Sensibilidad de las pruebas treponémicas en donantes de sangre del Hospital Pablo Tobón Uribe 2012-2014 / Sensitivity of treponemal tests in blood donors at Hospital Pablo Tobon Uribe 2012-2014 / Sensibilidade das provas treponêmicas em doadores de sangue do Hospital Pablo Tobón Uribe 2012-2014

Objetivo: el diagnóstico serológico de las pruebas para sífilis tiene un rango de falsos positivos que varía entre el 1 y 3% en el área del tamizaje de esta enfermedad infecciosa en donantes de sangre. El uso de las pruebas treponémicas y no treponémicas además de la implementación de nuevas técnicas como pruebas automáticas no treponémicas ha variado constantemente buscando mejorar sus parámetros de sensibilidad y especificidad. El objetivo de este estudio es evaluar la sensibilidad diagnóstica de las pruebas treponémicas y no treponémicas para el tamizaje de sífilis entre los donantes de sangre del Hospital Pablo Tobón Uribe. Metodología: estudio observacional de corte transversal en el Hospital Pablo Tobón Uribe en realizado entre enero de 2012 y diciembre de 2014. Se registraron los resultados de 342 pacientes con serología positiva para sífilis por pruebas iniciales de tamizaje treponémica y no treponémicas y se utilizó el FTA-ABS como gold estándar para valoración de la sensibilidad de estas en el escenario de donación de sangre. Resultados: los porcentajes de sensibilidad de las pruebas no treponémicas RPR y la prueba automatizada con sistema Architec fueron respectivamente: sensibilidad 29,3 % (IC 95% 22,9-35,6) y 99,53 (IC 95% 98,39-100). Conclusiones: la prueba treponémica Architect difiere en cuanto sensibilidad en comparación con la prueba no treponémica RPR, en el escenario del tamizaje para sífilis en donantes de sangre la utilización del estándar de referencia permite disminuir la brecha de errores al detectar la enfermedad.

Objective: The serological diagnosis of syphilis has a range of false positives varying from 1 to 3%. The use of treponemal and nontreponemal tests for screening as well as the implementation of automatic methods has been changing constantly in an effort to improve sensitivity and specificity parameters. We assessed the sensitivity for the syphilis screening of treponemal and nontreponemal tests in blood donors at Hospital Pablo Tobón Uribe. Methodology: An observational, cross-sectional study conducted from January 2012 to December 2014. Results from 342 patients were registered with positive serology by treponemal and nontreponemal tests, using the FTA-ABS as gold standard in the blood donors scenario. Results: The sensitivity percentages of the nontreponemal test RPR and the automatic test Architect were 29.3% (CI 95% 22.9-35.6) and 99.53% (CI 95% 98.39-100), respectively. Conclusion: the Architect treponemal test has a better sensitivity than the nontreponemal test RPR. In the scenario of syphilis screening in blood donors, the treponemal test reduces the mistakes when detecting the infectious disease.

Objetivo: o diagnóstico serológico das provas para sífilis tem uma faixa de falsos positivos que varia entre 1 e 3% na área da triagem desta doença infecciosa em doadores de sangue. O uso das provas treponêmicas e não treponêmicas ademais da implementação de novas técnicas como provas automáticas não treponêmicas há variado constantemente buscando melhorar seus parâmetros de sensibilidade e especificidade. O objetivo deste estudo é avaliar a sensibilidade diagnóstica das provas treponêmicas e não treponêmicas para a triagem de sífilis entre os doadores de sangue do Hospital Pablo Tobón Uribe. Metodologia: estudo observacional de corte transversal no Hospital Pablo Tobón Uribe realizado entre janeiro de 2012 e dezembro de 2014. Se registraram os resultados de 342 pacientes com serologia positiva para sífilis por provas iniciais de triagem treponêmica e não treponêmicas e se utilizou o FTA-ABS como gold padrão para valorização da sensibilidade destas no cenário de doação de sangue. Resultados: as porcentagens de sensibilidade das provas não treponémicas RPR e a prova automatizada com sistema Architec foram respectivamente: sensibilidade 29,3 % (IC 95% 22,9-35,6) y 99,53 (IC 95% 98,39-100). Conclusões: a prova treponémica Architect difere em quanto sensibilidade em comparação com a prova não treponémica RPR, no cenário da triagem para sífilis em doadores de sangue a utilização do padrão de referência permite diminuir a brecha de erros ao detectar a doença.

