Clinical impact of Doppler reference charts on management of small-for-gestational-age fetuses: need for standardization.

OBJECTIVE: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR). METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management. RESULTS: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol. CONCLUSIONS: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.

OBJECTIVE: Defective trophoblastic invasion is a key feature in many cases of pre-eclampsia (PE). Uterine artery (UtA) Doppler is a validated non-invasive proxy for trophoblastic invasion. The aim of this study was to explore whether low-dose aspirin, administered from the first trimester, improves trophoblastic invasion, evaluated by UtA Doppler during the second and third trimesters in women defined as high risk by abnormal first-trimester UtA Doppler. METHODS: This randomized Phase-II study had a triple-blind, parallel-arm, controlled design. Singleton pregnancies with abnormal mean UtA Doppler at 11-14 weeks and absence of other major risk factors for PE received 150 mg extended-release aspirin or identical-appearing placebo tablets from study inclusion to 28 weeks. Main outcome measure was UtA pulsatility index (PI) at 28 weeks' gestation. Secondary outcomes included frequency of development of PE and growth restriction/small-for-gestational age (SGA). RESULTS: A total of 155 women completed the follow-up and were analyzed. No difference in mean UtA-PI was found between women in the aspirin and placebo groups at 28 weeks (mean UtA-PI Z-score (mean ± SD), 0.99 ± 1.48 vs 0.85 ± 1.25; P = 0.52). Seven women developed PE: four (5%) in the aspirin group and three (4%) in the placebo group. There was a trend toward lower incidence of SGA in the aspirin group (8.8% vs 17.3%; P = 0.11). CONCLUSION: In women with defective trophoblastic invasion, as reflected by abnormal UtA Doppler, low-dose aspirin started in the first trimester does not have a significant effect on UtA impedance as pregnancy progresses; however, the study was underpowered to detect potential small effects . Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Proposal for a new microsurgical model for the study of induced endometriosis in Wistar rats. Preliminary results]. / Propuesta de un nuevo modelo microquirúrgico para el estudio de la endometriosis inducida en rata Wistar. Resultados preliminares.

The current knowledge status on the patogenesis of endometriosis as well as devastating consequences of disease evolution in women's reproductive health, have promoted researchers advances in a great manner during last years. The immunologic and neangiogenesis systems implication have opened new ways of knowledge over classic theories from the beginning of the xx century. The experimental resesearch, using animal induction models. Below we explain the first steps a new induction model ("PGR1-HotDog"), based on Wistar rats using a new disease autogeneration system, created for te study of the early stages of the endometriosis.

Early influence of aflatoxin B1 on the functional state of isolated rat hepatocytes.

The early effects (60 min) of aflatoxin B1 (AFB1) on membrane permeability and carbohydrate metabolism of liver cells were studied in fresh suspensions of rat hepatocytes. Evaluation by trypan blue exclusion, enzyme leakage, glycogen synthesis or degradation, and glyconeogenesis were chosen as viability tests. The results obtained showed an increase of lactate dehydrogenase (LDH), alanine aminotransferase (GPT) and aspartate aminotransferase (GOT) released into the medium and also an increase in the number of stained cells. These changes were significant at about 18 nmol/10(6) cells of AFB1, while a remarkable effect of the toxin on glyconeogenesis and glycogen synthesis or degradation was observed at 9 nmol/10(6) cells, doses commonly used for in vitro studies.

[Spontaneous intercostal pulmonary hernia: a case report]. / Hernia pulmonar intercostal espontánea: aportación de un caso.

In pulmonary hernia or pneumocele the lung protrudes through a defect in the chest wall. In this report of a case of spontaneous intercostal lung hernia, we describe the pathogenesis and classification of such hernias, including signs, symptoms, radiological findings and treatment methods. Our patient presented with severe chest pain at the base of the left hemithorax. A chest film and computed tomography of the region showed an left intercostal hernia. Surgical treatment was successful.

[Bronchial embolization in the treatment of hemoptysis]. / Embolización bronquial en el tratamiento de la hemoptisis.

