PubMed HealthSearch

Biomedical subjects

M Camilleri

Publications and source records attributed to M Camilleri.

At least 19 recordsLinked to original sources

Effect of chemical sympathectomy on scintigraphic gastric and small bowel transit in the rat.

Our aims were to measure gastric and small bowel transit of radiolabeled chow or liquids in rats and to assess the effect of pharmacologically induced chronic sympathectomy of at least 5 weeks duration. Three series of experiments were performed. In series I, four rats in each group underwent i.p. chloral hydrate anesthesia, tracheostomy with intubation and mechanical ventilation: they received by gavage 1.0 g rat chow dissolved in 1.5 ml saline labeled with 1.0 mCi 99mTc-DTPA In series II, four rats in each group were anesthetized with only i.p. chloral hydrate and received 1.5 ml labeled saline. Rats were placed on a gamma camera for dynamic acquisition of 1-min images for 7 h in series I, and 4 h in series II. Activity was quantitated in stomach and cecum; gastric emptying was analyzed by the power exponential model. In series III, four rats in each group were studied for 1 h on gamma camera and sacrificed after 5 h. At the end of each study, the stomach, small bowel, cecum and colon were removed and radioactivity counted in each organ in a dose calibrator. Quantitation of radioactivity by gamma camera was highly accurate: labeled chow in the stomach at 7 h was identical by external camera and counting of the excised organ (linear regression slope = 1.01, r = 0.97, P less than 0.0001). Similar precision was observed with labeled liquids (slope = 0.93, r = 0.93, P = 0.001). Chow emptied slower than liquid in both groups (P = 0.048). Ileocecal movement of isotope occurred by bolus transfers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The irritable bowel syndrome: mechanisms and a practical approach to management.

OBJECTIVE: To develop a practical strategy that facilitates the management of patients with the irritable bowel syndrome (IBS). STUDY SELECTION AND DATA EXTRACTION: Review of the pertinent literature published in major English-language journals for the last 25 years, describing the pathophysiology and treatment of subgroups of patients with IBS. RESULTS: A stepwise approach for practical management of patients with suspected IBS is identified. The first step includes a combination of positive diagnosis of symptoms with limited investigations to exclude underlying structural or biochemical disorders. In the second step, therapeutic trials focus on alleviating the predominant symptoms. For patients with intractable symptoms, the third step combines novel tests to assess altered function and therapeutic trials to correct the dysfunction identified in the individual patient. CONCLUSIONS: A practical approach has been developed for management of IBS. It is based on advances in our understanding of the mechanisms resulting in IBS and on targeting therapy to correct the dysfunctions in these patients.

Colonic Diseases, Functional

Ileocolonic transit does not change after right hemicolectomy.

The role of the human ileocolonic junction in the transit of solid contents through the entire gut was evaluated. Eight patients, well compensated after right hemicolectomy for localized colon cancer, and eight age-matched healthy controls were enrolled. Scintigraphic transit was quantified after subjects ingested a mixed meal containing 111In-labeled Amberlite beads (average diameter, 1 mm; Sigma Chemical Co., St. Louis, MO). Gastric emptying was initially faster in the postoperative group, but overall emptying was not different from controls; small bowel transit also did not differ between the groups. In patients in whom the distal ileum, ileocolonic sphincter, and proximal colon were absent, isotopes moved from small to large bowel in a manner that was qualitatively and quantitatively no different from that of controls. Major episodes of coloileal reflux could not be identified in either group. After hemicolectomy, the residual transverse colon, and to a lesser degree the descending colon, were able to store solid residue, although in lesser amounts than the unoperated large bowel. The ileocolonic sphincter in humans appears to play only a minor role, at most, in ileocolonic transit, and the colon remaining after right hemicolectomy stores residue so that bowel habits are not greatly disturbed.

Aged

Towards a relatively inexpensive, noninvasive, accurate test for colonic motility disorders.

Currently available clinical tests of colonic transit, such as the radiopaque marker method, are useful to detect delayed transit but may be less sensitive for rapid transit. The aim of this study was to develop a relatively inexpensive, noninvasive, accurate test of colonic transit using selected scintigraphic observations within the first 24 hours after ingestion of a pH-sensitive, methacrylate-coated, delayed-release capsule containing 111In-labeled resin pellets. The authors' previously published colonic transit data on 22 healthy subjects, 9 patients with diarrhea-predominant irritable bowel syndrome, and 7 patients with idiopathic constipation and previously unpublished data on 4 patients with carcinoid diarrhea were analyzed. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected combinations or simple summaries of transit. Among combined transit summaries, the emptying rate of the proximal colon was significantly different between healthy and constipation groups; the geometric center of isotope in the colon at 4 hours was significantly greater in the diarrhea group than in healthy controls; the geometric center at 24 hours was significantly lower in the constipation group than in the other two groups. From the logistic discriminant analysis, simple summaries of transit also had significant discriminant value; these included the isotopic contents in the ascending, transverse, and descending colon at 4 hours and the counts in the ascending and transverse colon and stool at 24 hours. At 90% sensitivity, the specificity of the transverse colon counts at 4 hours was 79%, which is identical to the specificity of the proximal colon emptying rate, both adjusted for age. Thus, quantitation of isotopic counts in colonic regions on scans taken at 4 and 24 hours provides an accurate summary of colonic transit, with acceptable specificity at a high sensitivity in the detection of motility disorders of the colon.

Adult

Human gastric and jejunal transit and motility after Roux gastrojejunostomy.

Upper gut transit and motility among 10 symptomatic and 9 asymptomatic patients with Roux gastrectomy were compared with those among 10 healthy, unoperated controls. Gastric emptying of solids and Roux limb and small intestinal transit of liquids were assessed scintigraphically. Motor patterns in the Roux limb or healthy jejunum were recorded manometrically. Whereas gastric emptying was sometimes faster and sometimes unchanged after Roux gastrectomy compared with controls, Roux limb transit in patients was consistently slower than jejunal transit in controls. Postprandially, the Roux limb showed decreased overall motility, fewer clustered waves, and less aboral migration of clustered waves than the healthy jejunum. Symptomatic Roux patients had jejunal transit and motor patterns similar to those of asymptomatic patients. Nonetheless, reflux from Roux limb to gastric remnant occurred in 4 of 10 symptomatic patients but in none of the asymptomatic patients. In conclusion, stasis and dysmotility are present in the Roux limb after Roux gastrectomy and Roux-gastric reflux can occur. Other factors, however, must have a role in determining whether symptoms appear.

Adult

Transit through the proximal colon influences stool weight in the irritable bowel syndrome.

The inherent variability of symptoms and motor abnormalities in patients with the irritable bowel syndrome has hampered the demonstration of motor abnormalities that could underlie symptoms. The aim in the current study was to evaluate whether altered regional capacitance or transit of solid residue through the unprepared human gut were factors in the diarrhea of patients with the irritable bowel syndrome. In 10 such patients and in 5 healthy controls, gastric and small bowel transits were evaluated scintigraphically by means of a mixed meal containing 99mTc-labeled resin pellets. Regional colonic transit was quantitated by 111In-labeled pellets delivered to the ileocecal region by a pH-sensitive, methacrylate-coated capsule. Symptomatic patients did not have significantly altered gastric or small bowel transits, but colonic transit was accelerated in 7 of 10 persons with the irritable bowel syndrome (P less than 0.02), in the proximal colon of five patients and in the left colon of two patients. The 24-hour stool weight was positively correlated with the rate at which solid residue emptied from the ascending and transverse colons (r = 0.78; P less than 0.01). There was also an inverse relationship between emptying rates and maximal volumes accommodated by the proximal colon (r = -0.58; P less than 0.05), although the maximum volume of the proximal colon was not significantly different in patients and healthy subjects. Thus, accelerated transit through the proximal colon is a factor in the pathophysiology of the irritable bowel syndrome and influences the stool weight of such patients. The capacitance of the proximal colon presumably influences its storage capacity and, hence, the rate at which it empties.

Adult

Colonic tone and motility in patients with irritable bowel syndrome.

In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period--3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 +/- 13 versus 152 +/- 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS (P < 0.05). The motility index during fasting was greater in patients with IBS than it was in healthy control subjects (3.2 +/- 0.6 versus 1.6 +/- 0.4; P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Balance studies and polymeric glucose solution to optimize therapy after massive intestinal resection.

The aim of this study was to determine whether fluid homeostasis could be maintained by using a hypo-osmolar (200 to 221 mosmol/kg), relatively low-sodium (50 to 52 mmol/liter) solution that contained a glucose polymer in a 54-year-old patient with high ileostomy output attributed to short-gut syndrome and resultant prerenal azotemia. Sequential balance studies were performed to assess stool and urinary output, stool fat, and urinary electrolytes initially during intravenous rehydration and subsequently during administration of the necessary fluids and nutrients exclusively by oral supplementation. The additional effects of high-fat and low-fat diet, loperamide hydrochloride, and octreotide acetate were evaluated. When the patient sipped a hypo-osmolar oral rehydration solution while she was awake during the day and received a high dose of loperamide and a 40-g fat, disaccharide-free diet, salt and water homeostasis was maintained. The addition of octreotide did not substantially enhance fluid balance; rather, it increased fecal fat and fluid losses from the small bowel. Thus, hypo-osmolar polymeric glucose solutions maintain fluid homeostasis in patients with the short-gut syndrome. In such patients, simple balance studies are useful for assessing the absorptive capacity of the residual intestine, for developing an optimal individualized treatment, and for eliminating the need for costly, long-term home parenteral nutrition.

Crohn Disease

Measurement of small bowel and colonic transit: indications and methods.

In this article, we review the currently available techniques for measuring small intestinal and colonic transit. In addition, we describe the characteristics of an ideal test that provided the rationale for the development and validation of a gastrointestinal and colonic transit test at the Mayo Clinic. This new technique assesses regional transit of solid radiolabeled particles of the same size through the entire digestive tract and provides further insights into motor physiologic processes of the gut. By means of a delayed-release methacrylate-coated capsule, isotopically labeled pellets are delivered to the colon as a single bolus; thereby, dispersion of isotope throughout the small bowel is avoided because of the gradual emptying of chyme from the stomach. Similar pellets labeled with a different isotope can be used to assess gastric and small bowel transit. These new methods for measuring transit have also led to insights into the pathogenesis of unexplained gastrointestinal symptoms and disease states. Thus, we demonstrated that in healthy subjects, ileocolonic transfer of chyme occurs in boluses; this transfer is impaired in patients with myopathic pseudo-obstruction. The emptying rate of the proximal colon is an important determinant of the pathophysiologic features of colonic disease; thus, colonic transit is delayed in cases of severe idiopathic constipation. In contrast, rapid emptying of the proximal colon influences stool weight in diarrhea-predominant irritable bowel syndrome. An integrated approach for studying gastric, small bowel, and colonic transit by using the same radiolabeled particle provides a useful, clinically applicable method for evaluating gastrointestinal symptoms and for measuring motor function of the entire digestive tract without need for intubation; cost and radiation exposure are acceptable.

Colon

Effects of erythromycin on gut transit in pseudo-obstruction due to hereditary coproporphyria.

We studied gastrointestinal transit in a 57-year-old man with chronic intestinal pseudo-obstruction along with peripheral and autonomic neuropathy due to hereditary coproporphyria and we evaluated the effects of acute and chronic therapy with erythromycin. Noninvasive scintigraphic studies of regional transit of solid residue through the gut were obtained before treatment, during the acute i.v. administration of 500 mg, every-8-h doses of erythromycin for 24 h and after 15 weeks of oral therapy (500 mg, three times daily). During acute i.v. administration, symptoms and transit measurements dramatically improved; however, all parameters and symptoms returned to pretreatment levels during chronic oral therapy. We conclude that hereditary coproporphyria with associated autonomic neuropathy results in significant delay in small bowel and colonic transit; chronic administration of 500 mg three times a day oral erythromycin was not associated with maintenance of the improvement in regional transit and symptoms observed following acute i.v. administration of the drug at the same dose.

Administration, Oral

Control of muscle tone in the human colon.

Human colonic muscle tone varies diurnally and postprandially in predictable ways. Increased tone reduces the capacity of the colon to store contents after a meal, whereas increased distensibility (lesser tone) during sleep enlarges the storage capabilities and may slow transit. We tested the hypothesis that antidiarrhoeal drugs would also alter tone which, in turn, might reduce diarrhoea by facilitating the storage and salvage of fluids. Using a colonic barostat to create low pressure, isobaric colonic distension in healthy volunteers, we found that intravenous atropine (0.01 mg/kg) relaxed the colon during fasting, reduced the postprandial increase in tone, and enhanced relaxation in the late (1-2 hour) postprandial period. Intravenous morphine (0.1 mg/kg) caused variable effects soon after injection but, in fasting subjects, the descending colon relaxed 70-90 minutes after morphine. These changes in colonic motility were not always obvious by conventional manometric recording. Colonic distensibility is increased by antidiarrhoeal drugs and this effect may contribute to their efficacy in slowing colonic transit and augmenting absorption.

Adult

Measurement of axial forces during emptying from the human stomach.

Our aim was to measure axial forces in the stomach and to evaluate their relation to circumferential contractions of the gastric walls and the emptying of gastric content. We used a combination of simultaneous radioscintigraphy, gastroduodenal manometry, and an axial force transducer with an inflatable 2-ml balloon fluoroscopically placed in the antrum. In vitro studies demonstrated that the axial force transducer records only antegrade forces along the longitudinal axis of this probe in an intensity-dependent manner. In vivo studies were performed in five healthy subjects for at least 3 h after ingestion of radiolabeled meals. When administered separately, the emptying of liquids or solids from the stomach is associated with generation of antral axial forces and coincident phasic pressure activity; however, almost 20% (average) of gastric axial forces during emptying of liquids or solids are unassociated with proximal or distal antral pressure activity ("isolated" forces). High amplitude antral axial forces and pressures occur during both lag and postlag emptying phases. During emptying of liquids, there is a trend for axial forces to be coincident more often with proximal than with distal antral pressure activity and vice versa for the emptying of solids (P = 0.015). These data suggest that when placed in the antrum, the transducer can semiquantitatively record axial forces during gastric emptying. By combining these observations with the data from in vitro studies, it appears that axial forces predominantly result from traction on the balloon by the longitudinal vector resulting from circumferential gastric contractions. The combination of radioscintigraphy and measurement of antral axial forces is a promising method to evaluate mechanical forces involved in the emptying of the human stomach.

Adult

Towards a less costly but accurate test of gastric emptying and small bowel transit.

Our aim is to develop a less costly but accurate test of stomach emptying and small bowel transit by utilizing selected scintigraphic observations 1-6 hr after ingestion of a radiolabeled solid meal. These selected data were compared with more detailed analyses that require multiple scans and labor-intensive technical support. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected summaries of scintigraphic transit measurements. We studied 14 patients with motility disorders (eight neuropathic and six myopathic, confirmed by standard gastrointestinal manometry) and 37 healthy subjects. The patient group had abnormal gastric emptying (GE) and small bowel transit time (SBTT). The proportion of radiolabel retained in the stomach from 2 to 4 hr (GE 2 hr, GE 3 hr, GE 4 hr), as well as the proportion filling the colon at 4 and 6 hr (CF 4 hr, CF 6 hr) were individually able to differentiate health from disease (P less than 0.05 for each). From the logistic discriminant model, an estimated sensitivity of 93% resulted in similar specificities for detailed and selected transit parameters for gastric emptying (range: 62-70%). Similarly, combining selected observations, such as GE 4 hr with CF 6 hr, had a specificity of 76%, which was similar to the specificity of combinations of more detailed analyses. Based on the present studies and future confirmation in a larger number of patients, including those with less severe motility disorders, the 2-, 4-, and 6-hr scans with quantitation of proportions of counts in stomach and colon should provide a useful, relatively inexpensive strategy to identify and monitor motility disorders in clinical and epidemiologic studies.

Adult

Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility.

We conducted a 12-month trial of cisapride (10 mg three times a day) in 21 patients with gastric stasis due to clinically and manometrically diagnosed gastroparesis (N = 9; seven due to diabetes) or chronic intestinal pseudo-obstruction (N = 12). Radionuclide solid-liquid gastric emptying tests were performed at baseline and at the end of the 12-month period. Symptoms were assessed monthly by diary and every three months by the investigators; frequency and severity of symptoms were scored in a standardized manner. For the whole group of 21 patients, gastric emptying of both solids and liquids improved significantly after one year of cisapride (P less than 0.05). Among chronic intestinal pseudoobstruction patients, there was predominantly an improvement in gastric emptying of solids; in contrast, patients with gastroparesis had a greater improvement in liquid emptying. Total symptom score improved significantly in the gastroparesis group (median score: 8 at baseline vs 6 at one year, P less than 0.05) but not in the chronic intestinal pseudoobstruction patients (median score at baseline 10 vs 9 at one year). Similarly, body weight showed a trend towards improvement in the gastroparesis group. No significant side effects were noted. We conclude that during a 12-month open trial, cisapride was effective in improving gastric emptying in patients with gastric stasis and consistently improved symptoms in those with gastroparesis.

Administration, Oral

Familial enteric neuropathy with pseudoobstruction.

We report a case of autosomal dominant chronic intestinal pseudoobstruction secondary to a familial enteric neuropathy. Esophagogastrointestinal manometry studies in the index case showed decreased postprandial contractile frequency with normal amplitude of pressure activity in the stomach and small bowel. Pupillary function and autonomic reflexes were all normal, excluding an extrinsic autonomic neuropathy of the viscera. Histologic examination of the small intestine by hematoxylin and eosin stains revealed normal smooth muscles but a reduced number of neurons in the myenteric plexus without inflammatory cells or neuroNal intranuclear inclusions. Histologic examination of the myenteric plexus using the sections taken along the longitudinal axis of the intestine, stained with silver by the Smith technique, disclosed decreased numbers of argyrophilic neurons and degeneration of neurons and axons; however, there was no reactive increase in the number of glial cell nuclei. The patient's mother had suffered from chronic intestinal pseudoobstruction, which did not abate following extensive small bowel resection. This is the third family reported with an autosomal dominant enteric neuropathy unassociated with evidence of extrinsic autonomic or peripheral neuropathy. Subtotal resection of the small bowel was followed by recurrence of the pseudoobstruction syndrome in both affected members of the family.

Adult

Variation of muscle tone in the human colon.

It was hypothesized that the human colon is able to relax or constrict to receive materials arriving from above or to hasten distal passage of contents. Dilatation is also a feature of several pathophysiological states and, therefore, the propensity of the colon to dilate might be important in disease. An electromechanical barostat was applied to the human colon, and changes in colonic tone were recorded in response to physiological perturbations. In 16 studies of 14 healthy volunteers, the colon was prepared for colonoscopy and a manometry-barostat assembly was positioned in the ascending (n = 5), transverse (n = 4), or descending (n = 7) colon. The influences of food and overnight sleep were recorded. The barostat continuously monitored, at a constant pressure, the volume of air within a highly compliant 10-cm bag. Changes in tone, as reflected by changes in bag volume, were usually unassociated with waves of intraluminal pressure recorded from adjacent manometric sites. Thus, the barostat revealed a motor phenomenon not readily apparent by conventional manometry. Food caused an immediate though slowly progressive increase in tone; however, bag volumes were greatest during overnight sleep and were decreased on waking. The barostat has the potential to explore another possibly important aspect of colonic function in humans.

Adolescent