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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 91 records · Page 5Linked to original sources
PubMed2000

Functional bowel disease: roles of sensation and motility.

Functional bowel disorders are collections of symptoms attributable to the mid or lower gastrointestinal tract. The two most common disorders, irritable bowel syndrome and functional dyspepsia, have common etiopathogenetic features, notably psychosocial disturbances, dysmotility and heightened sensitivity. The control mechanisms, pathophysiology, investigation and potential pharmacotherapies of these disorders are reviewed. Serotonergic and adrenergic agents are among the novel approaches that may have a significant impact on these disorders.

Colonic Diseases, Functional↗
PubMed2000

Gastrointestinal tract symptoms among persons with diabetes mellitus in the community.

BACKGROUND: Gastrointestinal (GI) tract symptoms are common among patients with diabetes mellitus (DM) seen in tertiary care centers. The degree to which this reflects referral bias is unclear. OBJECTIVES: To determine whether GI tract symptoms are more prevalent in unselected patients with DM from the general community compared with their age- and sex-matched counterparts without DM and to assess the association of GI tract symptoms in persons with DM with psychosomatic symptoms, medication use, and symptoms of autonomic neuropathy. METHODS: In this population-based, cross-sectional study, Olmsted County, Minnesota, residents with type 1 DM, a random sample of residents with type 2 DM, and 2 age- and sex-stratified random samples of nondiabetic residents (total of 1262 person for the 4 groups) were mailed a previously validated symptom questionnaire. RESULTS: Heartburn was less common in residents with type 1 DM vs controls (12% vs 23%; P<.05). No significant difference in prevalence was detected (residents with type 1 DM vs controls; residents with type 2 DM vs controls) for nausea or vomiting (12% vs 11%; 6% vs 6%), dyspepsia (19% vs 21%; 13% vs 17%), or constipation (17% vs 14%; 10% vs 12%). However, constipation and/or laxative use was slightly more common in residents with type 1 DM (27% vs 19%; P<.15), particularly in men, and was associated with the intake of calcium channel blockers. CONCLUSIONS: In the community, the prevalence of most GI tract symptoms is similar in persons with or without DM, except for a lower prevalence of heartburn and an increased prevalence of constipation or laxative use in residents with type 1 DM, especially in men. This difference is associated with calcium channel blocker use rather than symptoms of autonomic neuropathy. In community-based practices, physicians should not immediately assume that GI tract symptoms in patients with DM represent a complication of DM.

Adolescent↗
PubMed2000

Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with symptoms of abdominal pain, discomfort, and altered bowel function. Antagonists of the type 3 serotonin receptor (5-HT3) have shown promising results in the relief of IBS-associated symptoms. We aimed to confirm these findings by doing a randomised, placebo-controlled trial. METHODS: We studied 647 female IBS patients with diarrhoea-predominant or alternating bowel patterns (diarrhoea and constipation). 324 patients were assigned 1 mg alosetron and 323 placebo orally twice daily for 12 weeks, followed by a 4-week post-treatment period. Adequate relief of abdominal pain and discomfort was the primary endpoint; secondary endpoints included improvements in urgency, stool frequency, and stool consistency. Analysis was by intention to treat. FINDINGS: 79 (24%) of patients in the alosetron group and 53 (16%) in the placebo group dropped out. The difference in the drop-out rate between groups was mainly due to a greater occurrence of constipation in the alosetron group. A greater proportion of alosetron-treated patients than placebo-treated patients (133 [41%] vs 94 [29%], respectively) reported adequate relief for all 3 months of treatment (difference 12% [4.7-19.2]). Alosetron also significantly decreased urgency and stool frequency, and increased stool firmness. Constipation occurred in 30% and 3% of patients in the alosetron and placebo groups, respectively. INTERPRETATION: Alosetron was well tolerated and clinically effective in alleviating pain and bowel-related symptoms in this population of women with IBS.

Administration, Oral↗
PubMed2000

New therapies for functional bowel diseases.

During recent years, a greater understanding of the pathophysiology of functional bowel disease, and a surge of interest in this challenge among pharmacologists, basic scientists, and clinical investigators, have led to novel insights and promising therapies. The evidence to support current therapies in nonculcer dyspepsia and irritable bowel syndrome (IBS) is reviewed, and some of the novel therapeutic approaches on the threshold of clinical application are described.

Carbolines↗
PubMed2000

Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome.

BACKGROUND & AIMS: This study evaluated the effects of a partial 5-hydroxytryptamine (5-HT)(4) agonist, tegaserod, on gastric small bowel and colonic transit in constipation-predominant irritable bowel syndrome (IBS). METHODS: After a 1 week run-in period, 24 patients with constipation-predominant IBS were randomized to 1 week of tegaserod, 2 mg twice daily, or placebo treatment. Scintigraphic gastric emptying, small bowel transit, and colonic transit were determined before administration of study drug and after 1 week on the medication. Colonic transit was also measured using radiopaque markers and a single radiograph on day 5. RESULTS: Gastric emptying was unaltered by tegaserod. Proximal colonic filling at 6 hours, a measure of orocecal transit, was accelerated by tegaserod (70.4% +/- 1.3% [mean +/- SEM] vs. placebo, 46.4 +/- 1.9; P = 0.015). Proximal colonic emptying half-time and geometric center at 48 hours were also accelerated by tegaserod compared with baseline, but not compared with placebo. Mean colonic transit time was similar in both groups at baseline and after drug administration (tegaserod, 59.5 +/- 2.1 hours; placebo, 62.1 +/- 2.1 hours). CONCLUSIONS: Tegaserod accelerates orocecal transit, tends to accelerate colonic transit, and deserves further study in patients with constipation-predominant IBS.

Adult↗
PubMed2000

Towards identifying optimal doses for alpha-2 adrenergic modulation of colonic and rectal motor and sensory function.

RATIONALE: Visceral sensation and motility are important in functional gut disorders and are partly controlled by adrenergic innervation. OBJECTIVES: To characterize the alpha2-adrenergic control of motor and sensory function of descending colon and rectum. METHODS: In 32 healthy volunteers, we assessed compliance, fasting and postprandial tone, and sensations of gas, urgency and pain during phasic distentions. Each subject received one agent at clinically approved doses: clonidine (0.05, 0.1, 0.2 or 0.3 mg p.o. ); or the alpha2 antagonist yohimbine (0.0125 mg, 0.05 mg, 0.125 mg or 0.2 mg intravenously and infusion over 2.5 h). RESULTS: Clonidine increased colonic and rectal compliance, and reduced tone, pain, gas sensation and rectal urgency. Clonidine showed large pairwise differences in sensation and motility between 0.05 and 0.1 mg doses, which did not interfere with the colon's motor response to feeding. Conversely, yohimbine dose-dependently altered the compliance curve, increased tone and sensations of gas, pain and urgency. Drug effects in the colon were more marked at low distensions; alpha2 modulation of rectal sensation was observed at all levels of distension. CONCLUSIONS: alpha2-adrenergic mechanisms modulate colorectal sensations and motility; at doses as low as 0.05 mg, clonidine reduced colorectal sensation while the tone response to feeding was preserved. These studies provide insight into the potential use of alpha2 agents in disease states.

Adrenergic alpha-Agonists↗
PubMed2000

Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome.

BACKGROUND: Alosetron, a 5-HT3-receptor antagonist, relieves abdominal pain and improves bowel function in non-constipated, female patients with irritable bowel syndrome. 5-HT3 antagonists delay colonic transit, increase colonic compliance, and increase small intestinal water absorption. AIM: To evaluate the effects of alosetron on gastrointestinal and colonic transit, rectal compliance and rectal sensation in irritable bowel syndrome. METHODS: A double-blind, placebo-controlled, two-dose study of alosetron was performed in 25 non-constipated irritable bowel syndrome patients, with paired studies before and after 4 weeks of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal compliance and sensation were assessed by rectal balloon distention with a barostat. RESULTS: There was a trend (P=0.06) for 1 mg alosetron to increase rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non-significantly retarded proximal colonic transit. Alosetron and placebo reduced sensory scores relative to baseline values; none of the changes induced by alosetron was significant relative to placebo. CONCLUSIONS: Alosetron had no significant effect on gastrointestinal transit or rectal sensory and motor mechanisms in non-constipated irritable bowel syndrome patients in this study. Alosetron's effects on colonic sensorimotor function and central sensory mechanisms deserve further evaluation.

Adult↗
PubMed2000

Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans.

BACKGROUND & AIMS: The aim of this study was to assess the effects of recombinant human brain-derived neurotrophic factor (r-metHuBDNF) and recombinant human neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functions in healthy people and in patients with constipation. METHODS: Gastrointestinal and colonic transit was measured by scintigraphy before and after 2 weeks of treatment. Daily diaries documented symptoms over 6 weeks before, during, and after treatment. In a randomized study of healthy subjects, 40 received 100 microg/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation received 300 microg/kg r-metHuNT-3 SC thrice weekly. RESULTS: r-met-HuBDNF accelerated overall and proximal colonic emptying (P<0.05) in health. r-metHuNT-3 accelerated overall colonic transit in health and constipation (all P<0.05) and gastric and small bowel transit (both P<0.05) in health. r-metHuBDNF tended to increase stool frequency compared with placebo in health (P = 0.09). r-metHuNT-3 increased stool frequency (P = 0.05) and facilitated passage of stool (P < 0.01) in constipated patients. The effects on stool frequency started within 3 days of the beginning of neurotrophin administrations and lasted up to 5 days after treatment ended. r-metHu neurotrophic factors were well tolerated, although half of the participants in the 2 studies developed injection site reactions or paresthesiae. CONCLUSIONS: Exogenous neurotrophic factors stimulate human gut motility in health and constipation.

