During CO2 rebreathing, we measured the pressures generated at the mouth and in the esophagus during the first 0.1 sec of inspiratory effort against a closed airway in 6 normal subjects and 6 patients with chronic obstructive lung disease. Normal subjects showed similar responses to CO2 in terms of both mouth pressure and esophageal pressure. Patients' responses at the mouth to CO2 were decreased compared to those of normal subjects, but the responses in the esophagus were not significantly different. The patients demonstrated a greater response of occlusion pressure measured in the esophagus than at the mouth. In patients with altered mechanical properties of the lung, the change in mouth occlusion pressure might be influenced by problems of equalization of pressure within the airways due to unequal time constants, by problems of regional differences in pressure gradients over the pleural surface, or both. Esophageal pressure during airway occlusion 100 msec after the onset of inspiration may be a better...

Background: Outdoor air pollution is hazardous to human pulmonary health. Airway inflammation is an important cause of bronchial hyperresponsiveness. Information is not univocal about the potential effects of prolonged exposure to environmental air pollutants on lung function. Objectives: A cross-sectional study was performed to assess bronchial responsiveness to methacholine in children living in an air-polluted area. Afterwards, the same study protocol was repeated in children of similar age living in mountain valleys with virtually no air pollution. Methods: Every child underwent a lung function test, skin tests to common allergens, total serum levels of IgE, and a challenge to methacholine at increasing doses (PD20 FEV1). Subjects were 246 children 11–12 years old living in an air-polluted area, and 285 children 11–13 years old living in mountain valleys. Respectively, 156 and 161 were negative to skin tests and had serum total IgE <100 IU/ml, and had no asthma or other recurrent or ongoing respiratory symptoms. Results: Lung function data, adjusted for the effect of potential confounders showed significantly lower FVC, and even more so FEV1, in the children from the polluted area. After the exclusion of subjects with positive skin tests and serum total IgE >100 IU/ml and those with history of asthma or respiratory disorders, there were higher percentages of positive responses in the challenge to methacholine in children from the polluted area (28.9 vs. 15.5%, p < 0.001). Conclusions: These data may corroborate the possible importance of long exposure to air pollutants on the prevalence of bronchial aspecific hyperresponsiveness in otherwise normal children.

Background and purpose-To test the design and feasibility of a very large randomised controlled trial assessing the efficacy and safety of antithrombotic therapy started within 48 hours of symptom onset in patients with suspected acute ischaemic stroke. Design-Randomised controlled multicentre open study, with a 3 x 2 factorial design, allocating patients to: medium dose subcutaneous heparin (12 500 units twice per day), versus low dose subcutaneous heparin (5000 units twice per day) versus no heparin; and aspirin (300 mg daily) versus no aspirin. Treatment was given for two weeks or until discharge from hospital if sooner.Results-984 patients were randomised. CT was performed in 924 (94%) (before randomisation in 622/984 (63%)). Within 14 days: 97 patients had died (10%), 30 (3.0%) had a fatal or non-fatal recurrent ischaemic stroke, nine (0.9%) had fatal or non-fatal recurrent stroke due to intracranial haemorrhage, and eight (0.8%) had a fatal or non-fatal pulmonary embolus. At six months, vital status was known for 975 patients (99%), of whom treatments. 210 (22%) were dead, 373 (38%) were alive but dependent, and 225 (23%) were independent but not fully recovered.Conclusions-The trial procedures ELIGIBILITY proved practicable and a wide variety of patients were recruited. Sample size calculation based on the event rates confirmed that reliable evidence on the balance of risk and benefit of early antithrombotic therapy might require a study with more than 20000 patients. Recruitment rates in the pilot study indicated that if about 200 hospitals participated, recruitment could be completed by 1997.

In ischaemic stroke, thrombolytic drugs speed the recanalisation of intracerebral arteries. The effects of aspirin are not known. A trial was conducted to determine whether, separately or together, streptokinase and aspirin have clinical benefits in acute ischaemic stroke similar to those in acute myocardial infarction. 622 patients with acute ischaemic stroke within 6 hours of symptom onset were randomised with a 2x2 factorial design to (i) a 1-hour intravenous infusion of 1 . 5 MU streptokinase, (ii) 300 mg/day buffered aspirin for 10 days, (iii) both active treatments, or (iv) neither. Early results raised a question whether the trial should be continued.Streptokinase (alone or with aspirin) was associated with an excess of 10-day case fatality (odds ratio 2 . 7; 95% confidence interval 1 . 7-4 . 3; 2p<0.00001). Of the four groups randomised, only patients allocated to streptokinase plus aspirin had a significantly higher risk of early death than those given neither streptokinase nor aspirin (odds ratio 3 . 5; 95% CI 1 . 9-6 . 5; 2p<0.00001). Streptokinase (alone or with aspirin) and aspirin (alone or with streptokinase) reduced, albeit not significantly, the incidence of combined six-month case fatality and severe disability: odds ratio for streptokinase 0 . 9 (95% CI 0 . 7-1 . 3) and odds ratio for aspirin 0 . 9 (95% CI 0 . 6-1 . 3).The risk of early death with thrombolytic treatments should be weighed against the potential benefit of a marginal reduction of severe disability after the first six months.

