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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 55 records · Page 3Linked to original sources
PubMed2003

Effects of glucagon-like peptide-1 and feeding on gastric volumes in diabetes mellitus with cardio-vagal dysfunction.

Glucagon-like peptide-1 (GLP-1) increases gastric volume in humans possibly through the vagus nerve. Gastric volume response to feeding is preserved after vagal denervation in animals. We evaluated gastric volume responses to GLP-1 and placebo in seven diabetic patients with vagal neuropathy in a crossover study. We also compared gastric volume response to feeding in diabetes with that in healthy controls. We measured gastric volume using SPECT imaging. Data are median (interquartile range). In diabetic patients, GLP-1 did not increase gastric volume during fasting [5 mL (-3; 30)] relative to placebo [4 mL (-14; 50) P = 0.5], or postprandially [Delta postprandial minus fasting volume 469 mL (383; 563) with GLP-1 and 452 mL (400; 493) with placebo P = 0.3]. Change in gastric volume over fasting in diabetic patients on placebo was comparable to that of healthy controls [452 mL (400; 493)], P = 0.5. In contrast to effects in health, GLP-1 did not increase gastric volume in diabetics with vagal neuropathy, suggesting GLP-1's effects on stomach volume are vagally mediated. Normal gastric volume response to feeding in diabetics with vagal neuropathy suggests that other mechanisms compensate for vagal denervation.

Aged↗
PubMed2003

Effect of a somatostatin analogue on gastric motor and sensory functions in healthy humans.

BACKGROUND: Pharmacological approaches to alter satiation may have an impact on functional upper gastrointestinal disorders and potentially change food intake in obesity. AIM: Our aim was to compare the effects of two doses of octreotide and placebo on postprandial symptoms, gastric accommodation, and gastric emptying using validated non-invasive techniques. METHODS: In a randomised, parallel group, two dose, double blind, placebo controlled study, 39 healthy participants (13 per group) were randomised to 30 or 100 micro g octreotide or placebo, administered subcutaneously, 30 minutes before each study. Studies were performed on three separate days and included scintigraphic gastric emptying of solids and liquids, (99m)Tc SPECT imaging to measure fasting stomach volume and gastric accommodation following a 300 ml Ensure meal, and a standardised nutrient drink test to measure maximum tolerated volume and postprandial symptoms. RESULTS: Relative to placebo, both doses of octreotide delayed gastric emptying of solids (not liquids), increased fasting gastric volume, reduced the change in gastric volume post meal, and decreased the sensation of fullness after a satiating meal. CONCLUSION: The somatostatin analogue octreotide significantly alters human gastric functions, including inhibition of the normal reflex responses of gastric volume increase and emptying of the meal. These pharmacological effects suggest studies of the medication in disorders of satiation, including obesity and dyspepsia, are warranted.

Adaptation, Physiological↗
PubMed2002

Effects of 5-HT(3) antagonism on postprandial gastric volume and symptoms in humans.

BACKGROUND: Alosetron reduces symptoms of dyspepsia, but the physiological basis for the symptomatic benefit is unclear. AIM: To assess 5-HT3 antagonism on postprandial gastric volume and symptoms after ingestion of maximum tolerable volume of a liquid meal. METHODS: In 36 healthy volunteers, we assessed effects of placebo, 0.5 and 1 mg b.d. alosetron on fasting and postprandial gastric volumes (using single photon emission computed tomography) and symptoms based on 100 mm VAS, 30 min after maximum volume ingested. RESULTS: The 5-HT3 antagonist reduced postprandial symptoms (aggregate score: P < 0.05), nausea (P < 0.001), and tended to reduce bloating (P=0.08). Both 0.5 and 1 mg alosetron reduced nausea (P < 0.025); 1 mg alosetron reduced aggregate symptoms (P < 0.05) and bloating (P < 0.05). Effects on pain (P=0.19) and fullness (P=0.14) were not statistically significant. There were no significant effects of the 5-HT3 antagonist on volume of meal tolerated or on SPECT-measured fasting or postprandial gastric volumes. CONCLUSION: 5-HT3 antagonism reduces aggregate symptoms, nausea and bloating after a liquid meal without increase in gastric volumes, suggesting a role for 5-HT3 in afferent functions in healthy humans during the postprandial period.

Adult↗
PubMed2002

Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome.

This consensus document reviews the current status of the epidemiology, social impact, patient quality of life, pathophysiology, diagnosis and treatment of irritable bowel syndrome. Current evidence suggests that two major mechanisms may interact in irritable bowel syndrome: altered gastrointestinal motility and increased sensitivity of the intestine. However, other factors, such as psychosocial factors, intake of food and prior infection, may contribute to its development. Management of patients is based on a positive diagnosis of the symptom complex, careful history and physical examination to exclude 'red flags' as risk factors for organic disease, and, if indicated, investigations to exclude other disorders. Therapeutic choices include dietary fibre for constipation, opioid agents for diarrhoea and low-dose antidepressants or infrequent use of antispasmodics for pain, although the evidence basis for efficacy is limited or in some cases absent. Psychotherapy and hypnotherapy are the subject of ongoing study. Treatment should be tailored to patient needs and fears. Novel therapies are emerging, and drugs acting on serotonin receptors have proven efficacy and a scientific rationale and, if approved, should be useful in the overall management of patients with irritable bowel syndrome. Patient and physician education, early identification of psychosocial issues and better therapies are important strategies to reduce the suffering and societal cost of irritable bowel syndrome.

Adult↗
PubMed2002

Performance characteristics of scintigraphic transit measurements for studies of experimental therapies.

BACKGROUND: The intra- and inter-individual reproducibility of gastrointestinal and colonic transit tests require full characterization. AIMS: (i) To characterize the normal values and reproducibility effects of age and gender on the scintigraphic transit of solids in health. (ii) To compare scintigraphic and radio-opaque marker measurements of colonic transit. (iii) To estimate demonstrable effect sizes for different transit end-points based on observed variations. METHODS: A scintigraphic gastrointestinal and colonic transit study and the mean colonic transit time were measured using radio-opaque markers in 37 healthy volunteers; 21 subjects had a repeat scintigraphic test 3 weeks later. RESULTS: Gastric emptying at 4 h was highly reproducible (coefficient of variation, 4%) on repeat testing. The colonic measurement varied by more than 1 geometric centre unit in 37% of subjects at 24 h and in 26% of subjects at 48 h. There were no age- or gender-related differences in transit. Effect sizes demonstrable with 14 subjects per group were in the range previously shown to be clinically relevant: 25% change in gastric emptying at 4 h; 1.5 geometric centre unit change in colonic transit at 48 h. CONCLUSIONS: These data demonstrate the reproducibility and performance to be expected of transit measurements and are essential for designing studies in experimental therapeutics.

Adult↗
PubMed2002

Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus.

Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function.

Aged↗
PubMed2002

SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Single photon emission computed tomography.

BACKGROUND: Impaired gastric accommodation may lead to dyspeptic symptoms. A non-invasive method using single photon emission computed tomography (SPECT) has been developed to measure gastric volumes. AIMS AND METHODS: Our aims were: to assess the accuracy of SPECT with three dimensional image analysis to measure balloon volumes in vitro; to compare gastric barostat balloon volumes measured post-meal and post-distension with total gastric volumes measured simultaneously with SPECT; to present normal gastric volume data for healthy adults; and to compare SPECT data in health with symptomatic post-fundoplication patients. RESULTS: In vitro balloon volumes measured by SPECT were highly accurate (R(2)=0.99). When measured simultaneously by gastric barostat and SPECT, postprandial/fasting volume ratios (2.2 (0.12) (mean (SEM)) v 2.3 (0.15), respectively; p=0.6) and post-distension volume ratios (1.4 (0.1) v1.3 (0.1); p=0.2) were highly comparable. In females, postprandial gastric volumes (675 (14) v 744 (20) ml for males; p=0.004) and changes in gastric volumes (464 (14) ml v 521 (20) ml for males; p=0.01) measured by SPECT were significantly lower than in males. No effects of age or body mass index were noted. The postprandial/fasting gastric volume ratio by SPECT was lower in post-fundoplication patients (2.7 (0.2)) than in healthy controls (3.4 (0.1); p=0.003). CONCLUSIONS: SPECT provides a non-invasive estimate of the effect of a meal on total gastric volume that is comparable to changes in balloon volume observed with the gastric barostat. The SPECT technique is promising for investigation of gastric volumes in health and disease and the effects of pharmacological agents.

Adolescent↗
PubMed2002

Testing the sensitivity hypothesis in practice: tools and methods, assumptions and pitfalls.

Visceral hypersensitivity is widely regarded as the reason for the development of functional gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome. The principles and techniques involved in testing the hypothesis that visceral sensitivity is important are discussed, together with the controversies in the assumptions, methods, and interpretations of the data acquired to date.

Brain↗
PubMed2002

Serotonergic modulation of visceral sensation: lower gut.

The role of 5-HT agents in the modulation of lower gastrointestinal function is discussed. Selective serotonin reuptake inhibitors are of potential benefit in functional gastrointestinal diseases although formal evidence is lacking. Novel pharmacological approaches include 5-HT(3) antagonists and 5-HT(4) agonists. These pharmacological classes have shown beneficial effects on a global efficacy end point, and ameliorated more than one symptom of lower gut function in clinical trials. They offer promise for the development of novel therapies for the treatment and control of irritable bowel syndrome.

Colonic Diseases, Functional↗
PubMed2001

A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen in primary care practice. The symptoms of IBS, including abdominal pain, discomfort, and abnormal bowel function, may be modulated by activity of the serotonin type 3 receptor (5-HT(3)). The efficacy and tolerability of the 5-HT(3) receptor antagonist alosetron hydrochloride in nonconstipated female patients with IBS were evaluated in a double-blind, randomized, placebo-controlled trial. METHODS: Patients received either 1 mg of alosetron hydrochloride (n = 309) or placebo (n = 317) twice daily for 12 weeks, followed by a 4-week posttreatment period. Adequate relief of IBS pain and discomfort was the primary end point. Secondary end points included improvements in urgency, stool frequency, stool consistency, incomplete evacuation, and bloating. RESULTS: Seventy-one percent of patients were classified as having diarrhea-predominant IBS. Forty-three percent of alosetron-treated patients with diarrhea-predominant IBS reported adequate relief for all 3 months compared with 26% of placebo-treated patients (P<.001; percentage point difference = 17; 95% confidence interval, 8.0-25.4). Improvement with alosetron compared with placebo was observed by the end of the fourth week of treatment and persisted throughout the remainder of treatment. Alosetron significantly decreased urgency and stool frequency and caused firmer stools within 1 week of starting treatment. Effects were sustained throughout treatment and symptoms returned following treatment cessation. No significant improvement in the percentage of days with sense of incomplete evacuation or bloating was observed compared with placebo during the first month of treatment. Constipation was the most commonly reported adverse event. CONCLUSION: Alosetron hydrochloride, 1 mg twice daily for 12 weeks, is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS.

Administration, Oral↗
PubMed2001

Adynamic ileus in severe Guillain-Barré syndrome.

Adynamic ileus occurred in 17 of 114 patients (15%) with severe Guillain-Barré syndrome (GBS). Cardiovascular dysautonomia coincided with ileus in only five patients. In four patients, mechanical ventilation and immobilization could be implicated; and in eight patients, preexisting conditions such as prior abdominal surgery or incremental doses of opioids could be linked to ileus. Medical management was successful in all patients. Patients with GBS infrequently develop ileus as a manifestation of dysautonomia.

Aged↗
PubMed2001

Type I diabetes mellitus does not alter initial splanchnic glucose extraction or hepatic UDP-glucose flux during enteral glucose administration.

