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Biomedical subjects

D Fitzgerald

Publications and source records attributed to D Fitzgerald.

At least 55 records · Page 3Linked to original sources
PubMed1998

Higher SaO2 in chronic neonatal lung disease: does it improve sleep?

Sleep fragmentation, decreased rapid eye movement (REM) sleep time, and REM sleep hypoxemia have been reported in infants with chronic neonatal lung disease (CNLD) in early infancy despite an awake hemoglobin oxygen saturation (SaO2) >93%. Interestingly, higher inspired O2 concentrations have been demonstrated to reduce REM sleep fragmentation in CNLD patients in middle infancy. However, the effect of increased SaO2 on sleep architecture in infants with CNLD near the time of discharge from neonatal intensive care has not been reported. We performed paired overnight polysomnography in a sleep laboratory on 16 infants with CNLD (4 weeks median corrected age) in air or their usual inspired oxygen (SaO2 >93%) and again when receiving 0.25 L/min higher than baseline inspired oxygen via nasal catheters (SaO2 >97%). A control group of seven healthy preterm infants was similarly studied. For CNLD infants on supplemented O2, sleep duration decreased by 15% (422+/-66 min vs. 359+/-89 min; P< 0.005), and sleep efficiency decreased by 7% (73.2+/-10.6% vs. 66.4+/-14.0%; P < 0.005) but percentage of time in REM sleep (REM%) (31.5+/-8.9% vs. 29.8+/-8.6%; P=0.560), REM epoch duration (12.4+/-2.8 min vs. 13.4+/-4.3 min; P=0.420), and REM arousal index (18.6+/-6.5 vs. 18.8+/-7.2; P=0.990) were not significantly affected. Conversely, higher O2 did not alter sleep architecture in the control group. The mean non-REM (NREM) respiratory rate decreased (CNLD: P=0.003; controls: P=0.02), NREM SaO2 increased (P < 0.05), although the mean transcutaneous CO2 was unaltered in both CNLD and control groups. This study confirmed low REM% in CNLD infants in early infancy and demonstrated that a higher SaO2 adversely affected sleep time but did not influence REM sleep duration or arousal frequency. A target SaO2 >93% is, therefore, as efficacious as an SaO2 >97% in optimizing sleep architecture in CNLD infants.

Bronchopulmonary Dysplasia↗
PubMed1998

Sleep, respiratory rate, and growth hormone in chronic neonatal lung disease.

This study assessed whether respiratory rates (RRs) correlate with urinary growth hormone (U-GH) excretion and sleep architecture in infants with chronic neonatal lung disease (CNLD) in early (1 month), middle (6 months), and late (10 months) infancy. Twenty-three preterm infants (CNLD=16, controls=7) were studied on 51 occasions. CNLD infants were stratified according to mean non-REM sleep respiratory rate (NREM RR) in early infancy into "High RR CNLD" infants (mean NREM RR >2 SD higher than controls) and "Normal RR CNLD" infants (mean NREM RR within 2 SD of controls' mean). "High RR CNLD" infants (RR >45) had a lower mean birthweight (P=0.015), current weight (P=0.042), current length (P=0.02), and growth velocity in early infancy (grams/week gained: P=0.042) than "Normal RR CNLD" and control infants. Mean (95% CI) U-GH excretion (ng U-GH/g urinary creatinine) was higher in "High RR CNLD" infants in air or their usual O2 (1,932 [459, 3,406]) than "Normal RR CNLD" (394 [147, 642]) and controls (320 [147, 492]) (P=0.024). With resolution of tachypnea by mid-infancy, hemoglobin oxygen saturation (SaO2) >93%, mean growth parameters and U-GH excretion for the "High RR CNLD" group were not significantly different from "Normal RR CNLD" and control groups. CNLD infants demonstrated increased sleep efficiency (P=0.016), whereas controls had similar sleep efficiency between early and middle infancy (P=0.452). Mean percent time in REM sleep (REM%) and slow wave sleep (SWS%) were not significantly different between early and middle infancy and did not vary in relation to respiratory rate. We conclude that tachypneic infants with CNLD have slower growth and elevated U-GH excretion in early infancy. With resolution of tachypnea, growth improved, U-GH excretion decreased, and sleep consolidation occurred. An elevated U-GH in tachypneic CNLD infants may reflect stress, compromised nutrition (GH resistance), or a feedback loop involving a direct effect of GH on lung growth and repair.

