PubMed Health⌕ Search

Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 91 records · Page 5Linked to original sources
PubMed1994

Twelve messages from enteric infections for science and society.

Diarrheal diseases hold profound messages as well as opportunities that range from public health to basic science. From the spread of cholera around the world, we are reminded of the global impact of tropical diseases, that disease may provide a litmus test for poverty to drive a sanitary revolution, that disease spread may be worsened by political denial, and that many ecologic and epidemiologic secrets such as interepidemic microbial niches remain poorly understood. Diarrheal diseases other than cholera teach us that heavy disease burdens do not control population growth but are associated with population overgrowth (i.e., improved health is key to controlling the population explosion), the societal impact of diarrhea morbidity may exceed even that of its mortality, that new agents continue to emerge, and that nosocomial diarrhea is an underrecognized threat in our hospitals. Finally, from the laboratory of the developing world also come messages for basic science. Microbial toxins continue to elucidate a new understanding of cell signaling, and mechanisms once thought to be clear (such as that of cholera toxin) now appear much more complex. Traditional remedies hold new pharmacologic secrets, e.g., such as gingko extracts that inhibit platelet-activating factor. Finally, from basic physiology can come widely applicable practical solutions such as oral rehydration therapy and simplified diagnostics for inflammatory diarrhea. Health problems such as diarrheal diseases that plague the disadvantaged are linked to population overgrowth and provide some of the greatest challenges to modern science and the industrialized world.

Cholera↗
PubMed1993

Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial.

Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.

Adult↗
PubMed1993

Selective surveillance for nosocomial infections in a Brazilian hospital.

OBJECTIVE: To devise a system for surveying the frequency of nosocomial infections in a tertiary care hospital in a developing country. DESIGN: Prospective selective surveillance by nurses of the charts of patients at high risk for nosocomial infections, as identified by a form completed by resident physicians. The sensitivity, specificity, and predictive value of this method of selective surveillance were compared with those for total prospective chart review by two infectious disease specialists. SETTING: A university hospital in northeastern Brazil. PATIENTS: All patients hospitalized for more than 72 hours with an identified risk factor for nosocomial infection. RESULTS: The ratio of nosocomial infections to 100 discharges was 13.4 and the incidence density was 11.2/1,000 patient days. The surveillance method demonstrated a sensitivity of 74% and a specificity of 99.7%. Positive predictive value was 93%, negative predictive value was 99%, and overall accuracy was 98%. CONCLUSIONS: This method of selective surveillance for nosocomial infections based on risk factors identified by physicians demonstrated excellent predictive value and overall accuracy and may be of use to other hospitals that lack a nursing care plan book such as the Kardex. The relative frequency of nosocomial infections significantly exceeded the rates reported from hospitals in developed countries.

Brazil↗
PubMed1993

Assessment of enterotoxin production by Yersinia enterocolitica and identification of a novel heat-stable enterotoxin produced by a noninvasive Y. enterocolitica strain isolated from clinical material.

Twenty-eight clinical isolates of Yersinia enterocolitica were investigated for their abilities to produce heat-stable enterotoxin (YST). All 21 invasive strains (serogroup O3 biotype 4) carried the previously described gene for YST (yst), with toxin detectable in culture supernatants from 20 strains. One of seven noninvasive, biotype 1A strains also had enterotoxic activity, despite failure to hybridize with a probe for yst. The toxin produced by this noninvasive (serogroup O6) strain resembled YST in terms of molecular size, heat stability, and solubility in methanol. It differed from YST, however, with respect to regulation of its production by temperature and its mechanism of action, which did not appear to involve cyclic GMP.

Animals↗
PubMed1993

Metronidazole susceptibility testing for Helicobacter pylori: comparison of disk, broth, and agar dilution methods and their clinical relevance.

Since the methods for metronidazole susceptibility testing of Helicobacter pylori have not been standardized or validated, we compared three methods that are used to test the metronidazole susceptibilities of 25 isolates of H. pylori. Specifically, we examined the methods of Steer's replicator agar dilution, tube broth microdilution, and modified Kirby-Bauer disk diffusion. The metronidazole disk zone sizes obtained by the disk diffusion method correlated well (r = 0.74) with the MICs obtained by the agar dilution method. Afterward, the disk diffusion method was used to characterize the metronidazole susceptibilities of 44 isolates of H. pylori. Dual therapy (bismuth and metronidazole) proved to be highly effective against metronidazole-susceptible strains (81.6% eradication rate) but fared poorly against resistant strains (16.7% eradication rate; P < 0.01). Using agar dilution testing, we validated the modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of H. pylori and conclude that it is practical, accurate, and clinically applicable.

