Activation of c-Met leads to a wide spectrum of biological activities such as motility, angiogenesis, morphogenesis, cell survival and cell regeneration. c-Met is abnormally activated in many tumour types. Aberrant c-Met activation was found to induce tumour development, tumour cell migration and invasion, and the worst and final step in cancer progression, metastasis. In addition, c-Met activation in cells was also shown to confer resistance to apoptosis induced by UV damage or chemotherapeutic drugs. This study describes the development of monoclonal antibodies against c-Met as therapeutic molecules in cancer treatment/diagnostics. A panel of c-Met monoclonal antibodies was developed and characterised by epitope mapping, Western blotting, immunoprecipitation, agonist/antagonist effect in cell scatter assays and for their ability to recognise native c-Met by flow cytometry. We refer to these antibodies as Specifically Engaging Extracellular c-Met (seeMet). seeMet 2 and 13 bound strongly to native c-Met in flow cytometry and reduced SNU-5 cell growth. Interestingly, seeMet 2 binding was strongly reduced at 4°C when compared to 37°C. Detail mapping of the seeMet 2 epitope indicated a cryptic binding site hidden within the c-Met α-chain. The 1401349VNVXXXY1356VHV) in the carboxyl-terminal tail of c-Met [Hepatocyte growth factor (HGF) is the only known c-Met ligand. Upon HGF binding, c-Met receptor dimerises on the cell surface which results in autophosphorylation of tyrosine residues  in the kinase domain. Autophosphorylation of Y1234 and Y1235 is thought to induce a conformational change in c-Met, exposing the docking site , have been successful in the clinic. Herceptin is a chimeric antibody targeted against the tyrosine receptor kinase HER2, used for breast cancer treatment. With the success of therapeutic antibodies, attempts have been made to develop therapeutic antibodies against the Met-HGF axis. Neutralising antibodies targeted against HGF aimed to block Met-HGF interaction were developed. c-Met binding to HGF was only blocked when a combination of three different anti-HGF antibodies were used . Similaret al.  reported [et al.  developeet al. [in vivo. It is hypothesised that the bivalent binding of an antibody could mimic the dimerising effect of HGF, thus causing c-Met dimerisation upon antibody binding. To avoid c-Met activation by bivalent monoclonal antibodies, Pacchiana et al. [et al. [Developing therapeutic bivalent antibodies targeted against c-Met has been challenging. Prat et al.  developea et al.  engineera et al. . The onea et al. . Like DNa et al. . In conta et al. . Recentl [et al.  was the This study describes the development of a panel of bivalent anti-Met murine monoclonal antibodies. These antibodies were raised against the α-chain of human c-Met and are termed Specifically Engaging Extracellular c-Met (seeMet). seeMet antibodies were characterised by Western blotting, immunoprecipitation, flow cytometry, epitope mapping and agonist/antagonist activity towards c-Met. Surprisingly, none of these antibodies were c-Met agonists. Two antibodies, seeMet 2 and 13, showed the strongest binding to native c-Met by flow cytometry but work poorly to detect denatured c-Met on Western blots. In contrast seeMet 11 and seeMet 12 antibodies showed outstanding specificity in Western blot analysis. seeMet 2 was the most effective in reducing cell division. Further analysis of seeMet 2 on flow cytometry showed that its binding to c-Met on live cells is temperature sensitive. Detailed mapping of seeMet 2 epitope revealed that part of seeMet 2 epitope is buried within the reported native crystal structure of c-Met.The α-chain of human c-Met was prokaryotically expressed and purified. Purified α-chain was used to immunise BALB/c mice. To obtain hybridoma cells producing anti-α-chain c-Met antibodies, the spleen cells of immunised mice were fused with SP2./0-Ag14 cells. Hybridoma cells were single-cell cloned and cell supernatant from monoclonal hybridoma clones were screened for anti-α-chain c-Met reactivity mainly by Western blotting and cell staining. Post primary and secondary antibody screening , a panelEpitope mapping of the 21 seeMet monoclonal antibodies was determined by an ELISA-based assay (Pepscan). Consecutive, overlapping synthetic peptides that span the entire c-Met α-chain were biotinylated and added to strepatvidin-coated plates. Antibody was then added to the peptides and binding was determined colorimetrically. In total, 10 different antibody binding regions from the α-chain were identified from the 21 monoclonal cell supernatants tested, indicating that there is no one main region that is highly immunogenic. A simplified diagram of the antibody binding regions on c-Met α-chain is shown in Figure From the panel of 21 seeMet monoclonal antibodies, 11 antibodies were selected for production and purification. Purified antibodies were further characterised by Western blotting, immunoprecipitation, flow cytometry, and agonist/antagonist activity by cell scattering.seeMet monoclonal antibodies were purified using protein A beads. Purified antibody was resolved on a SDS-PAGE gel and stained with Coomassie blue dye (data not shown). Other than the expected two bands corresponding to the heavy (~51 kD) and light (~25 kD) chain of an antibody, no other protein bands were observed in the Coomassie-stained gel, suggesting that the purification of monoclonal antibodies was successful.To ensure that the monoclonal antibodies retained their anti-α-chain activity after production and purification, purified monoclonal antibodies were characterised by Western blotting Figure . 1 μg/mLTo further characterise the monoclonal antibodies reactivity against c-Met α-chain, the antibodies were used to immunoprecipitate endogenous c-Met from SNU-5 cell lysate. SNU-5 is a human gastric cell line that expresses high levels of c-Met. Immunoprecipitated cell lysates were analysed by Western blotting Figure  using thFlow cytometry was used to determine if our monoclonal antibodies could bind to native c-Met on live cells. SNU-5 cells were incubated with 1 µg/mL of monoclonal antibody. Binding of seeMet monoclonal antibodies to native c-Met expressed on the cell surface of SNU-5 cells was detected using anti-mouse secondary antibody conjugated with FITC dye. T47D, a human breast cancer cell line expressing low levels of c-Met, was used in this assay to determine if the antibodies bind non-specifically to the cell surface. The flow cytometry results of purified monoclonal antibody treated T47D cells were indistinguishable from the negative control (secondary antibody only), indicating that monoclonal antibodies do not bind non-specifically to the cell surface (data not shown). Flow cytometry results obtained with SNU-5 cells showed that the antibodies fell into three distinct groups with different fluorescence intensity towards native c-Met: strong fluorescence intensity, intermediate fluorescence intensity and weak fluorescence intensity  and O29 (QIEEPSQCPDCVVSA) with equal affinity Figure . This inIn the presence of 1 mM DTT, alanine scan analysis revealed that seeMet 2 failed to bind to peptides P1, P7, P8, P9, P10, P14, P15, P17, P19, P20 and P25 when the antibody was used at 0.05 µg/mL (data not shown). The substituted amino acid residues in these peptides are thus involved in seeMet 2 epitope. Interestingly, proline residues that form kinks in protein structures were observed to be important residues in the seeMet 2 epitope. This is supported by the loss of seeMet 2 binding due to the substitution of proline by alanine residues in peptides P14, P25 and P10. Using a higher range of seeMet 2 concentration, a detailed titration of seeMet 2 binding to the alanine scan peptides was performed to further define the relative contribution of different amino acids to the interaction Figure . These eseeMet 2 bound peptides P1, P8 and P14 the least, indicating that the substituted residues, ‘C’, ‘E’ and ‘P’ respectively, are most critical for seeMet 2 binding , revealed that the main epitope fell into two distinct clusters: residues 166 to 168 ‘IEE’ and 172 to 175 ‘CPDC’ Figure . The ‘IEc-Met is a tyrosine kinase receptor involved in a wide range of biological activities such as cell proliferation, cell motility, angiogenesis and morphogenesis. Aberrant expression of c-Met correlates with tumour aggression and cancer progression. Expression of c-Met is also known to cause drug resistance towards HER2, EGFR and B-RAF treatment -16. c-Meet al. [Many groups have used various mechanisms to inhibit c-Met activation. Small molecule kinase inhibitors such as the PHA-665752, AM7 and SU11274 were extremely successful in inhibiting c-Met activation -19. Howeet al.  reportedet al. -25. NK4 et al. .in vivo and their ability to recruit the host immune system to destroy tumour cells make this form of therapy clinically advantageous over other types of c-Met/HGF inhibitors [The success of using therapeutic monoclonal antibodies for cancer treatment is evident. Herceptin (Trastuzamab), a humanised IgG1 antibody targeted against the human epidermal growth factor receptor (HER2), is widely used for the treatment of breast cancer. Rituxan (Rituximab) targeting CD20 and Avastin (Bevaciumab) targeting vascular endothelial growth factor receptor (VEGFR), both chimeric IgG1 antibodies, have been successful in treatment of lymphomas and of colorectal and lung cancer respectively . Therapehibitors . In addiThere have been several reports of c-Met inhibition by anti-Met antibodies. The monovalent 5D5 antibody (MetMab) was shown to cause receptor downregulation while the monovalent DN-30 antibody was reported to inhibit c-Met signaling by causing c-Met ectodomain shedding , 29. Thiet al. [In this study, we have developed a panel of murine monoclonal antibodies against the α-chain of human c-Met. Here, we term the antibodies: Specifically Engaging Extracellular c-Met (seeMet). We characterised the antibodies by Western blotting, immunoprecipitation, flow cytometry, epitope mapping and agonist/antagonist activity towards c-Met. The α-chain was used as immunogen as it was best expressed and most immunogenic among other c-Met fragments . Comparison with the commercial antibodies (SC-10 and AF276) has revealed the superior performance of our new antibodies in immunoblotting. seeMet 11 and 12 were the best antibodies for Western blotting as they demonstrated good affinity and specificity towards c-Met. In addition, our antibodies are able to function in immunoprecipitation and ELISA. Antibodies that have higher affinity and specificity compared to the currently available commercial antibodies, and characterised in various biochemical techniques, will be valuable tools for c-Met further studies. Finally Pozner-Moulis et al.  questionDespite the use of prokaryotic-expressed denatured protein as immunogen, it was still possible to obtain antibodies that recognise native c-Met protein. Antibodies such as seeMet 13, showed poor affinity and poor specificity to c-Met by Western blotting, but, along with seeMet 2, produced the highest fluorescence staining determined by flow cytometry. Clearly, seeMet 2 and 13 epitopes lies in c-Met native conformation. In SNU-5 cells, seeMet 2 and 13 do not cause caspase activation and do not cause cell death as suggested by lack of annexin V staining (data not shown). Western blot analysis of antibody-treated cells using the senescence marker