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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 217 records · Page 12Linked to original sources

Cyclic adenosine monophosphate and alteration of Chinese hamster ovary cell morphology: a rapid, sensitive in vitro assay for the enterotoxins of Vibrio cholerae and Escherichia coli.

The major limitation to our understanding of the clinical importance of enterotoxigenic Escherichia coli in diarrheal illness has been the lack of a simple rapid assay for the enterotoxin produced by certain E. coli. On the basis of the activation of adenylate cyclase by heat-labile enterotoxin of E. coli (LT) and by cholera toxin (CT) in intestinal and other tissues, cultured Chinese hamster ovary (CHO) cells with known morphological responses to dibutyryl cyclic adenosine 5'-monophosphate (AMP) were exposed to these enterotoxins. Crude culture filtrates of LT-producing E. coli and CT stimulated cyclic AMP accumulation and cell elongation in CHO cells. The similarity of time course, concentration dependence, and potentiation by phosphodiesterase inhibitors suggested cyclic AMP mediation of the morphological change. Heat inactivated CT and LT in this system. Choleragenoid inhibited CT; antiserum against CT inhibited both enterotoxin effects. In contrast to culture filtrates of 16 strains of E. coli known to produce LT, culture filtrates from 13 E. coli that do not produce LT did not alter CHO cell morphology. The morphological change is a simple, specific assay for these enterotoxins and detect 3 x 10(-17) mol of CT or a 1:250 dilution of crude culture filtrate of LT-producing E. coli 334.

Animals↗

Effect of Escherichia coli on fluid transport across canine small bowel. Mechanism and time-course with enterotoxin and whole bacterial cells.

An Escherichia coli strain isolated from a patient with severe cholera-like diarrhea elaborates a partly heat-labile enterotoxin shown to cause prompt adenyl cyclase stimulation and isotonic fluid secretion by canine jejunum. Both responses disappear upon removal of the enterotoxin. The duration of action of a submaximal dose of this E. coli enterotoxin was brief, despite sustained exposure to the jejunum, suggesting inactivation of the enterotoxin by its interaction with the mucosa. Inoculation of whole bacterial cultures of this E. coli strain into canine duodenum was followed by bacterial survival and induction of net secretion after 4-7 h. The onset of fluid production was associated with increasing gut mucosal adenyl cyclase activity. Washed bacterial cells could also produce fluid secretion. In vivo multiplication of this enterotoxin-producing E. coli was demonstrated 6-12 h after intraduodenal inoculation of approximately 10(6) organisms. This was associated with fluid secretion. Intestinal fluid production occurred without microscopic pathology in the mucosa.

Adenylyl Cyclases↗

Effect of spironolactone on stool electrolyte losses during human cholera.

This study demonstrated that endogenous aldosterone, as determined by its transient competitive block by spironolactone, caused significant sodium and chloride retention during naturally acquired cholera. This beneficial effect of the hormone is accompanied, however, by a deleterious depletion of potassium. In addition, it was found that stool rate significantly altered the sodium and potassium concentrations in cholera stool despite minimal or absent aldosterone activity.

Adult↗

A rapid test for infectious and inflammatory enteritis.

BACKGROUND: Inflammatory illnesses are an indication for specific diagnostic studies and possible antimicrobial therapy. The presence of fecal leukocytes has been used as a marker of inflammatory diarrhea; however, microscopic examination of the fecal smear is unreliable if the specimen is transported, refrigerated, frozen, or collected by swab. OBJECTIVE: To evaluate a rapid, sensitive, semiquantitative test for detection of fecal leukocytes using antilactoferrin latex bead agglutination (LFLA), a test that remains sensitive even after specimens are refrigerated, frozen, or stored on swabs. METHODS: LFLA titers were determined in stool specimens from previously healthy volunteers before and after experimental infection with different enteric pathogens and from patients with nosocomial diarrhea caused by Clostridium difficile. RESULTS: Healthy controls and subjects with noninflammatory diarrhea caused by Vibrio cholerae consistently demonstrated LFLA titers less than 1:50. In contrast, subjects with inflammatory diarrhea caused by Shigella species and C difficile had markedly elevated titers. Titers for subjects with experimental shigellosis ranged from 1:50 to 1:3200, with seven (78%) of nine at 1:400 or greater. Titers for patients with C difficile enteritis ranged as high as 1:1200, with six (50%) of 12 at 1:400 or greater. Subjects with experimental enteropathogenic Escherichia coli infection also had elevated titers, ranging from 1:100 to 1:1600, with three (43%) of seven at 1:400 or greater. Titers for subjects with experimental enterotoxigenic E coli infection were moderately elevated, with nine (53%) of 17 ranging from 1:50 to 1:200 (only one [6%] of 17 was > or = 1:400), suggesting a mild inflammatory process. CONCLUSIONS: The fecal LFLA assay distinguishes inflammatory from noninflammatory diarrhea, may provide new information on mildly inflammatory processes, and may be a useful, rapid test in a diagnostic algorithm for acute, infectious diarrheal illnesses.

Communicable Diseases↗

Diarrhea in developed and developing countries: magnitude, special settings, and etiologies.

Diarrheal diseases are major causes of morbidity, with attack rates ranging from two to 12 or more illnesses per person per year in developed and developing countries. In addition, diarrheal illnesses account for an estimated 12,600 deaths each day in children in Asia, Africa, and Latin America. The causes of diarrhea include a wide array of viruses, bacteria, and parasites, many of which have been recognized only in the last decade or two. While enterotoxigenic Escherichia coli and rotaviruses predominate in developing areas, Norwalk-like viruses, Campylobacter jejuni, and cytotoxigenic Clostridium difficile are seen with increasing frequency in developed areas; and Shigella, Salmonella, Cryptosporidium species, and Giardia lamblia are found throughout the world. The rational management of infectious diarrhea requires the highly selective use of laboratory tests for these varied etiologic agents, depending on the clinical and epidemiologic setting. The purpose of this review is to provide an overview of the magnitude, special settings, and etiologies of diarrhea endemic to developed and developing countries. This information permits a practical approach to the diagnosis and management of common diarrheal illnesses in different settings.

Acquired Immunodeficiency Syndrome↗

A review of the parasite cellular mechanisms involved in the pathogenesis of amebiasis.

Amebiasis, a significant cause of morbidity and mortality on a global scale, is caused by invasion of the colonic mucosa by the cytolytic protozoan parasite Entamoeba histolytica. A review of the investigations into the mechanisms by which the parasite causes invasive disease is presented, including the relevant history, epidemiology, and pathology of amebiasis, the biology of the parasite, in vivo and in vitro studies of the pathogenesis of disease, the host immune responses, and possibilities for prevention and biologic control. New insights into the cell biology of E. histolytica, especially its adherence and cytolytic properties, offer several new approaches to biologic control of this invasive, destructive parasitic infection.

Amebiasis↗

Amebiasis: introduction, current status, and research questions.

This series of five papers on the worldwide problem of amebiasis, its current status, research needs, and opportunities for progress has grown out of a renewal of investigative interest in amebiasis. The recent development of in vitro culture methods and of means to distinguish strain differences and the application of modern tools of cellular biology and biochemistry have raised new questions regarding strain definitions, virulence traits, host defenses, and the mechanism of invasive disease sometimes caused by Entamoeba histolytica. The clinical manifestations of amebic infections range from prolonged asymptomatic carriage to extensive, invasive intestinal and extraintestinal disease. The virulence traits of the parasite, whether stable in each strain or alterable by environmental or genetic factors, and the host factors involved in the development of disease and in protection have been investigated. From this series of reviews on the definition of amebiasis, its manifestations, its global magnitude, the methods for its detection, and the current understanding of its epidemiology, pathogenesis, cellular biology, and host defenses, a list of key questions that can now be addressed in work on amebiasis has been derived. Amebiasis is the third leading parasitic cause of death in the world. The need for work in this field is great, and the time is ripe for the application of new research tools to a better understanding of this remarkable tissue-lysing protozoan parasite and to the control of the disease it causes.

Amebiasis↗

Social, behavioral, and practical factors affecting antibiotic use worldwide: report of Task Force 4.

In addressing its charge from the General Chairperson of this study, Task Force 4 decided to direct special attention to antibiotic use in developing nations because of the critical importance of the disease burden of bacterial infections in these regions of the world. The task force recognized the impact of respiratory and diarrheal diseases on morbidity and mortality among young children in developing nations. Another major concern was the potential for global spread of resistant strains. Emergence and spread of antibiotic-resistant bacteria is augmented in settings in which treatment may be inadequate because of socioeconomic constraints and where there is crowding and poor sanitation. Much of the information concerning the factors that govern antibiotic use in these countries is anecdotal. No two countries are identical in their use of antimicrobial agents, and patterns of use may differ greatly in regions within the same country. Efforts to improve the usage of antibiotics in developing countries must take into consideration the perception of health and disease of the populations, the availability of antibiotics, and the characteristics of the established systems of medical care.

Acute Disease↗

Prolonged and recurring diarrhea in the northeast of Brazil: examination of cases from a community-based study.

From prospective daily surveillance of diarrhea in a poor rural area of northeastern Brazil, this study of prolonged diarrheal episodes identified the 3% of diarrheal episodes that lasted 15 days or longer. These episodes also defined a subpopulation of children who spent over 16% of their days with diarrhea. Such children warrant further attention in an attempt to define potentially treatable causes as well as to assure appropriate nutritional support. There was no single season for these prolonged illnesses, but they appeared to involve both the wet, slightly warmer season of peak enterotoxigenic Escherichia coli diarrhea as well as the dry, slightly cooler season of peak rotaviral infections. Limited etiologic data support this idea that multiple pathogens are found, often in combination with each other, that may work together to contribute to the important problem of chronic diarrhea. Future studies should focus attention on further defining risk factors, mechanisms, and appropriate therapy for the subset of children who experience prolonged diarrhea in this type of setting.

Brazil↗

Use of a lactoferrin assay in the differential diagnosis of female genital tract infections and implications for the pathophysiology of bacterial vaginosis.

BACKGROUND AND OBJECTIVES: Lactoferrin has served as a marker for leukocytes (polymorphonuclear neutrophils [PMN]) in clinical specimens. GOAL: To investigate the potential of a lactoferrin latex agglutination test in the differential diagnosis of female genital infection. STUDY DESIGN: Lactoferrin was quantified in the vaginal discharge of women with genital infections. Polymorphonuclear neutrophils were added to vaginal discharge and observed over 8 hours. RESULTS: Vaginal lactoferrin titers were significantly elevated in women with trichomoniasis, candidiasis, and bacterial vaginosis (BV). Using a lactoferrin titer of > or = 1:40, the assay has a sensitivity of 79.3% and a specificity of 83.3% for the presence of trichomoniasis or bacterial vaginosis. Vaginal discharge from women with BV significantly destroyed added PMN. CONCLUSIONS: Vaginal lactoferrin determinations may provide a useful screen for inflammatory genital infections and identify individuals who require additional diagnostic evaluation. The observed absence of PMN in bacterial vaginosis may result from the destruction of PMN in vaginal discharge rather than the absence of a primary inflammatory response.

Agglutination Tests↗