Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.

Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.

Sociodemographic characteristics and their association with survival in women with cervical cancer.

BACKGROUND: In 2020, the highest incidence and mortality from cervical cancer (CC) were detected in low and middle-income countries. CC remains a health problem for women living in them. In Mexico, CC ranks second in cancer incidence and mortality in women. The main characteristics of this population are low income, low educational level, and inadequate medical coverage. The present study characterized the Mexican population by CC, and the sociodemographic variables that impacted overall survival (OS) were identified. METHODS: A retrospective study that included a cohort of patients with a confirmed diagnosis of CC at the Instituto Nacional de Cancerologia between 2003 and 2016. Information was collected on sociodemographic variables related to the disease and OS. RESULTS: Four thousand six hundred thirty-one patients were included. The median age was 51 years, 78.5% were unemployed, 44.4% lived in a rural/suburban area, 50.8% had a partner when collecting this information, and 74.3% were classified as having low socioeconomic status. Age, living in a rural/suburban area, more advanced stages of the disease, and not receiving cancer treatment were associated with lower OS. CONCLUSION: CC continues to affect mainly women with minimal resources, low educational levels, and living in marginalized areas. These characteristics influence the OS. Prevention and timely detection programs, education, and training focused on this population and with broader coverage are required to identify patients with CC at earlier stages.

Neighborhood influences on the development of self-regulation among children of color living in historically disinvested neighborhoods: Moderators and mediating mechanisms.

We present a conceptual model of the ways in which built and social environments shape the development of self-regulation in early childhood. Importantly, in centering children of color growing up in historically disinvested neighborhoods, we first describe how systemic structures of racism and social stratification have shaped neighborhood built and social environment features. We then present evidence linking these neighborhood features to children's development of self-regulation. Furthermore, we take a multilevel approach to examining three potential pathways linking neighborhood contexts to self-regulation: school environment and resources, home environment and resources, and child health behaviors. Finally, we consider how racial-ethnic-cultural strengths and multilevel interventions have the potential to buffer children's development of self-regulation in disinvested neighborhood contexts. Advancing multilevel approaches to understand the development of self-regulation among children of color living in historically disinvested neighborhoods is an important step in efforts to promote equity in health and education.

Factores clínico-demográficos asociados al miedo-evitación en sujetos con lumbalgia crónica inespecífica en atención primaria: análisis secundario de estudio de intervención / Clinical-demographic factors associated with fear-avoidance in subjects with non-specific chronic low back pain in Primary Care: secondary analysis of intervention study

Objetivo: Describir algunas características sociodemográficas y clínicas de los sujetos con lumbalgia crónica inespecífica (LCI) atendidos habitualmente en atención primaria (AP), así como investigar su asociación con el miedo-evitación (ME). Diseño: Descriptivo transversal. Análisis secundario de estudio de intervención. Emplazamiento: Zonas Básicas de Salud del Distrito Sanitario de AP Costa del Sol (Málaga). Participantes: Un total de 147 sujetos con LCI extraídos de la base de datos de un estudio de intervención previo en fisioterapia de AP. Características: edad, 18-65 años; comprensión del idioma español; ausencia de deterioro cognitivo, ausencia de fibromialgia, ausencia de cirugía dorsolumbar, y tolerancia al ejercicio físico. Mediciones principales: La variable principal fue el ME (FABQ y subescalas FABQ-PA y FABQ-W); las variables clínicas incluyeron: dolor (NRPS-11), discapacidad (RMQ), tiempo de evolución, tratamientos previos y diagnósticos de imagen; las variables sociodemográficas incluyeron: sexo, edad, nivel educativo y situación laboral. Resultados. El 51,7% de los sujetos presentaron elevado ME con la escala FABQ-PA. Incapacidad temporal (IT) [Beta = 24,45 (p = 0,009*); Beta =13,03 (p = 0,016*); Beta =14,04 (p = 0,011*) para FABQ, FABQ-PA y FABQ-W, respectivamente]; estudios primarios [Beta =15,09 (p = 0,01*); Beta = 9,73 (p = 0,01*) para FABQ y FABQ-PA], y discapacidad [Beta =1,45 (p < 0,001); Beta = 0,61 (p < 0,001); Beta =0,68 (p < 0,001) para FABQ, FABQ-PA y FABQ-W, respectivamente] aparecieron asociados al ME cuando fueron modelados por regresión multivariante. Conclusiones: Algunos rasgos sociodemográficos y clínicos de la población con LCI son presentados. Las pruebas de imagen (81,63%) y los tratamientos previos pasivos (55,78%) podrían reflejar problemas de adherencia a las recomendaciones de las GPC. IT, estudios primarios y discapacidad se asociaron al ME. Los hallazgos deben ser interpretados a la luz de las posibles limitaciones. Algunas sugerencias para la práctica clínica son aportadas

