ERK activation modulates invasiveness and Reactive Oxygen Species (ROS) production in triple negative breast cancer cell lines.

Triple negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis and still lacks a targeted therapy. In this study, we found increased ERK phosphorylation in TNBC cell lines and an important role for ERK in sustaining the migration of TNBC cells. Although ROS have been suggested to have an important role in sustaining MAPK signaling, antioxidant treatment increased ERK phosphorylation, probably suggesting increased invasive potential. Interestingly, treatment with PD0325901 (PD), a MEK inhibitor, decreased ROS levels in TNBC cells and decreased mitochondrial fragmentation in the MDAMB231 cell line. Our data supports an important role for MEK/ERK in TNBC, sustaining cellular migration, regulating mitochondrial dynamics and ROS production in this breast cancer subtype.

Reactive oxygen species: Role in carcinogenesis, cancer cell signaling and tumor progression.

Cancer is one of the major causes of death in the world and its global burden is expected to continue increasing. In several types of cancers, reactive oxygen species (ROS) have been extensively linked to carcinogenesis and cancer progression. However, studies have reported conflicting evidence regarding the role of ROS in cancer, mostly dependent on the cancer type or the step of the tumorigenic process. We review recent studies describing diverse aspects of the interplay of ROS with cancer in the different stages of cancer progression, with a special focus on their role in carcinogenesis, their importance for cancer cell signaling and their relationship to the most prevalent cancer risk factors.

OX40 agonists for cancer treatment: a patent review.

INTRODUCTION: OX40 is an immune checkpoint in cancer and its presence in cancer is a good prognosis, making it a highly relevant target for the development of new immunotherapies. AREAS COVERED: The patent literature reveals vital information on new trends in cancer therapies. The authors used the patent databases of the six major patent offices in the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Office of Intellectual Property of China and Korean Intellectual Property Office, to generate a panorama of patents related to OX40 agonists. Specific patents have been grouped into innovative patents and adoption patents. EXPERT OPINION: An increasing trend in the development of OX40 agonists in cancer, particularly in the years 2018 and 2019. United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986,178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists.

Colon carcinoma treatment using bispecific anti-GITR/CTLA-4 antibodies: a patent evaluation of WO2018091739.

Introduction: GITR is a receptor that increases the activation of T lymphocytes against tumor cells. There is a great need to discover and develop new therapies focused on activating GITR to increase the immune response in various types of cancer. The authors of WO2018091739 patent propose a method to eradicate cancer by using bispecific anti-GITR/anti-CTLA-4 antibodies.Areas covered: WO2018091739 patent describes anti-GITR/anti-CTLA-4 antibodies, pharmaceutical composition that contains it, and their application for cancer treatment, particularly colon carcinoma. Anti-GITR/anti-CTLA-4 antibodies are used at a dosage of 0.0003-3 mg antibody/kg patient weight and is suspended in an isotonic solution consisting of sodium phosphate, sucrose, NaCl, and polysorbate 80.Expert opinion: WO2018091739 only demonstrates that bispecific antibodies activate T cells, an antibody-dependent cellular cytotoxicity of CHO cells, and tumor inhibition in murine models of colon carcinoma. There are no clinical trials that show that treatment with bispecific antibodies can induce an antitumor response in cancer patients.

Cancer combinatorial immunotherapy using etigilimab and nivolumab: a patent evaluation of WO2018102536.

Introduction: TIGIT is an inhibitory receptor expressed by lymphocytes that suppresses the immune response against tumor cells. There is a great need to discover and develop new therapies focused on inhibiting the action of TIGIT and consequently improving the immune response in the various types of cancer. Authors of WO2018102536 patent propose a method to eradicate cancer utilizes anti-TIGIT antibody, etigilimab, in combination with anti-PD-1/PD-L1 antibody, nivolumab.Areas covered: WO2018102536 patent describes a method of cancer combinatorial treatment consisting of the utilization of either a pharmaceutical cocktail containing anti-TIGIT and an anti-PD-L1 antibody.Expert opinion: The results of the clinical trials only support trials regarding the tolerability of therapy with etigilimab, but does not show data related to the combined use of etigilimab and nivolumab.

