tbuckley/cabot-search huggingface dataset:
Prognostic and Predictive Significance of ErbB-2 Breast Tumor Levels Measured by Enzyme Immunoassay
Authors: Serenella Eppenberger-Castori, Willy Kueng, Christopher Benz, Rosmarie Caduff, Zsuzsanna Varga, Fridolin Bannwart, Daniel Fink, Holger Dieterich, Michael Hohl, Heinz Müller, Kaja Paris, Fabrice Schoumacher, Urs Eppenberger
Journal: Journal of Clinical Oncology (2001)

PURPOSE: A retrospective analysis to assess the prognostic and predictive clinical value of breast tumor ErbB-2 receptor expression quantified by enzyme immunoassay (EIA), to compare levels measured by EIA with ErbB-2 status determined by immunohistochemistry (IHC), and to correlate receptor content with levels of phosphorylated (Y1248-P) ErbB-2, a measure of functional tyrosine kinase activity. MATERIALS AND METHODS: EIA quantification of ErbB-2 was performed on membrane extracts from 3,208 well-characterized primary breast cancers. Overall, relapse-free, distant disease-free, and local/regional-free patient survival data were available on 1,123 of these tumors. IHC scoring for ErbB-2 status (HercepTest; DAKO, Glostrup, Denmark) was performed on adjacent sections of 151 cases, and receptor functionality was measured in 230 tumors by an antibody specific for phosphorylated (Y1248-P) ErbB-2. RESULTS: Unlike nonmalignant breast tissues, breast tumors showed increased ErbB-2 levels in a bimodal distribution, with 12% constituting a distinct set of ErbB-2–overexpressing tumors. The intermodal threshold value for ErbB-2 overexpression distinguished tumors with reduced estrogen and progesterone receptor content, high IHC score for ErbB-2, and significantly increased levels of phosphorylated (Y1248-P) ErbB-2 receptor. By multivariate analysis, EIA-determined ErbB-2 overexpression predicted significantly reduced patient survival that was unaffected by tamoxifen or cyclophosphamide, methotrexate, and fluorouracil adjuvant therapy. CONCLUSION: Determination of ErbB-2 receptor expression by EIA offers a clinically valuable alternative to semiquantitative IHC assessment of breast tumor ErbB-2 overexpression and affords the opportunity to evaluate ErbB-2 phosphorylation, which may represent an important predictive parameter of receptor functionality.
Cardiorespiratory fitness and peripheral muscle function in physically active adult smokers
Authors: Evancro Sperandio, Vinícius Lauria, Agatha Matheus, Rodrigo Silva, Flávio Almeida, Vítor Almeida, Mayara Silveira, Marcelo Romiti, Antônio Gagliardi, Rodolfo Arantes, Victor Dourado
Journal: European Respiratory Journal (2014)

Smoking may yield impairment in physical fitness. We hypothesized that adult smokers present decreased physical fitness despite a good level of physical activity in daily life (PADL). We aimed to compare the cardiorespiratory fitness (CRF) and peripheral muscle function in physically active adult smokers and non-smokers. Seventeen smokers (SG), free of lung disease, and 18 non-smokers (CG) aged 30 to 65 years were enrolled. The participants used a triaxial accelerometer for 7 days to assess PADL and those who performed l 2.5 h/wk of moderate to vigorous physical activity were excluded. Anthropometrics, body composition, spirometry, cardiopulmonary exercise testing (CPET), and isokinetic muscle function of the dominant upper and lower limb were assessed. The smoking load in the SG was 30 pack-yr and all the participants presented normal spirometry. There were no significant differences between SG and CG regarding the time spent in moderate–vigorous (5.2 ± 2.5  vs.  5.4 ± 2.0 h) and in vigorous–very vigorous PADL (0.16 ± 0.24  vs.  0.16 ± 0.23 h). The SG presented lower values of FEV 1  (88 ± 14  vs.  104 ± 12%pred.) and FVC (88 ± 15 vs. 104 ± 14%pred.). Peak V9O 2  in the CPET was significantly reduced in the SG (90 ± 12 vs. 101 ± 17%pred.). Despite the similar intensity of PADL, the SG showed increased time spent lying (7.2 ± 6.2 vs. 3.5 ± 2.4%) and tended to spend more time sitting (26 ± 9 vs. 21 ± 8%; p = 0.08). Peripheral muscle function and body composition were preserved in the SG. We may conclude that smoking affects cardiorespiratory fitness even in physically active adult smokers.
Depression in Viet Nam Veterans and Civilian Controls
Authors: John E. Helzer, Lee N. Robins, Eric Wish, Michl Hesselbrock
Journal: American Journal of Psychiatry (1979)

