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Biomedical subjects

Hugh O'Brodovich

Publications and source records attributed to Hugh O'Brodovich.

16 recordsLinked to original sources
PubMed2006

Clinical and education workload measurements using personal digital assistant-based software.

OBJECTIVE: There are no accepted and practical measures of the relative clinical and educational activities of pediatricians who work in an academic health science center. Such measures are necessary for justification of existing and future human resource plans and evaluation of the activities and performance of physicians. The limited literature on the measurement of physician workload usually focuses on a specific subspecialty group and does not account for such issues as indirect patient care, such as telephone calls or e-mail consultations; variables that affect the delivery of clinical care, including patient acuity and complexity; and the presence of students during the patient care activities. After completing a pilot study that assessed the educational workload of faculty members, we adapted existing personal digital assistant technology and software to document clinical and educational activities. METHODS: Twenty full-time physicians from 4 subspecialty pediatric divisions participated in a 2-week evaluation project in May through June 2005. Clinical activities, with and without trainees, and educational activities were collected with the use of personal digital assistants. Software allowed an individualized division-specific drop-down menu. Information that was collected included clinical (location of activity, diagnosis, and time requirement) and educational activities. After completion of a 2-week data collection period, each physician was asked to complete a 5-question evaluation form. RESULTS: The project was completed successfully with capture of additional clinical and educational activities. A 5-question evaluation form was completed by 70% of the participants at the end of the 2-week data collection. Data on clinical and educational activities were analyzed qualitatively and graphed. CONCLUSIONS: This method of workload data collection added significant information in capturing activities that are not measured in traditional workload evaluations for either clinical activities, such as e-mail, telephone, and patient information review, or educational endeavors, including mentoring and educational lectures and presentations.

Academic Medical Centers↗
PubMed2005

Oxygen and glucocorticoids modulate alphaENaC mRNA translation in fetal distal lung epithelium.

Glucocorticoid hormones play an important role in fetal lung maturation. It is unknown how they interact with changes in O2 tension, which play an important role in converting the lung from a fluid-secreting to a fluid-absorbing organ at birth. Airspace fluid absorption arises from active transepithelial Na+ transport with the amiloride-sensitive epithelial Na channel (ENaC), consisting of alpha, beta, and gamma subunits, representing the rate-limiting step under nonpathologic conditions. We investigated the individual and combined effects of dexamethasone (DEX) and PO2 on alphaENaC mRNA levels, rate of alphaENaC protein synthesis, and amiloride-sensitive short-circuit current in primary cultures of rat fetal distal lung epithelial cells. DEX significantly induced alphaENaC mRNA in fetal (3%) and postnatal (21%) O2, but increases in alphaENaC protein synthesis and function occurred only when epithelia were grown under a postnatal PO2. Sucrose density gradient analyses showed that DEX treatment of cells cultured at 3% O2 decreased the association of alphaENaC mRNA with large polysomes and enhanced the association with small polysomes. Conversely, incubation of DEX-treated cells in 21% O2 restored alphaENaC mRNA association with large polysomes. No significant changes were seen in the overall polyribosome profiles or in the distribution of mRNAs encoding beta and gamma subunits of ENaC or cytokeratin 18, indicating specific modulation of alphaENaC mRNA translation. These data suggest that postnatal O2 exposure may be important for efficient translation of the alphaENaC mRNA.

Animals↗
PubMed2005

Pulmonary edema in infants and children.

PURPOSE OF REVIEW: To provide an overview of the pathogenesis of pulmonary edema and describe recent discoveries related to the clearance of airspace fluid and potential new therapies for this life-threatening disorder. RECENT FINDINGS: It is clinically important to determine the mechanisms responsible for the clearance of fluid from the airspaces. At birth inadequate clearance of fetal lung liquid is one of the two mechanisms leading to respiratory distress syndrome in the premature infant. Adults with heart failure or adult respiratory distress syndrome survive when they had active absorption of airspace fluid, yet have greater morbidity or die when they show no evidence of active fluid clearance. Humans who are susceptible to high-altitude pulmonary edema have less ability to actively transport fluid across their respiratory epithelium. SUMMARY: New approaches to increase the active clearance of fluid from the airspaces, combined with further improvements in the intensive care and monitoring of patients with serious illnesses, will lead to improved care for patients with lung diseases characterized by increased lung water content.

Child↗
PubMed2005

Fitness to fly in an infant with congenital lobar emphysema.

Determining fitness to fly is a difficult task for physicians, especially for those caring for children with respiratory disorders, as the available information for guidance is scarce. This case describes the use of a flight simulation in a decompression chamber in order to assess fitness to fly in an 18-mo-old infant with congenital lobar emphysema (CLE). The case discussion focuses on the need for an understanding of flight physiology in order for physicians to determine the most appropriate method to assess fitness to fly in children with medical concerns.

