tbuckley/cabot-search huggingface dataset:
NIMG-40MRI TUMOR PROGRESSION PATTERNS IN THE GLARIUS TRIAL
Authors: Sied Kebir, Christina Schaub, Elke Hattingen, Nina Junold, Niklas Schäfer, Joachim P. Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Michael Niessen, Frederic Mack, Moritz Stuplich, Theophilos Tzaridis, Oliver Bähr, Martin Proescholdt, Martin Glas, Ulrich Herrlinger
Journal: Neuro-Oncology (2015)

BACKGROUND: We evaluated patterns of tumor progression in patients with primary glioblastoma who were assigned to undergo treatment with bevacizumab/irinotecan (BEV/IRI) versus standard temozolomide (TMZ) within the randomized phase II GLARIUS trial. METHODS: In 160 patients (106 BEV/IRI, 54 TMZ), we reviewed magnetic resonance imaging (MRI) scans at baseline and tumor progression. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) images we assessed tumor patterns and invasiveness. Tumor patterns were classified as either multifocal or local at baseline and progression; at progression, we additionally assessed whether distant lesions appeared. Invasiveness was determined as either diffuse or non-diffuse. Associations were calculated using Fisher's exact test. RESULTS: At baseline, 118 of 160 evaluable patients (73.8%) had a locally confined tumor. In the BEV/IRI arm 10% and in the TMZ arm 8% of patients with an initially local tumor growth changed to a multifocal pattern (p = 0.78); distant lesions were found in 24% in the BEV/IRI arm and 19% in the TMZ arm (p = 0.55). 8% of patients in the BEV/IRI arm and 11% in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern (p = 0.58). CONCLUSIONS: The tumor progression and invasiveness patterns do not differ between BEV/IRI and TMZ-treated patients in the GLARIUS trial. BEV/IRI did not increase the rate of multifocal, distant or highly invasive tumors at the time of progression.
Chronic<i>Bartonella quintana</i>Bacteremia in Homeless Patients
Authors: Philippe Brouqui, Bernard Lascola, Veronique Roux, Didier Raoult
Journal: New England Journal of Medicine (1999)

Infection with Bartonella quintana can cause trench fever, endocarditis, bacillary angiomatosis, and peliosis. An outbreak of bacteremia due to B. quintana has been reported among homeless people in Seattle, and the seroprevalence is high among homeless people in both the United States and Europe. Body lice are known to be the vectors of B. quintana.We studied all the homeless people who presented in 1997 to the emergency departments of the University Hospital, Marseilles, France. Blood was collected for microimmunofluorescence testing for antibodies against B. quintana and for culture of the bacterium. Body lice were collected and analyzed by the polymerase chain reaction and sequencing of a portion of the citrate synthase gene of B. quintana.In 10 of 71 homeless patients (14 percent), blood cultures were positive for B. quintana, and 21 of the patients (30 percent) had high titers of antibody against the organism. A total of 17 patients (24 percent) had evidence of recent infection (bacteremia or seroconversion). Tests of lice from 3 of the 15 patients from whom they were collected were positive for B. quintana. The homeless people with B. quintana bacteremia were more likely to have been exposed to lice (P=0.002), were more likely to have headaches (P=0.03) and severe leg pain (P<0.001), and had lower platelet counts (P=0.006) than the homeless people who were seronegative for B. quintana and did not have bacteremia; 8 of the 10 patients with bacteremia were afebrile. Five patients had chronic bacteremia, as indicated by positive blood cultures over a period of several weeks.In an outbreak of urban trench fever among homeless people in Marseilles, B. quintana infections were associated with body lice in patients with nonspecific symptoms or no symptoms.
Abstract PD2-07: Insulin receptor substrate (IRS) targeting by the tyrophostin NT157 inhibits breast cancer cell growth
Authors: D Yee, NA Temiz, A Levitzki, Y Yang
Journal: Cancer Research (2016)

