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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 109 records · Page 6Linked to original sources

Cotransport of sodium with glutamine, alanine and glucose in the isolated rabbit ileal mucosa.

To investigate the effect of substrates during oral rehydration therapy, we studied intestinal cation cotransport (ICC) with glutamine (Gln), alanine (Ala) and glucose (Glu). The specific aims were to determine the biological effects of these three different cotransport systems on intestinal function. Isolated rabbit ileal mucosa preparations mounted in Ussing chambers were studied. ICC was determined by measuring short-circuit current (Isc) and potential difference (PD) while monitoring tissue resistance (TR). The data are reported as the mean +/- SEM of 4-6 experiments for each amino acid concentration. Increasing concentrations of Gln (10(-5) to 10(-2) M), Ala (10(-5) to 10(-1) M) and Glu (10(-5) to 10(-2) M) caused a significant (P < 0.05) increase in ICC. Gln (30 mM) and Ala (0.1 M) had a maximal effect (Em(Gln) = 100% and Em(Ala) = 66%, P < 0.05) which was higher than that obtained with 30 mM Glu (Em(Glu) = 35%). When sodium was replaced with choline on the mucosal side, Ringer solution completely abolished the response with Gln, Ala and Glu. The presence of all three substrates (10(-2) M Gln, 10(-1) M Ala, and 10(-2) M Glu) in Ringer solution on the mucosal side caused a significant increase in ICC (delta increase of short circuit current = 111 +/- 43 microA, P < 0.05). These results demonstrate that Gln, Ala and Glu each increased sodium-dependent cation cotransport, and that sodium-dependent intestinal cation cotransport was higher with Gln than with Ala or Glu.

Alanine↗

Evaluation of diarrhea in the returning traveler.

Diarrhea in the returned traveler raises the possibility of a wide range of infectious, post-infectious, and idiopathic (e.g., inflammatory bowel disease) disorders that require a thoughtful evaluation. Specific clues in the history and clinical presentation are helpful in distinguishing inflammatory from noninflammatory processes and in suggesting persistent parasitic or other syndromes. The authors describe a practical approach to the diagnosis and management of diarrhea in the returned traveler.

Acute Disease↗

Effects of Vibrio cholerae recombinant strains on rabbit ileum in vivo. Enterotoxin production and myoelectric activity.

Previous studies have identified the effects of Vibrio cholerae and its enterotoxin, choleragen (CT A+B+), on the myoelectric activity of rabbit ileal loops in vivo. The response was defined as the migrating action potential complex, the single ring contraction that propels luminal contents aborad. In this study the same rabbit model is used to assess whether migrating action potential complex activity or fluid output is induced by recombinant strains of V. cholerae that produce no subunit of cholera toxin (CT A-B-) or only by the inactive binding subunit (CT A-B+). Three live strains were studied: El Tor wild-type N16961 (CT A+B+) and recombinant strains CVD106 (CT A-B+) and JBK70 (CT A-B-). Controls received sterile culture broth. Migrating action potential complex frequency in animals inoculated with CT A+B+ was significantly increased compared with that in all other experimental groups (P less than 0.01). Fluid output was also increased in animals inoculated with CT A+B+ compared with fluid output in all other groups (P less than 0.05). Migrating action potential complex frequency and fluid output in rabbits given CT A-B+ or CT A-B- did not differ from activity in controls. How these recombinant strains induce diarrhea is unknown, but the mechanism may involve bacterial colonization or production of an unknown toxin.

Animals↗

Patterns of antibiotic use among children in an urban Brazilian slum.

Antibiotics are utilized excessively in many areas of the world. To better define how often and why these drugs are used, we prospectively studied antibiotic use among a cohort of 105 children less than five years of age in a poor area of the northeastern Brazilian city of Fortaleza. During a 16-week period, 65 children took 137 courses of antibiotics. Physicians recommended 54% of these, mothers or their associates 39%, and pharmacy workers 7%. Mothers and pharmacy workers recommended drugs for shorter courses than physicians, and were more likely to recommend drugs inappropriate for children. Duration of illness was not a risk factor for antibiotic use, but both poor nutritional status and poor socioeconomic status were. Health care seeking behaviour was further studied in 58 diarrhoea episodes. The type of care sought was related to the duration of illness. Overall, antibiotic use was very common and often inappropriate among children in this poor urban area. More controlled use might decrease the use of potentially dangerous drugs and the use of these drugs when no benefit is likely.

Anti-Bacterial Agents↗

Acute respiratory viral infections in ambulatory children of urban northeast Brazil.

The morbidity of acute respiratory infections in young children and the role of respiratory viruses were evaluated in a 29-month household-based study in an impoverished urban population in Fortaleza, Brazil; subjects were 175 children less than 5 years of age in 63 families. Home visits were conducted three times weekly during which staff recorded the presence of respiratory and systemic symptoms and collected upper respiratory tract samples for viral isolation. A large and sustained burden of respiratory illness was observed, and respiratory viruses were isolated in 35% of the samples collected. Of the isolates, 45.6% were rhinoviruses, 16% parainfluenza viruses, 15.8% enteroviruses, 9.9% adenoviruses, 7.0% herpes simplex viruses, and 5.7% influenza viruses. The results indicate that poor children in northeast Brazil have a high prevalence of respiratory illness and that rhinovirus is the most frequent respiratory virus.

Acute Disease↗

Potential role of adherence traits of Escherichia coli in persistent diarrhea in an urban Brazilian slum.

We examined stools from 40 children with persistent diarrhea (duration, 14 days or more), from 50 children with acute diarrhea and from 38 control children to determine infectious etiologies for persistent diarrhea in Goncalves Dias, an urban favela (slum) in Fortaleza, Ceara, Brazil. Children with persistent diarrhea and children with acute diarrhea had similar rates of isolation of routine viral, bacterial and parasitic enteric pathogens. Routine pathogens were identified in at least 20% of cultures done more than 14 days into the diarrheal illness. We examined Escherichia coli isolated from these stools for adherence potential. Enteroaggregative E. coli were isolated significantly more often from children with persistent diarrhea than from control children or children with acute diarrhea (P less than 0.05). E. coli with hemagglutination patterns suggestive of adherence pili were also isolated more often from children with persistent diarrhea than from children with acute diarrhea (38% vs. 18%; P less than 0.05). Enterotoxigenic E. coli were isolated in combination with rotavirus more often from children with persistent diarrhea than from children with acute diarrhea. E. coli which were hydrophobic or exhibited hemagglutination were also seen more often in association with Giardia in children with persistent diarrhea. These findings suggest that the etiology of persistent diarrhea in children is complex and that the aggregative E. coli are associated with prolonged diarrheal illness. Although routine diarrheal pathogens may be present for more than 14 days, combinations of pathogens, including E. coli with adherence potential, may also contribute to prolonged diarrheal disease.

Animals↗

Antibiotic use among children in an urban Brazilian slum: a risk factor for diarrhea?

Among a cohort of children in a poor urban setting in Brazil, the relative risk for the occurrence of a new episode of diarrhea in the two weeks following antibiotic use vs all other weeks was 1.44 (95% confidence interval (CI) = 1.33, 2.45). Among children ever [corrected] exposed to antibiotics, the odds ratio was 1.34 (95% CI = 0.84, 2.16) after stratifying by individual child and controlling for previous diarrhea. Further research is needed to confirm whether antibiotics are a risk factor for diarrhea in such settings.

Age Factors↗

Intestinal cryptosporidiosis: pathophysiologic alterations and specific cellular and humoral immune responses in rnu/+ and rnu/rnu (athymic) rats.

In order to develop an experimental model of symptomatic cryptosporidiosis in an immunosuppressed mammal, we investigated the pathophysiology of infection with Cryptosporidium and the humoral and cellular host responses in rnu/rnu (athymic) rats and their heterozygous (rnu/+) littermates by challenging suckling rats with greater than or equal to 2.5 x 10(6) Cryptosporidium oocytes oro-gastrically. Normal and immunodeficient animals were followed for onset and duration of infection (fecal oocysts), physiologic consequences (diarrhea, impaired weight gain, brush-border enzyme activities), and immunologic response (both B- and T-lymphocyte-mediated). Homozygosity for the rnu gene was associated with protracted cryptosporidial infections; shedding for up to 52 days occurred, and delay in weight gain was noted in rnu/rnu-infected compared with rnu/rnu-uninfected rats (p less than 0.05). In contrast, cryptosporidial challenge of rnu/+ rats resulted in self-resolving infections, occasionally with transient diarrhea lasting four days or less occurring 10-15 days after oro-gastric challenge. The latter animals mounted a cell-mediated immune response to Cryptosporidium: three months after challenge, five of five rnu/+ rats demonstrated positive skin test responses to a subcutaneous 3.5 micrograms dose of cryptosporidial antigen. Further, sera from 6 rnu/+ rats taken two to three months after oro-gastric oocyst challenge exhibited specific anticryptosporidial immunoglobulin binding (A405 = 0.96), compared to that of seven uninfected rnu/+ controls (A405 = 0.09, P less than 0.02). Macromolecules of 150, 105, and 88 kD in the Cryptosporidium antigen preparation were bound by serum immunoglobulin from previously infected, recovered rnu/+ rats. Two brush-border enzymes (lactase and alkaline phosphatase) were markedly reduced in the ileum 8-10 days after oro-gastric challenge in rats with diarrhea and oocyst shedding. We find the rnu/rnu (athymic, nude) rat provides a useful model for study of prolonged cryptosporidial infection with impaired weight loss, brush-border enzyme alteration and intermittent diarrhea. These studies further suggest that a T-lymphocyte population is involved in recovery from Cryptosporidium infection and that this recovery is associated with both cellular and humoral immune responses to specific cryptosporidial antigenic macromolecules. This model should open further avenues for the study of the pathogenesis and protective immunity in cryptosporidial infection.

Animals↗

Mucolytic effects of Helicobacter pylori.

The mechanisms associated with colonization of human gastroduodenal mucosa by Helicobacter pylori remain unclear. To colonize gastric-type epithelium H. pylori must enter the gastric lumen, resist damage by all bactericidal factors operating within the acidic gastric milieu, penetrate the mucus gel despite highly viscous and hydrophobic properties of the mucus layer, and, finally, secure optimal conditions for its further multiplication. Since the H. pylori microorganism has been seen freely spread throughout the entire mucus layer thickness as well as in intimate contact with surface epithelium, the interrelationship between this spiral microorganism and the mucus seems to be of paramount importance. H. pylori has been shown to affect adversely the chemical and physical properties of the mucus layer. Therefore, the mucus layer compromised by the presence of this microorganism may become an easy target for acid and peptic damage, which ultimately leads to mucosal pathology, inflammation and/or peptic ulcer disease.

Bacterial Adhesion↗

Purified choleragenoid does not induce migrating action potential complex activity in rabbit ileum in vivo.

The migrating action potential complex (MAPC), a single ring contraction that propels luminal contents abroad, is elicited by Vibrio cholerae and its enterotoxin, choleragen (A1A2B5), in rabbit ileal loops in vivo. Choleragenoid (B5; the binding subunit) was shown previously to induce MAPCs without activating the adenylate cyclase system and without stimulating fluid output. We restudied purified B5 (extracted by high-performance liquid chromatography) to assess its effects on the myoelectric activity of rabbit ileum: can MAPC activity can be induced without associated fluid production? Four different B5 preparations and two controls, V. cholerae and sterile saline, were used. MAPC activity and ileal fluid output were significantly increased in animals inoculated with A1A2B5 (V. cholerae-El Tor) compared with all other preparations and controls. Importantly, MAPC activity and fluid output in all B5 groups did not differ from those in saline controls, demonstrating that purified B5 does not induce MAPC activity in rabbit ilium in vivo. The previous study showing B5-induced MAPCs may have resulted from A1A2B5 contamination. These results suggest A1A2B5-induced adenylate cyclase activation; myoelectric activity may be interrelated with holotoxin binding that causes a neural response.

Action Potentials↗

Enteric infections associated with exposure to animals or animal products.

The epidemiology and clinical presentation of enteric infections are discussed in this article. These include bacterial, viral, and parasitic illnesses, and are associated with the increasing popularity of drinking unpasteurized milk; eating raw fish and shellfish; consuming undercooked pork, poultry, and eggs; and having contact with pets. Salmonella, Campylobacter jejuni, Vibrio, Yersinia, Aeromonas, Edwardsiella, hepatitis A virus, Norwalk virus, Anisakis, Eustrongylides, Diphyllobothrium, Nanophyetus, Isospora, and Cryptosporidium are included. The importance of preventing these increasingly recognized enteric infections is emphasized.

Animals↗

A 20-minute breath test for helicobacter pylori.

In this study, we evaluated a simplified rapid 14C-urea breath test for the diagnosis of Helicobacter pylori. Fasting patients undergoing initial assessment for H. pylori drank 5 microCi of 14C-urea in 20 ml of water. Breath was collected at intervals for 30 min. Samples were counted in a beta-counter, and the results were expressed as counts per minute (cpm). In the same week, patients underwent endoscopy, and a blinded investigator examined biopsy samples of gastric mucosa by culture and histology for H. pylori. There were 49 H. pylori-negative (HP-) and 104 H. pylori-positive (HP+) patients in the study. HP+ patients expired a mean of 4398 cpm (SD 2468) per mmol CO2 in a sample taken 20 min after ingestion of the isotope. In contrast, HP--patients expired only 340 cpm (SD 196). If the mean +3 SD of HP- patients was used as a cutoff value, the 20-minute sample gave a sensitivity of 97% and a specificity of 100% for detecting H. pylori. The radiation exposure from this test is less than 1% of that received from an upper gastrointestinal series, and the short collection time makes it both convenient and cost effective.

Biopsy↗

Carbachol mimics phorbol esters in its ability to enhance cyclic GMP production by STa, the heat-stable toxin of Escherichia coli.

STa, the heat-stable enterotoxin of Escherichia coli, stimulates membrane-bound guanylate cyclase in enterocytes, elevates cyclic GMP, and results in intestinal secretion of ions and fluid. Using the T84 colon carcinoma cell line as a model. Weikel et al. reported that phorbol esters enhance STa-stimulated cyclic GMP production by 60-140% [(1990) Infect. Immun. 58, 1402-1407]. In the present report we demonstrate that the acetylcholine analog carbachol enhanced toxin-stimulated cyclic GMP accumulation in intact T84 cells by 50-100% and that this effect was blocked by 10 microM atropine and 10 microM sphingosine. Pertussis toxin treatment of the T84 cells did not affect the subsequent response to carbachol. Carbachol, which elevates intracellular calcium in these cells, may act through protein kinase C to enhance cyclic GMP production.

Animals↗

Urea protects Helicobacter (Campylobacter) pylori from the bactericidal effect of acid.

Colonization of the stomach with Helicobacter (Campylobacter) pylori is common in patients with duodenal ulcer disease, which is known for its high acid secretion. Although the bacterium is usually isolated by culture of a gastric biopsy specimen, viable organisms may sometimes be found in the acidic gastric juice. It was postulated that urease, by generating ammonia, protected H. pylori from acid. To test this hypothesis, the pH susceptibility of H. pylori, Proteus mirabilis, and the urease-negative Campylobacter jejuni was examined in the presence and absence of urea. It was found that without urea the three bacteria were all highly susceptible to acid. In striking contrast, the addition of 5 mmol/L of urea completely protected H. pylori but not P. mirabilis or C. jejuni from pH values as low as 1.5. Furthermore, the protective effect of urea on H. pylori was found with urea concentrations as low as 0.05 mmol/L. It is concluded that the high urease activity of H. pylori enables it to survive in gastric acid.

Campylobacter↗

Malnutrition is associated with increased diarrhoea incidence and duration among children in an urban Brazilian slum.

This study was undertaken to further define the relationship between malnutrition and subsequent diarrhoeal illness among children. A cohort of 61 children under five years of age was followed for two years in an urban Brazilian slum. Nutritional status was determined at two-month intervals and was used to predict the subsequent occurrence of diarrhoea. A significant, graded association between worsened nutritional status, as measured by length- or weight-for-age, and diarrhoea incidence was found. This relationship was present for both two-month and one-year periods following nutritional assessment. The average duration of diarrhoea was also significantly longer during the two-month periods which were preceded by the worst nutritional status. Overall, the most malnourished children had nearly twice the total number of days of diarrhoea that better nourished children had. These results provide additional evidence that a significant association between malnutrition and both increased diarrhoea incidence and duration exists.

Age Factors↗

A retrospective cohort study of nosocomial diarrhea as a risk factor for nosocomial infection.

Because most nosocomial infections are caused by enteric flora, it was undertaken to determine whether diarrhea predisposes to nosocomial infections by conducting a retrospective cohort study involving patients with and without nosocomial diarrhea who were hospitalized during a 12-month period. The rate of urinary tract infection per person-day after onset of diarrhea was significantly greater in patients with diarrhea (relative risk = 10.3; 95% confidence interval = 1.7-63.1, P = .006). When indwelling bladder catheter and duration of catheter placement were considered, diarrhea remained an independent risk factor for urinary tract infection in logistic regression analysis (P = .009). These data suggest that diarrhea and consequent urethral meatal contamination may be a cause of nosocomial urinary tract infection, especially in patients with a catheter, and that removal of the catheter should be considered whenever possible in patients with diarrhea.

Adolescent↗