The aim of this retrospective study was to evaluate the efficacy of bronchial artery embolization to treat hemoptysis. Eight hundred sixty-five patients were admitted to our hospital with hemoptysis during the study period. Bronchial arteriographs were obtained for 48, who suffered life-threatening hemoptysis refractory to medical treatment. The likely origin of bleeding was identified in 37: embolization was performed with particles measuring 250 to 1000 micra in size (Contour Emboli, Interventional Therapeutic Corporation, South San Francisco, California, USA) in 35 and with hemostatic collagen sponges in 2. The most common causes of hemoptysis were bronchiectasis (40%), pulmonary tuberculosis (33%), pulmonary aspergilloma (8%) and malignant neoplasm (8%), chronic bronchitis (6%); 4% of the cases were idiopathic. Immediate technical success was achieved in 34 patients (92%) as defined by the absence of hemorrhage for at least 24 hours. All embolized patients were followed until the first recurrence of bleeding or until discharge. Recurrence of hemoptysis (in the first month) was early in 5 patients (13.5%) and late (2 to 96 months) in 9 (24%). The severity of the initial and later episodes of hemoptysis was similar in all early recurrences and most late recurrences. A second embolization was performed six times, and medical and/or surgical treatment was given in all other cases. No significant complications attributable to the technique were observed. The results show that bronchial embolization is valid for the immediate control of life-threatening hemoptysis and has a low rate of severe complication; recurrence is relatively common.

[Effects of levofolinic acid on plasma homocysteine concentrations in healthy and young women in preconceptional care]. / Efecto del ácido levofolínico sobre las concentraciones de homocisteína plasmática en la mujer joven y sana en la consulta preconcepcional.

BACKGROUND: Increases in total plasmatic homocysteine (tHcy) represents a risk factor for neural tube defects. We studied the effects of levofolinic acid (l,5-formyl-tetrahydrofolic) on the plasmatic tHcylevels in women of child-bearing age. MATERIALS AND METHOD: Healthy women aged 18-35 years (n = 30) received levofolinic acid, 5 mg/day,orally for 30 days. Both tHcy and intraerythrocytic folate levels were measured before treatment (day 0), on days 2, 5, 10 and 30 within the treatment period and on days 30 (day 60) and 60 (day 90) after the treatment was finished. Plasmatic tHcy was measured by fluorescence polarisation immunoassay and intraerythrocyticfolates by chemiluminescent immunoassay. RESULTS: Plasmatic tHcy decreased from the second day of treatment onwards (day 0 vs. 2: mean of difference: -1.24 micromol/l; CI 95% = -0.84 to -1.63; p < 0.001). The maximum decline (32.3%) was observed after 30 days (mean of difference = -2.72 micromol/l; CI 95% = -2.20 to -3.24; p < 0.001).After finishing the treatment, the hypohomocysteinic effect persisted up to days 60 (mean of difference = -2.67 micromol/l; CI 95% = -2.07 to -3.26; p < 0.001)and 90 (mean of difference = -1.49 micromol/l; CI 95% = -0.94 to -2.03; p < 0.001). The response was greater when the plasmatic tHcy concentration was >= 9 micromol/l. CONCLUSIONS: Levofolinic acid leads to a earlier, intense and persistent drop of the plasmatictHcy levels.

Meckel's diverticulum adenocarcinoma: a rare malignant degeneration.

The case of a 40 year old male that, after the etiological study performed due to rectorrhages that was the only symptom he presented, was referred to an exploratory laparotomy. A disseminated adenocarcinoma arising in Meckels diverticulum was detected and palliative segmentary resection of the small bowel was performed. The lack of previous symptoms lead to the dissemination of the disease and to the impossibility of curative surgical resection of the tumor.

[Host plants of Aphis gossypii (Aphididae), vector of virus of Cucumis melo melon (Cucurbitaceae) in Costa Rica]. / Plantas hospederas de Aphis gossypii (Aphididae), vector de virus del melón Cucumis melo (Cucurbitaceae) en Costa Rica.

