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Biomedical subjects

Michael Camilleri

Publications and source records attributed to Michael Camilleri.

At least 19 recordsLinked to original sources
PubMed2026

Brief Review: Rethinking Colonic Redundancy in Gastroenterology.

BACKGROUND: Dolichocolon (DC), or colonic redundancy, is an elongated and tortuous colon described as early as 1820, yet it remains underrecognized in clinical gastroenterology. Advances in imaging and motility assessment offer new insights into its prevalence, mechanisms, and clinical implications. AIMS: To summarize current evidence on the anatomy, epidemiology, and potential clinical significance of DC and to explore possible pathophysiological mechanisms linking this variant to gastrointestinal disorders. METHODS: A targeted literature review of studies published between 1900 and 2024 was conducted using PubMed and Scopus with search terms including dolichocolon, colonic redundancy, and redundant colon. Publications addressing anatomy, motility, symptom associations, and disease relevance were included. RESULTS: Though epidemiological data are limited, it has been estimated that DC affects 10-20% of the population and is associated with constipation, volvulus, and, possibly, inflammatory bowel disease. Proposed mechanisms include segmental stasis and ischemia in redundant loops, altered neuromuscular signaling, and increased mucosal surface area promoting immune-microbiota interactions. Despite its potential importance, DC is rarely noted in modern radiology reports, contributing to under-recognition in clinical practice. CONCLUSIONS: Colonic redundancy represents a common anatomic variant with potentially overlooked clinical implications. Standardized radiologic characterization and prospective studies are needed to clarify its role in gastrointestinal disorders and to guide future diagnostic and therapeutic approaches.

Humans↗
PubMed2005

Genetics and genotypes in irritable bowel syndrome: implications for diagnosis and treatment.

Several twin studies and familial aggregation studies in IBS are consistent with either a genetic or a social learning hypothesis, and it is possible that both play a role. The prospect of identifying a genetic cause for IBS may be very important, because it raises the possibility of confirming that IBS isa disease entity, suggests new insight into the pathophysiology of the disorder, and provides new targets for drug development. Several candidate genetic markers including: those related to cytokines such as IL-10, TNF-alpha and TGF beta1; SERT-P; alpha-adrenergic receptors; and G proteins have been associated with certain aspects of IBS. Genetic polymorphisms,however, are common and may have no etiological or pathogenetic relevance. Searching for the genes in IBS is of potentially great relevance. Such studies may identify more specific phenotypes in IBS or potentially predict increased disease vulnerability, but it is unlikely that this strategy will lead to a diagnostic test, given the limited component of IBS that is likely to be genetically determined. Pharmaco genomic studies have potential to be important in the future. For this potential to be realized, it will be necessary to formally include genetic studies in trials of experimental drugs.This would enhance understanding of one of the roles of genetics for treating IBS.

GTP-Binding Proteins↗
PubMed2005

Gastric sensory and motor dysfunction in adolescents with functional dyspepsia.

OBJECTIVES: Validated, noninvasive studies were used to compare sensation and motor function of the upper gastrointestinal tract in adolescents with functional dyspepsia (FD) and in control subjects. STUDY DESIGN: Fifteen adolescents with FD and 15 healthy participants underwent standardized symptom assessment, a satiation nutrient drink test, and 13 C-Spirulina platensis breath test for gastric emptying of solids. Adolescents with FD also underwent measurements of fasting and postprandial gastric volume by means of single-photon emission computed tomography, and their results were compared with those from 15 healthy volunteers (age, 18 to 25 years). RESULTS: Compared with control subjects, adolescents with FD had significantly higher postprandial symptoms 30 minutes after reaching maximum satiation with the nutrient drink test and significant delay in the T 1/2 for gastric emptying of solids. Compared with healthy 18- to 25-year-old adults, adolescents had a diminished postprandial gastric volume response. By means of single-photon emission computed tomography, frequent baseline dyspeptic symptoms were associated with prolonged T 1/2 for gastric emptying and higher postprandial aggregate symptom score. A baseline increased severity of dyspepsia symptoms was associated with prolonged T 1/2 for gastric emptying. CONCLUSIONS: Adolescents with FD demonstrate increased postprandial symptoms after challenge, delayed gastric emptying, and a reduced gastric volume response to feeding.

Adolescent↗
PubMed2005

Gastric motor and sensory functions in obesity.

In the vast majority of affected individuals, obesity involves overconsumption of food relative to calorie requirements. The sensory function of the stomach may play a key role in the cessation of food ingestion. This sensation of the stomach is, in part, determined by its motor functions, such as tone and compliance and the rate of emptying. However, studies of gastric emptying in normal-weight and obese persons have shown inconsistent results. Gastric capacity was larger in obese persons when tested with an intragastric latex balloon filled with water. In contrast, other studies using the barostat or imaging (single-photon emission computed tomography) techniques reported no differences in gastric volume or compliance between obese and lean subjects. On the other hand, increased body mass and fasting gastric volume are independently associated with delayed satiation under standard laboratory conditions of food ingestion. These data suggest that changes in gastric motor and sensory functions in obesity may present useful targets to prevent and treat obesity. Further well-controlled, validated studies are needed to clarify the potential role of altering the stomach's function as a means of controlling food intake in obesity.

Diagnostic Imaging↗
PubMed2005

Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study.

BACKGROUND: Cholecystokinin (CCK) is involved in gastrointestinal motor response to meals. The potential role of CCK receptor antagonists in functional gastrointestinal disorders is unclear. AIMS: To evaluate the effects of dexloxiglumide, a CCK-1 receptor antagonist, on gastrointestinal transit (GIT) and symptoms in patients with constipation-predominant IBS (C-IBS); and to explore the influence of CCK-1 receptor polymorphisms on gut transit and the pharmacodynamic response to therapy. METHODS: A total of 36 patients with C-IBS and normal to slow baseline colonic transit (CT) were randomized (double-blind, parallel design) to 7 days of dexloxiglumide 200 mg or placebo t.i.d. Daily bowel habits diaries and weekly relief of IBS symptoms were recorded. At the end of treatment, GIT and CT were measured. Peripheral blood DNA was examined for polymorphisms in genes controlling CCK: four related to CCK-1, one to the CCK gene promoter, and one related to CCK-2. The distributions of allelic variants and association with gastric emptying in response to dexloxiglumide and placebo were assessed. RESULTS: Dexloxiglumide was associated with accelerated gastric emptying t(1/2) (p= 0.004), and slower ascending colon emptying t(1/2) (p < 0.01), with no significant effect on overall CT or satisfactory relief of IBS. There was an association between CCK 779T > C polymorphism and slower rate of gastric emptying (p= 0.04). CONCLUSIONS: Dexloxiglumide accelerates gastric emptying and delays proximal but not overall CT in patients with C-IBS. Dexloxiglumide does not accelerate transit in C-IBS. The role of CCK-1 gene polymorphisms in delaying gastric emptying and in determining response to therapy deserves further study.

Adult↗
PubMed2004

Treating irritable bowel syndrome: overview, perspective and future therapies.

This article summarizes the ongoing challenges in irritable bowel syndrome and the exciting opportunities for development of novel therapies for this common, enigmatic condition. The challenges include insufficient understanding of mechanisms, lack of specificity of symptoms, differentiation from other conditions, and lack of availability of noninvasive tests to identify dysfunctions. However, significant opportunities are reflected by the advances in clinical trial design and, particularly, clinically relevant end points for such trials, and the increasing understanding of basic neuroenteric science. The latter has delivered two new medications to the practice (alosetron and tegaserod), and other candidate therapies (other serotonergic, tachykininergic, opioid, cannabinoid modulators) are being carefully appraised as potential drugs for the future.

Analgesics, Opioid↗
PubMed2004

Effect of renzapride on transit in constipation-predominant irritable bowel syndrome.

BACKGROUND & AIMS: The aim of this study was to evaluate the dose-ranging pharmacodynamic effects of renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome (C-IBS). METHODS: Forty-eight patients (46 women) with C-IBS underwent recording of baseline symptoms for 1 week. Twelve patients per group were randomized (double-blind, parallel design) to 11-14 days of renzapride (1, 2, or 4 mg) or placebo, once daily. Daily bowel habits and weekly satisfactory relief of IBS symptoms were recorded. At the end of treatment, gastric emptying (GE), small bowel transit (SBT), and colon transit (CT) were measured by scintigraphy. The relationship between CT and bowel function was evaluated. RESULTS: A statistically significant linear dose response to renzapride was detected for CT (GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P = 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0 hours, respectively. Improved bowel function scores (stool form and ease of passage, but not frequency) were significantly (P < 0.05) associated with accelerated CT. Pharmacokinetic analysis showed linear kinetics of renzapride with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief were not significantly altered by renzapride, although a type II error cannot be excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG) effects were observed. CONCLUSIONS: Renzapride causes clinically significant dose-related acceleration of CT, particularly ascending colonic emptying; this acceleration of transit is associated with improvement of bowel function in female C-IBS patients.

Adult↗
PubMed2004

GIH clinical research 2003-2004: the year in review.

