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1.
Curr Comput Aided Drug Des ; 18(1): 1-8, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33535959

RESUMO

BACKGROUND: Many techniques to design chemical libraries for screening have been put forward over time. General use libraries are still important when screening against novel targets, and their design has relied on the use of molecular descriptors. In contrast, chemotype or scaffold analysis has been used less often. OBJECTIVE: We describe a simple method to assess chemical diversity based on counts of the chemotypes that offers an alternative to model chemical diversity. We describe a simple method to assess chemical diversity based on counts of the chemotypes that offers an alternative to model chemical diversity based on computed molecular properties. We show how chemotype counts can be used to evaluate the diversity of a library and compare diversity selection algorithms. We demonstrate an efficient compound selection algorithm based on chemotype analysis. METHODS: We use automated chemotype perception algorithms and compare them to traditional techniques for diversity analysis to check their effectiveness in designing diverse libraries for screening. RESULTS: The best type of molecular fingerprints for diversity selection in our analysis are extended circular fingerprints, but they can be outperformed by the use of a chemotype diversity algorithm, which can be more intuitive than traditional techniques based on molecular descriptors. Chemotype- -based algorithms retrieve a larger share of the chemotypes contained in a library when picking a subset of the chemicals in a collection. CONCLUSIONS: Chemotype analysis offers an alternative for the generation of a general-purpose screening library as it maximizes the number of chemotypes present in a subset with the smallest number of compounds. The applications of methods based on chemotype analysis that does not resort to the use of molecular descriptors are a very promising but seldom explored area of chemoinformatics.


Assuntos
Algoritmos , Bibliotecas de Moléculas Pequenas
2.
Am Soc Clin Oncol Educ Book ; 39: e121-e125, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099669

RESUMO

Incidence and mortality from cancer is increasing in most countries in the world, with the highest burden in developing countries. City Cancer Challenge (C/Can), an initiative launched in 2017, aims to improve access to quality cancer care in metropolitan areas (1 million inhabitants or more) in low- and upper-middle income countries by transforming the way stakeholders at the city, regional, and national levels collectively design, plan, and implement local cancer solutions. The approach is built on the core principle that local leaders in cities define their own needs and craft solutions with the support of a network of global, regional, and local partners that reflect an understanding of the unique local context. C/Can aims to build a collective movement of cities that can together deliver quality, equitable, and sustainable cancer control solutions for all.


Assuntos
Neoplasias/epidemiologia , Cidades , Prioridades em Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Incidência , Prática Associada , Avaliação de Programas e Projetos de Saúde , Vigilância em Saúde Pública , Regionalização da Saúde , População Urbana
4.
J Infect Dev Ctries ; 8(6): 699-704, 2014 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-24916867

RESUMO

INTRODUCTION: Knowledge of the etiology and antimicrobial susceptibility patterns of uropathogens is important for determining the best treatment option. This study aimed to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from adult male outpatients. METHODOLOGY: Between November 2012 and April 2013, 3,105 community urine samples were analyzed from adult male patients who attended the Laboratorio Hidalgo, Buenos Aires, Argentina. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method. Isolates resistant to third generation cephalosporin were tested for extended-spectrum beta-lactamase (ESBL) production using the double-disk synergy test. RESULTS: Of the 3,105 urine samples analyzed, 791 (25.5%) had significant bacteriuria. The frequency of positive urine cultures increased significantly with patient age. Escherichia coli was isolated most frequently (47.3%), followed by Enterococcus faecalis (13.6%), and Klebsiella pneumoniae (11.9%). Gram-negative organisms represented 78.8% of urinary pathogens. The highest activities against Gram-negative bacteria were found with imipenem (99.0%), amikacin (98.1%), ertapenem (94.2%), fosfomycin (90.7%), and piperacillin-tazobactam (90.1%). The frequencies of ESBLs among E. coli, K. pneumoniae, and P. mirabilis were 15.2 %, 22.3%, and 8%, respectively. Fosfomycin, piperacillin-tazobactam, and nitrofurantoin were most effective against Gram-positive organisms. CONCLUSIONS: Fosfomycin may be an excellent option for cystitis treatment in patients without risk factors, whereas piperacillin-tazobactam is preferred for the treatment of parenchymatous UTIs, complicated UTIs, and UTIs associated with risk factors. To ensure the optimal selection of antibiotics, physicians should have access to up-to-date information about the local prevalence of antimicrobial resistance.