and autophagy marker, p16 and LC-3 respectively, were negative for such events (data not shown). Through the binding of seeMet 2 or 13 to c-Met, the only functional effect these antibodies elicit is the reduction of SNU-5 cell division. Finally, our antibodies are non-agonistic towards c-Met in cell scatter assays.in vivo tumour imaging. This will provide valuable information on tumour physiology which will help improve cancer diagnosis, prognosis and therapy. c-Met antibodies may also be engineered to carry toxic payloads into tumour cells and cause tumour cell killing. The very encouraging clinical results reported with Kadcyla, a Herceptin mertansine-conjugate, just obtaining FDA approval for the treatment of advanced breast cancer strongly support this idea.Given the advances in antibody engineering, there are several ways antibodies may be engineered for cancer therapy and diagnosis. seeMet 2 and 13 bind to endogenous c-Met on live SNU-5 cells with high affinity and specificity. Immunofluorescence staining demonstrates that seeMet 2 and 13 are internalised into tumour cell, most likely mediated via endocytosis. Combining the technology in molecular imaging and nanotechology, c-Met antibodies may be engineered into powerful tools for et al. [So far, we have shown treatment of SNU-5 cells with 10 µg/mL of seeMet monoclonal antibody. Other groups have shown, and it is also plausible, to use higher concentrations of antibody treatment. Testing our antibodies at higher concentration might provide better insights into our antibodies’ mode of action. Interestingly, the bivalent LMH 87 antibody described by Greenall et al.  shares aet al. [et al. [Partial inhibition of c-Met-induced biological activities using monoclonal anti-Met antibodies has been described by Prat et al. . The antet al. . Cao et  [et al.  demonstr [et al. . Interes2 humidified incubator. HaCaT, U-87MG and murine NIH3T3 cells, cultured in Dulbecco's Modified Essential Medium (DMEM) high glucose with sodium pyruvate, were generous gifts from Birgit Lane , Singapore), Nick Leslie  and Axel Ullrich , Singapore) laboratories respectively. SNU-5 cells were purchased from Korean Cell Line Bank. T47D and SNU-5 cells were cultured in RPMI 1640 media. DMEM and RPMI were obtained from Invitrogen (U.S.A). All tissue culture medium was supplemented with 10% heat-inactivated fetal calf serum obtained from HyClone Laboratories/Thermo Scientific (U.S.A).All cells were maintained at 37˚C in 5% CORecombinant human HGF (#294-HG) and anti-human HGF (#MAB294) were purchased from R&D Systems (U.S.A). SU11274, the c-Met small molecule inhibitor, was purchased from Calbiochem/Merck . CellTracker Green BODIPY dye (Invitrogen #C2102) was resuspended in DMSO, according to manufacturer's protocol.Cell culture plates/dishes were rinsed with cold PBS before the cells were scraped off. Cells were collected by centrifugation. PBS was removed before quick freezing the cell pellet on dry ice. The frozen cell pellet was lysed on ice using NP40 lysis buffer  containing complete protease inhibitor . Cell lysate was centrifuged at 10,000 xg and the supernatant was recovered for analysis. Protein quantification was performed using a BCA kit (Pierce/Thermo Scientific), according to the manufacturer's protocol.c-Met α-chain was first cloned from the entry vector, containing full length human c-Met cDNA (Invitrogen #IOH36570), into pCR2.1 vector (Invitrogen) using the TOPO TA cloning kit (Invitrogen). Amplification of c-Met α-chain was performed using c-Met α-chain primers . All plasmid extraction, gel extraction and PCR product purification protocols were performed using Qiagen (United Kingdom) kits, according to manufacturer's protocol.600 0.4 to 0.6 was reached. Protein expression was induced by adding IPTG  to a final concentration of 1 mM. Cultures were allowed to grow for 3 hrs. Cells were recovered by centrifugation and resuspended in lysis buffer . Cell lysate was centrifuged at 33,000 xg. The cell pellet obtained was resuspended in lysis buffer containing 6 M urea and incubated overnight with gentle stirring. The resulting suspension was centrifuged and the supernatant obtained was used for protein purification.For prokaryotic expression, c-Met α-chain was subcloned from pCR2.1 vector into His-tag pET19b expression vector (Novagen/Merck) and transformed into BL21 pLysS cells (Invitrogen). Transformed cells were grown until an ODProkaryotically expressed c-Met α-chain was affinity purified on a 1 mL IMAC  Bio-Scale Mini Cartridge , using the automated Profinia protein purification system (Bio-Rad). c-Met α-chain was eluted and used to immunise mice for antibody production.Antibody production was performed by Moravian Biotechnology (Czech Republic). Briefly, mice were immunised with purified human c-Met α-chain expressed from bacteria. Each injection contained 40 μg of purified c-Met α-chain. Mouse tail bleeds were taken to test for immunological response against c-Met α-chain. Two mice that gave the highest immune response against c-Met α-chain were sacrificed for hybridoma cell fusion. Spleen cells from mice were fused with SP2./0-Ag14 cells which are mouse immortal myeloma cells. Hybridoma cells were grown in selection media containing hypoxanthine, aminopterin and thymidine. Only hybridoma cells which have been successfully fused between a spleen cell and an immortal cell will survive and grow in the selection media.Antibody screening was performed mainly by cell staining and Western blotting. An outline of monoclonal antibody screening is shown in Mouse monoclonal antibodies isotype were characterised using the commercially-available IsoQuick™ strips (Sigma-Aldrich). Isotyping strips were incubated in hybridoma cell supernatant for 5 mins.Peptides for Pepscan: Peptides that span the entire α-chain of c-Met were synthesised. A total of fifty-five peptides with consecutive, overlapping sequences were synthesised. Each peptide consists of 15 amino acid residues and overlapped the previous peptide by 10 amino acid residues.Peptides for alanine scan: Pepscan results showed that seeMet 2 bound to peptides O28 (CIFSPQIEEPSQCPD) and O29 (QIEEPSQCPDCVVSA). Variations of peptides O28 and O29, where each amino acid residue was sequentially substituted for an alanine residue, were synthesised.384, Molecular Device, U.S.A). The crystal structure of c-Met extracellular domain, accession number 1SHY, was obtained from Protein Data Base (PDB). Computer imaging of the epitopes were analysed by PyMol  software.All peptides were linked to biotin by an SGSG linker sequence at the N-terminus and were synthesised by Mimotopes . Streptavidin-coated plates  were blocked with 3% BSA/PBS at room temperature. The peptides were dissolved in DMSO and stored according to manufacturer's recommendation. Streptavidin-coated plates were coated with each peptide (5 μg/mL) overnight at room temperature. Wells were washed before hybridoma supernatant or purified monoclonal antibody was added to the each well. HRP-conjugated anti-mouse antibody was added to detect bound monoclonal antibodies. ELISA substrate (Bio-Rad #172-1067) solution was prepared freshly according to the manufacturer's instructions and added to the wells. Colour change was monitored by eye and the reaction was stopped by adding 100 mM sulphuric acid. Absorbance was read at 450 nM in a microplate reader  was raised against a peptide within the C-terminal cytoplasmic region of human c-Met and would be expected to recognise c-Met precursor (170 kD) and mature c-Met β-chain (145 kD) on Western blots. AF276 antibody (R&D systems) is a goat antibody raised against the extracellular domain of c-Met. AF276 antibody would be expected to recognise c-Met precursor, mature c-Met β-chain and mature c-Met α-chain on Western blots. Both SC-10 and AF276 antibodies were used at 1: 10 000 dilution on Western blotting. 1 µg/mL of seeMet monoclonal antibody was used for Western blotting.HRP conjugation to seeMet antibodies was performed using EZ-link Plus Activated Peroxidase (Pierce/Thermo Scientific). HRP conjugated antibodies were used at 1 µg/mL on Western blotting.Protein samples were mixed with 4X LDS sample buffer (Invitrogen) and 10X sample reducing agent (Invitrogen) before analysing on 4 -12% Bis-Tris gradient gels (Invitrogen) using MOPs buffer (Invitrogen). SeeBlue Plus2 protein ladder (Invitrogen) was used as molecular weight ladder. Transfer of proteins onto a nitrocellulose membrane  was performed using Bio-Rad wet transfer system for 2 hrs, at a constant current of 100 V. Transfer buffer contains 25 mM Tris, 192 mM glycine and 20% methanol. Blocking buffer was made up of 5% Marvel milk in PBST (1% Tween 20 in PBS). Non-specific sites on the membrane were blocked in blocking buffer before incubating with primary antibodies. The membrane was washed three times and secondary antibodies were added at 1:10 000 dilution in blocking buffer. Secondary antibodies conjugated to horseradish peroxidise (HRP) were obtained from Jacksons Laboratory/Stratech Scientific Ltd. (United Kingdom). Enhanced chemiluminescence (ECL)  was used for the detection of Western blots.Cells lysates were obtained by lysing cells in NP40 lysis buffer as described above. 1 µg of purified antibody was incubated overnight with cell lysate . Washed protein G beads  were added to the cell lysate. Beads were collected by centrifugation at 18,000 xg and washed several times with NP40 lysis buffer. Bound proteins were eluted by adding 2X LDS sample buffer and heated at 100°C. Beads were removed from eluate by centrifugating at 10,000 xg. The eluate was analysed by SDS-PAGE gel.Flow cytometry was performed with help from Flow Cytometry Core Facility .6 cells) were washed once in cold PBS before blocking in 1% BSA/PBS. Cells were washed twice before incubating with seeMet monoclonal antibodies. 1 μg/mL of seeMet monoclonal antibodies were used. Cells were incubated with goat anti-mouse IgG FITC-conjugated secondary antibodies (Invitrogen) and finally resuspended in 1% BSA/PBS. Flow cytometry was performed using Becton Dickinson (U.S.A) FACScan. Cell Quest (Becton Dickinson) and FlowJo  software was used for data analysis.SNU-5 cells . Cells were resuspended in 1% BSA/PBS and analysed by flow cytometry.100 - 200 HaCaT cells were seeded in 24-well plates and allowed to grow until small colonies were formed (approximately 7 days). Cells were serum-starved for 24 hrs. Cells were incubated with purified monoclonal antibodies (1 μg/mL) for 24 hrs before rinsing twice in cold PBS and fixing in ice-cold methanol. Cells were then stained in 1% crystal-violet (Sigma-Aldrich) solution. Cell staining was observed using Zeiss Axiovert 25 inverted microscope and pictures were taken using a Canon EOS 1000 D camera.5 cells) were seeded in each 96-well and treated for 72 hrs before analysis. Cell viability and caspase activation were performed according to manufacturer's protocol. Luminescence was read using the EnVision plate reader . While the CellTiter-Glo® luminescent cell viability assay is generally used as a cell viability assay, it actually measures cellular ATP levels. If a cell population fails to divide over the course of an assay (as seen in the study reported here) it can appear to have reduced “viability” (lower ATP levels) without, in fact, any loss of cell viability when compared to cell populations that increase in number during the assay.CellTiter-Glo® luminescent cell viability assay and Caspase-Glo® 3/7 assay  were used to determine cell viability and caspase activation respectively. SNU-5 cells .CellTracker Green BODIPY dye: SNU-5 cells were stained with 5 µM of CellTracker BODIPY dye for 30 mins. Stained cells were seeded and treated with seeMet monoclonal antibodies for 6 days. Cells were harvested and dye retention in live cells were analysed by flow cytometry.10 µg/mL of seeMet monoclonal antibody were incubated with live SNU-5 cells for 1 hr at 4°C or 37°C. Antibody-treated cells were washed once with PBS and deposited onto polylysine-coated slides  using the Thermo Shandon Cytospin 3 Cytofuge (Thermo Scientific) at 800 rpm for 5 mins and fixed immediately in 4% paraformaldehyde. Cells were then blocked and permeablised in PBS containing 0.4% Triton X-100 and 5% BSA. Bound seeMet antibodies were detected using anti-mouse Alexa Fluor®488-conjugated secondary antibody. Phallodin was added together with the secondary antibodies. Cells were washed before staining with 4',6'-diamidino-2-phenylindole (DAPI) and mounted with Hydromount  containing 2.5% DABCO (1,4- Diazabicyclo-[


