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Mary Corey

Publications and source records attributed to Mary Corey.

At least 19 recordsLinked to original sources
PubMed2006

Long-term docosahexaenoic acid therapy in a congenic murine model of cystic fibrosis.

We used a congenic C57Bl/6J cystic fibrosis transmembrane conductance regulator (Cftr)(-/-) mouse model, which develops cystic fibrosis (CF)-like pathology in all organs, to evaluate the short- and long-term therapeutic effects of dietary docosahexaenoic acid (DHA). Thirty-day-old Cftr(-/-) mice and wild-type littermates were randomized to receive a liquid diet with or without DHA (40 mg/day). Animals were killed for histological and lipid analysis after 7, 30, and 60 days of therapy. DHA had no significant therapeutic or harmful effect on the lung, pancreas, or ileum of the Cftr(-/-) mice or their wild-type littermates. In contrast, dietary DHA resulted in highly significant amelioration of the severity of liver disease in the Cftr(-/-) mice, primarily a reduction in the degree of peri-portal inflammation. Additionally, these detailed measurements confirm our previous findings that Cftr(-/-) mice have significant alterations in the pancreas (except external acinar diameter), ileum, liver, lung, and salivary (except sublingual) glands at all ages compared with their age-matched wild-type littermates. In conclusion, inhibition of cytokines and/or eicosanoid metabolism and release of endogenous inhibitors of inflammation by DHA may account for the anti-inflammatory effects in the liver of this congenic murine model of CF. The potential therapeutic benefits of DHA in severe CF-associated liver disease remain to be explored.

Administration, Oral↗
PubMed2006

Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials.

AIM: To examine the relationship between cystic fibrosis transmembrane regulator gene mutations (CFTR) and in vivo transepithelial potentials. METHODS: We prospectively evaluated 162 men including 31 healthy subjects, 21 obligate heterozygotes, 60 with congenital bilateral absence of the vas deferens (CBAVD) and 50 with CF by extensive CFTR genotyping, sweat chloride and nasal potential difference testing. RESULTS: Six (10%) men with CBAVD carried no CFTR mutations, 18 (30%) carried one mutation, including the 5T variant, and 36 (60%) carried mutations on both alleles, for a significantly higher rate carrying one or more mutations than healthy controls (90% versus 19%, p < 0.001). There was an overlapping spectrum of ion channel measurements among the men with CBAVD, ranging from values in the control and obligate heterozygote range at one extreme, to values in the CF range at the other. All pancreatic-sufficient patients with CF and 34 of 36 patients with CBAVD with mutations on both alleles carried at least one mild mutation. However, the distribution of mild mutations in the two groups differed greatly. Genotyping, sweat chloride and nasal potential difference (alone or in combination) excluded CF in all CBAVD men with no mutations. CF was confirmed in 56% and 67% of CBAVD men carrying 1 and 2 CFTR mutations, respectively. CONCLUSION: Abnormalities of CFTR transepithelial function correlate with the number and severity of CFTR gene mutations.

Alleles↗
PubMed2006

Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening.

OBJECTIVES: To characterize the time course and physiologic significance of decline in serum immunoreactive trypsinogen (IRT) levels in infants with cystic fibrosis (CF) by mode of diagnosis and genotype, and to examine IRT heritability. STUDY DESIGN: We studied longitudinal IRT measurements in 317 children with CF. We developed statistical models to describe IRT decline. Pancreatic disease severity (Mild or Severe) was assigned using CF genotype and was confirmed in 47 infants through fat malabsorption studies. RESULTS: Infants with severe disease exhibited IRT decline with non-detectable levels typically seen by 5 years of age. Infants with mild disease exhibited a decline in the first 2 years, asymptomatically approaching a level greater than published norms. IRT and fecal fat were inversely correlated. IRT values in infants with meconium ileus (MI) were significantly lower than newborn-screened infants at birth. The high proportion of shared variation in predicted IRT values among sibling pairs with severe disease suggests that IRT is heritable. CONCLUSIONS: IRT declines characteristically in infants with CF. Lower IRT values in newborns with MI suggest increased pancreatic injury. Furthermore, IRT is heritable among patients with severe disease suggesting genetic modifiers of early CF pancreatic injury. This study demonstrates heritability of a statistically modeled quantitative phenotype.

