No abstract

The high recolonization rate after monotherapy of Helicobacter pylori-positive gastritis may be due to insufficient local drug concentrations. To investigate the role of local diffusion, we measured levels of amoxicillin, a drug with good in vitro activity against H. pylori, in the mucosa and serum. One gram of amoxicillin was given to healthy volunteers as a tablet (n = 6) or as water-dissolved, fizzing "Tab" (n = 6). Gastroscopy with biopsies from the antrum, corpus, and fundus was performed at 30, 60, and 90 min. Concentrations in the mucosa were measured after homogenization with the agar diffusion method using BaciUlus subtilis as the biological indicator. Serum samples, taken basally and every 15 min, were analyzed by high-pressure liquid chromatography. Drug levels in the fundus and corpus remained far below those in the antrum for both application forms. The highest concentrations were reached after 30 min, with bactericidal levels in the antrum in two of six subjects who took the tablet form and five of six subjects who used Tabs. At 60 and 90 min, almost all values were below the MBC for 90% of the strains tested. The concentrations in serum, however, rose continuously, to reach a maximum after 75 or 90 min. These results show that incomplete elimination may be due to subbactericidal concentrations of antibiotics with high in vitro efficiency at the desired site of action in vivo and that local diffusion in the mucosa is essential for therapeutic effectiveness against H. pylor.Worldwide and in all age groups, Helicobacterpylori is the major etiologic factor in chronic active antral gastritis (8,9,20,28). There is also convincing evidence that H. pylon plays an important role in duodenal ulcer disease (2, 5, 12), especially since eradication of the bacterium is associated with a significantly lower recurrence rate compared with H2 receptor blocker therapy (6,13,19). Moreover, in up to 70% of patients with nonulcer dyspepsia, H. pylon-positive active antral gastritis can be diagnosed (18,25), and although controversy about the clinical relevance of chronic gastritis remains, several investigators have found that these patients profit from elimination of H. pylon in terms of symptomatic improvement (14,26). Bismuth salts, like colloidal bismuth subcitrate, and a variety of antibiotic drugs are able to eliminate the bacterium from the antral mucosa (15, 23), but recolonization within 1 month after therapy is the rule (24, 25). The reason for this incomplete elimination has not been sufficiently elucidated; it may be due either to reinfection from a bacterial reservoir in the upper gastrointestinal tract or to subbactericidal drug concentrations at the desired site of action during therapy. To investigate the latter possibility, we measured gastric mucosal concentrations of amoxicillin, a drug with excellent in vitro activity against H. pylori, given in the usual therapeutic dosage of 1 g in tablet form or in water-dissolved form. To compare the role of local diffusion of the drug with its systemic availabi...

The monoclonal antibody (MAb) Ki-67, which is directed against a proliferation-associated nuclear antigen, was used to measure tumor proliferation in 165 carcinomas of the esophagus, stomach, colon and rectum with an indirect immunoperoxidase technique. The percentage of Ki-67-positive tumor cells (Ki-67 index) was evaluated with the point-counting method. The Ki-67 index in gastric cancers (mean, 24.8%; standard deviation, 11.1%) was significantly lower than in tumors of the esophagus (35.7 +/- 12.6%), colon (37.6 +/- 15.2%), and rectum (34.3 +/- 16.4%). A wide range of the Ki-67 index (5.9-75.3%) could be observed within the various tumor types. In recurrent colorectal carcinomas, the Ki-67 index significantly increased to 51.9%. The Ki-67 index was independent of pathologic (e.g., TNM-stage, grading, tumor volume, tumor site) and clinical variables (age and gender of the patients). A marked heterogeneity of Ki-67 expression within different tumor stages was noted. Statistically significant regional variations in tumor proliferation existed between different areas within the same tumor.

Cell proliferation was measured by a three-step immunoperoxidase technique on cryostat sections of 61 resected colorectal adenocarcinomas using the monoclonal antibody Ki-67 that is directed against a proliferation-associated nuclear antigen. The percentage of Ki-67-positive cells was quantified with the point-counting method. The frequency distribution of the percentage of Ki-67-positive tumor cells in 52 unirradiated carcinomas was gaussian with a mean of 38.7% (range, 7.7% to 75.3%). Analysis of the unirradiated tumors showed no relation between Ki-67 staining and various clinicopathologic features including age, sex, tumor volume, tumor differentiation, location, and tumor stage. Although some tumors demonstrated intratumor heterogeneity of immunoreactivity, there was no significant difference in proliferative activity among peripheral, intermediate, and central tumor areas. Whereas the Ki-67 index increased to 47.1% in recurrent carcinomas, it decreased significantly to 24.7% in rectal carcinomas given radiotherapy before surgery. Therefore, Ki-67 immunostaining might be used as a tool to select and monitor patients with colorectal cancers who might benefit from radiotherapy. The marked differences of Ki-67 expression among different tumors may relate to heterogeneity in growth kinetics and may therefore carry prognostic implications.

Despite the introduction of effective medical treatment for peptic ulcer disease, no decrease in the incidence of bleeding has been observed. Unfortunately, most incidence studies rely on a questionable case ascertainment and poor data. We therefore conducted a prospective study, to achieve an unbiased estimate of incidence and pattern of peptic ulcer bleeding in Düsseldorf (Germany). In a 1-year period all patients with endoscopically verified peptic ulcer bleeding who were admitted to the departments of internal medicine or surgery in nine hospitals or seen by nine general practitioners offering endoscopic service were included in the study. Incidence rates were calculated in accordance with sociodemographic variables and expressed per 100,000 person-years of observation. The overall incidence of peptic ulcer bleeding was 51.4, with almost even rates for gastric (26.5) and duodenal (24.9) ulcer. Age was associated with an increased likelihood of bleeding in gastric ulcer patients of 19 per decade from about 40 years onwards (duodenal ulcer, 15). The incidence was about twice as high in men as in women (relative risk = 1.9). The pattern of peptic ulcer bleeding was similar in gastric and duodenal ulcers with regard to ulcer size, multiple lesions, and bleeding activity at endoscopy. However, patients with gastric ulcer bleeding had significantly more often accompanying or underlying diseases. No significant differences were observed between gastric and duodenal ulcer bleeding with regard to nonsteroidal antiinflammatory drug intake and ulcer history. The incidence rates in our study are in the upper range of the literature and comparable to rates from the USA and UK both before and after the introduction of H2 blockers. We hypothesize that the persistently high incidence rate is a superposition of two trends: higher incidences due to a more elderly and diseased population and more NSAID intake, and lower incidences due to effective medical treatment.