John Kellow

Level of chronic life stress predicts clinical outcome in irritable bowel syndrome

Background—Life stress contributes to symptom onset and exacerbation in the majority of patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD); research evidence is conflicting, however, as to the strength of these effects. Aims—To test prospectively the relation of chronic life stress threat to subsequent symptom intensity over time. Patients—One hundred and seventeen consecutive outpatients satisfying the modified Rome criteria for IBS (66% with one or more concurrent FD syndromes) participated. Methods—The life stress and symptom intensity measures were determined from interview data collected independently at entry, and at six and 16 months; these measures assessed the potency of chronic life stress threat during the prior six months or more, and the severity and frequency of IBS and FD symptoms during the following two weeks. Results—Chronic life stress threat was a powerful predictor of subsequent symptom intensity, explaining 97% of the variance on this measure over 16 months. No patient exposed to even one chronic highly threatening stressor improved clinically (by 50%) over the 16 months; all patients who improved did so in the absence of such a stressor. Conclusion—The level of chronic life stress threat predicts the clinical outcome in most patients with IBS/FD.

An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome

Background: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population. Aims: To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region. Patients: A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS. Methods: Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1–4) was the response to the question: “Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?” Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS. Results: The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1–4 (56% v 35%, respectively; p<0.0001) and weeks 1–12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo). Conclusions: Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.

Prolonged Ambulant Recordings of Small Bowel Motility Demonstrate Abnormalities in the Irritable Bowel Syndrome

Continuous 72-h recordings of duodenojejunal contractile activity were obtained from 20 freely ambulant subjects; pressure was detected by two strain-gauge sensors incorporated in a transnasal catheter attached to an encoder and a miniature tape recorder. The subjects were 12 patients with irritable bowel syndrome, 6 of whom were constipation predominant and 6 of whom were diarrhea predominant, and 8 healthy controls. The procedure was well tolerated by all subjects and did not interfere with sleep or normal activity. In all subjects, the diurnal migrating motor complex cycle was characterized by a brief phase 1 and a prolonged phase 2; this was reversed during sleep when phase 2 was virtually absent. All subjects showed a circadian variation in migrating motor complex propagation velocity, and there was no difference in the patterns of motor activity during sleep between any of the groups. During the day, the duration of postprandial motor activity was shorter in irritable bowel syndrome patients than in controls, and diurnal migrating motor complex intervals were shorter in diarrhea-predominant than in constipation-predominant irritable bowel syndrome. In 11 of 12 inflammatory bowel syndrome patients, episodes of clustered contractions recurring at 0.9-min intervals were noted; these episodes had a mean duration of 46 min and were often associated with transient abdominal pain and discomfort. In both groups of irritable bowel syndrome patients, defecation was significantly (p less than 0.01) prolonged with a greater number of voluntary abdominal contractions (p less than 0.01) than in controls. Prolonged ambulant monitoring of proximal bowel motor activity in subjects who are free to move, eat, and sleep as they choose has, for the first time, clearly defined the striking difference in motility between the sleeping and waking state and shown that abnormalities associated with irritable bowel syndrome are confined to the latter.

Intragastric distribution and gastric emptying of solids and liquids in functional dyspepsia

The relative contributions of altered gastric motor function andHelicobacter pylori-associated active chronic gastritis to the pathogenesis of functional dyspepsia are controversial. We therefore evaluated scintigraphically the intragastric distribution and gastric emptying of a mixed solid-liquid meal in 75 patients with functional dyspepsia; patients were subdivided on the basis of both specific symptom clusters and the presence or absence ofH. pylori gastritis. Twenty-one (28%) patients displayed abnormal solid and/or liquid gastric emptying, with prolonged solid lag time the most prominent alteration detected. The number of patients with abnormal scintigraphic patterns increased to 36 (48%) when intragastric distribution parameters (fundal half-emptying time and antral maximal fraction) were examined. Although patients with reflux-like dyspepsia (N=36) demonstrated significantly slower rates of liquid emptying at 45 and 70 min and a higher prevalence of abnormal liquid intragastric distribution when compared to patients with motility-like dyspepsia (N=39) or to controls (N-34), the absolute differences were small and unlikely to be of clinical significance. Patients withoutH. pylori gastritis (N=50) demonstrated a significantly more prolonged solid lag time when compared to those withH. pylori gastritis (N=25), but the difference was small and there were no other differences between these two subgroups. We conclude that in patients with functional dyspepsia: (1) abnormal solid gastric emptying is present in less than one third; (2) assessment of parameters of intragastric distribution enables more subtle gastric motor dysfunction to be identified; and (3) neither dividing patients into symptom subgroups nor accounting for the presence or absence ofH. pylori gastritis has a major influence on the prevalence or type of gastric motor dysfunction.

Functional gastrointestinal disorders: psychological, social, and somatic features

Background—Psychological, social, and extraintestinal (somatic) disturbances are prominent features of functional gastrointestinal disorders (FGID); little attention, however, has been given to differences in the nature of these disturbances in the various FGID subgroups. Aims—(1) To determine whether psychological, social, and extraintestinal factors are associated with specific FGID, and/or with the overall severity and extent of FGID disturbance (the number of coexistent FGID subgroups present in any individual); and (2) to determine whether chronic social stressors link gastrointestinal, extraintestinal, and emotional symptomatologies in FGID. Patients—One hundred and eighty eight outpatients, fulfilling standard criteria for one or more functional gastroduodenal or functional bowel disorders. Methods—Utilising detailed and objective interview and questionnaire methods, detailed gastrointestinal, extraintestinal, psychological, and social data were collected. Results—Chronic stressors and extraintestinal and emotional symptomatologies were prominent features of functional dyspepsia (FD) and irritable bowel syndrome (IBS) alone. These particular features were, however, highly specific for particular FD and/or IBS subgroups. The chronic threat component of social stressors predicted the nature and extent of multisystem (gastrointestinal, extraintestinal, and emotional) symptomatology. Conclusions—Notable differences between the various FGID subgroups support the symptom based classification of FGID. Chronic stressor provoked psychological and extraintestinal disturbance is most specific for the FD-IBS group of syndromes.

