Gastric dysmotility and low serum vitamin D levels in patients with gastroparesis.

Nutritional abnormalities are common in patients with gastroparesis (Gp), a disorder that may affect gastric motility and may delay emptying. The aim of this work was to identify relationships between serum nutrition markers including 25-OH vitamin D and gastric motility measures in Gp patients. We enrolled 59 consecutive gastric motility clinic patients (48 females, 11 males; mean age 44 years; 42 idiopathic; 17 diabetes mellitus) with Gp symptoms. The 25-OH vitamin D levels, for most patients slightly above the lower limit of normal (96.98 nmol/l ± 60.99), were lowest in diabetic range (DM) (75.68 nmol/l ± 34.22) vs. idiopathic (ID) (105.03 nmol/l ± 67.08) gastroparesis patients. First hour GET: one unit increase in 25-OH vitamin D level was associated 0.11% improvement (95% CI -0.22, 0.01 p=0.056) in gastric motility in all patients; this association, although marked in ID Gp patients, (-0.13, CI -0.25, -0.01 p=0.034), was not seen in DM Gp, (0.2, CI -0.45, 0.87, p=0.525). Fourth hour GET: Every unit increase of 25-OH vitamin D was associated with significant improvement in all patients, ( 0.11% CI -0.23, 0.01, p=0.053), and some weak improvement in ID group, (0.11% -0.24, 0.01, p=0.076) and absent in patients with DM (0.03, CI -0.66, 0.72, p=0.932). It is concluded that 25-OH vitamin D levels may influence gastric emptying. Underlying mechanisms for this observation might include the impact of 25-OH vitamin D on the health of the enteric nervous system. 25-OH vitamin D contributions to enteric nerve functions should be explored, particularly where autonomic nervous system comorbidities exist.

Multicenter, Phase 1, Open Prospective Trial of Gastric Electrical Stimulation for the Treatment of Obesity: First-in-Human Results with a Novel Implantable System.

BACKGROUND AND AIMS: To assess safety of the Exilis™ gastric electrical stimulation (GES) system and to investigate whether the settings can be adjusted for comfortable chronic use in subjects with morbid obesity. Gastric emptying and motility and meal intake were evaluated. METHOD: In a multicenter, phase 1, open prospective cohort study, 20 morbidly obese subjects (17 female, mean BMI of 40.8 ± 0.7 kg/m2) were implanted with the Exilis™ system. Amplitude of the Exilis™ system was individually set during titration visits. Subjects underwent two blinded baseline test days (GES ON vs. OFF), after which long-term, monthly follow-up continued for up to 52 weeks. RESULTS: The procedure was safe, and electrical stimulation was well tolerated and comfortable in all subjects. No significant differences in gastric emptying halftime (203 ± 16 vs. 212 ± 14 min, p > 0.05), food intake (713 ± 68 vs. 799 ± 69 kcal, p > 0.05), insulin AUC (2448 ± 347 vs. 2186 ± 204, p > 0.05), and glucose AUC (41 ± 2 vs.41 ± 2, p > 0.05) were found between GES ON and OFF. At week 4, 13, and 26, a significant (p < 0.01) reduction in weight loss was observed but not at week 52. At this time point, the mean excess weight loss (EWL) was 14.2 ± 4.5%. CONCLUSION: Gastric electrical stimulation with the Exilis™ system can be considered as safe. No significant effect on food intake, gastric emptying, or gastric motility was observed. The reduction in weight loss with Exilis™ GES was significant but short lasting. Further electrophysiological research is needed to gain more insight in optimal stimulation parameters and lead localization.

Intravenous immunoglobulin in drug and device refractory patients with the symptoms of gastroparesis-an open-label study.

BACKGROUND: Gastroparesis is a complex clinical entity; many aspects of which remain unknown. Although most patients have idiopathic, diabetic, or postsurgical gastroparesis, many are thought to have measurable neuromuscular abnormalities. Immunotherapy has recently been utilized to treat suspected autoimmune gastrointestinal dysmotility. METHODS: Fourteen patients with symptoms of gastroparesis (Gp) who were refractory to drug/device were selected from 443 Gp patients from 2013 to 2015 who were treated at the University of Louisville motility center. All patients underwent a structural and psychiatric evaluation along with detailed psychological and behavioral examination to rule out eating disorders. We performed detailed neuromuscular evaluation and all 14 patients received at least 12 weeks of intravenous immunoglobulin (400 mg/kg infusion weekly). Response was defined subjectively (symptomatic improvement) using standardized IDIOM score system. KEY RESULTS: All 14 patients had serological evidence and/or tissue evidence of immunological abnormality. Post-IVIG therapy, there was a significant improvement in symptoms scores for nausea, vomiting, early satiety, and abdominal pain. CONCLUSIONS AND INFERENCES: Although limited by the absence of placebo group, the data illustrate the role of autoimmunity and neuromuscular evaluation in patients with gastroparesis and support the utility of a diagnostic trial of immunotherapy in an effort to improve therapeutic outcomes for such patients.

