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- Gastric sensitivity and reflexes: basic mechanisms underlying clinical problems. [JOURNAL ARTICLE]
- J Gastroenterol 2013 Dec 4.
Both reflex and sensory mechanisms control the function of the stomach, and disturbances in these mechanisms may explain the pathophysiology of disorders of gastric function. The objective of this report is to perform a literature-based critical analysis of new, relevant or conflicting information on gastric sensitivity and reflexes, with particular emphasis on the comprehensive integration of basic and clinical research data. The stomach exerts both phasic and tonic muscular (contractile and relaxatory) activity. Gastric tone determines the capacity of the stomach and mediates both gastric accommodation to a meal as well as gastric emptying, by partial relaxation or progressive recontraction, respectively. Perception and reflex afferent pathways from the stomach are activated independently by specific stimuli, suggesting that the terminal nerve endings operate as specialized receptors. Particularly, perception appears to be related to stimulation of tension receptors, while the existence of volume receptors in the stomach is uncertain. Reliable techniques have been developed to measure gastric perception and reflexes both in experimental and clinical conditions, and have facilitated the identification of abnormal responses in patients with gastric disorders. Gastroparesis is characterised by impaired gastric tone and contractility, whereas patients with functional dyspepsia have impaired accommodation, associated with antral distention and increased gastric sensitivity. An integrated view of fragmented knowledge allows the design of pathophysiological models in an attempt to explain disorders of gastric function, and may facilitate the development of mechanistically orientated treatments.
- The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin. [JOURNAL ARTICLE]
- Neurogastroenterol Motil 2013 Nov 7.
Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action.Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin.Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 μg) to the lumbosacral spinal cord.Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.
- Gastrointestinal complications of diabetes. [Journal Article]
- Endocrinol Metab Clin North Am 2013 Dec; 42(4):809-32.
This review provides an overview of the vast gastrointestinal tract complications of diabetes that can occur from the mouth to the anus. The presentation, diagnosis, and management of gastrointestinal disorders, ranging from gastroparesis, celiac disease, and bacterial overgrowth to nonalcoholic fatty liver disease, are reviewed to heighten awareness. When managing care of patients with diabetes, one should keep in mind the potential gastrointestinal complications, as well as the frequent disorders that are not related to diabetes.
- Bodyweight in Patients with Idiopathic Gastroparesis: Roles of Symptoms, Caloric Intake, Physical Activity, and Body Metabolism. [JOURNAL ARTICLE]
- Neurogastroenterol Motil 2013 Nov 29.
Most gastroparetic patients are underweight probably because of frequently experienced early satiety, nausea, and vomiting. Some gastroparesis (GP) patients, however, are overweight, for reasons that are not well understood. The aim of this study was to evaluate the factors that influence bodyweight such as resting energy and exercise-related expenditure, symptoms of early satiety, nausea and vomiting, and caloric intake in patients with idiopathic GP and in healthy controls.Thirty-nine healthy controls and 29 subjects with idiopathic GP were studied. Resting energy expenditure (indirect calorimetry), body composition (bioelectrical impedance), dietary intake (Block Food Frequency Questionnaire), symptoms (Patient Assessment of Upper GI Symptoms), and physical activity (Paffenbarger exercise survey) were assessed.Both median caloric intake (1242 vs 1804 kcal; p = 0.005) and caloric expenditure (486 vs 2172 kcal; p < 0.01) were significantly lower in patients with GP as compared to controls although BMI (25.8 ± 5.8 vs 24.3 ± 4.0 kg/m(2) ) and resting energy expenditure (1327 ± 293 vs 1422 ± 243 kcal) were similar. On the other hand, the 12 GP patients who had gained weight (GW) since diagnosis had lower symptom severity (12.9 ± 4.4 vs 19.3 ± 6.3; p < 0.05), consumed more calories (1342 vs 1134 kcal; p = 0.08) and expended less calories for activity per week (406 vs 644 median kcal; p = 0.45) compared to the 17 GP patients who had lost weight or remained weight neutral (LW).Patients with GP, although in energy balance, consumed and expended less calories than healthy controls. A subgroup of patients with GP who were less symptomatic, gained weight because of increased caloric intake and reduced energy expenditure.
- A Biophysically Based Finite-State Machine Model for Analyzing Gastric Experimental Entrainment and Pacing Recordings. [JOURNAL ARTICLE]
- Ann Biomed Eng 2013 Nov 26.
Gastrointestinal motility is coordinated by slow waves (SWs) generated by the interstitial cells of Cajal (ICC). Experimental studies have shown that SWs spontaneously activate at different intrinsic frequencies in isolated tissue, whereas in intact tissues they are entrained to a single frequency. Gastric pacing has been used in an attempt to improve motility in disorders such as gastroparesis by modulating entrainment, but the optimal methods of pacing are currently unknown. Computational models can aid in the interpretation of complex in vivo recordings and help to determine optimal pacing strategies. However, previous computational models of SW entrainment are limited to the intrinsic pacing frequency as the primary determinant of the conduction velocity, and are not able to accurately represent the effects of external stimuli and electrical anisotropies. In this paper, we present a novel computationally efficient method for modeling SW propagation through the ICC network while accounting for conductivity parameters and fiber orientations. The method successfully reproduced experimental recordings of entrainment following gastric transection and the effects of gastric pacing on SW activity. It provides a reliable new tool for investigating gastric electrophysiology in normal and diseased states, and to guide and focus future experimental studies.