Bispecific anti-OX40/CTLA-4 antibodies for advanced solid tumors: a patent evaluation of WO2018202649.

Introduction: OX40 is a potent costimulatory receptor of the immune response in various types of cancer and has been used as a target for the generation of agonists of its function. Authors of WO2018202649 patent propose a method to eradicate cancer using a bispecific antibodies against OX40/CTLA-4.Areas covered: WO2018202649 patent describes several bispecific antibodies capable of specifically binding to OX40 and CTLA-4 that target regulatory T cells in the tumor microenvironment.Expert opinion: WO2018202649 patent demonstrates that bispecific antibodies against OX40/CTLA-4 have anti-tumor activity against colon, pancreatic and bladder cancer, and that there is a synergistic action with anti-PD-1 antibodies for the treatment of colon cancer. However, there is no evidence to conclude that bispecific antibodies can be used in cancers other than colon, pancreas and bladder. Likewise, the patent only describes the application in combinatorial therapy with anti-PD-1 antibodies, without presenting data relative to the combination with other immunotherapeutic agents against other checkpoint targets.

Breast Cancer Subtypes Present a Differential Production of Reactive Oxygen Species (ROS) and Susceptibility to Antioxidant Treatment.

Due to their crucial role in cell metabolism and homeostasis, alterations in mitochondrial biology and function have been related to the progression of diverse diseases including cancer. One of the consequences associated to mitochondrial dysfunction is the production of reactive oxygen species (ROS). ROS are known to have a controversial role during cancer initiation and progression and although several studies have tried to manipulate intracellular ROS levels using antioxidants or pro-oxidation conditions, it is not yet clear how to target oxidation for cancer therapy. In this study, we found differences in mitochondrial morphology in breast cancer cells when compared to a non-tumorigenic cell line and differences in mitochondrial function among breast cancer subtypes when exploring gene-expression data from the TCGA tumor dataset. Interestingly, we found increased ROS levels in triple negative breast cancer (TNBC) cell lines and a dependency on ROS for survival since antioxidant treatment induced cell death in TNBC cells but not in an estrogen receptor positive (ER+) cell line. Moreover, we identified the mitochondria as the main source of ROS in TNBC cell lines. Our results indicate a potential use for ROS as a target for therapy in the TNBC subtype which currently has the worst prognosis among all breast cancers and remains as the only breast cancer subtype which lacks a targeted therapy.

Cancer immunotherapy using anti-TIM3/PD-1 bispecific antibody: a patent evaluation of EP3356411A1.

Introduction: TIM3 and PD-1 are checkpoint inhibitors in cancer that coordinate the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of TIM3 and PD-1 and consequently improving the immune response in the various types of cancer. The authors of patent EP3356411A1 propose several anti-TIM3/anti-PD-1 bispecific antibodies, as well as the method for producing them and their pharmacological application in the treatment of cancer. Areas covered: Patent EP3356411A1 describes a method by producing anti-TIM3/anti-PD-1 bispecific antibodies and their potential in cancer treatment. Expert opinion: Data supporting the patent demonstrate the ability by producing anti-TIM3/anti-PD-1 bispecific antibodies. Although the proposed methodology is very interesting and promising, further studies are necessary to assess the clinical applicability of the inventions on cancer.

Cancer combinatorial immunotherapy using anti-OX40 agonist and anti-PD-L1 antagonist: a patent evaluation of US2018256711A1.

Introduction: OX40 is checkpoint inhibitor in cancer that coordinates the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of OX40 and consequently improving the immune response in the various types of cancer. Authors of patent US2018256711A1 propose a method to eradicate cancer that utilizes anti-OX40 agonist antibody in combination with anti-PD-L1 antagonist antibody. Areas covered: Patent US2018256711A1 describes a method of cancer combinatorial treatment consisting of the utilization of a pharmaceutical cocktail containing anti-OX40 and an anti-PD-L1 antibody. Expert opinion: The results of the clinical trials only support trials regarding the tolerability of combinatorial therapy, even when the objectives of determining the safety and pharmacokinetics of the treatment are proposed.