Bronchopulmonary Dysplasia↗
PubMed1998

Fluticasone propionate 750 micrograms/day versus beclomethasone dipropionate 1500 micrograms/day: comparison of efficacy and adrenal function in paediatric asthma.

BACKGROUND: Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function. METHODS: The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences. RESULTS: There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods. CONCLUSIONS: FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.

Administration, Inhalation↗
PubMed1998

Dexamethasone for pulmonary interstitial emphysema in preterm infants.

The efficacy of a 3-day course of dexamethasone (0.5 mg/kg/ day) in 10 preterm infants (< or = 30 weeks gestation) with pulmonary interstitial emphysema (PIE) was studied in a retrospective case review. PIE was diagnosed at a median age of 7.5 days and treatment with dexamethasone began at 8.5 days. Seven of the 10 subjects had at least 2 days of conservative treatment (lowered mean airway pressure) preceding dexamethasone during which the mean airway pressure (MAP), oxygenation index (OI) and mechanical ventilation index (MVI) were not significantly different although within 3 days of dexamethasone each variable improved significantly (p < 0.05). Similarly, for all 10 infants, OI and MAP were significantly lower at 3 and 7 days from baseline (p < 0.005). By day 7, FiO2 (p = 0.022) and MVI (p = 0.011) were significantly lower and PIE had resolved on chest X-ray in 7/9 (78%) and improved in the remaining 2/9 (22%). Nine of the 10 infants survived to term. Three days of dexamethasone was associated with significant clinical improvement in most of these infants. The mechanism may relate to reduced airway oedema and inflammation and reduced airway obstruction.

Dexamethasone↗
PubMed1998

Kentucky physicians' perspectives and preparedness for computing in medical education and practice.

PURPOSE: To examine the University of Kentucky College of Medicine's community-based faculty's (CBF) perspective on computing skills that students should acquire for future medical practice, and if the CBF currently use these skills in their daily practice. METHODS: A survey was mailed to 281 of the institution's CBF in the spring of 1997. The survey listed eight basic computing skills derived from our computing curricular objectives for students and asked respondents (a) if they use the skill, and (b) if students should learn the skill. RESULTS: 200 respondents returned a completed survey. 14 CBF (7.2%) indicated that they have all eight computer skills while 91 CBF (46.4%) indicated that students should learn all eight computer skills. 25 CBF (13%) indicated that they have none of the computer skills, while none of the CBF indicated students need none of the skills. A significant difference between primary care CBF and other specialist CBF was found with respect to self-report of computer use, but not regarding their opinions about students' need to learn computer skills. CONCLUSION: The majority of our CBF report using at least one computer skill in their practices. Regardless of specialty, CBF report that students should possess more computer skills than they themselves have. Medical educators should incorporate computing applications into the curriculum to provide appropriate computer training for future physicians.

Adult↗
PubMed1997

Differential gene expression of cytochrome P450 11beta-hydroxylase in rat adrenal cortex after in vivo activation.

In situ hybridization histochemistry was used to monitor the expression of 3beta-hydroxysteroid dehydrogenase, delta4-isomerase (3betaHSD) and cytochrome P450 11beta-hydroxylase (P45011beta) messenger RNA (mRNA) in adult rat adrenals after stimulation in vivo. In Exp 1, adrenals were collected from rats injected with saline or ACTH for 1, 2, 3, or 4 days. Adrenal sections from saline-treated rats showed uniform expression of 3betaHSD mRNA that extended from the adrenal capsule to the medullary border. In contrast, P45011beta mRNA showed high levels in the outer fasciculata and low levels in the inner fasciculata/reticularis. In response to ACTH, the integrated density of 3betaHSD hybridization did not increase until 4 days. The integrated density of P45011beta hybridization increased in ACTH-treated rats between 1-4 days due to increased hybridization in the inner fasciculata/reticularis. In Exp 2, rats were treated with ACTH or saline, and adrenals were harvested at 4, 8, or 24 h. The hybridization density of 3betaHSD did not change after ACTH or saline injection. Increased expression of P45011beta mRNA was observed at 4 and 8 h, but not 24 h post-ACTH. In Exp 3, to determine the response to acute stress, adrenals were collected from rats 24 h after surgical laparotomy. The integrated density of 3betaHSD labeling did not change, whereas both hybridization area and mean density of P45011beta increased. Increased expression of P45011beta mRNA was observed in the inner fasciculata similar to that observed after ACTH injection. In addition, adrenal cells were more responsive to ACTH in vitro after surgical stress. These results suggest that the rat adrenal cortex can respond to acute stress by up-regulation of the expression of steroidogenic enzyme genes and that this occurs in part by increasing the number of cells actively expressing P45011beta mRNA. The adrenal response after stress most likely results at least in part from stimulation by ACTH. These findings suggest that changes in adrenal steroidogenesis in response to ACTH may result from recruitment of steroidogenic cells to synthesize and secrete corticosteroids.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Identifying and treating femoral artery pseudoaneurysms following invasive cardiac procedures.

