Melvin Samsom

Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients

BACKGROUND & AIMS Although acid is likely to play a role in the genesis of symptoms in dyspeptic patients, most studies have failed to show an increase in gastric acid secretion. The aim of this study was to investigate clearance of acid from the duodenum and its relationship with symptoms in patients with functional dyspepsia. METHODS Twelve patients and 10 healthy volunteers were studied using an assembly allowing recording of pressures and pH. Acid and saline were infused intraduodenally during phase II and postprandially. Sensations were scored before and 1 and 5 minutes after each infusion. RESULTS After acid infusion in the fasting period, a greater increase in acidity in the duodenal bulb (P = 0.007) and fewer duodenal pressure waves (P = 0.002) were observed in dyspeptic patients. No significant differences in the time with pH < 4 and duodenal motor activity were observed in the postprandial period. Acid infusion reproducibly increased the sensation of nausea in patients (P < 0.001) but not in the controls. Saline infusion had no effect on upper gastrointestinal sensations. CONCLUSIONS In fasting dyspeptic patients, clearance of exogenous acid from the duodenal bulb and duodenal motor activity are decreased. The duodenal bulb in dyspeptic patients is hypersensitive to acid infusion, which induces the nausea.

Hyperglycemia induces abnormalities of gastric myoelectrical activity in patients with type I diabetes mellitus.

BACKGROUND/AIMS Blood glucose concentration has been shown to be an important factor in gastric motility. However, the effect of hyperglycemia on gastric myoelectrical activity has not yet been studied in patients with diabetes. METHODS Surface electrogastrography was performed in eight patients with type I diabetes mellitus under normoglycemic and hyperglycemic conditions (glucose clamp technique) and in eight normoglycemic control subjects. RESULTS In the early postprandial state, the frequency of the normal pacemaker rhythm tended to be higher during hyperglycemia than during normoglycemia (3.10 +/- 0.27 vs. 2.92 +/- 0.19 cycle/min; P = 0.061). The frequency decrease that occurs immediately after a meal was found less frequently during hyperglycemia (in 25% vs. 75% of the patients; P = 0.046). Higher harmonics of the 3-cycle/min component, indicating an electrogastrographic waveform change, were found less often during hyperglycemia (in 13% vs. 63% of the patients; P = 0.039). Dysrhythmias (in particular, tachygastrias) were more prevalent during hyperglycemia (40.6% vs. 6.5% of the time; P = 0.028). No differences were found between normoglycemic patients and control subjects. CONCLUSIONS This study has shown that hyperglycemia is an important factor in the generation of gastric myoelectrical disturbances and tachygastrias in particular.

Gastroesophageal Pressure Gradients in Gastroesophageal Reflux Disease: Relations With Hiatal Hernia, Body Mass Index, and Esophageal Acid Exposure

OBJECTIVES:The roles of intragastric pressure (IGP), intraesophageal pressure (IEP), gastroesophageal pressure gradient (GEPG), and body mass index (BMI) in the pathophysiology of gastroesophageal reflux disease (GERD) and hiatal hernia (HH) are only partly understood.METHODS:In total, 149 GERD patients underwent stationary esophageal manometry, 24-h pH-metry, and endoscopy.RESULTS:One hundred three patients had HH. Linear regression analysis showed that each kilogram per square meter of BMI caused a 0.047-kPa increase in inspiratory IGP (95% confidence interval [CI] 0.026–0.067) and a 0.031-kPa increase in inspiratory GEPG (95% CI 0.007–0.055). Each kilogram per square meter of BMI caused expiratory IGP to increase with 0.043 kPa (95% CI 0.025–0.060) and expiratory IEP with 0.052 kPa (95% CI 0.027–0.077). Each added year of age caused inspiratory IEP to decrease by 0.008 kPa (95% CI –0.015–−0.001) and inspiratory GEPG to increase by 0.008 kPa (95% CI 0.000–0.015). In binary logistic regression analysis, HH was predicted by inspiratory and expiratory IGP (odds ratio [OR] 2.93 and 2.62, respectively), inspiratory and expiratory GEPG (OR 3.19 and 2.68, respectively), and BMI (OR 1.72/5 kg/m2). In linear regression analysis, HH caused an average 5.09% increase in supine acid exposure (95% CI 0.96–9.22) and an average 3.46% increase in total acid exposure (95% CI 0.82–6.09). Each added year of age caused an average 0.10% increase in upright acid exposure and a 0.09% increase in total acid exposure (95% CI 0.00–0.20 and 0.00–0.18).CONCLUSIONS:BMI predicts IGP, inspiratory GEPG, and expiratory IEP. Age predicts inspiratory IEP and GEPG. Presence of HH is predicted by IGP, GEPG, and BMI. GEPG is not associated with acid exposure.

