Neutron-scattering measurements of spin excitations in LaFeAsO and Ba(Fe(0.953)Co(0.047))(2)As(2): evidence for a sharp enhancement of spin fluctuations by nematic order.

Inelastic neutron scattering is employed to investigate the impact of electronic nematic order on the magnetic spectra of LaFeAsO and Ba(Fe(0.953)Co(0.047))(2)As(2). These materials are ideal to study the paramagnetic-nematic state, since the nematic order, signaled by the tetragonal-to-orthorhombic transition at T(S), sets in well above the stripe antiferromagnetic ordering at T(N). We find that the temperature-dependent dynamic susceptibility displays an anomaly at T(S) followed by a sharp enhancement in the spin-spin correlation length, revealing a strong feedback effect of nematic order on the low-energy magnetic spectrum. Our findings can be consistently described by a model that attributes the structural or nematic transition to magnetic fluctuations, and unveils the key role played by nematic order in promoting the long-range stripe antiferromagnetic order in iron pnictides.

Efficacy of needleless transcutaneous electroacupuncture in synchronization with breathing for symptomatic idiopathic gastroparesis: A blinded and controlled acute treatment trial.

BACKGROUND: Needleless transcutaneous electroacupuncture (TEA) improves nausea and myoelectrical activity in diabetic gastroparesis (GP). Synchronized TEA (STEA), which combines synchronized breathing with TEA, is more potent than TEA in enhancing vagal activity in healthy subjects. AIMS: To investigate whether STEA improves symptoms, electrogastrogram (EGG) and vagal activity in idiopathic gastroparesis (IGP). METHODS: Eighteen IGP subjects underwent 2 randomized visits (sham at non-acupoints or real STEA at acupoints) consisted of a 30-minute baseline, an Ensure challenge to provoke nausea, followed by 60-minute treatment with sham or real STEA, and 15-minute observation period. Severity of nausea, EGG, and vagal activity (based on electrocardiogram and serum Pancreatic Polypeptide, PP) were recorded. RESULTS: In sham or STEA, the nausea scores of 2.7 ± 0.5 and 1.9 ± 0.5 at fasting baseline, respectively, increased to 5.9 ± 0.4 and 5.8 ± 0.3 during Ensure test (P < .05, vs baseline), subsequently reduced to 3.4 ± 0.6 with sham or 3.6 ± 0.6 with STEA, respectively (P < .05, vs Ensure period). Experiments with sham and STEA started with similar % of normal waves on EGG (66.4 ± 3.9 and 61.8 ± 3.0, respectively); decreased to 63. 5 ± 4.1 and 58.2 ± 2.8 during the Ensure test. After STEA, there was ~24% increase in % of normal waves, significantly different from the sham (6.0%) (P < .01). In sham or STEA, vagal activity was identical at baseline and after the Ensure. STEA induced a 3-fold increase in vagal activity compared with sham (P < .01). Ensure increased serum PP levels, and both treatments decreased the PP CONCLUSIONS: In IGP, STEA is not superior to Sham in decreasing nausea, but is more effective in improving gastric dysrhythmia.

Does a glucose-based hydrogen and methane breath test detect bacterial overgrowth in the jejunum?

