Measurement of gastric emptying of a high‐nutrient liquid by 3D ultrasonography in diabetic gastroparesis

Background Gastric emptying (GE) is delayed in 30–50% of patients with longstanding diabetes. Scintigraphy represents the ‘gold standard’ for measurement of GE, but is associated with a radiation burden. Three‐dimensional (3D) ultrasonography has recently been demonstrated to provide a valid measure of liquid GE in healthy subjects; however, the technique has not been validated in patients with gastroparesis. The primary aim of this study was to compare measurements of GE of a high‐nutrient glucose drink by 3D ultrasonography and scintigraphy in diabetic gastroparesis. Methods Ten patients (eight type 1, two type 2, 6M, 4F, aged 46.1 ± 4.5 years, BMI 29.1 ± 1.6 kg m^?2, duration 19.6 ± 3.3 years) with diabetic gastroparesis [defined as retention at 100 min of solid (100 g minced beef) ≥61% and/or 50% emptying time (T50) of liquid (150 mL 10% dextrose) ≥31 min], were studied. Concurrent measurements of GE by scintigraphy and 3D ultrasonography were performed following ingestion of 75 g glucose in 300 mL water labeled with 20 MBq ^99mTc‐sulfur colloid. Key Results There was no significant difference in GE between the two techniques (T50s: scintigraphy – 103.3 ± 10.0 min VS 3D ultrasonography – 98.8 ± 10.4 min; P = 0.60). There was a significant correlation between scintigraphic and ultrasonographic T50s (r = 0.67, P = 0.03). The limits of agreement for the T50s were ?57.22 min and +48.22 min (mean difference ?4.5 min). Blood glucose after the drink was greater when GE was relatively more rapid (e.g. at t = 60 min; scintigraphy: r = ?0.65, P = 0.04; 3D ultrasonography: r = ?0.78, P = 0.008). Conclusions & Inferences Three‐dimensional ultrasonography appears to provide a valid, and non‐invasive, measure of GE of high‐nutrient liquids in diabetic gastroparesis.     

Association of genetic variation in cannabinoid mechanisms and gastric motor functions and satiation in overweight and obesity

Background The endocannabinoid system is associated with food intake. We hypothesized that genes regulating cannabinoids are associated with obesity. Genetic variations in fatty acid amide hydroxylase (FAAH) and cannabinoid receptor 1 (CNR1) are associated with satiation and gastric motor function. Methods In 62 overweight or obese adults of European ancestry, single nucleotide polymorphisms of rs806378 (nearest gene CNR1) and rs324420 (nearest gene FAAH) were genotyped and the associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation [maximum tolerated volume (MTV) and symptoms after Ensure^® nutrient drink test] were explored using a dominant genetic model, with gender and BMI as covariates. Key Results rs806378 CC genotype was associated with reduced fasting GV (210.2 ± 11.0 mL for CC group compared to 242.5 ± 11.3 mL for CT/TT group, P = 0.031) and a modest, non‐significant association with GE of solids (P = 0.17). rs324420 genotype was not associated with alterations in gastric motor functions; however, there was a difference in the Ensure^® MTV (1174.6 ± 37.2 mL for CC group compared to 1395.0 ± 123.1 mL for CA/AA group, P = 0.046) suggesting higher satiation with CC genotype. Conclusions & Inferences Our data suggest that CNR1 and FAAH are associated with altered gastric functions or satiation that may predispose to obesity.     

The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging

Abstract Conventional measurement of gastric secretion is invasive and cannot assess the intra‐gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T₁ mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium‐DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double‐blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T₁ mapping. Data was described by the κ‐coefficient (volume change after meal ingestion), by GE half time (T₅₀) and maximal GE rate (GER_max) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [κ(GCV):1.6 ± 0.1 vs 0.6 ± 0.1; κ(TGV): 1.6 ± 0.1 vs 0.7 ± 0.1; P < 0.001]. T₁ maps revealed a secretion layer above the meal, the volume of which was associated with κ (R² = 83%, P < 0.001). TGV and GCV change were similar in both conditions (κ; P = ns). T₅₀ was higher for pentagastrin than for placebo (84 ± 7 vs 56 ± 4min, P < 0.001); however, GER_max was similar (5.9 ± 0.6 vs 4.9 ± 0.4 mL min^?1, P = ns). This study shows volume and distribution of gastric secretion can be quantified in‐vivo by non‐invasive MRI T₁ mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T₅₀; however, GE rate is unchanged.     

