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Biomedical subjects

N M Wilson

Publications and source records attributed to N M Wilson.

At least 19 recordsLinked to original sources

Implications of screening for abdominal aortic aneurysms on surgical workload.

BACKGROUND: The Multicentre Aneurysm Screening Study (MASS) provided strong evidence for both the clinical benefit and the cost-effectiveness of a screening programme for abdominal aortic aneurysms (AAAs) in men. If a national screening programme for AAA were adopted in the UK, it would be expected to increase the elective and decrease the emergency surgical workload. METHODS: The MASS trial randomized 67,800 men aged 65-74 years to be invited to attend for ultrasonographic screening for AAA or to a control group that received no invitation. Predictions of elective and emergency surgical workload were made for a 20-year interval after the introduction of a screening programme for 65-year-old men, based on surgical rates observed in the MASS trial and national mortality statistics. RESULTS: For a district general hospital serving a population of 400,000, there was an estimated reduction from nine emergency operations per year before introduction of the screening programme to three emergency operations annually in men aged 65 years and over by the end of the 20-year interval, and an increase from 24 to 43 AAA operations overall. The corresponding estimated annual costs for all AAA surgery increased by 47 per cent, from pound 209,000 to pound 308,000. These results were not affected by changes in the underlying assumptions. CONCLUSION: The results support the expectation of very few emergency operations, and principally elective operations, being performed following the introduction of a screening programme. For a typical district general hospital, a screening programme would be expected to lead to two additional elective AAA operations per month, and to save 11 AAA-related deaths per year.

Aged↗

Correlation of power Doppler with microvessel density in assessing prostate needle biopsy.

AIM: To correlate hypervascular power Doppler ultrasonography with the histological evaluation of microvasculature in the prostate using trans-rectal ultrasound (TRUS)-guided needle biopsy. MATERIALS AND METHODS: Ninety-six patients with a lower urinary tract symptoms (LUTS) and prostate specific antigen (PSA) value more than 4 ng/ml were evaluated using power Doppler ultrasonography before biopsy. The vascularity of the peripheral zone was graded on a scale of PZ0 to PZ2. Core needle biopsies were immunostained with CD31(DAKO) and counting was performed manually on separate high power fields (HPF; x 400) in areas containing the highest number of vessels. RESULTS: There was a significant correlation between the grading system used for power Doppler and the microvessel density (MVD; PZ0 28.61 +/- 8.97,PZ1 36.00 +/- 12.11 & PZ2 64.008 +/- 15.86; p < 0.001). There was also a significant difference in MVD between benign, malignant and tissue cores with atypia and prostatic intra-epithelial neoplasia (PIN; p < 0.001 and p < 0.018 respectively). There was a significant correlation between malignant tissue having a higher Gleason score and increased MVD (p < 0.001) Furthermore, cancer biopsies having a high flow PZ2 are nearly twice as likely (63.2%) to have a Gleason score of 7 or more when compared those having a Gleason score of less than 7 (36.8%). CONCLUSION: The grading system of assessing the power Doppler flow signals appears to be of value as an indicator of MVD. It also correlates with a higher Gleason score and this may reflect the clinical outcome in prostate cancer. It deserves further study and evaluation as a prognostic indicator.

Aged↗

Cough frequency in children with stable asthma: correlation with lung function, exhaled nitric oxide, and sputum eosinophil count.

BACKGROUND: A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. METHODS: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. RESULTS: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV1) and eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1-10.5), p<0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508, respectively). CONCLUSIONS: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.

Adolescent↗

Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance.

BACKGROUND: The levels of exhaled and nasal nitric oxide (eNO and nNO) in groups of patients with inflammatory lung diseases are well documented but the diagnostic use of these measurements in an individual is unknown. METHODS: The levels of nNO and eNO were compared in 31 children with primary ciliary dyskinesia (PCD), 21 with non-CF bronchiectasis (Bx), 17 with cystic fibrosis (CF), 35 with asthma (A), and 53 healthy controls (C) using a chemiluminescence NO analyser. A diagnostic receiver-operator characteristic (ROC) curve for PCD using NO was constructed. RESULTS: The median (range) levels of nNO in parts per billion (ppb) in PCD, Bx, CF, and C were 60.3 (3.3-920), 533.6 (80-2053), 491.3 (31-1140), and 716 (398-1437), respectively; nNO levels were significantly lower in PCD than in all other groups (p<0.05). The median (range) levels of eNO in ppb in PCD, Bx, CF, A, and C were 2.0 (0.2-5.2), 5.4 (1.0-22.1), 2.6 (0.8-12.9), 10.7 (1.6-46.7), and 4.85 (2.5-18.3), respectively. The difference in eNO levels in PCD reached significance (p<0.05) when compared with those in Bx, A and C but not when compared with CF. Using the ROC curve, nNO of 250 ppb showed a sensitivity of 97% and a specificity of 90% for the diagnosis of PCD. CONCLUSIONS: eNO and nNO cannot be used diagnostically to distinguish between most respiratory diseases. However, nNO in particular is a quick and useful diagnostic marker which may be used to screen patients with a clinical suspicion of PCD.

Adolescent↗

A survey of emergency vascular service provision.

Recommendations exist for the optimal management of vascular surgical emergency patients. A telephone survey of on-call surgical registrars was performed to assess the current state of emergency vascular service provision across the Wessex and South West regions in the UK. Of the 24 hospitals surveyed, 10 had formal on-call arrangements for vascular surgical cover, 14 had informal arrangements where the general surgical consultant on-call provided cover and could contact a vascular surgeon if they were available and 3 hospitals had no such arrangements. No difficulties had been experienced by the on-call staff surveyed with any of the existing arrangements. Only 5 of the hospitals had formal on-call arrangements for interventional radiologists. We conclude that current emergency vascular service provision is suboptimal compared to national guidelines and patients may be subject to unequitable access to services. This may not be tenable in the new era of clinical governance.

Emergency Service, Hospital↗

Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone.

Exhaled nitric oxide (FE(NO)) has been proposed as a noninvasive marker of airway inflammation in asthma, and may reflect airway eosinophilia. We examined the relationship between FE(NO) and eosinophilic inflammation in endobronchial biopsies from 31 children with difficult asthma (mean age [range] 11.9 [6-17] yr), following 2 wk of prednisolone (40 mg/d). Endobronchial biopsy was also performed in seven children without asthma. Biopsy eosinophils were detected using antibody to major basic protein, and point-counting used to derive an "eosinophil score." FE(NO) readings and suitable biopsies for analysis were both obtained in 21 of 31 children with asthma. Adherence to prednisolone was demonstrated in 17 of these 21. Within this group, there was a correlation between FE(NO) and eosinophil score (r = 0.54, p = 0.03). The relationship was strongest in patients with persistent symptoms after prednisolone, in whom FE(NO) > 7 ppb was associated with a raised eosinophil score. For all patients, FE(NO) < 7 ppb was associated with an eosinophil score within the nonasthmatic range, regardless of symptoms. We propose that FE(NO) is associated with eosinophilic inflammation in children with difficult asthma, following prednisolone, and may help in identifying patients in whom persistent symptoms are associated with airway eosinophilia.

Administration, Oral↗

Asthma severity and inflammation markers in children.

UNLABELLED: The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any METHOD: Neither did any marker of airway inflammation relate to recent symptoms, unlike PC20, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s (FEV1) and both NO and sputum ECP (r=-0.46, p=<0.001; r=-0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV1 (PC20) (r=-0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.

Adolescent↗

Relaxation and sleep compression for late-life insomnia: a placebo-controlled trial.

Older adults with insomnia were recruited from the community and randomized to treatments: relaxation, sleep compression, and placebo desensitization. Questionnaire data collected at baseline, posttreatment, and 1-year follow-up and polysomnography data collected at baseline and follow-up yielded the following conclusions: All treatments improved self-reported sleep, but objective sleep was unchanged. Clinical significance analyses yielded the strongest findings supporting the active treatments and suggested that sleep compression was most effective. Results partially supported the conclusion that individuals with high daytime impairment (i.e., fatigue) respond best to treatments that extend sleep, as in relaxation, and individuals with low daytime impairment respond best to treatments that consolidate sleep, as in sleep compression. Strong methodological features including a placebo condition and a treatment implementation scheme elevate the confidence due these findings.

Aged↗

Evidence for different subgroups of difficult asthma in children.

BACKGROUND: Children with difficult asthma experience frequent symptoms despite treatment with high dose inhaled steroids. Persistent symptoms may result from persistent airway inflammation which can be monitored by measuring exhaled nitric oxide (NO). This study aimed to assess the role of airway inflammation, using NO as a surrogate, in children with difficult asthma and to investigate the response to oral prednisolone. METHODS: NO was measured in 23 children (mean age 11.7 years) with difficult asthma, before and after 2 weeks of treatment with oral prednisolone. The clinical response was assessed by spirometric tests, peak flow, bronchodilator use, and symptoms. Adherence to treatment was assessed by measuring serum prednisolone and cortisol concentrations. NO was measured in 55 healthy children to establish a normal range. RESULTS: NO concentrations were higher in asthmatic patients than in controls (geometric mean 11.2 v 5.3 ppb, p<0.01). Using grouped data, the concentration of NO fell following prednisolone (11.2 v 7.5 ppb, p<0.01) accompanied by an improvement in morning peak flow (p<0.05). The baseline NO concentration was raised (>12.5 ppb) in nine asthmatic patients and remained high after prednisolone in five. Thirteen had normal levels of NO (<12.5 ppb) before and after prednisolone. Thirteen asthmatic patients remained symptomatic following prednisolone; NO levels were raised on both occasions in five of these and were normal in seven. CONCLUSIONS: As a group, the asthmatic subjects demonstrated evidence of airway inflammation which responded to prednisolone. At least two subgroups of patients were identified: one with persistently raised NO levels despite treatment with oral prednisolone indicating ongoing steroid insensitive inflammation, and another with normal levels of NO. Both subgroups included patients with persistent symptoms, which suggests that different patterns of difficult asthma in children exist.

Adolescent↗

Psychological treatment of secondary insomnia.

Psychological treatment of insomnia has focused on primary insomnia (i.e., having a psychological origin). Secondary insomnia, sleep disturbance caused by a psychiatric or medical disorder, although it is more common than primary insomnia, has received very little attention as a result of the belief that it would be refractory to treatment. The present study randomly assigned older adults with secondary insomnia to a treatment group, 4 sessions composed of relaxation and stimulus control, or a no-treatment control group. Self-report assessments conducted at pretreatment, posttreatment, and a 3-month follow-up revealed that treated participants showed significantly greater improvement on wake time during the night, sleep efficiency percentage, and sleep quality rating. The authors hypothesize that treatment success was probably due in part to difficulty in diagnostic discrimination between primary and secondary insomnia.

Aged↗

Induced sputum in children: feasibility, repeatability, and relation of findings to asthma severity.

BACKGROUND: The collection of induced sputum provides a non-invasive method of investigating airway inflammation. Few studies have been performed in children, so a study was undertaken to determine the feasibility of sputum induction, the repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP) levels, and the relation of these to current asthma severity. For comparison, serum ECP levels were also measured. METHODS: In a cross sectional study of children aged 5-15 years, 27 healthy children and 60 with asthma underwent sputum induction using inhaled nebulised hypertonic saline. The whole sputum sample was used for analysis. Ten children with stable asthma repeated the procedure within 10 days. RESULTS: A satisfactory sample (>500 non-squamous cells) was obtained in 61% of children with asthma and in 60% of healthy controls. The limits of agreement within subjects ranged from a 0.68 to 2.8 fold difference for eosinophil differential counts and from 0.38 to 4.4 fold for sputum ECP. Despite a median of 42% squamous cells, significant differences were found between asthma and healthy controls for the eosinophil differential count (p = 0.0004), total eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there was no correlation between any marker of airway inflammation and asthma severity, however expressed, including lung function. CONCLUSIONS: Sputum induction is only possible in a proportion of children. The repeatability of sputum cell counts and ECP levels, measured in a small number of children, was similar to that reported in adults. Sputum analysis revealed no evidence of airway inflammation in a number of highly symptomatic children with asthma.

Adolescent↗

Exhaled carbon monoxide in childhood asthma.

OBJECTIVES: Oxidative stress and inflammation induce the expression of heme oxygenase-1, which produces carbon monoxide (CO), and nitric oxide synthase, which produces nitric oxide (NO). Exhaled CO and NO levels are elevated in asthmatic patients and are decreased after corticosteroid treatment, suggesting that they may be useful as noninvasive markers of airway inflammation. STUDY DESIGN: We measured forced expiratory volume in the first second, PC(20), and exhaled CO and NO levels in 29 children (18 boys, mean age 11.5 +/- 0.53 years) with asthma of different severity and 40 nonsmoking children without asthma (21 boys, mean age 8.1 +/- 0.35 years). We also studied whether upper respiratory tract infections were associated with elevated exhaled CO. RESULTS: Exhaled CO levels (ppm) were significantly higher (2.17 +/- 0.21) in children with persistent asthma compared with those in children with infrequent episodic asthma (1.39 +/- 0.18, P <.05) and healthy children (1.01 +/- 0.12, P <.001). The CO levels in children with infrequent episodic asthma and the normal control group, however, were not different. In contrast, exhaled NO levels (ppb) were higher in children with persistent asthma (24.2 +/- 5.9, P <.001) and infrequent episodic asthma (14.5 +/- 3.73, P <.05) than in normal subjects (5.1 +/- 0.24), but no significant difference was seen between the 2 asthmatic groups. In healthy children with upper respiratory tract infections (n = 12), exhaled CO concentrations were significantly elevated (2.16 +/- 0.33) during the acute symptomatic phase. No correlation was found between exhaled CO and forced expiratory volume in the first second or PC(20). CONCLUSIONS: Noninvasive measurement of exhaled CO may provide complementary data for assessment of asthma control in children. However, elevated CO levels are nonspecific and may be found in association with an acute viral illness.

Asthma↗

Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia.

Exhaled nitric oxide can be detected in exhaled air and is readily measured by chemiluminescence. It is thought to be involved in both the regulation of ciliary motility and host defence. Recently, upper airway NO has been found to be reduced in a small number of children with primary ciliary dyskinesia (PCD) and its measurement has been recommended as a diagnostic test for this condition. The aim of this study was to compare the levels of NO in the upper and lower airways in a larger number of children with proven PCD with those found in healthy children. Exhaled NO was measured in the upper airway by direct nasal sampling during a breath-hold and in the lower airway as the end-tidal plateau level, using a chemiluminescence NO analyser. Upper airway NO levels were significantly lower in PCD (n = 21) than in the healthy children (n = 60) (mean +/-SD, 97+/-193, 664+/-298 parts per billion (ppb), respectively, p<0.0001). In PCD, the lower airway NO levels were also reduced (2.17+/-1.18, 5.94+/-3.49 ppb, respectively, p<0.0001). The levels were not associated with steroid use and did not correlate with lung function. Although there was some overlap between normal children and those with primary ciliary dyskinesia with regard to lower airway NO, nasal NO discriminated between the two groups in all but one child in each group. Measurement of nasal NO therefore may be a useful screening test for primary ciliary dyskinesia.

Breath Tests↗

Factors relating to the severity of symptoms at 5 yrs in children with severe wheeze in the first 2 yrs of life.

Wheezing in early childhood covers a wide spectrum of morbidity. Since little is known about the factors determining either the pattern or the severity of this range of symptoms, 51 children, admitted to hospital with acute wheeze in the first 2 yrs of life, were monitored prospectively between the ages of 4.5-5.5 yrs. Our hypothesis was that the predictors of severe episodes and of interval symptoms in 5 year olds would differ. Symptom diaries were kept, from which the symptom pattern and severity was assessed. The frequency and severity of acute episodes were analysed separately from day-to-day (interval) symptoms. A physiological assessment was made at 5 yrs. During the 12 month study period, 11 children were symptom-free, 15 were reported to wheeze only in response to viral infections, and 25 wheezed from multiple triggers. Bronchial responsiveness was significantly increased in those with a family history of asthma but was unrelated to any index of atopy. In a multiple logistic regression analysis, a family history of asthma and a personal history of allergy (but not results of skin-prick testing or serum immunoglobulin E (IgE) significantly predicted both attack severity and interval symptoms. An additive effect of two factors (atopy plus a family history of asthma or bronchial responsiveness) on symptom severity was suggested, without any evidence of an interaction. It is concluded that in this population of 5 year olds, with an early history of severe wheezing, familial bronchial responsiveness and atopy of operated independently to determine both interval symptoms and attack severity.

Acute Disease↗

Management of chylothorax.

BACKGROUND: Chylothorax is a rare primary or secondary condition the optimum management of which remains uncertain. METHODS: Twenty cases of chylothorax, including ten of primary chylothorax and ten secondary to either malignancy, subclavian vein thrombosis or lymphangioma treated between 1956 and 1986 have been reviewed. RESULTS: Open pleurectomy was the most successful treatment in preventing reaccumulation of the effusion. Three patients had thoracic duct-azygous vein anastomoses, but all anastomoses were probably occluded within a year of surgery. Three patients have been lost to follow-up and five died within 2 years of their treatment, but 12 patients were alive and free from an effusion 3-22 years after treatment. CONCLUSION: Patients with chylothorax should undergo lymphangiography to identify the cause and site of the lymphatic abnormality. Conservative treatment is successful in some patients but should be abandoned if the fluid loss exceeds 1.5 l/day for more than 5-7 days in an adult or more than 100 ml/day in a child. Parietal pleurectomy is the most successful treatment when no distinct chylous leak can be identified. Less commonly, an isolated chylous leak either in the chest or in the abdomen may be identified and this should be treated by direct ligation.

Adult↗

Evaluation of a new interrupter device for measuring bronchial responsiveness and the response to bronchodilator in 3 year old children.

The interrupter technique for measuring airway resistance is non-invasive and convenient, and therefore ideally suited for the assessment of induced changes in airway calibre in preschool children. The aim of this study was to evaluate a commercially available interrupter device (based on Microlab 4000), which calculates the interrupter resistance (Rint) from pressure and flow following a brief interruption of expiration during quiet breathing. The repeatability of Rint was assessed, and its response to methacholine challenge and the bronchodilator salbutamol were compared with an indirect technique, the fall in transcutaneous oxygen tension (Ptc,O2), using the sensitivity index (SI, i.e. the change after challenge expressed in multiples of the baseline standard deviation) in 12 wheezy children (aged 3 yrs +/- 2 months). The mean (SD) baseline value of Rint was 0.91 (0.20) kPa.L-1.s. Short-term repeatability and baseline variability were satisfactory for Rint (intraclass correlation coefficient = 0.6; mean intrasubject coefficient of variation = 13%). Although 10 of the 12 subjects obtained a significant response using Rint at maximal bronchoconstriction (i.e. SI > 2), overall, Rint was five times less sensitive than Ptc,O2 (geometric mean SI: Rint 3 vs Ptc,O2 16; p < 0.0001). Reversal of obstruction with administration of a bronchodilator was clearly demonstrated in almost all subjects: Rint after challenge (mean +/- SD) 1.25 (0.22) kPa.L-1.s; after salbutamol 0.78 (0.19) kPa.L-1.s; p < 0.001. In conclusion, the convenient interrupter resistance method appears more promising for detecting bronchodilator responses than induced bronchoconstriction in wheezy preschool children; however, measurement of transcutaneous oxygen tension provides a reliable indirect means of detecting induced airway obstruction in this age-group.

Airway Resistance↗