tbuckley/cabot-search huggingface dataset:
Her2/neu testing in gastric cancer: evaluating the risk of sampling errors
Authors: V.S. Warneke, H.-M. Behrens, C. Böger, T. Becker, F. Lordick, M.P.A. Ebert, C. Röcken
Journal: Annals of Oncology (2012)

<h2>ABSTRACT</h2><h3>Background</h3> We evaluated the risk of sampling errors in specimens of biopsy size, which may be caused by heterogeneous overexpression of Her2/neu in gastric cancer (GC). <h3>Patients and methods</h3> The study cohort comprised 454 gastrectomy patients with adenocarcinoma of the stomach or esophago-gastric junction. Tissue micro-arrays (TMAs) served as ‘biopsy procedure' and were generated from formalin-fixed and paraffin-embedded tissue: five tissue cylinders were collected randomly from each tumor, rendering 2230 core cylinders. These were compared with 454 whole tissue sections obtained from the same paraffin blocks. Her2/neu expression and gene amplification were analyzed by immunohistochemistry and <i>in situ</i> hybridization. The Her2/neu status was determined according to GC scoring system by two independent observers. <h3>Results</h3> In whole tissue sections, 37 (8.1%; observer 1) and 38 (8.4%; observer 2) of the GCs, and in the corresponding TMAs, 28 (6.3%; observer 1) and 28 (6.3%; observer 2) of the GCs were classified as Her2/neu-positive (kappa value 98.5% and 96.2%; <i>P</i> < 0001). Comparison of whole tissue sections with corresponding TMAs showed a false-negative rate of 24% and a false-positive rate of 3% for TMAs. <h3>Conclusion</h3> Assessment of the Her2/neu status in tissue biopsies carries a significant risk of sampling errors, thereby rendering patients unsuitable for treatment with trastuzumab.
Notch1 but Not Notch2 Is Essential for Generating Hematopoietic Stem Cells from Endothelial Cells
Authors: Keiki Kumano, Shigeru Chiba, Atsushi Kunisato, Masataka Sata, Toshiki Saito, Etsuko Nakagami-Yamaguchi, Tomoyuki Yamaguchi, Shigeo Masuda, Kiyoshi Shimizu, Tokiharu Takahashi, Seishi Ogawa, Yoshio Hamada, Hisamaru Hirai
Journal: Immunity (2003)
Chemosensory Physiology in an Age of Transition
Authors: V G Dethier
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Potentially Inappropriate Medication Use Among Elderly Home Care Patients in Europe
Authors: Daniela Fialová, Eva Topinková, Giovanni Gambassi, Harriet Finne-Soveri, Pálmi V Jónsson, Iain Carpenter, Marianne Schroll, Graziano Onder, Liv Wergeland Sørbye, Cordula Wagner, Jindra Reissigová, Roberto Bernabei
Journal: JAMA (2005)

