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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 73 records · Page 4Linked to original sources
PubMed2001

Pharmacological modulation of human gastric volumes demonstrated noninvasively using SPECT imaging.

Three-dimensional single-photon emission computed tomography (SPECT) imaging allows noninvasive measurement of human postprandial gastric accommodation. The aim of this study was to determine whether 99mTCO4-SPECT demonstrates effects on pre- and postprandial gastric volumes of intravenous (i.v.) erythromycin lactobionate and sublingual isosorbide dinitrate, as predicted from previous literature. Twenty volunteers received no medication (controls), while 12 were randomized to either i.v. erythromycin 2 mg kg-1 over 20 min, or 10 mg sublingual isosorbide. After a 10-min preprandial SPECT measurement, a standard 300-mL, 300-kcal liquid meal was ingested, followed by a 20-min postprandial measurement. Gastric images were reconstructed from transaxial images and total volume was measured using the Analyseeth software system. Fasting gastric volume was greater with isosorbide [223 +/- 14 (SE) mL vs. 174 +/- 9 mL, control; P < 0.05], and postprandial volume was lower with erythromycin [393 +/- 27 mL vs. 582 +/- 17 mL, control; P < 0.05]. The ratio of postprandial over fasting volume and mean difference between pre- and postprandial volumes were significantly lower in both drug groups compared to controls. We conclude that 99mTCO4-SPECT imaging is able to semiquantitatively demonstrate pharmacological modulation of fasting gastric volume and postprandial accommodation in humans.

Administration, Sublingual↗
PubMed2001

Validation of a stable isotope gastric emptying test for normal, accelerated or delayed gastric emptying.

To validate a 13C-Spirulina platensis breath test for measurement of accelerated or delayed gastric emptying, we measured gastric emptying of egg containing 13C-S. platensis and 99mTc-sulphur colloid by breath 13 CO2 every 15 min over 3 h and scintigraphy every 15-30 min over 5 h in 57 healthy volunteers. Thirty-three received no treatment, 10 received erythromycin, and 14 atropine. A generalized linear regression model predicted half-emptying time by scintigraphy (t1/2S) from breath 13CO2 (t1/2B) data. Accuracy was assessed by standard deviation (SD) of differences between t1/2S and t1/2B and by receiver operating characteristic (ROC) curves. Regression models using breath samples at baseline, and 45, 90, 105 and 120 min, predicted t1/2B (mean +/- SD) at 118 +/- 59 min, similar to t1/2S (118 +/- 67 min). Correlation between t1/2B and t1/2S was significant (r=0.88; P < 0.0001). Differences between t1/2S and t1/2B were: 18-19.2 min for t1/2 < 70-150 min, and 68.3 min for t1/2 > 150 min. Breath test detected abnormal emptying with a sensitivity of 86% and specificity of 80%. Thus, the 13C-S. platensis test measures gastric emptying t1/2 for solids, which is accelerated or delayed to mimic a range of conditions from dumping syndrome to severe gastroparesis, with high sensitivity and specificity. Additional breath samples are needed to increase sensitivity in detecting accelerated gastric emptying.

Adolescent↗
PubMed2001

Enteric nervous system disorders: genetic and molecular insights for the neurogastroenterologist.

The goals of this review are to summarize some of the novel observations on the genetic and molecular basis of enteric nervous system disorders, with particular emphasis on the relevance of these observations to the practicing neurogastroenterologist. In the last two decades, there has been a greater understanding of genetic loci involved in congenital forms of pseudo-obstruction and Hirschsprung's disease; and the contribution of endothelins and nuclear transcription factors to the development of the enteric nervous system. In addition, clarification of the molecules involved in the activation of the peristaltic reflex, the disorders of the interstitial cells of Cajal, the clinical manifestations of mitochondrial cytopathies affecting the gut, and the application of neurotrophic factors for disorders of colonic function have impacted on practical management of patients with gut dysmotility.

Embryonic and Fetal Development↗
PubMed2001

Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder.

BACKGROUND & AIMS: Prucalopride (PRU) is a selective benzofuran 5-hydroxytryptamine(4)-receptor agonist with gastrointestinal and colonic prokinetic activities. We evaluated the effects of PRU on gastrointestinal and colonic transit in patients with constipation. METHODS: Gastrointestinal and colonic transit were measured over 48 hours in 40 patients who fulfilled modified Rome I criteria for functional constipation. Patients had no evidence of a rectal evacuation disorder. Subjects were randomized to receive a daily dose of 2 or 4 mg PRU or placebo in a double-blind, parallel-group design. Each treatment lasted 7 days. The transit test was performed over the last 48 hours of the study. Effects on gastric emptying, small bowel transit, and colonic transit were analyzed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Of 61 patients screened, 40 were eligible and randomized. Two patients withdrew because of adverse events. PRU accelerated overall gastric emptying and small bowel transit. PRU tended to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying with the 4-mg dose. CONCLUSIONS: PRU accelerates transit through the stomach, small bowel, and colon in patients with constipation unassociated with a rectal evacuation disorder.

Adult↗
PubMed2001

Management of the irritable bowel syndrome.

Irritable bowel syndrome (IBS) is the most common disorder diagnosed by gastroenterologists and one of the more common ones encountered in general practice. The overall prevalence rate is similar (approximately 10%) in most industrialized countries; the illness has a large economic impact on health care use and indirect costs, chiefly through absenteeism. IBS is a biopsychosocial disorder in which 3 major mechanisms interact: psychosocial factors, altered motility, and/or heightened sensory function of the intestine. Subtle inflammatory changes suggest a role for inflammation, especially after infectious enteritis, but this has not yet resulted in changes in the approach to patient treatment. Treatment of patients is based on positive diagnosis of the symptom complex, limited exclusion of underlying organic disease, and institution of a therapeutic trial. If patient symptoms are intractable, further investigations are needed to exclude specific motility or other disorders. Symptoms fluctuate over time; treatment is often restricted to times when patients experience symptoms. Symptomatic treatment includes supplementing fiber to achieve a total intake of up to 30 g in those with constipation, those taking loperamide or other opioids for diarrhea, and those taking low-dose antidepressants or infrequently using antispasmodics for pain. Older conventional therapies do not address pain in IBS. Behavioral psychotherapy and hypnotherapy are also being evaluated. Novel approaches include alosetron; a 5-HT(3) antagonist, tegaserod, a partial 5-HT(4) agonist, kappa-opioid agonists, and neurokinin antagonists to address the remaining challenging symptoms of pain, constipation, and bloating. Understanding the brain-gut axis is key to the eventual development of effective therapies for IBS.

Antidiarrheals↗
PubMed2001

Paraneoplastic gastrointestinal motor dysfunction: clinical and laboratory characteristics.

OBJECTIVES: The aim of this study was to describe the clinical, manometric, and serological characteristics of 12 patients with paraneoplastic GI motor dysfunction and to assess the contributory role of diagnostic tests. METHODS: Twelve patients diagnosed with malignant tumors and GI motor dysfunction were identified at the Mayo Clinic from 1985 to 1996. RESULTS: Cancers identified were: nine small cell lung carcinoma (SCLC), one anaplastic lung adenocarcinoma, one retroperitoneal lymphoma, and one ovarian papillary serous adenocarcinoma. GI symptoms preceded the tumor diagnosis in all cases of SCLC (mean, -8.7 months, range, -1 to -24 months, n = 9). The diagnosis of a malignant tumor preceded the onset of GI symptoms in the three patients with other neoplasms (6, 12, and 24 months). Five of the nine patients found to have SCLC had no evidence of tumor on initial chest x-ray. One or more paraneoplastic autoantibodies were found in 10 of the 11 patients tested by autoimmune serology. Type 1 antineuronal nuclear antibody (ANNA-1 or anti-Hu) was detected in eight of the nine patients with SCLC (one patient was not tested). The patient with ovarian carcinoma had type 1 Purkinje cell cytoplasmic antibody (PCA-1 or anti-Yo). N-type calcium channel antibodies were found in one patient with SCLC, one with a retroperitoneal B cell lymphoma, and one with ovarian carcinoma. Gastric emptying was delayed in 89% (eight of nine tested) and 80% (four of five tested) had esophageal dysmotility. Autonomic reflex tests were abnormal in the seven patients tested. CONCLUSIONS: The diagnosis of paraneoplastic GI motor dysfunction requires a high index of clinical suspicion. A panel of serological tests for paraneoplastic autoantibodies, scintigraphic gastric emptying, and esophageal manometry are useful as first-line screening tests. Seropositivity for ANNA-1, PCA-1, or N-type calcium channel-binding antibodies should prompt further evaluation for an underlying malignancy even when routine imaging studies are negative.

