Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is -10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficUe colitis in man. (J.

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Previous studies indicated that the peptide substance P (SP) causes Cl−-dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10−8 to 10−6 M) induced a rapid, monophasic concentration and Cl−-dependent, bumetanide-sensitive short-circuit current ( I sc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1(SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced I sc increase without impairing forskolin- and carbachol-mediated I sc increase. We conclude that SP stimulates Cl−-dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.

Zusammenfassung. Grundlagen: Angabe der Biopsielokalisation (Ösophagus vs. Magen) ist notwendig, um die histologische Diagnose von Reflux-assoziierten Verän-derungen am Übergang Ösophagus/Magen zu erstellen. Wir haben den Wert der Videoendoskopie für die Diagnostik am ösophagogastralen Übergang untersucht.Methodik: 29 konsekutive Patienten (m:w = 17:12) mit gastroösophagealer Refluxkrankheit (GERD) wurden prospektiv endoskopiert (EGD). EGD und Biopsien wurden digital aufgezeichnet und danach analysiert. Nach initialer histologischer Diagnose basierend auf dem ersten EGD-Befund erfolgte eine revidierte Diagnose basierend auf dem Befund nach EGD-Review.Ergebnisse: Bei 17 Patienten (59 %) stimmten revidierter und erster Befund überein (normale Junktion: n = 4; abnormale Junktion mit Zylinderepithelsegment im Ösophagus [CLE]: n = 13). Die Histologie zeigte Karditis (n = 3) und Cardia-intestinale Metaplasie (n = 1) in Patienten mit normaler Junktion; CLE (n = 8) und Ösophagus-intestinale Metaplasie (EIM) (n = 5) bei abnormaler Junktion (CLE ≤ 0,5-7 cm). Bei 12 Patienten (41 %) mit CLE ≤ 0,5 cm unterschied sich die revidierte Diagnose von der Erstdiagnose (abnormale Junktion: n = 12). Die Histopathologie zeigte CLE (n = 9) und Ösophagus-intestinale Metaplasie (n = 3). Die Misinterpretation resultierte aus kurzer Dauer der Sequenzen mit unbeeinträchtigter Sicht zur EGJ (< 0,001) und war unabhängig von der zirkulä-ren Ausdehnung der CLE-Segmente (p = 0,160). EIM zeigte sich nur in cardiac, nicht aber in oxyntocardiac Mukosa.Schlussfolgerungen: Bei der EGD werden Zylinderepithelsegmente im Ösophagus ≤ 0,5 cm zwar biopsiert, aber dem falschen Organ zugeordnet (Magen vs. Öso-phagus) und somit Vorläuferläsionen zum Barrett Ösopha-gus übersehen.Schlüsselwörter: Barrett Ösophagus, Kardia Mukosa, intestinale Metaplasie.Summary. Background: Information on biopsy location (esophageal vs. stomach) is required for histopathologic diagnosis of reflux associated morphologic changes at the esophagogastric junction (EGJ). We evaluated the impact of digital recording of esophagogastroduodenoscopy (EGD) on diagnosis of epithelial disorders of the EGJ.Methods: 29 consecutive patients (male:female = 17:12) with gastroesophageal reflux disease (GERD) prospectively underwent EGD. EGD including biopsy sampling from EGJ was digitally recorded and reviewed. Initial histopathology report based on the initial EGD-report was followed by a revised histopathology report based on a revised evaluation of endoscopy recording.Results: In 17 patients (59%) revised evaluation was in agreement with initial diagnosis (normal junction: n = 4; abnormal junction with columnar lined esophagus [CLE]: n = 13). Histopathology showed carditis (n = 3) and cardia intestinal metaplasia (n = 1) in patients with normal junction; CLE (n = 8) and esophagus intestinal metaplasia (EIM) (n = 5) for abnormal junctions (CLE ≤ 0.5-7 cm). In 12 patients (41%) with CLE ≤ 0.5 cm revised evaluation differed from initial reports (abnormal junction: n = 12). Histopathology showed CLE...