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Biomedical subjects

L M Akkermans

Publications and source records attributed to L M Akkermans.

At least 19 recordsLinked to original sources

Disrupted bile flow affects interdigestive small bowel motility in rats.

BACKGROUND: The role of bile flow in the regulation of small bowel motility and the migrating myoelectric complex (MMC) is unclear. We aimed to study the effects of biliary diversion or obstruction on the MMC in a newly developed rat model. METHODS: In rats, myoelectrodes were implanted in the jejunum, and the proximal common bile duct (CBD) was cannulated and exteriorized at the head, enabling us to manipulate biliary flow without influencing pancreatic flow and without the need of anesthesia or additional surgery. Group A were controls without CBD cannulas. Biliary circulation was exteriorized but kept intact in group B; bile was diverted externally in group C; and the CBD was obstructed in group D. MMCs were recorded in unrestrained conditions by jejunal electromyography before and after biliary diversion or obstruction. Spontaneous recanalization of the CBD was monitored by measurement of serum bilirubin and by cholangiography. RESULTS: Exteriorization of the CBD without interruption of bile flow did not affect MMC duration (group A, 17.3 +/- 0.3 minutes [mean +/- SEM]; group B, 16.5 +/- 0.6 minutes). MMCs disappeared temporarily after CBD obstruction but not after biliary diversion. MMCs of increased duration were seen after 1 day in rats with biliary diversion or CBD obstruction (group C, 26.1 +/- 4.4 minutes; group D, 36.3 +/- 4.8 minutes [p < 0.05]). MMCs after biliary diversion or obstruction were characterized by an increased duration of phase II-like activity and decreased duration of phase I activity. CONCLUSIONS: We conclude that MMCs disappear temporarily early after CBD obstruction, but MMCs of increased duration are seen after 1 day of biliary diversion or obstruction. Thus disrupted bile flow affects interdigestive small bowel motility in rats.

Animals

Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus.

BACKGROUND: Hyperglycaemia delays gastric emptying, both in healthy controls and in patients with diabetes mellitus. The effect of hyperglycaemia on antroduodenal motility in diabetes has not yet been studied. AIM: To investigate the gastrointestinal motor mechanisms involved in the hyperglycaemia induced retardation of gastric emptying in patients with type I diabetes mellitus and autonomic neuropathy. In eight diabetic patients antroduodenal manometry was performed simultaneously with scintigraphic measurement of emptying of a mixed solid-liquid meal, during euglycaemia (5-8 mmol/l glucose) and hyperglycaemia (16-19 mmol/l glucose), on separate days, in random order. RESULTS: Hyperglycaemia decreased the cumulative antral motility index from 38.3 (range 24.2-47.6) to 30.8 (range 17.3-38.1) (p = 0.025) and reduced the number of antral pressure waves propagated over > or = 4.5 cm (p = 0.04). Duodenal phase III-like activity was seen irrespective of the glycaemic state (in three patients during euglycaemia and in four patients during hyperglycaemia). Hyperglycaemia significantly affected gastric emptying of the solid meal: it prolonged the lag phase from 20.0 minutes to 28.5 minutes (P = 0.02), increased the 50% emptying time from 73.5 minutes to 104.5 minutes (p = 0.03), and increased the percentage of isotope remaining in the stomach after 120 minutes from 33.5% to 46.5% (p = 0.02). The cumulative antral motility index was correlated with the 50% emptying time (r = 0.75, p = 0.02) during euglycaemia, but not during hyperglycaemia (r = 0.28, P = 0.31). Liquid emptying was not influenced by the blood glucose concentration. CONCLUSIONS: Hyperglycaemia reduces postprandial antral contractile activity and its organisation in patients with type I diabetes and autonomic neuropathy. These changes in antroduodenal motility are likely to constitute the mechanism through which gastric emptying of solids is delayed during high blood glucose concentrations in these diabetic patients.

Adult

Effects of the inflammatory mediator prostaglandin E2 on myenteric neurons in guinea pig ileum.

