Heartburn as a Marker of the Success of Acid Suppression Therapy in Chronic Cough.

PURPOSE: Gastro-oesophageal reflux disease (GORD) is commonly thought to play an important role in chronic cough and patients are often empirically treated with acid suppression therapy. We sought to investigate the response rate to acid suppression treatment in patients with and without heartburn attending two specialist cough clinics. METHODS: A retrospective review of 558 consecutive patients referred to two specialist cough clinics was performed (UK and USA). Patients who were treated with acid suppression were included and their documented response to treatment was collected. Binary logistic regression was used to ascertain the value of reported heartburn in predicting the response of chronic cough to acid suppression therapy. RESULTS: Of 558 consecutive referrals, 238 patients were excluded due to missing data or cough duration of < 8 weeks. The remaining 320 patients were predominantly female (76%), with mean age 61 yrs (± 13) and 96.8% non-smokers, with chronic cough for 36 (18-117) months. Of 72 patients with heartburn, 20 (28%) noted improvement in their cough with acid suppression, whereas of 248 without heartburn, only 35 (14%) responded. Patients reporting heartburn were 2.7 (95% C.I. 1.3-5.6) times more likely to respond to acid suppression therapy (p = 0.007). CONCLUSION: In specialist cough clinics, few patients report a response of their chronic cough to acid suppression therapy. Nonetheless, heartburn is a useful predictor substantially increasing the likelihood of benefit.

Esophageal dysmotility according to Chicago classification v3.0 vs v2.0: Implications for association with reflux, bolus clearance, and allograft failure post-lung transplantation.

BACKGROUND: Proximal reflux and incomplete transit of boluses swallowed are risk factors for obstructive chronic lung allograft dysfunction (o-CLAD) post-lung transplantation (LTx). Likewise, so is esophagogastric junction outflow obstruction (EGJOO), but not hypo-contractility, when diagnosed using Chicago Classification (CC) v3.0. Given, peristaltic breaks as defined using CCv2.0 can prolong esophageal clearance, both swallowed and refluxed, but which are deemed within normality using CCv3.0, our aim was to determine whether hypo-contractility as diagnosed using CCv2.0, influences the association with reflux, along with its clearance, and that of boluses swallowed, and thus its association to allograft failure. METHODS: Esophageal motility abnormalities were classified using CC v3.0 and v2.0 in 50 patients post-LTx (26 female, 55 years (20-73 years)). RESULTS: Reclassification from CCv3.0 to v2.0 resulted in 7 patients with normal motility being reclassified to hypo-contractility (n = 6) or hyper-contractility (n = 1); 2 patients with hypo-contractility to normal motility; and 3 patients with EGJOO without hyper-contractility to EGJOO with hyper-contractility. The main consequence of reclassification was that the sub-group exhibiting hypo-contractility became more likely to have abnormal numbers of reflux events (P = .025) and incomplete bolus transit (P = .002) than those with normal motility using CCv2.0; associations not seen using CCv3.0. Irrespective of CC used only patients with EGJOO appeared more likely to develop o-CLAD than those with normal motility (P < .05). CONCLUSIONS: Irrespective of CC used, o-CLAD appears linked to EGJOO. CCv2.0 however, accentuates the increased reflux and incomplete bolus transit associated with hypo-contractility post-LTx, suggesting that these motor abnormalities, though considered minor, may be of importance after lung transplant.

The effect of inflammation on serum zinc concentrations and the prevalence estimates of population-level zinc status among Congolese children aged 6-59 months.