Objective: To describe some sociodemographics and clinical characteristics of subjects with Non-specific Chronic Low Back Pain (NCLBP) in Primary Care, as well as to investigate their association with Fear-Avoidance (FA). Design: Cross-sectional. Secondary analysis of an intervention study. Location: Basic Health Areas in Costa del Sol Health District (Málaga, Spain). Participants: An analysis was performed on 147 subjects with NCLBP from a previous intervention study database in Primary Care Physiotherapy (PCP). Characteristics: age 18-65; understanding of the Spanish language; absence of cognitive disorders, fibromyalgia or dorsolumbar surgery, and to be able to perform physical exercise. Main measurements: The main variable was FA level (FABQ and the FABQ-PA and FABQ-W) sub-scales. Clinical variables included: pain (NRPS-11), disability (RMQ), evolution, previous treatments and diagnostic imaging. The sociodemographic variables included: gender, age, educational level, and employment status. Results: Just over half (51.7%) of the subjects had high FA on the FABQ-PA sub-scale. Sick leave (SL) [Beta = 24.45 (P = .009*); Beta = 13.03 (P = .016*); Beta = 14.04 (P =.011*) for FABQ, FABQ-PA and FABQ-W, respectively]; primary studies level [Beta = 15.09 (P = .01*); Beta = 9.73 (P = .01*) for FABQ and FABQ-PA], and disability [Beta = 1.45 (P < .001); Beta = 0.61 (P < .001); Beta = 0.68 (P < .001) for FABQ, FABQ-PA and FABQ-W, respectively] were associated with FA when they were modeled by multivariate regression. Conclusions: Some sociodemographic and clinical features of the NCLBP population are presented. Imaging tests (81.63%) and previous passive treatments (55.78%) could reflect problems of adherence to recommendations of CPGs. Sick leave, primary studies level, and disability were associated with FA. The findings should be interpreted in the light of possible limitations. Some suggestions for clinical practice are provided

[Clinical-demographic factors associated with fear-avoidance in subjects with non-specific chronic low back pain in Primary Care: secondary analysis of intervention study]. / Factores clínico-demográficos asociados al miedo-evitación en sujetos con lumbalgia crónica inespecífica en atención primaria: análisis secundario de estudio de intervención.