ContextCriteria for potentially inappropriate medication use among elderly patients have been used in the past decade in large US epidemiological surveys to identify populations at risk and specifically target risk-management strategies. In contrast, in Europe little information is available about potentially inappropriate medication use and is based on small studies with uncertain generalizability.ObjectiveTo estimate the prevalence and associated factors of potentially inappropriate medication use among elderly home care patients in European countries.Design, Setting, and ParticipantsRetrospective cross-sectional study of 2707 elderly patients receiving home care (mean [SD] age, 82.2 [ 7.2] years) representatively enrolled in metropolitan areas of the Czech Republic, Denmark, Finland, Iceland, Italy, the Netherlands, Norway, and the United Kingdom. Patients were prospectively assessed between September 2001 and January 2002 using the Minimum Data Set in Home Care instrument.Main Outcome MeasuresPrevalence of potentially inappropriate medication use was documented using all expert panels criteria for community-living elderly persons (Beers and McLeod). Patient-related characteristics independently associated with inappropriate medication use were identified with a multiple logistic regression model.ResultsCombining all 3 sets of criteria, we found that 19.8% of patients in the total sample used at least 1 inappropriate medication; using older 1997 criteria it was 9.8% to 10.9%. Substantial differences were documented between Eastern Europe (41.1% in the Czech Republic) and Western Europe (mean 15.8%, ranging from 5.8% in Denmark to 26.5% in Italy). Potentially inappropriate medication use was associated with patient's poor economic situation (adjusted relative risk [RR], 1.96; 95% confidence interval [CI], 1.58-2.36), polypharmacy (RR, 1.91; 95% CI, 1.62- 2.22), anxiolytic drug use (RR, 1.82; 95% CI, 1.51-2.15), and depression (RR, 1.29; 95% CI, 1.06-1.55). Negatively associated factors were age 85 years and older (RR, 0.78; 95% CI, 0.65-0.92) and living alone (RR, 0.76; 95% CI, 0.64-0.89). The odds of potentially inappropriate medication use significantly increased with the number of associated factors (P<.001).ConclusionsSubstantial differences in potentially inappropriate medication use exist between European countries and might be a consequence of different regulatory measures, clinical practices, or inequalities in socioeconomic background. Since financial resources and selected patient-related characteristics are associated with such prescribing, specific educational strategies and regulations should reflect these factors to improve prescribing quality in elderly individuals in Europe.
GM-CSF action in the CNS decreases food intake and body weight
Authors: J. A. Reed
Journal: Journal of Clinical Investigation (2005)

Many proinflammatory cytokines, such as leptin, play key roles in dynamic regulation of energy expenditure and food intake. The present work tested a role for the proinflammatory cytokine GM-CSF. Central but not peripheral administration of GM-CSF to adult rats significantly decreased food intake and body weight for at least 48 hours. Similar results were observed following central administration of GM-CSF in mice. GM-CSF receptor immunoreactivity was found on neurons within the paraventricular and arcuate nuclei of the hypothalamus. GM-CSF–deficient (GM–/–) mice weighed more and had significantly higher total body fat than wild-type (GM+/+) mice. Energy expenditure in GM–/– mice was decreased compared with that in GM+/+ mice. Taken together, these findings demonstrate that GM-CSF signaling in the CNS can regulate energy homeostasis.
Adenoid Cystic Carcinoma of the Lacrimal Gland: MYB Gene Activation, Genomic Imbalances, and Clinical Characteristics
Authors: Sarah L. von Holstein, André Fehr, Marta Persson, Marianne H. Therkildsen, Jan U. Prause, Steffen Heegaard, Göran Stenman
Journal: Ophthalmology (2013)
Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques.
Authors: K D O'Brien, D Gordon, S Deeb, M Ferguson, A Chait
Journal: Journal of Clinical Investigation (1992)

Lipoprotein lipase (LPL), hydrolyzes the core triglycerides of lipoproteins, thereby playing a role in their maturation. LPL may be important in the metabolic pathways that lead to atherosclerosis, since it is secreted in vitro by both of the predominant cell types of the atherosclerotic plaque, i.e., macrophages and smooth muscle cells. Because of uncertainty concerning the primary cellular source of LPL in atherosclerotic lesions, in situ hybridization assays for LPL mRNA were performed on 12 coronary arteries obtained from six cardiac allograft recipients. Macrophages and smooth muscle cells were identified on adjacent sections with cell-specific antibodies and foam cells were identified morphologically. LPL protein was localized using a polyclonal antibody. LPL mRNA was produced by a proportion of plaque macrophages, particularly macrophage-derived foam cells, but was not detected in association with any intimal or medial smooth muscle cells. These findings were confirmed by combined immunocytochemistry and in situ hybridization on the same tissue sections. LPL protein was detected in association with macrophage-derived foam cells, endothelial cells, adventitial adipocytes, and medial smooth muscle cells, and, to a lesser extent, in intimal smooth muscle cells and media underlying well-developed plaque. These results indicate that macrophage-derived foam cells are the primary source of LPL in atherosclerotic plaques and are consistent with a role for LPL in the pathogenesis of atherosclerosis.
Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice
Authors: O. Weingartner, C. Ulrich, D. Lutjohann, K. Ismail, S. H. Schirmer, T. Vanmierlo, M. Bohm, U. Laufs
Journal: Cardiovascular Research (2011)