Abstract Insulin and insulin-like growth factor (IGF) signaling systems regulate the malignant phenotype. However, targeting of the type I IGF receptor (IGF-IR) has shown little activity in clinical trials. One potential reason for these disappointing results is that activation of the closely related insulin receptor (InR) could compensate for IGF-IR blockade. Since both receptors phosphorylate the insulin receptor substrates (IRS), perhaps a better strategy would involving targeting of this key post-receptor protein. Two IRS proteins are expressed in breast cancer cells. IRS-1 is regulated by estradiol in breast cancer cell lines, while IRS-2 is the predominant IRS species in hormone receptor negative cells. NT157, a small-molecule tyrphostin, binds IGF-1R but does not affect receptor autophosphorylation. Instead, it downregulates IRS proteins in several model systems. In primary breast cancers, IRS-1 was positively correlated to ERα expression in the TCGA database. In ERα+ and basal-like breast cancer cell lines NT157 treatment suppressed IRS protein expression in a dose dependent manner. Short term exposure to NT157 treatment did not affect IGF-I, IGF-II, and insulin induced activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), but longer exposure resulted in inhibition of these signaling pathways. NT157 resulted in serine phosphorylation of IRS proteins and was dependent on MAPK activation. Serine phosphorylation resulted in disassociation between IRS proteins and their receptors resulting in IRS degradation. NT157 decreased S phase fraction, monolayer, and anchorage independent growth after IGF/insulin treatment in ERα+ breast cancer cells. NT157 downregulation of IRS protein expression also sensitized ERα+ breast cancer cells to rapamycin. Moreover, NT157 inhibited the growth of tamoxifen resistant ERα+ breast cancer cells. In the basal-like breast cancer cells (MDA-MB-231), NT157 repressed the proliferation (G2/M abrogation) and migration through downregulation of IRS1/2 protein. Given that both IGF-IR and InR play a role in cancer biology, targeting of IRS adapter proteins could be a more effective inhibitory strategy compared to receptor-targeting approaches. Citation Format: Yee D, Temiz NA, Levitzki A, Yang Y. Insulin receptor substrate (IRS) targeting by the tyrophostin NT157 inhibits breast cancer cell growth. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-07.
Investigation of Periostin and TARC Levels in the Search for a Non-Invasive Biomarker in Children and Adults with Eosinophilic Esophagitis
Authors: Anubha Tripathi, Lisa J. Workman, Kush S. Patel, Barrett H. Barnes, Thomas A.E. Platts-Mills, Scott P. Commins
Journal: Journal of Allergy and Clinical Immunology (2016)
Progressive Multifocal Leukoencephalopathy
Authors: P J Weiss, J K DeMarco
Journal: New England Journal of Medicine (1994)

Figure 1. Progressive Multifocal Leukoencephalopathy. Magnetic resonance images of the brain were obtained in a 40-year-old man with the acquired immunodeficiency syndrome who had a six-week history of decreased memory and visual impairment. The changes associated with progressive multifocal leukoencephalopathy are best seen on the T2-weighted image (Panel A) as high-intensity abnormalities isolated in the white matter (arrows). A large, bilateral parieto-occipital lesion crosses the splenium of the corpus callosum (open arrows); a smaller frontal-lobe lesion is also present (solid arrow). On the T1-weighted image (Panel B), the lesions appear as low-intensity abnormalities that are not . . .
Gene profiles of drug responsiveness in breast cancer cells
Authors: D. Tripathy, L. Girard, J. Shah, S. Scoggin, K. Tomenga, J. Minna
Journal: Journal of Clinical Oncology (2004)

