tbuckley/cabot-search huggingface dataset:
Expression of Amphiregulin and EGFRvIII Affect Outcome of Patients with Squamous Cell Carcinoma of the Head and Neck Receiving Cetuximab–Docetaxel Treatment
Authors: Ingeborg Tinhofer, Konrad Klinghammer, Wilko Weichert, Maren Knödler, Albrecht Stenzinger, Thomas Gauler, Volker Budach, Ulrich Keilholz
Journal: Clinical Cancer Research (2011)

Constitutive activation of epidermal growth factor receptor (EGFR) as a result of gene amplification, mutation, or overexpression of its ligands has been associated with response to EGFR targeting strategies. The role of these molecular mechanisms for the responsiveness of squamous cell carcinoma of the head and neck (SCCHN) to cetuximab-containing regimens remains unknown.Tumor biopsies from 47 patients, enrolled in a single-arm phase II multicenter study for second-line treatment of recurrent or metastatic SCCHN with cetuximab and docetaxel, were analyzed by immunohistochemistry for expression of EGFR, its deletion variant III (EGFRvIII) and its ligand amphiregulin (AREG). The relation between expression levels and disease control rate (DCR) was evaluated by logistic regression. Association between expression levels, progression-free survival (PFS), and overall survival (OS) was determined by Kaplan-Meier analysis, log-rank test, and uni- and multivariate Cox regression analysis.High expression of EGFR, EGFRvIII, and AREG was detected in 73%, 17%, and 45% of SCCHN cases, respectively. Expression levels of EGFR had no impact on PFS or OS. High expression levels of EGFRvIII were significantly associated with reduced DCR and shortened PFS (HR: 3.3, P = 0.005) but not with OS. Patients with high AREG expression in tumor cells had significantly shortened OS (HR: 2.2, P = 0.002) and PFS (HR 2.2, P = 0.019) compared with patients with low expression score. Multivariate Cox analysis revealed an independent association of AREG and EGFRvIII with PFS but only AREG was an independent prognosticator of OS.High EGFRvIII and AREG expression levels identify SCCHN patients who are less likely to benefit from combination treatment with cetuximab and docetaxel.
HHV8 associated Kaposi's sarcoma during triple immunosuppressive treatment with cyclosporin A, azathioprine, and prednisolone for ocular Behcet's disease and complete remission of both disorders with interferon alpha
Authors: I Kötter, C Aepinus, F Graepler, V Gärtner, A K Eckstein, N Stübiger, B Kaskas, M Zierhut, B Bültmann, R Kandolf, L Kanz
Journal: Annals of the Rheumatic Diseases (2001)

Behcet’s disease is a multisystem vasculitis with oral and genital aphthous ulcers, cutaneous vasculitis, uveitis, and arthritis as its main features. 1 Ocular manifestations, especially panuveitis, have a poor prognosis, resulting in blindness in most patients after five years, irrespective of treatment. Recent reports have shown significant improvement of visual prognosis by early and aggressive immunosuppressive treatment. 2 However, immunosuppressive treatment bears a risk of opportunistic infections, especially herpesvirus reactivation and increased incidence of malignancies. 3 Kaposi’s sarcoma is a rare malignant tumour (incidence 0.01%) of endothelia and vascular smooth muscle cells which has a markedly increased incidence in patients with AIDS (0.9%) 4 and iatrogenic immunosuppression (0.52%).
A levels and intelligence as predictors of medical careers in UK doctors: 20 year prospective study
Authors: I C McManus
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To assess whether A level grades (achievement) and intelligence (ability) predict doctors9 careers. <b>Design</b> Prospective cohort study with follow up after 20 years by postal questionnaire. <b>Setting</b> A UK medical school in London. <b>Participants</b> 511 doctors who had entered Westminster Medical School as clinical students between 1975 and 1982 were followed up in January 2002. <b>Main outcome measures</b> Time taken to reach different career grades in hospital or general practice, postgraduate qualifications obtained (membership/fellowships, diplomas, higher academic degrees), number of research publications, and measures of stress and burnout related to A level grades and intelligence (result of AH5 intelligence test) at entry to clinical school. General health questionnaire, Maslach burnout inventory, and questionnaire on satisfaction with career at follow up. <b>Results</b> 47 (9%) doctors were no longer on the Medical Register. They had lower A level grades than those who were still on the register (P &lt; 0.001). A levels also predicted performance in undergraduate training, performance in postregistration house officer posts, and time to achieve membership qualifications (Cox regression, P &lt; 0.001; b=0.376, SE=0.098, exp(b)=1.457). Intelligence did not independently predict dropping off the register, career outcome, or other measures. A levels did not predict diploma or higher academic qualifications, research publications, or stress or burnout. Diplomas, higher academic degrees, and research publications did, however, significantly correlate with personality measures. <b>Conclusions</b> Results of achievement tests, in this case A level grades, which are particularly used for selection of students in the United Kingdom, have long term predictive validity for undergraduate and postgraduate careers. In contrast, a test of ability or aptitude (AH5) was of little predictive validity for subsequent medical careers.
THE IMMUNOLOGICAL RELATIONSHIPS OF STREPTOCOCCUS VIRIDANS AND CERTAIN OF ITS CHEMICAL FRACTIONS
Authors: Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1925)

