Determination of the aldosterone/plasma renin activity ratio for the screening of primary hyperaldosteronism in essential hypertension: a multicentric study

El hiperaldosteronismo primario (HAP) es una afección caracterizada por la producción inapropiadamente elevada y una relativa autonomía del sistema renina-angiotensina. Estimaciones previas, basadas sólo en la evaluación de hipertensos con hipokalemia, consideraban al HAP como una causa poco frecuente de hipertensión (1%). Sin embargo, estudios actuales fundamentados en el cálculo de la relación aldosterona/ actividad de renina plasmática (RAA) arrojan una incidencia mayor (5-10%), siendo la hipertensión arterial (HTA) normokalémica la presentación más frecuente. Dada la amplitud de los valores de corte de la RAA, el Departamento de Suprarrenal de SAEM diseñó un estudio multicéntrico prospectivo en una población de Argentina con el objetivo de establecer nuestro propio valor y determinar así la prevalencia de HAP. Fueron estudiados 353 individuos de ambos sexos, 104 controles normotensos, sin antecedentes familiares de HTA y 249 pacientes hipertensos. Se indicó dieta normosódica y la suspensión de antihipertensivos que interfieran con el eje mineralocorticoideo. Las determinaciones de la actividad de renina plasmática (ARP), DIA-SorinRIA, y de aldosterona, RIA-DPC, fueron realizadas en un único laboratorio. Se realizó ionograma y se evaluaron parámetros clínicos y bioquímicos de síndrome metabólico. La RAA calculada según el percentilo 95 en los controles, fue establecida en la cifra de 36 como valor de corte para sospechar HAP en los hipertensos, requiriéndose una concentración de aldosterona >15 ng/ml. Con una RAA≥36, se realizaron pruebas confirmatorias de sobrecarga salina o de fludrocortisona. La RAA fue ≥36 en 31/249 pacientes, confirmándose HAP en 8 (7 adenomas y 1 hiperplasia), con una prevalencia del 3.2%. Los restantes no completaron estudios confirmatorios. La presencia de síndrome metabólico fue similar en los hipertensos con y sin HAP. En conclusión, este primer estudio multicéntrico argentino determinó nuestro valor de corte de la RAA en 36. Su aplicación permitió establecer una prevalencia de HAP del 3,2% que, aunque podría estar subestimada, resulta significativamente mayor que la previa histórica y concuerda con la incidencia referida en la bibliografía.Primary hyperaldosteronism (PHA) or Conn's disease was classically suspected in the presence of hypertension (H) and hypokalemia. It was previously considered as a rare cause of H, being reported in only 1% of hypertensive patients. It can be caused by an adrenal adenoma (the former usual presentation) or by adrenal hyperplasia. But since the use of the aldosterone/plasma renin activity ratio (AAR) as the screening method in the last years, it is currently considered as almost the most frequent cause of secondary H., accounting for 5-10% of essential H. Plasma rennin activity (PRA) determination is a laborious procedure with low reproducibility and it directly affects the AAR; thus each laboratory must assess its own cut-off value. Therefore, in the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM), we performed this multicentric prospective study of a population of Argentina with the aim of assessing our own AAR cut-off level in normotensive controls in order to apply it for PHA screening in essential hypertensive patients. We studied 353 adult subjects: 104 controls, aged 45,18 ± 13,78 years-old ( X±SD), with no history of arterial hypertension in their first-degree relatives and with two separate day-registry of blood pressure≤ 139/85 mmHg and 249 hypertensive patients, aged 51± 13,6 years-old ( X ± SD), with arterial blood pressure≥ 140/90 mmHg in the sitting position. Subjects with cardiac, renal, hepatic and neurological diseases were excluded as well as those with Cushing´s syndrome, hyperthyroidism, untreated hypothyroidism, diabetes mellitus and patients under glucocorticoids, oral contraceptive pills or estrogen therapy. A normal sodium diet was indicated and potassium was supplemented when needed. Blood was withdrawn between 8 and 10:00 a.m. with the subjects in the upright position. Aldosterone (A) was determined by DPC radioimmunoassay (RIA) and PRA, by DIA-Sorin RIA. The A normal levels are 4-30 ng/dl for ambulatory individuals on a normal sodium diet and the PRA normal values are < 3,3 ng/ml/h. In order to avoid false positive results in the hypertensive group, AAR was calculated when A was above 15 ng/dl. We measured the waist circumference and we determined the body mass index. Blood sodium, potassium, calcium, urea, creatinine, cholesterol, HDL-C, LDL-C, triglyceride and liver function tests were performed. Statistical Analysis and Results Since the AAR variable showed a non-normal distribution, the cut-off value was considered as the 95th percentile in the control group, which was calculated as 36. This is also in accordance to the function of the empirical distribution of Collings and Hamilton. In our 249 hypertensive patients, 31 had an AAR ≥ 36. PHA was confirmed in 8: seven has an adrenal adenoma and one had hyperplasia. The prevalence of PHA in our population was 3,2 %, with a 95th confidence interval ranging from 1,4 to 6,2 %. In the remaining 23 patients, confirmatory tests could not be completed. There was no correlation between the severity of the hypertension and the AAR value, with no statistical significant differences between those with or without PHA. Likewise, we found no correlation between PRA and advancing age. In hypertensive patients, metabolic syndrome was more prevalent than in controls, but it was present to the same extent in those with or without PHA. Conclusions To our knowledge, this is the first multicentric study performed in Argentina to determine the aldosterone/ plasma renin activity ratio in our normotensive control population. Our AAR value of 36 agrees with the levels reported in the international literature: thus an AAR ≥ 36 along with an aldosterone ≥ 15 ng/ml in hypertensive patients lead us to suspect PHA and to perform confirmatory tests. Applying these criteria, we found a prevalence of 3,2% of PHA in essential HTA. It is possible that this value may be underestimated due to the fact that confirmatory tests could not be completed in all the hypertensive subjects with an AAR≥ 36. In spite of this, our prevalence is significantly greater than the historical one and it lies in the range reported in the literature.Fil: Pardes, E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Belli, S.. Hospital Dr. C. Durand; ArgentinaFil: Cornaló, D.. Hospital Rivadavia; ArgentinaFil: Contreras, Liliana Noemi. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Costa, L.. Hospital Dr. A. Posadas; ArgentinaFil: Chervin. R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Damilano, S.. Laboratorio de Bioanalítica; ArgentinaFil: Fenili, C.. Laboratorio de Bioanalítica; ArgentinaFil: Gómez, R. M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Leal Reyna, M.. Complejo Médico Policial "Churruca"; ArgentinaFil: Lupi, S.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Martínez, M.. Hospital Francés; ArgentinaFil: Nofal, M.. Clínica Bazterrica; ArgentinaFil: Ruibal, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; Argentin