It is important to keep the level of antibiotic prescribing low to contain the development of resistant bacteria. This study was conducted to reveal new knowledge about how GPs think in relation to the prescribing of antibiotics - knowledge that could be used in efforts toward rational treatment of infectious diseases in primary care. The aim was to explore and describe the variations in GPs' perceptions of infectious disease management, with special reference to antibiotic prescribing.Twenty GPs working at primary care centres in a county in south-west Sweden were purposively selected based on the strategy of including GPs with different kinds of experience. The GPs were interviewed and perceptions among GPs were analysed by a phenomenographic approach.Five qualitatively different perceptions of infectious disease management were identified. They were: (A) the GP must help the patient to achieve health and well-being; (B) the management must meet the GP's perceived personal, professional and organisational demands; (C) restrictive antibiotic prescribing is time-consuming; (D) restrictive antibiotic prescribing can protect the effectiveness of antibiotics; and (E) patients benefit personally from restrictive antibiotic prescribing.Restrictive antibiotic prescribing was considered important in two perceptions, was not an issue as such in two others, and was considered in one perception although the actual prescribing was greatly influenced by the interaction between patient and GP. Accordingly, to encourage restrictive antibiotic prescribing several aspects must be addressed. Furthermore, different GPs need various kinds of support. Infectious disease management in primary care is complex and time-consuming, which must be acknowledged in healthcare organisation and planning. It has been demonstrated that the level of antibiotic use correlates with the level of antibiotic resistance -6. AccorAntibiotic prescribing in primary care in Sweden decreased continuously between the early 1990s and 2004, when the trend was broken and usage unexpectedly began to increase in all counties in Sweden except one . No paraThe aim was to explore and describe variations in GPs' perceptions of infectious disease management in primary care, with special reference to antibiotic prescribing.A phenomenographic approach was chosen . This apData were collected in interviews with GPs who worked in primary care in Halland, a county in south-west Sweden.It has been found that 20 interviews are generally sufficient to capture the variation of perceptions . This nuOne of the authors, the chairperson of the local Strama organisation (ME), sent an email to all GPs working in primary care in the county, at that time approximately 150. The email described the purpose of the study and GPs were asked to sign up as participants. The strategy was to recruit interviewees with different kinds of experience to obtain a rich variation of views. Therefore, we looked for GPs who varied in age, sex and number of professional years, and were furthermore working at primary care centres spread geographically over the county, from both urban and rural areas, and with varying levels of antibiotic prescribing. Individual data of the level of antibiotic prescribing were not available, and instead the level of antibiotic prescribing at the medical centre where the GP worked was used. From the total of 26 volunteer GPs, 20 were chosen. Although there were not many extra GPs to choose from, the variation of predefined background characteristics was considered acceptable  in March-April 2008. The interviews were held in a separate room at the GPs' primary care centres, with two exceptions. For practical reasons one participant chose to be interviewed at home and one chose a conference room in connection with a seminar arranged by the DTC.Three main questions were used during the interviews  conducted the analysis and MR acted as co-reader. Both researchers have worked with several phenomenographical studies. The analysis was furthermore presented and discussed at research group meetings visited by researchers with even longer experience of this method. The analysis process included seven steps , being a passive doctor (who is not acting), risking non-successful management of the infection (which could negatively affect the patient's trust in the physician as well as the self-confidence of the physician), or being reported to the Swedish National Medical Responsibility Board. Prescribing antibiotics had organisational advantages in terms of an effective care. The consultation usually ended quicker; more patients were treated and time was saved for other patients with more complicated diseases. When patients could not be followed up antibiotics were prescribed more frequently in order to keep control.However, in contrast to the above, there were also GPs expressing that it was the restrictive antibiotic prescribing that met their personal and professional demands.In this perception there was an awareness of restrictive antibiotic prescribing and that this should be considered. However, it was said that due to the general public's ignorance about symptoms and treatment of common infections there was a constant discussion with patients on infectious disease management. It was explained that primary care infections were often medically uncomplicated but nevertheless the encounter between GP and patient took a long time due to the need for discussion and education. Similar discussions were also held with professionals working at children's day-care centres or professionals working at old age homes or relatives of the elderly. An exception was parents of children with otitis media who had adopted the perception that these infections can be cured without antibiotics and thus a discussion was often easier. It was said that this was a result of previous information campaigns directed at the public.Here it was said that restrictive antibiotic prescribing must be practiced in order to protect the effectiveness of antibiotics. Not being able to treat infections in the future was considered a real threat. Of course some patients need antibiotics, but the most common infections can be cured without antibiotics. One or two days of extra suffering may not be convenient for the patient, but is not dangerous. Occasionally, a patient will develop a serious infection that probably could have been avoided if antibiotics had been prescribed at the first meeting. This is however something both patients and physicians must get used to. It was said that such situations were managed by instructing patients to observe their symptoms and contact the GP again if they got worse. An effect of a new healthcare policy in the county was that now it was easy for patients to contact their GPs.The perception in E has many similarities with perception D including the notion that antibiotics must be protected for the future. However, in this perception it was furthermore stated that the patients benefit personally from restrictive antibiotic prescribing. When the body cures the infection without antibiotics the patient's immune system is not negatively affected, as it is when antibiotics are used. As in perception D, patients were instructed to contact the GP again if symptoms worsened. Some GPs who expressed perception E said that their patients did not want antibiotics and just came to be assessed to make sure that antibiotics were not needed. These patients were said to be the GPs' "own" patients who had adopted the same attitude towards infectious disease management as the GP.The relationship among categories of description is presented in the outcome space Figure . Here a This study suggests that different GPs perceive infectious disease management in primary care in different ways, and also vary in their perceptions of the role of antibiotics in disease management. Two perceptions (D and E) were associated with a strong focus on restrictive antibiotic prescribing, whereas the others were not . This means that GPs who hold perceptions similar to D and E are more likely to apply restrictive antibiotic prescribing when they meet primary care patients with infectious disease symptoms.Our findings both support previous studies and give new information. One novelty lies in the descriptions of our findings, as a variation of perceptions among GPs. Perceptions are, according to phenomenographic theory, intertwined with the persons' lived experiences and actions , which mPrevious studies have explained that GPs must consider many factors besides the risk of antibiotic resistance, including the immediate duty to the patient, cost, patient pressure and legal issues -24. For Two recent studies used phenomenographic approaches to study perceptions of medical prescribing among physicians. One focused on antibiotic prescribing at hospitals . A majorIt was perceived that it was easier to prescribe antibiotics than to refrain, and one reason was that this would always satisfy the patient. Antibiotic prescribing as a method of satisfying patients has been documented before -31. DocuThus, it seems important not to take patients' expectations for granted. It is probably advantageous to involve patients in actions to prevent antibiotic resistance. When they are asked, patients express concern about antibiotic resistance and say they want to cooperate to decrease the problems ,38. MateHowever, in spite of the common notion among GPs that patients generally expected antibiotics, we found two perceptions in which GPs said they practiced restrictive prescribing (D and E). A major difference in these perceptions was that physicians perceived that the effect of antibiotics was a real threat and furthermore said that they had experienced that it was possible, or even beneficial, to refrain from antibiotics in most common infections. It was also said here that restrictive antibiotic prescribing was time-consuming (as in perception C), but discussions were considered necessary for the practice, not a hindrance. It has been shown that GPs can increase their communication ability in patient encounters without prolonging the counselling time . HoweverIn one of these perceptions (perception D) we traced a conflict between the desire to save the effectiveness of antibiotics for the future and the basic concept of helping patients who suffer (perception A). This