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever.

BACKGROUND: Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs) that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. OBJECTIVE: To explore the association of cytokine and socs levels with disease severity in dengue patients. METHODS: Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. RESULTS: Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF) with respect to those with dengue fever (DF) (p < 0.05). Negative correlations were found between socs1 and both IL-10 and socs3 (p < 0.01). The cutoff values of socs3 (>199.8-fold), socs1 (<1.94-fold), and IL-10 (>134 pg/ml) have the highest sensitivity and specificity to discriminate between DF and DHF. CONCLUSION: Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity.

Upregulation of the Suppressors of Cytokine Signaling 1 and 3 Is Associated with Arrest of Phosphorylated-STAT1 Nuclear Importation and Reduced Innate Response in Denguevirus-Infected Macrophages.

To clarify whether the suppressors of cytokine signaling (SOCS) are associated with denguevirus (DENV) evasion of the antiviral response, we analyzed the expression kinetics of SOCS1 and SOCS3 and of the antiviral genes MxA and OAS during DENV infection of U937 macrophages that were or not treated with interferon (IFN)-α. DENV infection produced a viral titer three times higher in untreated than in IFN-α-treated cells (p < 0.001 at 72 h postinfection [p.i.]). Partial inhibition of DENV replication was associated with reduced expression of MxA and OAS antiviral genes as well as higher SOCS1 and SOCS3 expression in DENV-infected cells than in cells treated only with IFN-α. Complete loss of phosphorylated-signal transducer and activator of transcription (p-STAT)2 and reduced nuclear importation of p-STAT1 were observed in DENV-infected cells compared to IFN-α treatment that induced p-STAT1 and p-STAT2. Our data thus suggest that overexpression of SOCS1 and SOCS3 induced by DENV infection leads to impairment of antiviral response through the inhibition of STAT functionality.

Protective Efficacy in Sheep of Adenovirus-Vectored Vaccines against Bluetongue Virus Is Associated with Specific T Cell Responses.

Bluetongue virus (BTV) is an economically important Orbivirus of the Reoviridae family that causes a hemorrhagic disease in ruminants. Its control has been achieved by inactivated-vaccines that have proven to protect against homologous BTV challenge although unable to induce long-term immunity. Therefore, a more efficient control strategy needs to be developed. Recombinant adenovirus vectors are lead vaccine candidates for protection of several diseases, mainly because of their potency to induce potent T cell immunity. Here we report the induction of humoral and T-cell mediated responses able to protect animals against BTV challenge by recombinant replication-defective human adenovirus serotype 5 (Ad5) expressing either VP7, VP2 or NS3 BTV proteins. First we used the IFNAR(-/-) mouse model system to establish a proof of principle, and afterwards we assayed the protective efficacy in sheep, the natural host of BTV. Mice were completely protected against BTV challenge, developing humoral and BTV-specific CD8+- and CD4+-T cell responses by vaccination with the different rAd5. Sheep vaccinated with Ad5-BTV-VP2 and Ad5-BTV-VP7 or only with Ad5-BTV-VP7 and challenged with BTV showed mild disease symptoms and reduced viremia. This partial protection was achieved in the absence of neutralizing antibodies but strong BTV-specific CD8+ T cell responses in those sheep vaccinated with Ad5-BTV-VP7. These data indicate that rAd5 is a suitable vaccine vector to induce T cell immunity during BTV vaccination and provide new data regarding the relevance of T cell responses in protection during BTV infection.

Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV). Two recombinant replication-defective human adenoviruses serotype 5 (Ad5) expressing either the highly immunogenic fusion protein (F) or hemagglutinin protein (H) from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

Physical-Verbal Aggression and Depression in Adolescents: The Role of Cognitive Emotion Regulation Strategies / Agresión físico-verbal y depresión en adolescentes: el papel de las estrategias cognitivas de regulación emocional

The present study examined the relationships between the use of cognitive emotion regulation strategies, physical-verbal aggression and depression in a sample of 248 adolescents. Specific emotion regulation strategies such as acceptance, rumination and catastrophizing explained significant variance in depression in adolescents. With respect to physical-verbal aggression, our results showed that the use of self-blame and rumination only predicted levels of aggression in boys but not girls. Regarding gender differences, girls tend to ruminate and to report more catastrophic thoughts than boys. Our findings suggest a profile of cognitive emotion regulation strategies related to physical-verbal aggression and depressive symptoms which might be taken into account in future socio-emotional learning programs for adolescents.

El presente estudio examinó la relación entre el uso de estrategias de regulación cognitivo-emocional, la agresividad físico-verbal y la depresión en una muestra de 248 adolescentes. Ciertas estrategias de regulación como aceptación, rumiación y catastrofismo explicaron varianza significativa de los niveles de depresión. Con respecto a la agresividad físico-verbal, los resultados indicaron que el uso de la autoculpa y la rumiación solo predecía la agresividad en los jóvenes pero no en las jóvenes quienes, comparativamente, mostraron mayor tendencia a rumiar y a informar más pensamientos catastrofistas. Los hallazgos sugieren un perfil en el uso de estrategias de regulación cognitivo-emocional que se relaciona con la agresividad físico-verbal y con los síntomas depresivos, el cual podría ser tomado en cuenta en futuros programas de aprendizaje socioemocional en adolescentes.

T cell responses to bluetongue virus are directed against multiple and identical CD4+ and CD8+ T cell epitopes from the VP7 core protein in mouse and sheep.

Bluetongue virus (BTV), an economically important orbivirus of the Reoviridae family, is a non-enveloped, dsRNA virus that causes a haemorrhagic disease mainly in sheep, but little is known of the cellular immunity elicited against BTV. We observed that vaccination of interferon type I-deficient mice (IFNAR((-/-))), or inoculation of the wild type C57BL/6 strain with BTV-8, induced a strong T cell response. Therefore, we proceeded to identify some of the T cell epitopes targeted by the immune system. We selected, using H-2(b)-binding predictive algorithms, 3 major histocompatibility complex (MHC)-class II-binding peptides and 7 MHC-class I binding peptides from the BTV-8 core protein VP7, as potential T cell epitopes. Peptide binding assays confirmed that all 7 MHC-class I predicted peptides bound MHC-class I molecules. Three MHC-class I and 2 MHC-class II binding peptide consistently elicited peptide-specific IFN-γ production (as measured by ELISPOT assays) in splenocytes from C57BL/6 BTV-8-inoculated mice and IFNAR((-/-))-vaccinated mice. The functionality of these T cells was confirmed by proliferation and cytotoxicity assays. Flow cytometry analysis demonstrated that CD8(+) T cells responded to MHC-class I binding peptides and CD4(+) T cells to MHC-class II binding peptides. Importantly, these 5 epitopes were also able to induced IFN-γ production in sheep inoculated with BTV-8. Taken together, these data demonstrate the activation of BTV-specific T cells during infection and vaccination. The characterisation of these novel T cell epitopes may also provide an opportunity to develop DIVA-compliant vaccination approach to BTV encompassing a broad-spectrum of serotypes.

Radioterapia de intensidad modulada en el tratamiento de tumores en pediatría, primeros casos en Cuba / Intensity Modulated Radiotherapy in treatment of tumors in children: first cases in Cuba