1. Agglutination and precipitation by the specific substance of Streptococcus viridans are parallel phenomena. Separate specific substances have been extracted from strains which are distinct by ordinary serological tests. Preliminary chemical examination indicates that the specific substances may be complex carbohydrates. 2. A close relationship between nucleoproteins from different strains of Streptococcus viridans is suggested by the existence of a certain amount of cross-precipitation and a larger degree of cross-complement fixation. But the occurrence of stronger reactions with homologous nucleoproteins than with heterologous indicates that there is some degree of individual difference in proteins from separate strains. 3. Two distinct antibodies are present in the sera antibacterial for Streptococcus viridans: one of high titer implicated in the parallel phenomena of agglutination and precipitation by the soluble specific substance, the other usually of low titer and involved in precipitation by nucleoproteins but probably little, if at all, in agglutination. The significance of these results obtained from the study of antibacterial sera will be considered in the general discussion of the antigenic components of Streptococcus viridans after the results from the study of antinucleoprotein sera have been presented in the succeeding paper.
Migraine--treatment of acute attack.
Authors: M Wilkinson
Journal: BMJ (1971)

The treatment of an acute attack of classical or common migraine is sleep, an antinauseant such as metoclopramide, an analgesic, either aspirin or paracetamol, and in some patients 1 or 2 mg of ergotamine tartrate. Treatment should be given as early in the attack as possible and all drugs should, if possible, be given in a soluble or effervescent form. When vomiting occurs early in the attack, treatment is best given by suppository, inhalation or intramuscular injection. Ergotamine tartrate is only necessary in about one third of attacks and when used is best given by suppository or inhalation. Doses of ergotamine tartrate higher than 2 mg per attack or 6 mgs per week may cause toxic symptoms as may the abuse of analgesics.
Intestinal epithelial cells preferentially attach to a biomatrix derived from human intestinal mucosa.
Authors: U Hahn, A Cho, D Schuppan, E G Hahn, H J Merker, E O Riecken
Journal: Gut (1987)

Primary intestinal epithelial cells have a very short lifespan in vitro when cultured free of mucosal elements. Support of the basal plasma membrane by a more natural substrate may thus enhance the initiation of primary cell cultures. A cell free biomatrix consisting of native interstitial collagens, basement membrane fragments and microfibrils was extracted from the lamina propria of human intestinal mucosa. Immunofluorescence revealed the presence of collagens type III, IV, and VI and procollagens type I and III as well as fibronectin, laminin and undulin. Primary crypt cells of suckling mice displayed a significantly increased affinity to pepsin and collagenase solubilised intestinal biomatrix when compared with plastic and fibronectin. Colonies of primary crypt cells survived for up to four days and longer on pepsin solubilised biomatrix but only for 48 hours on fibronectin. The intestinal biomatrix preparation has proved to be a useful substrate for the initiation and prolongation of primary intestinal cell cultures.
Clinical Analysis and Interpretation of Cancer Genome Data
Authors: Eliezer M. Van Allen, Nikhil Wagle, Mia A. Levy
Journal: Journal of Clinical Oncology (2013)

