Calidad de las prescripciones de medicamentos opioides posterior a una intervención educativa en médicos residentes / [Quality of opioid medication prescriptions after an educational intervention in resident doctors]

Objetivo: Evaluar el impacto de una intervención educativa en la calidad de las prescripciones de medicamentos opioides. Métodos: Se aplicó el instrumento IAM (Índice de Adecuación de la Medicación) a 10 médicos residentes de la subespecialidad de medicina paliativa y del dolor para determinar la calidad de las prescripciones de analgésicos opioides, antes y después de haber realizado una intervención educativa (IE) en farmacoterapia racional. Resultados: Se analizaron un total de 181 prescripciones, 55 antes y 126 después de la IE. Se mejoraron las puntuaciones del nivel de acuerdo en todos los ítems del perfil descriptivo de los médicos participantes. La calidad de la prescripción aumentó del 14,5% al 73%, mejorando en todas las áreas, excepto la duplicidad de tratamientos. Conclusiones: La IE mejoró la calidad de las prescripciones y el perfil prescriptivo de los médicos participantes. El instrumento IAM es útil para determinar la calidad de las prescripciones de opioides. (AU)

Objective: To assess the impact of an educational intervention on the quality of opioid drug prescriptions. Methods: The MAI (Medication Adequacy Index) instrument was applied to 10 resident physicians of the Palliative and Pain Medicine Subspeciality to determine the quality of opioid analgesic prescriptions before and after an educational intervention (EI) in rational pharmacotherapy. Results: A total of 181 prescriptions were analyzed, 55 before and 126 after the EI. The level of agreement scores improved for all items of the physicians’ descriptive profile. Prescription quality increased from 14.5% to 73%, improving in all areas except for duplicity of treatment. Conclusions: The EI improved the quality of the prescriptions and the physicians’ prescribing profile. The MAI instrument is useful to determine the quality of opioid prescriptions. (AU)

Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies.

BACKGROUND: Chronic psoriasis may require medication adjustments over time. OBJECTIVES: To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation. METHODS: Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28-52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week-28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200). RESULTS: Among T100/T100 and T200/T200 week-28 partial responders, the proportion of patients who achieved as-observed PASI 75 responses increased over time. Among T100/T200 week-28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week-28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week-28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated. CONCLUSIONS: Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double-blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long-term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability.

Efficacy of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials at weeks 12 and 28.

BACKGROUND: Efficacy of tildrakizumab for plaque psoriasis was demonstrated in randomized, placebo-controlled trials. OBJECTIVE: To consolidate tildrakizumab efficacy results by pooling data. METHODS: Data (N = 2081) from tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups in three trials were pooled. RESULTS: Proportions of Psoriasis Area and Severity Index (PASI) 75 responders at week 12 were better with tildrakizumab 100 mg (62.3%) and tildrakizumab 200 mg (64.8%) vs. placebo (5.6%; P < 0.0001) and for PASI 90, PASI 100 and Physician's Global Assessment (PGA) 'clear' or 'minimal' vs. placebo (P < 0.0001). Responses increased from weeks 12 to 28. Week 12 PASI and PGA responses to tildrakizumab vs. placebo were numerically greater in patients with lower vs. higher bodyweight and were better with tildrakizumab 200 mg than tildrakizumab 100 mg for patients with higher bodyweight. Week 12 PASI 75 responses vs. placebo with tildrakizumab 100 mg were similar between patients with (55.0%) or without (56.7%) prior biologics. PASI 90, PASI 100 and PGA responses were generally higher in patients without prior biologics. Week 8 PASI 50 response predicted PASI 90 response. CONCLUSION: Pooled data confirmed the efficacy of tildrakizumab for moderate-to-severe plaque psoriasis.

Safety of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials.