BACKGROUND/OBJECTIVES: Zinc is a negative acute-phase reactant; hence, its concentration decreases in the presence of inflammation. There is no current consensus on how to control for the effect of inflammation on serum zinc, which has implications for accurate estimates of population-level zinc status. We aimed to measure the association between inflammation and serum zinc concentrations and to compare the means and the prevalence of zinc deficiency using unadjusted and inflammation-adjusted serum zinc concentrations among Congolese children. SUBJECTS/METHODS: Non-fasting blood was collected in the afternoon in trace element-free vacutainers from 744 apparently healthy children aged 6-59 months in the Democratic Republic of the Congo. Serum was analyzed for zinc, C-reactive protein (CRP) and α-1 acid glycoprotein (AGP) for 665 children with complete data for all three biomarkers. Linear regression was used to generate correction factors (CFs) based on three stages of inflammation: incubation (CRP >5 mg/l and normal AGP), early convalescence (CRP >5 mg/l and AGP >1 g/l) and late convalescence (AGP >1 g/l and normal CRP), relative to no inflammation. RESULTS: Overall unadjusted mean±s.d. serum zinc concentration was 9.4±2.1 µmol/l. Study-generated CFs (95% confidence interval) for incubation, early and late convalescence were 1.01 (0.88, 1.14), 1.15 (1.11, 1.21) and 1.07 (1.03, 1.11), respectively. After applying the CFs, overall adjusted mean±s.d. serum zinc concentration was 10.1±2.2 µmol/l, and prevalence of zinc deficiency (<8.7 µmol/l) decreased from 35% (n=234/665) to 24% (n=160/665). CONCLUSIONS: Adjustment of zinc concentrations for inflammation is warranted when assessing population-level zinc status.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.127.

Predictors of vitamin D status in New Zealand preschool children.

Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross-sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late-winter to spring 2012. 25-Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger-prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50- < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17-3.14), other non-European ethnicities (not including Maori or Pacific) (3.51,1.89-6.50), had olive-dark skin colour (4.52,2.22-9.16), did not take vitamin D supplements (2.56,1.06-6.18), had mothers with less than secondary-school qualifications (5.00,2.44-10.21) and lived in more deprived households (1.27,1.06-1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area-under-curve 0.76(95%CI 0.67-0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children.

Phenotyping of subjects for large scale studies on patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

A meta-analysis of immunogenetic Case-Control Association Studies in irritable bowel syndrome.

BACKGROUND: To date, genetic-association studies of single nucleotide polymorphisms (SNP) in selected candidate genes with the symptom phenotype of irritable bowel syndrome (IBS) have typically involved hundreds to 2000 patients. SNPs in immune-related genes, such as cytokine and cytokine receptor encoding genes, have been reported to associate with IBS risk. METHODS: We conducted two independent case-control studies on 16 SNPs in IL1R1, IL4, IL6, IL8, IL10, IL23R, TNFA, and TNFSF15, one from the UK (194 patients and 92 healthy volunteers) and one from the USA (137 patients and 96 healthy volunteers). The main aim was to examine the relationship between inherited immunological diversity and IBS risk in a meta-analysis which included 12 additional, earlier studies. The meta-analysis comprised a total of 2894 patients (839 IBS-C, 1073 IBS-D, 502 IBS-M), and 3138 healthy volunteers with self-reported Caucasian ancestry. KEY RESULTS: The association of SNP rs4263839 (TNFSF15) was investigated in four studies and confirmed in the meta-analysis: IBS (OR 1.19, 95% CI 1.08-1.31), and IBS-C (OR 1.24, 95% CI 1.08-1.42). No additional SNPs residing in immunogenes associated with IBS symptom phenotypes. CONCLUSIONS & INFERENCES: Our meta-analysis could not confirm a major role of most investigated SNPs, but a moderate association between rs4263839 TNFSF15 and IBS, in particular IBS-C. The analysis emphasizes the importance of definition and phenotype homogeneity, adequate study size and representativeness of the patient and control collective.

Weak peristalsis with large breaks in chronic cough: association with poor esophageal clearance.

