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INTRODUCTION: Amino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis (RNC) and umour recurrence (TR) in brain tumours, but its use in our country is still limited. The aim of this work is to present our experience with 6-[18F]FDOPA PET/CT (FDOPA) in brain tumours (primary and M1), comparing these results with other published results. MATERIAL AND METHODS: Retrospective study of 62 patients with suspected tumour recurrence (TR): 42 brain metastases (M1) and 20 primary, who underwent FDOPA. Images were analysed visually and semi-quantitatively, obtaining SUVmax and SUVmaxlesion/SUVmaxstriatum (L/S) and SUVmaxlesion/SUVmaxcortex (L/C) ratios. The diagnostic validity of PET was analysed and the best performing cut-off points were calculated. PET results were compared with clinical-radiological follow-up and/or histopathology. RESULTS: TR was identified in 49% of M1 and 76% of brain primaries. The best performing FDOPA interpretation was visual and semi-quantitative, with a sensitivity and specificity in primaries of 94% and 80% and in M1s of 96% and 72% respectively. The cut-off points with the best diagnostic performance were L/C1.44 in M1 and L/C1.55 in primaries. There are discrepant results with other published results. CONCLUSION: FDOPA PET/CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours. It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level.
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Neoplasias Encefálicas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Di-Hidroxifenilalanina , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapiaRESUMO
INTRODUCTION: Stage IV rectal cancer with resectable disease presents challenging issues, as the radical treatment of the whole disease is difficult. Surgery and chemotherapy (CT) play an unquestionable role, but the contribution of pelvic radiotherapy (RT) is not very clear. METHODS: In 2009, we established a prospective treatment protocol that included CT, short-course preoperative radiotherapy (SCRT) with surgery of the primary tumour and all metastatic locations. RESULTS: Forty patients were included. Eight (20%) patients did not receive CT due to significant comorbidities. Radical surgery treatment was possible in 22 (55%) patients. The mean follow-up was 42.81 months (3.63-105.97). Overall survival at 24 and 36 months was 71.4% and 58.2%, respectively. There was good local control of the disease, as 97.2% of pelvic surgeries were R0 and there were no local recurrences. CONCLUSION: In stage IV with resectable metastatic disease, the proposed therapeutic regimen seems very appropriate in well selected patients able to tolerate the treatment. We bet on the role of pelvic RT, due to the good local control of the disease in our series.
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Adenocarcinoma/radioterapia , Neoplasias Pélvicas/radioterapia , Cuidados Pré-Operatórios , Radioterapia/métodos , Neoplasias Retais/radioterapia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/secundário , Neoplasias Pélvicas/cirurgia , Prognóstico , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Taxa de SobrevidaRESUMO
INTRODUCTION: Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. METHODS: Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. RESULTS: Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p < 0.001). CONCLUSIONS: The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time.
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Adenocarcinoma/radioterapia , Carcinoma de Células Escamosas/radioterapia , Atenção à Saúde/normas , Terapia Neoadjuvante/mortalidade , Melhoria de Qualidade , Radioterapia Adjuvante/mortalidade , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/patologia , Taxa de SobrevidaRESUMO
PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.
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Carcinoma de Mama in situ/radioterapia , Neoplasias da Mama/radioterapia , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Mama in situ/patologia , Carcinoma de Mama in situ/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Radioterapia Adjuvante , Reirradiação , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Several studies have reported greater success of fertilisation by ART in couples who were not infected by Ureaplasma. Increased semen quality and better results have also been observed in couples who were treated with antibiotics to eradicate the infection. The aim of this study was to determine the prevalence of genital mycoplasmas in urine samples from male partners enrolled in the Assisted Reproduction Program (ARP) in our healthcare area so that, positive cases can be treated prior to the use of ART in order to increase the quality of semen, improve the embryo implantation rates and minimize the risk of adverse effects during pregnancy. METHODS: This study included couples enrolled in the ARP during 2016. Mycoplasma detection was made using real-time PCR. In positive cases, both members of the couple were treated with antibiotics until eradication of the microorganism. The antibiotics used were: azithromycin, doxycycline, levofloxacin, moxifloxacin, and clindamycin. RESULTS: Of the 205 men studied, 33 were positive: Ureaplasma urealyticum 15.1%, Mycoplasma hominis 3.9%. Eradication treatment with azithromycin failed in 50% compared to 10.2% for doxycycline. Of the 5 cases treated with levofloxacin, only 2 achieved elimination of U. urealyticum. CONCLUSIONS: We consider that genital mycoplasma routine screening could be useful in order to increase the quality of semen which could simplify the in vitro fertilisation procedures and raise the success rate of embryo implantation and pregnancy, especially when fast, sensitive and specific technics as real time PCR are used.