Aircraft↗
PubMed2004

Expression of epithelial sodium channel alpha-subunit mRNAs with alternative 5'-untranslated regions in the developing human lung.

In preparation for birth, lung epithelia must switch from net fluid secretion, required for lung development, to net absorption, which prepares the lungs for postnatal gas exchange. The apical membrane amiloride-sensitive epithelial Na channel (ENaC) is the rate-limiting step for Na+ and fluid absorption. Expression of alpha-ENaC mRNA has been detected in human lung as early as the embryonic stage of development. However, humans express multiple transcripts for alpha-ENaC, containing differing 5'-untranslated regions (UTR) with unknown effects on protein translation, and different ontogenies for individual transcripts could provide a novel mechanism for developmental regulation of ENaC function. To assess the relative expression of the two most abundant alpha-ENaC transcripts (alpha-ENaC1 and alpha-ENaC2) during lung development, we performed nonradioactive in situ hybridization using probes specific to the alternative 5'-UTRs. Both transcripts were expressed throughout intrauterine lung development (8 to 40 wk gestation), and expression was localized to the surface epithelial cells of the conductive and respiratory airways in both ciliated cells and nonciliated Clara cells. alpha-ENaC mRNA expression was also identified in the serous cells of the submucosal glands surrounding the proximal airways. In the mature prenatal lung, subsets of alveolar type II (ATII) cells expressed one or both of the alpha-ENaC transcripts. Our observations demonstrate that a developmentally regulated switch between alpha-ENaC 5'-UTR variants is not the trigger by which the developing human lung becomes a fluid-absorbing organ at birth, that individual ATII cells express neither, one, or both of the alpha-ENaC transcripts, and that the overall expression is linked to epithelial cell differentiation and lung maturation.

5' Untranslated Regions↗
PubMed2004

Low expression of human epithelial sodium channel in airway epithelium of preterm infants with respiratory distress.

OBJECTIVE: Active ion transport is critical to postnatal clearance of lung fluid. The importance of epithelial sodium channel (ENaC) in this clearance has been demonstrated in animal studies in which alpha-ENaC knockout mice died postnatally as a result of respiratory insufficiency. In animals, the expression of alpha-ENaC in respiratory epithelium is dependent on gestational age, but when assessed by in situ hybridization in the human (h), the mRNA is present from the earliest stages of pulmonary development. Therefore, the purpose of the present investigation was to quantify mRNA of the alpha-, beta-, and gamma-hENaC subunits of newborn preterm infants with respiratory distress and compare the gene expression data against those detected in healthy term infants. In addition, the effect of systemic dexamethasone therapy on the 3 hENaC subunits was studied in 4 preterm infants who received prolonged assisted ventilation. METHODS: The expression of subunits of hENaC was determined in samples taken from nasal respiratory epithelium of 7 healthy term infants (gestation age: 39.3 +/- 0.9 weeks [mean +/- standard deviation) and 5 preterm infants (gestational age: 27.2 +/- 0.9 weeks) with respiratory distress syndrome within 5 hours of birth. Betamethasone had been given to all mothers of preterm infants. In 4 additional preterm infants who still required assisted ventilation at 43 +/- 6 days postnatal age, the expression of alpha-hENaC was determined in samples taken before and during treatment with dexamethasone. RESULTS: Preterm infants with respiratory distress syndrome had low expression of all hENaC subunits relative to healthy term infants (alpha-hENaC: 5.38 +/- 2.01 [amol/fmol cytokeratin 18] vs 9.13 +/- 2.26; beta-hENaC: 2.44 +/- 1.43 vs 4.25 +/- 1.10; gamma-hENaC: 2.43 +/- 0.11 vs 6.81 +/- 3.24). Each of the 4 preterm infants who were treated with dexamethasone at approximately 1 month of age showed an increase in expression of alpha-hENaC and beta-hENaC subunit normalized to cytokeratin 18. CONCLUSION: All 3 subunits of the hENaC are low in preterm relative to full-term infants. alpha-hENaC mRNA in respiratory epithelium is increased by therapeutic doses of glucocorticosteroid. Low expression of alpha-hENaC in human respiratory epithelium may play a role in the pathogenesis of respiratory distress in preterm infants.

Anti-Inflammatory Agents↗
PubMed2003

Differential translational efficiency of ENaC subunits during lung development.

