Gastrointestinal secretory immunologic system in health and disease.
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Agammaglobulinemia↗
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The selective recognition of antibody IgY for digestive system cancers.
Biological methods for cancer therapies are very important. A small and efficient target carrier is the key component for anti-cancer drugs. In our laboratory, the antibody IgY was extracted from egg yolk of a SPF hen. The SPF hen was immunized with an antigene of P110 protein which was purified from human stomach cancer MGC-803 cells. Results indicated that the antibody IgY can specifically recognize gastrointestinal system cancers. It may become an important carrier for antitumorigenic drugs.
Adenocarcinoma↗
[Use of SGOL-1-40 milk whey in the complex therapy of patients with acute chemical poisoning and burns of the gastrointestinal tract].
The use of "SGOL-1-40" milk whey in complex therapy of patients with acute chemical poisonings and their complications has been investigated. "SGOL-1-40" was prescribed twice per day with the dose of 1.5 g/kg of patient weight. On the 5th-6th day after therapy start the general state of patients improved; in the control group it happened on the 10th-12th day. It is ascertained that the ceasing of pneumonia takes place average 3 days earlier than usual. The lessening of endotoxicosis symptoms and the improvement of the patients state with chemical burns of gastrointestinal system went on more quickly.
Adult↗
Gastrointestinal manifestations of systemic vasculitis.
Systemic vasculitis is known to affect the gastrointestinal tract but the nature of the complication is poorly characterized. Out of 65 patients with systemic vasculitis, the majority of whom had renal disease, the intestine was found to be affected in 18. These comprised four of eight patients with polyarteritis nodosa, nine of seventeen with microscopic polyarteritis, four of thirty-six with Wegener's granulomatosis and one of four with Churg-Strauss syndrome. The features included abdominal pain (85 per cent), diarrhoea (50 per cent), gut haemorrhage (44 per cent) and abnormal liver function tests (50 per cent). Manifestations of gastrointestinal disease were evident at presentation in half the patients and led to a fetal outcome in five. Ileus, mucosal abnormalities, perforation and slow transit were evident radiographically, and selective visceral angiography showed aneurysms or organ infarcts in five patients. Histological assessment of gut biopsies (chiefly rectal) revealed non-specific inflammation or ulceration in nine patients and intramucosal haemorrhage in two. Focal areas of necrosis and ulceration in colonoscopic biopsies were highly suggestive of vasculitis whereas arteritis was only found in one full thickness biopsy. Hence the diagnosis of gastrointestinal complications depends largely on clinical evidence. In patients who survived, the gastrointestinal features remitted as the systemic illness improved following treatment with steroids, cyclophosphamide or plasma exchange.
Abdomen↗
Effects of BIBN4096BS on cardiac output distribution and on CGRP-induced carotid haemodynamic responses in the pig.
Calcitonin gene related peptide (CGRP) seems to be involved in the pathogenesis of migraine, since plasma CGRP levels increase during the headache phase. In the present study, we investigated the effects of a novel CGRP receptor antagonist, BIBN4096BS (1-piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl] amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [R-(R*,S*)]-), on the regional cardiac output distribution and on the carotid haemodynamic changes induced by alpha-CGRP in anaesthetised pigs. Treatment with BIBN4096BS (100, 300 and 1000 microg kg(-1), i.v.) did not affect the heart rate, mean arterial blood pressure or systemic vascular conductance, but a small decrease in cardiac output was noticed; the latter was, however, not significantly different from that in vehicle-treated animals. The highest dose of BIBN4096BS moderately decreased vascular conductance in the lungs, kidneys, spleen and adrenals. Vascular conductance in other tissues including the brain, heart, gastrointestinal system, skin and skeletal muscles remained unchanged. Intracarotid artery infusions of alpha-CGRP (10, 30 and 100 pmol kg(-1) min(-1) during 3 min) increased the total carotid blood flow and conductance, but decreased the arterial blood pressure. These responses were dose-dependently blocked by BIBN4096BS. The above results show that BIBN4096BS is a CGRP receptor antagonist in the porcine carotid and systemic circulations, but the endogenous CGRP does not seem to play an important physiological role in regulating basal vascular tone. These findings suggest that BIBN4096BS may have therapeutic usefulness in migraine.
Animals↗
Usefulness of (13)C-urea breath test in the diagnosis of gastric helicobacter pylori infection.
Helicobacter pylori chronically infects half of the human population and is associated with gastritis, peptic ulcer and gastric cancer. (13)C-urea breath test (UBT) is the main in vivo tool for the diagnosis of H. pylori infection. In this study, the safety and the accuracy of UBT were evaluated. A group of 492 dyspeptic patients was studied by UBT, the results were expressed as the difference over baseline at 30 min (DOB30). All patients were evaluated for systemic, gastrointestinal or allergic-type adverse reactions after ingestion of 75 mg (13)C-urea and citric acid in aqueous solution. The first 256 patients enrolled also underwent endoscopy and gastric biopsy. Patients positive on histology were considered infected. UBT was well tolerated and none of the 492 patients had any systemic or allergic-type adverse reaction. Among the 256 patients studied with histology, 116 were H. pylori positive on biopsies. Using 4 %o as cut-off value for DOB30,115 out of the 256 patients were positive on UBT, with only 2 false positive and 3 false negative. With this threshold, the sensitivity, specificity, and accuracy of the UBT were 97.4%, 98.5%, and 98.0%, respectively. (13)C-UBT has proven to be a safe and simple, yet accurate, test for the non-invasive diagnosis and monitoring of H. pylori infection.
Journal Article↗
Pharmacokinetics of antiretrovirals administered to HIV-infected children via gastrostomy tube.
BACKGROUND: Surgical placement of a gastrostomy tube (g-tube) directly into a patient's gastrointestinal system to support antiretroviral administration is occasionally used to increase adherence in HIV-infected children. Absorption and distribution characteristics of antiretrovirals after g-tube administration, however, are unknown. The goal of this pilot study was to describe the pharmacokinetic characteristics of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) when administered to HIV-infected children via g-tube. METHOD: Nine HIV-infected children who were receiving a PI- or NNRTI-containing regimen via g-tube were enrolled. All antiretrovirals (excluding efavirenz) were administered under direct observation for the pharmacokinetic evaluation. Blood samples were collected at predose and at 1, 2, 4, 8, and 12 hours postdose. Antiretroviral concentrations were measured in plasma using high performance liquid chromatography with ultraviolet detection. RESULTS: Systemic exposure of PIs and NNRTIs in our 9 patients was similar to data from historical oral administration controls. Due to likely drug interactions, LPV exposure was decreased and one patient had low exposure of all antiretrovirals. When doses were increased, adequate exposure was attained. CONCLUSION: This pilot study suggests that administration of most PIs and NNRTIs by a g-tube to HIV-infected children provides systemic exposure comparable with that achieved after oral administration.
Area Under Curve↗
Maintaining osmotic balance with an aglomerular kidney.
The gulf toadfish, Opsanus beta, is a marine teleost fish with an aglomerular kidney that is highly specialized to conserve water. Despite this adaptation, toadfish have the ability to survive when in dilute hypoosmotic seawater environments. The objectives of this study were to determine the joint role of the kidney and intestine in maintaining osmotic and ionic balance and to investigate whether toadfish take advantage of their urea production ability and use urea as an osmolyte. Toadfish were gradually acclimated to different salinities (0.5, 2.5, 5, 10, 15, 22, 33, 50 and 70 ppt (1.5%, 7.5%, 15%, 30%, 45%, 67%, 100%, 151% and 212% seawater)) and muscle tissue, urine, blood and intestinal fluids were analyzed for ion and in some cases urea concentration. The renal and intestinal ionoregulatory processes of toadfish responded to changes in salinity and when gradually acclimated, toadfish maintain a relatively constant plasma osmolality at environmental salinities of 5 to 50 ppt. However, at salinities lower (2.5 ppt) or higher (70 ppt) than this range, a significant deviation from resting plasma and urine osmolality as well as changes in muscle water content was measured, suggesting osmoregulatory difficulties at these salinities. The renal system compensates for dilute seawater by reducing Na+ reabsorption by the bladder, which allowed excess water to be excreted. In the case of hypersalinity, Na+ reabsorption was increased, which resulted in a conservation of water and the concentration of Mg2+, Cl-, SO(4)2- and urea. A similar pattern was observed within the gastrointestinal system. Notably, Mg2+, HCO3- and SO4(2-) were the dominant ions in the intestinal fluid under control and hypersaline conditions due to the absorption of Na+, Cl- and water. When exposed to dilute seawater conditions, the absorption of Na+ was greatly reduced which likely increased water elimination. As a result of decreased environmental levels and a reduction in drinking rate, Mg2+ and SO4(2-) in intestinal fluids under hypoosmotic conditions were greatly reduced. While urea did play a minor role in renal osmoregulation, toadfish appear to preferentially regulate Na+ and to some extend Cl- in urine and intestinal fluids.
Acclimatization↗
The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma.