BACKGROUND: Direct diagnosis of small intestinal bacterial overgrowth (SIBO) requires the collection and culture of fluid from the jejunal lumen, with a finding of over 105 viable bacteria per mL. More often, SIBO is diagnosed indirectly, using a non-invasive test of the exhaled hydrogen and methane generated by microbial fermentation when ingested glucose reaches the jejunum. Our objective was to determine how well this breath test detects chronic overgrowth of jejunal bacteria that is unrelated to gastrointestinal surgery. METHODS: Eighteen patients reporting symptoms consistent with SIBO received a glucose breath test. On a later day, the jejunal lumen was sampled via aspiration during enteroscopy. Jejunal aspirates were cultured on aerobic and anaerobic media. DNA was extracted from the same samples and analyzed by quantitative pan-bacterial PCR amplification of 16S ribosomal rRNA genes, which provided a culture-independent bacterial cell count. KEY RESULTS: Combined bacterial colony counts ranged from 5.7 x 103 to 7.9 x 106 CFU/mL. DNA-based yields ranged from 1.5 x 105 to 3.1 x 107 bacterial genomes per mL. Microbial viability ranged from 0.3% to near 100%. We found no significant correlation of glucose breath test results with either the number of bacterial colonies or with the DNA-based bacterial cell counts. Instead, higher signals in the hydrogen-methane breath test were significantly correlated with a lower viability of jejunal bacteria, at a P-value of .014. CONCLUSIONS & INFERENCES: The glucose-based hydrogen and methane breath test is not sensitive to the overgrowth of jejunal bacteria. However, a positive breath test may indicate altered jejunal function and microbial dysbiosis.

Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND & AIMS: Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. METHODS: PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I2 statistics where I2  ≤ 50% and I2  > 50% indicated fixed and random effect models, respectively. KEY RESULTS: Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3+ T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P = .001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P = .002). This was possibly in relation to higher CD4+ T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P = .04) as there were no differences in CD8+ T cells. CONCLUSIONS & INFERENCES: Mast cells and CD3+ T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation.

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.

Electrical and mechanical activity in the human lower esophageal sphincter during diaphragmatic contraction.

To determine the effect of contraction of the diaphragm on the lower esophageal sphincter (LES) pressure, we studied eight healthy volunteers during spontaneous breathing, maximal inspiration, and graded inspiratory efforts against a closed airway (Muller's maneuver). Electrical activity of the crural diaphragm (DEMG) was recorded from bipolar esophageal electrodes, transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures, and LES pressure was recorded using a sleeve device. During spontaneous breathing, phasic inspiratory DEMG was accompanied by phasic increases in Pdi and LES pressure. With maximal inspiration, DEMG increased 15-20-fold compared with spontaneous inspiration, and LES pressure rose from an end-expiratory pressure of 21 to 90 mmHg. Similar values were obtained during maximal Muller's maneuvers. LES pressure fell promptly when the diaphragm relaxed. Graded Muller's maneuver resulted in proportional increases in the Pdi, LES pressure, and DEMG. The LES pressure was always greater than Pdi and correlated with it in a linear fashion (P less than 0.001). We conclude that the contraction of the diaphragm exerts a sphincteric action at the LES, and that this effect is an important component of the antireflux barrier.

Mechanism of histamine-induced excitation of the cat pylorus.

Intravenous histamine causes high amplitude repetitive phasic contractions of the in vivo cat pylorus but has little effect on the antrum and duodenum. The genesis of this phasic response was studied using a pinned perfused catheter with openings at the pylorus, antrum, and duodenum. 2-Pyridylethylamine, an H1 agonist, produced phasic contractions similar to histamine whereas dimaprit, an H2 agonist, did not. Conversely, histamine-induced excitation is competitively antagonized by the H1 inhibitor diphenhydramine but not by the H2 inhibitor cimetidine. Thus histamine excitation is mediated through H1 receptor stimulation. Tetrodotoxin caused inhibition of the histamine response indicating that pyloric excitation is partly mediated through a neural pathway. To identify the nature of this pathway adrenergic and cholinergic blockers were used. Atropine, hexamethonium, and propranolol had no effect on the histamine response. Phentolamine and reserpine increased the magnitude of the histamine response. Conversely, phenylephrine blocked the histamine response. We conclude: histamine induces high phasic contractions in the pylorus; this effect is mediated through neural (nonadrenergic noncholinergic) and myogenic H1 receptors; alpha adrenergic stimulation inhibits the histamine response and alpha adrenergic blockade and catecholamine depletion increase it.

Efficacy of mitemcinal, a motilin agonist, on gastrointestinal symptoms in patients with symptoms suggesting diabetic gastropathy: a randomized, multi-center, placebo-controlled trial.

BACKGROUND: Mitemcinal, an oral motilin agonist, accelerates gastric emptying. AIM: To investigate if mitemcinal was superior to placebo in relief of symptoms attributed to gastroparesis. METHODS: In a randomized, double-blind design, 392 insulin-requiring diabetics with symptoms attributable to gastroparesis were treated for 3 months with placebo, mitemcinal 5 or 10 mg bid. On a weekly basis, patients assessed whether there was adequate relief of their gastroparesis symptoms. Patients were classified as Complete Responders (CR) if there were three consecutive positive monthly responses, which required at least 50% of their weekly responses in a month being positive. An Overall Responder (OR) had at least 75% positive weekly responses for the whole treatment period. RESULTS: Mitemcinal 10 mg produced a significantly better response rate than placebo with a 10.6% increase in the OR (P < 0.05 vs. placebo). Mitemcinal 10 mg also produced statistically significant increases in the CR and OR in the subgroup identified by baseline body mass index (<35 kg/m(2)) and haemoglobin A(1c) (<10%) (P < 0.01 vs. placebo). Adverse events did not differ from placebo frequency levels. CONCLUSIONS: Mitemcinal can induce a statistically significant response to treatment in a subset of diabetic gastroparesis where future prokinetic clinical trials should be focused.

Clinical trial: effect of mitemcinal (a motilin agonist) on gastric emptying in patients with gastroparesis - a randomized, multicentre, placebo-controlled study.

BACKGROUND: Mitemcinal is an orally active motilin agonist that could potentially improve gastric emptying. AIM: To investigate the effect of mitemcinal on gastric emptying in patients with idiopathic and diabetic gastroparesis. METHODS: In a randomized, double-blind design, 106 patients were randomized into four dosing regimens (22 to placebo and 21 each to mitemcinal 10 mg, 20 mg, 30 mg bid or 20 mg tid) for 28 days. A standardized scintigraphic gastric emptying test was performed at screening and again after completing the 4-week protocol. RESULTS: All doses of mitemcinal showed prokinetic activity. A significant improvement in meal retention at 240 min was noted even in the lowest dose group with the greatest improvement observed with 30 mg bid group (75% vs. 10% in placebo group). Diabetic patients responded better than the idiopathic subgroup. In diabetic patients, blood glucose at 1 h after a meal showed dose-dependent elevation. Although gastroparetic symptoms improved with both mitemcinal and placebo, the prominent placebo effect was not statistically exceeded by mitemcinal. Baseline scintigraphy results exhibited no clear correlation between the severity of gastroparetic symptoms and the status of gastric emptying. CONCLUSION: Mitemcinal is capable of accelerating gastric emptying in both diabetic and idiopathic patients with gastroparesis.

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.

Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis.

The aims were to determine symptom responses and long-term outcomes in gastroparetic patients receiving gastric electrical stimulation (GES) therapy beyond 3 years by presenting per protocol analysis and intention-to-treat (ITT) analysis. Data collected at baseline, 1 year and beyond 3 years in 55 patients included total symptom scores (TSS), nutritional status, weight, hospitalizations, the use of prokinetic and/or antiemetic medications, HbA1c in diabetics and adverse events. Of the 55 patients, 10 died of non-pacemaker-related complications, six had the devices removed and two could not be reached. The remaining 37 patients had the device activated for a mean of 45 months. Both per protocol and ITT analysis demonstrated that TSS, hospitalization days and the use of medications were all significantly reduced at 1 year and were sustained beyond 3 years. Average TSS decreased by 62.5% for the 37 patients completing 3 years of GES. At implantation, 15/37 patients required nutritional support and only five continued beyond 3 years. Mean HbA1c level in diabetics was significantly reduced from 9.5 to 7.9% at 3 years. We conclude that a significant improvement in symptoms and all measures of clinical outcome can be maintained for greater than 3 years with GES in patients with refractory gastroparesis.

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.

Thermodynamic database for the Co-Pr system.

In this article, we describe data on (1) compositions for both as-cast and heat treated specimens were summarized in Table 1; (2) the determined enthalpy of mixing of liquid phase is listed in Table 2; (3) thermodynamic database of the Co-Pr system in TDB format for the research articled entitle Chemical partitioning for the Co-Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase W.

Depleted interstitial cells of Cajal and fibrosis in the pylorus: Novel features of gastroparesis.

BACKGROUND: Depletion and ultrastructural changes of interstitial cells of Cajal (ICC) in the gastric body and antrum have been observed in gastroparesis. This research was performed to investigate the ICC population in the muscularis propria and fibrosis of the muscular layer of the pylorus in gastroparesis. METHODS: Full thickness pyloric and antral biopsies were obtained from 17 gastroparetic and 6 non-gastroparetic controls. Biopsies were stained with C-Kit for ICC and Trichrome for collagen fibrosis. Interstitial cells of Cajal depletion in the antrum was defined as mean ICC count <10 per 20 high power fields (HPF) based on established data. KEY RESULTS: The average pyloric ICC count was ≥10/HPF in the control patients. Twelve (70.5%) gastroparetic patients had pyloric ICC loss. Only five patients (29.4%) had ICC loss in the antrum. Gastric emptying (GE) was not significantly different in patients with depleted vs normal pyloric ICC. However, GE at 2 h was slower in patients with antral ICC <10/HPF compared to those with normal antral ICC populations. Collagen fibrosis was observed in the pylorus of 14 (82.3%) patients. Inclusion bodies in the muscularis propria of the pylorus were identified in four patients, all with diabetic gastroparesis. CONCLUSIONS & INFERENCES: In gastroparetic patients, ICC loss in the pylorus is twice as common as in the antrum and fibrosis in the pyloric smooth muscle is nearly three times more common than the antrum. These findings can provide one explanation for pyloric dysfunction which is a contributing factor to the pathophysiology 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.

Efficiency and efficacy of multi-channel gastric electrical stimulation.

Gastric electrical stimulation (GES) using single channel has been under investigation for its therapeutic potential for gastroparesis. The aim of this study was to study the efficacy and efficiency of multi-channel GES in accelerating gastric emptying in dogs. The study was performed in eight dogs, and gastric emptying of liquid was assessed in three randomized sessions of control, one-channel GES and four-channel GES. It was found that (i) GES of both one-channel and four-channel was able to completely entrain the slow waves in the entire stomach. However, the stimulation energy required by four-channel GES was only 1% of that required by one-channel GES. (ii) Four-channel, but not one-channel, GES significantly and substantially accelerated gastric emptying. An increase of 121.0 and 93.9% was noted with four-channel GES at 30 and 60 min after the meal, respectively. It was concluded that four-channel GES is substantially more efficient and effective than conventional single-channel GES in improving gastric emptying. It is worthy to explore its therapeutic potential for gastroparesis in clinical settings.

Transition from peristaltic esophageal contractions to diffuse esophageal spasm.

A patient with dysphagia and chest pain was shown by manometry to have high-amplitude peristaltic esophageal contractions (nutcracker esophagus). Worsening symptoms over the next two years led to the performance of repeated manometric studies, which showed diffuse esophageal spasm. This demonstration of a transition from nutcracker esophagus to diffuse esophageal spasm lends further support for consideration of the nutcracker esophagus as a manometric disorder associated with chest pain or dysphagia. Furthermore, it suggests a pathophysiologic relationship between the nutcracker esophagus, a disorder with preserved peristalsis, and diffuse esophageal spasm, the classic dysmotility considered to be of neurogenic origin.

Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial.

In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.