Experimental leptospirosis in pregnant ewes. V. Middle uterine artery inoculations.
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Biomedical subjects
Publications and source records attributed to G W Clark.
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The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett's esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett's esophagus were subdivided according to the length of Barrett's mucosa: short-segment Barrett's (<3 cm) and extended Barrett's (> or =3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett's mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett's and 37 (15%) had extended Barrett's esophagus. Patients with short-segment Barrett's esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett's esophagus had increased esophageal acid exposure as did 100% of those with extended Barrett's esophagus. All lengths of Barrett's mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett's esophagus had dysplasia. The length of Barrett's mucosa was > or =3 cm in 25% (4 of 16) of patients with early Barrett's adenocarcinoma. Short-segment Barrett's esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature.
When duodenal content is allowed to reflux into the esophagus of nitrosamine-treated rats, esophageal cancer is induced more rapidly and at higher frequency than after carcinogen treatment alone. The purpose of the present study was to identify the components of the duodenal content that are responsible for enhancing esophageal carcinogenesis. Eight-week-old Sprague-Dawley rats underwent one of four operations as follows: diversion of bile alone, pancreatic juice alone, both bile and pancreatic juice into the esophagus, or a control operation with no induced reflux. Two weeks after surgery, rats were treated with the esophageal carcinogen 2, 6-dimethylnitrosomorpholine (48 mg/kg [0.1 of LD50] intraperitoneally weekly for 20 weeks). The rats were killed at age 30 weeks. The esophagus was removed and full-length strips were examined under a microscope; separate segments were taken for flow cytometric evaluation. The prevalence of DNA aneuploidy and histologic esophageal papillomas or squamous cancer was increased in carcinogen-treated rats with pancreatic juice reflux (P <0.05 vs. control) and the combination of pancreatic and bile reflux (P <0.05 vs. control) but not in rats with bile reflux alone. We conclude that pancreatic juice is the most potent component of the duodenal refluxate in the promotion of esophageal carcinogenesis in rats.
The aim of the study was to assess whether endoscopic ultrasound (EUS) could accurately measure the locoregional response to chemoradiotherapy in patients with carcinoma of the esophagus. Seventeen patients with esophageal carcinoma underwent EUS examination before and on completion of chemoradiotherapy. The EUS findings were correlated with the results of histologic examination of the esophagectomy specimen. The accuracy of EUS in these patients was compared with the accuracy of EUS in a control group of 17 patients treated by surgery alone. In 16 of 17 patients EUS-determined tumor (T) stage was unchanged following treatment and in one patient there was T-stage progression. No patient demonstrated downstaging of the primary tumor according to classical EUS criteria. In 10 of 17 patients a reduction in maximum tumor depth of >/=2 mm was observed (range 2 to 18 mm). Histologic examination revealed that four patients with squamous cell carcinoma had experienced a complete pathologic response. These four patients had significantly lower posttreatment EUS tumor depths compared to patients without a complete response (5.0 vs. 9.0 mm; P <0.05). Based on the post-treatment EUS examination, the accuracy was 59% for T stage and 59&percnt for node (N) stage. The accuracy of EUS in patients treated by surgery alone was 94% for T stage and 94% for N stage, indicating a significant reduction in the accuracy of EUS in patients following chemoradiotherapy (P <0.05). The accuracy of EUS examination in patients with carcinoma of the esophagus treated by chemoradiotherapy was poor. EUS did not detect downstaging of the primary tumor, even in the presence of a complete pathologic response. EUS assessment of maximum tumor depth was a better measure of response to therapy.
Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux disease. The condition should be considered in all patients undergoing endoscopy for symptoms of reflux disease and is confirmed when any biopsy shows the presence of specialized intestinal metaplasia irrespective of the macroscopic appearance of the distal esophagus. Endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated for all medically fit patients with Barrett's esophagus. The diagnosis of dysplastic change within this abnormal mucosa requires histological examination of the biopsies by 2 independent but experienced pathologists. Identification of high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the differentiation between high-grade dysplasia and invasive adenocarcinoma is unreliable. Esophagectomy remains the treatment of choice for patients with high-grade dysplasia since adenocarcinoma of the esophagus carries such a poor prognosis.
Quaternary alkaloid extracts of Ptelea trifoliata showed potentially interesting antimicrobial activity. Chromatographic examination showed the presence of six components. Of these, choline and O-4-methyl ptelefolinium were known compounds. Rational structures are proposed for the new alkaloids, O-4-methylhydroxyluninium, neohydroxylunine and pteleatinium salts. Pteleatinium salt is responsible for the antimicrobial activity of the extracts of the plant.
From the weakly antibacterial non-quaternary alkaloidal fractions from Ptelea trifoliata L. (Rutaceae), ten tertiary quinol-2-one and quinol-4-one alkaloids were isolated and identified. In addition, beta-sitosterol, beta-sitosteryl-beta-D-glucoside and bergapten were isolated. None of these compounds possessed perceptible antimicrobial activity. The weak antimicrobial activity of the neutral and alkaloidal fractions was traced to small amounts of pteleatinium chloride which had not been completely separated by bulk processes. Alkaloids previously known to be present in P. trifoliata which were found in this study ptelefoline methyl ether, pteleine and skimmianine. Alkaloids previously known but new to this plant were lunidoine and isomaculasidine. Alkaloids newly found in nature were neohydroxylunine, hydroxylunidonine, 6-methoxylunidoine, 6-methoxylunineand 6-methoxy-hydroxylunidine. The structure of the latter three bases is proposed tentatively.
The antimicrobial activity seen in extracts of Hunnemmania fumariaefolia S. resides in the alkaloids. The activity seen in the non-polar fractions had been shown by chromatography, physicochemical measurements, and comparisons with authentic samples to be due to apparently artifactual formation of the pseudomethanolates and pseudoethanolates of the alkaloids sanguinarine and chelerythrine, which are abundant in the plant. The enhanced potency of the pseudoalcoholates of sanguinarine over the parent benzophenanthridine is discussed in comparison with the in vitro biopotencies of other analogs prepared for the purpose. It appears that the pseudoalcoholates may be useful prodrugs.
Further study of mother-liquors from ethanolic extracts of Thalictrum rugosum resulted in the identification or partial characterization of 10 alkaloids, bringing the total to 17 characterized in our work on this plant. Five of the new alkaloids were active in vitro against microorganisms. Structures, based upon spectroscopic properties and chemical transformations, are proposed for a new bisbenzylisoquinoline alkaloid named thalrugosaminine, and a protopine alkaloid named protothalipine. A phenanthrene base (thaliglucinone), an aporphine (thalphenine), and three protoberberine bases (columbamine, thalifendine and deoxythalidastine) were identified; three very minor bases of unknown identify were partially characterized.
Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux. The etiology of this condition is unknown but clinical and experimental data points to esophageal exposure to duodenal juice as the key factor in its development. Barrett's esophagus should be considered in all patients undergoing endoscopy for symptoms of reflux disease. It is confirmed by the presence of intestinal metaplasia in an area of columnar mucosa, regardless of the macroscopic appearances of the distal esophagus. Endoscopic surveillance with multiple biopsy of the columnar mucosa is indicated for all medically fit patients with Barrett's esophagus. Identification of intestinal metaplasia with high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Esophagectomy is the treatment of choice for patients with high-grade dysplasia, since occult early adenocarcinoma is identified in up to 50 percent of the esophageal specimens.