conflict was not present in perception E, where antibiotics were also to be saved for the future. Here restrictive antibiotic use moreover benefited the patients of today, who then did not have to be negatively affected by the antibiotic. Such a perception may aid GPs in following restrictive antibiotic prescription recommendations.The perception that restrictive antibiotic prescribing is time-consuming (C) contains an important message for the organisation and planning of healthcare. Primary healthcare policies supporting restrictive antibiotic prescription must allocate resources to give physicians room for discussions with patients. Infectious diseases in primary care may look simple from a biomedical point of view. However, from a psychosocial point of view they are complicated and complex. This understanding seems to be underestimated and not considered in healthcare today.Besides time allocation and patient involvement, some GPs must adopt new ideas to consider restrictive antibiotic prescribing in infectious disease management. For instance, GPs must believe that their actions make a difference. Documentation shows that physicians sometimes regard themselves as not being a part of the problem, and think that antibiotic resistance is a national problem in which they are not involved ,38,44. HParticipant selection aimed at including GPs with varying experiences, in order to get a rich description of the phenomenon . We aimeTo ensure high quality of collected material we used interview questions that 1) were similar to questions that have been useful in previous studies -13,17, aThe study describes the complex nature of infectious disease management in primary care and furthermore describes that GPs have different perceptions of the management as well as the role of antibiotics. Five different perceptions were identified. In two of the perceptions restrictive antibiotic prescribing was always practiced, and in one, sometimes practiced, depending on the interaction with the patient. To encourage restrictive antibiotic prescribing interventions must address several aspects; however, different GPs need different kinds of support. Some GPs need to learn about risks of resistant bacteria and to be aware of the impact they can play on the level of antibiotic resistance; others primarily need training in communication skills. Infectious disease management in primary care is complex and time-consuming, which must be acknowledged in the healthcare organisation and planning.The authors declare that they have no competing interests.ME and CSL prepared the study and designed it in cooperation with IB. IB carried out the interviews and drafted the manuscript. IB and MR analysed the interviews. ME, MR, and CSL read and gave comments on the manuscript. All authors approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/12/1/prepub


Aim. To determine the antibiotic prescribing habits for pulpal and periapical pathology among dentists in Hyderabad city, India. Methodology. A total of 246 questionnaires were distributed to all the dentists registered with the local dental branch. Demographic details and questions regarding type and dosage of antibiotics prescribed for allergic and nonallergic patients were recorded. Inferential statistics were performed, and P < 0.05 was considered statistically significant. Results. The response rate for the study was 87.8%. Around 148 (68.5%) of respondents regularly prescribed antibiotics for endodontic management. The first antibiotic of choice for patients with no history of medical allergies was a combination of amoxicillin and metronidazole, followed by amoxicillin alone (29.1%). The first antibiotic of choice in case of allergy to penicillin was erythromycin. Necrotic pulp with acute apical periodontitis with swelling and moderate/severe preoperative symptom was the condition most commonly identified for antibiotic therapy (92.1%). Conclusion. The present study reveals that the overall antibiotic prescribing practices among this group of dentists were quite high, and there is a need for more educational initiatives to rationalize the use of antibiotics in dentistry. In the health care industry, the advent of antibiotics constitutes one of the greatest revolutionary advancements. Dental infections are polymicrobial involving a combination of gram positive, gram negative, facultative anaerobes, and strict anaerobic bacteria . Thus, aPenicillin and other antibiotics, which were initially viewed as miracle drugs for their ability to cure serious and often life-threatening diseases, were challenged by some defiant strains. Antibiotic resistance has become a serious public health concern. Reasons for the development of antimicrobial resistance could be due to overprescription by health care providers and improper use by patients .In endodontics, it is recommended that antibiotics should be used only as an adjunct to definitive nonsurgical or surgical endodontic therapy . DespiteP < 0.05 was considered statistically significant.A cross-sectional survey was designed to determine the antibiotic prescribing habits amongst dentists of Hyderabad city, AP, India. A total of 246 questionnaires were distributed to all the dentists registered with the local dental association branch. Demographic details and questions regarding type and dosage of antibiotics prescribed for allergic and nonallergic patients were recorded. Data were computed and analyzed using SPSS software (version 12.00). Statistical analysis was done using chi-square test, and Ethical Committee Clearance from the Institutional Review Board was obtained.Of the 246 questionnaires distributed, 216 were returned completely filled (response rate: 87.8%). P = 0.5). Though it was noted that a variety of antibiotic combinations were recommended, the most common for patients with no history of medical allergies was a combination of amoxicillin 500 mg with metronidazole 400 mg, twice a day followed by amoxicillin 500 mg alone (29.1%) (148 (68.5%) of respondents regularly prescribed antibiotics for endodontic management. This was not significant when compared with those who did not advise ( (29.1%) . P = 0.04) with more of elder age group recommending for five days. Around 51.8% of this study population prescribed antibiotics for a duration of five days, and only five respondents (2.31%) have stated to prescribe it for seven days. A statistically significant difference was noted when comparison of age groups with the number of days of antibiotic prescription was done . The rationale for the choice of amoxicillin could have been its wide spectrum, low incidence of resistance, pharmacokinetic profile, tolerance, and dosage , 19; comIn case of allergy to penicillin, erythromycin was regarded as the drug of choice by 54.6% of the respondents. This could be attributed to the fact that erythromycin has similar spectrum of activity as amoxicillin.Though endodontic conditions like irreversible pulpitis with moderate/severe preoperative symptoms with or without acute periodontitis do not warrant antibiotic coverage, in the present study 60.6% and 65.2% respondents prescribed antibiotics. This finding is slightly higher than those reported in the previous studies , 12. NecIn the present study a higher percentage of dentists prescribed antibiotics for necrotic pulp with chronic apical periodontitis with sinus tract and no/mild preop. symptoms as compared to Spanish  and AmerIn endodontics, dental practitioners are dealing with a very small number of extremely virulent bacteria. A majority of these can be dealt with by the most common of antibiotics. Problems may arise from prescriptions that are issued for an inappropriate antibiotic, in inappropriate circumstances at inadequate daily dosage, and with no initial loading dose.The present study reveals that overall the antibiotic prescribing practices among this group of dentists were quite high. This study emphasizes the need for more educational initiatives to rationalize the use of antibiotics in dental practice. Also, prescription of antibiotics should be at the correct dosage and duration to prevent the development of resistant bacteria.


The available literature identifies that the addition of mineral admixture as partial replacement of cement improves the microstructure of the concrete  as well as increasing the mechanical characteristics such as drying shrinkage and creep, compressive strength, tensile strength, flexural strength, and modulus of elasticity; however, no single document is available in which review and comparison of the influence of the addition of these mineral admixtures on the mechanical characteristics of the hardened pozzolanic concretes are presented. In this paper, based on the reported results in the literature, mechanical characteristics of hardened concrete partially containing mineral admixtures including fly ash (FA), silica fume (SF), ground granulated blast furnace slag (GGBS), metakaolin (MK), and rice husk ash (RHA) are discussed and it is concluded that the content and particle size of mineral admixture are the parameters which significantly influence the mechanical properties of concrete. All mineral admixtures enhance the mechanical properties of concrete except FA and GGBS which do not show a significant effect on the strength of concrete at 28 days; however, gain in strength at later ages is considerable. Moreover, the comparison of the mechanical characteristics of different pozzolanic concretes suggests that RHA and SF are competitive. Many researchers addressed the deficiencies of concrete and some of them made significant efforts to improve the performance of concrete, especially permeability and durability of concrete as these are the immense concerns of the researchers. The existing literature related to pozzolanic concretes shows that the use of mineral admixtures reduces the porosity of concrete if cement content is partially replaced by mineral admixture; therefore, the demand of blended cement has increased globally to produce denser to impermeable concretes , along wAmong several available types, the most commonly used mineral admixtures are fly ash (FA), silica fume (SF), ground granulated blast furnace slag (GGBS), metakaolin (MK), and rice husk ash (RHA). Researchers well reviewed the properties of mortar and/or concrete containing different mineral admixtures , 4–6; foPerformance of concrete is evaluated from mechanical properties which include shrinkage and creep, compressive strength, tensile strength, flexural strength, and modulus of elasticity. But compressive strength of concrete is the most important characteristic and it is generally assumed that an improvement in concrete compressive strength will improve its mechanical properties; however, in case of concrete in which cement is partially replaced by mineral admixtures, all mechanical properties are not directly associated with compressive strength and the effects of the same amount of different mineral admixtures on the mechanical properties of hardened concrete are not same. This difference of the effects of different minerals on the mechanical properties is as follows.2) form. Due to less or limited solubility, this hydrated lime remains independent in the interstitial spaces. If moisture is available, mineral admixture reacts with lime to form tricalcium silicate which refines the pore configuration of the cement matrix. It is important to mention that the rate and speed of this reaction are