INTRODUCCIÓN. La radioterapia de intensidad modulada (IMRT) constituye una técnica de alta precisión basada en la definición volumétrica tridimensional de la anatomía del tumor y de los órganos críticos o en riesgo. Con el objetivo de asegurar la posibilidad de aplicar la IMRT en Cuba, en casos seleccionados de tumores en niños y adolescentes, se instrumentó un proyecto de investigación cuyos resultados se documentan en este informe. MÉTODOS. Se realizaron las primeras irradiaciones con IMRT en niños y adolescentes cubanos, con edades entre 6 y 18 años. La técnica empleada es la basada en aperturas geométricas y optimización inversa. Las irradiaciones fueron realizadas con un acelerador lineal con fotones de 6 MV, con colimador multiláminas. Las dosis de radiaciones administradas variaron según el tipo de tumor, y de acuerdo con las normas de radioterapia y la presencia de órganos críticos. Todos los pacientes fueron evaluados semanalmente, con controles radiológicos mediante placas portales electrónicas. RESULTADOS. Los pacientes irradiados (5) tenían los tumores siguientes: linfoma no-Hodgking del seno maxilar (1), glioma del tallo cerebral (1), linfoma no-Hodgking abdominal (1), condrosarcoma mesenquimatoso parameníngeo (1) y hemangiopericitoma parameníngeo (1). Las dosis de irradiación recibidas variaron entre 24 y 62 Gy. Fueron empleados entre 5 y 8 campos, con variaciones entre 10 y 20 segmentos. CONCLUSIONES. Se realizaron en Cuba las primeras irradiaciones con IMRT en niños y adolescentes, y se debe continuar extendiendo su empleo en aquellos casos donde su utilidad sea mayor

INTRODUCTION. The intensity modulated radiotherapy (IMRT) is a high performance technique based on the three-dimensional volumetric definition of tumor anatomy and of critical organs or at risk. To assure the possibility to apply the IMRT in Cuba in selected cases of tumors in children and adolescents, authors designed a research project whose results are documented in present report. METHODS. The first irradiations with IMRT in Cuban children and adolescents aged between 6 -18 were carried out. The technique used is that based on the geometric openings and inverse optimization. Irradiations were applied using a linear accelerator with 6 MV photons, with multileaf collimator. Doses administered varied according to the type of tumor, the radiotherapy standards and the presence of critical organs. All patients were assessed weekly with radiologic controls using electronic portal plates. RESULTS. Irradiated patients (5) had the following tumors: non-Hodgkin lymphoma of maxillary sinus (1), brain stem glioma (1), non-Hodgkin abdominal lymphoma (1), parameningeal mesenchymatous chondrosarcoma (1) and parameningeal hemangiopericytoma (1). Doses of radiation applied varied between 24 and 62 Gy. Between 5 and 8 fields were used with variations among 10 and 20 segments. CONCLUSIONS. In Cuba the first irradiations with IMRT in children and adolescents and its use must to be spreading to those cases where its usefulness is greater

Factores de riesgo cardiovascular en escolares entre 7 y 14 años en Cartagena, Colombia, 2009 / Cardiovascular risk factors among 7-and 14-year old schoolchildren in Cartagena, Colombia, 2009

Objetivo Identificar antecedentes familiares, dislipidemias, hiperglucemia, escasa actividad física y sobrepeso u obesidad como factores de riesgo cardiovascular en niños entre 7 y 14 años de Cartagena, 2009. Materiales y Métodos Se realizó un estudio descriptivo en 173 niños de Cartagena, Colombia. Se determinaron los parámetros bioquímicos en suero mediante técnicas espectrofotométricas. Los hábitos fueron indagados mediante entrevista y las alteraciones de peso fueron establecidas utilizando el índice de masa corporal. Resultados La muestra quedó conformada por 87 niñas y 86 niños con edad promedio de 9,9 años (IC95 por ciento 9,6-10,3). El 75,1 por ciento (IC95 por ciento 68,7-81.5) presentaron antecedentes familiares; 2,3 por ciento (IC95 por ciento 0,1-4,5) tuvieron sobrepeso y 1,7 por ciento (IC95 por ciento 0,0-3,6) obesidad. Más de la mitad de los niños presentaron niveles elevados de colesterol total (53,2 por ciento; IC95 por ciento 45,8-60,6) y LDL (57,2 por ciento; IC95 por ciento 49,8-64,6). El colesterol no HDL se halló incrementado en el 46,8 por ciento (IC95 por ciento 39,4-54,2). Las niñas presentaron mayor concentración de triglicéridos (94,1 mg/dL; IC95 por ciento 93,0-95,2 mg/dL) que los niños (81,7 mg/dL; IC95 por ciento 80,6-82,8 mg/dL) con diferencia significativa (p=0,005) y también presentaron con mayor frecuencia baja actividad física (niñas: 83,8 por ciento; IC95 por ciento 73,5-94,5 por ciento; varones: 44,2 por ciento; IC95 por ciento 45,4-66,6; p=0,0001). Conclusión Los factores de riesgo cardiovascular presentes en esta población, inclusive en ausencia de obesidad, muestran la necesidad de implementar programas que los identifiquen e intervengan de manera oportuna para disminuir su impacto en la calidad de vida futura.

Objective Identifying family history, dyslipidaemia, hyperglycaemia, low physical activity and being overweight or suffering from obesity as cardiovascular risk factors in children aged 7 to 14 years in Cartagena, 2009. Materials and Methods A descriptive study of 173 children from Cartagena, Colombia, was designed. Biochemical serum parameters were determined by spectrophotometric methods. Habits were investigated through interviews and altered body weight was established using the body mass index (BMI). Results The sample consisted of 87 girls and 86 boys, and mean age was 9.9 years (9.6-10.3, 95 percent CI). 75.1 percent (68.7-81.5, 95 percent CI) had a family history of being overweight; 2.3 percent (0.1-4.5, 95 percent CI) were overweight and 1.7 percent (0.0-3.6 95 percentCI) were obese. More than half of the children had hightotal cholesterol levels (53.2 percent; 45.8-60.695 percentCI) and LDL (57.2 percent; 49.8-64.6 95 percent CI). Non-HDL cholesterol was found to be increased by 46.8 percent (39.4-54.2 95 percent CI). There was a significant difference between genders for triglyceridemia (females: 94.1 mg/dL; 87.0-101.2 mg/dL 95 percent CI; males: 81.7 mg/dL; 75.0-88.5 mg/dL 95 percent CI; p=0.005) and low physical activity (females: 83.8 percent; 73.5-94.5 percent 95 percent CI; males: 44.2 percent; 45.4-66.6 percent 95 percent CI; p=0,0001). Conclusions Cardiovascular risk factors in these schoolchildren, even in those who were not obese, justify the need for the early detection of these factors as well as their strict controlto reduce their impact on people's future quality of life.

Patrones de resistencia antimicrobiana en uropatógenos gramnegativos aislados de pacientes ambulatorios y hospitalizados Cartagena, 2005-2008 / Antimicrobial resistance pattern for gram-negative uropathogens isolated from hospitalised patients and outpatients in Cartagena, 2005-2008

Objetivo Determinar el patrón de resistencia antimicrobiana de bacterias patógenas asociadas a infecciones urinarias en pacientes ambulatorios y hospitalizados. Métodos Se realizó un estudio descriptivo entre febrero de 2005 y noviembre de 2008 en el Laboratorio Clínico de la Universidad de San Buenaventura, Cartagena. La susceptibilidad antimicrobiana fue evaluada con el método de difusión en agar empleado la técnica de Kirby Bauer aplicando procedimientos normalizados. Resultados Del total de muestras de orina analizadas (1 384) durante el período de estudio, 32,9 por ciento (455) fueron urocultivos positivos, la mayoría de éstos (81,4 por ciento) provenían de mujeres. Los agentes bacterianos más frecuentes fueron Escherichia. coli (60,1 por ciento), Klebsiella pneumoniae (6,9 por ciento), Pseudomonas aeruginosa (6,6 por ciento), Proteus mirabilis (5,4 por ciento) y Acinetobacter baumannii (1,4 por ciento). Los aislamientos gramnegativos mostraron una alta resistencia a la ampicilina (84,3100 por ciento), amoxacilina/ácido clavulánico (66,5 80,0 por ciento) y ciprofloxacina (40,057,9 por ciento). Conclusión Las bacterias gramnegativas fueron los principales agentes asociados a infecciones urinarias en esta población siendo E. coli el aislamiento más frecuente. La interpretación de los perfiles de susceptibilidad encontrados permite considerar como prudente la administración empírica de cefalosporinas de tercera generación como tratamiento inicial de las infecciones urinarias en esta población.

Objective Determining the microbial aetiology spectrum and antibiotic resistance pattern of uropathogens causing urinary tract infections in hospitalised patients and outpatients. Methods A descriptive study was carried out between February 2005 and November 2008 at the San Buenaventura University's Clinical Laboratory in Cartagena. Antibiotic sensitivity was determined by the Kirby Bauer method. Results Out of the total specimens (1,384) analysed over the four-year study period, 455 of the urine samples (32.9 percent) were culture positive, most (81.4 percent) having come from females. The bacterium isolated most frequently was Escherichia coli (60.1 percent) followed by Klebsiella pneumoniae (6.9 percent), Pseudomonas aeruginosa (6.6 percent), Proteus mirabilis (5.4 percent) and Acinetobacter baumannii (1.4 percent). The Gram-negative isolates displayed a high level of resistance to ampicillin (range 84.3100 percent), amoxicillin/clavulanic acid (range 66.580 percent) and ciprofloxacin (range 4057.9 percent). Conclusion Gram-negative bacteria were responsible for urinary tract infections in the patients involved in this study. The most commonly isolated bacteria were E. coli. Empirical administration of a third-generation cephalosporin for initial treatment of urinary tract infections in this population appears prudent from the perspective of antimicrobial susceptibility.

Angiofibroma juvenil de nasofaringe:: actualización de los resultados de la radioterapia / Nasopharyngeal juvenile angiofribroma:: updating of radiotherapy results

INTRODUCCIÓN. El angiofibroma juvenil de nasofaringe es un tumor benigno infrecuente, compuesto de tejido conectivo fibroso y abundancia de espacios vasculares revestidos de endotelio. Es casi exclusivo del sexo masculino y de la adolescencia. El tratamiento de elección es la exéresis, sin descartar otras posibilidades como la radioterapia. El objetivo del presente estudio fue presentar los resultados de esta última como opción terapéutica. MÉTODOS. Se estudió una serie de 11 pacientes, todos del sexo masculino, con edades entre 9 y 16 años, que fueron tratados en el Instituto Nacional de Oncología y Radiobiología de La Habana entre 1990 y 2005. Los pacientes fueron seguidos entre 48 y 306 meses. La radioterapia aplicada consistió en la irradiación de todo el volumen tumoral, con un margen de seguridad, en dosis de 40 a 60 Gy, con 1,8 Gy por sesión. Asociado a la radioterapia se utilizó interferón, durante y después de la irradiación, y poliquimioterapia en 1 paciente. RESULTADOS. Se obtuvo la remisión completa mantenida, sin recidivas, en 10 pacientes. No hubo pacientes con un segundo tumor. Presentaron complicaciones tempranas todos los pacientes, y tardías, solo algunos. Entre las complicaciones tempranas se halló radiomucositis y conjuntivis radiógena, y las más graves de las tardías fueron la pérdida permanente de las pestañas del párpado inferior en un caso y cataratas radiógenas en 4 pacientes. CONCLUSIONES. La radioterapia es un tratamiento que conserva su utilidad e indicaciones específicas.

INTRODUCTION: The nasopharyngeal juvenile angiofribroma is a uncommon benign tumor composed of fibrous connective tissue and many vascular spaces covered by endothelium. It is almost exclusive of male sex and of adolescents. Choice treatment is the exeresis without obviate other possibilities as the radiotherapy. The aim of present study was to show the results of this latter as therapeutical option. METHODS: Authors studied a series of 11 male patients, aged between 9 and 16, seen in National Institute of Oncology and Radiobiology of La Habana between1990 and 2005. Patients were followed during 48 and 306 months. Radiotherapy applied was the irradiation of all the tumor volume with a accuracy margin in dose of 40 and 60 Gy, with 1,8 Gy by session. Together with radiotherapy we used Interferon, during and after irradiation and polychemotherapy in one patient. RESULTS: There was a maintained complete remission without relapses in 10 patients. There weren't patients with a second tumor. All patients had early complications and late in some of them. Among the early complications we found radiomucositis and radiogenic conjunctivitis and the more severe of the late complications were the permanent loss of eyelash of lower eyelid in a case and radiogenic cataract in 4 patients. CONCLUSIONS: Radiotherapy is a treatment maintaining its usefulness and specific indications.