Assuntos
Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Idoso , Idoso de 80 Anos ou mais , Argentina , Bacteriúria/tratamento farmacológico , Bacteriúria/microbiologia , Países em Desenvolvimento , Farmacorresistência Bacteriana , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pacientes Ambulatoriais
5.
Rev. esp. quimioter ; 27(1): 51-55, mar. 2014. tab
Artigo em Espanhol | IBECS | ID: ibc-119823

RESUMO

Introducción. Las infecciones por Escherichia coli productoras de BLEE son cada vez mas frecuentes en la comunidad. Ertapenem (ERT) presenta muy buena actividad frente a estas cepas y es una excelente indicación en infecciones severas en etapa de manejo ambulatorio. El objetivo de este trabajo fue determinar la frecuencia de selección de mutantes resistentes a carbapenemas en una colección de aislamientos clínicos de E. coli productoras de BLEE. Material y métodos. Se buscaron mutantes resistentes en uno y dos pasos a ERT, imipenem (IMI) y meropenem (MER) por inoculación de 109 ufc/ml en placas de agar Mueller Hinton conteniendo las carbapenemas a diferentes concentraciones. La concentración inhibitoria mínima (CMI) en las cepas originales y mutantes se determinó con el método epsilometrico Etest. Resultados. No se pudieron seleccionar mutantes resistentes con IMI y MER. Al utilizar ERT se obtuvieron mutantes resistentes en 13 de 57 aislamientos clínicos (22,8 %). Todos los mutantes resistentes fueron resistentes a ERT con CMI ≥ 1 mg/L pero mantuvieron sensibilidad a IMI y MER. Se obtuvieron 6 MR segundo paso con ERT las cuales presentaron resistencia de alto nivel a ERT (CMI ≥ 8 mg/L). Se observó resistencia cruzada a MER en 3 de ellas y en 1 a IMI. Los cuatro mutantes resistentes de segundo paso obtenidos con MER fueron resistentes a ERT y MER y en 2 de ellas se observó resistencia cruzada a IMI. Conclusiones. La selección de mutantes resistentes a ERT es frecuente en cepas de E. coli productoras de BLEE. Para obtener mutantes resistentes a MER e IMI es necesario un segundo paso de selección. El uso de ERT en infecciones con inóculo alto, focos no drenados y con cepas productoras de BLEE debería ser vigilado para reducir el riesgo de selección de resistencia (AU)


Introduction. The occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. These organisms are frequently resistant to many of the antimicrobial agents but remain susceptible to carbapenems. We investigated the in vitro emergence of carbapenem resistance in a collection of clinical isolates of ESBL -producing E. coli Material and methods. First and second-step resistant mutants were obtained from E. coli with ESBL. Aliquots of 50μl containing > 109 CFU were applied to Mueller-Hinton plates containing meropenem, imipenem or ertapenem. MICs for native strains and mutants were determined using the epsilometric test (E-test). Results. Resistant mutants were not selected with imipenem or meropenem. E. coli growth was observed on ertapenem (0.5 mg/L)-containing plates in 13 of 57 clinical isolates (22.8 %).The ertapenem MIC for these first-step mutants were ≥ 1 mg/L, remaining susceptible to imipenem and meropenem. The first-step mutants were used as native strains. Six second-step resistant mutants were selected with ertapenem. All were fully resistant (CMI ≥ 8 mg/L) to ertapenem, three were resistant to meropenem and one to imipenem. Four second-step resistant mutants were selected with meropenem. All were resistant to ertapenem, meropenem, and two of them were resistant to imipenem. Conclusions. Stable resistant mutants were easy to select with ertapenem among ESBL-producing E. coli. Two steps were necessary to select resistant mutants to meropenem or imipenem. The use of ertapenem in high-inoculum infections or in undrained focus of infection should be monitored to reduce the risk on selection of resistance (AU)


