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- Pre-operative opioid analgesia reduces clinical success of laparoscopic gastric electrical stimulation placement in patients with gastroparesis. [JOURNAL ARTICLE]
- Surg Endosc 2014 Aug 13.
Gastroparesis is a common chronic and costly disorder for which medical therapy is often unsuccessful. Gastric electrical stimulation (GES) has been used to treat refractory cases, however, response is variable and difficult to predict. This study aims to assess whether pre-operative opioid analgesics (OA) use affects clinical success of GES.Records of 128 patients who underwent laparoscopic GES placement from March 2001 to September 2012 were analyzed retrospectively. Data collected included demographics, surgical outcomes, and clinical parameters. Pre- and post-operative opioid analgesic dosing (No = 0 morphine equivalents (ME)/day, Low = 0-40 ME/day, Mid = 41-80 ME/day, High >80 ME/day), as well as clinical symptom assessment was collected for up to 3 years post-operatively. Clinical success was defined as (1) OA reduction of >50 %, (2) maintenance of weight, or (3) symptom improvement. Descriptive statistics were computed for all factors. A p < 0.05 was considered statistically significant.Fifty-three patients were on OA pre-operatively compared to 69 patients who were not. Patients not on OA pre-operatively were less likely than those on OA pre-op group to be on OA post-operatively (p = 0.005); however, there were no differences in weight or symptom improvement. Sub-group analysis of the 53 patients on OA demonstrated significant improvement in clinical symptoms in the low-morphine cohort compared to the mid-morphine cohort (p = 0.02), and OA dosing post-operatively in the low-morphine cohort diminished significantly compared to mid- and high-morphine cohort (p = 0.032). There was no significant difference in weight.OA dosing pre-operatively significantly affects clinical success of GES placement. Criteria for offering GES implantation may need to take OA dosing into consideration.
- Recent progress in gastric dysrhythmia: pathophysiology, clinical significance and future horizons. [JOURNAL ARTICLE]
- Clin Exp Pharmacol Physiol 2014 Aug 12.
Gastric dysrhythmia continues to be of uncertain diagnostic and therapeutic significance. However, recent progress has been substantial, with technical advances, theoretical insights and experimental discoveries offering new translational opportunities. The discoveries that interstitial cells of Cajal (ICC) generate slow waves and that ICC defects are associated with dysmotility have reinvigorated gastric dysrhythmia research. Increasing evidence now suggests that ICC depletion and damage, network disruption and channelopathies may lead to aberrant slow wave initiation and conduction. Histological and high-resolution (HR) electrical mapping studies have now redefined the human 'gastric conduction system', providing an improved baseline for dysrhythmia research. The application of HR mapping to dysrhythmia has also generated important new insights into the spatiotemporal dynamics of dysrhythmia onset and maintenance, resulting in the emergence of new provisional classification schemes. Meanwhile, the strong associations between gastric functional disorders and electrogastrography (EGG) abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting, and functional dyspepsia) continue to motivate deeper inquiries into the nature and causes of GI dysrhythmias. In future, technical progress in EGG methods, new HR mapping devices and software, wireless slow wave acquisition systems, and improved gastric pacing devices may achieve validated applications in clinical practice. Neurohormonal factors in dysrhythmogenesis also continue to be elucidated, and a deepening understanding of these mechanisms may open opportunities for drug design for treating dysrhythmias. However, for all translational goals, it still remains to be seen whether dysrhythmia can be corrected in a way that meaningfully improves organ function and symptoms in patients. This article is protected by copyright. All rights reserved.
- Major complications of cryoballoon catheter ablation for atrial fibrillation and their management. [JOURNAL ARTICLE]
- Expert Rev Cardiovasc Ther 2014 Aug 12.:1-8.
Atrial fibrillation (AF) is the most common symptomatic and sustained cardiac arrhythmia. It affects approximately 2-3 million people in the USA alone with an increased incidence and prevalence worldwide. It is associated, in addition to worsening quality of life, with increased morbidity and mortality especially in poorly controlled AF, affecting mostly those older than 65 years of age. Radiofrequency ablation was found to be a good strategy for focal isolation of pulmonary veins triggering from the vulnerable atrial substrate but is a time-consuming procedure and carries the risk of multiple complications like tamponade which could be fatal, atrioesophageal fistula and local thrombus formation at the site of ablation. Cryoballoon ablation with pulmonary vein isolation has emerged in the past few years as a breakthrough novel technology for the treatment of drug-refractory AF. It is a relatively simple alternative for point-by-point radiofrequency ablation of paroxysmal AF and is associated with fewer incidences of fatal complications such as cardiac perforation. As experience with this new tool accumulates, the field faces new challenges in the form of rare compilations including gastroparesis, phrenic nerve palsy, atrioesophageal fistula, pulmonary vein stenosis, thromboembolism pericardial effusion, and tamponade.
- Early human experience with per-oral endoscopic pyloromyotomy (POP). [JOURNAL ARTICLE]
- Surg Endosc 2014 Aug 9.
Gastroparesis is a condition characterized by delayed gastric emptying, and a constellation of symptoms, including nausea, vomiting, early satiety, and bloating. Although current surgical options such as pyloroplasty have been shown to be effective, an endoscopic submucosal myotomy technique may be applied to divide the pyloric sphincter without surgical access. Such endoscopic technique may provide the benefits of a natural orifice procedure, and improve gastric emptying in gastroparetic patients.Per-oral pyloromyotomy (POP) was performed in seven female patients aged 33-65 years (mean 51 years). All patients had a pre-operative work-up that included upper endoscopy, and a gastric emptying study. A pH study, and esophageal manometry were also performed when a concomitant fundoplication was considered.POP was technically successful in all seven cases. There were no immediate procedural complications. Perioperative, complications included: one patient with an upper GI bleed 2 weeks post-procedure, necessitating transfusions, and endoscopic clipping of a pyloric channel ulcer; one patient who experienced difficulty swallowing post operatively, delaying discharge by 1 day; and one patient who developed a hospital-acquired pneumonia, delaying discharge by several days. Six of the seven patients experienced significant symptomatic improvement following the procedure. Three month follow-up nuclear medicine solid-phase gastric emptying studies are currently available for 5 of the 7 patients. Normal gastric emptying at 4 h was noted in four of five patients (80 %). One patient did not respond to endoscopic management subsequently underwent an uneventful laparoscopic pyloroplasty, which also failed to significantly improve her symptoms.POP is a technically safe and feasible endoscopic procedure. Early follow-up suggests promising symptomatic improvement as well as objective improvement in gastric emptying. Additional clinical experience is required to establish the role of this technique in the management of gastroparesis.
- The effect of drugs and stimulants on gastric myoelectrical activity. [Journal Article, Review]
- Prz Gastroenterol 2014; 9(3):130-5.
Electrogastrography (EGG) is a non-invasive diagnostic method useful for the registration and analysis of gastric myoelectrical activity. Abnormalities within an electrogastrogram were found to correlate with a number of disorders and symptoms, like functional dyspepsia, diabetic gastroparesis and terminal hepatic or renal failure. The EGG is also a valuable diagnostic method enabling the evaluation of the effect of drugs on gastric myoelectrical activity, which can be intentional, as in the case of prokinetics, or can have an adverse character. Our review focuses on drugs with a proven impact on gastric myoelectrical activity and hence on the electrogastrogram. The paper assembles and discusses the results of investigations dealing with changes in the electrogastrograms evoked by various drugs. Moreover, the mechanisms of the influence on the gastric myoelectrical activity of drugs, curative substances and stimulants are presented.
- Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects. [JOURNAL ARTICLE]
- Neurogastroenterol Motil 2014 Jul 29.
Heme oxygenase 1 (HO-1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO-1 is beneficial in several diseases (e.g., postoperative ileus, gastroparesis, acute pancreatitis, and colitis). However, the only drugs (i.e., hemin and heme arginate) which pharmacologically upregulate HO-1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin, and simvastatin alone, and with α-lipoic acid, on HO-1 protein concentration and activity in humans.This randomized, double-blind, placebo-controlled study compared the effects of three oral regimens administered for 7 days, i.e., placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R- α-lipoic acid (NaRLA, 600 mg three times daily) on markers of HO-1 activation (i.e., plasma HO-1 protein concentration and venous monocyte HO-1 protein activity) in 18 healthy subjects (14 females). Markers of HO-1 activation were evaluated at baseline, days 2, and 7.Baseline HO-1 protein concentrations and activity were similar among the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO-1 protein concentration or activity at 2 or 7 days. HO-1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2.At therapeutic doses, aspirin, simvastatin, and α-lipoic acid do not increase plasma HO-1 protein concentration or venous monocyte HO-1 activity in healthy humans.
- [Nutritional support in the neurocritical patient]. [English Abstract, Journal Article]
- Nutr Hosp 2014 May.:22-31.
Neurocritical patients have a metabolic condition that makes them particularly sensitive to protein-caloric malnutrition in a short period of time. Due to this, it is essential nutritional support treatment. But the neurocritical patient has physiological connotations that makes it difficult to be able to establish an early nutrition: persistent gastroparesis for days and exacerbated metabolic response with hyperglycemia is a challenge to the therapist.This review intends to respond to nutritional difficulties in neurocritical patients and also review pharmaco-nutritients that may be helpful for the subsequent clinical course.
- Glucocorticoids induce gastroparesis in mice through depletion of L-arginine. [JOURNAL ARTICLE]
- Endocrinology 2014 Jul 24.:en20141246.
Glucocorticoids (GCs) constitute a highly pleiotropic class of drugs predominantly employed in the treatment of inflammatory diseases. In our search for new mechanisms of action we identified a hitherto unknown effect of GCs in the gastrointestinal tract. We found that oral administration of dexamethasone (Dex) to mice caused an enlargement of the stomach due to the induction of gastroparesis, and that this effect was abolished in GR(dim) mice carrying the A458T mutation in the GC receptor (GR). Gastroparesis was unrelated to the enhanced gastric acid secretion observed after Dex treatment although both effects were mediated by the same molecular mechanism of the GR. Using conditional GR knock-out mice we could further rule out that GC effects on enterocytes or myeloid cells were involved in the induction of gastroparesis. In contrast, we found that Dex up-regulated arginase 2 (Arg2) in the stomach both at the mRNA and protein level. This suggests that GC treatment leads to a depletion of L-arginine thereby impeding the production of nitric oxide (NO) which is required for gastric motility. We tested this hypothesis by supplementing the drinking water of the mice with exogenous L-arginine to compensate for the presumed shortage of this major substrate of NO synthases. Importantly, this measure completely prevented both the enlargement of the stomach and the induction of gastroparesis after Dex treatment. Our findings raise considerations of combining orally applied GCs with L-arginine to improve tolerability of GC treatment and provide a possible explanation for the anti-emetic effects of GCs widely exploited in chemotherapy.
- Measurement of gastric emptying in diabetes. [REVIEW]
- J Diabetes Complications 2014 Jun 17.
There has been a substantial evolution of concepts related to disordered gastric emptying in diabetes. While the traditional focus has hitherto related to the pathophysiology and management of upper gastrointestinal symptoms associated with gastroparesis, it is now apparent that the rate of gastric emptying is central to the regulation of postprandial glycemia. This recognition has stimulated the development of dietary and pharmacologic approaches to optimize glycemic control, at least in part, by slowing gastric emptying. With the increased clinical interest in this area, it has proved necessary to expand the traditional indications for gastric emptying studies, and consider the relative strengths and limitations of available techniques. Scintigraphy remains the 'gold standard' for the measurement of gastric emptying, however, there is a lack of standardization of the technique, and the optimal test meal for the evaluation of gastrointestinal symptoms may be discordant from that which is optimal to assess impaired glycemic control. The stable isotope breath test provides an alternative to scintigraphy and can be performed in an office-based setting. The effect of glucagon-like peptide-1 (GLP-1) and its agonists to reduce postprandial glycemia is dependent on the baseline rate of gastric emptying, as well as the magnitude of slowing. Because the effect of exogenous GLP-1 to slow gastric emptying is subject to tachyphylaxis with sustained receptor exposure, 'short acting' or 'prandial' GLP-1 agonists primarily target postprandial glycemia through slowing of gastric emptying, while 'long acting' or 'non-prandial' agents lower fasting glucose primarily through insulinotropic and glucagonostatic mechanisms. Accordingly, the indications for the therapeutic use of these different agents are likely to vary according to baseline gastric emptying rate and glycemic profiles.
- Relationship Between Glycemic Control and Gastric Emptying In Poorly Controlled Type 2 Diabetes. [JOURNAL ARTICLE]
- Clin Gastroenterol Hepatol 2014 Jul 17.
& Aims: Acute hyperglycemia delays gastric emptying in patients with diabetes. However, it is not clear whether improved control of glycemia affects gastric emptying in these patients. We investigated whether overnight and short-term (6 months) improvements in control of glycemia affect gastric emptying.We studied 30 patients with poorly controlled type 2 diabetes (levels of glycated hemoglobin >9%). We measured gastric emptying using the [(13)C]-spirulina platensis breath test on the patients' first visit (visit 1), after overnight administration of insulin or saline, 1 week later (visit 2), and 6 months after intensive therapy for diabetes. We also measured fasting and post-prandial plasma levels of C-peptide, GLP1, and amylin, as well as autonomic functions.At visit 1, gastric emptying was normal in 10 patients, delayed in 14, and accelerated in 6; 6 patients had gastrointestinal symptoms; vagal dysfunction was associated with delayed gastric emptying (P<.05). Higher fasting blood levels of glucose were associated with shorter half-times of gastric emptying (thalf) at visits 1 (r= -0.46, P=.01) and 2 (r= -0.43, P=.02). Although blood levels of glucose were lower after administration of insulin (132±7 mg/dl) than saline (211±15 mg/dl; P=0.0002), gastric emptying thalf was not lower after administration of insulin, compared with saline. After 6 months of intensive therapy, levels of glycated hemoglobin decreased from 10.6%±0.3% to 9%±0.4% (P=.0003), but gastric emptying thalf did not change (92±8 min before, 92±7 min after). Gastric emptying did not correlate with plasma levels of GLP1 and amylin.Two-thirds of patients with poorly-controlled type 2 diabetes have mostly asymptomatic yet abnormal gastric emptying. Higher fasting blood levels of glucose are associated with faster gastric emptying. Overnight and sustained (6 months) improvements in glycemic control do not affect gastric emptying.