There are no pediatric norms for gastric emptying (GE) measured by nuclear scintigraphy. The ¹³ C-labeled, stable isotope GE breath test (GEBT) is a non-radioactive alternative. We aimed to determine normative GEBT ranges in a cohort of healthy children and examine the influence of age, gender, puberty, and body surface area (BSA).

Healthy children ages 8-18 years completed the [¹³ C]-Spirulina platensis GEBT after an overnight fast. Breath samples were collected at baseline, every 15 min × 1 h, then every 30 min for 4 h total. The ¹³ CO₂ excretion rate was determined by the change in ¹³ CO₂ /¹² CO₂ over time in each breath sample, expressed as kPCD (Percent ¹³ C Dose excreted/min). A mixed model with random time was used for multivariable analysis and outcome fit into a quadratic model.

The 100 subjects completed the test meal within allotted time. Median (IQR) age was 13.5 (11.3-15.5) years; 51% were female. Females had lower ¹³ CO₂ excretion rates (slower GE) than males across time (p < 0.001) while decreased excretion rates correlated with higher BSA (p = 0.015). Gender differences were also noted within pubertal stages with females showing slower GE. Multivariable analysis suggested that pre-pubertal children have faster GE than both peri- and post-pubertal groups (p < 0.0001).

Gender, puberty, and BSA influence GE rates in healthy children more than age. Although further data are needed, pubertal stage and hormonal influences may be unique factors to consider when assessing GE in children.

¹³ C-gastric emptying breath tests (¹³ C-GEBT) are validated, reliable, and non-invasive tools for measurement of gastric emptying (GE) velocity of solids and liquids without radiation exposure or risk of toxicity. They are recommended and routinely used for clinical purposes in adult as well as pediatric patients and can be readily performed onsite or even at the patient's home. However, the underlying methodology is rather complex and test results can be influenced by dietary factors, physical activity, concurrent diseases, and medication. Moreover, epidemiological factors can influence gastric emptying as well as production and exhalation of ¹³ CO₂ , which is the ultimate metabolic product measured for all ¹³ C-breath tests. Accordingly, in this issue of Neurogastroenterology & Motility, Kovacic et al. report performance of the ¹³ C-Spirulina breath test in a large group of healthy children and show significant effects of gender, pubertal status, and body size on test results. The purpose of this mini-review is to evaluate the clinical use of ¹³ C-GEBT in adults and children, exploring available protocols, analytical methods, and essential prerequisites for test performance, as well as the role of GE measurements in the light of the current discussion on relevance of delayed GE for symptom generation.

A novel technique to assess gastric motility by measuring the pressure in a low-volume intragastric balloon was developed to monitor (disordered) motility. We previously showed that this technique allows measuring pharmacologically induced inhibition of motility. In this study, we assessed whether it is possible to measure pharmacologically induced stimulation of gastric motility using 200 mg erythromycin. Erythromycin is a highly effective stimulator of gastric emptying and contractility.

After an overnight fast, a nasogastric balloon catheter was introduced in healthy subjects. After inflation with 120 ml of air, the catheter was connected to a pressure sensor. Intraballoon pressure was continuously recorded for 4 h. After a baseline recording of 2 h, 200 mg erythromycin was infused intravenously over 20 min while the recording continued for 2 h. Epigastric symptoms were surveyed on 100-mm visual analogue scales. Motility was quantified from the pressure recording as a gastric balloon motility index. Wilcoxon signed-rank tests were performed. Data are shown as median (interquartile range).

Six subjects were enrolled and five completed the procedures (age: 28 (25-29) years, body mass index: 24.0 (23.8-24.5) kg m^-2 ). One subject could not tolerate tube placement. Bloating, nausea, and epigastric sensation scores were 0 (0-3), 0 (0-1), and 1 (0-1) mm, respectively. Erythromycin significantly increased the motility index from 0.48 (0.41-0.51) to 0.79 (0.70-0.82) (p = 0.03).

Gastric motility assessed via pressure measurement in a low-volume intragastric balloon is able to detect pharmacologically stimulated motility in healthy subjects, which further validates this technique.

Beneficial effects of some phenolic compounds in modulation of carbohydrate digestion and glycemic response have been reported, however effects of phenolics from processed potato products on these endpoints are not well known. The aims of this study were to characterize phenolic profiles of fresh potatoes (purple, red, or white fleshed; 2 varieties each) and chips, and to examine the potential for potato phenolic extracts (PPE) to modulate starch digestion and intestinal glucose transport in model systems. Following in vitro assessment, a pilot clinical study (n=11) assessed differences in glycemic response and gastric emptying between chips from pigmented and white potatoes. We hypothesized that phenolics from pigmented potato chips would be recovered through processing and result in a reduced acute glycemic response in humans relative to chips made from white potatoes. PPEs were rich in anthocyanins (~98, 11 and ND mg/100 g dw) and chlorogenic acids (~519, 425 and 157 mg/100 g dw) for purple, red and white varieties respectively. While no significant effects were observed on starch digestion by α-amylase and the α-glucosidases, PPEs significantly (p<0.05) decreased the rate of glucose transport, measured following transport of 1,2,3,4,5,6,6-d7 -glucose (d7-glu) across Caco-2 human intestinal cell monolayers, by 4.5-83.9%. Consistent with in vitro results, consumption of purple potato chips modestly but significantly (p<0.05) decreased blood glucose at 30 and 60 minutes post consumption compared to white chips without impacting gastric emptying. These results suggest that potato phenolics may play a modest role in modulation of glycemic response and these effects may result in subtle differences between consumer products.

In gastroenterological practice, breath tests (BTs) are diagnostic tools used for indirect, non-invasive assessment of several pathophysiological metabolic processes, by monitoring the appearance in breath of a metabolite of a specific substrate. Labelled substrates originally employed radioactive carbon 14 ((14)C) and, more recently, the stable carbon 13 isotope ((13)C) has been introduced to label specific substrates. The ingested (13)C-substrate is metabolized, and exhaled (13)CO2 is measured by mass spectrometry or infrared spectroscopy. Some (13)C-BTs evaluate specific (microsomal, cytosolic, and mitochondrial) hepatic metabolic pathways and can be employed in liver diseases (i.e. simple liver steatosis, non-alcoholic steato-hepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug and alcohol effects). Another field of clinical application for (13)C-BTs is the assessment of gastric emptying kinetics in response to liquids ((13)C-acetate) or solids ((13)C-octanoic acid in egg yolk or in a pre-packed muffin or the (13)C-Spirulina platensis given with a meal or a biscuit). Studies have shown that (13)C-BTs, used for gastric emptying studies, yield results that are comparable to scintigraphy and can be useful in detecting either delayed- (gastroparesis) or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects. Thus, (13)C-BTs represent an indirect, cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease, and several other potential applications are being studied.

Acotiamide is a first-in-class drug that is used to treat functional dyspepsia (FD). It is considered that acotiamide acts as an antagonist on muscarinic autoreceptors in the enteric nervous system and inhibits acetylcholinesterase activity. We examined the effect of acotiamide on gastric emptying in healthy adult humans.

Twelve healthy adult males were enrolled in this double-blind crossover study. Acotiamide or placebo was administered orally in the 12 subjects 30 min before ingestion of a nutritional liquid meal (400 Kcal/400 mL). Six of the 12 participants took 100 mg of acotiamide or placebo, and six of the 12 participants took 300 mg of acotiamide or placebo in a double-blind crossover fashion. All subjects underwent measurement of gastric emptying by the (13) C breath test.

After the meal with placebo was ingested, the %dose/h curve ascended. The %dose/h curve after a meal with 100 or 300 mg of acotiamide ascended in an identical manner compared with the results with placebo. No significant differences were observed at any studied time point, and there were no significant changes in gastric emptying parameters (gastric emptying coefficient, t-1/2ex and t-lag ex).

A single administration of 100 or 300 mg of acotiamide did not affect gastric emptying after a liquid meal in healthy adult humans. Acotiamide has profound effects on restoring delayed gastric emptying and impaired accommodation in patients with FD but may have no effect on gastric emptying in healthy subjects. Such pharmacological actions have not been observed in previous gastroprokinetic studies.

To understand whether any change in gastric emptying (GE) is physiologically relevant, it is important to identify its variability. Information regarding the variability of GE in overweight and obese individuals is lacking. The aim of this study was to determine the reproducibility of GE in overweight and obese males.

Fifteen overweight and obese males [body mass index 30.3 (4.9) kg/m(2)] completed two identical GE tests 7 days apart. GE of a standard pancake breakfast was assessed by (13)C-octanoic acid breath test. Data are presented as mean (±SD).

There were no significant differences in GE between test days (half time (t1/2): 179 (15) and 176 (19 min), p = 0.56; lag time (tlag): 108 (14) and 104 (8) min, p = 0.26). Mean intra-individual coefficient of variation for t1/2 was 7.9% and tlag 7.5%. Based on these findings, to detect a treatment effect in a paired design with a power of 80% and α = 0.05, minimum mean effect sizes for t1/2 would need to be ≥14.4 min and tlag ≥ 8.1 min.

These data show that GE is reproducible in overweight and obese males and provide minimum mean effect sizes required to detect a hypothetical treatment effect in this population.

Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis.

Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a (13) C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels.

Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL(-1) vs 29.9 ± 7.7 pg mL(-1), P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal.

Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis.

To investigate the phenomenon of remnant gastric motility and emptying after local resection.

Fifteen dogs were divided into three groups: a control (CONT) group, a group that underwent local resection of the greater (GREAT) curvature, and a group that underwent resection of the lesser (LESS) curvature. We conducted a strain gauge force transducer study, a [(13)C]octanoic acid breath test ((13)C-OBT), and a mosapride citrate effect test. Based on these results, we worked out the receptive relaxation (RR), motility index (MI), and postprandial period (PP) in the postprandial state, and the frequency, duration, and MI of phase III in the fasted state. The half emptying time (T (1/2)) of (13)C-OBT was also calculated. The MI was compared according to the mosapride effect test results.

Postprandial RR, antro-pyloro-duodenal coordination, and fasting contractions were maintained in all three groups. Receptive relaxation was significantly shorter in the LESS group than in the other groups. Motility index was significantly lower in both treatment groups than in the CONT group. The PP was significantly longer in the GREAT group than in the other two groups. The (13)CO(2) excretion curves did not differ significantly among the groups. The duration of phase III was remarkably less in the treatment groups than in the CONT group, and MI was significantly lower in the LESS group than in the other groups in the fasted state. The MI increased remarkably after mosapride administration in the CONT group, showing no differences in other objective groups.

Gastric function was maintained after gastric local resection, although its motility decreased.

The (13)C octanoic acid breath test (OBT) was first developed as an alternative method of measuring gastric emptying (GE) to scintigraphy. There has been much debate about the test duration and how often measurements need to be taken. This study aims to address these issues.