BACKGROUND: Gastroesophageal reflux plays an important role in chronic cough (CC). Whether disturbed esophageal motility contributes to increased esophageal reflux exposure or interferes with swallowed bolus clearance is unclear. This study used high resolution esophageal manometry and impedance (HRIM) together with Chicago Classification, and 24-h impedance pH (MII/pH) to address these questions in patients with CC compared with heartburn (HB). METHODS: A retrospective review of 32 patients with CC (mean age 57 [95% CI: 52-62] years) and 32 patients with symptoms of HB (55 [52-62] years) referred for HRIM and MII/pH between September 2012 and September 2013 was undertaken. KEY RESULTS: Weak peristalsis with large breaks (WPLBs) was observed in 34% of CC patients compared with only 12% of HB patients (p = 0.027). Pathological acid exposure time (AET) was identified in 81% of CC patients with WPLBs compared with 29% without (p = 0.011). Increased AET was associated with prolonged clearance time of refluxed events (p = 0.006) rather than increased number of events. AET correlated with the percentage of peristaltic events with large breaks in CC (ρ = 0.467, p = 0.007). Similar data were obtained for total bolus (acid and non-acid) exposure time. Only one of the CC patients with WPLBs exhibited complete bolus transit (CBT) on swallowing compared with 81% without WPLBs (p < 0.001). Moreover, the percentage of peristaltic events associated with CBT negatively correlated with the percentage of peristaltic events with large breaks (r = -0.653, p < 0.001) in CC. CONCLUSIONS & INFERENCES: One-third of CC patients exhibit WPLBs, which directly impacts on clearance of refluxed events and bolus's swallowed. These observations may have important implications for esophageal-bronchial interaction in CC.

5-hydroxytryptamine signalling in irritable bowel syndrome with diarrhoea: effects of gender and menstrual status.

BACKGROUND: Symptomatology and physiology differ between men and women and across the menstrual cycle in irritable bowel syndrome (IBS). Ovarian hormones influence 5-hydroxytryptamine (5-HT), an amine known to play a role in gut motor-sensory function. AIM: To assess the effects of gender and menstrual status on platelet-depleted plasma (PDP) 5-HT concentration in IBS patients with diarrhoea (IBS-D) patients compared with healthy volunteers (HV). METHODS: Platelet-depleted plasma 5-HT concentrations were assessed under fasting and fed conditions in 73 IBS-D patients (aged 18-58 years; 18 men) and 64 HV (aged 18-50 years; 24 men). Women were divided into those with low or high progesterone/oestrogen (P/O) levels. RESULTS: Irritable bowel syndrome patients with diarrhoea had higher PDP 5-HT concentrations than HV under fasting (P = 0.002) and fed (P = 0.049) conditions. This was particularly related to IBS-D men having higher PDP 5-HT concentrations than healthy controls (P = 0.002). Moreover, PDP 5-HT concentrations in IBS-D women with low P/O levels were similar to healthy controls. CONCLUSIONS: Similar to IBS-D women with high P/O levels, IBS-D men also have raised PDP 5-HT concentrations. 5-HT concentration normalizes at menses in IBS-D women, suggesting a shift in the mechanisms responsible for abnormal 5-HT signalling in these patients.

Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation.

BACKGROUND: A sensation of abdominal swelling (bloating) and actual increase in girth (distension) are troublesome features of irritable bowel syndrome (IBS), which is more common in patients with constipation, especially those with delayed transit. AIM: To establish whether a fermented dairy product containing Bifidobacterium lactis DN-173 010 reduces distension in association with acceleration of gastrointestinal transit and improvement of symptoms in IBS with constipation. METHODS: A single centre, randomized, double-blind, controlled, parallel group study in which patients consumed the test product or control product for 4 weeks. Distension, orocaecal and colonic transit and IBS symptoms were assessed on an intention-to-treat population of 34 patients. RESULTS: Compared with control product, the test product resulted in a significant reduction in the percentage change in maximal distension [median difference - 39%, 95% CI (-78, -5); P = 0.02] and a trend towards reduced mean distension during the day [-1.52 cm (-3.33, 0.39); P = 0.096]. An acceleration of orocaecal [-1.2 h (-2.3,0); P = 0.049] as well as colonic [-12.2 h (-22.8, -1.6); P = 0.026] transit was observed and overall symptom severity [-0.5 (-1.0, -0.05); P = 0.032] also improved. CONCLUSIONS: This probiotic resulted in improvements in objectively measured abdominal girth and gastrointestinal transit, as well as reduced symptomatology. These data support the concept that accelerating transit is a useful strategy for treating distension.

Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans.

Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK(3) receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK(3) receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants.

Sigmoid-colonic motility in health and irritable bowel syndrome: a role for 5-hydroxytryptamine.

Abstract Evidence suggests that sigmoid-colonic motility is increased in patients with irritable bowel syndrome (IBS). 5-Hydroxytryptamine (5-HT) plays a role in the control of motility, but its involvement in the dysmotility seen in IBS remains unclear. To investigate the relationship between platelet depleted plasma 5-HT (PDP 5-HT) concentration and sigmoid-colonic motility in patients with IBS and healthy volunteers. Pre- and postprandial PDP 5-HT concentrations were assessed while recording sigmoid-colonic motility in 35 IBS patients (aged 19-53 years, eight male) and 16 healthy volunteers (aged 18-39 years, six male). Motility was recorded using a five-channel solid-state catheter introduced to a depth of 35 cm into an unprepared bowel. 5-Hydroxytryptamine concentration was measured by reverse-phase HPLC with fluorimetric detection. Irritable bowel syndrome patients had elevated concentrations of PDP 5-HT under fasting (P < 0.004) and fed (P = 0.079) conditions compared with controls. Likewise, they exhibited increased sigmoid-colonic motility under fasting (activity index: P < 0.02) and fed (P < 0.05) conditions compared with controls. Platelet depleted plasma 5-HT concentration positively correlated with colonic activity index under both fasting (r = 0.402; P = 0.003) and fed (r = 0.439; P = 0.001) conditions. These data show a possible relationship between endogenous concentrations of 5-HT and sigmoid-colonic motility recorded in both IBS and healthy subjects.

Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the alpha(2)delta ligand pregabalin reduces both visceral allodynia and hyperalgesia, but is inactive on basal sensitivity. AIM: To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients. METHODS: Twenty-six patients with Rome-II-defined IBS (aged 18-46 years, 7 male) were included in a randomized, double-blind, placebo-controlled, parallel-group study in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1-3, 100 mg tid days 4-7, 150 mg tid days 8-11; fixed 200 mg tid days 12-21 +/-4) or placebo control. Rectal sensitivity was assessed using a barostat technique, in which sensory thresholds were determined using the ascending method of limits, followed by tracking both before and after treatment. Only patients with a pain threshold of

Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder, characterized by abdominal pain/discomfort, bloating and altered bowel habit. AIM: To conduct a systematic evidence-based review of pharmacological therapies currently used, or in clinical development, for the treatment of IBS in Europe. The safety and tolerability of these therapies are the subject of an accompanying review. METHODS: A literature search was completed for randomized controlled studies which included adult patients with IBS and an active or placebo control, assessed IBS symptoms, and were published in English between January 1980 and June 2005. The level of evidence for efficacy was graded according to the quality of the trial design and the study outcome. RESULTS: There is some evidence for improvement of individual IBS symptoms with antidiarrhoeals (diarrhoea), antispasmodics (abdominal pain/discomfort), bulking agents (constipation), tricyclic antidepressants (abdominal pain/discomfort) and behavioural therapy. In contrast, there is strong evidence for the improvement of global IBS symptoms with two new serotonergic agents: the 5-HT4 selective agonist tegaserod (IBS with constipation) and the 5-HT3 antagonist alosetron (IBS with diarrhoea). Further data are required for the 5-HT3 antagonist, cilansetron, and the mixed 5-HT3 antagonist/5-HT4 agonist renzapride before their utility in IBS can be appraised. CONCLUSIONS: There is limited evidence for the efficacy, safety and tolerability of therapies currently available in Europe for the treatment of IBS. Overall, there is an absence of pharmacological agents licensed specifically for the treatment of IBS subtypes, and new agents are awaited in Europe that will allow changes in clinical practice to focus on and improve global IBS symptoms.

Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility.

We assessed reproducibility of measurements of rectal compliance and sensation in health in studies conducted at two centres. We estimated samples size necessary to show clinically meaningful changes in future studies. We performed rectal barostat tests three times (day 1, day 1 after 4 h and 14-17 days later) in 34 healthy participants. We measured compliance and pressure thresholds for first sensation, urgency, discomfort and pain using ascending method of limits and symptom ratings for gas, urgency, discomfort and pain during four phasic distensions (12, 24, 36 and 48 mmHg) in random order. Results obtained at the two centres differed minimally. Reproducibility of sensory end points varies with type of sensation, pressure level and method of distension. Pressure threshold for pain and sensory ratings for non-painful sensations at 36 and 48 mmHg distension were most reproducible in the two centres. Sample size calculations suggested that crossover design is preferable in therapeutic trials: for each dose of medication tested, a sample of 21 should be sufficient to demonstrate 30% changes in all sensory thresholds and almost all sensory ratings. We conclude that reproducibility varies with sensation type, pressure level and distension method, but in a two-centre study, differences in observed results of sensation are minimal and pressure threshold for pain and sensory ratings at 36-48 mmHg of distension are reproducible.

Towards a better understanding of abdominal bloating and distension in functional gastrointestinal disorders.

Abdominal bloating is an extremely common symptom affecting up to 96% of patients with functional gastrointestinal disorders and even 30% of the general population. To date bloating has often been viewed as being synonymous with an actual increase in abdominal girth, but recent evidence suggests that this is not necessarily the case. This review examines the relationship between the symptom of bloating and the physical sign of abdominal distension, as well as examining the epidemiology, pathophysiology and treatment options available for this debilitating aspect of the functional gastrointestinal disorders. Pathophysiological mechanisms explored include psychological factors, intestinal gas accumulation, fluid retention, food intolerance and malabsorption of sugars, weakness of abdominal musculature, and altered sensorimotor function. Treatment options are currently rather limited but include dietary changes, pharmacological approaches, probiotics and hypnotherapy.

Inter-digestive and post-prandial antro-pyloro-duodenal motor activity in humans: effect of 5-hydroxytryptamine 1 receptor agonism.

BACKGROUND: Little is known about the effect of 5-hydroxytryptamine 1 (5-HT(1)) receptor agonism on the co-ordinated motor activity of the gastric antrum, pylorus and duodenum under fasting and fed conditions. AIM: To evaluate the effect of sumatriptan, a 5-HT(1) agonist, on fasting and fed antro-pyloro-duodenal motility. METHODS: In study 1, antro-pyloro-duodenal motility was recorded for two phase IIIs of the migrating motor complex and then, following either a subcutaneous injection of sumatriptan 6 mg or saline control, for at least one additional phase III in 11 healthy volunteers (21-36 years). In study 2, the post-prandial motility was recorded for 3 h after either a subcutaneous injection of sumatriptan 6 mg or saline control in 10 healthy volunteers (18-36 years). RESULTS: Sumatriptan prolonged the migrating motor complex cycle (P = 0.009) by increasing the duration of phase II (P = 0.02) but not phases I and III. Post-prandially, sumatriptan reduced the activity index (P = 0.017) by reducing the frequency of co-ordinated motor activity involving the antrum and/or the duodenum (P < 0.05). CONCLUSION: 5-HT(1) receptor agonism increases the periodicity of the migrating motor complex and reduces the occurrence of post-prandial co-ordinated motor activity involving the gastric antrum, pylorus and duodenum.

Diagnostic criteria for irritable bowel syndrome: utility and applicability in clinical practice.

BACKGROUND/AIMS: Symptom-based criteria have been introduced to aid the diagnosis of irritable bowel syndrome (IBS). Although they have been widely adopted and have proved useful for research purposes by ensuring homogeneity of study populations, there is little information about their utility in routine clinical practice. It was the aim of this study to assess the applicability of the Manning, Rome I and Rome II criteria in the clinical setting and to ascertain how often hospital specialists and general practitioners (GPs) use them. METHODS: Hundred secondary-care IBS patients were assessed for their conformity to these criteria. Forty-eight hospital specialists and 68 GPs were asked about their knowledge and utilization of these criteria. RESULTS: Seventy-three percent of IBS patients met Rome II diagnostic criteria with 82 and 94% meeting Rome I and Manning, respectively. Approximately 80% of GPs had no knowledge of any of the specific criteria, and only 4% had ever used them. The majority of specialists had knowledge of the criteria, with 70% having used them. CONCLUSION: The Rome II criteria are remarkably insensitive and if rigidly applied in the clinical situation would lead to much diagnostic uncertainty. The current lack of interest in them, especially amongst GPs, is unlikely to change unless they can be considerably improved.

Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome.

BACKGROUND: Meal ingestion is often associated with exacerbation of gastrointestinal symptoms in subjects with irritable bowel syndrome (IBS). Furthermore, recent preliminary data suggest that 5-hydroxytryptamine (5-HT) concentration in platelet poor plasma is elevated following meal ingestion in some subjects with diarrhoea predominant IBS (d-IBS) compared with healthy subjects, although it is not known whether this is related to postprandial symptomatology. AIM: To expand on previous data by evaluating a larger number of subjects but also to assess plasma 5-hydroxyindole acetic acid (5-HIAA) concentrations, 5-HT turnover, platelet 5-HT stores, and any relationship to symptomatology. METHODS: We assessed platelet depleted plasma 5-HT and 5-HIAA concentrations for two hours (60 minute intervals) under fasting conditions, and then for a further four hours (30 minute intervals) after a standard carbohydrate meal (457 kcal), together with fasting platelet 5-HT concentrations in 39 female subjects with d-IBS (aged 19-52 years; mean age 33) and 20 healthy female volunteers (aged 20-46 years, mean age 28). IBS symptomatology, in particular abdominal pain and bloating, and urgency to defecate were assessed throughout the study RESULTS: When related to fasting levels, there was no statistically significant difference in postprandial plasma 5-HT concentrations between d-IBS and healthy subjects. However, when fasting levels were not taken into consideration, d-IBS subjects exhibited higher postprandial plasma 5-HT concentrations compared with healthy subjects (p=0.040). Furthermore, d-IBS subjects who exhibited postprandial symptomatology had higher levels of postprandial plasma 5-HT, whether assessed with respect to fasting baseline levels (p=0.069) or not (p=0.047), compared with d-IBS subjects who did not report postprandial symptomatology. This appeared to be associated with a concomitant increase in plasma 5-HIAA (p=0.161) but reduction in turnover (p=0.058). Lastly, d-IBS subjects had higher platelet concentrations of 5-HT than healthy subjects (p=0.009). CONCLUSIONS: These data suggest that postprandial symptomatology may be associated with increased platelet depleted plasma 5-HT concentrations in female subjects with d-IBS. In addition, the presence of increased platelet stores of 5-HT may act as a useful marker for the diagnosis and management of d-IBS.

Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome.

BACKGROUND: We have previously shown that hypnotherapy alters rectal sensitivity in some patients with irritable bowel syndrome. However, this previous study used incremental volume distension of a latex balloon, which might be susceptible to subject response bias and might compromise the assessment of compliance. In addition, the study group was symptomatically rather than physiologically defined. AIM: To assess the effect of hypnotherapy on rectal sensitivity in hypersensitive, hyposensitive and normally sensitive irritable bowel syndrome patients using a distension technique (barostat) that addresses these technical issues. METHODS: Twenty-three irritable bowel syndrome (Rome I) patients (aged 24-72 years) were assessed before and after 12 weeks of hypnotherapy in terms of rectal sensitivity, symptomatology, anxiety and depression. Normal values for sensitivity were established in 17 healthy volunteers (aged 20-55 years). RESULTS: Compared with controls, 10 patients were hypersensitive, seven hyposensitive and six normally sensitive before treatment. Following hypnotherapy, the mean pain sensory threshold increased in the hypersensitive group (P = 0.04) and decreased in the hyposensitive group, although the latter failed to reach statistical significance (P = 0.19). Normal sensory perception was unchanged. Sensory improvement in the hypersensitive patients tended to correlate with a reduction in abdominal pain (r = 0.714, P = 0.07). CONCLUSION: Hypnotherapy improves abnormal sensory perception in irritable bowel syndrome, leaving normal sensation unchanged.