BACKGROUND: Short-term interleukin-23p19 inhibition by tildrakizumab improves plaque psoriasis and appears to be well tolerated. OBJECTIVES: Safety and tolerability were assessed for up to 64 weeks of tildrakizumab therapy using pooled data from three randomized controlled trials for moderate-to-severe psoriasis. METHODS: Data pools for the placebo-controlled (up to 16 weeks) and full trial periods (up to 64 weeks) were analysed (n = 2081). RESULTS: In the placebo-controlled period, frequencies of treatment-emergent adverse events (TEAEs; range 47·9-54·0%), serious TEAEs (range 1·4-2·3%), discontinuations due to AEs (range 0·6-1·9%), major adverse cardiovascular events (MACEs; range 0·0-0·1%) and severe infections (range 0·0-0·3%) were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept. In the full trial period, exposure-adjusted rates (patients per 100 patient-years) for TEAEs, serious TEAEs and discontinuations due to AEs with tildrakizumab 100 mg and 200 mg were lower than or comparable with the placebo rates, and lower than with etanercept. Exposure-adjusted rates of MACEs (range 0·0-0·5) and severe infections (range 0·9-2·0) were comparable among groups. No TEAEs of inflammatory bowel disease or suicide were reported. Candida skin infections were infrequent at frequencies of 0·1%, 0·3%, 0·0% and 0·0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively, in the placebo-controlled period, and exposure-adjusted rates of 0·2, 0·7, 0·0 and 0·0, respectively, in the full trial period. Oral candidiasis was also infrequent. CONCLUSIONS: Up to 64 weeks of tildrakizumab was well tolerated, with low rates of serious TEAEs, discontinuations due to AEs, and AEs of clinical interest.

Micosis fungoide. Experiencia en un hospital pediátrico / Mycosis Fungoides: Experience in a Pediatric Hospital

La micosis fungoide (MF) es el linfoma cutáneo primario de células T más frecuente. Su aparición en la infancia es excepcional. Objetivos: Describir las características epidemiológicas, clínicas, histopatológicas e inmunofenotípicas de los pacientes con MF. Describir los tratamientos utilizados y la evolución. Material y método: Se incluyeron todos los pacientes admitidos en el Hospital de Pediatría Dr. J. P. Garrahan (Argentina) en el período comprendido entre agosto de 1988 y julio de 2014 con diagnóstico clínico e histopatológico de MF. Resultados: Se diagnosticaron 14 pacientes con MF. La distribución por sexo fue M/F: 1:1,33. La edad media al diagnóstico fue de 11,23 años (rango: 8 a 15 años). El tiempo promedio de evolución hasta el momento del diagnóstico fue de 3 años y 6 meses (rango: 4 meses a 7 años). Todos los pacientes presentaron la forma clínica hipopigmentada y en el 42% se asoció la forma clásica. El 50% (n = 7) exhibió un inmunofenotipo CD8 positivo de forma exclusiva. El 78% presentó estadio IB. La fototerapia fue el tratamiento de elección. Cuatro pacientes tuvieron por lo menos una recaída y 3 demostraron progresión de su enfermedad a nivel cutáneo. La evolución fue favorable en todos los casos. Conclusiones: La MF es una entidad infrecuente en la infancia, siendo la forma hipopigmentada la más frecuente. Su diagnóstico es tardío debido a la similitud con otras enfermedades hipopigmentadas frecuentes en la niñez. A pesar de tener un buen pronóstico, presenta alta tasa de recidivas y requiere un seguimiento a largo plazo (AU)

Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is unusual in children. Objectives: We aimed to describe the epidemiologic, clinical, histopathologic, and immunophenotypic characteristics of MF as well as treatments and course of disease in a pediatric case series. Material and method: Data for all patients admitted to our pediatric hospital (Hospital Dr. J. P. Garrahan) in Argentina with a clinical and histopathologic diagnosis of MF between August 1988 and July 2014 were included. Results: A total of 14 patients were diagnosed with MF. The ratio of boys to girls was 1:1.33. The mean age at diagnosis was 11.23 years (range, 8-15 years). The mean time between onset and diagnosis was 3.5 years (range, 4 months-7 years). All patients had hypopigmented MF and 42% also presented the features of classic MF. Seven (50%) had the CD8+ immunophenotype exclusively. Seventy-eight percent were in stage IB at presentation. Phototherapy was the treatment of choice. Four patients relapsed at least once and skin lesions progressed in 3 patients. All patients improved. Conclusions: MF is unusual in children. The hypopigmented form is the most common. Diagnosis is delayed because the condition is similar to other hypopigmented diseases seen more often in childhood. Although prognosis is good, the rate of recurrence is high, so long-term follow-up is necessary (AU)

Mycosis Fungoides: Experience in a Pediatric Hospital. / Micosis fungoide. Experiencia en un hospital pediátrico.

Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is unusual in children. OBJECTIVES: We aimed to describe the epidemiologic, clinical, histopathologic, and immunophenotypic characteristics of MF as well as treatments and course of disease in a pediatric case series. MATERIAL AND METHOD: Data for all patients admitted to our pediatric hospital (Hospital Dr. J. P. Garrahan) in Argentina with a clinical and histopathologic diagnosis of MF between August 1988 and July 2014 were included. RESULTS: A total of 14 patients were diagnosed with MF. The ratio of boys to girls was 1:1.33. The mean age at diagnosis was 11.23 years (range, 8-15 years). The mean time between onset and diagnosis was 3.5 years (range, 4 months-7 years). All patients had hypopigmented MF and 42% also presented the features of classic MF. Seven (50%) had the CD8+ immunophenotype exclusively. Seventy-eight percent were in stage IB at presentation. Phototherapy was the treatment of choice. Four patients relapsed at least once and skin lesions progressed in 3 patients. All patients improved. CONCLUSIONS: MF is unusual in children. The hypopigmented form is the most common. Diagnosis is delayed because the condition is similar to other hypopigmented diseases seen more often in childhood. Although prognosis is good, the rate of recurrence is high, so long-term follow-up is necessary.

Gastric mucosa injury quantification in an ischemia - Reperfusion experimental model.

Gastric ischemia - reperfusion (I/R) injury is an important clinical problem, which is developed in more than 80% of critically ill patients. I/R is caused by interruption of blood supply to an organ or tissue followed by blood reflow into the exposed area, leading to multiple organ failure and death. Gastric reactance has been proposed to measure tissue injury caused by ischemia. The present study evaluates a new method to quantify gastric tissue damage due to I/R, and assess its relation to gastric reactance changes. Twenty Wistar rats were randomly assigned to 4 groups: control, ischemia, I/R 30 min, I/R 1 h. Local gastric ischemia was induced by clamping the celiac artery for 30 min and reperfusion was done for 30-60 min. In all groups, gastric impedance was measured, and then gastric mucosa samples were taken for light microscopy. There were statistical significant differences (p <;0.05) among the groups with respect to the index of gastric injury proposed, which was greater in I/R 1 h group. Also, impedance parameters increased in I/R groups with respect to control, and ischemia groups. The proposed index of gastric injury allowed gastric mucosa damage quantification, and it was related with gastric impedance increase, which is an objective method to evaluate tissue injury.

Influenza A H1N1 durante y post-pandemia 2009-2010 en el sistema de salud de un hospita de Lima / Influenza A H1N1 during and post-pandemic of 2009-2010 in the health's system of a hospital of Lima

Objetivo: Identificar el número de casos incidentes de Influenza A H1N1 durante y post Pandemia 2009-2010. El Estudio: Estudio observacional, descriptivo y transversal. Realizado en el Hospital Nacional Hipólito Unanue (HNHU). Se incluyeron a 809 pacientes sospechosos de Influenza A H1N1atendidos en el Hospital durante el 2009 (Mayo a Diciembre) y el 2010 (Enero a Setiembre). Hallazgos: 85 fueron hospitalizados y 11 fallecieron en el 2009. En el 2010 se notificó 89 casos sospechosos, y 7 dieron positivos. La tasa de Letalidad fue 0,21 por 100 casos y el grupo etáreo más frecuente los mayores de 60 años (15,7%).

Characterization of micellar systems produced by new amphiphilic conjugates of poly(ethylene glycol).

This study proposes polymeric micelles produced using new amphiphilic conjugates between amino- or carboxy-mPEG2000 and three different α-lipoamino acids (PEG-LAA). The characterization of these colloidal systems showed CMC values, in the order of 10(-5 )M, that are interesting in the view of an in vivo administration. The PEG-LAA micelles also showed a good stability at 37 °C and upon dilution in aqueous media. Using a colored probe as a model lipophilic compound, the loading efficiency and in vitro release profile were also outlined.

Expression levels of seven candidate genes in human peripheral blood mononuclear cells and their association with preeclampsia.

OBJECTIVE: To evaluate the peripheral blood mononuclear cell (PBMC) expression levels of hemeoxygenase 1 (HMOX-1), superoxide dismutase 1 (SOD-1), vascular endothelial growth factor A (VEGF-A), transforming growth factor beta 1 (TGF-ß1), interleukin (IL)-6, IL-15 and AdipoQ genes to study their association with preeclampsia (PE). METHODS: A total of 177 pregnant women were recruited: 108 cases and 69 controls. Quantification of gene expression was measured by quantitative real-time polymerase chain reaction (PCR) using TaqMan probes. RESULTS: Underexpression of VEGF-A and TGF-ß1 was a constant in most of the cases (80.91% and 76.36%, respectively) and their expression was associated with onset and/or severity of disease (p values < 0.05). IL-6, IL-15 and AdipoQ, showed low or no expression in PBMC samples evaluated. CONCLUSION: PBMC underexpression of VEGF-A and TGF-ß1 is a hallmark of PE in the study population.

Rasgos de trastornos conducta-alimentarios y consumo de sustancias psicoactivas en estudiantes de medicina humana / 113/5000 Traits of eating-eating disorders and consumption of psychoactive substances in human medicine students

Objetivo: Identificar la incidencia de rasgos de trastornos de conducta alimentaria y de consumo de sustancias psicoactivas en estudiantes de Medicina Humana de una Universidad Privada de Lima; 2012. Materiales y Métodos: Estudio de tipo observacional, descriptivo y transversal; de nivel descriptivo y de diseño epidemiológico. La población de estudio fueron estudiantes de primero a quinto ciclo de Medicina Humana de una Universidad Privada de Lima; de la cual se extrajo de manera Probabilística-Aleatoria Simple una muestra de 109 estudiantes. La técnica fue encuesta y se analizaron los datos mediante los programas Microsoft Excel 2010 y SPSS 19. Resultados: De los 109 (100%) estudiantes de Medicina Humana, los rasgos de trastornos de conducta alimentaria que obtuvieron una mayor frecuencia fueron de Conciencia Interoceptiva y de Inefectividad y Baja Autoestima, ambos con 53 (48,6%) estudiantes de Medicina Humana. Así mismo las sustancias psicoactivas más consumidas fueron en primer lugar el alcohol con 90 (82,5%) estudiantes, seguido por el tabaco con 26 (23,9%) de los mismos. Conclusiones: Se identificó que en los estudiantes de Medicina Humana del presente estudio, la incidencia para rasgos de trastornos de conducta alimentaria fue de 48,6% y para el consumo de sustancias psicoactivas fue de 82,5%.(AU)

Positive association between vascular endothelial growth factor (VEGF) -2578 C/A variant and prostate cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) gene is an important angiogenesis regulator related to cancer development and progression. We evaluated the association between -2578 C/A (rs699947) VEGF polymorphism and PCa in Mexican subjects, to contribute to knowledge of VEGF role in genetic epidemiology of prostate cancer (PCa). OBJECTIVE: The aim of this study was to evaluate the association between -2578 C/A VEGF variant and PCa in Mexican population. METHODS: A total of 249 men (77 PCa cases and 172 controls) from the Northwestern region of Mexico were screened for the -2578 C/A VEGF variant. The polymorphism was determined by polymerase chain reaction-based restriction analysis. RESULTS: Genotype frequencies for C/C, C/A, and A/A, were 0.48, 0.49, 0.03 for cases and 0.41, 0.45, 0.14 for controls respectively. Genotype A/A of -2578 VEGF variant reduces the risk of PCa in an 84% among studied population (Odds Ratio 0.16; 95% CI: 0.04-0.71, P=0.007). C/C carriers showed an increased PCa risk of 6.1 times among the study population. CONCLUSIONS: Inheritance of -2578 A/A genotype of VEGF gene may modify PCa susceptibility risk in Mexican population.

Grado de instrucción de embarazadas adolescentes / Educational status of pregnant teenagers

Objetivo: Identificar el grado de instrucción de las embarazadas adolescentes del Instituto Nacional Materno Perinatal (INMP) de Lima; 2012. Materiales y Métodos: Estudio observacional, descriptivo, transversal. La población de estudio estuvo conformada por las embarazadas adolescentes del INMP; extrayéndose una muestra de 90 embarazadas adolescentes. La técnica fue de documentación y se analizaron los datos cuantitativamente usando los programas Microsoft Excel 2010 y SPSS 19. Resultados: De las 90 embarazadas adolescentes, el 45,20% tiene una Secundaria Incompleta. El 69,54% se encontraba entre los 17 y 19 años. El 66,10% eran convivientes y el 37.78% provino del cono Este de Lima. Conclusión: Se identificó que el 53,8% de las embarazadas adolescentes, tienen un nivel educativo bajo y el 44% de las embarazadas adolescentes restantes se encuentran entre los grados de instrucción "Secundaria Completa", "Superior" y "Técnico".(AU)

Objetive: To identify educational status of pregnant teenagers from National Maternal Perinatal Institute of Lima; 2012.Materials and Methods: It is observational, descriptive, and transversal. The population were the pregnant teenagers of the INMP; extracting a sample of 90 pregnant teenagers. The technique was documentation and the data was analyzed using the programs Microsoft Excel 2010 and SPSS 19. Results: From 90 pregnant teenagers, the 45.20% have an Incomplete Secondary. The 69.54% was found between the ages of 17 and 19 years old. The 66.10% have the status of connivance and the 37.78% came from the East of Lima. Conclusion: We identify that the 53.8% of the pregnant teenagers from the total, have a low educational level. At this way, the 44% of the rest were found between the educational status "Complete Secondary", "Higher Education" and "Technical Studies".(AU)

Successful Outpatient Treatment of Full-thickness, Necrotic, Lower- extremity Ulcers Caused by Traumatic Hematomas in Anticoagulated Patients.

UNLABELLED: Outpatient wound care centers are encountering patients with more complex wounds and an increased incidence of concomi- tant complicating comorbidities. As the population ages, patients with chronic wounds are presenting with multiple active disease processes that cause initiation of the wounds, impede wound healing, and pre- clude safely proceeding with surgical procedures, under anesthesia, to treat those wounds. METHODS: Four warfarin-anticoagulated patients presented with large, full-thickness, necrotic, lower extremity wounds induced by hematomas from blunt trauma. Two of the wounds under- went scalpel debridement under local anesthesia while continuing anticoagulation. Following brief initial wound care with normal saline wet-to-moist dressing changes, continuous negative pressure therapy at 125 mmHg was initiated and continued for all wounds until the ex- pansive tissue defects were decreased for 23.8 ± 3.2 days. All wounds were treated with application of a living bilayered skin substitute (LSS) in an outpatient setting while maintaining therapeutic anticoagulation. RESULTS: All wounds completely epithelialized (100% closure) by 39.0 ± 21.9 weeks. One wound was completely relieved of its deep tissue defect to total epithelialization with one application of LSS. The largest wound (21.0 cm x 14.5 cm x 2.8 cm) with the greatest undermining (5 cm) was relieved of its tissue defect with a combination of nega- tive pressure therapy and three applications of the LSS. The second largest wound (8.6 cm x 24.0 cm x 2.1 cm), which had an exposed knee joint capsule, required two applications of LSS. These results indicate that patients with large, full-thickness, necrotic, lower extrem- ity wounds caused by traumatic hematomas while on anticoagulation therapy, can be appropriately managed as outpatients with aggressive sharp debridement under local anesthesia, negative pressure therapy for relief of the tissue defect, and bilayered skin substitute application to induce epithelial coverage. CONCLUSION: This approach eliminates the need for cessation of anticoagulation therapy and the use of more complex surgical procedures, such as myocutaneous flaps and skin grafts in patients with multiple underlying comorbid conditions.

Programmed death-1 receptor and interleukin-10 in liver transplant recipients at high risk for late cytomegalovirus disease.

Despite significant advances in antiviral treatment, solid organ transplant (SOT) recipients remain at heightened risk for developing late cytomegalovirus (CMV) disease. Elevated inhibitory immune signaling suggests a state of immune impairment in SOT recipients, who do not control CMV infection and develop severe clinical symptoms after discontinuation of antiviral prophylaxis. We longitudinally monitored the negative immune modulator programmed death (PD)-1 receptor on both CD4 and CD8 T cells, co-expressing the CD137 surface marker of recent activation, in a liver transplant cohort. Liver recipients who progressed to CMV disease expressed elevated levels of PD-1 on CD137(+) CD4 and CD8 T cells, following stimulation with either full-length peptide libraries or CMV lysate. This novel approach, applicable to a multitude of human leukocyte antigen types, enhances the usefulness of the PD-1 measurements as a clinical strategy to predict late CMV disease. In parallel, we detected an increased level of the immunosuppressive cytokine interleukin (IL)-10, in plasma of liver recipients diagnosed with CMV disease. CMV-specific T cells were still functional when both PD-1 and IL-10 were upregulated; however they showed a marked proliferation deficit, which may limit their ability to contain viremia and lead to CMV disease. Our preliminary observations support further investigation of dual monitoring of PD-1 and IL-10, as potential immune markers of CMV disease.

Entamoeba histolyticaEhGEF1 structure and mutational analysis: New specific residues critical for function.

This paper reports the EhGEF1-EhRacG and EhGEF1-EhRho1 molecular complexes from Entamoeba histolytica. The not conserved amino acids Gln201,Tyr299, Gln302, Lys312, Asn313, Phe314 and Ile324 were localized, by means of an in silico computational analysis, at the interface of the exposed face from the DH domain of EhGEF1, which are important to establish the contact with its target GTPases EhRacG and EhRho1. Functional studies of nucleotide exchange of Phe314Ala mutant showed a decrement of 80% on EhRacG GTPase; in contrast the Ile324Ala mutant exhibited a reduction of 77%, specifically on EhRho1; meanwhile the Gln302Ala mutant showed a reduction of approximately 50% on the exchange activity for both GTPases. Moreover, the functional studies of the protein EhGEF1 mutants in the conserved residues Thr194Ala, Asn366Ala and Glu367Ala indicated that contrary to what has been reported for other systems, the mutation of these residues did not alter considerably its catalytic activity.

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis.

Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the expression of ANGII receptors - AT1 and AT2 - and their relationship with prognosis. We studied 133 tumours from patients with diagnosis of astrocytoma who underwent surgery from 1997 to 2002. AT1 and AT2 were expressed in 52 and 44% of the tumours, respectively, when determined by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Ten per cent of low-grade astrocytomas were positive for AT1, whereas grade III and IV astrocytomas were positive in 67% (P<0.001). AT2 receptors were positive in 17% of low-grade astrocytomas and in 53% of high-grade astrocytomas (P=0.01). AT1-positive tumours showed higher cellular proliferation and vascular density. Patients with AT1-positive tumours had a lower survival rate than those with AT1-negative (P<0.001). No association to survival was found for AT2 in the multivariate analysis. Expression of AT1 and AT2 is associated with high grade of malignancy, increased cellular proliferation, and angiogenesis, and is thus related to poor prognosis. These findings suggest that ANGII receptors might be potential therapeutic targets for high-grade astrocytomas.

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector.

A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4(+) and CD8(+) T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4(+) and CD8(+) T cell subsets.

Neuroblastoma: primitivo oculto. Descripción de casos / Neuroblastoma with occult primary. Description of 2 cases

El neuroblastoma es el tumor extracraneal más frecuente en la infancia representando aproximadamente un 8 por ciento de las enfermedades malignas. Se analizó la forma de presentación clínica, evolución respuesta al tratamiento de dos pacientes que presentaron como diagnóstico neuroblastoma con tumor primitivo oculto. La forma de presentación de estos pacientes fue atípica. Caracterizada por la presencia de dolores óseos, radiografía de huesos largos patológicas y aspirado de médula ósea con infiltración neoplásica, sin evidencia de tumor tanto en examen clínico como en los estudios por imágenes. En niños, las neoplasias sólidas de origen desconocido correponden a menos del 1 por ciento del total, siendo esta incidencia algo mayor en el adulto. Un interrogatorio adecuado y dirigido, la evaluación radiológica correcta, la determinación de catecolaminas urinarias y el medulograma son herramientas útiles para arribar al diagnóstico en las presentaciones poco habituales de esta enfermedad.