The effects of the inflammatory mediator prostaglandin E2 (PGE2) on myenteric neurons were investigated by intracellular recordings in a conventional plexus preparation. Bath application of PGE2 (1-1,000 nM) evoked a concentration-dependent and reversible slow depolarization and an augmentation of excitability in 23 of 26 AH and 12 of 13 S neurons. The amplitude of the slow depolarization ranged from 4 +/- 1 mV at 1 nM to 13 +/- 3 mV at 1 microM in S and AH neurons. In AH neurons, PGE2 evoked an increase in membrane resistance and a reduction of afterhyperpolarization. In S neurons, PGE2 evoked either an increase or a decrease in membrane resistance. PGE2 slightly reduced the amplitude of electrically evoked fast excitatory postsynaptic potentials and had no effect on slow excitatory postsynaptic potentials. Moreover, PGE2 evoked bursts of fast excitatory postsynaptic potentials and action potentials in S neurons, indicative of cyclical neural activity in the myenteric plexus. It is concluded that the inflammatory mediator PGE2 can act as an excitatory neuromodulator of gastrointestinal motility through direct action on neurons in the myenteric plexus.

Animals

Effects of oral erythromycin on fasting and postprandial antroduodenal motility in patients with type I diabetes, measured with an ambulatory manometric technique.

OBJECTIVE: The aim of this double-blind crossover study was to evaluate the effects of oral erythromycin (250 mg t.i.d.) on fasting and postprandial gastrointestinal motility and gastrointestinal symptoms in patients with type I diabetes. RESEARCH DESIGN AND METHODS: Antroduodenal motility was recorded with an ambulatory manometric technique for a 20-h period, including a high-caloric high-fat dinner and a low-caloric low-fat breakfast and a long fasting period, after 2 weeks erythromycin and placebo treatment in 12 patients with type I diabetes. During the manometric study, plasma glucose concentrations were assessed by frequent self-testing. Gastrointestinal symptoms were scored daily to assess the severity of the symptoms (range 0-3). RESULTS: Oral erythromycin decreased the migrating motor complex cycle length from 118.9 +/- 46.0 to 86.2 +/- 25.3 min (P = 0.03) by shortening phase II from 68.7 +/- 23.5 to 48.5 +/- 19.4 min (P < 0.05). The total number of duodenal phase III increased from 48 to 62 (P = 0.075). However, the degree of antral participation to duodenal phase III did not increase. Erythromycin significantly decreased the duration of the postprandial period after dinner (from 417.0 +/- 137.9 to 348.8 +/- 93.8 min, P = 0.04). During this shorter postprandial period, the number of antral contractions (P < 0.01) and the antral motility index increased (P < 0.03), and early phase III activity at the level of the duodenum was abolished. In diabetic patients with antral hypomotility, after dinner, the mean symptom score improved significantly, from 2.07 +/- 0.86 to 1.52 +/- 0.63 (P = 0.018). CONCLUSIONS: This ambulatory antroduodenal manometric study showed that oral erythromycin (250 mg t.i.d.) improves both fasting and postprandial antroduodenal motor activity after a high-caloric meal in patients with type I diabetes. Furthermore, in diabetic subjects with postprandial antral hypomotility, erythromycin reduces dyspeptic symptoms.

Administration, Oral

Biofeedback training in treatment of childhood constipation: a randomised controlled study.

BACKGROUND: Because abnormal defaecation dynamics, which can be modified by biofeedback, are considered to be the underlying problem in constipation, biofeedback training may be a useful treatment for constipation. This treatment has mainly been studied in uncontrolled trials. We evaluated defaecation dynamics and clinical outcome in chronically constipated children in a randomised study comparing conventional treatment and conventional treatment with biofeedback training. METHODS: Patients, 5 to 16 years old, were referred to the Academic Medical Center in Amsterdam by general practitioners, school doctors, paediatricians, and psychiatrists. They had to fulfil at least two of four criteria for paediatric constipation and were included if they had been treated medically for at least one month before randomisation. Patients had a medical history, abdominal and rectal examination, and anorectal manometry at the start and end of the 6-week intervention period. The conventional group received laxative treatment with additional dietary advice, toilet training, and maintenance of a diary of bowel habits. The biofeedback group received the same conventional treatment and additionally five biofeedback training sessions. During the first 3 weeks, patients visited the outpatient clinic weekly; two subsequent visits were twice monthly. FINDINGS: 94 patients were randomised to conventional treatment (CT) and 98 to conventional treatment with additional biofeedback training (CT+BF). Normal defaecation dynamics increased in the CT group from 41% to 52% (not significant) and in the CT+BF group from 38% to 86% (p = 0.001). At 6 weeks, more patients in the CT+BF group showed normal defaecation dynamics, compared to the CT group (p < 0.001). This result was unaltered by controlling for baseline status in a logistic regression model. At 1 year, successful treatment (defaecation frequency > or = 3/week, soiling and/or encopresis < 2/month, and no laxatives) was accomplished in 59% of the CT and 50% of the CT+BF group (p = 0.24). The results were maintained after 1 1/2 years follow-up. No association was found between achievement of normal defaecation dynamics and clinical outcome. INTERPRETATION: Additional biofeedback training compared to conventional therapy did not result in higher success rates in chronically constipated children. Furthermore, achievement of normal defaecation dynamics was not associated with success: abnormal defaecation dynamics seem not to play a crucial role in the pathogenesis of childhood constipation. Intensive conventional laxative treatment should remain the first choice in chronically constipated children.

Adolescent

Objective determination of pH thresholds in the analysis of 24 h ambulatory oesophageal pH monitoring.

In 24 h oesophageal pH monitoring, pH 4 is widely but arbitrarily used as the threshold between reflux and non-reflux pH values. The aim of the study was to define pH thresholds objectively, based on Gaussian curve fitting of pH frequency distributions. Single-channel 24 h oesophageal pH monitoring was performed in 26 healthy volunteers and 26 patients with pathological gastro-oesophageal reflux, and five-channel pH-metry was performed in 14 healthy volunteers and 14 patients. The calculated pH thresholds varied between healthy volunteers from 5 center dot 0 to 6 center dot 4 in the upright position and from 4 center dot 5 to 5 center dot 7 in the supine position, but were constant between different oesophageal recording sites. In 15 and nine patients (single-channel and five-channel pH-metry respectively), pH thresholds could not be determined at the distal oesophageal sites. However, the calculated pH thresholds in the proximal oesophagus were in the same range as in the control subjects. The authors conclude that the use of the conventional threshold of pH 4 leads to underestimation of the extent of gastrooesophageal reflux, but are reluctant to advocate the use of higher thresholds in clinical practice.

Adult

Colonic transit time in constipated children: does pediatric slow-transit constipation exist?

In adults, slow-transit constipation is a well-established form of constipation with abdominal pain and an empty rectum on examination. Marker studies in these patients, mainly women, show a markedly slowed transit time in all colonic segments. No studies in constipated children are available that assess the existence of slow-transit constipation. In a prospective study, a total of 94 referred constipated pediatric patients, 63 boys and 31 girls (median age, 8.0 years), underwent colonic-transit-time measurements using radioopaque markers to evaluate the pattern of transit. In addition, orocecal-transit-time measurements using the hydrogen breath (lactulose) test, anorectal manometry, and behavior studies using the Child Behavior Checklist were performed in all children. Based on the upper limit (mean + 2 SD) of total colonic transit time (CTT) in constipated children, we arbitrarily separated patients into two groups. Children with CTTs > 100 h were said to have pediatric slow-transit constipation (PSTC), while patients with CTTs < 100 h were said to have normal- or delayed-transit constipation (NDTC). In 94 constipated children, PSTC was found in 24 children; in 70 children, total CTT was < 100 h (NDTC). Total and segmental CTTs were significantly prolonged in PSTC (median, 189 h; range, 104.4-384) versus NDTC (median, 46.8 h; range, 3.6-99.4) hours. No significant differences were found in orocecal transit time. Significant clinical differences in children with PSTC versus those with NDTC existed regarding nighttime soiling (71 vs. 11%); daytime soiling episodes (14 vs. 7 each week, median), and nighttime soiling episodes (5 vs. 0 each week, median); absent urge to defecate (33 vs. 14%); and palpable abdominal (71 vs. 39%) and/or rectal (71 vs. 13%) masses. All manometric parameters were comparable in the two groups, except for a significantly lower maximal squeeze pressure with PSTC. Using the Child Behavior Checklist, both groups differed significantly from controls (26 and 43%, respectively), with no significant differences in behavior problems found between the NDTC and the PSTC groups. In conclusion, based on objective marker studies, our findings suggest the existence of pediatric slow-transit constipation. This entity can be recognized by clinical features, most importantly nighttime soiling and a palpable rectal mass. The probability of PSTC with both of these symptoms was 0.82; in the absence of these two symptoms, it was 0.07. It is of interest that CTTs in PSTC are comparable with CTTs in adults with slow-transit constipation, although the clinical presentation is clearly different. Further studies are needed to investigate whether the prolonged CTT characterizes a distinct form of constipation in children or is an epiphenomenon of the underlying constipation itself. The mechanisms responsible for the slow transit in these children and the appropriate therapeutic approach need to be studied.

Adolescent

Small intestinal motor abnormalities in patients with functional dyspepsia demonstrated by ambulatory manometry.

AIMS/METHODS: In 30 patients with functional dyspepsia and in 20 healthy volunteers, ambulatory duodenojejunal manometry was performed to examine the interdigestive and postprandial small intestinal motility patterns in relation to symptoms. RESULTS: In the fasting state, the number of migrating motor complex cycles mean (SEM) was significantly lower in patients, especially in patients with dysmotility-like dyspepsia, than in control subjects (3.8 (0.4), 2.6 (0.5), and 5.3 (0.7) cycles, respectively; p < 0.05), due to a longer duration of phase II. Non-propagated and retrogradely propagated phase III activity was more prevalent in patients than in control subjects (48% v 15%; p = 0.020). During phase II and after dinner no differences were found in contraction incidence, mean amplitude or motility index. However, 1 1/2 hours after completing breakfast the motility index was higher in patients at all three recording levels (p < 0.05). Burst activity was more prevalent in patients than in control subjects (22% v 6% of the subjects; p = 0.003). In 41% of the patients the symptom index was > 75%. CONCLUSIONS: These results suggest that small intestinal motor abnormalities, especially during fasting, participate in the pathogenesis of symptoms in patients with functional dyspepsia. Ambulatory manometry of the small intestine is a valuable tool to demonstrate these abnormalities in outpatients pursuing their daily activities.

Adult

Sensitization of the colonic response to novel stress after previous stressful experience.

Stressful life events may be important causative or precipitating factors for functional gastrointestinal disorders such as the irritable bowel syndrome in humans. In the rat, a single session of foot shocks is known to sensitize the behavioral and hormonal responses to subsequent stress, but intestinal responses have not been investigated. Rats were fitted with bipolar electrodes on proximal colon and exposed to a single session of foot shocks (10 x 6 s in 15 min; preshocked) or no shocks (control). Weight gain after foot shocks was identical to that in controls. Two weeks after foot shocks, basal colonic spike burst frequency did not differ from controls or from that recorded before shock treatment. Unlike controls, however, preshocked rats showed a significant increase in colonic spike burst frequency to a novel stressful challenge in the home cage, an electrified prod. Because the behavioral responses to this challenge did not differ, colonic hyperresponsiveness in preshocked rats may represent a form of stress-induced autonomic sensitization. The model should be a useful tool to study mechanisms and pharmacotherapeutic approaches of the gastrointestinal consequences of traumatic stress.

Animals

Abnormalities of antroduodenal motility in type I diabetes.

OBJECTIVE: In the present study, a recently developed manometric technique was used to study antroduodenal motility in ambulant type I diabetic subjects. RESEARCH DESIGN AND METHODS: In 12 patients with type I diabetes, antroduodenal manometry was performed for 20 h during the fasting period and the postprandial period after a standardized dinner and breakfast. All patients had evidence of cardiac autonomic neuropathy and complained of dyspeptic symptoms. During the manometric study, the blood glucose levels were frequently monitored and kept close to euglycemia in the diabetic patients. The results were compared with 12 healthy control subjects. RESULTS: The migrating motor complex cycles observed in the diabetic subjects were longer than in the control subjects, 118.9 +/- 46.0 vs. 87.0 +/- 21.6 min (P < 0.05). This increase was attributable to a prolonged phase II, 78.0 +/- 35.5 vs. 37.7 +/- 18.5 min (P < 0.05). In the diabetic subjects, antral phase III was seen significantly less than in the control subjects, 16.7 vs. 43.3% (P < 0.005). In 50% of the diabetic patients, total absence of antral phase III was observed-this phenomenon was not seen in the healthy control subjects. After dinner, the antral motility index was less in diabetic subjects compared with the healthy volunteers, indicating antral hypomotility (P < 0.01). Six diabetic patients showed abnormal duodenal activity such as early recurrence of phase III and bursts after dinner. No significant differences in antral motility index or in duodenal motility patterns were observed after breakfast. Six diabetic patients complained of dyspeptic symptoms after dinner, whereas none had dyspeptic symptoms after breakfast. In 67% of the patients, nausea was reported after an early phase III or a burst. CONCLUSIONS: This study shows that prolonged ambulatory antroduodenal manometry is a feasible technique in patients. Recording multiple migrating motor complexes showed that interdigestive motor abnormalities of the stomach and duodenum are common in diabetic patients. Furthermore, it shows the occurrence of antral hypomotility and abnormal duodenal motility patterns after a high-calorie meal, with dyspeptic symptoms in diabetic patients being related to the composition of the meal.

Adult

Novel 5-HT2-like receptor mediates neurogenic relaxation of the guinea-pig proximal colon.

The aim of the current investigation was to characterize the 5-HT receptors that mediate neurogenic relaxation of the guinea-pig proximal colon. After blockade of 5-HT2A, 5-HT3 and 5-HT4 receptor-mediated contractions, 5-hydroxytryptamine (5-HT) induced relaxations yielding a biphasic concentration-response curve. Other tryptamines were also agonists with the following rank order of potency: 5-HT > 5-carboxamidotryptamine = 5-methoxytryptamine > or = alpha-methyl-5-HT (partial agonist) > tryptamine (partial agonist). 5-Hydroxytryptophan, 2-methyl-5-HT and N-methyltryptamine were virtually inactive as agonists. The curve to 5-HT was not affected by pargyline, citalopram, phentolamine, or by the 5-HT4 receptor antagonists 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205-557) and (1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan+ ++-5-carboxylate (SB 204070). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), 5-methoxy-3[1,2,3,6-tetrahydroxypyridin-4-yl]-1H-indole (RU 24969), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), 1-(3-chlorophenyl)piperazine (mCPP), 1-(m-trifluoromethylphenyl)-piperazine (TFMPP), flesinoxan, sumatriptan and 6-chloro-2-(piperazinyl)-pyrazine (MK212) were inactive as 5-HT receptor agonists. The first phase of the curve to 5-HT was inhibited by: metergoline (pA2 = 8.8 +/- 0.3, against 5-methoxytryptamine 9.3 +/- 0.3), methysergide (non-surmountable), methiothepin (non-surmountable), spiroxatrine (non-surmountable), MK212 (non-surmountable), mesulergine (7.8 +/- 0.3), mCPP (7.1 +/- 0.1), mianserin (7.0 +/- 0.4), ritanserin (8.9 +/- 0.2), rauwolscine (7.0 +/- 0.2), yohimbine (6.2 +/- 0.2), 1-(1-naphthyl)-piperazine (7.7 +/- 0.2) and RU 24969 (6.4 +/- 0.1), but not by 1-(2-methoxyphenyl)4-[4-(2-phthalimidobtyl]-piperazine (NAN-190), spiperone, sumatriptan, 8-OH-DPAT and flesinoxan. It is suggested that the 5-HT receptor under study could be considered an unknown 5-HT2-like receptor.

Animals

Somal size and location within the ganglia for electrophysiologically identified myenteric neurons of the guinea pig ileum.

The main goal of the present study was to examine the possibility of electrophysiologically identifying the excitable enteric S and AH neurons by use of one single criterion. Intracellular recordings were made from 189 cells of 64 ganglia in isolated preparations of the myenteric plexus of the guinea pig distal ileum. The recordings were made under visual control of the cells by using Hoffman Modulation Contrast optics at high magnification (600x). From photomicrographs, the soma size and the location within the ganglion of the individual (unstained) cells were determined. The cells were classified into three types according to their electrical excitability and the shape of the action potential. Excitable cells were classified as AH cells (n = 84) if the action potential showed a shoulder on the falling phase, otherwise as S cells (n = 56). Cells in which no action potential could be evoked by current injection were classified as nonspiking (NS) cells (n = 49). The three classes of cells showed significant differences with respect to membrane potential, input resistance and fast synaptic input. The AH cells had significantly larger somata (P < 0.01) than the S cells. The NS cells were significantly smaller than the AH and S cells (P < 0.01). AH and S cells were found to be randomly located in the ganglia, whereas the NS cells clustered (P < 0.008) in close proximity to the onsets of internodal strands. We conclude that the shoulder of the action potential can be used as a single criterion to distinguish "on line" S and AH neurons unequivocally.

Action Potentials

5-HT-induced neurogenic relaxations of the guinea-pig proximal colon: investigation into the role of ATP and VIP in addition to nitric oxide.

In the guinea-pig proximal colon, 5-hydroxytryptamine (5-HT) relaxes the longitudinal muscle by stimulating neuronal 5-HT receptors, which induces the release of nitric oxide (NO). It was investigated whether the inhibitory neurotransmitters adenosine 5'-triphosphate (ATP) and/or vasoactive intestinal polypeptide (VIP) could be involved as well. Antagonists to block the contractile response to 5-HT via 5-HT2, 5-HT3 or 5-HT4 receptors were present throughout the experiments and methacholine was administered to precontract the strips. ATP, VIP and 5-HT induced concentration-dependent relaxations, in the case of 5-HT yielding a non-monophasic concentration-response curve. Tetrodotoxin (TTX; 300 nM), NG-nitro-L-arginine (L-NNA, 100 microM) and their combination did not inhibit the relaxations induced by VIP (up to 0.3 microM) or 0.3-3 microM ATP but reduced those by 10 microM ATP. Suramin (300 microM) strongly inhibited the relaxations to ATP and VIP. L-NNA and suramin also inhibited the relaxations to 5-HT. In the presence of L-NNA (100 microM), suramin did not significantly inhibit the relaxations to 5-HT. Suramin did not affect the relaxations to isoprenaline, nitroglycerin or exogenous NO (1 microM), demonstrating its specificity. Apamin (30 nM) inhibited both the relaxations to ATP (by 70-100%) and to 5-HT; relaxations to isoprenaline were partially inhibited, indicating a non-specific component in the inhibitory action of apamin. However, relaxations to exogenous VIP (up to 0.3 microM), NO (1 microM) and to nitroglycerin were not inhibited. In the presence of L-NNA (100 microM), apamin inhibited the relaxations to 5-HT only at 30 microM. alpha, beta-methylene-ATP (alpha, beta-Me-ATP; 100 microM) did not desensitize the responses to ATP. Reactive blue 2 affected the relaxations to isoprenaline at concentrations necessary to significantly inhibit the relaxations to ATP (i.e. from 10 microM onwards). Thus, it was not possible to test either alpha, beta-Me-ATP or reactive blue 2 against the relaxations to 5-HT. alpha-Chymotrypsin (0.015 mg.ml-1) and trypsin (0.005 mg.ml-1) almost abolished the relaxations to VIP, but did not affect those to isoprenaline and 5-HT. The VIP receptor antagonists [p-Cl-D-Phe6, Leu17]VIP (1 microM) and VIP10-28 (1 and 3 microM) did not affect the concentration-response curve to VIP and were hence not tested against 5-HT. Phosphoramidon (1 microM) had no effect on the relaxations to VIP or 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate

Compliance of the proximal stomach and dyspeptic symptoms in patients with type I diabetes mellitus.

UNLABELLED: In the present study the function of the proximal stomach and its role in eliciting dyspeptic symptoms were evaluated in patients with diabetes mellitus. Eight type I diabetics with cardiovascular autonomic neuropathy and dyspeptic symptoms, and 10 healthy volunteers were studied using an electronic barostat device connected to a intragastric bag. The intragastric bag was inflated and deflated by stepwise pressure increments, creating pressure-volume curves. During the experiment the blood glucose concentrations were maintained within the euglycemic range in the diabetics. The volume-pressure curves showed a larger volume during the pressure increase in the diabetics than in the controls (P < 0.01). This resulted in a significant difference in compliance (dV/dP), 57.2 +/- 4.2 ml/mm Hg in diabetics and 43.7 +/- 3.5 ml/MM Hg in controls (P < 0.014). The volume-pressure curves during deflation of the intragastric balloon were different from the curves during inflation, creating a hysteresis loop. The area between the inflation and deflation curves was 827 ml/mm Hg in diabetics and 627 ml/mm Hg in the controls (P = 0.21). Gastric distension induced more upper gastrointestinal sensations in the patients than in the volunteers: nausea (P < 0.002), bloating (P < 0.003), upper abdominal pain (P < 0.001). IN CONCLUSION: this study showed that the compliance of the proximal stomach is increased in diabetic patients with autonomic neuropathy and gastrointestinal symptoms. This abnormality, probably due to autonomic neuropathy, is associated with increased symptom generation during gastric distension.

Adult

Mechanisms of gastroesophageal reflux in ambulant healthy human subjects.

BACKGROUND/AIMS: Investigation of the motor events underlying gastroesophageal reflux has largely been confined to resting, recumbent subjects. The motor events associated with reflux during physical activity remain unknown. The aim of this study was to investigate the patterns of lower esophageal sphincter (LES) function underlying reflux in healthy subjects and the effect of exercise and physical activity on reflux mechanisms. METHODS: LES pressure was recorded with a perfused sleeve sensor in 10 healthy subjects; intraluminal transducers recorded pressure in the stomach, esophagus, and pharynx, and pH was recorded 5 cm above the LES. Signals were stored in a portable data-logger. Recordings were made for 24 hours, including moderate physical activity, periods of rest and sleep, standardized meals, and standardized exercise. RESULTS: Most reflux episodes (81 of 123; 66%) occurred in the 3 hours after food intake; only 2 episodes occurred during exercise. LES pressure was < or = 3 cm H2O in 79% of reflux episodes. Transient LES relaxation was the mechanism of reflux in 82% of episodes, irrespective of activity or body position, whereas swallow-related LES relaxations accounted for 13% and persistently absent LES pressure accounted for 1%. Straining occurred in only 20% of episodes. CONCLUSIONS: In ambulant healthy subjects, accurate continuous recording of LES function is possible, reflux usually occurs during transient LES relaxations, and straining is not a major factor in the induction of reflux.

Acids

Symptom perception in gastroesophageal reflux disease is dependent on spatiotemporal reflux characteristics.

BACKGROUND/AIMS: The mechanisms responsible for the development of symptoms in gastroesophageal reflux disease (GERD) are poorly understood. The aims of this study were to identify differences in spatiotemporal reflux characteristics (proximal extent and duration of reflux episodes, ascending velocity of the refluxate) between symptomatic and asymptomatic reflux episodes and to assess the influence of different pH sensor positions on the yield of symptom analysis. METHODS: Esophageal pH was measured for 24 hours at 3, 6, 9, 12, and 15 cm above the lower esophageal sphincter (LES) in 18 symptomatic patients with GERD, and spatiotemporal reflux characteristics were assessed for symptomatic and asymptomatic reflux episodes. Additionally, the symptom-association probability (SAP) was calculated for each esophageal level. RESULTS: The median episode duration (at 3 cm above the LES) was longer and the proximal extent was higher in symptomatic than in asymptomatic reflux episodes (P = 0.006 and P = 0.01). The ascending velocity of the refluxate was not significantly different. The SAP decreased significantly (P < 0.05) from distal to proximal, but no significant differences were found between distal and proximal esophageal levels for the proportion of patients with positive (> 95%) SAP values. CONCLUSIONS: The perception of reflux symptoms depends on the duration of acid-exposure episodes and on the proximal extent of the refluxate. Small changes in pH-sensor position do not significantly influence the yield of symptom analysis.

Adult

Effects of novelty and conditioned fear on small intestinal and colonic motility and behaviour in the rat.

Novelty and conditioned fear were used to investigate the effects of psychological stress on fasting small intestinal and colonic myoelectric activity and their relation with behaviour in freely moving rats fitted with bipolar electrodes on proximal jejunum and colon. Rats in both novelty and conditioned fear groups spent a 15 min session in a novel box, where only rats in the fear group received unescapable, repeated foot shock (10 x 6 s, 0.5 mA). Behaviour in groups reexposed to the box on day 1 or day 7 indicated a profound difference in emotional state. Conditioned fear rats remained largely immobile, while novelty rats displayed active exploratory behaviour. Behaviour during conditioned fear did not differ significantly between rats reexposed to the box either 1 or 7 days after foot shock, while novelty animals appeared more aroused on day 7. Conditioned fear on day 1 caused a significant increase in colonic spike burst frequency compared to basal values in the home cage. A smaller but significant increase was found in novelty rats. In groups tested after 7 days, both novelty and conditioned fear resulted in small increases in colonic burst frequency that did not differ significantly from each other. No effects were found on the incidence of the fasting jejunal Migrating Motility Complex. Defecation was see only in conditioned fear rats, but did not differ quantitatively between day 1 and day 7. We conclude that, in the rat, colonic myoelectric spike burst activity is highly responsive to psychological stress, while the fasting pattern of small intestinal activity is more resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals