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C G Wathen

Publications and source records attributed to C G Wathen.

At least 19 recordsLinked to original sources
PubMed1998

Value of C-reactive protein measurements in exacerbations of chronic obstructive pulmonary disease.

C-reactive protein (CRP) has been shown to be a useful and sensitive indicator of pyogenic infections in many clinical situations, including acute pneumonia and infective pulmonary exacerbations in cystic fibrosis patients. Exacerbations of COPD are often, but not always, associated with demonstrable infection. The value of CRP measurement in this situation has not been assessed. We have evaluated CRP measurement in 50 patients [age 71 +/- 8 (SD) years] who were admitted to hospital with clinical evidence of exacerbation [PaO2 = 7.3 +/- 1.3 (SD) kPa, baseline FEV1 = 0.8 +/- 0.4 (SD) l]. These patients all had serial measurement of CRP [polarizing immunofluorescence (Abbot, TDx)], peripheral white cell count (WCC), body temperature, peak expiratory flow rate, Karnofsky performance status and chest X-ray, in addition to serial sputum bacteriological analysis carried out in a specialized laboratory. CRP was elevated (> 10 mg l-1) in all patients (n = 29) with proven infection [103 +/- 98 (SD) mg l-1]. Levels were markedly elevated in patients infected with Streptococcus pneumoniae (mean 156 mg l-1); there was also a rapid fall in the CRP with therapy. WCC fell with therapy, giving a correlation with CRP level (r = 0.44, P < 0.01). Since CRP elevation was observed in patients having exacerbation with proven infections and also in those where infection was not proven, it is possible that, while it is a marker for COPD exacerbation, it is not necessarily a marker of bacterial infection per se. However, it is evident from our study that it is of value in the assessment of exacerbations of COPD, where routine bacterial culture of sputum is often unreliable, and thus the measurement of serum CRP may provide an additional objective indicator of infection.

Acute Disease↗
PubMed1998

Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic suppurative lung disease characterised by irreversible dilation of the bronchi and persistent purulent sputum. The immunopathology of the disease was studied using a quantitative immunostaining technique with particular reference to T lymphocytes, macrophages, and granulocytes. METHODS: Bronchial mucosal biopsy specimens were obtained by fibreoptic bronchoscopy from 12 patients with bronchiectasis (six receiving inhaled steroids) and 11 normal healthy controls. Immunostaining (APAAP method) was performed on frozen cryostat sections with a panel of monoclonal antibodies to total leucocytes (CD45), T lymphocyte phenotypic markers (CD3, CD4, CD8), macrophages (CD68), eosinophils (EG2), and neutrophils (elastase). RESULTS: There was a mononuclear cell infiltrate in both patients with bronchiectasis and normal controls, but an overall increase in total leucocyte cell numbers (CD45+ cells) was identified in those with bronchiectasis (median values 422 cells/mm2 versus 113 cells/mm2 in control tissue, p < 0.001). Intense infiltration of CD3+ T lymphocytes was observed compared with healthy controls (292 cells/mm2 and 40 cells/mm2, respectively, p < 0.001). This comprised predominantly CD4+ T cells (118 cells/mm2) rather than CD8+ T cells (47 cells/mm2). CD3+ cells counts were reduced in those subjects on inhaled steroids compared with those not receiving inhaled steroids (197 cells/mm2 versus 369 cells/mm2, p < 0.05), as were CD4+ cell counts (82 cells/mm2 versus 190 cells/mm2, p < 0.05). Neutrophil and macrophage cell numbers were also increased in patients with bronchiectasis (114 cells/mm2 and 213 cells/mm2, respectively) compared with controls (41 neutrophils/mm2 and 40 macrophages/mm2). EG2+ (activated) eosinophil numbers were much lower than T cells, macrophages, and neutrophils in patients with bronchiectasis but were increased compared with controls (36 cells/mm2 versus 0 cells/mm2, p < 0.001). In view of the markedly increased neutrophil counts in patients with bronchiectasis, biopsy specimens were immunostained for interleukin 8 (IL-8) which was highly significantly increased compared with controls (47 cells/mm2 versus 15 cells/mm2, p < 0.01). IL-8+ cells were less prominent in steroid treated patients than in patients not receiving treatment (30 cells/mm2 versus 60 cells/mm2, p < 0.05). A further characteristic of bronchiectasis was mucous gland hypertrophy. Gland area comprised up to 40% of the tissue in some bronchiectasis sections while no hypertrophy was noted in control biopsy specimens (p < 0.05). CONCLUSION: Airway inflammation in bronchiectasis is characterised by tissue neutrophilia, a mononuclear cell infiltrate composed mainly of CD4+ T cells and CD68+ macrophages, and increased IL-8 expression. Inhaled corticosteroid treatment in patients with bronchiectasis is associated with a less marked infiltration by T cells and IL-8+ cells within the bronchial mucosa, although this finding requires confirmation in a prospective placebo controlled trial.

Adult↗
PubMed1997

Recurrent post-partum pulmonary eosinophilia.

In 1980 a 23 year old woman developed idiopathic eosinophilic pneumonia which was successfully treated with corticosteroids. She subsequently developed two identical relapses in the post-partum period.

Adult↗
PubMed1995

Effectiveness of nebulised salbutamol administered in ambulances to patients with severe acute asthma.

BACKGROUND: Nebulised salbutamol can now be administered by ambulance personnel to patients with severe acute asthma en route to hospital. This treatment, however, is not yet available in all ambulances. The safety and effectiveness of allowing ambulance crews to initiate treatment with nebulised salbutamol has been assessed in patients with acute severe asthma. METHODS: After a basic training course in the assessment of asthma and the use of a nebuliser, ambulance crews initiated treatment with nebulised salbutamol in asthmatic patients under the age of 40 years. Airflow obstruction was measured before and after treatment with a peak flow meter. A subjective assessment of any change in the patient's condition was also made. RESULTS: Nebuliser treatment was associated with a significant increase in peak flow in almost 80% of patients who had recordable values before and after treatment. The mean percentage increase in peak flow was 56.5%. Subjective assessments correlated well with peak flow measurements. No unwanted side effects were recorded. CONCLUSIONS: Nebulised salbutamol is an effective and safe treatment for acute asthma when administered by ambulance personnel after a short training course.

Acute Disease↗
PubMed1994

Changes in regional ventilation during histamine bronchial challenge in stable asthma.

Our objective was to examine the changes in regional ventilation during histamine-induced bronchoconstriction in stable asthma. We measured regional ventilation by a new method which measures regional distribution of inhaled 127Xe during tidal breathing by a gated method and, by simultaneously measuring 99mTc counts from labelled macroaggregates, allowed for changes in lung shape during the breathing cycle. We studied 10 asthmatic patients [forced expiratory volume in 1 s (FEV1 2.04-4.37 litres)] and measured, in addition to the regional ventilation, oxygen saturation (SaO2), minute ventilation (VE) and tidal volume (Vt) before and after inhaling enough histamine to lower FEV1 by > 20% and/or SaO2 by > 4%. Histamine inhalation reduced FEV1 by 0.44-1.15 liters and SaO2 by 0-4%. It increased VE and functional residual capacity (FRC) in 8 of the 10 patients. The FEV1 fall did not correlate with the SaO2 fall, VE or FRC changes. Histamine inhalation increased apical ventilation in most patients, but the changes in regional ventilation in the left and right lungs were asymmetrical in 17 out of the 30 lung regions studied (upper, middle and lower paired regions in 10 patients). These results demonstrate that histamine bronchial challenge causes uneven regional ventilation. Any resultant change in ventilation-perfusion balance may be the underlying mechanism of oxygen desaturation seen in this procedure and in spontaneous attacks of asthma.

Adult↗
PubMed1992

Lung cancer in young patients.

During 1981-1986 the Edinburgh Lung Cancer Group prespectively registered 3560 new patients with lung cancer of whom only 48 (1.3%) were aged less than 45 years. When compared with 3512 older patients aged more than 45 years, a similar proportion of young patients were female (17/48; 35% vs. 28% of the older patients) and had equally advanced disease (30/48; 62% vs. 58% in stage III). Slightly more young patients were in better Karnofsky performance status groups (28/48; 59% vs. 45%, score > 80) and duration of symptoms was considerably shorter (median 45 vs. 93 days); only three of the younger patients were non-smokers. A pathological diagnosis was obtained more often in young patients (47/48; 98% vs. 81%). The commonest cell type was small cell (16/48; 34% vs. 24%) with 10/48 adenocarcinoma (20% vs. 13%) and less squamous carcinoma (11/48; 23% vs. 48%). Although only 12/48 young patients (25% vs. 19%) underwent surgical resection, six of these were still alive after 5 years (50% vs. 30% in older patients). More young patients received chemotherapy either alone (14) or combined with radiotherapy (6)--42% vs. 16% in older patients. There were no long-term survivors and the median survival was 8 months in 13 patients with small cell and only 4 months in seven with non-small cell carcinoma.

Adenocarcinoma↗
PubMed1992

Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging.

BACKGROUND: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes. METHODS: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation. RESULTS: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without. CONCLUSIONS: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation.

Adenocarcinoma↗
PubMed1992

Factors affecting asthma mortality in Scotland.

Asthma mortality in the age group 5-44 years appeared to be stable in Scotland in both males and females at a rate of approximately 1.0 per 100,000 during the period 1970-1988 despite an increase in the hospital discharge rate for asthma of approximately 4% per annum during that period. Two-thirds of these deaths occurred outside hospital. There was evidence of a seasonal variation in asthma deaths with a peak mortality occurring in August, four to six weeks after the peak in total pollen counts. Monthly variation in atmospheric pollution did not appear to account for the variation in asthma mortality. It is suggested that the seasonal variation in asthma mortality provides a basis for further studies to elucidate the factors contributing to these deaths.

Adolescent↗
PubMed1991

Central and peripheral haemodynamic responses to felodipine in congestive heart failure.

Using non-invasive radionuclide techniques, we studied the arterial and venous effects of 0.1 mg/kg oral felodipine in 12 men with heart failure due to ischaemic heart disease aged 37-72 y. All were in New York Heart Association Class II or III, required frusemide 40-120 mg daily and were clinically stable. Felodipine produced significant falls in blood pressure (-19%) and systemic vascular resistance (-39%) with increases in cardiac index (+34%), heart rate (+12%) and left ventricular ejection fraction (from 0.25 to 0.32). Peripheral venous volume fell by 10.6% after felodipine indicating venoconstriction rather than venodilatation and may be caused by an acute sympathetic reflex associated with the increase in heart rate. Our results confirm that felodipine is an arterial vasodilator. The previously observed changes in cardiac filling pressures may simply represent improved ventricular function as a consequence of reduced afterload, not venodilatation.

Adult↗
PubMed1991

Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility.

In mammals, the cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) are a supergene family comprised of four multigene families, named alpha, mu, pi and theta. In man, within the mu class gene family there is a gene (the GSTmu 1 locus) that is polymorphic and is only expressed in 50-55% of individuals. It has previously been reported, using trans-stilbene oxide (tSBO) as a specific substrate for the expressed phenotype, that smokers with the null phenotype had a greater susceptibility to lung cancer. In a subsequent study, it was shown that on Southern blot analyses of human DNAs using a GSTmu 1 cDNA probe a DNA fragment was absent in certain individuals. The absence of this band correlated with the tSBO null phenotype. In the present work, DNA clones derived from GST mu class genomic sequences were used as probes in Southern blot analyses and confirmed the correlation between the lack of a DNA fragment and the null phenotype; moreover in this case, using radioimmunoassay for the GST mu protein, these probes were then used in a genotyping assay to investigate further the association of GSTmu 1 polymorphism with susceptibility to lung cancer. It was found that in a control group of 225 individuals, of unknown smoking history, 42% lacked the restriction fragment and were homozygous null, and therefore 58% were either heterozygous or were homozygous normal. Among 228 lung cancer patients, which included all tumour types, a similar distribution occurred, namely 43% were homozygous and 57% were heterozygous or homozygous normal. If, however, the tumours were analysed by tumour type a small but significant positive correlation with the homozygous null genotype was seen in squamous carcinoma of the lung, and an apparently negative correlation with adenocarcinoma of the lung.

Blotting, Southern↗
PubMed1991

Vindesine and etoposide chemotherapy in the management of patients with small cell lung cancer and poor prognosis.

Twenty-five patients with histologically proven small cell lung cancer who were in too poor physical condition to receive 'aggressive' chemotherapy were treated with vindesine and etoposide (VE). The median survival was 195 days, and there were 4 survivors of greater than 460 days. Eight patients died before the second pulse of chemotherapy, and these all had a Karnofsky score of less than or equal to 20 at diagnosis. Toxicity of the chemotherapy regimen was minimal, and the results suggest that VE chemotherapy may be suitable for the treatment of patients with small cell lung cancer who are unsuitable for more toxic chemotherapy.

Administration, Oral↗
PubMed1990

The haemodynamic effects of long term felodipine therapy in previously untreated essential hypertension.

Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of less than 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm-5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure.

Adult↗
PubMed1990

Radionuclide studies of left ventricular function in normal subjects.

The effects of age and exercise on cardiac function in a normal male population have been assessed by ECG-gated radionuclide ventriculography. Fifty-nine subjects aged from 25 to 54 years were studied (mean 44 +/- 10 S.D. years). Resting left ventricular ejection fraction (LVEF) was 0.54 +/- 0.07 and this increased by 0.07 +/- 0.05 during supine submaximal exercise at 75 watts. The mean increase in cardiac output on exercise was 93 +/- 30%. Stroke volume increased on exercise by 23 +/- 13% and end-systolic volume decreased by 10 +/- 16%. There was a weak correlation (P less than 0.05) between age and change in LVEF on exercise but the increase in cardiac output on exercise was not age dependent. It is important to use an age matched control population in any study of cardiac function.

Adult↗