Plant species associated with commercial melon crops and surrounding areas were examined to identity the natural host plants of Aphis gossypii Glover. The study was conducted in two farms located in different melon production areas and plant life zones of Costa Rica. Plant species diversity, percent coverage and distribution over time were recorded during one year. Differences between locations were observed. A total of 86 plant species (49 families) and 72 plant species (40 families) were identified associated to the crop in farms A and B, respectively. In both farms a total of 24 species plants (16 families) were colonized by A. gossypii and 16 (10 families) are new reports of host plant species for this aphid. The new reports are: Justicia comata, Tetramerium nervosum, Alternanthera pubiflora, Cassia massoni, C. reticulata, Cleome viscosa, C. spinosa, Croton argenteus, Caperonia palustris, Chamaesyce gyssopilopia, Phyllantus amarus, Sida decumbens, Ludwigia erecta, Passiflora foetida, Guazuma ulmifolia and Corchorus orinocensis.

Human toll-like receptor 1 T1805G polymorphism and susceptibility to pulmonary tuberculosis in northern Spain.

Toll-like receptors (TLRs) are key sensors of mycobacterial infections and play a crucial role in the initiation and coordination of the antimycobacterial innate immune response. T1805G, a functional TLR1 single nucleotide polymorphism (SNP), has been associated with susceptibility to pulmonary tuberculosis (PTB), but contradictory results among different populations have been reported. Our objective was to study this SNP in a genetically homogeneous population to evaluate its role in conferring susceptibility or resistance to PTB. In our population, the 1805G allele and the GG genotype (OR 2.04, 95%CI 1.26-3.31) influence susceptibility to PTB, in contrast with data observed in other populations.

[Detection of latent tuberculosis infection in peritoneal dialysis patients: new methods]. / Detección de la infección tuberculosa latente en pacientes en diálisis peritoneal: Nuevos métodos.

OBJECTIVE: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon-gamma have been developed. The aim of this study was to evaluate if Quantiferon® TB-gold In Tube (QFT-GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD). PATIENTS AND METHODS: Fifty-four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT-GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x-rays. Agreement between test results was determined. RESULTS: The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x-ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT-GIT and TST was fair (k=0.36; P=.006), as it was between TST and expert physician's evaluation (k=0.257; P=.06). CONCLUSIONS: According to our experience QFT-GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST.

Características clínicas de la epidemia de Dengue en el Servicio de urgencias del Hospital de clínicas / Clinical features of the Dengue epidemic in the emergency Department of the Hospital de clínicas

Introducción: El Dengue es una enfermedad infecciosa, sistémica y dinámica. Es una sola enfermedad, con diferentes presentaciones clínicas y evolución impredecible. Se hizo endémica en Paraguay desde el año 2002; el objetivo de este trabajo es determinar las características clínicas y epidemiológicas de la epidemia de diciembre de 2012 a febrero de 2013. Materiales y Métodos: Diseño descriptivo, retrospectivo, transversal. Fueron incluidos pacientes que desarrollaron criterios de casos probables de Dengue que consultaron al Servicio de Urgencias del Hospital de Clínicas. 1037 pacientes cumplían los criterios de inclusión. Resultados: La frecuencia de casos de Dengue fue del 14%. La edad promedio fue de 37,7 ± 16,3. El 56% era del sexo femenino. El 87% de los pacientes provenían del departamento Central. El mes de mayor número de casos con 48% fue febrero. El 83% de los pacientes fue tratado de forma ambulatoria. El promedio de días de internación fue de 2,39 ± 1,65. Sólo el 20% de los pacientes presentó algún tipo de comorbilidad. La fiebre estuvo presente en el 99,3% de los pacientes. El 20% de los pacientes tenía signos de alarma al momento de la consulta. La presión de pulso promedio fue 40,4 ± 12,1 La frecuencia cardiaca media fue de 93,8 ± 17,3. Promedio de hematocrito fue 42,2 ± 5,07. Promedio de plaquetas fue 111.500 ± 79972,1. Promedio de leucocitos 4561 ± 3717. Se registró un óbito. Conclusión: Este trabajo muestra las diferentes aristas de una de las epidemias más importantes desarrollada a nivel país. Palabras clave: dengue, características clínicas, hospital de clínicas

