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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 37 records · Page 2Linked to original sources
PubMed2005

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.

Adult↗
PubMed2004

Assessment of gastric accommodation: overview and evaluation of current methods.

Gastric accommodation is considered important in the pathophysiology of several upper gastrointestinal disorders including functional dyspepsia. The gold standard for its measurement is the barostat-balloon study which requires intubation. The aim was explore the reliability and performance characteristics of the techniques proposed for measurement of gastric accommodation. We undertook a literature search using MEDLINE with a broad range of key words. The accommodation reflex and its control are briefly described, based on human data. The performance characteristics of the intragastric barostat, transabdominal ultrasound, magnetic resonance imaging, single photon emission computed tomography, and satiation drinking tests are described. For each technique, we summarize the following: principle, validation studies, advantages, disadvantages, and potential applications. Three-dimensional methods to measure gastric volume non-invasively are promising and among the best validated to date. Simpler techniques would be of considerable appeal for clinical and research studies, but further validation is necessary before satiation drinking tests can be used as surrogates for more sophisticated measurements of gastric accommodation.

Diagnostic Imaging↗
PubMed2004

Opioids and the gut: pharmacology and current clinical experience.

This article reviews the pharmacology and physiology of opiate receptors and the current and potential uses of opioid agonists and antagonists in clinical gastroenterology. Mu-receptors are involved in motor and sensory functions, and their modulation is established for treatment of diarrhea. Mu-antagonists have potential to reverse endogenous (e.g., postoperative ileus) or iatrogenic dysmotility (e.g., opioid bowel dysfunction). Modulation of the function of kappa-receptors may be a novel approach to control visceral pain in functional gut disorders. Results of formal testing of novel opioid modulators are keenly awaited.

Animals↗
PubMed2004

Pathophysiology as a basis for understanding symptom complexes and therapeutic targets.

Sensorimotor disorders of the stomach, small intestine and colon have a limited repertoire of clinical manifestations, and there is the potential for more than one mechanism to lead to symptoms. In many recent clinical trial programs of novel agents in neurogastroenterology, the emphasis has been primarily on symptom assessment of broad groups of patients identified by the Rome criteria. Drugs of potential value have fallen by the wayside with this approach. We propose the current paradigm is partly to blame; physiological testing should provide the basis for identifying more homogeneous populations and therapeutic targets within functional bowel disease, and this applies to the upper and lower gut. Here we summarize the evidence that certain biomarkers can, in a limited fashion, be used to predict the success of an experimental medicine in common disorders of gastrointestinal function, including the irritable bowel syndrome and functional dyspepsia. Although the current evidence is limited and is most convincingly demonstrated with examples of transit measurements (for loperamide, alosetron, tegaserod and piboserod), we perceive this paradigm that studies using validated and responsive biomarkers have an important role to play in drug development.

Animals↗
PubMed2004

Comparison of gastric volumes in response to isocaloric liquid and mixed meals in humans.

AIMS: To compare gastric volume responses to ingestion of isocaloric liquid or mixed (solid-liquid) meals and document the intra- and interindividual reproducibility of gastric volume measurement using single photon emission computed tomography (SPECT) imaging after i.v. 99mTc-pertechnetate. METHODS: Eight healthy volunteers performed two studies at least 9 months apart. Gastric volumes were measured after a 317 kcal liquid nutrient meal. Within 2 weeks of the second liquid meal study, participants performed a third study, ingesting an isocaloric mixed meal. The order of the mixed and second liquid meals was randomized; Bland-Altman plot displayed data on repeated studies with liquid meal and paired t-test compared gastric volumes after mixed or liquid isocaloric meals. RESULTS: Fasting and postprandial gastric volumes associated with the two liquid meals were not significantly different; inter- and intra-individual coefficients of variation were 13 and 13.8%. In response to the mixed meal, there was a lower absolute postprandial volume and lower change in gastric volume over fasting volume compared with the response to the liquid meal (P = 0.0001). CONCLUSION: The SPECT measurement of gastric volumes in response to a nutrient liquid meal is reproducible. The magnitude of the volume response is greater after the liquid meal compared with the isocaloric mixed meal.

