Anne-Marie Carreau

Effects of postnatal smoke exposure on laryngeal chemoreflexes in newborn lambs.

Laryngeal chemoreflexes (LCR), which are elicited by the contact of liquids such as gastric refluxate with laryngeal mucosa, may trigger some cases of sudden infant death syndrome. Indeed, while LCR in mature mammals consist of protective responses, previous animal data have shown that LCR in immature newborns can include laryngospasm, apnea, bradycardia, and desaturation. The present study was aimed at testing the hypothesis that postnatal exposure to cigarette smoke is responsible for enhancing cardiorespiratory inhibition observed with LCR. Eight lambs were exposed to cigarette smoke (20 cigarettes/day) over 16 days and compared with seven control lambs. Urinary cotinine/creatinine ratio was measured at a level relevant to previously published levels in infants. On days 15 and 16, 0.5 ml of HCl (pH 2), milk, distilled water, or saline was injected onto the larynx via a chronic supraglottal catheter during sleep. Results showed that exposure to cigarette smoke enhanced respiratory inhibition (P < 0.05) and tended to enhance cardiac inhibition and decrease swallowing and arousal during LCR (P < 0.1). Overall, these results were observed independently of the state of alertness and the experimental solution tested. In conclusion, 16-day postnatal exposure to cigarette smoke increases cardiorespiratory inhibition and decreases protective mechanisms during LCR in nonsedated full-term lambs.

Effects of simulated reflux laryngitis on laryngeal chemoreflexes in newborn lambs

It has been suggested that reflux laryngitis (RL) is involved in apneas-bradycardias of the newborn. The aim of the present study was to develop a unique RL model in newborn lambs to test the hypothesis that RL enhances the cardiorespiratory components of the laryngeal chemoreflexes (LCR) in the neonatal period. Gastric juice surrogate (2 ml of normal saline solution with HCl pH 2 + pepsin 300 U/ml) (RL group, n = 6) or normal saline (control group, n = 6) was repeatedly injected onto the posterior aspect of the larynx, 3 times a day for 6 consecutive days, via a retrograde catheter introduced into the cervical esophagus. Lambs instilled with gastric juice surrogate presented clinical signs of RL, as well as moderate laryngitis on histological observation. Laryngeal chemoreflexes were thereafter induced during sleep by injection of 0.5 ml of HCl (pH 2), ewes milk, distilled water or saline into the laryngeal vestibule via a chronic, transcutaneous supraglottal catheter. Overall, RL led to a significantly greater respiratory inhibition compared with the control group during LCR, including longer apnea duration (P = 0.01), lower minimal respiratory rate (P = 0.002), and a more prominent decrease in arterial hemoglobin saturation (SpO(2)) (P = 0.03). No effects were observed on cardiac variables. In conclusion, 1) our unique neonatal ovine model presents clinical and histological characteristics of RL; and 2) the presence of RL in newborn lambs increases the respiratory inhibition observed with LCR, at times leading to severe apneas and desaturations.

PCOS in Adolescence and Type 2 Diabetes

Polycystic ovary syndrome is a frequent disorder in women of reproductive age that consists of a heterogeneous combination of hyperandrogenism, chronic anovulation, and polycystic ovaries. Hyperandrogenism and anovulation are clearly linked to insulin resistance and compensatory hyperinsulinism, with an ovarian androgenic hyperresponsiveness to circulating insulin. Evidence is increasing that suggests that lipotoxicity, which is a key mechanism in the development of insulin resistance and type 2 diabetes, could also explain the androgen overproduction. During adolescence, diagnosis of polycystic ovarian syndrome (PCOS) may be difficult but is of importance because PCOS increases future risk of type 2 diabetes and metabolic complications. Metabolic perturbations begin early in adolescence and also exist in adolescent relatives of women with PCOS, even before clinical signs of PCOS. Screening for impaired glucose tolerance or type 2 diabetes is also important in this population, and treatment should focus on PCOS clinical manifestations as well as long-term metabolic risk.

