tbuckley/cabot-search huggingface dataset:
Use of Metaphor in the Discourse on Cancer
Authors: Gary M. Reisfield, George R. Wilson
Journal: Journal of Clinical Oncology (2004)

With this metaphoric deluge, the oncologist lost a prospective new patient. A few hours later, Lance Armstrong was on a plane to Indianapolis, where he would establish a successful therapeutic relationship with the oncology team from Indiana University. Armstrong would, of course, survive widely metastatic testicular cancer and go on to win six Tours de France. While this epigraph may represent a wellintentioned effort by an oncologist to prepare a young man with an advanced, lifethreatening malignancy for a long and immensely difficult course of treatment, the image of violence had a devastating and unintended effect. Armstrong himself, probably unconsciously mirroring the oncologist’s martial metaphor, described the reaction in the consultation room as “shell shock.” The comments of both the physician and the patient are emblematic of the fact that metaphors—and especially martial metaphors— play a ubiquitous, but largely unrecognized role in medical and lay discourse. Indeed, as a reader of the Journal of Clinical Oncology recently noted, the “target” in the title of this section of the Journal is itself a military metaphor. And as the above comments suggest, metaphors can be more than mere rhetorical flourishes; they can have a powerful influence on the practice of medicine and the experience of illness. “The essence of metaphor is understanding and experiencing one kind of thing in terms of another.” Lakoff and Johnson have demonstrated that our conceptual systems are wired to operate metaphorically; that is, most concepts, particularly those that are abstract or complex, are at least partially understood in terms of other, more familiar concepts. Metaphors, then, are vehicles for understanding, mediating what is known and what is unknown. Mabeck and Oleson go further, arguing that metaphors don’t merely describe similarities; they create them. When metaphors enter our conceptual system, they alter that system and the knowledge, attitudes, and behaviors to which the system gives rise. For the physician, metaphors can be time-efficient tools for helping patients understand complex biologic processes. For patients, metaphors can impose order on a suddenly disordered world, helping them to understand, communicate, and thus symbolically control their illness. And for the therapeutic relationship, the language of metaphor can serve as the basis for the shared understanding of clinical reality. We will examine the use of metaphor in oncology. We will focus on the predominant metaphor, that of war, in terms of its strengths and limitations, in the contexts of the patientphysician relationship and the patient’s illness experience. Finally, we will briefly survey alternate metaphoric concepts.
CPAP holiday: are we there yet?
Authors: Valentina A. Rossi, John Stradling, Malcolm Kohler
Journal: European Respiratory Journal (2015)

We appreciate the interest shown by M. van Zeller and M. Drummond in our paper [1], who suggest a more cautious interpretation regarding the possibility of withdrawing continuous positive airway pressure (CPAP) therapy for short periods and raise some concerns about how to select candidates properly who might safely undergo this. Unconventional factors involved in OSA pathogenesis may vary over time and may be improved even by intermittent CPAP <http://ow.ly/DemVu>
Anaesthesia suitable for prolonged bronchoscopic examination
Authors: E. C. Attwood, W. Brooks, W. J. H. Leckie
Journal: Thorax (1970)

A technique of combined general and topical anaesthesia is described involving spontaneous ventilation. Patients aged 46 to 76 were examined in this way for periods varying between 5 and 25 minutes. Carbon dioxide elimination was satisfactory in all but 2 of 18 patients, and these 2 are discussed in detail. Capillary oxygen tension was maintained at a level of over 75 mm. Hg throughout all 11 examinations where oxygen was introduced at the proximal end of the bronchoscope, but dangerous hypoxaemia occurred in 2 patients in whom oxygen was not administered in this way.
Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial
Authors: Ganesh Raghu, David Lynch, J David Godwin, Richard Webb, Thomas V Colby, Kevin O Leslie, Juergen Behr, Kevin K Brown, James J Egan, Kevin R Flaherty, Fernando J Martinez, Athol U Wells, Lixin Shao, Huafeng Zhou, Patricia S Pedersen, Rohit Sood, A Bruce Montgomery, Thomas G O'Riordan
Journal: The Lancet Respiratory Medicine (2014)
Noninvasive detection of temozolomide in brain tumor xenografts by magnetic resonance spectroscopy†
Authors: Yoshinori Kato, David A. Holm, Baasil Okollie, Dmitri Artemov
Journal: Neuro-Oncology (2009)

