Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition.

BACKGROUND: Angiogenesis, the growth of new blood vessels, is a critical homeostatic mechanism which regulates vascular populations in response to physiological requirements and pathophysiological demand, including chronic inflammation and cancer. The importance of angiogenesis in gastrointestinal chronic inflammation and cancer has been defined, as antiangiogenic therapy has demonstrated benefit in models of inflammatory bowel disease and colon cancer treatment. Curcumin is a natural product undergoing evaluation for the treatment of chronic inflammation, including inflammatory bowel disease (IBD). The effect of curcumin on human intestinal angiogenesis is not defined. METHODS: The antiangiogenic effect of curcumin on in vitro angiogenesis was examined using primary cultures of human intestinal microvascular endothelial cells (HIMECs), stimulated with vascular endothelial growth factor (VEGF). RESULTS: Curcumin inhibited proliferation, cell migration and tube formation in HIMECs induced by VEGF. Activation of HIMECs by VEGF resulted in enhanced expression of cyclo-oxygenase-2 (COX-2) mRNA, protein and prostaglandin E(2) (PGE(2)) production. Pretreatment of HIMECs with 10 microM curcumin as well as 1 microM NS398, a selective inhibitor of COX-2, resulted in inhibition of COX-2 at the mRNA and protein level and PGE(2) production. Similarly COX-2 expression in HIMECs was significantly inhibited by Jun N-terminal kinase (JNK; SP600125) and p38 mitogen-activated protein kinase (MAPK; SB203580) inhibitors and was reduced by p44/42 MAPK inhibitor (PD098059). CONCLUSIONS: Taken together, these data demonstrate an important role for COX-2 in the regulation of angiogenesis in HIMECs via MAPKs. Moreover, curcumin inhibits microvascular endothelial cell angiogenesis through inhibition of COX-2 expression and PGE(2) production, suggesting that this natural product possesses antiangiogenic properties, which warrants further investigation as adjuvant treatment of IBD and cancer.

Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion.

Microvascular endothelial cells play a key role in inflammation by undergoing activation and recruiting circulating immune cells into tissues and foci of inflammation, an early and rate-limiting step in the inflammatory process. We have previously [Binion et al., Gastroenterology112:1898-1907, 1997] shown that human intestinal microvascular endothelial cells (HIMEC) isolated from surgically resected inflammatory bowel disease (IBD) patient tissue demonstrate significantly increased leukocyte binding in vitro compared to normal HIMEC. Our studies [Binion et al., Am. J. Physiol.275 (Gastrointest. Liver Physiol. 38):G592-G603, 1998] have also demonstrated that nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) normally plays a key role in downregulating HIMEC activation and leukocyte adhesion. Using primary cultures of HIMEC derived from normal and IBD patient tissues, we sought to determine whether alterations in iNOS-derived NO production underlies leukocyte hyperadhesion in IBD. Both nonselective (N(G)-monomethyl-L-arginine) and specific (N-Iminoethyl-L-lysine) inhibitors of iNOS significantly increased leukocyte binding by normal HIMEC activated with cytokines and lipopolysaccharide (LPS), but had no effect on leukocyte adhesion by similarly activated IBD HIMEC. When compared to normal HIMEC, IBD endothelial cells had significantly decreased levels of iNOS mRNA, protein, and NO production following activation. Addition of exogenous NO by co-culture with normal HIMEC or by pharmacologic delivery with the long-acting NO donor detaNONOate restored a normal leukocyte binding pattern in the IBD HIMEC. These data suggest that loss of iNOS expression is a feature of chronically inflamed microvascular endothelial cells, which leads to enhanced leukocyte binding, potentially contributing to chronic, destructive inflammation in IBD.

Altered motility causes the early gastrointestinal toxicity of irradiation.

PURPOSE: Total abdominal radiation produces symptoms of nausea, vomiting abdominal cramping and diarrhea. Each of these symptoms is associated with disordered intestinal motility. This article reviews studies of large and small intestinal contractile activity following radiation exposure. METHODS AND MATERIALS: Studies of motility utilize strain gauge transducers surgically implanted on the seromuscular layer of the small intestine. All studies were performed in mixed breed dogs to record the occurrence of normal contractions, giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) before, during and after irradiation (22.5 Gy in 9 fractions at 3 fractions/week). Giant migrating contractions and retrograde giant contractions are infrequent in the healthy state. However, in diseased states, GMCs are associated with abdominal cramps and diarrhea, and RGCs precede vomiting. RESULTS: In fasted animals, fractionated abdominal irradiation dramatically increased the frequency of GMCs, with the incidence peaking after the second dose. The increased frequency of GMCS occurred as early as a few hours after the first radiation fraction, and returned to normal within days of cessation of radiation. RGCs were also significantly increased after abdominal irradiation. The frequency of RGCs was greatest on the first and sixth dose of radiation. Clinically, the dogs developed nausea, vomiting and diarrhea as early as the first day of irradiation. In dogs studied in the fed state, decreased amplitude, duration, and frequency of postprandial contractions occurred. These changes may slow intestinal transit during irradiation. Radiation also produced a striking increase in the frequency of colonic GMCs; these changes in colonic motor activity were associated with diarrhea as early as the second irradiation. CONCLUSION: Changes in GI motility during fractionated irradiation precede the appearance of histopathological lesions in the GI tract. Thus, the symptoms of nausea, vomiting, and diarrhea experienced during radiotherapy (particularly those within the first week) are directly related to changes in bowel motility. It is hoped that further understanding of the etiology of these distressing symptoms will help to guide their treatment.

Acquired megacolon is associated with alteration of vasoactive intestinal peptide levels and acetylcholinesterase activity.

Based upon previous morphologic studies, we hypothesized that the development of acquired megacolon was associated with abnormalities of enteric neurotransmitter concentrations and enzymatic activities. Specimens were obtained at surgery from patients with normal descending-sigmoid colon (n = 13) and patients with sigmoid megacolon (n = 6; defined by radiologic measurement). Radioimmunoassays were used to measure the non-adrenergic, non-cholinergic inhibitory neuropeptide, vasoactive intestinal peptide, and the non-adrenergic, non-cholinergic excitatory neuropeptide, substance P, while spectrophotometric assays were used to quantitate acetylcholinesterase activity and choline acetyltransferase activity. There were significantly decreased concentrations of vasoactive intestinal peptide and decreased acetylcholinesterase activity in muscularis externa from patients with acquired megacolon. In megacolon, vasoactive intestinal peptide-containing nerve fibers appeared to be diminished in circular and longitudinal smooth muscle, and immunostaining of nerve cell bodies in the plexus submucosus externus appeared diminished. These results suggest the hypothesis that production of vasoactive intestinal peptide is altered allowing secondary colonic hypertrophy to develop from prolonged cholinergic nerve-mediated contractions of circular smooth muscle. As a corollary to this hypothesis, colonic dilatation might result from prolonged contraction of longitudinal smooth muscle.

Characterization of neuropeptides extracted from canine intestine.

Quantitative determination of neuropeptides in biologic tissues by radioimmunoassay requires both an efficient extraction of neuropeptides as well as maintenance of immunochemical reactivity. Vasoactive intestinal peptide, substance P, and met5-enkephalin were chosen for this study because they are neuropeptides which appear to be involved in multiple physiologic systems. Since all three neuropeptides have a methionine residue within their amino acid sequence, oxidation of methionine to methionine-sulfoxide during the extraction process could diminish their immunochemical reactivity. Multiple factors that might be important in extracting these neuropeptides from canine intestine, including pH of the solvent, tissue homogenization, heating, and addition of enzyme inhibitors, were examined. Concentrations of vasoactive intestinal peptide-like immunoreactivity and substance P-like immunoreactivity were significantly higher in acidic solvents, and tissue homogenization appeared to increase the concentrations of these two neuropeptides. Substance P-like immunoreactivity was increased by heating after tissue homogenization, suggesting heat-induced denaturation of tissue enzymes liberated by homogenization. Separation of acidic tissue extracts by high performance liquid chromatography followed by radioimmunoassay for all three neuropeptides revealed minor acid-induced oxidation of substance P. These results should be useful for planning the extraction of these three neuropeptides from other tissues.

Gene expression and transcript size of the prepro-peptide VIP/PHM-27 in normal human tissue.

The transcript size of VIP/PHM-27 mRNA (vasoactive intestinal peptide/peptide histidine methionine) and the relative distribution of VIP/PHM-27 gene expression in 10 normal human tissues was examined. After mRNA extraction from tissue, VIP/PHM-27 transcript size and relative abundance of mRNA was determined by Northern blot analysis and densitometry of the autoradiograms. VIP/PHM-27 mRNA was detectable in brain, pancreas, colon, ileum and striated muscle while no hybridization signal was observed in liver, kidney, lung, heart, prostate and placental tissue. VIP/PHM-27 transcript in human brain and gut was a single band of 1.7 kb; by contrast, a 7.0-kb transcript was detected in striated skeletal muscle. The highest relative levels of mRNA were observed in brain and pancreas.

Normal physiology of small intestinal motility.

The small intestine produces a number of different contractions in various spatial and temporal patterns that promote efficient digestion, absorption, and propulsion of ingested material. The small bowel also serves a protective role through the use of special situation contractions that rapidly propel enteric contents into the stomach or colon, from which they may be expelled. Contractile activity of the small intestine is coordinated by an interplay of myogenic, neural, and chemical controls.

Propagation of giant migrating contractions between the small intestine, cecum and colon during radiation.

BACKGROUND: Radiation increases the frequency of small intestinal and colonic giant migrating contractions (GMCs). These contractions contribute to the diarrhea and cramping after radiation therapy and are coordinated with one another across the ileocolonic (IC) junction. METHODS: We investigated the coordination of contractile activity between the small intestine, cecum and colon in five canines following circumferential myotomy on the ileum at the IC junction and compared it to intact animals. Studies were performed before and during a radiation schedule. KEY RESULTS: Myotomy increased the frequency of small intestinal GMCs prior to irradiation. In intact animals, the duration and amplitude of cecal GMCs decreased when multiple contractions occurred in rapid succession. This is in contrast to small intestinal and colonic GMCs and suggests a different mechanism of propagation for GMCs within the cecum. Ileal myotomy dramatically decreased the frequency of propagating radiation-induced colonic GMCs. The total number of colonic GMCs was not altered. Colonic contractile activity was disrupted in intact animals during irradiation. However, after ileal myotomy, irradiation did not affect the pattern of colonic contractile states. Diarrhea in irradiated animals with myotomy started earlier than intact animals. This may be related to the frequency of small intestinal GMCs. CONCLUSIONS & INFERENCES: Our findings suggest importance of the enteric neural connections at the IC region to contractile disorders of both the small and large intestine. The anatomic relationship between the canine IC junction is similar to the human ileo-appendiceal-colonic region and surgical manipulations of this area may likewise affect human contractile activity.

Radiation induced small bowel "web" formation is associated with acquired microvascular dysfunction.

BACKGROUND AND AIMS: Radiation therapy of abdominal and pelvic solid tumours results in late intestinal toxicity of a severe nature in approximately 5% of cases. These manifestations may include ischaemia and stricture formation, which may present as "webs". These webs are likely to play a role in the pathogenesis of recurrent bowel obstruction. The mechanisms of microvascular injury to the bowel in the setting of radiation have not been defined. We hypothesised that microvascular dysfunction with impaired vasodilation to acetylcholine (Ach) would be an acquired pathophysiological abnormality in radiation and "web" formation. METHODS: A 40 year old patient treated with radiation, two years previously, for an anal squamous cell cancer presented with recurrent small bowel obstruction. "Webs" in the distal ileum were detected using wireless capsule endoscopy, after small bowel barium radiographs failed to demonstrate a lesion. Following resection, freshly isolated 50-150 mum diameter arterioles from the "web" and adjacent normal calibre bowel were analysed with histology and microvessel physiological studies. RESULTS: After constriction (30-50%) with endothelin, dilation to graded doses of Ach (10(-9)-10(-4) M) was observed in vessels dissected from the stricture and the adjacent normal calibre area. Ach dilation was reduced in vessels from "web" (mean diameter 7 (2)%; n = 3, p < 0.01) compared with the adjacent unaffected bowel (mean diameter 85 (5)%). Dihydroethidine and dichlorofluorescein diacetate intravital staining demonstrated increased reactive oxygen species production in microvessels from "web" compared with adjacent normal calibre bowel. Histology from the strictured bowel demonstrated narrowing of the arterial lumen due to intimal and muscularis propria fibrosis, with endothelial preservation. CONCLUSIONS: External radiation is associated with acquired microvascular endothelial dysfunction and "web" formation in the small bowel.

Neural control of small intestinal giant migrating contractions.

We investigated the neural mechanisms of control of giant migrating contractions (GMCs) in five conscious dogs. After control recordings, a Thiry-Vella loop was prepared from the middle segment, and the remaining two segments were reanastomosed. GMCs were stimulated by intravenous administration of fentanyl and erythromycin lactobionate, oral administration of loperamide and erythromycin stearate, and gastric or intraluminal administration of cider vinegar in the loop. In the intact state, the agents stimulated GMCs in all three segments, and they propagated uninterruptedly from the point of their origin to the terminal ileum. The propagation velocity of GMCs increased, whereas that of migrating motor complexes (MMCs) decreased distally. After Thiry-Vella loop formation, the agents stimulated GMCs independently in the three segments, and they propagated only to the end of the segment in which they started. In the intact small intestine, the GMCs produced ascending and descending inhibition of spontaneous phase II contractions but did not interrupt the caudad propagation of the ongoing MMC. After Thiry-Vella loop formation, the ascending inhibition was unaltered, but the descending inhibition occurred only in the segment containing the GMC. We conclude that the propagation of GMCs in the small intestine is controlled by the enteric nerves. The extrinsic nerves control the ascending inhibition produced by GMCs, whereas the enteric nerves control the descending inhibition.

Small intestinal amyogenesia and dysmyogenesia induced by morphine and loperamide.

We studied the effects of morphine and loperamide on small bowel myoelectric and contractile activity in 12 conscious dogs. After initially producing premature migrating myoelectric complexes, both substances destabilized and obliterated electrical control activity (ECA). The obliteration of ECA occurred mainly in the proximal half of the small intestine. During ECA obliteration, the base line was almost flat at the usual amplification. At higher amplification, the base line exhibited irregular low level fluctuations that could not be related to electrical response activity (ERA) bursts or contractions. The mean time lag for obliteration of ECA in the proximal small intestine decreased at higher doses of morphine infusion. During the destabilization and obliteration of ECA, contractions and ERA bursts occurred in unusual patterns. The ERA bursts and contractions were generally discoordinated. However, in the proximal small intestine some contractions migrated rapidly and uninterrupted at 32 +/- 7 cm/s over long distances (124 +/- 24 cm). ECA destabilization and obliteration were reversed in approximately 15-30 min after the ingestion of a meal or intravenous administration of atropine, hexamethonium, or naloxone. We conclude that during the absence or destabilization of ECA, the ERA bursts and contractions occur in an uncontrolled manner. These two states were called "amyogenesia" and "dysmyogenesia," respectively. The unusual patterns of contractions during small intestinal amyogenesia and dysmyogenesia may be one of the factors in delayed intestinal transit produced by morphine and loperamide.

Small intestinal physiology and pathophysiology.

The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal material back to the colon. However, the major role of giant migrating contractions may be, in pathologic states, associated with abdominal cramping and diarrhea. Giant migrating contractions are associated with mass movements. Vomiting is preceded by a retrograde giant contraction. This contraction rapidly empties the contents of the proximal half of small intestine into the stomach in preparation for vomitus expulsion by contraction of abdominal and diaphragmatic muscles. The three basic mechanisms of control of spatial and temporal patterns of contractions are myogenic, neural, and chemical.(ABSTRACT TRUNCATED AT 400 WORDS)

Gastrointestinal motor effects of erythromycin.

We studied the small intestinal motor effects of oral and intravenous (iv) erythromycin in 10 conscious dogs. After control recordings with placebo, oral or iv erythromycin was given at 40% of the migrating motor complex (MMC) cycle. Recordings were made after administration until normal contractile activity had returned or 12 h postdrug administration. Low doses initiated a premature MMC. High doses, however, prolonged the MMC cycle length. Erythromycin reduced the MMC propagation velocity at all doses. Both oral and iv erythromycin induced amyogenesia. During this pattern, electrical control activity was obliterated in the proximal and destabilized in the distal small intestine. Erythromycin also increased the incidence of retrograde giant contractions (RGCs) and vomiting. These effects occurred within the first 2 h after oral and within the first 30 min after iv administration. The incidence of giant migrating contractions (GMCs) increased significantly from 5 to 12 h but not from 0 to 5 h after administration. The distance of origination of GMCs from the ileocolonic junction was significantly increased from 5 to 12 h. The amplitude ratio, duration, and velocity of migration of GMCs induced after erythromycin were similar to control values. Clusters of coordinated antral and duodenal contractions also occurred early after administration. Our findings suggest that erythromycin has multiple motor effects on the stomach and small intestine. Diarrhea, abdominal cramping, and vomiting associated with erythromycin may be related to increased incidence of GMCs and RGCs. Erythromycin has a biphasic effect on MMC cycle length, initiating premature MMCs at low doses and prolonging their cycle length at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastrointestinal motility: some basic concepts.

The spatial and temporal patterns of phasic contractions in the gastrointestinal tract are regulated by a complex interplay between the myogenic, neural and chemical control mechanisms. These contractions are largely responsible for the mixing and propulsive movements of the gut after a meal. In the fasted state, organized groups of contractions called cyclic motor activity and migrating motor complex keep the upper digestive tract clean of residual food and debris. In addition, the small intestine and the colon generate giant migrating contractions which are several-fold stronger than the postprandial phasic contractions and migrate uninterrupted over long distances. The giant migrating contractions are effective in rapid propulsion. The upper small intestine and the antrum generate retrograde giant contractions that generally precede vomiting.

Nitric oxide production is diminished in colonic circular muscle from acquired megacolon.

PURPOSE: Nitric oxide modulates human colonic smooth muscle function. To determine whether nitric oxide production is altered in colon from acquired megacolon, we measured cholinergic nerve-mediated contractions in vitro before and after inhibition of nitric oxide synthase. METHODS: Intramural nerves in circular smooth muscle from histologically normal colon (n = 12) and acquired megacolon (n = 3) were activated by electrical field stimulation. RESULTS: In controls blockade of nitric oxide synthase by N(G)-Nitro-L-Arginine induced increases (P < 0.05) in amplitude of contractions; these increases in amplitudes were blocked by L-Arginine (analysis of variance; P < 0.05). By contrast, blockade of nitric oxide synthase did not increase amplitudes of contractions with circular smooth muscle from acquired megacolon. An immediate phasic contraction was blocked by atropine sulfate. CONCLUSIONS: The results support the concept that nitric oxide production modulates cholinergic nerve-mediated contractions in normal colonic circular muscle, whereas acquired megacolon is associated with altered release of this inhibitory neurochemical. Potential explanations include depletion of tissue L-Arginine, decreased capacity to recycle citrulline to arginine, or decreased release of vasoactive intestinal peptide from circular smooth muscle in acquired megacolon.

Effects of fractionated doses of ionizing radiation on small intestinal motor activity.

The small intestinal motor effects of fractionated doses of ionizing radiation were studied in 6 conscious dogs. Eight strain-gauge transducers were implanted on the small intestine and a single gauge on the ascending colon, of each dog. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for 3 successive weeks (total dose, 2250 cGy). Recordings were then made for 4 wk of follow-up. Giant migrating contractions occurred 11 times in 520 h of control recordings in the fasted and fed state, with a mean distance of origin of 55 +/- 16 cm from the ileocolonic junction. Abdominal field irradiation significantly increased the incidence and distance of origin of these giant contractions to 438 in 745 recording hours and 158 +/- 7 cm from the ileocolonic junction, respectively. The incidence of giant migrating contractions peaked after the second dose of radiation. The amplitude ratio of radiation-induced giant migrating contractions to phase III contractions, and their duration and velocity of migration, were similar to the control state. The dogs developed diarrhea and vomiting as early as the first fraction of radiation. Irradiation also increased the incidence of retrograde giant contractions from 8 in 520 h of control recording to 42 in 745 h of recording during the radiation schedule. The radiation-induced retrograde giant contractions peaked in incidence on the day of the first fraction of radiation and were more likely to be associated with a vomiting episode than those occurring in the control period. Migrating motor complex cycling persisted during radiation and its cycle length was not different from the control or postradiation values. Our findings suggest that some of the side effects of radiation such as diarrhea, abdominal cramping, and vomiting may be related to the dramatically increased incidence of giant migrating contractions and retrograde giant contractions.

Local effect of substance P on colonic motor activity in different experimental states.

We studied the effects of close intra-arterial injections of substance P on colonic motor activity in the conscious state, during anesthesia, and during acute laparotomy. In the conscious state, with enteric nerves intact, substance P stimulated postsynaptic cholinergic neurons to induce a large amplitude and long duration contraction. This response was blocked by prior close intra-arterial injection of atropine and tetrodotoxin (TTX) but not hexamethonium. Hexamethonium and TTX given alone, close intra-arterially, induced a series of short-duration contractions. Prior close intra-arterial administration of hexamethonium significantly enhanced the colonic motor response to substance P. After blockade of nerve conduction by TTX, substance P induced a series of short-duration contractions with characteristics different from those when the nerves were functioning. Anesthesia alone had little effect on the colonic motor response to substance P, but laparotomy inhibited it significantly. Laparotomy similarly inhibited the contractile response to bethanechol. Gut handling had no further effect on this inhibition. We conclude that in the conscious state substance P acts preferentially on postsynaptic cholinergic neurons to contract colonic circular muscle. When the intrinsic nerves are blocked, substance P may act directly on the smooth muscle to induce circular muscle contractions with characteristics different from those induced when nerves are intact. Substance P also has a weak inhibitory motor effect by its action on presynaptic neurons that synapse on postganglionic intrinsic inhibitory neurons. Anesthetic doses of barbiturates have no major effects on the neuromuscular response to substance P, but laparotomy significantly inhibits the smooth muscle response and selectively blocks some neurons.

Fractionated doses of ionizing radiation alter postprandial small intestinal motor activity.

We investigated the effects of total abdominal fractionated irradiation on postprandial small intestinal motor activity in five dogs. Five strain-gauge transducers were attached to the seromuscular layer of the duodenum, jejunum, and ileum of each dog to record circular muscle contractions. Radiation (250 cGy) was administered three times a week on alternate days for three successive weeks (total dose, 2250 cGy). Postprandial 4-hr recordings were made once each week during radiation and at one and three weeks following completion of radiation. Duodenal mean amplitude and area under contractions did not change during or following the radiation schedule, but the mean frequency and duration of duodenal contractions decreased during the radiation schedule. Both parameters returned to baseline values postirradiation. Jejunal mean duration, amplitude, area, and frequency of contractions decreased during radiation; mean amplitude and area returned to baseline values postirradiation but not the duration and frequency of contractions. All parameters of ileal contractions decreased during radiation, and all but area and amplitudes remained depressed postirradiation. Significantly decreased strength and frequency of contractions, particularly in the jejunum and ileum occur during and following irradiation. These changes may potentially alter transit time.

Multidisciplinary management of altered body image in the patient with an ostomy.

Many clinical studies have found patients with ostomies to be a group facing multiple adjustment demands. One of these demands is coping with a significant change in body image. At the Medical College of Wisconsin, a team approach has been initiated; the ET nurse, the psychologist, and the surgeon deal with body image concerns together. Problems requiring counseling have included difficulty with personal acceptance, personal and social body-image disruption, sexual concerns, reduced self-care skills, and the management of surgical complications. This article represents a study employing a methology of selected case presentations. Cases were chosen to outline the types of problems encountered and were selected from referrals made for psychologic intervention by the surgeon and ET nurse. The patients included four women and three men, ranging in age from 22 to 79 years. Data were compiled by examining the records of the surgeon, ET nurse, and psychologist. The primary needs revolved around personal or social acceptance of altered body image. By addressing these needs in a straightforward, time-limited manner, postsurgical counseling was delivered effectively for these patients. In conclusion, we have demonstrated the multidisciplinary approach to be successful in facilitating adaptation to an altered body image.