BACKGROUND/AIMS: CA 19-9 and CEA were evaluated for their specificity and sensitivity in the early diagnosis of pancreatic carcinoma. METHODOLOGY: This prospective study included 40 patients with pancreatic carcinoma. A control group of 60 patients were divided into two subgroups as upper gastrointestinal system malignancies and benign pancreatic disorders. CEA and CA 19-9 levels were measured in all the patients. RESULTS: When the reference value of CA 19-9 was accepted as 74 U/mL, the specificity was 100% when pancreatic carcinoma was compared with benign disorders of the pancreas, but it's specificity for upper gastrointestinal malignancies was 60-90%. When the reference value of CEA was increased, the sensitivity had been decreased but the specificity had been increased when compared with the control group. If the reference value of CEA was accepted as 5 ng/mL, the specificity was 100% when pancreatic carcinoma was compared with acute or chronic pancreatitis, but it is less specific for the differential diagnosis of pancreatic carcinoma from the upper gastrointestinal malignancies. CONCLUSIONS: With the progression of the pancreatic carcinoma, serum CEA level and the specificity of CEA were elevated similar to that of CA 19-9. However, the elevation of CEA specificity when compared with the control group was lower than the specificity of the CA 19-9 and the sensitivity of CA 19-9 was superior to that of CEA for pancreatic carcinoma. The level of CA 19-9 was increased with the development of early pancreatic cancer and this elevation steadily continued with the progression of the cancer.
Adult↗
Medical devices; gastroenterology-urology devices; classification of the ingestible telemetric gastrointestinal capsule imaging system. Final rule.
The Food and Drug Administration (FDA) is classifying the ingestible telemetric gastrointestinal capsule imaging system device into class II (special controls). The special controls that will apply to this device are set forth below. The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the amendments), the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997 (FDAMA). The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.
Capsules↗
The response of the local immunoglobulin system to malignant lesions of the stomach. A new diagnostic test.
The response of the local secretory immunoglobulin system to tumor antigens was studied in 71 patients suspected of harboring a gastric malignancy. Gastric aspirates were obtained by fiberoptic endoscopy and measured on single radial immunodiffusion plates (Behring Diagnostics). Patients with malignant neoplasms of the stomach were divided into Type I and Type II lesions, based on the extent and stage of the disease. Secretory IgA titers were elevated in all patients with a Type I malignant tumor confirmed by histologic examination; mean 6.1 mg/100 (SD +/- 3.7 mg/100). This leads us to believe that the host's response to malignant cells of the gastrointestinal system is an altered and elevated secretion of IgA. Evaluation of local immunoglobulin titers may be of value when used in conjunction with other diagnostic modalities in determining the nature of gastrointestinal lesions, particularly when the lesion is not metastatic or massively involving the gastric wall.
Adult↗
Autologous stem-cell transplantation in progressing amyloidosis is associated with severe transplant-related toxicity.
BACKGROUND: Amyloid light-chain (AL) amyloidosis is a disorder of plasma cells in which depositions of immunoglobulin light-chain fragments cause progressive organ failure and death with a median survival of one year, but autologous stem-cell transplantation can induce high response rates, especially in isolated renal involvement. METHODS: Six patients aged between 43 and 59 years were diagnosed with AL-amyloidosis and had stem cells mobilized with either recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone (n = 2) or cyclophosphamide (2-4 g/m(2)) and rhG-CSF (n = 4). All six patients had kidney involvement and nephrotic syndrome, four had cardiac involvement and two involvement of the vascular, nervous and gastrointestinal systems. Five of the patients received high-dose melphalan (200 mg/m(2)) and autologous blood stem-cell support. RESULTS: One patient died as a result of sepsis after stem-cell mobilization. The other five patients received high-dose melphalan but experienced severe toxicity. One patient died as the result of gastrointestinal perforation on day 6, one presented with hyperfibrinolysis and spontaneous rupture of the spleen, and another experienced severe bleeding of the gastrointestine, tachyarrhythmia and hemolytic anemia. Four patients had acute renal failure: three required hemodialysis and one underwent renal transplant 21 months later. Restaging after a follow-up of 31-52 months revealed reversal of nephrotic syndrome in all three patients who regained adequate renal function. With respect to cardiac involvement (n = 2), one patient showed a decrease in NYHA class from II to I but baseline wall thickness remained stable. CONCLUSION: Treatment of selected patients with AL-amyloidosis by high-dose melphalan and stem-cell support results in reversal of amyloid-related disease in a substantial proportion of patients and improved survival.
Adult↗
Corticotropin-releasing factor receptors and stress-related alterations of gut motor function.