Assuntos
Humanos , Resistência Microbiana a Medicamentos , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Carbapenêmicos/uso terapêutico , beta-Lactamas
6.
J Chem Inf Model ; 53(10): 2774-9, 2013 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-24099460

RESUMO

The momentum gained by research on biologics has not been met yet with equal thrust on the informatics side. There is a noticeable lack of software for data management that empowers the bench scientists working on the development of biologic therapeutics. SARvision|Biologics is a tool to analyze data associated with biopolymers, including peptides, antibodies, and protein therapeutics programs. The program brings under a single user interface tools to filter, mine, and visualize data as well as those algorithms needed to organize sequences. As part of the data-analysis tools, we introduce two new concepts: mutation cliffs and invariant maps. Invariant maps show the variability of properties when a monomer is maintained constant in a position of the biopolymer. Mutation cliff maps draw attention to pairs of sequences where a single or limited number of point mutations elicit a large change in a property of interest. We illustrate the program and its applications using a peptide data set collected from the literature.


Assuntos
Algoritmos , Produtos Biológicos/farmacologia , Biologia Computacional/métodos , Interface Usuário-Computador , Antibacterianos/química , Antibacterianos/farmacologia , Anticorpos/química , Anticorpos/farmacologia , Produtos Biológicos/química , Biomarcadores Farmacológicos , Biologia Computacional/instrumentação , Biologia Computacional/estatística & dados numéricos , Humanos , Lactococcus lactis/efeitos dos fármacos , Lactococcus lactis/genética , Lactococcus lactis/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/genética , Micrococcus luteus/crescimento & desenvolvimento , Peptídeos/química , Peptídeos/farmacologia , Mutação Puntual , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade
7.
J Chemother ; 25(6): 324-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24091027

RESUMO

The aim of this study was to determine the prevalence of vaginal Escherichia coli colonization and perianal carriage of Enterobacteriaceae resistant to third generation cephalosporins in pregnant women. Vaginal and perianal samples from 259 pregnant women were studied. Vaginal swabs were inoculated onto MacConkey agar plates and perianal swabs were inoculated onto CHROMagar extended-spectrum beta-lactamase (ESBL) plates. The minimal inhibitory concentration of the isolates was determined using the Epsilometer test method. The phenotypic detection of ESBLs was performed by the combined disc method using cefotaxime versus cefotaxime plus clavulanate. The prevalence of vaginal E. coli colonization during pregnancy was 14.3%. The resistance rate to ampicillin, gentamicin, and cefotaxime was 48.6, 10.8, and 0.8%, respectively. Enterobacteriaceae resistant to third generation cephalosporins were recovered in 7.3% of all perianal specimens. Among them, 5.4% of pregnant women were colonized with E. coli ESBL-producer strains. The present study revealed that colonization with Enterobacteriaceae resistant to third generation cephalosporins is significant in pregnancy. ESBL-producing E. coli were the most prevalent organisms. Screening strategies designed to monitor for ESBL-producing E. coli could be useful in endemic areas to prevent perinatal transmission and the introduction of multiresistant strains to the maternity ward.


Assuntos
Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Vagina/microbiologia , beta-Lactamases/metabolismo , beta-Lactamases/farmacologia , Antibacterianos/farmacologia , Argentina , Cefotaxima/farmacologia , Cefalosporinas/farmacologia , Ácido Clavulânico/farmacologia , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Escherichia coli/efeitos dos fármacos , Feminino , Idade Gestacional , Humanos , Exposição Materna , Testes de Sensibilidade Microbiana , Gravidez , Prevalência
8.
J Infect Dev Ctries ; 7(8): 630-4, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23949299

RESUMO

INTRODUCTION: The aim of this study was to determine the prevalence of intestinal carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Gram-negative bacilli in the community in Buenos Aires, Argentina. METHODOLOGY: Faecal samples from 164 non-hospitalized patients were cultured on CHROMagar KPC and CHROMagar ESBL plates. Isolates resistant to third-generation cephalosporins or carbapenems were selected for further study. The minimal inhibitory concentration (MIC) of the isolates was determined using the E-test method. The phenotypic detection of ESBLs and carbapenemases was performed using the double-disc synergy test. RESULTS: The rate of faecal carriage of Enterobacteriaceae resistant to third-generation cephalosporins was 26.8%. Escherichia coli represented a large majority (75%) of the isolates recovered. Thirty-three ESBL-producing isolates were detected from 31 faecal samples (18.9% of the collected specimens). Eight carbapenem-resistant Gram-negative bacilli were recovered from eight specimens (4.9%). CONCLUSIONS: This study revealed a high prevalence of faecal carriage of multidrug-resistant Gram-negative bacteria, including ESBLs, in Buenos Aires. Therefore, the use of surveillance cultures will be helpful for tracking and monitoring the spread of ESBL-producing Enterobacteriaceae within community settings.


Assuntos
Carbapenêmicos/farmacologia , Portador Sadio/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Resistência beta-Lactâmica , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Argentina/epidemiologia , Portador Sadio/epidemiologia , Cefalosporinas/farmacologia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Fezes/microbiologia , Feminino , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
9.
Rev Esp Quimioter ; 26(2): 112-5, 2013 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-23817648

RESUMO

INTRODUCTION: Streptococcus agalactiae has become recognized as a cause of serious illness in newborns, pregnant women, and adults with chronic medical conditions. Optimal antimicrobial therapy for serious infections requires the use of synergistic combinations of a cell wall-active agent, such as a penicillin, with an aminoglycoside, which results in bactericidal activity against this organism. The synergistic effect is eliminated by the acquisition of high-level resistance (HLR) to aminoglycosides. The aim of our study was to determine the prevalence of HLR to gentamicin (GEN) and streptomycin (EST).The ability to detect HLR using a standard agar screen plate and high-content discs was investigated. METHODS: This study was conducted with 141 strains of S. agalactiae isolated from vaginal and rectal swabs of pregnant women at term. Minimum inhibitory concentrations (MICs) to GEN and STR were determined by the E-test method. Disks of GEN (120 µg) and STR (300 µg) were used to detect HLR. Agar screening plates were performed with GEN 100 mg/L, GEN 500 mg/L and STR 2000 mg/L. RESULTS: The HLR to GEN and STR was detected in 13.5% and 16.3% of the isolates respectively. Among 141 strains, 7.8% were simultaneously resistant to GEN and STR. With 120-µg GEN and 300-µg STR disks, strains for which MICs were ≥ 512 mg/L and ≥ 1024 mg/L had no zones of inhibition. Isolates with inhibitory zones for GEN and STR of ≥13 mm showed a MICs ≤ 64 mg/L and ≤ 512 mg/L. All the screening plates were negative for these isolates. HLR to aminoglycosides was associated (83.9%) with resistance to erythromycin and/or clindamycin. CONCLUSIONS: This study highlights the emergence of strains with HLR to aminoglycosides. The disk-agar diffusion test performed with high-content aminoglycoside disks and screening plates can provide laboratories with a convenient and reliable method for detecting S. agalactiae isolates that are resistant to aminoglycoside-betalactam synergy.


Assuntos
Antibacterianos/farmacologia , Gentamicinas/farmacologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Estreptomicina/farmacologia , Adulto , Argentina/epidemiologia , Farmacorresistência Bacteriana , Feminino , Humanos , Testes de Sensibilidade Microbiana , Gravidez
10.
Rev. esp. quimioter ; 26(2): 112-115, jun. 2013. tab
Artigo em Espanhol | IBECS | ID: ibc-113463

RESUMO

Introducción. Streptococcus agalactiae es responsable de infecciones en neonatos, gestantes, puérperas y adultos con enfermedad de base predisponente. En infecciones con riesgo de vida se recomienda la penicilina (PEN) o ampicilina en combinación con gentamicina (GEN). La resistencia de alto nivel (RAN) a los aminoglucósidos se asocia a una pérdida del efecto sinérgico bactericida de la combinación con un betalactámico. El objetivo de nuestro trabajo fue determinar la prevalencia de RAN a GEN y estreptomicina (EST) y establecer la utilidad de los discos de alta carga y las placas de corte para su detección. Métodos. El estudio se realizó con 141 cepas únicas de S. agalactiae aisladas de muestras vaginales o rectales de embarazadas a término. Se determinó la concentración mínima inhibitoria (CMI) a GEN y EST con el método Etest y se obtuvo el halo de inhibición con discos de GEN 120 mg y EST 300 mg. Se utilizaron placas de corte con GEN 100 mg/L, GEN 500 mg/L y EST 2000 mg/L para detectar la RAN. Resultados. La prevalencia de RAN fue 13,5% a GEN, 16,3% a EST y del 7,8% en forma simultánea. Las cepas con ausencia de halos en el disco de alta carga de GEN y EST tuvieron una CMI >=512 mg/L y >=1024 mg/L. Las cepas con halos >= 13 mm a GEN y EST mostraron una CMI <=64 mg/L y <= 512 mg/L respectivamente. En estos aislamientos las placas de corte fueron negativas. La RAN a aminoglucósidos se asoció (83,9%) con resistencia a eritromicina y/o clindamicina. Conclusiones. Destacamos la emergencia de cepas con RAN a los aminoglucósidos. El empleo de discos de alta carga y placas de corte de manera similar a Enterococcus spp. es una estrategia sencilla y aplicable a S. agalactiae(AU)


Introduction. Streptococcus agalactiae has become recognized as a cause of serious illness in newborns, pregnant women, and adults with chronic medical conditions. Optimal antimicrobial therapy for serious infections requires the use of synergistic combinations of a cell wall-active agent, such as a penicillin, with an aminoglycoside, which results in bactericidal activity against this organism. The synergistic effect is eliminated by the acquisition of high-level resistance (HLR) to aminoglycosides. The aim of our study was to determine the prevalence of HLR to gentamicin (GEN) and streptomycin (EST). The ability to detect HLR using a standard agar screen plate and high-content discs was investigated. Methods. This study was conducted with 141 strains of S. agalactiae isolated from vaginal and rectal swabs of pregnant women at term. Minimum inhibitory concentrations (MICs) to GEN and STR were determined by the E-test method. Disks of GEN (120 mg) and STR (300 mg) were used to detect HLR. Agar screening plates were performed with GEN 100 mg/L, GEN 500 mg/L and STR 2000 mg/L. Results. The HLR to GEN and STR was detected in 13.5% and 16.3% of the isolates respectively. Among 141 strains, 7.8% were simultaneously resistant to GEN and STR. With 120-mg GEN and 300-mg STR disks, strains for which MICs were >=512 mg/L and >=1024 mg/L had no zones of inhibition. Isolates with inhibitory zones for GEN and STR of >=13 mm showed a MICs <=4 mg/L and <=512 mg/L. All the screening plates were negative for these isolates. HLR to aminoglycosides was associated (83.9%) with resistance to erythromycin and/ or clindamycin. Conclusions. This study highlights the emergence of strains with HLR to aminoglycosides. The disk-agar diffusion test performed with high-content aminoglycoside disks and screening plates can provide laboratories with a convenient and reliable method for detecting S. agalactiae isolates that amiare resistant to aminoglycoside-betalactam synergy(AU)


Assuntos
Streptococcus agalactiae , Streptococcus agalactiae/isolamento & purificação , Gentamicinas/uso terapêutico , Estreptomicina/uso terapêutico , Eritromicina , Clindamicina/uso terapêutico , Testes de Sensibilidade Microbiana/instrumentação , Resistência a Medicamentos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Testes de Sensibilidade Microbiana/tendências , Resistência Microbiana a Medicamentos
13.
Rev. méd. hered ; 21(4): 187-196, oct.-dic. 2010. tab
Artigo em Inglês | LILACS, LIPECS | ID: lil-589495

RESUMO

Objetivo: Comparar la calidad de vida (CDV) de los egresados de una Escuela de Medicina peruana que migraron al extranjero y de los que permanecieron en el país. Material y método: Se utilizó un cuestionario basado en una combinación de dos herramientas para medir la CDV de proveedores de salud previamente validadas, para evaluar auto-satisfacción (grupo A), las relaciones interpersonales y sociales (grupo B) y los niveles de satisfacción personal (grupo C). Es cuestionario se envió por correo electrónico a los graduados de la Universidad Peruana Cayetano Heredia. Resultados: La tasa de respuesta fue 35%. Los niveles de ingreso económico fueron significativamente menores en los médicos que permanecieron en el Perú en comparación con los que migraron. En muy pocas preguntas se encontró diferencia significativa. En el grupo A, los médicos que migraron percibieron una CDV significativamente mayor solo en la expectativa de futuro. En el grupo B, esto se alcanzó diferencias sólo en el grado de apoyo y el nivel de conflicto entre colegas , y en el grupo C, en el nivel de información recibida acerca de los resultados de su trabajo (ôfeedbackõ), el esfuerzo físico del trabajo diario (estrés físico), las oportunidades de expresar lo que se piensa y necesita, el esfuerzo del hospital para mejorar la CDV de sus trabajadores, el entrenamiento necesario para realizar el trabajo diario, y la variedad en el trabajo. Los médicos que migraron percibieron una mayor aceptación en la profesión, en la sociedad en general y dentro de la comunidad donde viven. De manera significativa más médicos que migraron no tenían intenciones de cambiar sus niveles actuales de vida. Conclusiones: La CDV percibida de los médicos estudiados fue similar en la mayoría de preguntas examinadas entre ambos grupos, a pesar de la marcada diferencia encontrada en los niveles de ingreso económico.


Objective: To compare the quality of life (QOL) of the graduated from a Peruvian medical school who migrated abroad and those who remained in the country. We also intended to address the level of integration of Peruvian international medical graduates (IMGs) into the United States (US). Material and methods: A combination of two previously validated tools designed to measure QOL of health care practitioners (HCPs) was used to create a survey, including questions that analyzed self-satisfaction (group A), interpersonal/social relationships (Group B) and professional satisfaction (Group C), which was e-mailed to graduates from a Peruvian Medical School. Results: The response rate was 35%. Income levels were significantly lower for HCPs practicing in Peru than those practicing abroad. Very few question items reached statistical significant differences between groups. In group A, IMGs who migrated perceived a significantly higher QOL only in the perception of their future. In group B, was achieved only in the peer support and the conflict level with coworkerÆs categories. In group C, only in the work feedback, job physical discomfort, expression opportunities, hospital attempts to improve the QOL of their position, necessary training for job performance and work variety categories. However, of 41/44 items showed a better (more satisfied) response from the abroad group, of which 13 achieve statistical significance (8 at the 1% level). IMGs practicing abroad perceived a high acceptance into the foreign profession, society and living community. Significantly most IMGs do not intend to change their current status. Conclusions: Very few significant differences were noted in the perceived QOL of physicians between groups, in spite of a marked income discrepancy. However, there was a clear trend for dissatisfaction in the Peru group on several important items that, without reaching statistical significance, may indicate the adverse effect of Peruvian...


Assuntos
Humanos , Masculino , Feminino , Qualidade de Vida , Educação Médica , Emigração e Imigração , Médicos
15.
World J Gastroenterol ; 15(28): 3560-4, 2009 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-19630115

RESUMO

Primary neoplasms arising in the anal canal are relatively unusual. In particular, adenomas and adenocarcinomas are distinctly rare entities in this region. We describe an infiltrating, well-differentiated adenocarcinoma arising in a villous adenoma from the distal anal canal, in an otherwise healthy patient at low risk for gastrointestinal malignancy. This is the case of an octogenarian man with a several year history of hemorrhoids and intermittent rectal bleeding, more recently complaining of continuous hematochezia. Examination revealed a blood-covered pedunculated mass with a long stalk protruding from the anus. The lesion was amputated at the bedside. Microscopic evaluation revealed an infiltrating well-differentiated adenocarcinoma, arising from a villous adenoma. This was further evaluated under anesthesia and complete excision of distal anal tissue was performed. Our report is the first describing the possible malignant degeneration of a villous adenoma in the anal canal.


Assuntos
Adenocarcinoma/patologia , Adenoma Viloso/patologia , Canal Anal/patologia , Adenocarcinoma/cirurgia , Adenoma Viloso/cirurgia , Idoso de 80 Anos ou mais , Canal Anal/cirurgia , Transformação Celular Neoplásica/patologia , Progressão da Doença , Humanos , Masculino , Resultado do Tratamento
16.
Curr Opin Drug Discov Devel ; 12(3): 367-75, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19396738

RESUMO

The shift in the drug discovery paradigm that has resulted in increased dependence on large volumes of information for decision making has created new challenges and opportunities in chemoinformatics research. The large volumes of data that are now available present an opportunity for the development of better predictive models, for the selection of more promising drug candidates, and for more comprehensive decisions to be made by researchers in chemistry and biology. The progress of this approach in drug discovery has also introduced challenges associated with the need to develop better tools to manage the large volumes of data. For chemistry-related research in particular, there is a need for more effective retrieval methods and better tools for data analysis that incorporate good interface design to facilitate the use of such systems by the non-expert scientist. This article reviews recent developments in the mining of large volumes of chemistry data, with a focus on chemoinformatics tools for small-molecule drug discovery and tools developed for analysis and in-depth mining. External sources of data, such as a variety of web services, further expand the volume of data to be analyzed during any small-molecule discovery project. The impact of the generation of large volumes of data and the related research factors is reshaping chemoinformatics work.


Assuntos
Química Farmacêutica/métodos , Bases de Dados como Assunto , Descoberta de Drogas/métodos , Armazenamento e Recuperação da Informação/métodos , Metodologias Computacionais , Apresentação de Dados , Informática , Patentes como Assunto
17.
Expert Opin Drug Discov ; 4(12): 1215-20, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23480462

RESUMO

IMPORTANCE OF THE FIELD: The ultimate goal of discovery screening is to have a fast and cost-effective strategy to meet the demands of producing high-content lead series with improved prospects for clinical success. While high-throughput screening (HTS) dominates the drug discovery landscape, other processes and technologies have emerged, including high-content screening and fragment-based design to provide alternatives that may be more suitable for certain targets. There has been a growing interest in reducing the number of compounds to be screened to prevent the escalation in the costs, time and resources associated with HTS campaigns. Library design plays a central role in these efforts. AREAS COVERED IN THIS REVIEW: This opinion provides a survey of some recent developments in the diversity based library design process, but within a historical context. In particular, the importance of chemotyping and substructure analysis and the challenges presented by novel lead discovery technologies that require the design of libraries for screening are discussed. WHAT THE READER WILL GAIN: Readers will gain an appreciation of some developments in the field of library design and the factors that are driving the development of new library design technologies; specifically, challenges presented for chemoinformatics with the novel screening technologies in diversity based screening and compound filtering. TAKE HOME MESSAGE: Chemotyping and substrutural analysis are techniques that have been underutilized in the process of library design. However, they offer a direct way to evaluate libraries and have been successfully used to develop predictive methodologies. Tools are available to this end, but the full power of the approach has not been realized yet.

20.
World J Gastroenterol ; 13(44): 5954-6, 2007 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-17990363

RESUMO

To date, antegrade intussusception involving a Roux-en-Y reconstruction has been reported only once. We report a case of acute bowel obstruction due to an intussusception involving two Roux-en-Y limbs in a 40-year-old woman with a history of chronic pancreatitis due to pancreas divisum. Four years preceding this event, the patient had undergone a Whipple procedure, and three years prior to that, a Puestow operation. The patient was successfully treated with bowel resection and a side-to-side anastomosis between the most distal aspect of the bowel and the most distal Roux-en-Y reconstruction, which preserved both Roux-en-Y reconstructions.


Assuntos
Anastomose em-Y de Roux/efeitos adversos , Intussuscepção/etiologia , Doenças do Jejuno/etiologia , Pancreatite/cirurgia , Adulto , Feminino , Humanos , Intussuscepção/diagnóstico , Doenças do Jejuno/diagnóstico , Pâncreas/anormalidades , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Tomografia Computadorizada por Raios X
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