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Balloon probe for the colonoscopic small intestinal enema (CE).

The colonoscopic small intestinal enema (CE) permits the radiological examination of a large portion of the distal small intestine during colonoscopy. The colon (endoscopically) and the small intestine (radiologically) can thus be examined in one session. With a new balloon probe that can be passed through the instrumentation channel of the endoscope, it is no longer necessary to prepare the colonoscope by fitting a circular balloon as previously described, before introducing it into the patient. With the balloon probe, CE can be carried out at any time if an unexpected finding such as inflammation of the ileo-cecal valve makes the examination of the ileum desirable.

Catheterization↗

Alteration of cytokeratin 7 and cytokeratin 20 expression profile is uniquely associated with tumorigenesis of primary adenocarcinoma of the small intestine.

Twenty-four cases of primary nonampullary small intestinal adenocarcinoma were immunohistochemically examined for the expression of cytokeratin (CK) 7 and CK20 and compared with 23 colorectal adenocarcinomas secondarily involving the small intestine by direct extension or metastasis. While normal small intestinal mucosa was diffusely positive for CK20 and completely negative for CK7 expression, all small intestinal adenocarcinomas (24 of 24) showed a variable degree of CK7 expression. Specifically, the CK7 staining pattern was diffuse in 13 cases (54%) and focal in the remaining cases. Sixteen small intestinal adenocarcinomas (67%) coexpressed CK7 and CK20, and 8 (33%) completely lost CK20 immunoreactivity when compared with adjacent non-neoplastic small intestinal mucosa. In the latter cases, the loss of CK20 immunoreactivity with a reciprocal emergence of CK7 expression was evident. This was in contrast to secondary colorectal adenocarcinomas where 22 cases (96%) expressed CK20, among which only 1 case showed focal CK7 expression. The remaining 1 case was negative for both CK7 and CK20. Interestingly, adenomatous epithelium associated with small intestinal adenocarcinomas identified in 18 cases also exhibited CK7 positivity with a sharp transition from CK7-negative normal-appearing epithelium. Taken together, these observations delineate an alteration of CK7 and CK20 expression profile that occurs early in small intestinal tumorigenesis. This unique pattern may be of diagnostic value in distinguishing primary small intestinal adenocarcinoma from secondary colorectal adenocarcinoma.

Adenocarcinoma↗

Flow cytometric measurement of proliferation-associated nuclear antigen P105 and DNA content in immuno-proliferative small intestinal disease (IPSID).

Immunoproliferative small intestinal disease (IPSID), most common in Mediterranean countries, is characterized by lymphomatous infiltration of the small intestine and is usually associated with the synthesis of anomalous immunoglobulin alpha heavy chains. Flow cytometric analysis of DNA content, S phase fraction, and quantitative analysis of the proliferation-associated nuclear antigen, P105, were performed in 23 patients with IPSID to determine if they could be used as prognostic indicators in this disease. Eighteen patients had low-grade, two had intermediate-grade, and three had high-grade lymphoma. Eight patients had clinical stage IE disease, 12 had stage IIE, and three had stage IIIE disease. Eleven patients survived > 5 yr (good prognosis), four survived between 2-5 yr (intermediate prognosis), and eight survived 2 yr or less (poor prognosis). The S phase fraction of patients with poor prognosis was significantly higher than those with intermediate or good prognosis (P < 0.004). Flow cytometric evaluation of S phase fraction may offer important prognostic information in patients with IPSID and could be useful in the clinical management of patients with this highly variable clinical syndrome. Further studies evaluating the value of DNA flow cytometry in larger groups of patients with IPSID are warranted.

Adult↗

Alterations in piglet small intestinal structure at weaning.

The small intestinal mucosa of 112 piglets aged between 21 and 32 days was examined to identify the effects on its structure of weaning and of consumption of creep food. In unweaned control pigs a gradual increase in crypt depth occurred with age, while villus height altered little. In contrast, weaned pigs showed a highly significant increase in crypt depth and an increase in the complexity of villus morphology with a dramatic reduction in villus height. Crypts elongated most in the distal small intestine, while the loss of villus height was greatest proximally. No inflammatory reaction was seen and the alterations were not influenced by consumption of creep food before weaning. This failed to support the hypothesis that hypersensitivity to dietary antigens is involved in the aetiology of such intestinal changes. The reduction in small intestinal absorptive area and the appearance of a less mature enterocyte population help to explain the increased susceptibility of the pig to diarrhoea and growth checks in the post-weaning period.

Aging↗

Adaptive cancellation of the respiratory artifact in surface recording of small intestinal electrical activity.

In the human small intestine there is omnipresent electrical activity with a frequency of 0.15-0.2 Hz. The electrical activity of the small intestine can be measured by surface electrodes placed on the abdominal skin. The most annoying problem in the surface electrical recording is the respiratory artifact which is not discernible from the small intestinal signal. The frequency of the respiration is about 0.2-0.4 Hz, which is very close to that of small intestinal activity, making the use of the conventional bandpass filtering impractical. In this paper a selective frequency domain adaptive filter was proposed for the cancellation of the respiratory artifact. The basic principle of the selective frequency domain adaptive filter is that only selected filter weights are adapted based on the frequency characteristics of the respiratory artifact. Therefore, a substantial reduction of computation is achieved. A series of computer simulations was conducted for the optimization of the system parameters and for the investigation of the system performance. It was demonstrated in this paper that the selective frequency domain adaptive filter is as effective as, but more efficient than, the conventional frequency domain adaptive filter. The adaptive system for the cancellation of the respiratory artifact based on the selective frequency domain adaptive filter is very efficient in computation, has a fast convergence (about 100 adaptations), substantial reduction of the respiratory artifact and little effect (or distortion) on the small intestinal electrical signal.

Computer Simulation↗

[Elevated level of TGF-alpha in the mucosa of small intestine of the rat following massive small bowel resection].

This study was performed to determine the changes in TGF-alpha production during compensatory regeneration of small intestine. For this purpose rats underwent either 70% small bowel resection or sham operation. Levels of TGF-alpha production were evaluated by radioreceptor assay and Western blotting. When compared with sham operation, small bowel resection resulted in threefold increase in the production of TGF-alpha at postoperative day 3. Possible mechanisms of TGF-alpha involvement in intestinal adaptation following massive small bowel resection are discussed.

Adaptation, Physiological↗

Transcellular fluid secretion induced by cholera toxin and vasoactive intestinal polypeptide in the small intestine of the rat.

The permeation of intravenously administered 51Cr-EDTA and [14C]mannitol to the perfused intestinal lumen was measured in anaesthetized rats together with the net intestinal fluid. Net fluid secretion was induced by cholera toxin or by intravenous infusion of vasoactive intestinal polypeptide (VIP). The plasma clearance of Cr-EDTA and mannitol was 0.9 +/- 0.1 and 1.4 +/- 0.2 microliters min-1 g-1 intestine during the control period prior to the secretion and the net fluid absorption was about 7 +/- 5 microliters min-1 g-1. Cholera toxin induced a net fluid secretion of about 30 +/- 7 microliters min-1 g-1 but the clearance did not rise but decreased significantly. The findings for VIP-induced secretion were similar. No indication of solvent drag was seen. Thus it is concluded that the fluid was secreted in channels which were smaller than the probes and we propose that the secreted fluid entered the intestinal lumen through the epithelial cells and not by the paracellular route. The decreased permeation of Cr-EDTA and mannitol from plasma to lumen during volume secretion suggest that there was a decreased mucosal permeability during the secretion. The decrease in permeability was consistent with a decrease in pore size. One explanation of the data is that the pore radius contracted from about 35 to 15 A during cholera if we assume a homogenous pore population. However, the data indicated that there was not a uniform size of the pore.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Small intestinal manifestations of HIV infection.

The small intestine is a common site of involvement in patients infected with the human immunodeficiency virus (HIV). Although there are numerous mechanisms by which small intestinal disease may occur in HIV infected patients, the resulting clinical manifestations of these disorders are remarkably similar and include the development of diarrhoea, weight loss and nutrient deficiencies. In fact, the original designation of AIDS in African countries as the 'slim disease' underlines the importance of small intestinal involvement (most likely secondary to parasitic infections) which commonly occurs in Third World Countries. The current review will provide a clinically oriented overview of small intestinal disease in patients infected with HIV. Because specific data on treatment of small intestinal diseases in AIDS is often lacking, some presented information is based on the author's experience and opinions.

HIV Infections↗

Histological comparison of suction capsule and endoscopic small intestinal mucosal biopsies in children.

Small intestinal biopsies are part of the routine evaluation of children with chronic diarrhea and malabsorption, and are commonly performed via suction capsule. Because this technique entails x-ray exposure, longer procedure time, and technical failures, most small intestinal biopsies in adults are currently obtained via endoscopy. Endoscopy is believed to yield morphologically inferior specimens, and, therefore, its use for obtaining small intestinal biopsies in children has remained limited. The histological adequacy of biopsy specimens obtained in 30 children by endoscopy and in 30 children by suction capsule was compared. Biopsies were assessed for quality of orientation, size (length and depth), presence of Brunner's glands and crush artifact, and for the ability to confirm or exclude a mucosal abnormality. Small intestinal biopsies obtained via endoscopy were shown to yield tissue specimens that are histologically comparable to those obtained by suction capsule, and that are equally suitable for interpretation.

Biopsy↗

Tumors of the small intestine.

Tumors of the small intestine offer a unique challenge. As a result of their infrequent occurrence, they invariably present difficult problems in diagnosis and management. Although the prognosis for benign lesions is excellent, malignant small bowel tumors are perhaps the most devastating GI malignancies; at the time of diagnosis, only approximately 50% of these lesions are completely resectable for cure. Symptoms are often absent until the tumor has progressed to produce a complication. Even then, the presentation is often vague and nonspecific, intermittent pain, obstruction, and chronic anemia. The cornerstone of diagnosis is the contrast radiograph. However, in practice only about 50% of these lesions are diagnosed radiographically before surgery. This situation is further complicated by the variety of small bowel tumors, each with different symptoms and manifestations. Surgical excision is the treatment of choice for almost every small intestinal neoplasm. For most benign lesions simple excision is adequate. In contrast, for malignancies, segmental resection including as much adjacent mesentery as is reasonable, is required. In the duodenum, these tumors may necessitate pancreaticoduodenectomy; in the ileum, right colectomy may be required. In the case of advanced disease, palliative resection to relieve bleeding or obstruction may be indicated. The challenge of the future will be to reduce the morbidity and mortality of small bowel neoplasms not only by earlier recognition, diagnosis, and therapy but also through the development of alternative or adjunctive therapy for patients in whom surgical cure is not possible. This will require not only a high index of suspicion when confronted with patients with vague abdominal complaints but also an aggressive approach to diagnosis in the face of normal initial studies. In addition, multi-institutional trails of chemotherapy and radiation therapy of these tumors are needed.

Adenoma↗

[Inventory relating to roentgen diagnostics of the gastro-intestinal tract (especially of the small intestine, colon, and biliary tract) (author's transl)].

The article describes the authors' experience in their Department in Nijmegen (Holland) with the various types of x-ray equipment: in gastroenterology--especially in the examination of the small intestine, colon, and the bile ducts--and also within the framework of a general roentgenology diagnostics section. Problems of cost are also considered, relating on the one hand to the equipment required in an examination room, and on the other hand to gastroenterological examination. In conclusion, the authors suggest the most suitable type of apparatus to be acquired for a particular purpose.

Digestive System↗

Early morphologic changes in the intestine following massive resection of the small intestine and parenteral nutrition therapy.

Following massive resection of the small intestine, including the ileocecal valve in seven adult mongrel dogs, the remaining 20 centimeters of the proximal part of the jejunum was anastomised to the midtransverse portion of the colon. All dogs were given parenteral nutrition for four weeks. Six weeks after resection, the dogs underwent reexploration, and gross and microscopic examinations of the remaining part of the jejunum were carried out. Grossly, there was a 29.5 per cent increase in the length and a 31 per cent increase in the circumference of the intestine. Microscopically, there was a 23 per cent increase in the depth of the crypts, a 21 per cent increase in the number of villi and a 22 per cent increase in the width of the villi. No change was observed in the height of the villi.

Animals↗

Evidence that neuronally released vasoactive intestinal polypeptide inhibits the release of serotonin from enterochromaffin cells of the guinea pig small intestine.

Isolated small intestinal segments of the guinea pig were arterially perfused and the release of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were intra-arterially applied. The muscarine receptor agonist oxotremorine (1 mumol/l) inhibited the release of 5-hydroxytryptamine by about 50%. In the presence of the neurotoxin tetrodotoxin, oxotremorine enhanced the release of 5-hydroxytryptamine by 145%, indicating that the inhibitory effect of oxotremorine was mediated by the release of a neurotransmitter. Exogenous vasoactive intestinal polypeptide (1-100 pmol/l) inhibited the release of 5-hydroxytryptamine by about 50%, an effect antagonized by a specific antibody to vasoactive intestinal polypeptide. This antibody to vasoactive intestinal polypeptide, on its own, had no effect on the release of 5-hydroxytryptamine. However, it prevented the inhibitory effect of oxotremorine. In the presence of the antibody to vasoactive intestinal polypeptide, unlike in the presence of tetrodotoxin, oxotremorine did not stimulate the release of 5-hydroxytryptamine. In conclusion, activation of neuronal muscarine receptors in the guinea pig small intestine enhances the release of several neurotransmitters which can inhibit the release of 5-hydroxytryptamine. The present experiments provide good evidence that vasoactive intestinal polypeptide is one of them.

Animals↗

Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability.

The small intestinal metabolism of tacrolimus, which is used as an immunosuppressant in transplantation medicine, was investigated in this study. Tacrolimus was metabolized in vitro by isolated human, pig, and rat small intestinal microsomes. The metabolites generated were identified by HPLC/MS. Tacrolimus and its metabolites were quantified using HPLC or HPLC/MS. The cytochrome P450 (CYP) enzymes responsible for tacrolimus metabolism in small intestine were identified using specific CYP antibodies and inhibitors. For characterization of the interindividual variability, microsomes were isolated from small intestinal samples of patients who had undergone resection for various reasons. In an in vitro model using pig small intestinal microsomes, 32 drugs were analyzed for their interactions with tacrolimus metabolism. After incubation with human, rat, and pig small intestinal microsomes, the metabolites 13-O-demethyl and 13,15-O-demethyl tacrolimus were identified. The metabolism of tacrolimus by human small intestine was inhibited by anti-CYP3A, troleandomycin, and erythromycin, indicating that, as in the liver, CYP3A enzymes are the major enzymes for tacrolimus metabolism in the human small intestine. Metabolism of tacrolimus by small intestinal microsomes isolated from 14 different patients varied between 24 and 110 pmol/13-O-demethyl tacrolimus/min/mg microsomal protein, with a mean +/- SD of 54.2 +/- 29.2 pmol/min/mg. Of 32 drugs tested, 15 were found to inhibit small intestinal tacrolimus metabolism: bromocryptine, corticosterone, cyclosporine, dexamethasone, ergotamine, erythromycin, ethinyl estradiol, josamycin, ketoconazole, nifedipine, omeprazole, progesterone, rapamycin, troleandomycin, and verapamil. All of these drugs inhibited tacrolimus metabolism by human liver microsomes as well. It is concluded that tacrolimus is metabolized by cytochrome CYP3A enzymes in the small intestine. The rate of the CYP3A enzymatic activities varies about 5 times from patient to patient, and drugs that interfere with the in vitro metabolism of tacrolimus in the liver also inhibit its small intestinal metabolism.

Animals↗

Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine.

1. Substance P (SP) infusions were given close I.A. to the feline small intestine in vivo in a dose that produced plasma concentrations of 1-5 microM. This infusion regularly evoked a net fluid secretion measured with a gravimetric technique. Concomitantly, the release into blood of vasoactive intestinal polypeptide (VIP), a putative neurotransmitter of the enteric nervous system, increased. 2. The SP-induced fluid secretion was blocked by tetrodotoxin (7 micrograms close I.A.), a blocker of fast sodium channels in excitable tissues, and hexamethonium (10 mg (kg body wt)-1, I.V.), a nicotinic receptor antagonist, suggesting that the SP effect was mediated by the enteric nervous system. In line with this it was shown that the SP-evoked release of VIP was also significantly diminished by hexamethonium. 3. Close I.A. infusions of methionine enkephalin (Met-enkephalin; 7-23 nmol min-1) or electrical stimulation of the sympathetic nerve fibres (6 Hz) to the intestine markedly diminished net fluid secretion and the release of VIP caused by SP given close I.A. 4. The cyclo-oxygenase inhibitor diclofenac (5 mg (kg body wt)-1, I.V.) or the histamine-1 receptor antagonist pyrilamine (10 mg (kg body wt)-1, I.V.) did not influence the fluid secretion caused by SP, indicating that the effects of SP were not due to the actions of prostaglandins or histamine. 5. It is proposed that SP activates a nervous reflex arch that we have shown to be activated by various luminal stimuli, including cholera toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Do elevated plasma vasoactive intestinal polypeptide (VIP) levels cause small intestinal motor disturbances in humans?

Increased VIP plasma levels cause severe secretory diarrhea. Moreover, VIP is a major regulator of human intestinal motility. We hypothesized that VIP-mediated intestinal motility disturbances contribute to symptoms in elevated plasma VIP. Ten healthy volunteers were intubated twice with an orojejunal multilumen tube for duodenal manometry, jejunal perfusion of electrolyte and marker solution, and aspiration 10 and 40 cm more distally. All subjects randomly received intravenous infusion of saline and 300 pmol/kg x hr VIP for 5 hr. Results showed that VIP but not saline infusion induced netjejunal sodium secretion, watery diarrhea, and cardiovascular effects (P < 0.04). VIP did not alter intestinal motor activity or the mean duration of the interdigestive motility cycle or of phases I and II but nearly halved the duration of phase III (P = 0.0002). We conclude that increased plasma VIP markedly shortens human phase III activity without influencing other motility parameters. Hence, it is unlikely that VIP-mediated small intestinal motor disturbances cause symptoms in VIPOMA. Yet VIP may contribute to terminate phase III motility.

Gastrointestinal Motility↗