Predictors of gastric emptying in Parkinson''s disease

Predictors of gastric emptying (GE) in patients with idiopathic Parkinson's disease (PD) of a solid and liquid meal are not well defined. For measurement of GE 80 patients with PD were randomly assigned to receive either a solid meal (250 kcal) containing 13C-octanoate (n = 40) or a liquid meal (315 kcal) with 13C-acetate (n = 40). All patient groups were off medication affecting motility and were matched for age, gender, body mass index, disease duration and severity, using Unified Parkinson's Disease Rating Scale (UPDRS). Gastric emptying was compared with a healthy control group (n = 40). Multiple regression analysis was used to determine predictors of gastric emptying. Exactly 88% and 38% of PD patients had delayed GE of solids and liquids respectively. Solid and liquid emptying was similar in women and men. There were no differences in GE in PD patients < 65 years of age when compared with patients > or = 65 years. Multiple regression analysis showed that motor handicaps such as rigour and action tremor are independent predictors of solid GE (r = 0.68, P < 0.001). The severity of motor impairment, but not any other neurological symptom, as assessed by UPDRS is associated with gastroparesis in PD and solid emptying is more likely to be delayed.     

Upper gastrointestinal motility changes following spinal cord injury

Abstract  Spinal cord injury (SCI) is associated with severe autonomic dysfunction in both the acute and chronic phases. Upper gastrointestinal (GI) motor dysfunction has been previously reported in humans and rats. Gastric emptying (GE) of a solid meal – as measured by the [¹³C]-octanoic acid breath test – is delayed in the first 3 weeks after either spinal cord transection (SCT) or contusion (SCC) in rats. This is one of the main findings of a new paper by Qualls-Creekmore et al. in the current issue of this journal. Previous studies in rats only reported impairment of GE, intestinal and GI transit of liquid after SCI, but the authors observed that the delay of the GE of solid was more prominent after SCT than SCC. Recovery of the delay of GE of solid occurred at 6 weeks after SCC, but not after SCT. However, gastric motility changes persisted despite the functional normalization of the GE in rats with SCC. Bowel dysfunction is a major physical and psychological burden for SCI patients. Collaborative efforts, like the development of international standards to evaluate autonomic function after SCI will likely clarify the mechanisms of dysfunction and lead to the development of new therapeutic strategies.     

Effect of itopride on gastric emptying in longstanding diabetes mellitus

Abstract Delayed gastric emptying (GE) occurs in 30–50% of patients with longstanding type 1 or 2 diabetes, and represents a major cause of morbidity. Current therapeutic options are limited. We aimed at evaluating the effects of itopride on GE in patients with longstanding diabetes. Twenty‐five patients (20 type 1, 5 type 2; 10 males, 15 females; mean age 45.2 ± 2.7 years; body mass index 27.5 ± 0.9 kg m^?2; duration of diabetes 20.2 ± 2.4 years) were enrolled in a double‐blind, placebo‐controlled, randomized, crossover trial. Subjects received both itopride (200 mg) and placebo t.i.d. for 7 days, with a washout of 7–14 days. GE (scintigraphy), blood glucose (glucometer) and upper gastrointestinal (GI) symptoms (questionnaire) were measured following each treatment period. The test meal comprised 100 g ground beef (^99mTc‐sulphur colloid) and 150 mL of 10% dextrose [⁶⁷Ga‐ethylenediaminetetraacetic acid (EDTA)]. There was a slight trend for itopride to accelerate both solid (P = 0.09) and liquid (P = 0.09) GE. With itopride treatment, the emptying of both solids and liquids tended to be more accelerated, as the emptying with placebo was slower (solids: r = 0.39, P = 0.057; liquids: r = 0.44, P < 0.03). Twelve (48%) patients had delayed solid and/or liquid GE on placebo and in this group, itopride modestly accelerated liquid (P < 0.05), but not solid (P = 0.39), emptying. Itopride had no effect on mean blood glucose during the GE measurement (placebo: 9.8 ± 0.6 mmol L^?1vs itopride: 9.6 ±0.6 mmol L^?1), or GI symptoms (placebo: 1.4 ± 0.4 vs itopride: 1.8 ± 0.5). Itopride, in a dose of 200 mg t.i.d. for 7 days, tends to accelerate GE of liquids and solids in longstanding diabetes. The magnitude of this effect appears to be modest and possibly dependent on the rate of GE without itopride.     

