IMPLEMENTACIÓN DE LA SIMULACIÓN IN SITU EN UN HOSPITAL PEDIÁTRICO DE ALTA COMPLEJIDAD DURANTE LA PANDEMIA COVID-19 / IMPLEMENTATION OF THE IN-SITU SIMULATION IN A HOSPITAL DISCHARGE PEDIATRIC COMPLEXITY DURING THE COVID-19 PANDEMIC

Introducción: El aprendizaje basado en simulación se ha usado ampliamente para mejorar la respuesta de los integrantes del equipo de salud ante situaciones de crisis. La pandemia por COVID-19 planteó el desafío de utilizar la simulación in situ como estrategia de capacitación. Objetivo: Describir el impacto del entrenamiento en RCP en pacientes COVID-19 mediante simulación in situ según la autopercepción del equipo de salud participante y comparar los resultados entre aquellos que hicieron un taller previo de manejo de vía aérea y RCP en pacientes con SARS-CoV -2 y los que no lo realizaron. Material y Método: Estudio exploratorio-descriptivo, desde marzo a junio de 2020, por medio de un cuestionario anónimo estandarizado a los participantes luego de 30 escenarios de simulación in situ. Las variables cualitativas se registraron con valores del 0 al 5 donde 1: nada; 2: bajo; 3: medio; 4: alto y 5:máximo. Resultados: De los 55 participantes, el 38 % (n=21) habían realizado previamente un taller de manejo de vía aérea avanzada y RCP en paciente COVID-19. El 40,7% expresó que disminuyó el temor a la asistencia de un paciente sospechoso o positivo en un nivel máximo (31,5% nivel alto) 81,5 % manifestó que le sirvió en grado máximo para reconocer la importancia del trabajo en equipo y designación de roles (13% grado alto). Para el 65% tuvo una utilidad máxima (18,5% alta) en adecuación del carro de paro y elaboración de un kit específico. Se halló diferencia significativa en la disminución del temor a la asistencia al comparar el nivel de respuesta entre los que habían realizado un taller previo versus los que no ( p= 0,013) Conclusión: La simulación in situ resultó ser una herramienta útil que ayudó en gran medida a disminuir el temor, mejorar habilidades comunicacionales y el trabajo en equipo Los resultados obtenidos fueron aún mejores cuando el escenario fue complementado con un taller de manejo de vía aérea avanzada y RCP

Introduction: Simulation-based learning has been widely used to improve the response of health team members to crisis situations. The COVID-19 pandemic posed the challenge of using on-site simulation as a training strategy.Objective: Analyze the impact of CPR training in COVID-19 patients in situ simulation according to the self-perception of the health team and compare the results between those who did a previous workshop and those who did not. Material and Method: Exploratory-descriptive study, from March to June 2020, through a standardized anonymous questionnaire to the participants after 30 simulation scenarios in situ. The qualitative variables were registered with values from 0 to 5 where 1: nothing; 2: low; 3: medium; 4: high and 5: maximum. Results: Of the 55 participants, 21 (38%) have previously conducted a workshop on advanced airway management and CPR in a CO- VID-19 patient. 40,7% expressed that the fear of attending a suspicious or positive patient decreased at a maximum level (31,5% high level). 81,5% stated that it served them to a maximum degree to recognize the importance of teamwork and role designation (13% high degree). For 65% it had a maximum utility (18.5% high) in adapting the stop car and making a specific kit. When we compared the subgroup that carried out the previous workshop with the one that did not, differences were found in most of the variables, highlighting the decrease in fear. Conclusion: The in situ simulation turned out to be a useful tool that greatly helped reduce fear and improve communication skills and teamwork. The results were obtained even better when the scenario was complemented with an advanced airway management and CPR workshop

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Real-life use of remdesivir in hospitalized patients with COVID-19.

OBJECTIVE: Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain. METHODS: We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020. RESULTS: A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively. CONCLUSIONS: In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile.

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection.

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.

Prophylaxis of mould infections.

Invasive fungal infection continues to be an important cause of morbidity and mortality in haematological patients. Antifungal prophylaxis in these patients has remarkably increased survival since its introduction. In recent years, new antifungals have been on the rise, being more effective and having less toxicity than previous ones. Nonetheless, the number of patients at risk of fungal infection has also been increasing due to the continuous appearance of new immunosuppressive treatments. As a result of such, we face a changing situation that requires constant updating.

Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be used in stewardship de-escalation strategies.

OBJECTIVES: We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies. METHODS: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result. RESULTS: Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB. CONCLUSIONS: Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies.

Mice with sclerostin gene deletion are resistant to the severe sublesional bone loss induced by spinal cord injury.