Biomarkers↗
PubMed2006

Towards the ideal quantitative pancreatic function test: analysis of test variables that influence validity.

BACKGROUND & AIMS: Although pancreatic stimulation tests quantify acinar and ductal exocrine pancreatic function, no standard methodology exists. We evaluated the impact of several variables on test accuracy. METHODS: We performed a retrospective analysis of pancreatic stimulation tests, which involved continuous stimulation with cholecystokinin and secretin, 3 sampling periods (20-min each), and perfusion markers to correct for intestinal losses. Results were recalculated using the following variables: no correction for losses; shortened sampling time (20-min); no correction and shortened sampling time; and enzyme concentration. We examined how these variables influenced measurements of pancreatic secretion and classification of pancreatic function status (sufficient or insufficient). RESULTS: We analyzed 363 tests in control patients (20), and patients with cystic fibrosis (137), Shwachman-Diamond syndrome (40), or other pancreatic or intestinal disorders (166). Recovery of pancreatic juice varied markedly between tests (median, 59%; range, 4%-106%) and was significantly poorer during the first 20-minute period compared with the 2 subsequent periods (P < .01). Failure to correct for intestinal losses underestimated secretory capacity (median trypsin output reduced by >50%, P < .0001) and shortened sampling time increased test variability. Both variables together resulted in greater discrepancies. More than 25% of the pancreatic-sufficient patients with impaired pancreatic function were misclassified as pancreatic insufficient when uncorrected output plus a shortened sampling time or enzyme concentration were used to define categories. CONCLUSIONS: Pancreatic function tests using brief aspiration periods without marker perfusion or measures of concentration greatly underestimate pancreatic secretory capacity and misclassify the clinical status of an unacceptably large number of patients.

Female↗
PubMed2006

Evaluation of the ambulatory and home care record: Agreement between self-reports and administrative data.

OBJECTIVES: Although measuring the utilization of ambulatory and home-based healthcare resources is an essential component of economic analyses, very little methodological attention has been devoted to the development and evaluation of resource costing tools. This study evaluated a newly developed tool, the Ambulatory and Home Care Record (AHCR), which comprehensively evaluates costs incurred by the health system and care recipients and their unpaid caregivers. METHODS: The level of agreement between self-reports from 110 cystic fibrosis care recipients and administrative data was assessed for four categories of health services: home-based visits with healthcare professionals, ambulatory visits with healthcare professionals, laboratory and diagnostic tests, and prescription medications. RESULTS: Agreement between care recipients' reports on the AHCR and administrative data ranged from moderate (kappa = 0.41; 95 percent confidence interval, 0.16-0.61) for physician specialist visits to perfect (kappa = 1.0) for physiotherapy visits. CONCLUSIONS: By evaluating and standardizing a resource and costing tool, such as the AHCR, economic evaluations may be improved and comparisons of the resource implications for different services and for diverse populations are possible.

Adult↗
PubMed2006

Enteric-coated pancreatic enzyme with bicarbonate is equal to standard enteric-coated enzyme in treating malabsorption in cystic fibrosis.

