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Biomedical subjects

Aaron Chidekel

Publications and source records attributed to Aaron Chidekel.

12 recordsLinked to original sources
PubMed2005

Expression of matrix metalloproteinases 2, 7 and 9, and their tissue inhibitors 1 and 2, in developing rabbit tracheae.

BACKGROUND: Structural changes in the developing conducting airway impact the rigidity of the airway, altering the airway's ability to sustain its shape during ventilation. The developmental changes in airway compliance oppose the changes in compliance of the developing lung; thus the expression profiles of matrix modeling proteins likely are also opposite in these developing organs. OBJECTIVES: To determine the profiles of matrix metalloproteinases (MMPs) -2, -7, and -9 and tissue inhibitors (TIMPs) -1 and -2 in the developing trachea and test the hypothesis these profiles would contrast those previously reported for the lung. METHODS: Rabbits tracheae were harvested at 21 days of gestation, 3 and 17 days postgestation and at adulthood. Tissue homogenates were analyzed by substrate zymography for the activity of MMPs, and reverse zymography for TIMPs. Immunostainings on neonatal lamb tracheal rings were used to localize MMP-2 and 9. RESULTS: Analysis revealed an age-dependent decrease in total MMP-2 quantity and the ratio of active to latent forms. TIMP-2 shows a time-dependent increase throughout airway development. Total MMP-9 and TIMP-1 quantities were unchanged across these ages, although MMP-9 protein was found predominantly in its latent form during development and predominantly in its active form during adulthood. Respiratory epithelial cells reacted positive for both MMP-2 and 9 and trachealis muscle fibers were positive for MMP-2. No MMP-7 expression was identified in the rabbit airway. CONCLUSIONS: The opposing developmental patterns in MMP-2 expression between the airway and lung lead to speculation regarding the role of MMP-2 activity on changes in organ compliance.

Animals↗
PubMed2005

Hyperoxia-induced changes in human airway epithelial cells: the protective effect of perflubron.

OBJECTIVE: To determine the protective effect of perflubron (PFB), a type of perfluorochemical liquid, in hyperoxia-induced cellular injury in the human airway epithelial cells. DESIGN: A controlled, in vitro laboratory study. SETTING: Tertiary-care children's hospital. SUBJECTS: Human airway epithelial cells. INTERVENTIONS: Human airway epithelial cells, Calu-3 cells, grown on polycarbonate porous filters at an air-liquid interface culture were exposed to normoxic (Fico(2) = 5%, balance air) or hyperoxic (Fio(2) = 95%, balance CO(2)) conditions. Hyperoxia-induced cellular changes were monitored by measuring transepithelial resistance (TER) of monolayers, histology of cells, total protein, and interleukin-8 (IL-8) secretion in apical surface fluid (ASF) washings. Under hyperoxic conditions, the protective effect of PFB was assessed by directly adding PFB liquid to the apical surface of monolayers. MEASUREMENTS AND MAIN RESULTS: During hyperoxic gas-liquid interface culture, Calu-3 monolayers exhibited a loss of cellular integrity morphologically, decreased protein concentration, and IL-8 level in ASF washings. During hyperoxic PFB-liquid interface culture, there was an overall increase in TER value of monolayers, improved histology, decreased total protein secretion in ASF washings, and unaltered IL-8 secretion. Cytomorphologic observations of PFB-treated Calu-3 cells indicated the presence of varying numbers of differently sized intracellular vacuoles during both normoxic and hyperoxic conditions. CONCLUSIONS: We conclude that the air-liquid interface culture of Calu-3 may be helpful in understanding mechanisms of lung injuries caused in clinical practice, and PFB protects against hyperoxia-induced airway epithelial cell injury by promoting cellular integrity as well as cytologic modifications. PFB-liquid interface culture of Calu-3 may be a useful in vitro model for studying the cytoprotective role of liquid ventilation.

Cell Culture Techniques↗
PubMed2004

Regulation of apical surface fluid and protein secretion in human airway epithelial cell line Calu-3.

We evaluated the relationship between apical surface fluid (ASF) and protein secretion in Calu-3 cells grown at an air-liquid interface. Calu-3 monolayers responded to forskolin, a cystic fibrosis transmembrane regulator (CFTR) channel agonist, by secreting a significant amount of ASF. Such a response from Calu-3 monolayers was not observed with CFTR channel blockers glybenclamide and DPC. Other ion channel mediators, PGF-2alpha, PMA, DNDS, and DIDS, had no effect on Calu-3 ASF secretion. Forskolin decreased Calu-3 protein secretion and glybenclamide increased protein secretion. Similarly, forskolin decreased Calu-3 lysozyme secretion, whereas glybenclamide and DPC increased lysozyme secretion. We observed significant changes in Calu-3 fluid and protein secretions with ion channel mediators known to alter CFTR activity. Our results demonstrate a functional link between fluid and protein secretions in Calu-3 apical surface and suggested a possible involvement of CFTR in these processes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2004

Protein composition of apical surface fluid from the human airway cell line Calu-3: effect of ion transport mediators.

