PubMed Health⌕ Search

Biomedical subjects

Richard L Guerrant

Publications and source records attributed to Richard L Guerrant.

At least 37 records · Page 2Linked to original sources
PubMed2004

APOE4 protects the cognitive development in children with heavy diarrhea burdens in Northeast Brazil.

Polymorphisms in the apolipoprotein E (APOE) have constituted the major rationale to identify potential risk groups for developing late-onset Alzheimer's disease and help to predict recovery of cognitive function after brain injury. However, the APOE impact on cognitive development in children living in poor areas of the developing world, where we have discovered profound significant associations of early childhood diarrhea (at 0-2 y) with lasting impairments of growth, cognition, and school performance, is not known. Therefore, we conducted APOE genotyping in 72 Brazilian shantytown children under active surveillance since birth, using purified DNA extracted from buccal cell samples. We found a high frequency of APOE4 alleles (18% versus 9-11% expected) in children with lower diarrhea burdens. When we examined the children who experienced the heavier diarrhea burdens (greater than or equal to the median of seven illnesses in the first 2 y of life), those with APOE4 did significantly better in the coding subtest (p=0.01) when compared with APOE4-negative children with similar diarrhea burdens. Positive correlations between the APOE4 occurrence and coding scores remained, even after adjusting for family income, maternal education, and breast-feeding. Moreover, the APOE4-positive group, under heavy burdens of diarrhea, had preserved semantic fluency and the mean difference in fluency scores, p=0.025, a standardized coefficient for disproportional verbal fluency impairment. Our findings show that APOE4 is relatively common in favela children and suggest a protective role of the APOE4 allele in children with a history of heavy burdens of diarrhea in their first 2 y of life.

Alleles↗
PubMed2004

Laboratory diagnosis and susceptibility profile of Helicobacter pylori infection in the Philippines.

BACKGROUND: Helicobacter pylori diagnosis and susceptibility profile directs the applicability of recommended treatment regimens in our setting. To our knowledge, there is no published data on the culture and local susceptibility pattern of Helicobacter pylori in the Philippines. METHODS: 52 dyspeptic adult patients undergoing endoscopy from the Outpatient Gastroenterology clinic of the University of the Philippines-Philippine General Hospital underwent multiple gastric biopsy and specimens were submitted for gram stain, culture, antimicrobial sensitivity testing, rapid urease test and histology. Antimicrobial susceptibility testing was done by Epsilometer testing (Etest) method against metronidazole, clarithromycin, amoxicillin, and tetracycline. RESULTS: Sixty percent (60%) of the study population was positive for H. pylori infection (mean age of 44 years +/- 13), 70% were males. H. pylori culture showed a sensitivity of 45% (95% CI [29.5-62.1]), specificity of 98% (95%CI [81.5-100%]), positive likelihood ratio of 19.93 (95% CI [1.254-317.04]) and a negative likelihood ratio of 0.56 (95% CI [0.406-0.772]). All H. pylori strains isolated were sensitive to metronidazole, clarithromycin, amoxicillin and tetracycline. CONCLUSION: Knowledge of the antibiotic susceptibility patterns in our setting allows us to be more cautious in the choice of first-line agents. Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases.

Journal Article↗
PubMed2004

Diarrhea and reduced levels of antiretroviral drugs: improvement with glutamine or alanyl-glutamine in a randomized controlled trial in northeast Brazil.

The effects of therapy with glutamine and alanyl-glutamine on diarrhea and antiretroviral drug levels in patients with acquired immune deficiency syndrome (AIDS) were examined in a randomized, double-blinded, placebo-controlled study in northeast Brazil. Patients with AIDS and with diarrhea and/or wasting were randomized into 4 groups to determine the efficacy of glutamine or high- or low-dose alanyl-glutamine given for 7 days, compared with isonitrogenous glycine given to control subjects. All patients in whom baseline antiretroviral drug levels were determined had low levels 2 h after dosing. Gastrointestinal symptom scores improved with receipt of high-dose alanyl-glutamine (P<.05) or glutamine (P<.01). Antiretroviral drug levels increased in patients given alanyl-glutamine (P=.02) or glutamine (P=.03) by 113% (P=.02) and 14% (P=.01), respectively. Antiretroviral drug resistance mutations were common in all groups. The dose-related efficacy of alanyl-glutamine and glutamine in treating diarrhea and in increasing antiretroviral drug levels shows that these supplements may help to improve therapy for patients with AIDS who have diarrhea and/or wasting in developing, tropical areas.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Common infectious diseases and skin test anergy in children from an urban slum in northeast Brazil.