OBJECTIVES: To compare the efficacy of an enteric-coated buffered pancreatic enzyme (EC buffered PE) containing 1.5 mEq of bicarbonate per capsule with a conventional enteric-coated enzyme (EC-PE) capsule in cystic fibrosis patients with signs or symptoms of moderate to severe malabsorption. METHODS: In a double-blind crossover study, subjects were randomly assigned to two consecutive, 2-week phases using an EC buffered PE product and conventional EC-PE product. Seventy-two hour stool collections from each phase were analyzed for energy, fat, and nitrogen content and expressed as percent of estimated intake. RESULTS: Twenty-one patients with cystic fibrosis and pancreatic insufficiency (14 female, mean age 20.6 +/- 11.5 years, range 8.8-41.9) completed the study. There was no significant difference in percent malabsorption of energy (19.4% vs. 19.0%), fat (20.7% vs. 20.2%), or nitrogen (10.4% vs. 10.7%) between the EC buffered PE product and the conventional EC-PE product. However, patients taking the EC buffered PE product received less enzyme based on actual enzyme activity measured in vitro (3,468 +/- 1,434 U lipase/g fat vs. 3,978 +/- 1,474 U lipase/g fat, P < 0.02). CONCLUSIONS: In the doses used, nutrient absorption of patients taking EC buffered PE preparation offers no advantage over a conventional EC-PE preparation.

Adolescent↗
PubMed2006

Prevalence of vertebral fractures in adults with cystic fibrosis and their relationship to bone mineral density.

STUDY OBJECTIVES: The objectives of this study were to determine the prevalence of morphometric vertebral fractures in a large cohort of adult cystic fibrosis (CF) patients, and to examine the association between fractures and bone mineral density (BMD). DESIGN: Cross-sectional retrospective study. SETTING: A tertiary care academic hospital. PATIENTS: Adult CF patients who had undergone BMD testing and chest radiography within 1 month of each other. MEASUREMENTS AND RESULTS: BMD was measured by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (LS) and femoral neck (FN). Vertebral fractures were diagnosed using lateral chest radiographs. Several clinical and biochemical variables were assessed as correlates. Sixty subjects (36%) had z scores between -1.0 and -2.5, and 15 subjects (9%) had z scores of < -2.5. Twelve patients (7.2%) had 19 morphometric fractures. The mean BMD at the LS was 1.266 g/cm(2) in the fracture group and 1.112 g/cm(2) in the nonfracture group (p = 0.0002). The mean BMD at the FN was 1.129 g/cm(2) in the fracture group and 0.987 g/cm(2) in the nonfracture group (p = 0.0006). Both FEV(1) and body mass index were significantly associated with BMD at both the LS and the FN. CONCLUSION: Seven percent of adult patients with CF had vertebral fractures as determined by morphometry. Subjects in the fracture group had both clinically and statistically higher BMD as measured by DXA. Our findings raise the intriguing possibility that BMD may not be useful in identifying CF patients with fractures.

Absorptiometry, Photon↗
PubMed2006

Economic burden of ambulatory and home-based care for adults with cystic fibrosis.

OBJECTIVE: The purpose of this study was to measure costs associated with care for adults with cystic fibrosis, from a societal perspective. METHODS: Over a 4-week period, 110 participants completed the Ambulatory and Home Care Record, a self-administered data collection instrument that measures costs to the health system, costs to employers, care recipients' direct out-of-pocket expenditures, and time costs borne by care recipients and their family caregivers. Health system costs were based on the costs incurred through expenditures on physicians, hospital clinics, pharmaceuticals, and home care agencies. Out-of-pocket costs were obtained using self-reports by care recipients, and time losses were valued using the human capital approach. RESULTS: The annual mean societal costs of ambulatory care for cystic fibrosis was $Can29 885 per care recipient (year 2002 value). Time losses incurred by care recipients and their family caregivers accounted for the majority (72%) of these costs, and system costs accounted for the second highest percentage of costs (21%). Although almost all participants (109) recorded out-of-pocket expenditures, these costs accounted for only a small proportion (3%) of total costs. CONCLUSION: Measuring societal costs is necessary for practitioners, managers, and policy decision-makers, to ensure that care recipients and their families receive the necessary resources to provide care.

Adult↗
PubMed2005

Recursive partitioning models for linkage in COGA data.