BACKGROUND: Analysis of the protein components of airway secretions is a potential means of detecting and characterizing biochemical alterations associated with airway diseases. METHODS: We evaluated airway protein secretions using the airway epithelial cell line Calu-3 grown at an air-liquid interface. To observe changes in apically secreted proteins, we analyzed the protein content of apical surface fluid (ASF) washings of Calu-3 monolayers treated with ion transport mediators. RESULTS: Immunoassay screening for antibacterial and inflammatory proteins indicated the presence of measurable levels of lysozyme and IL-8 in Calu-3 ASF. RT-PCR and immunoassay studies indicated that Calu-3 cells do not produce clara cell 10 kDa protein (CC10). The total protein secretion of Calu-3 was not altered by bradykinin, but amiloride and adenosine significantly increased Calu-3 protein secretion. Lysozyme secretion was not altered by bradykinin, but amiloride and adenosine significantly reduced lysozyme secretion. IL-8 secretion was not altered by bradykinin or adenosine, but amiloride significantly decreased IL-8 secretion. CONCLUSION: Our results demonstrate the presence of antibacterial protein lysozyme and the pro-inflammatory cytokine IL-8 in Calu-3 ASF and that ion transport mediators such as bradykinin, amiloride and adenosine influence the secretion of Calu-3 ASF proteins.

Adenosine↗
PubMed2004

Association of interleukin-8 with inflammatory and innate immune components in bronchoalveolar lavage of children with chronic respiratory diseases.

BACKGROUND: The host inflammatory response and innate immunity play a complex role in respiratory diseases. METHODS: We evaluated the levels of inflammatory mediators and antibacterial proteins in children who required bronchoscopy and bronchoalveolar lavage fluid (BALF) for clinical indications such as chronic tracheostomy (n=15) and chronic suppurative lung disease (n=8). RESULTS: Our results suggested the presence of interleukin-1beta (IL-1beta) and IL-8 as major inflammatory mediators in BALF samples. The level of the antibacterial protein sIgA was higher than lactoferrin and lysozyme. BALF IL-8 levels significantly correlated with the presence of IL-1beta, IL-6, IL-10, IL-16, sIgA and lysozyme. BALF IL-8 levels did not correlate with the levels of immunomodulatory and anti-inflammatory clara cell 10 kDa protein (CC10) or lactoferrin. CONCLUSION: This study suggests that patients with high levels of BALF IL-8 could potentially have high levels of IL-6, IL-10, IL-16, lysozyme and sIgA. Evaluating the inflammatory mediators (IL-8) in relation to other BALF protein components provides insight into understanding the role of inflammatory mediators in the regulation of host defense and the response to lung inflammation and injury.

Biomarkers↗
PubMed2004

Effect of inhaled corticosteroids on markers of pulmonary inflammation and lung maturation in preterm infants with evolving chronic lung disease.

BACKGROUND: Chronic lung disease (CLD) is one of the most severely disabling conditions of extremely low-birth-weight infants. Systemic corticosteroids are effective but cause many adverse effects. Targeted therapy with inhaled corticosteroids may be an effective and less toxic alternative. STUDY OBJECTIVE: To evaluate the additive effect of inhaled corticosteroids on markers of lung inflammation in infants receiving a 7-day course of systemic steroids. METHODS: Preterm neonates weighing 1 kg or less and aged 12 to 28 days who were prescribed a 7-day course of systemic corticosteroids for evolving CLD were studied prospectively and randomized to receive either a tapering 4-week course of beclomethasone metered-dose inhaler (MDI) (n = 5) or placebo MDI (n = 6). Primary outcome variables were the levels of pro- and anti-inflammatory cytokines, IL-8, TNF-alpha, IL-1alpha, and sIL-2R. RESULTS: This study was terminated early following literature reports of the adverse neurodevelopmental effects of dexamethasone. Measurements of respiratory and serum IL-8, IL-1alpha and TNF-alpha were similar between the study group taking inhaled and systemic corticosteroids and the study group taking systemic steroids alone. No differences were found between the two groups in relation to dynamic compliance or resistance. CONCLUSIONS: The addition of inhaled corticosteroids to a 7-day systemic course of corticosteroids did not alter cytokine response or improve pulmonary function.

Administration, Inhalation↗
PubMed2004

Pediatric choking.

Choking episodes and foreign body aspiration can be life threatening or result in significant morbidity. Choking continues to be a direct cause of death among children, most commonly occurring between the ages of one and four years. Various strategies have been used to decrease choking risks and prevent adverse outcomes. These have included alterations in product design and public education campaigns. Although education has been partially successful, primary care physicians can play a critical role in increasing education efforts during each well child office visit through anticipatory guidance of choking risks. Management of a choking child often involves collaborative efforts from the primary care physician, emergency room physician, otolaryngologist, pulmonologist, and radiologist. The purpose of this brief review is to provide an overview of the epidemiology and pathophysiology of choking and foreign body aspiration in children and to highlight important aspects of prevention and patient education.