- Gastric electrical stimulation for treatment of clinically severe gastroparesis. [Journal Article]
- J Minim Access Surg 2013 Oct; 9(4):163-7.
Severe, drug-resistant gastroparesis is a debilitating condition. Several, but not all, patients can get significant relief from nausea and vomiting by gastric electrical stimulation (GES). A trial of temporary, endoscopically delivered GES may be of predictive value to select patients for laparoscopic-implantation of a permanent GES device.We conducted a clinical audit of consecutive gastroparesis patients, who had been selected for GES, from May 2008 to January 2012. Delayed gastric emptying was diagnosed by scintigraphy of ≥50% global improvement in symptom-severity and well-being was a good response.There were 71 patients (51 women, 72%) with a median age of 42 years (range: 14-69). The aetiology of gastroparesis was idiopathic (43 patients, 61%), diabetes (15, 21%), or post-surgical (anti-reflux surgery, 6 patients; Roux-en-Y gastric bypass, 3; subtotal gastrectomy, 1; cardiomyotomy, 1; other gastric surgery, 2) (18%). At presentation, oral nutrition was supplemented by naso-jejunal tube feeding in 7 patients, surgical jejunostomy in 8, or parenterally in 1 (total 16 patients; 22%). Previous intervention included endoscopic injection of botulinum toxin (botox) into the pylorus in 16 patients (22%), pyloroplasty in 2, distal gastrectomy in 1, and gastrojejunostomy in 1. It was decided to directly proceed with permanent GES in 4 patients. Of the remaining, 51 patients have currently completed a trial of temporary stimulation and 39 (77%) had a good response and were selected for permanent GES, which has been completed in 35 patients. Outcome data are currently available for 31 patients (idiopathic, 21 patients; diabetes, 3; post-surgical, 7) with a median follow-up period of 10 months (1-28); 22 patients (71%) had a good response to permanent GES, these included 14 (68%) with idiopathic, 5 (71%) with post-surgical, and remaining 3 with diabetic gastroparesis.Overall, 71% of well-selected patients with intractable gastroparesis had good response to permanent GES at follow-up of up to 2 years.
- Nausea and vomiting in advanced cancer. [JOURNAL ARTICLE]
- Eur J Pharmacol 2013 Nov 5.
Nausea and vomiting are very common symptoms in cancer both treatment and non-treatment related. Many complications of advanced cancer such as gastroparesis, bowel and outlet obstructions, and brain tumors may have nausea and vomiting or either symptom alone. In a non-obstructed situation, nausea may be more difficult to manage and is more objectionable to patients. There is little research on management of these symptoms except the literature on chemotherapy induced nausea where guidelines exist. This article will review the etiologies of nausea and vomiting in advanced cancer and the medications which have been used to treat them. An etiology based protocol to approach the symptom is outlined.
- Intractable vomiting: A case of severe gastroparesis after Ramsay Hunt syndrome. [Letter]
- J Clin Virol 2013 Dec; 58(4):753-4.
- Meta-analysis of acupuncture for relieving non-organic dyspeptic symptoms suggestive of diabetic gastroparesis. [JOURNAL ARTICLE]
- BMC Complement Altern Med 2013 Nov 9; 13(1):311.
Acupuncture is widely used to treat diabetic patients with dyspeptic symptoms suggestive of gastroparesis in China. We conducted this systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture for diabetic gastroparesis (DGP).We searched PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese databases including China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database (CBM) and WanFang Data up to January 2013 without language restriction. Eligible RCTs were designed to examine the efficacy of acupuncture in improving dyspeptic symptoms and gastric emptying in DGP. Risk of bias, study design and outcomes were extracted from trials. Relative risk (RR) was calculated for dichotomous data. Mean difference (MD) and standardized mean difference (SMD) were selected for continuous data to pool the overall effect.We searched 744 studies, among which 14 RCTs were considered eligible. Overall, acupuncture treatment had a high response rate than controls (RR, 1.20 [95% confidence interval (CI), 1.12 to 1.29], P < 0.00001), and significantly improved dyspeptic symptoms compared with the control group. There was no difference in solid gastric emptying between acupuncture and control. Acupuncture improved single dyspeptic symptom such as nausea and vomiting, loss of appetite and stomach fullness. Most studies were in unclear and high risk of bias and with small sample size (median = 62). The majority of the RCTs reported positive effect of acupuncture in improving dyspeptic symptoms.The results suggested that acupuncture might be effective to improve dyspeptic symptoms in DGP, while a definite conclusion about whether acupuncture was effective for DGP could not be drawn due to the low quality of trials and possibility of publication bias. Further large-scale, high-quality randomized clinical trials are needed to validate this claim and translate this result to clinical practice.
- Pseudodyslipidemia: are we over-treating dyslipidemia in diabetic patients with undiagnosed gastroparesis? [JOURNAL ARTICLE]
- Endocrine 2013 Oct 3.
Management of dyslipidemia in diabetic patients poses a major burden on both patients and healthcare providers. Gastroparesis, a condition in which gastric emptying is delayed, is a common condition in diabetes. Given the fact that normal values of plasma lipids are standardized to be measured after several hours of fasting, delayed transit of food and nutrients into the small bowel (as occurs in gastroparesis) may result in an artificial increase in plasma lipids, causing misdiagnosis of dyslipidemia (pseudodyslipidemia), and lead to overtreatment with lipid-lowering agents.