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Biomedical subjects

Gavin R Graff

Publications and source records attributed to Gavin R Graff.

14 recordsLinked to original sources
PubMed2006

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health.

The human surfactant protein A (SP-A) locus consists of two functional genes (SP-A1, SP-A2) with gene-specific products exhibiting qualitative and quantitative differences. The aim here was twofold: 1) generate SP-A1 gene-specific antibody, and 2) use this to assess gene-specific SP-A content in the bronchoalveolar lavage fluid (BALF). An SP-A1-specific polyclonal antibody (hSP-A1_Ab(68-88)_Col) was raised in chicken, and its specificity was determined by immunoblot and ELISA using mammalian Chinese hamster ovary (CHO) cell-expressed SP-A1 and SP-A2 variants and by immunofluorescence with stably transfected CHO cell lines expressing SP-A1 or SP-A2 variants. SP-A1 content was evaluated according to age and lung status. A gradual decrease (P < 0.05) in SP-A1/SP-A ratio was observed in healthy subjects (HS) with increased age, although no significant change was observed in total SP-A content among age groups. Total SP-A and SP-A1 content differed significantly between alveolar proteinosis (AP) patients and HS, with no significant difference observed in SP-A1/SP-A ratio between AP and HS. The cystic fibrosis (CF) ratio was significantly higher compared with AP, HS, and noncystic fibrosis (NCF), even though SP-A1 and total SP-A were decreased in CF compared with most of the other groups. The ratio was higher in culture-positive vs. culture-negative samples from CF and NCF (P = 0.031). A trend of an increased ratio was observed in culture-positive CF (0.590 +/- 0.10) compared with culture-positive NCF (0.368 +/- 0.085). In summary, we developed and characterized an SP-A1 gene-specific antibody and used it to identify gene-specific SP-A content in BALFs as a function of age and lung health.

Aging↗
PubMed2006

Validation study of fractional exhaled nitric oxide measurements using a handheld monitoring device.

We tested reproducibility of exhaled nitric oxide (FE(NO)) and inter-operator handling when measured with a handheld device, NIOX MINO. We enrolled 20 volunteers using a priori goals of acceptable reproducibility to be mean within-subject standard deviation less than 3 parts per billion (ppb) for FE(NO) measurements less than 30 ppb, and mean coefficient of variation less than 10% for FE(NO) measurements more than 30 ppb. Seventeen subjects with measurements less than 30 ppb displayed a mean standard deviation of 1.15, and 3 subjects with FE(NO) more than 30 ppb had a mean coefficient of variation of 2.4%. We conclude that NIOX MINO demonstrates excellent reproducibility for all ranges of FE(NO).

Adolescent↗
PubMed2005

Comparative sequencing of the serine-aspartate repeat-encoding region of the clumping factor B gene (clfB) for resolution within clonal groups of Staphylococcus aureus.

Molecular techniques such as spa typing and multilocus sequence typing use DNA sequence data for differentiating Staphylococcus aureus isolates. Although spa typing is capable of detecting both genetic micro- and macrovariation, it has less discriminatory power than the more labor-intensive pulsed-field gel electrophoresis (PFGE) and costly genomic DNA microarray analyses. This limitation hinders strain interrogation for newly emerging clones and outbreak investigations in hospital or community settings where robust clones are endemic. To overcome this constraint, we developed a typing system using DNA sequence analysis of the serine-aspartate (SD) repeat-encoding region within the gene encoding the keratin- and fibrinogen-binding clumping factor B (clfB typing) and tested whether it is capable of discriminating within clonal groups. We analyzed 116 S. aureus strains, and the repeat region was present in all isolates, varying in sequence and in length from 420 to 804 bp. In a sample of 36 well-characterized genetically diverse isolates, clfB typing subdivided identical spa and PFGE clusters which had been discriminated by whole-genome DNA microarray mapping. The combination of spa typing and clfB typing resulted in a discriminatory power (99.5%) substantially higher than that of spa typing alone and closely approached that of the whole-genome microarray (100.0%). clfB typing also successfully resolved genetic differences among isolates differentiated by PFGE that had been collected over short periods of time from single hospitals and that belonged to the most prevalent S. aureus clone in the United States. clfB typing demonstrated in vivo, in vitro, and interpatient transmission stability yet revealed that this locus may be recombinogenic in a primarily clonal population structure. Taken together, these data show that the SD repeat-encoding region of clfB is a highly stable marker of microvariation, that in conjunction with spa typing it may serve as a DNA sequence-based alternative to PFGE for investigating genetically similar strains, and that it is useful for analyzing collections of isolates in both long-term population-based and local epidemiologic studies.