Adult↗
PubMed2004

Human enteric neuropathies: morphology and molecular pathology.

The aim of this study is to review current understanding of the molecular and morphological pathology of the enteric neuropathies affecting motor function of the human gastrointestinal tract and to evaluate the described pathological entities in the literature to assess whether a new nosology may be proposed. The authors used PUBMED and MEDLINE searches to explore the literature pertinent to the molecular events and pathology of gastrointestinal motility disorders including achalasia, gastroparesis, intestinal pseudo-obstruction, colonic inertia and megacolon in order to characterize the disorders attributable to enteric gut neuropathies. This scholarly review has shown that the pathological features are not readily associated with clinical features, making it difficult for a patient to be classified into any specific category. Individual patients may manifest more than one of the morphological and molecular abnormalities that include: aganglionosis, neuronal intranuclear inclusions and apoptosis, neural degeneration, intestinal neuronal dysplasia, neuronal hyperplasia and ganglioneuromas, mitochondrial dysfunction (syndromic and non-syndromic), inflammatory neuropathies (caused by cellular or humoral immune mechanisms), neurotransmitter diseases and interstitial cell pathology. The pathology of enteric neuropathies requires further study before an effective nosology can be proposed. Carefully studied individual cases and small series provide the basic framework for standardizing the collection and histological evaluation of tissue obtained from such patients. Combined clinical and histopathological studies may facilitate the translation of basic science to the clinical management of patients with enteric neuropathies.

Animals↗
PubMed2004

Effect of cyclooxygenase-2 inhibitors on gastric emptying and small intestinal transit in humans.

Endogenous prostaglandins regulate smooth muscle activity; prostaglandins and cyclooxygenase (COX) inhibitors influence gastrointestinal motility in inflammatory states such as postoperative ileus in animal models. The objective of this study was to evaluate the effects of two COX-2 inhibitors on gastric emptying and intestinal transit in healthy humans. In a double-blind, placebo-controlled, parallel-group study, 66 healthy volunteers were randomized to one of two commercially available oral COX-2 inhibitors (celecoxib and rofecoxib), cisapride (positive control), or placebo. Following 7 days on therapy, study participants underwent a test of gastric emptying and small bowel transit of liquids and solids using scintigraphy. Data were analysed using Kruskal-Wallis (ANOVA on ranks)and Mann-Whitney rank sum tests. There were significant group effects on transit of solids: gastric emptying (ANOVA, P = 0.005) and small bowel transit (ANOVA, P = 0.056). However, neither COX-2 inhibitor significantly accelerated the liquid or solid gastric emptying or small bowel transit compared with placebo. The positive control, cisapride, accelerated gastric emptying of solids (post-lag slope of gastric emptying, P < 0.05), and small bowel transit of solids (t10%, P = 0.016). At maximum clinically approved dosages, celecoxib and rofecoxib have no significant effects on gastric emptying or small intestinal transit in healthy humans. Cisapride accelerates gastric emptying and small bowel transit in healthy humans.

Adolescent↗
PubMed2004

Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders.

BACKGROUND: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (alpha(2)) adrenoceptors, norepinephrine transporter, and serotonin transporter protein (soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and high somatic symptom scores. METHODS: Validated bowel and somatic symptom questionnaires characterised the phenotype: 90 with IBS constipation (IBS-C), 128 IBS diarrhoea, 38 IBS alternating bowel function, and 20 chronic abdominal pain. Logistic regression analyses assessed associations of different polymorphisms for alpha(2) adrenoceptor and SLC6A4 with IBS or chronic abdominal pain phenotypes and high somatic score. RESULTS: Two distinct polymorphisms independently appeared to be associated with the phenotype IBS-C: alpha(2C) Del 322-325 (odds ratio (OR) 2.48 (95% confidence interval (CI) 0.98, 6.28); p = 0.05) and alpha(2A) -1291 (C-->G) (OR 1.66 (95% CI 0.94, 2.92); p = 0.08) relative to wild-type. Overall, the alpha(2C) Del 322-325 polymorphism (alone or combined with other polymorphisms) was also significantly associated with a high somatic symptom score (OR 2.2 (95% CI 1.06, 4.64); p = 0.03). Combinations of polymorphisms were also associated with high somatic scores. CONCLUSION: Functionally distinct alpha(2A) and alpha(2C) adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear.