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Antibacterianos/uso terapêutico , Doenças dos Genitais Masculinos/tratamento farmacológico , Infecções por Mycoplasma/tratamento farmacológico , Técnicas de Reprodução Assistida , Análise do Sêmen , Adulto , Azitromicina/uso terapêutico , Clindamicina/uso terapêutico , Doxiciclina/uso terapêutico , Implantação do Embrião , Feminino , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Femininos/epidemiologia , Doenças dos Genitais Femininos/microbiologia , Doenças dos Genitais Masculinos/epidemiologia , Doenças dos Genitais Masculinos/microbiologia , Doenças dos Genitais Masculinos/urina , Humanos , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Moxifloxacina/uso terapêutico , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/urina , Mycoplasma hominis/efeitos dos fármacos , Mycoplasma hominis/genética , Mycoplasma hominis/isolamento & purificação , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Fatores Sexuais , Resultado do Tratamento , Infecções por Ureaplasma/tratamento farmacológico , Infecções por Ureaplasma/epidemiologia , Infecções por Ureaplasma/urina , Ureaplasma urealyticum/efeitos dos fármacos , Ureaplasma urealyticum/genética , Ureaplasma urealyticum/isolamento & purificação , Adulto JovemRESUMO
The plasma cell dyscrasias (PCDs) include a number of entities such as multiple myeloma, primary amyloidosis, and monoclonal immunoglobulin deposition disease. Hematopoietic cell transplant (HCT) is the only cure for a variety of hematologic and oncologic diseases. Clinically significant renal impairment is a common feature in plasma cell myeloma, affecting 20% to 55% of patients at initial diagnosis; 2% to 3% of patients present with failure sufficiently severe to require hemodialysis. This circumstance is associated with a high early mortality. The necessity for immunosuppression after HCT could complicate its management and may precipitate the development of complications. In some patients an effective alternative could be kidney transplant (KT); however, the presence of 2 transplants will require optimal adjustment of immunosuppression and management of complications. At present, there are few published cases of KT after HCT, and the experience of managing 2 transplants is limited. We would like to describe our experience with 4 patients who had a PCD and initially received HCT and received subsequent KT. In our experience the progress and outcome of KT after HCT were optimal. We would like to address that a higher incidence of cytopenia associated with the combination of immunosuppression (lenalidomide, tacrolimus, mycophenolate, etc.) and other drugs (ie, valganciclovir) should be considered together with an increased risk of opportunistic infections and PCD relapse.
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Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Paraproteinemias/complicações , Paraproteinemias/cirurgia , Insuficiência Renal/cirurgia , Adulto , Idoso , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologiaRESUMO
BACKGROUND: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. METHODS: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. RESULTS: The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. CONCLUSIONS: The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process.
