Gastrointestinal motility and neurogastroenterology

Abstract

Nordic research on gastrointestinal motility has since 1965 made substantial contributions to our current understanding of gastrointestinal function. During the last decade, the term neurogastroenterology has widened the concept of motility research into the study of gastrointestinal sensory-motor function, including the complex central nervous system interaction. The discovery of a non-adrenergic non-cholinergic (NANC) innervation of the gut in the sixties was made by considerable contributions from the Nordic countries with the Martinson group in Sweden as central innovators. Important discoveries regarding the intramural nerve ganglia as mediators of the autonomic nervous input has also been produced from this research. In clinical motility research, the study of the migrating motor complex in the small bowel has revealed its ability to act as a retroperistaltic pump in the proximal duodenum (Sweden) and its important role for gut microbial homeostasis (Norway). Also in the development of methodology to study gut sensory-motor function, the Nordic countries has contributed. Examples are the physical characteristics of the esophageal manometry catheter (Denmark), the use of ultrasound for assessment of gastric function (Norway), a temporary electrical stimulation method in patients with severe nausea and vomiting (Sweden), a rectal barostat method for clinical evaluation of recto-anal function and a colonic transit time method utilizing radio-opaque markers (Sweden). In later years, the research collaborations have increasingly become worldwide in a manner making it less easy to define pure Nordic contributions.     

Use of an external real-time image viewer coupled with prespecified actions enhanced the complete examinations for capsule endoscopy

Background and Aim: The clinical utility of capsule endoscopy (CE) is often limited by incomplete small‐bowel transit. The aim was to determine whether the use of an external real‐time viewer could reduce delays caused by delayed gastric emptying of the capsule or delayed intestinal transit and also improve the rate of positive findings. Methods: We compared the proportion of completed exams and positive results among a group of patients studied before introduction of real‐time viewer and a group in which capsule transit through the esophagus, stomach, and small bowel was regularly monitored and actions (e.g. administration of water or intravenous metoclopramide) were taken if it was delayed. Results: One hundred procedures in the viewer group and 100 control procedures in the age‐matched controls were analyzed. In the viewer group, additional water intake (22 cases) and/or administration of metoclopramide (26 cases) were required. Endoscopic‐assisted duodenal placement of the capsule was required in three cases. Overall one‐third (n = 33) of cases required viewer‐prompted interventions. The completion rate (86% vs 66%, P = 0.002) and the rate of positive findings (80% vs 67%, P = 0.04) were significantly higher in the viewer group compared to the no viewer group. Conclusions: Checking the progress of the capsule with the external real‐time viewer improved the diagnostic yield and completion rate of CE.     

成年人群功能性肠病与体质量指数的相关性研究

目的探讨成年人群功能性肠病与体质量指数的相关性。 方法回顾性分析2016年1月至2019年2月在宁夏回族自治区人民医院消化内科确诊的50例功能性肠病患者为病例组，同期行健康体检者50例为对照组。根据《中国成人超重和肥胖症预防控制指南》推荐的标准，以体质量指数作为不同体重分类依据，采用两独立样本t检验方法比较两者相关性。 结果病例组与对照组比较中，年龄、性别、民族、身高、体重比较差异无统计学意义(P>0.05)，而吸烟、饮酒、睡眠情况及进食辛辣食物比较差异有统计学意义(P>0.05)；体质量指数与功能性肠病无关(P>0.05)，但女性患者功能性肠病的占比较男性多；功能性肠病患者体重过低组占比达20.0%，而健康体检人群超重/肥胖所占比例达44.0%。 结论成年人群功能性肠病与吸烟、饮酒、睡眠情况及进食辛辣食物有关，而与年龄、性别、民族、体质量指数不存在相关性。     

The role of experimental models in developing new treatments for irritable bowel syndrome

Irritable bowel syndrome (IBS) is characterized by chronic, recurrent abdominal pain and altered bowel habits and is currently defined by symptom criteria and the absence of detectable organic disease. The underlying pathophysiology remains incompletely understood. Despite considerable efforts by the scientific community and the pharmaceutical industry to develop novel pharmacological treatments aimed at chronic visceral pain, the traditional approach to identifying and evaluating novel drugs for this target have largely failed to translate into effective IBS treatments. However, several novel drugs aimed at normalizing bowel movements have produced clinical effects, not only on the primary target, but also on pain and discomfort. While some of the commonly used experimental animal models for the pain dimension of IBS have some face and construct validity, the predictive validity of most of the models is either unknown, or has been disappointing. A reverse translational approach is proposed, which is based on identification and characterization of brain endophenotypes in patients, followed by translation of these endophenotypes for pharmacological studies in rodent models.     

Chronic intestinal pseudoobstruction with myopathy and ophthalmoplegia

Summary The association of chronic intestinal pseudoobstruction with ophthalmoplegia has been reported previously in visceral myopathies. We report a case of this association in which muscle mitochondria had a crystalline appearance, a dense core, and decreased cytochromec oxidase and succinate cytochromec reductase activities. The absence of evident mitochondrial DNA deletion in the skeletal muscle of this patient does not exclude the possibility of localized deletion or mutation of mitochondrial DNA in digestive muscle.     

Neuroendocrine gastro-enteropancreatic tumors – from eminence based to evidence-based medicine – A Scandinavian view

Abstract

Neuroendocrine tumors (NETs) comprise a heterogenous group of neoplasms with variable clinical expression and progression. The primary tumors most frequently occur in the lungs, intestine and the pancreas. The NET incidence is approximately 6.1/100,000 per year with a prevalence higher than 35/100,000 per year. A NET may be functioning with symptoms related to hormone overproduction or non-functioning, not presenting any hormone-related symptoms. From the early 1980s and onwards, Uppsala University Hospital has contributed significantly to diagnosis, just to mention immunohistochemistry, radio-immunoassays for hormones and peptides and molecular imaging. On the therapeutic side, treatments with cytotoxics as well as biologicals such as, somatostatin analogs and interferons have been evaluated. We have furthermore been involved in important phase III trials for registration of so called, new targeted agents such as, RADIANT-3 and RADIANT-2. Our group were also the first to localize the gene for MEN I on chromosome 11 locus q13. Most recent developments have been the establishments of new biomarkers such as, olfactory receptor E51E1 as well as micro-RNAs in carcinoid tumors of the intestine and lung. A new oncolytic virus, Ad-Vince, for treatment of most NETs has been developed and is ready for the clinic. Furthermore, we have been involved in establishing Nordic and international collaborations. Today, NETs is an area with rapid development and recognized by international organizations at conferences, with large attendance. The Nordic countries continue to be significant contributors to the field.     

Spiral enteroscopy: a preliminary experience in Asian population

Background and Aim: In spite of recent developments in the field of enteroscopy the small bowel remains the challenging organ to access. The spiral enteroscopy is a novel technique using a special over‐tube (Endo‐Ease Discovery SB) system for deep intubation of the small bowel. The aim of the present study was to evaluate the efficacy of spiral enteroscopy with an Olympus enteroscope (SIF Q 180) in an Asian subset of patients. Methods: Between January and March 2010, 11 patients underwent spiral enteroscopies. The indication for the procedure was obscure gastrointestinal bleeding in five patients, Crohn's disease in two, malabsorbtion syndrome in two, Peutz‐Jeghers syndrome in one and Osler Weber Rendu disease in one patient. Results: Eleven patients (five male and six female) mean age 41.6 years (range 21–62 years) underwent spiral enteroscopy. Spiral enteroscopy advancement was successful in all patients. The average depth of insertion was 249 cm (range 120–400 cm) past the ligament of Treitz, and the average time for the procedure was 27.8 min (range 20–32 min). The findings included ulcers (n = 3), polyps (n = 1), arteriovenous malformation (n = 2), ulcer with stricture (n = 1), and lymphangiectasia (n = 1). No major complications were observed. Conclusion: In conclusion, our initial experience with spiral enteroscopy shows that it is easy to perform, takes less time than balloon assisted enteroscopy and is relatively safe.     

Effects of enteral infusion of hypertonic saline and nutrients on canine jejunal motor patterns

The aim of the study was to clarify the effects of hypertonic solutions on jejunal motility. The study focused on differential effects of hypertonic saline and nutrients. Motility of the canine proximal jejunum was recorded with closely spaced strain-gauge transducers. During fasting, hyperosmotic solutions (up to 1520 mosmol/liter) of saline or nutrients (1 kcal/ml) were infused into the proximal jejunum (0.5–1.5 ml/min) up to 6 hr. The hyperosmotic solutions stimulated jejunal motility. With both increasing osmolarity of saline or increasing energy load of nutrients, jejunal motility linearly declined. The reduction of motility was associated with a change in motor pattern from a propulsive to a more segmenting one. Hypertonic glucose evoked a significantly smaller level of motor activity compared with both saline (at given osmolarities) and an elemental diet (at given energy loads). Motility parameters were not different between glucose and maltose, although osmolarity of maltose was less than half (760 vs 1520 mosmol/liter). In contrast, a mixture of glucose-fructose exerted a smaller inhibition of jejunal motility than glucose. The hypertonic solutions of saline or nutrients were tolerated over 2 hr; with hypertonic saline retrograde power contractions with or without vomiting occurred, whereas with hypertonic nutrients vomiting was preceded by strong inhibition of jejunal motility. Three conclusions can be derived from the present results: (1) The behavior of jejunal motility suggested that the motor activity was the result of both a local stimulation and an inhibitory feedback mechanism. (2) The different degree of inhibition between glucose and saline indicated that the nutrient itself played a major role in the inhibitory feedback regulation, whereas osmolarity was of minor importance. (3) Comparisons between different nutrients suggested a linkage between inhibitory control of motility and the absorptive capacity of the gut for the single nutrient.     

Pseudopneumoperitoneum in chronic intestinal pseudo-obstruction: a case report

Chronic intestinal pseudo-obstruction(CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic,on both clinical and radiological grounds,mechanical obstruction.We report a case of a 26-year-old woman who presented to our institution for plain abdominal radiography for referred long-lasting constipation with recurrent episodes of abdominal pain and distension.At X-ray,performed both in the upright and supine position,an isolated air-fluid level was depicted in the left flank...     

Long-term mucosal recovery and healing in celiac disease is the rule – not the exception

Objective: The prevalence of persistent villous atrophy (VA) in patients with celiac disease (CD) on a gluten-free diet (GFD) varies greatly between studies. Most studies show a relatively high prevalence of mucosal atrophy and inflammation in treated patients, a finding which have led to a concept of non-responsive CD. Few studies have examined the prevalence of long-term mucosal healing. Our study aimed to determine the extent of mucosal healing in a cohort of Norwegian patients with CD treated with GFD for several years.

Materials and methods: Adult patients diagnosed with VA between 1989 and 2009 were included. We performed a follow-up gastroscopy with duodenal biopsies. Two pathologists evaluated the biopsies according to the Marsh–Oberhuber classification. Mucosal healing was defined as Marsh 0 while mucosal recovery was defined as Marsh 0-2.

Results: Duodenal biopsies were obtained from 127 adult patients with established CD. After a follow-up time of 8.1 years (median, range 2.3–22.3), 103 (81%) of the patients showed mucosal healing, 120 patients (94%) showed mucosal recovery, and 7 patients (6%) showed persistent VA. In addition, 103 of the 127 patients (81%) had undergone a routine follow-up biopsy 12.6 months (median, range 5.2–28.8) after diagnosis. At the time of the routine follow-up, only 52 of these patients (50.5%) had achieved mucosal recovery.

Conclusions: Although half of the patients had persistent VA at the time of routine follow-up, both long-term mucosal recovery and healing is possible for the vast majority of adult patients with CD.     

Clinical consequences of polymerase chain reaction‐based diagnosis of intestinal parasitic infections

The implementation of polymerase chain reaction (PCR)‐based diagnostics of intestinal protozoa has led to higher sensitivity and (subtype) specificity, more convenient sampling, and the possibility for high‐throughput screening. PCR for routine detection of human intestinal protozoa in fecal samples is used by an increasing number of clinical laboratories. This paper discusses the recent developments in the diagnosis of intestinal protozoa, with an emphasis on PCR‐based diagnostics. Although many reviews have described the technical aspects of PCR‐based diagnostics, this review focuses on the clinical consequences that result from the shift from microscopic toward PCR‐based diagnostics. Despite its undisputed superiority, the use of PCR comes with challenges that clinicians should be aware of.     

PKA-mediated phosphorylation of EPEC-Tir at serine residues 434 and 463

Type-III or type-IV secretion systems of many Gram-negative bacterial pathogens inject effector proteins into host cells that modulate cellular functions in their favour. A preferred target of these effectors is the actin-cytoskeleton as shown by studies using the gastric pathogens Helicobacter pylori (H. pylori) and enteropathogenic Escherichia coli (EPEC). We recently developed a co-infection approach to study effector protein function and molecular mechanisms by which they highjack cellular signalling cascades. This is exemplified by our observation that EPEC profoundly blocks H. pylori-induced epithelial cell scattering and elongation, a disease-related event requiring the activity of small Rho GTPase Rac1. While this suppressive effect is dependent on the effector protein Tir and the outer-membrane protein Intimin, it unexpectedly revealed evidence for Tir-signalling independent of phosphorylation of Tir at tyrosine residues 454 and 474. Instead, our studies revealed a previously unidentified function for protein kinase A (PKA)-mediated phosphorylation of Tir at serine residues 434 and 463. We demonstrated that EPEC infection activates PKA for Tir phosphorylation. Activated PKA then phosphorylates Rac1 at its serine residue 71 associated with reduced GTP-load and inhibited cell elongation. Phosphorylation of Rho GTPases such as Rac1 might be an interesting novel strategy in microbial pathogenesis.     

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short-chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.