Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma:a translational study

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines.Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays.Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found.Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy

Diagnostic labelling as determinant of antibiotic prescribing for acute respiratory tract episodes in general practice

<p>Abstract</p> <p>Background</p> <p>Next to other GP characteristics, diagnostic labelling (the proportion of acute respiratory tract (RT) episodes to be labelled as infections) probably contributes to a higher volume of antibiotic prescriptions for acute RT episodes. However, it is unknown whether there is an independent association between diagnostic labelling and the volume of prescribed antibiotics, or whether diagnostic labelling is associated with the number of presented acute RT episodes and consequently with the number of antibiotics prescribed per patient per year.</p> <p>Methods</p> <p>Data were used from the Second Dutch National Survey of General Practice (DNSGP-2) with 163 GPs from 85 Dutch practices, serving a population of 359,625 patients. Data over a 12 month period were analysed by means of multiple linear regression analysis. Main outcome measure was the volume of antibiotic prescriptions for acute RT episodes per 1,000 patients.</p> <p>Results</p> <p>The incidence was 236.9 acute RT episodes/1,000 patients. GPs labelled about 70% of acute RT episodes as infections, and antibiotics were prescribed in 41% of all acute RT episodes. A higher incidence of acute RT episodes (beta 0.67), a stronger inclination to label episodes as infections (beta 0.24), a stronger endorsement of the need of antibiotics in case of white spots in the throat (beta 0.11) and being male (beta 0.11) were independent determinants of the prescribed volume of antibiotics for acute RT episodes, whereas diagnostic labelling was not correlated with the incidence of acute RT episodes.</p> <p>Conclusion</p> <p>Diagnostic labelling is a relevant factor in GPs' antibiotic prescribing independent from the incidence of acute RT episodes. Therefore, quality assurance programs and postgraduate courses should emphasise to use evidence based prognostic criteria (e.g. chronic respiratory co-morbidity and old age) as an indication to prescribe antibiotics in stead of single inflammation signs or diagnostic labels.</p

The influence of population characteristics on variation in general practice based morbidity estimations

Contains fulltext : 96442.pdf (publisher's version ) (Open Access

Usefulness of primary care electronic networks to assess the incidence of chlamydia, diagnosed by general practitioners

Background: Chlamydia is the most common curable sexually transmitted infection (STI) in the Netherlands. The majority of chlamydia diagnoses are made by general practitioners (GPs). Baseline data from primary care will facilitate the future evaluation of the ongoing large population-based screening in the Netherlands. The aim of this study was to assess the usefulness of electronic medical records for monitoring the incidence of chlamydia cases diagnosed in primary care in the Netherlands. Methods. In the electronic records of two regional and two national networks, we identified chlamydia diagnoses by means of ICPC codes (International Classification of Primary Care), laboratory results in free text and the prescription of antibiotics. The year of study was 2007 for the two regional networks and one national network, for the other national network the year of study was 2005. We calculated the incidence of diagnosed chlamydia cases per sex, age group and degree of urbanization. Results: A large diversity was observed in the way chlamydia episodes were coded in the four different GP networks and how easily information concerning chlamydia diagnoses could be extracted. The overall incidence ranged from 103.2/100,000 to 590.2/100,000. Differences were partly related to differences between patient populations. Nevertheless, we observed similar trends in the incidence of chlamydia diagnoses in all networks and findings were in line with earlier reports. Conclusions: Electronic patient records, originally intended for individual patient care in general practice, can be an additional source of data for monitoring chlamydia incidence in primary care and can be of use in assessing the future impact of population-based chlamydia screening programs. To increase the usefulness of data we recommend more efforts to standardize registration by (specific) ICPC code and laboratory results across the existing GP networks

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation.</p> <p>Methods</p> <p>The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [⁶⁰Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [⁶⁰Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [⁶⁰Co] γ-rays; Group C included cells treated with 8 Gy of [⁶⁰Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis.</p> <p>Results</p> <p>Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [⁶⁰Co] γ-rays (<it>P </it>< 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [⁶⁰Co] γ-rays (<it>P </it>< 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (<it>P </it>< 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased.</p> <p>Conclusions</p> <p>Compared with ��-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2.</p

A two-step target binding and selectivity support vector machines approach for virtual screening of dopamine receptor subtype-selective ligands

10.1371/journal.pone.0039076PLoS ONE76

Sexually transmitted infections, including HIV, in the Netherlands in 2008

Chlamydia, gonorroe, syfilis. Na een stabilisatie van het percentage positieve chlamydiatesten in 2007, is dit in 2008 weer toegenomen. Vooral onder jonge heteroseksuelen en bij mannen die seks hebben met mannen (MSM) komt chlamydia veel voor. Het percentage positieve gonorroe- en syfilistesten nam in 2008 verder af. Deze infecties werden het meest gediagnosticeerd bij MSM. Hiv. In 2008 werden 393 nieuwe hivdiagnoses gesteld in de soacentra, bijna de helft van de 851 hivpositieven die dat jaar landelijk werden gediagnosticeerd en geregistreerd in de hivcentra. Het percentage bezoekers van de soacentra dat zich in 2008 op hiv liet testen nam toe tot 90%. Eind 2008 waren in totaal 15.538 personen in Nederland met hiv geregistreerd. Het aandeel MSM onder de nieuwe hivinfecties nam in 2008 verder toe. MSM. Bij 22% van MSM werd een of meerdere soa gevonden; bij MSM die weten dat ze hivpositief zijn was dit 36%. Daarnaast wordt in deze groep sinds 2004 regelmatig lymfogranuloma venereum (LGV), een agressieve variant van chlamydia, en sinds 2007 acute hepatitis C geconstateerd. Jongeren. Sinds 2008 houden GGD'en speciaal voor jongeren onder de 25 jaar de zogeheten Sense-spreekuren. Daar kunnen zij met hun vragen over seks terecht en direct een afspraak maken voor een soa-onderzoek. In 2009 wordt het essentieel om de samenhang te intensiveren. tussen maatregelen die erop gericht zijn soa's te voorkomen en te genezen. De soacentra. De soacentra bieden zorg aan hoogrisicogroepen, waaronder jongeren, MSM en personen afkomstig uit gebieden waar soa's relatief veel voorkomen. In 2008 hebben ruim 88.000 personen zich laten testen, een toename van 13% ten opzichte van 2007