SEARCH

SEARCH BY CITATION

Keywords:

  • inter-subject;
  • intra-subject;
  • reproducibility;
  • variation

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

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 T1/2 (GE T1/2) 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 (COVinter) for GE T1/2 were similar in M and F: overall 24.5% (M 26.0%, F 22.5%); COV are predictably lowest for GE at 4 h (COVinter 9.6%). COVintra for T1/2 and GE at 4 h were overall 23.8% and 12.6%, and were similar to COVinter 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 T1/2 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 T1/2 similarly distributed across mean GE T1/2 100–155 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.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

Measurement of gastric emptying of solids is endorsed by national societies1 for use in clinical practice to identify gastric motor function abnormalities as in gastroparesis and dumping syndrome, to investigate pathophysiological mechanisms that may be associated with patients symptoms or syndromes, such as functional dyspepsia, and to evaluate the effects of treatment, such as prokinetic agents in the treatment of gastroparesis or intestinal pseudo-obstruction2 or octreotide3 which is used in the treatment of dumping syndrome.

The most widely applied method for measuring gastric emptying involves scintigraphy. The performance characteristics of this measurement have been scarcely documented in the literature. For example, we previously reported on 37 healthy human subjects of whom approximately a half underwent repeat measurements to appraise intra-individual variation.4 Given the relatively small number of participants in the prior study and the absence of any other large study to appraise the performance characteristics of gastric emptying of solids measured using scintigraphy, the aim of this study was to assess the inter- and intra-subject variations in scintigraphic gastric emptying parameters in healthy participants, to assess whether differences in gastric emptying T1/2 were related to the average T1/2 measurement between two studies, and to ascertain if intra-subject variability was related to the time lag between studies. A second aim was to assess the associations of age, gender, and body mass index (BMI) with gastric emptying of solids.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

Data source

Data were derived in a retrospective manner from a database of previously performed gastrointestinal transit studies conducted in healthy volunteers (see Appendix for references). These volunteers included postmenopausal women and overweight and obese people without other illnesses. All the participants were evaluated by the same research team (gastroenterologist, nurses, and coordinators) in a single clinical research unit, and all had clinical evaluation, including physical examination and review of the medical records, to ensure they were healthy and had no disease that could alter gastric emptying. A screening bowel symptom questionnaire using validated questions5 was used to exclude significant gastrointestinal symptoms at the times of study.

From this database, subjects participating in studies of pathophysiology or parallel-group design clinical trials were identified; only data obtained after randomization to a placebo group were included.

All participants had provided written consent in each of the previously conducted studies. The current analysis was approved by the Institutional Review Board (IRB) at Mayo Clinic, Rochester, Minnesota. Patients who had withdrawn authorization to use their records for future research purposes had their data removed from the analysis of the current study, as required by the Mayo Clinic IRB.

Gastrointestinal transit studies

To evaluate gastric emptying parameters, our established scintigraphic method was used.6–8 After an overnight fast, subjects ingested a 99mTc-labeled meal consisting of two scrambled eggs, one slice of whole wheat bread, and one glass of skim milk. Using a gamma camera, abdominal images with anterior and posterior cameras of 2 min duration were acquired immediately following ingestion of the radiolabeled meal and at specified time points during the subsequent 4 h period, typically every 15 min during the first 2 h and every 30 min during the subsequent 2 h. No participants were taking any medications prescription or over-the-counter for the week prior to and during the testing of gastric emptying.

Data analysis

Transit measurements  99mTc counts were quantified within a 140 keV (±20%) window. A variable region of interest program was employed to quantitate counts in the stomach.

Primary endpoint was GE T1/2, which was measured by linear interpolation of the imaging data acquired during the 4-h postprandial period. In addition, we quantitated GE at 1, 2, 3, and 4 h after ingestion of the radiolabeled meal, consistent with our previous documentation that these data provide clinically relevant information9,10 and with the subsequent studies by Tougas et al.11 which formed the basis for the society recommendations.

