tbuckley/cabot-search huggingface dataset:
Institutional Review of Compliance With NCCN Guidelines for Breast Cancer: Lessons Learned From Real-Time Multidimensional Synoptic Reporting
Authors: Titilayo O. Adegboyega, Jeffrey Landercasper, Jared H. Linebarger, Jeanne M. Johnson, Jeremiah J. Andersen, Leah L. Dietrich, Collin D. Driscoll, Meghana Raghavendra, Anusha R. Madadi, Mohammed Al-Hamadani, Choua A. Vang, Kristen A. Marcou, Jane Hudak, Ronald S. Go
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Variations exist in compliance with NCCN Guidelines. Prior reports of adherence to NCCN Guidelines contain limitations because of lack of contemporary review and incomplete listing of reasons for noncompliance. Purpose: To assess institutional compliance and assist national quality improvement strategies through identifying valid reasons for noncompliance. Methods: Compliance with NCCN Guidelines was recorded prospectively using electronic synoptic templates for patients with newly diagnosed breast cancer treated at a single institution between January 2010 and December 2011. Compliance with NCCN Guidelines was recorded. The accuracy of real-time synoptic auditing methods compared with retrospective chart review and reasons for noncompliance was assessed. SAS 9.3 software was used for data analysis. Results: Compliance with NCCN Guidelines among 395 patients was 94% for initial staging evaluation, 97% for surgery, 91% for chemotherapy, 89% for hormone therapy, 91% for radiation therapy, 85% for follow-up, and 100% for determination of estrogen receptor/progesterone receptor and HER2 status. Age, comorbidities, and stage influenced guideline compliance. The most common reasons for noncompliance were patient refusal, patient choice after shared decision-making, and overuse of testing. Synoptic templated reporting was accurate in 97% patients. Conclusions: High compliance with NCCN Guidelines was demonstrated. Reasons for noncompliance were identifiable. Compliance and nonadherence can be evaluated quickly with electronic synoptic reporting. This allows real-time action plans to address quality concerns and aids national risk adjustment for comparison and benchmarking.
Validity of volumetric vest respiratory measurements in preterm infants with changes in posture
Authors: Sarah Kent, Catherine Olden, Heike Rabe, Paul Seddon
Journal: European Respiratory Journal (2011)

Respiratory measurements in unsedated infants are problematic: applying a face mask causes arousal and changes respiratory pattern. We have previously validated a volumetric vest system (FloRight) in normal newborn infants. However, other calibrated chest wall measurements (eg Respitrace) lose validity if posture or chest shape changes.  In order to assess whether this system remained valid with chest distortion and changes in posture, we measured tidal breathing in 11 preterm infants (median 30 weeks at birth) simultaneously by mask/ultrasonic flowmeter and Floright, both in supine (S) and randomised right or left lateral position (L). The following tidal breathing parameters were compared over 20 breaths of stable breathing in quiet sleep: tidal volume (Vt), timing of peak tidal expiratory flow (t PTEF /t E ) and expiratory:inspiratory time ratio (t E /t I ).  FloRight measurements were closely correlated with mask measurements in both S and L: Vt S r=0.99, L r=0.99; t PTEF /t E  0.94 and 0.96, t E /t I  0.97 and 0.96. FloRight Vt measurements were slightly but significantly higher than mask, both in S (+2ml, p=0.02) and L (+4ml, p=0.001) but t PTEF /t E  and t E /t I  measurements were not significantly different.  FloRight accurately measures tidal flow timing parameters in small preterm infants both in supine and lateral posture. Tidal volume measurements are highly correlated but slightly overestimated compared to mask, especially in lateral lying: this could be due to the vest not fully conforming to chest distortion.
Phospholipase A2
Authors: R A Zager, D S Conrad, K Burkhart
Journal: Journal of the American Society of Nephrology (1996)