Adhesins, Bacterial↗
PubMed2004

Aortic hiatus gastric hernia.

Congenital diaphragmatic hernias are a relatively common anomaly that can present with significant respiratory morbidity and mortality. We report on a case of an aortic-hiatal gastric hernia that initially presented with repeated episodes of respiratory distress, which was diagnosed as asthma. The diagnosis of a diaphragmatic hernia was made at 18 months of age. In the operating room, it was noted that it was an aortic hiatal hernia, which was surgically repaired. Subsequently, there has been improvement in daily respiratory symptoms.

Acute Disease↗
PubMed2004

Administration of the first dose of palivizumab immunoprophylaxis against respiratory syncytial virus in infants before hospital discharge: what is the evidence for its benefit?

BACKGROUND: Palivizumab is 1 of 2 agents used to prevent severe lower respiratory tract disease due to respiratory syncytial virus (RSV) infection. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend administering the first dose of RSV immunoprophylaxis to eligible infants before hospital discharge. Unfortunately, third-party payers frequently do not separately reimburse administration of this therapy to hospitalized infants. OBJECTIVE: Because palivizumab is commonly used to provide RSV immunoprophylaxis, we systematically reviewed all published data on this drug to determine whether the evidence supports the recommendation of administering the first dose before hospital discharge. METHODS: MEDLINE was searched for all articles published in English from January 1, 1996, to October 31, 2003, using the search terms palivizumab and Synagis, and the following data were extracted onto a standardized form: author(s), year of publication, study design, patient population, sample size, criteria used for administration of RSV prophylaxis, location of palivizumab prophylaxis (inpatient or outpatient), parental satisfaction with administration of prophylaxis, incidence of RSV infection, and hospitalization rates for RSV. All selected publications were reviewed to determine whether they reported differences in the incidence of RSV infection or hospitalization in patients who received palivizumab before discharge compared with those who received it after discharge. Only those publications that specifically documented administration of the first dose of palivizumab before hospital discharge were included in the final analysis. RESULTS: Six of the 166 studies reviewed met the selection criteria. Although all 6 studies reported reduced RSV hospitalization rates with palivizumab prophylaxis, no study directly compared inpatient and outpatient administration with regard to parental satisfaction or rates of RSV infection or hospitalization. Furthermore, based on the data in these studies, it was not possible to detect any differences in parental satisfaction or rates of RSV infection or hospitalization between the 2 locations of administration. CONCLUSIONS: Based on our literature review, there is no evidence to support the recommendation that palivizumab be administered before hospital discharge in every infant who meets the criteria for RSV immunoprophylaxis. Eligible infants may be given the initial dose of RSV prophylaxis as outpatients, reducing the cost to institutions that currently provide palivizumab before hospital discharge.

Antibodies, Monoclonal↗
PubMed2004

Use of a remifentanil-propofol mixture for pediatric flexible fiberoptic bronchoscopy sedation.

BACKGROUND: Flexible fiberoptic bronchoscopy is an important diagnostic tool for pediatric pulmonologists. Because of its favorable respiratory profile, ketamine has become a popular sedative for this procedure, but may be associated with unpleasant emergence reactions in the older child. Remifentanil is a newer, ultra-short acting opioid that has been shown to provide effective sedation and cough suppression for fiberoptic bronchoscopy when combined with intermittent propofol boluses. However, delivery of these agents as a combined, single infusion has not been described. METHODS: Children > or =2 years of age undergoing fiberoptic bronchoscopy were enrolled. Remifentanil was mixed in a single syringe with undiluted propofol giving final drug concentrations of 10 mg x ml(-1) of propofol and 15-20 microg x ml(-1) of remifentanil. Sedation was induced with a bolus of approximately 0.1 ml x kg(-1) of this mixture and maintained by titrating the drip throughout the procedure. Vital signs, sedative effectiveness, recovery patterns, and complications were prospectively recorded. RESULTS: Fifteen patients aged 9.0 +/- 5.3 years were sedated. Sedation was induced with 1.2 +/- 0.4 mg x kg(-1) propofol (2.4 +/- 0.8 microg x kg(-1) remifentanil) and maintained with 4.1 +/- 1.8 mg x kg(-1) x h(-1) propofol (0.13 +/- 0.06 microg x kg(-1) x min(-1) remifentanil). Five patients received low-dose ketamine to augment sedation. The maximal decrease in respiratory rate was 6.1 +/- 5.3 b x min(-1) (27.6 +/- 21%) and no patient became hypoxemic. All procedures were completed easily without significant complication. Patients recovered to baseline 13.3 +/- 8.5 min following infusion discontinuation. CONCLUSIONS: A remifentanil/propofol mixture provided effective sedation and rapid recovery in pediatric patients undergoing fiberoptic bronchoscopy.