Principles of applied neurogastroenterology: physiology/motility–sensation

Many of the symptoms characteristic of the functional gastrointestinal disorders (FGID) are consistent with dysfunction of the motor and/or sensory apparatus of the digestive tract. Those aspects of sensorimotor dysfunction most relevant to the FGID include alterations in: gut contractile activity; myoelectrical activity; tone and compliance; and transit, as well as an enhanced sensitivity to distension, in each region of the gastrointestinal tract. Assessment of these phenomena involves a number of techniques, some well established and others requiring further validation. Using such techniques, researchers have reported a wide range of alterations in sensory and in motor function in the FGID. Importantly, however, relationships between such dysfunction and symptoms have been relatively weak, and so the clinical relevance of the former remains unclear. Moreover, the proportions of patients in the various symptom subgroups who display dysfunction, and the extent and severity of their symptoms, require better characterization. On a positive note, progress is occurring on several fronts, especially in relation to functional dyspepsia and irritable bowel syndrome, and based on the data gathered to date, a number of areas where further advances are required can be highlighted.

Disorders of gastrointestinal motility: towards a new classification.

can be learnt from the patient. In the last decade, the ‘Delphic’ technique has been used to try and define combinations of symptoms in the belief, or hope, that specific symptom patterns correspond to specific underlying disorders. The ‘Rome criteria’ for the definition and diagnosis of functional gastrointestinal disorders have received much attention. Unfortunately, consensus of opinions by experts does not, per se, confer scientific validity. Evidence-based medicine requires not consensus, but evidence. We have reappraised the problem of classifying motor disorders by relying on what can be established by the detection of abnormal motor patterns, usually, but not invariably, associated with the altered movement of the contents of the digestive tube. In some, but not yet all, disorders, this approach is reinforced by identification of underlying pathological change in enteric innervation or musculature. While we remain aware that the association between symptoms—the perception that drives patients to seek help—and motor abnormalities is not always clear, we have taken the view that objectively reproducible alterations in organ function provide a robust basis for taxonomy. Such problems are not unique to gastroenterology; as an example, the association between dyspnea and specific pulmonary pathologies is not always clear, but dyspnea is a useful indication of abnormal respiratory function indicative of disease. Clinicians may feel dismayed that we have not elected to define two commonly used terms: ‘functional dysINTRODUCTION

A global perspective on irritable bowel syndrome : a consensus statement of the world gastroenterology organisation summit task force on irritable bowel syndrome.

Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder.

Effects of Acute Psychologic Stress on Small-Intestinal Motility in Health and the Irritable Bowel Syndrome

Psychologic stress may be a provoking factor in the alterations in phase-2 motor activity of the migrating motor complex (MMC) which have been recorded in patients with the irritable bowel syndrome (IBS). To test this, changes in phase-2 duodenojejunal motor activity during 20 min of psychologic stress in 10 patients with IBS were compared with those shown by 10 healthy subjects. Autonomic arousal in response to the stressor was assessed by cardiovascular responses and self-reported levels of anxiety and tension. IBS and controls showed a significant cardiovascular and subjective response to stress which was comparable in the two groups. In general, duodenal phase-2 motor activity was suppressed during stress in both IBS and controls. Jejunal motor activity showed a similar inhibitory response in both groups, but the change in motility index was significant for controls only. Qualitatively, stress did not cause clustered contractions in either the IBS or the control group. However, in IBS patients with clustered contractions in the basal period there was inhibition of this pattern during stress. These findings suggest that acute psychologic stress profoundly suppresses, rather than enhances, duodenojejunal MMC phase-2 motility in healthy subjects. IBS patients, irrespective of their underlying phase-2 motor pattern show similar, although less marked, changes in motility.

Effects of cigarette smoking on solid and liquid intragastric distribution and gastric emptying

BACKGROUND The acute effects of cigarette smoking on gastric emptying are controversial, whereas its effects on the intragastric distribution of solids and liquids are not established. METHODS Dual isotope gastric scintigraphy was performed in 15 habitual smokers (studied twice, either sham smoking or actively smoking) and in 15 age- and sex-matched nonsmokers. RESULTS Acute smoking was associated with an increased prevalence of episodes of retrograde intragastric movement of solids (3 of 15 sham subjects vs. 12 of 15 actively smoking subjects; P < 0.01) and of liquids (0 of 15 vs. 7 of 15; P < 0.01) from distal to proximal stomach. Fundal half-emptying time (T1/2) for liquids was also prolonged by smoking (43 +/- 19 minutes sham vs. 125 +/- 216 minutes active; P < 0.05). Acute smoking delayed solid lag time (13 +/- 6 minutes sham vs. 32 +/- 18 active; P < 0.05) and liquid T1/2 (46 +/- 21 vs. 90 +/- 50 minutes; P < 0.05). In the nonsmokers, such episodes of proximal intragastric redistribution did not occur, and intragastric and overall emptying parameters did not differ significantly from those of habitual sham smokers. CONCLUSIONS Acute cigarette smoking produces excessive antrofundal redistribution of both solid and liquid contents and delays solid and liquid gastric emptying.