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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 199 records · Page 11Linked to original sources

Value of examination for fecal leukocytes in the early diagnosis of shigellosis.

Fecal specimens from 101 patients with diarrhea were cultured and also examined with methylene blue for leukocytes. Thirty-six patients had leukocytes in their stools and 29 had culture-proven shigellosis. The sensitivity of fecal leukocytes in shigellosis was 95% (19/20) when cup specimens were obtained, and 44% (4/9) when swab or diaper specimens were examined. Only 45% of the patients with shigellosis who provided cup specimens had grossly bloody dysentery. Twelve other patients had fecal leukocytes but no demonstrable invasive bacterial pathogens. Methylene blue examination was useful in identifying motile trophozoites of Giardia lamblia and eggs or larvae of other heavy intestinal paraistic infections. Among patients with naturally-acquired acute diarrhea, methylene blue examination of stools for leukocytes is much more sensitive than examination for blood in predicting a positive culture for Shigella spp. It is also of value in detecting parasites.

Acute Disease↗

Campylobacteriosis in man: pathogenic mechanisms and review of 91 bloodstream infections.

Five patients with Campylobacter fetus(previously called "Vibrio fetus") bacteremia are presented with enteric symptoms in four patients, a self-limited course in three, and with possible nosocomial infection in one patient who had disseminated malignancy. The clinical syndromes of 91 bacteremic patients with campylobacteriosis and C. fetus taxonomy and pathogenicity are reviewed. Studies of potential pathogenic mechanisms in enteric infections failed to reveal the production of either heat-stable or heat-labile, cholera-like enterotoxin, cytotoxicity or invasiveness. In comparison with different species of vibrio infections, C. fetus appears to produce disease by a different mechanism, one which involves a bloodstream infection, perhaps following penetration through the intestinal mucosa as has been demonstrated experimentally with salmonellae and yersinia. Such a pattern is consistent with the clinical pattern of C. fetus infections and the experimental studies reported herein.

Adult↗

Swiss and inbred mice in the infant mouse test for the assay of Escherichia coli thermostable enterotoxin.

Swiss and inbred mice (C3H, ASn, B10A, and C57) were used to assay different thermostable enterotoxins prepared from Escherichia coli strains 3 (human), E57 (swine), B41 (cattle), and S13 (sheep). All strains of mice detected enterotoxins, but some reacted better to a given thermostable enterotoxin preparation than other inbred strains. Since the results obtained with Swiss mice were more consistent than with inbred mice, the former are apparently more suitable in the infant mouse test.

Analysis of Variance↗

Interaction of polymorphonuclear neutrophils with Escherichia coli. Effect of enterotoxin on phagocytosis, killing, chemotaxis, and cyclic AMP.

Enterotoxigenic Escherichia coli are associated with noninflammatory diarrhea and stimulate adenylate cyclase activity of mammalian cells, thereby increasing intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP). Increased concentrations of cyclic AMP in polymorphonuclear neutrophils (PMN) inhibit phagocytosis, candidacidal activity, granule discharge, and chemotactic responsiveness. We examined the effect of enterotoxin on the interaction of human PMN with E. coli. Enterotoxigenic and nonenterotoxigenic strains, including serotypes of E. coli identical except for the presence or absence of the plasmid coding for enterotoxin production, were utilized. Enterotoxigenic and nonenterotoxigenic E. coli, tumbled with PMN, were phagocytized and killed (>97%) equally well, and these strains stimulated PMN hexose monophosphate shunt activity equivalently.However, a chemotaxis assay under agarose demonstrated that filtrates of 10 enterotoxigenic strains were less chemotactic for PMN by 15+/-2% total migration or 46+/-1% directed migration, when compared with 6 non-enterotoxigenic strains (P < 0.001). Inactivation of the enterotoxin by heat (65 degrees C for 30 min) or antibodies formed to E. coli enterotoxin eliminated the inhibitory effect of the enterotoxic filtrates for PMN chemotaxis. Addition of purified E. coli enterotoxin directly to the PMN decreased chemotaxis to E. coli filtrates by 32+/-2% (P < 0.001). These data suggest that the effect was due to the heat-labile enterotoxin. The phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), which potentiates effects due to an increase in intracellular cyclic AMP, further decreased total PMN migration (random plus directed) toward enterotoxic filtrates to 46% of that to nonenterotoxic filtrates (P < 0.001). Addition of cholera toxin (1 mug/ml), which is similar to E. coli enterotoxin, to the PMN inhibited total migration toward nonenterotoxic filtrates by 16+/-2% (P < 0.001). Exogenous dibutyryl cyclic AMP (2 mM) inhibited total PMN migration toward E. coli filtrates by 32% (P < 0.001). PMN intracellular cyclic AMP levels increased by 220% after 2 h of incubation with purified E. coli enterotoxin. The decreased chemotactic attractiveness of enterotoxic E. coli filtrates appears to be related to the ability of enterotoxin to increase cyclic AMP in PMN. Enterotoxin production by E. coli may be advantageous to the microbe by decreasing its chemotactic appeal for PMN.