In order to investigate the long-term psychological consequences of Viet Nam combat, the authors located and personally interviewed a group of 571 randomly selected Viet Nam veterans and 284 matched civilian controls 3 years after the veterans returned to the United States. In the veterans they found a weak association between combat and subsequent depressive symptoms, but the association did not persist after controlling for preservice factors. The incidence of depressive symptoms and syndromes was similar when veterans were compared with nonveterans. Results are contrasted with a 12-month follow-up study of the same veterans in which a stronger association between combat and later depression was found.
Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors : a study on behalf of the European Group for Blood and Marrow Transplantation
Authors: Ph. Guardiola, R. Pasquini, I. Dokal, J. J. Ortega, M. van Weel-Sipman, J. C. W. Marsh, S. E. Ball, F. Locatelli, C. Vermylen, R. Skinner, P. Ljungman, R. Miniero, P. J. Shaw, G. Souillet, M. Michallet, A. N. Bekassy, G. Krivan, P. Di Bartolomeo, C. Heilmann, L. Zanesco, J. Y. Cahn, W. Arcese, A. Bacigalupo, E. Gluckman
Journal: Blood (2000)
VOMIT—victim of medical investigative technology
Authors: U Shaikh, Huw Lewis-Jones
Journal: BMJ (2008)

Kmietowicz did not go far enough in highlighting the consumerist nature of commercial body CT scanning.1 Well, asymptomatic young and middle aged patients have a low pretest probability and wouldn’t benefit from a screening test. Furthermore, non-symptom led, non-focused investigations are rife for misinterpretation and error.2 The initial scanning centres in the United States targeted educated, affluent, health …
<i>EGFR</i> Kinase Domain Duplication (<i>EGFR</i>-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib
Authors: Jean-Nicolas Gallant, Jonathan H. Sheehan, Timothy M. Shaver, Mark Bailey, Doron Lipson, Raghu Chandramohan, Monica Red Brewer, Sally J. York, Mark G. Kris, Jennifer A. Pietenpol, Marc Ladanyi, Vincent A. Miller, Siraj M. Ali, Jens Meiler, Christine M. Lovly
Journal: Cancer Discovery (2015)

Oncogenic EGFR mutations are found in 10% to 35% of lung adenocarcinomas. Such mutations, which present most commonly as small in-frame deletions in exon 19 or point mutations in exon 21 (L858R), confer sensitivity to EGFR tyrosine kinase inhibitors (TKI). In analyzing the tumor from a 33-year-old male never-smoker, we identified a novel EGFR alteration in lung cancer: EGFR exon 18-25 kinase domain duplication (EGFR-KDD). Through analysis of a larger cohort of tumor samples, we detected additional cases of EGFR-KDD in lung, brain, and other cancers. In vitro, EGFR-KDD is constitutively active, and computational modeling provides potential mechanistic support for its auto-activation. EGFR-KDD-transformed cells are sensitive to EGFR TKIs and, consistent with these in vitro findings, the index patient had a partial response to the EGFR TKI afatinib. The patient eventually progressed, at which time resequencing revealed an EGFR-dependent mechanism of acquired resistance to afatinib, thereby validating EGFR-KDD as a driver alteration and therapeutic target.We identified oncogenic and drug-sensitive EGFR-KDD that is recurrent in lung, brain, and soft-tissue cancers and documented that a patient with metastatic lung adenocarcinoma harboring the EGFR-KDD derived significant antitumor response from treatment with the EGFR inhibitor afatinib. Findings from these studies will be immediately translatable, as there are already several approved EGFR inhibitors in clinical use.
Safety and efficacy of panitumumab (pmab) in HPV-positive (+) and HPV-negative (-) recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Analysis of the global phase III SPECTRUM trial.
Authors: Jan Stoehlmacher-Williams, Cristian Villanueva, Paolo Foa, Sylvie Rottey, Eric Winquist, Lisa F. Licitra, Irina Davidenko, Krzysztof A. Skladowski, Makoto Tahara, Sandrine J. Faivre, Kelly S. Oliner, Zhiying Pan, Bruce A. Bach, Jan Baptist Vermorken
Journal: Journal of Clinical Oncology (2012)