OBJECTIVE: To describe some sociodemographics and clinical characteristics of subjects with Non-specific Chronic Low Back Pain (NCLBP) in Primary Care, as well as to investigate their association with Fear-Avoidance (FA). DESIGN: Cross-sectional. Secondary analysis of an intervention study. LOCATION: Basic Health Areas in Costa del Sol Health District (Málaga, Spain). PARTICIPANTS: An analysis was performed on 147 subjects with NCLBP from a previous intervention study database in Primary Care Physiotherapy (PCP). Characteristics: age 18-65; understanding of the Spanish language; absence of cognitive disorders, fibromyalgia or dorsolumbar surgery, and to be able to perform physical exercise. MAIN MEASUREMENTS: The main variable was FA level (FABQ and the FABQ-PA and FABQ-W) sub-scales. Clinical variables included: pain (NRPS-11), disability (RMQ), evolution, previous treatments and diagnostic imaging. The sociodemographic variables included: gender, age, educational level, and employment status. RESULTS: Just over half (51.7%) of the subjects had high FA on the FABQ-PA sub-scale. Sick leave (SL) [ß=24.45 (P=.009*); ß=13.03 (P=.016*); ß=14.04 (P=.011*) for FABQ, FABQ-PA and FABQ-W, respectively]; primary studies level [ß=15.09 (P=.01*); ß=9.73 (P=.01*) for FABQ and FABQ-PA], and disability [ß=1.45 (P<.001); ß=0.61 (P<.001); ß=0.68 (P<.001) for FABQ, FABQ-PA and FABQ-W, respectively] were associated with FA when they were modeled by multivariate regression. CONCLUSIONS: Some sociodemographic and clinical features of the NCLBP population are presented. Imaging tests (81.63%) and previous passive treatments (55.78%) could reflect problems of adherence to recommendations of CPGs. Sick leave, primary studies level, and disability were associated with FA. The findings should be interpreted in the light of possible limitations. Some suggestions for clinical practice are provided.

Kinase gene fusions in defined subsets of melanoma.

Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations.

Ensayo no aleatorizado de una intervención educativa basada en principios cognitivo-conductuales para pacientes con lumbalgia crónica inespecífica atendidos en fisioterapia de atención primaria / Non-randomised trial of an educational intervention based on cognitive-behavioural principles for patients with chronic low back pain attended in Primary Care Physiotherapy

OBJETIVO: Valorar la influencia de una intervención educativa en la reducción del «miedo-evitación» (ME) y del «catastrofismo al dolor» (CAT) en población con lumbalgia crónica inespecífica (LCI) atendida en fisioterapia de atención primaria (AP). DISEÑO: Estudio cuasiexperimental. Emplazamiento: Centros de salud (CS) del Distrito Sanitario Costa del Sol. PARTICIPANTES: Pacientes con LCI entre 18-65 años con comprensión del idioma español; ausencia de intervenciones educativas paralelas; ausencia de banderas rojas; ausencia de deterioro cognitivo y/o fibromialgia; ausencia de cirugía dorsolumbar, y tolerancia al ejercicio físico. INTERVENCIONES: El grupo control recibió la EdE grupal habitual. El experimental recibió, además, un instrumento escrito para lectura domiciliaria, más la posterior puesta en común, aclaración de dudas y reestructuración de creencias y metas durante el desarrollo de las sesiones. Ambas intervenciones duraron unos 280 min (7 sesiones de 40 min). RESULTADOS: Las variables principales incluyeron ME y CAT. Secundariamente se valoraron dolor y discapacidad. Algunas variables «sociodemográficas» y «relacionadas con el trastorno» fueron tenidas en cuenta en el análisis. Se observaron diferencias estadísticamente significativas en el grupo experimental versus control en la variación del ME −14 (−25,5; 0) vs −4 (−13; 0) (p = 0,009), y del CAT −9 (−18; −4) vs −4,5 (−8,25; 0) (p = 0,000). Igualmente se observaron diferencias en discapacidad (p = 0,046), pero no en dolor (p = 0,280). CONCLUSIONES: Los resultados deben ser considerados a la luz de las posibles limitaciones que plantea el estudio. Su naturaleza pragmática permitiría una potencial transferencia a la dinámica asistencial habitual

