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PubMed2005

[Haemosuccus pancreaticus].

Haemosuccus pancreaticus is a rare cause of gastrointestinal bleeding. The blood is passing into the pancreatic duct through the route between an aneurysm of an artery close to the pancreas and pancreatic duct. The blood goes to the gastrointestinal system through Vater's papilla and the patient becomes anemic. The authors describe their own clinical observations. In the presented paper the pathogenesis of the disease as well as difficulties of diagnosis are discussed. The possible ways of treatment are mentioned, too. It is necessary to consider haemosuccus pancreaticus in patients with proved chronic pancreatitis and in patients with ethylic anamnesis. Duodenoscopy, ERCP and especially angiography help to set the diagnosis. For the treatment it is recommended to perform the embolization of the bleeding artery or an operation such as pancreas resection, artery ligation or alternatively a drainage operation.

Aged↗
PubMed2004

Safety and side effect profile of fluoxetine.

Fluoxetine was the first selective serotonin re-uptake inhibitor to be widely available for treatment of depression and numerous other neuropsychiatric disorders. Its attributes have been described in numerous scientific papers, and it has been the subject of a considerable volume of lay press. Fluoxetine is generally safe and well-tolerated. Common adverse events reported with the recommended dose of 20 mg/day are referable to the gastrointestinal system and the nervous system. The approved dose range is up to 80 mg/day, and when higher doses are used, adverse events are more common. The long half-life of fluoxetine and its active metabolite essentially preclude a withdrawal phenomenon. It is an inhibitor of cytochrome P450 (CYP) 2D6 and other CYP enzymes, which increases the potential for drug interactions. However, most of these are not clinically important. The purpose of this review is to provide an overview of some of the most important information related to safety and side effects of this drug.

Adolescent↗
PubMed1986

[General pharmacology of T-2588, a new oral cephem antibiotic].

A new oral cephem antibiotic, T-2588, the pivaloyloxymethyl ester of (+)-(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3- [(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2. 0]oct-2-ene-2-carboxylic acid (T-2525), is mainly absorbed from the intestinal tract and biotransformed to T-2525 thereafter. General pharmacological activities of T-2588 were studied and following results were obtained. On the central nervous system, T-2588 did not show any effects at oral doses of 500-2,000 mg/kg and T-2525 produced only a slight elevation of body temperature in rabbits without any other effects at an intravenous dose of 500 mg/kg. On the respiratory and cardiovascular systems, T-2525 caused a slight hypotension and increased both respiratory rate and femoral blood flow, but no changes were observed in heart rate and electrocardiogram in dogs at an intravenous dose of 500 mg/kg. The T-2525 exerted no significant influence on blood pressure response to isoproterenol, acetylcholine or histamine, but showed a slight tendency to decrease pressor response to adrenaline in dogs at intravenous doses of 100-500 mg/kg. For the renal function in rats, T-2588 had no effects on urine volume, electrolytes and PSP excretion at oral doses of 500-2,000 mg/kg. Intravenous administration of T-2525 caused an increase of sodium excretion at 500 mg/kg and dose-dependent increases of PSP excretion at 20-500 mg/kg. Hematological studies revealed that both T-2588 at oral doses of 500-2,000 mg/kg and T-2525 at intravenous doses of 100-500 mg/kg had no effects on bleeding time in mice, blood coagulation and platelet aggregation in rats. The T-2588 exerted no effect on the gastrointestinal system in rats or mice and had no antiinflammatory activity in rats at oral doses of 500-2,000 mg/kg. The T-2525 scarcely affected the motilities of isolated smooth muscle preparations in experimental animals including stomach, ileum, colon, uterus, vas deferens and trachea at a concentration as high as 10(-3) g/ml. The T-2525 increased bile secretion in rats at intravenous doses of 100-500 mg/kg. The T-2525 slightly decreased the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at an intravenous dose of 500 mg/kg. These results indicate that T-2588 is a pharmacologically inactive antibiotic.

Animals↗
PubMed2003

Malignant melanoma of the gastrointestinal tract presenting as a bleeding gastric ulcer.

Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a small percentage of patients with the disease. Presenting symptoms are often non-specific, causing a diagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary, however there is evidence that the tumour can arise de novo in the gastrointestinal system. We report a 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomatic gastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomy revealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach, multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limited small bowel resection was performed. Histology revealed the tumour to be composed of nests of epithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivity for S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be a diagnostic consideration in patients with gastric ulcer.

Aged↗
PubMed1997

Localization of Neuroendocrine Tumors Using Somatostatin Receptor Imaging With Indium-111-Pentetreotide (OctreoScan).

