PubMed Health⌕ Search

Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 127 records · Page 7Linked to original sources
PubMed1990

A prospective study of persistent diarrhea among children in an urban Brazilian slum. Patterns of occurrence and etiologic agents.

Persistent diarrhea is a major health problem among children in developing areas of the world. Since few community-based studies have addressed the epidemiology or etiology of this condition, we undertook prospective diarrheal surveillance among a cohort of 175 children less than 5 years of age over a 28-month period in an urban slum in northeastern Brazil. Very high diarrhea illness burdens were found. The children in this cohort had an average of 11 episodes per year and spent 82 days per year with diarrhea. A total of 65% of children had at least one episode of persistent diarrhea (greater than or equal to 14 days duration). These episodes accounted for 50% of all days of diarrhea and 11% of all episodes. The occurrence of at least one episode of persistent diarrhea identified all children who spent at least 15% percent of days with diarrhea. Among children with and without diarrhea, rotavirus was the agent isolated most frequently, followed by Giardia lamblia and enterotoxigenic coliforms. The agents isolated from children with acute and persistent diarrhea were similar, which suggests that other factors must be operative in the development of persistent diarrhea.

Brazil↗
PubMed1990

Characterization of binding of Escherichia coli strains which are enteropathogens to small-bowel mucin.

Before an enteropathogen binds to the small bowel, it must interact with the small-bowel mucus (SBM) layer. To determine whether this interaction involves specific binding of diarrheagenic Escherichia coli, we used a quantitative assay with labeled, purified rabbit SBM. Binding of SBM from an adult rabbit was significantly greater to strain 162, an agglutinating E. coli strain, than it was to RDEC-1, a rabbit pathogen, and was significantly greater to strain 2348/PMAR, an enteropathogenic E. coli strain, than it was to strains 1392+ and 1392-, which are enterotoxigenic E. coli strains with and without colonizing fimbriae, respectively. Binding of strains RDEC-1, 2348/PMAR, and 162-4 was significantly greater to SBM than to bovine serum albumin. Binding of all strains increased in a linear fashion with increasing amounts of SBM and was reproducible (r = 0.85). Binding was significantly greater at pH 5.7 than at pH 7.4 or 8.0 for all five strains. Temperature did not alter the binding of any strain. Strains 162-4 and RDEC-1 bound significantly more to proximal SBM than to rabbit distal SBM, while strains 1392+ and 1392- bound significantly more to distal SBM. Oxidation of sugars from SBM significantly decreased the binding of all strains. Each pathogenic E. coli strain bound distinctively to SBM; the SBM sugars appeared to mediate this binding for all E. coli strains. Binding was also dependent on mucin characteristics, as binding varied by region of the gut (increased for proximal SBM for strains 162-4 and RDEC-1 and for distal SBM for strains 1392+ and 1392-). The developmental age of the gut significantly affected binding only of the rabbit pathogen RDEC-1.

Age Factors↗
PubMed1990

Net fluid secretion and impaired villous function induced by colonization of the small intestine by nontoxigenic colonizing Escherichia coli.

The role of colonizing bacteria in the small bowel in causing diarrhea remains unclear. We examined whether colonizing, nontoxigenic Escherichia coli could alter small bowel function by determining net water and electrolyte fluxes and sucrase activity in colonized and noncolonized ileal segments by using the reversible-ileal-tie adult rabbit model. Colonization of the ileum with nontoxigenic E. coli for greater than or equal to 72 h at greater than or equal to 10(4)/cm2 was associated with significant functional derangements, as follows: (i) overt liquid diarrhea in 50% of animals colonized at greater than 10(4)/cm2; (ii) reversal of normal net ileal absorption to net secretion of water, sodium, and chloride; and (iii) significant decrease in mucosal sucrase activity. We conclude that small bowel colonization by colonizing, nontoxigenic E. coli impairs water and electrolyte absorption and sucrase activity in the absence of recognized enterotoxin, cytotoxin, invasion, or effacement traits.

Animals↗
PubMed1989

Ultrastructure of another spiral organism associated with human gastritis.

