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Vasodilatory effects of cholecystokinin: new role for an old peptide?

Cholecystokinin (CCK) peptides are involved in the control of multiple functions both in the central nervous system (CNS) and in the gastrointestinal tract where they act as neurotransmitters and regulate digestive functions. This review deals with the role of CCK peptides as vasoactive mediators. Recent work from our group demonstrates that CCK peptides induce neurogenic vasodilatation both in cerebral and mesenteric vessels. Such an effect is mediated by nitric oxide and seems to be presynaptic. These findings suggest that endogenous CCK peptides could be relevant vasodilatory agents involved in regulating both cerebral and splanchnic blood flow. We hypothesize here how such an effect could be useful in the interpretation of, in a new conceptual frame, the eventual contribution of CCK to some physiological and physiopathological events, such as splanchnic postprandial hyperaemia, panic attack or migraine.

Animals↗

Radiolabeled and near-infrared fluorescent fibrinogen derivatives create a system for the identification and repair of obscure gastrointestinal bleeding.

BACKGROUND: Gastrointesintal hemorrhage is often difficult to localize. A test that does not depend on active bleeding might prove clinically useful. We tested 2 novel fibrinogen (FBG)-based contrast agents for their ability to localize gastrointestinal (GI) hemorrhage after bleeding stopped. 125I-FBG permits gamma ray-based preoperative or intraoperative scanning, and near-infrared (NIR) flourescent FBG (FBG800) permits real-time intraoperative visualization of active clot. METHODS: Bovine FBG was radiolabeled with 125I or conjugated to the NIR fluorophore CW800. Sites of bleeding were created by gastrotomy, mucosal resection of the stomach, or laceration of a mesenteric vessel; then 1.7 mg/kg FBG800 or 15 microCi/kg 125I-FBG was injected intravenously into mice, rabbits, or pigs 30 minutes before or after injury. Sites of active clot were quantified by using gamma counting and were also imaged by using invisible NIR light intraoperatively, for up to 3 hours postinjection. RESULTS: After an injection of either 125I-FBG or FBG800, sites of prior bleeding could be identified in the absence of active bleeding. Blood clearance was such that a signal-to-background ratio of 2.0 or greater could be achieved within 20 minutes after injection. A similarly labeled human serum albumin did not accumulate at any site, with an SBR of 1.0 or less. CONCLUSIONS: Both radiolabeled (preoperative gamma scanning) and NIR fluorescent (intraoperative real-time imaging) FBG can be used in experimental situations to identify the location of prior bleeding in the absence of active bleeding. Taken together, these contrast agents create a system for the identification and control of obscure GI bleeding.

Animals↗

Radiological features of vascular compression of the duodenum occurring as a complication of the treatment of scoliosis (the cast syndrome).

The application of a body cast or the surgical correction of scoliosis is occasionally associated with acute obstructive vascular compression of the duodenum. The clinical and radiological manifestations observed in 10 such patients are described. All cases manifested abdominal distension and vomiting, while epigastric pain was present in 50%. Plain radiographs of the abdomen demonstrated duodenal distension with little gas in the remainder of the bowel in three cases. Barium studies in nine patients demonstrated an intact mucosal pattern and a duodenum dilated proximal to the site where the superior mesenteric vessels crossed it. All cases recovered with non-operative treatment which included nasogastric suction, intravenous fluids, change in position, particularly nursing in the prone position, and, occasionally, cast removal. The obstruction may sometimes persist or recur and then duodenojejunal side-to-side anastomosis is the surgical procedure of choice. The term "cast syndrome" is a misnomer as vascular compression of the duodenum may also occur in patients who are undergoing treatment for scoliosis without the use of a body cast.

Adolescent↗

Midgut malrotation diagnosed by ultrasound.

Ultrasound was used to demonstrate the abnormal orientation of the mesenteric vessels in six cases of midgut malrotation. Five of these patients were known to have an abnormality of rotation before the ultrasound scan. In one patient malrotation was predicted from the ultrasound scan and confirmed by a barium study and at operation.

Adult↗

Duplex Doppler endosonography in the diagnosis of splenic vein, portal vein, and portosystemic shunt thrombosis.

BACKGROUND/AIMS: Endoscopic ultrasonography is a promising procedure for imaging mesenteric vascular structures. METHODS: Duplex and color Doppler endosonography were used to prospectively evaluate 20 asymptomatic paid volunteers. Subsequently, 11 patients with nondiagnostic transabdominal ultrasound and suspected thrombosis of the splenic and/or portal veins or a portosystemic shunt were evaluated with duplex endosonography. The final diagnosis was based on CT, angiography, and/or surgery or autopsy findings in 9 of 11 patients. RESULTS: In normal volunteers, mesenteric vessel flow velocities and diameters were similar to previously described values. In 10 of the 11 patients with failed transabdominal ultrasound, duplex endosonography was able to provide the correct diagnosis (accuracy of ultrasound 0% versus EUS 91%, p < .001). Mean portal vein diameter was greater in the patient group than in the normal volunteers (18.5 mm versus 10.7 mm, p < .001) and all of the normal volunteers had a portal vein diameter less than 13 mm. No complications were experienced. CONCLUSION: Duplex endosonography allows visualization of the intra-abdominal vasculature and can be considered when transabdominal ultrasound is nondiagnostic in patients with suspected thrombosis of their splenic vein, portal vein, or portosystemic shunt. EUS is able to identify indirect findings of portal hypertension including portal vein enlargement and venous collaterals.

Adult↗

Further evidence on totally transanal one-stage pull-through procedure for Hirschsprung's disease.

BACKGROUND/PURPOSE: Fifteen consecutive children aged 20 days to 12 years with biopsy-proven Hirschsprung's Disease (HD) underwent a transanal pull-through procedure over a 17-month period. These patients have been divided into 2 groups. The first was a series of 9 patients, which helped us gain familiarity and confidence with technical and postoperative gestational problems, and the second series was of 6 patients, which fully corroborates and adds further evidence on the minimally invasive nature of the technique. Mucosectomy of aganglionic bowel, access to the peritoneal cavity, division of rectosigmoid mesenteric vessels, pull-through of normoganglionic colon, colectomy, and coloanal anastomosis all were performed transanally. Patients underwent a program of progressive anal dilatations and were assessed for postoperative clinical course, continence, constipation, diarrhea, postoperative enterocolitis, perianal excoriations, and anal stricture. RESULTS: Mucosectomy was done under direct vision. Operating time ranged from 150 to 350 minutes. The average length of bowel resected was 13.5 cm with a range of 8 cm to 25 cm. There were neither intraoperative nor significant postoperative complications. All but 2 patients accepted full oral feedings on postoperative day 2. Mean hospital stay in the first series of 9 patients was 7 days, range, 5 to 12 days; that of the second series of 6 patients was 5 days, range, 4 to 8 days. All children currently experience 1 to 6 bowel movements per day at a follow-up period of 1 to 17 months. CONCLUSIONS: A one-stage pull-through procedure for HD can be performed successfully with a completely transanal approach. This technique is associated with excellent early clinical results. Many more cases and a longer follow-up period will be required to compare long-term results with other one-stage procedures for definitive treatment of HD.

Anal Canal↗

Normal intestinal rotation with non-fixation: a cause of chronic abdominal pain.

The majority of clinically significant gastrointestinal rotational anomalies involve:(1) an arrest of rotation about the superior mesenteric vessels, (2) abnormal peritoneal bands, and (3) obstruction with or without volvulus. Between 1973 and 1978, six children had chronic intermittent volvulus secondary to a nonfixed but normally-rotated intestine; this is 10% of all infants and children treated for malrotation in our hospital during the same period. Barium studies showed normal duodenojejunal configuration and a colon that was normally situated on at least one study. All were labeled as functional complainers by their pediatricians. One died of a volvulus because her complaints were appreciated too late. At laparotomy, evidence of chronic intermittent volulus secondary to nonfixation from the ligament of Treitz to the transverse colon was found in all patients. A Ladd procedure with appendectomy was performed and immediate resolution of symptoms was noted in each surviving child. Children with a story of chronic abdominal pain deserve a carefully interpreted history and radiographic examination before being labeled as chronic complainers.

Abdomen↗

Right paraduodenal hernia in childhood: a case report.

A 7-year-old patient was recently treated surgically for a right paraduodenal hernia. Paraduodenal hernia is a rare cause of chronic abdominal complaints, as well as acute obstruction, and although it is not typical, it can manifest in childhood. The term "hernia" is a misnomer since this condition results from anomalous intestinal rotation. Knowledge of this embryology will prevent injury to vital mesenteric vessels during "repair" of a right paraduodenal hernia.

Child↗

The effect of cyclosporine in gut ischemic injury: a computerized morphometric and enzymatic analysis.

PURPOSE: Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A (CSA), a potent immunosuppressant, attenuates immune/inflammatory cellular reactions. CSA also might be useful for inhibiting cellular immune responses involved in tissue ischemia/reperfusion injury. The authors hypothesized that CSA would attenuate inflammatory cellular changes associated with gut ischemic injury and that these effects could be quantified by computerized morphometry. METHODS: Twenty Sprague-Dawley rats underwent 60 minutes of gut ischemia by vascular occlusion of the superior mesenteric vessels. After 1 hour of reperfusion, the ischemic small bowel was harvested for histopathological examination and computerized morphometry, as well as xanthine oxidase (XO, U/mg protein) and maltase (MALT, mmol/L substrate degraded/min/mg protein) assays. CSA (5 mg/kg/d subcutaneously) was given to experimental animals (CSA, n = 10) for 5 days before ischemia, and vehicle was given to controls (CON, n = 10). The computer morphometric parameters studied were: surface index (SI, mucosal surface length per linear unit of intestine), average villous thickness (AVT), and average villous height (AVH). RESULTS: Results are provided in Table 1. CONCLUSION: The results of this study show that CSA may play a role in attenuating ischemia/reperfusion injury in the gut. Enzymatic analysis showed a beneficial role in the preservation of mucosal cell function after gut ischemia/reperfusion injury, as demonstrated by an elevated maltose level. Computerized morphometry demonstrated significant differences in all parameters in the experimental group, showing that CSA does confer gut mucosal protection during ischemia.

Animals↗

Effect of BN 50727 on pathological findings and tissue platelet activating factor levels during ileal ischemia in newborn piglets.

The role of platelet activating factor (PAF), a potent ulcerogen mediator in the digestive tract, is thought to be important in the genesis of necrotizing enterocolitis. The aim of this study was to evaluate the role of PAF in the perpetuation and aggravation of gastrointestinal damage resulting from limited ischemia in the 2-day-old piglet using a natural PAF antagonist (BN 50727). Animals were separated into six groups: U4, controls; S, sham operated animals undergoing laparotomy; I4 and I9, ligation of the mesenteric vessels in the last ileal loop; IT4 and IT9, same procedure together with treatment with BN 50727 (50 mg/kg) orally before and after surgery and intraperitoneally during surgery. Animals were killed at day 4 in groups U4, S, I4 and IT4 and at day 9 in groups I9 and IT9, with histological studies and mediator measurements taken. Macroscopic and histological lesions of intestinal wall in groups I4, I9, IT4 and IT9 were similar to those of human neonatal necrotizing enterocolitis and did not vary according to the absence or the presence of BN 50727 treatment (P = .7, I4 v IT4 and P = .9, I9 v IT9). Peritoneal bands were significantly reduced in treated groups IT4 and IT9 as compared with untreated ones I4 and I9 (P = .003). Mucosal PAF levels in the terminal ileum were higher in group I4 than in groups U4 or I9. In the upper loop, mucosal PAF levels were comparable in all groups. An increase in stool PAF levels was observed only in group I9 (26.4 ng/g v 4.7 ng/g, I9 v U4 + S, P < .05), whereas values comparable to those observed in controls were detected in other groups (I4, 7.2 ng/g; IT4, 4.5 ng/g; IT9, 6.8 ng/g). Tumor necrosis factor alpha (TNF alpha) measurements did not exhibit any difference between groups. Using a PAF antagonist, the role of PAF in the aggravation of intestinal damage after ischemia was not remarkable because treatment did not induce any modifications of parietal intestinal lesions. PAF antagonists appeared to reduce significantly the local peritoneal consequences of local inflammation.

Animals↗

Transanal one-stage Soave procedure for infants with Hirschsprung's disease.

PURPOSE: Many centers perform a one-stage pull-through procedure for Hirschsprung's disease (HD) diagnosed in infancy. The authors have developed a one-stage pullthrough procedure using a transanal approach that eliminates the need for intraabdominal dissection. METHODS: Nine children aged 3 weeks to 18 months with biopsy-proven HD underwent a transanal pull-through procedure over a 13-month period. A rectal mucosectomy was performed starting 0.5 cm proximal to the dentate line, and extending proximally to the level of the intraperitoneal rectum. In the first eight children, intraperitoneal position was confirmed with a laparoscope placed through a 3- to 5-mm port in the base of the umbilicus. The muscular sleeve was divided circumferentially to allow full-thickness mobilization of the rectosigmoid junction. Manual transanal traction permitted direct visualization and division of mesenteric vessels with transanal mobilization above the transition zone. Ganglion cells were confirmed by frozen section, and the bowel was transected. The rectal muscular cuff was divided longitudinally, and the anastomosis was completed. The laparoscope confirmed orientation and adequate hemostasis. In a ninth patient, the identical procedure was performed, but with the laparoscope used only for confirmation at the end of the procedure. RESULTS: Operative time, including frozen sections, averaged 194 minutes (range, 169 to 250 minutes), and the average length of bowel resected was 12 cm (range, 7.5 to 22 cm). Four of the nine patients were discharged on postoperative day (POD) 1, four on POD 2, and one patient with Down's syndrome was discharged on POD 6. Median follow-up was 6 months (range, 3 to 14 months). One death occurred 2.5 months postoperatively secondary to sudden infant death syndrome. Complications included postoperative apnea spells (n = 1), mild enterocolitis (n = 2), constipation (n = 1), anastomotic stricture(n = 1), and muscularcuff narrowing (n = 1); each responded to nonoperative management. Stool output has ranged from four to eight per day. CONCLUSION: A one-stage pull-through for HD can be performed successfully using a transanal approach without intraperitoneal dissection. This procedure is associated with excellent clinical results and permits early postoperative feeding, early hospital discharge, and no visible scars.

Anal Canal↗

Etiology of cecal and hepatic lesions in mice after administration of gas-carrier contrast agents used in ultrasound imaging.

The aim of the study was to investigate the etiology of cecal and hepatic lesions in mice and rats after intravenous administration of gas-carrier contrast agents (GCAs). A modified fluorescein flowmetry technique and 24 h necropsy were used in mice (conventional and germ free), rats, and guinea pigs after GCA administration. Different diets and oral nonabsorbable antibiotics were used. Nonfluorescence, edema, congestion, hemorrhage, and mucosal erosion in cecum and colon and nonfluorescent areas in the liver were observed from 16 min after GCA administration in conventional mice on standard diet. Numerous gas bubbles (>50 microm) were observed in the vasculature around the nonfluorescent areas of cecum and colon and in mesenteric vessels draining to the portal vein. Acute inflammation, edema, hemorrhage, and ulceration of the cecum and colon and liver necrosis were seen 24 h after GCA administration in conventional mice on standard diet. When mice were maintained on either a diet with glucose as the only carbohydrate source or on a standard diet supplemented with antibiotics, uniform fluorescence and no organ lesions were observed after GCA administration. Uniform fluorescence and no organ lesions were observed in germ-free mice, rats, and guinea pigs dosed with GCAs and in control animals (mice, rats, and guinea pigs) dosed with sucrose. The results indicate that intravascular growth of GCA microbubbles occurs in the cecal and colonic wall of mice, leading to occlusive ischemia and necrosis in these intestinal segments and secondary gas embolisation in the liver. Transmural gas supersaturation in the cecal wall may explain the intravascular bubble growth in mice.

Albumins↗

Looking to the future: diabetic neuropathy and effects of rosuvastatin on neurovascular function in diabetes models.

Vascular defects contribute substantially to neuropathic changes associated with metabolic abnormalities in diabetes. Statins appear to exert beneficial effects on vascular function independent of cholesterol lowering. In studies of the streptozotocin-induced diabetes rat model, rosuvastatin treatment was shown to correct sciatic motor and saphenous sensory nerve conduction velocity deficits (large fiber defects), thermal hyperalgesia (small fiber defects) and deficits in sciatic nerve and superior cervical ganglion blood flow. Rosuvastatin reversed deficits in nitrergic nerve-mediated vasodilation in the corpus cavernosum and corrected deficits in endothelium-derived hyperpolarising factor-mediated vasodilation in mesenteric vessels. Rosuvastatin did not alter plasma cholesterol in diabetic animals (a characteristic effect in this model), but significantly lowered triglycerides at high doses. Treatment with mevalonate reversed the beneficial effects of rosuvastatin on nerve function and blood flow, suggesting that the effects are mediated by inhibition of the cholesterol biosynthesis pathway in the absence of cholesterol reduction. Thus, rosuvastatin has wide-ranging neurovascular actions in diabetic rats that may be independent of lipid-lowering activity.

Animals↗

Liver imaging with MDCT and high concentration contrast media.

Liver imaging has advanced greatly over the last 10 years with helical CT capability and more recently the addition of multidetector-row CT (MDCT). Multidetector CT technology facilitates imaging at faster speeds with improved image quality and less breathing artifact [Abdom. Imaging 25 (2000) 643]. Exquisite three-dimensional data sets can be obtained with thin collimation providing improved lesion detection, multiplanar imaging, and the ability to perform CT angiography of the liver and mesenteric vessels. New challenges arise with this advance in technology including safety considerations. The radiation dose to the patient has increased with MDCT and this is compounded by the ability to perform multi-phase liver imaging. Furthermore, issues of contrast media administration require reconsideration including optimal timing and rate of administration, the total volume of contrast needed and the ideal iodine concentration of the contrast media. Recently, the use of high concentration contrast media (HCCM) has been explored and study results to date will be reviewed.

Angiography↗

[Acute intestinal ischemia after voluntary drug poisoning].

A case is reported of a patient who suffered from ischaemic enteritis after having taken an overdose of several drugs. The 42-year-old woman was found out no more than 7 h after she had taken a mixture of benzodiazepines, tricyclic antidepressants and barbiturates (4 mg.l-1 blood level on admission). She had been lying against a bedpost, resulting in compression of her anterior abdominal wall below the umbilicus, involving her right femoral nerve. There was a severe rhabdomyolysis. Despite clinical improvement, the patient being extubated the following day, her abdomen remained painful and swollen. A CT abdominal scan showed a peritoneal effusion and a distended small bowel. Laparatomy revealed severe ischaemia of the terminal 80 cm of ileum, with some gangrenous areas. This was resected, and a right-sided ileostomy performed. Histopathological examination demonstrated a mucosal necrosis without mesenteric arterial thrombosis. A bilateral pleural effusion occurred during postoperative course, requiring drainage. Thereafter, the clinical course was uneventful, with intestinal continuity being re-established three months later. The femoral paralysis receded spontaneously. It is likely that this unusual postural complication of coma may be attributed to a transient compression of mesenteric vessels.

Acute Disease↗

[Mechanisms and prediction of hemorrhagic complications during surgery of thoraco-abdominal aortic aneurysms].

This study, including 33 consecutive patients was designed to assess the haemostatic alterations occurring during repair of thoracoabdominal aneurysms. The surgical procedure consisted in Dacron graft replacement of the diseased aorta, using neither cardiopulmonary bypass, nor any shunting technique, nor any heparin. Blood samples were drawn before anaesthesia, before and 30 min after unclamping, and on the first postoperative day. The measured parameters were: haematocrit, platelet count, bleeding, activated cephalin, thrombin and prothrombin times, and concentrations of fibrinogen, factors V, VII, X and II, anti-thrombin III, proteins C and S, fibrin degradation products, D-dimers, alpha 2-antiplasmin, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor, and serum protein. Eight patients developed severe multiple haemorrhages; 3 of them died during the procedure because of uncontrollable bleeding. Although the measured parameters were similar in the "bleeding" and control (n = 25) groups before surgery, there was, before unclamping in the first group, an important increase in activated cephalin and thrombin times, with a fall in concentrations of factor II and V, protein C, fibrinogen, and alpha 2-antiplasmin, and in platelet numbers. After unclamping, these changes worsened further, with an increase in prothrombin time and in fibrinogen levels (0,8 g.l-1), without any increase in fibrin degradation products. Abnormal bleeding started about 30 min after this in all the patients of the "bleeding" group. These changes, involving the fibrinolytic system as well as a fall in concentration of all the coagulation factors, can probably be partly explained by the clamping and unclamping of mesenteric vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Aneurysm↗

Minimally invasive endocrine surgery: laparoscopic resection of insulinomas.

Pancreatic insulinomas are mostly benign and solitary tumors. Successful management of patients with insulinoma relies on accurate localization of the tumors and the use of appropriate surgical techniques. However, preoperative radiological imaging studies often fail to localize the insulinomas because of the small tumor sizes. Conventional intraoperative ultrasonography combined with palpation has been widely used as the best localization tool. Since contact ultrasonography, a new technique for localizing pancreatic lesions, became available as a laparoscopic study, several surgeons have utilized laparoscopy for not only localization but also resection of insulinomas. Previous reports of laparoscopic ultrasonography for intraoperative identification of insulinomas showed a 100% success rate in cases with insulinoma localized by preoperative imaging studies, but a less satisfactory rate in cases with occult insulinoma. Laparoscopic resection of insulinomas located in the head of the pancreas is often difficult because of its anatomical relationship with important adjacent structures such as pancreatic duct and mesenteric vessels. In contrast, insulinomas located in the body or tail of the pancreas are laparoscopically resectable even when they are in close proximity to the major pancreatic duct. Laparoscopic procedure is a feasible technique with low morbidity for surgical management of insulinomas. Accurate preoperative localization is essential for safe performance of this minimally invasive procedure.

Endocrine Surgical Procedures↗

Retrosternal pedicled jejunum interposition: an alternative for reconstruction after total esophago-gastrectomy.

OBJECTIVE: If the colon cannot be used for reconstruction after total esophago-gastrectomy, alternatives have to be sought. METHODS: From 1990 to 2001, retrosternal jejunum loop interposition was performed in 35 patients (male/female: 29:6; mean age 59.2, range 16-83 years) due to cancer in 32 cases and to esophageal perforation in three cases. In all patients reconstruction with stomach or colon, respectively, was impossible on behalf of the underlying histology, of previous resection of the stomach and impedient colonic diseases. A jejunal segment with abundant arcades was chosen, preserving a strong, distal arteriovenous mesenteric pedicle, while 2-3 proximal mesenteric vessels were severed. The loop was pulled up retrosternally, establishing a cervical end-to-side esophagojejunostomy. A Roux-en-Y anastomosis was done in a convenient position. RESULTS: Two patients died perioperatively due to mediastinitis and consecutive multiorgan failure (one Boerhaave's syndrome, one suicidal ingestion of acid). In one case the oral part of the loop developed venous congestion and was replaced by a free jejunal transplant. The perioperative course of 32 patients was uneventful. Seventeen patients are up and well (1-8.5 years). Sixteen patients died of metastatic disease. The functional results are satisfactory. In about 50% of patients recurrent dilatations became necessary due to anastomotic scars. However, none of the patients complained about severe dysphagia. CONCLUSION: In cases of impedient colonic diseases, the pedicled, retrosternal jejunal loop with cervical anastomosis is an alternative for reconstruction after total esophagogastrectomy.

Adolescent↗