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At least 415 records · Page 23Linked to original sources
PubMed2003

Mouse models for genetic dissection of polygenic gastrointestinal diseases.

Many diseases with a major public health impact are the result of complex interactions between environmental factors and multiple genes. In the past decade, methods for genome analysis, in particular quantitative trait locus (QTL) analysis in animal models, were developed to identify and localize the genes responsible for multifactorial (polygenic) diseases; QTL analysis is based on experimental crosses between inbred strains with high and low genetic susceptibility. Recently the genes underlying several QTLs could be cloned successfully. Here we describe the impact of these genomic approaches in mice on our understanding of the multifactorial genetics of three gastrointestinal diseases related to metabolism (cholesterol cholelithiasis), development (gastroschisis), and colorectal cancer. The examples demonstrate how mouse models continue to be an invaluable tool in unravelling complex pathomechanisms and unlocking our understanding of human diseases.

Animals↗
PubMed1985

The effect of insulin infusion on whole-body protein metabolism in patients with gastrointestinal disease fed parenterally.

The effect of insulin infusion on whole-body protein metabolism was studied in six non-diabetic patients with gastrointestinal disease receiving constant total parenteral feeding, with each patient as his own control. Insulin added to the parenteral feed significantly raised the plasma insulin concentration and lowered the blood glucose. With insulin infusion there was a significant increase in the rates of urea output and ammonia excretion, but no change in 3-methylhistidine excretion or in the urinary 3-methylhistidine/creatinine ratio. Studies of whole-body protein turnover were performed with a tracer injection of 15N-glycine and both urea and ammonia as end products. Without insulin urea as end product gave an estimate of flux 18 per cent greater than that given by ammonia. With both end products rates of whole-body protein synthesis were significantly greater than rates of breakdown. When insulin was infused the estimate of flux from ammonia increased significantly, resulting in close agreement with the estimate from urea, and there was no longer a significant difference between rates of whole-body protein synthesis and breakdown. Our data, taken with the results of other studies, suggest that insulin infusion is not beneficial as a means of increasing nitrogen retention in non-diabetic parenterally-fed patients.

Adult↗
PubMed2005

Association of beta2 toxin production with Clostridium perfringens type A human gastrointestinal disease isolates carrying a plasmid enterotoxin gene.

Clostridium perfringens type A isolates carrying an enterotoxin (cpe) gene are an important cause of human gastrointestinal diseases, including food poisoning, antibiotic-associated diarrhoea (AAD) and sporadic diarrhoea (SD). Using polymerase chain reaction (PCR), the current study determined that the cpb2 gene encoding the recently discovered beta2 toxin is present in <15% of food poisoning isolates, which typically carry a chromosomal cpe gene. However, >75% of AAD/SD isolates, which usually carry a plasmid cpe gene, tested cpb2(+) by PCR. Western blot analysis demonstrated that >97% of those cpb2(+)/cpe(+) AAD/SD isolates can produce CPB2. Additional PCR analyses, sequencing studies and pulsed field gel electrophoresis experiments determined that AAD/SD isolates carry cpb2 and cpe on the same plasmid when IS1151 sequences are present downstream of cpe, but cpb2 and cpe are located on different plasmids in AAD/SD isolates where IS1470-like sequences are present downstream of cpe. Those analyses also demonstrated that two different CPB2 variants (named CPB2h1 or CPB2h2) can be produced by AAD/SD isolates, dependent on whether IS1470-like or IS1151 sequences are present downstream of their cpe gene. CPB2h1 is approximately 10-fold more cytotoxic for CaCo-2 cells than is CPB2h2. Collectively, these results suggest that CPB2 could be an accessory toxin in C. perfringens enterotoxin (CPE)-associated AAD/SD.

Amino Acid Sequence↗
PubMed2006

Complete sequencing and diversity analysis of the enterotoxin-encoding plasmids in Clostridium perfringens type A non-food-borne human gastrointestinal disease isolates.