Relationships between gastric slow wave frequency, velocity, and extracellular amplitude studied by a joint experimental-theoretical approach.

BACKGROUND: Gastric slow wave dysrhythmias are accompanied by deviations in frequency, velocity, and extracellular amplitude, but the inherent association between these parameters in normal activity still requires clarification. This study quantified these associations using a joint experimental-theoretical approach. METHODS: Gastric pacing was conducted in pigs with simultaneous high-resolution slow wave mapping (32-256 electrodes; 4-7.6 mm spacing). Relationships between period, velocity, and amplitude were quantified and correlated for each wavefront. Human data from two existing mapping control cohorts were analyzed to extract and correlate these same parameters. A validated biophysically based ICC model was also applied in silico to quantify velocity-period relationships during entrainment simulations and velocity-amplitude relationships from membrane potential equations. KEY RESULTS: Porcine pacing studies identified positive correlations for velocity-period (0.13 mm s-1 per 1 s, r2 =.63, P<.001) and amplitude-velocity (74 µV per 1 mm s-1 , r2 =.21, P=.002). In humans, positive correlations were also quantified for velocity-period (corpus: 0.11 mm s-1 per 1 s, r2 =.16, P<.001; antrum: 0.23 mm s-1 per 1 s, r2 =.55; P<.001), and amplitude-velocity (94 µV per 1 mm s-1 , r2 =.56; P<.001). Entrainment simulations matched the experimental velocity-period relationships and demonstrated dependence on the slow wave recovery phase. Simulated membrane potential relationships were close to these experimental results (100 µV per 1 mm s-1 ). CONCLUSIONS AND INFERENCES: These data quantify the relationships between slow wave frequency, velocity, and extracellular amplitude. The results from both human and porcine studies were in keeping with biophysical models, demonstrating concordance with ICC biophysics. These relationships are important in the regulation of gastric motility and will help to guide interpretations of dysrhythmias.

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis.

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum.

BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis. METHODS: Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index. RESULTS: Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.

Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing.

BACKGROUND: Early satiety (ES) and postprandial fullness (PPF) are often present in gastroparesis, but the importance of these symptoms in gastroparesis has not been well-described. The aims were: (i) Characterize ES and PPF in patients with gastroparesis. (ii) Assess relationships of ES and PPF with etiology of gastroparesis, quality of life, body weight, gastric emptying, and water load testing. METHODS: Gastroparetic patients filled out questionnaires assessing symptoms (PAGI-SYM) and quality of life (PAGI-QOL, SF-36v2). Patients underwent gastric emptying scintigraphy and water load testing. KEY RESULTS: 198 patients with gastroparesis (134 IG, 64 DG) were evaluated. Early satiety was severe or very severe in 50% of patients. Postprandial fullness was severe or very severe in 60% of patients. Severity scores for ES and PPF were similar between idiopathic and diabetic gastroparesis. Increasing severity of ES and PPF were associated with other gastroparesis symptoms including nausea/vomiting, satiety/early fullness, bloating, and upper abdominal pain and GERD subscores. Increasing severity of ES and PPF were associated with increasing gastroparesis severity, decreased BMI, decreased quality of life from PAGI-QOL and SF-36 physical health. Increasing severity of ES and PPF were associated with increasing gastric retention of a solid meal and decreased volume during water load test. CONCLUSIONS & INFERENCES: Early satiety and PPF are commonly severe symptoms in both diabetic and idiopathic gastroparesis. Early satiety and PPF severity are associated with other gastroparesis symptom severities, body weight, quality of life, gastric emptying, and water load testing. Thus, ES and PPF are important symptoms characterizing gastroparesis. ClinicalTrials.gov number: NCT NCT01696747.

An energy algorithm improves symptoms in some patients with gastroparesis and treated with gastric electrical stimulation.

Gastric electrical stimulation (GES) is effective to improve symptoms of nausea and vomiting in most patients, but very little is known about the effect of varying stimulation parameters. We analysed stimulation parameters in a pilot study of 22 patients (12 idiopathic, four diabetic and four postsurgical) with drug-refractory gastroparesis who did not respond optimally to initial settings. Patients underwent high-frequency/low energy GES using identical initial stimulation parameters: 5 mA of current, 330 micros pulse width, 14 Hz for 0.1 s on and 5.0 s off. Due to lack on optimal response, 22 patients underwent alteration of an algorithm using stimulation parameters. At follow-up (mean of 4.3 years) a dose-response relationship for charge, power and energy were compared with baseline for the whole group and for each diagnostic subgroup by anova data are reported as mean +/- SE. Based on the mean of individual dose-response curves, differences in data are charge, current per pulse and energy per pulse were noted for the whole group at follow up vs baseline. The subgroup of patients with postsurgical gastroparesis required the most energy using the algorithm. In conclusion, an algorithmic approach to identify optimal stimulation parameters in GES for individual patients is associated with symptom improvement. Also, certain subgroups appear to have different energy parameters. Based on this preliminary data, the use of an algorithm for some patients with GES is feasible and may have potential for clinical application. A randomized-controlled trial of different stimulation parameters for GES seems warranted.

Postinfectious gastroparesis related to autonomic failure: a case report.

BACKGROUND AND AIM: Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary and digestive dysfunction. Herein, we present a case of a 31-year-old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full-thickness small intestinal biopsies, cardiovagal testing and autopsy. HOSPITAL COURSE: This patient affected by a severe gastroparesis was treated with antiemetics, prokinetics, analgesics and gastric electrical stimulation to control symptoms. Nutritional support was made using jejunal feeding tube and, in the final stage of disease, with total parenteral nutrition. Autonomic studies revealed minimal heart rate variability and a disordered Valsalva manoeuvre although the enteric nervous system and the smooth muscle layer showed a normal appearance. Hospital courses were complicated by episodes of bacteraemia and fungemia. Serum antiphospholipid antibodies were noted but despite anticoagulation, she developed a pulmonary embolism and shortly thereafter the patient died. Autopsy revealed acute haemorrhagic Candida pneumonia with left main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased myelinated axons with vacuolar degeneration and patchy inflammation consistent with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the stomach and small bowel revealed no evidence of enteric neuropathy or myopathy. CONCLUSION: A Guillain-Barre-like disease with gastroparesis following acute gastroenteritis is supported by physiological and autonomic studies with histological findings.

Treatment of gastroparesis: a multidisciplinary clinical review.

This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.

Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes.

BACKGROUND: In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients. METHODS: Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes. KEY RESULTS: At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life. CONCLUSIONS & INFERENCES: Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis.

BACKGROUND: Nausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic gastroparesis (IG). METHODS: Gastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting. KEY RESULTS: Of 159 gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p = 0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating. CONCLUSIONS & INFERENCES: Nausea is present in essentially all patients with gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.

Is gastric electrical stimulation superior to standard pharmacologic therapy in improving GI symptoms, healthcare resources, and long-term health care benefits?

CONTEXT: Severe upper gastrointestinal (GI) motor disorders, including gastroparesis (GP), can consume significant health care resources. Many patients are refractory to traditional drug therapy. OBJECTIVE: To compare symptoms, healthcare resource utilization and costs in two groups of patients with the symptoms of GP: those treated via gastric electrical stimulation (GES) and those treated with traditional pharmacological agents in an intensive outpatient program (MED). DESIGN: A long-term comparison of patients with devices (n = 9) vs intensive medical therapy (n = 9). SETTING AND PATIENTS: A total of 18 eligible patients with the symptoms of GP reported for 1-year baseline and long-term treatment for 3 years. INTERVENTIONS: Patients with the symptoms of GP were treated by a GES or intensive medical therapy (MED). MAIN OUTCOME MEASURES: GP Symptoms, healthcare resource utilization using investigator-derived independent outcome measure score (IDIOMS) and total hospital (inpatient and outpatient) billing costs. RESULTS: Gastrointestinal symptoms were significantly different from baseline (F = 3.03, P < 0.017) with GP patients treated via GES showing more sustained improvement over 36 months than those treated via MED. Healthcare resource usage, measured via the IDIOMS, significantly improved at 12, 24 and 36 month follow-up for GES patients (F = 10.49, P < 0.001), compared with patients receiving medical therapy, who demonstrated further deterioration. GP patients treated via GES also proved superior to medical therapy at 24 and 36 months with regard to decreased costs (F = 4.85, P < 0.001). Within group comparisons indicated significantly reduced hospital days for both patient groups; however, no statistical differences were noted between groups in terms of hospital days. Three of nine patients in the MED group died primarily from i.v. access related problems; none of the GES patients died. CONCLUSION: We conclude that GES is more effective in improving long-term GI symptoms and costs, and decreasing use of healthcare resources than intensive medical therapy, in this sample of patients with the symptoms of GP followed for 3 years. Certain patients with GP form a high-risk group in terms of costs, quality of life, morbidity and mortality.

The impact of surgical excisions on human gastric slow wave conduction, defined by high-resolution electrical mapping and in silico modeling.

BACKGROUND: Gastric contractions are coordinated by slow waves, generated by interstitial cells of Cajal (ICC). Gastric surgery affects slow wave conduction, potentially contributing to postoperative gastric dysfunction. However, the impact of gastric cuts on slow waves has not been comprehensively evaluated. This study aimed to define consequences of surgical excisions on gastric slow waves by applying high-resolution (HR) electrical mapping and in silico modeling. METHODS: Patients undergoing gastric stimulator implantation (n = 10) underwent full-thickness stapled excisions (25 × 15 mm, distal corpus) for histological evaluation, enabling HR mapping (256 electrodes; 36 cm(2) ) over and adjacent to excisions. A biophysically based in silico model of bidirectionally coupled ICC networks was developed and applied to investigate the underlying conduction mechanisms and importance of excision orientation. KEY RESULTS: Normal gastric slow waves propagated aborally (3.0 ± 0.2 cpm). Excisions induced complete conduction block and wavelets that rotated around blocks, then propagated rapidly circumferentially distal to the blocks (8.5 ± 1.2 vs normal 3.6 ± 0.4 mm/s; p < 0.01). This 'conduction anisotropy' homeostatically restored antegrade propagating gastric wavefronts distal to excisions. Excisions were associated with complex dysrhythmias in five patients: retrograde propagation (3/10), ectopics (3/10), functional blocks (2/10), and collisions (1/10). Simulations demonstrated conduction anisotropy emerged from bidirectional coupling within ICC layers and showed transverse incision length and orientation correlated with the degree of conduction distortion. CONCLUSIONS & INFERENCES: Orienting incisions in the longitudinal gastric axis causes least disruption to electrical conduction and motility. However, if transverse incisions are made, a homeostatic mechanism of gastric conduction anisotropy compensates by restoring aborally propagating wavefronts. Complex dysrhythmias accompanying excisions could modify postoperative recovery in susceptible patients.

Idiopathic cyclic nausea and vomiting--a disorder of gastrointestinal motility?

Eight patients (five men and three women) with previously unexplained recurrent cyclic episodes of nausea and vomiting are described. In these patients, the symptoms developed a mean of once every 3.2 months and persisted a mean of 3.5 days. None of the patients had an identifiable cause of their symptoms on conventional diagnostic tests. A detailed investigation of the gastrointestinal motility during an asymptomatic period revealed abnormal findings in all eight patients. Gastric hypomotility was substantiated in five patients, small bowel dysmotility in six, delayed gastric emptying in two, and gastric dysrhythmia in two. The data demonstrate that abnormal gastrointestinal motility occurs during an asymptomatic state in patients with cyclic episodes of nausea and vomiting. Because all patients with this syndrome had abnormal gastrointestinal motility but normal results of other gastrointestinal studies, idiopathic cyclic nausea and vomiting may be related to altered gastrointestinal motility.

Entamoeba polecki infection in Southeast Asian refugees: multiple cases of a rarely reported parasite.

Recently, Entamoeba polecki was identified for the first time in our parasitology laboratory in stool specimens from eight Southeast Asian refugees. This ameba has been reported infrequently in the Western world; most reported cases have been from the New Guinea region. In most previously described patients and in our patients, no definite gastrointestinal symptoms could be directly attributed to E. polecki infection. Morphologically, E. polecki may mimic the pathogen E. histolytica and also nonpathogens such as E. coli. These species are most readily distinguished by studying encysted forms. In contrast to E. histolytica and E. coli, E. polecki characteristically has uninucleate cysts. Both pigs and monkeys naturally harbor E. polecki, but four of the patients in this series had no apparent contact with these animals. Other modes of infection may be human-to-human transmission or acquisition from other domestic animals. Six of our eight patients were treated successfully with one course of metronidazole in a regimen similar to that used for E. histolytica infection. In the two other patients, repeated courses of therapy eradicated the infection. Because of the recent increase in number of Southeast Asian immigrants to the United States, E. polecki may be identified more frequently than in the past. Physicians and laboratory personnel should be familiar with this organism, because it may be confused with E. histolytica or may act as a pathogen.

Effect of inhibition of prostaglandin synthesis on epinephrine-induced gastroduodenal electromechanical changes in humans.