Assessment of variation in gastric emptying measurements  The following principles were applied to select data for analysis:

1 Inter-subject variation was estimated by comparing the first complete set of transit parameters (GE T1/2, GE 1–4 h) among participants.

2 Intra-subject variation was derived from the first two transit values within short (<90 days), intermediate (90–360 days), and long (>360 day) intervals.

Statistical analysis

Endpoints of gastric emptying are expressed as mean ± SD and, where relevant, as median and 5th and 95th percentiles. Data are summarized for overall participants and by gender. Inter- and intra-subject coefficients of variation (COV) were calculated. The inter-subject COV was calculated by the SD divided by the mean and expressed as percentage. The intra-subject COV was calculated as the SD of the within subject differences divided by the overall (grand) mean of the corresponding transit measurements and expressed as a percentage. The associations of age, BMI, and gender with gastric emptying measurements were assessed using an analysis of covariance model with the gastric emptying endpoints as the response variables and age, gender, and BMI as predictors.

Bland–Altman plots12 were constructed to visually assess the intra-subject variation between gastric emptying values in a subset of subjects with repeat studies. The Pearson correlation was used to assess the relationship between differences in T1/2 measurements of gastric emptying from repeat studies and the overall mean of the two repeat studies.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

Subject characteristics

From the original database, 319 eligible subjects (214 female) were identified who had participated in a total of 22 studies which measured gastric emptying as part of specific research protocols (Appendix). The eligible participants’ characteristics are shown in Table 1.

Table 1.   Demographic Features (data show mean ± SD) (A) All participants with at least one measurement of gastric emptying (B) Participants with two measurements of gastric emptying
(A)
 All, n = 319Female, n = 214Male, n = 105
Age, year36.2 ± 13.137.2 ± 12.834.6 ± 13.3
BMI, kg m−226.9 ± 5.126.5 ± 5.327.8 ± 4.5
(B)
 All, n = 47Female, n = 31Male, n = 16
First studySecond studyFirst studySecond studyFirst studySecond study
  1. BMI, body mass index.

Age, year34.6 ± 11.136.6 ± 10.835.5 ± 10.637.7 ± 10.132.7 ± 12.234.4 ± 12.0
BMI, kg m−225.4 ± 4.325.6 ± 4.124.0 ± 3.524.3 ± 3.028.1 ± 4.628.0 ± 4.9

Intra-subject variation was estimated in 47 of the 319 participants (31 female, 16 male) in whom gastric emptying was assessed at least twice; when there were more than two studies, we selected the two that were closest in time (median 1.26 years apart, range 55 days–3.85 years).

Inter-subject variation in transit parameters

Inter-subject COV for all endpoints are summarized in Table 2A. Inter-subject COV for GE T1/2 were similar in males and females: overall 24.5% (males 26.0%, females 22.5%); COVs are predictably lowest for GE at 4 h (COVinter 9.6%).