The amiloride-sensitive epithelial Na(+) channel (ENaC), the rate-limiting step in epithelial Na(+) transport, consists of three subunits: alpha, beta, and gamma. The abundance of mRNA encoding the alpha-subunit far surpasses the amount for other subunits, and considerably exceeds the predicted subunit protein stoichiometry. We evaluated 5'-untranslated region (UTR) expression and found that fetal rat lung uses alternative 5'UTRs for alpha-ENaC during development. Sucrose density gradient analysis of postnuclear supernatants from fetal rat lung homogenates demonstrated that all three ENaC subunits were associated with high molecular weight polysomes, indicating active translation of the mRNAs, but translational efficiency was much lower for the alpha-subunit. Sucrose density gradient distributions were comparable for the endogenously expressed alpha-ENaC 5'UTRs in rat lung at Fetal Day 20 or Postnatal Day 1 using Northern analysis. Although birth resulted in a global decrease in lung mRNA translation, the loading of ribosomes on ENaC subunit mRNAs was largely unaffected. Evaluation of cytokeratin 18 and vimentin mRNAs in these gradients suggested a cell-specific effect. We conclude that there are different translational efficiencies for ENaC subunits and that perinatal processes globally modulate lung mRNA translation.

5' Untranslated Regions↗
PubMed2003

Evaluation of a peer-reviewed career development and compensation program for physicians at an academic health science center.

OBJECTIVE: The Department of Pediatrics at the Hospital for Sick Children, which is funded by an alternative payment plan, has implemented a novel career development and compensation program (CDCP). Job activity profiles were used to more clearly define job expectations, benchmarks guided career development, and peer review was used to assess performance. The objective of this study was to evaluate the departmental pediatricians' satisfaction with the CDCP. METHODS: Pediatricians, all of whom had undergone CDCP annual reviews, could participate if they had undergone the in-depth triennial CDCP review. Each received a 5-point Likert scale-based questionnaire that asked how well the CDCP had conformed to the principles identified by the department during the development of the CDCP. Anonymous, confidential responses were collated and used to guide focus groups that discussed areas of greatest concern and attempted to identify solutions. Focus groups were led by external facilitators who were experienced in qualitative research. They audiotaped the sessions, transcribed the comments, and analyzed the data with the assistance of a qualitative analysis application. RESULTS: Sixty of the eligible 88 pediatricians participated, and 74% of their responses were that the CDCP had addressed the original principles "somewhat," "to a great extent," or "extremely well." The remainder indicated that some of the principles were either "not addressed" or "only to a small extent" by the CDCP. Results from the 11 focus groups (46 participants) indicated that the CDCP was an improvement over the previous method of career development and determination of the rate of remuneration. Most were also still in agreement with the purpose and design principles. Although they did not want the CDCP to undergo a major redesign, they identified areas that need improvement. Short-, medium-, and long-term action plans to address these areas are under way. CONCLUSION: Pediatricians at the health science center of the Hospital for Sick Children remain supportive of the CDCP.

Academic Medical Centers↗
PubMed2002

Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na(+) transport and fluid absorption in the distal lung.

To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride-insensitive short circuit current (I(sc)) and Na(+)-K(+) ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl(-) transport or cGMP-gated cation channels had a significant (P < 0.05), but limited ability to block the increased I(sc). EF increased amiloride-insensitive, but not amiloride-sensitive, DLE apical membrane Na(+) conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (alpha, beta), or decreased (gamma, P < 0.05) in EF-exposed DLE. EF also induced an amiloride-insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild-type and alpha-ENaC-deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride-insensitive I(sc) in DLE and liquid absorption by distal lung explants. Thus proteins or protein-dependent factors within cardiogenic EF induce an alpha-ENaC-independent and amiloride-insensitive apical membrane Na(+) conductance and liquid absorption in the distal lung.

Absorption↗
PubMed2002

Pulmonary interstitial glycogenosis: a new variant of neonatal interstitial lung disease.

We present the clinical, radiologic, and pathologic findings in lung biopsies from seven infants with atypical neonatal lung disease. All seven infants presented with tachypnea, hypoxemia, and diffuse interstitial infiltrates with overinflated lungs on chest radiographs in the first month of life. Lung biopsies from all cases showed similar pathology, with expansion of the interstitium by spindle-shaped cells containing periodic acid-Schiff positive diastase labile material consistent with glycogen. Immunohistochemical staining showed these cells to be vimentin positive but negative for leucocyte common antigen, lysozyme, and other macrophage markers. Electron microscopy revealed primitive interstitial mesenchymal cells with few cytoplasmic organelles and abundant monoparticulate glycogen. Minimal or no glycogen was seen in the alveolar lining cells. Five cases were treated with pulse corticosteroids; hydroxychloroquine was added in one case. Six of seven infants have shown a favorable clinical outcome. One infant died from complications of extreme prematurity and bronchopulmonary dysplasia. Three cases that have been followed for at least 6 years have shown clinical resolution and radiographic improvement. We propose the term "pulmonary interstitial glycogenosis" of the neonate for this new entity to be differentiated from other forms of interstitial lung disease. Because abundant glycogen is not normally found in pulmonary interstitial cells, we postulate an abnormality in lung cytodifferentiation involving interstitial mesenchymal cells.

Adrenal Cortex Hormones↗