The scale of tumor genomic profiling is rapidly outpacing human cognitive capacity to make clinical decisions without the aid of tools. New frameworks are needed to help researchers and clinicians process the information emerging from the explosive growth in both the number of tumor genetic variants routinely tested and the respective knowledge to interpret their clinical significance. We review the current state, limitations, and future trends in methods to support the clinical analysis and interpretation of cancer genomes. This includes the processes of genome-scale variant identification, including tools for sequence alignment, tumor-germline comparison, and molecular annotation of variants. The process of clinical interpretation of tumor variants includes classification of the effect of the variant, reporting the results to clinicians, and enabling the clinician to make a clinical decision based on the genomic information integrated with other clinical features. We describe existing knowledge bases, databases, algorithms, and tools for identification and visualization of tumor variants and their actionable subsets. With the decreasing cost of tumor gene mutation testing and the increasing number of actionable therapeutics, we expect the methods for analysis and interpretation of cancer genomes to continue to evolve to meet the needs of patient-centered clinical decision making. The science of computational cancer medicine is still in its infancy; however, there is a clear need to continue the development of knowledge bases, best practices, tools, and validation experiments for successful clinical implementation in oncology.
Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use
Authors: Andrew T. Bender, Joseph A. Beavo
Journal: Pharmacological Reviews (2006)

Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the cellular levels of the second messengers, cAMP and cGMP, by controlling their rates of degradation. There are 11 different PDE families, with each family typically having several different isoforms and splice variants. These unique PDEs differ in their three-dimensional structure, kinetic properties, modes of regulation, intracellular localization, cellular expression, and inhibitor sensitivities. Current data suggest that individual isozymes modulate distinct regulatory pathways in the cell. These properties therefore offer the opportunity for selectively targeting specific PDEs for treatment of specific disease states. The feasibility of these enzymes as drug targets is exemplified by the commercial and clinical successes of the erectile dysfunction drugs, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). PDE inhibitors are also currently available or in development for treatment of a variety of other pathological conditions. In this review the basic biochemical properties, cellular regulation, expression patterns, and physiological functions of the different PDE isoforms will be discussed. How these properties relate to the current and future development of PDE inhibitors as pharmacological agents is especially considered. PDEs hold great promise as drug targets and recent research advances make this an exciting time for the field of PDE research.
Proximate and ultimate causes of punishment and strong reciprocity
Authors: Pat Barclay
Journal: Behavioral and Brain Sciences (2012)

Abstract While admirable, Guala's discussion of reciprocity suffers from a confusion between proximate causes (psychological mechanisms triggering behaviour) and ultimate causes (evolved function of those psychological mechanisms). Because much work on “strong reciprocity” commits this error, I clarify the difference between proximate and ultimate causes of cooperation and punishment. I also caution against hasty rejections of “wide readings” of experimental evidence.
Balance between Proinflammatory Cytokines and Their Inhibitors in Bronchial Lavage from Patients with Status Asthmaticus
Authors: ISABELLE TILLIE-LEBLOND, JÉRÔME PUGIN, CHARLES-HUGO MARQUETTE, CATHERINE LAMBLIN, FABIENNE SAULNIER, ANNE BRICHET, BENOIT WALLAERT, ANDRÉ-BERNARD TONNEL, PHILIPPE GOSSET
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Status asthmaticus (SA) is an acute respiratory failure combining an acute bronchospastic reaction with a severe airway inflammation. We previously reported an important influx of neutrophils and an increased secretion of interleukin-8 (IL-8) in patients with SA. The aim of this prospective study was to evaluate in bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation (MV) the concentrations of cytokines and related mediators which have the ability to modulate inflammation, either proinflammatory (interleukin-1 β [IL-1 β ], IL-6, tumor necrosis factor- α [TNF- α ]), or anti-inflammatory mediators (IL-10, transforming growth factor- β 1 [TGF- β 1]), interleukin-1 receptor antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine the relative importance of both pro- and anti-inflammatory mediators, the net inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549 epithelial cell line. These data were compared with those obtained from patients who required MV without respiratory disease (V, n = 4), controlled asthma (A, n = 11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF- α , and of the active form of TGF- β 1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF- β 1, and of the sTNFRI and II were not significantly different between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra and IL-1 β was significantly higher in patients with SA compared with the other groups, whereas there was no difference for the ratio between both types of sTNFR and TNF- α . Despite a marked increase of anti-inflammatory mediators in BL from patients with SA, the net inflammatory activity was found to be proinflammatory and mainly due to the presence of bioactive IL-1 β (79% inhibition of ICAM-1 expression with anti-IL-1 β antibodies) and to a lesser extent TNF- α (32% inhibition with anti-TNF- α antibodies).
Computer bronchophonography (CBPG) - Method of assessment of respiratory function in asthmatic children
Authors: Svetlana Shatalina, Natalya Geppe, Natalya Kolosova, Vladimir Malishev
Journal: European Respiratory Journal (2013)

