Severe Gastrointestinal Disease Research Articles

GRAVeDAD De LA GASTRoeNTeRITIS CAUSADA PoR Vibrio parahaemolyticus DeL GRUPo PANDÉMICo eN eL PeRÚ

Objective. To determine the epidemiological and clinic characteristics of gastroenteritis caused by Vibrio parahaemolyticus strains of the pandemic group in Peru. Material and methods. Clinical and laboratory records were searched in 100 cases of gastroenteritis caused by V parahaemolyticus, either of the pandemic or non pandemic group. Clinical and epidemiological data were collected and statistical analysis was done to evaluate if the severity of illness was associated with the pandemic group. Results. Epidemiological data were collected in 85% of cases, and clinical data were only available in 37% of cases, mainly on those hospitalized. Cases associated with the pandemic strains had a higher probability of liquid stools (96.3% vs. 62.5%, p<0.05), moderate or severe dehydration (100% vs. 60%, p<0.05), and hospital care (98% vs. 42.9%, p<0.0001). Cases aged thirty or older were associated with the pandemic strains (63% vs. 39.5%, p<0.05). Conclusions. Vibrio parahaemolyticus of the pandemic group causes more severe gastrointestinal disease than none pandemic strains, with higher probability of requiring hospital care. Based on this report, it is advisable to include the identification of V. parahaemolyticus in the etiological diagnosis of agents causing severe gastroenteritis in the Peruvian health system.

Gastrointestinal Disease in Simian Immunodeficiency Virus-Infected Rhesus Macaques Is Characterized by Proinflammatory Dysregulation of the Interleukin-6-Janus Kinase/Signal Transducer and Activator of Transcription3 Pathway

Gastrointestinal disease and inflammation are common sequelae of human and simian immunodeficiency virus (SIV) infection. Nevertheless, the molecular mechanisms that lead to gastrointestinal dysfunction remain unclear. We investigated regulation of the interleukin (IL)-6-JAK-STAT3 pathway in jejunum and colon, collected at necropsy, from 10 SIV-infected macaques with diarrhea (group 1), 10 non-SIV-infected macaques with diarrhea (group 2), and 7 control uninfected macaques (group 3). All group 1 and 2 macaques had chronic diarrhea, wasting, and colitis, but group 1 animals had more frequent and severe lesions in the jejunum. A significant increase in IL-6 and SOCS-3 gene expression along with constitutive STAT3 activation was observed in the colon of all group 1 and 2 macaques and in the jejunum of only group 1 macaques compared to controls. Further, in colon, histopathology severity scores correlated significantly with IL-6 (groups 1 and 2) and SOCS-3 (group 2) gene expression. In jejunum, a similar correlation was observed only in group 1 animals. Phosphorylated STAT3 (p-STAT3) was localized to lymphocytes (CD3+) and macrophages (CD68+), with fewer CD3+ lymphocytes expressing p-STAT3 in group 1 macaques. Despite high SOCS-3 expression, STAT3 remained constitutively active, providing a possible explanation for persistent intestinal inflammation and immune activation that may favor viral replication and disease pro-gression.

Disease activity, damage and survival in Mexican patients with acute severe systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a clinical syndrome of varying severity. Although the survival and prognosis of SLE have steadily improved, there is a group of patients who present an acute fatal outcome despite aggressive therapy. We designed this study to evaluate the factors associated with mortality in patients with acute severe SLE. During 2004-06, 41 Mexican SLE patients that could not be managed in the out-patient clinic and with acute severe major organ system involvement [nephritis, severe thrombocytopenia (platelet count below 20 000 per microL) acute neuropsychiatric pulmonary, gastrointestinal or cardiac disease and generalized vasculitis] were studied. During the first admission, disease activity (SLE Disease Activity Index (SLEDAI), SLE Activity Measured), damage [SLE International Collaborating Clinics (SLICC)], and therapy were assessed. Survival using Kaplan-Meier curves, odd ratios with 95% confidence interval and logistic regression analysis were used to determine risk factors for mortality. Ninety percent were female with a mean age of 29 +/- 19 years and mean disease duration of 21 +/- 9 months. The principal causes of first admission were renal (27%), SNC (22%) and cardiopulmonary (15%). After a mean follow-up of 9.7 +/- 6 months, 16 (39%) patients died. Deceased patients had significantly higher SLEDAI (P = 0.004), and SLICC (P = 0.03) scores. The manifestations associated with mortality were renal disease activity (odds ratio, OR 4.6, confidence interval, CI 95% 1.0-20.6), infections (OR 3.2 CI 95% 2.0-5.3) and thrombocytopenia (OR 4.0, CI 95% 1.0-15.9). The survival at 9.7 months was 72, 62 and 50% in patients with an SLEDAI score of 3-10, 11-20 and > or =21, respectively. The SLEDAI score, the presence of damage and infection were associated with death in patients with acute severe SLE.

Carbon Catabolite Repression of Type IV Pilus-Dependent Gliding Motility in the Anaerobic Pathogen Clostridium perfringens

Clostridium perfringens is an anaerobic, gram-positive, spore-forming bacterium responsible for the production of severe histotoxic and gastrointestinal diseases in humans and animals. In silico analysis of the three available genome-sequenced C. perfringens strains (13, SM101, and ATCC13124) revealed that genes that encode flagellar proteins and genes involved in chemotaxis are absent. However, those strains exhibit type IV pilus (TFP)-dependent gliding motility. Since carbon catabolite regulation has been implicated in the control of different bacterial behaviors, we investigated the effects of glucose and other readily metabolized carbohydrates on C. perfringens gliding motility. Our results demonstrate that carbon catabolite regulation constitutes an important physiological regulatory mechanism that reduces the proficiencies of the gliding motilities of a large number of unrelated human- and animal-derived pathogenic C. perfringens strains. Glucose produces a strong dose-dependent inhibition of gliding development without affecting vegetative growth. Maximum gliding inhibition was observed at a glucose concentration (1%) previously reported to also inhibit other important behaviors in C. perfringens, such as spore development. The inhibition of gliding development in the presence of glucose was due, at least in part, to the repression of the genes pilT and pilD, whose products are essential for TFP-dependent gliding proficiency. The inhibitory effects of glucose on pilT and pilD expression were under the control of the key regulatory protein CcpA (catabolite control protein A). The deficiency in CcpA activity of a ccpA knockout C. perfringens mutant strain restored the expressions of pilT and pilD and gliding proficiency in the presence of 1% glucose. The carbon catabolite repression of the gliding motility of the ccpA mutant strain was restored after the introduction of a complementing plasmid harboring a wild-type copy of ccpA. These results point to a central role for CcpA in orchestrating the negative effect of carbon catabolite regulation on C. perfringens gliding motility. Furthermore, we discovered a novel positive role for CcpA in pilT and pilD expression and gliding proficiency in the absence of catabolite regulation. Carbon catabolite repression of gliding motility and the dual role of CcpA, either as repressor or as activator of gliding, are analyzed in the context of the different social behaviors and diseases produced by C. perfringens.

Severe Gastrointestinal Disease Due to HIV-1-Seronegative AIDS

An HIV-1 seronegative man presented with odynophagia, dysphagia, diarrhea, tenesmus and a 50-lb weight loss. A large esophageal ulcer and a rectal fissure were identified endoscopically. Stool samples and biopsy specimens from the esophageal ulcer, duodenum, colon and rectum were negative for pathogens. Seronegative AIDS was suspected, and high levels of HIV-1 mRNA (> 242,000 copies/mL) were detected. The esophageal ulcer responded to oral steroids and the HIV-1 infection to highly active anti-retroviral therapy (HAART). The virus isolated from the patient and an HIV-1 seropositive, asymptomatic, female sex worker with whom he had recently terminated a one-year heterosexual relationship showed sequence homology, indicating her as the source of his virus. The unusual presentation of severe gastrointestinal disease in an HIV-1 seronegative man with HIV-1 viremia underscores the importance of including AIDS in the differential diagnosis of wasting syndrome (i. e., B-type symptoms such as fever, night sweats, weight loss) in patients who are HIV-1 seronegative but at risk for AIDS.

European Mathematical Genetics Meeting, Heidelberg, Germany, 12th–13th April 2007

European Mathematical Genetics Meeting, Heidelberg, Germany, 12^th–13^th April 2007

Comparison of two methodologies for detection of Giardia spp. cysts and Cryptosporidium spp. oocysts in activated sludge samples from a sewage treatment plant in the city of Campinas, São Paulo State, Brazil

Giardia spp. and Cryptosporidium spp. are recognized worldwide as highly infectious protozoan parasites that can cause severe gastrointestinal disease in humans and animals. The detection of these pathogens in activated sludge samples becomes interesting since there is an increasing trend for the use of sewage sludge (biosolids) in agriculture. A total of 22 samples were collected and evaluated by means of Centrifugal - Concentration, followed or not followed by a purification process (ether clarification and sucrose flotation). Student t tests for comparison of the two procedures indicated a higher recovery rate of Giardia cysts with Centrifugal - Concentration; with regard to Cryptosporidium oocysts, no significant differences were found between the two methods, as only two samples were positive. The Centrifugal - Concentration procedure was shown to be the simplest and cheapest to perform, as emphasized by the efficiency recovery results.

Novel Targets Against Helicobacter Pylori : A Bioinformatic Approach

Evaluation of: Duckworth M, Menard A, Megraud F, Mendz GL: Bioinformatic analysis of Helicobacter pylori XGPRTase: a potential therapeutic target.Helicobacter 11, 287–295 (2006). Helicobacter pylori is a globally spread pathogen, with roughly 50% of the human population being contaminated. It causes severe gastrointestinal diseases, such as chronic gastritis, peptic ulcers and gastric cancer, which lead to significant morbidity and mortality. Much effort is dedicated by scientists to design alternative strategies to treat this infection, due to the widespread emergence of resistance to the presently used pharmacological agents. The xanthine–guanine phosphoribosyltransferase (XGPRTase) enzyme of H. pylori may be one of these targets, as the enzyme was recently purified, characterized and shown to be essential to the life cycle of the parasite. Duckworth and colleagues used a bioinformatic approach to investigate this target. The parasite enzyme has been compared with those present in various bacteria, archaea and eukaryotes, and its main features have been deduced by using conserved domain analysis, multiple sequence alignment and phylognetic analysis, as well as protein 3D modeling. However, significant findings did not emerge after this work for the design of XGPRTase inhibitors.

Allergic Subjects Have More Numerous Respiratory Infections and Severe Gastrointestinal Infections Than Non-Allergic Subjects: Preliminary Results

Allergic disorders are characterized by Th2-polarization, thus physiological Th1-dependent mechanisms for fighting infectious diseases (ID) may be defective. This study aims at evaluating the number and duration of respiratory (RI) and gastrointestinal diseases (GI) in allergic and non-allergic subjects in a particular community: the crew of an operative warship consisting of 189 persons (171 males and 18 females). The study period lasted for 5 months during an operative mission. The number and duration (days) of RI and GI were evaluated. Allergic subjects experienced more numerous RI (p=0.0029) and more severe GI (p=0.0001) than non-allergic subjects. This preliminary study provides evidence that allergic subjects may have more numerous RI and prolonged GI than non-allergic subjects.