Over the past few decades, corticotropin-releasing factor (CRF) signaling pathways have been shown to be the main coordinators of the endocrine, behavioral, and immune responses to stress. Emerging evidence also links the activation of CRF receptors type 1 and type 2 with stress-related alterations of gut motor function. Here, we review the role of CRF receptors in both the brain and the gut as part of key mechanisms through which various stressors impact propulsive activity of the gastrointestinal system. We also examine how these mechanisms translate into the development of new approaches for irritable bowel syndrome, a multifactorial disorder for which stress has been implicated in the pathophysiology.
Anxiety↗
Analysis of ras gene mutations in gastrointestinal cancers.
Point mutations of c-Ki-ras genes were analyzed in 33 samples of human gastrointestinal malignancy. DNA extracted from the frozen tissue was amplified by polymerase chain reaction (PCR) and analyzed by direct sequencing and slot-blot hybridization at codons 12, 13 and 61 of c-Ki-ras. In 7 cases out of 19 colorectal cancers, point mutations were found: 3 cases at codon 12, 1 at codon 13, 2 at codon 61 of c-Ki-ras and one case had double mutations at codon 12 and codon 13. In 11 cases of gastric cancer, 4 showed point mutations: 1 at codon 12 and 3 at codon 13 of c-Ki-ras. In 3 pancreatic carcinomas, 2 had point mutations: one at codon 12 and the other at codon 13 of c-Ki-ras. The results indicate that c-Ki-ras gene point mutations are involved in the tumorigenesis of the human gastrointestinal system.
Adult↗
[Intraoperative endoscopy in pediatric surgery: indications and results].
Intraoperative endoscopy in pediatric surgery was first performed in Germany at the begining of 1972. This method is an optical support for the surgeon to recognize pathological-anatomical alterations by the effect of the diaphanoscopy. It concerns primarily the upper and lower gastrointestinal systems as well as the tracheobronchial system. The endoscope can be placed intraoperative at the predetermined morphological alteration level enabling the surgeon to perform the surgical procedure at that special circumscrip area. This avoids local intensive trauma and protects nerve fibers, blood supply and other organs. Main indications are H-fistulae, tracheal stenosis, esophageal diverticula and perforations, gastroesophageal reflux, gastrointestinal bleeding and supralevator anorectal anomalies. Between 1984 and 1995 we have performed an intraoperative endoscopy in 310 children between the age of one day and 16 years. In a high percent of the explorations the identification of the preoperative findings were confirmed. Advantages of this method are less intraoperative complications concerning bleeding, organic and neurological lesions and a faster functional recovery of the organ due to an atraumatic procedure.
Adolescent↗
Corrosive injury to upper gastrointestinal tract: Still a major surgical dilemma.
In the developed and developing countries, corrosive injury to the gastrointestinal system as a consequence of either accidental ingestion or as a result of self-harm has become a less common phenomenon compared to decades ago. This could partly be attributed to the tighter legislation imposed by the government in these countries on detergents and other corrosive products and general public awareness. Most busy upper gastrointestinal surgical units in these countries, especially in the developed countries will only encounter a small number of cases per year. Up to date knowledge on the best management approach is lacking. In this article, we present our experience of two contrasting cases of corrosive injury to the upper gastrointestinal tract in our thoracic unit in the last 2 years and an up-to-date Medline literature search has been carried out to highlight the areas of controversies in the management of corrosive injuries of the upper gastrointestinal tract. We concluded that the main principle in managing such patients requires a good understanding of the pathophysiology of corrosive injury in order to plan both acute and future management. Each patient must be evaluated individually as the clinical picture varies widely. Signs and symptoms alone are an unreliable guide to injury.
Adult↗
Review article: gene therapy in gastroenterology and hepatology.
Gene therapy for diseases of the gastrointestinal tract is an exciting prospect because of the fundamental cure that is potentially available. The gastrointestinal system, and especially the liver, is an area that will be central to the development of gene therapy. Techniques for gene replacement include homologous recombination and gene augmentation. For the treatment of cancer antisense strategy, pro-drug activation systems and gene immunotherapy are being investigated. Gene-carrying vectors divide into viral- and non-viral-based vectors, each with advantages and limitations. The accurate delivery of these vectors to sufficient numbers of target cells in vivo is still a major barrier to clinical use. Diseases that may be helped by gene therapy include: gastrointestinal malignancies, viral hepatitis, the haemophilias, hypercholesterolaemia, alpha 1-antitrypsin deficiency, and metabolic diseases of the liver and cystic fibrosis. In this review we will outline the principles of gene therapy, delivery vectors under investigation, diseases that may benefit from this technology and some of the remaining problems to be overcome.
Gastrointestinal Diseases↗
Central nervous system mechanisms contributing to the cachexia-anorexia syndrome.
The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.
Anorexia↗