A. A. M. Masclee

Motor and sensory function of the proximal stomach in reflux disease and after laparoscopic Nissen fundoplication

ObjectiveAfter Nissen fundoplication, dyspeptic symptoms such as fullness and early satiety develop in >30% of patients. These symptoms may result from alterations in proximal gastric motor and sensory function.MethodsWe have evaluated proximal gastric motor and sensory function using an electronic barostat in 12 patients after successful laparoscopic Nissen fundoplications (median follow-up; 12 months). Twelve age- and gender-matched patients with severe gastroesophageal reflux disease (GERD) and 12 healthy volunteers served as controls. Studies were performed in the fasting state and after meal ingestion. Gastric emptying tests were performed in all patients. Vagus nerve integrity was measured by the response of pancreatic polypeptide (PP) to insulin hypoglycemia.ResultsMinimal distending pressure and proximal gastric compliance were not significantly different between post-Nissen patients, GERD patients, and healthy controls. Postprandial relaxation of the stomach, however, was significantly (p < 0.05) reduced post-Nissen (267 ± 34 ml), compared with controls (400 ± 30 ml) and GERD (448 ± 30 ml). Postprandial relaxation was significantly (p < 0.01) prolonged in GERD patients. Postprandial relaxation of the stomach correlated with gastric emptying of solids (r = 0.62; p= 0.01). Gastric emptying of solids became significantly (p < 0.05) faster after fundoplication. Postprandial fullness was significantly (p < 0.05) increased in the operated patients.ConclusionsPost-Nissen patients have a significantly reduced postprandial gastric relaxation and significantly accelerated gastric emptying, which may explain postoperative dyspeptic symptoms. The abnormalities result from fundoplication and not from vagus nerve injury or reflux per se, because in reflux patients gastric relaxation and gastric emptying are prolonged.

Symptom Severity but Not Psychopathology Predicts Visceral Hypersensitivity in Irritable Bowel Syndrome

BACKGROUND & AIMSnVisceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS), but the relationship with clinical symptoms and psychological factors has not been fully established. We aimed to (1) evaluate these variables in a large cohort of IBS patients, recruited from both hospital and general practice, and in healthy controls and (2) assess which of these factors predicts the occurrence of visceral hypersensitivity in IBS.nnnMETHODSnRectal compliance and perception (intensity, perception thresholds; visual analogue scale, 0-100 mm) were assessed by a rectal barostat study (ramp distention) in 101 IBS patients and 40 healthy volunteers. IBS symptom severity was scored by using a 14-day 5-item diary. Anxiety, depression, somatization, vigilance, pain coping, dysfunctional cognitions, psychoneuroticism, and quality of life were assessed with psychometric questionnaires.nnnRESULTSnRectal compliance was significantly reduced in IBS patients compared with controls (P < .01), as were thresholds for pain (27 +/- 15 vs 35 +/- 8 mm Hg; P < .01) and urge (P < .05). Levels of anxiety, depression, neuroticism, somatization, and dysfunctional cognitions were significantly increased in IBS patients versus controls, whereas pain coping and quality of life were significantly worse. Hypersensitivity to rectal distention occurred in 33% of patients and was associated with increased symptom severity (P = .016), but not with demographic characteristics or psychological disturbances.nnnCONCLUSIONSnHypersensitivity to balloon distention occurs in 33% of IBS patients and is predicted by symptom severity but not by psychological or demographic characteristics.

Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome

Abstract u2003 Irritable bowel syndrome (IBS) consists of various subtypes. It is not known whether these subtypes share a common pathophysiology. Evaluation of motor and sensory function of the rectum using a barostat may help to explore a common pathophysiological background or differences in pathophysiology in subtypes of IBS. We have evaluated compliance, tone and sensitivity of the rectum, in both fasting state and postprandially, using a computerized barostat in 15 patients with diarrhoea‐predominant IBS (IBS‐D), 14 patients with constipation‐predominant IBS (IBS‐C) and compared the results with those obtained in 12 healthy controls. Rectal compliance as calculated over the steep part of the pressure–volume curve (17–23u2003mmHg) was decreased in both IBS groups (IBS‐D 8.0u2003±u20031.4u2003mLu2003mmHg−1; IBS‐C 5.6u2003±u20031.1u2003mLu2003mmHg−1) compared with controls (24.7u2003± 3.5u2003mLu2003mmHg−1). The perception of urge was increased only in IBS‐D patients, whereas pain perception was significantly increased in both IBS groups. Spontaneous adaptive relaxation was decreased in IBS‐D patients. Postprandially, rectal volume decreased significantly in the controls and in IBS‐D patients, but not in IBS‐C patients. In conclusion, both rectal motor and sensory characteristics are different between IBS‐D and IBS‐C patients. Therefore, testing of rectal visceroperception, adaptive relaxation and the rectal response to a meal may help distinguish groups of patients with different subtypes of irritable bowel syndrome.