Hepatic Portal Venous Gas: A Report of Two Cases and a Review of the Epidemiology, Pathogenesis, Diagnosis and Approach to Management

Hepatic portal venous gas (HPVG) is a rare condition that occurs when intraluminal gas and/or gas produced by intestinal bacteria enters the portal venous circulation. The most common precipitating factors include ischemia, intra-abdominal abscesses and inflammatory bowel disease. However, HPVG has recently been recognized as a rare complication of endoscopic and radiological procedures. Earlier studies advised immediate surgical intervention, but according to current recommendations, in some settings, HPVG can be managed conservatively. The present study reports two cases of HPVG; one that occurred following colonoscopy in a patient with severe Crohn's disease and one in a patient with graft-versus-host disease. The epidemiology, pathogenesis, diagnosis and management of HPVG are reviewed. Two case reports are presented, followed by the development of a management algorithm. Of the two patients that developed HPVG, one was an outpatient undergoing a colonoscopy for assessment of Crohn's disease activity and the other was an inpatient with graft-versus-host disease. Once the diagnosis of HPVG was made, both patients were managed conservatively with antibiotic therapy and management of their underlying disease. HPVG can occur in the setting of severe gastrointestinal disease states and following endoscopic procedures. It is critical that gastroenterologists are aware of the differential diagnosis, pathogenesis, diagnostic approach and management of HPVG.

Pregnancy-related diabetes mellitus in two dogs

CASE SUMMARIES: Two cases of diabetes mellitus occurring in bitches in association with pregnancy are reported. In the first case, a bitch with suspected acromegaly developed diabetes mellitus within 2 weeks of the due date. Despite insulin therapy, euglycaemia was not achieved. Tw o live, small pups were delivered by elective Caesarean section but died within 2 days. Signs consistent with acromegaly resolved but diabetes mellitus was permanent in the bitch. In the second case, diabetic ketosis with severe gastrointestinal disease was diagnosed 2 days after Caesarean section was performed due to dystocia. The pups delivered all died within 5 days. The bitch recovered fully from diabetes mellitus within 2 weeks and has remained euglycaemic without insulin for a period of at least 18 months. CLINICAL RELEVANCE: These two cases demonstrate that diabetes mellitus can occur in association with pregnancy in dogs, that diabetic ketosis can occur during transient diabetes mellitus in dogs, and suggest that acromegaly may occur during pregnancy-related dioestrus in dogs. The scarcity of previous reports of this nature, however, suggests that such cases are unusual. Lack of prompt resolution of hyperglycaemia may result in secondary diabetes mellitus becoming permanent. Management should focus on immediate insulin therapy or ovariohysterectomy to minimise this risk. Even mild hyperglycaemia should not be ignored during pregnancy. The insulin antagonistic effects of pregnancy, stressful illness, surgery and dystocia can be enough to result in diabetic ketosis in the absence of permanent insulin deficiency. Maternal hyperglycaemia may contribute to adverse fetal outcomes in dogs but further study is required regarding the nature of the risk.

Comparison of clinical history and dermatologic findings in 29 dogs with severe eosinophilic dermatitis: a retrospective analysis

The medical records and histopathological sections of 29 dogs diagnosed with a unique eosinophilic dermatitis resembling Wells' syndrome were reviewed in an attempt to elucidate the pathogenesis of this syndrome. The medical records were reviewed for information on dermatological lesion appearance, systemic signs in other organ systems, clinical analyte abnormalities, and drug therapy. Histological sections of dogs with moderate to severe eosinophilic dermatitis without folliculitis and furunculosis were reviewed and evaluated for the presence of collagen flame figures. Three categories of patients were found. Category 1 consisted of 17 dogs treated for vomiting and/or diarrhoea (often haematochezia or haematemesis) prior (mean: 4.6 days) to the onset of skin lesions. Fourteen category 1 dogs had erythematous lesions (macules, papules or plaques) that were most pronounced on the abdomen. Sixteen of the 17 dogs received multiple classes of drugs, and 59% were hypoalbuminemic. Category 2 consisted of five dogs that had skin lesions and gastrointestinal signs at presentation and four of these dogs were hypoalbuminemic. Category 3 included seven dogs without enteric illness. A positive drug score was found in six category 1 dogs and one each from categories 2 and 3. Eighteen cases had eosinophilic dermatitis without flame figures, seven cases had early flame figures and four had well-developed flame figures. These changes did not correlate with the categories of clinical presentation. More than 50% of the dogs developed eosinophilic dermatitis following treatment for severe gastrointestinal disease. The authors propose that this represents a unique syndrome that may have causal drug association.

