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Biomedical subjects

A Bush

Publications and source records attributed to A Bush.

At least 19 recordsLinked to original sources
PubMed1997

Retrospective review of the effects of rhDNase in children with cystic fibrosis.

Trials of rhDNase in mixed groups of adults and children with cystic fibrosis (CF) have demonstrated improvements in lung function and well-being. This has led to many pediatric CF patients receiving regular rhDNase therapy although their response to treatment may not be the same as that seen in adults. We have retrospectively reviewed the effects of rhDNase during the first year of therapy in 65 children receiving the drug at two tertiary referral centers. Outcome measures included changes in lung function, oxygen saturation, use of intravenous antibiotics, and subjective improvement. Median baseline lung function (% of predicted) was 45% for forced expiratory volume in 1 second (FEV1) and 58% for forced vital capacity (FVC). At 3-4 months following initiation of therapy the group demonstrated median (95% CI) increases of 14.2% (95% CI 7.3; 21.1%) in FEV1 and 7% (0; 14%) in FVC. Within this wide scatter of responses, one-quarter of children deteriorated, but almost 50% showed significant improvements of > 10%. A similar pattern was seen at 9 months, with median increases for the group of 11.1% (0; 18.8%) in FEV1 and 5.6% (0; 17%) in FVC, again with approximately one-third of the group deteriorating and one-half improving significantly. Intravenous antibiotic use decreased significantly. Almost all the children (89%), including those with a fall in lung function, described subjective improvement. There were no predictive markers at baseline of a good response to the drug. However, there was a good correlation between lung function response at 3 months and that at 6, 9, and 12 months. Thus, children respond to rhDNase at least as well as adults, and a therapeutic trial is justified in those over 5 years with significantly impaired lung function. Response is highly variable, making careful individual assessment mandatory. Baseline characteristics are not useful in predicting those children who will respond well to treatment, but long-term response to the drug can be predicted on the basis of spirometric improvement at 3 months. Therefore, this would be a useful time period for a therapeutic trial.

Adolescent↗
PubMed1997

Congenital diaphragmatic hernia misdiagnosed as tension pneumothorax.

Drainage of the pleural space is undertaken as an emergency when there is respiratory distress and the radiological appearance of mediastinal shift. We present two cases in which the initial diagnosis was tension pneumothorax and chest drains were inserted. In both cases, the diagnosis turned out to be congenital diaphragmatic hernia.

Child↗
PubMed1997

Attitudes toward standardized data collection.

BACKGROUND AND PURPOSE: Clinical databases will gain importance as physical therapists need to determine the effectiveness and justify the expense of treatment. Obstacles impeding participation in standardized data collection need to be identified and addressed to construct high-quality databases. SUBJECTS: Subjects were clinicians involved in patient care in a multisite physical therapy/occupational therapy practice that had initiated a standardized data collection program. METHODS: Questionnaires, asking about participation in the data collection project, were distributed to participating clinics. Factor analysis identified attitudes toward standardized data collection. Relationships between efforts to learn standardized methods, attitudes, clinic and clinician characteristics, and levels of participation in the project were investigated. RESULTS: Most respondents (66%) had made some effort to learn the standardized procedures. Five attitudes were identified: inconvenience, acceptance of operational definitions, automation, paperwork, and training. CONCLUSION AND DISCUSSION: Inconvenience of data collection and training in standardized methods need to be addressed to construct large, high-quality databases.

Adult↗
PubMed1997

Cardiovascular effects of intravenous midazolam after open heart surgery.

Midazolam is the sedating agent of choice in many paediatric intensive care units, and is usually administered as a continuous intravenous infusion with or without a preceding bolus dose. Ten haemodynamically stable children, ventilated in the early postoperative period after cardiac surgery and receiving intravenous morphine infusions, were given an intravenous bolus followed by a continuous infusion of midazolam. Haemodynamic data were recorded before the bolus, and 15 minutes and one hour later. A bolus of midazolam lowered the cardiac output by 24.1%. Arterial blood pressure, oxygen consumption, and mixed venous oxygen content fell significantly. There was a tendency for all variables subsequently to recover towards baseline values, within one hour, during a continuous infusion. An intravenous bolus of midazolam causes a transient but unwanted fall in cardiac output. It is suggested that in children who are receiving intravenous opiates, its use in the early postoperative period be limited to a continuous infusion.