We have developed a recursive-partitioning (RP) algorithm for identifying phenotype and covariate groupings that interact with the evidence for linkage. This data-mining approach for detecting gene x environment interactions uses genotype and covariate data on affected relative pairs to find evidence for linkage heterogeneity across covariate-defined subgroups. We adapted a likelihood-ratio based test of linkage parameterized with relative risks to a recursive partitioning framework, including a cross-validation based deviance measurement for choosing optimal tree size and a bootstrap sampling procedure for choosing robust tree structure. ALDX2 category 5 individuals were considered affected, categories 1 and 3 unaffected, and all others unknown. We sampled non-overlapping affected relative pairs from each family; therefore, we used 144 affected pairs in the RP model. Twenty pair-level covariates were defined from smoking status, maximum drinks, ethnicity, sex, and age at onset. Using the all-pairs score in GENEHUNTER, the nonparametric linkage tests showed no regions with suggestive linkage evidence. However, using the RP model, several suggestive regions were found on chromosomes 2, 4, 6, 14, and 20, with detection of associated covariates such as sex and age at onset.

Alcoholism↗
PubMed2005

Genetic modifiers of lung disease in cystic fibrosis.

BACKGROUND: Polymorphisms in genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene may modify the severity of pulmonary disease in patients with cystic fibrosis. METHODS: We performed two studies with different patient samples. We first tested 808 patients who were homozygous for the DeltaF508 mutation and were classified as having either severe or mild lung disease, as defined by the lowest or highest quartile of forced expiratory volume in one second (FEV1), respectively, for age. We genotyped 16 polymorphisms in 10 genes reported by others as modifiers of disease severity in cystic fibrosis and tested for an association in patients with severe disease (263 patients) or mild disease (545). In the replication (second) study, we tested 498 patients, with various CFTR genotypes and a range of FEV1 values, for an association of the TGFbeta1 codon 10 CC genotype with low FEV1. RESULTS: In the initial study, significant allelic and genotypic associations with phenotype were seen only for TGFbeta1 (the gene encoding transforming growth factor beta1), particularly the -509 and codon 10 polymorphisms (with P values obtained with the use of Fisher's exact test and logistic regression ranging from 0.006 to 0.0002). The odds ratio was about 2.2 for the highest-risk TGFbeta1 genotype (codon 10 CC) in association with the phenotype for severe lung disease. The replication study confirmed the association of the TGFbeta1 codon 10 CC genotype with more severe lung disease in comparisons with the use of dichotomized FEV1 for severity status (P=0.0002) and FEV1 values directly (P=0.02). CONCLUSIONS: Genetic variation in the 5' end of TGFbeta1 or a nearby upstream region modifies disease severity in cystic fibrosis.

Adolescent↗
PubMed2005

The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are associated with cystic fibrosis (CF)-related monosymptomatic conditions, including idiopathic pancreatitis. We evaluated prospectively enrolled patients who had idiopathic recurrent acute pancreatitis or idiopathic chronic pancreatitis, healthy controls, CF heterozygotes, and CF patients (pancreatic insufficient or sufficient) for evidence of CFTR gene mutations and abnormalities of ion transport by sweat chloride and nasal potential difference testing. DNA samples from anonymous blood donors were controls for genotyping. At least one CFTR mutation or variant was carried in 18 of 40 patients (45%) with idiopathic chronic pancreatitis and in 6 of 16 patients (38%) with idiopathic recurrent acute pancreatitis but in only 11 of the 50 controls (22%, P=0.005). Most identified mutations were rare and would not be identified in routine genetic screening. CFTR mutations were identified on both alleles in six patient (11%). Ion transport measurements in patients with pancreatitis showed a wide range of results, from the values in patients with classically diagnosed CF to those in the obligate heterozygotes and healthy controls. In general, ion channel measurements correlated with the number and severity of CFTR mutations. Twelve of 56 patients with pancreatitis (21%) fulfilled current clinical criteria for the diagnosis of CF, but CFTR genotyping alone confirmed the diagnosis in only two of these patients. We concluded that extensive genotyping and ion channel testing are useful to confirm or exclude the diagnosis of CF in the majority of patients with idiopathic pancreatitis.

