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To assess the rate of bone loss in patients with inflammatory bowel disease, we prospectively studied 35 patients (17 women) aged 36 +/- 13 (range 17-60) years, 14 of whom had Crohn's disease and 21 with ulcerative colitis (including 12 with ileoanal anastomosis). Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. The follow-up was 19 +/- 8 months. During this period, 14 patients received oral steroids. Lumbar bone density changes expressed as a percentage per year were -3.1 +/- 4.9%, -6.4 +/- 7.5% and +2.0 +/- 4.0% in Crohn's disease and ulcerative colitis without and with ileoanal anastomosis respectively (p = 0.007). The same pattern was observed at the femoral neck. Mean annual lumbar bone density changes were -6.2 +/- 7.0% and +0.9 +/- 3.9% in patients with and without steroids during follow-up (p = 0.002). We conclude that patients with inflammatory bowel disease are at risk of lumbar and femoral bone loss. However, bone loss is not observed in patients with ileoanal anastomosis.

Endoscopic ultrasonography (EUS) and endoscopy were prospectively performed and compared to the histopathologic findings of the resection specimens in 24 patients with primary gastric lymphoma (PGL). On EUS, three types of PGL could be differentiated, a superficial type (n = 10), an infiltrating type (n = 12) and a tumorous type (n = 2). In the correct assessment of surface extension of the tumors, endoscopy and EUS agreed in 37.5% of cases and EUS showed more extensive disease than endoscopy in 58% of cases. However, in comparison to the resection specimens, EUS still underestimated the tumor surface extension in 37.5% of cases; this was mainly in low grade malignant PGL. The depth of tumor infiltration was correctly determined on EUS compared to the resection specimens in 91.5% of cases. Sensitivity, specificity and accuracy of diagnosing lymph node metastases were 100%, 80% and 83%, respectively. We conclude that EUS is a useful pre-therapeutic staging tool for primary gastric lymphoma but there remain some problems in determining the longitudinal and circular tumor spread in order to accurately guide the extent of gastric resection.

PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments.

Recent studies have suggested that esophageal HPV infection could be a risk factor for esophageal squamous-cell carcinoma. The aims of our study were to assess the presence of HPV esophageal infection among French patients with esophageal squamous-cell carcinoma and to compare the prevalence of this infection among control patients exposed to similar known risk factors (alcohol and tobacco) and among non-exposed control patients. All patients had the following investigations: serum immunoglobulin level, T-lymphocyte subsets, cutaneous anergy test and endoscopy with biopsies from tumoral and normal areas. Three different methods were used for HPV-infection diagnosis: histological score, in situ hybridization intended for detection of HPV types 6, 11, 16, 18, 31 and 33, and dot blot intended for detection of HPV types 6/11 and 16/18. Five out of 12 patients with esophageal carcinoma had HPV esophageal infection. This infection did not result from impaired immune status. The most frequently observed types are HPV 16/18. None out of 17 exposed controls and only 1 out of 7 nonexposed controls had HPV esophageal infection (p less than 0.01). HPV infection may be implicated in the development of esophageal squamous-cell carcinoma in association with known risk factors.

Intracoronary brachytherapy aims at a reduction of in-stent restenosis by lessening neo-intimal proliferation. To assess its clinical potential, a systematic review of the literature indexed in the standard biomedical bibliographic databases selected eight prospective randomized clinical trials; seven of them, comparing coronary brachytherapy and non-treatment or placebo, have been included in the present meta-analysis. This analysis confirms the angiographic benefit of this procedure, as reported in the individual studies; it also shows, however an excess of clinical adverse effects not exhibited by any individual trial. Therefore, intracoronary brachytherapy cannot be recommended as routine practice, while one cannot rule out its interest in special situations.

Deep pelvic endometriosis may lead to severe pain, the treatment of which may require complete surgical resection of lesions. Digestive infiltration is a difficult therapeutic problem. Preoperative diagnosis is difficult and digestive infiltration may remain unknown with incomplete resection and sometimes repeated surgery. Both magnetic resonance imaging (MRI) and endoscopic ultrasonography are able to detect rectosigmoid infiltration but their usefulness in the preoperative staging is still to be evaluated. The aim of this work was to evaluate and compare both techniques in the preoperative detection of deep pelvic endometriosis, particularly digestive infiltration.From 1996 to 1998, 48 women with painful deep pelvic endometriosis had preoperative imaging exploration with endoscopic ultrasonography and MRI, and were operated on in order to attempt complete endometriosis resection. Patients were proposed for laparoscopic resection if endoscopic ultrasonography and/or MRI did not reveal digestive infiltration or for open resection if endoscopic ultrasonography and/or MRI were positive for digestive infiltration.Endoscopic ultrasonography and/or MRI led to suspicion of digestive endometriosis in 16 patients. Surgical resection was performed in 12 and digestive wall invasion was histologically demonstrated. At final follow-up, all patients had a dramatic decrease of their symptoms. The remaining 4 patients refused digestive resection and had only laparoscopic gynecologic resection. Infiltration although not histologically proven was very likely both on operative findings and clinical evolution. Digestive infiltration was preoperatively excluded in the 32 other patients. All had a laparoscopic treatment without digestive resection and pain diminished in all patients. In the 12 patients group who had digestive resection, digestive infiltration was correctly diagnosed by endoscopic ultrasonography in all cases (no false negative) whereas MRI, even with the use of endocoil antenna, led to correct diagnosis in 8 out of 12 cases. When endoscopic ultrasonography was negative for digestive infiltration, laparoscopic resection of lesions at surgery appeared complete in all cases. For the 16 patients with presumed digestive infiltration, sensitivity of endoscopic ultrasonography and MRI was 100 and 75% respectively, with a 100% specificity in both cases. MRI appeared very accurate for the detection of ovarian endometriotic locations. MRI was more sensitive but less specific than endoscopic ultrasonography for the diagnosis of isolated endometriotic recto-vaginal septum and utero-sacral ligaments lesions.Endoscopic ultrasonography was the best technique for the diagnosis of digestive endometriotic infiltration, which complicates the therapeutic strategy. MRI, however, allows more complete staging of other pelvic endometriotic lesions.

Cytogenetics studies have suggested that short arm deletion in chromosome 1 is involved in triggering colorectal tumor development. To elucidate the role of 1p under-representation in the tumoral process, we investigated by fluorescence in situ hybridization interphase cytogenetics, using simultaneously centromeric and p36 telomeric probes for chromosome 1, 27 primary adenocarcinomas, 5 metastases, 5 adenomas and as control 4 normal mucous membranes. The 1p under-representation in paradiploid tumoral cells, interpreted as a 1p deletion, was observed in 8/27 adenocarcinomas, 2/5 metastases and 3/5 adenomas. Thus, in diploid cells 1p deletion was observed in some tumors independently of the stage of the process. The 1p under-representation in total number of examined cells, i.e., diploid and aneuploid, was observed in 14/16 grade B1-B2 tumors, in 5/8 grade C1-C2 tumors, and all grade D tumors (3/3) and all metastases (5/5). There were no correlations with location or histological characteristics of cancers, gender or age of patients. These results show high frequency of 1p under-representation in intestinal tumors, and lead to separate the under-representation of 1p in diploid cells, which correspond to a 1p deletion probably implicated in the initiation of the process, from the under-representation in aneuploid cells, which mainly may be the consequence of complex rearrangements in relation to extension of the malignant process.

Nitric oxide synthase (NOS) activities are responsible for the enzymatic conversion of L-arginine into NO and L-citrulline. Relatively low amounts of NO are produced in intestinal epithelial cells or are released from nerve endings. The effects of NO production are related to the maintenance of epithelial integrity and permeability. A pathological role of an increased NO production has been suggested to play a role in models of experimental colitis. In humans, NOS activity in colon mucosa from patients with ulcerative colitis is clearly increased when compared with the activity of the control group. In contrast, an increase of NOS activity in the colon mucosa from patients with Crohn's disease remains controversial. In the present work, we have measured NOS activity in colon biopsies originating from the control group (n = 16), from patients with ulcerative colitis (n = 23) and Crohn's disease (n = 17) using the radiochemical method of the conversion of L-[guanido-14C] arginine into radioactive L-citrulline. In the control group, NOS activity was mainly of the inducible type (88% of total NOS activity) since it was characterised by its insensibility to the absence of calcium in the assay medium. In colon biopsies originating from patients with ulcerative colitis, inducible NOS activity was increased 3 fold (p < 0.005) and in patients with Crohn's disease, inducible NOS activity was increased 5 fold (p < 0.005). Correlations between NOS activity in colon biopsies and the intensity parameters of the disease i.e. Truelove index, endoscopic score and histological parameters were evidenced in patients with ulcerative colitis. In contrast, in patients with Crohn's disease, the high inducible NOS activity was not correlated with any intensity parameters of the disease. From these data, we concluded that although inducible NOS activity was increased several fold in colon biopsies originating from patients with both ulcerative colitis and Crohn's disease, a correlation between this activity and the severity of bowel inflammation was not found in either cases.

This study was aimed at elucidating the relation between the cytogenetic characteristics and the invasive ability of two human colonic adenocarcinoma cells lines, HT29 and CaCO2. These two cell lines have very different tumorigenic and metastatic capacities after intrasplenic injection into nude mice: high for HT29 and relatively weak for CaCO2. At the time of injection, cytogenetic studies of the two cell lines revealed shared abnormalities: paratriploidy with seven common extra chromosomes or chromosome regions and specific particularities. In HT29 cells, we observed a large marker of unknown origin, an isochromosome i(11)(q10) and 5, 12, 13, 15, 19, and (19q+) supernumerary chromosomes, and, finally, the absence of one chromosome 16. In CaCO2 cells, we observed a chromosome 1-derived marker with q24-31 duplication, 12q and 16 supernumerary chromosomes, and a der(16) marker. The most striking difference between the karyotypes of these two cell lines concerned chromosome 16 (under- and overexpressed in HT29 and CaCO2 cells, respectively), overexpression of chromosomes 13, 15, and 19 in HT29 cells, and the relative loss of 12p in CaCO2 cells. Although some differences may be due to the intrinsic characteristics of the stem line, the establishment of specific cytogenetic abnormalities points out the role of many regions of the genome in tumorigenic and metastatic capacities of malignant cells.

Esophageal involvement is frequent in Down syndrome. We report a case of dysphagia in a 21-year-old patient with Down syndrome and repaired esophageal atresia. Radiology, endoscopy, and manometry showed typical features of achalasia. The patient was treated first by botulinum toxin injection and afterwards by Heller myotomy with good result. The role of motor disorders associated with esophageal atresia or with primary achalasia in this patient is discussed.

Peliosis hepatis is an uncommon liver condition characterized by blood-filled cavities. We report the CT, angiographic and MR features of a case of peliosis hepatis with no obvious etiology and spontaneously regressing hemorrhagic necrosis. Helical CT showed multiple peripheral low-density regions with foci of spontaneous high density suggesting the presence of blood component. On MR imaging, the multiple peripheral lesions were hypointense on T1-weighted and hyperdense on T2-weighted images, with bright foci on all sequences suggesting subacute blood. Angiography showed no evidence of tumor or vascular malformation; multiple nodular vascular lesions filling in the parenchymal phase and persisting in the venous phase suggested blood-filled cavities. Pathological examination showed blood-filled spaces with no endothelial lining, characteristic of the parenchymal type of peliosis. Knowledge of the imaging features of hemorrhagic necrosis due to peliosis hepatis is important since it can be responsive to antibiotic therapy. Furthermore, differentiating hemorrhagic necrosis from hepatic abscess avoids dangerous and sometimes fatal percutaneous drainage.

The pleiotropic cytokine leukemia inhibitory factor (LIF) possesses proinflammatory properties in common with tumor necrosis factor (TNF-alpha), interleukine (IL) -1 and -6, such as the induction of acute phase protein synthesis. LIF may have chemotactic activity through the induction of IL-8 production. LIF is produced by normal and tumoral cells and appears to facilitate in vivo rat colon carcinoma cells growth. Inflammatory bowel diseases, ulcerative colitis (UC) in particular, are histologically characterized by the infiltration of the colonic mucosa with activated neutrophils, macrophages and lymphocytes. Cytokines with their inflammatory as well as their regulatory activities may play a role in the perpetuation and possibly the initiation of inflammation in this disease and its local and/or systemic complications. Moreover, colorectal cancer is a late well identified complication in patients with long standing inflammatory bowel disease, UC in particular. Taken together, these results suggest that LIF could be involved in tumorigenic and/or metastatic processes of colorectal cells in UC patients. The aims of the present study was to quantify and to compare the colonic and systemic productions of LIF in UC patients. We showed for the first time in patients with UC, a high local production of LIF well correlated with IL-8 production. We also analyzed the effect of LIF on a human colon carcinoma cell line HT29. We demonstrated that LIF stimulated HT29 cell growth in a dose dependent-manner. These results suggest that LIF may play a critical role in the susceptibility of colonic host cells to tumor growth in patients with UC.

A radiological examination of the small bowel is often performed in case of gastrointestinal bleeding of obscure origin. More recently, push-type enteroscopy has been reported as a valuable tool in this indication. The purpose of this study was to compare the diagnosis efficiency of these two procedures.From February 1994 to February 1996, 40 patients (mean age: 52 years) with obscure gastrointestinal bleeding (iron-deficiency anemia without obvious cause of blood loss or malabsorption: n = 17; macroscopic gastrointestinal bleeding: n = 23) were examined by small bowel follow-through and push-type enteroscopy (jejunoscopy n = 19; double way examination n = 21). Each patient had negative upper and lower gastrointestinal tract endoscopies prior to small bowel examinations.Small bowel follow-through revealed only one lesion potentially responsible for blood loss (2.5%), corresponding to a jejunal leiomyoma. Push-type enteroscopy detected small bowel lesions potentially responsible for blood loss in 6 patients (15%). The lesions were located in the jejunum in 5 cases (arteriovenous malformations: n = 3; metastasis: n = 1; leiomyoma: n = 1), in the ileum in 1 case (leiomyoma). The efficiency of push-type enteroscopy for the detection of a small bowel lesion was of 22% in case of macroscopic bleeding and of 6% in case of iron-deficiency anemia. Push-type enteroscopy also revealed lesions previously undetected by gastroscopy or colonoscopy in 8 patients (20%).Push-type enteroscopy was more effective than small bowel follow-through to detect the origin of obscure gastrointestinal bleeding. Push-type enteroscopy revealed a cause of bleeding in 35% of patients, located in the small bowel in only 15% of the patients.

Rats transgenic for HLA-B27 and human beta 2-microglobulin develop a spontaneous, multisystem, inflammatory disease that resembles human B27-associated disease and that involves the gut mucosa. This model predominantly affects the colon and is characterized by an extensive infiltration of the mucosa by inflammatory cells, largely composed of mononuclear cells. In addition, an increased plasma level of nitric oxide (NO)-derived metabolites was described in this model. Deficiency in the anti-inflammatory cytokine, interleukin-10 (IL-10), leads to the development of colitis in IL-10 knockout mice, suggesting that IL-10 plays a major role in the control of gut inflammation. The objectives of this work were to study the mechanisms of the inflammatory bowel disease (IBD) in HLA-B27 rats and to determine the effects of treatment with IL-10. The 33-3 line of HLA-B27 recombinant rats with established disease was treated in two consecutive experiments with murine recombinant IL-10 for five weeks. Assessment of the effect of this treatment was performed, based on clinical, histological and biological (myeloperoxidase and inducible NO synthase activities; tumor necrosis factor-alpha, interferon-delta, CD3, iNOS and beta-actin mRNA expression. In 33-3 rats with established disease, mesenteric lymph nodes were hyperplastic, and colonic cellularity and MPO and iNOS activities in the colonic mucosa were increased without any detectable effects of IL-10 administration. IFN-gamma and iNOS mRNA were only detected in the colon of transgenic rats. Despite a lack of effect on disease expression, IL-10 strikingly reduced the level of IFN-gamma mRNA in gut mucosa. Up-regulation of IFN-gamma mRNA suggests that the IBD of HLA-B27 rats is mediated by T-helper 1 lymphocytes. Sustained administration of IL-10, in HLA-B27 rats with established disease, efficiently inhibited IFN-gamma mRNA expression but did not influence disease expression: these results indicate that IFN-gamma may exert a critical role at an earlier stage of the disease rather in the maintenance of the lesions.

Cytogenetic anomalies described in colo-rectal tumors are numerous. Despite the complexity and the number of the anomalies observed, a combined study of their frequency and of the stage of prognosis of the tumors suggests that the evolution from colonic adenoma to carcinoma often follows a sequence of events comprising a 5q15-22 deletion (DCC), and a 17p deletion (P53). It even seems likely that in many cases, these events are not constant and that others might lead to the same phenotypic transformation. Chromosome 1 involvement in structural rearrangements has been demonstrated in numerous forms of cancers, malignant blood disorders and in solid tumors. In colorectal adenocarcinoma anomalies have been described on short and/or long arms. In a case of adenoma with mild dysplasia a deletion of the distal part of the short arm of chromosome 1 was observed as an isolated cytogenetic anomaly, suggesting it would be an early, perhaps triggering, event for the tumour development. A cytogenetic study in a series of colo-rectal tumours, researches on loss of heterozygosity and microsatellite instability lead to consider deletions at chromosome 1p as an early event in human colorectal tumourigenesis.

Patients with ulcerative colitis are at risk of low bone mineral density (BMD). Proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis diminishes the risk of bone disease. The aims of this study were to assess the mechanism of low BMD and to measure bone density changes after IPAA.Twenty patients with IPAA for ulcerative colitis, of mean(s.d.) age 38(9) (range 21-58) years, had measurements of lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry, a mean(s.d.) 28(23) (range 3-84) months after proctocolectomy. Serum levels of calcium, phosphate, parathyroid hormone, osteocalcin and 25-hydroxy vitamin D were determined. Fifteen patients were followed for 28(12) (range 8-50) months.At baseline, six patients had spine BMD more than two standard deviations below the normal value, and three had vertebral crush fractures. Mean vitamin D values were normal and no patient had osteomalacia. BMD increased with time elapsed since IPAA (spine: r = 0.71, P = 0.005). During follow-up, mean(s.d.) changes in bone density were +2.3(3.8) and +2.1(5.6) per cent per year at the spine and femoral neck respectively.These results suggest that in patients with IPAA for ulcerative colitis, low BMD is not associated with vitamin D malabsorption and may be reversible after surgery.

Background: Intravenous erythromycin has previously been reported to stimulate gastric emptying, to inhibit gastric acid secretion and to stimulate pancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers. Aim: The aim of this study was to evaluate the effects of oral erythromycin (160 mg/h) on gastrointestinal function under these conditions in seven healthy subjects. Method: This randomized double-blind cross-over study measured the gastric emptying rate of nutrients, gastric acid secretion, gastric pH, jejunal flow rate as well as biliopancreatic secretion and duodeno-caecal transit time during a 19.9 kJ/min continuous infusion of a nutrient solution (4.18 kJ/mL) in the antrum over a 6-h period by a perfusion method. Results: The nutrition was well tolerated except by one subject with placebo perfusion. During the 6-h period, total gastric volume and gastric volume of nutrient decreased during erythromycin administration by 22±8 and 22±6%, respectively. Gastric acid secretion was not modified by erythromycin. Lipase and bile salt outputs were significantly higher with erythromycin. The duodeno-caecal transit time was not statistically different with drug and placebo (169±15 and 146±19 min, respectively). Conclusion: During continuous gastric infusion of a liquid diet, the effect of oral erythromycin on gastric emptying could be useful to optimize cyclic enteral nutrition or to enhance the tolerance of enteral nutrition.

The aim of this study was to place Forlax in its therapeutic class comparing its efficacy and its tolerance with Transipeg in the treatment of adult's chronic constipation. A total of 256 outpatients suffering from chronical idiopathic constipation (38 males and 218 females, mean age 51) have been included in a double blind multicentric study run on two parallel groups. Patients have been treated with 1 to 3 intakes daily, adapting themselves the posology to obtain the therapeutic result that would give them satisfaction. The length of the study was of 4 weeks with 3 consultations on D0, D14 and D28. Patients collected every day the frequency and consistency of their stools, the conditions of evacuation, the presence of digestive symptoms; each week the global improvement of the constipation on a visual analogical scale (VAS) and at the end of the period, their opinion on the global digestive state, the quality of life during the study and the taste of the medicine (VAS). The physician also was giving an efficacy score at the end of the study. Frequency and intensity of adverse events were low and identical in both groups. Forlax is significantly more effective than Transipeg: as much on the global improvement of the constipation expressed by the patient (p0.001), as on the evolution of the number of stools (p0.001). Efficacy has been noticed by the follow-up of the physician who gave a 76.1 score to Forlax against a 56.2 score to Transipeg (p0.001) and only with Forlax a stool per day was obtain after the first week of administration. Patients are more satisfied with Forlax which improve significantly their global digestive satisfactory index (p0.001) with favourable repercussion on their quality of life (p0.001). The taste of Forlax was very much appreciated by the patients (p0.001).

A case of a malignant peritoneal mesothelioma revealed by recurrent episodes of peritonitis is reported. This presentation had never been described. A 54 year-old man presented successive episodes of appendicitis, cholecystitis and sigmoiditis associated with purulent aseptic peritonitis. There were no signs of immunodepression or vasculitis. Initial analysis of peritoneal biopsies showed non specific inflammation. Because of long-term asbestos exposure, these biopsies were reviewed. A diagnosis of peritoneal mesothelioma was made on subserous infiltration by mesothelioma cells, and confirmed by immunohistochemistry. The patient died ten months after the diagnosis of mesothelioma despite chemotherapy (cisplatine+interferon).

Erythromycin, a macrolide antibiotic, has been reported to increase gastric emptying. The aim of this study was to evaluate the effects of intravenous erythromycin (150 mg/h) on gastric emptying, small intestinal transit time, gastric and biliopancreatic secretions during gastric infusion of a liquid diet in healthy volunteers.A randomized double-blind crossover study (erythromycin versus placebo).Gastric emptying rates of nutrients, gastric acid secretion, gastric pH, jejunal flow rates, as well as biliopancreatic secretions and duodeno-caecal transit time, were evaluated during a continuous infusion at 4.5 kcal/min of a nutrient solution (1 kcal/ml) in the antrum, over a 6 h period, by a perfusion method.During the 6 h period, total gastric volume and gastric acid secretion decreased during erythromycin administration of 37 and 22%, respectively (area under the curves). Lipase outputs were significantly higher with erythromycin than placebo. Bile salt output was not significantly different between erythromycin and placebo. Duodeno-caecal transit time increased significantly during erythromycin infusion compared with placebo (191 +/- 12 versus 159 +/- 17 min; P0.05).During continuous gastric infusion of a liquid diet, intravenous erythromycin has a powerful effect on gastrointestinal function. The motor and secretory effects may enhance the tolerance and the efficiency of enteral nutrition in humans.

The appearance in plasma of sulphapyridine after oral administration of salicylazosulphapyridine (Salazopyrin) was shown to be useful for measuring the orocecal transit time in normal subjects. The purpose of this study was to use this method in diarrhea with accelerated intestinal transit time. A two-step study was performed in 12 healthy volunteers: a) under resting conditions; b) 2 weeks later with ricinoleic acid 40 ml (n = 6) or senna 19 mg (X-Prep = 1.2 g; n = 6) administration. In each step, Salazopyrin (2 g) and 20 radiopaque markers were ingested with a 200 kcal meal (Polydiet TCM = 200 ml). The following parameters were determined: a) plasmatic level of sulphapyridine (spectrophotometry) at 30 min intervals during 12 h; b) 2-day stool frequency and weight; c) oro-anal transit time (passage of the first marker and half of the markers in stools). In one subject, no sulphapyridine level was detected after administration of ricinoleic acid. With senna, 2 day stool frequency and weight increased by 80 and 131 percent respectively: orocecal transit time decreased from 6.1 +/- 1.3 to 4.8 +/- 1.2 h (m +/- SD; P less than 0.01) and oro-anal transit time (first marker) decreased from 31.8 +/- 9.6 to 20.7 +/- 8.9 (P less than 0.05). With ricinoleic acid, 2 day stool frequency and weight increased by 212 and 350 percent respectively; orocecal transit time decreased from 5.8 +/- 1.8 to 2.2 +/- 0.7 (P less than 0.01) and oroanal transit time (first marker) decreased from 25.3 +/- 7.1 to 8.0 +/- 6.8 h (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Achalasia is the best known primary motility disorder of the esophagus. Dysphagia is the main symptom, intermittent at the beginning, but becoming more marked with evolution. Although some peculiarities are noted, they are not sufficiently characteristic to establish the diagnosis. Chest pain is often associated with dysphagia and may be the prominent complaint in the early stage of the disease. Dynamic investigations, mainly esophageal manometry, are needed for the diagnosis and follow-up after treatment. Three findings are commonly recorded: increase in lower esophageal sphincter pressure, lack of relaxation and absence of peristalsis, the latter being indispensable for the diagnosis of achalasia. On the basis of manometric findings, achalasia is easily differentiated from other primary motility disorders, i.e. diffuse esophageal spasm, nutcracker esophagus, but non-specific esophageal motility disorders are frequent. Manometry is also an objective method of assessing the effectiveness of treatment--i.e. surgical myotomy or balloon dilatation--of the lower esophageal sphincter.

1. Cisapride is a novel prokinetic drug which facilitates or restores motility throughout the gastrointestinal tract. Its mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. 2. The effect of intravenous cisapride 10 mg on gastro-oesophageal dysfunction was investigated in 20 patients with systemic sclerosis, using a double-blind, randomised, cross-over, placebo-controlled manometric study design. 3. The increase in lower oesophageal sphincter pressure was significantly higher after cisapride (mean +/- s.e. mean, 8.3 +/- 2.1 cm H2O) than after placebo (mean +/- s.e. mean. 0.1 +/- 0.3 cm H2O) (P less than 0.001). The increase in the number of fundic gastric contractions during the 30 min study period was significantly higher after cisapride (mean +/- s.e. mean, 7.7 +/- 2.3) than after placebo (mean +/- s.e. mean, 0.9 +/- 0.6) (P less than 0.01). 4. No serious clinical adverse effects were observed. 5. The study demonstrates that intravenous cisapride induces a significant increase in lower oesophageal sphincter pressure and in the number of fundic gastric contractions, which may be beneficial in the treatment of scleroderma gastro-oesophageal dysfunction. Further long-term studies of the effect of oral cisapride in patients with systemic sclerosis are warranted.

In 1987 and 1988, 340 consecutive patients attended the endoscopy centre of Cochin hospital, Paris, and underwent oesophago-gastroduodenal endoscopy in a search for Giardia lamblia parasitology and histology. Two-hundred and eight of these patients presented with non-ulcer dyspepsia and entered a prospective study aimed at determining the advisability of a systematic search for Giardia lamblia in this population. Six biopsies were positive for giardiasis, including 3 in patients with acquired immunodeficiency, 1 in a case of chronic diarrhoea with atrophic villi and 2 in dyspeptic patients. Giardiasis, therefore, cannot be regarded as a cause of non-ulcer dyspepsia, and a systematic search for the parasite is of little interest in such cases. However, giardiasis remains a cosmopolitan parasitic disease with a non-negligible prevalence in France among subjects at risk, such as communities, children, travellers, homosexuals and immunodeficient patients.

Pouchitis is the most poorly understood complication of ileoanal anastomosis. The incidence reported in the literature ranges from 7 to 42% as there are no diagnostic criteria. The various clinical symptoms and endoscopic findings raise the possibility that pouchitis is a heterogenous disease, in which the role of bacterial overgrowth and recurrence of inflammatory bowel disease must be clarified.

Defecography is a useful paraclinical examination to explore disturbances of continence or defecation. The purpose of this study was to present a simplified defecography technique and assess its validity in subjects without defecation problems (n = 10) and in patients complaining of idiopathic chronic constipation (n = 35). The anorectal angle at rest (RAA) and when straining at stool was not significantly different in constipated patients and in controls. Defecography often gave abnormal results. Anterior rectocele was found in almost 50 percent (17/35) of constipated patients and in 20 percent (2/10) of controls (P less than 0.05). None of the patients had posterior rectocele. Persistent imprint of the puborectal muscle during straining was present in 36 percent (9/35) of constipated patients and in 10 percent (1/10) of controls (NS). The imprint was not always associated with closure of the RAA between rest and straining; this closure was never found in controls but was observed in 6 out of 17 constipated patients (35 percent; P less than 0.05). Perineal descent (PD) varied from 0.6 to 3.7 cm (mean +/- s.e.m.: 2.0 +/- 0.63 cm) in controls, as against 0.6 to 7.9 cm (mean +/- s.e.m.: 2.7 +/- 0.45 cm) in constipated patients. In 24 percent of the constipated patients PD was greater than 3.7 cm (the maximum value recorded in controls). All constipated patients with closure of the RAA during defecation had a PD of less than 1 cm, thus confirming the concept of "pelvic floor muscle hypertonia". Disorders of rectal statics are more frequent in subjects with constipation, but their significance is varied. Some abnormalities could be the cause of constipation (e.g. anismus) and others its consequence (anterior rectal prolapse, anterior rectocele, PD).

The presently available methods of study of small bowel motility in humans include manometry (or electromyography) which records the temporospatial organization of bowel contractions and determination of intestinal transit time. Investigation of subjects with the irritable bowel syndrome has shown that the small intestine has its part in the motor disturbances. The characteristics of normal motility of the small intestine are well known: the migrating motor complex (MMC) develops during the interdigestive period, typical contractions are seen during phases 2 and 3 of the MMC, the nature and the duration of the motor response to alimentation have been described. In patients with IBS, the production of the MMC is irregular during the day hours; this is most likely due to environmental solicitations and it is recognized that intensive aliess can cause transient interruption of the development of cycles. On the other hand, the MMC develops normally during sleeping hours. Contraction derangements such as non propulsed repeated contractions in the proximal intestine and contractions propulsed too frequently in the small intestine may be found during phase 2. Some of the abnormal contractions coincide with abdominal pain. After meals, the duration of interruption of the MMC is shorter than in the normal subject. Transit time is shortened in patients with diarrhea, lengthened in patients with constipation. Patients with IBS respond excessively to certain stimuli: for instance, the motor response to cholecystokinin is increased compared to the normal subject. Intake of fatty ingesta is followed by the same type of reaction: pain is often associated with abnormal contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

As in the haemopathies, the application of cytogenetics to epithelial cancers could aid in the study of their pathogenesis evaluation. In this context we performed chromosome analyses on a series of human colo-rectal cancers. The technique was consistently reliable since the modal number of chromosomes could be determined in all 24 cases. In 22, karyotypes could also be established. Each tumour was characterized by a single cell clone in 21 cases and by a mosaic of 2 populations in 3 cases. Numerical anomalies were not due to chance: they enabled near-diploid (11 cases), near-triploid (9 cases), mosaic (3 cases) and highly polyploid (1 case) cancers to be distinguished. Supernumerary chromosomes were primarily in groups C and F. The most frequent markers before denaturation techniques were No 2q +, No F and minutes. Each time double-minutes were observed (5 cases), they were in invasive cancers (B and C Dukes classification). Cells were generally diploid in non-invasive cancers with fewer quantitative and structural anomalies. Tumour cytogenetics were related to the histological type and localization in the colon, as well as to the local and metastatic spread. Images Fig. 2 Fig. 3 Fig. 4

Trimebutine meleate and metoclopramide increase small bowel motility. The present manometric study of the human normal interdigestive duodeno-jejunal motility demonstrated two different pharmacological effects in 15 healthy volunteers. Trimebutine constantly induced a premature phase 3 activity (0.81 +/- 0.4 min after a 100-mg intravenous injection) with patterns similar to spontaneous phase 3. Metoclopramide increased the motility index (contractile activity) during phase 2 without inducing a premature phase 3. No significant variations in plasma motilin concentration were noticed after either trimebutine or metoclopramide. The pancreatic polypeptide concentration rose significantly after metoclopramide injection.

Five patients presenting with HBs Ag and HBe Ag-positive chronic hepatitis were treated with adenosine arabinoside (Vidarabine) in doses of 15 mg/kg/day. The drug was administered by intravenous infusion in 2 series of 5 infusions each separated by 2-day intervals. Two patients had a second course 4 months after the first one. There were no clinical or biochemical adverse reactions. Following treatment, serum transaminase levels returned to normal. All patients became HB Ag-negative, with presence of anti-HBe antibody in three; two patients became HBs Ag-negative, with presence of anti-HBs antibody in one. Although very short, this series should encourage further therapeutic studies, including a controlled, randomized trial in a large number of patients.

The method described by Arhan et al. for measuring colon mean transit time requires plain films of the abdomen during 7 consecutive days (0.007 Gy). A new method is described for measuring the mean segmental transit time of radio opaque markers through the human colon which aims at decreasing ray exposure. While on a diet containing 20 g of bran, a dose of 20 markers was given to the subject for three consecutive days (D1, D2, D3) at the same hours. Each dose of markers was of different shape. A plain film of the abdomen was taken at D4, D7, D10 at the same time as the ingestion of the markers. The first X ray demonstrated the number of markers at 24, 48, 72 h simultaneously and so on from 96 to 216 h for the X ray taken at D7 and D10. Mean transit time in the right, left, rectosigmoid and the whole colon was measured in 22 volunteers and was respectively 6.9 h, 9.1 h, 18.4 h, 34.4 h. The upper limit of the mean transit time (m + 2 SD) was respectively 24 h, 30 h, 44 h, 67 h in the right, left, rectosigmoid and the whole colon. This method has been validated in 20 subjects (10 volunteers and 10 constipated patients) by comparing the mean segmental transit time with the mean segmental transit time measured by the method of Arhan et al. This new method could allow to explore patients with idiopathic constipation more frequently and to better assess the treatment of constipation.

The authors describe four cases of deglutition disorders, even resulting in aphagia in two cases, in which the constrictor muscles of the pharynx were quite clearly entirely responsible. Electromanometry made diagnosis possibe for these patients and it is the only method capable of distinguishing crico-pharyngeal achalasis from paralysis of the constrictor muscles. The authors draw attention to the fundamental importance of this method of investigation in the pathology of deglutition. The propellent role of the constrictors, emphasized by some authors, rather than the upthrust of the tongues seems to be the borne theory out by these cases. Despite surgical ablation as recommended by most authors, or the spontaneous pathological disappearance of the crico-pharyngeal, the condition of the patients described was not improved; therefore it would seem wise, if a decision is taken to operate, not to make any promises to the patients about improvement of function insofar as aphagia is due to paralysis of the constrictors. Diagnosis, it should be remembered, can only be made after electromanometric investigation which is an essential preliminary to any therapeutic decision.

Enkephalins are short lived peptides which are rapidly cleaved by 2 membrane peptidases: an enkephalinase and a carboxypeptidase. Enkephalin-like immuno-reactivity has been demonstrated in the smooth muscle and in the myenteric plexus of the human lower esophageal sphincter (LES). Opioid receptors have been found in the gastrointestinal tract and recently an enkephalin analog has been shown to inhibit LES relaxation and modify the peristaltic progression of the esophageal contractions. Acetorphan is an enkephalinase inhibitor which prevents, at least to some extent, the hydrolysis of endogenous enkephalins. Thus, the present work was designed to study the effect of acetorphan on esophageal motility. Ten healthy volunteers (mean age: 23 years) were studied. On 2 separate days, each subject received in random order acetorphan (2.5 mg/kg intravenously at a constant rate in 20 min) or placebo. Esophageal manometry was performed with a Dentsleeve. Wet swallows (5 ml) were performed at 1 min intervals during 80 min and results were pooled in 10 min periods. Acetorphan inhibited significantly (p less than 0.02) LES relaxation 20 min after the beginning of the infusion and throughout the study. The maximal effect occurred 50 min after the beginning of acetorphan infusion and LES relaxation (m +/- SEM) was reduced from 92 +/- 2.6 to 79.5 +/- 2.9 p. 100 (p less than 0.01). Duration, amplitude, and velocity of esophageal contractions were not modified. Acetorphan an enkephalinase inhibitor, is able to reproduce the effect of IV exogenous enkephalins on LES relaxation in man. This result suggest that endogenous enkephalins might play a role in the normal control of the LES relaxation.

A 35-year-old HIV positive patient with skin and gastrointestinal localization of a Kaposi's sarcoma was admitted for severe diffuse edema. Increased alpha-I-antitrypsin clearance (150 ml/24 h) allowed us to confirm the diagnosis of protein loosing enteropathy resulting from sarcoma infiltration in the stomach, the duodenum and the entire small bowel. At autopsy, ileal ulcerations were found. Gastrointestinal involvement occurring during Kaposi's sarcoma is common and usually symptomless. The discovery of a protein loosing enteropathy in our patient suggests that this gastrointestinal involvement could play a role in the hypoalbuminemia often found in these patients.

Measurement of the transit time by addition of a marker to the natural alimentary bolus permits an overall evaluation of colonic motricity. Bismuth and barium salts, dyes and radioactive compounds have been used, each of these methods having its own drawbacks, such as insufficient or impossible quantification, influence on transit or partial intestinal absorption. Radio-opaque pellets do not modify transit, are not absorbed, provide quantification readily and measure transit selectively in the ascending colon, the descending colon, the sigmoid colon and the rectum. The progression of pellets is followed by radiography of the abdomen. The number of radiograms can be reduced to 3 or even 1 by graded administration of the pellets over 3 consecutive days. The results obtained in normal subjects are similar in different studies; they are not influenced by age or by the amount of fibrous material present in food. Total and right segmental transit times are longer in women than in men. Measurement of the colonic transit time is indicated in severe constipation to differentiate between colonic inertia and terminal obstruction which have different mechanisms and treatments. Such measurements are also useful for an objective evaluation of constipation.

The effects of trimebutine, a drug used in the treatment of various gastrointestinal motility disorders, have been investigated fed and fasted healthy subjects. Duodenojejunal motility was recorded manometrically with a 4-lumen probe. Trimebutine 50 or 100 mg was injected i.v. 3 or 25 min after observing a spontaneous Phase 3 complex in the fasted state. Other experiments were done in the postprandial state and after intravenous naloxone 0.8 mg. In the fasted state, trimebutine 100 mg, injected 25 min after a spontaneous Phase 3 complex consistently induced a premature Phase 3 complex. The mean duration of the migrating motor complex cycle decreased from 86.4 +/- 10.8 min to 32.5 +/- 1.0 min. Trimebutine 50 mg injected 3 and 25 min after a spontaneous Phase 3 complex did not significantly modify the periodicity of the migrating motor complex. Trimebutine 100 mg initiated Phase 3-like activity in the post-prandial state. Previous intravenous administration of naloxone 0.8 mg (Narcan) suppressed the stimulatory action of TMB. Thus, trimebutine is able to modify the motility pattern in the small intestine of man, possibly by acting at opioid receptors.