'Functional foods' supplemented with plant sterol esters (PSE) and plant stanol esters (PSA) are therapeutic options for the management of hypercholesterolaemia. However, their effects on blood monocytes, endothelial function, atherogenesis, and sterol tissue concentrations are poorly understood. Male apoE−/− mice (n= 30) were randomized to three different diets for 6 weeks (n= 10 per group): high-cholesterol (1.25%) western-type diet (WTD), WTD + 2% PSE, and WTD + 2% PSA. Both supplements reduced serum cholesterol. WTD + PSE resulted in increased plant sterol serum concentrations and increased inflammatory Ly-6C(high) monocyte numbers. WTD + PSA increased plant stanol serum concentrations and Ly-6C-monocyte numbers, but decreased vascular superoxide release, lipid hydroperoxides, and inflammatory cytokines in aortic tissue, in plasma, and in circulating monocytes. Despite reduced serum cholesterol concentrations, both supplements impaired endothelial vasodilation compared with WTD. WTD + PSA reduced the development of atherosclerotic lesions compared with WTD alone (12.7 ± 3.7 vs. 28.3 ± 3.5%), and WTD + PSE was less effective (17.5 ± 3.7%). WTD + PSE and WTD + PSA reduced the cholesterol content in the liver, but not in the brain. However, WTD + PSE and WTD + PSA increased plant sterol and plant stanol concentrations in the liver as well as in the brain. PSE and PSA supplementation reduced serum cholesterol, but increased plant sterol and plant stanol concentrations. Elevated levels of PSE and PSA were associated with endothelial dysfunction and increased central nervous system depositions. Atherosclerotic lesion retardation was more pronounced in WTD + PSA, coinciding with higher regenerative monocyte numbers, decreased oxidative stress, and decreased inflammatory cytokines compared with WTD + PSE.
Lung injury in patients following thoracotomy.
Authors: J P Hayes, E A Williams, P Goldstraw, T W Evans
Journal: Thorax (1995)

Postoperative lung injury is a recognised complication of thoracotomy for which there are few data regarding incidence and outcome.In a case controlled study the notes of all adult patients who developed acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) following thoracotomy between 1991 and 1994 were examined and classified according to the guidelines of the American Thoracic Society/European Respiratory Society for ALI/ARDS. The predictive value of a routine preoperative assessment and duration of anaesthesia in determining those patients most likely to develop ALI/ARDS was assessed.Between 1991 and 1994 231 lobectomies, 103 pneumonectomies, and 135 wedge resections and segmentectomies were performed. The overall incidence of lung injury was 5.1%; 17 patients developed ARDS (two survived) and seven developed ALI (five survived). There was no significant difference compared with case matched controls in preoperative spirometric values, arterial oxygen tension (PaO2), or duration of anaesthesia. None of these parameters was useful in predicting those patients most likely to develop lung injury.Lung injury after thoracotomy is associated with a high mortality. Conventional parameters for preoperative assessment do not predict those patients most likely to develop ALI/ARDS in these circumstances.
Diagnostic importance of pulmonary interleukin-1 and interleukin-8 in ventilator-associated pneumonia
Authors: A. Conway Morris, K. Kefala, T. S Wilkinson, O. L. Moncayo-Nieto, K. Dhaliwal, L. Farrell, T. S Walsh, S. J Mackenzie, D. G Swann, P. J. Andrews, N. Anderson, J. R. Govan, I. F Laurenson, H. Reid, D. J Davidson, C. Haslett, J.-M. Sallenave, A J. Simpson
Journal: Thorax (2009)