OBJECTIVE: To assess the influence of an educational intervention in reducing «fear-avoidance» (FA) and «pain catastrophising» (CAT) in a population with unspecific chronic low back pain (UCLBP), attending physiotherapy in Primary Health Care. A pragmatic quasi-experimental study was conducted in Health Centres of a Costa del Sol Health District. DESIGN: Quasi-experimental study. SETTING: Primary Health Care physiotherapy Back Schools in Health Centres of a Costa del Sol Health District. PARTICIPANTS: The selection criteria were: UCLBP; 18-65 years; understanding of the Spanish language; absence of parallel educational interventions; absence of red flags; not showing cognitive impairment or fibromyalgia; absence of thoracic-lumbar surgery, and exercise tolerance. INTERVENTIONS: The control group received the usual Back Schools program. The experimental group also received a written document for home reading, plus the subsequent sharing, clarifying doubts, and beliefs and goals restructuring during the development of the sessions. Both interventions lasted about 280 minutes (7 sessions × 40min). RESULTS: The main variables included FA and CAT. Pain and disability were also assessed. Some «demographic» and «related disorder» variables were considered in the analysis. Statistically significant differences were observed in the experimental group versus control, in the variation of FA −14 (−25.5; 0) vs −4 (−13; 0) (P=.009), and CAT −9 (−18; −4) vs −4,5 (−8.25; 0) (P=.000), were observed. Also differences in disability (P=.046), but not in pain (P=.280). CONCLUSIONS: These results should be considered in light of possible limits imposed by the study. Its pragmatic nature would allow a potential transfer to usual care

Efecto del bloqueo del factor de necrosis tumoral α sobre el metabolismo óseo en las enfermedades inflamatorias articulares crónicas / Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases

Fundamento y objetivo: Evaluar el efecto de los tratamientos anti-TNF sobre la densidad mineral ósea (DMO), los marcadores de remodelado óseo (MRO) y la ratio receptor activator for nuclear factor κB ligand (RANKL, «ligando del receptor activador del factor nuclear κB»)/osteoprotegerina (OPG) en los pacientes con enfermedades inflamatorias articulares crónicas. Métodos: Estudio longitudinal prospectivo en condiciones de práctica clínica sobre 31 pacientes diagnosticados de artritis reumatoide, artropatía psoriásica y espondilitis anquilosante que estuvieron durante un año en tratamiento con fármacos anti-TNF alfa. Al inicio y al final del estudio se evaluaron la DMO, la OPG y la forma soluble de RANKL (sRANKL), y durante el estudio (0, 3, 6, 9 y 12 meses), la actividad de la enfermedad (SDAI, BASDAI y PCR), la capacidad funcional (HAQ, BASFI), los MRO y la vitamina D. Resultados: La DMO no se modificó después de un año de tratamiento. Los pacientes que consumieron corticoides tuvieron una pérdida media de masa ósea del 3% en el raquis lumbar (± 1,6, p = 0,02). En cuanto a los MRO, no experimentaron cambios significativos a lo largo del estudio. Disminuyó la actividad de la enfermedad, tanto SDAI (p = 0,002) como BASDAI (p = 0,002). La OPG se mantuvo sin cambios durante el año de tratamiento, mientras que disminuyeron significativamente tanto el sRANKL (0,28 ± 0,22, p = 0,013) como la ratio sRANKL/OPG (0,04 ± 0,03, p = 0,031). Conclusión: Los pacientes en tratamiento con anti-TNF no presentaron una pérdida de DMO significativa durante el seguimiento (un año), a la vez que experimentaron una mejora de la actividad de la enfermedad. Estos resultados han sido más evidentes en los pacientes respondedores (AU)

Background and objective: To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. Methods: A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. Results: BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (± 1.6, P = .02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P = .002) and BASDAI (P = .002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28 ± 0.22, P = .013) and sRANKL/OPG ratio significantly decreased (0.04 ± 0.03,P = .031). Conclusion: The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients (AU)

[Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases]. / Efecto del bloqueo del factor de necrosis tumoral α sobre el metabolismo óseo en las enfermedades inflamatorias articulares crónicas.

BACKGROUND AND OBJECTIVE: To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. METHODS: A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. RESULTS: BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). CONCLUSION: The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients.

[Non-randomised trial of an educational intervention based on cognitive-behavioural principles for patients with chronic low back pain attended in Primary Care Physiotherapy]. / Ensayo no aleatorizado de una intervención educativa basada en principios cognitivo-conductuales para pacientes con lumbalgia crónica inespecífica atendidos en fisioterapia de atención primaria.

OBJECTIVE: To assess the influence of an educational intervention in reducing «fear-avoidance¼ (FA) and «pain catastrophising¼ (CAT) in a population with unspecific chronic low back pain (UCLBP), attending physiotherapy in Primary Health Care. A pragmatic quasi-experimental study was conducted in Health Centres of a Costa del Sol Health District. DESIGN: Quasi-experimental study. SETTING: Primary Health Care physiotherapy Back Schools in Health Centres of a Costa del Sol Health District. PARTICIPANTS: The selection criteria were: UCLBP; 18-65years; understanding of the Spanish language; absence of parallel educational interventions; absence of red flags; not showing cognitive impairment or fibromyalgia; absence of thoracic-lumbar surgery, and exercise tolerance. INTERVENTIONS: The control group received the usual Back Schools program. The experimental group also received a written document for home reading, plus the subsequent sharing, clarifying doubts, and beliefs and goals restructuring during the development of the sessions. Both interventions lasted about 280minutes (7 sessions×40min). RESULTS: The main variables included FA and CAT. Pain and disability were also assessed. Some «demographic¼ and «related disorder¼ variables were considered in the analysis. Statistically significant differences were observed in the experimental group versus control, in the variation of FA -14 (-25.5; 0) vs -4 (-13; 0) (P=.009), and CAT -9 (-18; -4) vs -4,5 (-8.25; 0) (P=.000), were observed. Also differences in disability (P=.046), but not in pain (P=.280). CONCLUSIONS: These results should be considered in light of possible limits imposed by the study. Its pragmatic nature would allow a potential transfer to usual care.

Perspectives on bullying among children who present to the emergency department with behavioral misconduct: a qualitative study.

UNLABELLED: The problem of bullying is an increasing public health threat encountered by emergency physicians especially in inner city emergency departments (EDs). Bullying may result in emotional disturbances and psychological trauma in children. Many children sent to the ED because of behavioral misconduct require immediate stabilization and treatment. The emergency physician performs an initial assessment and stabilization. Emergency departments are increasingly on the frontline of the bullying problem. OBJECTIVES: Our objective was to explore children's perspective of bullying and their views of potential solutions. METHODS: A qualitative study was conducted in a cohort of 50 children (age, 8-17 years), who were referred to the ED from school because of their behavioral misconduct. An interview survey tool about bullying was administered. It focused on what bullying meant to them and what advice they have for a child who is bullied. They were also asked what advice they would have for adults who try to help. We used grounded theory to analyze the data. Similar concepts were grouped, and the categories with similar properties and dimensions were defined. Common themes were then identified. RESULTS: We interviewed 50 children, of whom 27 were boys and 23 were girls. Their mean (SD) age was 12.5 (2.12) years (range, 8-17 years). Bullying was identified by children as including physical, verbal, and emotional actions. Several themes emerged. First, a power imbalance between a bully and victim may render an individual vulnerable to bullying. Being different and weak also increases the risk of being bullied. Second, bullying is wrong, and the bully should be punished. Third, children should learn how to handle bullying situations and develop resilience against bullying. Finally, adults need to be more proactive to prevent or stop bullying. CONCLUSIONS: Our results provide insights into the perceptions of children regarding bullying. We have garnered a better understanding of what these children feel adults should do to prevent bullying.

Reflexões sobre o processo ensino-aprendizagem da relação médico-paciente / Reflections on the teaching/learning process of the physician-patient relationship

O texto aborda o processo ensino-aprendizagem da relação médico-paciente considerando o novo paradigma do ensino médico, as Diretrizes Curriculares Nacionais. Argumenta a respeito da necessidade de formação ampla, que inclua áreas afins como filosofia, bioética, teologia e sociologia. Aponta para a necessidade do ensino-aprendizagem destacando o respeito àá alteridade e àá autonomia, procurando refletir sobre o processo teoria/prática em relação a esses conteúdos no viver dos estudantes de medicina. Também procura enfocar modelos explicativos, leigos e médicos, discorrendo a respeito da necessidade de lidar de forma harmoniosa com as diferenças. Por fim, apresenta a teoria de Balint e suas categorias, que ampliam a compreensão do processo saúde-doença do paciente, bem como examina o necessário desenvolvimento da inteligência emocional do estudante de medicina. O texto intenta pautar a reflexão dos profissionais que, de alguma forma, influenciam a formação de futuros médicos.

La extensión de la enfermedad coronaria determina la movilización de las células progenitoras endoteliales y las citocinas tras un primer infarto de miocardio con elevación del ST / Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation

Introducción y objetivos. La enfermedad coronaria multivaso es un importante factor pronóstico postinfarto a pesar de nuevas formas de reperfusión como la angioplastia primaria. El objetivo del presente estudio es determinar la secuencia de variación de diferentes poblaciones de células progenitoras endoteliales y factores angiogénicos (factor de crecimiento endotelial vascular, factor de crecimiento hepatocitario) según el grado de extensión de la enfermedad coronaria. Métodos. Estudiamos la cinética de liberación en 32 pacientes ingresados por un primer infarto, agrupados según tuvieran enfermedad coronaria monovaso o multivaso y 26 sujetos que constituyen el grupo control. Resultados. Los pacientes presentaban un mayor número de células progenitoras endoteliales y citocinas angiogénicas que los controles en las tres determinaciones realizadas (al ingreso, día 3 y día 7) de las siguientes subpoblaciones: CD34, CD34+CD133+, CD34+KDR+ y CD34+CD133+KDR+CD45+ (débil); este último era mayor el día 7. Los valores de las tres poblaciones analizadas eran mayores en los pacientes con enfermedad coronaria monovaso en las tres determinaciones. Las cifras del factor de crecimiento endotelial vascular subían durante la primera semana y las del factor de crecimiento hepatocitario mostraron un pico precoz al ingreso. No apreciamos diferencias significativas en las variaciones de citocinas según el grado de extensión de la enfermedad coronaria. Conclusiones. Aunque las cinéticas de liberación de diferentes poblaciones de células progenitoras endoteliales en pacientes con un primer infarto agudo de miocardio con enfermedad monovaso con enfermedad multivaso fueron similares, su número fue mayor en los pacientes con enfermedad coronaria monovaso. Las cifras del factor de crecimiento endotelial vascular ascendieron durante la primera semana y las del factor de crecimiento hepatocitario muestran un pico precoz al ingreso (AU)

Introduction and objectives. Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. Methods. We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. Results. The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. Conclusions. Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission (AU)

[Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation]. / La extensión de la enfermedad coronaria determina la movilización de las células progenitoras endoteliales y las citocinas tras un primer infarto de miocardio con elevación del ST.

INTRODUCTION AND OBJECTIVES: Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. METHODS: We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. RESULTS: The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. CONCLUSIONS: Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission.

Deformación ventricular izquierda en ecocardiografía bidimensional: valores y tiempos en sujetos normales / Left ventricular deformation and two-dimensional echocardiography: temporal and other parameter values in normal subjects

El análisis de la deformación o strain y la tasa de deformación o strain rate podrían valorar cuantitativamente la contractilidad segmentaria. Esto es factible con Doppler tisular y, más recientemente, también con ecografía bidimensional mediante el rastreo de señales miocárdicas (speckle tracking). Este trabajo se diseñó para conocer el valor de estos parámetros en sujetos sanos y su reproducibilidad. Se estudió a 105 sujetos sanos —55 mujeres (52,45%); edad, 38,8 ± 9,5 (20-59) años— mediante speckle tracking con la aplicación Vector Velocity Imaging. Se obtuvieron los valores medios de strain y strain rate de cada segmento, así como el tiempo hasta el pico máximo, normalizado con la longitud del ciclo (TpN). Los valores medios fueron: strain circunferencial, 22,2 ± 4,81% con TpN 0,39 ± 0,06; strain longitudinal, 19,84 ± 4,59% con TpN 0,42 ± 0,06; strain rate circunferencial, 1,64 ± 0,48 1/s con TpN 0,23 ± 0,06; strain rate longitudinal, 1,3 ± 0,49 1/s con TpN 0,21 ± 0,09. Las variabilidades del observador y entre observadores fueron moderadas (AU)

Segmental contractility can be assessed quantitatively by analyzing deformation, or strain, and the rate of deformation, or the strain rate. This type of analysis can be performed using either tissue Doppler imaging or, more recently, two-dimensional speckle-tracking echocardiography. The aim of this study was to determine typical parameter values in healthy subjects and their reproducibility. The study involved 105 healthy individuals, including 55 women (52.45%). Their mean age was 38.8±9.5 years (range, 20-59 years). All underwent speckle-tracking echocardiography with velocity vector imaging. Mean values for the strain and strain rate for each segment as well as for the time-to-peak normalized by the length of the cycle (TPN) were obtained. The resulting mean values were: circumferential strain, 22.2±4.81% with a TPN of 0.39±0.06; longitudinal strain, 19.84±4.59% with a TPN of 0.42±0.06; circumferential strain rate, 1.64±0.48 1/s with a TPN of 0.23±0.06; and longitudinal strain rate, 1.3±0.49 1/s with a TPN of 0.21±0.09. Intra- and interobserver variability were moderate in magnitude (AU)

Left ventricular deformation and two-dimensional echocardiography: temporal and other parameter values in normal subjects.

Segmental contractility can be assessed quantitatively by analyzing deformation, or strain, and the rate of deformation, or the strain rate. This type of analysis can be performed using either tissue Doppler imaging or, more recently, two-dimensional speckle-tracking echocardiography. The aim of this study was to determine typical parameter values in healthy subjects and their reproducibility. The study involved 105 healthy individuals, including 55 women (52.45%). Their mean age was 38.8 ± 9.5 years (range, 20-59 years). All underwent speckle-tracking echocardiography with velocity vector imaging. Mean values for the strain and strain rate for each segment as well as for the time-to-peak normalized by the length of the cycle (TPN) were obtained. The resulting mean values were: circumferential strain, 22.2 ± 4.81% with a TPN of 0.39 ± 0.06; longitudinal strain, 19.84 ± 4.59% with a TPN of 0.42 ± 0.06; circumferential strain rate, 1.64 ± 0.48 1/s with a TPN of 0.23 ± 0.06; and longitudinal strain rate, 1.3 ± 0.49 1/s with a TPN of 0.21 ± 0.09. Intra- and inter-observer variability were moderate in magnitude.

Octreotide therapy for recurrent refractory hypoglycemia due to sulfonylurea in diabetes-related kidney failure.

OBJECTIVE: To describe a patient with kidney insufficiency from diabetes treated with glyburide, who presented with prolonged and recurrent hypoglycemia unresponsive to large intravenous doses of glucose, which was treated successfully with intravenously administered octreotide, and to review the therapeutic options for hypoglycemia. METHODS: We present a case report of a 66-year-old man with diabetes causing chronic kidney disease, who was treated with orally administered glyburide, 7.5 mg twice a day. He initially presented to another hospital because of hypoglycemia and was treated with intravenously administered glucose and discharged. The next day, his family brought him to our emergency department because of recurring low blood glucose levels and symptoms of sweating, fever, and nightmares. Laboratory tests revealed a blood glucose level of 33 mg/dL and a creatinine concentration of 6.2 mg/dL. RESULTS: The patient was treated with a 5% dextrose and, subsequently, a 10% dextrose infusion without any sustained improvement. The blood glucose level remained low despite the additional administration of 3 ampules of 50% dextrose in water. The patient was given a bolus of octreotide (50 mug subcutaneously) 14 hours after his second presentation. He received another 50-mug dose of octreotide 6 hours later. After this bolus, the hypoglycemia resolved, and he no longer required intravenous administration of glucose to maintain euglycemia. CONCLUSION: Patients with diabetes and kidney disease frequently have persistent and difficult-to-treat hypoglycemia, unresponsive to conventional therapy. Octreotide is an effective and safe treatment for patients with refractory hypoglycemia attributable to sulfonylureas.

Impairment of fetal endothelium-dependent relaxation in a rat model of preeclampsia by chronic nitric oxide synthase inhibition.

OBJECTIVE: We studied fetal endothelial function in a model of preeclampsia induced by Nomega-nitro-l-arginine methylester (L-NAME) administration in pregnant rats. METHODS: Aortic segments from term fetuses and 2-day-old Wistar rats treated with L-NAME (0.5 mg/mL in drinking water) (fetuses from hypertensive rats, FH, and newborns from hypertensive rats, NH) and from untreated rats (fetuses from normotensive rats, FN, and newborns from normotensive rats, NN) were obtained. Endothelium-dependent and -independent relaxations were determined by the response to 1 microM acetylcholine (ACh) and 1 microM sodium nitroprusside (SNP), respectively, after precontraction with 3 microM prostaglandin F2alpha. The role of nitric oxide in ACh relaxation was assessed by incubation with 0.1 mM N(G)-monomethyl-l-arginine (L-NMMA) or 0.1 mM l-arginine (l-Arg). Precontraction with 50 mM potassium chloride assessed the role of hyperpolarizing mechanisms. RESULTS: In FH, ACh-induced relaxation was reduced (FH 34.2 +/- 4%, FN 45.8 +/- 2%, P < .05), whereas that of SNP was enhanced (FH 68.4 +/- 5%, FN 50.4 +/- 4%, P < .05). l-Arg did not reverse the impairment of ACh relaxation. L-NMMA reduced ACh relaxation in FN but increased it in FH; this increase was abolished by potassium chloride precontraction and by 1 microM capsaicine, a calcitonin-gene related peptide inhibitor. The hyperpolarizing component of ACh relaxation was reduced in FH as compared with FN. By contrast, ACh relaxation was greater in NH than in NN, with the relative participation of nitric oxide and hyperpolarizing-related components being similar in both groups. CONCLUSION: Fetal ACh relaxation was impaired in this preeclampsia-like model. This impairment is probably not exclusively an effect of L-NAME but could reflect endothelial dysfunction that disappears after birth.

Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia.

This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.

Administration of N(omega)-L-arginine methyl ester (L-NAME) impairs endothelium-dependent relaxation in gravid but not nongravid rats.

OBJECTIVE: To characterize the impairment of endothelium-dependent relaxation induced by administration of the nitric oxide synthase (NOS) inhibitor N(omega)-L-arginine methyl ester (L-NAME) to gravid rats and to determine whether L-NAME affects nongravid rats in a similar manner. METHODS: Acetylcholine (ACh; 0.01-10 microM) relaxation was studied in aortic segments (contracted with 10 nM norepinephrine) from Wistar rats that were hypertensive after receiving L-NAME (0.5 mg/mL in drinking water) before gravidity (hypertensive virgin rats [HVR]), during gravidity (hypertensive gravid rats [HGR]), or during the last 10 days of gravidity to 24 hours postpartum (hypertensive puerperal rats [HPR]). We also studied aortic segments from corresponding groups of untreated normotensive rats (normotensive gravid rats [NGR], normotensive puerperal rats [NPR], and normotensive virgin rats [NVR]). The approximate participations of NO and the hyperpolarizing mechanisms in ACh relaxation were calculated from the reduction of relaxation observed, respectively, after incubation with the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 0.1 mM) or after contraction with 50 mM of potassium chloride. Expression of endothelial NOS protein was studied by Western blot in segments of HGR and NGR. RESULTS: Acetylcholine relaxation was reduced in HGR compared with NGR, and this reduction correlated with the severity of hypertension. In contrast, ACh relaxation in HVR was similar to that in NVR, and that of HPR was similar to that in NPR. The NO component of relaxation was reduced in HGR but preserved in the other groups. Nevertheless, there were no differences in endothelial NOS protein expression between NGR and HGR. The hyperpolarizing component in relaxation was enhanced in HVR and HPR but not HGR. CONCLUSION: Administration of L-NAME induced an impairment of endothelium-dependent relaxation, involving both nitric oxide- and hyperpolarizing-dependent mechanisms in gravid but not virgin rats; this impairment resolved with delivery.