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Biomedical subjects

W MacNee

Publications and source records attributed to W MacNee.

154 records · Page 9Linked to original sources

Diagnosis of pulmonary emphysema by computerised tomography.

Eleven patients with peripheral bronchial carcinoma had computerised tomographic (CT) scans before operation. The resected specimens from six of these patients showed mild centri-acinar emphysema. Preoperatively the two groups had not differed significantly in spirometric findings or lung volumes. The frequency distribution curves of EMI numbers within the lung fields of patients who proved to have centri-acinar emphysema differed significantly from those of the group who did not, there being more pixels in the EMI range -450 to -500 in the emphysematous group (p less than 0.001). Detailed assessment of lung density by CT scanning may be useful in the diagnosis of emphysema in life.

Adult↗

Effects of pirbuterol and sodium nitroprusside on pulmonary haemodynamics in hypoxic cor pulmonale.

The acute haemodynamic effects of oral pirbuterol (a beta-agonist) were contrasted with those of sodium nitroprusside, a vasodilator, in six patients with hypoxic chronic bronchitis and emphysema. Sodium nitroprusside (1-5 mg/kg intravenously) reduced mean pulmonary arterial pressure and total pulmonary vascular resistance significantly (p less than 0.01) without change in cardiac output or right ventricular ejection fraction, measured by radionuclide ventriculography. Oral pirbuterol (22.5 mg) produced a greater reduction in total pulmonary vascular resistance than sodium nitroprusside, largely as a result of increasing cardiac output. Right ventricular ejection fraction also increased significantly after pirbuterol (p less than 0.01). Pirbuterol in a lower dosage (15 mg by mouth) in six further patients with hypoxic chronic bronchitis and emphysema produced similar changes in total pulmonary vascular resistance and right ventricular ejection fraction. Nine of the patients who were studied acutely thereafter received pirbuterol 15 mg thrice daily for six weeks, which produced a significant fall in systolic pulmonary arterial pressure and a rise in right ventricular ejection fraction (p less than 0.01), without a significant fall in arterial oxygen tension. Pirbuterol acts as a vasodilator on the pulmonary circulation in these patients and may in addition improve right ventricular performance by an inotropic action.

Adrenergic beta-Agonists↗

The dependence of maximal flow in man on the airway gas physical properties.

The changes in maximum expiratory flow rates after washing out lung air with a helium/oxygen mixture (He/O2, 80 : 20) were measured in 24 patients with chronic irreversible airflow obstruction (FEV1 1.77 +/- SD 0.39 litres; FVC 3.62 +/- 0.59 litres), and in six normal subjects. The percentage increase in flow breathing He/O2 was variable; however, it was similar in normal subjects and in patients with airflow obstruction, and in both groups decreased at low lung volumes. Contrary to previous studies, only three patients with chronic airflow obstruction failed consistently to increase flow rates by greater than or equal to 20% when breathing He/O2 at all lung volumes measured. In six normal subjects and 12 patients with chronic airflow obstruction airway gas viscosity was increased by breathing a neon/oxygen mixture (Ne/O2, 80 : 20). The response to Ne/O2 was again variable (normal subjects delta Vmax.40 4 +/- SD 14%; patients delta Vmax.40 18 +/- 8%). Only two normal subjects and one patient with airflow obstruction consistently reduced their flow rates when breathing Ne/O2. These results indicate either that there is no difference in the distribution of airflow resistance in normal subjects and in patients with chronic airflow obstruction, or that density as well as viscosity is an important determinant of flow in very small airways. In either case, He/O2 breathing is not a good discriminator of the site of airflow obstruction.

Adult↗

Can right ventricular performance be assessed by equilibrium radionuclide ventriculography?