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BACKGROUND AND PURPOSE: Current protocols in patients with glioblastoma include performing an MR examination shortly after surgery and then 2-6 weeks after ending concomitant chemoradiotherapy. The assessment of this first postradiotherapy examination is challenging because the pseudoprogression phenomenon may appear. The aim of this study was to explore if performing an MR examination shortly before radiation therapy (preradiotherapy MR imaging) could improve the radiologic assessment of patients with glioblastoma. MATERIALS AND METHODS: A preradiotherapy MR imaging examination was prospectively performed before the start of radiation therapy in 28 consecutive patients with glioblastoma who had undergone surgical resection. Tumor response to chemoradiotherapy was assessed twice: with the early postoperative MR examination as baseline and with the preradiotherapy MR imaging examination as baseline. In addition, tumor growth in the preradiotherapy MR imaging examination was evaluated, and its correlation with patient survival was assessed with Kaplan-Meier analysis and Cox regression. RESULTS: Tumor progression after radiation therapy was found in 16 patients, corresponding to pseudoprogression in 7 of them (44%). Four assessments of pseudoprogression switched to partial response or stable disease when preradiotherapy MR imaging was the baseline examination, and the ratio of pseudoprogression was reduced to 25% (3 of 12). Significant differences in survival were found when patients were stratified according to the pattern of tumor growth on preradiotherapy MR imaging (median overall survival "no-growth," 837 days; "focal-growth," 582 days; "global-growth," 344 days; P = .001). CONCLUSIONS: Performing a preradiotherapy MR imaging examination may improve the clinical management of patients with glioblastoma by reducing the ratio of pseudoprogression assessments and providing prognostic information.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Progressão da Doença , Feminino , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Projetos Piloto , Prognóstico , Estudos ProspectivosRESUMO
The swelling behaviour of poly(styrene-co-divinylbenzene), P(S-DVB), ion exchange resins in 1-butanol (BuOH) has been studied by means of atomistic classical molecular dynamics simulations (MD). The topological characteristics reported for the resin in the dry state, which exhibited complex internal loops (macropores), were considered for the starting models used to examine the swelling induced by BuOH contents ranging from 10% to 50% w/w. Experimental measurements using a laser diffraction particle size analyzer indicate that swelling causes a volume variation with respect to the dry resin of 21%. According to MD simulations, such a volume increment corresponds to a BuOH absorption of 31-32% w/w, which is in excellent agreement with the indirect experimental estimation (i.e. 31% w/w). Simulations reveal that, independently of the content of BuOH, the density of the swelled resin is higher than that of the dry resin, evidencing that the alcohol provokes important structural changes in the polymeric matrix. Thus, BuOH molecules cause a collapse of the resin macropores when the content of alcohol is ≤20% w/w. In contrast, when the concentration of BuOH is close to the experimental value (â¼30% w/w), P(S-DVB) chains remain separated by pores faciliting the access of the reactants to the reaction centers. On the other hand, evaluation of both bonding and non-bonding interactions indicates that the mixing energy is the most important contribution to the absorption of BuOH into the P(S-DVB) resin. Overall, the results displayed in this work represent a starting point for the theoretical study of the catalytic conversion of BuOH into di-n-butyl ether in P(S-DVB) ion exchange resins using sophisticated electronic methods.
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1-Butanol/química , Resinas de Troca Iônica/química , Poliestirenos/química , Catálise , Simulação de Dinâmica MolecularRESUMO
A prototype is introduced based on the transversal modulation ion mobility spectrometry (TMIMS) technique, which provides a continuous output of mobility-selected ions, greatly easing the synchronization between different analyzing stages. In the new architecture, two stages of filtration are used to drastically reduce the background produced by one stage alone. Two-stages TMIMS was coupled with two different atmospheric pressure interface mass spectrometers (MS). The new system enables IMS-IMS-MS analysis and other modes of operation: IMS prefiltration, IMS-IMS, and full transmission mode. It provides a resolving power R > 60 in IMS mode, and R > 40 in each stage of IMS-IMS mode. 2-Propanol vapors were introduced in one of the stages to enhance the mobility variations, and their effect was studied on a set of tetraalkylammonium ions. We found that concentrations as low as 1% (in partial pressure) produce mobility variations as high as 20%, which suggest that IMS-IMS separation using dried N2 (in one stage) and a dopant (in the other stage), could be a very powerful way to enhance the separation capacity of the IMS-IMS prefiltration approach.