Resección mesorrectal total y anastomosis coloanal con reservorio colónico en J para el tratamiento de los cánceres de recto medio y bajo / Total mesorectum resection and coloanal anastomosis with J colonic reservoir for treatment of medium and low rectum cancer

INTRODUCCIÓN. La proctosigmoidectomía con resección mesorrectal total, reservorio en J y anastomosis coloanal es útil en los pacientes con cánceres de recto medio y bajo, para evitar la colostomía terminal definitiva. El objetivo de este trabajo fue analizar la factibilidad de dicha técnica quirúrgica, el tratamiento integral multidisciplinario y los resultados obtenidos. MÉTODOS. Se estudiaron 15 pacientes que padecían adenocarcinomas de recto medio y bajo, tratados entre enero de 1996 y diciembre de 2002 en el servicio de Cirugía Esplácnica del Instituto Nacional de Oncología y Radiobiología de La Habana. El tratamiento consistió en una combinación de radioterapia más quimioterapia concurrentes neoadyuvantes, seguidas de cirugía y quimioterapia adyuvante. RESULTADOS. La edad promedio de los pacientes fue de 56 años. El adenocarcinoma fue el tipo histológico diagnosticado en todos los pacientes. La estadificación de los tumores fue la siguiente: T1 y T2, 4 pacientes (27 por ciento, respectivamente); T3, 7 pacientes (46 por ciento). Cuatro pacientes (20 por ciento) se complicaron como consecuencia del tratamiento radiante y 5 (33,3 por ciento), a causa del tratamiento quirúrgico. La mortalidad quirúrgica fue de 1 paciente (6,6 por ciento) y 11 pacientes (73,3 por ciento) sobrevivieron más de 5 años. Ningún paciente presentó recidiva tumoral pélvica ni de la anastomosis coloanal. Se logró buena continencia esfinteriana. CONCLUSIONES. La resección mesorrectal total y anastomosis coloanal con reservorio colónico en J evita la colostomía terminal definitiva, cura a un alto porcentaje de pacientes con cánceres de recto medio y bajo, no transgrede los principios de la cirugía oncológica, es bien aceptada por los pacientes y es factible en nuestro medio(AU)

INTRODUCTION: Proctosigmoidectomy with total mesorectum resection, reservoir in J and colorectal is useful in patients with low and middle rectum cancer, to avoid the definite terminal colostomy. The aim of present paper was to analyze the feasibility of such surgical technique, the multidisciplinary integral treatment and the results obtained. METHODS: Fifteen patients were studied suffering of low and middle adenocarcinoma treated between January, 1996 and December, 2002 in Splanchnic Surgery Service of National Institute of Oncology and Radiobiology of La Habana City. Treatment included a combination of radiotherapy plus neocoadjuvant concurrent chemotherapy, followed by adjuvant chemotherapy and surgery. RESULTS: Mean age of patients was of 56 years. The adenocarcinoma was the histological type diagnosed in all patients. Tumor staging the following: T1 and T2, in four patients (27 percent, respectively); T3 in seven patients (46 percent). Four patients (20 percent) had complications due to radiation treatment and five (33,3 percent), by surgical treatment. Surgical mortality occurred in one patient (6,6 percent) and eleven patients (73,3 percent) survived over 5 years. Neither patient had pelvic tumor relapse or by colorectal anastomosis. There was good sphincter continence. CONCLUSIONS: Total mesorectum resection and colorectal anastomosis with a colonic reservoir in J prevent the definite terminal colostomy, to cure a high percentage of patients with low and middle rectum cancer without respecting the oncology surgery principles, is well accepted by patients and it is feasible in our practice(AU)