Advances in interventional cardiology offer new choices for patients with coronary artery disease. Unfortunately, these new procedures are associated with complications, such as femoral artery pseudoaneurysms. Accurate and timely vascular assessments by adult health nurses can detect this problem and result in prompt treatment, sometimes including ultrasound-guided compression.

Adult↗
PubMed1997

Do nurses have the information resources and skills for research utilization?

While access to information resources and the skills to use them do not ensure that nurses will use nursing research in their practice, they are important facilitators. Mailed questionnaires to assess existing information resources, the information management skills of nurses, and what additional resources and training are required were returned by 67 of the 71 vice-presidents or directors of nursing in hospitals in two regions of Ontario. The two regions have similar information resources, nursing staff with research expertise, and opportunities for training in research and information management but there is variation among hospitals. Most vice-presidents agreed that nurses need better information resources and skills to access and evaluate professional literature. The rapidly developing field of information technology, including the Internet, provides potential for sharing resources and expertise. Nursing administrators can minimize barriers and help staff nurses recognize that information management skills enhance professional development and improve patient care.

Computer User Training↗
PubMed1996

Diaphragmatic pacemaker failure in congenital central hypoventilation syndrome: a tale of two twiddlers.

Two patients with congenital central hypoventilation syndrome (CCHS) experienced phrenic nerve pacer failure due to deliberate manipulation of the internal receiver implant ("twiddling"). The patients, aged 7 and 12 years, presented with repeated episodes of pacer failure associated with local pain over a period of 18 months. They had progressively coiled the pacing wires to the point of breakage, which only became apparent at surgery. The breaks were not recognized radiologically, although in retrospect progressive twisting of the wires was evident on serial chest radiographs. Both patients required replacement of the internal receivers under general anesthesia. We recommend that the chest radiograph that is undertaken to investigate the cause of pacer dysfunction include the internal receiver. A plain chest radiograph that demonstrates progressive coiling of the subcutaneous pacing wire should raise suspicion of pacer wire breakage regardless of the patient's age.

Child↗
PubMed1996

Why toxins!

Toxins are potent cytotoxic proteins which gain access to the interior of mammalian cells by receptor-mediated endocytosis. However, the trafficking pathways within mammalian cells are complex and toxins must be processed to active forms while avoiding degradation by the lysosomal system. Once delivered to an appropriate intracellular location, the active toxin fragment translocates to the cell cytosol and inhibits protein synthesis. Chimeric toxins are constructed by removing the toxins natural binding domain and replacing it with an antibody or cell-binding ligand that redirects cell killing activity to cancer cells. Gaining an understanding of how toxins manoeuvre within cells is vital for improving the effectiveness of chimeric toxins.

ADP Ribose Transferases↗
PubMed1996

Death following elective tracheostomy decannulation in chronic neonatal lung disease.

Widespread air leak as a fatal complication of elective tracheostomy decannulation in a child aged 20 months with chronic neonatal lung disease (CNLD) is reported. We discuss likely mechanisms for the development of air leak following tracheostomy tube removal in young children with obstructive airways disease and suggest that this procedure be performed in an intensive care or high dependency unit.

Fatal Outcome↗
PubMed1996

Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup.

