In the present study the vasorelaxing capacity of cromakalim, an ATP-sensitive potassium-channel (KATP channel) activator, and that of levosimendan, a new positive inotropic and vasodilating drug with calcium sensitizing and potassium-channel-activating properties, were compared in human isolated portal vein. Based on the 50% effective concentrations (EC50), levosimendan was found to be about 16-fold more potent (EC50 = 0.281+/-0.03 microM) as a relaxing agent than cromakalim (EC50 = 4.53+/-0.12 microM) in noradrenaline-precontracted portal venous preparations. Glibenclamide, the known inhibitor of KATP channels, was able to prevent the cromakalim-induced venodilation completely. Glibenclamide (15 microM) decreased the quasi-maximal effect of levosimendan (at 1.27 microm by about 60%) and also the effects of those submicromolar concentrations of the inodilator (at 0.1 microM by 23%, at 0.3 microM by 27% and at 0.7 microM by 19%, on average) which were therapeutically effective in preliminary human studies. These findings indicate that, in the human portal vein, both cromakalim and levosimendan are powerful vasorelaxants and that a considerable part of the relaxing effect induced by levosimendan is of cromakalim type.
The involvement of potassium channels in the venodilating capacity of the inodilator levosimendan in human saphenous vein preparations was investigated. Levosimendan caused relaxation with 50% effective concentration (EC50) of 0.32 +/- 0.04 microM in isolated veins contracted by 5-hydroxytryptamine. Fifteen microM glibenclamide, a blocker of the ATP-sensitive potassium channels (K(ATP)), partially inhibited the relaxing effect of the inodilator. In the presence of iberiotoxin, the selective blocker of large conductance calcium-activated potassium channels (BK(Ca)), levosimendan induced contraction with EC50 of 0.21 +/- 0.06 microM. We presume that levosimendan dilates human saphenous veins by interacting with hyperpolarizing potassium channels (K(ATP) and BK(Ca)).
The number of patients with scar carcinoma of the oesophagus developing on the basis of a corrosive stricture seems to have been rising in the past two decades. 36 patients of this kind were treated surgically between 1965 and 1984; this is the second largest series in the literature. The patients with scar cancer comprised 7.2% of the overall oesophageal carcinoma cases; this ratio is currently the highest of all in the literature. The interval between the caustic burn and the diagnosis of scar carcinoma was found to be 46.1 years; this is higher than the 30-35 years generally accepted so far. It was 50.9 years in those patients who drank lye before the age of 12, but 14 years less when it happened in adulthood. The long-term survival time proved to be excellent: 45.6% of the resected cases were alive after 5 years and 14.4% after 10 years. The explanation of the good prognosis lies in the fact that carcinoma developing in a lye stricture is at first surrounded by a rigid scar which allows only its intraluminal growth, and it causes early dysphagia through luminal obstruction. Early dissemination is prevented for the same reason. One-stage resection and replacement is suggested in the radically operable cases. In patients with oesophageal corrosive stricture which needs operation, both a by-pass procedure and resection can be adopted, but it should be pointed out that malignancy may develop even years after the operation in the remaining part of the gullet. Total oesophagectomy is therefore suggested instead of bypass.
Treatment is required only if cysts are highly symptomatic or if growth is detected. Interventional radiological methods do not prove more favorable than surgery. Laparoscopic fenestration is preferred because of its low morbidity and the short period of hospitalization. Traditional surgical methods should be reserved merely for cases in which laparoscopic deroofing is not feasible.
Oral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9 mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response
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