very much dependent on the pozzolanic nature of the mineral admixture; therefore to attain good results, silica in mineral admixture should be amorphous, glassy, or reactive. Thus, the parameters representing the pore configuration, that is, pore size and porosity, are significantly different for each partially replaced cement pastes with different mineral admixtures, even if the amount of cement replacement and water binder ratio is the constant.Mechanical properties of concrete are closely related to its porosity and pore dispersion . It is rIn hydrated cement research, mercury intrusion porosimetry (MIP) has been used as a tool for years to quantify the distribution of pore sizes in cement pastes. Poon et al.  presenteμm; however, pore radii were observed to be decreased for those specimens in which MK content was higher and they were cured for the longer period. Moreover, they [μm and the porosity of MK incorporating cement pastes was higher than OPC except for those cement pastes in which content of cement replacement was 10 and 20%.Khatib and Wild  presenteer, they  observeder, they  examineder, they  also repCollins and Sanjayan  verified2/g) [Drying shrinkage property of pastes and/or concrete is usually associated with the loss of adsorbed water from the material. This property is very much significant in porous concrete, especially aerated concrete due to higher total porosity (40–80%) and specific surface of pores (around 30 m2/g) . Decreas2/g) ; however2/g) , pore ra2/g)  confirme2/g) . Lohtia 2/g)  observed2/g)  reported2/g)  reported2/g)  show tha2/g) . On the 2/g) . However2/g) , and it 2/g) .Chung , after rThe inclusion of MK reduces the porosity and permeability of the concrete and consequently reduces the drying shrinkage. Zhang and Malhotra  through Habeeb and Fayyadh  proposedCompressive strength of concrete is an indexing property as concrete is designed to carry compressive loadings. Therefore, determining this important property is the foremost priority while dealing with any type of concrete. Almusallam  determin2 and GGBS [Similar to FA concrete, early strength gain with GGBS is slower than the ordinary Portland cement concrete possibly due to slow hydration process and higher amount of slag content, but long-term strength is higher than ordinary concrete if moisture remains available for further reaction between primary hydration product Ca(OH)and GGBS , 27. Jiaand GGBS  comparedIn pure cement replaced concrete, high compressive strength is generally the first property which is related to the SF concrete. It has been reported in the literature that the compressive strength of concrete increases if concrete contains SF between 30 and 100 . SF concEffect of incorporating the GGBS and MK on the strength of concrete is investigated by Khatib and Hibbert  who partPoon et al.  achieved2 resulting in higher production of calcium silicate hydrate (C–S–H). Positive influence on the compressive strength at a young age was observed by Rodríguez de Sensale [Givi et al.  reported Sensale  who anal Sensale , increas Sensale  who desc Sensale  presente Sensale  presente Sensale  reported Sensale .Splitting tensile strength is the measure of tensile strength of the concrete which is determined by splitting the cylinder across its diameter. Siddique  reportedThe tensile strength of GGBS concrete is reported to be slightly higher than that of ordinary Portland concrete . WhereasSplitting tensile strength of MK concrete is increased with the increase in MK content as cement replacing material. This has been confirmed by Qian and Li  who usedAccording to Zhang and Malhotra , the splSiddique  observedFlexural strength of SF concrete depends on compressive strength. An increase in compressive strength results in the increase in flexural strength. Moreover, it is also dependent on the young age curing method . Zhang aThe increase in 28-day bending strength of concrete with 10 to 15% MK content as partial replacement of cement is reported as 32 and 38% whereas, at 80 days, bending strength of MK concrete is reported as 13 and 24%, respectively; however a small effect on the bending strength of MK concrete has been reported for replacement level of 5%  reportedThe addition of RHA does not cause a positive effect on the flexural strength of concrete at 28 days ; howeverModulus of elasticity is an important property to assess the resistance of concrete against freezing and thawing. This property can be determined by static as well as dynamic compression test. The literature reveals that the elastic modulus of FA concrete is generally equal to or slightly better than equivalent grade of concrete . Ghosh aAlmusallam  determinIn comparison to normal concrete, use of GGBS will slightly increase the elastic modulus for a given compressive strength . The addAccording to Zhang and Malhotra , the modAccording to Habeeb and Fayyadh , the staAddition of mineral admixtures reduces pore size with increasing pore size distribution which in turn reduces porosity, permeability, shrinkage, and creep. The reduction of average pore diameter is highly and oppositely dependent on volume of cement replacement and age of concrete or paste; that is, with age and increasing volume of replacement of cement, average pore diameter and total porosity reduce.Drying shrinkage and creep strains increase with the increasing age and volume of cement replacement and rate of increase in these strains is observed to be lower in pozzolanic concretes as compared to plain concrete.Inclusion of mineral admixture improves the compressive strength of concrete. However, FA and GGBS are those mineral admixtures which enhance the later age compressive strength instead of early age due to their slow pozzolanic reactivity and/or lesser surface area. Since, in structural designing, 28-day compressive strength is important and use of these mineral admixtures may influence the design, therefore, based on the recommendations and quoted examples in the literature, combined use of slow and highly active mineral admixture can improve the performance of these mineral admixtures, such as MK and condensed SF.Alongside compressive strength, addition of mineral admixtures slightly improves the tensile strength, flexural strength, and modulus of elasticity of concrete with the increase in replacement level. However, the case of FA is quite different from other mineral admixtures. The reported tensile and flexural strength of FA containing concrete is lesser due to slow compressive strength gain. The reported results of flexural and the splitting tensile strengths, modulus of elasticity, and drying shrinkage of the concrete incorporating RHA or SF showed that these two mineral admixtures are comparable. Therefore, any of the two can be chosen economically.The purpose of this review was to have an idea about the role of different mineral admixtures on the mechanical characteristics of concrete because, in the designing of any structural element, these mechanical properties as well as the contribution of different mineral admixtures must be known. Prior to concluding this review, one should keep this fact in mind that these conclusions are general and purely based on the studies reported in this paper and the reported results may vary in different circumstances; for example, curing duration and period, casting methodology and workmanship, different particle sizes and different geographical source of mineral admixture and/or cement, and so forth may alter the properties of the concrete. Apart from this, the following conclusions are drawn.


General practitioners often prescribe antibiotics for diagnoses that do not require antibiotic treatment, partially because of the fear of treatment failure . They are also strongly influenced by patients’ requests, and the empirical use of antibiotics is the main way of infection treatment in general practice in the Czech Republic. All this leads to non-adherence to the clinical recommendations for infections treatment. However, the regular monitoring of total antibiotic consumption does not reveal the critical areas of antibiotic prescription. Therefore, we used the database of a health insurance company to evaluate the antibiotic prescribing habits of general practitioners in an age-stratified population. In this short text, we report our findings on the prescribing of penicillins  as an example.The methodology based on the Anatomical Therapeutic Chemical/Defied Daily Doses system (ATC/DDD) has been used to survey antibiotic consumption worldwide and it allows making of international comparisons. However, it remains questionable whether this methodology is suitable to evaluate antibiotic prescribing in children and a more appropriate methodology should be developed . ResearcIn our analysis from 2006-2010, we revealed considerable differences in narrow spectrum penicillins prescribing for different age groups. With advancing age, there was a dramatic decline in their overall consumption, which represented only about 5% of the total antibiotic prescribing for patients over 70 years of age. The opposite results were found in teenagers, where the consumption of narrow spectrum penicillins comprised almost 30% of the total antimicrobial consumption. This higher consumption rate may be partially explained by a higher incidence of streptococcal infections. An overall decreasing consumption of narrow-spectrum penicillins may be in part explained by the reluctance of patients to use penicillin because they believe that it is an obsolete and ineffective drug or the fear of allergy (past negative experience).On the other hand, the use of broad-spectrum penicillins, namely co-amoxiclav, got higher in all age groups, including children. The use of aminopenicillins combined with beta-lactamase inhibitor in children younger than one year was four times higher than the use of aminopenicilins. It remains to be established whether higher consumption rate contributes to the high prevalence of resistant bacterial strains carriage in children .Despite the fact that the total antimicrobial consumption in last few years has been relatively stable , we observed striking variations in antibiotic prescribing in different age categories, confirming different but often stereotypical approaches of pediatricians and GPs to the treatment of infections and lack of adherence to the clinical guidelines.Although the database of an insurance company provides only limited medical information, it enables the evaluation of the antibiotic use concerning the type of prescriber and population characteristics, which has not been routinely performed in the Czech Republic so far.