Comparison of calculations to estimate gastric emptying half‐time of solids in humans

Background Measuring solid gastric emptying (GE) at 4 h is used to identify gastroparesis. GE half‐time (GE T_1/2) is useful to assess overall and early GE. Aim To examine the validity of hourly imaging as a measurement of GE T_1/2 compared with estimates from more detailed imaging. Methods 155 human subjects (99 female, 56 male) underwent scintigraphic GE of a solid–liquid meal. We calculated the GE T_1/2 using linear interpolation based on a full set of abdominal images obtained over 4 h, and the GE T_1/2 based on images at 1, 2, 3, and 4 h after the meal with interpolation of data. Key Results Differences in GE T_1/2 values (entire set of scan times compared with just the hourly scans) were small [overall median (5th, 95th percentiles) = ?0.2[?7.5, 4.6] min] with slightly greater differences in males compared with females. The agreement between the two methods was very high [concordance correlation coefficient (CCC) (95% CI) = 0.993 (0.990, 0.995)] and a Bland–Altman plot indicated the variation in the results between the two methods did not change appreciably across the range of GE studied (within ±10 min for all but four subjects). Calculated GE T_1/2 values, omitting the 3‐h data from the hourly measurements, were associated with similar high accuracy overall and for fast GE, but were less accurate with slow GE. Conclusions & Inferences Results of GE T_1/2 solids, using hourly imaging over 4 h, are accurate in the range 75–235 min which reflects the typical range of GE of solids in health and disease.     

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.     

Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized,double-blind,placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m²) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.     

Neural mechanisms involved in the delay of gastric emptying and gastrointestinal transit of liquid after thoracic spinal cord transection in awake rats

Spinal cord transection (SCT) delays gastric emptying (GE), and intestinal and gastrointestinal (GI) transit of liquid in awake rats. This study evaluates the neural mechanisms involved in this phenomenon. Male Wistar rats (N = 147) were fasted for 16 h and had the left jugular vein cannulated followed by laminectomy or laminectomy + complete SCT between T4 and T5 vertebrae. The next day, a test meal (1.5 ml of a phenol red solution, 0.5 mg/ml in 5% glucose) was administered by gavage feeding and 10 min later cervical dislocation was performed. Dye recovery in the stomach, and proximal, mid and distal small intestine was determined by spectrophotometry. SCT inhibited GE and GI transit since it increased gastric recovery by 71.3% and decreased mid small intestine recovery by 100% (P < 0.05). Subdiaphragmatic vagotomy, celiac ganglionectomy + section of the splanchnic nerves, i.v. hexamethonium (20 mg/kg) or yohimbine (3 mg/kg) prevented the development of the SCT effect on GE and GI transit. Pretreatment with i.v. naloxone (2 mg/kg), L-NAME (3 mg/kg) or propranolol (2 mg/kg) was ineffective. Bilateral adrenalectomy or guanethidine (10 mg/kg) increased the magnitude of the GE inhibition, while i.v. prazosin (1 mg/kg) or atropine (0.5 mg/kg) decreased the magnitude but did not abolish the GE inhibition. In summary, the inhibition of GI motility observed 1 day after thoracic SCT in awake rats seems to involve vagal and possibly splanchnic pathways.     

Anxiety symptoms in patients with frontal lobe epilepsy versus generalized epilepsy

PurposeThe aim of this study was to compare the frequency of anxiety symptoms between patients with frontal lobe epilepsy (FLE) and generalized epilepsy (GE).MethodsForty and 78 patients with FLE and GE respectively were enrolled in the study. Anxiety symptoms were measured with the Hamilton anxiety rating scale (HARS) and the anxiety subscale of the hospital anxiety and depression scale (HADSA).ResultsCompared to the GE group, the FLE group had significantly higher HARS (10.9 ± 8.7 vs. 7.9 ± 6.8, p = 0.039) scores. Significant correlations were also found between anxiety symptoms and epilepsy-related variables, particularly with the seizure frequency and the number of currently taken anti-epileptic drugs.ConclusionAnxiety symptoms are more common in patients with FLE in comparison to those with GE. Further studies are warranted to clarify the relationship between anxiety symptoms and FLE.     