Although right ventricular function may be examined by following the passage (first pass) of a bolus of radionuclide through the right heart before it reaches the left heart, the counts detected with conventional gamma cameras in such a short time interval are low; moreover, repeated determinations would result in an unacceptable radiation burden to the patient. We have modified the gated equilibrium blood pool method to allow repeated assessment of the right ventricular ejection fraction (RVEF) and have compared the results with the first-pass method in 43 patients. Good agreement was obtained between the two methods (r = 0.91, p less than 0.001). The mean difference between the two methods was 0.04 with an intra-observer variation for the equilibrium studies of 0.03 and an inter-observer difference of 0.04. The mean difference in RVEF for seven patients studied on two separate occasions 30 minutes apart was only 0.02. In four patients the mean RVEF measured at rest was 0.44 +/- 0.05 (SEM) and after exercise it was 0.48 +/- 0.06. After infusion of isoprenaline at 1 microgram/min the mean rose to 0.64 +/- 0.04 (p less than 0.02) and after infusion of a new beta 1-sympathomimetic agent, prenalterol, at doses of 1 and 2 mg it was 0.56 +/- 0.02 (p less than 0.02) and 0.59 +/- 0.03 (p less than 0.01) respectively, where the significance levels are relative to the resting values. In nine patients with good ventricular function the vasodilator nifedipine caused right and left ventricular ejection fractions to increase by the same amount; while in six patients with severe impairment of left ventricular function due to ischaemic heart disease the RVEF increased from 0.58 +/- 0.03 to 0.73 +/- 0.03 (p less than 0.01) after 2 mg of prenalterol, but the left ventricular ejection fraction increased only from 0.22 +/- 0.04 to 0.26 +/- 0.04. We conclude that repeated estimation of right ventricular performance is possible by equilibrium radionuclide ventriculography.

Adrenergic beta-Agonists↗

Assessment by radionuclide angiography of right and left ventricular function in chronic bronchitis and emphysema.

Non-invasive measurements of right and left ventricular ejection fraction (RVEF, LVEF) by multiple-gated equilibrium radionuclide ventriculography were performed in 18 control subjects, 16 patients with angina pectoris, and 45 patients with hypoxic chronic bronchitis and emphysema. The mean RVEF in the control subjects was 0.62 +/- 0.09 (SD), which was not significantly different from the mean RVEF in the patients with angina (0.60 +/- 0.09), but was significantly higher (p less than 0.01) than the mean value in patients with chronic bronchitis and emphysema (0.45 +/- 0.11). LVEF was not significantly different in the groups studied. There was a significant correlation between LVEF and RVEF only in patients with chronic bronchitis and emphysema (p less than 0.001). Those patients with chronic bronchitis and emphysema who had clinical evidence of cor pulmonale at the time of the study had significantly lower values of RVEF and LVEF (p less than 0.001) than patients with no previous cor pulmonale or those who had had cor pulmonale in the past. There was a significant correlation between RVEF and arterial oxygen (p less than 0.01) and carbon dioxide tensions (p less than 0.05). Reduced RVEF in patients with chronic bronchitis and emphysema may be an early indicator of the development of cor pulmonale and may be useful as a non-invasive method of assessing the effects of therapeutic interventions.

Adult↗

Treatment of small cell carcinoma of the bronchus by combined chemotherapy--clinicopathological correlation with response.

Thirty-seven consecutive patients, referred to a respiratory unit with a histological diagnosis of small cell carcinoma of the bronchus, were treated with a combined chemotherapy regime of adriamycin, vincristine and cyclophosphamide. Palliative radiotherapy was given for the control of symptoms. Thirty of 37 patients responded to treatment, 11/37 having a complete and 19/37 a partial response. The median survival of those patients with a complete response was 55 weeks, significantly higher (P less than 0.01) than either those with partial or no response to treatment. Those patients with limited disease survived longer. A high proportion of patients relapsed at the primary site of the tumour in the lungs. The relationship between the therapeutic response and the histological subtype of small cell carcinoma suffered from the limitations of the available pathological material. However, more of the patients with a complete response were of the lymphocytic-like pattern of small cell carcinoma. Useful survival in these patients with inoperable small cell carcinoma was achieved using this regime of chemotherapy, even in those patients with extensive disease, five of whom had survived for over one year.

Adult↗

Effects of inhalation of beta-sympathomimetic and atropine-like drugs on airway calibre in normal subjects.

