Summary Proteases are important for neoplastic invasion but a specific role for the plasminogen activator system in the progression of colorectal epithelial dysplasia to adenomatous lesions remains unclear. Consecutive tissue cryosections of 51 adenomas, 49 distant mucosa samples and five mucosa samples from control subjects were histopathologically analysed for dysplasia grade and tissue type, urokinase plasminogen activator levels and plasminogen activator inhibitor type 1 (PAI-1) using immunosorbent methods. Plasminogen activation and urokinase-mediated proteolytic activity levels were assessed using in situ zymography. Plasminogen activation and tissue-type activator levels were lower in adenomas than in mucosae (P < 0.001). PAI-1 concentration and urokinase levels were higher in adenomas than in mucosae (P < 0.001 and P < 0.001 respectively). In adenomas, urokinase concentration increased in parallel with PAI-1, but only the urokinase levels correlated with the dysplasia grade (P < 0.01). Thus, the alterations in plasminogen activation correlated with epithelial cell dysplasia grading. In the mucosa to adenoma transition, a marked decrease in tissue-type plasminogen activator occurred. In adenomas, this decrease was accompanied by a concomitant increase in urokinase and PAI-1. The urokinase level only continued to rise in parallel with the dysplasia grade. Resulting protease-antiprotease imbalance in high-grade dysplasia may represent the phenotypic change associated with malignant transformation and invasive behaviour.Keywords: colorectal adenoma; epithelial cell dysplasia; plasminogen activator inhibitor type 1; tissue-type plasminogen activator; urokinase-type plasminogen activator A series of phenotypic changes are associated with the malignant conversion of the colorectal epithelium. The grade of epithelial cell dysplasia is a hallmark of malignant potential in the process known as the adenoma-carcinoma sequence (Muto et al, 1975;O'Brien et al, 1990;Hamilton, 1992). While the morphological changes taking place during the development and progression of colorectal dysplasia can readily be detected by histopathology, the proteolytic alterations underlying these multiple events remain unclear.It has been shown that components of the plasminogen activation system are key participants in the regulation of extracellular matrix turnover during cell migration, tissue modelling and malignant invasion (Konishi et al, 1982;Vassalli et al, 1991;Blasi, 1993). Previous studies have shown that tissue extracts from colorectal carcinomas have increased levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors (PAI) and decreased levels of tissue-type plasminogen activator (tPA) compared with morphologically normal adjacent mucosa (Gelister et al, 1986;Sier et al, 1991a). In adenomas, the levels of activators and inhibitors appear to be between those found in normal mucosa and those found in carcinoma (Gelister et al, 1986;Bruin et al, 1987;Sim et al, 1988;Suzumiya et al, 1988;Sier et al, ...

After swallowing a non-sterilised pH electrode a 25-year-old medical student developed an influenza-like illness followed by hypo- and achlorhydria for several weeks, acute leukocyte-gastrititis, and epithelial defects of the antrum. This possibly represents an infectious disease which can be transmitted by contaminated electrodes or probes.

During treatment with doxycycline capsules three patients (aged 24, 34, and 39 years, respectively) developed acute oesophageal ulcers with dysphagia as the cardinal symptoms. They became symptom-free and the ulcers healed promptly on symptomatic treatment. In-vitro experiments in rats indicated that doxycycline accumulates within the erythrocyte membrane and epithelial cells of the oesophagus. This accumulation is followed by cell destruction. It is assumed that doxycycline capsules remain within the oesophageal lumen and release doxycycline, causing epithelial destruction. This will occur more often after dry swallows of the capsules before going to bed.

In order to assess whether in reflux esophagitis morphological and functional disorders persist after macroscopic healing, cimetidine was given for 6-12 weeks at a dose of 1.6 g/day to 30 patients with acid gastroesophageal reflux and esophagitis. The mucosal defects healed in 6 patients, improved in 14 patients, and remained unchanged in 10 patients. Lower esophageal sphincter pressure, acid clearance, acid perfusion test, and histological signs of mucosal inflammation were assessed before and after treatment. The histological and functional findings did not improve after healing of the mucosal defects. Therefore, endoscopic normalization in patients with reflux esophagitis is not associated with the disappearance of inflammation and abnormal motor function. The persistence of these abnormalities might explain the tendency of esophagitis to recur after symptomatic and endoscopic "healing."