Pyloromyotomy for infantile hypertrophic pyloric stenosis using a modification of the Tan and Bianchi circumumbilical approach

Background/purpose Different approaches have been advocated for pyloromyotomy.  Since the introduction of umbilical pyloromyotomy, a number of studies have shown that it is as safe as the traditional right upper quadrant approach with superior  cosmetic results. The aim of this study was to assess the feasibility and the safety  of pyloromyotomy for infantile hyprtrophic pyloric stenosis using a modification of the Tan–Bianchi approach.Patients and methods Over a period of 2 years, 20 infants with infantile  hypertrophic pyloric stenosis have been clinically evaluated. The umbilical approach was modified so that a transverse muscle cutting incision rather than a longitudinal midline linea alba incision was performed.Results The total number of cases included in this study was 20 [16 male (80%)  and four female (20%) patients]. Their ages ranged from 23 to 60 days (average  42.6 ±13.54 days), and their weights ranged from 2700 to 4000 g (mean 3605± 437.4 g). Pyloromyotomy was performed safely with negligible blood loss. Four cases of serosal tear occurred, with an incidence of 20%. None of our cases showed significant complications. The mean operating time was 52.5 ± 5.073 min. The postoperative hospital stay ranged from 24 to 72 h. The postoperative course was uneventful in all patients, and, on follow-up, the circumumbilical incision left an almost undetectable scar.Conclusion Pyloromyotomy for infantile hypertrophic pyloric stenosis using the modified Tan and Bianchi technique is feasible and safe, having an accepted operative time, early initiation of postoperative feeding, and short hospital stay. This modification combines the advantage of circumumbilical incision with its better cosmetic results and right transverse upper abdominal approach with its easy and feasible access to the pyloric mass.Keywords: operative intervention, pyloric stenosis, Tan–Bianchi approac

ЭФФЕКТ ВОЗДЕЙСТВИЯ 1,5-БИС(3,5-ДИМЕТИЛПИРАЗОЛ-1-ИЛ)-3-ОКСАПЕНТАН-ДИАЦЕТАТОМЕДИ НА ОБЩЕЕ СОСТОЯНИЕ ОРГАНИЗМА КРЫС В УСЛОВИЯХ ЭКСПЕРИМЕНТА

Многие производные пиразола проявляют разнообразные фармакологические свойства. Им характерны антиоксидантная, антивирусная активность, противовоспалительные, иммуномодулирующие свойства, а также антидепрессивный и противоопухолевый эффекты. Данная работа основана на результатах морфометрических показателей массы тела и печени и биохимического анализа крови здоровых взрослых самцов белых крыс после однократного и многократного внутрибрюшинного введения 1,5-бис(3,5-диметилпиразол-1-ил)-3-оксапентан-диацетатомеди, растворенного в свежеприготовленном физиологическом растворе (доза 12 мг / кг массы тела). Результаты исследования показали, что при введении препарата в организм крыс проявляются различные эффекты. Установлено, что исследуемое вещество имеет гипогликемический эффект, о чем свидетельствует снижение уровня глюкозы в крови и увеличение количества гликогена в печени. Антилиполитический его эффект подтверждается снижением уровня свободных жирных кислот в крови. Токсическое воздействие препарата проявляется повышением уровня печеночных ферментов аланин аминотрансферазы и аспартат аминотрансферазы, а также снижением уровня альбумина в сыворотке крови и уменьшением массы тела и печени. Эти эффекты проявляются и сохраняются только при многократном ежедневном применении этого препарата в течение 6 недель