BACKGROUND: Acute respiratory infection (ARI), diarrheal disease (DD) and infective dermatitis (ID) are important causes of morbidity in children under five, in Northeast Brazil. OBJECTIVES: (a) to evaluate the morbidity of ARI, DD and ID; and (b) to determine their association with cellular immunity in poor urban children from Fortaleza, Brazil. MATERIALS AND METHODS: A prospective cohort study. At enrollment, multipuncture skin-tests (Multitest CMI) were performed and interpreted according to standard procedures. Children were followed for infectious diseases by weekly home visits. RESULTS: Seventy-one children aged 6 to 21 months were recruited in an ongoing cohort of newborns. A mean of 39 (6 to 63) home visits per child were made, which detected 184.5 symptomatic days per child-year of observation. ARI was present in 62% of the days of illness (6,378 out of 10,221), DD in 23% (2,296 days), ID in 6% (597) and other infections in 4% (373). Episodes per child-year were: 10 for ARI, 7 for DD and 1 for ID. Twelve (17%) out of 71 children were anergic. The incidences of ARI, DD and ID were similar in responsive versus anergic children. The mean duration of ID in anergy was 8.5 days, while it was 4.3 in the responsive group (P=0.007). Anergy was independent of age, sex and nutritional status. CONCLUSIONS: A high incidence of ARI and DD was found in these poor urban children. Skin-test responsiveness was not related to malnutrition, nor to morbidity due to ARI and DD, however anergic children had a longer duration of infective dermatitis.

Brazil↗
PubMed2004

Alanyl-glutamine hastens morphologic recovery from 5-fluorouracil-induced mucositis in mice.

OBJECTIVE: In this study, we postulated the beneficial role of oral alanyl-glutamine, a more stable glutamine derivative to decrease 5-fluorouracil (5-FU)-induced mucositis in mice. METHODS: We measured different morphologic parameters to assess structural changes over time in the small bowel, including crypt depth, villus height, villus area, mitotic and apoptotic indices at the crypt level using terminal deoxyuridine triphosphate nick end labeling, and hematoxylin-eosin staining of ileal tissue. In addition, we analyzed the effect of different alanyl-glutamine concentrations on animal weight curves after 5-FU treatment. RESULTS: Neither glutamine nor alanyl- glutamine prevented the 5-FU intestinal structural damage or apoptosis in crypt enterocytes at 24 h after 5-FU challenge. However, we found that alanyl-glutamine, but not glutamine, speeds intestinal recovery when compared with 5-FU-treated controls (P < 0.05), predominantly by enhancing mitotic activity and crypt length. CONCLUSION: Our findings provide important data to support clinical studies of oral alanyl-glutamine in 5-FU-induced mucositis.

Animals↗
PubMed2003

AIDS-associated diarrhea and wasting in Northeast Brazil is associated with subtherapeutic plasma levels of antiretroviral medications and with both bovine and human subtypes of Cryptosporidium parvum.

Advanced HIV infection is frequently complicated by diarrhea, disruption of bowel structure and function, and malnutrition. Resulting malabsorption of or pharmacokinetic changes in antiretroviral agents might lead to subtherapeutic drug dosing and treatment failure in individual patients, and could require dose adjustment and/or dietary supplements during periods of diarrheal illness. We determined the plasma levels of antiretroviral medications in patients that had already been started on medication by their physicians, in an urban infectious diseases hospital in northeast Brazil. We also obtained blood samples from patients hospitalized for diarrhea or AIDS-associated wasting, and we found reduced stavudine and didanosine levels in comparison with outpatients without diarrhea or wasting who had been treated at the same hospital clinic. There was a predominance of the protozoal pathogens Cryptosporidium and Isospora belli, typical opportunistic pathogens of AIDS-infected humans, in the stool samples of inpatients with diarrhea. We conclude that severe diarrhea and wasting in this population is associated with both protozoal pathogens and subtherapeutic levels of antiretroviral medications.

AIDS-Related Opportunistic Infections↗
PubMed2003

Cholera, diarrhea, and oral rehydration therapy: triumph and indictment.