Adolescent↗
PubMed2003

Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health.

AIM: To evaluate the effect of single administrations of asimadoline, a kappa-opioid agonist, on satiation volume, postprandial symptoms and gastric volumes. METHODS: Healthy subjects received oral placebo, or 0.5 or 1.5 mg asimadoline in a randomized, double-blind fashion 1 h prior to testing. We assessed effects on the volume of Ensure to achieve full satiation and postprandial symptoms 30 min after meal, and on gastric volume (fasting and postprandial) measured by 99mTc-single photon emission tomography (SPECT) imaging. RESULTS: Thirteen healthy subjects were studied in each treatment arm. Compared to placebo, asimadoline 0.5 mg decreased postprandial fullness (P = 0.027) without affecting the volume ingested at full satiation (P = 0.6). Asimadoline 1.5 mg decreased satiation during meal, allowing increased satiation volumes (P = 0.008) and tended to decrease postprandial fullness (P = 0.067), despite higher volumes ingested. There was a significant treatment-gender interaction in the effect of asimadoline on gastric volumes (P < 0.05). Asimadoline 0.5 mg (not 1.5 mg) increased fasting (P = 0.047) and postprandial (P = 0.009) gastric volumes in females but decreased fasting volumes in males (P = 0.008). The effect of asimadoline on gastric volume did not explain the effect observed on satiation volume (P = 0.371) or postprandial fullness (P = 0.399). CONCLUSION: A single oral administration of asimadoline decreases satiation and postprandial fullness in humans independently of its effects on gastric volume.

Acetamides↗
PubMed2003

Meta-analysis: the relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease.

BACKGROUND: The relationship between Helicobacter pylori infection and its treatment and gastro-oesophageal reflux disease (GERD) is controversial. AIMS: To establish if H. pylori infection is associated with the presence of GERD and if anti-H. pylori treatment leads to de novo GERD or rebound/exacerbation of GERD. METHODS: A search of MEDLINE and EMBASE databases was made. Pooled odds ratios (OR) were calculated for de novo GERD and rebound/exacerbated GERD after anti-H. pylori therapy in case-control studies and in therapeutic trials. RESULTS: Fourteen case-control studies and 10 clinical trials were included. Among case-control studies, pooled OR for the association between H. pylori negative status and GERD was 1.34 [95% confidence interval (CI) 1.15-1.55]. Among therapeutic trials, pooled OR for the association anti-H. pylori therapy - GERD was 2.54 (95% CI 1.92-3.37). The OR for de novo GERD was 3.25 (95% CI 2.09-5.33), and for rebound/exacerbated GERD was 2.39 (95% CI 1.75-3.34). Associations were higher among Asian studies than among North American and European studies. CONCLUSIONS: This meta-analysis shows significant association between absence of H. pylori infection and GERD symptoms, and a positive association between anti-H. pylori therapy and occurrence of both de novo and rebound/exacerbated GERD. The significance of these associations appears to have been inflated by the effect of single trials and by geographical variations.

Case-Control Studies↗
PubMed2003

Systematic review and meta-analysis: does gall-bladder ejection fraction on cholecystokinin cholescintigraphy predict outcome after cholecystectomy in suspected functional biliary pain?

BACKGROUND: Patients with suspected functional biliary pain often undergo cholecystectomy if a decreased gall-bladder ejection fraction (GBEF <35%) is demonstrated by cholecystokinin cholescintigraphy. However, the validity of GBEF in predicting which patients will have symptomatic relief following cholecystectomy is unclear. AIM: To determine whether patients with suspected functional biliary pain with decreased GBEF have a better symptomatic outcome after cholecystectomy than those with normal GBEF. METHODS: Systematic review and meta-analysis of the published literature through MEDLINE and EMBASE databases. RESULTS: We included nine studies with a total of 974 patients with suspected functional biliary pain; 362 patients underwent cholecystectomy. Most studies assessed outcome by direct patient interview. Mean ages across the studies ranged from 35 to 47 years; 78% of all patients were female. Mean duration of follow-up after surgery ranged from 1 to 2.5 years. After cholecystectomy, 94% of the patients with reduced GBEF had a positive outcome compared to 85% among those with normal GBEF. The pooled Mantel-Haenszel odds ratio for positive outcome was 1.37 (95% confidence interval 0.56-3.34), P=0.56. CONCLUSION: These data do not support the use of GBEF to select patients with suspected functional biliary pain for cholecystectomy. Prospective randomized trials are required if this practice is to be evidence-based.

Cholecystectomy↗
PubMed2003

A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.

AIM: To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea. METHODS: Twenty-five patients with diarrhoea-predominant irritable bowel syndrome were randomly assigned to receive VSL#3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2-week run-in period. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily in a diary during the 10-week study, which was powered to detect a 50% change in the primary colonic transit end-point. RESULTS: There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre- or post-therapy. Differences in abdominal bloating scores between treatments were borderline significant (P = 0.09, analysis of covariance). Further analysis revealed that abdominal bloating was reduced (P = 0.046) with VSL#3 [mean post- minus pre-treatment score, - 13.7; 95% confidence interval (CI), - 2.5 to - 24.9], but not with placebo (P = 0.54) (mean post- minus pre-treatment score, - 1.7; 95% CI, 7.1 to - 10.4). With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency. All patients tolerated VSL#3 well. CONCLUSION: VSL#3 appears to be promising in the relief of abdominal bloating in patients with diarrhoea-predominant irritable bowel syndrome. This is unrelated to an alteration in gastrointestinal or colonic transit.

Adolescent↗
PubMed2003

[Clinical management of acute colonic pseudo-obstruction in patients: a systematic review of the literature].

Intestinal pseudoobstruction is a clinical syndrome characterized by impairment of intestinal propulsion, which may resemble intestinal obstruction, in the absence of a mechanical cause. It usually affects the colon but the small intestine may also be involved, and may present in acute, subacute or chronic forms. We have performed a systematic review of the acute form of pseudoobstruction, also referred to as Ogilvie's syndrome. We discuss proposed pathophysiological mechanisms, manifestations and management of this clinical condition in post-surgery and critically ill patients. The hallmark of the syndrome is massive intestinal distension, which is detected on clinical inspection and plain abdominal radiography. The underlying pathophysiological mechanisms are not fully understood. Therefore, treatment has focussed on preventing intestinal perforation, which is associated with a 21% mortality rate.

Acute Disease↗
PubMed2003

Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials.

The 5HT3 receptor antagonist alosetron has been tested in several trials on irritable bowel syndrome (IBS) patients. The aim of the present meta-analysis was to determine its effect on adequate relief of pain or global improvement of symptoms in IBS patients. Six large, multicentre, randomized, placebo-controlled trials fulfilled pre-set criteria for high quality and were included in the meta-analysis; 1762 patients were randomized to alosetron treatment and 1356 to placebo. Seventy-five per cent of the patients experienced diarrhoea-predominant IBS and 93% were females. The pooled odds ratio for adequate relief of pain or global symptoms improvement was 1.81 [95% confidence interval (CI) 1.57-2.10). The average number of patients needed to treat with alosetron for one patient to achieve improvement over placebo treatment was seven (95% CI 5.74-9.43). The present analysis shows that alosetron 1 mg b.i.d. positively impacts global symptoms, and pain and discomfort in non-constipated IBS female patients. One in four patients treated with alosetron may develop constipation. The efficacy of alosetron is unclear in male patients.

Carbolines↗