During the course of O2 deprivation-induced proximal tubular injury, profound alterations in ATP homeostasis exist. This study sought to characterize direct cellular determinants of these abnormalities further. Mouse proximal tubular segments (PTS) were isolated and their adenine nucleotide profiles were determined during hypoxic-reoxygenation injury. The extent of oxidant stress, Ca2+ overload, cytoskeletal disruption, and phospholipase activity were experimentally manipulated by H2O2, Ca2+ ionophore, cytochalasin D, or PLA2 addition, respectively. Hypoxia induced the expected deterioration in adenylate profiles, and a persistent defect in ATP homeostasis was observed during reoxygenation (decreased ATP/ADP ratios and absolute ATP content). H2O2, Ca2+ ionophore, and cytochalasin D had no significant impact on adenylate profiles. However, doses of PLA2 that had no overt effect on normal tubules caused 50 to 75% reductions in both hypoxic and reoxygenation ATP/ADP ratios and absolute ATP content. This effect was completely reproduced by the addition of arachidonic acid (C20:4). No other test fatty acid (C16:0, C18:1, C18:3) reproduced this result. Despite its profound negative impact on hypoxic/reoxygenation ATP concentrations, PLA2 and C20:4 each decreased lethal cell injury (lactate dehydrogenase release), as previously reported. The reductions in ATP and lethal cell injury were not mechanistically linked, because C18:1 and C18:3 reproduced the protective action of C20:4 without altering adenine nucleotide profiles. Ouabain, mannitol, or plasma membrane fatty acid "scavenger" therapy (albumin) did not improve the posthypoxic/PLA2-induced depressions in ATP. The addition of C20:4 caused a modest decrease in posthypoxic tubule oxygen consumption, compared to controls. It was concluded that: (1) PLA2 can be a major determinant of ATP concentrations during both hypoxic and reoxygenation tubular injury; (2) this action is mediated via C20:4 release; (3) a primary defect in mitochondrial ATP production, rather than increased ATP consumption, is likely to be responsible for this action.
Inhibition of Human Tumor Colony Formation by the New Alkyl Lysophospholipid Ilmofosine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H A Neumann, D B Herrmann, D Boerner
Journal: JNCI Journal of the National Cancer Institute (1987)

The cytostatic-cytotoxic effect of the new thioether alkyl lysophospholipid analogue Ilmofosine (1-hexadecylthio-2-methoxymethyl-rac-glycero-3-phosphocholine, BM 41.440) on colony formation of 30 different spontaneous human tumors was investigated in vitro with the use of a methylcellulose monolayer assay. Twenty-five neoplasms were sensitive to Ilmofosine within the concentration range tested (0-16 micrograms/ml). The most susceptible tumors were 2 colon carcinomas, 2 squamous cell carcinomas and 1 small-cell carcinoma of the lungs, 2 myosarcomas, 2 ovarian carcinomas, 1 gallbladder carcinoma, and 1 pleural mesothelioma with 50% colony formation inhibition doses ranging from 1.5 to 4.0 micrograms/ml. Due to the sensitivity criteria of the U.S. National Cancer Institute (greater than or equal to 70% inhibition of colony formation at 10 micrograms/ml), 15 of 30 tumors tested have to be considered as susceptible to Ilmofosine.
Modification of In Vitro and In Vivo BCG Cell Wall-Induced Immunosuppression by Treatment with Chemotherapeutic Agents or Indomethacin&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M A DeSilva, H T Wepsic, Y Mizushima, D A Nikcevich, C H Larson
Journal: JNCI Journal of the National Cancer Institute (1985)

The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30–40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin.
Cytotoxic Effects of Hyperthermia and Adriamycin on Chinese Hamster Cells2
Authors: George M. Hahn, Douglas P. Strande
Journal: JNCI Journal of the National Cancer Institute (1976)

Chinese hamster cells, exposed to simultaneous hyperthermia (43° C) and adriamycin (ADM), were initially sensitized to the cytotoxic activity of ADM. If the duration of the combined treatment exceeded about 30 minutes, however, the cells became refractory to additional killing by ADM. If heat was applied before ADM exposure, the cells also could be rendered insensitive; this state persisted so that 24 hours after a 50-minute exposure to 43° C, the cells still showed considerable resistance to ADM. The most reasonable explanation for the findings was that cell membrane permeability to ADM was initially increased by hyperthermia, but prolonged (>30 min) heat exposure reversed this situation and inhibited additional ADM from penetrating to sensitive sites. However, the data yield no hints as to the precise mechanisms involved nor are they sufficiently precise to exclude other explanations. The results do point to precautions that must be observed if the combination of ADM and hyperthermia is to be used clinically.
Heterogeneous Response to X-Ray and Ultraviolet Light Irradiations of Cultured Skin Fibroblasts in Two Families With Gardner's Syndrome&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: T J Kinsella, J B Little, J Nove, R R Weichselbaum, F P Li, R J Meyer, D J Marchetto, W B Patterson
Journal: JNCI Journal of the National Cancer Institute (1982)

A heterogeneous response to X-ray and far UV (254 nm) light irradiations was found in cultured skin fibroblast lines from 2 separate families with Gardner's syndrome. When compared to 2 normal control cultures and cultures from 2 patients with nonfamilial colon cancer, cultures from 4 clinically affected members of family 1 showed increased sensitivity to the lethal effects of both X-ray and UV light irradiations. These cells also showed a delayed pattern of X-ray potentially lethal damage repair (PLDR) and absent UV PLDR. In contrast, cultures from 3 members of family 2 (2 of whom were clinically affected) showed a normal response of survival and PLDR to both X-ray and UV light irradiations. Thus increased sensitivity of cultured skin fibroblasts to X-ray and UV light irradiations was not a consistent in vitro finding in patients with Gardner's syndrome. However, in families with Gardner's syndrome who demonstrate in vitro radiosensitivity, additional studies are needed to assess the usefulness of these techniques in detecting affected individuals prior to the development of colon carcinoma and other manifestations.
A novel method of chest wall movement analysis using structured light plethysmography: A study on elite athletes vs normal subjects
Authors: Irisz Levai, Kathryn Kimber, Willem de Boer, John Beier, Richard Iles, Joan Lasenby
Journal: European Respiratory Journal (2013)

Introduction: Structured Light Plethysmography (SLP) is a non-invasive, non-contact method of assessing the movement of the rib cage and abdominal wall. SLP projects a grid of light onto the subject’s chest and abdomen, the movement of the grid allows both the analysis of compartment volume change and assessment of the surface motion. We present a novel method of breaking down the surface motion of tidal breathing that we believe to be able to characterise a subject’s healthy, diseased, or highly trained state.  Aims and objectives: To use tidal breathing measurements to analyse respiratory movements and to categorise according to specific patterns.  Methods: Tidal Breathing data was collected from 10 elite rowers (av Age 22) and compared to a group of 10 non-athletes (otherwise healthy) (av Age 22). Surface modes for each subject were obtained using a tensor decomposition technique and used as characteristics of elite-athlete vs normal.  Results: 100% correct classification was obtained using an energy deformation metric (which tells us how similar one surface mode is to another). Each dataset was classified using the other datasets as training data. For elite athletes there is a clear delineation of movement into pulmonary rib cage, abdominal rib cage and abdomen, while other normal subjects exhibit a predominantly two compartment movement.  Conclusions: Analysis of chest wall movement clearly indicates specific differences between the breathing patterns of elite athletes and normal non-athletes. Surface movement analysis of other subject groups will be investigated as a next stage.
What have overprescription of NSAIDs, overtraining and modelling physical activity for kids got to do with Barack Obama in Berlin?
Authors: Karim Khan
Journal: British Journal of Sports Medicine (2008)

September already! Can you believe it? Are you exhausted from the Olympics? Has it motivated your patients to be active? Interestingly, when Australians were interviewed before and just after the Sydney Games, there was an increase in people thinking about doing physical activity. Unfortunately, a year later physical activity levels had remained unchanged.1 Not to worry, the Olympics contribute to world peace. So we eagerly anticipate more peace during upcoming Olympics in Vancouver (2010), London (2012) and, we hope, Tromso (2018).

