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Biomedical subjects

Andrew Bush

Publications and source records attributed to Andrew Bush.

At least 91 records · Page 5Linked to original sources
PubMed2003

Measured versus estimated oxygen consumption in ventilated patients with congenital heart disease: the validity of predictive equations.

OBJECTIVE: To determine the validity of predictive equations in calculating oxygen consumption (Vo(2)) in ventilated patients with congenital heart disease. DESIGN: Prospective study. SETTING: Cardiac catheterization laboratories and intensive care units of two university teaching hospitals. PATIENTS: A total of 126 patients with congenital heart disease were studied. Of these, 75 patients received anesthesia in the pediatric cardiac catheterization laboratory, and 51 were deeply sedated in the intensive care unit after open heart surgery. MEASUREMENTS AND MAIN RESULTS: Vo(2) was measured directly in all patients using respiratory mass spectrometry. Estimated values for absolute Vo(2) (mL/min) and indexed Vo(2) (mL.min-1.m-2) were calculated from the four predictive equations published by LaFarge and Miettinen, Lundell et al., Wessel et al., and Lindahl. The agreement between measured and estimated Vo(2) was evaluated by calculating their bias and limits of agreement. A failure of agreement between measured and estimated Vo(2) was noted in both groups of patients, irrespective the equation used, and the agreement was poorer in patients in the intensive care unit. The equation by LaFarge and Miettinen produced the closest estimation in patients at cardiac catheterization with a bias of 4.5 mL/min for absolute Vo(2) and 6.9 mL.min-1.m-2 for indexed Vo(2). A systematic error of overestimating lower and underestimating higher indexed Vo(2) mL.min-1.m-2 was introduced in both groups. CONCLUSION: Predictive equations do not accurately estimate Vo(2) in ventilated patients with congenital heart disease.

Adolescent↗
PubMed2003

Nitric oxide metabolites are not reduced in exhaled breath condensate of patients with primary ciliary dyskinesia.

STUDY OBJECTIVES: To investigate whether nitric oxide (NO) metabolites would be reduced in children affected by primary ciliary dyskinesia (PCD). DESIGN: Single-center observational study. PATIENTS: Fifteen children with PCD (seven boys; mean [+/- SEM] age, 10.3 +/- 0.7 years; mean FEV(1), 73 +/- 2.1% predicted) were recruited along with 14 healthy age-matched subjects (seven boys; mean age, 11.5 +/- 0.4 years; mean FEV(1), 103 +/- 5% predicted). INTERVENTIONS: We assessed the levels of nitrite (NO(2)(-)), NO(2)(-)/NO(3)(-) (NO(2)(-)/NO(3)(-)), and S-nitrosothiol in exhaled breath condensate, exhaled NO, and nasal NO from children with PCD compared to those in healthy children. MEASUREMENTS AND RESULTS: The mean exhaled and nasal NO levels were markedly decreased in children with PCD compared to those without PCD (3.2 +/- 0.2 vs 8.5 +/- 0.9 parts per billion [ppb], respectively [p < 0.0001]; 59.6 +/- 12.2 vs 505.5 +/- 66.8 ppb, respectively [p < 0.001]). Despite the lower levels of exhaled NO in children with PCD, no differences were found in the mean levels of NO(2)(-) (2.9 +/- 0.4 vs 3.5 +/- 0.3 microM, respectively), NO(2)(-)/NO(3)(-) (35.2 +/- 5.0 vs 34.3 +/- 4.5 microM, respectively), or S-nitrosothiol (1.0 +/- 0.2 vs 0.6 +/- 0.1 microM, respectively) between children with PCD and healthy subjects. CONCLUSION: These findings suggest that NO synthase activity may not be decreased as much as might be expected on the basis of low exhaled and nasal NO levels.

Breath Tests↗
PubMed2003

Safety of medicines in children.

Unlicensed and off-label prescribing is common in children. This is likely to be due to a combination of the difficulty in carrying out reliable clinical trials in children and the lack of financial reward for the industry. The term 'paediatric' encompasses preterm babies to near adult-sized adolescents, and all aspects of drug handling differ over this age range, making extrapolation very problematic. Recently, adrenal failure with inhaled corticosteroid use in children has been highlighted. Examination reveals that this is due to a combination of factors common in paediatric prescribing; including the assumption that adult diseases are the same as paediatric diseases, the lack of good diagnostic tools in small children and lack of thought about problems of drug delivery. Although some steps are being taken to improve paediatric prescribing, much more needs to be done. One approach may be to offer incentives to the pharmaceutical industry. The present state of affairs is unsatisfactory and cannot be allowed to continue.

Child↗
PubMed2003

Thyroid dysfunction in patients with type 1 diabetes: a longitudinal study.

OBJECTIVE: Cross-sectional studies have reported that the risk of thyroid dysfunction in patients with type 1 diabetes is two- to threefold higher than in the general population. However, longitudinal studies to determine the natural history of thyroid dysfunction in patients with type 1 diabetes are lacking. RESEARCH DESIGN AND METHODS: We analyzed the incidence of thyroid dysfunction over time in a cohort of 58 patients (26 men and 32 women) enrolled in the Diabetes Control and Complications Trial at the University of Tennessee Health Science Center in 1983 and prospectively followed for 18 years. Patients underwent measurement of thyroid function tests (thyroid-stimulating hormone [TSH], thyroxine, and triiodothyronine) every year and thyroid peroxidase (TPO) antibodies at 4-year intervals. RESULTS: A total of 18 patients had hypothyroidism, and 1 patient experienced transient hyperthyroidism. Two subjects developed hypothyroidism 7 and 18 years before the development of diabetes and were excluded from the analysis. The mean age of diagnosis was 19 +/- 2 years for type 1 diabetes and 29 +/- 3 years for hypothyroidism. Hypothyroidism was more common in female (41%) than in male (19%) subjects and in patients with positive TPO antibodies. Patients who were TPO positive were 17.91 times as likely to develop hypothyroidism as patients who were TPO negative (95% CI 3.89-82.54). There were no differences in BMI, lipid profile, and HbA(1c) between patients with and without thyroid dysfunction. CONCLUSIONS: This longitudinal study confirms the association between autoimmune thyroid dysfunction and type 1 diabetes. Our results indicate that all subjects with type 1 diabetes should undergo annual screening by serum TSH measurement to detect asymptomatic thyroid dysfunction, particularly those with positive TPO antibodies.

Autoimmune Diseases↗
PubMed2002

Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis.

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.

Age Factors↗
PubMed2002

Increased leukotrienes in exhaled breath condensate in childhood asthma.

Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7-14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.

Adolescent↗
PubMed2002

Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis.

Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.

Adolescent↗
PubMed2002

Increased interleukin-4 and decreased interferon-gamma in exhaled breath condensate of children with asthma.

Exhaled breath condensate analysis for noninvasive quantification of airway inflammation in asthma is a potentially useful research tool in children. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4, and Th1 cells, which secrete interferon (IFN)-gamma, in asthma. We measured concentrations of IL-4 and IFN-gamma in breath condensates of 37 children (11 normal, 12 steroid-naive, and 14 steroid-treated children with asthma). Exhaled IFN-gamma was significantly lower in steroid-naive and steroid-treated children with asthma compared with normal control subjects (3.7 +/- 0.2 versus 5.1 +/- 0.4 pg/ml, p < 0.01 and 4.1 versus 5.1 pg/ml, p < 0.05). By contrast, mean exhaled IL-4 was elevated in asthma (53.7 +/- 4.2 pg/ml) compared with normal children (35.7 +/- 6.2 pg/ml, p < 0.05) and concentrations were lower with steroid treatment (37.5 +/- 5.6 pg/ml, p < 0.05). Exhaled IL-4 was significantly lower in children with asthma on more than 600 microg inhaled steroid/day. The IL-4/IFN-gamma ratio was significantly greater in children with asthma compared with control children and the children with asthma on inhaled steroid therapy. We have shown for the first time that IFN-gamma and IL-4 can be assayed in exhaled breath condensate and shows an increased ratio of IL-4/IFN-gamma, consistent with predominance of Th2 cells in airways of children with asthma. Exhaled breath condensate analysis may have a useful role in studying allergic inflammation in childhood asthma.

Adolescent↗
PubMed2002

Cystic fibrosis: keeping it in the family.

Nearly all men with cystic fibrosis (CF) are infertile, although assisted conception has allowed an increasing number of women with CF to become pregnant. We report on the case of a couple investigated for infertility who conceived a child with CF. The father had previously undergone a laparotomy for meconium peritonitis as a neonate, and the mother had recently been given a diagnosis of asthma. Both parents fulfilled the United States Cystic Fibrosis Foundation diagnostic criteria for cystic fibrosis. We discuss the mild CF phenotype and the impact of the diagnosis on this family.