Blood Bactericidal Activity↗

Characterization of the Chinese hamster ovary cell assay for the enterotoxins of Vibrio cholerae and Escherichia coli and for specific antisera, and toxoid.

The morphologic change in Chinese hamster ovary (CHO) cells that is associated with increased intracellular concentrations of adenosine 3':5'-cyclic phosphate (cyclic AMP) provided a highly sensitive assay for the heat-liable enterotoxins of Vibrio cholerae and Escherichia coli. The similarity between the responses of CHO cells and those of intestinal mucosa to enterotoxins was demonstrated by the inhibition of these effects by the ganglioside galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide (GM1), as well as by specific antisera. The antisera against either enterotoxin were more effective in inhibiting the effects of homologous toxin than those of heterologous toxin, but cross-neutralization also occurred in both cases. When choleragenoid, the natural toxoid of cholera toxin, was incubated with the CHO cells, the subsequent effects of the toxin on the morphology of the cells were prevented as were the effects of the toxin on intestinal secretion. However, choleragenoid did not prevent the effects of E. coli toxin. The similarity between the action of enterotoxins on CHO cell morphology and on secretion by the small intestine suggests that there are similar binding sites in these tissues. The potential usefulness of the CHO cell assay in quantitative measurement of antitoxic immunity is thus demonstrated.

Animals↗

Epidemic diarrhea at Crater Lake from enterotoxigenic Escherichia coli. A large waterborne outbreak.

In June and July 1975, Gastrointestinal illness occurred in more than 200 staff members and 2000 visitors to an American national park. In was characterized by prolonged diarrhea, cramps, nausea, and vomiting, lasted a median duration of 8 days, and was significantly associated with consumption of park water (P less than 0.001), which had been contaminated by raw sewage. Enterotoxigenic Escherichia coli serotype 06:K15:H16 was isolated from 20 of 49 ill park residents and from the park's water supply, but not from 71 residents who had never been ill or had been well for at least 4 days. No other bacterial, viral, or parasitic pathogens were isolated from ill or well persons. This outbreak is the first waterborne epidemic of diarrheal illness shown to be due to enterotoxigenic. E. coli, and this study documents one mode of transmission of this pathogen. This investigation also suggests the relative insensitivity of current methods for identifying persons infected with this organism, either by the culturing of randomly selected isolates or by measuring serologic responses.

Diarrhea↗

Tickborne oculoglandular tularemia: case report and review of seasonal and vectorial associations in 106 cases.

A patient acquired tickborne oculoglandular tularemia in early summer in rural Virginia. Tick exposure may be a clue to the diagnosis of tularemia in the eastern as well as the western United States, especially in summer months. A review of the experience with tularemia in Virginia for the last 13 years shows a bimodal seasonal incidence of tularemia with an associated vector exposure in 77.4% of 106 cases. The majority of cases occurring during winter months have been associated with rabbit exposure, while those in summer months are often associated with tick exposure.

Aged↗

Toxigenic bacterial diarrhea: nursery outbreak involving multiple bacterial strains.

An outbreak of watery diarrhea occurred in 14 of 15 infants in a special care unit over a four-day period. Using the CHO cell assay for enterotoxin, we found that 11 of these patients had toxigenic bacteria in their stools. These bacteria comprised nine different serotypes of three species of organisms: Escherichia coli, Klebsiella, and Citrobacter. None of the three serotypes of E. coli were classic enteropathogenic serotypes. Rectal swab specimens from all 15 infants were examined for the presence of viruses by electron microscopic and cell culture techniques as well as by studies in suckling mice. None had parvovirus- or reovirus-like agents and two had adenoviruses. No other viral agents were detected. Of 38 bacterial strains isolated from ten control infants without diarrhea, three Klebsiella strains from two individuals were found to be toxigenic. Analysis of a total of 136 enteric isolates showed that toxigenicity as measured by the CHO assay was strongly associated with strains isolated during acute diarrheal illness when compared with strains isolated in convalescence (p less than 10(-5)) or with strains from control infants without diarrhea (p less than 10(-5)). This study raises the possibility of an outbreak of disease caused by a transmissible plasmid responsible for a cholera-like enterotoxin production in several enteric bacterial strains.

Adenoviruses, Human↗

Comparative pharmacology of josamycin and erythromycin stearate.

Two macrolide antibiotics, josamycin and erythromycin stearate, were administered orally to healthy, adult male volunteers for a comparative study of their pharmacological properties. In comparable doses, josamycin and erythromycin produced similar plasma concentrations, with similar half-lives and elimination constants. An initial loading dose of 1.5 g of josamycin produced greater peak concentrations of antibiotic throughout a 10-day period with a regimen of every 6 h. In addition, josamycin tended to reach higher peak and trough concentrations after regimens of every 6 or 8 h were maintained for 2 days. Josamycin penetrated into saliva, sweat, and tears, and it was better tolerated in fasting subjects than was erythromycin stearate.

Adult↗

Role of toxigenic and invasive bacteria in acute diarrhea of childhood.

The cause of pediatric diarrhea in Brazil was investigated with use of assays for toxigenic and invasive bacteria. Potential etiologic agents were identified in 31 of 40 consecutive children with diarrhea: toxigenic Escherichia coli or klebsiella in 20 patients (50 per cent); invasive Esch, coli or salmonella in four (10 per cent), and both toxigenic and invasive organisms in seven (18 per cent). Fecal leukocytes were present in nine of the 11 patients (82 per cent) with invasive pathogens. All 27 patients with toxigenic isolates had organisms that produced heat-labile cholera-like toxin; three patients had Esch. coli that also produced a heat-stable toxin. Among 20 controls without diarrhea there were no organisms that produced heat-labile toxin or tissue invasion, but there was one Esch. coli that produced only heat-stable toxin and one salmonella. In this pediatric population Esch. coli appears to cause most acute diarrheas due to toxigenic and invasive pathogenic mechanisms.

Acute Disease↗

Diarrheagenic effect of volume expansion: intestinal fluid secretion without mucosal adenyl cyclase stimulation.

Rapid intravenous saline infusion causes secretion of isotonic fluid by the canine duodenum. The duodenal fluid secretion is not accompanied either by increased adenyl cyclase activity in the mucosal epithelial cells or by widening of the "tight junctions" between epithelial cells. These data clearly indicate that the diarrheagenic effect of volume expansion is not mediated by the adenyl cyclase system. Furthermore, these data provide support for the concept that, when increased mucosal adenyl cyclase activity is associated with gut fluid secretion, the adenyl cyclase stimulation is a primary event, and is not secondary to the transmucosal isotonic fluid movement.

Adenylyl Cyclases↗