Background: Children with poorly controlled asthma have exacerbations and persistent airflow obstruction despite treatment with ICS and LABAs that requires regular assessment of lung function.   Aim:  To estimate lung function by CBPG during the first 20 minutes after the inhalation of BUD/FORM versus SABA and LABA in children with bronchial asthma.   Materials and methods:  40 patients (age 6- 16 years) with poorly controlled asthma were divided in 2 parallel groups. On Day 1 children in Group 1 inhaled ICS/LABA (bud/form 80/4,5μg), on Day 2 – LABA (form 9μg) and on Day 3 - SABA (salbutamol 200μg). Children in Group 2 inhaled bronchodilators in reverse order: SABA, LABA, ICS/LABA. We evaluated CBPG data before and 20 minutes after inhalation of bronchodilators and compared these with spirometry data. Registration of respiratory sounds was recorded by high sensitivity transducer in wide range of frequencies during quiet breathing.   Results:  In both groups the results of spirometry were similar. FEV1 after BUD/FORM increased from 82,1%±2,1% to 92%±2,2% (p≤0,002), after LABA – from 79,1%±2,3% to 87,9%±3,4% (p≤0,013), after SABA from 72,5%±3,7% to 82,8%±4,6% (p≤0,004). ACBW decreased in high-frequency zone from 0,35+0,04mcJ to 0,15+0,02mcJ (p=0,001) after BUD/FORM, from 0,33+0,05mcJ to 0,18+0,03mcJ (p=0,005) after LABA, from 0,33+0,04mcJ Ao 0,15+0,04mcJ (p=0,001) after SABA.   Conclusions:  The intensity of the acoustic component of breathing in the high frequency zone (ACBW, mcJ) correlated with bronchial obstruction. Due to the combined bronchodilator and anti-inflammatory actions BUD/FORM can treat both bronchoconstriction and inflammation at the early stages of exacerbations.
Rapid Microvessel Rarefaction With Elevated Salt Intake and Reduced Renal Mass Hypertension in Rats
Authors: Fay M. Hansen-Smith, Laura W. Morris, Andrew S. Greene, Julian H. Lombard
Journal: Circulation Research (1996)

To identify the sequence of events associated with the development of reduced vessel density (rarefaction) in hypertension, microvessel density and ultrastructure were assessed in the cremaster muscle of rats subjected to a 75% surgical reduction of renal mass and normotensive sham-operated control rats. Rats with reduced renal mass (RRM rats) and sham-operated rats were then maintained on either a high salt (4.0% NaCl) or a low salt (0.4% NaCl) diet for 3 days. Acute exposure to the high salt diet significantly increased mean arterial pressure in RRM rats but did not affect sham-operated control rats. Quantitative fluorescence microscopy of cremaster muscle whole mounts using rhodamine-labeled Griffonia simplicifolia I lectin revealed substantial rarefaction of microvessels in both RRM hypertensive rats and normotensive sham-operated rats on a high salt diet relative to corresponding control rats on a low salt diet. Confocal microscopy revealed a heterogeneous distribution of microvessels in RRM rats on a high salt diet, with some areas largely devoid of vessels. RRM and sham-operated rats on a high salt diet both exhibited changes in arteriolar ultrastructure, which included a loss of basement membranes and a dissociation of the endothelial and smooth muscle components of the vascular wall, resulting in a loss of vessel integrity. These observations demonstrate that a rapid loss of microvessels can occur not only in rats with RRM hypertension but also in normotensive rats on a high salt diet. This loss of microvessels results from structural alterations, which differ from the degenerative processes associated with microvascular rarefaction in rats with chronic RRM hypertension.
Partitioning of the contributions of rib cage and abdomen to ventilation in ankylosing spondylitis
Authors: G. Grimby, A. R. Fugl-Meyer, A. Blomstrand
Journal: Thorax (1974)

<b>Grimby, G., Fugl-Meyer, A. R., and Blomstrand, A. (1974).</b><i>Thorax,</i><b>29,</b> 179-184. <b>Partitioning of the contributions of rib cage and abdomen to ventilation in ankylosing spondylitis.</b> The relative contributions of the rib cage and abdomen to ventilation were studied in the sitting position in patients with ankylosing spondylitis, using measurements of changes in the anteroposterior diameters. The functional impairment of the spine and adjacent joints was also evaluated. In most patients vital capacity and total lung capacity were reduced, but functional residual capacity was normal. The relative contribution of the rib cage to ventilation was reduced at rest compared to normal subjects, and decreased further during hyperventilation induced by rebreathing. The end-expiratory level of the abdomen decreased more markedly during hyperventilation than in normal subjects and even the end-inspiratory level of the abdomen increased somewhat. The findings are consistent with a reduced mobility of the ribs and a greater than normal excursion of the diaphragm during breathing.
Feasibility of Resuming Peritoneal Dialysis after Severe Peritonitis and Tenckhoff Catheter Removal
Authors: Cheuk-Chun Szeto, Kai-Ming Chow, Teresa Yuk-Hwa Wong, Chi-Bon Leung, Angela Yee-Moon Wang, Siu-Fai Lui, Philip Kam-Tao Li
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Published guidelines suggest that after an episode of severe peritonitis that requires Tenckhoff catheter removal, peritoneal dialysis can be resumed after a minimum of 3 wk. However, the feasibility of resuming peritoneal dialysis after Tenckhoff catheter removal remains unknown. One hundred patients were identified with peritonitis that did not respond to standard antibiotic therapy in a specific center. Their clinical course was reviewed; in all of them, Tenckhoff catheters were removed and reinsertion was attempted at least 4 wk later. In 51 patients, the Tenckhoff catheter was successfully reinserted and peritoneal dialysis was resumed (success group). In the other 49 pateints, reinsertion failed and the patient was put on long-term hemodialysis (fail group). The patients were followed for 18.5 ± 16.8 mo. The overall technique survival was 30.8% at 24 mo. In the success group, 11 patients were changed to long-term hemodialysis within 8 mo after their return to continuous ambulatory peritoneal dialysis. In the fail group, 18 of the 20 deaths occurred within 12 mo after conversion to long-term hemodialysis. After resuming peritoneal dialysis, there was a significant decline in net ultrafiltration volume (0.38 ± 0.16 to 0.21 ± 0.19 L; P = 0.03) and a trend of rise in dialysate-to-plasma ratios of creatinine at 4 h (0.664 ± 0.095 to 0.725 ± 0.095; P = 0.15). Forty-five patients (88.2%) required additional dialysis exchanges or hypertonic dialysate to compensate for the loss of solute clearance or ultrafiltration, although there was no significant change in dialysis adequacy or nutritional status. It was concluded that after an episode of severe peritonitis that required Tenckhoff catheter removal, only a small group of patients could return to peritoneal dialysis. An early assessment of peritoneal function after Tenckhoff catheter reinsertion may be valuable.