Insulin,but not proinsulin C-peptide,enhances platelet fibrinogen binding in vitro in Type 1 diabetes mellitus patients and healthy subjects

INTRODUCTION: Insulin treatment is essential in Type 1 diabetes mellitus (DM). However, previous studies have shown complex effects of insulin on platelet function. Proinsulin C-peptide has shown beneficial effects in Type 1 DM, but it is not known if it can affect platelet activation. We thus investigated how insulin, C-peptide, and their combination influence platelets from DM patients and healthy subjects. MATERIALS AND METHODS: Hirudinized blood from patients (n = 10) and healthy subjects (n = 10) was preincubated in the absence or presence of insulin (10 and 100 microU/ml), C-peptide (0.3, 1, and 10 nM), or the combination (1 nM C-peptide + 100 microU/ml insulin or 10 nM C-peptide + 100 microU/ml insulin) and further incubated without or with 10(-6) M ADP. Platelet activation was monitored by platelet fibrinogen binding and P-selectin expression using whole blood flow cytometry. Data are presented as binding index (BI), which integrates the percentage of activated cells and their mean fluorescence intensity. RESULTS: Insulin enhanced ADP-induced platelet fibrinogen binding in both Type 1 DM patients and healthy subjects. For example, ADP-stimulated platelet fibrinogen BI increased from 4.25 +/- 0.74 to 8.63 +/- 2.00 with 10 microU/ml insulin (P < .05) in Type 1 DM patients. However, insulin did not increase platelet P-selectin expression. Proinsulin C-peptide did not influence platelet fibrinogen binding or P-selectin expression in either Type 1 DM patients or healthy subjects. The combination of C-peptide and insulin had similar effects as insulin alone. CONCLUSIONS: Insulin at physiological concentrations enhances platelet fibrinogen binding in both Type 1 DM patients and healthy subjects, whilst C-peptide does not influence platelet activation.     

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.     

Effects of risperidone on glucose metabolism in Chinese patients with schizophrenia: A prospective study

BackgroundWhile most of the second generation antipsychotic agents are associated with abnormal glucose metabolism, previous studies have shown that risperidone has relatively little effect upon blood glucose levels. This study aimed to explore the effect of risperidone on the glucose-regulating mechanism of patients with schizophrenia by using the oral glucose tolerance test (OGTT), measuring insulin and C-peptide levels.MethodsThirty inpatients with schizophrenia taking risperidone were studied. All the patients were given a simplified OGTT at baseline and six weeks after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured at fasting, then 1 and 2 h after OGTT respectively. Other data, including demographic characteristics and plasma drug concentrations, were also recorded.Results(1) There was no significant increase in the proportion of patients demonstrating abnormal plasma glucose levels compared with baseline (p = 1.000, McNemar test); (2) risperidone was associated with elevated insulin concentrations (p = 0.013), C-peptide levels (p = 0.020), insulin/glucose ratio (p = 0.020) and BMI (p < 0.01); (3) no sex differences in glucose-related measures were observed.ConclusionRisperidone treatment may be associated with alterations in glucose-regulating mechanisms in patients with schizophrenia.     

Spectrum of gastric emptying patterns in adult patients with cyclic vomiting syndrome

Background Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom‐free intervals. Both rapid and delayed gastric emptying (GE) have been observed but the reports involved small numbers of CVS patients. Methods We performed a retrospective study of 92 adult patients who met Rome Ш diagnostic criteria for CVS between 2003 and 2009 at the Kansas University Medical Center. Gastric emptying was measured by a standardized scintigraphic method involving a low fat (2%) isotope labeled egg white meal of 250 Kcal, with anterior and posterior gastric imaging in the standing position obtained at 0, 1, 2, 4 h after meal ingestion. Rapid GE was defined as <50% isotope retention at 1st h and/or <30% at 2nd h and delayed GE as >10% at 4 h. Key Results Ninety two patients were analyzed: 47 males and 45 females mean of age 37 ± 12 years (range: 20–68 years). There were 27 patients with a personal history of migraine headache, 30 with history of marijuana use, 12 had diabetes mellitus (DM) and 10 had irritable bowel syndrome (IBS) as an accompanying diagnosis. Fifty four patients (59%) met criteria for rapid GE, 25 (27%) had normal GE and 13 (14%) had slow GE. Eighty percent of patients with co‐existing IBS symptoms were identified as rapid. The subset with delayed emptying was often associated with narcotics use, DM and marijuana use (P < 0.05). Conclusions & Inferences (i) In adult CVS patients, GE is generally either rapid or normal. (ii) Cyclic vomiting syndrome is an important new etiology to explain the finding of rapid GE on a radionuclide test. (iii) The small subset of CVS patients (14%) whose GE was slow were explained by the role of narcotics and/or marijuana.     