Adolescent↗
PubMed1997

Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis.

OBJECTIVES: Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis. METHODS: Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1). RESULTS: The mean height SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD score -0.26 (1.4). The body mass index SD score declined with increasing age (r = -0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r = -0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r = 0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r = 0.33) and FEV1 (r = 0.17). CONCLUSIONS: The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores correlated with other measures of clinical status such as the Shwachman score and FEV1.

Adolescent↗
PubMed1997

Diaphragm thickness and inspiratory strength in patients with Duchenne muscular dystrophy.

BACKGROUND: There is little information on the morphometric characteristics of the diaphragm in patients with Duchenne muscular dystrophy. METHODS: The thickness of the diaphragm was measured at the zone of apposition using B mode ultrasonography in 10 boys with Duchenne muscular dystrophy of mean (SD) age 10.3 (1.3) years and 12 normal controls of mean (SD) age 11.3 (2.0) years during relaxation (DiTrelax) and during maximum effort inspiratory manoeuvres (DiTPimax) at functional residual capacity. RESULTS: DiTrelax was greater in the patients with Duchenne muscular dystrophy (1.74 (0.21) mm) than in controls (1.48 (0.20) mm), mean difference (95% CI) 0.26 (0.08 to 0.44), despite considerable impairment of maximum effort inspiratory mouth pressure (Pimax) (patients with Duchenne muscular dystrophy -37 (8) cm H2O, controls -80 (33) cm H2O), mean difference (95% CI) 43 (65 to 20). During a Pimax manoeuvre, compared with measurements taken during relaxation, the diaphragm thickened 1.6 times in patients with Duchenne muscular dystrophy and 2.3 times in controls (DiTPimax 2.62 (0.7) mm and 3.5 (0.85) mm, respectively), mean difference (95% CI) -0.88 (-1.58 to -0.18). CONCLUSIONS: Resting diaphragm thickness is increased in young patients with Duchenne muscular dystrophy with impaired respiratory muscle force. This finding could be analogous to the pseudo-hypertrophy that is observed in some limb muscle groups.

Child↗
PubMed1997

CFTR gene transfer reduces the binding of Pseudomonas aeruginosa to cystic fibrosis respiratory epithelium.

Much of the morbidity and mortality seen in cystic fibrosis (CF) is related to chronic infection of the respiratory tract with Pseudomonas aeruginosa. Some studies have attributed the strong relationship between CF and Pseudomonas colonization to the presence of increased numbers of specific cell-surface receptors, although other work suggests that this relates to the presence of mucus. Several groups are now assessing the use of gene transfer as a novel form of treatment for CF. We have examined whether P. aeruginosa binding to freshly obtained CF respiratory epithelial cells is increased, and have studied the effects of transfer of the CF transmembrane conductance regulator (CFTR) gene on this attachment. Binding of P. aeruginosa to noncultured nasal epithelial cells from both CF patients (n = 31) and healthy controls (n = 15) was studied with scanning electron microscopy. Binding was also assessed for CF cells following transfection with CFTR/liposome complexes. Epifluorescence microscopy was used to assess the effects of gene transfer on chloride fluxes. Adherence of P. aeruginosa directly to the cell surface of CF airway epithelium was significantly (P < 0.001) increased over that in non-CF controls. Liposome-mediated CFTR gene transfer resulted in a significant (P < 0.01) reduction in the numbers of bacteria bound to ciliated epithelial cells. Fluorescence microscopy confirmed correction of the basic chloride defect. Thus, in CF, the absence of normal CFTR results in increased binding of P. aeruginosa to respiratory epithelial cells. This abnormality can be corrected in vitro by restoration of CFTR function. This has important implications both for the pathogenesis of CF and for the future application and assessment of gene therapy for this disease.

Bacterial Adhesion↗
PubMed1997

Is nitric oxide in exhaled air produced at airway or alveolar level?

The aim of this study was to determine whether the nitric oxide (NO) measured in exhaled air is produced at airway or alveolar level. Exhaled NO was measured using a chemiluminescence analyser, and carbon dioxide (CO2 concentration using a Morgan capnograph in single exhalations in 12 healthy subjects (mean age 32 yrs; 6 males and 6 females). For each subject, five exhalations were made directly into the NO analyser and five were made through a T-piece system, which allowed measurement of expiratory flow rate. The peak NO levels measured via the T-piece system were 41.2 (SEM 10.8) parts per billion (ppb), significantly lower than direct levels 84.8 (14.0) ppb (p<0.001). The levels of NO tended to rise to an early peak and plateau, while the CO2 levels continued to rise to peak late in the exhalation. The mean times to reach peak NO levels were 32.2 s (direct) and 23.1 s (T-piece), which were significantly different from that of peak CO2 levels 50.5 s (direct) and 51.4 s (T-piece) (p<0.001). At peak NO level, the simultaneous CO2 level mean 4.9% (SEM 0.14)%, was significantly lower than the peak CO2 reached, 5.8 (0.21)% (p<0.001). We conclude that peak nitric oxide levels are dependent on measurement conditions. There are significant differences between the time to peak of carbon dioxide and nitric oxide. Therefore, most nitric oxide, unlike carbon dioxide, is produced in airways and not at alveolar level.

Adolescent↗
PubMed1997

Inhaled glucocorticoid therapy of childhood asthma is associated with reduced peripheral blood T cell activation and 'Th2-type' cytokine mRNA expression.

OBJECTIVE: To investigate the role of activated T cells and their cytokine products in the pathogenesis of childhood asthma. METHODS: PBMC were obtained from 17 symptomatic asthmatic children (age 7 to 15 yr) and 7 nonasthmatic controls matched for age and atopic status. Asthmatics were placed in 2 groups with initial prebronchodilator FEV1 <75% (Group I, n = 9) or >/=75% (Group II, n = 8) predicted. Expression of activation markers on peripheral blood T cells (asthmatics), and expression of cytokine mRNA (asthmatics and controls) were measured using flow cytometry and in situ hybridization respectively. Measurements were repeated in the asthmatics 3 to 6 months later following initiation or escalation of inhaled GC therapy for control of symptoms. RESULTS: The more severe (Group I) as compared with the milder (Group II) asthmatics showed evidence of increased peripheral blood T cell activation, with elevated percentages of CD4 cells expressing the activation markers CD25 and HLA-DR, and CD8 cells expressing CD25. Elevated percentages of CD4 cells also expressed CD45RO, consistent with ongoing cellular activation. The asthmatics had higher percentages of PBMC expressing mRNA encoding IL-5, IL-4, GM-CSF and IL-2, but not IFN-gamma, as compared with controls. The percentages of PBMC expressing IL-5 mRNA correlated with disease severity (% predicted FEV1). During follow up, patients in both groups required increased mean daily dosages of inhaled GC. In Group I this was associated with improvements in PEFR, FEV1 and night time wheeze and reduced percentages of CD4/CD25 and CD4/HLA-DR peripheral blood T cells. Reductions in the percentages of CD4/CD25 T cells correlated with improvements in baseline FEV1. Group II patients showed improvement in FEV1 and day time cough and wheeze but no significant changes in PEFR, other symptoms or peripheral blood T cell marker expression. Increased GC therapy of both groups taken together was associated with significant reductions in the percentages of PBMC expressing mRNA encoding IL-5, IL-4 and IL-2 and an increase in those expressing IFN-gamma mRNA. CONCLUSIONS: Compared with controls, children with symptomatic asthma have higher percentages of activated peripheral blood T cells synthesising cytokines believed to regulate bronchial mucosal eosinophilic inflammation. Clinical improvement with increased inhaled GC therapy is associated with reduced T cell activation and cytokine mRNA expression.

Administration, Inhalation↗
PubMed1996

Biparous: a novel bHLH gene expressed in neuronal and glial precursors in Drosophila.

Genetic studies have uncovered many genes that are involved in the first steps of neuronal development in Drosophila. Less is known about the intermediate steps during which individual precursor cells follow either the neuronal pathway or the glial pathway. We report the identification of a novel bHLH gene, biparous, expressed in neuronal and glial precursors in Drosophila. Unlike most bHLH genes, biparous expression continues to the final stages of neurogenesis in the embryo. Expression of biparous is not observed in end stage postmitotic neurons and precedes the expression of repo, a gene activated in later stages of glial differentiation. The bHLH domain is sufficiently different from previously described bHLH domains to imply a novel function.

Amino Acid Sequence↗
PubMed1996

Negative-pressure ventilation improves cardiac output after right heart surgery.

BACKGROUND: A low cardiac output state can complicate the postoperative course of patients undergoing Fontan-type operations and tetralogy of Fallot repair. METHODS AND RESULTS: We investigated the effect of negative-pressure ventilation on cardiac output in 11 children in the early postoperative period after right heart surgery. All patients were initially ventilated with volume-cycled intermittent positive-pressure ventilation, and negative-pressure ventilation was delivered with the Hayek external high-frequency oscillator. Cardiac output was calculated by the direct Fick method, oxygen consumption being measured by respiratory mass spectrometry. Cardiac output was measured during intermittent positive-pressure ventilation and after 15 minutes of negative-pressure ventilation. Negative-pressure ventilation improved the cardiac output by a mean of 46% (P = .005). Heart rate did not change, and stroke volume increased by a mean of 48.5% (P = .005). Mixed venous saturation increased by 4.6% (P < .02), and consequently arteriovenous oxygen content difference fell significantly (P = .01). The systemic and pulmonary vascular resistances were reduced significantly during negative-pressure ventilation (P < .05 and P < .03, respectively). CONCLUSIONS: Negative-pressure ventilation improves cardiac output in children after total cavopulmonary connection and tetralogy of Fallot repair and may prove to be an important therapeutic option in children with the low cardiac output state.

Adolescent↗
PubMed1996

Surgical treatment of parapneumonic empyema.

The management of parapneumonic empyema remains controversial. We present the management of 20 children with empyema who were referred to The Royal Brompton Hospital, over a 5-year period from January 1990 to December 1994. Prior to referral, only 12 of the 20 patients had undergone thoracocentesis, all confirming the diagnosis of empyema. Six of these 12 patients then underwent closed chest tube drainage. There was a 2 to 32 day (median, 8 days) delay from initial hospital presentation to referral. Following referral 13 of the 20 patients were assessed as having persistence of clinical symptoms and radiological appearances making recovery with continued conservative management unlikely. These patients had a thoracotomy with decortication within 2 days. The remaining 7 were initially treated with closed chest tube drainage, but 5 subsequently required decortication. All patients made an uneventful postoperative recovery and were discharged within 3-11 days (mean. 6.8 days) Four patients were subsequently found to have a significant underlying immunological defect We conclude that there is a lack of agreement regarding the initial management of parapneumonic empyema. In our experience, decortication gives excellent results in those children not responding to medical treatment within 7-0 days. In experienced hands this technique is safe with rapid resolution. All patients who present with empyema should be screened for immunological abnormalities.

Chest Tubes↗
PubMed1996

Measurement of expired nitric oxide levels in children.