Drug Resistance, Microbial↗
PubMed1993

Evaluation of an antigen capture enzyme-linked immunosorbent assay for detection of Cryptosporidium oocysts.

The diagnosis of the small (4- to 6-microns) Cryptosporidium oocysts is labor intensive and relies on stool concentration, with subsequent staining and microscopy. The primary purpose of this study was to evaluate the clinical utility of an antigen capture enzyme-linked immunosorbent assay (ELISA) (LMD Laboratories, Carlsbad, Calif.) in detecting Cryptosporidium oocysts in human stools. A total of 591 specimens (76 diarrheal, 515 control) obtained from 213 inhabitants of an urban slum in northeastern Brazil were examined by both ELISA and conventional microscopic examination (CME) of formalin-ethyl acetate-concentrated stool samples stained with modified acid-fast and auramine stains. Forty-eight diarrheal stools (63.2%) were positive for Cryptosporidium oocysts by CME, with 40 of these positive by ELISA. Thirty-five control stools (6.8%) had Cryptosporidium oocysts detected by CME, with 15 of these also positive by ELISA. All of the 480 nondiarrheal stools and all but one of the diarrheal stools negative by CME were negative by ELISA. The test had an overall sensitivity of 66.3% and a specificity of 99.8% (positive predictive value, 98.2%; negative predictive value, 94.8%). In the evaluation of human diarrheal stool samples, the test sensitivity increased to 83.3%, with a specificity of 96.4%, and, in analysis of samples from individual patients with diarrhea, the sensitivity was 87.9%, with a specificity of 100%. These results indicate that this stool ELISA is sensitive and specific for the detection of Cryptosporidium oocysts in human diarrheal stool specimens but has limited use in epidemiologic studies for the diagnosis of asymptomatic Cryptosporidium infection.

Animals↗
PubMed1993

Environmental sources of Cryptosporidium in an urban slum in northeastern Brazil.

Cryptosporidium is an important cause of diarrheal disease in children worldwide. To elucidate the environmental sources of this parasite, we selected an urban slum in Fortaleza, Brazil, a community with a known high incidence of cryptosporidiosis, and examined both stool smears from household animals (n = 127) and filtrates from local water sources (n = 18) for Cryptosporidium oocysts. Because previous work in this community has demonstrated the seasonal nature of human infection with Cryptosporidium, collections were made separately for the dry and rainy seasons. Of the 64 stools collected during the dry season (September-December 1990), four (6.3%) were positive by acid-fast staining for Cryptosporidium. Of the 63 rainy season samples (March-May 1991), nine (14.3%) were positive. Overall, oocysts were detected in 13 (10.2%) of 127 animal stool samples. Freshwater samples were obtained from a variety of sources including open and closed wells, and running city water and then processed. Four of 18 samples (22.2%), including a sample from city water were positive by at least one of two staining techniques (acid-fast and immunofluorescence). In summary, animals may serve as a reservoir of Cryptosporidium, with potential for the contamination of immediate household water sources. These findings may help to explain the high incidence of cryptosporidiosis among infants in this impoverished community.

Animals↗
PubMed1993

Partial characterization of an ANF/urodilatin-like substance released from perfused rabbit kidney under hypoxia.

An ANF-like material was detected by radioimmunoassay in the isolated perfused rabbit kidney. The production of ANF-like material after 90 min of perfusion under hypoxia was 3000 pg/ml vs 500 pg/ml under normoxia or control conditions. This material is partially inactivated by heat treatment at 100 degrees C for 5 min and is absorbed on a SEP-PAK column (C18, Waters) but, unlike ANF, cannot be recovered from the column. On Sephadex G25 chromatography, elution in water yielded two active fractions, one corresponding to the solvent front and the second obtained after one column volume. Four fractions with biological activity were eluted with water from Sephacryl 200. Several fractions were tested on rabbit aorta preconstricted with 1 microM phenylephrine, without removal of endothelial cells. Treatment of T84 cells in culture by the crude material promoted a dose-related increase (1:2, 1:5, 1:10) of the generation of cyclic GMP. In contrast to our material, ANF (atriopeptin III, 1 microM-10 fM) failed to activate guanylate cyclase in T84 cells, while the heat-stable E. coli enterotoxin (STa) significantly increased cyclic GMP levels at the dose of 5 microM. We propose that a new ANF/urodilatin/ST-like material was generated by the hypoxic kidney under perfusion, which we name FNS (Factor Natriureticus Similis).

Animals↗
PubMed1992

Cryptosporidiosis: Pathogenesis and immunology.