Effect of mianserin on gastric sensorimotor function and gastric emptying: a randomized,placebo‐controlled,double‐blind,crossover study in healthy volunteers

Background Antidepressants such as mianserin can improve symptoms in some functional dyspeptic patients but their mechanism of action remains unclear. We aimed to assess the effects of mianserin on gastric sensorimotor function in man. Methods In this randomized, placebo‐controlled, double‐blind, crossover study 12 healthy subjects (six men) underwent a gastric barostat study and a gastric emptying breath test after 7 days pretreatment with placebo or mianserin (20 mg; p.o.). Graded isobaric and isovolumetric distentions were performed to determine gastric compliance and sensitivity. Subsequently, intrabag pressure was held constant and the volume increase after administration of a liquid meal (200 mL; 300 kcal) was studied. Breath was sampled before and after ingestion of a test meal and half‐emptying times for solids and liquids were determined from the breath samples. Mianserin was compared to placebo using t‐tests and mixed model analysis (mean ± SD). Key Results Mianserin did not affect pressures or volumes needed to induce first perception or discomfort. During isovolumetric distensions compliance was decreased after mianserin treatment (1.8 ± 0.4 vs 2.0 ± 0.3 mmHg 100 mL^?1; P < 0.05). Premeal volumes were comparable in both treatment arms (221 ± 99 vs 220 ± 88 mL), but meal‐induced relaxation during the first 30 min was significantly inhibited after mianserin treatment (F_6,40 = 2.58, P < 0.05). Mianserin did not affect either solid or liquid gastric emptying. Conclusions & Inferences Mianserin does not alter gastric emptying rate or sensitivity to gastric distension, but inhibits gastric accommodation to a meal in its early phase. These observations provide no explanation for the effects of mianserin in functional dyspeptic patients.     

9The TANTALUSTM System for obesity: effect on gastric emptying of solids

Background: Gastric electrical stimulation (GES) is currently investigated for the treatment of obesity. The TANTALUS System delivers gastric contractility modulation (GCM) signals in synchrony with gastric slow waves, resulting in significant augmentation of gastric contractions during food intake. We hypothesized that such modulation of contractile activity may affect gastric emptying and plasma ghrelin levels. Aim: To test the effect of GCM of the gastric antrum on gastric emptying of solids and ghrelin levels. Methods: 12 obese subjects were implanted with 2 pairs of antral electrodes and an implantable pulse generator (IPG, TANTALUS ^TM) Gastric emptying test (GE) for solids was performed twice, on separate days, in each subject, starting few weeks after implantation: 1) control, before the start of stimulation, and 2) with stimulation, after device was turned on. Blood samples for ghrelin, were taken at baseline, and at 15, 30, 60 and 120 min after the test meal. Results as mean + SD, analysis by t‐test and p < 0.05. Results: 11 females, 1 male, age: 39.1 ± 8.9 years, BMI: 41.6 ± 3.4, 3 subjects with type 2 diabetes. One diabetic patient did not complete GE test because of technical issues. GCM significantly accelerated gastric emptying: retention at 2 hours 18.7 ± 12.2% vs. 31.9 ± 16.4%, stimulation vs. control respectively, p = 0.008. T ^1/2 78.3 ± 23.5 vs. 95 ± 31.7 min, stimulation vs. control respectively, p = 0.04. Mean results for gastric emptying were within normal at both baseline and stimulation. Meal ingestion induced only minimal, insignificant reduction in ghrelin levels. There was no significant difference in AUC of ghrelin between control and stimulation. Conclusions: After GCM stimulation, there is significant acceleration of gastric emptying of solids in obese patients, without affect on ghrelin levels. The obese subjects did not exhibit the significant, meal‐induced reduction in ghrelin.      

