Biomedical subjects

Lesley A Houghton

Publications and source records attributed to Lesley A Houghton.

7 recordsLinked to original sources

PubMed2006

Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit.

BACKGROUND & AIMS: The relationship between the sensation of bloating, often ranked as the most bothersome symptom by patients with irritable bowel syndrome (IBS), and actual distention manifest as an increase in abdominal girth is controversial. Investigation of this problem has been hampered by the lack of a reliable ambulatory technique to measure abdominal girth. The aim of this study was to use the technique of abdominal inductance plethysmography to compare diurnal variation in girth in IBS patients and healthy volunteers, relating these changes to the sensation of bloating. METHODS: Abdominal girth was recorded for 24 hours in 20 IBS-constipation (age, 18-73 y), 20 IBS-diarrhea (age, 25-62 y) and 10 IBS-alternating (age, 21-59 y) female patients meeting Rome II criteria and 20 healthy female controls (age, 18-67 y). All subjects pursued normal daily activities, recording their symptoms of bloating and pain together with bowel habit. RESULTS: All patients with IBS, irrespective of bowel habit, reported significantly greater bloating than controls (P < .0001). Forty-eight percent of patients also showed distention beyond the 90% control range, with this being most prominent in IBS-constipation. Bloating correlated strongly only with distention in IBS-constipation (r > or = 0.48; P < or = .02). Neither bloating nor distention in IBS was related to body mass index, age, parity, or psychologic status. CONCLUSIONS: Abdominal distention is a clearly definable phenomenon in IBS that can reach 12 cm. However, it only occurs in half of patients reporting bloating, and the 2 only correlate in IBS-constipation. Bloating and distention may differ pathophysiologically and this appears to be reflected in the bowel habit subtype.

Abdomen↗

PubMed2006

Validation of the measurement of low concentrations of 5-hydroxytryptamine in plasma using high performance liquid chromatography.

A sensitive and rapid assay is described for the measurement of low concentrations of 5-hydroxytryptamine (5-HT) present in human platelet-depleted plasma (PDP) using reverse-phase high performance liquid chromatography (HPLC) with fluorimetric detection. With an analysis time of 12 min, this method is particularly useful for large-scale clinical trials investigating small differences in PDP 5-HT concentrations in conditions such as functional gastrointestinal disorders (FGID). The limit of detection and quantification were 1 and 3 nmol/l, respectively, and the calibration curve linear between 1 and 1000 nmol/l. The within-day and between-day precision were 4.3 and <13.6%, respectively.

Chromatography, High Pressure Liquid↗

PubMed2006

Effects of cilomilast, a selective phosphodiesterase 4 inhibitor, on esophageal motility and pH, and orocecal and colonic transit: two single-center, randomized, double-blind, placebo-controlled, two-part crossover studies in healthy volunteers.

BACKGROUND: Phase IIb studies have reported that cilomilast, a selective phosphodiesterase 4 inhibitor being developed for the treatment of chronic obstructive pulmonary disease, is associated with gastrointestinal (GI) adverse effects (AEs) in a small proportion (approximately 5%) of individuals. OBJECTIVES: The aims of these 2 studies were to investigate the effects of cilomilast 15 mg BID on: (1) lower esophageal sphincter pressure (LESP) and esophageal body motility and pH (study 1); and (2) orocecal and whole-gut transit times (OCTT and WGTT, respectively) (study 2) in healthy volunteers. METHODS: These 2 randomized, double-blind, placebo-controlled, 2-part crossover studies were conducted at the Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, United Kingdom (study 1) and GlaxoSmithKline, Harlow, United Kingdom (study 2). In study 1, subjects were randomly assigned to receive either cilomilast (15 mg BID) or matched placebo (control) for 7 days (13 doses; subjects were not given the evening dose on day 7), and in study 2, cilomilast (15 mg BID) or matched placebo (control) for 9 days (18 doses) in each of 2 treatment periods. After study drug administration, combined esophageal motility and pH were recorded for 2 hours before and 4 hours after the administration of a standardized meal (2400 kJ [573 kcal]). Sequences of 6 consecutive 5-mL water swallows (separated by 20 seconds) were carried out 60 and 90 minutes (fasting) and 150, 180, 210, 240, 300, and 360 minutes (fed) after study drug administration. OCTT was determined from the increase in breath hydrogen after the meal. WGTT was determined from the time taken to excrete at least 16 of 20 ingested radiopaque markers, ingested as 2 capsules, each containing 10 radiopaque markers, with 240 mL of water. AEs were elicited at specified times throughout each session using nonleading questions, spontaneously reported AEs, and diary cards. RESULTS: Study 1 enrolled 20 subjects (11 men, 9 women; age range, 20-52 years). Study 2 enrolled 16 subjects (10 men, 6 women; age range, 19-48 years). No clinically significant differences in the amplitude (mean difference in postprandial-preprandial AUC0-t/t, 6.09 mm Hg; 95% CI, -10.66 to 22.84), duration (difference, -0.08 second; 95% CI, -0.54 to 0.37), or velocity of propagation (difference, 0.90 cm/s; 95% CI, -0.66 to 2.46) of esophageal contractions, LESP (difference, -0.39 mm Hg; 95% CI, -5.23 to 4.45), or preprandial or postprandial percentage time pH<4 (median differences: preprandial, 0.47% [95% CI, -0.45 to 1.27]; postprandial, -0.005% [95% CI, -1.30 to 6.27]) were found with cilomilast compared with placebo. No significant differences in OCTT (difference, -0.37 hour; 95% CI, -1.59 to 0.84) or WGTT (difference, -2.96 hours; 95% CI, -20.76 to 14.84) were found with cilomilast compared with controls. In both studies, the most frequently reported AEs with cilomilast use were nausea (8/18 in study 1 and 3/16 in study 2) and headache (8/18 in study 1 and 6/16 in study 2); however, these were generally of mild to moderate intensity. Overall, GI AEs did not correlate with changes in GI motility. CONCLUSION: The results of these 2 studies suggest that cilomilast was not associated with significant changes in esophageal motility and pH or GI transit in these healthy volunteers.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome.

