[Remitting seronegative symetrical synovitis with pitting edema. One case report]. / Sinovitis simétrica seronegativa remitente con edema y fóvea. Presentación de un caso.

Background: RS3PE (remitting seronegative symmetrical synovitis with edema and pitting) is a rare entity of unknown etiology that has been related to genetic predisposition due to the presence of HLA-A2 in 50% of cases and less frequently HLA-B7. Its pathogenesis is unknown, but it has been related to growth factors, and some mediators (TNF, IL-6). It is common in elderly people and the course of this illness presents with acute symmetrical polyarthritis, accompanied by edema in hands and feet. The diagnosis requires a high index of suspicion and to differentiate it from other entities such as rheumatoid arthritis, complex regional pain syndrome, rheumatic polymyalgia, in addition to ruling out malignant neoplasms, since there are many reports of its association with both solid and hematological neoplasms, being of bad prognosis when there is association. When there is no association with cancer, it responds well to the use of low doses of steroids and its prognosis is usually favorable. Clinical case: 80-year-old woman with an acute onset with polyarthralgia, functional limitation associated with pitting edema in hands and feet. After approaching the patient and ruling out associated neoplasms, it was diagnosed RS3PE. It was managed with prednisone, observing a good response, with remission of the manifestations at 6 weeks and subsequent suspension of the steroid. Conclusions: RS3PE is a rare entity, and a high index of suspicion is required for the diagnosis. A complete approach is important to rule out cancer in patients affected with this syndrome. Prednisone continues to be the best therapeutic option.

Introducción: la RS3PE (sinovitis simétrica seronegativa remitente con edema y fóvea) es una entidad rara de etiología desconocida que se ha relacionado con predisposición genética por la presencia de HLA-A2 en el 50% de los casos y con menor frecuencia HLA-B7. Se desconoce su patogenia, pero se ha relacionado con factores de crecimiento y algunos mediadores (TNF, IL-6). Se presenta en personas de edad avanzada, cursa con poliartritis aguda simétrica, acompañada de edema en manos y pies. El diagnóstico requiere de un alto índice de sospecha y diferenciarlo de otras entidades como artritis reumatoide, síndrome de dolor regional complejo, polimialgia reumática, además de descartar neoplasias malignas, ya que existen muchos reportes de su asociación con neoplasias tanto sólidas como hematológicas y es de mal pronóstico cuando existe asociación. Cuando no existe asociación con cáncer tiene buena respuesta al uso de dosis bajas de esteroides y su pronóstico suele ser favorable. Caso clínico: mujer de 80 años con un cuadro de inicio agudo con poliartralgias, limitación funcional asociada a edema de manos y pies con fóvea. Después del abordaje y de descartar neoplasias asociadas, se diagnosticó RS3PE. Se manejó con prednisona y hubo buena respuesta, con remisión de las manifestaciones a las 6 semanas y suspensión posterior del esteroide. Conclusiones: la RS3PE es una entidad rara y para diagnosticarla se requiere un alto índice de sospecha. Es importante el abordaje completo para descartar cáncer en los pacientes afectados con este síndrome. La prednisona continúa siendo la mejor opción terapéutica.

Influence of Genetic Admixture Components on CYP3A5*3 Allele-Associated Hypertension in Amerindian Populations From Northwest Mexico.

CYP3A5 metabolizes endogenous substrates and ~30% of prescription drugs. The CYP3A5 gene contains an active CYP3A5*1 allele, and a non-functional version, the CYP3A5*3 (rs776746), with consequences for drug therapeutic responses and side effects. Both CYP3A5*1 and *3 have been associated with hypertension. The frequency of CYP3A5*3 varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of CYP3A5*3 in drug response and hypertension development, the aim of the present study was to evaluate the frequency of this polymorphism and its association with hypertension in vulnerable indigenous populations in Mexico. A total of 372 subjects were recruited from eight ethnic groups in Northwest Mexico. Systolic (SBP), diastolic (DBP), and median (MBP) blood pressures as well as body mass index (BMI) were measured. Ancestry was evaluated through STR analysis, and the CYP3A5*1/*3 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of CYP3A5*1 and *3 were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The CYP3A5*3/*3 genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the *1 allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17-0.83, p = 0.001) and DBP (OR 0.38, 95% CI 0.18-0.81, p = 0.007) in women. This association remained significant after adjusting for BMI and age for diastolic (OR, 0.38; 95% CI, 0.17-0.84, p = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15-0.76, p = 0.005) BP levels in women. Thus, the frequency of CYP3A5*3 varies between groups and seems to depend on ancestry, and CYP3A5*1 decreases the risk of hypertension in Mexican indigenous women. This population analysis of CYP3A5*1/*3 has profound implications not only for the susceptibility to diseases, such as hypertension, but also for safer drug administration regimens, assuring better therapeutic responses and fewer side effects.

The paternal polymorphism rs5370 in the EDN1 gene decreases the risk of preeclampsia.

OBJECTIVE: To evaluate whether the maternal, paternal or the combined maternal/paternal contribution of SNP rs5370 of the EDN1 gene is associated with preeclampsia and drove its expression in placenta. STUDY DESIGN: This case-control study included 61 preeclamptic patients and their partners and 49 healthy pregnant women and their partners. The population was sub-divided into three groups: women-only, men-only and combined (women/men). The analysis included genotyping of rs5370 in mothers and fathers and evaluating the expression profile of the EDN1 gene in placenta. Comparisons of categorical variables were performed using chi-square and/or Fisher's exact tests. The intergroup comparisons were analysed with the Mann-Whitney U test. The association between the polymorphism and the disease was evaluated through multivariate regression analysis. Spearman's correlation was performed to test the relationship between pre-gestational history and clinical features of the affected patients with EDN1 gene expression. RESULTS: The analysis of paternal risk factors associated with preeclampsia revealed no differences between groups. A negative association between SNP rs5370 and preeclampsia was found in men group (OR 0.42; CI 95% 0.18-0.94, p=0.034) but not in women or combined groups. The adjustment for paternal protective factors increased the observed negative association, and the opposite was observed in the presence of paternal risk factors. The expression of the EDN1 gene in the placenta was significantly higher in the group of cases and was not associated with the rs5370 polymorphism. CONCLUSION: The paternal rs5370 polymorphism decreases the risk for preeclampsia and is not associated with placental expression of the EDN1 gene.

Experience preferred: insights from our newest public health professionals on how internships/practicums promote career development.

Universities offering undergraduate degrees in health promotion or health education and/or graduate degrees in public health typically require an internship, practicum, or fieldwork experience. This type of mentored experience is an important aspect of career development for the next generation of public health professionals and benefits not only the students but also the profession and the communities in which they work. This article provides perspectives from four public health professionals who have recently graduated from designated minority-serving institutions and highlights the ways in which internship, practicum, or fieldwork experiences have contributed to their career development. From a career development perspective, internships provide unique opportunities to develop professional networks, practice competencies learned in the classroom, gain experience in different environments, and share lessons learned with others in our field. The diversification of the public health research and practice workforce is increasingly recognized as crucial in building health equity. Internship programs that focus specifically on the academic and professional development of students underrepresented in public health provide experiences that meet or supplement academic requirements, and provide students with real-world experience and an expanded network of mentors and role models.

[Cystic fibrosis: molecular update and clinical implications]. / Fibrosis quística: la frontera del conocimiento molecular y sus aplicaciones clínicas.

