Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu

Montréal, Canada

Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu

Montréal, Canada
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Coderre L.,Institute Of Recherches Cliniques Of Montreal | Coderre L.,University of Montréal | Fadainia C.,Institute Of Recherches Cliniques Of Montreal | Belson L.,Institute Of Recherches Cliniques Of Montreal | And 11 more authors.
Journal of Cystic Fibrosis | Year: 2012

Background: The median life expectancy of cystic fibrosis (CF) patients has increased dramatically over the last few years and we now observe a subset of patients with a body mass index (BMI) exceeding 25kg/m2. The aim of this study was to characterize these individuals and to identify factors associated with higher BMI. Methods: This is a cross sectional study including 187 adult CF subjects. Percent predicted forced expiratory volume in 1s (%FEV1), blood lipid profiles as well as fasting glucose and insulin levels were evaluated. Subjects also had an oral glucose tolerance test (OGTT) and the area under the curve (AUC) for glucose and insulin was calculated. CF subjects were then stratified according to the following BMI categories: underweight: BMI≤18.5kg/m2; normal weight: 18.5kg/m2


Ama V.,University of Yaounde I | Kengne A.P.,University of Cape Town | Nansseu N.J.R.,University of Yaounde I | Nouthe B.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | And 2 more authors.
Diabetic Medicine | Year: 2012

Aims To determine the prevalence and effects of sickle cell trait on metabolic control in a Cameroonian diabetic population in a tertiary care setup. Methods This was a cross-sectional study involving 73 consecutive outpatients with Type 2 diabetes recruited from the Yaounde National Diabetes and Obesity Centre. Sickle cell trait status was based on haemoglobin electrophoresis. Metabolic control was assessed by plasma glucose and HbA1c, and comparisons made between participants with and without sickle cell trait, with adjustment for confounders through linear regressions models Results The prevalence of sickle cell trait was 19%, without sex difference, and comparable with figures in individuals without diabetes in this setting. Participants with diabetes and sickle cell trait were older than the non-trait participants (66 vs. 58years, P=0.02). Otherwise, clinical and biological profile including indicators of metabolic control were similarly distributed between trait and non-trait participants (all P>0.08). After adjustment for confounders, sickle cell trait was unrelated to fasting glucose (β=0.02; 95% confidence interval -37.68-43.30) and HbA1c (β=-0.03, 95% confidence interval -1.18-0.93), and did not affect the relationship between the two markers of diabetes control (β=-0.03, 95% confidence interval -1.18-0.89). Conclusions Sickle cell trait was as frequent in this subgroup of patients with Type 2 diabetes as in the general population, suggesting no specific association with diabetes. It does not affect the metabolic control of diabetes. However, how this translates into long-term outcome needs to be fully elucidated in this setting, with an increasing population with both sickle cell trait and diabetes mellitus. © 2012 Diabetes UK.


Laurin L.-P.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Jobin V.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Bellemare F.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu
Canadian Respiratory Journal | Year: 2012

Background: A greater structural expansion of the rib cage in females compared with males has been described in cystic fibrosis (CF) patients; however, conflicting data exist as to whether an elongation of the bony ribs and sternum contributes to this expansion. objectives: To compare height-adjusted anthropometric measures and sternum length between a group of normal subjects and a group of CF patients of both sexes. Methods: Anthropometric measurements including body weight, height, upper and lower limb lengths, biacromial distance and pelvic width were measured in the standing position in 30 CF patients (13 males) and 28 normal subjects (14 males). Body surface measurements of anterior-posterior and lateral diameters of the rib cage at functional residual capacity, and sternum length were also obtained. Results : Compared with normal subjects, CF patients had lower body weight, shorter standing height and shorter height-adjusted upper and lower limb lengths. Rib cage diameters were greater in CF patients than in normal subjects of either sex, but height-adjusted sternum length was not different. Conclusion: Significant differences in bodily proportions were found between normal subjects and CF patients, suggesting a differential growth pattern for the trunk and limbs. However, increased rib cage dimensions with lung hyperinflation and airway obstruction was not associated with an elongation of the sternum. ©2012 Pulsus Group Inc. All rights reserved.