For 78 GE tests using the (13)C OBT, GE lag phase (T(lag)) was calculated while sampling more frequently than the recommended every 15 min. Comparisons between T(lag) were completed using Bland-Altman plots. Similarly, 4 or 6 h test durations were assessed to establish if they yield the same GE half time (T(half)). From one volunteer, samples were taken every 1 min for the first 30 min and then every 15 min until 6 h. GE times were then calculated using different combinations of sampling times. Evidence of a visible T(lag) was also explored from this data.

Findings indicated that taking samples every 5 min for the first 30 min instead of every 15 min did not change the GE T(lag) based on Bland-Altman plots. The correlation between these two methods was also high (r(2) = 0.9957). The findings showed that the difference between the two sampling durations 4 and 6 h was large and the correlation between the methods was low (r(2) = 0.8335). Samples taken at a rate of one breath per min indicated lack of a visible T(lag).

Sampling for the (13)C OBT should be completed every 15 min for 6 h.

Standardization of the (13)C-octanoic acid breath test is still lacking.

To evaluate the accuracy of the (13)C-octanoic acid breath test using a new standardized ready-to-eat, gluten-, glucose-, and lactose-free muffin.

Healthy subjects were recruited and sorted by sex and age. Patients with diabetic gastroparesis and untreated celiac disease with known gastric motility disorders were also tested with the new labelled muffin. Expired breath (13)CO(2) was analysed and t(1/2) was calculated.

Overall, 131 healthy subjects were enrolled. The reference range of t(1/2) was 88+/-29min with the value of 146min as the upper limit of normal range. No significant difference in t(1/2) was found among subjects sorted by sex or age. The within-subject variability of t(1/2) was 17%. Mean (+/-standard deviation) t(1/2) values were 179+/-50min in patients with diabetic gastroparesis (n=8) and 151+/-20min in those with untreated celiac disease (n=11) (p

CONCLUSIONS

A new standardized test meal simplifies the execution of the (13)C-octanoic acid breath test, is not influenced by sex or age, has low intra-individual variability, is palatable, does not cause side effects, and is able to evaluate gastric emptying in both patients and healthy controls. Moreover, it can be used in subjects with lactose intolerance, diabetes, and celiac disease.

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The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin, GLP-1, and GIP, and gastric emptying (by a breath test) in 7 healthy humans after intragastric infusions of 1) 50 g sucrose in water to a total volume of 500 ml (approximately 290 mosmol/l), 2) 80 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 0.4 mM sucralose), 3) 800 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 4 mM sucralose), and 4) 500 ml normal saline (approximately 300 mosmol/l), all labeled with 150 mg 13C-acetate. Blood glucose increased only in response to sucrose (P<0.05). GLP-1, GIP, and insulin also increased after sucrose (P=0.0001) but not after either load of sucralose or saline. Gastric emptying of sucrose was slower than that of saline (t50: 87.4+/-4.1 min vs. 74.7+/-3.2 min, P<0.005), whereas there were no differences in t50 between sucralose 0.4 mM (73.7+/-3.1 min) or 4 mM (76.7+/-3.1 min) and saline. We conclude that sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans.

Impairment of gastric emptying is well recognized in patients with diabetes mellitus (DM), especially long-standing insulin-dependent diabetes mellitus (IDDM). The aim of this study was to evaluate the cause of delayed gastric emptying in DM patients.

In 16 controls, 16 non-insulin-dependent diabetes mellitus (NIDDM) patients and 23 IDDM patients, gastric emptying was studied using the (13)C octanoic acid breath test. Breath samples were taken before a test meal labeled with 100 mg of (13)C octanoic acid, and at 15-min intervals over a 300-min period postprandially.

In all DM patients, the gastric emptying coefficient was lower than that in the controls (P < 0.05), and lag time and half-emptying time were significantly longer (P < 0.05). Both NIDDM and IDDM patients showed delayed (13)CO(2) excretion compared with the controls, but IDDM patients showed more delayed gastric emptying than NIDDM patients (P < 0.05). There were no significant differences in sex, HbA1c level, or the rate of neuropathy between the two groups.

IDDM patients showed delayed gastric emptying compared with NIDDM patients, and the (13)C octanoic acid breath test is useful for evaluating DM patients with delayed gastric emptying.

Disturbance of gastric emptying leads to a variety of symptoms. Furthermore, gastric motility disorders might play a role in the pathophysiology of functional dyspepsia. In previous studies 13C breath tests were validated as non-invasive tools in the measurement of gastric emptying time. So far, reliable reference values of healthy subjects are missing and the impact of constitutional traits (age, sex, body mass index [BMI]) needs to be clarified.

A study was conducted in 90 healthy individuals (45 men, 45 women) that assessed the correlation of parameters of gastric emptying (half gastric emptying time [T1/2] and time of fastest gastric emptying [T(lag)]) with age, sex and BMI for fluid and solid test meals by 13C breath tests. 100 mg of sodium acetate or sodium octanoate, respectively, were used as tracers. Breath probes were analyzed by non-dispersive infrared spectroscopy.

The mean +/- SD of half gastric emptying time (T1/2) of a fluid test meal was determined to be 80.5 +/- 22.1 min and for T(lag) to be 40.3 +/- 10.2 min. However, the T1/2 and T(lag) of solid meals did not fit to normal distribution and thus median and percentiles were determined. The median time of T1/2 for solids was 127 min (25-75% percentiles: 112.0-168.3 min) and 81.5 min for T(lag) (25-75% percentiles: 65.5-102.0 min). No significant correlation was found between gastric emptying and age, sex or BMI.