But on to BJSM business and Barack. In this issue we learn that 10% of FIFA World Cup players took NSAIDs prior to every match ( see p 725 )! Would paracetamol/acetaminophen have been better choices? Or a placebo? As sports clinicians working with the “healthy elite athlete” is this OK? Futhermore, supplement use was rampant—the champion ingester took 7.4 different supplements before every game! Clearly this player couldn’t play in the Football Association for the Visually Impaired (http://www.favi.co.uk) because his stomach rattle would have him confused for the ball. This is a landmark paper not only for athlete health but also for the terrific collaboration among team physicians—Hippocrates would approve. Fortunately the supplement creatine does not produce liver or kidney damage ( see p 731 ). Good thing. But the question remains—does it provide athletes any benefit? Pluim argued that there is no evidence for its use in tennis.2 Another expensive placebo?3 Share your thoughts on the BJSM Blog http://blogs.bmj.com/bjsm/.

The second cover page controversy relates to overtraining/overreaching. IOC Medical Commission Chairman, …
Respiratory symptoms, lung function and use of health services among unemployed young adults in Spain. Spanish Group of the European Community Respiratory Health Survey
Authors: M Kogevinas, JM Anto, A Tobias, J Alonso, J Soriano, E Almar, N Muniozguren, F Payo, A Pereira, J Sunyer
Journal: European Respiratory Journal (1998)

The association of respiratory symptoms, lung function and use of health services with employment status was examined in Spain, a country with a high rate of unemployment. A population sample comprising 179 unemployed and 1,868 employed subjects aged 20-44 yrs in 1993, was randomly selected from a base population of about 170,000 people in five urban and rural areas of Spain. Subjects completed a questionnaire on respiratory symptoms, sociodemographic and lifestyle factors, occupational exposure and use of health services, and performed a forced spirometry, a methacholine challenge test and blood tests. Unemployed subjects had a higher risk of simple chronic bronchitis (odds ratio=2.06, 95% confidence interval 1.30-3.24) and of bronchitis-type symptoms, than those who were employed. These risks were, in part, due to the higher prevalence of smoking, poorer housing and prior occupational exposures among unemployed than among employed people. Smaller differences were found between employed and unemployed subjects for asthma-type symptoms, atopia and lung function tests. Use of health services among subjects with respiratory symptoms was similar among employed and unemployed subjects, except that the latter consistently reported less frequent contact with specialized practitioners. Unemployed subjects had a higher risk of bronchitis-type symptoms than employed subjects. In Spain's national, free-access healthcare system, the differential use of specialized health services by employment status is likely to imply differences in the characteristics of the healthcare provided.
Tamoxifen's agonist effect on breast cancer growth is mediated by activation of EGFR/HER-2 with preservation of its antagonist effect on ER-dependent gene expression
Authors: S. Massarweh, C. K. Osborne, M. Dipietro, A. E. Wakeling, R. Schiff
Journal: Journal of Clinical Oncology (2004)

541 Background: Tamoxifen (TAM) is an estrogen receptor (ER) modulator that has both agonist and antagonist properties depending on the molecular profile of its target. We have shown that when HER-2 is overexpressed in MCF-7 tumors, TAM becomes a de novo estrogen-like agonist while fulvestrant (FUL) and estrogen deprivation (ED) remain effective endocrine therapies. Methods: To determine if this TAM agonist effect is mediated by classical ER-regulated transcription activation or by non-classical activity through growth factor pathways, we studied expression of ER-dependent genes and HER-2 signaling elements using western blot analysis. Results: TAM-stimulated MCF-7/HER-2 tumors, which express ER, had reduced levels of ER-dependent genes, just like tumors regressing on ED or FUL. In contrast, levels of p-HER-2 and p-MAPK were elevated in the TAM-stimulated tumors and control E2-stimulated tumors, but were markedly reduced in the ED and FUL-treated tumors, suggesting that activation of HER-2 mediates the de novo agonist effect of TAM. Interestingly, in wild type MCF-7 tumors which acquire TAM-stimulated growth after long-term treatment, TAM also remains an effective antagonist on ER-dependent genes, but EGFR increases markedly at the time of resistance, suggesting that EGFR mediates the acquired agonist effect of TAM. Next, we proceeded to treat mice bearing MCF-7/HER-2 tumors with ED, TAM, or FUL either in the presence or in the absence of E2. While TAM stimulated growth in ED mice, it inhibited E2-stimulated tumor growth. FUL inhibited E2-stimulated growth, but in contrast to TAM, its antitumor effect was greater in ED mice, probably because FUL has no known agonist activity of its own. Conclusions: In this breast cancer model, TAM agonist effects are mediated by EGFR/HER-2, but it remains an effective antagonist on at least some classical ER-dependent transcription activation functions. The data suggest that the use of growth factor pathway inhibitors may improve TAM benefit by eliminating its agonist effect, and that ED may further improve the antitumor effect of FUL but not that of TAM. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca
Induction of Hepatic Cell Carcinomas in Monkeys With &lt;italic&gt;N&lt;/italic&gt;-Nitrosodiethylamine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Margaret G. Kelly, Roger W. O'Gara, Richard H. Adamson, Kumudini Gadekar, Constance C. Botkin, William H. Reese, William T. Kerber
Journal: JNCI Journal of the National Cancer Institute (1966)