Sex differences in seizure types and symptoms

BackgroundDespite the increasing interest in sex differences in disease manifestations and responses to treatment, very few data are available on sex differences in seizure types and semiology. The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, multi-institutional, collaborative study that aims to create a comprehensive repository of detailed clinical information and DNA samples from a large cohort of people with epilepsy. We used this well-characterized cohort to explore differences in seizure types as well as focal seizure symptoms between males and females.MethodsWe reviewed the EPGP database and identified individuals with generalized epilepsy of unknown etiology (GE) (n = 760; female: 446, male: 314), nonacquired focal epilepsy (NAFE) (n = 476; female: 245, male: 231), or both (n = 64; female: 33, male: 31). Demographic data along with characterization of seizure type and focal seizure semiologies were examined.ResultsIn GE, males reported atonic seizures more frequently than females (6.5% vs. 1.7%; p < 0.001). No differences were observed in other generalized seizure types. In NAFE, no sex differences were seen for seizure types with or without alteration of consciousness or progression to secondary generalization. Autonomic (16.4% vs. 26.6%; p = 0.005), psychic (26.7% vs. 40.3%; p = 0.001), and visual (10.3% vs. 19.9%; p = 0.002) symptoms were more frequently reported in females than males. Specifically, of psychic symptoms, more females than males endorsed déjà vu (p = 0.001) but not forced thoughts, derealization/depersonalization, jamais vu, or fear. With corrections for multiple comparisons, there were no significant differences in aphasic, motor, somatosensory, gustatory, olfactory, auditory, vertiginous, or ictal headache symptoms between sexes.ConclusionsSignificant differences between the sexes were observed in the reporting of atonic seizures, which were more common in males with GE, and for autonomic, visual, and psychic symptoms associated with NAFE, which were more common in females.     

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.     

Geraniol Ameliorates the Motor Behavior and Neurotrophic Factors Inadequacy in MPTP-Induced Mice Model of Parkinson’s Disease

Many experiments affirm the notion that augmentation of neurotrophic factors (NTFs) activity, especially brain-derived neurotrophic factors and glial cell-derived neurotrophic factors, could prevent or halt the progress of neurodegeneration in Parkinson’s disease (PD). In this study, we investigated the therapeutic accomplishment of geraniol (GE 100 mg/kg) on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mice model of PD. Current investigation proved that pretreatment with GE ameliorates the MPTP-induced alterations in behavioral, biochemical, immunohistochemical, and immunoblotting manifestations in mice. Systematically, the loss of dopaminergic neurons and reduced NTFs mRNA expressions induced by MPTP was ameliorated to a significant extent by pretreatment with GE. We found that GE confers a potent neuroprotective agent against MPTP-induced dopaminergic denervation and may become a potential therapeutic agent for PD and/or its progression.     

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.     

Optimizing analysis of stable isotope breath tests to estimate gastric emptying of solids

Abstract  Breath tests (BT) using ¹³C–substrates have been proposed for the measurement of gastric emptying (GE). The mathematical analysis of the breath ¹³CO₂ excretion that most accurately predicts GE t _1/2 from simultaneous scintigraphy is unresolved. To compare five mathematical methods to estimate GE t _1/2 by BT with t _1/2 from simultaneous scintigraphy. Data acquired from a dual-labelled solid–liquid meal containing ^99mTc sulphur colloid and ¹³C- Spirulina platensis from 57 healthy volunteers were used to compare four mathematical methods reported in the literature [Ghoos method; generalized linear regression (Viramontes); linear regression (Szarka); Wagner–Nelson method] and the total cumulative breath ¹³CO₂ excretion with ≥12 breath samples collected over at least 4 h. The concordance correlation coefficient (CCC) for the t _1/2 results obtained with each method using BT data was compared with the results obtained with scintigraphy. The linear regression and generalized linear regression methods used five samples at 45, 90, 120, 150 and 180 min. All methods, except for the Wagner–Nelson method, resulted in mean GE t _1/2 that approximated t _1/2 obtained with scintigraphy. The highest CCC was observed with the linear regression method. Simple cumulative excretion of breath ¹³CO₂ provides a better CCC than the Ghoos method. The linear regression and generalized linear regression methods (which also require relatively few breath samples) provide the most accurate analyses of breath ¹³CO₂ excretion in stable isotope GEBT.     