Table 2.    (A) Values of gastric emptying at different times and inter-individual variation (B) Values of gastric emptying T1/2 on two repeat studies, and intra-individual variation
(A)
 GE T1/2 minGE 1 h, %GE 2 h, %GE 3 h, %GE 4 h, %
All participants
 Mean ± SD121.7 ± 29.818.1 ± 9.551.4 ± 15.778.1 ± 14.593.2 ± 8.9
 Median (5th, 95th %ile)120 (78.4, 174.0)17 (4.4, 35.0)50 (25.0, 78.5)80 (52.0, 98.0)96 (76.2, 100.0)
 N319319319314315
 COVinter, %24.552.730.618.69.6
Females
 Mean ± SD127.7 ± 28.716.5 ± 8.347.8 ± 14.375.3 ± 14.292.1 ± 9.4
 Median (5th, 95th %ile)125 (89.0, 180.0)16 (4.3, 31.4)47.2 (25.0, 71.0)76 (50.0, 95.9)94.8 (76.2, 100.0)
 N214214214211211
 COVinter, %22.550.529.918.810.2
Males
 Mean ± SD109.9 ± 28.621.3 ± 10.958.6 ± 15.183.8 ± 13.692.1 ± 9.4
 Median (5th, 95th %ile)105 (73.2, 165.0)19 (4.7, 40.0)60.0 (28.4, 82.0)88 (55.0, 100.0)98.3 (77.0, 100.0)
 N105105105103104
 COVinter, %26.051.327.516.27.7
(B)
All participants
 GE T1/2 Mean ± SD128.4 ± 25.1
 Delta GE T1/2 Mean ± SD−1.6 ± 30.6
 N47
 COVintra, %23.8
Female participants
 Mean ± SD130.1 ± 27.2
 Median (5th, 95th %ile)−5.2 ± 38.9
 N31
 COVintra, %22.2
Male participants
 Mean ± SD125.2 ± 20.7
 Median (5th, 95th %ile)5.5 ± 33.5
 N16
 COVintra, %26.7

Intra-subject variation in transit parameters

COVintra for T1/2 was 23.8% and was similar to the COVinter values (Table 2B). Replicate GE T1/2 results from 47 participants (Fig. 1) showed significant correlation [Pearson r = 0.46; P = 0.0012; the concordance correlation coefficient was also 0.46 (95%CI 0.20–0.65)], with a median difference of −6 min (mean −1.6, range −56 to 72 min). Although the range of these differences is wide, this plot demonstrates that, based on the 5th and 95th percentiles of 78 and 174 min, respectively (Table 2A), 37/47 (79%) were within this interval on both occasions, only 7/47 subjects were delayed (>174 min) on one of the two studies, 1/47 delayed on both occasions, and 2/47 had accelerated (<78 min) emptying on one of their studies.

image

Figure 1.  Pearson correlation between first and second measurements of gastric emptying T1/2.

Download figure to PowerPoint

A Bland-Altman plot showed the intra-subject variation for repeat measurements in relation to the average gastric emptying T1/2 (Fig. 2). The Bland–Altman plots assessing differences in replicate results showed that delta values were similarly distributed across mean GE T1/2 values ranging between 100 and 155 min; fewer patients had gastric emptying outside these values, limiting this assessment. The differences in T1/2 values over the time between studies are shown in Fig. 3 Again, the differences in T1/2 values were consistent in repeat studies conducted between 90 and 600 days. A lower variation was observed in 10 subjects with repeat studies >1000 days apart.

image

Figure 2.  Bland–Altman plots showing intra-subject variation in gastric emptying T1/2. Plot shows 1 standard deviation as the interrupted lines. Note most data are well within 1 SD which is 30.6 min.

Download figure to PowerPoint

image

Figure 3.  Bland–Altman plots showing effect of time interval in years between consecutive measurements of gastric emptying T1/2. There does not appear to be a difference in the variation in gastric emptying when the interval is between 90 and 500 days.

Download figure to PowerPoint

Effect of age, gender, and body mass index

Table 2 shows the data broken down by gender. There was no significant effect of age or BMI (Fig. 4); however, gender was significantly associated with GE T1/2 (P < 0.0001) and with GE at 1 h (P < 0.0001) and 2 h (P < 0.0001).

image

Figure 4.  Relationship of body mass index (left panel), age (right panel), and gastric emptying T1/2. Note that no significant relationships were identified.

Download figure to PowerPoint

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

Our results show that scintigraphic assessment of gastric emptying is reproducible over the short-, intermediate-, and long-term in healthy volunteers.

Inter-subject variation was considerable (∼25%) and comparable to those previously published by Cremonini et al.4 in a smaller cohort of 37 healthy volunteers and in other studies from our laboratory.9,10 The slightly higher COV in males is probably the result of the lower mean GE T1/2 in males. In this study, we identified that the intra-subject COV was similar (24%) to the inter-subject COV. However, the COVintra was somewhat higher than the ∼13%, previously reported in a small sample of healthy participants studied in our laboratory.9,10 This wider COVintra has important implications in the planning of therapeutic studies, as it implies that the effect size demonstrable may be similar in parallel-group design compared with crossover studies, and the former design may be preferable as it avoids potential pitfalls, such as failure of participants to complete both arms of a study and the potential confounding caused by an order effect. In summary, the current data showing that the intra-subject COV was similar to the inter-subject COV argue in favor of parallel-group studies, as the number of measurements would be only modestly greater than the number in a crossover study with the potential of showing the same effect sizes. Table 3 shows an estimate of the sample sizes per treatment group that would be required to detect effect sizes ranging from 10% to 30%. In general, a clinical benefit can be anticipated with a 20%–30% difference in gastric emptying T1/2.

Table 3.   Numbers of subjects (*based on a two-sample t-test with 80% power) needed in a two-arm study to detect various effect sizes (%) for gastric emptying T1/2 based on mean of 122 (SD = 29.8) min. Effect size is the difference between groups as a percentage of the overall mean of the two groups
Effect size (%)Number per group* to detect listed effect size
1084
1536
2021
2513
309

Over the short- and medium-term, gastric transit parameters were reproducible within subjects, and this characteristic is also critical in planning pre- and post-treatment transit measurements to study drug effects of even up to 1 year’s duration. Beyond about 3 years, our limited observations on replicate studies still show stability in the measured GE T1/2, possibly with lower variation than with shorter durations. This is important in the planning of natural history studies, although ideally this stability would be demonstrated in disease states like gastroparesis. The literature does suggest this is the case, based on a relatively small study conducted by Jones et al. who demonstrated virtually identical gastric emptying of solids during at least 12 years’ follow-up in a cohort of patients with diabetic gastroparesis.13

Given the variation observed in gastric emptying by scintigraphy, it might be considered that other methods might prove more reproducible. However, when tested head-to-head in relatively small numbers of participants, the intra- and inter-individual variations in gastric emptying by scintigraphy and by breath test were very similar.9,10 Therefore, we perceive that the variation measured reflects the intrinsic variation in the physiological process rather than a methodological artifact. Future research with repeat studies using different techniques to measure gastric emptying, such as stable isotope breath test or wireless motility capsules, is required to address this issue.

Our current study has also shown a highly significant gender association, with gastric emptying being, on average, about 15% slower in females; the reason and mechanisms explaining the slower gastric emptying of solids in females remains unclear. However, there are at least three important perspectives on the effect of gender on gastric emptying in the literature. Firstly, increased body weight is associated with faster gastric emptying of solids and liquids,14 and the female participants had lower BMI in our study. Secondly, administration of sex hormones to 49 postmenopausal females randomized to receive for 7 days, 400 mg day−1, micronized progesterone, 0.2 mg day−1 estradiol, combination of the two or placebo showed no significant effects on gastric emptying.15 The levels of estradiol and progesterone administered were selected to mimic the physiological levels of these sex hormones, and those data suggest that sex hormones alone are unlikely to explain the slower gastric emptying observed in females. Thirdly, in the National Institutes of Health (NIH) gastroparesis consortium, there is a higher prevalence of females among those with idiopathic gastroparesis, although the reason is also unclear.16

On the other hand, there were no statistically significant effects of age (in the range 18–65 years) or BMI. The lack of association with BMI contrasts with the previously demonstrated associations of BMI with other motor functions, such as accelerated colonic transit17 and volume of nutrient drink intake to achieve maximum satiation.18 Our findings of a lack of association of gastric emptying with body mass are consistent with many prior studies in the literature, summarized elsewhere.19 We had also previously investigated gastric fasting and postprandial accommodation volumes in non-bulimic, asymptomatic obese subjects and observed no differences compared with normal BMI participants.20

