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Peripheral T-cell lymphoma of AILD (angioimmunoblastic lymphadenopathy with dysproteinemia) type involving gastrointestinal tract. A morphologic, phenotypic and genotypic study.

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki-67 antibody and antibodies against surface antigens demonstrated that CD3+, CD4+, and/or T-cell receptor (TCR) beta+ cells were predominant (67-68%) among the population of proliferating Ki-67% cells, rather than CD8+ or CD22+ cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T-cell lymphoma.

Antigens, CD↗

Surgical stress and the gastrointestinal tract.

Surgery on any part of the body results in a wide spectrum of alterations in normal body homeostasis. The gastrointestinal tract is extremely sensitive to surgical stress, even at remote locations. It is now evident that the G.I. tract also plays an important role in development of postoperative complications, such as the systemic immune response syndrome and multiple organ failure syndrome. The amount of information available on the cellular and subcellular changes occurring in the gastrointestinal tract after surgical stress is scant. These changes are important since they would act as initiators of tissue damage seen at a later stage, which in turn lead to postoperative complications. This review looks at the information available on the effect of surgical stress on the small intestine, the role of oxygen free radicals in this process, and the changes occurring at the cellular level.

Animals↗

[The clinical variants of psychosomatic pathology of the gastrointestinal tract].

Clinico-dynamic and experimental pathological methods were used to examine 650 patients with functional and organic psychosomatoses of the gastrointestinal tract. In the psychosomatic process, four stages were distinguished and described: reactive depression, psychosomatic reactions, formation of the psychosomatic cycles, and characteristic changes. Examination of the given pathology in the log demonstrates that psychosomatoses of the gastrointestinal tract (functional ones in particular) lead to the so-called psychosomatic development of the personality, fairly close to the neurotic development pattern.

Adolescent↗

[Irritative activity of antiinflammatory agents, betamethasone 17-valerate, beclomethasone 17, 21-dipropionate, betamethasone 17, 21-dipropionate, or indomethacin on the gastrointestinal tract in rats and dogs (author's transl)].

Irritative effects of three steroidal anti-inflammatory drugs on the gastrointestinal tract of rats and dogs were determined. With either single or repeated subcutaneous administration these drugs dose dependently irritated the gastric mucosa of both species. The intestinal mucosa was less affected. Concomitant oral administration of aspirin or subcutaneous administration of indomethacin revealed an aggravation of aspirin-induced gastric ulcers by betamethasone valerate and inhibition of indomethacin-induced intestinal ulcers by beta-methasone dipropionate. These two steroidal drugs had no noxious effect on healing of chronic gastric ulcers induced in rats and dogs. Betamethasone valerate, however, delayed the healing of gastric ulcer in rats. Indomethacin, a non-steroidal anti-inflammatory drug, also induced serious damage to the gastric and intestinal mucosa both of rats and dogs. Indomethacin ingestion delayed the healing of chronic gastric ulcer in rats but not in dogs. Since both steroidal and non-steroidal drugs induce damage to the gastrointestinal tract, a careful monitoring of the patients' complaints should be carried out when these compounds are used as a systemic treatment. Steroidal drugs used in this study, however, appear to be highly safe from the point of dose inasmuch as they are used as a topical treatment.

Animals↗

Prediction of response to neoadjuvant chemotherapy in carcinomas of the upper gastrointestinal tract.

Multimodal treatment protocols are increasingly employed to improve the survival of patients with locally advanced adenocarcinomas of the upper gastrointestinal tract, however, only 30-40% per year of the patients respond to 5-FU and cisplatin-based neoadjuvant chemotherapy. The goal of our studies is the identification of reliable genetic markers, on the genomic DNA-level, mRNA, or protein level that could predict response of upper gastrointestinal carcinomas prior to neoadjuvant chemotherapy. In esophageal carcinomas, a higher gene expression of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, was more frequently found in responding patients. In addition high gene expression of caldesmon and of the two drug carrier proteins, MRP1 and MDR1 was associated with response to therapy. By performing a genome-wide profiling on the protein level in a small group of patients, new potential markers were identified, which have to be validated in ongoing studies. In gastric carcinomas, mutations of the p53 gene revealed no association with response or survival, but tumors with a high rate of loss of heterozygosity (LOH), determined by microsatellite analysis, showed a better response to a cisplatin-based chemotherapy. Analysis of expression of 5-FU-(e.g., TS, DPD, and TP) and cisplatin-(e.g., ERCC1, ERCC4, GADD45A, and KU80) related genes, demonstrated an association of DPD expression with response and survival. The combined consideration of TP and GADD45 gene expression, showed the most obvious association with therapy response in this tumor. Our studies point to promising markers with potential use for chemotherapy response prediction of adenocarcinomas of the upper gastrointestinal tract, but prospective studies for validation are necessary.

Antineoplastic Agents↗

Wasting in gastrointestinal tract cancers: clinical and etiologic aspects.

One of the major complications found in patients affected by malignancy of the gastrointestinal tract is represented by an alteration of nutritional status, up to real cachexia. The factors responsible for the severe nutritional deficiencies are: metabolic alterations, which involve carbohydrate, lipid and protein metabolism; the reduced availability of nutritional substrates, due to neoplastic growth that, by expanding locally or destroying the affected organ, determines alterations of deglutition, digestion and food absorption; the effects of surgical therapy, radiotherapy and chemotherapy, which are able to cause temporary or permanent nutritional deficiencies; the effects of immunological mediators, and above all of tumor necrosis factor-alpha (TNF-alpha). In fact, TNF-alpha is considered the main mediator of cancer cachexia as it is responsible for different metabolic alterations, both directly and by the activation of other mediators, such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). In addition, a negative energy balance in cancer patients could occur as a consequence of increased energy requirements. In this connection, patients with different neoplasia localisation, show high or within the normal range energy expenditure values. These data indicate that the increase in energy metabolism is not likely to represent the main determining factor in neoplastic cachexia. In conclusion, since patients affected by malignancy of the gastrointestinal tract showed a reduction in body weight, fat and fat-free mass, accurate evaluation of nutritional status should be useful in the management and follow-up of these patients.

Journal Article↗

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract.

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150-200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.

Adult↗

Ontogenic development of neurotensin-like immunoreactivity in the gastrointestinal tract and the influence of dietary changes in rats.

The ontogenic development of neurotensin-like immunoreactivity (NTLI) in the gastrointestinal tract was studied in three groups of male rats on different diets. Group I rats were weaned physiologically. Group II rats received only mother's milk until 25 days of age. Group III rats were fed mother's milk alone for 20 days and then switched abruptly to laboratory chow. The NTLI concentration in the gastrointestinal tract from the esophagus to the small intestine was almost the same as that in adult rats before weaning. It increased after weaning to a peak on day 20 or 25, and then decreased to the adult level. The NTLI concentration in the cecum and large intestine, however, decreased from high neonatal level, reaching the adult level on day 20 or 25, and it remained constant thereafter. Prolonged mother's milk feeding alone enhanced neurotensin production in the esophagus and postponed the physiological decrement of NTLI concentrations in the duodenum and small intestine. The sudden change from mother's milk to laboratory chow accelerated the decrement of intestinal NTLI concentrations.

Animals↗

[Surgical and adjuvant therapy of neuroendocrine tumors of the gastrointestinal tract and their metastases. A retrospective analysis of personal patient group].

INTRODUCTION: Carcinoid tumors are the most common neuroendocrine tumors of the gastrointestinal tract. Surgical treatment and prognosis depend on the location of the tumor. METHOD: Between 01.01.1985 and 31.12.1999 25 patients with neuroendocrine tumors of the gastrointestinal tract or their metastases were treated in our institution. The records of these patients were reviewed retrospectively. Patients still alive were reexamined clinically. RESULTS AND CONCLUSIONS: The most frequent primary sites were the ileum and jejunum (36%), appendix (36%), stomach (12%), pancreas (8%), colon (4%) and bronchus with hepatic metastasis (4%). A malignant carcinoid syndrome was present in 8 patients. In patients with neuroendocrine tumors, curative, radical tumor removal should be attempted. Some patients with advanced disease needed some surgery for tumor debulking and resection of metastases. In non-resectable liver metastases hepatic arterial chemotherapy and chemoembolization after implantation of port catheters seem to be very beneficial therapeutic options. A fixed part of the therapeutic regime in progressive disease is adjuvant chemotherapy with 5-fluorouracil and streptozotocin and symptomatic therapy with octreotide.

Adult↗

Computed tomography of the gastrointestinal tract: lesion recognition and pitfalls.

Abnormalities in the gastrointestinal tract will be found on computed tomography (CT) scans performed for other indications if they are carefully searched for. This potential will increase as CT is used earlier in the investigation of suspected abnormalities of the pancreas. retroperitoneum, and liver. Additionally, CT may be valuable in assessing the extent of a known primary lesion of the alimentary tract.

Aged↗

"Missed" upper gastrointestinal tract lesions may explain "occult" bleeding.

BACKGROUND AND STUDY AIMS: Enteroscopy has been shown to be an effective diagnostic method in patients with obscure gastrointestinal bleeding. Arteriovenous malformations (AVMs) of the small bowel are the most common lesions discovered at enteroscopy. However, bleeding lesions may still be detected in the upper gastrointestinal tract even in patients who have previously undergone esophagogastroduodenoscopy. The aim of this study was to focus on these "missed" upper gastrointestinal lesions. PATIENTS AND METHODS: A retrospective review was conducted of all enteroscopic examinations carried out in patients with suspected gastrointestinal bleeding or overt gastrointestinal bleeding treated at our institution between 1993 and 1997. All patients had previously undergone an esophagogastroduodenoscopy. The push enteroscope (Olympus XSIF-100) was used in all of them. RESULTS: Push enteroscopy was performed in 233 patients (124 men and 109 women; mean age 63). A suspected bleeding lesion was observed in 53 % of the cases. AVMs represented 63% of the detected lesions. "Missed" upper gastrointestinal lesions were described in 25 patients (10.2 %). In half of these cases, the lesion was located in the upper part of the fundus. Wirsungorrhagia was the cause of bleeding in two cases. CONCLUSIONS: The study confirmed that push enteroscopy is an effective method of detecting lesions responsible for occult gastrointestinal bleeding. In this study, the overall diagnostic yield was 53%. In 10% of the patients, the lesion was located in the upper gastrointestinal tract, despite an initial esophagogastroduodenoscopy. The lesions were mainly located in the fundus. Although it is a rare condition, Wirsungorrhagia must be considered in patients with occult gastrointestinal bleeding.

Adolescent↗

Interleukin 6 production during abdominal aortic aneurysm repair arises from the gastrointestinal tract and not the legs.

BACKGROUND: Abdominal aortic aneurysm (AAA) repair is associated with a systemic inflammatory response. This inflammatory response probably arises as a result of an ischaemia-reperfusion injury to the legs and gastrointestinal tract. In this study the relative contributions of these areas to the inflammatory response were assessed during elective AAA repair. METHODS: Blood was sampled from the femoral vein, portal vein and radial artery of 14 patients undergoing elective AAA repair at five time points during the procedure. Plasma was snap-frozen for subsequent batch analysis of interleukin (IL) 6. RESULTS: The plasma IL-6 concentration rose steadily throughout the procedure at all three locations. The increase in plasma IL-6 was significantly greater in the portal vein than in the radial artery during ischaemia (P = 0.020). The plasma IL-6 concentration was also significantly higher in the portal vein than in the femoral vein (P < 0.001) and radial artery (P < 0.001) during reperfusion. There were no significant differences between radial artery and femoral vein IL-6 levels at any time point. CONCLUSION: Ischaemia and reperfusion during AAA repair were associated with a marked increase in IL-6 concentration in the portal vein, suggesting that IL-6 was produced by the gastrointestinal tract.

Analysis of Variance↗

[Absorption of 249Bk from the gastrointestinal tract of rats].

In experiments with albino mongrel female rats a study was made of the absorption of 249Bk from the gastrointestinal tract after a single per os administration. The bulk of 249Bk (96 per cent) administered either intravenously or per os was mainly deposited in the skeleton and liver. The value of 249Bk absorption from the gastrointestinal tract by days 4 and 8 following administration was 0.05 per cent.

Administration, Oral↗

Effects of drugs and electrical stimulation on rainbow lizard (Agama agama Linn.) isolated gastrointestinal tract smooth muscles.

The effects of some autonomic drugs and transmural electrical stimulation have been investigated on different isolated regions (oesophagus, stomach, duodenum, ileum, colon, and rectum) of the rainbow lizard (Agama agama Linn.) alimentary canal. Acetylcholine and its natural or synthetic analogues (5 X 10(-10)-10(-6)M) contracted the rainbow lizard isolated oesophagus, duodenum, ileum, colon, and rectum (but not the stomach) in a concentration-dependent manner. Acetylcholine cholinoceptors on the lizard gut were classified as "muscarinic" since acetylcholine-induced contractions of the muscle preparations were inhibited or abolished by relatively low concentrations of atropine (10(-9)-10(-6)M), but not by d-tubocurarine or hexamethonium (at the same concentration levels. Atropine exhibited characteristics of competitive antagonism and gave a high mean pA2 value (9.40 +/- 0.25) against acetylcholine on lizard isolated rectum. Physostigmine (eserine, 10(-8)-10(-4)M) did not contract any isolated region of the lizard gut. However, low to medium concentrations of eserine (10(-8)-10(-6)M) potentiated acetylcholine-but not carbachol-induced contractions of the isolated smooth muscle segments taken from different regions of the rainbow lizard alimentary canal. The selective potentiation of ACh-elicited contractions of the muscle preparations by eserine is therefore thought to suggest the presence of acetylcholinesterases in the tissues, and their inhibition by physostigmine. Dimethylphenylpiperazinium (DMPP) or nicotine (10(-8)-10(-5)M) did not contract any of the isolated segments from the different regions of the rainbow lizard alimentary canal. Adrenaline and all its analogues examined (10(-8)-10(-5)M) dose-dependently relaxed isolated segments from different regions (except the stomach) of the rainbow lizard gastrointestinal tract. The catecholamine-induced relaxations of the lizard gut smooth muscles were inhibited or abolished by low concentrations of phentolamine (10(-7)-2.5 X 10(-6)M). This observation probably suggests the presence of "alpha" adrenoceptors on rainbow lizard gastrointestinal tract. Repetitive transmural electrical excitation induced tetrodotoxin- (and atropine-) resistant, frequency-dependent contractions of all isolated segments taken from different regions (except the stomach) of the lizard alimentary canal. The findings that medium to high concentrations of physostigmine (10(-6)-10(-4)M), DMPP and nicotine (10(-6)-10(-5)M) failed to elicit intrinsic nerve-mediated contractions, coupled with the fact that tetanic transmural electrical stimulation caused tetrodotoxin-resistant contractions of the rainbow lizard isolated gut muscles, strongly suggest that the autonomic innervation of this reptilian alimentary canal differs from that of a conventional mammalian (e.g. guinea-pig) gastrointestinal tract...

5-Hydroxytryptophan↗

Effects of colostrum feeding and dexamethasone treatment on mRNA levels of insulin-like growth factors (IGF)-I and -II, IGF binding proteins-2 and -3, and on receptors for growth hormone, IGF-I, IGF-II, and insulin in the gastrointestinal tract of neonatal calves.

The somatotropic axis regulates growth of the gastrointestinal tract (GIT). In addition, colostrum feeding and glucocorticoids affect maturation of the GIT around birth in mammals. We have measured mRNA levels of members of the somatotropic axis to test the hypothesis that colostrum intake and dexamethasone treatment affect respective gene expression in the GIT. Calves were fed either colostrum or an isoenergetic milk-based formula, and in each feeding group, half of the calves were treated with dexamethasone (DEXA; 30 microg/kg body weight per day). Individual parameters of the somatotropic axis differed (P < 0.05) among different GIT sections and formula feeding increased (P < 0.05) mRNA levels of individual parameters at various sites of the GIT. Effects of DEXA on the somatotropic axis in the GIT partly depended on different feeding. In colostrum-fed calves, DEXA decreased (P < 0.05) mRNA levels of IGF-I (esophagus, fundus, duodenum, and ileum), IGF-II (fundus), IGFBP-2 (fundus), IGFBP-3 (fundus), IGF1R (esophagus, ileum, and colon), IGF2R (fundus), GHR (fundus), and InsR (esophagus, fundus), but in formula-fed calves DEXA increased mRNA levels of IGF-I (esophagus, rumen, jejunum, and colon). Furthermore, DEXA increased (P < 0.05) mRNA levels of IGF-II (pylorus), IGFBP-3 (duodenum), IGF2R (pylorus), and GHR (ileum), but decreased mRNA levels of IGFBP-2 (ileum), and IGF1R (fundus). Whereas formula feeding had stimulating effects, effects of DEXA treatment on the gene expression of parameters of the somatotropic axis varied among GIT sites and partly depended on feeding.

Animals↗

Site-specific drug delivery in the gastrointestinal tract.

In recent years there has been a significant increase in available strategies for site-specific delivery in the gastrointestinal tract both to maximize a therapeutic response and to reduce side effects. However, in only a few instances has there been close attention paid to how these products will perform in the heterogeneous environment of the human gut. Targeted oral delivery requires a multidisciplinary approach to research, involving contributions not only from polymer and pharmaceutical scientists but also from experts in gastroenterology and product evaluation. The objective of this article is, therefore, to examine our current understanding of human gastrointestinal physiology and to review the current "state of the art" of available targeting strategies. Emphasis will be placed on human data and, in particular, the interaction between the delivery system and the gastrointestinal tract, as assessed by product visualization studies.

Digestive System↗

Management of carcinoid tumors of the gastrointestinal tract.

Sixty-five patients seen at the Massachusetts General Hospital between 1951 and 1974 with carcinoid tumors of the gastrointestinal tract are reviewed. Sixty-two patients were operated upon, and only one carcinoid was discovered for the first time at autopsy. Although corrected actual five and ten year survival rates of more than 60% were attained, only one of 15 patients was alive five years after the discovery of liver metastases. Patients less than 60 years of age, with tumors of less than 0.5 centimeter in diameter and with no history of weight loss, survived best. Most rectal and appendiceal carcinoids were small, and there were no deaths in patients who had undergone local resection. Only 33% of the patients with small intestinal carcinoids survived for five years; none survived for more than one year after diagnosis of the carcinoid syndrome was made. All colonic carcinoids had metastasized by the time the operation was performed. Carcinoids of less than 0.5 centimeter in diameter located anywhere in the gastrointestinal tract can be managed by simple local resection. Tumors 1 centimeter in diameter warrant consideration of a more extensive operation. A radical excision usually is required for tumors of more than 2 centimeters in diameter, even in the presence of metastatic disease.

Adenoma↗

[The development of immunoreactive corticotropin-releasing factor (IR-CRF) in the hypothalamus, pancreas and gastrointestinal tract of immature rats].

Corticotropin-releasing factor (CRF), a hypothalamic releasing hormone, is now known to be widely distributed in extrahypothalamic tissues such as the pancreas and gastrointestinal tract. There are, however, no data concerning the development of CRF in the gastrointestinal tract in immature animals. Using a specific RIA technique for rat CRF, we have determined the IR-CRF concentrations in acid extracts of hypothalamic, pancreatic and gastrointestinal tissues in immature rats. Gel filtration of the extracts was also undertaken in order to investigate the molecular characteristics of the IR-CRF in the digestive system. Pregnant rats were decapitated at 20 days of gestation and the male fetuses (1 day before birth) were removed by hysterotomy. The male pups were also killed by decapitation immediately after birth and at 1, 3, 7, 14, 21, 28 and 42 days postnatally. The rats older than 3 days were divided into fed and 15-h-fasted groups. Pups were weaned at 21 days. The hypothalamus, pancreas, gastric antrum, duodenum and proxymal jejunum were removed immediately after decapitation. The individual tissue fragments were homogenized in 2N acetic acid and boiled for 5 min. The homogenates were centrifuged at 15,000g at 4 degrees C for 30 min and supernatants were removed, lyophilized and stored frozen until assay. Gel filtration was performed at 4 degrees C on a Sephadex G-50 (fine) column (1.6 X 82 cm). A 3 ml of sample was applied to the column and eluted with 0.2N acetic acid containing 0.25% BSA. Fractions of 3 ml were collected and stored at -20 degrees C until assay. The reagents for RIA were purchased from Peninsula Lab., INC. (Belmont, CA.). 125I-Tyr degrees-rat-CRF was labelled by chloramine-T method. Rabbit anti-CRF serum was used at the final dilution of 1:33,000. The antigen bound antibody was separated from the free antigen by the double antibody method using goat anti-rabbit IgG serum. The sensitivity of this RIA was 2-4 pg/tube. The average coefficients of variation for interassay and intraassay were 11.2% and 9.0%, respectively. Extracts of the pancreas, duodenum and jejunum of immature rats gave dilution curves that were parallel to the rat CRF standard curve as well as that of the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