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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 127 records · Page 7Linked to original sources
PubMed1999

Development of a test to measure gastric accommodation in humans.

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of (99m)Tc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 +/- 11 (SE) ml and mean postprandial volume was 690 +/- 32 ml (P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Adolescent↗
PubMed1999

Motor function in irritable bowel syndrome.

The evidence supporting a role of abnormal motor function in irritable bowel syndrome (IBS) is reviewed. Symptoms commonly present in IBS patients, such as vomiting, diarrhea, constipation or incomplete rectal evacuation, indicate that a motor disorder is implicit as either a primary or secondary disturbance. Physiological studies implicate a disturbance of transit through the small bowel and proximal colon, and abnormal motor responses of the rectum to distention in IBS patients. Intestinal contractions (physiological or 'abnormal') are associated with the sensation of pain, suggesting that these contractions are interactions between abnormal motor and sensory functions in IBS. Therapies aimed at correcting abnormal transit or antispasmodics are the main pharmacological approaches to the relief of IBS, and, although the latter are not always effective in the long term response to treatment, they support the role of dysmotility in IBS. Most novel therapies under trial probably modulate both sensory and motor functions, and are discussed briefly. In summary, the weight of clinical, physiological and pharmacological evidence supports a role of abnormal motility in IBS.

Cholinergic Antagonists↗
PubMed1999

Review article: clinical evidence to support current therapies of irritable bowel syndrome.

This review summarizes the clinical evidence to support current therapies in irritable bowel syndrome (IBS). Fibre is indicated at a dose of at least 12 g per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhoea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone. In general, smooth muscle relaxants are best used sparingly, on an 'as needed' basis, as their overall efficacy is unclear. Psychotropic agents are important in relieving depression and of proven benefit for pain and diarrhoea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors (SSRIs) are awaited. Psychological treatments including hypnotherapy are less widely available, but may play an important role in relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. New therapies are needed to more effectively relieve this syndrome, not just symptoms.

Antidiarrheals↗
PubMed1999

Clinical subgroups of chronic constipation: exploring the potential of polyethylene glycol.

This brief review has explored the rationale for therapy of polyethylene glycol electrolyte solutions in subgroups of patients with chronic constipation. There appears to be a good rationale for their use in patients with colonic inertia or those with extrinsic denervation. However, first-line therapies such as dietary fibre and bulking agents should be tried initially prior to resorting to osmotic agents such as polyethylene glycol electrolyte solutions.

Cathartics↗
PubMed1998

Measurement of gastrointestinal motility in the GI laboratory.

Current tests of gastric and small intestinal motor function provide relevant physiological information, but their clinical utility is controversial. This article reviews the current procedures, indications, significance, pitfalls, and guidelines for gastrointestinal motility measurements by scintigraphy, gastroduodenojejunal manometry, and surface electrogastrography in humans. Methods included review of literature and discussions in closed and open fora among investigators, including presentations for peer review at focused (Iowa City American Motility Society Symposium, December 1995) and national meetings (American Gastroenterological Association, May 1996, and American Motility Society, September 1996). The current tests are generally complementary; scintigraphy is typically the first test in the evaluation of gastric motor function and often confirms the clinical suspicion of dysmotility. Manometry identifies patterns suggestive of myopathy, neuropathy, or obstruction but may be most helpful when it shows entirely normal findings, because manometry helps in part to exclude dysmotility as a cause of symptoms. Electrogastrography may identify dysrhythmias or failure of signal power to increase postprandially; rhythm abnormalities may be independent of impaired emptying among dyspeptic patients. The best validated and clinically most significant results pertain to transit tests; manometry may contribute importantly to the diagnostic process; and the significance of electrogastrography remains to be fully elucidated.

Digestive System↗
PubMed1998

Effects of glucagon on postprandial carbohydrate metabolism in nondiabetic humans.

The present experiments sought to determine whether glucagon concentrations mimicking those observed in people with diabetes mellitus alter postprandial carbohydrate metabolism in nondiabetic humans. We measured the gastric emptying of solids and liquids, the systemic rate of appearance of ingested glucose, and endogenous glucose production either when postprandial suppression of glucagon was prevented by infusing glucagon at a rate of 0.65 ng/kg/min, when postprandial glucagon concentrations were elevated by infusing glucagon at a rate of 3.0 ng/kg/min, or when postprandial suppression of glucagon was permitted by infusion of saline. Despite marked differences in glucagon concentrations, postprandial glucose and insulin concentrations did not differ on any occasion. Although gastric emptying of liquids and solids was comparable on all three occasions, the high-dose, but not the low-dose, glucagon infusion caused a slight delay in the systemic appearance of ingested glucose and a significant decrease (P < .01) in postprandial D-xylose concentrations, suggesting a delay in carbohydrate absorption. However, this was offset by an increase (P < .05) in endogenous glucose production, resulting in no difference in postprandial glucose appearance. We conclude that in the absence of insulin deficiency, neither a lack of suppression of glucagon nor an elevation of glucagon to levels encountered in uncontrolled diabetes mellitus cause postprandial hyperglycemia in nondiabetic humans.

Blood Glucose↗
PubMed1998

Influence of H. pylori infection on gastric motor and sensory function in asymptomatic volunteers.

The effect of H. pylori infection on gastric motility and sensation is unclear. Our hypothesis is that H. pylori infection increases gastric sensation and reduces gastric accommodation and emptying. In eight H. pylori-positive and eight H. pylori-negative asymptomatic subjects, infection was proven by antral histology or culture. We evaluated: (1) gastric emptying of solids, (2) proximal gastric compliance, (3) fasting and postprandial proximal gastric tone and phasic contractions, (4) gastric sensation during balloon inflations or ingestion of cold water, and (5) abdominal vagal function. H. pylori infection was associated with lower gastric accommodation (median 75% postprandial increase in barostat balloon volume compared to fasting) when compared to the accommodation in uninfected volunteers (median 211% change from fasting). One H. pylori-positive subject had an abnormal abdominal vagal function test and her gastric accommodation response was reduced. Other motor and sensory functions in the two groups were similar. In asymptomatic volunteers, H. pylori infection and gastritis result in reduced accommodation (diastolic dysfunction) but no change in overall sensation or motor functions of the stomach.

Adult↗
PubMed1998

Pilot study of pathophysiology of constipation among community diabetics.

We aimed to compare gastrointestinal transit and defecatory function in a random sample of people with or without diabetes mellitus in a US community who reported constipation or laxative use. In this pilot study we measured: gastric, small bowel, and colonic transit by scintigraphy; vector manometry of anal sphincters at rest and during squeeze; defecatory dynamics by balloon expulsion test; and scintigraphic measurement of anorectal angle at rest and during defecation. Autonomic function tests were performed in diabetics. Diabetics with constipation had a higher prevalence of abnormal evacuation or prolonged colonic transit during the first 24 hr than controls (P = 0.07): three had prolonged 24-hr colonic transit, and three abnormal evacuation. Among constipated controls, only one had anismus. Overall, diabetics had slower colonic transit during the first 24 hr than nondiabetics (P < 0.05). Community diabetics who experience constipation or use laxatives have a greater prevalence of delayed 24-hr colonic transit or evacuatory dysfunction than community controls.

Adult↗
PubMed1998

Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders.

AIM: To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea. SOURCE: Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these. RESULTS: In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT3 antagonists. CONCLUSION: Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.

Colon↗
PubMed1998

Activated charcoal as a potential radioactive marker for gastrointestinal studies.

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.

Charcoal↗
PubMed1998

Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders.

OBJECTIVE: The aim of this study was to characterize the clinical and motility findings in 62 patients with systemic sclerosis or related disorders referred for evaluation of upper gastrointestinal (GI) symptoms. METHODS: Methods included retrospective clinical record review and quantitation of esophageal, LES antral, and duodenal motility (3 h fasting, 2 h fed) were compared with results of 10 symptomatic patients with normal gastric emptying. RESULTS: A total of 46 patients had systemic sclerosis, eight mixed connective tissue disease, and eight polymyositis-systemic sclerosis overlap; systemic manifestations were almost invariably present. GI symptoms were: heartburn (77%), nausea/vomiting (58%), dysphagia (61%), diarrhea (53%), constipation (31%), and fecal incontinence (13%). Anatomical studies showed esophageal erosions or GERD (53%), aperistalsis (34%), stricture (29%), and Barrett's metaplasia (16%); megaduodenum, small bowel dilation, or diverticulae (42%); and pneumatosis intestinalis (8%). A total of 36 patients underwent esophageal and 26 esophagogastrointestinal manometry. Postprandial antral motility index was abnormal in 22 of 26; amplitudes and frequency in the antrum (34 +/- 3 mm Hg and 0.6 +/- 0.1/min, respectively) and duodenum (7.3 +/- 0.9 mm Hg and 1.8 +/- 0.5/min) were significantly lower than controls (p < 0.05). CONCLUSION: In patients with GI symptoms associated with systemic sclerosis and related disorders, the amplitude and frequency of intestinal contractions are typically <10 mm Hg and <2/min. Antral amplitude is low (<40 mm Hg) when antral hypomotility is observed.

Adolescent↗
PubMed1998

Reproducibility and simplification of 13C-octanoic acid breath test for gastric emptying of solids.