This article summarizes the clinical research advances in gastroenterology and hepatology that were reviewed during the Plenary Session of the American Gastroenterological Association's Annual Meeting in May 2004 in New Orleans, Louisiana. The clinical research advances included the efficacy of infliximab in the treatment of fistulizing Crohn's disease, survival after isolated intestinal transplantation, the role of endoscopic treatment of bleeding peptic ulcers and Barrett's esophagus, the recurrence of cancer after laparoscopic colectomy, the impact of microsatellite instability on the response to adjuvant chemotherapy with 5-fluorouracil (5-FU), the epidemiology of obesity and its response to low-carbohydrate diets, the potential role of gastrointestinal factors in the development of obesity, and, the newly appreciated condition, autoimmune pancreatitis with associated cholangitis. Clinical research advances will impact the management of digestive diseases.

Biomedical Research↗
PubMed2004

A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia.

BACKGROUND & AIMS: Dyspepsia is common in clinical practice and in the community. The relationship of the symptoms to meals and the pathophysiology in community dyspeptic patients is unclear. The purpose of this study was to measure symptoms, demographic features, and gastric motor and sensory functions associated with dyspepsia in the community. METHODS: A Modified Bowel Disease Questionnaire was mailed to a random sample of Olmsted County, MN, residents. Dyspeptic patients and healthy controls identified among community respondents completed further questionnaires, Helicobacter pylori serology, gastric emptying by scintigraphy, gastric accommodation by 99mTc-single-photon emission computed tomography imaging, and postprandial symptoms and satiation by a nutrient drink test. RESULTS: A total of 34.1% of community respondents reported dyspepsia within the past year, frequent (at least 25% of the time in the past year) in 17.5%, and 18.4% reported meal-related dyspepsia. Dyspepsia was frequent and related to meals in 10.8% of respondents. Compared with nondyspeptic controls, community dyspepsia was associated with higher aggregate symptom scores and bloating after a fully satiating meal. Community dyspepsia also was associated with higher somatization scores (P = .001), reporting of other somatic symptoms (P = .07), and general severity score on the symptom checklist 90 (P = .01), but not with disordered motor or sensory function. Gastric volumes, gastric emptying, and maximum tolerated volumes were not significantly different between community controls and dyspeptic patients. CONCLUSIONS: Meal-related dyspepsia is an important component of dyspepsia in the community. Community dyspeptic patients have higher symptom scores after a fully satiating meal, consistent with gastric hypersensitivity. This is associated with higher somatization scores rather than disorders of gastric emptying or volumes.

Adult↗
PubMed2004

Independent influences of body mass and gastric volumes on satiation in humans.

BACKGROUND & AIMS: We assessed the association of body mass and gastric volumes (fasting and postprandial) with satiation and postprandial symptoms. METHODS: Healthy obese and nonobese subjects underwent measurement of caloric intake at maximum satiation; postprandial symptoms were measured with visual analogue scales 30 minutes after a meal. Gastric volume during fasting and after 300 mL of Ensure was measured with technetium-99m single-photon emission computed tomography imaging. We used multiple regression analysis to assess the associations among variables. RESULTS: Among 134 participants (81 women and 53 men), the median age was 26 years (range, 12-58 years), and the median body mass index was 24 kg/m(2) (range, 17-48 kg/m(2)). Increased body mass index, but not height, was associated with delayed satiation (P < 0.003, adjusted for sex). Overweight and obese subjects ingested, on average, 225 +/- 57 more kilocalories (945 +/- 239 kJ) at maximum satiation compared with normal weight individuals. Increased fasting gastric volume was not associated with body mass index or height, but it was significantly associated with delayed satiation (P = 0.001, adjusted for body mass index and sex). An increase of 50 mL in the fasting gastric volume was associated with 114 +/- 32 kcal (479 +/- 134 kJ) more ingested at maximum satiation. Increased body mass index was associated with lower fullness scores 30 minutes after a meal (P = 0.0012, adjusted for sex and volume of Ensure ingested). In contrast, scores of postprandial bloating and pain were higher with increased body mass index (both P < 0.05, adjusted for sex and volume of Ensure ingested). CONCLUSIONS: Greater body mass index and fasting gastric volume are associated with reduced satiation. Increased body mass index or height was not associated with greater gastric volumes.

Adolescent↗
PubMed2004

Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia.