This study has a number of strengths, including the large sample size with the inclusion of >300 healthy volunteers. Participation in more than one study was not specifically planned through any targeted recruitment, and we believe that this cohort of 47 people self-selected in a random fashion. While it is conceivable that their prior positive experience with the studies and familiarity with the research may constitute a form of bias, there were no characteristics (e.g. demographics) of this group that suggested they were different from the larger group who participated in a single study. Other potential weaknesses to consider include the retrospective manner in which data were obtained, the absence of patients with established gastric motor disorders, and the absence of patients with significantly increased BMI, as the 95th percentiles of the entire cohort was 37.4 kg m−2. In addition, the observations on variation in a single center, which has standardized the procedures and has extensive experience, might be optimistic, and variation might be even greater when scintigraphic gastric emptying is used in a multicenter study.

In summary, although there is an inherent inter-individual variation in gastric emptying, these effects likely reflect true day-to-day variation in gastric function, rather than variations with the measurement technique. The degree of reproducibility allows for planning of studies to compare gastric emptying between disease groups and to demonstrate the effects of medication, thus further validating the use of scintigraphy for assessing gastric emptying in clinical or research settings.

Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

This work was supported by grant PO1-DK-68055 from National Institutes of Health. Dr. Camilleri’s work on gastric function is supported in part by grant RO1-DK-67071 from National Institutes of Health.

Authors’ contributions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

MC Lead investigator, PI of all projects included except for three projects, conceptualization of project, manuscript authorship; JI Fellow co-investigator, manuscript authorship; AEB Staff co-investigator and PI of three projects that are included in the analysis, manuscript authorship; DB lead technologist conducted all analyses of gastric emptying tests in the studies; AS and IDJ verification of data and manuscript authorship; ARZ conceptualization of project, statistical analysis, and manuscript authorship.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix
  • 1
    Abell TL, Camilleri M, Donohoe K et al. Consensus recommendations for gastric emptying scintigraphy. A joint report of the society of nuclear medicine and the American neurogastroenterology and motility society. Am J Gastroenterol 2008; 103: 75363.
    Direct Link:
  • 2
    Camilleri M, Malagelada JR, Abell TL, Brown ML, Hench V, Zinsmeister AR. Effect of six weeks of treatment with cisapride in gastroparesis and intestinal pseudoobstruction. Gastroenterology 1989; 96: 70412.
  • 3
