James A.T.,The Rotunda Hospital |
Corcoran J.D.,The Rotunda Hospital |
Jain A.,Mount Sinai Hospital |
Jain A.,University of Toronto |
And 5 more authors.
Early Human Development | Year: 2014
Background: The transitional circulation and its effect on myocardial performance are poorly understood in preterm infants. Aims: We assessed myocardial performance in infants less than 29. weeks gestation in the first 48. h of life using a comprehensive echocardiographic assessment. Design: Infants < 29. weeks gestation were prospectively enrolled. Small for gestation, infants on inotropes and/or inhaled nitric oxide and septic infants were excluded. Conventional echocardiography, left ventricular (LV), septal and right ventricular (RV) tissue Doppler imaging (TDI) and tissue Doppler-derived strain and strain rate (SR), tricuspid annular plane systolic excursion (TAPSE) and global RV fractional area change (FAC) were assessed at a median of 10 and 45. h post-delivery. Results: Fifty-four infants with a median [IQR] gestation and birth weight of 26.5 weeks [25.8-28.0 weeks] and 915 g [758-1142 g] were included. There was no change in shortening or ejection fraction across the two time points. Systolic and diastolic TDI of the LV, septum and RV increased across the two time points (all p values ≤ 0.01). There was an increase in septal peak systolic and early diastolic SR (p = 0.002). Septal systolic strain and late diastolic SR did not change. With the exception of RV strain and early diastolic SR, all RV functional parameters including SR, late diastolic SR, TAPSE, and FAC increased across the two time points (all p values. <. 0.01). Conclusion: Describing the normal hemodynamic adaptations in stable preterm infants during the transitional period provides the necessary information for the assessment of those parameters in various disease states. © 2014 Elsevier Ltd. Source
Dorfman R.,Genetics and Genome Biology |
Nalpathamkalam T.,Genetics and Genome Biology |
Taylor C.,Child Health Evaluative science |
Gonska T.,University of Toronto |
And 6 more authors.
Clinical Genetics | Year: 2010
Computational methods are used to predict the molecular consequences of amino-acid substitutions on the basis of evolutionary conservation or protein structure, but their utility in clinical diagnosis or prediction of disease outcome has not been well validated. We evaluated three popular computer programs, namely, PANTHER, SIFT and P. olyP. hen, by comparing the predicted clinical outcomes for a group of known CFTR missense mutations against the diagnosis of cystic fibrosis (CF) and clinical manifestations in cohorts of subjects with CF-disease and CFTR-related disorders carrying these mutations. Owing to poor specificity, none of tools reliably distinguished between individual mutations that confer CF disease from mutations found in subjects with a CFTR-related disorder or no disease. Prediction scores for CFTR mutations derived from PANTHER showed a significant overall statistical correlation with the spectrum of disease severity associated with mutations in the CFTR gene. In contrast, P. olyP. hen- and SIFT-derived scores only showed significant differences between CF-causing and non-CF variants. Current computational methods are not recommended for establishing or excluding a CF diagnosis, notably as a newborn screening strategy or in patients with equivocal test results. © 2010 John Wiley & Sons A/S. Source
Litvack M.L.,Lung Innate Immunity Research Laboratory |
Litvack M.L.,University of Toronto |
Post M.,Physiology and Experimental Medicine |
Post M.,University of Toronto |
And 2 more authors.
PLoS ONE | Year: 2011
Background: Antibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a size-dependent effect on clearance. Methodology/Principal Findings: We used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal) and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1-2 micron) by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2-5 micron) and apoptotic microparticles (<2 μm) released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads. Conclusions/Significance: Therefore, while the shape of the particles is important for non-opsonized particle uptake, the particle size matters for antibody-mediated clearance by macrophages. IgM particularly promotes the clearance of small size particles. This finding may have wider implications in IgM-mediated clearing of antigens, microbial pathogens and dying cells by the host. © 2011 Litvack et al. Source
Sinopoli K.J.,Physiology and Experimental Medicine |
Sinopoli K.J.,University of Toronto |
Schachar R.,Neurosciences and Mental Health |
Schachar R.,University of Toronto |
And 2 more authors.
Journal of Clinical and Experimental Neuropsychology | Year: 2011
Poor inhibitory control and abnormalities in responding to rewards are characteristic of the developmental or primary form of attention-deficit/ hyperactivity disorder (P-ADHD). A secondary form of ADHD (S-ADHD) may occur as a consequence of childhood traumatic brain injury (TBI), but the similarities and differences between these two forms of ADHD have not been well characterized. To address these issues, we studied two inhibitory control tasks under different reward conditions in four groups of children and adolescents: TBI who did not exhibit S-ADHD, TBI who did exhibit S-ADHD, P-ADHD, and healthy controls. Participants with TBI exhibited poor cancellation inhibition relative to controls. Although reward facilitated both cancellation and restraint inhibition similarly across groups, poor performance persisted in the P-ADHD group, and participants with S-ADHD exhibited a selective deficit in cancellation inhibition. © 2011 Psychology Press. Source
James A.T.,Rotunda Hospital |
Bee C.,Rotunda Hospital |
Corcoran J.D.,Rotunda Hospital |
Mcnamara P.J.,Physiology and Experimental Medicine |
And 3 more authors.
Journal of Perinatology | Year: 2015
Objective:Milrinone has been proposed as an effective treatment for pulmonary hypertension (PH) and right ventricular (RV) dysfunction. We aimed to determine the effect of milrinone therapy on clinical and echocardiography parameters of PH in preterm infants with elevated pulmonary pressures.Study Design:A retrospective case review was conducted on infants <32 weeks gestation who received milrinone for the treatment of PH and reduced RV function. Echocardiographic data were collected before and after treatment with milrinone, and serial clinical parameters were recorded over a 72hperiod.Result:Seven infants met the inclusion criteria with a median gestation and birth weight of 27.3 weeks and 1140 g, respectively. Four infants had a diagnosis of pulmonary hypoplasia with PH, and three infants were recipients in twin-to-twin transfusion syndrome who also developed PH. Nitric oxide was used in six infants before commencement of milrinone. Milrinone was commenced at a dose of 0.33 μg kg -1 min -1 to 0.5 μg kg -1 min -1 and continued for a median duration of 70 h. Use of milrinone was associated with a fall in oxygenation index and inhaled nitric oxide dose. Following an initial fall in blood pressure over the first 6 h, there was an increase in blood pressure over the subsequent 72 h. Echocardiographic data demonstrated an increase in indicators of myocardial performance and PH. One infant died before discharge.Conclusion:This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction. This data support the need for a randomised control trial to confirm its efficacy. © 2015 Nature America, Inc. Source