OBJECTIVE: The accuracy of the 13C-octanoic acid breath test is enhanced by breath sampling over 6 h rather than 4 h, but this increases the cost of the test. Our aim was to validate a less costly but accurate sequence of breath sampling for measuring gastric emptying of solids. METHODS: We performed the 13C-octanoic acid breath test and tested its reproducibility relative to simultaneous scintigraphy in 30 healthy volunteers. RESULTS: There was a significant but weak correlation between t1/2 measured by the two tests (rs = 0.54, p < 0.005), but not between the duration of the lag phase. The differences in the t1/2 measurements between the tests were different between subjects but were highly reproducible within subjects. Within- and between-subject variations of measurements of gastric emptying with the 13C-octanoic acid breath test were not significantly different from the variations observed with scintigraphy. A subset of 11 breath samples collected over 6 h (24 samples) predicted (r2 > 0.95) the variables characterizing the cumulative appearance of 13CO2 in breath; these samples were at 35, 50, 95, 110, 140, 155, 215, 245, 260, 290, and 335 min. The accuracy of this subset of sampling times was confirmed in a separate set of breath test samples over 6 h from the same 30 subjects. CONCLUSIONS: The 13C-octanoic acid breath test for gastric emptying of solids is as reproducible as scintigraphy. A subset of 11 sampling times provides sufficient information to characterize the whole breath-test curve, but the sampling period should be extended to 6 h after dosing.

Adolescent↗
PubMed1998

The effect of flufenamic acid on gastrointestinal myoelectrical activity and transit time in dogs.

BACKGROUND: Flufenamic acid, a fenamate, has been shown to alter markedly the membrane potential of small intestinal smooth muscle and increase intracellular calcium in single cells. AIMS: To determine the effects of flufenamic acid on myoelectrical motor activity and gastrointestinal transit in the intact animal. METHODS: Myoelectrical motor activity was recorded via seromuscular platinum electrodes sutured at regular intervals in the stomach and throughout the small intestine. Fasted and fed gastrointestinal transit was assessed using technetium-99m (99mTc) as the radioactive marker linked to 1 mm amberlite pellets or added to the meal. RESULTS: Flufenamic acid (600 mg, intravenously) induced intense spike activity in the small intestine. The mean duration of irregular spike activity was 250 (7) minutes. Spike activity was more pronounced in the lower small intestine. Flufenamic acid also accelerated initial gastric emptying and markedly shortened transit time in the small intestine. In the fasted state the 50% transit time in the small intestine was 54 (8) minutes with infusion of flufenamic acid compared with 105 (10) minutes in the control group; in the fed state 99mTc first reached the colon at 220 (10) minutes compared with 270 (12) minutes in the control group. CONCLUSIONS: Flufenamic acid had marked effects on both myoelectrical motor complex activity and small intestinal transit in the dog. The observed effects suggest that flufenamic acid may be of potential use as a prokinetic agent.

Animals↗
PubMed1998

Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea.

BACKGROUND: Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoid patients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. RESULTS: There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. CONCLUSIONS: Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.

Adult↗
PubMed1998

Rectal tone, distensibility, and perception: reproducibility and response to different distensions.

Increasing interest is focusing on the role of intestinal tone, distensibility, and mechanosensation in the genesis of abdominal symptoms. Experimental approaches usually feature balloon distension of the bowel with measurements of perception, tone, and compliance and/or elastance; however, the methodologies are standardized incompletely. We examined the reproducibility of repeated assessments of sensory perception, basal tone, and compliance and/or elastance of the rectum during distension. We also evaluated the response to inflations that varied in regard to control of pressure or volume, pattern of distension, and rate of inflation. Five healthy volunteers were studied under two separate protocols. The first featured a series of experiments on each of 5 days; the other consisted of 2 separate days of study. Repeated distensions evoked reproducible responses of sensation and compliance and/or elastance on a single day, providing a conditioning distension preceded them. Day-to-day variability was also sufficiently small to allow valid comparisons to be made on different days in healthy persons. The configuration of the distension profile (phasic, staircase, or ramp) and the rate of inflation (from 1 to 40 ml/s) had little effect on distensibility or perception. Perceptions were sometimes transient and sometimes constant, but no relationship was found between these temporal features and the magnitude of the stimulus. These observations help provide a basis as to how the responses to rectal distension can be best studied.

Adult↗
PubMed1998

Gastric mechanosensory and lower esophageal sphincter function in rumination syndrome.

Our hypothesis was that rumination syndrome is associated with gastric sensory and motor dysfunction. We studied gastric and somatic sensitivity, reflex relaxation of the lower esophageal sphincter (LES), and gastric compliance and accommodation postprandially and postglucagon. A barostatically controlled gastric bag and esophageal manometry were used to compare gastric sensorimotor functions and LES relaxation to gastric distension in 12 patients with rumination syndrome and 12 controls. During bag distensions, patients had greater nausea, bloating, and aggregate score, but not pain, compared with controls (P < 0.05). At 4 and 8 mmHg gastric distension, LES tone reduction was greater in patients than in controls (P < 0.05). Gastric compliance, accommodation to a standard meal, and response to glucagon were not different in patients and controls; however, 6 of 12 patients had no gastric accommodation; the latter patients had significantly greater pain perception during distension (P < 0.05) but normal somatic sensitivity compared with healthy controls. Rumination syndrome is characterized by higher gastric sensitivity and LES relaxation during gastric distension. A subgroup of patients also had absent postprandial accommodation.

Adolescent↗