Cholera drove the sanitary revolution in the industrialized world in the 19th century and now is driving the development of oral rehydration therapy (ORT) in the developing world. Despite the long history of cholera, only in the 1960s and 1970s was ORT fully developed. Scientists described this treatment after the discovery of the intact sodium-glucose intestinal cotransport in patients with cholera. This new understanding sparked clinical studies that revealed the ability of ORT to reduce the mortality associated with acute diarrheal disease. Despite the steady reductions in mortality due to acute dehydrating diarrheal diseases achieved by ORT, the costly morbidity due to these diseases remains, the result of a failure to globalize sanitation and to control the developmental impact of diarrheal diseases and their associated malnutrition. New advances in oral rehydration and nutrition therapy and new methods to recognize its costs are discussed in this review.

Biomedical Research↗
PubMed2003

The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000.

Current estimates of the global burden of disease for diarrhoea are reported and compared with previous estimates made using data collected in 1954-79 and 1980-89. A structured literature review was used to identify studies that characterized morbidity rates by prospective surveillance of stable populations and studies that characterized mortality attributable to diarrhoea through active surveillance. For children under 5 years of age in developing areas and countries, there was a median of 3.2 episodes of diarrhoea per child-year. This indicated little change from previously described incidences. Estimates of mortality revealed that 4.9 children per 1000 per year in these areas and countries died as a result of diarrhoeal illness in the first 5 years of life, a decline from the previous estimates of 13.6 and 5.6 per 1000 per year. The decrease was most pronounced in children aged under 1 year. Despite improving trends in mortality rates, diarrhoea accounted for a median of 21% of all deaths of children aged under 5 years in these areas and countries, being responsible for 2.5 million deaths per year. There has not been a concurrent decrease in morbidity rates attributable to diarrhoea. As population growth is focused in the poorest areas, the total morbidity component of the disease burden is greater than previously.

Child, Preschool↗
PubMed2003

Age-specific Helicobacter pylori seropositivity rates of children in an impoverished urban area of northeast Brazil.

We determined age-specific Helicobacter pylori seropositivity rates of 166 children and 39 mothers in an urban shantytown in northeast Brazil. Seropositivity rates increased from 23.1% at 0 to 11 months of age to only 39.3% by 96 to 131 months of age and were 82.1% at maturity. We observed no correlation between the seropositivity of the mothers and the seropositivity of their children.

Age Factors↗
PubMed2003

Interleukin-8, tumor necrosis factor-alpha, and lactoferrin in immunocompetent hosts with experimental and Brazilian children with acquired cryptosporidiosis.

To examine the importance of intestinal inflammation in the diagnosis and pathogenesis of human cryptosporidiosis, stools of healthy adult volunteers before and after experimental infection were tested for fecal lactoferrin, interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha). Stool samples of Brazilian children with well-defined Cryptosporidium infection, with or without diarrhea, were also tested for IL-8 and TNF-alpha. Only one of the 14 volunteers challenged with Cryptosporidium had increased fecal lactoferrin. However, of 17 stool specimens from children with only Cryptosporidium infection from a previous study, 12 had mild to moderately elevated lactoferrin despite negative work-up for inflammatory enteritides. One of 10 adult volunteers who developed diarrhea with experimental cryptosporidiosis and three of 11 children with cryptosporidiosis and diarrhea had detectable fecal IL-8. The level of TNF-alpha was increased only in one of 14 volunteers and in none of the children. Although considered relatively non-inflammatory. cryptosporidiosis is often associated with mild inflammation, especially in children in an endemic area.

Adult↗
PubMed2003

Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil.

To examine the association of intestinal barrier function with vitamin A deficiency and whether supplementation of micronutrients improves intestinal function and/or linear growth, height-for-age z-score (HAZ), concentrations of serum retinol and zinc, and intestinal permeability were determined in a cross-sectional sample of 75 children in northeastern Brazil. Effects of vitamin A and supplementation of zinc on intestinal permeability and growth were also determined comparing results before and after treatment in 20 children and age-matched controls. Lactulose:mannitol (L/M) permeability ratios inversely correlated with serum retinol concentrations (r = -0.55, p < 0.0005). Increased L/M permeability ratios with reduced concentrations of serum retinol were predominantly attributable to lower absorption of mannitol (r = 0.28, p = 0.02). L/M permeability ratios (p = 0.001) and HAZ scores (p = 0.007) improved with supplementation. It is concluded that impaired intestinal barrier function and linear growth shortfalls improve following supplementation of vitamin A and zinc in this setting.