Airway Obstruction↗
PubMed2003

A snapshot of tobacco-related messages relayed in pediatric offices in Delaware.

OBJECTIVE: Much research exists demonstrating that pediatricians should counsel patients and families about tobacco. However, few data are available about tobacco-related messages relayed in pediatric offices. Since an anti-tobacco office environment can be a strong component of an active tobacco prevention program, we evaluated pediatric offices in Delaware to characterize tobacco-related messages. METHODS: A convenience sample of 32 of 63 (51%) pediatric offices in Delaware was directly evaluated for the presence of tobacco-related messages. Fifty-five of 63 (87%) pediatric practices in Delaware were contacted by telephone to inquire about the presence of a tobacco coordinator. RESULTS: The 32 practices represented 71 physicians, were located in all three counties throughout the state, and were urban and non-urban in setting. The same investigator evaluated practices in a single site visit. All were located in smoke-free buildings. At one office, people were seen smoking outside; however, the presence of discarded cigarettes was much more common. Thirteen practices (41%) employed smokers, most of whom smoked outside during work hours. Twenty-one of 28 practices (75%) had waiting room magazines containing tobacco advertisements. Fifteen practices (47%) offered anti-tobacco literature while six practices (19%) displayed visual media, none exclusively addressing tobacco. Nine practices (28%) use chart flags to identify smokers. None of 55 pediatric practices in Delaware contacted by telephone identified an office tobacco prevention coordinator. CONCLUSIONS: Our data indicate that, in Delaware, the pediatric offices we visited overall convey a limited message about tobacco and could strengthen tobacco prevention strategies. Research measuring the impact of office-based anti-tobacco messages is needed. If these messages are effective in preventing tobacco use, practitioners can supplement active counseling with indirect interventions that require minimal maintenance once established and that place no additional demands on their time.

Delaware↗
PubMed2002

Effects of an inadvertent dose of cytarabine in a child with Fanconi's anemia: reducing medication errors.

We report the case of a 7-year-old boy with Fanconi's anemia, who underwent a bone marrow transplant using an unrelated donor, and who received an inadvertent dose of cytarabine (cytosine arabinoside). The cytarabine was given by mistake 6 months following transplant. This caused excessive toxicity to many systems, including the pulmonary and renal systems. The patient recovered from the episode, but this article further highlights the acute adverse effects of cytarabine. Furthermore, it is the first report of excessive toxicity to cytarabine in a child with Fanconi's anemia. The article also highlights the problems of medication administration errors, particularly in those exquisitely sensitive to the effects of toxic drugs.

Bone Marrow Transplantation↗
PubMed2002

Home delivery of palivizumab: outcomes and compliance in regional preterm infants.

Palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), has been shown to be effective in preventing RSV-related hospitalization in preterm infants; however, ensuring infants receive the desired monthly injections remains a challenge. We studied two cohorts of preterm infants and the rate of documented RSV illness in infants receiving palivizumab at home between 1998 and 2000. Medical records were reviewed for the number of doses received, hospitalization for RSV illness, and other demographic data. Parents in Cohort 1, 1998-1999, were prospectively surveyed to determine satisfaction with delivery of palivizumab. In Cohort 1, the home group (n = 32) received 89 +/- 19 percent of their scheduled course as compared to 66 +/- 32 percent in the office group (n = 41, p < .01), with 67 percent in the home group receiving their entire scheduled course as compared to 36 percent in the office group (p = .02). Of the parents surveyed, 70 percent in the home group indicated that they were satisfied with the way palivizumab was administered as compared to 76 percent in the office group (p = .44). In Cohort 2, 1999-2000, 175 infants received palivizumab at home, and 161 of these (92 percent) completed therapy as ordered. None of the infants had a documented infection with RSV. In our population infants receiving palivizumab at home were more likely to receive their entire scheduled course and less likely to miss doses than infants receiving palivizumab in an office setting. The high rate of compliance with home delivery is associated with a low rate of documented severe RSV illness.

Antibodies, Monoclonal↗
PubMedDate not supplied

Arnold-Chiari malformation type I and sleep-disordered breathing: an uncommon manifestation of an important pediatric problem.

A case review of a healthy 3-year-old toddler with a chief complaint of sleep-disordered breathing is presented. The child underwent a pneumogram sleep study with significant abnormal findings. Magnetic resonance imaging led to a diagnosis of Arnold-Chiari type I malformation and the need for posterior fossa decompression. The child has been monitored, and 1 year postoperatively, her sleep apnea has resolved and day-time function and development remain normal. Definitions of the different types of Arnold-Chiari malformation are discussed, with sleep apnea presenting as the only symptom. The importance of a sleep history as part of the practitioner's pediatric assessment is explored.

Arnold-Chiari Malformation↗