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic pneumopathy, pancreatic insufficiency, elevated sweat chloride levels and male infertility. It is caused by defects in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as a chloride channel. The identification of the CF-causing gene was a landmark in molecular medicine. Currently, over 1,300 disease-causing mutations have been reported to the Cystic fibrosis genetic analysis consortium. deltaF508 mutation is the most common CF allele, however a high heterogeneity of the CFTR mutations spectrum has been observed in populations, particularly in southern Europe and Latin America. Depending on the effect at the protein level, CFTR mutations can be divided in at least 5 classes. These mutations could cause totally (classes I-III) or partially (classes IV and V) loss of the protein function. The molecular defects resulting from different mutations in CFTR partially explain the clinical heterogeneity of the disease, suggesting the existence of modifier genes that are involved in modulating the phenotype and severity of the CF. In this review, we discuss the fundamental aspects and the recent progress that could give to the lector, the knowledge to understand the CFTR gene structure, the function of the CFTR protein, how CF mutations disrupt it, its phenotype consequences and finally, the strategies to design new therapies for the disease.

Fibrosis quística: la frontera del conocimiento molecular y sus aplicaciones clínicas / Cystic fibrosis: molecular update and clinical implications

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic pneumopathy, pancreatic insufficiency, elevated sweat chloride levels and male infertility. It is caused by defects in the CF trans membrane conductance regulator (CFTR) gene, which encodes a protein that functions as a chloride channel. The identification of the CF-causing gene was a landmark in molecular medicine. Currently, over 1,300 disease-causing mutations have been reported to the Cystic fibrosis genetic analysis consortium. ÁF508 mutation is the most common CF alíele, however a high heterogeneity of the CFTR mutations spectrum has been observed in populations, particularly in southern Europe and Latin America. Depending on the effect at the protein level, CFTR mutations can be divided in at least 5 classes. These mutations could cause totally (classes I-III) or partially (classes IV and V) loss of the protein function. The molecular defects resulting from different mutations in CFTR partially explain the clinical heterogeneity of the disease, suggesting the existence of modifier genes that are involved in modulating the phenotype and severity of the CF. In this review, we discuss the fundamental aspects and the recent progress that could give to the lector, the knowledge to understand the CFTR gene structure, the function of the CFTR protein, how CF mutations disrupt it, its phenotype consequences and finally, the strategies to design new therapies for the disease.

La fibrosis quística (FQ) es un padecimiento autosómico recesivo que se caracteriza por neumopatía crónica, insuficiencia pancreática, elevación de cloruros en sudor e infertilidad masculina. Esta patología es causada por la presencia de mutaciones en el gen CFTR que codifica para un canal de cloro denominado proteína reguladora de la conductancia transmembranal (CFTR). Hasta la fecha se han reportado alrededor de 1,300 mutaciones diferentes, cuya frecuencia varía entre los diversos grupos étnicos. Estas mutaciones condicionan la pérdida total (clases I, II y III) o parcial (clases IV y V) de la función de la proteína y causan un defecto en el transporte de electrólitos en la membrana apical de las células epiteliales. Con excepción de la función pancreática, las manifestaciones clínicas de la FQ son variables aun en pacientes con el mismo genotipo, por lo que la presencia de las diferentes mutaciones en el CFTR explica sólo parcialmente la heterogeneidad clínica de la FQ. Recientemente se ha propuesto que otros genes denominados genes modificadores participan en la gravedad del cuadro clínico. Así, la FQ es una enfermedad genética que resulta en un amplio espectro de manifestaciones clínicas que pueden ir desde muy leves hasta conducir a la muerte durante los primeros meses de vida, por lo que en algunos casos el diagnóstico es sumamente complejo. En los últimos años, el gran alud de conocimientos ha permitido entender el defecto básico de la enfermedad y los mecanismos que la condicionan, por lo que en esta revisión se discuten los fundamentos para el entendimiento de la fisiopatología de la FQ, desde los aspectos clínicos hasta los avances moleculares más recientes.

