Publications by authors named "John Cardinal"

The recognition and treatment of high-altitude illness (HAI) is increasingly important in global emergency medicine. High altitude related hypobaric hypoxia can lead to acute mountain sickness (AMS), which may relate to increased expression of vascular endothelial growth factor (VEGF), and subsequent blood-brain barrier (BBB) compromise. This study aimed to establish the relationship between AMS and changes in plasma VEGF levels during a high-altitude ascent.

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The spectrin repeat-containing nuclear envelope protein 1 () gene encodes a family of spectrin structural proteins that are associated with anchoring the plasma membrane to the actin cytoskeleton. -related disease is most commonly reported in autosomal recessive spinocerebellar ataxia 8, which demonstrates variable age of onset with a median of 30 years of age. However pathogenic mutations in are also causative of arthrogryposis multiplex congenital, a severe congenital neuromuscular condition.

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Mendelian disorders of cholesterol biosynthesis typically result in multi-system clinical phenotypes, underlining the importance of cholesterol in embryogenesis and development. FDFT1 encodes for an evolutionarily conserved enzyme, squalene synthase (SS, farnesyl-pyrophosphate farnesyl-transferase 1), which catalyzes the first committed step in cholesterol biosynthesis. We report three individuals with profound developmental delay, brain abnormalities, 2-3 syndactyly of the toes, and facial dysmorphisms, resembling Smith-Lemli-Opitz syndrome, the most common cholesterol biogenesis defect.

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In this study, we report a paediatric patient with a lethal phenotype of respiratory distress, failure to thrive, pancreatic insufficiency, liver dysfunction, hypertrophic cardiomyopathy, bone marrow suppression, humoral and cellular immune deficiency. To identify the genetic basis of this unusual clinical phenotype and potentially make available the option of future prenatal testing, whole exome sequencing (WES) was used followed by functional studies in a bid to confirm pathogenicity. The WES we identified a homozygous novel variant, AK298328; c.

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Objective: Adolescent obesity is difficult to treat and the optimal dietary pattern, particularly in relation to macronutrient composition, remains controversial. This study tested the effect of two structured diets with differing macronutrient composition versus control, on weight, body composition and metabolic parameters in obese adolescents.

Design: A randomized controlled trial conducted in a children's hospital.

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Objectives: To measure tissue glucocorticoid sensitivity in patients with septic shock and determine its relationship to standard measurements of adrenal function and of outcome.

Design: Prospective observational trial.

Setting: Teaching hospital ICU.

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Insulin resistance (IR) and inflammation are associated with an increased risk of cardiovascular disease and may contribute to obesity cardiomyopathy. The earliest sign of obesity cardiomyopathy is impaired left ventricular (LV) diastolic function, which may be evident in obese children and adolescents. However, the precise metabolic basis of the impaired LV diastolic function remains unknown.

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Objective: Damage to the blood-brain barrier (BBB) is an important secondary mechanism that occurs following traumatic brain injury (TBI) and may provide a potential therapeutic target to improve patient outcome. For such a progress to be realised, an accurate assessment of BBB compromise needs to be established.

Methods: Fourteen patients with TBI were prospectively recruited.

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Current efforts to identify the genetic contribution to abdominal aortic aneurysm (AAA) have mainly focused on the assessment of germ-line variants such as single-nucleotide polymorphisms. The aim of the present study was to assess the presence of acquired chromosomal aberrations in human AAA. Microarray data of ten biopsies obtained from the site of main AAA dilatation (AAA body) and three control biopsies obtained from the macroscopically non-dilated neck of the AAA (AAA neck) were initially compared with identified chromosomal aneuploidies using the Chromosomal Aberration Region Miner (ChARM) software.

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Objectives: Ascent to high altitude may result in a hypobaric hypoxic brain injury. The development of acute mountain sickness (AMS) is considered a multifactorial process with hypoxia-induced blood-brain barrier (BBB) dysfunction and resultant vasogenic oedema cited as one potential mechanism. Peripheral S100B is considered a biomarker of BBB dysfunction.

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AAA (abdominal aortic aneurysm) is a potentially life-threatening late-onset degenerative condition. miRNAs (microRNAs), the small non-coding RNA molecules that regulate gene expression, have been shown previously to be associated with a broad range of human pathologies, including cardiovascular diseases. The aim of the present study was to identify AAA-associated miRNAs potentially contributing to AAA pathology.

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Background: Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are biomarkers of kidney injury and function, respectively. This study assessed whether plasma NGAL and/or serum cystatin C predicted baseline estimated glomerular filtration rate (eGFR) and urinary protein excretion, rate of change of eGFR and urinary protein excretion and whether atorvastatin influenced changes in these biomarkers in patients with chronic kidney disease (CKD).

Methods: This is a post hoc analysis of the Lipid Lowering and Onset of Renal Disease trial, a randomized double-blind, placebo-controlled trial where 88 patients with Stages 2-4 CKD received atorvastatin 10 mg/day (48) or placebo (40).

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Background: Despite the recognition of obesity in young people as a key health issue, there is limited evidence to inform health professionals regarding the most appropriate treatment options. The Eat Smart study aims to contribute to the knowledge base of effective dietary strategies for the clinical management of the obese adolescent and examine the cardiometablic effects of a reduced carbohydrate diet versus a low fat diet.

Methods And Design: Eat Smart is a randomised controlled trial and aims to recruit 100 adolescents over a 2 1/2 year period.

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Introduction: Glucocorticoid resistance due to mutations of the glucocorticoid receptor (NR3C1) are rare, but reduced glucocorticoid sensitivity may play a role in steroid-resistant asthma, inflammatory bowel disease, and septic shock. A rapid and sensitive functional assay to detect glucocorticoid resistance will be advantageous.

Method: We describe a rapid in vitro monocyte dexamethasone suppression of cytokine production (DSCP) assay with a 3-h incubation.

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Background And Objective: Increased BMI is a risk factor for asthma in children and may be related to adipokines. Adipokines affect insulin-stimulated glucose uptake in vitro but, to date there is little evidence for such a role in vivo. We explored relationships between obesity and allergic asthma in children.

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Dendritic cell (DC) differentiation is abnormal in type 1 diabetes mellitus (T1DM). However, the nature of the relationship between this abnormality and disease pathogenesis is unknown. We studied the LPS response in monocytes and monocyte-derived DCs isolated from T1DM patients and from non-T1DM controls.

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Familial hyperparathyroidism, a disease of the parathyroid glands, may occur in conjunction with pituitary and pancreatic tumors (multiple endocrine neoplasia type I), kidney and bone tumors (hyperparathyroidism jaw tumor syndrome), or alone (familial isolated hyperparathyroidism). This study describes the development and validation of rapid scanning for mutations in two tumor suppressor genes linked to familial hyperparathyroidism-MEN1 and HRPT2. Denaturing high-performance liquid chromatography mutation scanning for MEN1 was performed using a set of 10 amplicons covering the nine coding exons and flanking intronic regions and for HRPT2 using a set of three amplicons for exons 1, 2, and 7 and flanking intronic regions, in which 80% of the mutations identified to date are located.

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