Biomedical subjects
Publications and source records attributed to C P Cheney.
In the latter half of the 20th century, HCV emerged as the most common cause of chronic liver disease, and will likely remain so. Since its initial discovery in 1989, rapid progress has been made in our understanding of the virology, epidemiology, natural history, diagnosis, and treatment of HCV. Over the next few decades, as further advancements are made, superior treatment options will become available.
Congenital bronchoesophageal fistula is a rare anomaly that may go undiagnosed for many years. There are <200 reported cases in the literature. Patients usually present with chronic cough, a history of multiple pneumonias, and, less often, hemoptysis. The most sensitive test to diagnose a bronchoesophageal fistula is barium esophagogram. Surgical resection is the treatment of choice and is definitive in almost all cases. We present the case of a 52-yr-old woman with a history of cough and multiple pneumonias who sought medical treatment for abdominal pain. We discuss the presentation and the radiographic, endoscopic, and surgical findings, along with a review of the literature.
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Esophagogastric fistula formation as a complication of esophageal Crohn's has been reported in only one case in the literature. In addition, only eight cases of esophageal fistulae of any type have been reported in the setting of Crohn's disease. Unlike the more often described superficial, aphthous disease of the esophagus, response of fistulae to medical therapy has been disappointing, and recurrence and progression are likely. Surgery remains the primary modality for refractory disease. The roles of salicylates, antibiotics, immunosuppressive agents, sealants, and intralesional steroid injections have not been well defined. We present a case of severe, refractory Crohn's disease with fistula formation between the esophagus and stomach, and concomitant involvement of the oropharynx, duodenum, terminal ileum, and cecum.
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Diarrhea continues to be a major cause of mortality and morbidity in third world countries as well as a major symptomatic complaint in the primary care setting in the United States. The etiologic pathogen depends on an exposure history to include recent travel to foreign countries, consuming fecally contaminated water or food, prior use of antibiotics, or homosexual behavior. A careful history from patients directed at attempting to identify particular risk factors may help in making a diagnosis. Not all patients require a diagnostic workup. A large number of patients may only require oral rehydration, careful observation over time with or without use of antimotility agents. In toxic appearing patients or patients with fever, however, bloody stools, abdominal pain or tenesmus, a selective diagnostic workup is indicated. Antimicrobial treatments are not always required, some pathogens clearly call for treatment while some have less clear indications and other pathogens are not responsive to antimicrobial agents at all. Finally, one needs to remember that the differential diagnosis of acute diarrhea includes many noninfectious origins.
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Adherence studies using the rabbit enteropathogenic Escherichia coli strain RDEC-1 indicate that this strain attaches in a species-specific manner to receptors located on its host intestinal epithelial cells. Because intestinal epithelial cells undergo marked developmental changes within the first few weeks of life, we designed a study to determine whether the presence of bacterial receptors on rabbit brush borders changed during this time. The adherence of RDEC-1 to rabbit brush borders isolated from rabbits aged 2-35 days and from adult rabbits was examined. No adherence of RDEC-1 was detected to rabbit brush borders isolated from rabbits 15 days or younger. Receptors for RDEC-1 were first detected on rabbit brush borders from 21-day-old rabbits and by 35 days, RDEC-1 receptor activity on rabbit brush borders had reached adult levels. Piliated, enteroadherent, human Escherichia coli pathogens did not adhere to rabbit brush borders of any age group indicating that nonspecific adherence did not occur.
Escherichia coli strain RDEC-1 avidly adheres to rabbit ileal brush borders. Two separate experiments were designed to determine whether pili promote this adherence. (1) Adherence of strain RDEC-1 was phenotypically suppressed by changing the culture medium. Loss of adherence was correlated with the absence of pili. Thus, growth of strain RDEC-1 in Penassay broth (Difco Laboratories, Detroit, Mich.) promoted both adherence and expression of pili on greater than or equal to 90% of organisms, whereas growth in brain-heart infusion medium suppressed adherence and reduced the percentage of piliated organisms to less than or equal to 13%. (2) The adherence ability of strain RDEC-1 was genetically transferred to previously nonadherent and nonpiliated Shigella flexneri. The Shigella exconjugants that inherited the adherence ability were uniformly piliated, while all nonadherent Shigella exconjugants were nonpiliated. Finally, the pili on both RDEC-1 and the Shigella exconjugant strains were shown to be distinct from type 1 pili. Therefore, unique pili confer upon strain RDEC-1 the ability to adhere to rabbit intestinal brush borders.
The human enterotoxigenic Escherichia coli pathogen designated H10407 expresses two different types of surface pili, one designated type 1 pili and the other designated colonization factor antigen I (CFA/I), CFA/I pili are thought to promote the adherence of H10407 to the mucosa of the human small bowel. H10407 was grown under conditions which promoted the expression of either type 1 pili or CFA/I pili, and in each case, the adherence of H10407 to purified human intestinal brush borders was quantitated. The adherence assays revealed that H10407 adhered to human brush borders only when it expressed CFA/I pili. It appears that in vitro adherence of H10407 to human intestinal epithelial cells is dependent on the expression of CFA/I.
Species-specific colonization of rabbit intestine by RDEC-1 Escherichia coli is an accepted animal model for bacterial mucosal adherence. To determine whether RDEC-1 pili are functional as adherence factors for this organism, we grew the organism under conditions that promoted pilus expression; we isolated the pili, documented their purity, and compared their mucosal adherence properties with those of whole organisms using an indirect immunofluorescence technique. Frozen sections of rabbit, rat, guinea pig, and human small intestine were incubated with either piliated or nonpiliated RDEC-1 organisms or purified RDEC-1 pili and observed for the distribution and intensity (0-4+) of fluorescence. Piliated RDEC-1 organisms fluoresced brightly (4+) and were distributed along the entire mucosal surface of the rabbit ileum. Only a few nonpiliated RDEC-1 attached to rabbit ileum, and they were randomly scattered across the entire section of tissue. Rabbit ileum overlain with pure RDEC-1 pili showed a specific, D-mannose resistant (2-3+) fluorescence on the mucosal surface from the crypts to the villus tips. No fluorescence was seen on the guinea pig, rat, or human mucosal surface overlain with RDEC-1 pili. Purified RDEC-1 pili adhere to the rabbit intestinal mucosa in a species-specific manner and with the same distribution as whole piliated organisms. The data suggest that RDEC-1 produce pili (distinct from type 1 pili) that determine the specificity of the mucosal adherence of RDEC-1 to rabbit ileum.
We have previously described an in vitro assay for examining the mucosal adherence of a rabbit diarrheagenic Escherichia coli, RDEC-1. That assay defined the in vitro characteristics of RDEC-1 adherence to brush borders isolated from rabbit ileal epithelial cells. The present study was conducted to examine the species specificity of both in vitro RDEC-1 adherence and in vivo infectivity of RDEC-1 and to compare these specificities. Species specificity in vitro adherence was examined by using brush borders prepared from intestinal epithelial cells of rats, guinea pigs, and rabbits, as well as from a surgically resected specimen of human ileum. Strain RDEC-1 adherence to rabbit brush borders in vitro was significantly greater (P < 0.001) than its adherence to brush borders from any of the other species. Regional specificity of in vitro adherence of RDEC-1 to ileal segments of rabbit intestinal mucosa was also demonstrated. There was significantly greater adherence of RDEC-1 to rabbit ileal brush borders as compared to rabbit jejunal brush borders (P < 0.05). In vivo infectivity was assessed by inoculating RDEC-1 into rats, guinea pigs, and rabbits. RDEC-1 elicited diarrhea in all inoculated rabbits with the mean onset of illness occurring 5 days after inoculation. In contrast, none of the RDEC-1-inoculated rats or guinea pigs developed diarrhea. Furthermore, colonization studies in these animals revealed that RDEC-1 heavily colonized the ileum and cecum (10(9) RDEC-1 colony-forming units/g of tissue) of rabbits; however, only minimal colonization was observed in guinea pigs and rats. In conclusion, the correlation between in vitro adherence and in vivo infectivity that we have observed suggests that the presence of receptors, specific for bacteria, on the surface of the host intestinal mucosa determines species susceptibility to enteric colonization and infectivity by certain strains of enteropathogenic E. coli.
Two assays were developed to quantitate the adherence of an Escherichia coli strain (RDEC-1) known to colonize the mucosal surface of the small intestine of rabbits to brush borders isolated from rabbit intestinal epithelial cells. In the first assay, the mean adherence per rabbit brush border was determined by counting the number of organisms adhering to each of 40 brush borders under phase microscopy. The mean adherence of RDEC-1 (11.5 +/- 0.7 per rabbit brush border) was significantly greater than adherence of two nonpathogenic strains: HS (2.7 +/- 0.4 per rabbit brush border) and 640 (0.8 +/- 0.1 per rabbit brush border). A similar distinction between the adherence of RDEC-1 and the control (nonadherent) organisms could be made more rapidly by determining the percentage of the total number of brush borders which had 10 or more adherent organisms; this second assay was used to define the optimum conditions for adherence. Maximum adherence was seen within 15 min. Adherence was temperature dependent, with adherence after 1 min at 37 degrees C being fourfold greater than that at 4 degrees C. The pH optimum for adherence was between 6.5 and 7.0, and adherence was abolished below pH 5.0. With the first, more sensitive assay, the effect of electrolytes and a number of hexoses and hexosamines on adherence was analyzed. RDEC-1 adherence was inhibited at high ionic strengths; however, adherence was not influenced at moderately high concentrations (20 mg/ml) by either d-mannose or l-fucose, in contrast to the case for other reported enteric pathogens. These two quantitative in vitro assays for adherence produce consistent results and have been used to partially characterize the adherence of RDEC-1 to rabbit brush borders.
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Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7--11 months of feeding a high fat--high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat--high cholesterol diet on subcellular membranes.