OBJECTIVE: Nebulized budesonide and nebulized adrenaline have been shown to be effective in the treatment of moderately severe croup. However, there has been no direct comparison of these therapies. We undertook a multicenter, randomized, double-blind, parallel group study in 66 hospitalized children with viral or spasmodic croup. METHODS: Children 0.5 to 6 years of age were assessed using a validated croup symptom score (stridor, 0 through 4; cough, 0 through 3; retractions, 0 through 3; dyspnea, 0 through 3; and color, 0 through 4) at 0.5, 1, 1.5, 2, 12, and 24 hours after nebulization. Patients received either budesonide (2 mg/4 mL) or L-adrenaline (4 mg/4 mL) via nebulization. The primary outcome measure was change in the total croup symptom score. RESULTS: Thirty-five children received budesonide and 31 received adrenaline. There was no significant difference in baseline features, including croup score (mean [95% confidence interval]: budesonide, 7.1 [6.7-7.5]; adrenaline, 7.7 [7.3-8.1]). All patients had significant improvement from baseline, and there was not significant difference between the two treatments, as measured by change in croup scores, change in oxygen saturation, duration of hospitalization, number of subsequent treatments with systemic steroids or adrenaline, and adverse events. No child required intubation. CONCLUSION: This study does not show any difference in efficacy and safety between nebulized budesonide and nebulized adrenaline in the treatment of acute upper airway obstruction in patients with moderately severe croup.

Administration, Topical↗
PubMed1996

Argatroban: a synthetic thrombin inhibitor of low relative molecular mass.

Argatroban is an arginine derivative that is a highly specific thrombin inhibitor. Experimentally, it is more effective than heparin but it is not known whether this is the case in humans. The trials reported with argatroban to date have been too small to define either the efficacy or the safety of the drug. Large-scale clinical trials are under way in a variety of settings, including unstable angina, coronary angioplasty and acute myocardial infarction.

Animals↗
PubMed1995

Pharmacokinetics of computer-controlled alfentanil administration in children undergoing cardiac surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) induces changes in the pharmacokinetics of drugs. The purpose of this study was to model the pharmacokinetics of alfentanil in children undergoing cardiac surgery to provide accurate dosage titration intraoperatively as well as in the postoperative period. METHODS: Fourteen children (aged 3 months to 8 yr) undergoing cardiac surgery with CPB were administered alfentanil via a computer-controlled infusion pump. During surgery, the computer-controlled infusion pump was set to target plasma alfentanil concentrations of 500-2500 micrograms/ml. After surgery, the computer-controlled infusion pump was set to target plasma concentrations of 200-500 micrograms/ml. Parameters for children previously published by Goresky et al. were programmed into the device. Arterial blood samples were taken throughout the infusion. Plasma samples were assayed by radioimmunoassay. Alfentanil pharmacokinetics were estimated using a pooled-data approach with a simple weight-proportional, three-compartment mamillary model with parameters expressed in volumes and clearances as well as a CPB-adjusted, three-compartment model in which the parameters were allowed to change before, during, and after CPB. The accuracy of the three models was compared using cross-validation. RESULTS: Plasma alfentanil concentrations during computer-controlled infusion pump administration exceeded target concentrations for the first 10 min of drug administration, and from 300 min to the end of the study. The median absolute performance error was 33%. Pharmacokinetic modeling estimated a set of parameters for a simple three-compartment model with a median absolute weighted residual of 18.4%. A CPB-adjusted model nominally decreased the median absolute weighted residual to 17.0%. The performance of these models as measured by cross-validation performance was 18.9% median absolute performance error for the simple model and 18.4% median absolute performance error for the CPB-adjusted model. Parameters for the simple three-compartment model are: V1 = 19.2 ml.kg-1; V2 = 99 ml.kg-1; V3 = 2344 ml.kg-1; Cl1 = 2.5 ml.kg-1.min-1; Cl2 = 38 ml.kg-1.min-1; and Cl3 = 15 ml.kg-1.min-1. In the CPB-adjusted model V1, V2, and Cl2 changed with the onset of CPB. After CPB, V1 and Cl2 returned to the initial values, while V2 was described by a third value. CONCLUSIONS: The population pharmacokinetics of alfentanil in children undergoing cardiac surgery were well described by both a simple weight-proportional, three-compartment model and a weight-proportional, CPB-adjusted three-compartment model. Cross-validation estimated an expected median inaccuracy of approximately 18-20% with the estimated models in identical experimental circumstances. The flexible CPB-adjusted pharmacokinetic model could be used for modeling any drug with linear pharmacokinetics given in the context of CPB.

Alfentanil↗