Enterotoxin-producing Clostridium perfringens type A isolates are an important cause of food poisoning and non-food-borne human gastrointestinal diseases, e.g., sporadic diarrhea (SPOR) and antibiotic-associated diarrhea (AAD). The enterotoxin gene (cpe) is usually chromosomal in food poisoning isolates but plasmid-borne in AAD/SPOR isolates. Previous studies determined that type A SPOR isolate F5603 has a plasmid (pCPF5603) carrying cpe, IS1151, and the beta2 toxin gene (cpb2), while type A SPOR isolate F4969 has a plasmid (pCPF4969) lacking cpb2 and IS1151 but carrying cpe and IS1470-like sequences. By completely sequencing these two cpe plasmids, the current study identified pCPF5603 as a 75.3-kb plasmid carrying 73 open reading frames (ORFs) and pCPF4969 as a 70.5-kb plasmid carrying 62 ORFs. These plasmids share an approximately 35-kb conserved region that potentially encodes virulence factors and carries ORFs found on the conjugative transposon Tn916. The 34.5-kb pCPF4969 variable region contains ORFs that putatively encode two bacteriocins and a two-component regulator similar to VirR/VirS, while the approximately 43.6-kb pCPF5603 variable region contains a functional cpb2 gene and several metabolic genes. Diversity studies indicated that other type A plasmid cpe+/IS1151 SPOR/AAD isolates carry a pCPF5603-like plasmid, while other type A plasmid cpe+/IS1470-like SPOR/AAD isolates carry a pCPF4969-like plasmid. Tn916-related ORFs similar to those in pCPF4969 (known to transfer conjugatively) were detected in the cpe plasmids of other type A SPOR/AAD isolates, as well as in representative C. perfringens type B to D isolates carrying other virulence plasmids, possibly suggesting that most or all C. perfringens virulence plasmids transfer conjugatively.

Clostridium Infections↗
PubMed1999

Whipple endocarditis without overt gastrointestinal disease: report of four cases.

BACKGROUND: Cardiac manifestations of Whipple disease are rarely diagnosed before death. OBJECTIVE: To describe four patients with endocarditis caused by Tropheryma whippelii who did not have overt gastrointestinal disease. DESIGN: Case series. SETTING: Five hospitals in eastern Switzerland. PATIENTS: Three men and one woman undergoing replacement of insufficient heart valves. MEASUREMENTS: Histologic characteristics of heart valves and intestinal biopsy; broad-range and specific polymerase chain reaction for T. whippelii. RESULTS: Tropheryma whippelii was found in the heart valves (three aortic valves and one mitral valve) of four patients with culture-negative endocarditis necessitating valve replacement. All patients had arthralgia for different lengths of time. Only one patient had mild gastrointestinal symptoms. Histologic characteristics of intestinal mucosa were normal in all patients, and polymerase chain reaction on intestinal biopsy was positive for T. whippelii in only one patient, who did not have diarrhea. In all patients, arthralgia resolved promptly after institution of antibiotic therapy. Disease did not recur in any patient after prolonged antibiotic therapy with cotrimoxazole. CONCLUSION: In patients with culture-negative endocarditis, the absence of clinical, microscopic, or microbiological evidence of gastrointestinal disease did not rule out T. whippelii.

Actinobacteria↗
PubMed1998

Enteral feeding in critical care, gastrointestinal diseases, and cancer.

This article discusses the many advantages and changes that have occurred in the nutritional management of critically-ill patients, patients with gastrointestinal diseases, and patients with selected cancers. Mechanical obstruction is the only absolute contraindication to enteral nutrition. This article reviews the present aggressive approach to the use of enteral nutrition.

Contraindications↗
PubMed1992

Prevalence of upper gastrointestinal disease in relation to age: radiologic and clinical implications.

Reports of 1126 endoscopies were reviewed to determine the age-related prevalence of upper gastrointestinal (UGI) diseases as a guide to radiologists performing UGI examinations. Results indicate that (1) there were positive findings in 78% of all endoscopic examinations, and thus most symptomatic patients can be expected to have at least one UGI abnormality; (2) many patients with UGI symptoms have two or more reportable disease processes; (3) the prevalence of serious or life-threatening disease, such as cancer or large ulcers, rises steadily with age; and (4) after age 60, approximately 60% of symptomatic patients have a serious UGI disease. Based on these findings, radiologists should not hesitate to make the diagnosis of multiple abnormalities and should expect to diagnose at least one abnormality in most symptomatic patients having an UGI study. Also, because of the high prevalence of serious lesions in the elderly, endoscopy should be considered for the initial examination of an elderly patient if poor physical status would render the radiologic examination difficult or unreliable.

Adolescent↗
PubMed1987

Primary prevention of gastrointestinal diseases.

In the belief that available information can provide reasonable guidance, we review the evidence identifying factors which increase or decrease the risk of developing several gastrointestinal diseases. In the absence of controlled studies, we review case control and other studies. As results from animal studies cannot be readily transferred to humans, we interpret them cautiously. We recommend appropriate personal behavior to reduce risk when they seem reasonably justified by the evidence.

Alcohol Drinking↗
PubMed1998

Immaturity of gastrointestinal host defense in newborns and gastrointestinal disease states.