Adult↗
PubMed2002

Salbutamol dry powder inhaler: efficacy, tolerability, and acceptability study.

Dry powder inhaler (DPI) devices are frequently used in children over 5 years of age in order to avoid coordination difficulties often seen with the use of pressurized metered dose inhalers (pMDI). This study assessed the efficacy, tolerability, and acceptability of salbutamol delivered via two delivery systems, in a population of pediatric patients. The primary aim of the study was to investigate the bronchodilator efficacy of a single dose (100 microg) of salbutamol administered via a dry powder inhaler (Clickhaler) compared to a similar dose administered by a pressurized metered dose inhaler via a large-valved holding chamber (VHC) to children with asthma. The study comprised two phases: the first comparator phase, followed by an open 4-week treatment period. Sixty-one children with a mean (SD) age of 11.3 years (2.9) (range, 6-17) and mild or moderate asthma completed the study. The primary efficacy endpoint, forced expiratory volume in 1 sec (FEV1), indicated that there was no clinically or statistically significant difference between the bronchodilator effects of salbutamol delivered via either device, with a maximum posttreatment percentage change in FEV1 (SD) of 12.4% (10.0) and 14.15 (9.3) for Clickhaler and pMDI plus VHC, respectively. Most patients rated the Clickhaler as easy to use (97%) and liked the device (84%). Both treatments were well--tolerated. These results support the suitability of salbutamol Clickhaler as an acceptable, well-tolerated, and effective alternative to a pMDI plus VHC in mild to moderate asthmatic children over age 6 years.

Administration, Inhalation↗
PubMed2002

Subcutaneous terbutaline in children with chronic severe asthma.

A continuous subcutaneous infusion of terbutaline (CSIT) was used to treat 8 children with chronic severe asthma who continued to experience frequent symptoms, despite treatment with regular oral prednisolone. Five patients experienced a symptomatic improvement from CSIT, leading to a reduction in regular medication. Three patients did not experience any lasting benefit from CSIT. The most common side effects were related to the infusion site (bruising and local infection). CSIT may lead to an improvement in symptoms and a reduction in oral steroid dose in selected children with chronic severe asthma. These initial findings support the need for further controlled studies to evaluate the use of CSIT in severe childhood asthma.

Adolescent↗
PubMed2002

Amphotericin B-induced hepatorenal failure in cystic fibrosis.

Although nephrotoxicity is a common and well-recognized side effect of amphotericin B, hepatotoxicity is rare. We report on a 9-year-old girl with cystic fibrosis who developed fulminant renal and hepatic dysfunction following a short course of intravenous amphotericin B for a suspected aspergillus infection, although she did not have clinical evidence of invasive aspergillosis. The toxicity became apparent after changing to liposomal amphotericin. This association of renal and hepatotoxicity with liposomal amphotericin B has not previously been reported in children.

Amebicides↗
PubMed2002

Bone marrow stem cells do not repopulate the healthy upper respiratory tract.

Recent studies reported differentiation of both bone marrow and tissue-specific stem cells into cells of other organs. The demonstration that bone marrow stem cells differentiate into human hepatocytes in vivo has raised the possibility of new therapeutic approaches for liver disease. For diseases such as cystic fibrosis (CF), correction of the respiratory epithelium is being attempted by gene therapy. Differentiation of bone marrow stem cells into epithelium of the lung and airway was recently reported in an animal model, and would provide an alternative approach. We examined the nasal epithelium of female patients up to 15 years after gender-mismatched bone marrow transplantation. Donor-derived epithelial cells were sought with a combination of Y-chromosome fluorescence in situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from 6 transplant-recipients, a median of 2.5% (range, 0.7-18.1%) of nuclei was male and identified as being of donor-origin. However, a complete absence of staining with anti-cytokeratin antibodies confirmed that these were not epithelial cells, but were likely to be either intraepithelial lymphocytes or mesenchymal cells. Following whole bone marrow transplantation, bone marrow progenitor cells do not differentiate into respiratory epithelium of the healthy upper airway. The differences between this and other studies could relate to the cells transplanted, to differential rates of turnover, or to the requirement for specific triggers to stimulate migration and differentiation. In the absence of such conditions, whole bone marrow transplantation is unlikely to provide a route for correction of the CF airway.

Adolescent↗
PubMed2002

Objective monitoring of cough in children with cystic fibrosis.

Increased cough frequency is a common symptom associated with infective pulmonary exacerbations of cystic fibrosis (CF), but subjective assessment of cough is very unreliable. The aims of this study were: 1) to validate a modification of our previously described ambulatory cough recording device (LR 100); 2) to determine how accurately children with CF assess levels of cough; and 3) to assess the change in cough in children with CF when treated with intravenous antibiotics for a respiratory exacerbation, and whether the children themselves were able accurately to perceive any change. Fourteen CF children (aged 13.6 +/- 2.6 years) were included in the study. All 14 children were simultaneously recorded with the LR 100 cough recorder and a conventional tape recorder during a chest physiotherapy session on the first or second day of admission for an infective exacerbation diagnosed by standard criteria. The difference between the two was an underestimate of 0.5 epoch/session by the tape recorder. Ten children were recorded on admission with the LR 100 cough recorder for a complete cycle (17 hr and 40 min), and we also assessed their day and night-time cough with cough scores and visual analogue scores (VAS). In 8 of these children, the same assessments were repeated on discharge. There was no significant correlation between any of the admission or discharge cough scores, daytime or night-time cough scores, and daytime or night-time VAS scores, with the actual number of coughs recorded on the LR 100 cough recorder. For the 8 children who had cough monitoring on admission and on discharge, there was no significant improvement in daytime or night-time cough scores or VAS on discharge, despite significant improvements in spirometry. There was also no significant improvement on daytime and night-time cough counts with the cough monitor on discharge, and no significant correlation with changes in lung function. There were weak correlations only between change in daytime VAS scores and change in forced expired volume in 1 sec (r = -0.794, P = 0.019) and forced vital capacity (r = -0.723, P = 0.04). In conclusion, we describe a reliable and well-tolerated method for obtaining cough counts objectively. The use of this objective method showed that CF children did not assess their cough frequency well. In addition, treatment of respiratory exacerbation improved neither subjective nor objective measures of cough in CF children.

Adolescent↗
PubMed2002

Paediatric problems of cough.

All children cough, but most children are normal. In a child with isolated cough, a detailed history and examination, followed in a small number of cases by targeted investigations, should allow the child to be placed in one of five diagnostic categories. These are normal child; the child with a serious illness such as cystic fibrosis, tuberculosis etc. the child with non-serious, but treatable causes of cough and wheeze, for example gastro-oesophageal reflux or postnasal drip; the child with an asthma syndrome and an overestimation of symptoms for psychological or other reasons by either or both of child or family. Treatment is of the underlying condition if appropriate. Non-specific treatment with cough syrups are not useful. Attention to environmental factors such as active and passive smoking, and exposure to dust and pets is important. The diagnosis of cough variant asthma should only be made in older children after variable airflow obstruction and response to bronchodilator has been demonstrated physiologically. In younger children, rational diagnostic criteria are an abnormally increased cough, with no evidence of any non-asthma diagnosis, a clear-cut response to a therapeutic trial of asthma medication, usually moderate dose inhaled corticosteroids, and relapse on stopping medications with second response to recommencing them. Some such children go on to develop more typical asthma, with wheeze and bronchial hyper-reactivity. It is important however, not to over-diagnose asthma in children who in fact have a chronic non-specific cough. Such children require no treatment, get better with time, and have normal long-term lung function.

Asthma↗
PubMed2002

Decisions facing the cystic fibrosis clinician at first isolation of Pseudomonas aeruginosa.

Chronic endobronchial infection with shape Pseudomonas aeruginosa in patients with cystic fibrosis is associated with more serious disease and reduced survival. Methods for reducing or preventing chronic infection with P. aeruginosa involve rigorous infection control measures and avoidance of cross-infection, which may include segregation of clinics according to microbiological status. The strains of shape P. aeruginosa first isolated from the lungs of cystic fibrosis patients are generally of a non-mucoid phenotype and sensitive to antibiotic therapy. There is some evidence that early aggressive antibiotic treatment may delay chronic infection, improve lung function and improve survival. Further research is needed into the accurate diagnosis of early infection with shape P. aeruginosa, which is often intermittent. In addition, the optimal treatment of patients at first isolation and early colonisation needs to be researched, including choice of antibiotic(s) and route, dosage and duration of antibiotic therapy.

Adult↗