9616 Background: Heterogeneity at the genomic, gene expression and protein levels likely explains variable responses to chemotherapy for cancer. We have developed and characterized a panel of human breast cancer cell lines including some derived from primary breast tumors. Using this model, we set out to define genes and gene sets in relation to responsiveness to chemotherapy drugs used for breast cancer. Methods: Chemotherapy concentrations that inhibit in vitro growth by 50% (IC50) were determined for 14 cell lines by incubation at varying concentrations of cisplatin (C), doxorubicin (D), paclitaxel (P), or vinorelbine (V) for 4 days. Gene expression levels of 25,000 genes were determined for each cell line using Affymetrix HG-U133A/B microarray chips. Resistant (r) and sensitive (s) cell lines were defined by having IC50 values at least 1 log apart. For each drug, relative gene expression levels of r and s cell lines were averaged and compared. Pearson's correlation (R) coefficients between IC50 and gene expression levels for all cell lines were determined. Results: IC50 values varied across cell lines for all drugs, ranging over 2 logs for D and 4 logs for C and V. Gene expression profiles revealed 3 distinct cell line subsets by unsupervised hierarchical clustering. Many gene expression levels varied by at least 4 fold up or down in r compared s cells, with fewer also exhibiting absolute R values ≥ 0.5. Few genes were associated with responsiveness to several drugs, with greatest overlap between C and D. Very few genes showed overlapping sensitivity or resistance to 3 or 4 drugs; these included transcriptional factors and signal transduction components. Conclusions: Significant variation in breast cancer cell line responsiveness to chemotherapy is associated with distinct and drug-specific gene expression patterns. Profiles and individual genes associated with drug response may lead to better predictive tools and new pharmacological targets. No significant financial relationships to disclose.
Transient Enhanced Uptake of<sup>123</sup>I-Metaiodobenzylguanidine in the Contralateral Adrenal Region after Resection of an Adrenal Pheochromocytoma
Authors: Hendrikus H. Boersma, Johanna W. Wensing, T. Liang Kho, L. Maurits de Brauw, Ing Han Liem, Marinus J.P.G. van Kroonenburgh
Journal: New England Journal of Medicine (2000)

To the Editor: Grines et al. (Dec.23 issue) 1 found that the benefit of coronary stenting after myocardial infarction was attributable only to the marked decrease in the rate of revascularization at six months.However, the unblinded study design may have biased decisions about revascularization in a way that could have favored the stent group.Did the independent clinical-events committee assess the appropriateness of the revascularization procedures used?Were the patients who did not undergo revascularization assessed for potential underuse of these procedures?Before worrying about the ethics of withholding stents from patients with acute infarction, the investigators should first address the possibility that their results may have been confounded by diagnostic-suspicion bias.
Diagnostic value of immunohistochemistry on formalin-fixed, paraffin-embedded skin biopsy specimens for bullous pemphigoid
Authors: S. Glauser, M. Rutz, S. Cazzaniga, I. Hegyi, L. Borradori, H. Beltraminelli
Journal: British Journal of Dermatology (2016)

Direct immunofluorescence microscopy (DIF) studies constitute the gold standard for diagnosis of bullous pemphigoid (BP) but depend on the availability of specialized laboratories and often on an additional skin biopsy specimen. To assess the value of immunohistochemical analyses (IHCA) in the diagnosis of BP using formalin‐fixed, paraffin‐embedded skin biopsy specimens as an alternative to DIF; and to study the correlation between the results of IHCA and the presence of histological subepidermal blister formation and of circulating autoantibodies by indirect immunofluorescence studies using split skin or by enzyme‐linked immunosorbent assays. We included all patients newly diagnosed with BP evaluated between 2008 and 2010. There were 51 consecutive skin biopsy specimens obtained from 38 patients with BP with positive DIF. By IHCA, deposits of immunoreactants were found in 45% of all tested cases. Deposits of C3d, IgG, IgM, IgE and IgA were found in 37%, 23%, 2%, 0% and 0% of cases, respectively. Deposits of C3d and/or IgG were found in 79% of the 24 cases with a blister and in 83% of the 12 cases with subepidermal blistering and positive immunoserological analyses, respectively. In contrast to previous studies, our findings in an unselected patient cohort indicate that IHCA are not sufficiently sensitive to replace DIF studies for confirming the diagnosis of BP. IHCA sensitivity significantly increases in the presence of histological blistering and/or of circulating autoantibodies. IHCA represents a potential rescue diagnostic technique only if specialized laboratories and/or a second biopsy specimen for DIF are unavailable.
Plasmacytoma of Lymph Node
Authors: Morris A. Simon, S. Eidlow
Journal: New England Journal of Medicine (1950)

IN A comprehensive review of 127 extramedullary plasmacytomas in 1943, Hellwig1 found only 4 cases in which plasmacytoma appeared to originate in lymph nodes. Search of the subsequent literature reveals only a single additional example.2 Because plasmacytoma of lymph nodes may be associated with grave prognostic significance, the case presented below, which was followed for three and a half years, is considered worthy of comment.Case ReportA 52-year-old man entered the hospital on June 27, 1946, because of a painless swelling in the right inguinal region of 4 weeks' duration. Except for a history of phlebitis of the right . . .
Candidate Surrogate End Points for ESRD after AKI
Authors: Morgan E. Grams, Yingying Sang, Josef Coresh, Shoshana H. Ballew, Kunihiro Matsushita, Andrew S. Levey, Tom H. Greene, Miklos Z. Molnar, Zoltan Szabo, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
Journal: Journal of the American Society of Nephrology (2016)

AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%-40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.
P155 Fluticasone furoate (FF)/Vilanterol (VI) once daily reduces rescue medication use both day and night
Authors: LA Jacques, R Forth, L Yates, DA Leather
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> FF/VI is the first once daily inhaled corticosteroid/long-acting b<sub>2</sub>-agonist combination available for the treatment of asthma. Data from five phase III studies that have previously been presented have generally demonstrated a sustained 24 h improvement in lung function and improvement in rescue-free 24 h periods compared with placebo (P), FF alone or fluticasone propionate (FP). Due to differences in study comparators, duration of study and primary endpoints, integration of the study results has not been possible therefore each study is considered separately. <h3>Methods</h3> Post-hoc analyses of diary card data from the 5 studies were performed to examine whether there was any difference in the contribution of the day and night time rescue medication use to the 24 h rescue-free period. Patients recorded in an electronic diary card the number of inhalations of rescue salbutamol/albuterol inhalation aerosol used during the day and night. To be counted as rescue-free during the day or night the patient needed to record a no use of rescue medication during that period. <h3>Results</h3> The post-hoc analyses demonstrated that the improvements in day and night time rescue –free periods were similar to the 24 h rescue free periods. See Figure 1 below. <h3>Conclusions</h3> In general the benefit of FF/VI on rescue free 24 h periods is reflected in the improvements seen in day and night time rescue use.
Recovery from Hyperthermic Damage and Development of Thermotolerance in Unfed Plateau-Phase Cells in Vitro&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: O S Nielsen
Journal: JNCI Journal of the National Cancer Institute (1981)

The hyperthermic responses of unfed plateauphase cells and exponentially growing mouse lung cell L 1A2 heated to 42° C were compared in vitro. No difference in sensitivity to a single treatment up to 4 hours was found. However, in unfed cells the recovery from hyperthermic damage demonstrated during two-dose hyperthermic fractionation (1.5 hr at 42° C each) was reduced approximately 50% relative to that for cells in exponential growth. Preheating for 1.5 hours at 42° C induced thermal resistance to a second heat treatment at 42° C (thermotolerance). With a 10-hour interval, the degree of thermotolerance in unfed cells was reduced to approximately 55% compared to that for exponentially growing cells. Although the pH of the unfed culture was 6.8, adjustment of the pH to 7.2 either during the entire treatment, during the interval separating the two treatments, or during the second treatment resulted in a reduced development of thermotolerance similar to that observed in unfed cells treated without pH adjustment. Therefore, the reduced development of thermotolerance in unfed plateau-phase L1A2 cells was not due to an increased environmental acidity. The results in this study may indicate a way of increasing the therapeutic ratio with the use of fractionated hyperthermic schedules inasmuch as poorly vascularized parts of tumors may be characterized by nutritional depletion and a higher acidity as compared to the surrounding normal tissue.
Maternal plasma total neopterin and kynurenine/tryptophan levels during pregnancy in relation to asthma development in the offspring
Authors: Maria C. Magnus, Øystein Karlstad, Øivind Midtun, Siri E. Håberg, Gro Tunheim, Christine L. Parr, Per Nafstad, Stephanie J. London, Roy M. Nilsen, Per M. Ueland, Wenche Nystad
Journal: Journal of Allergy and Clinical Immunology (2016)
ATPS-53SURGICAL THERAPY FOR CEREBRAL VENTRICLE TUMOR IN INFANTS
Authors: Jie Ma, Wei Meng
Journal: Neuro-Oncology (2015)

BACKGROUND: Surgical treatment for infant ventricle tumors is a tough procedure.We summarize the clinical information, surgical experience and perioperative therapy for 14 patients.METHODS: The patients contained 8 males, 6 females and were treated from 2010-1 to 2014-12.The age ranged from 4 to 24 months with an average of 11.5 months.We used the approach of trigone area for 3 cases, interhemispheric transcallosal for 5 cases, and suboccipital medline for 6 cases.RESULTS: Resection extent: 10 total resection (including 2 subtotal resection), 4 partial resection.Pathology categories: 5 choroid plexus papilomas (CPP), 1 choroid plexus carcinoma,1 mature teratoma, 1 anaplastic CPP, 3 anaplastic ependymoma (WHO III), 1 ependymoma (WHO I-II ), 1 glioma, 1 medulloblastoma.PROGNOSIS: 7 cases survive (4 cases survive with different complications); 5 infants died (all died for abandoning treatment); 1 case was lost.Overall, the prognosis is poor.CONCLUSIONS: 1. Infant cerebral ventricle tumors are often large before symptoms come up.Tumor's proximity to important brain regions makes it difficult for total resection.2. Infants have a small blood volume and poor tolerance to operation, since great blood loss usually occurs intraoperation.Time-consuming operations, such as those for total resection, require a great deal of time under anaesthesia and blood loss.It's preferable to choose a stage operation when severe blood loss occurs.3. Acute resection is a better choice to relieve hydrocephalus rather than drainage.4. Close contact of qualified, specialist medical staff is necessary.Intensive care and nutritional support are important for postoperation therapy.
P55 The occupations associated with COPD risk in the large population-based UK Biobank cohort study
Authors: S De Matteis, D Jarvis, S Hutchings, A Darnton, L Rushton, P Cullinan
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> COPD is one of the leading causes of morbidity and mortality worldwide. Exposure to occupational hazards is an important and preventable risk factor. However, the contribution of each occupation to COPD risk in a general population is uncertain. Our aim was to investigate the association of COPD with occupation in a large UK population-based study. <h3>Methods</h3> Between 2006 and 2010 the UK Biobank cohort recruited 502,649 subjects aged 40–69 years. COPD cases were defined by spirometry-based FEV<sub>1</sub>/FVC &lt;LLN according to ATS/ERS guidelines. Individual current occupation was coded using the Standard Occupation Classification (SOC) 2000. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of COPD for exposure to each SOC-coded job were estimated using a robust Poisson model adjusted for sex, age, study centre and lifetime tobacco smoking. <h3>Results</h3> Of the 353 SOC-coded jobs reported by 228,614 current working participants several occupations showed a significantly increased COPD risk. The occupations at highest COPD risk were Seafarers (PR = 2.64;95% CI:1.59–4.38), Coal mine operatives (PR = 2.30;95% CI:1.00–5.31), Cleaners (Industrial: PR = 1.96;95% CI:1.16–3.31 and Domestic: PR = 1.43;95% CI:1.28–1.59), Roofers/tilers (PR = 1.86;95% CI:1.29–2.67), Packers/bottlers/canners/fillers (PR = 1.60;95% CI:1.15–2.22), Food, drink and tobacco process operatives (PR = 1.46;95% CI:1.11–1.93), Floorers and wall tillers (PR = 1.41;95% CI:1.00–2.00), Postal workers/couriers (PR = 1.35; 95% CI:1.15–1.59), Labourers in building and woodworking trades (PR = 1.32; 95% CI:1.04–1.68), School mid-day assistants (PR = 1.32; 95% CI:1.01–1.74), and Kitchen/catering assistants (PR = 1.30; 95% CI:1.10–1.53). Associations were similar in analyses restricted to never smokers and to subjects never reporting a doctor’s diagnosis of asthma. <h3>Conclusions</h3> Selected occupations are associated with increased COPD risk in a large cross-sectional population-based UK study. Further analyses to investigate the underlying occupational hazards are planned. Occupational health surveillance among these occupations should be strengthened.
Suppression of Alcohol-Induced Hypertension by Dexamethasone
Authors: Denis Randin, Peter Vollenweider, Luc Tappy, Eric Jéquier, Pascal Nicod, Urs Scherrer
Journal: New England Journal of Medicine (1995)

Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympathoexcitatory effects when administered centrally.