Respiratory hygiene in emergency departments: Compliance, beliefs, and perceptions

Background Low respiratory hygiene compliance among health care workers of emergency departments has become a major concern in the spread of respiratory infections. Our objective was to determine the compliance with respiratory hygiene of triage nurses at 2 university hospital centers and to identify factors influencing compliance to the respiratory hygiene principles of emergency health care workers. Methods A 2-part, cross-sectional, descriptive study was conducted at 2 training centers. An anonymous observation of compliance with respiratory hygiene by triage emergency nurses was performed. A self-administered, voluntary questionnaire on attitudes, perceptions, and knowledge of respiratory hygiene guidelines was distributed to the health care workers at the emergency department of the 2 hospital sites. Results Median objective compliance with respiratory hygiene measures of triage nurses was 22% (interquartile range [IQR], 11%-33%). Median perceived compliance of the health care workers was 68% (IQR, 61%-79%). Median actual knowledge score was 75% (IQR, 75%-100%). Overall, 91.9% of respondents believed that the mask was an effective preventive measure. The main obstacles toward mask wearing by the health care worker were “tendency to forget” (37.8%) and “discomfort” (35.1%). Conclusion The compliance rate at our institution is very low. We identified a few factors affecting adherence to respiratory hygiene measures that are of potential use in targeting groups and formulating recommendations.

Pregnancy after Bariatric Surgery: Balancing Risks and Benefits

The majority of bariatric surgeries in Canada are performed in women of reproductive age. Clinicians encounter more and more often pregnancies that occur after bariatric surgeries. The appropriate management and education of women who want to conceive after bariatric surgery is still unclear due to the lack of consistent data about maternal and neonatal outcomes following bariatric surgery. Maternal obesity during pregnancy confers a higher risk for gestational diabetes, hypertensive disorders, congenital malformations, prematurity and perinatal mortality. Generally, pregnancies in severely obese women who have undergone bariatric surgery are safe, and the women are at significantly lower risk for gestational diabetes, hypertensive disorders and large-for-gestational-age neonates, but the surgery confers a higher risk for small-for-gestational-age infants and prematurity. This review aims to provide evidence from recent publications about the risks and benefits of bariatric surgeries in the context of future pregnancies.

Fatty Acid Metabolic Remodeling During Type 2 Diabetes Remission After Bariatric Surgery

Hypertrophic remodeling of white adipose tissues is associated with overexposure of lean organs to circulating triglycerides (TGs) and nonesterified fatty acids (NEFAs), ultimately leading to insulin resistance. Bariatric surgery promotes type 2 diabetes (T2D) remission through a succession of weight loss–dependent and –independent mechanisms. However, the longitudinal contribution of adipocyte size reduction and fatty acid metabolic handling remain unknown. Here we show that severely obese participants with T2D display hypertriglyceridemia and excessive systemic lipolysis during intravenous lipid overload. Three days after biliopancreatic diversion with duodenal switch (DS), whole-body glycerol turnover was normalized and associated with lower HOMA–insulin resistance index. A mean excess weight loss of 84% was achieved 12 months after DS. The smaller subcutaneous adipocyte size predicted better glycemic control in T2D. TG disposal and acylcarnitine production during lipid overload, along with muscle insulin sensitivity, improved with weight loss. Nevertheless, systemic NEFA fluxes and NEFA spillover remained similar, suggesting that increased NEFA storage capacity per volume of adipose tissue exactly compensated for the decrease in fat mass during weight loss. In conclusion, T2D remission after DS is mainly associated with greater circulating TG disposal, lower systemic lipolysis, and better fatty acid handling by lean tissues.

Circulating steroid levels as correlates of adipose tissue phenotype in premenopausal women

Abstract Background Obesity-related alterations in the circulating steroid hormone profile remain equivocal in women. Our objective was to identify circulating steroid levels that relate to increased adiposity and altered adipose phenotype in premenopausal women. Materials and methods In a sample of 42 premenopausal women [age 46 ± 3 years; body mass index (BMI) 27.1 ± 4.2 kg/m2], 19 plasma steroids were quantified by electrospray ionization-liquid chromatography-tandem mass spectroscopy (ESI-LC-MS/MS). Body composition and fat distribution were assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. Markers of adipose tissue function including adipocyte size distributions, radiological attenuation and macrophage infiltration were also analyzed in surgically obtained visceral and subcutaneous fat samples. Results Many negative correlations were observed between adiposity measurements such as BMI, body fat percentage or total abdominal adipose tissue area and plasma levels of androstenedione (Δ4) (r = −0.33 to −0.39, p ≤ 0.04), androsterone (ADT) (r = −0.30 to −0.38, p ≤ 0.05) and steroid precursor pregnenolone (PREG) (r = −0.36 to −0.46, p ≤ 0.02). Visceral adipocyte hypertrophy was observed in patients with low PREG concentrations (p < 0.05). Visceral adipose tissue radiologic attenuation, a potential marker of adipocyte size, was also positively correlated with PREG levels (r = 0.33, p < 0.05). Low levels of PREG were related to increased number of macrophages infiltrating visceral and subcutaneous adipose tissue (p < 0.05). Conclusion Plasma levels of androgens and their precursors are lower in women with increased adiposity and visceral adipocyte hypertrophy. Low circulating PREG concentration may represent a marker of adipose tissue dysfunction.