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

Objective:Barretts esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barretts esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barretts patients than in patients with moderate or severe endoscopic esophagitis.Methods:Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy ≤3 months before pH-metry. Included were 51 patients with Barretts esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects.Results:Patients with Barretts esophagus had significantly increased acid reflux time (p < 0.01–0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01–0.05) reduced in patients with Barretts esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis.Conclusion:Although acid reflux is increased in patients with Barretts esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barretts esophagus.

Effects of hyperglycemia and hyperinsulinemia on satiety in humans

Hyperglycemia may influence satiety. One mechanism by which glucose could influence food intake is hyperinsulinemia. Therefore, we investigated the short-term effects of acute hyperglycemia and euglycemic hyperinsulinemia on satiety. Six healthy volunteers (aged 20 to 26 years) were studied for 240 minutes on three separate occasions in random order during (1) intravenous (i.v.) saline (control), (2) acute hyperglycemic hyperinsulinemia (HG) with plasma glucose at 15 mmol/L, and (3) euglycemic hyperinsulinemia (HI) with plasma insulin at 80 mU/L and glucose at 4 to 5 mmol/L. Subjective criteria for appetite like the wish to eat, prospective feeding intentions (How much food do you think you can eat?), and feelings of hunger and fullness were scored on a 100-mm visual analog scale (VAS) at 30-minute intervals. Appetite was also measured every 60 minutes with the use of a food selection list (FSL). Appetite (prospective feeding intentions, feelings of hunger, and the wish to eat) gradually increased over basal levels during control conditions and HI. In contrast, prospective feeding intentions and feelings of hunger gradually decreased during HG and were significantly (P < .05) reduced versus basal and control levels during the last hour of the experiment. The wish to eat followed the same pattern. Feelings of fullness did not significantly change in all three experiments. Total food selection was not significantly decreased during HG, but the preference for fat-rich or carbohydrate-rich items tended to be reduced. The study suggests that in humans hyperglycemia induces satiety. This effect seems not to be mediated by insulin, since HI had no effect on appetite. However, a potentiating effect of endogenous insulin on the satiating effect of high blood glucose levels cannot be excluded.

Provocation of transient lower esophageal sphincter relaxations by gastric distension with air

OBJECTIVES:Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism permitting not only gastroesophageal reflux but also venting of air from the stomach. Triggering of TLESRs is provoked by gastric distension. Antireflux surgery is associated with impaired ability to belch. It is not known whether a reduced capacity to belch results from postoperative reduction in TLESRs.METHODS:We studied the occurrence of TLESRs, common cavities (indicator for gas gastroesophageal reflux), and belching after standardized acute gastric distension by air insufflation (750 ml). Control subjects (n = 10), patients with gastroesophageal reflux disease (GERD) (n = 22), and patients after fundoplication (n = 24) were studied. LES and esophageal motilities were recorded with perfusion manometry.RESULTS:Gastric distension with air significantly (p < 0.05) increased TLESR frequency in controls (1.6 ± 0.3 to 3.5 ± 1.0 per 20 min), GERD patients (1.2 ± 0.3 to 3.1 ± 0.5 per 20 min), and patients after fundoplication (0.5 ± 0.1 to 1.8 ± 0.6 per 20 min). Postfundoplication the number of TLESRs was significantly reduced (p < 0.05) both under fasting conditions and after air insufflation. The number of common cavities and belches after gastric air distension also was significantly reduced (p < 0.05) after fundoplication: 2.3 ± 0.6 versus 4.7 ± 0.4 in controls and 4.1 ± 0.4 in GERD patients. About half of the common cavities occurred during TLESRs, and half during other mechanisms. An impaired ability to belch in daily life correlated with an impaired belching response during the test. An impaired ability to belch occurred only in patients with complete fundoplication and not in patients with partial fundoplication and was associated with a reduced number of common cavities after gastric air insufflation.CONCLUSIONS:Short-lasting gastric air distension 1) provokes TLESRs but does not differentiate GERD patients from controls, 2) reveals impaired belching capacity in patients after complete fundoplication, and 3) shows that common cavities do not exclusively occur during TLESRs.

Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans

BACKGROUND/AIMSnAcute hyperglycemia inhibits gallbladder contraction. In non-diabetic subjects this inhibitory effect may result from endogenous hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated gallbladder motility.nnnMETHODSnGallbladder volume (ultrasonography) and duodenal bilirubin output were studied simultaneously in nine healthy volunteers (age 20-52 years) on 3 separate occasions in random order during: (a) saline infusion (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by another 60 min at 0.5 IDU x kg(-1) x h(-1).nnnRESULTSnHI and HG significantly (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal gallbladder volume did not change. At the low dose cholecystokinin, gallbladder emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced compared to control (61+/-4%). The inhibitory effect of HG was significantly (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin output was observed with the high dose of cholecystokinin.nnnCONCLUSIONSnIn healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose cholecystokinin. These results suggest that insulin is involved in the inhibitory effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder motility.

Octreotide therapy in dumping syndrome: Analysis of long-term results

Octreotide therapy is effective in controlling severe dumping symptoms during short‐term follow‐up but little is known about long‐term results.

Effect of CCK on proximal gastric motor function in humans

We have studied the effect of CCK on proximal gastric motor function in humans. Seven healthy volunteers participated in three experiments performed in random order during continuous intravenous infusion of 1) saline (control), 2) 0.5 IDU ⋅ kg-1 ⋅ h-1CCK, and 3) 1.0 IDU ⋅ kg-1 ⋅ h-1CCK. Proximal gastric mechanics were measured by an electronic barostat, and abdominal symptoms were scored by visual analog scales. Infusion of 0.5 and 1.0 IDU ⋅ kg-1 ⋅ h-1CCK resulted in plasma CCK levels (RIA) in the postprandial range. CCK induced gastric relaxation; at 2 mmHg above intra-abdominal pressure the intragastric volume during 1.0 IDU ⋅ kg-1 ⋅ h-1CCK was significantly increased over saline (363 ± 44 vs. 195 ± 34 ml; P < 0.01) but not during 0.5 IDU ⋅ kg-1 ⋅ h-1CCK (195 ± 14 ml; not significant). During both isovolumetric and isobaric distensions, 1.0 IDU ⋅ kg-1 ⋅ h-1CCK significantly ( P < 0.05) increased proximal gastric compliance compared with saline. However, 0.5 IDU ⋅ kg-1 ⋅ h-1CCK had no significant effect on gastric compliance. During volume distensions, but not during fixed pressure distensions, 1.0 IDU ⋅ kg-1 ⋅ h-1CCK significantly ( P < 0.05) reduced visceral perception. These results suggest that in humans CCK may have a physiological role in regulating proximal gastric mechanics.We have studied the effect of CCK on proximal gastric motor function in humans. Seven healthy volunteers participated in three experiments performed in random order during continuous intravenous infusion of 1) saline (control), 2) 0.5 IDU.kg-1.h-1 CCK, and 3) 1.0 IDU.kg-1.h-1 CCK. Proximal gastric mechanics were measured by an electronic barostat, and abdominal symptoms were scored by visual analog scales. Infusion of 0.5 and 1.0 IDU.kg-1.h-1 CCK resulted in plasma CCK levels (RIA) in the postprandial range. CCK induced gastric relaxation; at 2 mmHg above intra-abdominal pressure the intragastric volume during 1.0 IDU.kg-1.h-1 CCK was significantly increased over saline (363 +/- 44 vs. 195 +/- 34 ml; P < 0.01) but not during 0.5 IDU.kg-1.h-1 CCK (195 +/- 14 ml; not significant). During both isovolumetric and isobaric distensions, 1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) increased proximal gastric compliance compared with saline. However, 0.5 IDU.kg-1.h-1 CCK had no significant effect on gastric compliance. During volume distensions, but not during fixed pressure distensions, 1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) reduced visceral perception. These results suggest that in humans CCK may have a physiological role in regulating proximal gastric mechanics.

Effect of gastrin on antroduodenal motility: role of intraluminal acidity

The effect of gastrin on the migrating motility complex (MMC) was studied in seven healthy subjects. It was hypothesized that a potential effect of gastrin on the MMC may result from intraluminal acidification through increased gastric acid secretion. Therefore, antroduodenal manometry and intraluminal acidity were recorded simultaneously. The effect of gastric acid inhibition, with and without administration of gastrin, on antroduodenal motility and intraluminal acidity was also evaluated and compared with saline infusion (control). Continuous infusion of gastrin-17 (20 pmol ⋅ kg-1 ⋅ h-1) increased intragastric and intraduodenal acidity and suppressed phase II and phase III motor activity in both antrum and duodenum. Concomitant gastric acid inhibition with intravenous famotidine, as demonstrated by intragastric neutralization of pH, completely antagonized the effect of gastrin on the MMC. In fact, famotidine infusion, both with and without administration of gastrin, significantly shortened MMC cycle length. It is concluded that the effect of gastrin on interdigestive antroduodenal motility results from increased intraluminal acidity.The effect of gastrin on the migrating motility complex (MMC) was studied in seven healthy subjects. It was hypothesized that a potential effect of gastrin on the MMC may result from intraluminal acidification through increased gastric acid secretion. Therefore, antroduodenal manometry and intraluminal acidity were recorded simultaneously. The effect of gastric acid inhibition, with and without administration of gastrin, on antroduodenal motility and intraluminal acidity was also evaluated and compared with saline infusion (control). Continuous infusion of gastrin-17 (20 pmol. kg-1. h-1) increased intragastric and intraduodenal acidity and suppressed phase II and phase III motor activity in both antrum and duodenum. Concomitant gastric acid inhibition with intravenous famotidine, as demonstrated by intragastric neutralization of pH, completely antagonized the effect of gastrin on the MMC. In fact, famotidine infusion, both with and without administration of gastrin, significantly shortened MMC cycle length. It is concluded that the effect of gastrin on interdigestive antroduodenal motility results from increased intraluminal acidity.