Some controversial issues exist whether regional cerebral blood flow (rCBF) changes are present both in migraine with and without aura during the interictal period. For this reason we have studied rCBF characteristics in migraine patients when headache-free. rCBF examinations were performed by the 133Xe inhalation method on 39 normal subjects (24 aged 45 or less and 15 older than 45), on 10 migraine patients with (A+) and on 10 without (A-) aura. The values of each patient were compared with the age-matched control population mean by a computer-assisted mapping system that allows statistical analysis in real time. To compare inter-individual variability 10 subjects, out of 39 normals, constituted an age-, sex- and CO2-matched control group (C). 8 A+ patients and 7 A- showed significant alterations of CBF in comparison with the age-matched control population. The analysis between the age-, sex- and CO2 matched groups showed significant differences of the inter-hemispheric (F = 6.669, p = 0.004) and of the frontal (F = 7.480 p = 0.0008) asymmetries. These data show that in the headache-free period a derangement of the cerebral perfusion is present in both migraine with and without aura, suggesting they are due to the same disease process. Furthermore they show the usefulness of a computer-assisted mapping system, suitable for clinical use, in discovering small alterations in cerebral perfusion.

The renal abnormality which causes hypertension in the Milan hypertensive strain of rats disappears as hypertension develops. Because of the many analogies between the condition in these rats and "essential" hypertension in man, the same pattern of change may occur if a renal abnormality is the cause of essential hypertension in man. This hypothesis was tested in two groups of young normotensive subjects matched for age, sex, and body-surface area; in the first group both parents were hypertensive, and in the second group both parents were normotensive. Renal plasma-flow, glomerular filtration-rate, plasma-volume, plasma-renin activity, plasma-concentrations of Na+, K+, and catecholamines, 24 h urinary excretion of Na+, K+, and aldosterone, and the cardiac index were measured so that renal function and the role of factors affecting blood-pressure regulation could be assessed. Renal plasma-flow was significantly higher (p less than 0.01) in the first group, whereas results of tests for all the other factors were almost the same in both groups. The hypothesis that a primary kidney abnormality causes hypertension in a proportion of patients with essential hypertension is proposed.

1. Almost all the factors that may cause a rise in blood pressure are, in turn, influenced by the increase in blood pressure per se. Thus any primary involvement of one or more of these factors in the pathogenesis of essential hypertension must be evaluated before or during the development of hypertension. 2. Young normotensive subjects both of whose parents are hypertensive have a much higher probability of developing hypertension than those whose parents are both normotensive. 3. The following measurements were made in 56 subjects of the first group (both parents hypertensive) and 35 of the second group (both parents normotensive), matched for age, sex and body surface area: renal plasma flow and glomerular filtration rate, using p-aminohippurate and inulin clearance; 24 h urinary excretion of aldosterone, protein and electrolytes; plasma renin activity; plasma volume. Plasma catecholamines and cardiac index were also measured in 26 subjects of the first group and 25 subjects of the second group using a radioenzymic method and echocardiography. 4. All these factors were similar in the two groups except that renal plasma flow was higher in the first group (767·2 ± 30 versus 650·7 ± 17 ml/min, P < 0·01). Plasma renin activity tended to be lower in subjects with a higher renal plasma flow, but there was no significant negative correlation between the two factors. 5. The possibility that the higher renal plasma flow in subjects with a high probability of developing hypertension is a compensatory mechanism for a primary intrarenal defect is discussed.

During CO2 rebreathing, we measured the pressures generated at the mouth and in the esophagus during the first 0.1 sec of inspiratory effort against a closed airway in 6 normal subjects and 6 patients with chronic obstructive lung disease. Normal subjects showed similar reponses to CO2 in terms of both mouth pressure and esophageal pressure. Patients' responses at the mouth to CO2 were decreased compared to those of normal subjects, but the responses in the esophagus were not significantly different. The patients demonstrated a greater response of occlusion pressure measured in the esophagus than at the mouth. In patients with altered mechanical properties of the lung, the change in mouth occlusion pressure might be influenced by problems of equalization of pressure within the airways due to unequal time constants, by problems of regional differences in pressure gradients over the pleural surface, or both. Esophageal pressure during airway occlusion 100 msec after the onset of inspiration may be better measure of respiratory drive than mouth pressure in patients with intrinsic increase of airway resistance.