Fermín Mearin

The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects.

Aim : To determine the prevalence, symptom pattern and impact of the irritable bowel syndrome, across eight European countries, using a standardized methodology.

The origin of symptoms on the brain-gut axis in functional dyspepsia

It was hypothesized that symptoms in functional dyspepsia are originated by an altered mechanism at the brain-gut axis (one or several) in the process of gastric accommodation to a meal. To test the key mechanisms potentially involved in symptomatic gastric accommodation, the sensorial responses (on a 0-10 perception score) and the gastric tone responses (by electronic barostat) to either gastric accommodation (n = 10) or to cold stress (n = 10) were measured in 20 patients with functional dyspepsia and 20 healthy controls. The mechanical accommodation of the stomach to gastric distention (compliance) was similar in patients (52 +/- 8 mL/mm Hg) and controls (57 +/- 6 mL/mm Hg). However, isobaric gastric distention elicited more upper abdominal discomfort in dyspeptics than in controls (perception scores, 4.7 +/- 0.9 vs. 1.1 +/- 0.5, respectively; mean +/- SE; P less than 0.005). Cold stress induced a similar gastric relaxatory response in dyspeptics and controls (delta vol, 145 mL +/- 40 mL vs. 141 mL +/- 42 mL, respectively); hand perception (scores, 8.3 +/- 0.4 vs. 7.9 +/- 0.4, respectively) and autonomic responses were also similar. It is concluded that an abnormal afferent sensorial pathway (altered gastric perception) may be a major mechanism of symptom production in functional dyspepsia.

Patients with achalasia lack nitric oxide synthase in the gastro‐oesophageal junction

Abstract. The abnormal function of the lower oesophageal sphincter in achalasia is likely to be due to impaired nonadrenergic, noncholinergic (NANC) inhibitory input. Since recent studies in animals suggest that nitric oxide (NO) is implicated physiologically in the inhibitory responses of the lower oesophageal sphincter, we have investigated whether the synthesis of NO is altered in the gastro‐oesophageal junction of patients with achalasia. NO synthase activity was investigated in samples of tissue from the gastro‐oesophageal junction obtained during surgery in eight patients with typical achalasia and six non‐achalasic controls who underwent oesophagectomy for reasons other than sphincter dysfunction. The NO synthase activity was determined by the transformation of 14C‐L‐arginine into 14C‐L‐citrulline in tissue homogenates. In addition, immunohistochemical staining of the tissues was performed using a polyclonal antibody raised against a peptide sequence of rat brain NO synthase. Furthermore, the relaxant response to an exogenous NO donor (sodium nitroprusside, SNP) was measured in vitro in muscle strips obtained from two patients with achalasia and in two non‐achalasic controls. NO synthase activity was detected in each of the samples obtained from six control patients (0.59 ±0.21 pmol mg‐1 min‐1; mean æ). By contrast, none of the samples obtained from the eight patients with achalasia had any detectable NO synthase activity. Immunohistochemical studies confirmed the presence of NO synthase in the myenteric plexus of the gastro‐oesophageal junction of control patients and its absence in achalasia. SNP relaxed muscle strips precontracted with bethanechol in both control samples and those from patients with achalasia. We suggest that the absence of NO synthase in the myenteric plexus of the gastro‐oesophageal junction explains the impaired function of the lower oesophageal sphincter in achalasia.

Gastric tone determines the sensitivity of the stomach to distention

BACKGROUND/AIMS Whether meal-related symptoms such as postcibal epigastric fullness and discomfort are caused by hypotonic gastric expansion or gastric hypertension is unknown. This study investigated whether symptoms in healthy individuals in response to gastric distention are produced by gastric expansion or by an increase in intragastric pressure. METHODS Increasing gastric distentions (for 5 minutes at 5-minute intervals) at fixed pressure levels (in 2-mm Hg increments) and at fixed volume levels (in 200-mL increments) were performed in 10 healthy subjects per group; perception was measured on a 0-6 scale. Distentions were performed during intravenous infusion of saline (basal) and during gastric relaxation by intravenous administration of glucagon (4.8-micrograms/kg bolus plus 9.6 micrograms.kg-1.h-1 infusion). RESULTS The same distending pressure tested produced 30% +/- 9% larger intragastric volumes and 80% +/- 44% higher perception scores when the stomach was relaxed by glucagon (P < 0.05 vs. basal for both). In contrast, the same distending volumes tested produced 25% +/- 7% lower intragastric pressures and 21% +/- 12% lower perception scores when the stomach was relaxed (P < 0.05 vs. basal for both). CONCLUSIONS Epigastric symptoms in response to gastric distention are influenced by both the intragastric pressure and the intragastric volume.

Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.

Severity in Irritable Bowel Syndrome: A Rome Foundation Working Team Report

OBJECTIVES:The concept of severity in irritable bowel syndrome (IBS) is clinically recognized and operative in diagnostic decision making and treatment planning. Yet, there is no consensus on its definition, and there are limited data on the prevalence of severity subgroups, its medical and psychosocial determinants, and its association with other health status measures. The aims of the Rome Foundation Working Team Committee were to summarize current research, to develop a consensus of understanding on this concept, and to make recommendations for its use in research and clinical care.METHODS:In 2006, a multinational committee of clinical investigators with expertise in IBS and/or psychometric research methods undertook a systematic review of the literature relating to severity in IBS. Owing to limited data, the Foundation commissioned three clinical studies to better characterize the concept of severity in IBS, and summary information and recommendations for future research and clinical care were developed.RESULTS:The main findings were: (i) severity in IBS is defined as a biopsychosocial composite of patient-reported gastrointestinal and extraintestinal symptoms, degree of disability, and illness-related perceptions and behaviors; (ii) both visceral and central nervous system physiological factors affect severity; as severity increases, the central nervous system provides a greater contribution; (iii) severity is related to and influences health-related quality of life and health behaviors and also guides diagnostic and therapeutic clinical decision making; (iv) severity can be subcategorized into clinically meaningful subgroups as mild (∼40%), moderate (∼35%), and severe (∼25%), and this provides a working model for use in future research and clinical care.CONCLUSIONS:Future work is required to understand more precisely the factors contributing to severity and to develop a valid patient-reported instrument to measure severity in IBS.

Bowel Habit Subtypes and Temporal Patterns in Irritable Bowel Syndrome: Systematic Review

Irritable bowel syndrome (IBS) is a heterogeneous condition characterized by the presence of abdominal discomfort or pain and bowel habit alterations: constipation (C-IBS), diarrhea (D-IBS), or alternating C and D (A-IBS). Its clinical course is poorly known.OBJECTIVES:(i) To compare bowel habit subtypes distribution in IBS according to sample origin and diagnosis criteria; (ii) To evaluate IBS temporal patterns based on follow-up studies.METHODS:A literature search (1966–2003) was conducted in the MEDLINE and EMBASE databases. A total of 72 studies were found and 22 were finally selected.RESULTS:Population-based studies from the United States (Manning) found similar distribution among C-IBS, D-IBS, and A-IBS, while European studies (Rome I, Rome II, or self-reporting) showed either C-IBS or A-IBS as the most prevalent subtypes. Primary care office-based studies (Rome I or Rome II) showed A-IBS as the most prevalent group. Gastroenterology specialized office-based studies found either C-IBS or D-IBS as the most frequently reported subtype. Prospective follow-up investigations showed that the most frequent IBS temporal pattern profile consists of mild to moderate symptoms appearing in cluster in an intermittent way, about once a week, and lasting 2–5 days on average.CONCLUSION:IBS clinical subtypes distribution differs depending on the population evaluated, the geographical location, and the criteria employed to define IBS and bowel habit subtypes. In most cases, clinical course is characterized by the presence of mild-to-moderate symptoms appearing sequentially. Prospective studies, using clear and stable diagnostic criteria and subtype definitions, and based on daily data collection should further characterize IBS clinical course.

Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management

Delayed gastric emptying can be due to muscular, neural, or humoral abnormalities. In the absence of an identified cause, gastroparesis is labelled as idiopathic. We present the case of a patient with severe idiopathic gastroparesis. Pharmacological approaches failed, as well as reduction in gastric emptying resistance with pyloric injection of botulinum toxin and pyloroplasty. Therefore, subtotal gastrectomy was performed. Histological and immunohistochemical study of the resected specimen showed hypoganglionosis, neuronal dysplasia, and a marked reduction in both myenteric and intramuscular interstitial cells of Cajal. To our knowledge, this is the first time these rare histological findings have been described in a patient with idiopathic gastroparesis.

Clinical patterns over time in irritable bowel syndrome: symptom instability and severity variability.

OBJECTIVES:The clinical course of irritable bowel syndrome (IBS) remains poorly known. In 209 IBS patients meeting Rome II criteria (137 females and 72 males) we evaluated: (1) changes in frequency and intensity of abdominal pain/discomfort, abnormal number of bowel movements, loose or watery stools, defecatory urgency, hard or lumpy stools, straining during bowel movements, and feeling of incomplete evacuation); (2) use of resources, HRQoL, and psychological well being.METHODS:Observational, prospective, multicenter study. Symptoms were registered in a diary over two 28-day periods with an interval of 4 wk; direct resource use and indirect costs were noted weekly. Three HRQoL questionnaires were administered.RESULTS:High-intensity symptoms were present on more than 50% of the days. Sixty-one percent were classified in the same IBS subtype on both occasions (κ= 0.48), while 49% had the same symptom predominance and intensity (κ= 0.40). The greatest instability was observed among diarrhea (D-IBS) and constipation (C-IBS) subtypes: only 46% and 51% remained in the same pattern with a tendency to shift to alternating diarrhea/constipation subtype (A-IBS); however, practically no patient changed from D-IBS to C-IBS, or vice versa. The most reliable symptom characteristic was frequency, followed by intensity and number of episodes. Symptom frequency and intensity were directly related to resource use and HRQoL impairment.CONCLUSIONS:IBS symptoms are instable over time and variables in intensity. Many patients with D-IBS or C-IBS move to A-IBS; however, shift from D-IBS to C-IBS, or vice versa, is very infrequent.

Effect of obesity on gastroesophageal resistance to flow in man.

Chronic (obesity) and acute intraabdominal, pressure increases appear to favor gastroesophageal reflux, but the mechanism is not completely understood. We hypothesized that it could be due to an alteration in the resistance gradient between the stomach and the gastroesophageal junction, even increasing intragastric resistance above resistance at the gastroesophageal junction. Hence, we used a pneumatic resistometer to measure gastric and gastroesophageal resistance to flow in 11 lean healthy controls and eight morbidly obese individuals without gastroesophageal reflux disease. Resistance was quantified at rest and during acute intraabdominal pressure increases, both in the recumbent and sitting positions. We found that gastroesophageal junction resistance was higher than gastric resistance in lean as well as in obese subjects (P<0.001). In obese individuals both gastric and gastroesophageal junction resistance were increased (P<0.001), thus a normal gastric-gastroesophageal junction resistance gradient was maintained. Body position did not modify resistance. Acute increases in intraabdominal pressure decreased the gastric-gastroesophageal junction resistance gradient similarly in obese and lean subjects. We conclude that obesity by itself does not appear to predispose to gastroesophageal reflux, but it creates intraabdominal conditions that may favor reflux whenever the gastroesophageal barrier becomes weakened.