Not only is the gastrointestinal tract the largest immune organ in the body, but it also contains one of the most important and interesting immunologic compartments. Host protection against pathogens and injurious agents by the gastrointestinal tract is essential for an individual's survival. The intestinal mucosal immune system, which is linked with other mucosal surfaces and together represents the common mucosal immune system, prevents the passage of potentially harmful antigens and pathogens into the systemic circulation of the host. In a healthy host, antigens crossing the mucosal barrier in physiologic quantities evoke the appropriate immune response, which includes polymeric IgA antibody production to the antigen and systemic tolerance.

Animals↗
PubMed2000

[Intraluminal sonography in the diagnosis of gastrointestinal diseases].

Endosonography is an imaging method whereby a high frequency ultrasound probe is inserted into a body cavity with or without under endoscopic control. Examination of the gastrointestinal tract is performed using special echo-endoscopes or trans-endoscopic mini-probes. The gastrointestinal wall, mediastinum, pancreas, bile ducts, retroperitoneum, and other structures surrounding the gastrointestinal tract are target organs for endosonography. A detailed image of pathological processes can thus be obtained. The method can be used both for primary diagnosis of lesions and in follow-up of gastrointestinal diseases. It is accurate in local staging of cancer and in detecting small lesions. There are some limitations for optimal examination like stenoses or other factors prohibiting a precise positioning of the ultrasound transducer. The clinical importance of endo-sonographic examinations must be continuously evaluated on the basis of new technical modalities and changes in therapeutic procedures.

Endosonography↗
PubMed1978

Upper gastrointestinal disease in chronic renal failure. A prospective evaluation.

A prospective study was undertaken to determine the incidence of upper gastrointestinal disease in 85 chronic renal failure (CRF) patients on hemodialysis. Upper gastrointestinal x-rays were obtained for 83 patients, and enlarged gastric and duodenal folds were seen in 12% (10/83) and 42% (35/83) of the cases, respectively. Panendoscopy performed on 60 persons revealed gastritis in 22% (13/60), nodular duodenitis in 60% (35/60), and esophagitis in 13% (8/60). No peptic ulcers were identified either radiologically or endoscopically. Pathologic examination of mucosal biopsy specimens demonstrated gastritis in 46% (21/46) and duodenitis in 43% (22/51) of patients. A highly significant correlation was found between endoscopic and radiologic duodenitis (P less than .0001) and also between endoscopic and pathologic duodenitis. We have demonstrated a high incidence of mucosal inflammation but not ulcer disease in CRF patients. These lesions may predispose these individuals to gastrointestinal bleeding following renal transplantation.

Adolescent↗
PubMed2006

Review article: modulation of the brain-gut axis as a therapeutic approach in gastrointestinal disease.

BACKGROUND: The importance of bi-directional brain-gut interactions in gastrointestinal illness is increasingly being recognized, most prominently in the area of functional gastrointestinal disorders. Numerous current and emerging therapies aimed at normalizing brain-gut interactions are a focus of interest, particularly for irritable bowel syndrome and functional dyspepsia. METHODS: A literature search was completed for preclinical and clinical studies related to central modulation of gastrointestinal functions and published in English between 1980 and 2006. RESULTS: Existing data, while sparse, support the use of different classes of antidepressant drugs, including tricyclics, and selective and non-selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin receptor agonists and antagonists with peripheral and possibly central effects are effective in treating specific subtypes of irritable bowel syndrome. Based largely on theoretical and preclinical evidence, several novel compounds that selectively target receptors at multiple levels within the brain-gut axis such as neurokinin, somatostatin and corticotropin-releasing factor receptor antagonists are promising. CONCLUSIONS: This review discusses the rationale for modulation of the brain-gut axis in the treatment of functional gastrointestinal disorders and highlights the most promising current and future therapeutic strategies.

Adrenergic alpha-Agonists↗
PubMed1976

Histamine and peptic ulcer: a prospective study of mucosal histamine concentration in duodenal ulcer patients and in control subjects suffering from various gastrointestinal diseases.

In a prospective study the histamine content of the mucosa of the body of the stomach was measured in 100 patients consisting of control subjects, patients with duodenal ulcer and patients suffering from various gastrointestinal diseases. The histamine content was found to be 43 mug/g in male control subjects (median) while in duodenal ulcer patients levels attained were significantly lower by about 30 per cent. In all the other groups of patients histamine concentrations in gastric mucosa were found to be "normal". Since in most species it is extremely diffcult to alter the mucosal histamine concentration by any form of treatment, the diminished histamine content of the gastric mucosa in patients with duodenal ulcer seems remarkable. Among several possible explanations offered for this finding we think the most likely is that histamine release is increased in duodenal ulcer disease.

Duodenal Ulcer↗