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A new method for automatic analysis of resting lower esophageal sphincter pressure and postdeglutitive motor activity of esophageal body and lower esophageal sphincter (LES) is validated by comparing the results obtained with automatic and manual analysis of 11,700 esophageal body pressure peaks, 390 resting LES pressure measurements, and 3900 LES relaxations. The automatic analysis is based on the on-line transformation of pressure recordings into a mathematical formula using B-spline functions, which allows one to use the same parameters as those generally applied in manual analysis of esophageal manometric recordings. Statistical evaluation of the results indicates that this method provides a faithful analysis of the pressure tracings. The difference between manual and automatic analysis (mean ± SD) was only + 1.49 ± 4.26 mm Hg for wave amplitude, -0.15 ± 0.61 seconds for wave duration, +0.37 ± 1.05 cm/second for progression velocity, +0.95 ± 1.38 mm Hg for resting LES pressure, and -2.0 ± 1.67 mm Hg for residual LES pressure after deglutition. Wave form was correctly recognized in 95.3% of the waves. Pressure recordings were obtained from a study on the effect of the PGE1 analogue rioprostil (600 and 300 μg), administered orally on esophageal motor function in 10 normal volunteers. The drug increased both the resting LES pressure and the amplitude of esophageal body contractions and decreased the completeness of LES relaxation after swallowing.

ERYTHROMYCIN A appears to be a motilin agonist, although motilin (a peptide) and erythromycin A (a 14-member macrolide antibiotic carrying two sugar substituents) are structurally totally unrelated. To obtain information concerning the structural requirements for erythromycin's interaction with the motilin receptor, we studied 60 derivatives and seven fragments of erythromycin, and six macrolides with a 16-member ring structure. For every compound the ability to displace motilin bound to a crude homogenate of rabbit antral smooth muscle tissue and the ability to induce contractions in rabbit duodenal segments were determined. For both parameters dose-response curves were obtained, and the negative logarithms of the concentrations inhibiting 50% of the binding (pIC-50) or inducing 50% of the maximum response to a maximal contractile dose of acetylcholine (pEC-50) were determined. All macrolides with a 16-member ring structure were inactive in both types of experiments. In all erythromycin derivatives variations of the ring structure had a marked effect. For both parameters the order of potency was enol ether > pseudo–enol ether > parent ring > pseudo-hemiketal > anhydro. The two sugars attached to the ring were important too, because removing either or both of them resulted in an inactive compound. Modifications of the dimethylamino group of the desosamine sugar affect the potency, while the orientation of the cladinose moiety seems to be important too. For all active compounds, both parameters studied were well correlated (r= 0.80, p < 0.001). Our results support the concept that erythomycin-like macrolides are motilin agonists. The structural requirements of these “motilides” involve the ring structure, especially the part that can be transformed into an enol ether, and both attached sugars. Potent derivatives may prove to be useful as gastrokinetic agents with a very specific target zone.

Whipple's disease is a multisystem disorder with protean manifestations and with poorly understood aetiopathogenesis. It is unclear how the immune system reacts, whether it functions normally or not, whether it protects the organism or is defeated in one way or another by the 'Whipple bacillus'. The purpose of our study was to assess humoral and cellular immunity at the level of the intestinal mucosa. This histochemical, immunocytochemical and electronmicroscopic study, based on 16 cases, has shown that the changes in components of the mucosal immune system in Whipple's disease are quite different from normal. The phagocytic capacity of the macrophages, assessed microscopically, is abnormal, the number of intra-epithelial lymphocytes is increased, the CD 4/CD 8 cell ratio is decreased and the IgM positive cells in the lamina propria outnumber the IgA positive cells. These changes may be inter-dependent.

Recently, we developed a disposable acid exposure sensor whose in vitro response to acid below pH 4 is linearly determined by the duration of exposure and the degree of acidity. The aim of the present study was to compare the SR to simultaneous esophageal pH and duodenogastroesophageal reflux (DGER) monitoring (Bilitec) in patients investigated for presumed gastroesophageal reflux disease (GERD). Twenty-six patients (16 men, mean age 46 ± 2 years) with symptoms suggestive of GERD underwent 24-hr ambulatory pH monitoring and SR monitoring at 5 cm proximal to the LES. DGER monitoring was performed in 21 patients. Exposure of the esophagus to acid and to DGER were analyzed. These data were compared to SR. A significant correlation was found between the exposure of the distal esophagus to acid and SR (R = 0.85; P 5% of time were 91% and 93%, respectively conclusion, the response of the acid exposure sensor is strongly correlated with the results of simultaneous esophageal pH monitoring. The sensor seems able to reliably predict pathological esophageal acid exposure. These findings warrant larger studies of the clinical potential of the acid exposure sensor in the diagnosis and quantification of GERD.

The development of a disposable probe to measure the acid burden over an extended period of time is reported. The probe consists of a screen-printed matrix that shows decomposition as a function of pH and exposure time. The concept development and realisation of the probe is discussed, and experimental results, both in vitro and under pre-clinical in vivo conditions, are presented. The in vitro experiments prove the validity of the concept and the feasibility of the approach. The in vivo experiments indicate that there is a good correlation between the probe response and the oesophageal epithelial cell damage produced by oesophageal acid perfusion of the feline oesophagus.