Poor drug delivery to brain tumors caused by aberrant tumor vasculature and a partly intact blood-brain barrier (BBB) and blood-brain tumor barrier (BTB) can significantly impair the efficacy of chemotherapy. Determining drug delivery to brain tumors is a challenging problem, and the noninvasive detection of drug directly in the tumor can be critically important for accessing, predicting, and eventually improving effectiveness of therapy. In this study, in vivo magnetic resonance spectroscopy (MRS) was used to detect an anticancer agent, temozolomide (TMZ), in vivo in murine xenotransplants of U87MG human brain cancer. Dynamic magnetic resonance imaging (MRI) with the low-molecular-weight contrast agent, gadolinium diethylenetriaminepentaacetic acid (GdDTPA), was used to evaluate tumor vascular parameters. Carbon-13-labeled TMZ ([13C]TMZ, 99%) was intraperitoneally administered at a dose of ∼140 mg/kg (450 mg/m2, well within the maximal clinical dose of 1000 mg/m2 used in humans) during the course of in vivo MRS experiments. Heteronuclear multiple-quantum coherence (HMQC) MRS of brain tumors was performed before and after i.p. administration of [13C]TMZ. Dynamic MRI experiments demonstrated slower recovery of MRI signal following an intravenous bolus injection of GdDTPA, higher vascular flow and volume obtained by T*2-weighted MRI, as well as enhanced uptake of the contrast agent in the brain tumor compared with normal brain detected by T1-weighted MRI. These data demonstrate partial breakdown of the BBB/BTB and good vascularization in U87MG xenografts. A [13C]TMZ peak was detected at 3.9 ppm by HMQC from a selected volume of about 0.15 cm3 within the brain tumor with HMQC pulse sequences. This study clearly demonstrates the noninvasive detection of [13C]TMZ in xenografted U87MG brain tumors with MRS. Noninvasive tracking of antineoplastic agents using MRS can have a significant impact on brain tumor chemotherapy.
Comparison of Pharmacokinetics and Pharmacodynamics of Docetaxel and Cisplatin in Elderly and Non-Elderly Patients: Why Is Toxicity Increased in Elderly Patients?
Authors: Hironobu Minami, Yuichi Ohe, Seiji Niho, Koichi Goto, Hironobu Ohmatsu, Kaoru Kubota, Ryutaro Kakinuma, Yutaka Nishiwaki, Hiroshi Nokihara, Ikuo Sekine, Nagahiro Saijo, Kazuhiko Hanada, Hiroyasu Ogata
Journal: Journal of Clinical Oncology (2004)

Following phase I studies of docetaxel and cisplatin in patients with non-small-cell lung cancer, the recommended doses of docetaxel were different for elderly (> or = 75 years) and non-elderly (< 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients.Twenty-seven elderly and 25 non-elderly patients were treated with three weekly administrations of docetaxel and cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m(2) for elderly and non-elderly patients, respectively. All patients received 25 mg/m(2) of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients.There were no differences in pharmacokinetics of docetaxel or cisplatin between elderly versus non-elderly patients with regard to clearance and volume of distribution. In the pharmacodynamic analysis, neutropenia was positively correlated with the area under the concentration-time curve for docetaxel but not for cisplatin. In evaluating the relationship between neutropenia and the area under the concentration-time curve of docetaxel, elderly patients experienced greater neutropenia than those predicted by a pharmacodynamic model developed in non-elderly patients; the residual for prediction of the percent change in neutrophil count was -11.2% (95% CI, -21.8 to -0.5%).The pharmacokinetics of docetaxel and unchanged cisplatin were not different between elderly and non-elderly patients. The elderly patients were more sensitive to docetaxel exposure than the non-elderly patients, resulting in the different recommended doses for the phase II studies.
1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload
Authors: T. D. O'Connell
Journal: Journal of Clinical Investigation (2006)

An α1-adrenergic receptor (α1-AR) antagonist increased heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to α1-AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main α1-AR subtypes in the heart, α1A (Adra1a) and α1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and β-AR stimulation, and β-ARs were desensitized. Thus, α1-AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that α1-signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of α1-antagonists in clinical trials are due to loss of α1-signaling in myocytes, emphasizing concern about clinical use of α1-antagonists, and point to a revised perspective on sympathetic activation in heart failure.
Measuring the Efficacy of a Quality Improvement Program in Dialysis Adequacy with Changes in Center Effects
Authors: Jeffrey C. Fink, Min Zhan, Steven A. Blahut, Michael Soucie, William M. McClellan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. End-stage renal disease (ESRD) patients treated with hemodialysis have a high mortality rate, which is largely due to inadequate dialysis. Dialysis adequacy, measured by the urea reduction ratio (URR), tends to be correlated within dialysis facilities with wide variations in average center adequacy. These are characteristics of a center effect, which can have an important impact on dialysis adequacy. This study measured the center effect observed in an ESRD Network before and after a successful quality improvement project (QIP). URR values were recorded on patients sampled from 196 facilities in ESRD Network 6 before (pre-QIP, n = 5309) and after (post-QIP, n = 5753). These data was used to determine the within center correlation (ρ) of individual URR values and between center variation in aggregate URR values in both samples. The overall mean URR improved from the pre- to post-QIP sample (mean URR 64.7 ± 0.1 versus 69.8 ± 0.1, respectively; P = 0.001). There was a high degree of within center correlation in dialysis adequacy across the facilities, which significantly diminished post-QIP (ρ, 0.15 [95% CI, 0.12 to 0.18] versus ρ, 0.06 [95% CI, 0.04 to 0.08]). The between center variation in mean URR also declined from the pre-QIP to the post-QIP sample (SD, 3.6 versus 2.8). In conclusion, there is a center effect on dialysis adequacy measurable in an ESRD Network, which diminishes after a successful QIP; therefore, when implementing a QIP to improve dialysis adequacy, changes in the center effect should be considered a potential indicator of the efficacy of the intervention.
A case of OXA-48 carbapenemase-producing Klebsiella pneumoniae in a patient transferred to Slovenia from Libya, November 2011
Authors: M Pirš, A Andlovic, T Cerar, T Žohar-Čretnik, L Kobola, J Kolman, T Frelih, M Prešern-Štrukelj, E Ružić-Sabljić, K Seme
Journal: Eurosurveillance (2011)

We report the first documented case of OXA-48-producing Klebsiella pneumoniae in Slovenia isolated from rectal surveillance cultures from a patient transferred from Libya. The patient was colonised with both ESBL-producing Escherichia coli and ESBL- and OXA-48-producing K. pneumoniae. Three further patients were colonised with ESBL-producing E. coli. This underscores the importance of an early warning system on European level and screening upon admission of patients transferred across borders and between healthcare systems.
Pharmacological Agents That Directly Modulate Insulin Secretion
Authors: Máire E. Doyle, Josephine M. Egan
Journal: Pharmacological Reviews (2003)

Blood glucose levels are sensed and controlled by the release of hormones from the islets of Langerhans in the pancreas. The β-cell, the insulin-secreting cell in the islet, can detect subtle increases in circulating glucose levels and a cascade of molecular events spanning the initial depolarization of the β-cell membrane culminates in exocytosis and optimal insulin secretion. Here we review these processes in the context of pharmacological agents that have been shown to directly interact with any stage of insulin secretion. Drugs that modulate insulin secretion do so by opening the K<sub>ATP</sub>channels, by interacting with cell-surface receptors, by altering second-messenger responses, by disrupting the β-cell cytoskeletal framework, by influencing the molecular reactions at the stages of transcription and translation of insulin, and/or by perturbing exocytosis of the insulin secretory vesicles. Drugs acting primarily at the K<sub>ATP</sub> channels are the sulfonylureas, the benzoic acid derivatives, the imidazolines, and the quinolines, which are channel openers, and finally diazoxide, which closes these channels. Methylxanthines also work at the cell membrane level by antagonizing the purinergic receptors and thus increase insulin secretion. Other drugs have effects at multiple levels, such as the calcineurin inhibitors and somatostatin. Some drugs used extensively in research, e.g., colchicine, which is used to study vesicular transport, have no effect at the pharmacological doses used in clinical practice. We also briefly discuss those drugs that have been shown to disrupt β-cell function in a clinical setting but for which there is scant information on their mechanism of action.
Bridging Community Intervention and Mental Health Services Research
Authors: Kenneth Wells, Jeanne Miranda, Martha L Bruce, Margarita Alegria, Nina Wallerstein
Journal: American Journal of Psychiatry (2004)

This article explores the potential of community intervention perspectives for increasing the relevance, reach, and public health impact of mental health services research.The authors reviewed community intervention strategies, including public health and community development and empowerment interventions, and contrast community intervention with practice-based quality improvement and policy research.A model was proposed to integrate health services and community intervention research, building on the evidence-based strength of quality improvement and participatory methods of community intervention to produce complementary functions, such as linking community-based case finding and referral with practice-based quality improvement, enhanced by community-based social support for treatment adherence.The community intervention approach is a major paradigm for affecting public health or addressing health disparities. Despite challenges in implementation and evaluation, it represents a promising approach for extending the reach of mental health services interventions into diverse communities.
Primary diaphragmatic haemangiopericytoma
Authors: D. Seaton
Journal: Thorax (1974)

