Browsing by Author "Solari, Sandra"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
Item Clinical, Biochemical, and Genetic Characteristics of “Nonclassic” Apparent Mineralocorticoid Excess Syndrome(Oxford University Press, 2019) Tapia-Castillo, Alejandra; Baudrand, Rene; Vaidya, Anand; Campino, Carmen; Allende, Fidel; Valdivia, Carolina; Vecchiola, Andrea; Lagos, Carlos; Fuentes, Cristóbal; Solari, Sandra; Martínez-Aguayo, Alejandro; García, Hernán; Carvajal, Cristian; Fardella, CarlosContext Classical apparent mineralocorticoid excess (AME) is a rare recessive disorder, caused by severe 11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) deficiency. AME manifests as low-renin pediatric hypertension, hypokalemia and high cortisol/cortisone (F/E) ratio. Objective To evaluate nonclassic AME (NC-AME) due to partial 11β-HSD2 insufficiency and its association with hypertension, mineralocorticoid receptor (MR) activation, and inflammatory parameters. Design Cross-sectional study. Setting Primary care cohort. Participants We recruited 127 adolescents and adults. Subjects with secondary hypertension were excluded. We measured clinical, biochemical, renal, vascular, and inflammatory variables. Sequencing of HSD11B2 gene was performed in all subjects. Main Outcome Measure NC-AME. Results Serum F/E ratio was positively associated with systolic blood pressure (BP), microalbuminuria, and high-sensitivity C-reactive protein (hs-CRP). Serum cortisone correlated with MR activation parameters even when adjusted for age, body mass index, and sex: lower cortisone with higher potassium excretion (partial r = −0.29, P = 0.002) and with lower plasma renin activity (PRA) (partial r = 0.29, P = 0.001). Consistently, we identified 9 in 127 subjects (7.1%) with high F/E ratios (first quartile) and low cortisone (last quartile), suggestive of NC-AME. These subjects had higher systolic BP, 141.4 ± 25.7 mm Hg vs 127.3 ± 18.1 mm Hg, P = 0.03; lower PRA, 0.36 ± 0.19 ng/L*s vs 0.64 ± 0.47 ng/L*s, P < 0.0001; and greater potassium excretion, microalbuminuria, hs-CRP, and plasminogen activator inhibitor. We only found in 2 out of 9 subjects with NC-AME heterozygous mutations in the HSD11B2 gene. Conclusions These findings suggest a spectrum of partial 11β-HSD2 insufficiency in a primary care cohort without the classic phenotype and genotype of AME. NC-AME may represent a phenotype of MR activation and cardiovascular risk, suggesting that these subjects could be treated with MR antagonists.Item Depressive symptoms are associated with higher morning plasma cortisol in primary care subjects(2018) Capponi, Valentina; Carrasco, Carmen; Macchiavello, Stefano; Undurraga, Juan; Campino, Carmen; Carvajal, Cristian; Gómez, Teresita; Weiss, Cristian; Aedo, Igor; Vecchiola, Andrea; Allende, Fidel; Solari, Sandra; Fardella, Carlos; Baudrand, RenéBACKGROUND: Cortisol dysregulation has a potential role in depression. AIM AND METHODS: We evaluated depressive symptoms using the Hamilton Rat- ing Scale for Depression in 48 primary care subjects without history of previous or current depression and its association with cortisol dysregulation (morning plasma cortisol, 24-hour urinary free cortisol and cortisol metabolites). Presence of metabolic syndrome and inflammatory parameters were also assessed. RESULTS: Hamilton Rating Scale for Depression correlated significantly with morning cortisol, but not with urinary free cortisol or metabolites. A significant increase in morning cortisol by Hamilton groups (asymptomatic ≤8; mild to moderate: 9–18; moderate to severe: ≥19) was observed even when adjusted by age/gender. We observed no association of depressive symptoms with metabolic or inflammatory parameters. CONCLUSIONS: Depressive symptoms in primary care subjects not consulting for their mood are associated with higher morning plasma cortisol, but not urinary cortisol or its metabolites. These observations suggest that systemic hypercorti- solism and related metabolic disorders are not observed in mild/initial states of depressive disorders.Item Performance evaluation of paediatric propofol pharmacokinetic models in healthy young children(2011) Sepúlveda, Pablo; Cortinez, Ignacio; Sáez, Claudia; Penna, Antonello; Solari, Sandra; Guerra, I.; Absalom, Anthony R.Background. The performance of eight currently available paediatric propofol pharmacokinetic models in target-controlled infusions (TCIs) was assessed, in healthy children from 3 to 26 months of age. Methods. Forty-one, ASA I-II children, aged 3-26 months were studied. After the induction of general anaesthesia with sevoflurane and remifentanil, a propofol bolus dose of 2.5 mg kg 21 followed by an infusion of 8 mg kg 21 h 21 was given. Arterial blood samples were collected at 1, 2, 3, 5, 10, 20, 40, and 60 min post-bolus, at the end of surgery, and at 1, 3, 5, 30, 60, and 120 min after stopping the infusion. Model performance was visually inspected with measured/predicted plots. Median performance error (MDPE) and the median absolute performance error (MDAPE) were calculated to measure bias and accuracy of each model. Results. Performance of the eight models tested differed markedly during the different stages of propofol administration. Most models underestimated propofol concentration 1 min after the bolus dose, suggesting an overestimation of the initial volume of distribution. Six of the eight models tested were within the accepted limits of performance (MDPE<20% and MDAPE<30%). The model derived by Short and colleagues performed best. Conclusions. Our results suggest that six of the eight models tested perform well in young children. Since most models overestimate the initial volume of distribution, the use for TCI might result in the administration of larger bolus doses than necessary.Item Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis(Lippincott Williams & Wilkins, 2014) Cortínez, Luis; De la Fuente, Natalia; Eleveld, Douglas; Oliveros, Ana; Crovari, Fernando; Sepúlveda, Pablo; Ibacache, Mauricio; Solari, SandraBACKGROUND: Obesity is associated with important physiologic changes that can potentially affect the pharmacokinetic (PK) and pharmacodynamic (PD) profile of anesthetic drugs. We designed this study to assess the predictive performance of 5 currently available propofol PK models in morbidly obese patients and to characterize the Bispectral Index (BIS) response in this population. METHODS: Twenty obese patients (body mass index >35 kg/m), aged 20 to 60 years, scheduled for laparoscopic bariatric surgery, were studied. Anesthesia was administered using propofol by target-controlled infusion and remifentanil by manually controlled infusion. BIS data and propofol infusion schemes were recorded. Arterial blood samples to measure propofol were collected during induction, maintenance, and the first 2 postoperative hours. Median performance errors (MDPEs) and median absolute performance errors (MDAPEs) were calculated to measure model performance. A PKPD model was developed using NONMEM to characterize the propofol concentration-BIS dynamic relationship in the presence of remifentanil. RESULTS: We studied 20 obese adults (mean weight: 106 kg, range: 85-141 kg; mean age: 33.7 years, range: 21-53 years; mean body mass index: 41.4 kg/m, range: 35-52 kg/m). We obtained 294 arterial samples and analyzed 1431 measured BIS values. When total body weight (TBW) was used as input of patient weight, the Eleveld allometric model showed the best (P < 0.0001) performance with MDPE = 18.2% and MDAPE = 27.5%. The 5 tested PK models, however, showed a tendency to underestimate propofol concentrations. The use of an adjusted body weight with the Schnider and Marsh models improved the performance of both models achieving the lowest predictive errors (MDPE = <10% and MDAPE = <25%; all P < 0.0001). A 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (ke0) adequately described the propofol concentration-BIS data. A lag time parameter of 0.44 minutes (SE = 0.04 minutes) to account for the delay in BIS response improved the fit. A simulated effect-site target of 3.2 μg/mL (SE = 0.17 μg/mL) was estimated to obtain BIS of 50, in the presence of remifentanil, for a typical patient in our study. CONCLUSIONS: The Eleveld allometric PK model proved to be superior to all other tested models using TBW. All models, however, showed a trend to underestimate propofol concentrations. The use of adjusted body weight instead of TBW with the traditional Schnider and Marsh models markedly improved their performance achieving the lowest predictive errors of all tested models. Our results suggest no relevant effect of obesity on both the time profile of BIS response and the propofol concentration-BIS relationship.Item Screening of COVID-19 cases through a Bayesian network symptoms model and psychophysical olfactory test(2021) Eyheramendy, Susana; Saa, Pedro A.; Undurraga, Eduardo A.; Valencia, Carlos; López, Carolina; Méndez Alcamán, Luis; Pizarro-Berdichevsky, Javier; Finkelstein-Kulka, Andrés; Solari, Sandra; Salas, Nicolás; Bahamondes, Pedro; Ugarte, Martín; Barceló, Pablo; Arenas, Marcelo; Agosin, EduardoThe sudden loss of smell is among the earliest and most prevalent symptoms of COVID-19 when measured with a clinical psychophysical test. Research has shown the potential impact of frequent screening for olfactory dysfunction, but existing tests are expensive and time consuming. We developed a low-cost ($0.50/test) rapid psychophysical olfactory test (KOR) for frequent testing and a model-based COVID-19 screening framework using a Bayes Network symptoms model. We trained and validated the model on two samples: suspected COVID-19 cases in five healthcare centers (n = 926; 33% prevalence, 309 RT-PCR confirmed) and healthy miners (n = 1,365; 1.1% prevalence, 15 RT-PCR confirmed). The model predicted COVID-19 status with 76% and 96% accuracy in the healthcare and miners samples, respectively (healthcare: AUC = 0.79 [0.75–0.82], sensitivity: 59%, specificity: 87%; miners: AUC = 0.71 [0.63–0.79], sensitivity: 40%, specificity: 97%, at 0.50 infection probability threshold). Our results highlight the potential for low-cost, frequent, accessible, routine COVID-19 testing to support society's reopening.Item Serum Cortisol and Cortisone as Potential Biomarkers of Partial 11β-Hydroxysteroid Dehydrogenase Type 2 Deficiency(2018) Carvajal, Cristian; Tapia, Alejandra; Valdivia, Carolina; Allende, Fidel; Solari, Sandra; Lagos, Carlos; Campino, Carmen; Martínez, Alejandro; Vecchiola, Andrea; Pinochet, Constanza; Godoy, Claudia; Iturrieta, Virginia; Baudrand, Rene; Fardella, CarlosBackground: Pathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11βHSD2 deficiency in those heterozygous subjects. Methods: We studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses. Results: The normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21-3.69] and 2.54 [2.35-2.88], and in adults were 4.42 [3.70-4.90] and 2.23 [1.92-2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls. Conclusion: Serum F/E ratio and cortisone allow to identify partial 11βHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension.