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Biomedical subjects

Michael Camilleri

Publications and source records attributed to Michael Camilleri.

At least 19 recordsLinked to original sources

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↗

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↗

Diagnosis and treatment of enteric neuromuscular diseases.

Gastrointestinal symptoms occur in a variety of neuromuscular diseases that may affect the neural access from the brain down to the peripheral nerve. This review addresses the clinical diagnosis of the gastrointestinal manifestations that occur in neuromuscular diseases. Prototypic examples are diabetic autonomic neuropathy, parkinsonism, and scleroderma. However, there is increasing recognition of the importance of disorders of the development of the enteric nervous system. For example, disturbances of the interstitial cells of Cajal (the pacemakers of the intestine) result in neuromuscular disorders and metabolic disorders of oxidative phosphorylation manifest as mitochondrial cytopathies that affect all muscle including the gut. The reviewer will discuss the use of specialized gastrointestinal measurements to detect dysfunction of different regions of the gut, including transit, volumetric measurements of the stomach, and manometry. The principles of management are treatment of the neurological disease itself, support of hydration and nutrition, symptom relief, suppression of bacterial overgrowth, correction of dysmotility with selective agonists and antagonists of neurotransmitter receptors and neurotrophic factors, and, rarely, surgery.

Enteric Nervous System↗

Pseudo-obstruction in the critically ill.

Intestinal pseudo-obstruction is defined as a clinical syndrome characterized by impairment of intestinal propulsion, which may resemble intestinal obstruction, in the absence of a mechanical cause. It may involve the small and/or the large bowel, and may present in acute, subacute or chronic forms. We have performed a systematic review of acute pseudo-obstruction, also referred to as Ogilvie's syndrome in the literature, and focused on proposed mechanisms, manifestations and management of post-surgery and critically ill patients who suffer from one or more underlying clinical conditions. 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 focuses on preventing intestinal perforation, which is associated with an average 21% mortality rate.

Critical Illness↗

Functional dyspepsia, upper gastrointestinal symptoms, and transit in children.

OBJECTIVE: To assess the prevalence of abnormal gastric emptying and small bowel transit in children with functional dyspepsia at a tertiary care center, and the relationship between abnormal gastric and small bowel transit and symptoms in pediatric patients with functional gastrointestinal disorders. STUDY DESIGN: Patients were selected by a cross-sectional chart review based on the following inclusion criteria: (1) completion of scintigraphic study of the gastric emptying of solids at 2 hours (GE2), 4 hours (GE4), and small bowel transit at 6 hours (SBT) using a standardized egg meal labeled with 99mTechnetium sulfur colloid, and (2) gastrointestinal (GI) complaints without mucosal or organic disease. Logistic regression analysis was used to assess the association between the presence of upper GI symptoms, and each parameter of gastric and small bowel transit. RESULTS: Children with upper GI symptoms (n=96) were identified. Among 57 children with functional dyspepsia, 40% had slow SBT. Fast GE at 4 hours, and slow SBT were independently associated with bloating. Children with fast SBT were less likely to report abdominal pain. CONCLUSION: Incorporating assessments of gastric and small bowel transit may be useful in the evaluation of pediatric patients with upper GI symptoms and functional dyspepsia.

Abdominal Pain↗

Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation.

OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Adolescent↗

Enteral infusion of glucose at rates approximating EGP enhances glucose disposal but does not cause hypoglycemia.