Twenty-four normal subjects and 64 symptomatic patients with various degrees of reflux disease (24 with reflux symptoms without esophagitis and 21 with mild and 19 with severe esophagitis) underwent quantitative 24-hr intraesophageal pH monitoring. Various reflux parameters during supine, interprandial, and postprandial periods were examined by binary logistic regression and by CART analysis to determine the sensitivity and specificity to separate the various groups of subjects and patients. The distinction was excellent between asymptomatic controls and patients with severe erosive esophagitis (sensitivity and specificity both 100% by logistic regression and 95% and 88%, respectively, by CART), but discrimination was poor when asymptomatic controls were compared to symptomatic patients without esophagitis (71% and 79% by logistic regression and 75% and 92% by CART), which is the most important indication for pH recording in clinical practice. A 3-hr postprandial pH recording was inadequate to distinguish the various groups. The acidity of the reflux episodes during the night appeared to be a crucial factor in the development of severe erosive esophagitis. The duration of esophageal acid exposure was another important factor in the development of reflux lesions.

Human papillomaviruses (HPV) are associated with benign lesions and show specificity towards the location or tissues that they infect. HPVs are responsible for warts. Among more than 60 different HPV types known to occur in humans, a strong association has been found between types 16 and 18 and cervical cancer, and such an association is also suspected for types 31, 33, 35, 45, 51, 52, and 56. We describe the effects of (S)-1-(3-hydroxy-2-phosphonyl-methoxypropy Dcytosine (HPMPC), following local intratumoral injection, in a 69-year-old woman with hypopharyngeal and esophageal papillomatous lesions, polymerase chain reaction (PCR) positive for HPV types 16 and 18, that relapsed after surgery and that also failed to respond to Nd-Yag laser photocoagulation and al-pha-interferon treatment (6 × 106 U five times a week for 4 weeks followed by three times a week for 2 months). HPMPC was given at 1.25 mg/kg, with a sclerosing needle, through the biopsy channel of a video-endoscope, directly into the tumor, from March until July 1993 at seven different occasions. The first four injections were given at an interval of 1 week at the level of the hypopharynx. The next three injections were given at an interval of 3 to 5 weeks. During the fourth to the seventh session, half of the dose was injected into the hypopharyngeal and the other half into the esophageal tumor. Three further injections of HPMPC were administered at the level of the esophageal tumor in September 1993 with 2-week intervals. After HPMPC treatment, the lesions became smaller and flat until they completely disappeared. Endoscopic examination in February 1994 did not show any sign of papilloma in the esophagus or hypopharynx. These results suggest an in vivo efficacy of HPMPC for the treatment of papillomatous lesions due to HPV. © 1995 Wiley-Liss, Inc.

Permeability tests are widely used to investigate the pathogenesis of various gastrointestinal diseases including coeliac disease, infectious diarrhoea, and inflammatory bowel disease. In Crohn's disease they are used as activity parameters by some investigators. Lack of standardisation, however, makes it very difficult to compare data reported in different studies. The aim of this study was to gather permeation data in well controlled test conditions to standardise the methods. Nine healthy volunteers each received five consecutive permeability tests by mouth using polyethylene glycol-400 (PEG-400) and 51Cr-EDTA as probe molecules. The probes were dissolved in water, a glucose solution, a starch solution, a hyperosmolar lactulose-mannitol solution, and a liquid meal. A significantly decreased permeation for both probes was found when given with the hyperosmolar solution. The 51Cr-EDTA permeation was also decreased with water. The permeability index, 51Cr-EDTA/PEG-400, corrected for influencing factors, confirmed that the lactulose-mannitol solution and plain water yield lower values of macro-molecule permeation than starch, glucose or liquid meal. Hyperosmolarity was clearly accompanied by a decrease in permeability probably caused by reversed solvent drag. Interindividual variability of probe permeation and permeability index is very low with a standard liquid meal. It is proposed that for permeability studies a standard liquid meal is always used.

The *C (13C or 14C) labelled octanoic acid breath test was recently developed to measure the gastric emptying rate of solids. This study aimed to investigate whether it is sensitive enough to detect pharmacologically induced changes in the gastric emptying rate. Nine healthy volunteers were studied in basal condition, after intravenous administration of 200 mg erythromycin, and after peroral administration of 30 mg propantheline. Erythromycin significantly enhanced gastric emptying in all subjects, with an increase of the gastric emptying coefficient (p = 0.0043) in eight of nine and a fall in both the gastric half emptying time (p = 0.0020) and the lag phase (p = 0.0044) in all nine. Propantheline significantly reduced the gastric emptying rate, with a decreased gastric emptying coefficient (p = 0.0007) and an increased gastric half emptying time (p = 0.0168) in all subjects, but no change in the lag phase (p = 0.1214). Further mathematical analysis showed that breath sampling at 15 minutes intervals over a four hour period is recommended to guarantee accuracy and the discriminative value of the breath test in various gastric emptying patterns. In conclusion the *C labelled octanoic acid breath test is sufficiently sensitive to show pharmacologically induced changes of gastric emptying rates of solids.

We demonstrate binding of [125I][Nle13-po]motilin to homogenates of cat gastric and small intestinal, but not to colonic smooth muscle tissue. The density was ( B max in fmol/mg protein): 0 (fundus); 12 ± 2 (corpus); 22 ± 3 (antrum); 55 ± 12 (duodenum); 44 ± 10 (jejunum); 17 ± 1 (ileum); 0 (colon). A significant ( p ) difference was found between the dissociation constant for motilin in the stomach ( pK d = 8.84 ± 0.06 ) and in the small intestine ( pK d = 8.58 ± 0.08 ). The motilides erythromycin-A (EM-A), EM-523, and EM-A N- oxide displaced labeled [Nle13-po]motilin bound to cat duodenal receptor with potencies ( pK d ) of 5.47 ± 0.23 , 7.60 ± 0.24 , and N- terminus of motilin interacts with the receptor. In the tissue bath, duodenal strips mounted in the longitudinal direction responded to motilin, EM-523, and EM-A (pEC50: 8.29 ± 0.08 ; 7.12 ± 0.12 ; 5.99 ± 0.15 ). The compounds had a comparable intrinsic activity ( 83 ± 3% ; 80 ± 5% ; 82 ± 5% of the response to ACh), which was unaffected by atropine, TTX, hexamethonium, and zacopride but reduced by verapamil and calcium-free medium. Cat stomach and small intestine possess smooth muscle motilin receptors, which have comparable properties as those found in man and in rabbit.

Motilin was isolated from cat small intestine by a series of chromatographic steps. Using a radioreceptor assay, based upon binding of iodinated porcine motilin to rabbit antral smooth muscle membranes, it was shown that cat duodenal mucosa contains about 495 ng/g tissue, the jejunal mucosa 161 ng/g tissue and the ileal mucosa 95 ng/g tissue motilin. The duodenal mucosa was extracted with 6% acetic acid and concentrated on a cation exchange Whatman CM-52 gel. After lyophilization the material was further purified by gel filtration (Sephadex G-50), followed by reverse phase (C 18 ), cation exchange HPLC (Mono S) and three runs on a reverse phase HPLC (Nucleosil 300-5C 18 ) column. The UV absorbance and the radioreceptor assay were used to monitor the purification. After Mono S chromatography two forms of motilin were detected. The major peak corresponded to a 22 amino acid peptide, which differed only from canine motilin at position 12, where Lys is replaced by Arg. The smaller peak probably corresponds to a deamidated form of this peptide. The sequence homology between cat and porcine/human motilin or cat and rabbit motilin is 81.8% and 72.7%, respectively. The conservation of the first six amino acids in all five species studied is striking, confirming that the biological acitivity of the peptide resides in the N-terminal part.

The final diagnosis of granulomatous gastritis is based on morphological findings and clinical and laboratory data. Detailed analysis of the morphological features of the granulomas together with associated mucosal changes could generate more information on aetiology and pathogenesis. Biopsies from 71 patients diagnosed as having granulomatous gastritis were reviewed. Thirty-seven of these patients (52%) had Crohn's disease. In 18 patients (25%) an isolated granulomatous gastritis was diagnosed. In seven patients (10%) the final diagnosis was a foreign body reaction. Of the remaining cases, four (7%) corresponded to tumour-associated granulomas and one case each of sarcoidosis (1%), Whipple's disease (1%) and vasculitis-associated disease (1%). Two cases (3%) were unclassifiable. The granulomas were mainly found in the antrum (64% antrum only, 11% antrum and corpus, 6% transitional mucosa corpus-antrum). Granulomas were usually small. This was particularly true for those found in patients with Crohn's disease. Multiple granulomas were observed in the sarcoidosis, the Whipple's disease and vasculitis-associated cases. A pattern of chronic gastritis with atrophy was present in 95% of the biopsies (68/71 patients). Helicobacter pylori was detected in 92% of the biopsies (64/71 patients).

Objective To investigate the acute, long-term and persisting effect of oestrogen—progesterone therapy on bleeding frequency and on transfusion requirements in patients with bleeding gastrointestinal vascular malformations. Design A double-blind randomized placebo-controlled, cross-over trial was performed using 0.050 mg ethinyloestradiol and 1 mg norethisterone. Results Oestrogen—progesterone therapy was very effective in reducing transfusion requirements: 2.8 compared with 11.2 units of packed cells over a 6-month treatment period (P = 0.002). Only three out of 13 patients treated with ethinyloestradiol and norethisterone required transfusion for persistent bleeding, while 12 out of 13 patients in the placebo group required transfusion (P = 0.001). After finishing hormonal therapy, patients who responded to this therapy did not need transfusion for a mean of 9.6 months. The post-treatment transfusion requirements were significantly lower than those prior to hormonal treatment: 0.31 units packed cells per patient per month compared with 1.39 (P = 0.006). A second course of hormonal therapy was effective in preventing haemorrhage and transfusion. Conclusions Oestrogen-progesterone therapy stops bleeding in patients with severely bleeding gastrointestinal vascular malformations. This effect persists for a mean period of about 10 months.

Background: The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing. Methods: A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase. Results: There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = −0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test. Conclusions: It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids.

L’œsophage de Barrett est caracterise par le remplacement de l’epithelium malpighien de l’œsophage distal par un epithelium de type glandulaire. Cette entite pathologique est causee, dans la majorite des cas, par un reflux gastro-œsophagien severe. Le risque de developper un adenocarcinome œsophagien est multiplie par 30 a 40 chez les patients atteints de cette pathologie. A l’heure actuelle seule la recherche systematique de la dysplasie par biopsie endoscopique a une valeur predictive certaine.

Die Ileokoloskopie ist eine sehr gute diagnostische Untersuchungsmethode zur Beurteilung von entzundlichen Darmerkrankungen. Diese Untersuchung ist nur dann gerechtfertigt, wenn das Untersuchungsergeb

The metabolism of erythritol was assessed in six normal volunteers by measuring the amount of 13CO2 excretion and H2 excretion in breath, and erythritol in urine after intake of 25 g 13C-labelled erythritol. The results were compared with the same variables obtained after intake of 25 g 13C-labelled glucose and13C-labelled lactitol. In addition, the H2 production by faecal flora supplemented with small amounts of erythritol, glucose and lactitol was measured in vitro, as an index of bacterial metabolism of non-absorbed substrate. In contrast to the results obtained after intake of glucose and lactitol, no increase in breath 13CO2 and H2 was observed after intake of erythritol, and erythritol was nearly completely recovered in urine. The in vitro experiments showed that no H2 was formed by faecal flora from erythritol as compared with glucose and lactitol. It is concluded that erythritol is a substrate that is readily absorbed, and undergoes no metabolism by the host. If part of it escapes absorption, it is not metabolized by faecal flora.

Animal studies have shown that primary esophageal peristalsis is preceded by a wave of inhibition spreading rapidly down the esophagus and lasting longer in more distal segments. In humans, its presence in the esophageal body cannot be demonstrated manometrically because of the absence of tone. To study deglutitive inhibition in humans, an artificial high-pressure zone was created by inflating an intraesophageal balloon to a critical level. The pressure changes at the interface between the balloon and the esophageal wall at various levels along the esophagus were measured. In this artificial high-pressure zone, deglutition induced a relaxation beginning simultaneously at various levels of the esophagus but lasting progressively longer in progressively more distal segments. Latency from onset of deglutition to onset of relaxation at 13 cm and 8 cm above the lower esophageal sphincter and at the lower esophageal sphincter was 0.06 +/- 0.19 seconds, 0.10 +/- 0.31 seconds, and 0.89 +/- 0.53 seconds, respectively; latency to contraction was 4.45 +/- 0.54 seconds, 6.04 +/- 0.79 seconds, and 9.14 +/- 1.04 seconds, respectively. This is the first direct evidence that deglutition produces in the human esophagus a wave of inhibition that precedes the primary peristaltic contraction.

The quantitative relation between slow-wave periods and spiking activity was evaluated in vivo in canine small intestine during the fasted state. Experiments were performed in three conscious dogs with three bipolar electrodes, implanted respectively 10, 25 and 40 cm beyond the ligament of Treitz. Digitized electrical recordings were automatically processed for the individual slow-wave periods and spike-burst intensities using a set of computer programs developed in our laboratory. A linear correlation existed between the degree of spiking activity and the average length of the preceding slow-wave period. The slopes of the regression lines were less steep for more distal electrodes. A second series of experiments showed that an increase in the slow-wave period precedes the onset of phase 3 of the migrating myoelectric complex and that a fall in slow-wave period precedes the end of phase 3. These data show that a low slow-wave frequency is accompanied by a facilitation of spiking activity, whereas shortening of the slow-wave period is accompanied by a decrease in spike burst intensity. This relation between slow-wave period and spiking activity shows an aboral trend that may be related to intrinsic slow-wave frequency.

The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase-3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications.

Erythromycin has been shown to act as a motilin agonist by binding to motilin receptors on gastrointestinal smooth muscle and to improve the severely impaired gastric emptying in patients with diabetic gastroparesis. To elucidate the motor pattern that accounts for this accelerated emptying, the effect of 200 mg erythromycin vs. placebo on postprandial motility of the stomach and the upper small intestine was examined in 13 normal subjects. Erythromycin significantly increased the amplitude of the antral contractions during the 2-hour postprandial study period (maximal difference in mean amplitude of distal antral contractions between erythromycin and placebo recorded from 80 to 90 minutes after meal: 123 +/- 17 vs. 44 +/- 12 mm Hg; P less than 0.005). The total number of antral contractions was not affected, but the contractions could be recorded manometrically higher up in the stomach after erythromycin than after placebo (9-12 vs. 3-6 cm above the pylorus). Antroduodenal coordination was significantly improved during the first postprandial hour, and the first normal phase 3 of the migrating motor complex, indicating the reappearance of fasting motility, occurred earlier after erythromycin than after placebo (128.3 +/- 14.3 vs. 173.4 +/- 16.1 minutes; P less than 0.05). These changes in postprandial motility induced by erythromycin may well account for its accelerating effect on gastric emptying.

The long-term effects of endoscopic dilation of colonic or ileo-colonic Crohn's disease strictures were analyzed. In 18 patients with a Crohn's disease-related low gastrointestinal stricture, the stenosis was dilated using through-the-scope (TTS) balloon catheters. A dilation to a diameter of 18 mm was always attempted. Treatment was successfully carried out in 16 patients, and was followed by immediate symptomatic relief in 14 patients. Long-term success was observed in nine patients. There were no complications. Balloon catheter dilation of a colonic stricture or stricture of an ileo-colonic anastomosis was found to be safe and effective. This treatment modality can be an alternative to surgery in a selected group of patients.

Aphthous lesions recur in the neoterminal ileum within the first few months after curative resection of the distal ileum in patients with Crohn's disease. These lesions do not originate from microscopic disease that is already present at the time of surgery. To investigate the importance of faecal stream in the pathogenesis of recurrent Crohn's lesions, we have studied 5 patients with Crohn's disease who had ileal resection. After curative resection and ileocolonic anastomosis, a diverting terminal ileostomy was constructed 25-35 cm proximal to the anastomosis thereby excluding the neoterminal ileum, the anastomosis, and the colon from intestinal transit. After six months of exclusion, endoscopy of the ileocolon was undertaken and biopsy specimens were taken. Transit was then restored. Six months after reanastomosis further biopsy specimens were taken. These patients were compared with a control group of 75 patients with Crohn's disease who underwent a one-step ileal resection and ileocolonic anastomosis. None of the 5 patients had endoscopic lesions in the neoterminal ileum after six months of exclusion and biopsies did not show inflammatory changes characteristic of Crohn's disease. By contrast, 53 of 75 patients with one-step surgery had endoscopic recurrence in the neoterminal ileum within six months of surgery. All 5 patients had an important recurrence of disease, both endoscopically and histologically, at ileocolonoscopy six months after reanastomosis. Our findings strongly support the view that recurrence of Crohn's disease in the neoterminal ileum after curative ileal resection is dependent on faecal stream.

Standardization of technique of esophageal manometry, method of analysis, and system of classification of data will improve consitency of diagnosis, promote computer analysis, and facilitate communication between clinians and scientists. Esophageal manometry should include a quantitative study of LES and distal (smooth muscle) esophagus and a qualitative study of the striated part of the gullet. Three recording ports 5 cm apart and radially oriented are minimum requirements. Resting LES pressure is expressed as mean of the peaks during pull-through. Number of LES relaxations and peristaltic performance of body contractions are reported as percentage of total number of swallows. Residual LES pressure after swallowing and amplitude, duration, and progression velocity of esophageal body contraction as well as their shape are to be determined. Classification of data should be primarily descriptive, and normal values should stay outside the classification to allow for continuous adaptation.

Vitamin B12 is essential as a cofactor in several vital enzymatic reactions. Determination of methylmalonic acid (MMA) in urine is considered as the standard test for vitamin B12 deficiency and GC-MS as the preferred analytical technique. Quantitation is improved by using isotope dilution, but accurate determination of dicarboxylic acids as their trimethylsilyl derivatives is difficult because electron ionization yields low molecular-ion peaks, while other fragment ions are common to all. It is shown that chemical ionization with isobutane as the reactant gas improves molecular-ion formation. MMA is separated from urine by solid-phase extraction and derivatized with trimethylchlorosilane/ hexamethyldisilazane. With the ion-trap detector, naturally occurring MMA yields a peak at m/z 263 (M + 1)+; the corresponding peak for deuterated MMA is m/z 266. The calibration curve covers the range 1–50 μg ml−1 MMA. Recoveries were in the range 90–110%.

Short-chain carboxylic acids include formic, acetic, propionic, butyric, isobutyric, valeric, isovaleric and caproic acids. The formation of these acids in fecal samples is considered to be representative of bacterial fermentation activity. A recently-published method in which the tert -butyldimethylsilyl derivatives are formed prior to gas chromatography- mass spectrometry, is applied for determination of the acids in fecal samples. An ion-trap detector is used and the conditions for accurate quantitation are described. Calibration plots show linear dynamic ranges of about three orders of magnitude for each acid, e.g., 0.03–30 ng of acetic acid injected, corresponding to 0.26–260 mmol l −1 in the original sample. Recovery studies indicate that results are reproducible within ± 10% (or ± 20% for formic acid).

The influence of metabolic substrates on the formation of volatile compounds by the colonic flora was measured in a fecal incubation system. The presence of carbohydrates (0, 25, and 50 mg/20 mL fecal suspension) led to a dose-related increase in the formation of alcohols and H2 and to a dose-related decrease in the formation of toxic mercaptans. This effect seemed to be independent of pH. The presence of albumin or fat (50 mg/20 mL fecal suspension) as substrates for the colonic flora gave rise to the formation of significantly higher amounts of methanethiol. Small amounts of pentane were found in the headspace after incubation with oil. These data show that the formation of volatile metabolites by the colonic flora is greatly influenced by the available substrates.

A solitary hepatic metastasis is amenable to surgery. However, if surgery is contraindicated or if multiple lesions are present in both liver lobes, other treatment modalities have to be considered. We compared the effect of interstitial laser hyperthermia with damage caused by alcoholization. Six anaesthetized beagle dogs were studied. Three animals were treated with laser hyperthermia. A bare laser fibre (400μm diameter) was introduced through a 17-gauge needle, length 170 mm, positioned into the liver under real time ultrasonographic guidance. Lesions were produced by continuous 500-s exposure of 1W YAG laser (Medilas MBB 40N) power. Three dogs were subjected to an injection of 4 ml of 98% pure ethanol into the liver through the same needle system. Two days after the procedure the animals were killed and the livers examined. The surface of the livers treated with the YAG laser were entirely normal; superficial lesions were, however, clearly visible. Laserinduced lesions were well reproducible, clearly demarcated, roughly spherical with a mean diameter of 1.01±0.23 cm (n=16). In contrast, the dogs treated with alcohol had free intraperitoneal serohaemorrhagic fluid and the surface of the liver was diffusely abnormal. The lesions had a more or less cylindrical shape, 1.22±0.43 cm on 0.40±0.10 cm (n=12) although exact measurement was often difficult. The border of the lesions was irregular and there was a clear necrotic zone along the puncture track. On microscopic examination the laser-induced lesions consisted of a central evaporation area, a zone of carbonized material and an outer zone of coagulation necrosis. The alcohol-induced lesions were characterized by both ‘fixation’ necrosis and coagulative necrosis but surprisingly, there was also necrosis present at a distance of the lesions extending along the centrilobular and even portal veins. These data show that laser-induced interstitial necrosis in the liver is better controlled and more reproducible than necrosis induced by injection of pure ethanol. Moreover, pure ethanol may cause damage to the liver surface and even at a distance of the injection site.

The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.

Recent studies suggested that certain erythromycin A (EM-A) derivatives are motilin receptor agonists. As proposed by Itoh they may be called "motilides". We have investigated the Ca2(+)-dependence of contractions induced by two potent motilides, ME-34 [de(N-methyl) 8,9-anhydroeryhtromycin A 6,9-hemiacetal] and EM-523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal], in duodenal tissues and compared the results with those previously obtained with motilin. Isometric and isotonic contractile responses of isolated longitudinal muscle sheets from the rabbit duodenum were tested under normal, Ca2(+)-free and depolarizing conditions. Prior to stimulation with motilides, the maximal response to acetylcholine was recorded and all responses were always expressed as a percentage of this response. Both motilides induced contractions in normally polarized tissue, with an EC50 of 26 +/- 5 nM for ME-34 (n = 7), and 27 +/- 5 nM for EM-523 (n = 16) and maximal responses of respectively 88 +/- 4% and 80 +/- 3%. Like motilin, both compounds induced an 'extra'-contraction in depolarized tissues. The EM-523 response in 140 mM K+ under isotonic conditions was 84 +/- 3% (n = 5) at 10(-5) M, with an EC50 that was shifted to 65 +/- 18 nM. Similar figures were obtained for ME-34. When Ca2+ was added to Ca2(+)-depleted strips, half-maximal Ca2+ values (in mM) were 1.10 +/- 0.11 (n = 9) for EM-523 and 1.13 +/- 0.12 (n = 3) for ME-34, as compared with 1.12 +/- 0.13 (n = 7) for motilin and 2.8 +/- 1.1 (n = 9) for K+. Both ME-34 and EM-523 also induced a transient contraction in Ca2(+)-free solutions under isometric conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding studies with iodinated motilin revealed that in the small intestine motilin receptor density decreased aborally, disappeared in the caecum but returned in the colon and rectum. The highest density was in the distal colon (112 +/-/11 fmol/mg protein). The dissociation constant was the same in all regions (overall mean 1.10 +/- 0.22 nM). The ability of erythromycin-A (EM-A) and of two derivatives, EM-A N-oxide and EM-523, to displace motilin showed no difference between the tissues studied. Their order of potency was: motilin greater than EM-523 greater than EM-A greater than EM-A N-oxide. Proximal circular colonic smooth muscle strips showed maximal contractile responses towards motilin, EM-523 and EM-A of, respectively, 80 +/- 3%, 78 +/- 4% and 84 +/- 2% relative to the maximum obtained with acetylcholine. In proximal longitudinal muscle only a response of +/- 20% was obtained. Similar responses were obtained in the distal colon. The order of potency to induce contractions as reflected in the pED50 values was: motilin (8.03 +/- 0.1) greater than EM-523 (7.55 +/- 0.03) greater than EM-A (5.84 +/- 0.04) in proximal circular colon. The responses were not blocked by TTX (10(-6) M) or atropine (10(-6) M), but were reduced by verapamil (10(-6)M). The abundance of motilin receptors in colonic smooth muscle, if applicable to other species, opens new perspectives for the therapeutic applications of macrolides with motilin agonist properties.

With the use of the radionuclide gastric-emptying test and a new data processing method, the contraction characteristics of the stomach were analyzed. After ingestion of a radiolabeled test meal, dynamic images of the stomach were acquired and analyzed to determine the frequency, amplitude, and rate of gastric contractions in healthy subjects. The frequency of antral contractions was found to be inversely related with food retention in the stomach; in contrast, the amplitude of the contractions decreased progressively during the course of gastric emptying. The peaks of both antral contraction and filling rate and the time of their occurrence remained constant throughout gastric emptying. The observed patterns of phase distribution and sequential phase changes of the food in the stomach confirmed noninvasively what was already known from invasive technique, i.e., that the proximal stomach does not undergo phasic contractions and that, in the distal stomach, smooth muscle contraction originates in midcorpus and propagates aborally to the pylorus. The scintigraphic test can be used to noninvasively and quantitatively characterize gastric motor function and to delineate the spatial sequence of gastric contractions. This technique can be applied to study the pathophysiology of gastric emptying in various motor disorders.

The recording of the human, gastric myoelectrical activity, by means of cutaneous electrodes is called electrogastrography (EGG). It provides a noninvasive method of studying electrogastric behaviour. The normal frequency of the gastric signal is about 0·05 Hz. However, sudden changes of its frequency have been observed and are generally considered to be related to gastric motility disorders. Thus, spectral analysis, especially online spectral analysis, can serve as a valuable tool for practical purposes. The paper presents a new method of the adaptive spectral analysis of cutaneous electrogastric signals using autoregressive moving average (ARMA) modelling. It is based on an adaptive ARMA filter and provides both time and frequency information of the signal. Its performance is investigated in comparison with the conventional FFT-based periodogram method. Its properties in tracking time-varying instantaneous frequencies are shown. Its applications to the running spectral analysis of cutaneous electrogastric signals are presented. The proposed adaptive ARMA spectral analysis method is easy to implement and is efficient in computations. The results presented in the paper show that this new method provides a better performance and is very useful for the online monitoring of cutaneous electrogastric signals.

Fifty patients with non-cardiac chest pain underwent 24 hour intraoesophageal pH and pressure recording and provocation tests to determine the relative value of both techniques in establishing the oesophageal origin of the chest pain. Twenty six patients (52%) had at least one positive provocation test: the acid perfusion test was positive related in 18 patients (36%), the edrophonium test in 16 patients (32%), the vasopressin test in five patients (10%), and the balloon distension test (performed in only 20 patients) in one (5%). The 24 hour pH and pressure recording correlated spontaneous chest pain attacks with abnormal motility or gastro-oesophageal reflux in 19 patients (38%). Fourteen of these patients also had at least one positive provocation test. Therefore, 24 hour pH and pressure recordings are only slightly better than a set of provocation tests in identifying the oesophagus as the cause of chest pain (10% diagnostic gain). In the case of oesophageal chest pain, however, 24 hour recording appeared to be the only way to identify the nature of the underlying oesophageal abnormality that caused the spontaneous pain attacks--for example, gastro-oesophageal reflux, motility disorders, or irritability of the oesophagus.

13CO2 starch breath test was used to study the effect of physicochemical characteristics of starch digestion. As starch is hydrolysed to glucose, which is subsequently oxidised to CO2, differences in 13CO2 excretion after ingestion of different starch products must be caused by differences in hydrolysis rate. To study the effect of the degree of chain branching, waxy starch, containing 98% amylopectin, was compared with high amylose starch, containing 30% amylopectin, and normal crystalline starch, containing 74% amylopectin. The effect of the extent of gelatinisation was studied by comparing extruded starch and crystalline starch. Finally, the possible inhibitory effect of adding wheat fibre to extruded starch on the hydrolysis rate was studied. The 13CO2 excretion from two to four hours after intake of crystalline starch was significantly lower than that of extruded starch. Waxy starch was hydrolysed much faster than high amylose starch, but there was no significant difference between waxy starch and normal crystalline starch. Addition of wheat fibre did not influence the hydrolysis rate. The 13CO2 starch breath test is an attractive test for the study of factors affecting carbohydrate assimilation.

Human electrogastric signals can be detected by properly locating electrodes on the abdominal skin. The detailed waveform analysis for medical researches or clinical use is, however, hindered by its poor quality. A modified adaptive enhancing technique is described in the paper for eliminating noise and interference while keeping the modification of the characteristics of the gastric signal component as small as possible. According to the specific properties of the human cutaneous gastric signal the technique used is a two stage adaptive enhancing system of which the first stage is simply an adaptive line enhancer and the last stage is a combination of conventional FIR filering and multichannel adaptive enhancing. The system has been testified by both computer simulations and real measurement processing, and performs well, namely, the noise and disturbance are cancelled and the characteristics of gastric signal component are little affected.

Diagnosing and treating gastrointestinal disorders in elderly patients requires that the physician be acquainted with both psychological and physical alterations induced by aging. Diseases of the oesophagus in elderly patients may be associated with the classic complaints of dysphagia, regurgitation, chest pain, and heartburn. However, atypical presentations are more common in this age group, and there is a greater likelihood of concurrent disease that may confound the interpretation of symptoms. Elderly patients are also more susceptible to complications that may accompany inadequately treated or long-standing oesophageal disease, such as aspiration, malnutrition or Barrett’s adenocarcinoma. Oesophageal function in elderly patients has been studied in several cross-sectional studies. Only one prospective study on the effect of aging on oesophageal function was reported, in a rather young group of healthy volunteers.1 Earlier literature suggested a rather common degeneration of oesophageal function with aging. The term presbyoesophagus was proposed to describe an age related decrease in contractile amplitude, polyphasic waves in the oesophageal body, incomplete sphincter relaxation, and oesophageal dilatation.2 This notion has been abandoned more recently as it was felt that most motility disorders in old age are related to medical problems that accumulate during aging, such as diabetes mellitus, neurological disorders and the intake of numerous drugs. Investigations in healthy elderly people have shown only minor to mild alterations in oesophageal motility. A gradual decrease in upper oesophageal sphincter (UOS) pressure occurs with age, with a delay in UOS relaxation after deglutition.3 4 Pharyngeal contraction pressures and pharyngo-oesophageal wave velocity are notably increased.3 4 The changes are attributed to increased resistance to flow across the UOS as a result of loss of compliance with age. The sensory threshold for the initiation of deglutition may also be increased with age.5 With increasing age, there is a significantly increased …

Most measurements of human electrical activity contain large amounts of electrical heart activity (electrocardiogram, ECG). Whenever other sources of lower energy are of interest, a need arises to eliminate this ECG. Some applications allow a frequency domain operation (e.g. gastro-intestinal slow wave detection), or even a time domain operation (e.g. blanking of QRS complex of an ECG). Usually none of these methods are adequate. The proposed method uses a totally different approach, in this sense that it manipulates geometrically all measurements at the same time. It decomposes the measurements on the basis of an oriented energy, by means of the singular value decomposition. After an introduction to the problem and a definition of some useful concepts, the basic idea of the method is presented in a low dimensional geometrical example, and generalized to higher dimensions. It is shown that the method can easily be applied under realistic clinical conditions. A discussion is given about : the influence of noise; considerations on correlations between source signals; number and location of electrodes; certain dynamical problems like interference. Results on real data are given, in order to illustrate and verify the main features of the method : the multidimensional approach to the estimation of equivalent dipole vector sources; the insensitivity of ECG elimination quality to actual electrode positions; the minimal rank representation of the source signals and the resulting signal to noise ratio improvement; 50 Hz or 60 Hz interference elimination.

Defining risk factors for ulcerative colitis (UC) is important to better understand the pathogenesis of this idiopathic disease. One factor modulating the disease is smoking. A pilot study showed the absence of appendectomy in the medical history of patients with ulcerative colitis. The aim of the present case control study was to compare the relative risk of developing UC after appendectomy with the relative risk of developing UC with an intact appendix. One hundred seventy-four (84 females and 90 males, mean age 34.9 years) consecutive UC patients examined at our inflammatory bowel disease clinic or hospital ward, were included. Fifty-six had pancolitis (32%) and 118 (68%) suffered from left-sided colitis. The control group consisted of 161 consecutive patients examined at the orthopedic clinic (86 females and 75 males, mean age 40.9 years). Two parameters, absence of appendectomy and smoking, were closely related to the development of UC. Before the onset of UC, only 1 of the 174 patients (0.6%) had undergone an appendectomy. Of the 161 controls, 41 (25.4%) had undergone an appendectomy. The difference between the two groups was highly significant with an odds ratio of 59.1 (95% CI, 18-189; P

In vitro studies of a recently developed acid exposure sensor show that the sensor response (SR) to acidpH 4 is linearly determined by the duration and degree of acidity. The aim was to determine whether SR correlates with the severity of acid-induced esophageal mucosal lesions and acid-induced heartburn.HCl pH 1.5 or saline was infused into the feline esophagus for 5-20 min. Simultaneously, sensor measurements were performed below the infusion port. The histological damage was scored by an independent pathologist. In 15 normal subjects, HCl pH 1 was infused into the esophagus and the severity of the heartburn (0-5) was scored at 5-min intervals. In 10 subjects who experienced heartburn during acid perfusion, initial perfusion with HCl was repeated during heartburn induction time minus 5 min, followed by perfusion with the subject's own gastric juice, titrated to pH 2; heartburn severity was again scored at 5-min intervals. Acid exposure sensors positioned below the infusion port were removed at heartburn scores 1, 2 and 3.A good correlation was found between SR and the histological score for mucosal damage in the cat esophagus (r = 0.64, P0.005). There was a good relation between heartburn severity score and acid exposure time (r = 0.84, P0.001), and a significant but weaker relation between heartburn severity and SR.In cats, there is a good relation between the severity of acid-induced esophageal mucosal lesions and SR. In men, there is a significant correlation between the severity of acid-induced heartburn and the simultaneously measured SR. Therefore, SR measurement has the potential of yielding clinically relevant information in the investigation of GERD.

Seventy five patients with severely bleeding peptic ulcer were included in a controlled comparative trial to assess the efficacy and safety of endoscopic injection therapy in preventing rebleeding from peptic ulcers that presented at endoscopy with a protruding vessel. Twenty five patients were treated with injection of epinephrine followed by polidocanol, 25 were treated with injection of absolute alcohol, and 25 with sham injection. Rebleeding occurred in 44% of patients in the sham group, 40% of those treated with epinephrine and polidocanol, and in 20% of those treated with absolute ethanol. The difference in the haemostasis rate between the control and ethanol treated subjects nearly reached significance (p = 0.07). A second therapy session resulted in haemostasis rates of 68% in the epinephrine-polidocanol group and of 88% in the absolute ethanol group. These rates after two treatments as well as the emergency surgery rates (32% in the epinephrine-polidocanol group and 8% in the absolute ethanol group; p = 0.07) were not significantly different. In eight of the 11 patients with rebleeding in the sham treatment group, definitive haemostasis was achieved by elective injection therapy. Overall transfusion requirements were mean (SD) 6.0 (0.7) units in the sham group, 6.0 (0.9) in the epinephrine-polidocanol group, and 3.9 (0.5) in the absolute ethanol group. Only the difference between ethanol and sham was significant (p = 0.02). This study shows that injection with absolute ethanol reduces rebleeding in these patients and significantly lowers transfusion requirements. Absolute ethanol was superior to epinephrine-polidocanol, which was not significantly better than sham therapy.

During the session on diagnostic testing, various diagnostic tests used to identify the cause of chest pain were discussed. This critique of diagnostic assessments of the complex etiology of chest pain is presented as a contribution toward further investigation and clarification of this difficult clinical syndrome. The first step in the evaluation process is to exclude coronary artery disease. Patients with angina and normal coronary artery flow may have atypical disease, such as microvascular angina or syndrome X. The precise relationship between these disorders and esophageal disease or gastroesophageal reflux, as well as their possible involvement in chest pain of undetermined origin, requires further definition. A limitation of esophageal provocation tests is that they may identify the esophagus as the source of pain without determining the specific esophageal disorder that causes the pain. Problems associated with 24-hour pH and pressure monitoring include (a) poor correlation between reflux episodes and heartburn symptoms, (b) the lack of a good functioning swallowing signal, and (c) the huge amount of data that must be analyzed, along with shortcomings in computer-aided analysis. Nevertheless, the various available diagnostic tests can provide important information to the clinician.

From the start of 1994 until 1996 ten patients (eight adults and two children) received cochlear implants after careful preoperative selection in our department. Only the deaf adults implanted with the LAURA cochlear implant were included in this retrospective analysis. In this study, the additional hospital costs associated with cochlear implantations were estimated. In doing this, a differentiation was made between ‘fixed’ costs and ‘variable’ costs. In general, the average cost of cochlear implantation was 1,186,741 BF (29,418.54 EUR) per implanted adult and a direct fixed cost of 262,880 BF (6,516.62 EUR) was needed for the computer requisites. In general, the cochlear implant enhance speech-perception scores in the postlingually deafened patients as well as in the prelingually deafened adults. After intensive training, all implanted adults of the University Hospital Leuven could recognize the segmental aspects of speech with scores above the level of significance.

Forceful dilation of the cardia is the treatment of choice for achalasia. This therapy can be carried out using a homemade system or using commercially available dilators. Pneumatic dilation yields 77% good or excellent results in patients with achalasia, while 8.7% have moderate improvement and 14.4% are not improved. The main complication is perforation, occurring in 2.5%. Perforation can be treated medically with success. In the authors' series of now almost 1000 patients, only one died. Pneumatic dilation is a safe and effective procedure for the treatment of achalasia.

BACKGROUND & AIMS: Gastroesophageal reflux frequently occurs during spontaneous transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to determine the motor activity in the body of the esophagus during TLESRs in 10 healthy subjects. METHODS: Esophageal contractions were recorded 13,8,and 3 cm above a sleeve that measured LES pressure. A balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction (artificial high-pressure zone). RESULTS: No relaxation of the artificial high-pressure zone was detected at the onset or during spontaneous TLESRs before gastroesophageal reflux. Esophageal acidification provoked no changes or increased the pressure in the artificial high-pressure zone by 47.9% +/- 12% When gastroesophageal reflux abruptly distended the esophagus (common cavity), a relaxation of the artificial high-pressure zone of 51.1% +/- 6.6% was observed in 78% of the instances. Deglutitive or secondary contractions during spontaneous TLESRs traveled down the esophagus in 96.5% of the instances. CONCLUSIONS: Stimuli that induced spontaneous TLESRs did not by themselves inhibit muscle contractility in the body of the esophagus. Acidification without distention of the lower esophagus frequently increased esophageal tonic contractility. Abrupt lower esophageal distention by reflux of air or acid partially relaxed the artificial high-pressure zone in the esophageal body, probably to assist gastric venting. (Gastroenterology 1996 Mar;110(3):659-68)

We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids.

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.