<h3>Background</h3> Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP. <h3>Methods</h3> A prospective, observational cohort study was carried out in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers. Growth of pathogens at &gt;10<sup>4</sup> colony-forming units (cfu)/ml of bronchoalveolar lavage fluid (BALF) distinguished VAP from "non-VAP". Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves. <h3>Results</h3> Seventy-two patients had recoverable lavage—24% had VAP. BALF interleukin-1β (IL-1β), IL-8, granulocyte colony-stimulating factor and macrophage inflammatory protein-1α were significantly higher in the VAP group (all p&lt;0.005). Using a cut-off of 10 pg/ml, BALF IL-1β generated negative likelihood ratios for VAP of 0.09. In patients with BALF IL-1β &lt;10 pg/ml the post-test probability of VAP was 2.8%. Using a cut-off value for IL-8 of 2 ng/ml, the positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of &lt;10<sup>4</sup> cfu/ml. <h3>Conclusions</h3> BALF IL-1β and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.
Antiretroviral Medication and HIV Prevention: New Steps Forward and New Questions
Authors: Kenneth H. Mayer, Douglas Krakower
Journal: Annals of Internal Medicine (2012)

During the past 2 years, several pivotal clinical trials have proven that the use of antiretrovirals by HIV-infected and at-risk uninfected persons can decrease the probability of HIV being transmitted sexually. The initial chemoprophylaxis studies evaluated tenofovir administered topically or orally (with or without emtricitabine). However, several questions remain. Some subsequent primary prevention studies did not replicate the results of the initial studies, raising questions about differences in the behaviors of participants in each study (in particular about medication adherence), as well as whether pharmacologic or local mucosal factors might explain the variable efficacy estimates. Other antiretrovirals and delivery systems are being evaluated to maximize the efficacy of primary chemoprophylactic approaches. At present, increasing access to antiretroviral treatment globally is a priority, because expanding access to medication that can prevent morbidity and mortality is itself an important public health goal and may reasonably be expected to decrease HIV incidence. However, for treatment as prevention to be maximally effective, increases in HIV testing, health care workers, and infrastructure are needed, in addition to medications and laboratory support for clinical monitoring. A combination of approaches is needed to most quickly decrease the current trends in HIV incidence, including early diagnosis and initiation of treatment for HIV-infected persons. These approaches can be coupled with appropriately tailored interventions for populations at greatest risk for infection (for example, men who have sex with men and sex workers), including male circumcision, behavioral interventions, and chemoprophylaxis. However, a substantial gap exists between current expenditures and unmet needs, which suggests that mobilization of political will is needed for this combination approach to be successful.
Immunohistochemical Detection of Somatostatin Receptor (SSTR) Subtypes 2A and 5 in Pituitary Adenoma from Acromegalic Patients: Good Correlation with Preoperative Response to Octreotide
Authors: Mao Takei, Masanori Suzuki, Hanako Kajiya, Yudo Ishii, Shigeyuki Tahara, Takashi Miyakoshi, Noboru Egashira, Susumu Takekoshi, Naoko Sanno, Akira Teramoto, Robert Yoshiyuki Osamura
Journal: Endocrine Pathology (2007)
Prediction of outcomes for patients with brain parenchymal metastases from breast cancer (BC): a new BC-specific prognostic model and a nomogram
Authors: H. K. Ahn, S. Lee, Y. H. Park, J. H. Sohn, J.-C. Jo, J.-H. Ahn, K. H. Jung, S. Park, E. Y. Cho, J. I. Lee, W. Park, D. H. Choi, S. J. Huh, J. S. Ahn, S.-B. Kim, Y.-H. Im
Journal: Neuro-Oncology (2012)

