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Absorption differences of ciprofloxacin along the human gastrointestinal tract determined using a remote-control drug delivery device (HF-capsule).

The single-dose absorption kinetics of ciprofloxacin in different regions of the human gastrointestinal tract were investigated using a remote-control drug delivery device (HF-capsule). Doses of 180 to 200 mg ciprofloxacin (as a lactic acid solution) were placed in the HF-capsule and administered to four healthy male adults. The position of the HF-capsule in the gastrointestinal tract was checked via radiographic examination. The release of the solution from the HF-capsule was induced by a radio signal. In each volunteer, the solution was released into five different regions of the gastrointestinal tract: the stomach (B), jejunum (C1), ileum (C2), ascending colon (D1), and descending colon (D2). Two control runs (A1, A2), involving oral administration of the solution, were used as a reference for calculation of area under the curve. The oral administration of a conventional 250-mg tablet (A3) was also studied. The plasma concentration of ciprofloxacin and urine concentrations of ciprofloxacin, desethylene- (M1), sulfo- (M2), and oxociprofloxacin (M3) were determined fluorimetrically by high-performance liquid chromatography. Intraindividual comparisons indicated a progressive decrease in the amount of ciprofloxacin absorbed (100 percent = mean of AUCA1 and AUCA2) from the jejunum (-61 percent, median), ileum (-75 percent), colon ascendens (-90 percent), and colon descendens (-95 percent). Absolute amounts of renally excreted ciprofloxacin and metabolites decreased due to the reduced absorption of ciprofloxacin, but the metabolite pattern was unchanged. It is concluded that the main absorption site for ciprofloxacin is the upper part of the intestinal tract (duodenum, jejunum).

Adult↗

Extrusion of a screw into the gastrointestinal tract after anterior cervical spine plating.

In this case report of a screw extrusion into the gastrointestinal tract of a patient 16 months after anterior cervical discectomy and fusion (ACDF), the authors describe a rare but potentially lethal complication and review the literature on this topic. A 70-year-old white man with a surgical history of ACDF at C3-4 underwent an ACDF at C5-6 with autologous bone graft and a dynamic plate using locking, expanding screws. Sixteen months after the operation the patient presented with severe dysphagia. Radiographic findings indicating pulling out of the implanted plate and screws prompted a surgical removal of the instrumentation. One of the screws was not found during the operation and was visualized after surgery by abdominal radiography in the right lower abdominal quadrant. A subsequent Gastrografin swallowing test revealed an esophageal tear. The screw was removed endoscopically and the patient received antibiotics and had no oral intake for 4 days. He was discharged without symptoms on a soft mechanical diet; at 24 weeks, follow-up revealed no changes or symptoms. Screw extrusion into the gastrointestinal tract following ACDF is a rare but potentially lethal complication. The use of locking, expanding screws does not extinguish the risk of this complication, particularly in cases of suboptimal initial placement of the anterior instrumentation. Close follow-up is of paramount importance in detecting any pull-out of the implanted plate. Any signs of postoperative dysphagia or throat soreness should prompt immediate evaluation of the patient and, if indicated, surgical removal of the failed instrumentation.

Aged↗

Expression and distribution of monocarboxylate transporter 1 (MCT1) in the gastrointestinal tract of calves.

In the present study the expression and distribution of monocarboxylate transporter 1 (MCT1) along the gastrointestinal tract (rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum and colon) of calves were investigated on both mRNA and protein levels. The expression of MCT1 protein and its distribution were determined by Western blotting and immunohistochemical staining, respectively by using antibody for MCT1. MCT1 protein was visualized as a 43-kDa band on immunoblots of the membrane proteins prepared from the various regions examined, and it was more highly expressed in forestomach and large intestine than in abomasum and small intestine. With the use of reverse transcriptase-polymerase chain reaction, mRNA encoding for MCT1 was demonstrated in the different tissues examined. The immunohistochemical study confirmed the Western blot findings and showed strong MCT1 immunopositive staining in the stratified squamous epithelia of the forestomach as well as the epithelial cells lining the digestive tract in the cecum, proximal colon, and distal colon. The results suggest that MCT1 may play a role in the transport of SCFA and their metabolites in the gastrointestinal tract of bovines.

Amino Acid Sequence↗

Ghrelin expression in neuroendocrine tumours of the gastrointestinal tract with multiple endocrine neoplasia type 1.

Ghrelin is a novel gastrointestinal-brain hormone that was first described by Kojima et al. as a growth-hormone-releasing peptide. It can be isolated and purified from different tissues. Evidence of antiproliferative effects in neoplastic cells (binding to normal and neoplastic tissues) supports the hypothesis that ghrelin also plays an important role in endocrine regulation. Whether ghrelin may be involved in formation of neuroendocrine tumours (NET) of the gastrointestinal tract (GIT) in cases of MEN-1 is under discussion. Over the last sixteen years, 227 patients with GIT NET were treated at our institution. Mutations of the menin gene were identified in twelve patients. Eleven of these tumours (islet cell tumours) were localized in the pancreas and one in the stomach. Tissues from these tumours were resected, fixed in formalin and embedded in paraffin. Sections were examined by immunohistochemistry with a primary antibody for ghrelin. Three out of twelve NET in MEN-1 patients (25%) showed ghrelin expression by immunohistochemistry. Comparison between ghrelin-positive and ghrelin-negative tumours regarding biological activity, morphological aspects and clinicopathological parameters shows no substantial differences. The reported incidence of ghrelin expression in NET of the gastrointestinal tract by MEN-1 was not seen in our patients. Whether or not ghrelin has an influence on neuroendocrine tumour development related to deficient menin-genes is unknown.

Adult↗

[Methods of correction of humoral and cellular immunity in patients with burns and erosive-ulcerative lesions of the gastrointestinal tract].

The levels of immunoglobulins G, IgA, M and T-rosette-forming lymphocytes were determined in parallel in 137 patients with burns. The endoscopic examination has revealed acute erosive-ulcerous lesions of the gastrointestinal tract in 48 of the patients. Interrelationship between the degree of morphological changes in the gastrointestinal tract, level of immunoglobulins G, IgA and amount of T-lymphocytes was established. It was found that against the background of complex therapy Levamisole, antioxidants, hyperbaric oxygenation facilitated most rapid recovery of the immunological status in burned patients, prevented the development of acute ulceration of the gastrointestinal tract and are considered as curative measures in their development.

Adolescent↗

Tachykinins increase vascular permeability in the gastrointestinal tract of the rat.

The occurrence of inflammation as indicated by extravasation of Evans blue bound to plasma proteins was examined in various parts of the gastrointestinal tract in the rat, following administration of tachykinins, capsaicin and hydrochloric acid. Intravenous neurokinin A dose-dependently induced extravasation in stomach, duodenum, jejunum, caecum and colon, but had no effect in ileum. Neurokinin B equipotently induced extravasation in the stomach but had no effect in other parts of the gut and substance P had no effects on extravasation of Evans blue in any of the examined parts of the gastrointestinal tract. Capsaicin given intraperitoneally increased vascular permeability in stomach and duodenum only, while extravasation of Evans blue after capsaicin given intraluminally did not differ from the effect of the vehicle alone. As a comparison, HCl given intraluminally in the duodenum was found to induce a prominent extravasation of Evans blue of a greater magnitude than than of tachykinins. We suggest that tachykinins, and in particular neurokinin A, may be of importance for extravasation of plasma proteins as part of inflammatory reactions in the upper and lower gastrointestinal tract.

Animals↗

[X-ray examination of the gastrointestinal tract in systemic cutaneous disease].

An X-ray examination of the gastrointestinal tract was performed on 56 patients with systemic cutaneous disease that is often considered associated with internal malignancies. Found were one case of esophageal cancer, two cases of gastric cancer, and two cases of colon cancer. The prevalence of gastric and colon cancer in these patients showed a statistically significant increase compared to the general population. The rate of gastric cancer was 16.26 times higher than the general population and that of colon cancer 32.26. X-ray examination of the gastrointestinal tract in patients with systemic cutaneous disease is useful for detecting malignancy.

Aged↗

Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen.

BACKGROUND: The risk of gastrointestinal tract bleeding requiring hospitalization associated with naproxen sodium was compared with that with ibuprofen, using a prescription database to approximate over-the-counter dosing. OBJECTIVE: To evaluate the safety of naproxen sodium. METHODS: A claims database containing Ohio Medicaid data from January 1986 through February 1993 and Michigan Medicaid data from April 1983 through July 1993 was used to compare 101,318 patients dispensed naproxen sodium with 277,601 patients dispensed ibuprofen. Using a case-cohort design, all 59 patients from the full cohort who had been hospitalized with upper gastrointestinal tract bleeding (UGIB) that developed within 14 days after the first prescription for the study drugs were compared with a subcohort made up of a 10% random sample of subjects selected from the combined drug cohorts. RESULTS: The incidence of UGIB occurring within 14 days after the first prescription in the naproxen sodium cohort was 26 (0.026%) of 101,318 (95% confidence interval [CI], 0.017%-0.038%), compared with 33 (0.012%) of 277,601 patients (95% CI, 0.008%-0.017%) in the ibuprofen cohort. Overall, the use of naproxen sodium vs ibuprofen was associated with an adjusted relative risk of 2.0 (95% CI, 1.1-3.8). Among people with multiple prescriptions, the crude relative risk for those receiving therapy in a dose typical of over-the-counter use was 4.1 (95% CI, 1.2-13.8). CONCLUSIONS: The overall incidence of UGIB is low with both drugs. There is little additional absolute risk posed by the use of low-dose naproxen sodium, compared with low-dose ibuprofen, despite an increased relative risk. However, given the widespread use of these drugs, a substantial number of additional cases of UGIB could result from use of naproxen sodium. This increased risk should be considered, especially for patients whose baseline risk of UGIB is elevated.

Adolescent↗

Gastrointestinal tract evaluation in patients with iron deficiency anemia.

Iron deficiency anemia is the most common form of anemia encountered in clinical practice and is an extremely common manifestation of chronic occult gastrointestinal bleeding. Current evidence suggests that a large proportion of men and postmenopausal women with iron deficiency anemia harbor significant gastrointestinal tract pathological lesions as the source of blood loss. As such, the evaluation of patients with iron deficiency anemia is generally focused on the gastrointestinal tract. Importantly, the diagnosis of iron deficiency anemia should be firmly established before an extensive evaluation is undertaken. Management strategies for patients with iron deficiency anemia are reviewed; an important general point is that clinical features (ie, symptoms) may help direct specific investigation. The role of small-intestinal investigation in patients with iron deficiency anemia is controversial and should probably be reserved for patients with iron deficiency anemia and persistent gastrointestinal symptoms or those who fail to respond to appropriate therapy. The treatment and prognosis of patients with iron deficiency anemia and the majority of gastrointestinal tract lesions are straightforward. However, patients with vascular ectasias as the source of blood loss can represent a true management challenge.

Adenocarcinoma↗

Inflammatory fibroid polyps of the gastrointestinal tract: radiologic evaluation.

Inflammatory fibroid polyps (IFPs) are uncommon lesions of the gastrointestinal tract. Only scattered case reports have appeared in the radiology literature. The authors reviewed the cases of 33 patients (20 women and 13 men; average age, 45 years) to determine if these polyps had any distinctive diagnostic radiologic features. The IFPs were located in the stomach (n = 16), small bowel (n = 13), and colon (n = 4). The lesions originated in the submucosa and were composed of fibroblasts, inflammatory cells, and a network of blood vessels. Gastric IFPs were most often located in the antrum and were usually ulcerated. Most of the patients presented with clinical evidence of gastrointestinal blood loss. Small bowel polyps were usually located in the ileum, and patients were typically older women with intestinal obstruction due to intussusception. Most of the lesions appeared as large, intramural masses at radiologic examination. Some of the lesions were pedunculated, and all were solitary. There were no distinctive features to differentiate IFPs from other mural or intraluminal lesions of the gastrointestinal tract.

Colonic Neoplasms↗

Identification of Campylobacter jejuni genes involved in commensal colonization of the chick gastrointestinal tract.

Campylobacter jejuni is the leading cause of bacterial gastroenteritis in humans in developed countries throughout the world. This bacterium frequently promotes a commensal lifestyle in the gastrointestinal tracts of many animals including birds and consumption or handling of poultry meats is a prevalent source of C. jejuni for infection in humans. To understand how the bacterium promotes commensalism, we used signature-tagged transposon mutagenesis and identified 29 mutants representing 22 different genes of C. jejuni strain 81-176 involved in colonization of the chick gastrointestinal tract. Among the determinants identified were two adjacent genes, one encoding a methyl-accepting chemotaxis protein (MCP), presumably required for proper chemotaxis to a specific environmental component, and another gene encoding a putative cytochrome c peroxidase that may function to reduce periplasmic hydrogen peroxide stress during in vivo growth. Deletion of either gene resulted in attenuation for growth throughout the gastrointestinal tract. Further examination of 10 other putative MCPs or MCP-domain containing proteins of C. jejuni revealed one other required for wild-type levels of caecal colonization. This study represents one of the first genetic screens focusing on the bacterial requirements necessary for promoting commensalism in a vertebrate host.

Animals↗

Distribution and coexistence of peptides in nerve fibers of the external muscle of the human gastrointestinal tract.

The nerve fibers that supply the external muscle of the human gastrointestinal tract were examined for their immunoreactivity to the neuropeptides enkephalin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide, for tyrosine hydroxylase (a catecholamine-synthesizing enzyme), and for coexistence between immunoreactivities in nerve fibers. Studies on coexistence revealed that the majority of reactive nerve fibers could be placed in one of two classes: (a) those fibers with reactivity to enkephalin or substance P, or both, and (b) fibers containing one or both of the peptides neuropeptide Y and vasoactive intestinal peptide. Many fibers immunoreactive for vasoactive intestinal peptide or neuropeptide Y, or both, were found throughout the external smooth muscle of the gastrointestinal tract, but neuropeptide Y-reactive fibers were less common in the small and large intestines than in the stomach and esophagus. Fibers immunoreactive for enkephalin or substance P, or both, were sparse in the esophagus, increased in numbers to reach maximal frequency in the pylorus, and maintained a similar frequency in the small and large intestines. Fibers with somatostatin or tyrosine hydroxylase immunoreactivity were rare. In general, sphincter regions were similar to nonsphincter regions in peptide-immunoreactive fiber numbers and types, except that the internal anal sphincter had no enkephalin-immunoreactive fibers and very few substance P-reactive fibers. Moderate numbers of fibers reactive for neuropeptide Y and vasoactive intestinal peptide were found in the internal anal sphincter. It is suggested that enkephalin and substance P are in excitatory fibers and that vasoactive intestinal peptide and neuropeptide Y are in fibers inhibitory to the external muscle.

Adult↗

Intramucosal pH and oxygen extraction in the gastrointestinal tract after major liver resection in rats.

OBJECTIVE: To assess the influence of 70% and 90% liver resection on oxygen extraction and intramucosal and intraluminal pH in the gastrointestinal tract in rats. DESIGN: Random control trial. MATERIAL: 63 adult male Sprague-Dawley rats. INTERVENTIONS: Laparotomy with separation of liver from surrounding tissue (sham operation), 70% hepatectomy, or 90% hepatectomy (n = 21 in each group). At 1, 2, and 4 hours (n = 7/timepoint), the animals in each of the three groups had the following variables studied: intestinal oxygen delivery; blood gas analysis of arterial, caval, and portal venous blood; and direct intraluminal pH together with indirect measurements of intramucosal pH of the gastrointestinal tract. RESULTS: There was a temporary increase in the pH of arterial blood two hours after 70% hepatectomy. There was a reduction in intramucosal pH after 90% hepatectomy which started two hours after operation and became significant at four hours. The intraluminal pH of the gastrointestinal tract was increased two and four hours after both 70% and 90% hepatectomy, compared with the sham operated group. Systemic oxygen extraction increased immediately after hepatectomy. Gastrointestinal oxygen extraction increased gradually in the rats that had undergone 70% hepatectomy, but was reduced in those subjected to 90% hepatectomy. CONCLUSIONS: Major liver resection induces alterations in both systemic and gut physiology. These may go some way towards explaining the disturbances in enteric bacterial ecology, the increase in bacterial adherence on the surface of the intestine, and the translocation of bacteria from the gut, after major liver resection in rats.

Animals↗

Immunohistochemical characterization of microvascular endothelial cells in primary B cell lymphoma of the gastrointestinal tract.

Microvascular endothelial cells (EnC) in primary B cell lymphoma of the gastrointestinal tract were immunohistochemically studied. Based on the morphological structure, the microvasculatures were divided into high endothelial cell vessels (HEV) and flat endothelial cell vessels (FEV). There were distinct phenotypic differences between HEV and FEV in lymphoma tissues. HEV were characterized as OKM1- OKM5-, accompanied by the cluster of non-neoplastic T lymphocytes, and FEV were OKM1- OKM5+ not accompanied by T lymphocyte infiltration. Factor VIII-related antigen was clearly identified in both EnC, and major histocompatibility complex (MHC) class II antigens and interleukin 1 were absent or only faintly visible on EnC in lymphoma tissues, whereas they were expressed on EnC in non-lymphoma tissues. These findings suggest that microvascular EnC in primary B cell lymphoma of the gastrointestinal tract lack a property as antigen-presenting cells, and that HEV are involved in the migration of non-neoplastic T lymphocytes.

Endothelium, Vascular↗

Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal tract.

BACKGROUND & AIMS: The gastrointestinal (GI) tract is a major source and target of somatostatin (SRIF). Recently, five pharmacologically different SRIF receptors (sst1-5) were cloned. The cellular and tissue distribution of the sst1-5 messenger RNAs (mRNAs) were studied in the rat GI tract using in situ hybridization histochemistry (ISHH). METHODS: Two sets of (35)S-uridine triphosphate (UTP)-labeled antisense and sense riboprobes were prepared for each sst. ISHH was conducted on frozen tissue samples from rat stomach, duodenum, jejunum, ileum, colon, and pancreas. RESULTS: mRNAs of all five sst-s are widely expressed in the rat GI tract. The distribution pattern for each sst mRNA was identical with both antisense probes. No specific signal was found with any of the sense probes. Each layer of the different parts of the gut expressed mRNAs of multiple sst subtypes. All organs expressed sst3 mRNA very intensely. The lowest levels of mRNA expression for all five subtypes within the GI tract were found in the pancreas. CONCLUSIONS: The widespread expression of sst mRNAs suggests a significant role for SRIF in the regulation of GI function.

Animals↗

[Results of endoscopic polypectomy in the upper gastrointestinal tract--a multicenter study].

The results of 1416 endoscopic polypectomies of the upper gastrointestinal tract are reported, realised in 15 endoscopic centers of the GDR. In 2,8% a polypoid carcinoma, in 0,7% a carcinoid and in 1,3% mesenchymic polyps were found. Complications was bleedings in 3,1% and perforations in 0,7%. Then the whole rate of complications was 3,17%. 5 patients (0.35%) had to be operated as a consequence of complications. One patient (0.07%) died from a fulminat hepatitis after transfusion. These results correspond with those reported in international literature on endoscopic polypectomies in the upper gastrointestinal tract.

Carcinoid Tumor↗

Quantification of circulating peptides and assessment of peptide uptake across the gastrointestinal tract of sheep.

Gastrointestinal absorption of peptides was examined in sheep fed a forage-based diet. Peptide concentrations were determined in arterial, portal, and mesenteric blood and plasma by quantification of amino acid concentrations before and after acid hydrolysis of samples that had been first deproteinized then subjected to Sephadex G-15 gel-filtration to remove residual protein. In contrast to other studies of ruminants, peptide concentrations for individual amino acids were lower than for the corresponding free amino acids with peptide (expressed as a proportion of total nonprotein amino acid) representing not more than .25 to .3 of total amino acid. Peptide concentrations in arterial, mesenteric, and portal blood and plasma were similar, indicating that on this diet there was no net uptake of peptides from the small intestine (mesenteric-drained viscera, MDV) or the whole tract (portal-drained viscera, PDV). Increasing the intake of alfalfa pellets from 800 to 1,200 g/d, while increasing the absorption and net flux across the MDV and PDV of free amino acids, had no effect on peptide absorption. Preparation of blood and plasma samples for peptide analysis with methods used in studies in which substantial peptide absorption has been reported indicated no net MDV or PDV flux of peptide. Such conflicting data on the extent of gastrointestinal peptide flux are discussed in the context of methodological differences and the importance of diet and physiological state of the animal.

Amino Acids↗

Nuclear magnetic resonance contrast enhancement study of the gastrointestinal tract of rats and a human volunteer using nontoxic oral iron solutions.

Two dilute oral iron solutions, made from commonly available nonprescription dietary supplements, were found to enhance the gastrointestinal tract in nuclear magnetic resonance imaging of live rats and one human volunteer. The paramagnetic and pharmacologic properties of ferric ammonium citrate were more favorable than those of ferrous sulfate heptahydrate. The paramagnetic iron solutions shorten T1 and T2 relaxation times of water protons in the contrast media-filled gastrointestinal tract, producing easily observable change in NMR intensity. Because these iron solutions are available commercially and are known to be well tolerated, the clinical use of iron-containing NMR contrast agents for the gastrointestinal tract is feasible.

Animals↗