MacKenzie Feder J.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Bourdeau I.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Vallette S.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Beauregard H.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | And 2 more authors.
Pituitary | Year: 2014

Results: Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3–6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 μg daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient.Conclusions: Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.Purpose: A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushing’s disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control.Methods: The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed. © 2013, Springer Science+Business Media New York.


Mailhot G.,University of Montréal | Rabasa-Lhoret R.,University of Montréal | Moreau A.,University of Montréal | Berthiaume Y.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Levy E.,University of Montréal
PLoS ONE | Year: 2010

Background: Abnormal fatty acid composition (FA) in plasma and tissue lipids frequently occurs in homozygous and even in heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The mechanism(s) underlying these abnormalities remained, however, poorly understood despite the potentially CFTR contributing role. Methodology/Principal Findings: The aim of the present study was to investigate the impact of CFTR depletion on FA uptake, composition and metabolism using the intestinal Caco-2/15 cell line. shRNA-mediated cftr gene silencing induced qualitative and quantitative modifications in FA composition in differentiated enterocytes as determined by gas-liquid chromatography. With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls. The activity of delta-7 desaturase, estimated by the 16:1(n-7)/ 16:0, was significantly higher in knockdown cells and consistent with the striking elevation of the n-7 FA family. When incubated with [14C]-oleic acid, CFTR-depleted cells were capable of quick incorporation and export to the medium concomitantly with the high protein expression of L-FABP known to promote intracellular FA trafficking. Accordingly, lipoprotein vehicles (CM, VLDL, LDL and HDL), isolated from CFTR knockdown cells, exhibited higher levels of radiolabeled FA. Moreover, in the presence of [14C]-acetate, knockdown cells exhibited enhanced secretion of newly synthesized phospholipids, triglycerides, cholesteryl esters and free FA, thereby suggesting a stimulation of the lipogenic pathway. Conformably, gene expression of SREBP-1c, a key lipogenic transcription factor, was increased while protein expression of the phosphorylated and inactive form of acetylCoA carboxylase was reduced, confirming lipogenesis induction. Finally, CFTR-depleted cells exhibited lower gene expression of transcription factors (PPARα, LXRα, LXRβ and RXRα). Conclusions/Significance: Collectively, our results indicate that CFTR depletion may disrupt FA homeostasis in intestinal cells through alterations in FA uptake and transport combined with stimulation of lipogenesis that occurs by an LXR/RXRindependent mechanism. These findings exclude a contributing role of CFTR in CF-associated fat malabsorption. © 2010 Mailhot et al.


Damphousse V.,University of Montréal | Mailhot M.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Berthiaume Y.,Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu | Berthiaume Y.,Institute Of Recherches Cliniques Of Montreal | And 5 more authors.
Journal of Trace Elements in Medicine and Biology | Year: 2014

Background: Zinc status has been previously documented in cystic fibrosis (CF) infants, children and adolescents. However, despite the increasing life expectancy observed in CF populations, data regarding zinc status of CF adults are surprisingly lacking. The objectives of this study were to (1) characterize zinc status and (2) explore associations between zinc status and clinical outcomes of CF adult patients. Methods: A retrospective chart review was performed for patients who had their plasma zinc measured between 2009 and 2012. Data included demographics, clinical characteristics, biochemical parameters and co-morbid conditions. Results: A total of 304 CF patients were included in the study. These patients displayed a good nutritional status (mean BMI±SD: 22.7±3.5) and moderate lung disease (mean FEV1±SD: 66.3±22.2). Low plasma zinc concentration (<9.2μmol/L) was found in 68 out of 304 CF patients (22.4%). Compared to patients with normal zinc, those with low zinc had significantly lower forced vital capacity and forced expiratory volume in one second. 72% of CF adults with low zinc suffered from bone disease (vs 49% with normal zinc, p=0.037) and 79% had impaired glycemic status (vs 58%, p=0.016). Accordingly, negative correlations were found between plasma zinc and glucose (r=-0.139, p=0.0001), HbA1c (r=-0.237, p=0.0001) and fructosamine (r=-0.134, p=0.034). In multiple linear regression, albumin and glycemic status were significant predictors of plasma zinc. Conclusion: Our data indicated that nearly one quarter of CF adults with good nutritional status and moderate lung disease had low plasma zinc concentration and that low zinc status was associated with worse clinical outcomes. © 2013 Elsevier GmbH.