Adolescent↗
PubMed2004

Safety and efficacy of ketamine sedation for infant flexible fiberoptic bronchoscopy.

OBJECTIVE: To describe our experience with ketamine sedation during infant flexible fiberoptic bronchoscopy. DESIGN: Retrospective chart review. Infants were sedated with midazolam and ketamine with or without fentanyl. The sedation regimen, final procedure performed, procedure duration, and complications were recorded. Complication rates between infants 6 months of age and between infants with upper vs lower airway symptoms were compared by chi(2) test with a contingency table. RESULTS: Fifty-nine procedures were performed in 55 patients aged 6.1 +/- 3.1 months (mean +/- SD). Sedation was achieved with ketamine and midazolam (n = 30) or ketamine, midazolam, and fentanyl (n = 29). Bronchoscopy with BAL was performed in 44 patients and bronchoscopy alone in 3 patients. In 11 patients, severe upper airway obstruction and/or anomalies prevented subglottic passage of the bronchoscope. One patient could not be adequately sedated. There were no major complications. Minor complications occurred in 14 patients (23.7%), most commonly mild hypoxemia (n = 9). Brief central apnea developed in three patients. Complication rates were unaffected by age or indication for bronchoscopy. CONCLUSIONS: Infant flexible fiberoptic bronchoscopy can be safely and effectively performed using ketamine sedation. Complications, especially mild hypoxemia, appear more common in infants, likely due to smaller airway diameter. Regardless of the sedative(s) used, additional vigilance is required when performing bronchoscopy in this population.

Anesthetics, Dissociative↗
PubMed2003

Montelukast pharmacokinetics in cystic fibrosis.

OBJECTIVES: To determine if patients with cystic fibrosis (CF) have an altered pharmacokinetic profile of montelukast, we studied the single-dose pharmacokinetics in 12 patients with CF and 12 age- and gender-matched controls after they received a 10-mg oral dose. METHODS: Plasma samples were collected before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours after drug administration. The specimens were analyzed by high-performance liquid chromatography (HPLC). RESULTS: The mean systemic clearance (mL/min) values (+/- SD) were not statistically different between the CF subjects (55.53 +/- 44.0 mL/min) and the controls (57.12 +/- 18.42 mL/min), nor were the results significantly different when normalized to body surface area or body weight. The mean value for elimination half-life, elimination rate constant, area under the plasma concentration versus time curve, and maximum concentration for controls was 2.37 +/- 0.38 hours, 0.30 +/- 0.05 hours(-1), 2,680.0 +/- 693.6 ng. min/mL, and 448.9 +/- 165.3 ng/mL; and for the CF patients it was 2.97 +/- 1.21 hours, 0.28 +/- 0.13 hrs(-1), 3976.1 +/- 2073.4 ng. min/mL, 606.7 +/- 237.8 ng/mL. There were no statistically significant differences (all P >.05) in the measured pharmacokinetic parameters between the CF and control subjects. CONCLUSIONS: We conclude that the dose of montelukast and the dosing interval does not need to be modified if the goal is to mimic the serum concentration used to treat asthma. The effectiveness of these concentrations for the inflammatory lung disease of patients with CF is unknown.

Acetates↗
PubMed2003

Internet-enabled interactive multimedia asthma education program: a randomized trial.

OBJECTIVE: To determine whether health outcomes of children who have asthma can be improved through the use of an Internet-enabled interactive multimedia asthma education program. METHODS: Two hundred twenty-eight children with asthma visiting a pediatric pulmonary clinic were randomly assigned to control and intervention groups. Children and caregivers in both groups received traditional patient education based on the National Asthma Education and Prevention Program. Intervention group participants received additional self-management education through the Interactive Multimedia Program for Asthma Control and Tracking. Pediatric Asthma Care Knowledge Survey, Pediatric Asthma Caregiver's Quality of Life Questionnaire, asthma symptom history, spirometry, and health services utilization data were collected at the initial visit and at 3 and 12 months. RESULTS: Interactive Multimedia Program for Asthma Control and Tracking significantly increased asthma knowledge of children and caregivers, decreased asthma symptom days (81 vs 51 per year), and decreased number of emergency department visits (1.93 vs 0.62 per year) among the intervention group participants. The intervention group children were also using a significantly lower average daily dose of inhaled corticosteroids (434 vs 754 micro g [beclomethasone equivalents]) at visit 3. Asthma knowledge of all 7- to 17-year-old children correlated with fewer urgent physician visits (r = 0.37) and less frequent use of quick-relief medicines (r = 0.30). CONCLUSIONS: Supplementing conventional asthma care with interactive multimedia education can significantly improve asthma knowledge and reduce the burden of childhood asthma.

Adolescent↗
PubMed2002

Factors affecting the incidence of Stenotrophomonas maltophilia isolation in cystic fibrosis.

STUDY OBJECTIVES: To identify factors predisposing cystic fibrosis (CF) patients to Stenotrophomonas maltophilia infection and to determine whether coinfection with S maltophilia affects the clinical response to therapy with tobramycin solution for inhalation (TSI), 300 mg bid. DESIGN: Retrospective review of data collected from two identical, 6-month, randomized, placebo-controlled trials. SETTING: Sixty-nine CF centers in the United States. INTERVENTIONS: Active drug administration of 300 mg TSI. PATIENTS: Five hundred twenty CF patients with chronic Pseudomonas aeruginosa endobronchial infections. MEASUREMENTS AND RESULTS: A logistic regression analysis identified factors contributing to increased S maltophilia isolation frequency. In this multivariate analysis, the only significant predictors of S maltophilia isolation during the last month of the trial were the concomitant use of oral quinolones (primarily ciprofloxacin; p = 0.0015) and S maltophilia isolation prior to treatment (p < 0.0001). Treatment group, gender, age, use of systemic or inhaled steroids, use of oral sulfonamide, IV cephalosporins, or penicillin antibiotics, baseline FEV(1) percent predicted, and pretreatment Aspergillus isolation were not significant predictors of subsequent S maltophilia infection. In addition, S maltophilia-positive culture frequency was compared to the change in pulmonary function. Patients who either never had culture results positive for S maltophilia or who were positive at <25% of observations had greater clinical response to TSI at the final study visit compared to patients who were positive at > or = 25% of observations. CONCLUSIONS: TSI therapy did not result in a greater risk for isolation of S maltophilia than standard care alone. In contrast, oral quinolone antibiotic use during the trial was associated with a 2.7-fold increased risk of having a culture positive for S maltophilia (p = 0.0015). The use of TSI to suppress P aeruginosa resulted in improved lung function, regardless of S maltophilia culture frequency. However, improvement was not as great among patients who were persistently coinfected with S maltophilia.

Administration, Inhalation↗
PubMed2002

Chronic lung disease after activated charcoal aspiration.

The ingestion of toxic substances is a common pediatric emergency. Activated charcoal is part of the standard treatment for most toxic ingestions and is considered a benign therapy. We report a case of inadvertent administration of activated charcoal into the trachea that resulted in the development of chronic lung disease.

Biopsy↗
PubMedDate not supplied

Nebulized fentanyl for palliation of dyspnea in a cystic fibrosis patient.

Dyspnea, the subjective symptom feeling of breathlessness, is a common symptom in terminally ill patients with cystic fibrosis (CF). The palliation of the dyspnea is a reasonable goal to improve patient comfort as the progression of the disease worsens. We report the successful use of inhaled fentanyl for 3 days in a 17-year-old female with terminal CF lung disease, as measured by improved oxygenation and a reduction in the modified Borg score, and the subjective feeling of less air hunger reported by parents and patient.

Administration, Inhalation↗
PubMedDate not supplied

Patterns of helium-oxygen (heliox) usage in the critical care environment.

The objective of this study was to describe the patterns of heliox use in critical care units of an academic medical center. The design was a prospective case series involving 7 critical care units of an academic medical center. All patients receiving heliox therapy over a 4-year period were studied, with prospective recording of patient demographics and the location, mode, indication for, and duration of heliox use. Use pattern comparisons based on anatomic location (upper vs lower airway) and age group (pediatric vs adult) were performed by alpha(2) analysis and unpaired Student t test. Eighty-nine patients, aged 17.4 +/- 20.9 years, received heliox for 30.5 +/- 44.6 hours on 92 occasions. Pediatric (</= 18 years) applications accounted for 72.8% of heliox use. Use was greater in frequency and scope during the final 2 study years, particularly in adults. Applications were split between upper airway (47%) and lower airway (53%) disorders. Airway manipulation was required in more adults (7/16) than in children (3/27) with upper airway obstruction (P < .05). The use patterns mirrored current literature emphases on postextubation stridor and asthma. This is the first description of heliox use patterns in the tertiary care critical care environment. Heliox use may be as dependent on practitioner experience as on published data. As a benign and relatively inexpensive therapy, heliox use should continue to be attractive, although ongoing study regarding efficacy in a number of settings is indicated.

Academic Medical Centers↗