Hepatic cell carcinomas were induced within 27 months (earliest tumor, 14 months; median time to tumor formation, 23 months) in 5 of 11 macaques and 1 of 4 cebus monkeys given N-nitrosodiethylamine (DENA) orally, and in 2 cercopithicus monkeys given the compound intraperitoneally. The hepatocarcinomas were multicentric, and one monkey had metastases in the lungs and the pancreatic and biliary lymph nodes. The most frequently observed prodromal change in the livers of monkeys given DENA was toxic hepatitis, characterized by sequential degeneration, transformation, and proliferation of hepatic cells. The macaques received the first dose of DENA as newborns, the cebus as adults, and the cercopithicus monkeys at the age of 6 months. The cumulative oral dosage ranged from 6 to 24 g per monkey, while the cumulative intraperitoneal dose was about 2 g per monkey. Intermittent administration of DENA (oral or intraperitoneal) was less toxic than continuous dosage. Hemograms were taken at intervals over a 2-year period on the macaques that had received DENA orally beginning at birth, and the data do not indicate any hematological changes due to treatment.
Taking a Measured Approach to Toxicity Data in Phase I Oncology Clinical Trials
Authors: Manish R. Sharma, Mark J. Ratain
Journal: Clinical Cancer Research (2015)

The standard categorical system for assessing attribution of toxicity to study drug(s) in phase I trials is cumbersome and uninformative. Although a binary system ("related" vs. "unrelated") would be sufficient to define maximum tolerated dose (MTD), a probability estimation would better support dose selection for randomized dose-ranging phase II trials.
Spontaneous Cessation of Friend Murine Leukemia Virus Production by Leukemia Cell Line Y57: Overgrowth by Nonproducer Cells
Authors: J K Collins, B Chesebro
Journal: JNCI Journal of the National Cancer Institute (1980)

Cell line Y57, obtained from a (C57BL/10 X A.BY)F1 mouse made leukemic with Friend virus complex (FV), spontaneously ceased FV production in vitro after 20 passages. By limiting dilution cloning, the incidence of non-virus-producing cells was found to increase with sequential passage. Nonproducer cells apparently arose spontaneously and were able to increase in number relative to producer cells because the growth rate of nonproducer cells was more rapid than the rate at which virus could reinfect them. Nonproducer clones all contained the defective spleen focus-forming virus in a latent but rescuable form but showed defects in helper virus env and gag gene product synthesis. Stable long-term virus-producing clones were obtained both by cloning at early in vitro passages or by cloning immediately after reinfection of nonproducer cells with FV.
Pleuropulmonary changes during treatment of Parkinson's disease with a long-acting ergot derivative, cabergoline
Authors: E Frans, R Dom, M Demedts
Journal: European Respiratory Journal (1992)

A patient with Parkinson's disease, initially treated with bromocriptine and subsequently with cabergoline, developed progressive pleuropulmonary abnormalities during the latter therapy. These lesions even worsened for some weeks after interruption of cabergoline, which may possibly be related to the prolonged action of this drug. Thus cabergoline may cause similar pleuropulmonary abnormalities to bromocriptine.