<b>Seaton, D. (1974).</b><i>Thorax,</i><b>29,</b> 595-598. <b>Primary diaphragmatic haemangiopericytoma.</b> Haemangiopericytomas are tumours consisting of vascular spaces surrounded by proliferating pericytes. Since this neoplasm was first described (Stout and Murray, 1942) over 300 cases have been reported. All tumours of the diaphragm are rare, and a primary diaphragmatic haemangiopericytoma has not been previously recorded in the English literature. Such a case is described and the features of haemangiopericytomas are discussed.
S125 Potential interactions of CRACM ion channels with the calcium activated potassium channel KCa3.1 in human lung mast cells
Authors: I. Ashmole, M. Patel, S. M. Duffy, M. Leyland, P. Bradding
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> The influx of extracellular Ca<sup>2+</sup> is essential for the IgE-dependent release of both preformed mediators and newly-generated autacoids and cytokines from human lung mast cells (HLMC). Members of the recently discovered CRACM (also known as Orai) ion channel family may be responsible for this influx. These channels carry Ca<sup>2+</sup> selective currents (I<sub>CRAC</sub>) that are activated when endoplasmic reticulum Ca<sup>2+</sup> stores are emptied. The major K<sup>+</sup> selective conductance in HLMC is generated by the Ca<sup>2+</sup>-activated K<sup>+</sup> channel K<sub>Ca</sub>3.1. There appears to be a close functional relationship between CRACM and K<sub>Ca</sub>3.1 channels. K<sub>Ca</sub>3.1 channels activated by the influx of extracellular Ca<sup>2+</sup> act to hyperpolarise the cell membrane, thus maintaining the driving force on CRACM channels. Here we investigate whether CRACM and K<sub>Ca</sub>3.1 channels physically interact. <h3>Methods</h3> Vectors were assembled directing the expression of either CRACM1 or CRACM2 channels tagged at their N-terminus with the c-Myc epitope and human K<sub>Ca</sub>3.1 tagged at its C-terminus with the FLAG epitope. HEK293 cells were transiently transfected to express either a single epitope tagged channel or both a CRACM-myc channel and K<sub>Ca</sub>3.1-FLAG. Cell lysates were prepared and potential interactions between CRACM and K<sub>Ca</sub>3.1 proteins tested by immunoprecipitation and immunoblotting. <h3>Results</h3> Expression of CRACM1-myc, CRACM2-myc and K<sub>Ca</sub>3.1-FLAG proteins was confirmed by immunoblotting of lysates of HEK293 cells transiently transfected with the appropriate vector(s). Using an anti c-myc antibody to immunoprecipitate CRACM1-myc protein, K<sub>Ca</sub>3.1-FLAG was found to be co-immunoprecipitated. Co-immunoprecipitation of K<sub>Ca</sub>3.1-FLAG was observed only when it was co-expressed with CRACM1-myc. Similarly, using an anti-FLAG antibody to immunoprecipitate K<sub>Ca</sub>3.1-FLAG protein, CRACM1-myc was co-immunoprecipitated. Again co-immunoprecipitation was dependent on both the CRACM1-myc and K<sub>Ca</sub>3.1-FLAG proteins being expressed together. In contrast, under identical reaction conditions, no co-immunoprecipitation of K<sub>Ca</sub>3.1-FLAG was observed when co-expressed with CRACM2-myc. <h3>Conclusions</h3> The co-immunoprecipitation of K<sub>Ca</sub>3.1-FLAG with CRACM1-myc and vice versa provides evidence that these channels do physically interact. Such an interaction in HLMC would make both channels a potential therapeutic target in the treatment of asthma and would allow K<sub>Ca</sub>3.1 to be added to the growing list of CRACM1 protein binding partners.
Lower Incidence of Biliary Carcinoma in Patients With Primary Sclerosing Cholangitis and High Serum Levels of Immunoglobulin E
Authors: Kenji Hirano, Minoru Tada, Suguru Mizuno, Hiroyuki Isayama, Naminatsu Takahara, Rie Nagano, Tsuyoshi Hamada, Koji Miyabayashi, Yukiko Ito, Dai Mohri, Kazumichi Kawakubo, Takashi Sasaki, Hirofumi Kogure, Natsuyo Yamamoto, Naoki Sasahira, Noriyo Yamashiki, Yasuhiko Sugawara, Norihiro Kokudo, Nobuo Toda, Kazuhiko Koike
Journal: Clinical Gastroenterology and Hepatology (2011)
Associations Between Drug Metabolism Genotype, Chemotherapy Pharmacokinetics, and Overall Survival in Patients With Breast Cancer
Authors: William P. Petros, Penelope J. Hopkins, Susan Spruill, Gloria Broadwater, James J. Vredenburgh, O. Michael Colvin, William P. Peters, Roy B. Jones, Jeff Hall, Jeffrey R. Marks
Journal: Journal of Clinical Oncology (2005)

To evaluate associations between patient survival, pharmacokinetics, and drug metabolism-related genetic polymorphisms in patients receiving a combination chemotherapy regimen for breast cancer.A genotype association study was conducted on 85 chemotherapy-naïve patients with metastatic or inflammatory breast cancer that were evaluated for an extended period after receiving standard-dose chemotherapy followed by high-dose cyclophosphamide, cisplatin, and carmustine. Blood pharmacokinetics were evaluated, and DNA was genotyped for 29 polymorphisms in 17 drug metabolism genes.Patients with cyclophosphamide plasma exposures above the median (implying slower metabolic activation) had a shorter survival than those below the median (1.8 v 3.8 years, respectively; P = .042). Patients having a variant genotype of cytochrome P450 3A4 displayed higher blood concentrations of parent (inactive) cyclophosphamide with the second and third doses (P = .024 and .028, respectively) in addition to slower cyclophosphamide activation over the three doses (P = .031). Median survival for these patients was 1.3 years compared with 2.7 years for those without the variant (P = .043). Similar results were observed for patients carrying a genetic variant of P450 3A5. Median survival for patients with deletions of glutathione-S-transferase M1 gene was 3.5 v 1.5 years for patients with one or both copies (P = .041). Patients with a polymorphism in a gene regulating metallothionein had lower platinum concentrations and shorter survival (P = .033).These data suggest that pretreatment evaluation of drug metabolism genes may explain some interindividual differences in both anticancer drug pharmacokinetics and response. The correlations found here may have implications for other commonly used anticancer drugs.