Brazil↗
PubMed2002

Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells.

This study is an investigation into the mechanism of Clostridium difficile toxin A-induced apoptosis in human intestinal epithelial cells. Toxin A induced apoptosis of T84 cells in a dose- and time-dependent fashion. Toxin A-induced apoptosis was completely inhibited by blocking toxin enzymatic activity on Rho GTPases with uridine 5'-diphosphate-2',3'-dialdehyde by a nonspecific caspase inhibitor and was partially inhibited by caspase-1, -3, -6, -8, and -9 inhibitors. Caspases 3, 6, 8, and 9 and Bid activation were detected. Toxin A also induced changes in mitochondrial membrane potential and cytochrome c release at 18-24 h, a time course similar to caspase-9 activation. In conclusion, toxin A induces apoptosis by a mechanism dependent on inactivation of Rho, activation of caspases 3, 6, 8, and 9 and Bid, and mitochondrial damage followed by cytochrome c release. Toxin A proapoptotic activity may contribute to the mucosal disruption seen in toxin A-induced enteritis.

Annexin A5↗
PubMed2002

Clostridium difficile toxin A alters in vitro-adherent neutrophil morphology and function.

The effects of purified toxin A in vitro on the shape and function of polymorphonuclear leukocytes (PMNL) were examined. Toxin A induced changes in adherent PMNL shape from a compact spherical or pyramidal shape to a thin and rope-like shape. This change in shape was accompanied by rearrangement of the F-actin cytoskeleton into aggregates. Toxin A-treated PMNL exhibited increased adherence and expressed less L-selectin and more Mac-1, compared with untreated PMNL. In contrast to these proinflammatory actions, toxin A impaired both directed and non-directed PMNL migration in response to N-formylmethionylleucylphenylalanine. In addition, toxin A decreased the oxidative activity of adherent PMNL stimulated by recombinant human tumor necrosis factor-alpha. These effects could be explained by toxin A-induced glucosylation of the signaling small-size guanine 5'-triphosphate-binding proteins of the Rho family in human PMNL.

Bacterial Toxins↗
PubMed2002

Effects of an alanyl-glutamine-based oral rehydration and nutrition therapy solution on electrolyte and water absorption in a rat model of secretory diarrhea induced by cholera toxin.

OBJECTIVES: Recurring diarrhea and persistent diarrhea are commonly associated with malnutrition and long-term functional deficits. A beneficial approach would be to develop an alanyl-glutamine (AlaGln)-based oral rehydration and nutrition therapy (ORNT). We investigated the effect of an AlaGln-ORNT solution on electrolyte and water absorption in a rat model of secretory diarrhea induced by cholera toxin. METHODS: Phenolsulfonphthalein (50 microg/mL) was used as a non-absorbable marker for calculation of net water and electrolyte transport. Solutions tested were Ringer's solution, a glutamine-based ORNT (Gln-ORNT) solution, and an AlaGln-ORNT solution. Cholera toxin (1 microg/mL) was injected into lumen of rat small intestinal segments and incubated for 18 h before the initiation of the perfusion. RESULTS: Cholera toxin induced significant secretion of electrolyte and water in the control Ringer's solution. AlaGln-ORNT and Gln-ORNT solutions reduced the sodium secretory effect of cholera toxin by 128% and 36%, respectively. The net water secretion also was reduced by 95% and 60%, respectively, with the AlaGln-ORNT and Gln-ORTN solutions. CONCLUSIONS: These results showed that AlaGln-ORNT solution can enhance water and electrolyte intestinal absorption even better than glutamine or glucose and thus provide a potential novel approach for ORNT to break the vicious cycle of diarrhea and malnutrition. Clinical trials are now needed in children and adults with diarrhea and malnutrition.

Animals↗
PubMed2002

Cryptosporidiosis: epidemiology and impact.

Cryptosporidium was first recognized in humans in 1976 and came to prominence in the 1980s and 1990s as a cause of severe diarrheal illness in patients with AIDS. Its hardy, chlorine-resistant oocysts, tiny size, low infectious dose, fully infectious development when shed and zoonotic potential make it a threat in drinking and recreational water, contaminated food, day care centers, hospitals, and in persons with exposure to animals or unsanitary conditions, with potentially huge, long-term impact in malnourished children, as reviewed herein.

Animals↗