Effects of 6-Month Vitamin D Supplementation on Insulin Sensitivity and Secretion: A Randomized, Placebo-Controlled Trial

Objective: To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemic-euglycemic clamp. Design: This single-center, double-blind, placebo-controlled trial randomized 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5,000 IU daily or placebo for 6 months. Methods: We assessed at baseline and 6 months: 1) primary aim: peripheral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); 2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2h-oral glucose tolerance test (OGTT); ß-cell function (disposition index: M-value x insulinogenic index); fasting and 2-h glucose post-OGTT; HbA1c; anthropometry. Results: Baseline characteristics were similar between groups (% or mean±SD): women 38.5%; age 58.7±9.4 years; BMI 32.2±4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25hydroxyvitamin D (25(OH)D) 51.1±14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6±26.3 nmol/L and 51.8±16.5 nmol/L in the treatment and placebo groups, respectively (p<0.001). A beneficial effect of vitamin D3 compared with placebo was observed on Mvalue (mean change (95% CI): 0.92 (0.24 to 1.59) versus -0.03 (-0.73 to 0.67); p=0.009) and disposition index (mean change (95% CI): 267.0 (-343.4 to 877.4) versus -55.5 (-696.3 to 585.3); p=0.039) after 6 months. No effect was seen on other outcomes. Conclusions: In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and ß-cell function, suggesting that it may slow metabolic deterioration in this population. Page 3 of 42 Accepted Manuscript published as EJE-19-0156.R2. Accepted for publication: 03-Jul-2019 Copyright

Increased body fat mass explains the positive association between circulating estradiol and insulin resistance in postmenopausal women

The relationship between circulating estrogen levels and cardiometabolic risk factors such as insulin resistance is unclear in postmenopausal women. High estradiol (E2) levels have been reported to predict increased risk of type 2 diabetes in this population. We aimed to examine associations among estrogen levels, adiposity measurements, and cardiometabolic risk variables including insulin resistance in postmenopausal women. One hundred-one healthy participants (mean ± SD: age 57 ± 4 yr, BMI 27.9 ± 4.8 kg/m2) were included in the analysis. Fifteen plasma steroids or metabolites were measured by liquid chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were determined with hydrostatic weighing and computed tomography, respectively. Blood lipids and circulating cytokines were also measured. Circulating E2 was positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001) except waist-to-hip ratio. E2 was positively correlated with VLDL-cholesterol, plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL-cholesterol, adiponectin, and insulin sensitivity ( r = -0.36 to -0.20, P < 0.02). With adjustments for percent body fat, correlations between E2 and metabolic risk variables were no longer significant. Similar results were observed for circulating estrone (E1) and estrone-sulfate (E1-S) levels. In conclusion, circulating estrogen concentrations are proportional to adipose mass in postmenopausal women, although they remain in the low range. Insulin resistance as well as altered blood lipids and cytokines are observed when circulating estrogen levels are high within that range, but these differences are explained by concomitant variation in total adiposity.

Effects of reflux laryngitis on non-nutritive swallowing in newborn lambs

Reflux laryngitis in infants may be involved not only in laryngeal disorders, but also in disorders of cardiorespiratory control through its impact on laryngeal function. Our objective was to study the effect of reflux laryngitis on non-nutritive swallowing (NNS) and NNS-breathing coordination. Two groups of six newborn lambs, randomized into laryngitis and control groups, were surgically instrumented for recording states of alertness, swallowing and cardiorespiratory variables without sedation. A mild to moderate reflux laryngitis was induced in lambs from the experimental group. A significant decrease in the number of NNS bursts and apneas was observed in the laryngitis group in active sleep (p=0.03). In addition, lower heart and respiratory rates, as well as prolonged apnea duration (p<0.0001) were observed. No physiologically significant alterations in NNS-breathing coordination were observed in the laryngitis group. We conclude that a mild to moderate reflux laryngitis alters NNS burst frequency and autonomous control of cardiac activity and respiration in lambs.