Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-antagonist ondansetron

In an outbreak of waterborne giardiasis where 1300 subjects were diagnosed, with Giardia lamblia, 139 continued to have abdominal symptoms of whom two of three had negative stool culture and microscopy. These were considered to have a postinfectious functional gastrointestinal disorder. We investigated visceral hypersensitivity in patients with persisting abdominal symptoms after Giardia infection and assessed the effect of 5HT(3)-antagonist ondansetron. Twenty-two patients with Giardia negative stools and 19 controls were included. A subset of patients (n = 15) had both irritable bowel syndrome (IBS) and functional dyspepsia (FD). All subjects underwent a satiety test with a soup combined with three-dimensional ultrasound. Fifteen of 22 patients underwent double-blind, randomized, placebo-controlled study with the 5-HT(3) antagonist ondansetron given orally. Drinking capacity was lower in patients than in controls (P < 0.01) and gastric emptying was reduced (P < 0.05). Patients had more symptoms both fasting and postprandially (P < 0.001) compared to controls. Ondansetron had no effect on these parameters except from less nausea postprandially (P < 0.05). In conclusion, patients with Giardia-induced gastrointestinal symptoms developed both IBS and FD. They exhibited gastric hypersensitivity with lower drinking capacity and delayed gastric emptying. The 5-HT(3) antagonist ondansetron did not improve drinking capacity, gastric emptying or symptoms except nausea.     

Acotiamide (Z‐338) as a possible candidate for the treatment of functional dyspepsia

Acotiamide hydrochloride is a novel upper gastrointestinal (GI) motility modulator and stress regulator currently being developed for the treatment of functional dyspepsia (FD). The mechanism underlying the enhancement of GI motility by this agent has been proposed to be based on its muscarinic antagonism and inhibitory effects on acetylcholinesterase activity. Pathophysiological studies showed that acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress‐induced model, but did not affect both normal gastric emptying and feeding in intact animals, indicating that acotiamide exerted effects only on the impaired gastric emptying and feeding behavior. According to the clinical pilot study in Europe, acotiamide, at the dose of 100 mg t.i.d., showed to improve the symptoms and quality of life of patients with FD, indicating the need for larger scale symptomatic studies on the efficacy of acotiamide in patients with FD. The recent phase II studies conducted in Japan presented in this issue of the journal also confirmed that acotiamide, at the optimal dose of 100 mg, has potential therapeutic efficacy, especially for meal‐related FD symptoms. Although a phase III study is on going, acotiamide is now expected as a novel treatment option for FD.     

Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force

The objective of this document is to present the consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of electrogastrography (EGG). EGG is a non-invasive means of recording human gastric myoelectrical activity or slow waves from cutaneous leads placed over the stomach. In healthy volunteers, EGG tracings exhibit sinusoidal waveforms with a predominant frequency of 3 cycles per minute (cpm). Clinical studies have shown good correlation of these cutaneous recordings with those acquired from serosally implanted electrodes. The amplitude of the EGG waveform increases with ingestion of caloric or non-caloric meals. Some patients with nausea, vomiting, or other dyspeptic symptoms exhibit EGG rhythm disturbances or blunting of meal-evoked EGG signal amplitude increases. These abnormalities correlate to some degree with delayed gastric emptying of solids. In selected patients, EGG may be complementary to gastric emptying testing. To date, no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.     

Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease

To characterize proximal and distal stomach emptying in functional dyspepsia (FD) and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of upper gastrointestinal symptoms and were divided into three groups: FD (n = 25), GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric retention were determined scintigraphically and compared with normal controls. Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD + GORD (55%). Greater proximal gastric retention was observed after meal ingestion in GORD compared to FD. Greater distal gastric retention was observed in FD and FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety, distention and regurgitation were associated with proximal gastric retention whereas there was no symptom associated with distal gastric retention. Multiple regression demonstrated total gastric retention at 30 min and 1 h was positively correlated with regurgitation whereas early proximal gastric retention was positively correlated with regurgitation and negatively correlated with nausea. Selective abnormalities of proximal and distal stomach emptying were demonstrated in GORD and FD. GORD and FD symptoms were associated with proximal gastric retention suggesting that proximal stomach motor function may be important in the pathogenesis of symptoms associated with these disorders.     

Association between changes in symptoms and gastric emptying in gastroparetic patients treated with gastric electrical stimulation

Abstract  To investigate whether there is an association between gastric emptying rate and symptom improvement in gastroparetic patients treated with gastric electrical stimulation (GES), we retrospectively reviewed 63 gastroparetic patients who received GES therapy for at least 1 year. Patient characteristics, seven upper gastrointestinal (GI) symptoms and 4-h standardized gastric emptying test (GET) were evaluated at baseline and at 1 year of GES. All symptoms were significantly reduced ( P  <   0.001). Mean gastric retention was reduced by 7% ( P  =   0.102) for measurement at 4 h. Of the 63 patients, 14 had their GET normalized and 49 remained delayed after 1 year. Normalized GET patients had a similar symptom improvement as those whose GET remained delayed. Of all upper GI symptoms, the improvements in vomiting ( P  =   0.04), nausea ( P  =   0.002) and epigastric pain ( P  =   0.001) were significantly correlated with reduction in 4-h gastric retention between baseline and 12 months of GES therapy for patients with normalized gastric emptying but there were no correlations with any symptoms and change in gastric emptying for those patients who remained delayed. In summary, overall gastric emptying is not significantly accelerated at 4 h after successful symptomatic improvement with GES but nausea, vomiting and epigastric pain can be correlated with normalization of GET in a subset of patients.     

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous 13C-acetate breath test

Abstract The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and ¹³C‐acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of ¹³C‐acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half‐times (T½) for MRI and BT were calculated (mean ± SD). We found: (i) Initial GCV was lower in FD than in HC (762 ± 22 vs 810 ± 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T½_MRI was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 ± 30 min vs FD 138 ± 42 min, ns; 800 mL: HC 71 ± 16 min vs FD 78 ± 27 min, ns). In contrast, T½_BT was similar between meals and groups (200 mL: HC 111 ± 11 min vs FD 116 ± 19 min; 800 mL: HC 114 ± 14 min vs FD: 113 ± 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non‐invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high‐volume compared to low‐volume liquid nutrient meals in HC or FD.     

Assessment of gastric sensorimotor function in paediatric patients with unexplained dyspeptic symptoms and poor weight gain

Recent studies indicate that impaired meal accommodation or hypersensitivity to distention are highly prevalent in adult functional dyspepsia (FD). Our aim was to investigate whether similar abnormalities also occur in paediatric FD. Sixteen FD patients (15 girls, 10-16 years) were studied. The severity (0-3; 0, absent; 3, severe) of eight dyspeptic symptoms (epigastric pain, fullness, bloating, early satiety, nausea, vomiting, belching and epigastric burning) and the amount of weight loss were determined by questionnaire. All children underwent a gastric barostat study after an overnight fast to determine sensitivity to distention and meal-induced accommodation, which were compared with normal values in young adults (18-22 years). On a separate day, all patients underwent a gastric emptying breath test. A mean weight loss of 4.8 +/- 0.9 kg was present in 14 children. Compared with controls, patients had lower discomfort thresholds to gastric distention (8.8 +/- 1.0 mmHg vs 13.9 +/- 1.9 mmHg, P < 0.02) and gastric accommodation (87 +/- 25 mL vs 154 +/- 20 mL P < 0.04). Hypersensitivity to distention and impaired accommodation were present in respectively nine (56%) and 11 (69%) patients. No relationship was found between barostat and gastric emptying, which was delayed in only three patients. The majority of children with unexplained epigastric symptoms have abnormalities of gastric sensorimotor function.     

39Gastrointestinal electrical stimulation in post-surgical gastroparesis improves symptoms independently while gastric emptying response is dependent on baseline emptying

Introduction:  Temporary GES (tempGES) can improve both gastric emptying and symptoms in post-surgical gastroparesis (PS-GP). (SSAT 2004). Long-term effects on GI symptoms and gastric emptying are unknown. Since many PS-GP patients have non-delayed emptying, the long-term effect on baseline normal or rapid emptying is also unknown.
Patients:  36 pts (6 M, 30 F, mean age 42 years) with post-surgical: Bilroth I ( n  = 11), Bilroth II ( n  = 4), other gastric surgery ( n  = 21) disordered gastric emptying were evaluated.
Methods:  GI symptoms (vomiting = V, Total = TSS), and solid meal gastric emptying (GET) at 1 and 4 h, were compared at baseline (Base), after temporary (tempGES) and permanent (permGES) gastric electrical stimulation as previously described (NGM, 2004; 16: 635.) Long-term follow-up for permanent GES ranged from 6 month to 10 years. Results were compared by t-tests, and are reported as means ± SEM.
Results:  29 of the 36 patients were able to tolerate food for baseline quantitative gastric emptying testing. 20 patients had delayed and 9 patients had non-delayed gastric emptying, with 7/9 being rapid. With both tempGES and permGES, GI symptoms improved (p < 0.05). Both tempGES and permGES showed accelerated GET for delayed patients and generally slowed GET for non-delayed (p < 0.05 for 1 h values). See tables below.
Conclusions:  In a large group of post-surgical GP patients, temporary and permanent gastrointestinal electrical stimulation improved GI symptoms independent of gastric emptying and for a prolonged time. GES improves symptoms independent of baseline gastric emptying, and improves GET dependent on the baseline gastric emptying.
 

     

Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats

Abstract  Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as γ -aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD.     

Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms

Background Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin‐treated diabetes. Methods On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire. Key Results We included 115 patients with insulin‐treated diabetes (median age 53, range 21–69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P < 0.0001). Eighty‐three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P < 0.001) and nausea/vomiting (r = 0.30; P < 0.001). Conclusions & Inferences A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.     

G-protein β3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese

Background G‐protein dysfunction related alteration of intracellular signal transduction might be linked to various abnormalities of functional gastrointestinal (GI) disorders. Serotonin (5‐hydroxytryptamine; 5‐HT) as well as G‐protein is also key signaling molecule sensorimotor functions in the GI tract. Thus, this study aims to evaluate the correlation between gastric emptying and GNβ3 and 5‐HTs polymorphisms in functional dyspepsia (FD) as defined by Rome III classification. Methods Seventy‐four patients presenting with typical symptoms of FD (epigastric pain syndrome: EPS, n = 24; postprandial distress syndrome: PDS, n = 51) and sixty‐four healthy volunteers were enrolled. Gastric motility was evaluated with the T_max value using the ¹³C‐acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and SRQ‐D scores to determine depression status. GNβ3‐C825T, 5‐HT_1A‐C1019G, 5‐HT_2A‐G1438A, 5‐HT_3A‐C42T, and 5‐HT_4A‐G353 + 6A polymorphisms were analyzed in DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. Key Results There was a significant relationship (P = 0.045) between GNβ3 825CC genotype and PDS patients without gastro‐esophageal reflux symptoms with impaired gastric emptying. In Japanese, GNβ3 825CC genotype in FD patients was significantly associated (P = 0.0485) with the feeling of hunger compared with GNβ3 825CT and TT genotypes. Conclusions & Inferences Our results suggest that the GNβ3 825CC genotype is significantly associated with PDS patients without gastro‐esophageal reflux with impairments of gastric emptying and also with the feeling of hunger in patients with FD. Further studies are needed to clarify whether the GNβ3 825CC genotype is linked to disturbances of gastric emptying via altered signal transduction responses.     

Intolerance to visceral distension in functional dyspepsia or irritable bowel syndrome: an organ specific defect or a pan intestinal dysregulation?

Functional gastrointestinal disorders (FGID) are characterized by visceral hypersensitivity that could be specific to a region of the gut or reflect a diffuse pan-intestinal disorder. Sensory thresholds to distension at two visceral sites in patients with different FGIDs were determined. According to Rome II criteria, 30 patients from three groups were studied: patients with (i) functional dyspepsia (FD) or (ii) irritable bowel syndrome (IBS), and (iii) patients with concomitant symptoms of FD and IBS. Pain thresholds to balloon distension were determined in stomach and rectum. In FD patients, gastric intolerance to balloon distension was found in 91% patients; rectal hypersensitivity was documented in 18% patients. In IBS patients, rectal hypersensitivity was seen in 75% patients; while gastric hypersensitivity was never found. In patients with concomitant symptoms of FD + IBS, gastric and rectal intolerance to distension were present respectively in 82 and 91% patients. In the whole group, visceral intolerance to distension was documented at one site in 90% patients and at both sites, i.e. stomach and rectum, in 33% patients. Visceral intolerance to distension can be pan-intestinal in patients with multiple sites of symptoms, but appears organ-specific in patients exhibiting a specific site of symptoms.     

A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia

Abstract  Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and ¹³C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation ( P  = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating ( P  = 0.001) and overall symptom score ( P  = 0.022), and at week 3 for bloating ( P  = 0.008) and heartburn ( P  = 0.041). 100 mg was also better than placebo for QOL (physical function) ( P  = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.     

2Endoscopic temporary gastric electrical stimulation – results of 140 consecutive patients

Background: Gastric emptying is a function of gastric contraction, electrical activity, pyloric and duodenal resistance. Pylorospasm (basal pyloric pressures >10 mmHg; Mearin et al. Gastro 1986) has been implicated in gastroparesis. Currently, pyloric pressures can be measured invasively, using a Dent sleeve (Mui Scientific, Inc.) manometry catheter. Electrogastrography (EGG) is a noninvasive tool for measuring gastric myoelectrical activity. EGG has been shown to distinguish gastric outlet obstruction from idiopathic gastroparesis (Brzana et al. Amer J Gastro 1998). Aims: The aims of this study were to 1) determine whether EGG can distinguish patients with gastroparesis who have pylorospasm and 2) correlate basal pyloric pressure with various EGG parameters. Methods and Results: 23 patients with gastroparesis (19 diabetics, mean age 40.4 ± 2.3, mean 4 hr gastric retention 43.0 ± 5.1%) had basal pyloric pressure measurements and EGG. Stationary basal pyloric pressures were measured using a Dent sleeve that was placed across the pyloric channel during endoscopy with fluoroscopic guidance. 60.9% (14/23) of patients had elevated pyloric pressures (21.8 ± 3.4 mmHg vs. 5.5 ± 0.8 mmHg). There was no difference in the postprandial power ratio and gastric emptying as measured by scintigraphy between the 2 groups. The fasting dominant slow wave frequency (SWF) in the elevated pyloric pressure group was significantly higher compared to the normal pyloric pressure group (3.1 ± 0.1 cpm vs. 2.4 ± 0.3 cpm; p = 0.013). There was significantly less dysrhythmia in the elevated pyloric pressure group (75.5 ± 6.0% normal rhythm vs. 54.8 ± 9.7% normal; p = 0.03). More patients in the elevated pyloric pressure group had normal fasting electrical rhythm (>70% normal electrical rhythm) compared to the normal pyloric pressure group (64.3% vs. 22.2%; p = 0.03). There was a correlation between pyloric pressure and fasting slow wave frequency (r = 0.53, p = 0.005) but no correlation with the percentage of dysrhythmia, postprandial power ratio or gastric emptying. Conclusion: Patients with normal pyloric pressure and delayed gastric emptying have significantly more abnormalities in slow wave frequency and dysrhythmia compared to patients with abnormal pyloric pressure. This suggests that patients with delayed gastric emptying with normal pyloric pressures have abnormalities in gastric conduction as a cause of their gastroparesis.     

Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis

Abstract  Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4-h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC− group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC− group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC− group was significantly more than in the ICC+ group both in the fasting (32 ± 8% vs 11 ± 2%) and fed states (27 ± 9% vs 12 ± 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.     

Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson's disease? An analysis using the 13C-acetate breath test

During the pre-symptomatic stage of Parkinson's disease (PD), the idiopathic PD related abnormal synuclein immunostaining is confined to the medulla oblongata and olfactory bulb, according to Braak. In the study of the enteric nervous system of PD, it has reported that Lewy bodies were found in the Auerbach's and Meissner's plexuses. These lesions may cause dysfunction of the gastrointestinal tract (GI) as pre-clinical symptoms of PD. However, because L: -dopa therapy itself may worsen the symptoms of the digestive tract function, it is needed to evaluate the gastrointestinal tract function in patients with early-stage, untreated (de novo) PD. In the present study, using the (13)C-acetate breath test ((13)C-ABT), we investigated gastric emptying in 20 untreated, early-stage PD patients and 40 treated, advanced-stage PD patients, and 20 healthy volunteers. Gastric emptying was examined by the (13)C-ABT [the half emptying time (HET), the peak time of the (13)C% dose-excess curve (T (max))]. The T (max) and HET of gastric emptying as assessed using the (13)C-ABT was significantly delayed in untreated, early-stage PD patients as compared to the controls (P < 0.001). The T (max) and HET of gastric emptying were not significantly delayed in untreated, early-stage PD patients as compared to treated, advanced-stage PD patients. The results demonstrated that delay in gastric emptying did not differ between untreated, early-stage and treated, advanced-stage PD patients. Gastric emptying of untreated, early-stage PD is already delayed. Delayed gastric emptying may be one of markers of the pre-clinical stage of PD.     

23A multi-component model can predict gastric emptying in diabetic gastroparesis

Introduction:  We have previously reported that a multi-component model of autonomic and enteric factors can help predict gastric emptying in diabetes mellitus. (Aslam N. Abell T. A four component model can quantitatively profile gastric emptying in diabetic gastropathy. Supplement to Gastroenterology Vol 118, April 2000, Number 4, Suppl 2. (Abstract No. 5341).
Patients:  Eighty-seven patients with Diabetes mellitus presenting with signs and symptoms of Gastroparesis. It included 38 males, 49 females with mean age of 39 ± 10 years.
Methods:  Autonomic tests included adrenergic tests by VC (vasoconstriction to cold) and PAR (postural ratio), and cholinergic function measured by EKG R to R interval (RRI). The Enteric measure (EGG) was measured by cutaneous electrogastrogram. The data was compared to results of standardized solid gastric emptying T50 in minutes (GE above), by linear regression.
Results:  The patients were distributed in five groups according to mean T50 of solid gastric emptying: 24 (28%) were very delayed, 13 (15%) delayed, 19 (22%) were normal, 15 (17%) were rapid, and 16 (18%) very rapid. There were statistically significant differences among the five group means for VC, RRI, and EGG, but not for PAR. (See table).
Conclusions:  In this group of patients with symptoms of Diabetic gastropathy, there is a wide range of gastric emptying values. A multi-component model demonstrates specific autonomic and enteric differences in subgroups of diabetic gastroparesis. Therapies for diabetic gastropathy, including drug and device studies, may need to take into account these physiologic differences when looking at therapeutic outcomes. Autonomic and enteric measure appear useful as part of the evaluation of patients with symptoms of diabetic gastropathy.
Means
 

     

Intersubject and intrasubject variability of gastric volumes in response to isocaloric liquid meals in functional dyspepsia and health.

Gastric emptying (GE) has a considerable variability, but data on reproducibility of gastric volume measurements are sparse. We aimed to study the reproducibility of postprandial gastric volume responses and GE using magnetic resonance imaging (MRI) in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent a MRI study on two occasions. MR images were acquired in seated position before and up to 120 min after liquid meal administration (200 mL, 300 kcal). Fasting (V0), initial postprandial stomach volumes (V1), volume changes (V1 - V0) and meal emptying half-times (T 1/2) were determined. Intersubject and intrasubject coefficients of variation (CV(inter), CV(intra)) and Pearson's correlation coefficients (r) were calculated. T 1/2 on both occasions were (mean +/- SD) 113 +/- 28 and 121 +/- 30 min in HC (ns) and 127 +/- 31 and 128 +/- 37 min in FD (ns), respectively. In HC, CV(inter), CV(intra), r were 31%, 23%, 0.49 for V0; 13%, 7%, 0.68 for V1; 10%, 4%, 0.71 for V1 - V0 and 25%, 7%, 0.90 for T 1/2. In FD these parameters were for V0: 42%, 41%, -0.06; for V1: 18%, 10%, 0.40; for V1 - V0: 20%, 14%, 0.74 and for T 1/2: 26%, 10%, 0.84. The stomach accommodates to a given meal volume, resulting in similar and reproducible postprandial volumes within- and between-subjects. MRI provides reproducible measurements of gastric volume responses in health and disease.     

Low-Resolution Electrogastrogram at Baseline and Response to Temporary Gastric Electrical Stimulation—A Comparison of Cutaneous With Mucosal Recordings

IntroductionGastric electrical stimulation (GES) is a widely accepted therapy for gastroparesis symptoms, but how a brief cutaneous electrogastrogram (EGG) can be used in conjunction with GES has not been well defined. We evaluated the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and gastrointestinal symptoms before and after temporary GES (tGES).Materials and MethodsWe studied 1345 patients; 991 had complete data. EGG measurements like frequency and amplitude were recorded at baseline and five days post-tGES using short recording periods. A total of 266 participants having additional cutaneous propagation values were separately analyzed. Patients underwent solid GET before and after tGES and self-reported symptoms using standardized traditional patient-reported outcomes (TradPRO) scores. Pearson correlations were assessed at baseline, post-stimulation, and their changes over the follow-up period.ResultsEGG measures correlated with symptoms and GET results. Patients with abnormal baseline cutaneous frequency had higher baseline total symptom scores (p < 0.003). Post-tGES, one-hour gastric emptying was significantly changed (p < 0.0001) and was mainly observed with abnormal baseline cutaneous frequencies (p < 0.0001). Cutaneous frequency significantly increased after tGES (p < 0.0001), correlating positively with TradPRO scores and one-hour gastric emptying. Mucosal and cutaneous measures correlated pre- and post-treatment. Of the 266 patients, 153 changed propagation states between baseline and temporary; changing states from lower at baseline to higher at temporary was more likely than vice versa. Short EGG recording times can demonstrate changes after the bioelectric therapy of GES.ConclusionEGG is valuable in the diagnosis of delayed gastric emptying and comparable with mEG. It is less invasive and can identify patients who may require GES. Frequency, amplitude, their ratio (frequency-amplitude ratio), and propagation appear to be reliable measures of EGG. EGG provides cost-effective measurement of electrophysiological properties and significantly correlates with important clinical measures. Shorter EGG recording times may be adequate to see changes from bioelectric therapies.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03876288.     

Symptom pattern and pathophysiological correlates of weight loss in tertiary-referred functional dyspepsia

Abstract  In patients with gastrointestinal symptoms, weight loss is an alarm symptom, indicative of organic disease. Recent studies reported weight loss in subsets of functional dyspepsia (FD) patients. The aim of this study was to analyse symptom patterns associated with weight loss in tertiary care FD. Six hundred and thirty-six FD patients (67% female, mean age 43 years) completed a dyspepsia questionnaire, and underwent gastric emptying and gastric barostat studies. After identifying independent symptom domains through orthogonal factor analysis, patients were clustered on the basis of symptom profile. Clusters were compared in terms of their association with weight loss and gastric emptying or sensorimotor function. Weight loss (4.2 kg on average) correlated most strongly with early satiety followed by nausea and vomiting ( ρ respectively 0.38, 0.28 and 0.23, all P  < 0.0001). Factor analysis revealed three factors: Factor 1 characterized by nausea, vomiting and early satiety; factor 2 by early satiety, postprandial fullness and bloating; and factor 3 by pain, epigastric burning and belching. Subsequent cluster analysis revealed six patient clusters. The most severe cluster, which loaded high on all three factors, and a cluster dominated factor 2 were associated with the highest average weight loss (6.8 and 8.0 kg, respectively). The former cluster was also characterized by visceral hypersensitivity and delayed gastric emptying. The lowest weight loss occurred in the two clusters that had depressed scores for both early satiety associated factors (2.4 and 2.5 kg, respectively). In tertiary care FD, weight loss is strongly associated with two early satiety associated symptom clusters.