Bone loss after spinal cord injury (SCI) is rapid, severe, and refractory to interventions studied to date. Mice with sclerostin gene deletion are resistant to the severe sublesional bone loss induced by SCI, further indicating pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging medical problem. INTRODUCTION: The bone loss secondary to spinal cord injury (SCI) is associated with several unique pathological features, including the permanent immobilization, neurological dysfunction, and systemic hormonal alternations. It remains unclear how these complex pathophysiological changes are linked to molecular alterations that influence bone metabolism in SCI. Sclerostin is a key negative regulator of bone formation and bone mass. We hypothesized that sclerostin could function as a major mediator of bone loss following SCI. METHODS: To test this hypothesis, 10-week-old female sclerostin knockout (SOST KO) and wild type (WT) mice underwent complete spinal cord transection or laminectomy (Sham). RESULTS: At 8 weeks after SCI, substantial loss of bone mineral density was observed at the distal femur and proximal tibia in WT mice but not in SOST KO mice. By µCT, trabecular bone volume of the distal femur was markedly decreased by 64 % in WT mice after SCI. In striking contrast, there was no significant reduction of bone volume in SOST KO/SCI mice compared with SOST KO/sham. Histomorphometric analysis of trabecular bone revealed that the significant reduction in bone formation rate following SCI was observed in WT mice but not in SOST KO mice. Moreover, SCI did not alter osteoblastogenesis of marrow stromal cells in SOST KO mice. CONCLUSION: Our findings demonstrate that SOST KO mice were protected from the major sublesional bone loss that invariably follows SCI. The evidence indicates that sclerostin is an important mediator of the marked sublesional bone loss after SCI, and that pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging clinical problem.

Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius.

STUDY DESIGN: Descriptive study. OBJECTIVES: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius. SETTING: This study was conducted in Bronx, NY, USA. METHODS: Three-month-old male Wistar rats were exposed to either a sham surgery (n=10) or complete T4 spinal cord transection (n=10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated. RESULTS: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the α7 or ß1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the α7 or ß1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI. CONCLUSION: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury.

Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.

Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.

Conocimiento sobre el Virus del Papiloma Humano en estudiantes de Citotecnología de una Universidad Nacional / Knowledge on the human papilloma virus in students of Cytotechnology of a National University

Las infecciones de transmisión sexual incluyendo el Virus de Papiloma Humano (VPH) son muy comunes a nivel mundial. Objetivo. Determinar el conocimiento sobre el VPH en estudiantes de Citotecnología. Métodos. Investigación descriptiva. Se aplicó un cuestionario a 73 alumnos que incluyó edad, procedencia, ejercicio de función sexual, parejas sexuales, etiología del VPH, modo de transmisión, clínica y prevención. Resultados. La mediana de la edad fue 20 ± 0,5 años. Predominó significativamente el sexo femenino (Z = 8,28; p < 0,001) y los estudiantes que refirieron no tener más de una pareja sexual (42 de 73, 57,5%), con Z = 3,34; p < 0,001. Al existir 95,9% con un conocimiento muy bueno o excelente y significativamente mayor que quienes lo presentaron como bueno, (4,11%), no hubo diferencias estadísticamente significativas entre la medianas de puntajes de sexo. Conclusión: El conocimiento se puede asociar a un ejercicio responsable de la sexualidad en ambos géneros. Se recomienda reforzar las campañas de información y formación a los adolescentes respecto al VPH.

The sexual transmission infections including the Human Papilloma Virus (HPV) infection are very common in the world. Objective. To determine the knowledge on HPV in students of Cytotechnology. Methods. Descriptive investigation. A questionnaire was applied in 73 students, was included age, origin, exercise of sexual function, sex partners, etiology of HPV, transmission way, clinic and prevention. Results. The median of age was 20 ± 0.5 years. There was a significant predominance of female gender (Z = 8.28; p <0.001) and the students which refer to have more than a sexual partner (42 de 73, 57.5 %), with Z = 3.34; p < 0.001. There was a 95.9% a very good or excellent knowledge and significantly higher than whom had a good one (4.11%), whithout statistically significant differences between the medians of scores according sex, it is concluded that this knowledge could be associated to a responsible excercise of sexuality in both genders. It is recommended reinforce the information and tuition to the adolescents in respect of HPV.

Effects of low intensity vibration on bone and muscle in rats with spinal cord injury.

UNLABELLED: Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI. INTRODUCTION: Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI. METHODS: The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord. RESULTS: Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI. CONCLUSION: The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass.

Las proteínas del plasma seminal incrementan la viabilidad espermática post-descongelación del semen de toros Sanmartinero / Seminal plasma proteins increase the post-thaw sperm viability of Sanmartinero bull’s semen

Objetivo. El objetivo de este trabajo fue evaluar el efecto de la adición de proteínas del plasma seminal sobre el porcentaje de espermatozoides bovinos viables post-descongelación. Materiales y métodos. Los espermatozoides se congelaron usando dos medios (citrato-fructosa-yema y Bioxcell®) y la obtención de proteínas de plasma seminal de bajo peso molecular se realizó por medio de cromatografía líquida de baja presión. Las proteínas de interés eluyeron en las fracciones 21-25 y se sometieron a electroforésis en una y dos dimensiones. Los espermatozoides se incubaron a 37°C durante una hora, con 0.5, 1.0, 1.5 y 2.0 mg de la fracción 21-25. Se incluyeron dos tratamientos adicionales: uno con proteínas totales del plasma seminal y otro sin proteína. Resultados. La electroforésis bidimensional de las fracciones confirmó la presencia de siete puntos de proteína de bajo peso molecular (14-16 kDa y punto Isoeléctrico de 5.0 - 5.5). La adición de estas proteínas aumentó 20% (p<0.05), el porcentaje de espermatozoides viables post-descongelación en muestras congeladas en medio citrato-fructosa-yema (con dosis de 1 ó 1.5 mg de proteína/106 espermatozoides), y 25% (p<0.05) en muestras congeladas en medio Bioxcell® (con dosis de 0.5 mg de proteína/106 espermatozoides). Conclusiones. Los resultados de esta investigación sugieren el posible uso de proteínas de bajo peso molecular del plasma seminal, para disminuir el efecto deletéreo de la criopreservación en los espermatozoides.

Objective.This study was performed to evaluate the effect of the addition of proteins on the post-thawing viability of spermatozoa. Materials and methods. Spermatozoa were frozen with two different media: Citrate-fructose and Bioxcell®. The isolation of seminal plasma proteins of low molecular weight was performed through low pressure liquid chromatography. It was determined that the proteins of interest eluted in fractions 21-25, and two dimensional electrophoresis was performed. Thawed sperm was incubated at 37°C for one hour with 0.5, 1, 1.5 and 2.0 mg of 21-25 fraction protein. Two additional treatments were included: one with seminal plasma total protein, and another one without protein. Results. Two dimensional electrophoresis of protein confirmed the presence of two bands of 14 and 16 kDa and seven spots with iso-electric points between 5.0 - 5.5 respectively. Incubation of the spermatozoa with the 21-25 fraction showed that sperm viability increases by 20% with doses of 1 and 1.5 mg of protein/106 spermatozoa in the citrate-fructose medium, and 25% with 0.5 mg of protein/106 spermatozoa in Bioxcell® medium. A positive effect in sperm viability was demonstrated although it depends on the doses of protein and the cryopreservation medium used. Conclusions. This investigation suggests that the use of seminal plasma proteins can be useful for reducing the harmful effect on sperm cryopreservation.

Características epidemiológicas de pacientes atendidas en la consulta de endometriosis de un hospital universitario / Epidemiological characteristics of patients attended at the outpatient clinic of endometriosis in universitary hospital

Establecer las características epidemiológicas de pacientes con endometriosis. Es un trabajo descriptivo y transversal. La población fue de 54 pacientes. La recolección de la información mediante la revisión documental en una ficha. Consulta de endometriosis del Hospital Universitario Dr. Angel Larralde de Valencia. Edad promedio 30 ± 5,8 años. Motivos de consulta: dismenorrea (70,7 por ciento), dolor pélvico (58,5 por ciento) y dispareunia (36,6 por ciento). Edad promedio de menarquía 12 años. El 29 por ciento reportó algún tipo de trastorno menstrual, el más frecuente la metrorragia (17 por ciento). El 41,5 por ciento refirió uso previo de anticonceptivos orales. El 34 por ciento de las pacientes no habían estado embarazadas, 26,88 por ciento primigesta. Entre los antecedentes quirúrgicos gineco-obstétricos, 39 por ciento reportó cesáreas, 26,88 por ciento ooforectomía y 19,55 por ciento legrado uterino. Las endometriosis más frecuentes fueron la ovárica (56,09 por ciento) y en cicatriz abdominal postcesárea (24,39 por ciento). La endometriosis es una patología típica de la mujer en edad reproductiva, que puede darse inclusive en la adolescencia.

Occult lymph node metastases posterior to the internal jugular vein.

Supraomohyoid neck dissection is a reliable staging procedure in patients with oral or oropharyngeal squamous cell carcinoma and no clinical evidence of node metastases. We have recorded the yield and distribution of occult lymph node metastases in the fibro-fatty strip of tissue posterior to the internal jugular vein and beneath the sternomastoid in 35 neck dissections. Occult lymph node metastases were found in 12/35 (34%); 3 of these had metastases in the posterior strip, which were never in isolation. We think that it is worthwhile to sample the posterior strip. Firstly it removes tumour that would have been left behind in a small number of cases had a conventional supraomohyoid neck dissection been done, and secondly it enables postoperative radiotherapy to be targeted at the anterior triangle alone when the posterior strip is clear of tumour.

Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor.

Cdc37 is a molecular chaperone closely associated with the folding of protein kinases. Results from studies using a yeast model system showed that it was also important for activation of the human androgen receptor (AR). Based on results from the yeast model system (Fliss, A. E., Fang, Y., Boschelli, F., and Caplan, A. J. (1997) Mol. Biol. Cell 8, 2501-2509), we initiated studies to address whether AR and Cdc37 interact with each other in animal cell systems. Our results show that Cdc37 binds to AR but not to glucocorticoid receptors (GR) synthesized in rabbit reticulocyte lysates. This binding occurs via the ligand-binding domain of the AR in a manner that is partially dependent on Hsp90 and the presence of hormone. Further studies using the yeast system showed that Cdc37 is not interchangeable with Hsp90, suggesting that it functions at a distinct step in the activation pathway. Expression of a dominant negative form of Cdc37 in animal cells down-regulates full-length AR but has very little effect on an AR truncation lacking the ligand-binding domain or full-length GR. These results reveal differences in the mechanisms by which AR and GR become active transcription factors and strengthen the notion that Cdc37 has a wider range of polypeptide clients than was realized previously.

Control of LMP7 expression in human endothelial cells by cytokines regulating cellular and humoral immunity.

Formation of antigenic peptides by the multicatalytic proteinase complex (MPC, proteasome) is facilitated by incorporation of three subunits (LMP2, LMP7 and LMP10) that are inducible by IFN-gamma and TNF-alpha. These cytokines, or their functional homologues (e.g. TNF-beta), are released from many cells including Th(1)lymphocytes. To learn more about the relationship between control of cellular immunity and expression of LMP subunits, we measured LMP7 levels in human umbilical vein endothelial cells of cytokines promoting cellular immunity (IL-12, IFN-gamma, TNF-alpha) or humoral immunity (IL-10, IL-6). Little or no effect was seen when cells were exposed to IL-6, IL-10 or IL-12 alone. IFN-gamma upregulated LMP7 levels, as did TNF-alpha to a lesser extent. IL-10 downregulated IFN-gamma-induced increases in LMP7 levels, as did IL-12. The findings indicate that regulation of levels of LMP7 is similar to and may be coupled with that of other molecules required for MHC class I-dependent immunity, and depends primarily on cytokines released by Th(1)helper lymphocytes.

Proteasome from cytokine-treated human cells shows stimulated BrAAP activity and depressed PGPH activity.

The branched chain amino acid-preferring (BrAAP) activity of multicatalytic proteinase complex isolated from human umbilical vein endothelial cells and treated with interferon-gamma was increased more than 2-fold, which was associated with a marked increase in LMP7 expression and decreased peptidylglutamyl peptide-hydrolyzing activity. Increases in BrAAP activity in supernatants from cells treated with interferon-gamma, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, or lipopolysaccharide paralleled the increases in LMP7 expression. These findings are consistent with the conclusion that the increased BrAAP activity of LMP-containing multicatalytic proteinase complex results from incorporation of LMP7 or other LMP subunits.

DNA vaccine encoding nucleocapsid and surface proteins of wild type canine distemper virus protects its natural host against distemper.

Canine distemper virus (CDV), a member of the genus Morbillivirus induces a highly infectious, frequently lethal disease in dogs and other carnivores. Current vaccines against canine distemper consisting of attenuated viruses have been in use for many years and have greatly reduced the incidence of distemper in the dog population. However, certain strains may not guarantee adequate protection and others can induce post vaccinal encephalitis. We tested a DNA vaccine for its ability to protect dogs, the natural host of CDV, against distemper. We constructed plasmids containing the nucleocapsid, the fusion, and the attachment protein genes of a virulent canine distemper virus strain. Mice inoculated with these plasmids developed humoral and cellular immune responses against CDV antigens. Dogs immunized with the expression plasmids developed virus-neutralizing antibodies. Significantly, vaccinated dogs were protected against challenge with virulent CDV, whereas unvaccinated animals succumbed to distemper.