Tissue ghrelin level and gastric emptying rate in adult patients with celiac disease

Abstract Celiac disease (CD) patients show a number of gastrointestinal motor abnormalities. Ghrelin, a gastric peptide implicated in short‐term feeding control and long‐term body weight regulation, has been recently considered a key regulator of gastric motility. The aim of this study was to evaluate the gastric emptying rate of solids and the density of ghrelin‐immunopositive cells in adult CD patients before and at least 1 year after starting a gluten‐free diet. Twenty CD patients (M 8/F 12; mean age 36 years) and 10 controls underwent endoscopy with gastric and duodenal biopsies and ¹³C‐octanoic acid breath test to measure gastric emptying of solids. Celiac disease patients repeated the protocol at least 1 year after starting gluten‐free diet. Ghrelin tissue levels were evaluated by immunohistochemistry on gastric mucosa specimens. Gastric emptying time was normal in all control subjects (t_1/2 = 89 ± 16 min) while it was delayed in CD patients prior to gluten‐free diet (t_1/2 = 252 ± 101 min; P < 0.005). The mean number of ghrelin‐positive cells/field (×400) was 14.4 ± 2.7 in controls and 25.3 ± 5.7 in CD patients respectively (P < 0.0001). Gluten withdrawal was effective in normalizing gastric emptying time in all CD patients (97 ± 14 min; P < 0.0001) and resulted in a significant reduction of the density of ghrelin‐immunopositive cells (19.8 ± 5.4; P < 0.0001). The density of ghrelin‐positive cells correlated directly with the degree of duodenal damage (P < 0.001) and inversely with the body mass index of CD patients (P < 0.0001). However, in neither CD patients nor controls, a correlation between tissue ghrelin levels and gastric emptying rate was detected. In conclusion, tissue ghrelin level does not correlate with gastric emptying rate in adult CD patients and in controls.     

Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study

Abstract Gastric emptying (GE) may be driven by tonic contraction of the stomach (‘pressure pump’) or antral contraction waves (ACW) (‘peristaltic pump’). The mechanism underlying GE was studied by contrasting the effects of clonidine (α₂‐adrenergic agonist) and sumatriptan (5‐HT₁ agonist) on gastric function. Magnetic resonance imaging provided non‐invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min^?1 IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r² = 49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r² = 15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the ‘pressure pump’ mechanism.     

Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants

Background Gastric emptying (GE) is measured in pharmacodynamic and diagnostic studies. Our aim was to assess inter‐ and intra‐subject coefficients of variation (COV) of scintigraphic GE measurements in healthy subjects, and associations of GE with gender and body mass index (BMI). Methods Data from participants with scintigraphic measurements of gastric emptying of solids were analyzed. Primary endpoints were gastric emptying T_1/2 (GE T_1/2) and GE at 1, 2, 3, and 4 h. Key Results The patient cohort consisted of 105 males and 214 females; at least two studies were performed in 47 subjects [16 males (M), 32 females (F)]. Inter‐subject COV (COV_inter) for GE T_1/2 were similar in M and F: overall 24.5% (M 26.0%, F 22.5%); COV are predictably lowest for GE at 4 h (COV_inter 9.6%). COV_intra for T_1/2 and GE at 4 h were overall 23.8% and 12.6%, and were similar to COV_inter values. Gender (but not age or BMI) was significantly associated with GE T1/2 [P < 0.001, F 127.6 ± 28.7 (SD) min; M 109.9 ± 28.6 min] and with GE at 1 h and 2 h. Repeat GE T_1/2 values in 47 participants were significantly correlated (r = 0.459, P < 0.001) with median difference of ?6 min (mean ?1.6, range ?56 to 72 min). Bland–Altman plots showed Δ GE T_1/2 similarly distributed across mean GE T_1/2 100–155 min, and across studies conducted 90–600 days apart. Conclusions & Inferences Inter‐subject variations in scintigraphic GE results are only slightly higher than the intra‐subject measurements, which are also reproducible over time in healthy volunteers. Gender, but not BMI, is significantly associated with GE results.     

