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New enteric vaccines: application of new knowledge of receptors and recognition in enteric infections.

Advances in understanding of the "receptors and recognition" mechanisms of virulence factors of enteric pathogens have been important in the development of enteric vaccines. Sophisticated techniques of molecular biology have proved essential to this endeavour. This review summarizes progress in development of vaccines against disease due to Vibrio cholerae, Escherichia coli, Salmonella typhi, Shigella and rotavirus enteric infections. All of these vaccines are undergoing, or are about to undergo, field trials.

Animals↗

Mucosal immunity: an overview and studies of enteric and respiratory coronavirus infections in a swine model of enteric disease.

Based on the tenet of a common mucosal immune system, antigenic stimulation at one mucosal site results in the distribution of antigen-specific IgA precursor cells to distant mucosal sites. However, recent studies suggest that functional compartmentalization and limited reciprocity may exist within some components of the common mucosal immune system. Although oral immunization is often very effective in inducing immunity to respiratory pathogens, the converse (respiratory immunization to prevent enteric diseases) may not be as effective. To address this question and to study interactions between the bronchus-associated (BALT) and gut-associated (GALT) lymphoid tissues related to protective immunity, we used as a model two antigenically related porcine coronaviruses which replicate primarily in the intestine (transmissible gastroenteritis virus, TGEV) or respiratory tract (porcine respiratory coronavirus, PRCV). The tissue distribution and magnitude of the antibody secreting cell (ASC) responses (measured by ELISPOT) and cell-mediated immune responses (measured by lymphoproliferative assays, LPA) coincided with the viral tissue tropisms. Immunization via GALT (gut infection with TGEV) elicited high numbers of IgA ASC and high LPA responses in GALT (gut lamina propria, LP or mesenteric lymph nodes, MLN), but lower responses in BALT (bronchial lymph nodes, BLN) and induced complete protection against enteric TGEV challenge. In contrast immunization via BALT (respiratory infection with PRCV) elicited systemic type responses (high numbers of IgG ASC in the BLN), but few ASC and low LPA responses in the gut LP or MLN and induced only partial protection against enteric TGEV challenge. Thus administration of vaccines intranasally may not be optimally effective for inducing intestinal immunity in contrast to the reported efficacy of oral vaccines for inducing respiratory immunity.

Administration, Intranasal↗

Enteric viruses and diarrhea in HIV-infected patients. Enteric Opportunistic Infections Working Group.

BACKGROUND: Diarrhea occurs frequently among persons with the acquired immunodeficiency syndrome, but the cause often remains unknown. We used a group of diagnostic assays to determine which viruses were etiologic agents of diarrhea in a group of persons infected with the human immunodeficiency virus (HIV). METHODS: Stool and serum specimens were obtained from HIV-infected patients enrolled in a longitudinal study in Atlanta. Fecal specimens from patients with diarrhea and from control patients without diarrhea were screened by electron microscopy, polyacrylamide-gel electrophoresis, and enzyme immunoassays for rotaviruses, enteric adenoviruses, caliciviruses, picobirnaviruses, and astroviruses. Paired serum samples were tested for antibody responses to Norwalk virus and picobirnavirus. RESULTS: Viruses were detected in 35 percent of 109 fecal specimens from patients with diarrhea but in only 12 percent of 113 specimens from those without diarrhea (P < 0.001). Specimens from patients with diarrhea were more likely than those from patients without diarrhea to have astrovirus (12 percent vs. 2 percent, P = 0.003); picobirnavirus (9 percent vs. 2 percent, P = 0.017); caliciviruses, including small round structured viruses (6 percent vs. 1 percent, P = 0.062); and adenoviruses (9 percent vs. 3 percent, P = 0.047). They were also more likely to have a mixed viral infection (6 percent vs. 0 percent, P = 0.006). With the use of polyacrylamide-gel electrophoresis to analyze concentrated RNA extracts from stool, picobirnavirus was detected in fecal specimens from 6 of the 65 patients with diarrhea and was associated with prolonged viral shedding and chronic diarrhea. No rotaviruses, enteric adenoviruses, or instances of seroconversion to positivity for Norwalk virus were observed. CONCLUSIONS: Novel enteric viruses such as astrovirus and picobirnavirus may be more important etiologic agents of diarrhea in HIV-infected patients than previously recognized and may be more common than either bacterial or parasitic enteropathogens.

Adenoviruses, Human↗

A prospective comparison of simultaneous kidney-pancreas transplantation with systemic-enteric versus portal-enteric drainage.

OBJECTIVE: To compare pancreas transplantation with systemic-enteric (SE) versus portal-enteric (PE) drainage in a prospective fashion. SUMMARY BACKGROUND DATA: To improve the physiology of pancreas transplantation, the authors developed a new technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions. METHODS: During a 26-month period, the authors prospectively alternated 54 consecutive simultaneous kidney and pancreas transplants to either SE (n = 27) or PE (n = 27) drainage. The two groups were well matched for numerous characteristics. Maintenance immunosuppression in both groups consisted of tacrolimus, mycophenolate mofetil, and steroids. RESULTS: Patient survival rates were 93% SE versus 96% PE; kidney graft survival rates were 93% in both groups. Pancreas transplantation survival (complete insulin independence) was 74% after SE versus 85% after PE drainage with a mean follow-up of 17 months. The mean length of initial hospital stay was 12.4 days in the SE group and 12.8 days in the PE group. The SE group was characterized by a slight increase in the number of readmissions. The incidences of acute rejection (33%) and major infection (52%) were similar in both groups. The incidence of intraabdominal infection was slightly higher in the SE group. However, the early relaparotomy rate was similar between groups. The composite endpoint of no rejection, graft loss, or death was attained in 56% of SE versus 59% of PE patients. CONCLUSIONS: These results suggest that simultaneous kidney and pancreas transplantation with SE or PE drainage can be performed with comparable short-term outcomes.

Adult↗

A circulating exogenous protein can enter enteric nervous tissue in the rat.

Previous studies of the permeation of circulating protein tracers yielded conflicting results in the enteric nervous system. We show that within 5 min of intravenous injection, horseradish peroxidase (HRP) enters all the extracellular spaces of the ganglia and connecting strands of the submucous and myenteric plexuses of the rat's small intestine, including the clefts between neuroglial cells and neurons. The tracer is still there after 10 min, but is nearly all gone 30 min after injection. Enteric neurons, like others with somata in peripheral ganglia, are therefore probably accessible to plasma proteins and to substances with smaller molecules that are protein-bound when circulating in the blood.

Animals↗

A new plating medium for the isolation of enteric pathogens. II. Comparison of hektoen enteric agar with SS and EMB agar.

During this study, 2,855 stool specimens from patients at Cook County Hospital were cultured for enteric pathogens. Hektoen Enteric Agar (HE) was compared with E M B and S S Agars by replicate samplings with both direct and indirect methods. Shigella species were recovered more than twice as often on HE Agar as on S S Agar by both methods. With the direct method only, out of 98 Shigella isolated, 97 were isolated from HE Agar, 74 were recovered from E M B Agar, and 40 were found on S S Agar. In addition, HE yielded better isolation of Salmonella strains than did S S or E M B by either direct or indirect methods. The greater efficiency of HE medium is discussed with respect to colonial recognition of enteric pathogens.

Agar↗

Ins and outs of enteral access. Part 1: short-term enteral access.

Proper selection of the type of enteral access in a given clinical situation is important to maximize the benefit to the patient and minimize the discomfort to the patient, the morbidity and mortality, and the cost. This decision is based on whether or not the patient needs short-term (<4-6 weeks) or long-term enteral nutrition support. This article focuses on short-term access including nasogastric (NG) and nasoenteric (NE) tubes and reviews each of these enteral access tubes along with their indications, contraindications, advantages, and disadvantages.

Journal Article↗

Postoperative enteral hyperalimentation for cryptosporidial acute cholecystitis associated with AIDS and enteritis.

A homosexual youth presented with undiagnosed acute cryptosporidial cholecystitis, a fever of 102.8 degrees F and a WBC of 3500/mm3. This was preceded by several months of watery diarrhea and 20% weight loss. Following cholecystectomy, G-I function was maintained by efficient esophageal aspiration of swallowed air, with simultaneous immediate duodenal feeding of elemental diet. He absorbed 160 g amino acids and 4200 kcal, and was safely self-sufficient when discharged 26 hours postoperatively. Reappearance of the persistent cryptosporidial enteritis was followed by diagnoses of the offending organism and the associated AIDS. He failed to respond to specific spiramycin therapy, and 8 months after cholecystectomy he succumbed to pneumocystis carinii pneumonia. For this malnourished and particularly vulnerable patient, preservation of postoperative G-I function and its exploitation for enteral support may have been essential to enhance "immune competence" and lead to a remarkably smooth and rapid recovery.

Acquired Immunodeficiency Syndrome↗

Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis.

A randomized, controlled clinical trial investigated the effect of early enteral nutrition (EN) on intestinal permeability, intestinal protein loss, and outcome in parvoviral enteritis. Dogs were randomized into 2 groups: 15 dogs received no food until vomiting had ceased for 12 hours (mean 50 hours after admission; NPO group), and 15 dogs received early EN by nasoesophageal tube from 12 hours after admission (EEN group). All other treatments were identical. Intestinal permeability was assessed by 6-hour urinary lactulose (L) and rhamnose (R) recoveries (%L, %R) and L/R recovery ratios. Intestinal protein loss was quantified by fecal alpha1-proteinase inhibitor concentrations (alpha1-PI). Median time to normalization of demeanor, appetite, vomiting, and diarrhea was 1 day shorter for the EEN group for each variable. Body weight increased insignificantly from admission in the NPO group (day 3: 2.5 +/- 2.8%; day 6: 4.3 +/- 2.3%; mean +/- SE), whereas the EEN group exhibited significant weight gain (day 3: 8.1 +/- 2.7%; day 6: 9.7 +/- 2.1%). Mean urinary %L was increased, %R reduced, and L/R recovery ratios increased compared to reference values throughout the study for both groups. Percent lactulose recovery decreased in the EEN group (admission: 22.6 +/- 8.0%; day 6: 17.9 +/- 2.3%) and increased in the NPO group (admission: 11.0 +/- 2.6%; day 6: 22.5 +/- 4.6%, P = .035). Fecal alpha1-PI was above reference values in both groups and declined progressively. No significant differences occurred for %R, L/R ratios, or alpha1-PI between groups. Thirteen NPO dogs and all EEN dogs survived (P = .48). The EEN group showed earlier clinical improvement and significant weight gain. The significantly decreased %L in the EEN versus NPO group might reflect improved gut barrier function, which could limit bacterial or endotoxin translocation.

Animals↗

A comparison of enteric coated microspheres with enteric coated tablet pancreatic enzyme preparations in cystic fibrosis. A controlled study.

A comparative study of the efficacy of pH sensitive enteric coated microspheres (ECM) with an enteric coated tablet (ECT) pancreatic enzyme preparation was carried out in 20 children with cystic fibrosis in a double-blind double-placebo crossover manner. Steatorrhoea was assessed by 3 day faecal fat analysis and dosage of medication, stool frequency and consistency; abdominal pain and appetite were documented by a patient-kept diary card. ECM controlled steatorrhoea (11.8 +/- 9.2 g vs 23.2 +/- 18.9 g, P less than 0.02), stool frequency (1.7 +/- 0.6 vs 2.1 +/- 0.9, P less than 0.01) and abdominal pain (8.8 +/- 13.8 vs 23.4 +/- 24.1, P less than 0.05) significantly better than ECT. Out of 20 patients 17 preferred ECM to ECT (P less than 0.00036). ECM preparations should allow more satisfactory dietary management of patients with cystic fibrosis with longterm beneficial effect.

Adolescent↗

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group.

OBJECTIVES: Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS. DESIGN: Prospective, multicentered, double-blind, randomized controlled trial. SETTING: Intensive care units of five academic and teaching hospitals in the United States. PATIENTS: We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study. INTERVENTIONS: Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015). CONCLUSIONS: The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Antioxidants↗

Enteric-coated pancreatic enzyme with bicarbonate is equal to standard enteric-coated enzyme in treating malabsorption in cystic fibrosis.

OBJECTIVES: To compare the efficacy of an enteric-coated buffered pancreatic enzyme (EC buffered PE) containing 1.5 mEq of bicarbonate per capsule with a conventional enteric-coated enzyme (EC-PE) capsule in cystic fibrosis patients with signs or symptoms of moderate to severe malabsorption. METHODS: In a double-blind crossover study, subjects were randomly assigned to two consecutive, 2-week phases using an EC buffered PE product and conventional EC-PE product. Seventy-two hour stool collections from each phase were analyzed for energy, fat, and nitrogen content and expressed as percent of estimated intake. RESULTS: Twenty-one patients with cystic fibrosis and pancreatic insufficiency (14 female, mean age 20.6 +/- 11.5 years, range 8.8-41.9) completed the study. There was no significant difference in percent malabsorption of energy (19.4% vs. 19.0%), fat (20.7% vs. 20.2%), or nitrogen (10.4% vs. 10.7%) between the EC buffered PE product and the conventional EC-PE product. However, patients taking the EC buffered PE product received less enzyme based on actual enzyme activity measured in vitro (3,468 +/- 1,434 U lipase/g fat vs. 3,978 +/- 1,474 U lipase/g fat, P < 0.02). CONCLUSIONS: In the doses used, nutrient absorption of patients taking EC buffered PE preparation offers no advantage over a conventional EC-PE preparation.

Adolescent↗

[A clinical experience of rokitamycin on Campylobacter enteritis. Research Group of Rokitamycin on Infectious Enteritis].

Rokitamycin, a newly developed macrolide, was administered to a total of 107 cases, 16 years old or more, in order to evaluate its clinical efficacy, safety and usefulness on Campylobacter enteritis. Daily dosage of 600 mg of rokitamycin was administered orally in three divided doses for 5 days. Bacteriological and clinical efficacies were judged by the attending doctors from the evaluation criteria made by the committee and from the days required for improvement of diarrhea, defervescence and so on, respectively. Antibacterial activities against the isolates were tested of rokitamycin (RKM), erythromycin (EM), josamycin (JM) and ofloxacin (OFLX). The results were as follows; 41 symptomatic patients and 5 carriers were evaluated. Clinical efficacy (n = 41) was 100% (excellent; 34.1%, good; 65.9%). Bacteriological efficacy (n = 41) was 97.6%. Eight of the 9 cases with consecutive stool cultures were free of the bacteria on and after one day of the drug administration. Clinical usefulness (n = 46) was 97.8%. Slight epigastric pain was seen in only one as a side effect. The items of abnormal laboratory findings were 4 elevated GPT and/or GOT and one increased number of WBC in 4 cases. MIC90 of RKM, EM, JM and OFLX against 41 clinical isolates of C. jejuni were 1.56, 3.13, 3.13 and 0.78 micrograms/ml, respectively. Rokitamycin was considered clinically useful to treat Campylobacter enteritis.

Adolescent↗

[Basic and clinical studies of pazufloxacin on infectious enteritis research group of T-3761 on infectious enteritis].

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

4-Quinolones↗

Effect of early postoperative enteral feeding on the healing of colonic anastomoses in rats. Comparison of three different enteral diets.

This experimental study compares the effects of early postoperative administration of three enteral diets of different compositions on the healing of colonic anastomoses. Sixty Wistar rats were subjected to colonic anastomoses. Following surgery, the rats were randomly allocated to four groups of 15 each. The rats in control group A received an electrolyte and glucose solution, the rats in group B received a complete balanced nutrition, in group C a complete balanced nutrition supplemented with fiber and in group D an isocaloric specialized elemental nutrition enriched with glutamine. The rats were sacrificed on day 7 following operation. Rupture of the anastomosis was higher in rats of the control group compared to the other three groups. Adhesion formation was more extensive in group A in comparison to the other three groups. The anastomotic bursting pressures were statistically significantly higher in groups C and D compared to the other two groups (p < 0.05). There was no statistically significant difference between group C and D (p > 0.05) while a statistically significant difference was noted between group B and group A (p < 0.05). Histological examination showed more profound inflammatory reaction in group A compared to the other three groups. There was also a statistically significant difference between group B and groups C and D while inflammatory reaction was of no statistically significant difference between group C and group D. Healing of the anastomoses was statistically significantly impaired in group A compared to the other three groups. There was no statistically significant difference between group C and group D while a statistically significant difference was found between group B and groups C and D. In conclusion, early postoperative enteral feeding improves healing of experimental colonic anastomoses in rats. This effect was more evident when fiber-supplemented diets or diets enriched with glutamine were administered.

Anastomosis, Surgical↗

Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated and standard formulations.

Enteric coated naproxen (Nycopren) was compared with standard naproxen in a double blind comparative trial of 348 patients with either rheumatoid or osteoarthritis. There were slightly fewer gastric side effects and slightly fewer withdrawals because of side effects in the enteric coated naproxen group but the differences did not reach statistical significance. There was no significant difference in the efficacy of the two formulations. A satisfaction index was used to assess the therapeutic ratio with visual analogue scales assigned to both efficacy and side effects. The scale performed as intended and is worthy of further exploration.

Adult↗

Efficacy of avirulent hemorrhagic enteritis virus propagated in turkey leukocyte cultures for vaccination against hemorrhagic enteritis in turkeys.

Avirulent hemorrhagic enteritis virus (HEV-A) propagated in turkey leukocyte cell culture was tested as a vaccine to prevent hemorrhagic enteritis (HE) in turkeys in experimental and field trials. Immunization of turkeys with live HEV-A resulted in protection against a challenge with virulent HEV (HEV-V) as measured by the serological response and the absence of clinical disease and HEV antigen in spleens. In field trials, 19 out of 20 flocks seroconverted within 21 days after vaccination with live HEV-A distributed in the drinking water. The average immune response of the turkeys in these flocks was 96%. Most importantly, neither clinical HE nor other adverse effects caused by HEV-A vaccination were observed in any of the vaccinated flocks. Because maternal antibodies can interfere with the immune response to the vaccine, the optimum time for vaccination was determined. Using an established half-life value of 4.25 days for turkey antibody, and knowing the enzyme-linked immunosorbent assay titer of the maternal antibodies and age of the turkey, the time of vaccination could be calculated taking into account that maternal antibody titers should be lower than 40 to vaccinate the turkeys successfully and induce protection. In vivo tests with HEV-A preparations confirmed the replication of the virus in turkey leukocyte cultures and the potential to pass it in culture. Furthermore, in vivo analysis showed that most infectious virus was associated with preparations of the nonadherent cell population, confirming the results obtained by in vitro analysis. The potency of HEV-A preparations was dependent on the production method and varied from an average of 570 to 8135 doses per ml.

Adenoviridae↗