Trypodendron retusum (LeConte). In Steve’s words, “The attraction was immediate and permanent.” His interest in natural history lead him to attend Utah State University where he received his B. S. degree in 1946 and M. S. degree in 1948, majoring in Entomology. His Masters thesis was a survey of the Scolytidae of Logan Canyon in Utah and their host plants (publication #1). He received his Ph.D. in 1953 from the University of Kansas with a dissertation on a taxonomic revision of the North American Cryphalini (publication #4). During his graduate studies Steve met and interacted with the leaders in the field of bark beetle systematics, which highlighted his burgeoning career  Thatcher, a specialist in scolytid systematics, who sent him into the woods to begin an insect collection for a class project. Steve dug his pocketknife into a pinhole in an aspen tree and eased out a small beetle, g career .Coleoptera Emeritus until ill health forced him to terminate his activities in 2008.After graduation, Steve joined the staff of the Canadian National Collection of Insects, Ottawa, Ontario, and remained there for three years until family considerations and the call of the Utah mountains inspired him to change employment. In 1956, he accepted the position of Assistant Professor in the Department of Zoology and Entomology at Brigham Young University in Provo, Utah and remained there until his death. After retirement, Steve continued his association and his research at BYU at the Monte L. Bean Life Sciences Museum as Professor Emeritus and Curator of Coleoptera collection in the Life Science Museum until his retirement . Monte L. Bean Life Science Museum, Brigham Young University. 900 pp.109) Wood SL (2007) Bark and Ambrosia beetles of South America (Platypodidae (Coleoptera). Great Basin Naturalist 53: 259–281.108) Wood SL (1993) Revision of the genera of Scolytidae and Platypodidae (Coleoptera). Part 2: Taxonomic Index, Volumes A & B. Memoirs of the Great Basin Naturalist 13. 1553 pp.107) Wood SL, Bright  DE (1992) A catalog of the of the Platypodidae and Scolytidae (Coleoptera). Great Basin Naturalist 52: 78–88.106) Wood SL (1992) Nomenclatural changes and new species of Scolytidae and Platypodidae (Coleoptera). Great Basin Naturalist 52: 89–92.105) Wood SL (1992) Nomenclatural changes in Scolytidae (Coleoptera) de Costa Rica. Clave de la subfamilia Scolytinae, Tribu: Corthylini. Revista de Biologia Tropical 40: 247–286.104) Wood SL, Stevens GC, Lezama HJ (1992) Los Scolytidae de Costa Rica: clave de géneros y de la subfamilia Hylesinae (Coleoptera). Revista de Biologia Tropical 39: 125–148.103) Wood SL, Stevens GC, Lezama HJ (1991) Los Scolytidae (Coleoptera) de Costa Rica II. Clave para la subfamilia Scolytinae, tribus: Scolytini, Ctenophorini, Micracini, Ipini, Dryocoetini, Xyleborini y Cryphalini. Revista de Biologia Tropical 39: 279–306.102) Wood SL, Stevens GC, Lezama HJ (1991) Scolytidae (Coleoptera), Part IV. Great Basin Naturalist 49: 167–185.101) Wood SL (1989) Nomenclatural changes and new species of Scolytidae (Coleoptera). Proceedings of the International Congress of Entomology 18: 410.100) Wood SL (1988) Recent advances in knowledge of the distribution and classification of the Scolytidae and Platypodidae (Coleoptera). Proceedings of the International Congress of Entomology 18: 40.99) Wood SL (1988) Systematic position of the Scolytidae (Coleoptera), Part III. Great Basin Naturalist 48: 188–195.98) Wood SL (1988) Nomenclatural changes and new species of Scolytidae (Coleoptera). Great Basin Naturalist 48: 31–38.97) Wood SL (1988) Nomenclatural changes and new species of Scolytidae (Coleoptera) from Mexico. Great Basin Naturalist 47: 547–550.PageBreak96) Wood SL (1987) Six new Scolytidae and Platypodidae (Coleoptera). Part 1. Bibliography. Memoirs of the Great Basin Naturalist 11. 685 pp.95) Wood SL, Bright DE (1987) A Catalog of the of the Scolytidae (Coleoptera). Memoirs of the Great Basin Naturalist 9. 126 pp.94) Wood SL (1986) A reclassification of the genera of Scolytidae (Coleoptera) from Asia. Great Basin Naturalist 46: 465–467.93) Wood SL, Huang FS (1986) New genus of Coleoptera: Scolytidae), Part XI. Great Basin Naturalist 46: 265–273.92) Wood SL (1986) New synonymy and new species of American bark beetles (Pseudoxylechinus (Coleoptera: Scolytidae) from India. Great Basin Naturalist 43: 468.91) Wood SL (1986) New Scolytidae (Coleoptera) from Asia. Great Basin Naturalist 46: 465–467.90) Wood SL, Huang F (1986) New genus of Scolytidae (Coleoptera) in Asia. Great Basin Naturalist 46: 461–464.89) Wood SL, Yin F (1986) Relict occurrence of three “American” Coleoptera: Scolytidae). Great Basin Naturalist 45: 266–275.88) Wood SL (1985) New synonymy and new species of bark beetles (Scolytidae (Coleoptera). Great Basin Naturalist 44: 223–230.87) Wood SL (1984) New generic synonymy and new genera of Hypocryphalus mangiferae  : proposed conservation under the plenary powers. Bulletin of Zoological Nomenclature 41: 189–190.86) Wood SL (1984) 85) Wood SL (1984) Review of: J. B. Mitton and K. B. Sturgeon (Eds), Bark beetles of North American conifers. New York Entomological Society Journal 92: 93–94.Coleoptera: Scolytidae), Part X. Great Basin Naturalist 43: 113–119.84) Wood SL (1984) New synonymy and new species of American bark beetles (Coleoptera: Scolytidae), Part IX. Great Basin Naturalist 43: 647–659.83) Wood SL (1983) New synonymy and new species of American bark beetles . In: Jansen DH (Ed) Costa Rican NaturalHistory. University of Chicago Press, 758–759.82) Wood SL (1983) Coleoptera: Scolytidae). Great Basin Naturalist 42: 223–231.81) Wood SL (1982) New species of American bark beetles (Coleoptera: Scolytidae), a taxonomic monograph. Memoirs of the Great Basin Naturalist 6. 1359 pp.80) Wood SL (1982) The bark and ambrosia beetles of North and Central America (P1atypodidae and Scolytidae (Coleoptera). Great Basin Naturalist 41: 121–128.79) Wood SL (1981) Nomenclatural changes and new species in Scolytidae de Mexico. In: Premer simposio nacional sobre parasitologia forestal, 18–19 de Febrero de 1980, Uruapan, Michoacan, Mexico. Memoria Sociedad Mexicana de Emtomologia, 13–57.78) Wood SL (1980) Los Coleoptera: Scolytidae), with two recently introduced species. Great Basin Naturalist 40: 353–358.77) Wood SL (1980) New American bark beetles (Scolytidae (Coleoptera). Great Basin Naturalist 40: 89–97.76) Wood SL (1980) New genera and new generic synonymy in Coleoptera: Scolytidae), Part VIII. Great Basin Naturalist 39: 133–142.75) Wood SL (1979) New synonymy and new species of American bark beetles  Wood SL (1979) A catalog of the Coleoptera: Scolytidae), Part VII. Great Basin Naturalist 38: 397–405.73) Wood SL (1978) New synonymy and new species of American bark beetles (Scolytidae (Coleoptera). Annales of the Societe Entomologique de France 14: 95–122.72) Wood SL (1978) A reclassification of the subfamilies and tribes of Coleoptera: Scolytidae), Part VI. Great Basin Naturalist 37: 511–522.71) Wood SL (1977) New synonymy and new species of American bark beetles (Coleoptera: Scolytidae), Part V. Great Basin Naturalist 37: 383–394.70) Wood SL (1977) New synonymy and new species of American bark beetles (Coleoptera: Scolytidae), Part IV. Great Basin Naturalist 37: 207–220.69) Wood SL (1977) New synonymy and new species of American bark beetles (Scolytidae (Coleoptera). Great Basin Naturalist 37: 57–74.68) Wood SL (1977) Introduced and exported American Coleoptera: Scolytidae), Part III. Great Basin Naturalist 35: 347–355.67) Wood SL (1976) New synonymy and new species of American bark beetles . Bulletin of Zoological Nomenclature 33: 4pp.66) Wood SL (1976) Reply to comments on the proposal to conserve Phloeotribus Latreille, 1804 . Bulletin of Zoological Nomenclature 32: 122–123.65) Wood SL (1975) Proposed conservation under the plenary powers of the name Coleoptera: Scolytidae, Part II. Great Basin Naturalist 35: 391–401.64) Wood SL (1975) New synonymy and new species of American bark beetles (Coleoptera: Scolytidae). Great Basin Naturalist 35: 21–32.63) Wood SL (1975) New synonymy and new species of American bark beetles (Coleoptera: Scolytidae). Great Basin Naturalist 34: 277–290.62) Wood SL (1974) New synonymy and records of American bark beetles . Bulletin of Zoological Nomenclature 31: 232–233.61) Wood SL (1974) Proposed conservation under the plenary powers of the name Xyleborus Eichhoff, 1864 . Bulletin of Zoological Nomenclature 31: 230–231.60) Wood SL (1974) Proposed conservation under the plenary powers of the name Phloeosinus Chapuis, 1869 . Bulletin of Zoological Nomenclature 31: 236–237.59) Wood SL (1974) Proposed conservation under the plenary powers of the name Liparthrum Wollaston, 1864 . Bulletin of Zoological Nomenclature 31: 234–235.PageBreak58) Wood SL (1974) Proposed conservation under the plenary powers of the name Phloeotribus Latreille, 1804 . Bulletin of Zoological Nomenclature 31: 122–123.57) Wood SL (1974) Proposed conservation under the plenary powers of the name Corthylus (Coleoptera: Scolytidae). Great Basin Naturalist 34: 181–202.56) Wood SL (1974) New species of American Corthylini (Coleoptera: Scolytidae). Great Basin Naturalist 34: 135–150.55) Wood SL (1974) New species of American Coleoptera: Scolytidae). Brigham Young University Science Bulletin, Biological Series 19. 67 pp.54) Wood SL (1974) New species of American bark beetles (Microcorthylus (Coleoptera: Scolytidae). Great Basin Naturalist 33: 265–275.53) Wood SL (1973) New species of American Scolytidae: Coleoptera). Part III. Great Basin Naturalist 33: 169–188.52) Wood SL (1973) New synonymy in American bark beetles (Platypodidae and Scolytidae (Coleoptera). Great Basin Naturalist 33: 77–90.51) Wood SL (1973) On the taxonomic status of Platypus parallelus (Fabricius) (Coleoptera: Platypodidae). The Coleopterists Bulletin 27: 51–52.50) Wood SL (1973) A correction in the taxonomic identity of Platypodidae Coleoptera. Science 178: 1085–1086.49) Wood SL (1972) Review of K. E. Schedl, Monographie der familie Scolytini (Coleoptera: Scolytidae). Bulletin of Entomological Researeh 62: 243–246.48) Wood SL (1972) Notes on the classification of the tribe Cryphalini (Coleoptera: Scolytidae). Great Basin Naturalist 32: 40–54.47) Wood SL (1972) New synonymy in the bark beetle tribe Scolytidae: Coleoptera). Part II. Great Basin Naturalist 32: 190–201.46) Wood SL (1972) New synonymy in American bark beetles (Scolytidae: Coleoptera). Great Basin Naturalist 31: 140–152.45) Wood SL (1972) New synonymy in American bark beetles (Scolytidae (Ipidae). In: M. H. Hatch, The beetles of the Pacific Northwest, Part 5. University of Washington, Publications in Biology 16, 395–428.44) Wood SL (1972) Family Platypodidae (Coleoptera). Great Basin Naturalist 31: 243–253.43) Wood SL (1972) New records and species of American Scolytidae: Coleoptera) from western North America. Great Basin Naturalist 31: 69–76.42) Wood SL (1972) New species of bark beetles (Scolytidae: Coleoptera). Part V. Brigham Young University Science Bulletin, Biological Series 15(3). 54 pp.41) Wood SL (1971) New records and species of neotropical bark beetles (Platypodidae and Scolytidae (Coleoptera). Great Basin Naturalist 29: 113–128.40) Wood SL (1969) New synonymy and records of Cactopinus Schwarz (Scolytidae). The Coleopterists Bulletin 23: 42–51.39) Wood SL (1969) Additions to the horned bark beetle genus Scolytidae: Coleoptera). Part IV. Brigham Young University Science Bulletin, Biological Series 10(2). 46 pp.38) Wood SL (1969) New records and species of neotropical bark beetles (Cnesinus LeConte (Coleoptera: Scolytidae) of North and Central America. Great Basin Naturalist 28: 88–110.37) Wood SL (1968) A key to the species of the genus Scolytidae: Coleoptera). Part III. Great Basin Naturalist 28: 1–15.36) Wood SL (1968) New records and species of neotropical bark beetles (PageBreakScolytidae: Coleoptera). Part II. Great Basin Naturalist. 