Campylobacter pylori may not be the only organism that causes active chronic gastritis in man. We report two cases of gastric infection with a spiral organism distinct from C. pylori. The first patient is a 36-year-old female who presented with epigastric pain and abdominal colic present since childhood and who had 14 cats. Endoscopy was normal. The second patient kept two dogs. Histology of gastric mucosal biopsy specimens in both patients revealed active chronic gastritis, most severe in body mucosa. Giemsa stain revealed bacteria with four to eight spirals, 0.5 micron in diameter and 3-7 micron in length. The organisms had multiple sheathed flagella at the pole and smooth cell walls without axial filaments. The organisms resembled the gastric spirillum that has been seen in cats, dogs, and nonhuman primates. After antibacterial therapy with bismuth subsalicylate, amoxicillin, and metronidazole, the organisms disappeared in both patients and the gastritis healed. Unlike C. pylori, this new spirillum prefers to colonize gastric mucosa containing parietal cells. Whereas this type of organism is a common commensal in other mammals, it appears to be associated with and a possible cause of gastritis in humans.

Adult↗
PubMed1989

Clinical and immunologic significance of cholera-like toxin and cytotoxin production by Campylobacter species in patients with acute inflammatory diarrhea in the USA.

The humoral immune response to both Campylobacter jejuni cell surface antigens and to potential toxins of the organism was studied in 64 adults with inflammatory diarrhea. In an enzyme-linked immunosorbent assay (ELISA) for surface antigens, 17 (71%) of 24 persons with Campylobacter enteritis showed seroconversion in more than one immunoglobulin class, versus only 2 (5%) of 40 patients with non-Campylobacter enteritis. In a GM1, ganglioside-based ELISA for detecting serum IgG to cholera-like enterotoxin, only one patient studied showed seroconversion to the enterotoxin. Of 22 Campylobacter isolates studied for production of cholera-like toxin, none of the supernatants from the Campylobacter strains were positive. Supernatants were also tested for enterotoxin and cytotoxic activity on Chinese hamster ovary cells; all isolates were negative for enterotoxin activity. In contrast, cytotoxin was produced by 7 (32%) isolates but was usually low-level and was not neutralized by patient's serum. These findings indicate that production of cholera-like toxin and cytotoxin by Campylobacter strains in the United States occurs in few strains and that host immune response is absent; their biologic significance in the pathogenesis of Campylobacter infections remains unclear.

Acute Disease↗
PubMed1989

Early treatment of Campylobacter jejuni enteritis.

The bacteriologic and clinical effects of early antibiotic treatment of Campylobacter jejuni enteritis were studied. Erythromycin rapidly eliminated C. jejuni from stools, whereas trimethoprim-sulfamethoxazole did not. Despite its bacteriologic effectiveness, erythromycin did not reduce the duration or severity of diarrhea, abdominal pain, or other symptoms.

Adult↗
PubMed1989

Clostridium difficile toxin A. Interactions with mucus and early sequential histopathologic effects in rabbit small intestine.

Clostridium difficile produces two toxins, A (enterotoxic) and B (cytopathic), that are implicated in the pathogenesis of pseudomembranous colitis. However, the relationship of the secretory effect and the early histopathologic events is still unclear. We examined the early histopathologic effect of purified C. difficile toxin A in rabbit ileal loops and correlated the mucosal damage with the secretory response. As early as 2 hours after inoculation, toxin A at 1.0 micrograms caused cytolysis of the basal portion of the apical epithelia cells. Electron microscopy showed the basal portions of the absorptive epithelial cells necrotic. No significant fluid accumulation occurred after 2 or 4 hours in ileal loops inoculated with either 0.1 or 1.0 micrograms toxin A. In contrast, with 3-10 micrograms toxin A there was significant hemorrhagic fluid accumulation after 2 hours that correlated with the severity of the histologic lesions. An early mucoid exudate was demonstrated not to be related to a mucus secretagogue effect of toxin A. Prior exposure of toxin A to rabbit intestinal mucus preparations did not alter its subsequent enterotoxic or cytopathic (Chinese hamster ovary cells) effects. These studies demonstrate that the early intestinal tissue damage by toxin A was dose and time dependent and involved disruption of the basal portions of the absorptive epithelial cells with marked separation of the cells along the mucosal surfaces that preceded the secretory response.

Animals↗
PubMed1988

Pneumocystis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome.

The authors describe a patient with acquired immune deficiency syndrome (AIDS) who presented with an acute abdomen. A plaque-like tumor of the small intestine was resected and found to consist of masses of Pneumocystis carinii organisms. The organisms also exhibited a perivascular and intravascular distribution. Identical changes were found in regional lymph nodes. In addition to silver stains and electron microscopy, an immunohistochemical method for the demonstration of P. carinii was employed. The technique may have advantages over silver staining, as it identifies trophozoites in addition to cysts. A review of the literature concerning extrapulmonary pneumocystosis indicates that affected patients nearly always have concurrent pulmonary infection. The pattern of organ involvement and the finding of perivascular and intravascular organisms are consistent with lymphatic or hematogenous dissemination from the pulmonary focus. Pulmonary pneumocystosis was not documented in the patient described herein, although there were radiographic densities in one pulmonary lobe.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro.

Clostridium difficile is recognized as the major cause of antibiotic-associated colitis. C. difficile produces two toxins, A (enterotoxin) and B (cytotoxin), that are implicated in the pathogenesis of the colitis. We examined the dose responses, time course, and synergism of these two toxins in ligated rabbit intestinal loops and in tissue culture. In rabbit small intestinal loops, toxin A caused histologically demonstrable intestinal tissue damage as early as 2 h. The secretory response greater than or equal to 8 h was similar to that of a cholera toxin control. The effect of toxin A on tissue damage or secretion was seen even if toxin was removed after 5 min. Purified toxin A caused significant net accumulation of sodium, chloride, potassium, and total protein and slightly increased osmolality of the fluid content at 6 h; these effects were similar to those caused by crude C. difficile culture filtrates containing toxins A and B. Crude C. difficile toxin caused fluid accumulation with a delayed time course in the rabbit large intestine, and in contrast to its effect in small intestine, crude toxin caused net accumulation of bicarbonate and increased pH. In tissue culture, toxin A caused a rounding up of CHO and T-84 colonic carcinoma cells. A monoclonal antibody (PCG-4) that has no effect on tissue culture cytotoxicity with toxins A and B completely inhibited the secretory and tissue-damaging effects in the intestine. Toxins A and B were synergistic in the gut only at high doses of toxin B (greater than or equal to 10 micrograms/ml), and they were additive in tissue culture. The cytopathic effect in tissue culture was not consistently associated with trypan blue uptake. The cytopathic effect of toxin A in tissue culture did not appear to involve inhibitable Ca2+-dependent or prostaglandin synthesis pathways or intact microfilament or microtubule function for its activity and was not inhibited by reducing or lysosomotropic agents. Our results suggest that toxins A and B have independent and distinct effects in vivo and in vitro.

Animals↗
PubMed1988

Seven possible mechanisms for Escherichia coli diarrhea.

Escherichia coli has long been recognized as a potential enteric pathogen. This versatile organism has taught us much about the virulence traits responsible for a wide range of types of diarrheal diseases and their pathogenesis. Seven possible mechanisms for E. coli diarrhea are presented in this article.

Colitis↗
PubMed1987

Production of a unique cytotoxin by Campylobacter jejuni.

Campylobacter jejuni is an important diarrheal pathogen worldwide; the mechanisms by which it causes disease remain unclear. Because of its association with inflammatory diarrhea, we postulated that C. jejuni might produce a cytotoxin similar to that produced by Shigella sp., enterohemorrhagic Escherichia coli O157, or Clostridium difficile. Filtrates of 12 polymyxin-treated isolates of C. jejuni were placed on HeLa cells (sensitive to Shiga toxin cytotoxicity) and Chinese hamster ovary (CHO) cells. Of 12 isolates of C. jejuni tested, 5 killed 50% of the cells at greater than or equal to 1:4 dilutions of filtered suspensions of 10(9) bacteria per ml; killing was similar in HeLa and CHO cells (the CHO cells being insensitive to Shiga cytotoxin). One isolate produced a titer of 1:32 to 1:128. The relative potency in HeLa cells was comparable to that of E. coli strains that produce intermediate amounts of Shiga-like toxin. The other seven strains showed no cytotoxic effect, nor did the control diluents, polymyxin B, or supernatants of C. jejuni not treated with polymyxin B. Sonication also released active cytotoxin, but slightly less well than did polymyxin. The cytotoxic effect was dose dependent. Concentration of the C. jejuni in suspension by 10-fold before treatment with polymyxin B resulted in a 10-fold increase in the 50% cytotoxic dose. The cytotoxin effect was not neutralized by Shiga toxin immune serum against either Shiga-like toxin I or II or by anti-Clostridium difficile antiserum. The C jejuni cytotoxin was partially labile to trypsin (0.25%) and to heating to greater than or equal to 60 degrees C. Cytotoxicity was retained in Scientific Products dialysis tubing D1615-1 (Mr cutoff, 12,000 to 14,000). Some isolates of C. jejuni release a substance lethal to HeLa or CHO cells in vitro that is distinct from Shiga-like or Clostridium difficile toxin. This cytotoxin may contribute to the colonic mucosal invasive process that characterizes C. jejuni enteritis.

Animals↗
PubMed1987

Small-bowel colonization alone is a cause of diarrhea.

Bacterial overgrowth in the small bowel is known to occur in patients with persistent diarrhea, but it has been unclear if colonization alone causes fluid secretion. We studied isogenic, nontoxigenic Escherichia coli strains with colonizing factor antigen II (CFA/II) (1392+) and without CFA/II (1392-) in 18-h rabbit ileal loops. Neither strain produced fluid, but quantitative cultures of rabbit ileal loops with the CFA/II-positive strain had a mean of 10(3) more CFU of bacteria per cm2 than did cultures of rabbit ileal loops with the CFA/II-negative strain or a negative control (P less than 0.05). Of 11 rabbits given strain 1392+ via the small bowel in the reversible ileal tie model, 7 became colonized (mean, 10(10.4) +/- 1.6 CFU/cm2) over 72 h, and all 7 developed diarrhea and had gross gut fluid accumulation, versus none of 10 rabbits given strain 1392- (mean, 10(3.6) +/- 1.9 CFU/cm2) (P less than 0.05). Both strains grew equivalently in vitro. The mechanism by which this E. coli strain which colonizes small-bowel mucosa but produces no recognized toxins causes fluid accumulation and diarrhea in a rabbit model at 72 h remains to be elucidated.

Animals↗
PubMed1987

Viral hepatitis and gastroenteritis transmitted by shellfish and water.

The epidemiology and clinical presentation of water-borne viral diseases, including shellfish-associated viral illnesses, are discussed in this article. Hepatitis A virus, Non A-Non B hepatitis and the agents of viral gastroenteritis, Norwalk agent, Snow Mountain agent, rotavirus, the small round viruses, caliciviruses, and astroviruses are included. The technical problems associated with evaluating the viral contamination of water or shellfish are noted.

Disease Outbreaks↗
PubMed1987

Seroepidemiology of hepatitis D (delta agent) and hepatitis B among Virginia State prisoners.

A serosurvey of hepatitis D (HDV) and hepatitis B (HBV) was conducted in an asymptomatic population of newly incarcerated prison inmates in Virginia. Of 459 men entering the prison, 445 provided both sera and demographic and personal information. Six (1.3%) had antibody to HDV (anti-HDV). Evidence of past infection with HBV was found in 146 (32.8%); 9 (2.0%) were positive for HBV surface antigen (HBsAg). HBV seropositivity correlated with intravenous drug abuse, nonwhite race, and tattoos acquired in prison. Sera obtained after an interval of seven to ten months revealed seroconversion to anti-HDV in one of two HBsAg-positive men who admitted to parenteral drug use while incarcerated. Because he had been incarcerated elsewhere for more than one year before entering this prison, it is concluded that HDV transmission occurred in prison. The association of HDV infection with progression to chronic active and fulminant hepatitis suggests that serologic surveillance of HBsAg-positive inmates may be indicated for identification of possible HDV index cases.

Adolescent↗
PubMed1986

In vivo and in vitro effects of a novel enterotoxin, STb, produced by Escherichia coli.

Escherichia coli may produce a heat-labile enterotoxin (LT) or two heat-stable enterotoxins (STa, STb). STb consistently causes secretion in vivo in 5-hr weaned-pig intestinal loops (P less than .0001). In Ussing chambers in vitro, crude culture filtrates of STb initiate a prompt increase in short circuit current (SCC; P less than or equal to .0001) and potential difference (P less than or equal to .0001) when compared with nontoxigenic culture filtrates. In bidirectional in vitro studies of ion flux (22Na and 36Cl), STb did not alter 22Na or 36Cl unidirectional or net fluxes. The calculated residual ion flux increased significantly (P less than .03), however, in tissues treated with STb and fully accounted for the STb-induced increase in SCC. Measurement of the electrolyte content of ligated intestinal segments in vivo further suggested that STb stimulated bicarbonate secretion. Relative to controls, significant accumulation of Na and Cl also occurred intraluminally in vivo. These data indicate that STb is a unique enterotoxin that causes net secretion in pig jejunum in vivo. In vitro and in vivo studies show that STb stimulates active secretion of nonchloride anion. We postulate that STb causes active bicarbonate secretion in weaned-piglet jejunum.

Animals↗
PubMed1986

Species specificity and lack of production of STb enterotoxin by Escherichia coli strains isolated from humans with diarrheal illness.

Escherichia coli strains produce at least two heat-stable enterotoxins, STa and STb. STa is well known to be important in the pathogenesis of human diarrheal disease; the role of STb has not been defined. Fifty-two E. coli strains recovered from human diarrheal illness in northeast Brazil or Bangladesh were examined in weaned porcine ligated intestinal segments for STb activity. A total of 113 E. coli strains from human diarrheal disease in northeast Brazil and 28 E. coli strains from Bangladesh were examined for DNA hybridization to a STb gene probe. None of these strains produced STb as detected by enterotoxic activity or by the gene probe. We also examined adult human ileal mucosa for responses to STb in the Ussing chamber in vitro. In contrast to piglet jejunum, which consistently responds electrogenically to crude STb, human ileal tissue showed no response to STb but responded electrogenically to theophylline (10 mM). These results suggest that STb-producing E. coli strains are not a major cause of diarrheal illness in humans.

Bacterial Toxins↗
PubMed1986

Susceptibility of Campylobacter jejuni to strain-specific bactericidal activity in sera of infected patients.

Campylobacter jejuni is a common cause of inflammatory enteritis, which in normal hosts is usually self-limited and resolves without antibiotic therapy. C. jejuni bacteremia is very rare. We examined sera for bactericidal activity that might be important in limiting the extent of C. jejuni infection in man. We studied the ability of nonimmune sera and homologous and heterologous immune sera from infected patients to kill different fresh case isolates of C. jejuni in vitro. The reduction of the log10 concentration of viable C. jejuni (log10 killing) by fresh sera from nonimmune donors was only 0.2. Log10 killing by homologous acute sera varied from 0 to 3.8 (mean, 1.8). Convalescent sera showed remarkable log10 killing of only homologous C. jejuni, with values of 2.7 to 4.4 (mean, 3.7). The bactericidal effects of acute and convalescent sera were abrogated by heat and EDTA chelation, indicating mediation by complement. The role of classical complement pathway activation was supported by chelating sera with magnesium EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid] and by reconstitution experiments with heat-inactivated sera, C2-deficient serum, and purified C2. The requirement of specific antibody for the serum bactericidal effect was indicated by the loss of bactericidal activity when immune sera were absorbed with homologous but not heterologous whole C. jejuni isolates. The presence of specific antibodies was further documented by agglutination of only homologous C. jejuni suspensions by heat-inactivated immune sera. Studies with polymorphonuclear leukocytes suggested that ingestion and killing of two C. jejuni strains were modest and variable in the presence of heat-inactivated homologous serum. In summary, the data document a potent serum bactericidal effect that develops rapidly and specifically during C. jejuni enteritis and may be an important factor in host defense against C. jejuni.

Antibodies, Bacterial↗