Lipid Metabolites Enhance Secretion Acting on SNARE Microdomains and Altering the Extent and Kinetics of Single Release Events in Bovine Adrenal Chromaffin Cells

Lipid molecules such as arachidonic acid (AA) and sphingolipid metabolites have been implicated in modulation of neuronal and endocrine secretion. Here we compare the effects of these lipids on secretion from cultured bovine chromaffin cells. First, we demonstrate that exogenous sphingosine and AA interact with the secretory apparatus as confirmed by FRET experiments. Examination of plasma membrane SNARE microdomains and chromaffin granule dynamics using total internal reflection fluorescent microscopy (TIRFM) suggests that sphingosine production promotes granule tethering while arachidonic acid promotes full docking. Our analysis of single granule release kinetics by amperometry demonstrated that both sphingomyelinase and AA treatments enhanced drastically the amount of catecholamines released per individual event by either altering the onset phase of or by prolonging the off phase of single granule catecholamine release kinetics. Together these results demonstrate that the kinetics and extent of the exocytotic fusion pore formation can be modulated by specific signalling lipids through related functional mechanisms

IMPACT OF VIRTUAL REALITY EXPERIENCE ON ACCESSIBILITY OF CULTURAL HERITAGE

Accessibility plays a main role among the aspects that contribute to the conservation of Cultural Heritage sites. Seismic stability, fragility of the artefacts, conflicts, deterioration, natural disasters, climate change and visitors’ impact are only some of the possible causes that might lead to the inaccessibility of a heritage site for both researchers and visitors.The increasing potential of Information and Communication Technologies (ICT) in the conservation field has resulted in the development of Augmented and Virtual reality (AR and VR) experiences. These ones can be very effective for what concerns the description of the visual experience, but also improve the understanding of a site and even became analytic research tools.This paper presents an inaccessible Buddhist temple in the Myanmar city of Bagan as a case study for the realization of a VR experience that aims at providing accessibility to knowledge and therefore a better understanding of the cultural value. In order to evaluate the effectiveness of the VR for this purpose, a user study has been conducted and its results are reported.</p

A direct measure of positive feedback loop-gain due to reverse bias damage in thin-film solar cells using lock-in thermography

In this work, we present a method to study thermal runaway effects in thin-film solar cells. Partial shading of solar cells often leads to permanent damage to shaded cells and degrades the performance of solar modules over time. Under partial shading, the shaded cells may experience a reverse bias junction breakdown. In large-area devices such as solar cells, this junction breakdown tends to take place very locally, thus leading to very local heating and so-called “hot-spots”. Previously, it was shown that a positive feedback effect exists in Cu(In,Ga)Se2 (CIGS) thin-film solar cells, where a highly localized power dissipation is amplified, which may lead to an unstable thermal runaway process. Furthermore, we introduced a novel characterization technique, laser induced Hot-Spot Lock-In Thermography (HS-LIT), which visualizes the positive feedback effect. In this paper, we present a modified HS-LIT technique that allows us to quantify directly a loop-gain for hot-spot formation. By quantifying the loop-gain we obtain a direct measure of how unstable a local hot-spot is, which allows the non-destructive study of hot-spot formation under various conditions and in various cells and cell types. We discuss the modified HS-LIT setup for the direct measurement of the loop-gain. Furthermore, we demonstrate the new method by measuring the loop-gain of the thermal runaway effect in a CIGS solar cell as a function of reverse bias voltage

Multi-hazard socio-physical resilience assessment of hurricane-induced hazards on coastal communities

Hurricane-induced hazards can result in significant damage to the built environment cascading into major impacts to the households, social institutions, and local economy. Although quantifying physical impacts of hurricane-induced hazards is essential for risk analysis, it is necessary but not sufficient for community resilience planning. While there have been several studies on hurricane risk and recovery assessment at the building- and community-level, few studies have focused on the nexus of coupled physical and social disruptions, particularly when characterizing recovery in the face of coastal multi-hazards. Therefore, this study presents an integrated approach to quantify the socio-physical disruption following hurricane-induced multi-hazards (e.g., wind, storm surge, wave) by considering the physical damage and functionality of the built environment along with the population dynamics over time. Specifically, high-resolution fragility models of buildings, and power and transportation infrastructures capture the combined impacts of hurricane loading on the built environment. Beyond simulating recovery by tracking infrastructure network performance metrics, such as access to essential facilities, this coupled socio-physical approach affords projection of post-hazard population dislocation and temporal evolution of housing and household recovery constrained by the building and infrastructure recovery. The results reveal the relative importance of multi-hazard consideration in the damage and recovery assessment of communities, along with the role of interdependent socio-physical system modeling when evaluating metrics such as housing recovery or the need for emergency shelter. Furthermore, the methodology presented here provides a foundation for resilience-informed decisions for coastal communities

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112