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Espectrometria de Massas/instrumentação , 2-Propanol/química , Compostos de Amônio/química , Desenho de Equipamento , Íons/químicaRESUMO
Recent technological advances have made it possible to detect circulating tumor cells (CTCs) as a prognostic marker in operable breast cancer patients. Whether the presence of CTCs in cancer patients correlates with molecular alterations in the primary tumor has not been widely explored. We identified 14 primary breast cancer specimens with known CTC status, in order to evaluate the presence of differential genetic aberrations by using SNP array assay. There was a global increase of altered genome, CNA, and copy-neutral loss of heterozygosity (cn-LOH) observed in the CTC-positive (CTC(+)) versus CTC-negative (CTC(-)) cases. As the preliminary results showed a higher proportion of copy number alteration (CNA) at 8q24 (MYC loci) and the available evidence supporting the role of MYC in the processes cancer metastases is conflicting, MYC status was determined in tissue microarray sections in a larger series of patients (n = 49) with known CTC status using FISH. MYC was altered in 62% (16/26) CTC(+) patients and in 43% (6/14) CTC(-) patients (p = 0.25). Based on the observation in our study, future studies involving a larger number of patients should be performed in order to definitively define if this correlation exists.
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Neoplasias da Mama/genética , Variações do Número de Cópias de DNA/genética , Genes myc/genética , Perda de Heterozigosidade/genética , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Biofilms are organized bacterial communities embedded in an extracellular polymeric matrix attached to living or abiotic surfaces. The development of biofilms is currently recognized as one of the most relevant drivers of persistent infections. Among them, chronic respiratory infection by Pseudomonas aeruginosa in cystic fibrosis patients is probably the most intensively studied. The lack of correlation between conventional susceptibility test results and therapeutic success in chronic infections is probably a consequence of the use of planktonically growing instead of biofilm-growing bacteria. Therefore, several in vitro models to evaluate antimicrobial activity on biofilms have been implemented over the last decade. Microtitre plate-based assays, the Calgary device, substratum suspending reactors and the flow cell system are some of the most used in vitro biofilm models for susceptibility studies. Likewise, new pharmacodynamic parameters, including minimal biofilm inhibitory concentration, minimal biofilm-eradication concentration, biofilm bactericidal concentration, and biofilm-prevention concentration, have been defined in recent years to quantify antibiotic activity in biofilms. Using these parameters, several studies have shown very significant quantitative and qualitative differences for the effects of most antibiotics when acting on planktonic or biofilm bacteria. Nevertheless, standardization of the procedures, parameters and breakpoints, by official agencies, is needed before they are implemented in clinical microbiology laboratories for routine susceptibility testing. Research efforts should also be directed to obtaining a deeper understanding of biofilm resistance mechanisms, the evaluation of optimal pharmacokinetic/pharmacodynamic models for biofilm growth, and correlation with clinical outcome.
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Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Anti-Infecciosos/farmacocinética , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana/normas , Modelos Biológicos , Plâncton/efeitos dos fármacosRESUMO
The Syrian hamster Harderian gland (HG) is an organ that undergoes physiological autophagy in response to oxidative stress induced by porphyrin production. Porphyrin production in the HG has marked sex differences and is closely linked to reproductive function. In the present study, we observed that the estrous cycle and associated estrogen variations may affect oxidative-stress-induced proteolytic processes. In particular, significant changes in autophagic activity were detected during the estrous cycle. Notably, increased activation of macroautophagy as well as chaperone-mediated autophagy in the estrus phase coincided with a minimal antioxidant capability and the highest protein damage levels. By contrast, autophagic machinery was found to be blocked in the diestrus phase, likely due to mammalian target of rapamycin activation, which could be corroborated by the subsequent pS6K activation. Analogous results were observed regarding proteasome activity, which also showed maximal activity in the estrus phase. Interestingly, all these mechanisms were associated with important morphological changes in the HG during the estrous cycle. We observed statistically significant increases in Type II cells, which may be related to extensive autophagy in the estrus phase. Physiologically, this would result in a significant release of porphyrins specifically when females are more receptive. These data support the role of porphyrins as pheromones, as other authors have previously suggested, thus making the HG a scent organ. In addition, these results suggest a porphyrin-based approach to the treatment of porphyria during pregnancy, a condition for which no treatment is currently known.