5504^ Background: SPECTRUM evaluated the safety and efficacy of pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, with platinum‑based chemotherapy (CT) vs CT alone in patients (pts) with R/M SCCHN. This predefined analysis presents outcomes by tumor HPV status. Methods: All tumor samples were centrally reviewed. HPV status was determined using a validated immunohistochemistry assay to p16 INK4A by an independent lab blinded to treatment assignments. Tumor samples were scored positive or negative according to prespecified criteria. Results: Of 657 enrolled pts (ITT), 443 (67%) had samples evaluable for HPV testing. Ninety‑nine (22%) tumors were HPV + and 344 (78%) were HPV - . HPV + rates varied by site (37% oropharynx, 19% larynx, 15% oral cavity, and 13% hypopharynx) and geographic region (44% N America, 22% W Europe, 21% Asia Pacific, 19% S America, and 18% E Europe). Demographics were generally balanced except pts with HPV + vs HPV - tumors were more often non‑smokers (31% vs 14%), had oropharyngeal tumors (47% vs 23%), and had poorly differentiated tumors (30% vs 13%). Efficacy results are shown (Table). Adverse events were generally balanced between HPV + and HPV - pts. Conclusions: Pts with HPV - R/M SCCHN administered pmab + CT had improved overall survival (OS) and progression‑free survival (PFS), whereas no improvement in OS or PFS was observed in pts with HPV + tumors. [Table: see text]
Specificity and negative predictive value of the QuantiFERON-TB®-Gold In Tube testing on trainees in healthcare settings
Authors: Anja Schablon, Genia Diner, Ute Anske, Albert Nienhaus
Journal: European Respiratory Journal (2011)

Evidence is growing of high sensitivity and specificity of the interferon-gamma release assays (IGRA) for the detection of latent TB infection. A further question is that of the reliability of their negative results. A few studies have evaluated the outcome of Healthcare workers and trainees with negative IGRA results over time. We analysed the specificity and the negative predictive value (NVP) of the Quantiferon-Gold In-Tube (QFT) in trainees in healthcare settings.   Methods:  A cohort of trainees at the Vivantes healthcare training institute in Berlin established between October 2008 and July 2010 was tested with the QFT at the beginning and after the first year of training.   Results:  The study population comprised 194 trainees. Two trainees were excluded from the specificity analysis: one due to indeterminate QFT-IT result and one following a history of TB. Of the 192 trainees at baseline, 153 were still in training. At the beginning of training two trainees were QFT positive (1%). The specificity was estimated as 99%. 151 trainees showed persistently negative QFT results. One trainee was QFT positive during the follow-up. One conversion occurred in one case and one reversion occurred. The NVP in this healthy trainee group was 99.3%.   Conclusion:  Our data confirms the findings of a recent meta-analysis (1). This analysis determined a specificity of 99.4% in individuals belonging to low risk groups. The high specificity and the good NPV support the use of QFT for serial testing of HCWs.   Reference:   1Diel R, et al. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis Eur Respir J 2011 37:88-99.
Can red blood cell morphology be an indicator for COPD exacerbations
Authors: Kemal Can Tertemiz, Aylin Ozgen Alpaydin, Seda Salman, Begum Ergan, Arif Hikmet Cimrin
Journal: European Respiratory Journal (2014)

Introduction: RDW is a laboratory parameter showing red blood cell distribution width. RDW can be effected by systemic inflammation. Recent papers showed that RDW could have a relationship between prognosis and mortality in cardiac diseases. We investigated the usability of RDW as an indicator for COPD exacerbations.  Method: We have analysed 100 in patients diagnosed as COPD according to GOLD guideline and COPD exacerbation according to Antonissen criteria. Annual exacerbations, CRP, RDW and blood gase analyses were evaluated in all patients.  Results: Mean age was 70 years, median hospitalisation duration was 12(3-76)days and median annual exacerbation rate was zero(0-7). We have seen that discharging CRP, pCO2, PaO2 and oxygen saturations were improved significantly with respect to interning values (p  Conclusion: We have seen that RDW levels were significantly higher in COPD exacerbations compared with stable period and were elevated during the hospitalisation. This increase shows that RDW is effected like other inflamamtory markers in COPD exacerbations. Unfortunately RDW is inadequate to show criticaly care requirement and mortality prediction.
Genetic snapshots of the Rhizobiumspecies NGR234 genome
Authors: Virginie Viprey, André Rosenthal, William J Broughton, Xavier Perret
Journal: Genome biology (2000)