Cryptosporidium parvum is an increasingly recognized agent of intestinal infection in normal and immunocompromised humans, and in many other animals. The intraepithelial cell infection results in villous atrophy, mild submucosal inflammation, reduction of brush-border enzymes and a characteristic persistent watery diarrhea. The infection is self-limiting in immunocompetent hosts, probably because of specific acquired immunity; specific serum and secretory antibody responses develop that may be required for clearance and protection against reinfection. Passive milk antibody, especially i f in high titers, may be partially protective but severe, persistent infection in athymic rodents and humans with AIDS demonstrate that T cells are essential for controlling the infection. Specific anti-bodies and lymphocyte extracts have been tested in cases of cryptosporidiosis but the interpretation of the results remains controversial. Here, Shu-Xian Zu, Guo-Dong Fang, Ronald Foyer and Richard Guerrant emphasize that effective treatment and prevention remain dependent on advances in our understanding of the host cell-parasite relationship.

Journal Article↗
PubMed1992

Persistent diarrhea in northeast Brazil: etiologies and interactions with malnutrition.

With the improved control of acute diarrheal illness mortality with oral rehydration therapy, persistent diarrhea is now emerging as a major cause of childhood mortality in tropical developing areas like the impoverished populations in Brazil's Northeast. "Graveyard surveillance" in the rural community of Guaiuba in northeastern Brazil revealed fully half of the 70% diarrhea mortality was due to persistent diarrheal illnesses. Furthermore, 11% of 14 or more diarrheal illnesses per child per year in an urban slum in Fortaleza persisted beyond 14 days, a definition that clearly identified the high risk children for heavy diarrhea burdens. Not only did heavy diarrhea burdens ablate the key "catch-up" growth seen in severely malnourished children and in children following previous diarrheal illnesses, but malnutrition significantly predisposed children to a greater incidence and duration of diarrhea as well as a greater incidence of persistent diarrhea. Etiologic studies of 37 children presenting with persistent diarrhea to Hospital das Clinicas in Fortaleza revealed that Cryptosporidium (in 13%) and enteroadherent E. coli (36% with aggregative, 29% with diffuse and 13% with localized adherence to HEp-2 cells) were the predominant potential pathogens found in the stool or upper small bowel. These findings suggest that persistent diarrhea is emerging as an important health problem in Brazil's Northeast, that it identifies a high risk child for heavy diarrhea burdens, that important interactions occur with malnutrition and that Cryptosporidium and enteroadherent E. coli warrant further study as potential etiologies of this major cause of morbidity and mortality.

Animals↗
PubMed1992

Pathogen and host differences in bacterial adherence to human buccal epithelial cells in a northeast Brazilian community.

The adherence of several strains of Escherichia coli to human buccal epithelial cells was studied, using cells obtained from five groups: healthy adults, healthy children, children with acute diarrhea, children with persistent diarrhea associated with cryptosporidial parasites, and children with noncryptosporidial persistent diarrhea. All groups lived or worked in an urban slum in northeastern Brazil. Samples of buccal epithelial cells from subjects in each of these groups were incubated with wild-type E. coli K-12 (strain C600), the enteroaggregative E. coli strains 17-2 and PDAS 30-5, CFA/II-positive E. coli 1392+ and its plasmid-cured derivative 1392-, and hydrophobic E. coli 132-3. Samples were evaluated microscopically to determine background contamination and the percentage of cells with more than 15% of their surface area obscured by adherent bacteria after incubation and washing. The assay was tested under field conditions and was shown to produce reliable and consistent results. Both enteroaggregative strains of E. coli were shown to adhere to a significantly higher percentage of all groups of human buccal epithelial cells than any of the other tested strains. In addition, buccal epithelial cells from children with nonparasitic persistent diarrhea showed substantially more bacterial adherence in both the native state and with all tested strains of E. coli than did cells from children with persistent cryptosporidial diarrhea or acute diarrhea or from healthy controls. This study provides evidence that enteroaggregative strains of E. coli demonstrate increased adherence to human buccal epithelial cells (as well as to cultured HEp-2 cells) and that buccal epithelial cells from children with noncryptosporidial persistent diarrhea appear to be more susceptible to bacterial adherence and colonization than buccal epithelial cells from control groups. These findings suggest that host differences as well as pathogen differences are important in the pathogenesis of persistent diarrhea and have implications for a potential role for buccal epithelial cell analysis in the diagnosis or risk stratification of children susceptible to noncryptosporidial persistent diarrhea.

Bacterial Adhesion↗
PubMed1992

Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C.