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Autofagia , Ciclo Estral/metabolismo , Glândula de Harder/metabolismo , Porfirinas/metabolismo , Proteólise , Animais , Estrogênios/metabolismo , Feminino , Humanos , Mesocricetus , Porfirias/metabolismo , Porfirias/patologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologiaRESUMO
A carbapenem-resistant Acinetobacter baumannii clinical isolate belonging to European clone II and sequence type 2 was recovered from a patient in the Son Espases hospital in Mallorca, Spain. Genetic analysis showed the presence of the bla(OXA-23) gene in association with the widely disseminated transposon Tn2006. This is the first reported identification of A. baumannii carrying bla(OXA-23) in Spain.
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Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Cromossomos Bacterianos , Elementos de DNA Transponíveis , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Eletroforese em Gel de Campo Pulsado , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , EspanhaRESUMO
In secondary electrospray ionization (SESI) systems, gaseous analytes exposed to an elecrospray plume become ionized after charge is transferred from the charging electrosprayed particles to the sample species. Current SESI systems have shown a certain potential. However, their ionization efficiency is limited by space charge repulsion and by the high sample flows required to prevent vapor dilution. As a result, they have a poor conversion ratio of vapor into ions. We have developed and tested a new SESI configuration, termed low-flow SESI, that permits the reduction of the required sample flows. Although the ion to vapor concentration ratio is limited, the ionic flow to sample vapor flow ratio theoretically is not. The new ionizer is coupled to a planar differential mobility analyzer (DMA) and requires only 0.2 lpm of vapor sample flow to produce 3.5 lpm of ionic flow. The achieved ionization efficiency is 1/700 (one ion for every 700 molecules) for TNT and, thus, compared with previous SESI ionizers coupled with atmospheric pressure ionization-mass spectrometry (API-MS) (Mesonero, E.; Sillero, J. A.; Hernández, M.; Fernandez de la Mora, J. Philadelphia PA, 2009) has been improved by a large factor of at least 50-100 (our measurements indicate 70). The new ionizer coupled with the planar DMA and a triple quadrupole mass spectrometer (ABSciex API5000) requires only 20 fg (50 million molecules) to produce a discernible signal after mobility and MS(2) analysis.
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The analysis of ions according to their mobility is a technique that is attracting increasing interest. The new technology presented here, which we have termed Transversal Modulation Ion Mobility Spectrometry (TM-IMS), utilizes only electric fields, operates at atmospheric pressure, produces a continuous output of mobility selected ions (according to their true mobility and not to nonlinear effects), and has a very accessible inlet and outlet. These features would make it an ideal choice for tandem IMS-MS analysis in combination with most commercial Atmospheric Pressure Interface MS (API-MS) systems. We modeled and evaluated two different TM-IMS configurations (TM-IMS, and multistage TM-IMS), and we concluded that the most promising configuration would be a two-stage TM-IMS. We developed and tested a TM-IMS, and the measured resolving power is R = 55. The TM-IMS behaves similarly to the planar Differential Mobility Analyzer, but the TM-IMS utilizes only electric fields, and no fragile flow with high Reynolds numbers is required. We tested the robustness of the TM-IMS, which proves to be a very robust and reliable analyzer: the required voltage accuracy is 5 V in 10 kV, and the mechanical precision is 1 mm in 5 cm.
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Modelos Teóricos , Pressão Atmosférica , Íons/química , Análise Espectral/instrumentação , Análise Espectral/métodosRESUMO
INTRODUCTION: Important differences in patient survival exist between peritoneal dialysis (PD) and haemodialysis (HD). Several different studies have shown that PD yields a better survival rate than HD in the first and second years of treatment, especially in younger patients and non-diabetic patients with low comorbidity, whereas HD produces better results in diabetic patients, elderly patients, and in patients with greater comorbidity. In recent years, interesting changes have occurred in PD units in the Canary Islands, such as the introduction of peritoneal dialysis solutions with bicarbonate dialysate and low content of glucose degradation products, extended use of automated dialysis, and continuity of physicians and nurses in PD units, in addition to enhancing visits for advanced chronic kidney disease (ACKD). OBJECTIVE: This situation led us to perform our study with the primary objective of comparing medium-term survival among incident dialysis patients on HD versus PD in recent years in the Canary Islands, and as a secondary objective, to compare survival between these two types of dialysis by subgroups as defined by age, sex and diabetes. MATERIAL AND METHODS: This was a retrospective cohort study comparing survival between HD and PD patients starting dialysis in the Canary Islands between 01/01/2006 and 31/12/2009, with adjustment based on the propensity score analysis. We analysed data from the RERCAN database, which collects data on demographic variables, changes in type of dialysis, province and hospital of the patient, and mortality and its causes. We calculated Kaplan-Meier estimates of survival based on the overall population and stratified by age, sex and diabetes. We applied a Cox proportional hazards model for survival to estimate the relative mortality risk of PD compared with HD, using as independent variables: age, sex, quartiles of propensity score, the province of the patient, and diabetes. Finally, we applied a Cox model with time-dependent effects, using as a fixed risk factor the initial type of dialysis in order to assess the effect of PD versus HD on short and medium-term survival. RESULTS: The cohort included 1469 patients (173 PD and 1296 HD), with a mean age of 62.5 years, 65% male. Mean follow-up was 16.2±12.4 months. Factors associated with greater probability of choosing PD were younger age and living in the province of Las Palmas. The cumulative mortality in the intention to treat (ITT) analysis was 27.1% in the HD group and 8.7% in the PD group, P<.0001. The cumulative probability of survival by ITT using PD vs HD was 96.6% versus 89% at 6 months (P<.001), 96% versus 80% at 12 months (P<.001), 90% versus 65% at 24 months (P<.001), 82% versus 58% at 36 months (P<.001) and 73% versus 45% at 46 months (P<.001). In the subgroup analysis, survival was also higher in PD patients compared to HD patients both over and under 65 years old, in both diabetic and non-diabetic patients, and in both genders. The same analysis from the 90th day onward produced similar results. In the ITT analysis, the Cox-adjusted mortality risk for PD was 61% lower than for HD (RR: 0.398, 95% CI 0.237-0.669, P=.001), adjusted for age, diabetes, sex, patient's province and propensity score. Broken down by years of survival on the technique used, the relative risk of death for PD compared with HD in the first year was also significantly lower (RR 0.509, 95% CI: 0.259-0.999, P=.049). From year 2 onwards, only age was a risk factor for mortality (RR: 2.785, 95% CI: 1.525-5.086, P=.001) and no differences were shown between the two dialysis techniques. CONCLUSION: In the Canary Islands, PD has demonstrated survival advantages over HD in the short and medium term. It is remarkable that this benefit was found in young and old patients, men and women, and diabetic and non-diabetic patients, and that this advantage was maintained even after years of being on dialysis.
Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal , Adulto , Fatores Etários , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Estudos de Coortes , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/terapia , Feminino , Humanos , Infecções/mortalidade , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Diálise Peritoneal/estatística & dados numéricos , Modelos de Riscos Proporcionais , Sistema de Registros , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Resultado do TratamentoRESUMO
The transcription factor Pit-1/Pou1f1 regulates GH and prolactin (PRL) secretion in the pituitary gland. Pit-1 expression and GH regulation by Pit-1 have also been demonstrated in mammary gland. However, no data are available on the role of Pit-1 on breast PRL. To evaluate this role, several human breast cancer cell lines were transfected with either the Pit-1 expression vector or a Pit-1 small interference RNA construct, followed by PRL mRNA and protein evaluation. In addition, transient transfection of MCF-7 cells by a reporter construct containing the proximal PRL promoter, and ChIP assays were performed. Our data indicate that Pit-1 regulates mammary PRL at transcriptional level by binding to the proximal PRL promoter. We also found that Pit-1 raises cyclin D1 expression before increasing PRL levels, suggesting a PRL-independent effect of Pit-1 on cell proliferation. By using immunohistochemistry, we found a significant correlation between Pit-1 and PRL expression in 94 human breast invasive ductal carcinomas. Considering the possible role of PRL in breast cancer disorders, the function of Pit-1 in breast should be the focus of further research.