Portal infusion of glucose at rates approximating endogenous glucose production (EGP) causes paradoxical hypoglycemia in wild-type but not GLUT2 null mice, implying activation of a specific portal glucose sensor. To determine whether this occurs in humans, glucose containing [3-3H]glucose was infused intraduodenally at rates of 3.1 mg. kg-1. min-1 (n = 5), 1.55 mg. kg-1. min-1 (n = 9), or 0/0.1 mg. kg-1. min-1 (n = 9) for 7 h in healthy nondiabetic subjects. [6,6-2H2]glucose was infused intravenously to enable simultaneous measurement of EGP, glucose disappearance, and the rate of appearance of the intraduodenally infused glucose. Plasma glucose concentrations fell (P < 0.01) from 90 +/- 1 to 84 +/- 2 mg/dl during the 0/0.1 mg. kg-1. min-1 id infusions but increased (P < 0.001) to 104 +/- 5 and 107 +/- 3 mg/dl, respectively, during the 1.55 and 3.1 mg. kg-1. min-1 id infusions. In contrast, insulin increased (P < 0.05) during the 1.55 and 3.0 mg. kg-1. min-1 infusions, reaching a peak of 10 +/- 2 and 18 +/- 5 micro U/ml, respectively, by 2 h. Insulin concentrations then fell back to concentrations that no longer differed by study end (7 +/- 1 vs. 8 +/- 1 micro U/ml). This resulted in comparable suppression of EGP by study end (0.84 +/- 0.2 and 0.63 +/- 0.1 mg. kg-1. min-1). Glucose disappearance was higher (P < 0.01) during the final hour of the 3.1 than 1.55 mg. kg-1. min-1 id infusion (4.47 +/- 0.2 vs. 2.6 +/- 0.1 mg. kg-1. min-1), likely because of the slightly, but not significantly, higher glucose and insulin concentrations. We conclude that, in contrast to mice, selective portal glucose delivery at rates approximating EGP does not cause hypoglycemia in humans.

Adult↗

Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health.

This study evaluated the effects of serotonergic psychoactive agents on gastrointestinal functions in healthy human subjects. Participants received one of four regimens in a randomized, double-blind manner: buspirone, a 5-HT(1A) receptor agonist (10 mg twice daily); paroxetine, a selective serotonin reuptake inhibitor (20 mg daily); venlafaxine-XR, a selective serotonin and norepinephrine reuptake inhibitor (75 mg daily); or placebo for 11 days. Physiological testing performed on days 8-11 included scintigraphic assessment of gastrointestinal and colonic transit, the nutrient drink test, and assessment of the postprandial change in gastric volume. Fifty-one healthy adults (40 females, 11 males) participated in this study. No effects on gastric emptying or colonic transit were identified with any agent. Small bowel transit of a solid meal was accelerated by paroxetine. Buspirone decreased postprandial aggregate symptom and nausea scores. Venlafaxine-XR increased the postprandial change in gastric volume. Buspirone, paroxetine, and venlafaxine-XR affect upper gastrointestinal functions in healthy humans. These data support the need for clinical and physiological studies of these agents in functional gastrointestinal disorders.

Adult↗

Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans.

To compare the effects of the kappa-opioid agonist asimadoline and placebo on visceral sensation and gastrointestinal (GI) motor functions in humans, 91 healthy participants were randomized in a double-blind fashion to 0.15, 0.5, or 1.5 mg of asimadoline or placebo orally twice a day for 9 days. We assessed satiation (nutrient drink test), colonic compliance, tone, perception of colonic distension (barostat), and whole gut transit (scintigraphy). Treatment effect was assessed by analysis of covariance. Asimadoline increased nutrient drink intake (P = 0.03). Asimadoline decreased colonic tone during fasting (P = 0.03) without affecting postprandial colonic contraction, compliance, or transit. Gas scores in response to colonic distension were decreased with 0.5 mg of asimadoline at low levels (8 mmHg above operating pressure) of distension (P = 0.04) but not at higher levels of distension. Asimadoline at 1.5 mg increased gas scores at 16 mmHg of distension (P = 0.03) and pain scores at distensions of 8 and 16 mmHg (P = 0.003 and 0.03, respectively) but not at higher levels of distension. Further studies of this compound in diseases with altered satiation or visceral sensation are warranted.

Acetamides↗

Rumination syndrome in children and adolescents: diagnosis, treatment, and prognosis.

OBJECTIVES: To characterize the clinical features, results of diagnostic testing, and treatment outcomes for children and adolescents with rumination syndrome. METHODS: Review of the medical records for all 147 patients ages 5 to 20 diagnosed with rumination syndrome at our institution between 1975 and 2000. Data are presented as mean +/- the standard error of the mean. RESULTS: Sixty-eight percent were female. Age at diagnosis was 15.0 +/- 0.3 years. Symptom duration before diagnosis was 2.2 +/- 0.3 years, 73% missed school/work, and 46% had been hospitalized because of symptoms. Before diagnosis, 16 (11%) underwent surgery for evaluation or management of symptoms. Twenty-four (16%) had psychiatric disorders; 3.4% had anorexia or bulimia nervosa. All patients described postprandial regurgitation after almost every meal (2.7 +/- 0.1 meals per day). Weight loss was described by 42.2% (median: 7 kg). Additional symptoms included: abdominal pain, 38%; constipation, 21%; nausea, 17%; and diarrhea, 8%. Structural studies were normal. Gastric emptying of solids at 4 hours was delayed in 26 of 56 patients. Esophageal pH testing in 24 patients showed reflux/regurgitation in 54%. Gastroduodenal manometry in 65 patients showed characteristic rumination-waves in 40%. Outcome data (at median follow-up 10 months) were available for 54 patients. Symptoms resolved in 16 (30%) and improved in 30 (56%). CONCLUSIONS: Recognition of the clinical features of rumination syndrome in children and adolescents is essential; the diagnosis is often delayed and associated with morbidity. Extensive diagnostic testing is unnecessary. Early behavioral therapy is advocated, and patient outcomes are generally favorable.

Adolescent↗

Drugs targeting functional bowel disorders: lessons from drug trials.

Recent insights in the field of functional gastrointestinal disorders have opened the way for novel pharmacological treatments directed at the central nervous system or peripheral targets. Now, universally accepted guidelines on therapeutic trial design and in the conduct and reporting of results of large clinical trials in these functional disorders are required. Several lessons have been learned from recent clinical and pharmacological trials of novel agents in irritable bowel syndrome and diabetic dyspepsia. Approaches that carefully characterize the pharmacokinetics, mechanism of action and pharmacodynamics of a drug, and that select subgroups of patients after a thorough understanding of the drug's effects, should facilitate and enhance the likelihood of accurate assessment of potential therapies.

Clinical Trials as Topic↗

A nutrient drink test to assess maximum tolerated volume and postprandial symptoms: effects of gender, body mass index and age in health.

To assess the effects of age, gender and body mass index on the maximum tolerated volume of a nutrient drink and postprandial symptoms in health. Healthy adolescents (15 M, 15 F, aged 13-17 years) and adults (15 M, 25 F, aged 19-51 years) ingested Ensure (1 kcal mL-1) at a rate of 30 mL min-1. The maximum tolerated volume was recorded. Thirty minutes later, bloating, fullness, nausea and pain were rated using visual analogue scales. The Mann-Whitney test was used for comparisons between groups using body mass index and maximum tolerated volume as covariates. Age-related differences in maximum tolerated volume were noted between adolescents and adults, and were observed in both genders. Adults had higher scores for bloating and pain, and lower scores for fullness. Gender-related differences in maximum tolerated volume were noted in the group as a whole, and separately for adolescents and adults. Females had higher scores for nausea and pain. Gender and age-related differences in the maximum tolerated volume of a nutrient drink and postprandial symptoms should be considered in future studies of upper gastrointestinal symptoms in disease. Body mass index does not appear to influence maximum tolerated volume beyond its association with age and gender.

Adolescent↗

Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome.

BACKGROUND & AIMS: A serotonin (5-HT)(3) receptor antagonist relieves symptoms in women with diarrhea-predominant irritable bowel syndrome (D-IBS). 5-HT undergoes reuptake by a transporter protein (SERT). Polymorphisms in the promoter for synthesis of SERT (SERT-P) influence response to serotonergic medications in depression. Our hypothesis is that polymorphisms of the promoter region for the SERT influence colonic transit in response to treatment with alosetron in D-IBS. METHODS: Thirty patients (15 men, 15 women) with D-IBS received 1 mg twice a day alosetron for 6 weeks; colonic transit was measured by scintigraphy at baseline and at the end of treatment. Twenty-three patients consented to provide blood DNA samples. Long, short, and heterozygous SERT polymorphisms were identified by polymerase chain reaction-based restriction fragment length polymorphisms and confirmed by direct sequencing. We sought pharmacogenomic association of long, short, and heterozygote polymorphisms with a change in colonic transit and with an a priori-defined, clinically meaningful change in transit at 24 hours (>1.1 colonic regions). RESULTS: SERT polymorphisms tended to be associated with colonic transit response (P = 0.075); there was a greater response in those with long homozygous than heterozygous polymorphisms (P = 0.039). Slowing of transit by >1.1 colonic region was observed in 9 women and 3 men and was more frequent in long homozygous than heterozygous patients (P = 0.024). Age, gender, and duration of IBS were not significantly different in the 3 groups. CONCLUSIONS: Genetic polymorphisms at the SERT promoter influence response to a 5-HT(3) antagonist in D-IBS and may influence benefit-risk ratio with this class of compounds.

Adult↗