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.     

The nitric oxide synthase inhibitor, Ng-nitro-l-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans

Abstract The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N^g‐nitro‐l ‐arginine‐methyl‐ester (l ‐NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four‐way randomized crossover (hyperglycaemia vs euglycaemia; l ‐NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 ± 3.8 years; body mass index (BMI) 23.6 ± 1.2 kg m^?2] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L^?1 using a glucose/insulin clamp. An intravenous infusion of l ‐NAME (180 μg kg^?1 h^?1) or placebo (0.9% saline) was commenced (T = ?30 min) and continued for 150 min. At T = ?2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by l ‐NAME. l ‐NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 ± 0.8 (hyperglycaemia) vs 6.5 ± 0.6 (euglycaemia); P < 0.01]; l ‐NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 (l ‐NAME) vs 5.1 ± 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of l ‐NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.     

A new gastric‐emptying mouse model based on in vivo non‐invasive bioluminescence imaging

Background Different techniques were used to assess gastric emptying (GE) in small animals; most of them require sophisticated equipment, animal sacrifice and are expensive. In the present investigation a simple, non‐invasive method based on bioluminescence imaging (BLI) is reported to study GE, using light‐emitting Escherichia coli cells as a marker of the gastric content. Methods A new thermostable red‐emitting luciferase was chosen as reporter gene to transform E. coli cells. Bioluminescent (BL) bacteria were administered to fasting mice, after a solid meal, and in response to different doses of metoclopramide (MET) and hyoscine butylbromide (HY). Bioluminescence imaging allowed to evaluate the real time 2D spatial and temporal distribution of bacteria along the gastrointestinal tract in animals and to calculate GE rate in basal conditions and following pharmacological stimulation. Key Results The administered BL bacteria were easily imaged and localized in the stomach and subsequently followed in the duodenum and upper intestine allowing to accurately calculate GE. Gastric emptying after the test meal was significantly slower (T_1/2 16 ± 3 min) than that obtained in fasting conditions (T_1/2 2 ± 1 min); administration of HY (1 mg kg⁻¹ b.w.) significantly (P < 0.05) increased T_1/2 that was delayed up to 25 ± 4 min; MET (1 mg kg⁻¹ b.w.) significantly (P < 0.05) accelerated T_1/2, that was achieved within 8 ± 2 min. Conclusion & Inferences The reported model is simple, inexpensive, reliable, sensitive and accurate; it can detect both acceleration and slowdown of GE. The model is useful in the investigation of new drug‐induced alterations of gastric motility allowing to reduce the number of experimental animals.     

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying

Background Symptoms of gastroparesis based on patient recall correlate poorly with gastric emptying. The aim of this study is to determine if symptoms recorded during gastric emptying scintigraphy (GES) correlate with gastric emptying and with symptoms based on patient recall. Methods Patients undergoing GES completed the Patient Assessment of GI Symptoms (PAGI‐SYM) assessing symptoms over the prior 2 weeks and a questionnaire for which patients graded six symptoms during GES. A Symptom Severity Index (SSI) represented the mean of six symptoms at each time point. Key Results A total of 560 patients underwent GES for clinical evaluation of symptoms. Of 388 patients included in the study: 232 patients had normal GES (NGES), 156 delayed GES (DGES), and 11 rapid GES (RGES). Symptom severity index increased pre to postprandial for each group: NGES: 0.51 ± 0.07 to 0.92 ± 0.03, DGES: 0.60 ± 0.09 to 1.13 ± 0.05, and RGES: 0.56 ± 0.12 to 0.79 ± 0.13. Delayed gastric emptying scintigraphy patients had a higher postprandial SSI than NGES patients (1.13 ± 0.05 vs 0.92 ± 0.03, P < 0.05). Postprandial symptoms of stomach fullness (1.9 ± 0.12 vs 1.5 ± 0.09; P = 0.011), bloating (1.4 ± 0.11 vs 1.1 ± 0.09; P = 0.033), and abdominal pain (1.1 ± 0.08 vs 0.7 ± 0.12; P = 0.012) were higher in DGES than NGES. Symptom severity based on PAGI‐SYM for 2 weeks prior to GES correlated with symptoms during the test for nausea (NGES, r = 0.61; DGES, r = 0.70), stomach fullness (NGES, r = 0.47; DGES, r = 0.60), and bloating (NGES, r = 0.62, DGES, r = 0.66). Conclusions & Inferences Stomach fullness, bloating, and abdominal pain recorded during GES were higher in patients with delayed gastric emptying than in patients with normal gastric emptying. Symptoms recorded during GES correlated with those during daily life by patient recall.     

