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- Methanogens, Methane and Gastrointestinal Motility. [REVIEW]
- J Neurogastroenterol Motil 2014 Jan; 20(1):31-40.
Anaerobic fermentation of the undigested polysaccharide fraction of carbohydrates produces hydrogen in the intestine which is the substrate for methane production by intestinal methanogens. Hydrogen and methane are excreted in the flatus and in breath giving the opportunity to indirectly measure their production using breath testing. Although methane is detected in 30%-50% of the healthy adult population worldwide, its production has been epidemiologically and clinically associated with constipation related diseases, like constipation predominant irritable bowel syndrome and chronic constipation. While a causative relation is not proven yet, there is strong evidence from animal studies that methane delays intestinal transit, possibly acting as a neuromuscular transmitter. This evidence is further supported by the universal finding that methane production (measured by breath test) is associated with delayed transit time in clinical studies. There is also preliminary evidence that antibiotic reduction of methanogens (as evidenced by reduced methane production) predicts the clinical response in terms of symptomatic improvement in patients with constipation predominant irritable bowel syndrome. However, we have not identified yet the mechanism of action of methane on intestinal motility, and since methane production does not account for all constipation associated cases, there is need for high quality clinical trials to examine methane as a biomarker for the diagnosis or as a biomarker that predicts antibiotic treatment response in patients with constipation related disorders.
- Diabetic Neuropathies: Diagnosis and Management. [JOURNAL ARTICLE]
- Neuroendocrinology 2014 Jan 22.:267-280.
Introduction: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. Methods: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. Conclusion: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective. © 2014 S. Karger AG, Basel.
- Dietary Herb Extract Rikkunshi-To Ameliorates Gastroparesis in Parkinson's Disease: A Pilot Study. [JOURNAL ARTICLE]
- Eur Neurol 2014 Jan 21; 71(3-4):193-195.
Objective: To perform an open trial on the effects of the extract of the dietary herb Rikkunshi-to (RKT) on gastroparesis in Parkinson's disease (PD) patients, using objective parameters given by the (13)C-sodium acetate expiration breath test (gastric emptying study). Methods: Twenty patients with PD were enrolled into this study. Eleven patients were male and 9 were female, with the following characteristics (mean ± SD): age, 69.4 ± 8.17 years; disease duration, 4.34 ± 4.03 years; modified Hoehn and Yahr stage, 2.37 ± 0.98, and Unified Parkinson's Disease Rating Scale Part 3 motor score, 16.6 ± 7.37. Fourteen patients came to the clinic due to constipation; 16 patients were taking 288 ± 72 mg/day levodopa/carbidopa, 2 were taking dopamine agonists, and the others were not treated yet. All patients underwent the breath test. Statistical analysis was performed using Student's t test. Results: RKT was well tolerated by all patients and none experienced abdominal pain or other adverse effects, except for its bitter taste. RKT significantly reduced the peak time of the (13)C-dose-excess curve (p < 0.05). Conclusion: In this pilot trial, we found a significant shortening of the gastric emptying time after administration of the dietary herb extract RKT in PD patients. Further studies examining both gastric emptying and delayed-on in PD are warranted. © 2014 S. Karger AG, Basel.
- [Thinking of laparoscopic anatomy of laparoscopic distal D2 radical gastrectomy]. [English Abstract, Journal Article]
- Zhonghua Wai Ke Za Zhi 2013 Nov; 51(11):991-5.
To discuss laparoscopic assisted radical D2 resection of distal gastric anatomy application ideas.Collected the clinical data from January 2009 to January 2012 who underwent laparoscopic distal gastric resection in patients with D2 349 cases. There were 180 male and 169 female patients, and the age were (57 ± 3) years old (range 29-86 years), the body mass index of patients were (26.0 ± 2.0) kg/m(2) (range 20.5-32.8 kg/m(2)). The relevant surgical anatomy ideas had summarized.In addition to 5 cases of obese patients with conversion to open, the remaining patients underwent laparoscopic distal gastric D2 resection. The operation is divided into 7 operating anatomical view. The operation time were 120-210 minutes and the blood loss were 50-200 ml. Postoperative complications occurred in 11 cases, including 5 cases of duodenal stump leakage, 2 cases of gastroparesis, 3 cases of small bowel obstruction, and abdominal bleeding in 1 case. All patients were discharged.Use zoning, exterior to interior of the anatomy, more conducive to master the operation of laparoscopic radical gastrectomy and standardized cleaning, to improve the operation efficiency and shorten the surgical learning curve and improve the quality of surgery has an important role.
- Ghrelin and motilin receptor agonists: time to introduce bias into drug design. [Journal Article, Research Support, Non-U.S. Gov't]
- Neurogastroenterol Motil 2014 Feb; 26(2):149-55.
Ghrelin and motilin receptor agonists increase gastric motility and are attractive drug targets. However, 14 years after the receptors were described (18-24 years since ligands became available) the inactivity of the ghrelin agonist TZP-102 in patients with gastroparesis joins the list of unsuccessful motilin agonists. Fundamental questions must be asked. Pustovit et al., have now shown that the ghrelin agonist ulimorelin evokes prolonged increases in rat colorectal propulsion yet responses to other ghrelin agonists fade. Similarly, different motilin agonists induce short- or long-lasting effects in a cell-dependent manner. Together, these and other data create the hypothesis that the receptors can be induced to preferentially signal ('biased agonism') via particular pathways to evoke different responses with therapeutic advantages/disadvantages. Biased agonism has been demonstrated for ghrelin. Are motilin agonists which cause long-lasting facilitation of human stomach cholinergic function (compared with motilin) biased agonists (e.g., camicinal, under development for patients with gastric hypo-motility)? For ghrelin, additional complications exist because the therapeutic aims/mechanisms of action are uncertain, making it difficult to select the best (biased) agonist. Will ghrelin agonists be useful treatments of nausea and/or as suggested by Pustovit et al., chronic constipation? How does ghrelin increase gastric motility? As gastroparesis symptoms poorly correlate with delayed gastric emptying (yet gastro-prokinetic drugs can provide relief: e.g., low-dose erythromycin), would low doses of ghrelin and motilin agonists relieve symptoms simply by restoring neuromuscular rhythm? These questions on design and functions need addressing if ghrelin and motilin agonists are to reach patients as drugs.
- SIBO in Gastroparesis: Sci-fi or Science Fact? [Journal Article]
- Dig Dis Sci 2014 Mar; 59(3):510-2.
- New Approaches to Management of PPI-Refractory Gastroesophageal Reflux Disease. [Journal Article]
- Curr Treat Options Gastroenterol 2014 Mar; 12(1):18-33.
"Refractory GERD" is one the most common misnomers in the area of gastroesophageal reflux disease. The term implies reflux as the underlying etiology despite unresponsiveness to aggressive, often twice-daily proton pump inhibitor therapy. The term should be replaced with "refractory symptoms." We must acknowledge that in many patients, symptoms of reflux often overlap with non-GERD causes such as gastroparesis, dyspepsia, hypersensitive esophagus, and functional disorders. Lack of response to aggressive acid suppressive therapy often leads to esophagogastroduodenoscopy followed by pH or impedance monitoring. In the majority of patients these tests are normal. The role of non-acid reflux measured by impedance pH testing in this group is uncertain at best and the results from this test alone should not be used to refer patients to surgical fundoplication. In patients unresponsive to acid suppressive therapy, reflux is most commonly not causal and a search for non-GERD causes must ensue.
- A small particle size diet reduces upper gastrointestinal symptoms in patients with diabetic gastroparesis: a randomized controlled trial. [Journal Article]
- Am J Gastroenterol 2014 Mar; 109(3):375-85.
Gastroparesis is a well-known complication to diabetes mellitus (DM). Dietary advice is considered to be of importance to reduce gastrointestinal (GI) symptoms in patients with diabetic gastroparesis, but no randomized controlled trials exist. Our aim was to compare GI symptoms in insulin treated DM subjects with gastroparesis eating a diet with small particle size ("intervention diet") with the recommended diet for DM ("control diet").56 subjects with insulin treated DM and gastroparesis were randomized to the intervention diet or the control diet. The patients received dietary advice by a dietitian at 7 occasions during 20 weeks. GI symptom severity, nutrient intake and glycemic control were measured before and after the intervention.A significantly greater reduction of the severity of the key gastroparetic symptoms-nausea/vomiting (P=0.01), postprandial fullness (P=0.02) and bloating (P=0.006)-were seen in patients who received the intervention diet compared with the control diet, and this was also true for regurgitation/heartburn (P=0.02), but not for abdominal pain. Anxiety was reduced after the intervention diet, but not after the control diet, whereas no effect on depression or quality of life was noted in any of the groups. A higher fat intake in the intervention group was noted, but otherwise no differences in body weight, HbA1c or nutrient intake were seen.A small particle diet improves the key symptoms of gastroparesis in patients with diabetes mellitus. (ClinicalTrials.gov NCT01557296).
- Incidental and ablation-induced findings during upper gastrointestinal endoscopy in patients after ablation of atrial fibrillation: A retrospective study of 425 patients. [JOURNAL ARTICLE]
- Heart Rhythm 2014 Jan 10.
Although rare, atrioesophageal fistula is a serious and often lethal complication of radiofrequency catheter ablation in patients with atrial fibrillation (AF). Consequently, esophagogastroduodenoscopy after AF catheter ablation has been suggested to detect thermal esophageal lesions.To report the incidence of thermal lesions and other incidental gastrointestinal (GI) pathologies in patients with AF after radiofrequency catheter ablation.Four hundred twenty-five (mean age 59 ± 10 years; 64% men) consecutive patients with symptomatic AF who underwent left atrial radiofrequency catheter ablation were scheduled for upper GI endoscopy 1-3 days after the procedure. Patients were asymptomatic for GI diseases, that is, exhibiting no dysphagia, heart burn, or abdominal pain.Pathological GI findings were observed in 328 (77%) patients and included gastral erosions (22%), esophageal erythema (21%), gastroparesis (17%), hiatal hernia (16%), reflux esophagitis (12%), thermal esophageal lesion (11%), and suspected Barrett's esophagus (5%). Biopsies were performed in 70 patients, showing gastritis (84%), Helicobacter pylori colonization (17%) and mucosa-associated lymphoid tissue (17%), esophagitis (9%), and Barrett's esophagus (4%). Further diagnostic workup or treatment was initiated in 105 (25%) patients.Upper GI pathologies are observed frequently in asymptomatic patients. Half of all patients have a requirement for treatment. Among the findings, thermal esophageal lesions and gastroparesis can be attributed to AF catheter ablation. The high incidence of gastroparesis is a novel finding that deserves further investigation.
- The role of the vagal pathway and gastric dopamine in the gastroparesis of rats after a 6-hydroxydopamine microinjection in the substantia nigra. [JOURNAL ARTICLE]
- Acta Physiol (Oxf) 2014 Jan 11.
Gastroparesis is a common non-motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the impaired gastric motility in 6-hydroxydopamine (6-OHDA) rats, which were treated with a bilateral microinjection of 6-OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD.A strain gauge force transducer, digital X-ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study.Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6-OHDA. 6-OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6-OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6-OHDA rats.Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.