In nitrate-poor soils, many leguminous plants form nitrogen-fixing symbioses with members of the bacterial family Rhizobiaceae. We selected Rhizobium sp. NGR234 for its exceptionally broad host range, which includes more than I 12 genera of legumes. Unlike the genome of Bradyrhizobium japonicum, which is composed of a single 8.7 Mb chromosome, that of NGR234 is partitioned into three replicons: a chromosome of about 3.5 Mb, a megaplasmid of more than 2 Mb (pNGR234b) and pNGR234a, a 536,165 bp plasmid that carries most of the genes required for symbioses with legumes. Symbiotic loci represent only a small portion of all the genes coded by rhizobial genomes, however. To rapidly characterize the two largest replicons of NGR234, the genome of strain ANU265 (a derivative strain cured of pNGR234a) was analyzed by shotgun sequencing.Homology searches of public databases with 2,275 random sequences of strain ANU265 resulted in the identification of 1,130 putative protein-coding sequences, of which 922 (41%) could be classified into functional groups. In contrast to the 18% of insertion-like sequences (ISs) found on the symbiotic plasmid pNGR234a, only 2.2% of the shotgun sequences represent known ISs, suggesting that pNGR234a is enriched in such elements. Hybridization data also indicate that the density of known transposable elements is higher in pNGR234b (the megaplasmid) than on the chromosome. Rhizobium-specific intergenic mosaic elements (RIMEs) were found in 35 shotgun sequences, 6 of which carry RIME2 repeats previously thought to be present only in Rhizobium meliloti. As non-overlapping shotgun sequences together represent approximately 10% of ANU265 genome, the chromosome and megaplasmid may carry a total of over 200 RIMEs.'Skimming' the genome of Rhizobium sp. NGR234 sheds new light on the fine structure and evolution of its replicons, as well as on the integration of symbiotic functions in the genome of a soil bacterium. Although most putative coding sequences could be distributed into functional classes similar to those in Bacillus subtilis, functions related to transposable elements were more abundant in NGR234. In contrast to ISs that accumulated in pNGR234a and pNGR234b, the hundreds of RIME elements seem mostly attributes of the chromosome.
Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe
Authors: R. Ozaras, G. Corti, S. Ruta, K. Lacombe, M.U. Mondelli, W.L. Irwing, M. Puoti, A. Khalighi, M.L. Santos, A. Harxhi, I. Lazarevic, V. Soriano, J. Gervain, H. Leblebicioglu, D. Salmon, J.E. Arends
Journal: Clinical Microbiology and Infection (2015)
Abstract 3594: Serotonin in Adipose Tissue Acts as an Autocrine Factor Required for Adipocyte Differentiation and Lipolysis
Authors: Koh Ono, Takahiro Horie, Yukiko Abe, Teruhisa Kawamura, Minako Kinoshita, Hitoo Nishi, Kazuya Nagao, Noriko Satoh, Akira Shimatsu, Toru Kita, Koji Hasegawa
Journal: Circulation (2007)

The differentiation of preadiopocytes (preAdps) into mature adipocytes (Adps) is closely associated with the expression of adipocyte (Adp)-specific gene products that are deeply involved in insulin resistance; therefore, it is critical to identify genes required for Adp differentiation. We used retrovirus insertion-mediated random mutagenesis to generate 3T3-L1 preAdp cells which lose their ability to differentiate into mature Adps. Using this approach, we discovered that tryptophan hydroxylase-1 (TPH1), a rate-limiting enzyme for the biosynthesis of serotonin (Ser), was required for Adp differentiation. While differentiation was clearly reduced in a mutant 3T3-L1 cell line that lacked expression of the normal TPH1 gene, reconstitution of the TPH1 gene in this cell line restored its differentiation potential. The administration of Ser enhanced differentiation in 3T3-L1 cells and in cells of the stromal vascular fraction from adult mice. On the other hand, differentiation was inhibited by 5-hydroxy tryptophan type 2A (5HT2A) receptor antagonists as well as the Ser synthesis inhibitor. Differentiation into mature Adp was significantly impaired in preAdps prepared from TPH1−/− mice compared to those from wild-type mice. We observed no differences in the histology of adipose tissue between TPH1−/−and wild-type mice at the basal state; however, after obesity was induced by a high-fat diet, increases in body weight and mesenteric fat weight were more prominent in TPH1−/− mice than in wild-type mice. In obese groups, we observed extremely large (140μm∼) Adps without any small Adps in TPH1−/− mice, in contrast to usually hypertrophied (μ80∼m) Adps and small Adps in wild-type mice. Interestingly, Ser treatment of mature cultured Adps enhanced lipolysis, which was blocked by the 5HT7 receptor antagonist but not by the 5HT2A receptor antagonist. Oral administration of 5HT2A receptor antagonist in high fat diet-induced obese mice reduced mesenteric fat weight and the number of small adipocytes; however, it did not increase the number of extremely large adipocytes as seen in TPH1−/−mice. Thus, Ser in adipose tissue acts as an autocrine factor required for Adp differentiation and lipolysis. Distinct receptor subtypes appear to mediate these two processes.
The prevalence of pyrazinamide resistance in multidrug resistant tuberculosis cases in the Netherlands
Authors: Sami Simons, Jakko van Ingen, Martin Boeree, Dick Van Soolingen
Journal: European Respiratory Journal (2012)