We conducted a double-blind randomized study to investigate the role of endogenous prostaglandins in epinephrine-induced changes in human gastric electromechanical activity. Intravenous administration of a pharmacologic dosage of epinephrine (222 ng/kg per min) caused gastric dysrhythmia in 8 of 12 healthy subjects. After indomethacin treatment, the incidence of epinephrine-induced gastric dysrhythmia was reduced to 4 of 12 healthy subjects, which is similar to the incidence of gastric dysrhythmia noted in the placebo group. The difference, however, was not statistically significant (P = 0.2). Epinephrine also substantially inhibited both the amplitude and the frequency of antral contractions. Indomethacin treatment partially reversed the reduction in the amplitude but not the frequency of antral contractions. These results suggest that endogenous prostaglandins may, in part, regulate the amplitude of human antral contractions; however, the role of prostaglandins in epinephrine-induced gastric dysrhythmia in humans remains uncertain.

A model of gastric electrical activity in health and disease.

The idea of diagnosing gastric dysfunction from noninvasive measurements of gastric electrical activity (GEA) is intuitively appealing, but the predictive accuracy of the cutaneous signal, especially that of its amplitude, is still in question. Mathematical modeling provides a means of investigating, analyzing, and predicting GEA measured percutaneously. In this study, a model of GEA applicable both in health and disease was developed and simulated for a cylindrical body surface. Body-surface maps of the simulated electrogastrogram (EGG) were generated at a 20 by 20 array of sites on the model's surface, and the accuracy of the percutaneous method in detecting simulated gastric electrical abnormalities was determined. The relationship between the amplitude of the simulated surface EGG and the velocity of propagation of the myogenic activity was also investigated. This was compared to a similar investigation of the fluctuations in the amplitude of the surface EGG with the velocity of propagation of the serosal activity measured in humans. The diagnostic accuracy of the measured cutaneous EGG in humans was also determined. The results obtained from the mathematical model show that the amplitude of the electrogastrogram increases with the propagation velocity of GEA. Similar results were obtained from the experimental measurements. The amplitude of the simulated and measured cutaneous signal correlated well (p < 0.05) with the phase shift of the simulated and measured activities, (-0.85, -0.54), respectively. Serosal normal activity, tachygastria, and uncoupling were detected 67%, 90%, and 0% of the time, respectively, at the cutaneous electrode in humans. In simulations, normal activity and tachygastria were accurately detected at all 400 sites on the surface. Uncoupling simulated with 50% of the myogenic sources "diseased" was detected at only 20 of the 400 sites. The results confirm that the amplitude of the cutaneous signal is a function of the velocity of propagation of the myogenic signal. It also confirms that while GEA in health may be accurately predicted from percutaneous recordings, frequency and phase/coupling abnormalities are poorly detected from single-channel electrogastrograms. This suggests the use of multiple-channel surface recordings in clinical electrogastrography.

Effect of cisapride therapy for severe dyspepsia on gastrointestinal symptoms and quality of life.

Quality of life measures have received little attention in evaluation of therapy for dyspepsia. To examine the effect of cisapride on gastrointestinal symptoms and quality of life measures, we studied eight patients with chronic, severe dyspepsia, before and after therapy with cisapride (20 mg three times daily) for 12 months. Gastrointestinal (GI) Total Symptom Score (TSS), Overall Patient Assessment (OPA), and quality of life by both trait (Minnesota Multiphasic Personality Inventory (MMPI)) and physical function (Sickness Impact Profile (SIP)) were measured at base line and at month 12 of cisapride therapy. Results showed significant improvement in TSS, OPA, and the MMPI Depression and Anxiety scales (all, p < 0.05). Improvement in the SIP physical dimension score approached significance (p = 0.065). We conclude that, in this group of patients with severe dyspepsia, both GI symptoms and quality of life measures improved with 12 months of cisapride therapy. These quality of life measures may prove useful in evaluating the efficacy of drug treatment for dyspepsia.

Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.

BACKGROUND: There is increasing evidence for specific cellular changes in the stomach of patients with diabetic (DG) and idiopathic (IG) gastroparesis. The most significant findings are loss of interstitial cells of Cajal (ICC), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD206+ and iNOS+ cells. To investigate associations between cellular phenotypes and ICC. METHODS: Full thickness gastric body biopsies were obtained from non-diabetic controls (C), diabetic controls (DC), DG, and IG patients. Sections were labeled for CD45, CD206, Kit, iNOS, and putative human macrophage markers (HAM56, CD68, and EMR1). Immunoreactive cells were quantified from the circular muscle layer. KEY RESULTS: Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between iNOS+ cells and ICC in the DC group, but not the other groups. CD68 and HAM56 reliably labeled the same cell populations, but EMR1 labeled other cell types. CONCLUSIONS & INFERENCES: Depletion of ICC and correlation with changes in CD206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.