Schistosomiasis mansoni and severe gastrointestinal cytomegalovirus disease in a patient with acquired immunodeficiency syndrome

The behavior of the Schistosoma mansoni infection in patients with AIDS has not been explored. The case of a young woman with schistosomiasis mansoni, AIDS, and cytomegalovirus disease is reported. The authors suggest that the helminth was not a bystander in this case, or rather, by interfering with the host's immune response, it set the stage for the development and/or aggravation of the viral infection.

Multiplex PCR for Direct Detection of Shiga Toxigenic Escherichia coli Strains Producing the Novel Subtilase Cytotoxin

We have recently described a novel AB5 subtilase cytotoxin produced by certain Shiga toxigenic Escherichia coli (STEC) strains. This potentially lethal toxin may contribute to severe gastrointestinal and systemic disease in humans. In this study we have developed a trivalent PCR assay for the detection of the novel toxin A subunit gene subA, as well as stx1 and stx2. The three primer pairs used in the assay do not interfere with each other and generate amplification products of 556, 180, and 255 bp, respectively. The assay can be used for determining the toxin genotype of STEC isolates, as well as for direct detection of toxin genes in primary fecal culture extracts.

Helicobacter pylori: current status and future prospects.

Helicobacter pylori is a global pathogen that causes severe gastrointestinal diseases leading to a significant morbidity and mortality. There is an effective treatment for peptic ulcer disease, however, this is being compromised by an increase in the prevalence of antibiotic resistance. Although alternative rescue regimens have been advocated, the best strategy would be to prevent disease, especially in the case of gastric cancer for which there is still no treatment. One approach is to inhibit the first step in the pathogenic process - adhesion of the organism to the host tissue. Another and probably a better approach is vaccination, but clinical trials have so far been unsuccessful. There is still a large uncertainty in relation to how H. pylori causes disease. Knowledge from genomics, proteomics, and the relationship between polymorphism of the bacterium and the host, as well as the continuing investigation of the role played by important virulence factors in the outcome of the disease, will help both in understanding pathogenesis of disease and in the design of the best vaccine.

Exploring how to tell the truth and preserve hope: can a balance between communication and empathy be calculated?

Background & Aims: When told the harsh truth about severe disease, a patient might despair and lose all hope. Without knowing the truth, however, the patient cannot participate in decision making and adjust life according to his illness. The present study aims to analyze the relationships between hope and truth in the decision on how much information to disclose to a patient with severe gastrointestinal disease. Methods: The decision analysis is based on the economic concepts of indifference curves and utility function. An inverse linear relationship exists between hope and truth; as more truth becomes revealed, the amount of hope declines. The utility function and the corresponding indifference curve of hope plotted versus truth describe the patient’s personal choices among different combinations of hope and truth. The optimal choice among various combinations of hope and truth corresponds with the point at which the inverse hope-truth line meets the indifference curve. Results: In situations in which hope drops steeply as more medical facts are being revealed, the utility to the patient is maximized with less truth being told. With a less pronounced truth-related decline in hope, utility is maximized at higher levels of truth, and, occasionally, utility is maximized only after all medical facts have been disclosed. The lesser the impact of truth on hope, the more truth is being tolerated. Conclusions: A caring gastroenterologist trying to optimize his/her patient’s well-being should try to assess the potential influence of truth on the patient’s psyche and dispense it accordingly.

Optimizing nutrition in cow's milk-sensitive enteropathy

Infants with severe gastrointestinal disease need adequate and optimized nutritional treatment, such as semi-elemental diets. We tested a renovated semi-elemental diet in 40 sick infants. In total, 533 l of New Alfare were consumed during 775 trial days. No serious adverse event occurred. The mean intake per infant was 85.8±26.8 kcal/kg per day or 122.5±38.3 ml/kg per day. Weight evolution during the 4-week trial was exactly within the expected normal range according to the Eurogrowth data, corresponding to the 50th percentile of the normal range. In addition, after 4 weeks of full oral feeding with New Alfare, the bone mineral index increased from 11.67 to 13.84 kg/m2 resulting in a significant increase of BMI-for-age Z-score (from −0.91±2.00 to −0.42±1.81; p=0.02). Nutritional parameters remained within normal ranges. The renovated Alfare is well tolerated and provides optimal nutrition.

Nutritional management of gastrointestinal disease

The gastrointestinal (GI) tract is primarily responsible for acquiring and digesting food, absorbing nutrients and water, and expelling wastes from the body as feces. A proper diet and normally functioning GI tract are integral for the delivery of nutrients, prevention of nutrient deficiencies and malnutrition, repair of damaged intestinal epithelium, restoration of normal luminal bacterial populations, promotion of normal GI motility, and maintenance of normal immune functions (eg, both tolerance and protection from pathogens). The amount of food, its form, the frequency of feeding, and the composition of diet each have important effects on GI function and may be used to help ameliorate signs of GI disease. Although both nutrients and nonnutritional components of a diet are important to GI health, they also may cause or influence the development of GI pathology (eg, antibiotic responsive diarrhea, inflammatory bowel disease, dietary intolerance, or sensitivity and/or allergy). The appropriate diet may have a profound effect on intestinal recovery and successful management of chronic or severe GI disease.

Development of an immunomagnetic separation-polymerase chain reaction (IMS-PCR) assay specific for Enterocytozoon bieneusi in water samples.

Microsporidia have become widely recognized as important human pathogens. Among Microsporidia, Enterocytozoon bieneusi is responsible for severe gastrointestinal disease. To date, no current therapy has been proven effective. Their mode of transmission and environmental occurrence are poorly documented because of the lack of detection methods that are both species-specific and sensitive. In this study, we developed a sensitive and specific molecular method to detect E. bieneusi spores in water samples. The molecular assay combined immunomagnetic separation (IMS) and polymerase chain reaction (PCR) amplification to detect E. bieneusi spores. A comparison was made of IMS magnetic beads coated with two different monoclonal antibodies, one specific for the Encephalitozoon genus that cross-reacts with E. bieneusi and the other specific only for the E. bieneusi species itself. Immunotech beads coated with the antibody specific for E. bieneusi were found to be the most effective combination. The highly specific IMS-PCR assay developed in this study provides a rapid and sensitive means of screening water samples for the presence of E. bieneusi spores.

High prevalence of toxin A-negative toxin B-positive Clostridium difficile in hospitalized patients with gastrointestinal disease

The incidence of Clostridium difficile toxin A-negative toxin B-positive in hospitalized patients with severe gastrointestinal disease was evaluated. Of 530 stool specimens tested in parallel by two immunoassay tests, Tox A and Tox A/B (TechLab, Inc., Blacksburg, VA), 422 produced negative results on both tests. One hundred eight specimens (20.4%) tested positive by Tox A/B assay, and only 47 of them were also positive by Tox A. The 61 specimens with discrepant results were confirmed to be positive for toxin B by tissue culture cytotoxicity assay. Furthermore, 3 of the 422 specimens that were negative by enzyme immunoassay tested positive by cytotoxicity assay. The sensitivity and specificity of the Tox A/B test were 95.3% and 100%, respectively, with negative and positive predictive values of 99.3% and 100%, respectively, and a correlation rate of 99.4%. The high prevalence (56.5%) of specimens from symptomatic patients having detectable toxin B, but undetectable toxin A emphasizes the importance of using diagnostic tests that include toxin B. Furthermore, our data support the potential role of toxin B in the pathogenesis of toxigenic Clostridium difficile.