The purpose of this study is to validate the recently published Breast–Graded Prognostic Assessment (GPA) and propose a new prognostic model and nomogram for patients with brain parenchymal metastases (BM) from breast cancer (BC). We retrospectively investigated 171 consecutive patients who received a diagnosis of BM from BC during 2000–2008. We appraised the recently proposed Sperduto's BC-specific GPA in training cohort through Kaplan-Meier survival curve using log-rank test and area under the curve for the BC-GPA predicting overall survival at 1 year and developed a new nomogram to predict outcomes using multivariate Cox-regression analysis. By putting the Sperduto's Breast-GPA together with our nomogram, we developed a new prognostic model. We validated our new prognostic model with an independent external patient cohort from 2 institutes for the same period. On the basis of our Cox-regression analysis, therapeutic effect of trastuzumab and status of extracranial systemic disease control were incorporated into our new prognostic model in addition to Karnofsky performance status, age, and hormonal status. Our new prognostic model showed significant discrimination in median survival time, with 3.7 months for class I (n = 15), 7.8 months for class II (n = 82), 10.7 months for class III (n = 42), and 19.2 months for class IV (n = 32; P < .0001). The new prognostic model accurately predicted survival among patients with BC from BM in an external validation cohort (P < .0001). We propose a new prognostic model and a nomogram reflecting the different biological features of BC, including treatment effect and status of extracranial disease control, which was excellently validated in an independent external cohort.
Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group
Authors: Tracey A. O'Brien, Susan J. Russell, Marcus R. Vowels, Cecilia M. Oswald, Karin Tiedemann, Peter J. Shaw, Liane Lockwood, Lochie Teague, Michael Rice, Glenn M. Marshall
Journal: Blood (2002)
CYP2D6 Genotyping and the Use of Tamoxifen in Breast Cancer
Authors: D. Berry
Journal: JNCI Journal of the National Cancer Institute (2013)

Donald Berry in his recent editorial (1) regarding the role of CYP2D6 and tamoxifen highlights several controversies that exist in the clinical and biomarker field for women with breast cancer. The International Tamoxifen Pharmacogenomics Consortium (ITPC) was formed with the intent to aggregate, curate, and analyze the data available in published breast cancer studies with the hope of answering the question, “Should CYP2D6 genotyping guide the use of tamoxifen in breast cancer?” The ITPC analyzed nearly 5000 patients regarding the association between CYP2D6 and clinical outcomes (2). These data demonstrated that CYP2D6 genotype was associated with the risk of recurrence or death in those patients who received tamoxifen monotherapy for 5 years but not in patients who received different doses or duration of tamoxifen or those who received chemotherapy along with tamoxifen. We are in agreement with Berry that further research is required to understand these complex relationships, and our intent has always been that others will be able to use the ITPC dataset to understand the data as fully as possible in conjunction with their own research efforts. The complete dataset of genotypes and clinical variables, the analysis code, and the full analyses are transparently available at PharmGKB (http://www.pharmgkb. org). Although we disagree with Berry about his conclusion in answering the allimportant question of whether CYP2D6guided genotype therapy is appropriate, we invite other researchers and practitioners to examine the data from their own perspectives and engage in ongoing efforts to use these data to the benefit of patients with breast cancer.
HER2 Fragmentation and Breast Cancer Stratification
Authors: Joaquín Arribas, Josep Lluís Parra-Palau, Kim Pedersen
Journal: Clinical Cancer Research (2010)

HER2 is a tyrosine kinase receptor whose overexpression in breast cancers correlates with poor prognosis. A subset of HER2-positive tumors also expresses a series of HER2 fragments, collectively known as p95HER2. These fragments are emerging as a valuable biomarker for this subset of patients, who have a particularly poor prognosis.
Flight-related complications are infrequent in patients with hereditary haemorrhagic telangiectasia/pulmonary arteriovenous malformations, despite low oxygen saturations and anaemia: Figure 1
Authors: Christopher G Mason, Claire L Shovlin
Journal: Thorax (2011)

Individuals with pulmonary arteriovenous malformations (PAVMs) and hereditary haemorrhagic telangiectasia (HHT) commonly have low oxygen saturations and anaemia, two parameters generally used to indicate medical fitness to fly. Using a retrospective questionnaire-based study, the authors examined in-flight complications and predictors in 145 HHT patients (96 with PAVMs) who reported 3950 flights, totalling 18 943 flight hours. Dyspnoea and thrombotic complications were less common than expected, and could not be predicted from sea level oxygen saturations or haemoglobin concentrations. Nosebleeds that can bar individuals from boarding a flight occurred in 13.6% (11.5% to 15.8%) of long-haul flights. The findings should influence preflight advice.