BACKGROUND & AIMS: Evidence suggests that postprandial platelet-depleted plasma 5-hydroxytryptamine (5-HT) concentrations may be abnormal in irritable bowel syndrome (IBS). However, interpretation of the data has been hampered by the variable methodology and rather small numbers used in previous studies. Therefore, the aim of this study was to measure concentrations of platelet-depleted plasma 5-HT and its metabolite 5-HIAA under fasting and fed conditions in a large group of patients with diarrhea-predominant (d-) and constipation-predominant (c-) IBS, compared with controls. The ratio of plasma 5-HIAA:5-HT and platelet stores was also assessed. METHODS: Twenty-nine c-IBS patients (aged, 19-53 years), 55 d-IBS patients (aged, 19-52 years), and 35 healthy volunteers (aged, 18-46 years) had platelet-depleted plasma 5-HT/5-HIAA concentrations measured using reverse-phase, high-performance liquid chromatography with fluorimetric detection before and after a standard meal. RESULTS: d-IBS patients had raised platelet-depleted plasma 5-HT concentrations under fasting and fed conditions (P < .05). However, the postprandial relative to fasting concentration was similar to controls. In contrast, c-IBS patients failed to show an increase in platelet-depleted plasma 5-HT concentration with meal ingestion compared with controls (P < .01). c-IBS was associated with decreased 5-HIAA (P < .01) but normal 5-HIAA:5-HT ratio and d-IBS with normal 5-HIAA concentrations but reduced 5-HIAA:5-HT ratio (P < .005). C-IBS but not d-IBS patients had increased platelet 5-HT. CONCLUSIONS: These results support the concept that d-IBS is characterized by reduced 5-HT reuptake, whereas impaired release may be a feature of c-IBS. These results also provide a rational basis for current pharmacologic approaches involving modulation of different 5-HT receptors in c- and d-IBS.

Adult↗

PubMed2006

Functional bowel disorders.

Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset > or =6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD. Irritable bowel syndrome (IBS), functional bloating, functional constipation, and functional diarrhea are best identified by symptom-based approaches. Subtyping of IBS is controversial, and we suggest it be based on stool form, which can be aided by use of the Bristol Stool Form Scale. Diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. Treatment of FBDs is based on an individualized evaluation, explanation, and reassurance. Alterations in diet, drug treatment aimed at predominant symptoms, and psychotherapy may be beneficial.

Constipation↗

PubMed2006

The rationale, efficacy and safety evidence for tegaserod in the treatment of irritable bowel syndrome.

A growing body of evidence implicates abnormal serotonergic regulation of gastrointestinal function in the pathogenesis of the irritable bowel syndrome (IBS). Drugs targeting this system are therefore attractive concepts. The partial 5-HT4 receptor agonist tegaserod might be predicted to have positive therapeutic effects on a constipated and uncomfortable gut. However, IBS runs a chronic, benign course and carries no associated mortality, so it is imperative that the safety profile of new pharmacological agents made available to physicians is exemplary. The authors review the evidence for 5-HT in the aetiology of IBS and its symptoms, and the data available concerning the partial 5-HT4 receptor agonist tegaserod, in terms of rationale, efficacy and safety.

Biological Availability↗

PubMed2002

Hypnotherapy in irritable bowel syndrome: a large-scale audit of a clinical service with examination of factors influencing responsiveness.

OBJECTIVES: Hypnotherapy has been shown to be effective in the treatment of irritable bowel syndrome in a number of previous research studies. This has led to the establishment of the first unit in the United Kingdom staffed by six therapists that provides this treatment as a clinical service. This study presents an audit on the first 250 unselected patients treated, and these large numbers have also allowed analysis of data in terms of a variety of other factors, such as gender and bowel habit type, that might affect outcome. METHODS: Patients underwent 12 sessions of hypnotherapy over a 3-month period and were required to practice techniques in between sessions. At the beginning and end of the course of treatment, patients completed questionnaires to score bowel and extracolonic symptoms, quality of life, and anxiety and depression, allowing comparisons to be made. RESULTS: Marked improvement was seen in all symptom measures, quality of life, and anxiety and depression (all ps < 0.001), in keeping with previous studies. All subgroups of patients appeared to do equally well, with the notable exception of males with diarrhea, who improved far less than other patients (p < 0.001). No factors, such as anxiety and depression or other prehypnotherapy variables, could explain this lack of improvement. CONCLUSIONS: This study clearly demonstrates that hypnotherapy remains an extremely effective treatment for irritable bowel syndrome and should prove more cost-effective as new, more expensive drugs come on to the market. It may be less useful in males with diarrhea-predominant bowel habit, a finding that may have pathophysiological implications.

Adult↗