1. Bronchodilatation was produced in eight normal subjects by inhalation, on separate occasions, of the atropine-like drug ipratropium bromide (0.16 mg by pressurized inhaler; 1 mg nebulized) and the beta 2-sympathomimetic salbutamol (0.8 mg by pressurized inhaler; 5 mg nebulized). 2. Mean specific airways conductance (sGaw) increased from a mean value of 0.185 +/- SE 0.002 to 0.292 +/- 0.023 s-1 kPa-1 after ipratropium bromide, and from 0.184 +/- 0.020 to 0.303 +/- 0.026 s-1 kPa-1 after salbutamol. These increases in sGaw were not significantly different from each other. 3. During both maximal and partial expiratory flow volume manoeuvres similar increases in flow rates were produced by each drug, at all lung volumes, from 40 to 20% of vital capacity. 4. Changes in maximal and partial flow volume curves after washout of lung air with helium/oxygen (4:1) were measured before and after each drug. Flow rates increased in all subjects and the percentage increase in maximum flow when helium was breathed was not significantly different, when repeated after each drug. 5. Thus our results suggest that salbutamol and ipratropium have similar sites of action, both affecting both large and small airways, and produce similar degrees of bronchodilatation. This is supported by our results after the helium/oxygen breathing, where the lack of change in density dependence of maximal flow suggests that there was no change in the distribution of airways resistance after the drugs.

Adult↗

Reduction of the proteolytic activity of neutrophils by exposure to cigarette smoke in vitro.

Human peripheral blood neutrophils were exposed in vitro, in a tonometer, to two different fractions of cigarette smoke-designated particulate phase and vapor phase. The proteolytic activity of the cells following exposure was assessed by measuring their elastase release and ability to degrade fibronectin. At levels of smoke exposure that were physiologically attainable, neither smoke fraction caused an increase in elastase release or fibronectin degradation. In most experiments, fibronectin proteolysis was suppressed by smoke exposure--an effect that was reversible on treatment with phorbol myristate acetate. These data provide evidence that the proteolytic activity of neutrophils is not enhanced by a direct effect of cigarette smoke on these cells.

Carboxyhemoglobin↗

Inhibition of neutrophil adherence and movement by acute cigarette smoke exposure.

Peripheral blood neutrophils were harvested and exposed acutely in vitro to physiologically attainable levels of cigarette smoke. The adherence of radiolabeled neutrophils subsequently to alveolar epithelial cell monolayers was measured. In contrast to control cells, smoke-exposed neutrophils were significantly less adherent and failed to increase their adherence following stimulation with phorbol ester or f-met-leu-phe (fMLP). Flow cytometric analysis of the cell surface adhesion protein CD18 demonstrated no significant change in expression following in vitro smoke exposure and, furthermore, no increase in surface CD18 of smoke-exposed cells following consecutive fMLP stimulation was demonstrated. Acute in vivo cigarette smoking of up to 4 cigarettes also did not alter peripheral blood neutrophil CD18 expression. Cell spreading and chemokinesis, but not chemotaxis, was also impaired following in vitro smoke exposure. These data suggest that acute cigarette smoke may impair the crucial neutrophil functions of adherence and movement. However, the chronic effects of cigarette smoke exposure may clearly differ.

Adult↗

Factors affecting neutrophil transit during acute pulmonary inflammation: minireview.

Recent studies confirm data that for over a century have suggested that the lungs are an important source of noncirculating neutrophils. Many factors control how neutrophils pass through the normal lungs, including the unique and complex structure of the pulmonary capillary bed, local hemodynamic factors, neutrophil deformability, and neutrophil-endothelial interactions. Alterations in these factors are likely to influence neutrophil traffic in the lungs in disease processes where neutrophil-induced lung injury has been implicated. In recent years experimental approaches using in vitro techniques have been used to study neutrophil function. Such studies, together with in vivo studies in whole animals and to a limited extent in humans, will help to elucidate the important mechanisms in neutrophil sequestration in the acute and chronically inflamed lung. Novel avenues of therapeutic intervention in neutrophil traffic through the lungs may then be possible. However, whether interference with this cell, which forms a major defense mechanism in the lungs, is advisable, remains a matter for debate.

Acute Disease↗