27: 119–141.35) Wood SL (1967) New records and species of neotropical bark beetles (Scolytidae: Coleoptera). Great Basin Naturalist 27: 79–97.34) Wood SL (1967) New records and species of neotropical bark beetles (Coleoptera: Scolytidae), mostly Mexican. Part VII. Great Basin Naturalist 27: 37–57.33) Wood SL (1967) New species of bark beetles : proposed designation of a type-species under the plenary powers. Bulletin of Zoological Nomenclature 24: 121–122.32) Wood SL (1967) Platypodidae (Coleoptera). Great Basin Naturalist 26: 45–70.31) Wood SL (1966) New records and species of neotropical Platypodidae and Scolytidae (Coleoptera). Great Basin Naturalist 26: 17–33.30) Wood SL (1966) New synonymy in the Eupagiocerus Blandford (Scolytidae: Coleoptera). Great Basin Naturalist 25: 31–35.29) Wood SL (1965) The genus Pityophthorus Eichhoff (Coleoptera: Scolytidae). Great Basin Naturalist 24: 59–70.28) Wood SL (1964) New species of North American Dendroctonus Erichson (Coleoptera: Scolytidae). Great Basin Naturalist 23: 1–117.27) Wood SL (1963) A revision of the bark beetle genus Scolytidae (Coleoptera). Great Basin Naturalist 22: 76–82.26) Wood SL (1962) Miscellaneous taxonomic notes on Coleoptera: Scolytidae) mostly Mexican, Part VI. Great Basin Naturalist 21: 87–107.25) Wood SL (1961) New species of bark beetles  from the Philippine Islands. Great Basin Naturalist 21: 8–9.24) Wood SL (1961) A new Scolytidae (Coleoptera) from Colombia. Great Basin Naturalist 21: 1–7.23) Wood SL (1961) New records and species of Myelophilus Eichhoff, 1878. (Insecta: Coleoptera). Bulletin of Zoological Nomenclature 18(5): 319–321.22) Wood SL (1961) An alternate proposal to the suggested validation of Scolytidae. The Coleopterists Bulletin 15: 41–48.21) Wood SL (1961) A key to the North American genera of Scolytidae (Coleoptera) from western North America. Great Basin Naturalist 20: 59–69.20) Wood SL (1960) New records and species of Coleoptera: Platypodidae and Scolytidae. Insects of Micronesia 18(1): 1–73.19) Wood SL (1960) Coleoptera: Scolytidae). Great Basin Naturalist 19: 57–62.18) Wood SL (1959) New records and species of Arizona bark beetles (Coleoptera: Scolytidae), mostly Mexican, Part V. Great Basin Naturalist 19: 1–7.17) Wood SL (1959) New species of bark beetles (Pityoborus Blackman (Coleoptera: Scolytidae). Great Basin Naturalist 18: 46–56.PageBreak16) Wood SL (1958) Bark Beetles of the genus Platypodidae (Coleoptera). Great Basin Naturalist 18: 37–40.15) Wood SL (1958) Some virtually unknown North American Coleoptera: Scolytidae), mostly Mexican, Part IV. Great Basin Naturalist 17: 105–110.14) Wood SL (1957) New species of bark beetles (Coleoptera: Platypodidae). Great Basin Naturalist 17: 103–104.13) Wood SL (1957) A new generic name for and some biological data on an unusual Central American beetle (Coleoptera: Platypodidae and Scolytidae. Bulletin Institut francis d’Afrique Noire 19: 1272–1273.12) Wood SL (1957) Results from the Danish expedition to the French Cameroons 1949–50. XXIII. Scolytidae (Coleoptera). The Canadian Entomologist 89: 396–403.11) Wood SL (1957) Distributional notes on and synonymies of some North American Xyloterini (Coleoptera: Scolytidae) in North America. The Canadian Entomologist 89: 337–354.10) Wood SL (1957) Ambrosia beetles of the tribe Hylobius piceus (De Geer) (Coleoptera: Curculionidae). The Canadian Entomologist 89: 37–43.9) Wood SL (1957) The North American allies of Coleoptera: Scolytidae), mostly Mexican, Part III. The Canadian Entomologist 88: 247–258.8) Wood SL (1956) New species of bark beetles (Coleoptera: Scolytidae), mostly Mexican, Part II. The Canadian Entomologist 88: 231–240.7) Wood SL (1956) New species of bark beetles (Coleoptera: Scolytidae), mostly Mexican, Part I. The Canadian Entomologist 88: 141–154.6) Wood SL (1956) New species of bark beetles (Carphoborus Eichhoff (Coleoptera: Scolytidae) in North America. The Canadian Entomologist 86: 502–5265) Wood SL (1954) Bark beetles of the genus Cryphalini (Scolytidae: Coleoptera). University of Kansas Science Bulletin 36: 959–1090.4) Wood SL (1954) A revision of North American Coleoptera. Annals of the Entomological Society of America 45: 613–617.3) Wood SL (1952) Observations of the homologies of the copulatory apparatus in male Scolytidae (Coleoptera) from Utah. Journal of the Kansas Entomological Society 24: 31–32.2) Wood SL (1951) Two new species and a new genus of Scolytidae of the Logan Canyon area of Utah and their host plants. Utah Academy of Sciences, Arts and Letters 26: 127–128.1) Wood SL (1951) The


Escherichia coli could be determined. In addition, E. coli susceptibility and antibiotic prescriptions were compared with data from a similar UTI study among women and with data collected 7 years earlier. Of 367 uropathogens (66%) identified (≥103 cfu/mL), most were Gram-negative (83%) and E. coli being isolated most frequently (51%). Antibiotic susceptibility to ciprofloxacin, norfloxacin and nitrofurantoin was 94%, 92% and 88%, respectively, whereas co-amoxiclav (76%) and co-trimoxazole (80%) showed lower susceptibilities. One ESBL (0.5%) was found. A significantly higher proportion of female UTIs was caused by E. coli compared with men . E. coli susceptibility tended to be lower in men compared with women, although not reaching statistical significance. No changes in E. coli susceptibility were observed over time . Co-amoxiclav and nitrofurantoin prescriptions increased over time , whereas co-trimoxazole prescriptions decreased . In conclusion, given the observed gender differences in uropathogen distribution and (tendency in) E. coli antibiotic susceptibility, empirical male UTI treatment options should be based on surveillance studies including men only. When awaiting the culture result is clinically not possible, fluoroquinolones are advised as first-choice antibiotics for male UTIs in Dutch general practices based on current antibiotic susceptibility data. The prevalence of ESBL-producers was low and no differences were observed in antibiotic susceptibility over a 7-year period. In addition, antibiotic prescriptions changed in accordance with national guidelines during this time period.Few studies have been performed on urinary tract infections (UTIs) in men. In the present study, general practitioners (n = 42) from the Dutch Sentinel General Practice Network collected urinary samples from 560 male patients (≥18 years) suspected of UTI and recorded prescribed antibiotic treatment. In this way, the antibiotic susceptibility of Gram-negative uropathogens, including extended-spectrum beta-lactamase (ESBL-) producing  Most studies of urinary tract infections (UTIs) focus on female patients because of the higher incidence in women than in men. For this reason, most UTI guidelines are based on studies performed among women, despite the obvious genito-urinary differences Several authors have stressed the importance that gender-stratified UTI surveillance studies should be performed, because of observed differences in antimicrobial susceptibility E. coli susceptibility between male and female patients.In the Netherlands, regular surveillance studies are performed on unselected urinary isolates of both men and women to evaluate empirical treatment options in general practice, from which the female data have recently been reported Furthermore, the current treatment options for male UTIs could be evaluated as stated in the guidelines of the Dutch College of General Practitioners (NHG). These are based on the presence of symptoms of tissue invasion (i.e. high fever (>38°C), chills, malaise, flank or perineal pain) with nitrofurantoin as first-choice agent and trimethoprim as second option for men without these symptoms. Male UTI with symptoms of tissue invasion should preferably be treated with co-amoxiclav followed by fluoroquinolones and co-trimoxazole as shared second-choice E. coli was assessed, as male gender has been identified as a risk factor for ESBL-producing Enterobacteriaceae Also, the prevalence of extended-spectrum beta-lactamase (ESBL-) producing Finally, differences in antibiotic susceptibility results over time could be determined for men, because a similar UTI surveillance study was performed between January 2003 and December 2004 All data in this study were analyzed anonymously, only diagnostic specimens sent for diagnostic investigations and clinical data were used. Therefore, no consent was required from the patient and the ethics committee did not have to be approached. This is in agreement with the Medical Research Involving Human Subjects Act, the code for proper use of human tissue as formulated by the Dutch Federation of Medical Scientific Societies and the policy of the Medical Ethics Committee of the Maastricht University Medical Centre.General practices (n = 42) from the Dutch NIVEL Sentinel General Practice Network were used for the recruitment of patients. The patient population of this network is nationally representative by age, gender, region and population density From January 2009 to June 2011, GPs included male general practice patients (≥18 years of age) with symptoms of UTI, i.e. dysuria, urinary frequency and/or urgency. Catheterized patients and patients suspected of having a sexually transmitted disease were excluded. With the exception of benign prostate hypertrophy, patients were also excluded when having urological or nephrological co-morbidity, diabetes mellitus or other immunocompromising diseases.For all eligible patients, GPs filled in a patient form including age, symptoms of tissue invasion (fever (>38°C), flank pain) (yes/no) and empirical antibiotic treatment prescribed during the patient's visit (yes/no and if yes the prescribed agent was specified).Patients provided a fresh-voided (midstream) urine sample, which was used to prepare a dipslide  according to the manufacturer's instructions. For incubation and further microbiological analysis, dipslides were sent to the microbiological laboratory of Maastricht University Medical Centre, The Netherlands.3 cfu/mL Bacterial growth was determined on the day of arrival and was considered positive at ≥10E. coli ATCC 35218 and ATCC 25922 were used as control strains. The susceptibility of Gram-negative isolates was determined using the microdilution method for the following antibiotics: amoxicillin, co-amoxiclav, trimethoprim, co-trimoxazole, norfloxacin, ciprofloxacin and nitrofurantoin. E. coli strains were selected on the basis of resistance to co-amoxiclav Putative ESBL-producing From January 2009 to July 2009, a similar surveillance study among women suspected of UTI was performed E. coli susceptibility breakpoints, i.e. CLSI (2004) and EUCAST (2011). Since both studies were performed by the same research group, the original MIC values from the 2004 study were available and 2004 susceptibility data could be recalculated according to the EUCAST guidelines.The chosen categories (uropathogens and antibiotics) and all methods, including the network of the participating GPs, were the same in both studies, except for the guidelines used for the For the comparison of two groups, a Pearson's Chi-square test was used for categorical variables and an independent-samples t-test for continuous variables when parametric assumptions were met. The Mantel-Haenszel extension test for trend was used to determine a trend between more than two categorical variables. The programme PSAW 18.0 for Windows was used for statistical analyses and P<0.05 was considered statistically significant.In total, 603 men were included with a median age of 65 years (range 18–97 years). Patients were considered eligible for analyses when data from the patient form were complete . The median age of population with complete data did not differ from the full patient population. Of these 560 patients, 137 (24%) had symptoms of tissue invasion. The median age of the populations with and without signs of tissue invasion was similar .A positive culture result was found in 367 (66%) men, of whom 100 (27%) had symptoms of tissue invasion. The probability of a culture being positive increased with age, with men aged 70+ having a 3-times higher chance of a positive culture than men below the age of 50 years .E. coli being most commonly found . Differences in uropathogen distribution per age category were not observed , whereas a lower susceptibility was found to trimethoprim (75%). Co-amoxiclav, the first-choice agent for men with signs of tissue invasion according to NHG, showed a relatively low antibiotic susceptibility (76%), as well as co-trimoxazole (80%). On the other hand, the fluoroquinolones (i.e. norfloxacin and ciprofloxacin) had a high susceptibility to the Gram negatives (92% and 94% respectively) . When thEmpirical antibiotic treatment was prescribed to 359 patients (64%), of whom 284 (79%) were later confirmed as being culture positive. 