This is the first study to examine gastric emptying in an adequate number of healthy subjects by 13C breath tests. No significant correlation was found with age, sex and BMI. Although there is considerable standard deviation in gastric emptying time, these results may nevertheless serve as reference values for further studies.

The dynamic change in gastric emptying on a minute-by-minute basis (gastric velocity) is evaluated by the 13C-octanoate breath test with deconvolution analysis. However, deconvolution is impractical, because it requires dual experiments to obtain 13CO2 excretion profiles following intraduodenal and oral administration of 13C-octanoate. We investigated whether the Wagner-Nelson method, used in drug absorption studies, can determine the velocity profile based on a single experiment as accurately as deconvolution, and whether the velocity assessed by the Wagner-Nelson method is sensitive enough to detect subtle changes in gastric emptying induced by butylscopolamine.

Five male volunteers underwent a 4-h breath test twice, after intraduodenal administration of 20 ml normal saline containing 100 mg 13C-octanoate and after ingestion of a 320-kcal muffin containing 100 mg 13C-octanoate. Deconvolution determined the velocity profile by subtracting duodenal from oral data, and the Wagner-Nelson method produced it from only oral data. The velocity profiles were compared between the two methods. Another six male subjects underwent the breath test by ingesting a muffin twice, once with and once without 20 mg oral butylscopolamine. The velocity profiles generated by the Wagner-Nelson analysis and the conventional 13CO2 excretion curves were compared between the two occasions.

The two techniques yielded identical velocity profiles. The velocity profile detected a significant change in the emptying pattern induced by butylscopolamine (initial acceleration with subsequent deceleration), while the conventional breath curves failed to detect this change.

Velocity assessment by a Wagner-Nelson analysis can precisely describe altered gastric emptying, based on a single experiment.

1. In the [(13)C]-octanoic acid breath test, the time versus pulmonary [(13)CO(2)] excretion rate curve is analysed using mathematical curve-fitting techniques to calculate gastric emptying parameters. Thus, the goodness-of-fit highly influences the accuracy of the breath test. However, a double-peaked [(13)CO(2)] excretion curve, which occasionally develops owing to the presence of an interval of quiescent gastric emptying (the plateau phase), is likely to be fitted poorly. 2. In pharmacokinetics, the Wagner-Nelson method has been used to describe precisely the absorption kinetics of orally administered drugs and its reliability is independent of the nature of gastric emptying. A recent study has shown the potential of the Wagner-Nelson method to generate a realistic gastric emptying flow curve from [(13)CO(2)] excretion data. In the present report, we have demonstrated that the Wagner-Nelson method can visualize the plateau emptying phase responsible for the cases of double peaks. 3. Wagner-Nelson analysis applied to the breath test described precisely the characteristic emptying pattern of the two emptying phases being interrupted by the plateau phase. Conventional analysis for the breath test failed to detect the plateau phase. 4. The Wagner-Nelson method is a useful tool for analysing atypical double-peaking [(13)CO(2)] excretion curves.

To compare the effectiveness of 70-mg and 200-mg doses of intravenous erythromycin in improving gastric emptying in critically ill patients.

Gastric emptying was measured on consecutive days; day 1 (pre-treatment), day 2 (post-treatment) after an intravenous infusion of either 70 or 200 mg erythromycin or saline placebo (0.9%), in a randomized double-blind fashion.

Mixed medical/surgical intensive care unit, tertiary referral.

Thirty-five randomly selected, mechanically ventilated, enterally fed critically ill patients (median APACHE II score 19 on admission).

On day 2 either 70 or 200 mg erythromycin or saline was administered intravenously over 20 min.

Gastric emptying was measured using the [13C]octanoic acid breath test. The gastric emptying coefficient (GEC) and half-emptying time (t1/2) were calculated from the area under the 13CO2-recovery curve. Pre-treatment gastric emptying measurements were similar in all three patient groups. Treatment with both doses of erythromycin significantly reduced the gastric t1/2: 70 mg, 98 min (IQR 88-112); 200 mg, 86 min (75-104); vs. placebo, 122 min (102-190) (p<0.05). The GEC was higher with both doses of erythromycin: 70 mg, 3.8 (3.3-4.0); 200 mg, 4.0 (3.6-4.2); vs. placebo, 2.9 (2.5-3.7) (p<0.05). There was no difference in gastric emptying post-treatment between the two doses of erythromycin. The effect of erythromycin was greatest in patients with delayed gastric emptying.

Treatment with 70 and 200 mg intravenous erythromycin are equally effective in accelerating gastric emptying in the critically ill.

Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers.

The (13)C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs (13)CO(2) excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*beta*e(-k*t)*(1 - e(-k*t))(beta-1), and the parameters of k and beta were determined: under the crossover protocol, a larger (smaller) beta indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half (13)CO(2) excretion time (t(1/2b) = -[ln(1 - 2(-1/beta))]/k) and the time of maximal (13)CO(2) excretion rate (t(max) = [lnbeta]/k) were also calculated. Between the two occasions, k, beta, t(1/2b), and t(max) were compared by the Wilcoxon signed-rank test.

After smoking, k was significantly increased. No significant differences were found in beta, t(1/2), and t(max) between the two occasions.

The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers.

After a meal, the proximal stomach relaxes probably through the activation of nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of this study was to investigate the effect of sildenafil, a selective PDE-5 inhibitor, on fasting and postprandial proximal gastric volume and on gastric emptying rates in humans. A gastric barostat was used to study gastric compliance and perception to isobaric distension in healthy subjects before and after placebo (n = 13) or sildenafil, 50 mg (n = 15). In 10 healthy subjects, two gastric barostat studies were performed in randomized order to study the effect of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil significantly increased fasting intragastric volume (141 +/- 15 vs. 163 +/- 15 ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and prolonged gastric relaxation either at 30 min (357 +/- 38 vs. 253 +/- 42 ml, P < 0.05) or 60 min (348 +/- 49 vs. 247 +/- 38 ml, P < 0.05) after the meal. Sildenafil did not alter solid half-emptying time but significantly delayed liquid emptying (43 +/- 4 vs. 56 +/- 4 min, P < 0.01). In conclusion, sildenafil significantly increases postprandial gastric volume and slows liquid emptying rate, confirming that meal-induced accommodation in humans involves the activation of a nitrergic pathway. The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation.

Radioscintigraphy is the gold standard for evaluation of gastric emptying in children, but requires exposure to ionising radiation. Therefore, the aim of the study was to validate the non-radioactive 13C-acetate breath test in children in comparison to radioscintigraphy as reference method.

Twenty-nine children with dyspeptic or respiratory symptoms were tested for gastric emptying disorders simultaneously performing the 13C-acetate breath test and radioscintigraphy.

A semisolid oatmeal was doubly labelled with 150 mg 13C-acetate and 50 MBq 99mTechnetium. Breath samples were collected every 5-10 min for 4 h. After mass spectrometrical 13C-analysis, curve fitting of the 13C-cumulative recovery to the modified power exponential function Y = m(1 - e(-kt) calculated the half emptying times of the breath test (t 1/2 (breath)). Scintigraphic image acquisition began immediately after the ingestion of the 99mTechnetium-labelled testmeal at a rate of one frame every 60 s for 1 h.

Six children showed delayed gastric emptying in scintigraphy (t 1/2(scinti) > 60 min). All these children had prolonged half emptying times t 1/2 (breath) in the 13C-acetate breath test. Using a cut-off t 1/2(breath) > 90 min, the 13C-acetate breath test had a sensitivity of 100% and a specificity of 85%. Scintigraphic and breath test half emptying times were linearly correlated (Y = 0.80x + 47.68, r = 0.76, P < 0.00001).

The 13C-acetate breath test proves to be a reliable, non-radioactive alternative for measuring gastric emptying in children.

The aim of this study was to develop a stomach-specific drug delivery system to increase the efficacy of amoxicillin against Helicobacter pylori. Polyacrylic acid (PAA), chitosan (CS), and amoxicillin (A) were employed to obtain polyionic complexes. The design of the hydrogel delivery system was based on the swellable approach; with a floating feature to prolong the Gastric Residence Time (GRT). The polyionic complex (PAA:CS:A 2.5:5:2) showed a sustained drug release profile in enzyme-free simulated gastric fluid (SGF) and pH 4.0. A pH independent swelling-eroding pattern with adequate maximum swelling ratios of 17.76 and 13.42 was obtained at in SGF and pH 4.0, respectively, with similar eroding profiles in both pH media. This network carrier provides an amoxicillin protective effect towards the hydrolytic degradation in SGF. The in vivo study was performed on healthy volunteers, using the [13C] octanoic acid breath test. The proposed hydrogel showed a prolonged GRT of up to 3 h. The preliminary results from this study suggest that amoxicillin polyionic complexes have potential for improving local antibiotic therapy against H. pylori.

In patients with diabetic gastroparesis, delayed food delivery to the intestine may become a major obstacle to post-prandial glycaemic control.

To investigate whether cisapride accelerates gastric emptying in the long term or improves diabetes control in patients with diabetic gastroparesis.

Eighty-five patients with long-standing insulin-dependent diabetes mellitus (glycosylated haemoglobin (HbA1c) > 7.0%), dyspepsia and diabetic neuropathy were tested for impaired gastric emptying of solids by the 13C-octanoate breath test. Nineteen of these patients with severe diabetic gastroparesis (i.e. t1/2 > 170 min) were randomly treated with 10 mg cisapride t.d.s. (n=9) or placebo (n=10) for 12 months. Thereafter, the breath test, dyspeptic symptoms and HbA1c values were reassessed.

Half emptying times in nine patients with diabetic gastroparesis were significantly shortened by cisapride (175 +/- 46 min vs. 227 +/- 40 min; P < 0.03). Half emptying times in the 10 patients taking placebo did not change (205 +/- 37 min vs. 211 +/- 36 min, P=0.54). Cisapride significantly reduced dyspepsia (score: 4.1 +/- 1.6 vs. 2.0 +/- 0.5, P=0.002). HbA1c values after 12 months of treatment were not different (cisapride: 7.7 +/- 0.4% vs. 7.6 +/- 0.9%, P=0.76; placebo: 7.5 +/- 0.6% vs. 7.6 +/- 1.5%, P=0.89).

Prokinetic treatment with cisapride accelerates gastric emptying of solids and improves dyspeptic symptoms in diabetic gastroparesis. Glycaemic control, however, is not affected by cisapride.

Delayed gastric emptying and/or gastrointestinal symptoms occur in 30-50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA(1c), thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology.

Gastric emptying of solids and liquids (measured by (13)C-octanoic acid and (13)C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 +/- 15 years; mean HbA(1c) 7.8 +/- 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed.

Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA(1c) level (beta = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA(1c), autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic neuropathy score (r = -0.79, P = 0.001).

We found that approximately 50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.

Noninvasive breath tests may have significant utility for the measurement of gastric emptying in mice, but the tests' sensitivity for detection of changes in gastric emptying has not been evaluated.

Hydroxypropyl methyl cellulose was incorporated into a liquid meal to delay gastric emptying, and mice were injected with erythromycin to accelerate emptying of a liquid or solid meal. All test meals were labelled with (13)C-acetic acid or (13)C-octanoic acid. Breath samples collected at intervals were analysed for (13)CO(2) content, and gastric emptying rates were calculated from the resultant (13)CO(2) excretion curves.

As predicted, hydroxypropyl methyl cellulose slowed emptying compared with water (14.21 +/- 0.94 min vs. 9.17 +/- 0.47 min, P < 0.001), while erythromycin treatment accelerated emptying of liquids (10.96 +/- 0.78 min vs. 16.41 +/- 1.94 min, P < 0.05) and solids (108.81 +/- 18.06 vs. 157.95 +/- 12.01 min, P < 0.05) compared with the saline injected controls.

These data indicate that in mice the breath test is sensitive enough to detect differences in gastric emptying induced by meal composition and pharmacological agents. Noninvasive measurement of gastric emptying in mice will be useful as a method to evaluate the effect of nutrients or drugs on the motility of the gastrointestinal tract.

Breath tests have been used in research laboratories for over 25 y. Originally, the tests were based on the use of (14)C, rather than on the nonradioactive isotope, (13)C. When (13)C became widely available at a reasonable cost, research groups in the United States and Europe developed methodologies to measure (13)C abundance in samples of CO(2). The tests used a variety of substrates and measured pancreatic function, fat absorption, bacterial overgrowth and P(450) mixed-function oxidase. Thus far, the only test to be approved by the Food and Drug Administration is the (13)C-urea breath test. This manuscript describes the process by which approval is gained, and indicates the steps necessary for other tests to receive Food and Drug Administration approval.

1. Gastric emptying studies in small laboratory animals are hampered by the deficiency of a technique that is non-invasive and repeatable. The aim of the present study was to adapt the non-invasive [13C]-octanoic acid breath test, which has been validated in humans, to assess both liquid and solid gastric emptying in the mouse. 2. Gastric emptying rates were investigated for a liquid meal (Intralipid; Kabi Pharmacia AB, Stockholm, Sweden; n = 7) and two solid meals (egg yolk and mouse chow; n = 7) incorporating [13C]-octanoic acid. All meals were analysed for natural enrichment of [13C]. Mathematical analysis of the 13CO2 excretion rate allowed the determination of gastric emptying parameters. 3. Gastric emptying of Intralipid was more rapid than egg yolk (P < 0.0001). Gastric emptying of mouse chow could not be assessed due to intragastric separation of [13C]-octanoic acid and natural [13C] enrichment of the pellet. 4. The [13C]-octanoic acid breath test can reproducibly assess both liquid and solid gastric emptying non-invasively in the mouse. This method can now be used to assess gastric emptying in drug studies and disease studies for which there are established mouse models.

The 13C-octanoic breath test (13C-OBT), a recently developed technique to evaluate gastric emptying of solids, has been validated in comparison to scintigraphy with low caloric meals (250 kcal). However, there is consensus that for clinical studies total caloric load should be in excess of 300 kcal, but studies comparing 13C-OBT results after low and medium caloric meals are lacking.

Ten healthy subjects were given a 250-kcal and a 550-kcal meal in randomized order. Gastric emptying was assessed simultaneously by ultrasonography and 13C-OBT. Breath samples were taken according to both classic (21 samples over 5 h) and simplified (11 samples) schedules.

Increasing the meal energy content resulted in significantly longer half emptying time (T(1/2)) estimates by both ultrasonography (P < 0.01, Wilcoxon test) and 13C-OBT (P < 0.05). T(1/2) estimates by the two methods significantly correlated for both the 250 (r(s) = 0.733, P = 0.018) and the 550 (r(s) = 0.637, P = 0.035) kcal meal. However, differences between T(1/2) estimates by 13C-OBT and ultrasonography were greater after the 550- than the 250-kcal meal (median 172.5 versus 76.5 min, P < 0.05). Interindividual variability was also 2-fold greater for indexes estimated by 13C-OBT with the 550-kcal meal compared with the 250-kcal meal. For both meals 13C-OBT yielded similar results with the classic and simplified schedules.

In healthy subjects caloric intake is a major determinant of gastric emptying rate. However, after a medium caloric meal 13C-OBT shows some inaccuracy, which raises questions about its routine clinical application. Nevertheless, when using 13C-OBT one must take into account that the simplified schedule is just as effective as the classic one, and is far lower in cost.

To evaluate capsaicin's effects on heartburn, dyspepsia, gastric acidity and emptying, and gastro-oesophageal reflux, and to test the hypothesis that capsaicin induces heartburn and exacerbates symptoms by sensitizing the oesophagus.

Eleven heartburn sufferers underwent two separate pH monitoring sessions and assessments of gastric emptying (13C-octanoic acid breath test), heartburn and dyspepsia (100 mm VAS) after a non-irritant meal. The meal consisted of a sausage biscuit with egg, cheese and 30 g raw onion, 8 oz chocolate milk and a peppermint patty. Thirty minutes prior to meal consumption, subjects were administered a placebo capsule. On visit 1, subjects consumed the meal containing 100 microl 13C-octanoic acid cooked in the egg, over 15 min. On visit 2, subjects consumed the meal plus 5 mg capsaicin in gelatin capsules.

Oesophageal and gastric pH profiles and gastric emptying were not different between meals. Capsaicin did not alter mean heartburn and dyspepsia scores (P > 0.05), but significantly decreased time to peak heartburn (120 min vs. 247 min; P < 0.003). Time to peak dyspepsia was not altered by capsaicin (P > 0.05).

Capsaicin enhances noxious postprandial heartburn, presumably by direct effects on sensory neurons.

There is controversy in the literature on the effects of anticholinergic drugs on gastroesophageal reflux. Our aim was to study more extensively the effects of an oral anticholinergic drug on esophageal motility and gastroesophageal reflux in normal ambulant subjects under different circumstances: upright, supine, fed, and fasted state.

Fifteen healthy subjects (seven men, eight women), mean age 34 yr (range, 22-61 yr) underwent randomized placebo-controlled 16-h evening and overnight ambulatory esophageal motility/pH study. After a 3-day loading dose of either oral dicyclomine (Dic) 20 mg four times daily or placebo (Pla), an ambulatory esophageal motility/pH study was performed while taking medication or placebo. Each study was analyzed for meal, first and second h postprandial, upright and supine periods, and first 2 h supine after bedtime snack.

The mean number of reflux episodes decreased with dicyclomine during the first h postprandial (Dic, 1.9 vs Pla, 2.5; p < 0.05). During the first 2 h supine, mean number of reflux episodes increased with dicyclomine (Dic, 1.4 vs Pla, 0.8; p < 0.09), as did mean percent time pH < 4 (Dic, 2.6 vs Pla, 0.5; p < 0.04), with an increase in clearance time (Dic, 0.9 vs Pla, 0.3; p < 0.05; in min). Mean peristaltic amplitude decreased with dicyclomine during the 2nd h postprandial (Dic, 48.8 vs Pla, 56.3; p < 0.04).

Oral dicyclomine caused a decrease in early postprandial upright reflux episodes, but also significantly increased the percent time pH < 4 during the first two h supine. Therefore, its effects are dependent on body position and fasted or fed state. Our results justify additional studies with oral anticholinergic agents in patients with gastroesophageal reflux disease.

Since there is a need for a widely applicable non-invasive test to assess gastric emptying in diabetic patients, we evaluated the sensitivity, specificity, and reproducibility of the [13C]octanoic acid breath test as compared with scintigraphy. Moreover, we examined the relationship between the breath test indices and gastric symptoms, cardiovascular autonomic function, and metabolic parameters. Forty healthy control subjects and 34 diabetic patients were studied. Three indices of gastric emptying, assessed by the breath test, were computed: half-emptying time (t1/2breath), gastric emptying coefficient (GEC), and lag phase. Furthermore, the half-emptying time, measured by scintigraphy (t1/2scint), was calculated and gastric symptoms and cardiovascular autonomic neuropathy (CAN) were scored. The coefficients of variation of day-to-day reproducibility in 10 healthy subjects were 29.6% for t1/2breath, 7.4% for GEC, and 46.5% for lag phase. An abnormal delay for t1/2scint (> 100 min) or t1/2breath (> 200 min) was noted in 12 patients. Based on the results for t1/2scint, the sensitivity of t1/2breath and GEC was 75% and the specificity was 86%. Both t1/2breath (rs = 0.523; p < 0.05) and GEC (r2 = -0.594; p < 0.05) were significantly associated with the gastric symptom score. A significant relationship to the CAN score was demonstrated for t1/2breath (rs = 0.448; p < 0.05), GEC (rs = -0.467; p < 0.05), and t1/2scint (rs = 0.602; p < 0.05). There were no significant associations of the breath test indices with the blood glucose levels during the test, HbA1c, age, and duration of diabetes. In patients with abnormal t1/2scint (n = 12) not only was t1/2breath significantly prolonged and GEC reduced, but also the scores of CAN and gastric symptoms were significantly increased as compared with those who had a normal t1/2scint (n = 22). We conclude that the [13C]octanoic acid breath test represents a suitable measure of delayed gastric emptying in diabetic patients which is associated with the severity of gastric symptoms and CAN but not affected by the blood glucose level.

Ultrasound measurement of gastric emptying has potential advantages over scintigraphy, but there is little information about its accuracy.

The relation between ultrasonographic measurements of antral area and (a) scintigraphic measurements of gastric emptying and intragastric distribution of liquids (b) postprandial satiation, were evaluated.

Seven normal volunteers were studied.

Each subject drank 75 g dextrose dissolved in 350 ml of water (300 kcal) or beef soup (20 kcal), both labelled with technetium-99m sulphur colloid on separate days and had measurement of gastric emptying by scintigraphy and ultrasound.

Scintigraphic and ultrasound 50% emptying times (T50s) were comparable and longer (p < 0.001) for dextrose than soup mean (SEM) (dextrose 107 (16) min v 108 (18) min, soup 24 (4) min v 23 (5) min). There were close correlations between scintigraphic and ultrasound T50s (dextrose r = 0.94, p < 0.005, soup r = 0.97, p < 0.001) and between the time at which the distal stomach content decreased from its maximum value by 50% (measured scintigraphically) and the ultrasound T50 (dextrose r = 0.95, p < 0.005, soup r = 0.99, p < 0.0001). In contrast, there was no significant relation between the distal stomach content when expressed as a percentage of the maximum content in the total stomach and the ultrasound T50. After dextrose, fullness was related (r = 0.92, p < 0.01) to the postprandial increase in antral area measured by ultrasound.

Ultrasound measurements of gastric emptying are: (a) of comparable sensitivity to scintigraphy in quantifying emptying of both low and high nutrient liquids (b) correlate with postprandial satiation, suggesting that the latter may be mediated by antral distension.

Currently, stable isotope techniques in breath tests using 13C-labeled substrates are limited to a few centers equipped with expensive and complex isotope ratio mass spectrometry (IRMS). Although breath samples can be mailed to these centers, widespread application of 13C breath tests would be more feasible with a cheaper and more practicable analysis system at hand.

We therefore tested the newly developed nondispersive isotope-selective infrared spectrometer (NDIRS) with reference to IRMS in a clinical setting comparing the results of both techniques in 538 consecutive 13C-urea breath tests performed for the detection of Helicobacter pylori infection.

With NDIRS five false-positive and three false-negative results were observed; that is, the sensitivity of NDIRS was 98.3%, and the specificity was 98.6%. The delta over base-line values of both devices correlated linearly (Y = 0.87 +/- 0.01 X + 0.29 +/- 1.5; r = 0.95; p < 0.0001; n = 538).

When running this large number of breath tests in 3 days, the NDIRS proved to be a reliable, stable, and easy-to-operate analytical tool, which is well qualified for gastroenterologic application in the diagnostic routine. Both the price and the easy handling of NDIRS will facilitate the widespread use of the noninvasive stable isotope technique for 13C breath tests.

[13C]Acetate and [13C]octanoate breath tests were used to analyze the gastric emptying of liquids and solids in healthy controls and patients with functional dyspepsia both with and without cisapride. A standard test meal was labeled with either 150 mg [13C]acetate (liquid phase labeled in the water) or with 100 mg [13C]octanoate (solid phase labeled in the egg yolk). Six patients with dyspepsia and six healthy controls underwent a 4-hr breath test four times, ie, both the [13C]acetate and [13C]octanoate test with and without cisapride. Duplicate [13C]acetate or [13C]octanoate breath tests were performed in another 12 healthy controls in order to assess day-to-day variability of gastric emptying for liquids and solids. The mass spectrometric data were fitted to a power exponential function allowing mathematical analysis of half-emptying times and lag times. In patients with dyspepsia, gastric half emptying times of solids were significantly delayed as compared to the emptying of solids in the controls (203 +/- 41 vs 148 +/- 35 min; P < 0.05). With cisapride, gastric emptying of solids was significantly accelerated (P < 0.05) both in the patients (166 +/- 58 min) and in the controls (117 +/- 27 min). The gastric emptying of liquids did not differ in patients and controls, and cisapride had no effect on the emptying of liquids within the normal range. In the healthy controls, half emptying times both for liquids and solids were reproducible on the two different days (CVintra: 5.58% for liquids, 20.01% for solids).(ABSTRACT TRUNCATED AT 250 WORDS)

The current standard for gastric emptying studies are radioactive isotope methods. [13C]breath tests have been developed as a nonradioactive alternative. The aim of this study was to validate a [13C]acetate breath test as a measure of gastric emptying of the liquid phase both in liquid and semisolid test meals by simultaneous radioscintigraphy.

Thirty-five patients with dyspeptic symptoms and 20 healthy volunteers were tested using a semisolid oatmeal or a liquid test meal. Both test meals were labeled by 150 mg sodium [13C]acetate and (in patients) by 45 MBq 99mTc-albumin colloid. Half-time of gastric emptying was calculated after curve fitting of the 13C exhalation to a modified power exponential function. 99mTc-albumin emptying was measured by conventional radioscintigraphy.

The half-emptying times for the [13C]acetate breath test closely correlated to those measured by radioscintigraphy both for semisolids (r = 0.87) and liquids (r = 0.95). The time of maximum 13CO2 exhalation was itself a reliable parameter compared with the half-emptying times obtained by scintigraphy (r = 0.85 for semisolids; r = 0.94 for liquids).

The [13C]acetate breath test is a reliable and noninvasive tool for the analysis of gastric emptying rates of liquid phases without radiation exposure.

Measurement of gastric emptying rate of solids in children is difficult because the available methods are either invasive or induce a substantial radiation burden. In this study the newly developed 13C octanoic acid breath test was used to examine the gastric emptying rate of solids and milk in healthy children and to compare gastric emptying in children and adults. Fifteen healthy children and three groups of nine healthy adults were studied, using three different test meals labelled with 50 mg of 13C octanoic acid: a low caloric pancake (150 kcal), a high caloric pancake (250 kcal), and 210 ml of milk (134 kcal). Breath samples were taken before and at regular intervals after ingestion of the test meal, and analysed by isotope ratio mass spectrometry. The gastric emptying parameters were derived from the 13CO2 excretion curves by non-linear regression analysis. No significant difference was found between children and adults in the emptying rate of the low caloric solid test meal. In children as well as in adults, increasing the energy content of the solid meal resulted in a significantly slower emptying rate. The milk test meal, however, was emptied at a faster rate in adults and at slower rate in children compared with the low caloric solid test meal. Moreover, the emptying rate of milk in children was significantly slower than in adults. In conclusion, a similar gastric emptying rate of solids but a slower emptying of full cream milk was shown in children of school age compared with adults, using the non-radioactive 13C octanoic acid breath test.

We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids.