Biomedical subjects
Publications and source records attributed to A Bush.
Five children with severe asthma requiring at least 10 mg of prednisolone daily were treated with cyclosporin. Three were weaned from prednisolone, but one quickly relapsed. One girl had her steroid dose lowered but suffered unacceptable hirsutism and one child failed to respond. Cyclosporin may be useful in refractory childhood asthma. A prospective study is required to confirm this.
OBJECTIVE: To investigate the effects of cuirass negative pressure ventilation on the cardiac output of a group of anaesthetised children after occlusion of an asymptomatic persistent arterial duct, and a group of paediatric patients in the early postoperative period following cardiopulmonary bypass. DESIGN: Prospective study. SETTING: The paediatric intensive care unit and catheter laboratory of a tertiary care centre. PATIENTS: 16 mechanically ventilated children were studied: seven had undergone surgery for congenital heart disease, and nine cardiac catheterisation for transcatheter occlusion of an isolated asymptomatic persistent arterial duct. INTERVENTIONS: Cardiac output was measured using the direct Fick method during intermittent positive pressure ventilation and again after a short period of negative pressure ventilation. In five of the postoperative patients a third measurement was made following reinstitution of positive pressure ventilation. RESULTS: Negative pressure ventilation was delivered without complication, with no significant change in systemic arterial oxygen and carbon dioxide tension. The mixed venous saturation increased from 74% to 75.8% in the healthy children, and from 58.9% to 62.3% in the postoperative group. Negative pressure ventilation increased the cardiac index from 4.0 to 4.5 l/min/m2 in the healthy children, and from 2.8 to 3.5 l/min/m2 in the surgical group. The increase was significantly higher in the postoperative patients (28.1%) than the healthy children (10.8%). CONCLUSIONS: While offering similar ventilatory efficiency to positive pressure ventilation, cuirass negative pressure ventilation led to a modest improvement in the cardiac output of healthy children, and to a greater increase in postoperative patients. There are important cardiopulmonary interactions in normal children and in children after cardiopulmonary bypass, and by having beneficial effects on these interactions, negative pressure ventilation has haemodynamic advantages over conventional positive pressure ventilation.
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.
BACKGROUND: It is possible to measure nitric oxide (NO) levels in exhaled air. The absolute concentrations of exhaled NO obtained by separate workers in similar patient groups and normal subjects with apparently similar techniques have been very different. A study was undertaken to determine whether changes in measurement conditions alter the concentration of exhaled NO. METHOD: NO concentrations measured by a chemiluminescence analyser (Dasibi Environmental Corporation) and carbon dioxide (CO2) measured by a Morgan capnograph were analysed in single exhalations from total lung capacity in healthy volunteers (mean age 35.9 years). Ten subjects performed five exhalations at four different expiratory flow rates, at four different expiratory mouth pressures, and before and after drinking hot (n = 5) or cold (n = 5) water. Three subjects performed five exhalations on a day of high background NO (mean NO level 134 ppb) before and after a set of five exhalations made while both the subject and analysers were sampling from a low NO/NO-free reservoir system. RESULTS: The mean peak concentration of NO decreased by 35 ppb (95% CI 25.7 to 43.4) from a mean (SE) of 79.0 (15.5) ppb at an expiratory flow rate of 250 ml/min to 54.1 (10.7) ppb at 1100 ml/min. The mean peak concentration of NO did not change significantly with change in mouth pressure. The mean (SE) peak NO concentration decreased from 94.4 (20.8) ppb to 70.8 (16.5) ppb (p = 0.002, 95% CI 12.9 to 33.1) with water consumption. The mean NO concentration with machine and subject sampling from the low NO reservoir was 123.1 (19.4) ppb, an increase from results obtained before (81.9 (10.2) ppb, p = 0.001, 95% CI -19.9 to -62.7) and after (94.2 (18.3) ppb, p = 0.017, 95% CI 6.0 to 51.8) sampling with high ambient NO. CONCLUSIONS: The measurement of exhaled NO must be performed in a carefully standardised manner to enable different teams of investigators to compare results.
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.
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.
Both acetylene (Ac) and carbon dioxide can be used to measure effective pulmonary blood flow (Q'eff) noninvasively. They are safe and reasonably accurate in adults during rest and exercise, but there have been no simultaneous comparisons in children. One hundred and six healthy children (55 males and 51 females, aged 8-17 yrs) were studied using an Innovision quadrupole mass spectrometer. They all underwent five rebreathing manoeuvres at rest, and then single measurements were again taken after 9 min of bicycle exercise. Mixed venous CO2 levels were calculated either by a linear (L) or curvilinear (C) extrapolation method. At rest, the coefficients of variation for Q'eff were Ac 8%, L 20%, and C 16% (p<0.001). The median resting values were: Ac 3.2 (95% confidence interval (95% CI) 3.1-3.4) L 5.1 (95 % CI 4.6-5.4) and C 4.7 (95 % CI 4.3-5.1) L x min(-1) x m(-2), (p<0.001). Compared to Ac, only 14 and 17% of L and C values, respectively, were +/-0.5 L x min(-1) x m(-2), whilst 41 and 29%, respectively were more than +/-2 L x min(-1) x m(-2). During exercise, median values were: Ac 6.7 (95% CI 6.3-7.0); L 8.0 (95% CI 7.3-8.4); and C 7.2 (95% CI 6.5-7.9) L x min(-1) x m(-2). L was significantly greater than C (p<0.001), but C was similar to Ac (p=0.06). More than 50% of L and C values could not be calculated for various reasons, whereas all 106 Ac values could be calculated. Neither carbon dioxide method is sufficiently reliable to be used in children in a clinical setting. Acetylene was safe, reliable, accurate and preferred.
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.
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.
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.
Explore the source record for details and available documents.
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.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
Congenital and pediatric interstitial lung disease (ILD) is set in the context of the maturing lung and immune system, and thus differs completely from its adult equivalents in presentation, therapy, and outcome. We first establish the background by briefly reviewing normal maturational changes and then describe recent advances in diagnosis. We then highlight three specific topics: drugs and the lung (treatment and iatrogenic ILD); the histiocytic disorders of the lung; and congenital ILD (specifically congenital surfactant protein deficiency).
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.