Diarrea poscolecistectomía, enfoque diagnóstico y terapéutico / Postcholecystectomy diarrhea, diagnostic and therapeutic approach / Postcholecystectomy diarrhea, aplicação diagnóstica e terapêutica

RESUMEN La colelitiasis es una enfermedad muy prevalente en la población general. El tratamiento de la colelitiasis, cuando se torna sintomática, es fundamentalmente quirúrgico. Una de sus complicaciones es la diarrea pos-colecistectomía que se define como la presencia de 3 o más deposiciones diarreicas por día por más de cuatro semanas en pacientes con el antecedente de colecistectomía, en ausencia de otra causa que explique la sintomatología. Debido a la incidencia reportada en la literatura alrededor del 15%, esta revisión presenta la epidemiologia, fisiopatología, diagnóstico, clasificación y tratamiento de esta patología. Adicionalmente se plantea una nueva clasificación de la patología que se correlacione con la fisiopatología.

ABSTRACT Cholelithiasis is a highly prevalent disease in general population. Treatment of cholelithiasis when it becomes symptomatic is fundamentally surgical. One of its complications is postcholecystectomy diarrhea that is defined as the presence of 3 or more watery depositions for a period longer than 4 weeks in patients with the surgical background in the absence of another cause that explains symptoms. Due to incidence reported in literature of 15%, this review presents epidemiology, physiopathology, diagnosis, classification and treatment of this disease. Additionally, a new classification of the pathology is proposed that correlates with the physiopathology.

RESUMO A colelitíase é uma doença altamente prevalente na população em geral. O tratamento da colelitíase quando se torna sintomático é fundamentalmente cirúrgico. Uma das suas complicações é a diarréia pós-elelectomicária que é definida como a presença de 3 ou mais deposições aquosas por um período superior a 4 semanas em pacientes com fundo cirúrgico na ausência de outra causa que explica sintomas. Devido à incidência relatada na literatura de 15%, esta revisão apresenta epidemiologia, fisiopatología, diagnóstico, classificação e tratamento desta doença. Além disso, propõe-se uma nova classificação da patologia que se correlaciona com a fisiopatologia.

Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim growth factor support in acute myeloid leukemia.

The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol. Time from start to chemotherapy until hematologic recovery with white blood cells >1.0 G/l and neutrophils >0.5 G/l was in median 4 days shorter in patients receiving HDAC-123 compared with HDAC-135 (P<0.0001, each), and further reduced by 2 days (P<0.0001) by pegfilgrastim. Rates of infections were reduced by HDAC-123 (P<0.0001) and pegfilgrastim (P=0.002). Days in hospital and platelet transfusions were significantly reduced by HDAC-123 compared with HDAC-135. Survival was neither affected by HDAC-123 versus HDAC-135 nor by pegfilgrastim. In conclusion, consolidation therapy with HDAC-123 leads to faster hematologic recovery and less infections, platelet transfusions as well as days in hospital without affecting survival.

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)

Valores de hemoglobina y hematocrito en más de 100 mil donantes del banco de sangre del Hospital Pablo Tobón Uribe, Medellín-Colombia (1538 msnm) / Hemoglobin and hematocrit values in over one hundred thousand donors at the blood bank at Hospital Pablo Tobón Uribe in Medellin, Colombia (1,538 masl) / Valores de hemoglobina e hematócrito em mais de 100 mil doadores do banco de sangue do hospital Pablo Tobón Uribe, Medellín-Colômbia (1538 Msnm)

Objetivo: determinar los valores de hemoglobina y hematocrito en donantes de sangre entre los años 2000-2009. Metodología: estudio observacional descriptivo con una muestra de 103.690 donantes compuesta por hombres y mujeres adultos que donaron hemoderivados de forma voluntaria en el banco de sangre del Hospital Pablo Tobón Uribe (HPTU). Las variables evaluadas en el estudio fueron sexo, edad, valores de hemoglobina y hematocrito. Resultados: el 50,7% de la muestra está compuesto por el sexo masculino, el 90,7% de los donantes reside en Medellín, la edad promedio fue 32,5 (±11,5) años. En hombres el promedio para hemoglobina y hematocrito fue 15,96 g/dl (±1,11) y 46,93% (±3,27) respectivamente; en mujeres el promedio fue 14,10 g/dl (±1,00) y 41,64% (±2,96), respectivamente. Conclusiones: los valores de hemoglobina y hematocrito están determinados por variables como sexo, edad, ancestría y la altura sobre el nivel del mar. Por esta razón es menester que cada población conozca sus valores en relación con sus propios determinantes.