Background: Dengue is an infectious disease, systemic and dynamic. It presents several clinical manifestations and unpredictable outcome. It is endemic in Paraguay since year 2002; the aim of this research is to determine clinical and epidemiologic characters of the epidemic from December 2012 to February 2013. Methods: It was designed an cross sectional study, observational and retrospective. They were included patients that developed criteria of dengue cases that consulted in Emergencies Service of Clinics Hospital. Results: Frequency of Cases dengue were 14%. Age mean was 37, 7 ± 16,3. 56% were women. 87% of the patients came from Central Department. February was the month with mostly cases with 48%. 83% patients did not require internment. The average days of hospitalization were 2.39 ± 1.65. 20% of patient had some comorbidity. Fever was detected in 99,3% of patients. 20% had signs alarms at the moment of the consult. The average pulse pressure was 40,4 ± 12,1. The average cardiac frecuency was 93,8 ± 17,3. The average hematocrit was 42,2 ± 5,07. The average of platelets was 111.500 ± 79.972,1. The Average of leukocytes was 4561 ± 3717. One death was recorded. Conclusion: This paper shows the different aspects of one of the most important epidemics developed in our country. Keywords: dengue, clinical, hospital clinics.

Alergia y salud mental. Estudio epidemiológico interdisciplinario / Allergy and mental health. Interdisciplinary epidemiological study

Fundamento. La asociación bidireccional entre factores psicosociales y afecciones alérgicas ha sido abordada históricamente con resultados poco concluyentes y el número de estudios que la abordan es escaso en Argentina. Objetivo. Valorar la asociación entre prevalencia de enfermedades alérgicas y variables del contexto de la salud mental. Lugar de aplicación. Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Argentina. Diseño. Estudio observacional de corte transversal. Población. Se integró con 3.183 adultos jóvenes, 66,3% mujeres, entre 17 y 36 años. Método. Se utilizaron cuestionarios para enfermedades alérgicas y factores psicológicos y familiares. Resultados. Se observó ansiedad significativa en asociación con asma, rinitis, eccema, urticaria y angioedema. Se halló dificultad para identificar y distinguir sentimientos de sensaciones corporales y para describir sentimientos en los individuos sintomáticos. Se encontró mayor frecuencia de padres ausentes entre individuos que manifestaban asma o rinitis y de primogénitos en sujetos que referían rinitis. Todas las enfermedades se asociaron a la presencia de antecedentes familiares y al tabaquismo. Conclusión. La significativa asociación entre factores psicológicos y alergia agrega evidencias para sugerir la necesidad del abordaje interdisciplinario de alergia tanto en el campo de la investigación fisiopatológica o epidemiológica como en el terreno de la promoción, prevención y atención de la salud integral de las personas(AU)

Background. Bidirectional relationship between psychosocial factors and allergic processes has been historically assessed but remain inconclusive and not much explored in Argentine. Objective. To asses associations between allergic conditions prevalence and some factors related to mental health. Setting. Medical Sciences Faculty, National University of Rosario, Argentina. Design. Observational cross sectional study. Population. 3183 young adults, 66,3% female aged 17 to 36 years. Methods. Statement with different instruments for the symptomatic exploration of allergy and some psychological and familiar factors. Results. Significant anxiety in association with asthma, rhinitis, eczema, urticaria and angioedema were observed. Difficult to identify and distinguish feelings from corporal sensations and to describe feelings were observed in all allergic conditions. Individual which had shown asthma and rhinitis had more frequently the absence of father alive. Among rhinitis subjects the first order of birth was significantly observed. All diseases were associated with the presence of family history and smoking. Conclusion. Significant association between psychological factors and allergic condition were shown. Factors analyzed were related to genetic heritage as much as individual development in familiar and sociocultural environment. They constitute evidence enough to suggest the need of the interdisciplinary boarding of allergy so much at the field of the physiopathologic or epidemiologic investigation as in the ground of promotion, prevention and attention of the people comprehensive health.(AU)