AIMS/HYPOTHESIS: Our aim was to determine whether an alteration in splanchnic glucose metabolism could contribute to postprandial hyperglycaemia in people with Type I (insulin-dependent) diabetes mellitus. METHODS: Splanchnic glucose extraction, hepatic glycogen synthesis and endogenous glucose production were compared in 8 Type I diabetic patients and in 11 control subjects. Endogenous hormone secretion was inhibited with somatostatin while insulin (approximately 550 pmol/l) and glucagon (approximately 130 ng/l) concentrations were matched with exogenous hormone infusions. Glucose containing [3-3H] glucose was infused into the duodenum at a rate of 20 micromol.kg(-1).min(-1). Plasma glucose concentrations were maintained at about 8.5 mmol/l in both groups by means of a separate variable intravenous glucose infusion. RESULTS: Initial splanchnic glucose uptake, calculated by subtracting the systemic rate of appearance of [3-3H] glucose from the rate of infusion of [3-3H] glucose into the duodenum, did not differ in the diabetic and non-diabetic patients (4.1 +/- 0.8 vs 3.0 +/- 1.0 micromol/kg/min). In addition, hepatic glycogen synthesis, measured using the acetaminophen glucuronide method did not differ (10.7 +/- 2.4 vs 10.1 +/- 2.7 micromol.kg(-1).min(-1)). On the other hand, suppression of endogenous glucose production, measured by an intravenous infusion of [6,6-2H2] glucose, was greater (p < 0.05) in the diabetic than in the non-diabetic subjects (1.7 +/- 1.6 vs 5.8 +/- 1.9 micromol.kg(-1).min(-1)). CONCLUSION/INTERPRETATION: When glucose, insulin and glucagon concentrations are matched in individuals with relatively good chronic glycaemic control, Type I diabetes does not alter initial splanchnic glucose uptake of enterally delivered glucose or hepatic glycogen synthesis. Alterations in splanchnic glucose metabolism are not likely to contribute to postprandial hyperglycaemia in people with well controlled Type I diabetes.

Blood Glucose↗
PubMed2001

Functional abdominal pain in the elderly.

Although aging per se affects function throughout the gut, particularly after age 70, the observed changes are relatively modest and often asymptomatic, perhaps because of the vast reserve of neuromuscular functional elements in the gut. The proximal esophagus, anus, and pelvic floor are possible exceptions to this generalization, and the combination of aging and factors such as minor strokes or obstetric damage often results in dysphagia, constipation, or fecal incontinence. Managing elderly patients with functional abdominal pain demands clinical acumen, tact, understanding, and patience. Further studies are required to elucidate the consequences of aging on gastrointestinal sensorimotor function at several levels of the digestive tract. With the expected explosion in the proportion of the population older than age 75, this field should become a high priority for clinical and research efforts. Also required will be a major campaign to educate patients and practitioners and multidisciplinary collaborations among primary care practitioners, gastroenterologists, psychologists, and physiatrists to provide optimal pain management in the elderly.

Abdominal Pain↗
PubMed2001

Is there a role for gastric accommodation and satiety in asymptomatic obese people?

OBJECTIVE: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non-obese asymptomatic subjects. RESEARCH METHODS AND PROCEDURES: In 13 obese (body mass index [BMI] > or = 30 kg/m(2); mean BMI, 37.0 +/- 4.9 kg/m(2)) and 19 non-obese control subjects (BMI < 30 kg/m(2); mean BMI, 26.2 +/- 2.9 kg/m(2)), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. RESULTS: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. DISCUSSION: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m(2)) did not show either increased postprandial gastric accommodation or reduced satiety. These data suggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.

Adult↗
PubMed2001

Review article: tegaserod.

Tegaserod (Zelmac), an aminoguanidine indole derivative of serotonin, is a selective partial agonist highly selective for 5-HT(4) receptor with an affinity constant in the nanomolar range. Tegaserod does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and distributes widely into tissues. Pharmacokinetics of oral tegaserod are linear in the 2--12 mg dose range. After oral administration tegaserod is metabolized mainly pre-systemically; when absorbed, intact tegaserod is excreted as N-glucuronides mainly via the bile. No clinically relevant drug--drug interactions were identified. Tegaserod has proven safe in toxicity studies. In pharmacodynamic studies, tegaserod stimulated the peristaltic reflex in vitro, increased canine intestinal and colonic motility and transit, reduced visceral afferent firing or sensation in response to distension in animals, and accelerated gastric, small bowel and colonic transit in healthy patients, and small bowel transit in patients with constipation-predominant irritable bowel syndrome. Three large phase III randomized, double-blinded, and placebo-controlled trials were performed predominantly in females (approximately 85%) with constipation-predominant irritable bowel syndrome. Overall, phase III results support efficacy as assessed by the subject's global assessment of relief with significant improvement in secondary endpoints such as abdominal pain, bowel frequency and consistency. Tegaserod was well-tolerated; the most frequent adverse event was transient diarrhoea.

Abdominal Pain↗
PubMed2001

Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects.

BACKGROUND: Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation. AIMS: (i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine's effects on colonic motor functions in patients and healthy subjects. METHODS: In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients. RESULTS: In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high-dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low-dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis. CONCLUSIONS: Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose-dependent effects on colonic motor activity in healthy subjects.

Adult↗