Sandra Solari

Endothelial Dysfunction: A Link Among Preeclampsia, Recurrent Pregnancy Loss, and Future Cardiovascular Events?

We tested the hypothesis that endothelial dysfunction could cause placentation-related defects, persist after the complicated pregnancy, and probably cause cardiovascular disease later in life. Brachial arterial reactivity and factors related to endothelial dysfunction, such as circulating cholesterol, uric acid, nitrites, l-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1, in women with previous healthy pregnancies (n=22), patients with severe preeclampsia (n=25), or patients with recurrent pregnancy loss (n=29), at day 10 of the luteal phase of an ovulatory cycle an average of 11 to 27 months after pregnancy were evaluated. Both groups with placentation defects had a significant decrease in endothelium-dependent dilatation, a higher rate of endothelial dysfunction, lower serum nitrites, and higher cholesterol as compared with control subjects; subjects with previous preeclampsia additionally had higher normal blood pressures and a greater parental prevalence of cardiovascular disease. Patients with recurrent pregnancy loss also demonstrated a significantly lower endothelium-independent vasodilatation. A trend to an inverse correlation was found between serum cholesterol serum and endothelial-mediated vasodilatation in the whole study population. Uric acid, l-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1 were similar in all of the groups. We postulate that endothelial dysfunction may represent a link between preeclampsia and increased cardiovascular disease latter in life and propose that women with unexplained recurrent miscarriages are also at increased cardiovascular risk. The identification and correction of endothelial dysfunction detected during the reproductive stage on obstetric outcome and on cardiovascular diseases needs to be elucidated.

Performance of Propofol Target-Controlled Infusion Models in the Obese: Pharmacokinetic and Pharmacodynamic Analysis

BACKGROUND: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/m2), 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/m2, range: 35–52 kg/m2). 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 &mgr;g/mL (SE = 0.17 &mgr;g/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.

Evaluation of the effect of intravenous lidocaine on propofol requirements during total intravenous anaesthesia as measured by bispectral index

BACKGROUND I.V. lidocaine is increasingly used as an adjuvant during general anaesthesia. The aim of this study was to evaluate the effect of i.v. lidocaine in reducing propofol anaesthetic requirements during total i.v. anaesthesia (TIVA) maintenance and to evaluate its effect on early recovery from anaesthesia. METHODS Forty adult patients undergoing elective laparoscopic cholecystectomy under TIVA were randomly allocated into the lidocaine group (administered 1.5 mg kg(-1) i.v. lidocaine over 5 min followed by 2 mg kg(-1) h(-1)) and the control group (administered an equal volume of saline). Propofol was administered using a target-controlled infusion to maintain the bispectral index values between 40 and 60. After surgery, all infusions were discontinued and the time to extubation was recorded. Serial arterial blood samples were drawn to assess drug plasma levels. RESULTS The maintenance dose of propofol was significantly lower in the lidocaine group [6.00 (0.97) mg kg(-1) h(-1)] vs the control group [7.25 (1.13) mg kg(-1) h(-1); P=0.01]. Propofol plasma levels measured at the end of the infusion were 3.71 (0.89) μg ml(-1) in the lidocaine group and 3.67 (1.28) μg ml(-1) in the control group (P=0.91). The median time to extubation was longer (11.0 min; range: 10.0-21.0) in the lidocaine group vs the control group (8.3 min; range: 5.5-12.5; P=0.02). CONCLUSIONS I.V. lidocaine reduces propofol requirements during the maintenance phase of TIVA, particularly during surgical stimulation. This sparing effect is associated with an increased time to extubation. Owing to its effect on early recovery from anaesthesia, i.v. lidocaine should be taken into account when used as a component of i.v. anaesthesia.

Feeding and bone turnover in gastric bypass.

CONTEXT Roux-en-Y gastric bypass (RYGB) is associated with high bone turnover. In healthy subjects, feeding causes acute reduction of bone resorption, which is regulated by several intestinal and pancreatic peptides. OBJECTIVE Our objective was to assess bone turnover after feeding in patients with RYGB. DESIGN AND SETTING This was a cross-sectional case-control study at a university hospital. PARTICIPANTS Fifteen postmenopausal women who underwent RYGB 7.4 ± 4.1 years previously were matched by age and body mass index with 15 nonoperated women (controls). MAIN OUTCOMES Serum PTH, calcium, phosphorus, insulin, carboxy telopeptide (CTX), procollagen type I N-terminal propeptide (P1NP), and glucagon-like peptide 2 (GLP-2) were measured while fasting and after a standard meal (SM). RESULTS The fasting calcium, phosphorus, and PTH were similar in both groups and exhibited similar decreases after an SM. The fasting CTX level was higher in the RYGB than in the control group (0.589 ± 0.18 vs 0.382 ± 0.11 ng/mL; P < .05) and fell to a nadir of 42.2% of the basal value in the RYGB and 53.9% in controls (P < .05). The fasting and postprandial P1NP levels were similar in both groups and fell to a nadir of 85.8% in the RYGB and 89.3% in controls. Insulin and GLP-2 levels were similar during fasting in both groups. RYGB patients had exaggerated postprandial insulin and GLP-2 response compared with the controls with the insulin and GLP-2 area under the curve being significantly higher in the RYGB group. There was a significant negative correlation between the peak of insulin levels and the CTX changes. CONCLUSION The acute reduction in bone resorption after feeding is preserved in RYGB and is even higher than in nonoperated subjects. This phenomenon is related to the increase of postprandial levels of insulin. These findings suggest a bone-protecting mechanism in RYGB that may counteract the elevated bone resorption that occurs during fasting.

Pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in children younger than 3 years.

BACKGROUND: Caudal administration of levobupivacaine (2.5 mg/kg) in children is used frequently in some hospitals. However, no reports of levobupivacaine concentrations have been published with this dosing scheme. We report the results of a study on the pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in children younger than 3 yr. METHODS: Ten children, aged 1–36 mo and scheduled for subumbilical surgery were studied under sevoflurane anesthesia. After caudal injection of 0.25% levobupivacaine (2.5 mg/kg), serial venous blood samples were taken for 3 h to measure total plasma concentration levels of levobupivacaine. Median (range) levobupivacaine Cmax and Tmax measured were 1.48 (0.62–2.40) &mgr;g/mL and 37 (10–60) min. The highest individual Cmax was observed in a 1-mo-old infant 30 min after caudal block. CONCLUSIONS: The highest Cmax reached in this study was close to the toxic threshold of adult patients. Although no adverse events have been reported, care must be taken, especially in small infants, after caudal administration of levobupivacaine (2.5 mg/kg).

Identificación bacteriana basada en el espectro de masas de proteínas: Una nueva mirada a la microbiología del siglo XXI

Bacterial identification is important for the proper treatment of infected patients hospitalized with serious infections especially in critical care units. Identification by conventional methods used in microbiology laboratories takes at least 16 hours since a culture is positive. The introduction of mass spectrometry, specifically MALDI-TOF MS (matrix-assisted laser desorption/ ionization time-of-flight mass spectrometer) in the microbiology laboratory could mean a radical change in the identification accuracy, turn around time (6 minutes per bacteria) and cost (about 5 times cheaper than conventional identification). Since its introduction in clinical microbiology laboratories in 2008, many reports about its usefulness in identifying microorganisms from colonies, as well as directly from positive blood cultures and urine samples have been published. This review describes MALDI-TOF MS methodology, its identification performance for bacteria (aerobic and anaerobic), mycobacterium and yeasts, its future applications in microbiology and its main disadvantages.

Bile acids synthesis decreases after laparoscopic sleeve gastrectomy

BACKGROUND Bariatric surgery is the most effective treatment alternative in morbid obesity. The mechanisms contributing to these benefits remain poorly understood. Bile acids (BAs) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure. Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy (SG). OBJECTIVES The aim of this study was to evaluate the effect of SG on BA synthesis. SETTING University Hospital. Santiago, Chile. METHODS Obese patients were evaluated before and after SG (1, 3, 6, and 12 months). BA synthesis was evaluated through the serum marker, 7 α-hydroxy-4-cholesten-3-one (C4). Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with tandem mass spectrometry detection (HPLC-MS/MS). RESULTS From June 2013 to January 2014, 19 patients (age 37.6±7.8 years; BMI 35.8±3.5 kg/m(2); 79% female) were included in this study. Mean weight loss at 1, 3, 6, and 12 months was 11.3, 17.5, 23.6, and 25.4 kg, respectively, equivalent to 11.8, 18.6, 24.8, and 26.9 of total body water percentage (%TBW) (P<.0001), respectively and 43.2, 68.2, 91, and 98.8 of percentage of excess weight loss (%EWL), respectively (P<.001). Serum C4 levels at baseline, 1, 3, 6, and 12 months were 23.4±21.1, 4.9±8.2, 8.7±12.1, 13.8±12.9, and 18.8±16.8 ng/mL (P<.0001), respectively. Fibroblast growth factor 19 (FGF19) levels at baseline, 1, 3, 6, and 12 months were 71±33.3, 130.5±66.2, 117.8±57.2, 134.6±91.7, and 124.3±85.9 pg/mL (P = .019), respectively. CONCLUSION Serum levels of C4 decrease after SG, indicating a reduction in the synthesis of BA. FGF19 may play a role in decreasing BA synthesis. Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis.

Polymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population

BACKGROUND The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, G>A) and rs836478 (intron 3, T>C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort. METHODS Two hundred two normotensive (NT) subjects (aged 4-16 years) were divided into 2 groups: NT subjects with hypertensive parents (NH; n = 103) and NT subjects with NT parents (NN; n = 99). We measured markers of inflammation (high-sensitivity C-reactive protein, interleukin 6 (IL-6), interleukin 8, and tumor necrosis factor α), endothelial damage (Plasminogen activator inhibitor-1 metalloproteinase-9, and metalloproteinase-2), and oxidative stress (malondialdehyde). Data were expressed as median and interquartile range (IQR). RESULTS We found differences in polymorphism rs836478 (intron 3, C>T) in both genotypic (χ(2) = 15.2, 2 df; P = 0.0005) and allelic (X(2)=5.5, 1 df; P = 0.01) frequencies in NH vs. NN subjects. NH subjects with a TT genotype showed increase MMP9 expression (median = 2.3, IQR - 1.6-3.2; vs. median = 1.6, IQR = 1.6-2.3 AU; P = 0.01) and lower IL-6 expression (median = 8.8, IQR = 7.0-11.8; vs. median = 12.1, IQR = 8.2-14.7 pg/ml; P = 0.02) compared with subjects with TC/CC genotype. No difference in the allelic frequency distribution was seen in the polymorphism rs10951982 (NH vs. NN: χ(2)=0.2, 1 df; P = 0.6). For this SNP, NN subjects with GA/AA genotype showed decreased diastolic BP indexes compared with subjects with native GG genotype (median = 1.08, IQR = 1.0-1.2; vs. median = 0.99, IQR = 0.94-1.1; P = 0.02). CONCLUSIONS We report the frequency of polymorphisms rs836478 and rs10951982 of the RAC1 gene in a Spanish-Amerindian cohort. The polymorphism rs836478 was associated with an increased expression in markers of inflammation and endothelial damage (MMP9 and IL-6) in pediatric subjects with a hypertensive genetic background.

Elevada frecuencia de enfermedad tiroidea funcional en embarazadas chilenas sin antecedentes de patología tiroidea utilizando el estándar de TSH internacional

BACKGROUND Thyroid hormones play an important role in fetal neural and cognitive development. Therefore thyroid abnormalities should be detected and treated early during pregnancy. AIM To assess the frequency and risk factors for functional thyroid disorders during the first trimester of pregnancy. MATERIAL AND METHODS A blood sample was obtained from women during their first trimester of pregnancy, consulting in a prenatal care facility. Women with known thyroid diseases were excluded from the study. Thyroid stimulating hormone (TSH), total thyroxine (T4) and free thyroxine (fT4) were measured by electrochemoluminiscence. Antithyroid peroxidase antibodies (anti TPO) were measured by enzyme immunoassay. RESULTS Five hundred and ten women aged 25.7 ± 6.6 years were assessed. The frequency of clinical hypothyroidism was 0.6%, subclinical hypothyroidism 35.3% and clinical hyperthyroidism 1%. Five percent of women with hypothyroidism and 3.5% of euthyroid women had positive anti TPO antibodies. There was no association between the frequency of thyroid diseases and risk factors for thyroid diseases. CONCLUSIONS There is a high frequency of subclinical thyroid diseases among women consulting in this prenatal care clinic.Background: Thyroid hormones play an important role in fetal neural and cognitive development. Therefore thyroid abnormalities should be detected and treated early during pregnancy. Aim: To assess the frequency and risk factors for functional thyroid disorders during the first trimester of pregnancy. Material and Methods: A blood sample was obtained from women during their first trimester of pregnancy, consulting in a prenatal care facility. Women with known thyroid diseases were excluded from the study. Thyroid stimulating hormone (TSH), total thyroxine (T4) and free thyroxine (fT4) were measured by electrochemoluminiscence. Antithyroid peroxidase antibodies (anti TPO) were measured by enzyme immunoassay. Results: Five hundred and ten women aged 25.7 ± 6.6 years were assessed. The frequency of clinical hypothyroidism was 0.6%, subclinical hypothyroidism 35.3% and clinical hyperthyroidism 1%. Five percent of women with hypothyroidism and 3.5% of euthyroid women had positive anti TPO antibodies. There was no association between the frequency of thyroid diseases and risk factors for thyroid diseases. Conclusions: There is a high frequency of subclinical thyroid diseases among women consulting in this prenatal care clinic.

Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension

Objective: To identify novel biomarkers associated with pediatric primary hypertension. Methods: We recruited 350 participants (4–16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. Results: In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P < 0.001), HOMA-IR (r = 0.211, P < 0.001), MMP-9 activity (r = 0.215, P < 0.001) and the cortisol/cortisone ratio (r = 0.231, P < 0.001). DBP showed similar correlations with these variables. No correlation was observed with aldosterone or plasma renin activity. Participants were categorized as hypertensive (n = 59) or nonhypertensive (n = 261). In the univariate analysis, hypertensive patients had higher BMI-SDS (P < 0.001), HOMA-IR (P < 0.001), high-sensitivity C-reactive protein (P < 0.001), MMP-9 activity (P < 0.001), plasminogen activator inhibitor type 1 (P < 0.001) and cortisol/cortisone ratio (P < 0.001) than nonhypertensive patients. Multiple regression analysis showed that the variables that remained associated with hypertension were higher BMI-SDS [odds ratio (OR) = 3.74; 95% confidence interval (CI) = 1.84–7.58], a higher cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98–7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15–8.32). Conclusion: We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.