Objective: Determine hemoglobin and hematocrit values in blood donors between the years 2000-2009. Methods: An observational descriptive study with a sample of 103,690 donors composed of men and women adults who voluntarily donated blood in the blood bank of the Hospital Pablo Tobón Uribe (HPTU). The variables evaluated in the study were sex, age, hemoglobin and hematocrit. Results: The 50,7% of the sample composed of males, 90,7% of donors living in Medellin, the average age was 32,5 (±11,5) years. In men the average hemoglobin and hematocrit was 15,96g/dl (±1,11) and 46,93% (±3,27), respectively, in women the average was 14,10 g/dl (±1,00) and 41,64% (±2,96) respectively. Conclusions: The hemoglobin and hematocrit values are determined by variables such as sex, age, ancestry and height above sea level, therefore it is important that each population know about their values in relation to their own determinants.

Objetivo: determinar os valores de hemoglobina e hematócrito em doadores de sangue entre os anos 2000-2009. Metodologia: estudo observacional descritivo com uma mostra de 103.690 doadoras composta por homens e mulheres adultos que doaram hemoderivados de forma voluntária no banco de sangue do Hospital Pablo Tobón Uribe (HPTU). As variáveis avaliadas no estudo foram sexo, idade, valores de hemoglobina e hematócrito. Resultados: 50,7% da mostra está composto pelo sexo masculino, 90,7% dos doadores reside em Medellín, a idade média foi 32,5 (±11,5) anos. Em homens a média para hemoglobina e hematócrito foi 15,96 g/dl (±1,11) e 46,93% (±3,27), respectivamente; em mulheres a média foi 14,10 g/dl (±1,00) e 41,64% (±2,96), respectivamente. Conclusões: os valores de hemoglobina e hematócrito estão determinados por variáveis como sexo, idade, ancestrais e a altura sobre o nível do mar. Por esta razão é mister que cada população conheça seus valores em relação com seus próprios determinantes.

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)

Informes periciales por presunta responsabilidad médica en Bogotá / Forensic expert report on alleged medical liability in Bogotá

Antecedentes. La información sobre las demandas por responsabilidad profesional médica es clave para la formulación y ejecución de las políticas y programas alrededor de la seguridad del paciente. Actualmente, el sector de la salud en Colombia no posee información sistemática sobre los resultados adversos que conducen a demandas por responsabilidad médica.Objetivo. Caracterizar los casos por presunta falla en la responsabilidad profesional entre 2006-2010, en el Grupo de Clínica Forense, Regional Bogotá perteneciente al Instituto Nacional de Medicina Legal y Ciencias Forenses de Colombia. Métodos. Análisis descriptivo uni y bivariado de los informes periciales disponibles. Resultados. Se recolectó la información de 402 casos. El 77 % de los casos fue de la ciudad de Bogotá. 69,2 % en mujeres. El promedio de edad fue de 36,4 años. Los prestadores de salud privados fueron el 52 %. El 80 % de las demandas fueron contra el Estado y directamente contra los profesionales, el 59 % de las demandas fueron penales. El tipo de especialidades médicas más frecuentes en los casos analizados fueron 41 % en ginecológica y obstetricia, 45 % en otras áreas quirúrgicas, 6 % en áreas clínicas y 5 % en pediatría. Los diagnósticos más frecuentes fueron la muerte fetal de causa no especificada, la punción o laceración accidental durante un procedimiento. 45 %, de los informes fueron hechos por especialistas clínicos o quirúrgicos. En 225 informes se concluyó que se trataba de una complicación y en 165 que la atención se apartaba de la norma de atención.

Background. Information on medical liability lawsuits is critical for the formulation and implementation of policies, programs and actions pertaining to patient safety. There is no systematic information at present in the Colombian health sector regarding adverse outcomes resulting in professional liability lawsuits. Objective. To characterize the cases of alleged professional liability analyzed in the Bogota Chapter of the Clinical Forensics Group of the National Legal Medicine and Forensic Sciences Institute of Colombia between 2006-2010. Methods. A descriptive, uni and bivariate analysis of the forensic expert reports available was conducted. Results. Information was gathered for 402 cases. 77 % occurred in Bogota, 69.2 % were associated with women, the mean age was 36.4 years, and the private healthcare providers accounted for 52 % of the total. 80 % of the lawsuits were filed against the State and directly against the practitioners, and 59 % were criminal cases. The percentage of medical specialties involved most frequently was distributed as follows: 41 % in obstetrics and gynecology, 45 % in other surgical areas, 6 % in clinical areas and 5 % in pediatrics. The most frequent diagnoses were: fetal death of unexplained cause, accidental puncture or laceration during a procedure. 45 % of forensic reports were prepared by clinical or surgical specialists. The conclusion in 225 reports was that the case was the result of a complication, whereas in 165 the conclusion referred to a deviation from standard practice.

Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKCθ expression. Is there any advantage in using several markers?

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKCθ was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to determine the sensitivity and diagnostic value of these markers. KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified by PCR and sequenced. A total of 94/99 (94%) GISTs stained positive for CD117, 81/99 (82%) for PKCθ and 90/99 (91%) for DOG-1. A significant correlation was noted between CD117 and DOG-1 expression (p=0.0001). All three markers were expressed in 74% (73/99) of GISTs. Of the five CD117-negative cases, two were PKCθ-negative/DOG1-negative and had mutations in KIT exon 11. Two were PKCθ-positive/DOG1-positive and had mutations in PDGFRA (one each in exons 12 and 18), and one was DOG1-negative/PKCθ-positive, with a PDGFRA exon 18 mutation. The most sensitive marker was CD117, followed by DOG-1 and PKCθ. Although PKCθ was less sensitive, and its staining is more challenging and difficult to interpret, the use of this marker is highly recommended, particularly in CD117-negative/DOG-1-negative GISTs.

Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors.

AIM: To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression. MATERIALS AND METHODS: Ninety-nine paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117, IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and pS6 expression were investigated using immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and sequenced. RESULTS: Significant differences were found in the expression of phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R expression and either mutational status or pathway activation. CONCLUSION: There appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs, irrespective of mutational status, displayed no IGFR1 expression; tumors positive for IGFR1 showed no preferential activation of the MAPK or AKT pathways.

Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.

OBJECTIVES: To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. METHODS: Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. RESULTS: Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90). CONCLUSIONS: Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study.

OBJECTIVE: To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed. INTERVENTION: Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.

Flavonoid profile of green asparagus genotypes.

The determination of flavonoid profiles from different genotypes of triguero asparagus and their comparison to those from green asparagus commercial hybrids was the main goal of this study. The samples consisted of 32 commercial hybrids and 65 genotypes from the Huetor-Tajar population variety (triguero). The analysis of individual flavonoids by HPLC-DAD-MS has allowed the determination of eight naturally occurring flavonol derivatives in several genotypes of triguero asparagus. Those compounds included mono-, di-, and triglycosides of three flavonols, that is, quercetin, isorhamnetin, and kaempferol. The detailed analysis of the flavonoid profiles revealed significant differences among the distinct genotypes. These have been classified in three distinct groups as the result of a k-means clustering analysis, two of them containing both commercial hybrids and triguero asparagus and another cluster constituted by 21 genotypes of triguero asparagus, which contain several key flavonol derivatives able to differentiate them. Hence, the triglycosides tentatively identified as quercetin-3-rhamnosyl-rutinoside, isorhamnetin-3-rhamnosyl-rutinoside, and isorhamnetin-3-O-glucoside have been detected only in the genotypes grouped in the above-mentioned cluster. On the other hand, the compound tentatively identified as isorhamnetin-3-glucosyl-rutinoside was present in most genotypes of triguero asparagus, whereas it has not been detected in any of the commercial hybrids.

Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD).

BACKGROUND: Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. PURPOSE: and methods We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. RESULTS: IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. LIMITATIONS: The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. CONCLUSIONS: Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships.

Frecuencia de miomatosis uterina en pacientes de consulta externa: Hospital Universitario Central tipo IV Dr. Antonio María Pineda Barquisimeto estado Lara / Frequency of miomatosis uterina in patients of external consultation: Hospital Universitario Central type IV

El objetivo es Determinar la frecuencia de miomatosis uterina en las pacientes que acudieron a la consulta externa de ginecología y obstetricia. Se realizó un estudio descriptivo de corte transversal a la población de 1437 pacientes que acudieron a la consulta. El ambiente utilizado fue: Hospital Central Universitario Tipo IV "Dr. Antonio María Pineda" de Barquisimeto, enero a marzo de 2001. De esta población el 6,40 por ciento (92 casos) presentó miomatosis uterina, constituyendo la muestra del estudio. El 57,61 por ciento (53 casos) tenían edades entre 36-45 años. El 23,91 por ciento (22 pacientes) refirió hábito tabáquico, 14 casos (15,22 por ciento) eran nuligestas, 24 pacientes (26,09 por ciento) utilizaron anticoncepción oral y 32 pacientes presentaron patología médica de las cuales 12 (13,04 por ciento) tenían hipertensión arterial. La frecuencia de miomatosis uterina reportada, es significativa tomando en cuenta que todos eran casos sintomáticos y que su tratamiento genera costos elevados además de riesgos quirúrgicos

Rapid communication: development of in vitro resistance to macrophage-tropic- and T-cell-line-adapted HIV-1 strains among HIV-positive volunteers treated with highly active antiretroviral therapy.

We have described a peripheral blood mononuclear cell (PBMC) culture system in which control of endogenous virus and resistance to exogenous HIV-1 correlates with low viremia among HIV-1-positive people. Nineteen patients remained consistently resistant or susceptible for more than 5 years of follow-up. On the fifth year, 5 consistently susceptible volunteers with high viral loads began receiving highly active anti-retroviral therapy (HAART). After >6 months on HAART, 5 of 5 became completely or predominantly resistant on four visits over the next 6 months. Among HIV-1-positive donors, we had never observed reversal of PBMC phenotype from consistently susceptible to consistently resistant. Resistance correlated with suppression of plasma viremia and rebound in CD4+ T-cell counts and percentages. When resistant PBMCs were challenged after CD8+ T-cell depletion, 38 of 41 and 40 of 59 cultures became susceptible to HIV-1MN and HIV-1BaL, respectively. After combined CD8+ T-cell depletion and antibody neutralization of beta-chemokines, 16 of 18 cultures became susceptible to HIV-1BaL. Overall, the finding that >90% of these cultures depleted of relevant antiviral effector arms could become infected indicates resistance was not due to residual antiretroviral drug metabolites in vitro. For 2 volunteers who discontinued therapy because of side effects, pretreatment viral load correlated with loss of in vitro resistance and viral rebound. In addition to resistance to laboratory strains of HIV-1, all patients developed resistance to at least one of two CCR5-tropic, clade B primary isolates: HIV-1P15 and HIV-1P27.

Resistance to human immunodeficiency virus type 1 in vitro as a surrogate of vaccine-induced protective immunity.

An in vitro assay developed as a correlate of vaccine-induced protection from human immunodeficiency virus (HIV) was validated in populations with relative resistance to HIV-1 as well as in HIV vaccine recipients. Cultures of peripheral blood mononuclear cells (PBMC) were challenged with 10 TCID50 of HIV-1MN or HIV-1BaL, titered in PBMC from normal controls (n=57). PBMC from HIV-1-infected persons with low viremia (n=17), exposed uninfected persons (n=23), and HIV-2-infected Senegalese prostitutes (n=9) were significantly resistant to HIV-1BaL and/or HIV-1MN (P<.001). Among 34 HIV vaccine recipients of live canarypox vector expressing multiple HIV-1 gene products with or without rgp120 booster, PBMC from postvaccination samples were significantly resistant to both strains (P<.001), and cytotoxic T lymphocyte precursor-positive samples were significantly more resistant than were precursor-negative samples (P<.03). This is the first evidence of the induction by vaccination of a validated correlate of protection. This assay should serve as a useful criterion for assessing experimental HIV vaccines before phase III efficacy trials.

A novel factor produced by placental cells with activity against HIV-1.

The factors controlling the dynamics of HIV-1 transmission from mother to infant are not clearly known. Previous studies have suggested the existence of maternal and placental protective mechanisms that inhibit viral replication in utero. Preliminary studies from our laboratory revealed that supernatant from placental stromal cells protected HIV-1-infected PBMC from virus-induced apoptosis and suppressed virus production. We have attempted to characterize the antiviral activity of this placental factor (PF) and delineate the stages of HIV-1 replication affected. This activity was not due to the presence of any known cytokine reported to have anti-HIV effect. Direct exposure to PF had no suppressive effect on the infectivity of cell-free HIV-1, and envelope-mediated membrane fusion appeared to be unaffected. Western blot analysis of HIV-1 from infected PBMC treated with PF revealed that expression of all viral proteins was reduced proportionately, both intracellularly and in released virions. However, exposure of HIV-1-infected cells to PF resulted in production of virions with 10-100-fold-reduced infectivity. PF-treated virions contained two- to threefold reduced ratios of cyclophilin A:Gag protein as compared with untreated virus. Reduced cyclophilin A content resulting in decreased binding of cyclophilin A to Gag could account, in part, for the observed reduction in infectivity. Our results suggest that placental cells produce an antiviral factor that protects the fetus during gestation and may have therapeutic potential.

Synergistic transcriptional activation of the mouse urokinase plasminogen activator (uPA) gene and of its enhancer activator protein 1 (AP1) site by cAMP and retinoic acid.

We have investigated the mechanism whereby all-trans retinoic acid (tRA) potentiates the 8-bromo-cAMP (8-BrcAMP)-dependent transcription of the urokinase plasminogen activator (uPA) gene in SC115 mouse mammary carcinoma cells. Photoaffinity labelling experiments showed that tRA did not alter the cellular content of cAMP-dependent protein kinase regulatory subunits I and II. In agreement with this, nuclear run-on analysis in the presence of the translational inhibitor puromycin demonstrated that the effect of 8-BrcAMP and its potentiation by tRA were independent of protein synthesis. A transiently transfected 6.6 kb uPA 5'-flanking region-chloramphenicol acetyltransferase (CAT) fusion gene mimicked the response of the endogenous uPA gene. Thus 1 mM 8-BrcAMP induced a 100-200% increase in CAT content, 100 nM tRA had no effect and 100 nM tRA+1 mM 8-BrcAMP induced a 300-500% increase in cells co-transfected with tRA receptor and/or 9-cis-RA receptor. Analysis of 5'-deleted constructs showed that the tRA effect required at least two cis regions: -2657 to -2186, encompassing the 100 bp uPA enhancer, and -709 to -324, which exhibited silencing activity. Neither region contained a tRA-response element-like motif. Because tRA receptor and 9-cis-RA receptor interact with activator protein 1 (AP1), we tested whether tRA regulated the uPA enhancer AP1 site in the presence of 8-BrcAMP. We found that a dimer of this site fused to a minimal uPA-CAT fusion gene was responsive to 1 mM 8-BrcAMP (100% CAT increase), not responsive to 100 nM tRA, and synergistically responsive to 100 nM tRA+1 mM 8-BrcAMP (240% CAT increase) in cells co-transfected with Fos and Jun. Synergistic activation of the same construct and of the 6.6 kb uPA-CAT fusion gene was also obtained using tRA and 100 nM PMA. We conclude that multiple cis elements, probably including the uPA enhancer AP1 site, mediate the tRA potentiation of uPA transcription.

Chemokine-independent in vitro resistance to human immunodeficiency virus (HIV-1) correlating with low viremia in long-term and recently infected HIV-1-positive persons.

Chemokines have been implicated as protective factors against human immunodeficiency virus (HIV) infection, competing for binding to receptors that also function as coreceptors for HIV. In this study of HIV-positive donors, peripheral blood mononuclear cell (PBMC) culture resistance to endogenous and exogenous HIV correlated with low plasma viremia and high in vitro RANTES production. However, resistant cells were not rendered susceptible by neutralization of C-C chemokines, and addition of C-C chemokines did not consistently suppress endogenous virus or exogenous HIV-1MN. In contrast, CD8 T cell depletion markedly decreased the frequency of resistant cultures without reducing C-C chemokine production. Among newly infected persons, half exhibited phenotype switching from preinfection susceptibility to postinfection resistance, suggesting that genetically predetermined constitutive cytokine production or allelic receptor expression are not generally responsible for in vitro resistance and nonprogression.