involving 2 EMS systems; 1 urban and 1 rural. Data from 2,062 subjects transported to a Level 1 Trauma, Academic Medical Center, and 6 Community Hospitals were analyzed. Subjects evaluated were advanced life support transports. Traditional vital signs (blood pressure, heart rate, respiratory rate) and POC lactate (Lactate Pro) were measured during initial EMS assessment. Outcome variables [Death, ED disposition, type of admission (ICU or non-ICU)], were recorded for each ED visit. Receiving ED physicians were blinded to the pre-hospital lactate levels.  Results: Independent predictors of death and hospital admission were identified by using a logistic regression analysis. All hospitals were included in the analysis. Pre-hospital independent predictors of death included: POC lactate (OR 2.14; CI 1.19–3.85), HR (OR 1.04; CI 1.02–1.05), and age (OR 1.04; CI 1.02–1.07). Pre-hospital independent predictors of hospital admission were only POC lactate (OR 1.43; CI 1.17–1.75), and age (OR 1.03; CI 1.02–1.04).  Conclusions: POC lactate outperformed all pre-hospital vital signs in predicting ED disposition and mortality. Pre-hospital POC lactate allows providers to identify patients with a higher severity of illness not demonstrated by traditional vital signs Future knowledge of pre-hospital lactate values may enhance pre-hospital triage, transport and treatment decisions.
Treatment based on a combination of the CYP2B1/cyclophosphamide system and p53 delivery enhances tumour regression in human pancreatic cancer.
Authors: E. Mercadé, M. Cascalló, M. Carrió, J. Calbó, A. Gómez-Treviño, C. Fillat, A.M. Gómez-Foix, A. Mazo
Journal: Annals of Oncology (2001)
The compliance of Greek chest physicians with IDSA/ATS and the Greek national guidelines for CAP
Authors: Charalampos Triantafyllidis, Vasilios Kapordelis, Elissavet-Christina Filippidou, Maria Apostolidou, Georgios Papaetis, Dora Orfanidou, Ioannis Nikolopoulos, Angelos Pefanis
Journal: European Respiratory Journal (2014)

BACKGROUND:  The compliance of Greek chest physicians with practice guidelines for CAP and its impact on cost and patients9 outcome remain unknown.   MATERIAL & METHOD:  A prospective observational study incorporating 250 immunocompetent hospitalized pts with CAP. The aim was to investigate whether the 2007 IDSA/ATS and the Greek national guidelines for CAP are implemented by chest physicians in “Sotiria” hospital, Athens. We: a) assessed whether the decision of hospital admission was correct or not and b) evaluated whether the administered antimicrobial regimen was in accordance to guidelines. Fine score (PSI) was applied by the authors to determine the severity of CAP. 161 pts were male and 89 female. Comorbidities presented in 173 pts.   RESULTS : The mortality rate was 12.8%. A microbial pathogen was identified in 55 (22%) cases and  Streptococcus pn.  was the predominant pathogen isolated (38.46%). COPD pts performed a strong trend towards higher mortality compared to non COPD pts (22.73% vs 10.68% respectively, p=0.055). Implementation of CAP guidelines as far as the initial antimicrobial regimen is concerned was poor (149 pts, 59.6%). Patients treated with an initial antimicrobial in accordance to guidelines, performed a trend towards lower mortality and shorter LOS, compared to those in discordance to guidelines (p=0.078 & p=0.062). 120 (48%) pts were admitted to the hospital, despite they were classified as risk class I or II and therefore could be treated as outpatients.   CONCLUSION : The implementation of CAP guidelines by Greek chest physicians is poor. Improvement of adherence may improve patients9 outcome, shorten the LOS and reduce the financial burden for the national health system.
A historic overview of the paper An excitatory nociceptive cardiac reflex elicited by bradykinin and potentiated by prostaglandins and myocardial ischaemia (1976)
Authors: J Staszewska-Woolley
Journal: Cardiovascular Research (2000)

The work described in this paper has a long and complex history. Its origin can be traced back to 1964 when, after receiving my M.D. degree, I was offered by Dr. John Vane (whom I had met in Poland in 1963) a postdoctoral fellowship in his laboratory in the Deptartment of Pharmacology, Royal College of Surgeons of England in London. My work there made use of the original blood-bathed organ (BBO) bioassay technique of Vane [1] to study the release of catecholamines by histamine and by peptides, including bradykinin. This was my first introduction into the pharmacology of bradykinin, which turned out to be of great value for its subsequent use in studies of cardiac reflexes.

My interest in cardiac reflexes had been stimulated by studies of the adrenergic response associated with acute myocardial infarction in dogs, which were carried out in collaboration with Dr. L. Ceremuzynski during 1967–1970 in the Medical Research Centre of the Polish Academy of Sciences …
Incidence of Sudden Cardiac Death in China
Authors: Wei Hua, Lin-Feng Zhang, Yang-Feng Wu, Xiao-Qing Liu, Dong-Shuang Guo, Hong-Ling Zhou, Zhi-Ping Gou, Lian-Cheng Zhao, Hong-Xia Niu, Ke-Ping Chen, Jin-Zhuang Mai, Li-Nan Chu, Shu Zhang
Journal: Journal of the American College of Cardiology (2009)
Tissue proteases convert CCL23 into potent monocyte chemoattractants in patients with chronic rhinosinusitis
Authors: Julie A. Poposki, Anjeni Keswani, Julie K. Kim, Aiko I. Klingler, Lydia A. Suh, James Norton, Roderick G. Carter, Anju T. Peters, Kathryn E. Hulse, Leslie C. Grammer, Bruce K. Tan, David B. Conley, Juan C. Jaen, Thomas J. Schall, Robert C. Kern, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2015)
Granulocyte Colony-Stimulating Factor–Mobilized Allogeneic Stem Cell Transplantation Maintains Graft-Versus-Leukemia Effects Through a Perforin-Dependent Pathway While Preventing Graft-Versus-Host Disease
Authors: Luying Pan, Takanori Teshima, Geoffrey R. Hill, David Bungard, Yani S. Brinson, Vijay S. Reddy, Kenneth R. Cooke, James L.M. Ferrara
Journal: Blood (1999)
Epstein-Barr Virus Antibodies in Sudanese Patients With Nasopharyngeal Carcinoma: A Preliminary Report&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M O Malik, J Banatvala, M S Hutt, A Y Abu-Sin, A Hidaytallah, A E El-Hadi
Journal: JNCI Journal of the National Cancer Institute (1979)

With the use of an immunofluorescence technique Epstein-Barr viral capsid antigen antibody titers were determined in the sera from 226 Sudanese: 41 with nasopharyngeal carcinoma (NPC), 77 with other head and neck cancers, 21 with malignant lymphomas, 63 with other cancers, 6 with specific granulomas, and 18 normal controls. Of the NPC patients, 87.8% had titers of 320 or greater and 43.9% had titers of 2,560 or more, whereas none had titers of less than 40. Their geometric mean titer (GMT) level was 1,855. However, compared to the NPC patients, the other patients and normal controls showed significantly higher percentages of sera with low titers and lower percentages of sera with high titers and they had a GMT that was 4--16 times lower. The high NPC titers were independent of age, sex, tribe, or locality of patients. The preliminary results indicated the importance of future immunovirologic and immunogenetic field investigations on the natural history of the Epstein-Barr virus and on the genetics of the host.
Engineered Models of Confined Cell Migration
Authors: Colin D. Paul, Wei-Chien Hung, Denis Wirtz, Konstantinos Konstantopoulos
Journal: Annual Review of Biomedical Engineering (2016)

Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell-substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact.