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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 19 recordsLinked to original sources
PubMed1999

Modulation of gastric sensory and motor functions by nitrergic and alpha2-adrenergic agents in humans.

BACKGROUND & AIMS: Disturbed gastric accommodation and sensation contribute to postprandial symptoms in dyspepsia, but the controlling mechanisms are unclear. Nitrergic and alpha2-adrenergic modulation of gastric sensory and motor function were assessed in this study. METHODS: Using a factorial design, we assessed drug effects on gastric sensation during isobaric distentions and fasting and postprandial gastric motor function in 32 healthy volunteers. Each participant received one treatment: placebo; 0.3 or 0.5 microgram. kg-1. min-1 intravenous nitroglycerin; 0.0125, 0.025, or 0.1 mg clonidine orally; or combined nitroglycerin plus clonidine. In 16 other healthy subjects, the effects of clonidine and placebo on gastric emptying of solids were evaluated using the 13C-octanoic acid breath test. RESULTS: Clonidine and nitroglycerin increased gastric compliance, but normal postprandial accommodation was still observed despite the induced relaxation. Clonidine but not nitroglycerin reduced aggregate and pain perception averaged over four distention levels. There were no significant drug interactions. No dose effect of clonidine was observed on gastric emptying. CONCLUSIONS: Clonidine relaxes the stomach and reduces gastric sensation without inhibiting accommodation or emptying. Nitroglycerin relaxes the stomach without altering perception. Studies of the effects of clonidine on these gastric functions and symptoms in disease are warranted.

Administration, Oral↗
PubMed1999

Descending perineum syndrome: audit of clinical and laboratory features and outcome of pelvic floor retraining.

OBJECTIVE: Our aim was to retrospectively analyze the Mayo Clinic experience of descending perineum syndrome from 1987-1997. METHODS: Clinical records were abstracted for demographic features, risk factors, results of anorectal and defecation tests, and a mailed questionnaire evaluated outcome and current symptoms. RESULTS: All results are mean +/- SD. Clinically, 39 patients (38 women, one man), mean age 53+/-14 yr, presented with constipation (97%), incomplete rectal evacuation (92%), excessive straining (97%), digital rectal evacuation (38%), and fecal incontinence (15%). Laboratory tests showed anal sphincter resting pressure was 54+/-26 mm Hg, and squeeze pressure was 96+/-35 mm Hg; expulsion from the rectum of a 50-ml balloon required > 200 g added weight in 27%; perineal descent was 4.4+/-1 cm (normal < 4 cm) by scintigraphy. Scintigraphic evacuation, rectoanal angle change during defecation, and perineal descent were abnormal in 23%, 57%, and 78% of the patients, respectively. Associated features included female gender (96%), multiparity with vaginal delivery (55%), hysterectomy or cystocele/rectocele repair (74%). On follow-up, 64% responded; 17 of these 25 responders underwent pelvic floor retraining. At 2-yr median follow-up (range, 1-6 yr), 12 still experienced constipation or excessive straining; their perineal descent was greater than in patients who responded to retraining (p = 0.005). CONCLUSIONS: Descending perineum syndrome is identifiable by clinical history and examination, and the most prevalent abnormality on testing is perineal descent > 4 cm; rectal balloon expulsion is an insensitive screening test for descending perineum syndrome. Pelvic floor retraining is a suboptimal treatment for this chronic disorder of rectal evacuation; the extent of perineal descent appears to be a useful predictor of response to retraining.

Anal Canal↗
PubMed1999

Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function.

BACKGROUND: The pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood. AIMS: To compare gastric motor and sensory functions in Helicobacter pylori positive or negative patients with non-ulcer dyspepsia. PATIENTS: Seventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls. METHODS: The following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI). RESULTS: Gastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated to H pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent among H pylori positive patients (4/5 H pylori positive versus 4/12 H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI. CONCLUSION: Impaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.

Adult↗
PubMed1999

Intestinal pseudo-obstruction.

Pseudo-obstruction syndromes are increasingly recognized in clinical practice. They result from impairment of intrinsic neuromuscular or extrinsic control of gut motility. Typically, pseudo-obstruction syndromes result in features suggestive of mechanical obstruction and bowel dilatation in the absence of any demonstrable obstruction or mucosal disease. The syndrome may affect any region of the gut. Less severe variants without bowel dilatation are diagnosed by measurement of gastrointestinal transit and pressure profiles. The aims of treatment are restoration of nutrition and hydration, symptom relief, normalization of intestinal propulsion with prokinetics, and suppression of bacterial overgrowth. Surgery plays a limited role, adjunctive to medical treatment, facilitating enteral nutrition and decompression by means of jejunostomy. Infrequently, resection of localized disease or intestinal transplantation are indicated. The roles of intestinal pacemakers (interstitial cells of Cajal) and genetic mutations in the etiology of pseudo-obstruction, as well as the cost-benefit ratio of transplantation for pseudo-obstruction, will be clarified in the future.

Dilatation, Pathologic↗
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↗