Nitric oxide (NO) can be measured directly in expired air in adults. The purpose of our study was to measure NO levels in children and to compare these values with adults. Exhaled NO was measured in 39 normal prepubertal children (23 girls), aged 9-11 years (mean 9.9 years). Exhaled NO was measured by the chemiluminescence method that is sensitive in a range of 2 to 4,000 ppb of NO on an adapted analyzer (Dasibi Environmental). Wearing a nose clip. 5 measurements were recorded in each child with exhalation 1) directly into the NO analyzer (flow rate 240 mL/min) with measurements of NO, carbon dioxide, and mouth pressure; and 2) using a T-piece to allow measurements at a different flow rate. For all measurements, background NO levels were less than 10 ppb. The mean direct level was 49.6 ppb, SD 37.8 (range, 11.5-197.2 ppb) compared with T-piece levels of 29.2 ppb. SD 27.1 (range, 5.1-141.2 ppb). There was no significant difference between boys and girls for direct or T-piece recordings. Mean direct NO in boys was 43.1 ppb, SD 40.5 and in girls 55.2 ppb, SD 35.4; mean T-piece in boys was 25.6 ppb. SD 29.2 and in girls 33.8 ppb, SD 25.1. Mean NO levels in prepubertal children are lower than in adults and show no difference between males and females.

Adult↗
PubMed1996

Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history. DESIGN: A cross-sectional study of insulin sensitivity and lipids in a cohort of PCO subjects compared to weight and ethnic group matched controls. PATIENTS AND METHODS: We have therefore investigated glucose tolerance, plasma lipids and lipoproteins in 19 lean (LP) and 55 obese (OP) patients with PCO and compared the results with those in 22 lean (LC) and 15 obese (OC) control women. Insulin sensitivity was measured in the same subjects with a short insulin (0.05 U/kg i.v. insulin) tolerance test (LP, n = 18; OP, n = 20; LC, n = 19; OC, n = 11). RESULTS: Results are expressed as mean +/- SEM or median (interquartile range). Fasting plasma glucose levels were similar in the four groups but the plasma glucose area was higher after oral glucose (75 g) in both the lean and obese PCOS groups than in their controls (LC 32.4 +/- 0.7 vs LP 35.2 +/- 1.2, P < 0.01; OC 34.7 +/- 1.8 vs OP 37.8 +/- 1.5 mmol/l/3 h, P < 0.01). Insulin sensitivity was significantly reduced in obese PCOS women (LC 196 +/- 9 vs LP 179 +/- 9, NS; OC 168 +/- 12 vs OP 133 +/- 9 mmol/l/min, P < 0.01). Total serum cholesterol levels were similar in the four groups but HDL2-cholesterol was reduced in both obese and lean PCOS (LC 0.42 (0.38-0.62), LP 0.31 (0.26-0.44), P < 0.05; OC 0.34 (0.21-0.47), OP 0.21 (0.12-0.32) mmol/l, P < 0.01). Total HDL-cholesterol was decreased significantly only in the obese PCOS group. Body mass index correlated significantly and negatively with total HDL-cholesterol and with HDL2-cholesterol levels both within the PCOS group and the control women. Using multiple regression insulin insensitivity contributes significantly beyond BMI to the low HDL-cholesterol in women with polycystic ovaries. CONCLUSION: Polycystic ovary syndrome is associated with biochemical risk factors for premature vascular disease, which cannot be explained by obesity alone.

Adult↗
PubMed1996

How much coughing is normal?

A new multiparametric device (RBC-7) was used for recording cough in ambulatory children over a 24 hour period. The number of coughs and the pattern of coughing can easily be studied with the aid of a personal computer and dedicated computer software. Forty one 'normal' children were recorded, identified from a primary school with the aid of a questionnaire. They were free from any respiratory infection for one month, and had a normal examination and spirometry immediately before recording. Cough frequency was 11.3, range 1 to 34, cough episodes per 24 hours. This was unaffected by passive smoking or the presence of furry pets in the home. Nocturnal and prolonged coughing was unusual in these children. The device was highly acceptable to the children, and no adverse effects were reported. Such objective data on cough outside the laboratory setting are unique, help to determine what is normal, and may help in the diagnosis and assessment of many respiratory diseases.

Child↗