BACKGROUND & AIMS: The aim was to assess relative contributions of gastric volumes (GV) and gastric emptying (GE) to meal size and postprandial symptoms in patients with functional dyspepsia. METHODS: Patients with chronic upper gastrointestinal symptoms were prospectively evaluated. GV during fasting and after 300 mL Ensure was measured with 99m Tc-single-photon emission computed tomography imaging and solid GE (99m Tc-egg) by scintigraphy. Maximum tolerated volume (MTV) and symptoms were measured after Ensure challenge. RESULTS: Of 57 adult patients evaluated, 39 (23 women, 16 men) met Rome II criteria for functional dyspepsia and had no other diagnosis to account for dyspepsia. The most frequent symptoms were abdominal pain (90%), pain predominantly after meals (76%), nausea (85%), and early fullness after meals (79%). Relative to established laboratory normal values, MTV was abnormal in 82%, aggregate symptom score >209 in 72%, GE (at 1 hour) accelerated in 41%, GE (at 4 hours) delayed in 41%, and postmeal GV reduced in 52%. Lower body mass was associated with lower MTV and higher postchallenge symptoms. Lower fasting (not postprandial) GV and faster GE were independent predictors of lower MTV, explaining 18% of the variance after adjusting for body weight (32% of variance). GE was an independent predictor of postchallenge symptoms (10% of variance) after adjusting for volume ingested (10%), age (20%), and weight (10%). CONCLUSIONS: In adults with functional dyspepsia seen in a tertiary referral practice, decreased meal size and postmeal symptoms are associated with low fasting GV and faster GE. These data provide physiologic targets for ameliorating symptoms of functional dyspepsia.

Adolescent↗
PubMed2004

The gastrointestinal tract and glucose tolerance.

PURPOSE OF REVIEW: The development of incretin hormones and incretin analogues for the therapy of diabetes highlights the importance of the gastrointestinal tract in the maintenance of glucose tolerance. RECENT FINDINGS: The review focuses on recent information on the role of incretins and their breakdown products on insulin secretion, gastric emptying, and satiety. The importance of gastric emptying and its absorptive potential as well as of dietary composition on gastric emptying and glucose tolerance is highlighted. The concept of a portal glucose sensor in humans has been the subject of some controversy but has been recently revisited. SUMMARY: The gastrointestinal tract plays an important part in glucose tolerance. In this review we have examined how factors altering gastric emptying, insulin secretion in response to meal ingestion, and gastric emptying contribute to the maintenance and deterioration of glucose tolerance.

Blood Glucose↗
PubMed2004

The role of pelvic floor dysfunction and slow colonic transit in adolescents with refractory constipation.

OBJECTIVE: Although pelvic floor dysfunction (PFD) is recognized as a cause of refractory constipation in adults, this diagnosis is not frequently considered in children and adolescents with refractory constipation. The purpose of this study was to examine the symptoms and colonic transit in adolescents with constipation evaluated for a disorder in pelvic floor function. METHODS: Adolescents with refractory constipation who had undergone anorectal manometry (ARM) and balloon expulsion test (BET) were identified by retrospective review of records. Initial symptoms and the clinician's assessment were used to categorize patients by pediatric Rome II criteria, that is, functional constipation (FC), constipation-predominant irritable bowel syndrome (C-IBS) or functional fecal retention (FFR). Results of scintigraphic colonic transit studies were evaluated. A chi2 test was used to assess the association between individual clinical symptoms and Rome II criteria. RESULTS: Sixty-seven adolescents underwent evaluation of pelvic floor function by tests for PFD: BET was abnormal in 42%. There was no underlying disease or alternative diagnosis to account for the constipation in these patients. Among the 41 patients who also underwent scintigraphic colonic transit, 30% had slow transit constipation and 12% had both slow colonic transit and abnormal BET. Patients classified as C-IBS were more likely to report weight loss (p = 0.03), bloating (p = 0.04), and incomplete rectal evacuation (p = 0.03). CONCLUSION: Abnormal pelvic floor function and delayed colonic transit are demonstrable as single or combined problems in adolescents with refractory constipation.

Adolescent↗
PubMed2004

Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study.

OBJECTIVES: Perception of sensations arising from the gastrointestinal tract may be diminished in obese subjects and thus facilitate overeating. Alternatively, excess food intake may cause gastrointestinal (GI) symptoms in obese patients. We evaluated the relationship between body mass index (BMI) and specific GI symptoms in the community. METHODS: Residents of Olmsted County, MN were selected at random to receive by mail one of two validated questionnaires. The association of reported GI symptoms with BMI (kg/m(2)) was assessed using a logistic regression analysis adjusting for age, gender, psychosomatic symptom score, and alcohol and tobacco use. RESULTS: Response rate was 74% (1,963 of 2,660). The prevalence of obesity (BMI > or = 30 kg/m(2)) was 23%. There was a positive relationship between BMI and frequent vomiting (p= 0.02), upper abdominal pain (p= 0.03), bloating (p= 0.002), and diarrhea (p= 0.01). The prevalence of frequent lower abdominal pain, nausea, and constipation was increased among obese (BMI > or = 30 kg/m(2)) compared to normal weight participants, however, no significant association was found between BMI and these symptoms. CONCLUSIONS: In the community, increasing BMI is associated with increased upper GI symptoms, bloating, and diarrhea. Clarification of the cause-and-effect relationships and the mechanisms of these associations require further investigation.

Adult↗
PubMed2004

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers.

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.

Adult↗