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To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P = 0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P = 0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.

This study examined the effects of changes in body position on different swallowing parameters derived from manofluorographic examinations. Quantitative data were obtained in a group of 12 young healthy volunteers. They were all tested in the upright position; six of them were also evaluated in the supine position, and the other six in the upside down position. In the different positions all volunteers were able to swallow a liquid bolus without aspiration or stasis. However, the dynamics of the swallow became different. Lying down resulted in a pharyngeal transit time comparable with the upright position. The tongue driving force was higher and the hypopharyngeal suction power weakened. In the upside down position, the pharyngeal transit time became longer and the tongue driving force was even more powerful. There was no apparent difference in the traditional manometric parameters; the amplitude, duration, and propagation velocity of the pharyngeal contraction on swallowing did not change obviously in the different body positions.

Primary esophageal motility disorders (achalasia, diffuse esophageal spasm, and intermediate forms) are suggested to be caused by different degrees of inhibitory dysfunction; however, direct evidence for this hypothesis has never been presented in humans. The aim of this study was to measure the degree of inhibition that precedes deglutitive contractions in patients with primary motility disorders.Deglutitive inhibition was examined in patients with primary motility disorders: 9 with achalasia, 6 with symptomatic diffuse esophageal spasm, and 5 with intermediate forms. An artificial high-pressure zone was created in the esophageal body by inflating a balloon to a critical level, and pressure changes were measured at the interface between the balloon and esophageal wall. Inhibition was visualized as a relaxation of the artificial high-pressure zone.An inverse relationship was found between the degree of inhibition and the propagation velocity of the deglutitive contraction (r = 0.75; P0.001). Normally propagated contractions were preceded by an inhibition of 84.2% +/- 3.6%; fast-propagating contractions were preceded by partial inhibition of 40.6% +/- 6.2%; and, in case of simultaneous contractions, inhibition was absent, i.e., 2.6% +/- 1.6%.The spectrum of primary motility disorders is an expression of a progressively failing deglutitive inhibition.

At endoscopy, the duodenum in Whipple's disease frequently appears abnormal and some clinical features such as gastrointestinal blood loss and anaemia suggest epithelial damage. However, the intestinal epithelial cells themselves appear to be normal on light and electron microscopy. The aims of this study were to analyse in detail the cytological changes in epithelial cells over time and in response to therapy in biopsies obtained from 20 patients, to investigate the functional repercussion on digestive enzymes such as lactase, and to assess the expression by the epithelial cells of MHC antigens. Cytological changes were minimal at both the light- and the electron-microscopic level and MHC class I expression was preserved. However, changes indicative of functional deficits were demonstrated. Lactase and MHC class II expression were reduced or even absent. Antibiotic therapy resulted in normalization within 3-6 months. These findings are consistent with the clinical evolution and are of interest with regard to the importance of the immune response in aetiopathogenesis.

We carried out a clinical and endoscopic follow-up study of 14 patients with Crohn's disease of the esophagus. The diagnosis was based on the combination of endoscopic and histologic examinations with exclusion of all other possible causes. All patients had other gastrointestinal localizations of Crohn's disease, including oral and anal disease, and the majority also had serious extra-intestinal manifestations. Complete healing of the lesions was accomplished with corticosteroids in 9/14 patients after 2 to 4 weeks. During a total follow-up of 83 years for the 14 patients, 26 "flare-ups" of intestinal and systemic symptoms having a Crohn's disease activity index greater than 200 were diagnosed, on which occasions UGI endoscopy was performed before adjusting therapy. Three patterns of evolution could be distinguished: (1) in eight patients (total 17 flare-ups), neither endoscopic esophageal lesions nor UGI symptoms were apparent during follow-up. (2) Three patients (1 flare-up each) had persistent lesions despite corticosteroid therapy. (3) Three patients (6 flare-ups, 2 each) had relapse of both symptoms and esophageal lesions on each endoscopy, although these lesions had completely disappeared initially.

Anorectal ulceration eventually leading to rectal stenosis was observed in 10 patients who abused analgetic suppositories containing acetylsalicylic acid, acetaminophen, and codeine. Most patients were middle-aged women with a neurotic or psychiatric background. Perianal skin lesions were present in half of the patients. The endoscopic aspect of the sharply demarcated distal rectal lesions with squamous and transitional epithelium (anoderm) ascending from the anal canal was rather typical, but the appearances on biopsy were nonspecific. Possible pathophysiological mechanisms include mucosal prostaglandin depletion secondary to blockade of cycloxygenase and shift to lipoxygenase products in the arachidonic acid cascade. Treatment options include drug cessation, topical steroids, and endoscopic dilatation. Supporting psychological therapy often is necessary.

The frequency and characteristics of non-deglutitive motor activity of the human oesophagus and its relation to motility patterns in the antrum and upper small intestine were studied in 25 fasted healthy subjects. Motility of the oesophagus, antrum, and upper small intestine was recorded by means of a manometric perfused catheter system. The most striking non-deglutitive motility pattern consisted of repetitive bursts of non-sequential pressure peaks occurring in the smooth muscle portion of the oesophagus. The mean number of pressure peaks per burst was 2.7 (SD 2) waves with a mean amplitude of 19.5 (SD 9.9) mm Hg and a duration of 3.09 (SD 0.22) seconds. The highest amplitude was 80 mm Hg and the longest burst consisted of 13 repetitive waves. The bursts were recorded up to a distance of 15-20 cm above the lower oesophageal sphincter. Ninety five per cent of the bursts occurred during a 15 minute period before the onset of phase 3 of the migrating motor complex in the antral or upper small intestinal area, or during the lower oesophageal sphincter component of the migrating motor complex. In conclusion, spontaneous bursts of non-sequential pressure peaks occurred in the smooth muscle part of the human oesophagus in relation to phase 3 of the migrating motor complex. They represent the oesophageal body component of phase 3 of the migrating motor complex and are not a sign of oesophageal motor abnormalities.

The occurrence and pathogenic properties of Helicobacter pylori have been studied extensively in the stomach [1–7] and in the duodenum [8–11]. Despite the prevalent nature of acid–related disorders in the oesophagus, the role of Helicobacter pylori in this localisation has received little or no attention and therefore remains to a large extent unknown.

In the present study, the motilin receptor was characterized by enzymatic digestion studies and by solubilization of the motilin-receptor complex from prelabeled membranes using the anionic detergent cholic acid. Motilin binding was significantly decreased by preincubation of membranes of rabbit antral tissue with trypsin, phospholipase A2, C, D, dithiothreitol and 2-mercaptoethanol but not by neuraminidase and beta-galactosidase. Treatment of prelabeled membranes with 1% cholic acid resulted in solubilization of 24 +/- 5% of the proteins and 65 +/- 3% of the radioactivity. The latter was for 77 +/- 4% due to the presence of the motilin-receptor complex as estimated with PEG-precipitation. Upon gel-filtration on Superose 6 the complex partially dissociated but 43 +/- 3% eluted with macromolecular components in the void volume. This peak was not detected when membranes were first incubated with unlabeled motilin. Further disaggregation was accomplished by the addition of 0.5 M NaCl to the elution buffer. The chromatographic profile then showed a peak of about 370 kDa and a second one of 100 kDa. The latter value probably reflects the molecular mass of a single 125I-motilin-receptor-complex.

Widespread alterations of the gut autonomic nervous system have been described in Crohn's disease. Immunohistochemistry shows that these alterations are associated with the expression of major histocompatibility (MHC) class II antigens (HLA-DR) on enteroglial cells in the ganglia of the submucous and myenteric plexuses and on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and extensions do not express MHC class II antigens. The class II expression is associated with the presence of UCHL1-positive T lymphocytes. MHC class II expression can also be found on endothelial cells and vascular smooth muscle cells but not on smooth muscle cells of the muscularis mucosae or propria. The intensity of MHC class II expression on the glial cells of the enteric nervous plexus and on endothelial cells correlates well with the intensity of class II expression on epithelial cells.

The effect of acarbose on hydrolysis of a pure starch meal was investigated in normal subjects and ileostomy patients by means of 13CO2 breath tests and blood glucose levels as parameters of absorption, and of H2 breath tests, serum acetate levels, and ileal loss of carbohydrate as parameters of malabsorption. Additional information on the effect of acarbose on alpha-amylase activity was obtained by in vitro experiments. Acarbose (200 and 400 mg) significantly delayed starch absorption. Serum acetate was found to be a less sensitive marker of malabsorption than breath H2 excretion. After intake of 50 g starch plus 400 mg acarbose, 23-71% of the starch load was lost in the ileostomy effluent, for a large part as starch. This suggests that acarbose considerably inhibits alpha-amylase, and not only brush-border enzymes. In vitro experiments confirm that an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose.

We tested the efficacy of rifabutin and ethambutol in combination in healing severe recurrent Crohn's disease in the neoterminal ileum. Sixteen patients who had undergone an ileal resection with partial colectomy and ileocolonic anastomosis and who had severe recurrent lesions in the neoterminal ileum at baseline ileocolonoscopy were included in the study. The patients received rifabutin in a dose of 5 mg/kg together with ethambutol, 20 mg/kg. Ten patients were treated for 6 months; six patients dropped out because of adverse events. As no effect was observed after 6 months, five patients completed a 12-month therapy course. Follow-up ileocolonoscopy was performed at 3, 6, and 12 months. In none of the 10 patients who completed the 6-month trial and in none of the five patients who completed 12 months of therapy was endoscopic improvement of the lesions observed. In four patients the disease was clinically progressive, and two patients underwent a reresection after 6 and 8 months, respectively. This study shows that long-term therapy with rifabutin and ethambutol does not heal Crohn's disease in the neoterminal ileum and does not prevent recurrence of symptoms and complications.

An esophageal origin of noncardiac chest pain is generally accepted if prolonged pH and pressure recordings show that the pain episodes correlate in time with acid reflux, esophageal motor abnormalities, or a combination of both, or if provocative testing (acid perfusion, edrophonium, balloon distention) is positive. Many patients with noncardiac chest pain of esophageal origin are said to have an irritable esophagus. Irritable esophagus has been defined in two ways. Some researchers suggest it is actually a lowered esophageal pain threshold, based on the finding that such patients feel chest pain at lower balloon volumes than controls during intraesophageal balloon distention; they are said to be hypersensitive to balloon distention. Hypersensitivity to an esophageal stimulus is generally found in patients with noncardiac chest pain of esophageal origin, and hypersensitivity to a single stimulus is one criterion for a diagnosis. Our group defines irritable esophagus as a condition in which several different stimuli result in the same type of chest pain. Accordingly, we have grouped patients with esophageal chest pain into three categories: (a) patients with an acid-sensitive esophagus, in whom spontaneous pain episodes can be related to acid reflux (with or without accompanying motor disorders), and/or the acid perfusion test is positive; (b) patients with a mechano-sensitive esophagus, in whom the spontaneous pain episodes can be related to motility disturbances (without reflux), and/or the edrophonium test or balloon distention test is positive; (c) patients with an irritable esophagus, in whom some spontaneous pain episodes are related to reflux, while others are related to abnormal motility (without reflux). The last group includes patients whose spontaneous chest pain is related to reflux, with a positive motility tests; whose pain is related to abnormal motility, with a positive reflux test; and patients with positive tests for both reflux and abnormal motility. Seven studies examined a total of 281 noncardiac chest pain patients using prolonged pH and pressure recordings and provocative tests. An acid-sensitive, a mechano-sensitive, or an irritable esophagus was found in 20%, 14%, and 24% of patients, respectively.

Classic diaphragmatic flutter, a rare disorder associated with dyspnoea, thoracic or abdominal wall pain, and epigastric pulsations, is caused by involuntary contractions of the diaphragm with a frequency of 0·5-8·0 Hz. We have seen three patients with diaphragmatic flutter of higher frequency not associated with respiratory disease. The patients presented with longstanding oesophageal belching, hiccups, and retching, respectively. The diagnosis was established by the presence on electromyography of the diaphragm and scalene and parasternal intercostal muscles of repetitive discharges of 9-15 Hz. Spirographic tracings, especially those of volume or flow vs time, showed similar high-frequency oscillations superimposed on tidal respiratory movements. Treatment with carbamazepine 200-400 mg three times daily led to disappearance or great improvement of flutter and clinical symptoms in all three patients. The phenomenon was not seen in other patients with chronic hiccups or oesophageal belching or in patients without these symptoms who had undergone electromyography or spirography for other reasons. Thus, high-frequency diaphragmatic flutter seems to be a new disease entity. The response to carbamazepine, which suggests that the flutter causes the symptoms, requires further study.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.

Slow waves determine rhythm and polarity of spike bursts. We measured the variation of slow-wave frequency (swf) and locking (swl) in the canine jejunum during the various phases of the migrating myoelectric complex (MMC) and during induced phase III (erythromycin 125 micrograms/kg iv bolus or somatostatin 2.5 micrograms.kg-1.h-1 iv infusion), blocked phase III (atropine 20 micrograms/kg iv bolus), and so-called stationary phase III activity (cisapride 150 micrograms/kg iv bolus). The EMG of 4 dogs, implanted with 10 bipolar electrodes, was recorded on a polygraph. Our results indicate that swf and swl change during the MMC from a stepwise swf gradient with slow waves locked in plateaus during phase I to a continuous swf gradient without or with significantly reduced phase locking during phase III. The length of the first swf plateau decreases significantly from 42 +/- 12 cm post Treitz during phase I to 11 +/- 4 cm during spontaneous phase III. Atropine block of phase III activity prevents phase unlocking and development of a continuous swf gradient. Our hypothesis is that phase unlocking may be one of the induction mechanisms of spike-burst activity.

Prostaglandin analogues, used in the treatment of duodenal and benign gastric ulcer and in the prevention of gastric ulceration caused by non-steroidal anti-inflammatory drugs, are frequently associated with gastrointestinal side effects, particularly diarrhoea and abdominal cramps. We investigated the effects of misoprostol, a prostaglandin E1 derivative, on bowel motility and faecal loss of fat, water and bile acids in relation to its postprandial vs. preprandial administration. Twelve healthy subjects participated in a double-blind crossover study comparing three 5-day courses of therapy with a washout period of 1-2 weeks between courses. Following a Latin Square design, the dosing regimens were (a) 400 micrograms misoprostol b.d. after meals and placebo b.d. before meals; (b) 400 micrograms misoprostol b.d. before meals and placebo b.d. after meals; (c) placebo before and after meals. Orocaecal transit time measured by H2 breath tests following lactulose administration, was shortest during pre-prandial dosing but was also significantly decreased during post-prandial dosing. The overall treatment difference was highly significant (P less than 0.001), and the difference between each pair of treatments was also statistically significant. Whole bowel transit time studied by means of 3H-PEG 4000 determination in stools, was shorter for the two misoprostol regimens but statistical significance was borderline. The number of stools passed per day was similar in the three groups. During both misoprostol dosing periods, stools were less formed and their content of water, fat and bile acids was higher. There was also more urgency, flatulence, abdominal pain and nausea. It is concluded that the gastrointestinal side effects caused by misoprostol are mainly based on an increased orocaecal transit time. The effects are more important when the drug is administered before meals than after meals.

Eighty-nine patients who had been treated by ileal resection for Crohn's disease between 1979 and 1984 were included in a prospective cohort follow up to study the natural course of early postoperative lesions. Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73% of the patients, although only 20% of the patients had symptoms. Three years after surgery, the endoscopic recurrence rate had increased to 85% and symptomatic recurrence occurred in 34%. The ultimate course of the disease was best predicted by the severity of the early postoperative lesions, as observed at ileoscopy. Clinical parameters that influenced outcome were preoperative disease activity, the indication for surgery, and the number of surgical resections. When patients were stratified for preoperative disease activity, the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence. In 22 other patients submitted to "curative" ileal resection and ileocolonic anastomosis, the segment to be used as neoterminal ileum was carefully examined during surgery, and two large biopsies were taken before making the anastomosis. An ileoscopy was performed 6 months after surgery. Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery, 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment (range, 4-30 cm), and 20 had unequivocal microscopic lesions on biopsies. These studies suggest that early lesions in the neoterminal ileum after Crohn's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery. The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn's disease and also to evaluate new therapeutic modalities, either to prevent development of these early lesions or to treat progressive recurrence.

The development of the motilin receptor was studied through contraction and binding studies of groups of three rabbits aged between 2 and 289 days. The contractility of small intestinal smooth muscle strips was measured isotonically. The aborally decreasing gradient in response to motilin, known to exist in adult rabbits, was already present at day 8 (maximum contractile responses expressed as a percent of the maximal response to acetylcholine were 77% +/- 9%, 34% +/- 10%, and 25% +/- 8% for duodenal, jejunal, and ileal strips, respectively). Throughout the observation period, the doses of motilin and its agonist erythromycin that were required to induce 50% of the response remained constant and were not significantly different from doses required for adults (their negative logarithms were 8.55 +/- 0.35 and 5.70 +/- 0.25, respectively). The correlation between the maximum contractile response toward motilin and erythromycin was almost perfect (r2 = 0.82). Binding studies with iodinated norleucine13-porcine motilin were performed using antral smooth muscle tissue homogenates. The maximum number of binding sites increased rapidly after 8 days (3.3 +/- 0.4 fmol/mg protein) and reached a peak at 21 days (20.7 +/- 1.4 fmol/mg protein), but decreased at that point toward the adult value (40 days, 10.6 +/- 1.3; 289 days, 9.8 +/- 1.1 fmol/mg protein). The dissociation constant, however, remained unchanged. The peak value of receptor density occurred at about the time that the rate of increase of the length of the intestine and of the weight of the antrum were at maximum levels (at 18 and 27 days, respectively). Motilin receptors are expressed early postnatally, and the regional gradient in sensitivity towards motilin is also established soon after birth. If applicable to humans, an early response to erythromycin may have therapeutic value.

In intact sheets of the guinea pig ileal longitudinal muscle, loaded with fura-2, both substance P (SP)- and K(+)-induced contractile responses are preceded by cytoplasmic free Ca2+ ([Ca2+]i) variations. In response to SP (10(-10)-10(-7) M), [Ca2+]i and force increased concentration dependently. From 10(-9) M on, the response was biphasic: an initial Ca2+ spike and force transient were followed by a tonic component. The [Ca2+]i and force vs. log [SP] curves were sigmoidal for the initial phasic component, while a homologous receptor desensitization caused a reduced tonic component of the [Ca2+]i and contractile response at higher concentrations of SP. Both intracellular Ca2+ release and Ca2+ influx play a role in the effect of the peptide. In depolarizing solutions (140 mM K+) and in Ca2(+)-free medium (2 mM EGTA), SP induced a transient increase in [Ca2+]i and force. The Ca2+ stores used by SP and acetylcholine (ACh) overlap. [Ca2+]i and force fell to base-line levels when the extracellular Ca2+ was reduced from 1.2 to 0.2 mM during stimulation with SP. Verapamil reduced the tonic response. We also studied the relation between [Ca2+]i and force for the peak and steady-state values after stimulation with increasing concentrations of SP and K+. The phasic force response was linearly related to log [Ca2+]i. During the sustained response to K+, the Ca2+ sensitivity of the contractile/regulatory proteins was decreased, whereas no changes were observed during prolonged stimulation with the peptide.

This report describes the utility and the advantages of endoscopy in diagnosing and following the course of Whipple's disease. Sixteen patients, diagnosed over a period of 22 years, were identified via pathology records and retrospectively reviewed. Five patients were diagnosed before 1980 by means of peroral suction biopsy of the small intestine. The 11 patients diagnosed after 1980 all had upper gastrointestinal endoscopy and endoscopic small intestinal biopsies. Gross endoscopic lesions were observed in 9 of the 11 patients and disappeared in 5 of 6 treated patients at 6 months. These lesions include erosions, yellow plaques, and a pale yellow shaggy mucosa. The latter two lesions are macroscopicaily suggestive of Whipple's disease. After endoscopic "healing", periodic acid-Schiff-positive macrophages remained present in the endoscopic biopsies lor years. The patients were followed for a median period of 4 years and 5 months. All patients were treated with antibiotics (eight tetracycline alone, four tetracycline + streptomycin + penicillin, and four trimethoprim). Five patients (lour of the tetracycline alone group, none of the trimethoprim group) relapsed 2 to 11 years after the initial treatment.

Erythromycin may stimulate gastrointestinal motor activity via its effect upon motilin receptors. We have studied the ability of the derivative EM-523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal] to induce contractions in duodenal smooth muscle strips and to displace labeled motilin bound to antral smooth muscle, in man and in rabbit. In both species EM-523 approached the potency of motilin for inducing contractions. Thus pED50 values were 7.84 +/- 0.11 and 8.69 +/- 0.12 for motilin in, respectively, man and rabbit, against 6.08 +/- 0.13 and 8.19 +/- 0.10 for EM-523. In rabbit the efficacy of both compounds decreased in parallel aborally, the responses to EM-523 could not be blocked by atropine (10(-7) M) or TTX (10(-7) M), and both compounds were unable to further enhance the maximum effect to the other compound. In binding studies the order of potency was the same as in the contraction studies. The pIC50 values were: motilin (8.84 +/- 0.31, 9.17 +/- 0.20) greater than EM-523 (7.89 +/- 0.1, 8.40 +/- 0.10). A Schild plot revealed that EM-523 was a competitive inhibitor of motilin receptor binding in man and in rabbit. We conclude that EM-523 is a potent motilin agonist.

10 patients with frequent and severe bleeding from gastrointestinal vascular malformations took part in a double-blind, placebo-controlled, cross-over trial of a daily dose of 0.05 mg ethinyloestradiol plus 1 mg norethisterone given by mouth. Each arm of the trial lasted 6 months. Oestrogen-progesterone significantly decreased the transfusion need from 10.9 to 1.1 units packed cells (p less than 0.003). While on oestrogen-progesterone 2 of 9 patients required transfusions (mean 1.1 units packed cells per patient over 6 months), whereas all patients had to be transfused while on placebo (mean 10.9 units per patient over 6 months; p = 0.002 for number of patients). No significant excess of side-effects was noted with the active agents. The findings indicate that oestrogen-progesterone is an effective treatment for severely bleeding gastrointestinal vascular malformations.

Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.

The electrogastric signal can be measured cutaneously on the abdomen. This is attractive because it is harmless to patients or volunteers. However, the poor quality of the cutaneous measurements necessitates signal enhancements. Hence, in this paper, an adaptive multichannel signal enhancing system is proposed. The mu-vector least mean square (LMS) algorithm is applied to adjust the weights of the adaptive filters in the system. The detailed description and the performance analysis of the system is given in the paper. Applying the proposed system, the respiratory artifact, the electrode-skin noise, some of motion artifacts, and the electrocardiography (ECG) can be efficiently reduced while the characteristics of the relevant gastric signal is less affected.

The three main symptoms of esophageal disease or disorder are dysphagia, chest pain, and heartburn. Dysphagia in achalasia is mainly due to a non-relaxing lower esophageal sphincter (LES). The mechanism of dysphagia in diffuse esophageal spasm and related motor disorders is related to a combination of several factors including incomplete LES relaxation, failed or weak peristalsis (pressure less than 30 mmHg in the distal esophagus, and orad positive pressure gradient). Meal manometry and balloon distention may prove to be useful provocation tests. Chest pain of esophageal origin may be due to gastroesophageal reflux and esophageal motility disorders; it may also be a manifestation of an irritable esophagus, in which the esophagus is hypersensitive to various stimuli (chemical, mechanical, ischemic). Esophageal provocation tests may suggest the esophageal origin of the pain but do not give information on the nature of the esophageal disorder. Twenty-four-hour pH and pressure measurements may, however, yield this information. Heartburn and acid regurgitations are the most typical symptoms of gastroesophageal reflux. Transient relaxations of the LES are considered to be an important contributory mechanism of reflux. Absent basal LES pressure is another mechanism, which accounts for about one-fourth of the reflux episodes in patients with severe reflux esophagitis. During long-lasting inappropriate relaxations, swallows often produce deglutitive contraction waves that die out in the upper esophagus, suggesting that reflux often occurs during periods of inhibition of both LES tone and peristaltic esophageal activity.

In a 4-year period 45 patients were admitted to our gastroenterological u nit with acute infective colitis. The endemic pathogens responsible for the colitis were Yersinia enterocolitica (46%), Campylobacter fetus jejuni (20%), common Salmonellae (13%), less virulent strains of Shigella (9%), Entamoeba hystolytica (7%) and Cytomegalovirus (4%). These microorganisms caused very severe disease in 18% of the patients, who were mostly predisposed. While Salmonella- and amoebic colitis always mimicked ulcerative colitis by the presence of diffuse lesions, the other pathogens caused focal colitis, thus necessitating differential diagnosis vis a vis Crohn's colitis. Two patients (4%) died of complications, while 93% of the patients were cured by proper antimicrobial therapy. In the same period 12 patients were admitted with an acute attack of inflammatory bowel disease due to an intercurrent infection with the same pathogens. In most of these patients clinical remission of IBD was achieved by treating the intercurrent infection. These data indicate that in the presence of an acute attack of colitis an infective etiologic agent must always be sought, and that an attack of chronic idiopathic inflammatory bowel disease may be caused by an intercurrent infection.

A 56-year-old woman with Osler-Weber-Rendu disease had longstanding iron deficiency anemia from recurrent melena. Since neither laser photocoagulation nor surgery were successful in stopping the increasing transfusion need, combined estrogen-progesterone therapy was started. Except for slight bleeding from a temporary ileostomy, the bleeding and need for transfusion terminated promptly. This experience confirms that estrogen-progesterone therapy may promote cessation of bleeding gastrointestinal telangiectasias and indicates the need for controlled investigations.

In a randomized study, Nd-YAG laser therapy by the endoscopic contact low-power method was compared with the non-contact high-power method for its palliative action on colorectal carcinoma. With the contact technique, more therapy sessions were required to achieve good recanalization of the bowel than with non-contact therapy (5.0±1.9 sessionsversus 3.0±1.5 sessions;P

A method is described for the rapid and Quantitative extraction of bile acid derivates by Sep-PakTM C18 cartridge. The method is used for the preparation of bile acid methyl ester acetates. The method was validated by determining the efficiency and the recovery of radiolabelled taurine-conjugated and free bile acids and of bile acid containing biological samples, by thin-layer chromatography with zonal scanning after each step and by internal standardization withing the gas-chromatographic analysis. The recovery of bile acids after hydrolysis amounted to 93.7% ± 2.7%, 97.7% ± 3.6% and 100% ± 2.3% for gallbladder bile, serum bile and mixtures of pure bile acids resp. The recovery of cholic acid methyl ester acetate and chenodeoxycholic acid methyl ester acetate after the entire procedure, including hydrolysis Sep-PakTM -extraction, methylation, acetylation and again Sep-PakTM -extraction, amounted to 85.6% ± 4.6%, 88.4% ± 5.3% and 89.3% ± 3.5% for gallbladder bile acids, serum bile acids and bile ...

Une augmentation de frequence de maladie de Crohn a ete observee dans diverses parties du monde au cours des dix dernieres annees [7].

Intraduodenal pH, bicarbonate and amylase secretion, and gastric acid and pepsin output were studied in relation to the migrating motor complex in man. The occurrence of a motor complex in the duodenum was preceded by an increase in gastric acid and pepsin output and followed by a peak in bicarbonate and amylase secretion. It is concluded that the interdigestive phase in man is characterized by periodic activity complexes comprising both motor and secretory components. These observations may have important implications for the interpretation of currently used functional tests of gastrointestinal secretion.

Alpha-I-antitrypsin immunoreactivity was demonstrated by immunofluorescence in epithelial cells of the normal human small intestine. Its presence was also confirmed in biopsies of patients with Crohn's disease. Specific fluorescence was observed in only four out of 14 adult patients with coeliac disease. These results implicate the human small intestinal epithelium as a possible source of alpha-I-antitrypsin. The absence of positive cells may have implications in the aetiology of coeliac disease.

Angina-like chest pain of non-cardiac origin is a major diagnostic and therapeutic problem. The oesophagus is frequently suspected to be the cause of the chest pain in these patients. However, a positive statement for the oesophageal origin of the pain can only be made when during manometry or pH-monitoring the familiar pain attack appears to be accompanied by reflux, severe motor disorders or a combination of both. Due to the intermittent nature of the pain this is only rarely the case during short-listing conventional examinations. Provocation tests have been used to induce the familiar chest pain. The Bernstein acid perfusion test and the edrophonium test yield the best results. Prolonged (24-hour) ambulatory recording of intra-oesophageal pressure and pH to increase the chances of recording chest pain concomitantly with an episode of reflux and/or motor disorders appears to be the most sensitive and also the most physiological test. It is the only test that provides reliable information on the underlying mechanism of the pain, especially in patients with the syndrome of irritable oesophagus, thus contributing in establishing the appropriate therapy for these patients.

Fifty-six symptomatic patients, who had had a partial gastrectomy 10--24 years previously for benign disease, were examined by endoscopy and multiple mucosal biopsies. No patient had a completely normal gastric mucosa. Varying degrees of gastritis, intestinal metaplasia, foveolar hyperplasia and dysplasia were seen. Seventeen patients (30%) had extensive areas of dysplasia associated with acute or chronic inflammation. Severe dysplasis, however, was detected in only one case. In five patients a "diffuse type" carcinoma of the gastric stump was found. While it is generally accepted that significant dysplasia (moderate or severe dysplasis) is premalignant, the degree of risk is unknown. This makes management of individual patients difficult.