David Chitayat

Bio: David Chitayat is an academic researcher from Toronto General Hospital. The author has contributed to research in topics: Cystic fibrosis & Epidemiology. The author has an hindex of 3, co-authored 4 publications receiving 960 citations.

Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies

Abstract: Background Corticosteroids are first-line drugs for the treatment of a variety of conditions in women of childbearing age Information regarding human pregnancy outcome with corticosteroids is limited Methods We collected prospectively and followed up 184 women exposed to prednisone in pregnancy and 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure The primary outcome was the rate of major birth defects A meta-analysis of all epidemiological studies was conducted The Mantel-Haenszel summary odds ratio was calculated for the pooled studies with 95% confidence intervals A cumulative summary odds ratio was also calculated by combining studies in chronological order Chi-squared for homogeneity was determined to establish the comparability of the studies Results In our prospective study, there was no statistical difference in the rate of major anomalies between the corticosteroid-exposed and control groups In the meta-analysis, the Mantel-Haenszel summary odds ratio for major malformations with all cohort studies was 145 [95% CI 080, 260] and 303 [95% CI 108, 854] when Heinonen et al ('77) was removed This suggests a marginally increased risk of major malformations after first-trimester exposure to corticosteroids In addition, summary odds ratio for case-control studies examining oral clefts was significant (335 [95% CI 197, 569]) Conclusions Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 34-fold the risk of oral cleft, which is consistent with the existing animal studies Teratology 62:385–392, 2000 © 2000 Wiley-Liss, Inc

Cell-specific localization of CFTR mRNA shows developmentally regulated expression in human fetal tissues

Abstract: An improved understanding of the expression of the cystic fibrosis gene (CFTR) will assist our approach to preventing the organ damage caused by cystic fibrosis (CF). We have studied the expression of CFTR in human fetal tissues at different gestational ages using in situ hybridization to detect CFTR mRNA. CFTR was principally expressed in less differentiated cells of endodermal origin. The highest levels were seen in specific areas of the developing pancreas, liver, gall bladder and intestine, with lower but significant levels in lung and trachea. Expression was also seen in reproductive tissues, such as epididymis and third trimester uterus and fallopian tubes, and in addition, sweat and salivary glands. No detection of CFTR mRNA was found in many other relevant tissues. The detection of CFTR transcript in these organs is consistent with the clinical manifestations of CF and the function of CFTR as a chloride channel early in development. The localization and levels of expression described have implications regarding the pathogenesis of organ damage and the potential gains that can be achieved by early therapy in the disease.

Regional expression of CFTR in developing human respiratory tissues.

Abstract: Morbidity and mortality in cystic fibrosis (CF) patients is strongly related to their respiratory disease. We have analyzed, by means of in situ hybridization, the localization and levels of CFTR mRNA in fetal, newborn, and infant respiratory tissues. Measurable levels of CFTR transcript are present in the fetal primordial epithelium of the pseudoglandular stage lung. During the following stages of lung development, CFTR expression decreases in cells of the future alveolar spaces and is gradually limited to the epithelium of the small airways. After birth, expression decreases in the small airways and is not detected in alveolar epithelia. In trachea and large bronchi, a differential pattern of expression is also observed. No CFTR expression is found in fetal submucosal glands during fetal development, but appears gradually in the newborn period. Since CFTR codes for a secretory Cl- channel, these data probably reflect the changes that occur in the lung transition from a fluid-secreting to an absorbing or...

Neurodevelopment in children exposed in utero to cyclosporine and azathioprine following maternal renal transplant: preliminary results

Abstract: Background Cyclosporine and azathioprine are the most commonly used drugs to prevent rejection of transplanted organs. Pregnancy following renal transplantation can be associated with risks for both the mother and the fetus, therefore it is essential to study the reproductive safety of these drugs. Objectives To evaluate the prenatal effects of cyclosporine and azathioprine on children's neurodevelopment following maternal renal transplant, and to compare to control children. Study design Prospective cohort with matched controls. Methods Exposed children were assessed using the Wechsler Preschool and Primary Scales of Intelligence–Revised, the Wechsler Intelligence Scale for Children-III, the Developmental Neuropsychological Assessment, the Preschool Language Scale-III, and the Clinical Evaluation of Language Fundamentals-III. The preliminary results of the exposed children were compared to standard norms. Results Currently, the 20 exposed children (age 3 to13 years) were not significantly different from the norms on Global, Verbal, and Performance IQ (103 + 15; 105 + 16; and 101 + 14 respectively). The exposed children appear to have language scores (Total 112 + 8; Expressive 111 + 10; and Auditory 112 + 7) in the upper range of the norms. Conclusion These preliminary results are reassuring and may contribute to informed decision making, by pregnant women and health professionals. Clinical Pharmacology & Therapeutics (2004) 75, P74–P74; doi: 10.1016/j.clpt.2003.11.278

Pathophysiology and management of pulmonary infections in cystic fibrosis.

Abstract: This comprehensive State of the Art review summarizes the current published knowledge base regarding the pathophysiology and microbiology of pulmonary disease in cystic fibrosis (CF). The molecular basis of CF lung disease including the impact of defective cystic fibrosis transmembrane regulator (CFTR) protein function on airway physiology, mucociliary clearance, and establishment of Pseudomonas aeruginosa infection is described. An extensive review of the microbiology of CF lung disease with particular reference to infection with P. aeruginosa is provided. Other pathogens commonly associated with CF lung disease including Staphylococcal aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and atypical mycobacteria are also described. Clinical presentation and assessment of CF lung disease including diagnostic microbiology and other measures of pulmonary health are reviewed. Current recommendations for management of CF lung disease are provided. An extensive review of antipseudomonal therapies in the settings of treatment for early P. aeruginosa infection, maintenance for patients with chronic P. aeruginosa infection, and treatment of exacerbation in pulmonary symptoms, as well as antibiotic therapies for other CF respiratory pathogens, are included. In addition, the article discusses infection control policies, therapies to optimize airway clearance and reduce inflammation, and potential future therapies.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Abstract: This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

British guideline on the management of asthma: A national clinical guideline

Abstract: These guidelines have been replaced by British Guideline on the Management of Asthma. A national clinical guideline. Superseded By 2012 Revision Of 2008 Guideline: British Guideline on the Management of Asthma. Thorax 2008 May; 63(Suppl 4): 1–121.