Adult↗
PubMed2005

Increased vitamin A and E levels in adult cystic fibrosis patients after lung transplantation.

Most patients with cystic fibrosis (CF) and pancreatic insufficiency require supplementation with fat-soluble vitamins to maintain normal serum levels. Even with supplementation, toxicity is rare. We evaluated serum vitamin A and E levels in 23 adult patients with CF who underwent double lung transplantation. Twenty-one of the subjects were pancreatic insufficient. Fifteen subjects had serum vitamin levels before and after transplant. The median time posttransplantation for these subjects was 9 months. Mean serum vitamin A and E levels were significantly higher posttransplantation (P<0.0001, P<0.001, respectively). Eight subjects who only had posttransplant vitamin levels also had abnormally high vitamin A levels. Although the etiology of this novel finding is unclear, possibilities include altered absorption, drug interactions, impaired retinol metabolism, or increased hepatic synthesis of retinol binding protein.

Adult↗
PubMed2005

Combining unprotected pancreatic enzymes with pH-sensitive enteric-coated microspheres does not improve nutrient digestion in patients with cystic fibrosis.

OBJECTIVES: To assess the efficacy of combining unprotected powder enzymes and oral enteric-coated microsphere (ECM) and to ECM alone in treating nutrient maldigestion in patients with cystic fibrosis. STUDY DESIGN: Patients were randomly assigned into 2 consecutive, 2-week phases; ECM alone, and ECM plus unprotected powder enzymes. Fecal fat, energy, and nitrogen output were compared with intake at the end of each phase. Two-tailed, paired t tests were performed to compare outcomes. RESULTS: The mean age of the 14 patients (3 girls) was 5.7 +/- 3.2 years (range, 1.9 to 13.4 years). There was no significant difference in percent malabsorption of fat (15.6% vs 18.2%), energy (13.3% vs 13.4%), or nitrogen (11.8% vs 11.3%) between phases. CONCLUSIONS: The addition of powder enzymes to ECM did not improve nutrient maldigestion compared with ECM alone.

Adolescent↗
PubMed2005

Cystic fibrosis birth rates in Canada: a decreasing trend since the onset of genetic testing.

OBJECTIVE: To estimate cystic fibrosis (CF) birth rates in Canada from 1971 to 2000 and to assess the population impact of genetic testing in families with a history of CF, after identification of the CF transmembrane conductance regulator gene in 1989. STUDY DESIGN: Age-at-diagnosis data were obtained from the Canadian Cystic Fibrosis Foundation Patient Data Registry and Canadian births for the corresponding years from Canadian Vital Statistics. Estimates of the CF birth rate in each year were based on a nonparametric model that allows the birth rate to vary across the years and adjusts for censoring of currently undiagnosed patients. RESULTS: The overall CF birth rate from 1971-1987 was 1/2714 with no increasing or decreasing trend. Beginning in 1988, 1 year before identification of the CF transmembrane conductance regulator gene, estimated CF birth rates followed a linear decline to an estimated rate of 1/3608 in 2000. CF birth rates may have stabilized in the last few years, but further decline may occur with implementation of carrier screening in the general population. CONCLUSIONS: These results demonstrate the temporal association of genetic testing and declining CF birth rates in Canada. They may assist in decisions relating to the allocation of resources for prenatal and neonatal CF screening programs.

Birth Rate↗
PubMed2005

Growth assessment in infants and toddlers using three different reference charts.

OBJECTIVE: To determine if the proportion of children < or =24 months old in a tertiary care facility defined as at risk of undernutrition or overnutrition differs according to different references used for assessment: the Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS) or Tanner-Whitehouse (Tanner) growth charts for weight-for-age and length-for-age. METHODS: Lengths and weights were measured on infants (207 female, 341 male) aged < or =24 months admitted from or attending clinics in the General Pediatric or Respiratory Medicine Programs at The Hospital for Sick Children, Toronto. Weight-for-age and length-for-age percentiles and percent ideal body weight were electronically computed. RESULTS: The proportion of all children whose weight-for-age was <3rd percentile (at risk of undernutrition) was greatest using the CDC growth charts (22.5%) compared with the NCHS (15.9%) or Tanner (19.2%) growth charts. Likewise, the proportion of all infants/toddlers with percent ideal body weight <90 (at risk of undernutrition) was greatest using the CDC (32.3%) compared with the NCHS (22.1%) or Tanner (25.9%) growth charts. In contrast, the percentage of children whose percent ideal body weight was > or =110% (at risk of overnutrition) was least using the CDC (18.1%) compared with the NCHS (26.1%) or Tanner (22.4%) growth charts. CONCLUSION: More children aged < or =24 months will be defined as at risk of undernutrition and fewer at risk of overnutrition when using weight-for-age or percent ideal body weight and the CDC growth charts compared with the NCHS or Tanner growth charts. As a result, requests for a more detailed nutritional assessment for undernutrition will likely follow implementation of the CDC growth charts in a tertiary care setting. As the CDC, NCHS and Tanner growth charts are growth "references" rather than "standards," other than for screening purposes, they should not be used in isolation when assessing growth and nutritional status.

Age Factors↗
PubMed2004

Disease severity in siblings with cystic fibrosis.

Since cross-infection occurs between cystic fibrosis (CF) siblings, we hypothesized that subsequent siblings may acquire respiratory pathogens at an earlier age and have a more severe course of pulmonary disease. We studied a retrospective cohort of 31 sibling pairs from the CF database at the Hospital for Sick Children. Kaplan-Meier curves and modified log-rank tests were used to test sibling differences in age of acquisition of Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), or any positive culture. Differences in disease severity outcomes were explored. Older siblings were more likely to have both SA and any CF pathogen first isolated from respiratory culture at an older age than younger siblings (P = 0.0050 and P = 0.0008, respectively, by modified log-rank tests). However, more of the older siblings were positive on first culture at time of diagnosis, introducing an age-of-diagnosis bias. Hospitalization rates, courses of oral antibiotics, FEV(1) % predicted, and weight and height measurements were not better in the older children. No differences in clinical parameters were found between older and younger siblings. The apparent finding of younger age at first isolation of pathogens from respiratory cultures in younger siblings is likely because many older siblings were already infected with these organisms at time of diagnosis.

Age of Onset↗
PubMed2004

Comparison of spirometric reference values.

Lung-function reference values play a vital role in the management of respiratory disorders. There are many proposed reference equations for pediatric spirometry. Recently, spirometric reference equations were proposed, using data from people aged 8-80 years living in the US compiled by the third National Health and Nutrition Examination Survey. Our objective was to compare the predictive value of wider age-range reference equations to established pediatric reference equations for the pediatric population. Spirometry, height, and weight were obtained from 70 normal children aged 6-18 years. The difference between measured and predicted values as suggested by different reference equations was compared. Predicted values from general equations significantly differed from those generated from pediatric equations and from measured values in this population. The difference between measured and predicted values from the wider age-range equations varied between 7-16% for forced expired volume in 1 sec (FEV1) and forced vital capacity (FVC). The difference between measured and predicted values for the pediatric equations varied between 1-4%. Although wider age-range equations provide continuity through age ranges, their predictive accuracy may be low in the pediatric age group, especially for the youngest, smallest children. Extrapolating reference equations beyond the age range of subjects used to generate then is not recommended.

Adolescent↗