Duodenal ulcer disease,gastroduodenal motor function and reflux esophagitis – a cross‐sectional survey in a subset of Taiwanese patients

Background To investigate the association between the gastric emptying rate and the presence of erosive esophagitis in duodenal ulcer (DU) patients among a population with high prevalence of Helicobacter pylori infection. Methods Cross‐sectional survey was performed in a cohort of 60 male patients with either active or healed DU, with or without the presence of erosive esophagitis. Clinical and social‐demographic data, blood level of fasting gastrin, pepsinogen I & I/II ratio, and scintigraphic measurement of half emptying time (t_1/2) of the solid phase gastric emptying were evaluated. Key Results Patients with active DU and erosive esophagitis tended to have higher plasma level of fasting gastrin than those without erosive esophagitis (75.11 ± 13.74 vs 45.81 ± 5.06 pg mL^?1, P = 0.059). In the absence of H. pylori infection, patients with healed DU and erosive esophagitis had a trend to have longer half‐emptying time (t_1/2: 96.5 ± 6.4 vs 69.1 ± 11.3 min, P = 0.0572) than those without erosive esophagitis, and statistically significant longer after excluding those diagnosed with hiatal hernia (t_1/2: 100.8 ± 7.9 min vs 69.1 ± 11.3 min, P < 0.05) from the former group. Among the healed DU patients, those with negative H. pylori infection, hiatal hernia and overweight (body mass index ≥24) had significantly increased risk of severe esophagitis. Conclusions & Inferences Presence of erosive esophagitis in a subset of Taiwanese patients with healed DU and negative H. pylori status was associated with slower solid phase gastric emptying.     

Role of endogenous opioids in the control of gastric sensorimotor function

Abstract Endogenous opioids have been implicated not only in the process of feeding but also in the control of gastric sensitivity and gastric motor responses, and impairment of antinociceptive opioid pathways has been hypothesized to contribute to the pathogenesis of functional dyspepsia. Our aim was to study the effect of suppression of endogenous opioid action by naloxone on gastric sensorimotor function in healthy volunteers. During intravenous administration of saline or naloxone (0.4 mg intravenous bolus followed by continuous infusion 20 μg kg^?1 h^?1), sensitivity to gastric distension, gastric accommodation and fundic phasic contractility were evaluated by barostat in 15 subjects. Nutrient tolerance and meal‐related symptoms were assessed using a satiety drinking test (n = 13), and solid and liquid gastric emptying were evaluated by breath test (n = 14). Naloxone did not influence gastric compliance and sensitivity. No effect on preprandial gastric tone was found but meal‐induced accommodation was significantly inhibited by naloxone (P = 0.031). Subjects receiving naloxone demonstrated a higher motility index before (20.8 ± 2.4 vs 28.0 ± 1.9 mL s^?1, P = 0.007) and after (15.2 ± 2.0 vs 22.7 ± 1.5 mL s^?1, P = 0.0006) the meal. Naloxone significantly decreased the amount of food ingested at maximum satiety (715.4 ± 77.7 vs 617.3 ± 61.3 mL, P = 0.03). No effect of naloxone on gastric emptying was observed and intensity of postprandial symptoms was unchanged. These observations suggest that endogenous opioids are involved in the control of gastric accommodation and phasic contractility but not in the control of sensitivity to gastric distension or gastric emptying in healthy volunteers.     

Gastric tone,volume and emptying after implantation of an intragastric balloon for weight control

Background The intragastric balloon, filled with air or liquid is used before elective bariatric surgery because its efficacy is limited. This might be the consequence of altered gastric functions. Therefore, we aimed to investigate, in an animal model, the changes in gastric motility and emptying induced by long‐term insertion of a balloon used for weight reduction. Methods Ten Göttingen mini‐pigs were allocated into two groups with and without an intragastric balloon for 5 months. Balloons were inserted under endoscopy during general anesthesia and were filled with 350 mL of air. Gastric emptying was evaluated by scintigraphy. Gastric volume was measured by single photon emission computed tomography and proximal gastric compliance obtained using an electronic barostat. Changes in vagal tone were assessed by heart rate variability (HRV). Key Results After balloon insertion, gastric volume was significantly increased (2047 ± 114.8 cm³ after vs 1674 ± 142.5 cm³ before insertion, P < 0.05). Gastric compliance was also larger in balloon group (219 ± 23.4 mL mmHg^?1 in balloon vs 168 ± 7.7 mL mmHg^?1 in control group). Gastric emptying was reduced after insertion of the balloon (T_1/2 = 204 ± 28.8 min vs 159 ± 25.4 before vs after insertion). High frequency components of the spectral analysis of HRV, representing vagal tone, were increased in balloon group. Conclusions & Inferences The proximal stomach was enlarged after the insertion of a balloon in the stomach as a consequence of an increased gastric compliance. This change in compliance was probably causative for a reduction in gastric emptying rate of solids. These alterations were associated with increased vagal tone.     

Effect of caffeine ingestion on torque and muscle activity during resistance exercise in men

Introduction: We examined the effect of caffeine ingestion on muscle torque production and muscle activity at different contraction speeds in trained men. Methods: 10 men (mean age ± SD = 22 ± 1.1 years) volunteered to participate. A double‐blind, randomized cross‐over design was used. Sixty minutes postingestion of caffeine (6 mg kg^?1) or placebo, participants completed 6 repetitions of isokientic knee extension at 3 angular velocities (30°s^?1, 150°s^?1, 300°s^?1) from which peak torque was determined. Electromyographic activity of the vastus medialis was also collected. Results: Repeated measures analysis of variance indicated that muscle torque production was significantly higher (P = 0.02) with caffeine compared with placebo. A significant (P = 0.02) substance by velocity interaction for muscle activity indicated significantly higher vastus medialis muscle activity in the presence of caffeine versus placebo, and this difference was amplified as angular velocity increased. Conclusions: Acute caffeine ingestion improves muscle performance and increases muscle activity during short‐duration maximal dynamic contractions. Muscle Nerve 50: 523–527, 2014     

Influence of clinical parameters on the results of 13C-octanoic acid breath tests: examination of different mathematical models in a large patient cohort

Abstract It is assumed, although not proven, that ¹³CO₂‐excretion following ingestion of ¹³C‐octanoic acid (¹³C‐OA) does not only depend on gastric emptying (GE) but also on absorption and metabolism of ¹³C‐OA and endogenous CO₂‐production. Our aims were (i) to test the effects of patient characteristics and of diseases that may impair ¹³C‐OA‐metabolism on GE parameters. (ii) To compare different GE endpoints. Therefore, we investigated effects of age, gender, BMI and diseases with potential impact on ¹³C‐OA‐metabolism (including pancreatic, liver and lung disease, diabetes, IBD) on cumulative 4h‐¹³CO₂‐excretion (4h‐CUM) and T½ calculated by non‐linear regression model (NL, determined by shape of breath test curve) and generalized linear regression model (GLR, reflects absolute ¹³CO₂‐excretion) in 1279 patients and 19 healthy controls who underwent a standardized ¹³C‐OA‐breath test. Digestive and metabolic disturbances hardly influenced 4h‐CUM or T½ calculated by NL or GLR models. In the multivariate linear regression models, 4h‐CUM was significantly predicted by diabetes adjusted for age, gender and IBD but influence of these parameters was small (R² = 0.028, P < 0.0001). T½_NL and 4h‐CUM were weakly correlated, even after exclusion of tests with unrealistically high estimates for T½_NL (n = 1095, R² = 0.029, P < 0.0001). Conversely, 4h‐CUM was closely associated with T½_GLR (exponential correlation, R² = 0.774, P < 0.00001, n = 1279). We conclude that influences of digestive and metabolic disturbances on ¹³CO₂‐excretion following ¹³C‐OA‐application are generally low. Thus, our findings resolve an important criticism of methods using absolute ¹³CO₂‐excretion for evaluation of ¹³C‐OA‐breath tests and suggest that such models may correctly identify T½ in a mixed patient population.     

A double‐blind,placebo‐controlled trial of rosiglitazone for clozapine‐induced glucose metabolism impairment in patients with Schizophrenia

Objective: The primary purpose of this 8‐week double‐blind, placebo‐controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine‐treated subjects with schizophrenia with insulin resistance. Method: Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results: Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non‐significant improvement in SG (0.016 ± 0.006–0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8–7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low‐density lipoprotein cholesterol (LDL‐C) particle number (987 ± 443–694 ± 415, effect size = 0.30, P = 0.04). Conclusion: Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine.     

Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia

Fan X, Borba CPC, Copeland P, Hayden D, Freudenreich O, Goff DC, Henderson DC. Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia. Objective: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine‐treated patients with schizophrenia. Method: In an 8‐week randomized, double‐blind, placebo‐controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole‐body dual‐energy X‐ray absorptiometry (DXA). Results: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. ?0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low‐density lipoprotein (LDL) levels (?15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (?376 ± 632 vs. ?36 ± 301 nm , P = 0.035). Further, there was a significant reduction in the lean mass (?1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole‐body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. Conclusion: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine‐treated patients with schizophrenia.     

Increased severity of dyspeptic symptoms related to mental stress is associated with sympathetic hyperactivity and enhanced endocrine response in patients with postprandial distress syndrome

Background Mental stress (MS) may alter gastric sensory‐motor function. The aim of the study was to assess postprandial autonomic nervous system activity and stress hormones in response to acute mental stress in dyspeptic patients. Methods A total of 25 patients with postprandial distress syndrome (PDS; 11 mol L^?1, age 35.9 ± 9.3 years) and 12 healthy controls (5 mol L^?1, age 25.8 ± 4.6 years) underwent electrogastrography and ¹³C‐octanoate gastric emptying study using a 480 kcal solid meal. Heart rate variability (LF/HF ratio) and corticotrophin‐releasing factor, adrenocorticotropic hormone (ACTH), and cortisol serum levels were also evaluated. Dyspeptic symptoms were scored by analogue visual scale and expressed as symptoms total score (TS). The protocol was repeated twice in each subject, with and without a mental stress test before the meal. Key Results Mental stress significantly increased postprandial symptoms severity in patients (TS: stress 111 ± 18 vs basal 50 ± 10; P < 0.05). Low‐/high‐frequency component ratio was significantly higher in patients after MS at 120 min (stress 5.46 ± 0.41 vs basal 3.41 ± 0.64; P < 0.01) and 180 min (stress 5.29 ± 0.2 vs basal 3.58 ± 0.19; P < 0.05). During stress session, in patients we found a significantly higher ACTH level than baseline at 30, 60, 90, 150, 210, 240, and 270 min and a significantly higher cortisol level at 30, 60, 90, 120, 210, and 270 min. Gastric emptying rate and electrical activity were not influenced by MS. Conclusions & Inferences In PDS patients, administration of MS before meal increases symptoms severity by inducing sympathetic hyperactivity and increased stress hormones levels. As the gastric emptying looks not altered, we conclude that these neurohormonal responses mainly affect sensitive function.