Gastrointestinal motility and gastric tube feeding in mechanically ventilated patients

OBJECTIVE To determine the fasted and fed gastrointestinal motility characteristics that are possibly responsible for gastric retention in mechanically ventilated patients. DESIGN Prospective, case series. SETTING Surgical intensive care unit of a university hospital. PATIENTS Seven patients who required mechanical ventilation for thoracic or combined thoracic-neurologic injuries and nine healthy volunteers. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Antroduodenal manometry was performed during fasting and gastric feeding with a polymeric diet in patients during mechanical ventilation, weaning, and after detubation. Gastric retention volumes were determined during gastric tube feeding. Motility data were compared with recordings from nine healthy volunteers. During the fasting state, under sedation and morphine, the migrating motor complex in patients was significantly (p < .001) shortened: median 32.0 vs. 101.0 mins in healthy volunteers. During gastric tube feeding, the motility pattern did not convert to a normal postprandial pattern until morphine was discontinued. An interdigestive or mixed interdigestive-postprandial pattern was seen during gastric tube feeding in most patients during morphine administration. Most (94%) of the activity fronts during gastric feeding started in the duodenum. Gastric retention percentages during gastric tube feeding were negatively correlated (r2=.44; p < .01) with antral motor activity. CONCLUSIONS These data suggest that morphine administration affects antroduodenal motility in mechanically ventilated patients. The gastrointestinal motor pattern involved in impaired gastric emptying in morphine-treated patients is characterized by antral hypomotility and persisting duodenal activity fronts during continuous intragastric feeding. The observed motility patterns suggest that early administration of enteral feeding might be more effective into the duodenum or jejunum than into the stomach of mechanically ventilated patients.

Multichannel intraluminal impedance monitoring in the evaluation of patients with non-obstructive Dysphagia

BACKGROUND:Non-obstructive dysphagia (NOD) often poses diagnostic problems. The aim of this study was to evaluate the value of the addition of multichannel intraluminal impedance (MII) recording to esophageal manometry in the work-up of patients with NOD.METHODS:A total of 40 consecutive patients with NOD underwent combined esophageal MII recording and perfusion manometry. Ten liquid and 10 viscous boluses were tested in each patient. Values for bolus presence time (BPT) at each of the four recording sites and total bolus transit time (TBTT) were calculated. Bolus transit (BT) was considered to be normal when BPT at all sites and TBTT were within the normal limits defined in 42 healthy subjects. Patients were judged to have normal transit if ≥80% of liquid and ≥70% of viscous swallows showed normal transit.RESULTS:The following manometric diagnoses were made: normal motility (20), ineffective esophageal motility (IEM) (13), diffuse esophageal spasm (DES) (4), and achalasia (3). Abnormal transit for liquid and/or viscous boluses was found in 35.3% of patients with normal motility, in 66.7% of DES patients, and in 100% of achalasia patients. In patients with achalasia quantification of BT was often made impossible by low initial impedance baseline. Two IEM patients (15.4%) showed normal liquid and viscous transit. Swallows showing normal transit had significantly longer duration of LES relaxation in patients with normal manometry and IEM (p < 0.05).CONCLUSIONS:MII recording identifies esophageal function abnormalities in NOD patients with normal manometry, IEM, and DES. The MII technique seems to be less suitable for the most severe end of the dysphagia spectrum like achalasia.

Impact of delayed gastric emptying on the outcome of antireflux surgery.

ObjectiveTo study the effect of Nissen fundoplication on the pattern of gastric emptying and intragastric distribution of symptoms in patients with normal and delayed gastric emptying before surgery, especially in those with delayed emptying before surgery. Summary Background DataGastroesophageal reflux disease is associated with delayed gastric emptying and dyspeptic symptoms in approximately 40% of the patients. After Nissen fundoplication, dyspeptic symptoms are also not uncommon. MethodsThirty-six patients (26 men, 10 women, mean age 43.1) were studied before and 3 months after Nissen fundoplication. Gastric emptying (dual-isotope, expressed in lag phase, emptying rate, T50, and intragastric distribution) was not included in the decision for surgery. Reflux-related and dyspeptic symptoms were scored before and at 3, 6, and 12 months after surgery. ResultsTwenty-six patients had normal and 10 had delayed gastric emptying before surgery. Nissen fundoplication on average enhanced gastric emptying for solids in both subgroups by a combination of a decrease in mean lag phase, emptying rate, and T50. The preoperative difference in intragastric distribution between patients with and without delayed gastric emptying was abolished by fundoplication. Patients with normal gastric emptying before surgery showed an increase in early postprandial satiety; in those with delayed emptying, this was not observed. A correlation was found between preoperative T50 for liquid gastric emptying and postoperative nausea at 3 months in patients with normal gastric emptying. In patients with delayed emptying, preoperative correlations between lag phase for liquids and nausea respectively early satiety were significant, as well as for T50 for liquids and vomiting. ConclusionsNissen fundoplication equalizes the preoperative difference in intragastric distribution and accelerates gastric emptying without an effect on symptoms in patients with preexisting delayed gastric emptying, but with an increase in early satiety in patients with normal gastric emptying. Delayed gastric emptying is not a contraindication for antireflux surgery.

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 < 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.

SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine.

Colorectal visceral hypersensitivity has been demonstrated in a subset of irritable bowel syndrome (IBS) patients. Serine protease and serotonergic signaling modulate gastrointestinal visceral sensitivity. We evaluated whether altered mucosal serine protease and serotonergic pathway components are related to rectal visceral hypersensitivity in IBS patients. Colorectal mucosal biopsies of 23 IBS patients and 15 controls were collected. Gene transcripts of protease-activated receptor (PAR)-2, trypsinogen IV, tryptophan hydroxylase (TPH)-1, and serotonin reuptake transporter (SERT) were quantified using real-time polymerase chain reaction. Substance P and 5-HT contents were measured by ELISA. The number of enterochromaffin cells, mast cells, and intraepithelial lymphocytes was determined using immunohistochemistry. Rectal visceral sensitivity was determined in IBS patients using barostat programmed for phasic ascending distension. Rectal hypersensitivity (+) and (-) IBS patients showed lower TPH-1 and SERT mRNA levels in the rectum compared with controls (P ≤ 0.05). Rectal hypersensitivity (+) IBS patients (n = 12) showed lower TPH-1 mRNA level in the sigmoid compared with controls (P = 0.015). No significant differences were observed in PAR-2 and trypsinogen IV expression between controls and IBS patients. Rectal substance P content was increased in IBS patients compared with controls (P = 0.045). No significant differences were found in transcript levels, cell counts, and substance P and 5-HT contents between rectal hypersensitivity (+) and (-) IBS patients. In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients.

Abnormal Gastric and Small Intestinal Motor Function in Diabetes mellitus

It is now well recognized that the prevalence of delayed gastric emptying in both insulin-dependent as well as noninsulin-dependent diabetes mellitus is high. Recently performed studies have shown that motor disorders of several parts of the upper gastrointestinal tract contribute to this delay in gastric emptying. Traditionally, disordered motility in diabetes mellitus has been attributed to irreversible autonomic nerve damage. However, recent observations indicate that hyperglycemia causes a reversible impairment of motility in various regions of the gastrointestinal tract. Upper gastrointestinal symptoms are highly prevalent in diabetes mellitus. These dyspeptic symptoms are not only induced by delayed gastric emptying, but altered visceroperception also plays a role in the genesis of dyspeptic symptoms. There is increasing evidence that impaired gastric emptying influences glycemia control, but the clinical consequences of these observations need further investigation. At present dyspeptic symptoms form the rationale for the treatment of delayed gastric emptying with prokinetic drugs.

Interdigestive gallbladder emptying, antroduodenal motility, and motilin release patterns are altered in cholesterol gallstone patients

The role of interdigestive gallbladder emptying in gallstone formation is unknown. In fasting healthy subjects, gallbladder emptying is associated with antral phase III of the migrating motor complex (MMC) and high plasma motilin. Therefore, gallbladder volumes and motilin levels were measured during 13 MMC cycles in 10 cholesterol gallstone patients and compared with 20 MMC cycles in 10 healthy subjects. MMC cycle length was longer in gallstone patients than in healthy subjects (158.2 ± 17.0 vs 105.5 ± 10.4 min, respectively; P < 0.05), due to longer phase I (39.8 ± 5.7 vs 17.2 ± 3.7 min, respectively; P < 0.05). In contrast to healthy subjects, gallstone patients had no significant fluctuations of gallbladder volume during the MMC cycle, and motilin concentrations were not different in MMC cycles with phase III originating in antrum or duodenum. During MMC cycles with phase III originating in the duodenum, motilin levels were twice as high in gallstone patients as in healthy subjects (P < 0.002). In conclusion, cholesterol gallstone patients have an abnormal MMC and motilin release pattern. Their interdigestive gallbladder emptying is reduced and dissociated from the MMC. These disturbances may contribute to gallstone formation.