70+ year old men had a 2-times higher chance to receive antibiotic treatment empirically compared with 18-50 year old men . Fluoroquinolones showed the highest prevalence of prescription (29%), followed by co-amoxiclav (28%), nitrofurantoin (23%) and co-trimoxazole (14%).In E. coli accounted for 72% of the total isolates, compared with 51% in men (P<0.001). Except for nitrofurantoin, E. coli susceptibilities tended to be lower in men compared with women: amoxicillin (65% versus 66%), co-amoxiclav (84% versus 87%), trimethoprim (77% versus 81%), co-trimoxazole (78% versus 84%), fluoroquinolones (94% versus 97%) and nitrofurantoin (both 100%), without being significant for the antibiotics tested .In women, E. coli antibiotic susceptibilities in the 2004 and 2011 studies (E. coli were found in 2004 and one (0.5%) in 2011 (P = 0.44).No differences were observed between  studies . This alE. coli susceptibilities (EUCAST) were observed between 2004 and 2011 study When comparing the antibiotic prescriptions between 2004 and 2011, GPs prescribed more co-amoxiclav and nitrofurantoin  and less co-trimoxazole  in 2011. For fluoroquinolones, amoxicillin and trimethoprim the prevalence of prescription was similar in the two studies .No significant differences in E. coli susceptibilities tended to be lower among men compared with women. For male UTIs, fluoroquinolones showed the highest prevalence of susceptibility to isolated Gram-negative uropathogens, followed by nitrofurantoin. ESBL-producing E. coli prevalence was low and no differences in E. coli susceptibility were observed over a 7-year period.In this study of UTIs in Dutch general practice, differences were observed between men and women regarding the distribution of uropathogens, and uropathogenic The important feature of this study is the participation of general practices from the NIVEL Sentinel General Practice Network. This network has a nationally representative patient population, making it possible to generalize our conclusions to the whole Dutch outpatient population. Moreover, to our knowledge, no other study has been able to include over 600 unselected urinary samples from men suspected of UTI in an outpatient setting.E. coli susceptibilities, covering 75–95% of the total spectrum of uropathogens in female UTIs The fact that no susceptibilities were determined for Gram-positive bacteria could be seen as a limitation. However, empirical treatment for uncomplicated female UTIs is often primarily based on Also, our study population could be regarded as heterogeneous with the inclusion of men aged 18+, because pathophysiology of male UTI differs with age 2 and 105 cfu/mL as cut-off values to determine a UTI 2 cfu/mL as cut-off, was still lower than our prevalence. The fact that only 36% of the patients included were prescribed an antibiotic in that study and that GPs suspected a UTI in just over 50% of the included patients, suggests that their patient population was at lower risk of UTI than our population with a prescription rate of 64%. In addition, their results were derived from a relatively small patient population (n = 79), resulting in estimates with large confidence intervals. Our choice to use 103 cfu/mL as cut-off value for the diagnosis of male UTI was based on the European urinalysis guidelines and is supported by Lipsky et al. UTI in men has also been studied by Hummers-Pradier et al. and they used 10The prevalence of positive culture (66%) we found was also slightly higher than the one reported in the 2004 study (56%) E. coli versus 72% of the UTIs in women. Moreover, uropathogenic E. coli susceptibilities tended to be lower in men in women, although no statistical significance was reached. The difference in these important characteristics for determining optimal empirical treatment, show that men with UTI should be considered as a specific patient category.Only 51% of the uropathogens causing male UTI was Given the more heterogeneous population of uropathogens that causes a UTI in men compared with women, empirical treatment should best be avoided for male UTI. When immediate treatment is necessary based on clinical judgement, our data can be used for the optimal choice of empirical treatment. Our recommendations can be applied to all men aged 18+ suspected of UTI in the Dutch GP setting, because no differences in uropathogen distribution and antibiotic susceptibility per age category were observed.We found that fluoroquinolones showed a higher prevalence of susceptibility than co-amoxiclav, the current first-choice for men with symptoms of tissue invasion E. coli susceptibility to co-amoxiclav. Using EUCAST breakpoints, the E. coli susceptibility to co-amoxiclav in 2004 decreased from 100% to 89%. The current prevalence of susceptibility of Gram-negatives to co-amoxiclav (77%) is below the proposed threshold (80%) for antibiotics to still be effective as empirical treatment for UTI The choice for EUCAST instead of CLSI guidelines had an impact on the Based on these findings, fluoroquinolones may be regarded as the current preferred treatment in men with tissue invasion. However, in addition to antibiotic resistance data, side effects of the drugs related to age, financial consequences and patient characteristics should be included in the choice of the preferred antibiotics.Proteus species and non-fermenters, high antibiotic susceptibilities (≥87%) to Gram-negatives were also found for nitrofurantoin. Similar results were described by Guay Except for For male UTIs, second-choice agents (i.e. fluoroquinolones) were still prescribed most, although overall compliance with national guidelines improved in comparison with prescription data from 2004. This was shown by an increase in co-amoxiclav and nitrofurantoin prescriptions, the first-choice agents for men with and without symptoms of tissue invasion respectively.E. coli susceptibilities from 2004 and 2009 were compared, and also no differences in time trend were observed E. coli is in accordance with these findings.In the surveillance study on female UTIs in Dutch general practices, E. coli originating from Dutch male GP patients suspected of UTI, the prevalence of ESBL-producers was low and no differences were observed in antibiotic susceptibility over a 7-year period. In addition, antibiotic prescriptions changed in accordance with national guidelines during this time period. For male UTIs in Dutch general practice, fluoroquinolones may be regarded as the best treatment option on the basis of current susceptibility data. Differences in uropathogen distribution, together with the tendency of a lower E. coli antibiotic susceptibility in men versus women, make it necessary to base male UTI treatment recommendations on UTI studies performed among men only.In conclusion, among unselected


We describe the first reported case of an IgG4-related autoimmune fibrosclerosing pseudotumour located in the stomach of a 75-year old woman presenting with weight loss and vomiting. A lesion was detected in the gastric body at endoscopy. Subsequent characterisation by CT was suggestive of a gastrointestinal stromal tumour. Following laparoscopic resection, the patient recovered uneventfully. Histological examination of the resected specimen revealed an IgG4-related fibrosclerosing pseudotumour, a novel location for this histopathological entity. IgG4-related autoimmune fibrosclerosing pseudotumour was first reported to be found in various organs of patients with autoimmune pancreatitis (AIP), a form of chronic sclerosing pancreatitis associated with an infiltration of T cells and IgG4-expressing plasma cells. There are multiple recognised clinical manifestations of IgG4 sclerosing disease including sclerosing cholangitis, cholecystitis, retroperitoneal fibrosis, interstitial pneumonia, tubulointerstitial nephritis-and inflammatory pseudotumour . We presA 75-year-old woman presented to the fast track endoscopy service with a two-month history of vomiting, weight loss, and anaemia. She had no previous medical history of note and was independent. Initial gastroscopy revealed a large polypoid lesion in the gastric body  with abnThe patient subsequently went on to have a laparoscopic resection of the lesion from the posterior aspect of the lesser curvature. This was performed by making an anterior gastrotomy and resecting the lesion using a laparoscopic linear stapler. Following an intraluminal bleed which was managed conservatively, she made an uneventful recovery and was discharged home on day 10 postoperatively.Histological examination of the specimen  showed iThe patient was seen in clinic two weeks later, by which time she had made a full recovery after surgery. Subsequent blood tests revealed that her serum IgG4 was within normal range (1.09); however, levels had not been examined prior to resection as an IgG4 autoimmune fibrosclerosing pseudotumour had not been suspected.IgG4-related autoimmune fibrosclerosing pseudotumours have been documented in a variety of different anatomical sites including the liver , lungs , and pitHistologically, inflammatory pseudotumours are characterised by an irregular proliferation of myofibroblasts with a surrounding inflammatory cell infiltrate, composed predominantly of T lymphocytes and plasma cells. The IgG-related inflammatory pseudotumours are characterised by dense infiltration of IgG4-positive plasma cells and lymphocytes associated with fibrosis. However, the mechanism by which increased IgG4 levels can induce pseudotumour formation is unclear, and typically the pseudotumour presents as the sole systemic manifestation of “Hyper IgG4”disease. Such IgG4-related inflammatory pseudotumours have been most commonly reported in the lungs with only occasional reports of extrapulmonary locations. Nine cases of lung IgG4-related pseudotumours were described by Zen et al. , 8 of whTo conclude, we present the first case report of a patient presenting with an IgG4-related pseudotumour within the stomach lining. There was no evidence of any other organ involvement in this patient. This case highlights how such a lesion can masquerade as another type of tumour, in this case a GIST, and as such, although rare, ought to be considered as part of the differential diagnosis for spindle cell lesions. The histopathological entity of IgG4-autoimmune fibrosclerosing pseudotumour is becoming recognised more frequently in a variety of locations, requiring treatment with steroids rather than surgery.