Autoimmune Diseases↗
PubMed2001

An open trial of octreotide long-acting release in the management of short bowel syndrome.

OBJECTIVES: The aim of this study was to assess the effects of the long-acting release (LAR) depot octreotide preparation Sandostatin LAR Depot on stool water and electrolyte losses, fecal fat excretion, and GI transit in patients with short bowel syndrome. METHODS: We performed a 15-wk, prospective, open-label study of intramuscular (i.m.) Sandostatin LAR Depot, 20 mg, at 0, 3, 7, and 11 wk. Balance studies were performed before and at the end of the 15-wk study. Baseline and posttreatment measurements of body weight, stool fat, sodium and potassium, and gastric and small bowel transit of a radiolabeled egg meal were compared by paired analysis. RESULTS: We studied eight patients with short bowel syndrome (five women and three men; mean age 52 yr, range 37-72 yr) who had been TPN dependent for a mean of 11.8 yr (range 1.5-22 yr). The underlying diagnoses were Crohn's disease (n = 6), intestinal ischemia (n = 1), and resection for carcinoid tumor (n = 1). Treatment with Sandostatin LAR Depot significantly increased small bowel transit time (p = 0.03). Changes in body weight, urine volume, stool weight, fecal fat excretion, stool sodium and potassium excretion, or gastric emptying rate were highly variable, and no overall significance was observed. CONCLUSIONS: Sandostatin LAR Depot for 15 wk significantly prolonged small bowel transit time. Body weight and stool parameters in response to Sandostatin LAR Depot treatment needs to be assessed further in multicenter studies assessing dose, frequency of administration, and a larger sample size.

Adult↗
PubMed2001

Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: To evaluate the influence of gender on the effect of a 5-HT3 antagonist, alosetron, 1 mg b.i.d., on GI and colonic transit in D-IBS. METHODS: Thirty patients (15 male, 15 female) with D-IBS received 1 mg b.i.d. alosetron for 6 wk. Transit was measured by scintigraphy at baseline and at the end of treatment. RESULTS: Alosetron, 1 mg b.i.d., significantly retarded small bowel and, proximal and overall colonic transit in the 30 patients with D-IBS. The effect of alosetron on the primary endpoint, colonic geometric center at 24 h, was significantly greater in females than in males (p < 0.05). However, two females showed no slowing of colonic transit on treatment. Among male patients, two of 15 had a slowing of colonic transit at 24 h that was greater than the mean change in female patients, suggesting responsiveness to alosetron among a subgroup of males. CONCLUSION: A 5-HT3 antagonist, alosetron, significantly retards small intestinal and colonic transit in diarrhea-predominant IBS patients, with significantly greater female to male responsiveness. Gender partly contributes to differences in the serotonergic control of intestinal and colonic transit in patients with D-IBS.

Adult↗
PubMed2001

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia.

OBJECTIVES: Postprandial symptoms are associated with impaired postprandial gastric accommodation. The aims of this study were to apply a noninvasive method to measure accommodation of the entire stomach in healthy subjects and in patients with idiopathic dyspeptic symptoms, and to assess the frequency of abnormal gastric accommodation and emptying of solids in these patients. METHODS: In 20 healthy volunteers and 32 tertiary referral patients, we used i.v. 99mTc-single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes; we expressed the volume response to feeding ("accommodation") as the change in gastric volume and the ratio of postprandial/fasting volumes. The stomach was identified in transaxial SPECT tomographic images using a semiautomated, intensity-based extraction algorithm. Whole gastric volumes were measured using AnalyzeAVW software. Gastric emptying in patients was measured by scintigraphy. We also assessed dyspeptic symptoms and the association with normal or reduced accommodation. RESULTS: SPECT imaging detects the postprandial change in gastric volume ("accommodation") in health and disease. Among healthy subjects (eight men, 12 women), the postprandial/fasting gastric volume ratio was 4.9+/-1.7 (mean +/- SD; fifth through 95th percentiles 3-8, median 4.6). Thirteen (41%) patients with idiopathic nonulcer dyspepsia had reduced postprandial "accommodation." Gastric emptying was fast in four (13%), normal in 25 (78%), and slow in three (9%) patients. Both tests were normal in 50% of patients. Weight loss of >10 pounds tended to be more frequently observed in those with reduced "accommodation" (62% vs 32%, p = 0.09). CONCLUSIONS: SPECT imaging noninvasively measures fasting and postprandial gastric volumes in humans. Half the patients with idiopathic nonulcer dyspepsia had impaired gastric accommodation or emptying. Reduced gastric "accommodation" was observed in 41% of a group with idiopathic nonulcer dyspepsia. Abnormal gastric emptying is less frequent (22%).

Adult↗
PubMed2001

Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans.

To characterize alpha(2)-adrenergic control of motor and sensory functions of gastrointestinal tract and colon, we studied dose-related effects of clonidine (placebo or up to 0.3 mg po) by random assignment in 55 healthy humans. Gastrointestinal transit was measured in all subjects; in 35, we assessed colonic compliance, tone, and sensations of gas and pain during phasic distensions. Clonidine did not significantly alter gastrointestinal or colonic transit, but it increased colonic compliance and reduced fasting tone without altering colonic response to a meal. Clonidine significantly reduced aggregate sensation to distensions overall and had significant linear dose-related sensory effects at 8- and 24-mmHg distensions. Effect on pain (including dose-response relationship) was due to 0.3-mg dose for distensions at 24 mmHg. We confirmed that clonidine relaxes fasting colonic tone and reduces sensation of pain. In this study, gut transit was not altered by clonidine, and novel dose-response characteristics and clonidine's effect on gas sensation are provided. Doses as low as 0.05 mg may be effective and potentially useful in reducing colonic tone and gas sensation.

Adrenergic alpha-Agonists↗
PubMed2001

Pathophysiology in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a distressing condition that impairs quality of life, and it deserves to be treated. It also has a large economic impact on healthcare utilization and absenteeism. IBS is a disorder in which three major mechanisms interact: altered gastrointestinal motility, increased sensory function of the intestine and psychosocial factors. The role of prior infection in the development of IBS is the subject of ongoing study. This article focuses on pathophysiological mechanisms, including the potential roles of mucosal changes and neurobiology in the development of IBS. Novel pharmacological agents are being developed to target neural mediators of IBS; they appear promising, and their role in clinical practice will be clarified with regulatory approval and clinical use.

Journal Article↗
PubMed2001

Effect of glucagon-like peptide-1(7-36)-amide on initial splanchnic glucose uptake and insulin action in humans with type 1 diabetes.

In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at approximately 5.5 mmo/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3H]glucose) was infused via an intraduodenal tube at a rate of 20 micromol.kg(-1).min(-1). Insulin concentrations were increased to approximately 500 pmol/l while glucose was clamped at approximately 8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2H2]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P = 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 +/- 1.5 vs. 4.8 +/- 0.8 micromol.kg(-1).min(-1)). On the other hand, flux through the hepatic uridine-diphosphate- glucose pool did not differ between study days (14.2 +/- 5.5 vs. 13.0 +/- 4.2 micromol.kg(-1).min(-1)), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 +/- 2.9 vs. 1.3 +/- 1.4 micromol.kg(-1).min(-1)), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 +/- 10.0 vs. 69.3 +/- 6.3 micromol.kg(-1).min(-1); P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes.

Blood Glucose↗
PubMed2001

Dyspepsia, irritable bowel syndrome, and constipation: review and what's new.

Functional gastrointestinal disorders are collections of symptoms attributable to the gastrointestinal tract in the absence of mucosal, structural, or biochemical disease. The two most common disorders, irritable bowel syndrome and functional dyspepsia, have common etiopathogenetic features, notably psychosocial disturbances, dysmotility, heightened sensitivity, and, possibly, an association with a postinfective state. The third condition is constipation, in which transit disorders and abnormal evacuation represent disturbances of function that are amenable to therapy. This review is an update of the control mechanisms, pathophysiology, investigation, and potential pharmacotherapies of these disorders. Serotonergic and adrenergic agents and neurotrophic factors are among the novel approaches that may have a significant impact on these disorders.

Colonic Diseases, Functional↗