Adult↗
PubMed2000

Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people.

OBJECTIVES: To review the epidemiology, pathophysiology and mechanisms of irritable bowel syndrome (IBS), constipation, and diverticulosis, for the purpose of addressing these three common conditions in older adults (>65 years of age). DESIGN: Using a MEDLINE search, we identified original English language journal articles and reviews from 1965 to December 1998. We also selected articles published before 1965 or after 1998 that were cross-referenced or pertinent to the topics researched. RESULTS: The prevalence of constipation and diverticulosis is higher in older than in younger adults. Significant risk factors for constipation in older women are failure of the anorectal angle to open or excessive perineal descent, which represent disturbances of pelvic floor function and rectal evacuation. In contrast, the prevalence of IBS is no greater than in younger adults. Nevertheless, these syndromes impact on the patient's functional status and quality of life. The mechanisms resulting in these gastrointestinal syndromes are unclear. Uncoordinated colonic activity and colonic segmentation may lead to IBS and diverticulosis, respectively, and these pathophysiological findings suggest disorders of inhibitory control of neuromuscular function. The total number of neurons in the myenteric plexus is decreased, and collagen deposited in the distal colon is increased with aging in humans. Animal studies suggest that senescent colonic muscle responds less to excitatory factors in vitro, and neural injury in older animals may result from apoptosis, defects of mitochondrial metabolism, and inadequate levels or response to neurotrophins. Future investigations will reveal whether similar mechanisms underlie human disease. Currently, treatment is aimed at relief of symptoms of IBS or constipation or dealing with the complications of diverticulosis. CONCLUSIONS: Constipation, IBS, and diverticulosis are common problems of aging. There is a need for further systematic research of the basic mechanisms in neuromuscular dysfunction with aging, including the studies of physical characteristics of the colonic wall, pelvic floor function (particularly in women with excessive perineal descent), and neurohormonal control of motility and sensation. Insights on the pathophysiology and mechanisms of neural injury may lead to more specific treatments in the future, e.g., serotonergic agents and neurotrophins. Meanwhile, collaborations between primary care physicians, geriatricians, and gastroenterologists can optimize management of these three common conditions that significantly impact the quality of life of older adults.

Age Distribution↗
PubMed2000

Coloanal motor coordination in association with high-amplitude colonic contractions after pharmacological stimulation.

OBJECTIVE: The rectoanal inhibitory reflex facilitates defecation by relaxation of the internal anal sphincter during rectal distention by gas or stool. Defecation is sometimes preceded by high-amplitude propagated contractions (HAPCs). Our objective was to seek evidence for motor coordination between human colonic and anal sphincter functions. METHODS: As part of a study of alpha2 modulation of colonic and anal motor functions in 32 healthy volunteers, we studied the relationship between high HAPCs and anal sphincter pressure with colonic manometry, barostat, and a Dent sleeve in the anal canal. RESULTS: Twenty-two HAPCs were observed; in 19/22 HAPCs there was optimal positioning of the Dent sleeve to assess the anal sphincter. Eighteen of 19 HAPCs occurred postprandially; 14 HAPCs occurred after administration of yohimbine, three after clonidine, and one before any drug administration. Seven followed experimental balloon distention. Anal sphincter relaxation occurred (14 +/- 4 s) before the recorded onset of HAPC in the descending colon and 88 +/- 7 s before the arrival of the HAPC in the rectum. After or during the HAPCs, anal sphincter pressure decreased by 40 +/- 4% and increased by 56 +/- 8% in the postrelaxation phase. CONCLUSIONS: The close temporal association between anal sphincter relaxation and onset of HAPC in the descending colon suggests a coloanal reflex that may facilitate defecation during mass movements independently of the rectoanal inhibitory reflex.

Adrenergic alpha-Agonists↗
PubMed2000

Psychological disorders in patients with evacuation disorders and constipation in a tertiary practice.

OBJECTIVE: We aimed to evaluate the prevalence of psychological impairment in patients with rectal evacuation disorders and the influence of psychological disorder on the early outcome of behavioral treatment. METHODS: We retrospectively reviewed the medical records of patients with rectal evacuation disorders referred for biofeedback retraining at a tertiary referral center. The psychological disorder was classified using the DSM IV criteria. Outcome of biofeedback treatment of evacuation at 2 wk was based on symptoms or on the ability to spontaneously expel a balloon placed in the rectum. Improvements in the groups without versus with a psychological disorder or an eating disorder were compared by Fisher's exact test. RESULTS: In the 60 patients (55 women; 5 men; mean age, 38 yr), psychological disorders were identified in 39 (65%); also noted were eating disorder (n = 5), rumination syndrome (n = 3), pain disorder (n = 6), anxiety-depression (n = 10), a combination of depression and pain disorder (n = 3), and a combination of eating disorder with anxiety-depression and pain disorder (n = 12). There was an association between psychological status and outcome at 2 wk of behavioral treatment for evacuation disorder (p = 0.03). The coexistence of eating disorder and psychological disorder resulted in an unfavorable outcome (p = 0.02), compared with those without psychological disorder. CONCLUSION: Psychological impairment was identified in 65% of the patients with evacuation disorder and constipation in a tertiary care practice, and has a significant negative impact on the outcome of behavioral treatment. These data reinforce the importance of a multidisciplinary approach in the management of these patients.

Adolescent↗
PubMed2000

Toward office-based measurement of gastric emptying in symptomatic diabetics using [13C]octanoic acid breath test.

OBJECTIVE: Current methods for measuring gastric emptying by breath test require sampling over several hours and are too inaccurate for clinical use. The aim of this study was to develop an office-based method for measuring gastric emptying of solids in patients with diabetes using a [13C]octanoic acid breath test. METHODS: In 22 symptomatic diabetic patients (17 insulin-dependent diabetes, 5 non-insulin-dependent diabetes) and 6 controls, we simultaneously measured gastric emptying of an egg meal (420 kcal) by scintigraphy and [13C]octanoic acid breath test. Conventional (nonlinear) methods for scintigraphic and [13C]octanoic acid breath test emptying and generalized linear regression method to predict scintigraphic half-life (t(1/2)) using four breath samples obtained during the first 3 h. RESULTS: Despite 8 h of breath sampling, the t(1/2) estimate using the conventional method was markedly different from the scintigraphic value (delta t(1/2): median, 113 min; range, 19-282 min). The generalized linear model (using samples at baseline, 30, and 120 or 150 min) yielded predicted scintigraphic tLAG and t(1/2) that were more accurate than the conventional method; mean standard deviations of differences were 16 and 27 min, respectively. Breath test correctly assessed normal or prolonged emptying in 21 of 22 patients. CONCLUSIONS: The [13C]octanoic acid breath test can be simplified to measure gastric tLAG and t(1/2) and can be expected to correctly identify normal t(1/2) in symptomatic diabetics. Further refinement of the model will need to include studies of patients with markedly delayed t(1/2).

Adult↗
PubMed2000

Novel testing of human gastric motor and sensory functions: rationale, methods, and potential applications in clinical practice.

Sensitive and reproducible tests are essential to investigate the mechanisms of gastric motility and sensation in healthy humans and patients with unexplained upper gastrointestinal symptoms. Electrogastrography, manometry, scintigraphic emptying, and barostat studies with an intragastric balloon were initially used to understand physiology and pathophysiology of gastric motility. However, manometry and barostat studies are time-consuming, costly, and invasive, thus reducing their widespread clinical application. To overcome these shortcomings, several novel approaches have been proposed: water/nutrient drink test, paracetamol absorption test, 13C-octanoic acid or spirulina breath tests, ultrasonography, magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and tensostat. The water/nutrient (satiety) test is a noninvasive test proposed as an alternative to sensory studies performed with an intragastric balloon. The satiety test cannot measure gastric accommodation; interpretation of sensory tests usually has required independent assessment of accommodation or compliance. The tensostat can be used as a gastric sensation test because it measures gastric wall tension, which is related to the perception of gastric distention. To measure gastric emptying, the paracetamol absorption test, 13C breath tests, ultrasound, or MRI can be used. The paracetamol absorption test can measure the gastric emptying of liquids. 13C breath test can measure the gastric emptying of solids or liquids and can achieve accuracy comparable with gastric scintigraphy. Ultrasonography requires special skills, and MRI requires costly equipment. To measure gastric accommodation to a meal, ultrasound, MRI, and SPECT have been proposed. The recently introduced SPECT requires an intravenous injection of 99mTc-pertechnetate, which the gastric mucosa specifically takes up, and specialized imaging and analysis, which have potential to be automated. Thus, novel, noninvasive approaches assess different dimensions of gastric motility and sensation testing. With further development of these techniques, refinement of their conduct and analysis, and validation of clinical usefulness, they are likely to be applicable in clinical practice to enhance cost-effective, evidence-based management of upper gastrointestinal symptoms. Such applications may provide an alternative to sequential empirical trials for symptoms.

Acetaminophen↗