Bronquio traqueal derecho y persistencia de conducto arterioso diagnosticados por tomografía axial computarizada en un enfermo con síntomas sugestivos de asma / Computerized axial tomography in the diagnosis of a right tracheal bronchus and patent ductus arteriosus in a patient with an asthma-like syndrome

Un varón de 12 años, con sintomatología respiratoria desde los tres meses de vida fue manejado como asmático desde los cinco años, con esteroides y agentes beta dos inhalados, además de inmunoterapia específica durante 18 meses, sin mejoría. La tomografía computada de tórax reveló disminución de calibre de la tráquea con emergencia, por debajo de la misma, de un bronquio traqueal (BT) en la pared lateral derecha de la tráquea, independizando el lóbulo superior derecho del árbol bronquial. Se observó también la persistencia del conducto arterioso (PCA) y una variante anatómica hepática. Estudios de reconstrucción multiplanar, broncoscopía virtual, cateterismo hemodinámico y broncoscopía confirmaron los diagnósticos. No se encontró Tetralogía de Fallot como defecto cardiaco congénito más comúnmente asociado a la variante del BT para lóbulo superior derecho. Posteriormente al cierre programado de PCA, egresó por mejoría clínica.

A 12 year old male had symptoms suggesting asthma since the third month of age; he was managed with inhaled steroids and bronchodilatadors and specific immunotherapy for 18 months, without improvement. Conventional computed tomography (CT) showed tracheai narrowing and a bronchi emerging from the right lateral wall of the trachea, separating the right upper lobe from the tracheobronchial tree. The CT also revealed a patent ductus arteriosus and an anatomic variant of the liver. Helical CT scans, virtual bronchoscopy, cardiac catherization and bronchoscopy confirmed the diagnoses. In this case, Fallot's tetralogy, the commonest cardiac anomaly associated with tracheai bronchi to the right upper lobe, was not found. Symptoms improved after surgical division of the patent ductus arteriosus.

Quiste broncogéiico: reporte de dos casos y revisión de la literatura

El quiste broncogénico es una malformación de la porción ventral del intestino primitivo que ocasiona alteración en el desarrollo del árbol traqueo bronquial. Reportamos dos casos de quistes broncogénicos en niños, ambos con síntomas respiratorios crónicos, uno de localización mediastinal a nivel paratraqueal derecho y, el otro, intraperenquimatoso en lóbulo superior derecho. La radiográfia y tomografía de tórax permitieron evaluar el tipo de lesión, localización y tamaño, así como la compresión de la vía áerea. Ambos pacientes fueron intervenidos quirúrgicamente no se presentaron complicaciones y los síntomas respiratorios desaparecieron. El estudio histopatológico confirmó el diagnóstico.

Bronchogenic cyst arises from abnormal budding of the diverticulum of the foregut that leads to abnormality of the tracheobronquial tree. We report two cases of these cysts in children with respiratory chronic symptom. One was localized in paratraqueal mediastinum and other, intrapulmonary in lower upper right side. The chest radiography and computed tomography allowed evaluation as to the type, site and size of lesion as well as airway compression. Both patients underwent surgery; there were no complications and the respiratory symptoms disappeared. Histologic features confirm the diagnosis.

Using multiple cutpoints for the free-to-total prostate specific antigen ratio improves the accuracy of prostate cancer detection.

BACKGROUND: Using a single cutpoint for the free-to-total (F/T) prostate specific antigen (PSA) ratio loses important diagnostic information. We evaluated the performance of multiple F/T PSA cutpoints in detecting prostate cancer in men with nonspecific PSA values. METHODS: We extracted sensitivity and specificity data from 12 studies reporting on >or=30 cancer patients with PSA values between 2.0 and 10.0 ng/mL. We calculated stratum-specific likelihood ratios (LR) and areas under the receiver operating characteristic (ROC) curves. RESULTS: Multiple cutpoints for the F/T PSA ratio significantly increased the area under the ROC (0.70) compared with the single investigator-selected cutpoint (0.62), P < 0.004. The LR for the most positive cutpoint stratum (2.62) was significantly higher than the LR for a positive test from the single cutpoint (1.36), P < 0.004. CONCLUSIONS: Using multiple cutpoints increased the discriminating power of the F/T PSA ratio and led to greater probability revisions in the most positive test-result strata.