Gastric emptying after semi–solid food in multiple system atrophy and Parkinson disease

Background Gastrointestinal symptoms such as nausea, abdominal pain, and bloating are frequent complaints in patients with Parkinson disease (PD) and in patients with multiple system atrophy (MSA), and may be associated with delayed gastric emptying (GE). Although several GE studies in patients with PD have been performed, scant data exist in patients with MSA. Methods We assessed GE half–times (T50) in 12 patients with MSA and compared them with those of 12 patients with PD and 12 age–matched healthy controls.GE was estimated scintigraphically using the left anterior oblique method after ingestion of a ^99mTc colloid–labeled balanced semi–solid meal (yogurt). GE data were obtained every 15 minutes until there was complete emptying of the stomach. Blood pressure, heart rate, plasma glucose and glucosylated hemoglobin were regularly determined. Results Reproducibility of the GE technique was excellent (Bland–Altman analysis, limits of agreement: –2.3 to 2.8). T50 was longer in MSA (82 ± 3.4 min) and in PD (90.6 ± 3.9 min) patients compared with controls (46.2 ± 0.7) (two–way ANOVA, p <0.0001). T50 did not differ between patients with MSA and those with PD. No correlation existed between T50 and age, duration of the disease, magnitude of postprandial hypotension, levels of plasma glucose and glucosylated hemoglobin (Kendall’s tau, p > 0.05). Conclusions Our results suggest that patients with MSA have GE rates similar to those of patients with PD, but slower than healthy agematched individuals. It remains to be investigated whether gastrointestinal dysfunction in MSA is related to both brain and peripheral pathology, as is presumed for PD.     

Indirect vs direct assessment of gastric emptying: A randomized crossover trial comparing C‐isotope breath analysis and MRI

Background

Indirect methods to assess gastric emptying (GE), such as ¹³C breath tests (BT), are commonly used. However, BT usually use a sampling time of 4+ hours. The current study aims to assess the validity of BT for four liquid meals differing in physicochemical properties. To this aim, we compared them to MRI GE‐measurements.

Methods

Fifteen healthy males (age 22.6 ± 2.4 years, BMI 22.6 ± 1.8 kg/m²) participated in a randomized 2 × 2 crossover experiment. Test foods were liquid meals, which were either thin/thick and 100/500 kcal, labeled with 100 mg of ¹³C‐octanoate. GE was measured with MRI and assessed by ¹³C recovery from breath. Participants were scanned every 10 minutes and at six time points breath samples were collected up to t = 90 minutes. Two curves were fitted to the data to estimate emptying halftime (t_{50 Ghoos} and t_{50 Bluck}). T₅₀ times were ranked per participant and compared between methods.

Key Results

On average, MRI and BT showed similar t₅₀ rankings for the four liquid meals. In comparison to MRI, t_{50 Ghoos} overestimated, while t_{50 Bluck} underestimated GE time_. Moreover, more viscous foods were overestimated. In most participants individual t₅₀ time rankings differed significantly between methods.

Conclusions & Inferences

BT can assess relative emptying differences on group level and collecting breath data for 90 minutes constitutes a lower burden for participants and the research facility. However, BT has severe shortcomings compared to MRI for individual GE assessment. Notably, food matrix effects should be considered when interpreting the results of BT.     

Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo-controlled study

We studied effects of i.v. atilmotin (BAX-ACC-1638, a novel motilin agonist, circulating t(1/2) < 10 min) on gastrointestinal transit in humans using a randomized, parallel-group, dose-response double-blind study of i.v. atilmotin, 6, 30, 60 microg or vehicle (placebo) given 2 min after standardized breakfast, lunch and dinner. The breakfast meal contained (99m)Tc-eggs and (111)In-milk. Full gastrointestinal transit was measured by scintigraphy. Primary endpoints were % gastric emptying (GE) at 30 min, GE t(1/2), colonic filling (CF) at 6 h, and geometric centre of colonic transit at 24 h. Analysis included adjustment for age, gender and body mass index, with Bonferroni correction applied for multiple comparisons. A significant treatment effect of atilmotin was detected for GE (%) at 30 min for solids and liquids (P < 0.01 for both). There were no significant effects on CF or CT and no significant adverse clinical events. Thus, atilmotin accelerates GE of solids and liquids in healthy humans. These data suggest that, at the doses tested, atilmotin should be considered for treatment of stomach motility disorders.