The heat-stable enterotoxin of Escherichia coli (STa) stimulates membrane-bound guanylate cyclase in intestinal epithelium and induces fluid and ion secretion. Using the T84 human colon carcinoma cell line as a model, we observed that phorbol esters markedly enhanced STa-stimulated cyclic GMP accumulation in T84 cells (C. S. Weikel, C. L. Spann, C. P. Chambers, J. K. Crane, J. Linden, and E. L. Hewlett, Infect. Immun. 58:1402-1407, 1990). In this study we document that the phorbol ester treatment increases 125I-STa-binding sites as well as membrane-bound guanylate cyclase activity in T84 cells and provide evidence that both effects are mediated by phosphorylation. Guanylate cyclase activity was increased approximately 50% in membranes prepared from intact T84 cells treated with phorbol-12,13-dibutyrate (beta-PDB) and after treatment of homogenates with beta-PDB in a manner dependent on ATP, MgCl2, and cytosol. Similarly, treatment of membranes with purified bovine brain protein kinase C in the presence of appropriate cofactors and beta-PDB resulted in an increase in STa-stimulated guanylate cyclase activity of about 70%. Likewise, the number of 125I-STa-binding sites was increased by about 25 to 40% in membranes prepared from intact cells or homogenates treated with beta-PDB; no effect on binding affinity (Kd = 0.15 nM) was noted. These experiments suggest that protein kinase C may phosphorylate the STa receptor-guanylate cyclase or a closely related protein and increase guanylate cyclase activity. The stimulatory effects of protein kinase C on STa-sensitive guanylate cyclase are opposite in direction to the profound inhibitory effects of the kinase on atrial natriuretic peptide-stimulated guanylate cyclase, demonstrating differential regulation by protein kinases within the guanylate cyclase-receptor family.

Adenosine Triphosphate↗
PubMed1992

Measurement of fecal lactoferrin as a marker of fecal leukocytes.

While diarrheal illnesses are extremely common in communities and hospitals throughout the world, an etiologic diagnosis may be expensive and cost-ineffective. Although the presence of fecal leukocytes are helpful in the diagnosis and specific therapy of inflammatory diarrheas, this requires prompt microscopic examination of fecal specimens (preferably obtained in a cup rather than a swab or diaper) by a trained observer. We developed a simple, sensitive test for the detection of leukocytes in fecal specimens using antilactoferrin antibody. Whereas radial immunodiffusion detected 0.02 micrograms of lactoferrin (LF) per microliter or greater than or equal to 2,000 leukocytes per microliter, latex agglutination (LA) readily detected greater than or equal to 0.001 micrograms of LF per microliter or greater than or equal to 200 leukocytes per microliter added to stool specimens. Despite the destruction or loss of morphologic leukocytes on storage for 1 to 7 days at 4 degrees C or placement of specimens on swabs, measurable LF remained stable. Initial studies of stool specimens from six patients with Salmonella or Clostridium difficile enteritis were positive and those from three controls were negative for LF by LA. Of 17 children in Brazil with inflammatory diarrhea (greater than or equal to 1 leukocyte per high-power field), 16 (94%) had LF titers of greater than 1:50 by LA, whereas only 3 of 12 fecal specimens with less than 1 leukocyte per high-power field on methylene blue examination and none of 7 normal control specimens had an LF titer of greater than 1:50 by LA. Of 16 fecal specimens from patients with C. difficile diarrhea (cytotoxin titers, >/= 1:1,000), 95% (n = 15) had detectable LF by LA (in titers of 1:100 to 1: 800). Finally, of 48 fecal specimens from healthy adult U.S. volunteers before and after experimental shigellosis and of 29 fecal specimens from children with documented shigellosis and hospitalized controls in northeastern Brazil, fecal LF titers ranged from 1:200 to >/= 1:5,000 in 96% (25 of 26) samples from patients with shigellosis (and reported positive for fecal leukocytes), while 51 controls consistently had fecal LF titers of </= 1:200. We conclude that fecal LF is a useful marker for fecal leukocytes, even when they are morphologically lost swab specimens or when they are destroyed on transport or storage or by cytotoxic fecal specimens.

Feces↗
PubMed1992

Diarrhea as a cause and an effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases diarrhea frequency and duration.

Diarrhea and malnutrition, alone or together, constitute major causes of morbidity and mortality among children throughout the tropical world. Data from northeast Brazil, taken with numerous other studies, clearly show that diarrhea is both a cause and an effect of malnutrition. Diarrheal illnesses impair weight as well as height gains, with the greatest effects being seen with recurrent illnesses, which reduce the critical catch-up growth that otherwise occurs after diarrheal illnesses or severe malnutrition. Malnutrition (whether assessed by impaired weight or height for age) leads to increased frequencies and durations of diarrheal illnesses, with a 37% increase in frequency and a 73% increase in duration accounting for a doubling of the diarrhea burden (days of diarrhea) in malnourished children. A multi-pronged approach focusing on those with prolonged diarrhea and severe malnutrition is suggested.

Brazil↗