    Foxx-Orenstein A, Camilleri M, Stephens D, Burton D. Effect of somatostatin analog on gastric motor and sensory functions in healthy humans. Gut 2003; 52: 155561.
  • 4
    Cremonini F, Mullan BP, Camilleri M, Burton DD, Rank MR. Performance characteristics of scintigraphic transit measurements for studies of experimental therapies. Aliment Pharm Ther 2002; 16: 178190.
  • 5
    Talley NJ, Phillips SF, Wiltgen CM, Zinsmeister AR, Melton LJ 3rd. Assessment of functional gastrointestinal disease: the bowel disease questionnaire. Mayo Clin Proc 1990; 65: 145679.
  • 6
    Camilleri M, Colemont LJ, Phillips SF et al. Human gastric emptying and colonic filling of solids characterized by a new method. Am J Physiol 1989; 257: G28490.
  • 7
    Camilleri M, Zinsmeister AR, Greydanus MP, Brown ML, Proano M. Towards a less costly but accurate test of gastric emptying and small bowel transit. Dig Dis Sci 1991; 36: 60915.
  • 8
    Thomforde GM, Camilleri M, Phillips SF, Forstrom LA. Evaluation of an inexpensive screening scintigraphic test of gastric emptying. J Nucl Med 1995; 36: 936.
  • 9
    Choi MG, Camilleri M, Burton DD, Zinsmeister AR, Forstrom LA, Nair KS. [13C]octanoic acid breath test for gastric emptying of solids: accuracy, reproducibility, and comparison with scintigraphy. Gastroenterology 1997; 112: 115562.
  • 10
    Choi MG, Camilleri M, Burton DD, Zinsmeister AR, Forstrom LA, Nair KS. Reproducibility and simplification of 13C-octanoic acid breath test for gastric emptying of solids. Am J Gastroenterol 1998; 93: 928.
    Direct Link:
  • 11
    Tougas G, Eaker EY, Abell TL et al. Assessment of gastric emptying using a low fat meal: establishment of international control values. Am J Gastroenterol 2000; 95: 145662.
    Direct Link:
  • 12
    Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; I(8476): 30710.
  • 13
    Jones KL, Russo A, Berry MK, Stevens JE, Wishart JM, Horowitz M. A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. Am J Med 2002; 113: 44955.
  • 14
    Vazquez Roque MI, Camilleri M, Stephens DA et al. Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people. Gastroenterology 2006; 131: 171724.
  • 15
    Gonenne J, Esfandyari T, Camilleri M et al. Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women. Neurogastroenterol Motil 2006; 18: 9118.
  • 16
    Parkman HP, Yates K, Hasler WL et al. Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity. Gastroenterology. 2011; 140: 10115
  • 17
    Delgado-Aros S, Camilleri M, Garcia MA, Burton D, Busciglio I. High body mass alters colonic-sensory motor function and transit in humans. Am J Physiol 2008; 295: G3828.
  • 18
    Delgado-Aros S, Cremonini F, Castillo EJ et al. Independent influences of body mass and gastric volumes on satiation in humans. Gastroenterology 2004; 126: 43240.
  • 19
    Park M-I, Camilleri M. Gastric motor and sensory functions in obesity. Obesity Res 2005; 13: 491500.
  • 20
    Kim D-Y, Camilleri M, Murray JA, Stephens DA, Levine JA, Burton DD. Is there a role for gastric accommodation and satiety in asymptomatic obese people? Obesity Res 2001; 9: 65561.

Appendix

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Funding
  8. Disclosures
  9. Authors’ contributions
  10. References
  11. Appendix

Appendix: Papers published previously from which the current database was constructed

1. Bharucha AE, Ravi K, Zinsmeister AR. Comparison of selective M3 and nonselective muscarinic receptor antagonists on gastrointestinal transit and bowel habits in humans. Am J Physiol 2010; 299: G215–9.
2. Bharucha AE, Seide B, Guan Z, Andrews CN, Zinsmeister AR. Effect of tolterodine on gastrointestinal transit and bowel habits in healthy subjects. Neurogastroenterol Motil 2008; 20: 643–8.
3. Bharucha AE, Skaar T, Andrews CN, Camilleri M, Philips S, Seide B, Burton D, Baxter K, Zinsmeister AR. Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil 2008; 20: 891–9.
4. Camilleri M, Bharucha AE, Ueno R, Burton D, Thomforde GM, Baxter K, McKinzie S, Zinsmeister AR. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol 2006; 290: G942–7.
5. Viramontes BE, Malcolm A, Camilleri M, Szarka LA, McKinzie S, Burton DD, Zinsmeister AR. Effects of α2-adrenergic agonist on gastrointestinal transit, colonic motility and sensation in humans. Am J Physiol 2001; 281: G1468–76.
6. Camilleri M, Vazquez-Roque MI, Burton D, Ford T, McKinzie S, Zinsmeister AR, Druzgala P. Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans. Neurogastroenterol Motil 2007; 19: 30–8.
7. Castillo EJ, Camilleri M, Locke GR, Burton DD, Stephens DA, Geno DM, Zinsmeister AR. A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia. Clin Gastroenterol Hepatol 2004; 2: 985–96.
8. Castillo EJ, Delgado-Aros S, Camilleri M, Burton D, Stephens D, O’Connor-Semmes R, Walker A, Shachoy-Clark A, Zinsmeister AR. Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers. Am J Physiol 2004; 287: G363–9.
9. Cremonini F, Camilleri M, Vazquez Roque M, McKinzie S, Burton D, Baxter K, Zinsmeister AR. Obesity does not increase effects of synthetic ghrelin on human gastric motor functions. Gastroenterology 2006; 131: 1431–9.
10. Delgado-Aros S, Chial HJ, Camilleri M, Szarka LA, Weber FT, Jacob J, Ferber I, McKinzie S, Burton DD, Zinsmeister AR. Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans. Am J Physiol 2003; 284: G558–66.
11. Esfandyari T, Camilleri M, Ferber I, Burton D, Baxter K, Zinsmeister AR. Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo-controlled study. Neurogastroenterol Motil 2006; 18: 831–8.
12. Gonenne J, Camilleri M, Ferber I, Burton D, Baxter K, Keyashian K, Foss J, Wallin B, Du W, Zinsmeister AR. Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study. Clin Gastroenterol Hepatol 2005; 3: 784–91.
13. Gonenne J, Esfandyari T, Camilleri M, Burton DD, Stephens DA, Baxter KL, Zinsmeister AR, Bharucha AE. Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women. Neurogastroenterol Motil 2006; 18: 911–8.
14. Grudell AB, Camilleri M, Jensen KL, Foxx-Orenstein AE, Burton DD, Ryks MD, Baxter KL, Cox DS, Dukes GE, Kelleher DL, Zinsmeister AR. Dose–response effect of a beta3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health. Am J Physiol 2008; 294: G1114–9.
15. Jeong ID, Camilleri M, Shin A, Iturrino J, Boldingh A, Busciglio I, Burton D, Ryks M, Rhoten D, Zinsmeister AR. A randomised, placebo-controlled trial comparing the effects of tapentadol and oxycodone on gastrointestinal and colonic transit in healthy humans. Aliment Pharmacol Ther 2012 Feb 21. doi: 10.1111/j.1365-2036.2012.05040.x. [Epub ahead of print]
16. Manabe N, Camilleri M, Rao A, Wong BS, Burton D, Busciglio I, Zinsmeister AR, Haruma K. Effect of daikenchuto (TU-100) on gastrointestinal and colonic transit in humans. Am J Physiol 2010; 298: G970–5.
17. Manini ML, Camilleri M, Goldberg M, Sweetser S, McKinzie S, Burton D, Wong S, Kitt MM, Li YP, Zinsmeister AR. Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation. Neurogastroenterol Motil 2010; 22: 42–9, e7–8.
18. Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IA, Lamsam J, Singh R, Zinsmeister AR. Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function. Clin Gastroenterol Hepatol 2010; 8:159–65.
19. Odunsi ST, Vázquez-Roque MI, Camilleri M, Papathanasopoulos A, Clark MM, Wodrich L, Lempke M, McKinzie S, Ryks M, Burton D, Zinsmeister AR. Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity. Obesity 2010; 18: 1579–84.
20. Park MI, Ferber I, Camilleri M, Allenby K, Trillo R, Burton D, Zinsmeister AR. Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo-controlled study. Neurogastroenterol Motil 2006; 18: 28–36.
21. Vazquez Roque MI, Camilleri M, Clark MM, Tepoel DA, Jensen MD, Graszer KM, Kalsy SA, Burton DD, Baxter KL, Zinsmeister AR. Alteration of gastric functions and candidate genes associated with weight reduction in response to sibutramine. Clin Gastroenterol Hepatol 2007; 5: 829–37.
22. Wong BS, Rao AS, Camilleri M, Manabe N, McKinzie S, Busciglio I, Burton DD, Ryks M, Zinsmeister AR. The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. Aliment Pharmacol Ther 2010; 32: 884–93.