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Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 145 records · Page 8Linked to original sources

Dose-related effects of N-demethyl-N-isopropyl-8, 9-anhydroerythromycin A 6,9-hemiacetal on gastric emptying of solids in healthy human volunteers.

The purpose of our study was to evaluate the effects of a new nonantibiotic motilide derived from erythromycin, EM574, on gastric emptying and to evaluate its safety. Thirty healthy volunteers received one of five oral doses of EM574 (5, 10, 20, 30 mg and placebo) in a randomized, double-blind, five-period, cross-over design; each dosing period was separated by 1-wk washout. Gastric emptying was measured by 13C-octanoic acid breath test. A total of 10, 20, 30 mg of EM574 significantly accelerated both lag phase and gastric half-emptying time (P < .001) compared to placebo. The 5-mg dose of EM574 also significantly shortened the gastric half-emptying time (P < .05). Mean gastric half-emptying times were 173, 158, 147, 149 min with EM574 5, 10, 20, 30 mg, respectively (placebo, mean 189 min). EM574 accelerated gastric emptying in a dose-related manner (P < .001 for linear trend, P < .05 for quadratic trend). However, the 30-mg dose did not accelerate gastric emptying more than the 20-mg dose. EM574 was well tolerated; 7 of 56 participants receiving the 20- or 30-mg dose developed nausea, and only 2 of 28 receiving the 30-mg dose experienced vomiting. EM574 accelerates gastric emptying in a dose-dependent manner with minimal side effects after a single administration of up to 20 mg. EM574 shows promise for treatment of patients with impaired gastric emptying.

Abdominal Pain↗

Linear IgA bullous dermatosis induced by piroxicam.

Linear IgA bullous dermatosis (LABD) is an acquired, autoimmune, heterogeneous subepidermal blistering disorder usually idiopathic in nature, but in recent years a variety of drugs have been reported to induce this disorder. We describe the first reported patient who developed LABD after ingestion of the non-steroidal anti-inflammatory agent (NSAID) piroxicam.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension.

UNLABELLED: Our aims were to evaluate to role of superior mesenteric blood flow in the pathophysiology of orthostatic hypotension in patients with generalized autonomic failure. METHODS: Twelve patients with symptomatic neurogenic orthostatic hypotension and 12 healthy controls underwent superior mesenteric artery flow measurements using Doppler ultrasonography during head-up tilt and tilt plus meal ingestion. Autonomic failure was assessed using standard tests of the function of the sympathetic adrenergic, cardiovagal and postganglionic sympathetic sudomotor function. RESULTS: Superior mesenteric flow volume and time-averaged velocity were similar in patients and controls at supine rest; however, responses to cold pressor test and upright tilt were attenuated (p < 0.05) in patients compared to controls. Head-up tilt after the meal evoked a profound fall of blood pressure and mesenteric blood flow in the patients; the reduction of mesenteric blood flow correlated (r = 0.89) with the fall of blood pressure in these patients, providing another manifestation of failed baroreflexes. We make the novel finding that the severity of postprandial orthostatic hypotension regressed negatively with the postprandial increase in mesenteric flow in patients with orthostatic hypotension. CONCLUSION: Mesenteric flow is under baroreflex control, which when defective, results in, or worsens orthostatic hypotension. Its large size and baroreflexivity renders it quantitatively important in the maintenance of postural normotension. The effects of orthostatic stress can be significantly attenuated by reducing the splanchnic-mesenteric volume increase in response to food. Evaluation of mesenteric flow in response to eating and head-up tilt provide important information on intra-abdominal sympathetic adrenergic function, and the ability of the patient to cope with orthostatic stress.

Adult↗

[13C]octanoic acid breath test for gastric emptying of solids: accuracy, reproducibility, and comparison with scintigraphy.

BACKGROUND & AIMS: Previous work suggested that a breath test using 13C accurately measures gastric emptying of solids. Thus, breath test half emptying time (t1/2) minus 66 minutes was claimed to estimate accurately t1/2 by scintigraphy. The aim of this study was to evaluate the accuracy and reproducibility of this breath test in healthy subjects. METHODS: Fifteen volunteers (8 men and 7 women; mean age, 41 +/- 13 years) underwent simultaneous scintigraphy and [13C]octanoic acid breath test. Scans and breath samples were obtained every 15 minutes for 4 and 6 hours, respectively. The breath test was repeated three times within a 3-week period. RESULTS: Parameters from scintigraphy and breath test were not correlated significantly. Differences of lag phase and t1/2 between the two tests were highly variable (range for t1/2, -33.1 to 169.6; mean, 48.0 minutes). Increasing breath test "duration" (samples over 4, 5, or 6 hours) yielded decreasing estimates of the lag phase and t1/2. Although widely different values were observed in some subjects, repeated breath tests showed a high degree of reproducibility within individuals (mean coefficient of variation, 12%). CONCLUSIONS: [13C]Octanoic acid breath test for gastric emptying of solids requires further validation before it can substitute for scintigraphy as a diagnostic test, but it seems useful for intraindividual comparisons.

Adult↗

Rumination syndrome.

Rumination is a syndrome characterized by repetitive regurgitation of small amounts of food from the stomach. The food is then partially or completely rechewed, reswallowed, or expelled. This syndrome is relatively common in infants and mentally challenged persons, but it also occurs in adults with normal intelligence. The rumination syndrome is an underappreciated condition in adults who frequently receive a misdiagnosis of vomiting due to gastroparesis or gastroesophageal reflux. Difficulties in establishing the correct diagnosis may be caused by a lack of awareness of the condition among physicians. This syndrome must be considered in the differential diagnosis of a patient with regurgitation, vomiting (especially postprandial), and weight loss. Reassurance, explanations, and behavioral therapy are currently the mainstays of treatment in adults with normal intelligence who have the rumination syndrome. Appropriately controlled trials are needed to establish the best therapy.

Adolescent↗

Effect of cholecystokinin octapeptide and atropine on human colonic motility, tone, and transit.

The role of cholecystokinin (CCK) in postprandial control of colonic motility is controversial. To test the hypothesis that CCK stimulates colonic tone, motility, and transit we measured these colonic functions in 16 healthy subjects using intraluminal manometry, barostatic balloon measurements, and radioscintigraphy. This was a randomized-order, double-blind, sequential study design in each subject of saline and either atropine (0.01 mg/kg stat and 0.01 mg/kg/hr by infusion) or CCK-octapeptide (OP, 30 ng/kg stat and 60 ng/kg/hr by infusion). Atropine was used as control to demonstrate responsiveness of selected parameters of colonic motility. Atropine significantly reduced whole colon (change from fasting = 52 +/- 11%) and left colon (change from fasting 61 +/- 8%) phasic pressure activity and transverse colon tone (change from fasting 159 +/- 40%); CCK-OP had no significant effects on phasic contractility, tone or transit. Thus, a CCK-OP infusion that maximally stimulates pancreatic exocrine secretion and gallbladder contraction has no effect on motor function or transit in prepared colon of healthy subjects.

Adult↗

Review article: irritable bowel syndrome.

Irritable bowel syndrome is a disease that can be diagnosed positively on the basis of an established series of criteria and limited exclusion of organic disease. It is the most common disease diagnosed by gastroenterologists and affects about 20% of all people at any one time. Symptoms fluctuate, and the overall prevalence rate is relatively constant in Western communities. Ten per cent of patients present to their physicians; the illness has a large economic impact on health-care utilization and absenteeism. Irritable bowel syndrome is a biopsychosocial disorder in which three major mechanisms interact: psychosocial factors; altered motility; and/or sensory function of the intestine. Management 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 significant motility or other disorders. Symptomatic treatment includes fibre for constipation, loperamide for diarrhoea and low-dose antidepressants or infrequent use of antispasmodics for pain; novel pharmacological agents, psychotherapy and hypnotherapy are being evaluated.

Colonic Diseases, Functional↗

Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: a randomized, controlled study.

BACKGROUND & AIMS: The effects of parenteral growth hormone, glutamine supplementation, and a high carbohydrate-low fat (HCLF) diet on gut adaptation in short-bowel syndrome are unclear. The aim of this study was to compare effects of this treatment regimen and placebo in patients with short-bowel syndrome. METHODS: A randomized, 6-week, double-blind, placebo-controlled, crossover study in 8 patients with short-bowel syndrome (average small bowel length, 71 cm; mean duration, 12.9 years) was performed. Active treatment was growth hormone (0.14 mg.kg-1.day-1), oral glutamine (0.63 g.kg-1.day-1), and the HCLF diet for 21 days. The weight, basal metabolic rate, nutrient and electrolyte balance, serum insulin-like growth factor I levels, D-xylose absorption, morphology and DNA proliferation of small intestinal mucosa, and gastrointestinal transit were evaluated. Treatments were compared by paired t test. RESULTS: Active treatment transiently increased body weight, significantly but modestly increased the absorption of sodium and potassium, and decreased gastric emptying. The assimilation of macronutrients, stool volumes, and morphometry of small bowel mucosa were not statistically different in the two treatment arms. CONCLUSIONS: Although treatment with growth hormone, glutamine, and HCLF diet for 3 weeks resulted in modest improvements in electrolyte absorption and delayed gastric emptying, there were no improvements in small bowel morphology, stool losses, or macronutrient absorption.

Acclimatization↗

Effect of acute hyperglycemia on colorectal motor and sensory function in humans.

Increased use of laxatives and constipation are more common among people with diabetes mellitus than matched nondiabetic people in the same community. The mechanism of constipation in diabetes is unclear. Acute hyperglycemia was previously reported to reduce the gastrocolonic response. Our aim was to determine the effects of acute hyperglycemia on the colon compliance and motor response to feeding and on the sensory function of the colon and rectum in healthy human subjects. Eleven healthy individuals were studied under conditions of hyperglycemia (mean blood glucose 280 +/- 13 mg/dl) and euglycemia. We evaluated three parameters: 1) colonic motility and compliance by a multilumen manometry and barostatic balloon assembly in the descending colon (motility was studied during fasting and for 2 h postprandially); 2) perception of isobaric distensions of polyethylene balloons in the rectum and colon; and 3) rectal compliance. Initial tonic response to meal ingestion (0-5 min) was slightly lower during hyperglycemia (P = 0.3). However, colonic tone, motility, compliance, and sensation, as well as rectal compliance and sensation, were not significantly different under the conditions of euglycemia and acute hyperglycemia. In healthy individuals, acute hyperglycemia does not significantly change colonic or rectal motor functions or the perception of mechanosensory stimuli in the colon or rectum compared with euglycemia. These results do not support the hypothesis that hyperglycemia abolishes the colonic response to feeding.

Adult↗

Alpha 2-adrenergic modulation of colonic tone during hyperventilation.

Our aims were to assess the role of adrenergic modulation in the hyperventilation-induced increase in colonic tone. Of 40 healthy volunteers, 12 received placebo (saline) and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. Time-frequency mapping of heart rate based on Wigner distribution assessed variations in parasympathetic and sympathetic activity during hyperventilation. Tone in the descending colon was recorded by a barostat balloon before, during, and after 5 min of hyperventilation. Heart rate spectral analysis suggested diminished sympathetic and vagal activity during hyperventilation and increased sympathetic and vagal activity after hyperventilation. Adrenergic agents influenced (P = 0.01) the tonic response after, but not during, hyperventilation. Yohimbine reduced the increment in colonic tone after hyperventilation compared with saline (P < 0.05) and clonidine (P = 0.002); phenylephrine and ritodrine had no effects. Different mechanisms modulate the increase in colonic tone during and after hyperventilation. Yohimbine attenuates the increase in colonic tone after hyperventilation probably by enhancing inhibitory sympathetic input to the colon.

Adrenergic alpha-Agonists↗

Adrenergic modulation of human colonic motor and sensory function.

The effects of pharmacological modulation of adrenergic receptors on colonic motor and sensory function are unclear. We studied 40 healthy volunteers in a single-blind design; 12 received saline, and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. A barostat-manometric assembly in the left colon recorded drug effects on fasting and postprandial motor function, compliance, and sensation in response to standardized phasic balloon distensions delivered in random order. Clonidine reduced and yohimbine increased fasting, but not postprandial tone, by 63.2 +/- 22.3% and 24.8 +/- 8.8% (SE), respectively. Clonidine tended to reduce fasting phasic activity in the descending and sigmoid colon. A power exponential model provided the best fit to the compliance curve. Clonidine significantly increased colonic compliance. Clonidine reduced and yohimbine increased colonic perception of pain but not gas sensation during distension. Phenylephrine and ritodrine did not influence colonic motor or sensory function in the present studies. Thus alpha 2-receptors modulate fasting colonic tone and compliance and alter perception of pain but not gas during mechanical stimulation of the colon.

Adrenergic Agents↗

Duodenal obstruction: diagnosis by gastroduodenal manometry.

Establishing the diagnosis of adenocarcinoma of the distal duodenum is often difficult based on findings on barium radiography and routine endoscopy of the upper gastrointestinal tract. A characteristic manometric pattern of simultaneous, prolonged contractions of the small intestine after a meal has been associated with mechanical obstruction of the small intestine. Herein we describe a 68-year-old woman who had a 4-month history of nausea, vomiting, and weight loss. Findings on endoscopy of the upper gastrointestinal tract and a barium contrast examination of the stomach, duodenum, and small bowel were interpreted as normal. A radionuclide scan suggested mildly delayed gastric emptying. Gastroduodenal manometry revealed high-amplitude, simultaneous contractions in the third and fourth portions of the duodenum but not in the jejunum, findings highly suggestive of a mechanical obstruction in the distal duodenum. At laparotomy, an obstructing adenocarcinoma of the duodenum proximal to the ligament of Treitz was resected. Subtle abnormalities were detected retrospectively on the barium contrast study of the small bowel. In patients with features suggestive of intestinal obstruction, gastroduodenal manometry may be helpful in distinguishing mechanical causes from pseudo-obstruction.

Adenocarcinoma↗