Cigarette smoke-induced airway oedema due to activation of capsaicin-sensitive vagal afferents and substance P release

Exposure of rats to smoke from one cigarette caused local oedema due to a marked increase in vascular permeability from the epiglottis down to bronchioli, as indicated by extravasation of Evans blue in the airway mucosa. The cigarette smoke-induced extravasation of Evans blue was still present after removal of the tar and nicotine content of the smoke, suggesting that chemical irritants in the vapour phase were the main mediators of the vascular permeability response. Local or systemic pretreatment with capsaicin or [d-Arg¹, d-Pro², D-Trp^7,9, Leu¹¹] SP, a substance P antagonist, abolished or significantly reduced the airway oedema induced by cigarette smoke or vagal nerve stimulation. No reduction of the cigarette smoke or vagally induced tracheal oedema was seen upon pretreatment with mepyramine plus cimetidine, fentanyl, disodiumchromoglycate, methylprednisolone or terbutaline.

The results thus indicate that the cigarette smoke or vagally induced tracheal oedema is most likely to be due to substance P release from local capsaicin-sensitive afferent neurons in the airway mucosa. Local administration of substance P antagonists may be considered as a pharmacological means of inhibiting local mucosal oedema in the airways caused by airway irritants such as cigarette smoke.     

Recurrences 1 to 10 years after highly selective vagotomy in prepyloric and duodenal ulcer disease. Frequency, pattern, and predictors.

Three hundred and six (94%) of all consecutive patients with prepyloric or duodenal ulcer disease undergoing highly selective vagotomy at a District General Hospital were followed up after 1 to 10 completed years of observation. The 5- and 10-year cumulative recurrence rates were 11.6% and 16.8%, respectively. These figures were not related to age, sex, duration of ulcer disease, or preoperative peak acid output. Prepyloric ulcers had a significantly higher recurrence rate than duodenal ulcers during the first 5 years but this difference was eliminated at 10 years. The recurrence rates varied highly significantly between different surgeons. The 5-year recurrence rate in patients operated during the first 5-year period amounted to 13.4% and was steadily increasing. A corresponding figure for those operated during the second 5-year period was 5.3% and remained constant after 3 years of observation. This difference might reflect an improved surgical technique initiated by repeated evaluation of the clinical results.     

β-Receptor Blockade and Neurolept Anaesthesia. Withdrawal vs Continuation of Long-Term Therapy in Gall-Bladder and Carotid Artery Surgery

Forty-eight chronically (greater than 3 months) beta-receptor-blocked patients with ischaemic heart disease and/or hypertension were studied on 49 occasions after random distribution to a 4-day, gradual preoperative withdrawal (n = 26) or a continuation (n = 23) of beta-receptor blockers. The patients were scheduled for either a cholecystectomy (n = 28) or a carotid thrombendarterectomy (n = 21) under neurolept anaesthesia. Three patients were excluded from the randomized part of the study due to complications (tachycardia, hypertension, severe angina) after therapy withdrawal. In subgroups, central haemodynamics (beta-receptor blockers withdrawn n = 6, continued n = 8) and creatinine-kinase B (beta-receptor blockers withdrawn n = 9, continued n = 11) were studied. Withdrawal of beta-receptor blockers was associated with high heart rates, supraventricular tachyarrhythmias and a hyperkinetic circulation during pain stimuli. Significantly more postoperative ECG changes (P less than 0.02) indicative of myocardial ischaemia were found than in beta-receptor blocked patients. These patients had low heart rates but also pronounced increases in pulmonary capillary wedge pressures, which in single patients could be associated with myocardial damage. These results imply that beta-receptor blockers should be continued before surgery and that a concomitant vasodilatatory therapy is likely to avoid the drawbacks of an increased cardiac afterload.