Introduction    Pyrazinamide is very important in the treatment of multidrug resistant tuberculosis (MDR TB). Unfortunately, studies on the prevalence of pyrazinamide resistance in MDR TB cases are scarce and mainly come from non-European countries.    Aims and Objectives    Our aim was to determine the prevalence of pyrazinamide resistance in MDR TB cases from the Netherlands.    Methods    We retrospectively analyzed pyrazinamide resistance in all MDR TB cases from the Netherlands found in 2007-2011. Drug susceptibility testing was performed using the Mycobacterial Growth Indicator Tube (MGIT) method. Also, in every resistant isolate the  pncA  gene was sequenced. Resistance was determind using a diagnostic algorithm described recently by our group incorporating both methods (Simons, S.O.,  et al . JCM 2012; 50:428-34).    Results    61 cases of multidrug resistant tuberculosis were seen in the Netherlands from 2007-2011. Pyrazinamide resistance testing was possible in 59 cases. In 17 MDR TB cases pyrazinamide resistance was observed (29%). 16 out of these 17 cases carried a nonsynonymous mutation in the  pncA  gene.    Conclusions    Our data suggest that among MDR TB cases in the Netherlands pyrazinamide resistance is around 29%. Strategies are required to determine the optimal diagnostic algorithm in this population.
Pulmonary hydatic cyst: Analysis of 1024 cases
Authors: Reza Bagheri, Seied Ziaoolah Haghi
Journal: European Respiratory Journal (2011)

Objective:  Pulmonary hydatic cyst is a parasitic disease and health care problem in developing countries. In this study we evaluated treatment outcomes of pulmonary hydatic disease in our Department.   Methods:  Patients admitted with pulmonary hydatic cyst from 1981 to 2008 enrolled in this study and demographic data, site and number of cysts, diagnostic methods, type of operations, outcomes and rate of recurrence were statistically analyzed.   Results:  In 1024 patients, mean age was (30.6±16.1) years and M/F=1.09. The most common symptom was cough (55.1%).  Only 1% was asymptomatic. 53.8% had right side involvement, 40% had left side involvement and 6.2% had bilateral disease. Inferior lobe was the most common involved lobe. The cyst was intact in 539 (52.6%) patients and other, were complicated or perforated. The most common surgical technique was removing the cyst membrane without resection of pericyst and closure of orifice of air ways (67.2%). The cyst was enucleated in 21.2% and parenchymal resection was performed in 10.3%. The mortality rate was (0.2%) and morbidity occurred in 8.4% of patients. The most common complications were residual spaces with prolonged airleak and wound infection. The recurrence rate was 2.5% mostly managed by surgery (82.6%).   Conclusion:  The best treatment for pulmonary hydatic cyst disease is surgery with low mortality and morbidity. The most common and acceptable treatment is extraction of cyst membrane without manipulation of pericyst and closure of small air ways. Pulmonary resection should be reserved for complicated forms of disease.
Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies.
Authors: K Mross, P Bewermeier, W Krüger, M Stockschläder, A Zander, D K Hossfeld
Journal: Journal of Clinical Oncology (1994)

We used two different methods to administer high-dose etoposide (VP-16) during a myeloablative conditioning chemotherapy regimen before bone marrow transplantation (BMT). VP-16 was administered either diluted (0.5 mg/mL) or undiluted (20 mg/mL), with or without busulfan.Blood samples were drawn from 17 patients during the infusion (6 hours) and thereafter daily until 2 days after BMT. VP-16 concentrations were measured in all plasma samples by high-performance liquid chromatography (HPLC) and electrochemical detection, and the results were analyzed with a pharmacokinetic data analysis system.All calculated pharmacokinetic parameters in the two patient groups (VP-16 administered diluted or undiluted) were similar. There were no statistically significant differences in half-lives, mean residence time (MRT), volume of distribution, total clearance, or area under the curve (AUC). VP-16 was found in blood samples from eight of 17 patients at the time of BMT. Significant differences in systemic drug exposure and systemic clearance were found when patients were grouped according to treatment with busulfan or with total-body irradiation (TBI).The two administration modes for VP-16, either diluted or undiluted, are bioequivalent in pharmacokinetic terms. The terminal half-lives were longer than expected and resulted in significant VP-16 plasma levels at the time of BMT. The biologic significance remains unclear. Busulfan and/or concomitant medication with phenytoin influence plasma clearance (clp) and systemic drug exposure significantly.