PubMed | Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu
Type: | Journal: AIDS research and therapy | Year: 2012

Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs) play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART)-related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART.The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1): twice while on optimal cART (first, during long-term and second, during short term cART) and twice during 2 cART interruptions when HIV viral load (VL) was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2) with suboptimal cART (detectable VL) and from 28 healthy adults (G3). Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels.During optimal cART, G1 participants had drastically reduced RAs (0.5 0.3 g/dL; P < 0.01) but the highest ROL (82 3.0 g/dL) concentrations. During cART interruptions in these patients, RAs slightly increased whereas ROL levels diminished significantly (P < 0.05). G3 had the highest RAs levels (7.2 1.1 g/dL) and serum ROL comparable to values in North Americans. Serum ROL was decreased in G2 (37.7 3.2 g/dL; P < 0.01). No correlations were noted between RA and ROL levels or between retinoid concentrations and CD4+ T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01).Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess concomitant serum and intracellular retinoid levels in different clinical situations in larger, homogenous populations.


PubMed | University of Montréal and Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu
Type: Journal Article | Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) | Year: 2013

Zinc status has been previously documented in cystic fibrosis (CF) infants, children and adolescents. However, despite the increasing life expectancy observed in CF populations, data regarding zinc status of CF adults are surprisingly lacking. The objectives of this study were to (1) characterize zinc status and (2) explore associations between zinc status and clinical outcomes of CF adult patients.A retrospective chart review was performed for patients who had their plasma zinc measured between 2009 and 2012. Data included demographics, clinical characteristics, biochemical parameters and co-morbid conditions.A total of 304 CF patients were included in the study. These patients displayed a good nutritional status (mean BMISD: 22.73.5) and moderate lung disease (mean FEV1SD: 66.322.2). Low plasma zinc concentration (<9.2mol/L) was found in 68 out of 304 CF patients (22.4%). Compared to patients with normal zinc, those with low zinc had significantly lower forced vital capacity and forced expiratory volume in one second. 72% of CF adults with low zinc suffered from bone disease (vs 49% with normal zinc, p=0.037) and 79% had impaired glycemic status (vs 58%, p=0.016). Accordingly, negative correlations were found between plasma zinc and glucose (r=-0.139, p=0.0001), HbA1c (r=-0.237, p=0.0001) and fructosamine (r=-0.134, p=0.034). In multiple linear regression, albumin and glycemic status were significant predictors of plasma zinc.Our data indicated that nearly one quarter of CF adults with good nutritional status and moderate lung disease had low plasma zinc concentration and that low zinc status was associated with worse clinical outcomes.


PubMed | University of British Columbia, University of Québec and Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu
Type: | Journal: Respiratory medicine case reports | Year: 2016

Patients with Cystic Fibrosis are subject to repeated respiratory tract infections, with recent increasing isolation of unusual pathogens. Ralstonia species have lately been isolated at our institution, an organism historically frequently misidentified as Burkholderia or Pseudomonas. The prevalence of Ralstonia spp. in cystic fibrosis populations has yet to be determined, along with its clinical implications.Seven patients out of the 301 followed at our cystic fibrosis clinic have had Ralstonia strains identified in their respiratory tract. Most strains identified were multi-drug resistant. After aquisition of Ralstonia spp., the patients clinical course was characterized by more frequent and more severe respiratory infections along with prolonged hospitalizations, greater decline of lung function, and greater mortality. The mortality rate in this group of patients was 86%. No other factor that could explain such a dramatic evolution was identified upon review of patient data. Some of the strains involved were recognized as clones on Pulse Field Electrophoresis Gel, raising the question of person-to-person transmission.New pathogens are identified with the evolution of the microbiota in cystic fibrosis respiratory tracts. In our cohort of patients, acquisition of Ralstonia spp. was associated with dramatic outcomes in terms of disease acceleration and raised mortality rates. It is of critical importance to continue to better define the prevalence and clinical impact of Ralstonia in cystic fibrosis populations.


PubMed | Center Hospitalier Of Luniversite Of Montreal Chum Hotel Dieu
Type: Case Reports | Journal: Pituitary | Year: 2014

A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushings disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control.The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed.Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3-6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 g daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient.Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.

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