BACKGROUND: Many imaging methods have been used to detect neuroendocrine tumors of the gastrointestinal system. There is no gold standard for identifying the location of primary tumors and their potential metastases, and most conventional imaging techniques cannot detect tumors less than 1.0 cm in size. METHODS: The authors have investigated the use of 111-In-pentetreotide as an imaging agent for abdominal neuroendocrine tumors. RESULTS: The agent is cleared rapidly by the kidneys and is primarily excreted intact with a biologic half-life of six hours. The largest radiation burden is to the spleen and kidneys. A nine-center study conducted in Europe involved 365 patients with gastroenteropancreatic neuroendocrine tumors that were also imaged by other methods. The results of 111-In-pentetreotide were in agreement with those obtained by other methods for 79% of tumor locations. An additional 110 tumor localizations were detected that were not seen with conventional methods. The smallest gastrinoma imaged by 111-In-pentetreotide was a 4-mm duodenal tumor. CONCLUSIONS: Scintigraphy with 111-In-pentetreotide is effective in visualizing various somatostatin receptors characteristic of neuroendocrine tumors of the gastrointestinal tract. Insulinomas, however, are not well imaged. Concurrent computed tomography scanning is advised to minimize the risk of missing liver metastases.

Journal Article↗
PubMed2000

Regulation of intestinal blood flow.

The gastrointestinal system anatomically is positioned to perform two distinct functions: to digest and absorb ingested nutrients and to sustain barrier function to prevent transepithelial migration of bacteria and antigens. Alterations in these basic functions contribute to a variety of clinical scenarios. These primary functions intrinsically require splanchnic blood flow at both the macrovascular and microvascular levels of perfusion. Therefore, a greater understanding of the mechanisms that regulate intestinal vascular perfusion in the normal state and during pathophysiological conditions would be beneficial. The purpose of this review is to summarize the current understanding regarding the regulatory mechanisms of intestinal blood flow in fasted and fed conditions and during pathological stress.

Animals↗
PubMed2003

Necrotizing enterotyphlocolitis in dogs treated with a potent antimuscarinic.

To assess the safety of a potent muscarinic receptor antagonist (antimuscarinic) for human clinical testing, repeat-dose oral toxicity studies were conducted in the Beagle dog. Treatment resulted in unexpected gastrointestinal system effects that were likely mediated by the exaggerated pharmacologic effects of the antimuscarinic on intestinal motility. Dogs developed profound anorexia followed by severe bloody diarrhea, and at necropsy, the intestinal tract was distended, filled with red-tinged fluid, and the mucosa was reddened. Histologically, intestinal lesions consisted of severe epithelial necrosis and mucosal atrophy localized predominantly to the ileum and large intestine. Feces from dogs with diarrhea were culture-positive for Clostridium perfringens (CP), suggesting that CP might be the etiologic agent; however, the intestinal lesions were not consistent with histologic findings reported in dogs with hemorrhagic canine enteritis.

Animals↗
PubMed2006

Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse.

BACKGROUND & AIMS: The G-protein-coupled receptor GPR39 is a member of a family that includes the receptors for ghrelin and motilin. Recently the peptide obestatin was identified as a natural ligand for GPR39. The objective of this study was to gain insight into the biological function of the GPR39 receptor. METHODS: GPR39(-/-) mice were generated and analyzed. RESULTS: Endogenous GPR39 expression was detected in the brain (septum-amygdala) and the gastrointestinal system (parietal cells, enterocytes, neurons, and pancreas). Gastric emptying of a solid meal (measured by the (14)C octanoic breath test) in GPR39(-/-) mice was accelerated significantly with a gastric half-emptying time of 49.5 +/- 2.2 minutes compared with 86.9 +/- 8.4 minutes in GPR39(+/+) mice. A more effective expulsion of distally located pellets (30%-75% of length) was observed in the colon of GPR39(-/-) mice. Four hours after pylorus ligation, the volume of gastric secretion was increased significantly (GPR39(-/-): 638 +/- 336 microL; GPR39(+/+): 225 +/- 170 microL), but gastric acid secretion was unchanged. The mature body weight and body fat composition of GPR39(-/-) mice was significantly higher compared with GPR39(+/+) mice, but this was not related to hyperphagia because 24-hour food intake did not differ between both genotypes. In contrast, deficiency of the GPR39 receptor led to reduced hyperphagia after fasting. The cholesterol levels were increased significantly in the GPR39(-/-) mice. CONCLUSIONS: Our data partially confirm and extend the described in vivo effects of obestatin and suggest that this peptide plays a functional role in the regulation of gastrointestinal and metabolic function through interaction with the GPR39 receptor.

Amino Acid Sequence↗
PubMed1980

Lymphoscintigraphy with radionuclide-labeled antibodies to carcinoembryonic antigen.

Upper- and lower-extremity lymphoscintigraphy was performed on 50 patients with proven carcinoma of the breast, gastrointestinal system, genitourinary tract, lung, and vulva; 42 patients had 131I-antibodies to carcinoembryonic antigen (CEA) and 8 patients had 131I-normal goat immunoglobulin G. All metastases in the axillary or inguinal lymph nodes were detected with the CEA antibodies. In nine patients without metastases, radioactivity was observed in inguinal or axillary nodes. It is postulated that the nodal sequestration of antibody in the absence of metastatic carcinoma is due to captured CEA in lymph nodes draining the tumor site. This study has demonstrated the high sensitivity for detecting nodal metastases by labeled antibodies to CEA draining from primary or recurrent tumors.

Antibodies, Neoplasm↗
PubMed1999

[Changes in the mRNA concentration of preprocholecystokinin in rat cerebral cortex and hippocampus after gastric distension].

Cholecyctokinin-octapeptide (CCK-8) is one of the brain-gut peptides widely distributed in neurons of the central nervous system, especially in cerebral cortex and hippocampus. This peptide is thought as a neurotransmitter or modulator. The role of central CCK in the integration of gastric motility and food intake is still unclear. The present investigation was undertaken to see whether the gastric distension exerts some effect on the expression of CCK mRNA in cerebral cortex and hippocampus by means of in situ hybridization and semi-quantitative RT-PCR techniques. The results are as follows. (1) Discrete positive hybridization cells were seen in cerebral cortex and hippocampus in control group. (2) Significant increases of CCK mRNA expression in cerebral cortex and hippocampus produced by gastric distention observed by increased of the volume, the number, the IOD and the SA of positive cells. (3) Amplified bands of the expected size of 158 base pairs were found in cerebral cortex and hippocampus, and signals of gastric distention group were higher than those of control group. The results from RT-PCR assay are in agreement with those based on in situ hybridization. These results imply that biosynthesis of CCK-containing neurons in cerebral cortex and hippocampus is accelerated by afferent signals from gastrointestinal system and may be involved in regulation of gastric motility and food intake.

Animals↗
PubMed1994

Rate of digesta passage in the philippine flying lemur, Cynocephalus volans.

The rate of digesta passage was measured in five captive Philippine flying lemurs (Cynocephalus volans). These animals were force fed capsules containing known quantities of either particulate or soluble markers. The volumes of the gastrointestinal tracts of three flying lemurs were determined based on the wet weight of the contents of each section of the gut. The mean rate of digesta passage was 14.37 +/- 3.31 h when determined using the particulate marker and 21.9 +/- 0.03 h when determined using the soluble marker. The values based on the particulate marker are between 2% and 10% of similar values for other arboreal folivores. The morphology of the gastrointestinal system of the Philippine flying lemur is similar to that of other hindgut fermenters. Flying lemurs have a simple stomach and a large caecum. The total gut capacity of the Philippine flying lemur is similar to that of other herbivores, but is slightly smaller than that of either the koala (Phascolarctos cinereus), a hindgut fermenter, or the three-toed sloth (Bradypus variegatus), a foregut fermenter. These data suggest that flying lemurs deal with the problems of a folivorous diet very differently than some other arboreal mammals. Phascolarctos cinereus and Bradypus variegatus may represent one extreme with Cynocephalus volans representing the other extreme along a continuum of foraging strategies that are compatible with the arboreal folivore lifestyle.

Animals↗
PubMed1999

Corticotropin-releasing factor and the brain-gut motor response to stress.

The characterization of corticotropin-releasing factor (CRF) and CRF receptors, and the development of specific CRF receptor antagonists selective for the receptor subtypes have paved the way to the understanding of the biochemical coding of stress-related alterations of gut motor function. Reports have consistently established that central administration of CRF acts in the brain to inhibit gastric emptying while stimulating colonic motor function through modulation of the vagal and sacral parasympathetic outflow in rodents. Endogenous CRF in the brain plays a role in mediating various forms of stressor-induced gastric stasis, including postoperative gastric ileus, and activates colonic transit and fecal excretion elicited by psychologically aversive or fearful stimuli. It is known that brain CRF is involved in the cross-talk between the immune and gastrointestinal systems because systemic or central administration of interleukin-1-beta delays gastric emptying while stimulating colonic motor activity through activation of CRF release in the brain. The paraventricular nucleus of the hypothalamus and the dorsal vagal complex are important sites of action for CRF to inhibit gastric motor function, while the paraventricular nucleus of the hypothalamus and the locus coeruleus complex are sites of action for CRF to stimulate colonic motor function. The inhibition of gastric emptying by CRF may be mediated by the interaction with the CRF2 receptors, while the anxiogenic and colonic motor responses may involve CRF1 receptors. Hypersecretion of CRF in the brain may contribute to the pathophysiology of stress-related exacerbation of irritable bowel syndrome.

Animals↗
PubMedDate not supplied

It is not what you eat, but how you eat it digestion, life-style, nutrition.

Each year, over 30 million Americans suffer from acute or chronic digestive dysfunction. Much of this dysfunction is associated with occupational and behavioral stresses, which, although not life threatening, cause absenteeism and claim considerable health services. Central nervous system gastrointestinal (GI) peptide hormones partly control the quantity and quality of food eaten and its digestion. Because digestion is modified by occupational stress and behavior patterns, including smoking and consumption of alcohol and coffee, the physiological status of the individual plays a major role in the absorption of luminal nutrients. Whereas a Western, versus vegetarian, diet has been associated with an increase in coronary heart disease and diet-related cancers, inadequate attention has been given to the effects of life-style and occupation. This review is concerned with the adverse environmental effects on digestion that act via changes in GI function. To reduce the incidence of digestive dysfunction and diet-related diseases, more attention must be given to environmental factors other than diet, which affects the absorption of nutrients.

Diet↗
PubMed2003

Gastroesophageal reflux as a possible co-promoting factor in the development of the squamous-cell carcinoma of the oral cavity, of the larynx and of the pharynx.

According to recent advances it is assumed that the gastroesophageal reflux (GER) is a possible co-promoting factor of the squamous-cell carcinoma development in the upper parts of the gastro-intestinal and respiratory systems, considering the higher frequency of lesions due to acid in the studied population interested by GER. The aim of this study is to investigate 274 patients with malignant neoplasm of the oral cavity, of the pharynx and of the larynx, by esophago-gastro-duodenoscopy (EGD) and to compare the incidence of GER in this group with a control group of healthy patients from their hospital. Acid exposure in the upper level of the esophagus often remains unknown using traditional pH-monitoring, especially if no pharyngeal probe is used. When necessary a good diagnostic test is EGD with mucosa biopsy; it allows to directly examine the lesion. We retrospectively studied the data of 274 patients suffering from a cancer of the upper aero-digestive tracts by EGD in order to diagnose lesions caused by GER. We compared non-smoking patients affected by GER and tumours a control group of healthy patients. Statistical analysis revealed a significant difference between the two groups using the z-Test (p = 0.0001). In our study, based on endoscopic data, we observed a high percentage of non-smoking patients affected by GER and squamous-cell carcinoma of the upper parts of the airways and the gastrointestinal system. For this reason we consider GER as a possible co-promoting factor of cancer in some patients.

Adult↗
PubMed2005

Gastrointestinal hormones and food intake.

Despite dramatic fluctuations in calorie intake, animals maintain a very stable body weight. The reason is that energy intake and expenditure are precisely matched. Long-term regulation of energy balance is dependent on the coordination and interpretation of signals such as those given by insulin and leptin indicating sufficient long-term energy stores as well as short-term, meal-related signals such as those given by cholecystokinin (CCK). Within the last 30 years, our knowledge of short-term signals has increased dramatically. Throughout the cephalo-caudal axis of the gastrointestinal system, discrete enteroendocrine cells respond to both mechanical and chemical stimulation. Meal-associated hormone release is dependent on the concentration and composition of the nutrients ingested. Released signals are transmitted neurally through vagal afferents or humorally as circulating ligands for specific receptor populations in the periphery and central nervous system. These signals are interpreted by the CNS and manifested as a behavioral modification of feeding. This review will present past and recent literature in support of gut hormones and their roles as mediators of satiety. Evidence from pharmacologic and physiologic studies involving both humans and rodents will be presented, along with a short section outlining the knowledge gained through the use of murine knockout models. Last, the contribution of satiety hormones as likely mediators of the effectiveness seen following obesity surgery will be reviewed. Although traditionally thought of as short-term, meal-related signals, enhanced, chronic hormone secretion and signaling resulting from gut reconstruction as seen with gastric bypass surgery most likely contributes to the superior efficacy of surgery as a treatment for obesity.

Animals↗
PubMed1991

Imaging and therapy of gastrointestinal cancers with radiolabeled antibodies.

Radiolabeled antibodies are gaining in application for the imaging and therapy of cancers. Much progress has been made in the use of these new biological reagents for tumors of the gastrointestinal system, and the current status, problems and prospects are reviewed in this paper. It is apparent that murine monoclonal antibodies against cancer-associated antigens are safe and useful for revealing a high percentage of sites of tumor, including some missed by conventional radiological methods. Tumors as small as 0.5 cm can be disclosed, even in organs that are difficult for CT scan interpretation. Major advances in cancer imaging have involved the use of antibody fragments and simple, direct labeling methods for 99mTc, the most widely used radionuclide in nuclear medicine. The use of radiolabeled antibodies for cancer therapy has been a more difficult endeavor, particularly because of the delivery of inadequate rad doses to tumor. Advances include humanization of monoclonal antibodies and the improved attachment of therapeutic radionuclides, such as 90Y and 186Re or 188Re.

Carcinoma, Hepatocellular↗
PubMed1987

Disposition and excretion of 2,3,4,7,8-pentachlorodibenzofuran in the rat.

The disposition of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), a highly toxic environmental contaminant which accumulates in human tissues, was examined in the male Fischer rat after iv and oral exposure. Greater than 70% of an oral dose of 0.1, 0.5, or 1.0 mumol PeCDF/kg body wt was absorbed by the gastrointestinal system. After either oral or iv administration of 0.1 mumol/kg, the dibenzofuran was rapidly removed from the blood and accumulated in the liver and adipose tissue and to a lesser extent in the skin and muscle. Three days after administration, 70% of the iv dose of PeCDF was found in the liver, 7% in the fat, 1% in the skin, and 0.5% in the muscle. Route of exposure had little effect on tissue distribution. TLC analyses indicated that greater than 99% of the [14C]-PeCDF-derived radioactivity which had accumulated in the liver and adipose tissue was unmetabolized PeCDF which was eliminated very slowly (t1/2 = 193 and 69 days, respectively). The whole body half-life calculated from the daily fecal excretion rate was approximately 64 days. Excretion occurred primarily via the feces. No radioactivity was detected in expired air and less than 0.02% was detected in the urine. TLC analysis of fecal extracts indicated greater than 90% of the [14C]PeCDF-derived radioactivity in the feces was polar metabolites of the parent compound. Pretreatment with 500 micrograms PeCDF/kg body wt caused biliary excretion to nearly double. Treatment of bile with beta-glucuronidase or arylsulfatase had little effect on the chromatographic profile. Therefore, PeCDF was readily absorbed from the gastrointestinal tract, concentrated primarily in the liver, and was slowly eliminated from the body as polar metabolites. The long half-life and high body burden of PeCDF suggest that the toxicity of this chemical may be enhanced due to bioaccumulation upon chronic low-level exposure.

Animals↗
PubMedDate not supplied

Hepatic and gastrointestinal effects in an occupational cohort exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin.

OBJECTIVE: To examine the effect of occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on the liver and gastrointestinal system. DESIGN: A medical survey. PARTICIPANTS: The exposed participants were employed at two chemical plants more than 15 years earlier in the manufacture of sodium trichlorophenol and its derivatives. The reference group consisted of individuals with no occupational exposure to phenoxy herbicides and who lived within the communities of the workers. A total of 281 workers and 260 unexposed referents participated in the medical study. MEASUREMENTS AND MAIN RESULTS: The workers had substantial exposure to substances contaminated with TCDD, as evidenced by a mean serum TCDD level, lipid adjusted, of 220 pg per gram of lipid compared with a mean of 7 pg per gram of lipid in the referents. Compared with the unexposed reference group, workers had a statistically significantly elevated risk for an out-of-range gamma-glutamyltransferase (GGT) level (odds ratio, 2.27; 95% confidence interval, 1.17 to 4.39 [unadjusted for confounders]). In multivariate analyses run with logistic regression, a statistically significant interaction was found between TCDD exposure and lifetime alcohol consumption, indicating that the elevated risk for an out-of-range GGT was confined to those workers with a history of alcohol consumption and that the risk among the alcohol-consuming workers for an out-of-range GGT increased with increasing TCDD level. No difference was found between workers and referents for any of the other liver and gastrointestinal outcomes of interest. CONCLUSIONS: This study found no evidence of an elevated risk for clinical hepatic or gastrointestinal disease in a group of workers with high exposure to TCDD. However, TCDD-exposed workers with a history of sufficient alcohol consumption were found to have a statistically significantly elevated risk for an out-of-range GGT compared with referents.

Cross-Sectional Studies↗