Original Article
Effect of Octreotide on Intestinal Motility and Bacterial Overgrowth in Scleroderma
N Engl J Med 1991; 325:1461-1467November 21, 1991
- Abstract
- Abstract
Background.
Patients with scleroderma may have abnormal motility of the small intestine, with pseudoobstruction and bacterial overgrowth. Standard stimulatory agents are often ineffective in such patients. Because the somatostatin analogue octreotide evokes intestinal motor activity in normal subjects, we hypothesized that it might increase motility in patients with scleroderma.
Methods.
We studied the effects of octreotide on intestinal motility and plasma motilin concentrations in five fasting patients with scleroderma who had bacterial overgrowth and in six fasting normal subjects. The motor effects of octreotide were correlated with its effects on abdominal symptoms and bacterial overgrowth as determined by the level of breath hydrogen excretion.
Results.
In the normal subjects, octreotide (10 μg subcutaneously) increased the mean (±SD) frequency of intestinal migrating complexes, which reflect intestinal motility, from 1.5±1.0 to 4.1 ±1.1 every three hours. In the patients with scleroderma, who had no spontaneous migrating complexes, octreotide (100 μ̵g) induced 3.6±2.3 complexes every three hours. These complexes propagated at the same velocity and had two-thirds the amplitude of the spontaneous complexes in normal subjects. Plasma motilin concentrations, which were higher in the patients with scleroderma (229 ±74 pmol per liter) than in the normal subjects (112±37 pmol per liter), were inhibited by octreotide, suggesting that intestinal activity evoked by octreotide is independent of motilin. Treatment of the patients with scleroderma with octreotide (50 μg every evening) for three weeks reduced breath hydrogen excretion while they were fasting from 25 ±5 to 4±2 ppm (P = 0.001 ) and breath hydrogen excretion after they ingested 50 g of glucose from 46±24 to 8±7 ppm (P = 0.015); these reductions were accompanied by a significant decrease in nausea, bloating, and abdominal pain and by less frequent emesis.
Conclusions.
Octreotide stimulates intestinal motility in normal subjects and in patients with scleroderma. In such patients, the short-term administration of octreotide reduces bacterial overgrowth and improves abdominal symptoms. This agent may be useful for the treatment of intestinal dysmotility in patients with scleroderma. (N Engl J Med 1991;325:1461–7.)
Media in This Article
Figure 1
Intestinal Manometric Tracings in a Normal Subject and a Patient with Scleroderma.Figure 2
Effect of Three Weeks of Treatment with Octreotide (50 μg Every Evening) in Patients with Scleroderma.Article Activity
- Article
GASTROINTESTINAL involvement is common in patients with scleroderma.1 2 3 Although abnormalities of esophageal and anorectal function predominate,4 5 6 7 approximately one half of those with scleroderma have small-bowel dysfunction.8 , 9 In such patients, manometry reveals disordered or absent cycling of the normal contractile pattern (known as the migrating motor complex) in the small intestine during fasting,10 , 11 and this may be manifested clinically as intestinal pseudoobstruction and bacterial overgrowth. These problems are difficult to treat because standard stimulatory (prokinetic) agents are not very effective motor stimulants in scleroderma.10
In normal subjects, somatostatin initiates a propagative pattern of motor stimulation in the duodenum, with a cycle length of 40 minutes.12 The long-acting somatostatin analogue octreotide, used in the treatment of endocrine tumors,13 evokes a similar intestinal pattern of contraction in dogs.14 Octreotide therapy has been well tolerated by patients, although abdominal cramping, diarrhea, or tenesmus develops in some, presumably because of the gastrointestinal motor effects of the medication.15 Malabsorption and biliary colic due to the inhibitory effects of octreotide on the pancreas and biliary tract have been reported but are rare.15
We undertook this study to determine the effects of octreotide in patients with scleroderma who have abdominal pain, nausea, bloating, and altered intestinal contractility. We studied the changes in intestinal motility and in plasma concentrations of motilin, a gastrointestinal hormone that stimulates intestinal motor activity, after single injections of octreotide. We also studied the clinical responses and changes in breath hydrogen excretion (as a measure of intestinal bacterial overgrowth) in patients with scleroderma given octreotide for three weeks.
Methods
Selection Criteria and Characteristics
We studied six normal subjects (two women and four men 21 to 28 years old) and five patients with scleroderma (two women and three men 55 to 65 years old). The diagnosis of scleroderma was established in all five patients according to criteria developed by the Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee.16 All five patients had tightness, thickening, or nonpitting induration of the skin of the extremities, neck, face, or trunk with associated sclerodactyly, as well as multisystem involvement, and were considered to have systemic sclerosis with diffuse cutaneous scleroderma (Table 1Table 1
Clinical Characteristics of Patients with Scleroderma and Intestinal Pseudoobstruction.). All had had abdominal pain, bloating, nausea, diarrhea, and constipation consistent with abnormal intestinal motility for at least six months before the study, and all had been hospitalized more than six weeks earlier for the treatment of intestinal pseudoobstruction with nasogastric suction, intravenous hydration, and (in some instances) hyperalimentation. All the patients also reported heartburn, dysphagia, or both and had manometric evidence of abnormal esophageal motility, including aperistalsis and decreased gastroesophageal-sphincter pressure, and all had breath hydrogen values at least 12 ppm higher than basal values after the ingestion of 50 g of glucose, indicating intestinal bacterial overgrowth. None of the patients had undergone gastroduodenal surgery or vagotomy, and none had evidence of anatomical bowel obstruction on barium radiography at the time of the study, although all had dilated loops of bowel. The studies were approved by the University of Michigan Human Use Committee, and each subject gave written informed consent.Gastroduodenal Manometric Recording
After an overnight fast, a water-perfused eight-lumen polyvinyl manometric catheter (Arndorfer Medical Specialties, Greendale, Wis.) was placed in the small intestine perorally under fluoroscopic guidance in all subjects. Medications known to modify gastrointestinal motility were discontinued 72 hours before the study began. The catheter was placed so that six channels spanned the distal antrum and pylorus and there were duodenal channels 12 cm (proximal duodenal site) and 24 cm (distal duodenal site) distal to the pylorus. The catheter was connected by means of a pneumohydraulic water-perfusion apparatus (perfusion rate, 0.25 ml per minute; Arndorfer Medical Specialties) to force transducers (model P23xL, Gould, Oxnard, Calif.) that relayed information to a chart recorder (model R611, Beckman Instruments, Schiller Park, Ill.) for continuous monitoring of motor activity.
Basal motor activity was recorded in the normal subjects until two cycles of the migrating motor complex had progressed through the distal duodenal site. One complete cycle of the migrating motor complex characteristically consists of three phases. Phase 1 is a period of motor quiescence that lasts 45 to 60 minutes. This is followed by phase 2, a period of irregular phasic contractile activity that lasts 30 to 60 minutes. The cycle culminates in phase 3, a 5-to-10-minute period of intense phasic motor activity that begins in the stomach and propagates through much of the length of the small intestine.17 At the end of a phase 3 complex, a new migrating motor complex begins, with a return to phase 1 activity. Phase 3 is associated with the rapid transit of gastrointestinal contents.18 Basal motor activity recorded for four hours in the patients with scleroderma showed no organized migrating motor activity. After the basal recording period, octreotide (Sandoz, East Hanover, N.J.) was administered subcutaneously in doses of 10 μg to the normal subjects and 100 μg to the patients with scleroderma, and motor activity was recorded for an additional 3 to 3.5 hours. In the normal subjects, octreotide was administered 15 minutes after the end of a duodenal phase 3 complex. In preliminary studies, we found the response to octreotide to be dose-dependent, with the minimal effective dose for duodenal motor stimulation being 1 μg in normal subjects and 30 μg in patients with scleroderma; the doses producing the maximal intestinal motor response were 10 μg in the normal subjects and 100 μg in the patients with scleroderma.
We analyzed the manometric tracings visually to determine the duration and amplitude of phase 1, 2, and 3 activity in the antrum and duodenum, using previously established criteria.17 The propagation velocities of duodenal phase 3 activity were measured by dividing the distance between the two duodenal recording sites by the time needed for the phase 3 contraction at the proximal duodenal site to pass to the distal duodenal site. Indexes of duodenal motility were determined by calculating the areas under the pressure curves with a Bit Pad Two digitizer (Summagraphics, Fairfield, Conn.) connected to a personal computer with the program Easydij (Version 3.0, Geocomp, Golden, Colo.). The manometric recording was placed on the digitizer tablet and traced with an electric stylus to transfer the digitized signal to the computer. The pressure—time relations for individual motor complexes were integrated to calculate areas under the pressure curves. Motility indexes were expressed as millimeters of mercury multiplied by minutes of recording.
Plasma Motilin Determination
An intravenous line was inserted during the motility studies in all subjects. Patency of the line was maintained with periodic infusions of heparin flush-lock solution (100 USP units per milliliter). Blood samples were withdrawn every 15 minutes and at the beginning and end of all duodenal phase 3 complexes. The samples were immediately centrifuged, and the plasma was frozen and stored at — 20°C. Plasma motilin was measured by radioimmunoassay with a motilin antiserum specific to the carboxyl terminal.19 Porcine motilin was iodinated by the chloramine-T method and purified by molecular sieve and ion-exchange chromatography.20 Highly purified porcine motilin was used as the assay standard. Plasma was assayed at a dilution of 1:6. Antibody-bound and free Radio-labeled motilin was separated by adsorption of the free hormone to 0.25 percent dextran—coated 1 percent charcoal. The sensitivity of the assay was 2 pg per tube, and the intraassay and interassay coefficients of variation were 5 percent and 10 percent, respectively.
Hydrogen Breath Testing
Increases in breath hydrogen excretion after the ingestion of glucose, as well as increased breath hydrogen levels in the fasting state, are used as indicators of bacterial overgrowth in the intestine21 for this diagnosis, the measurement of breath hydrogen after the ingestion of glucose has a positive predictive value of 86 percent and a negative predictive value of 88 percent.21 This technique is based on the finding that in most people the bacterial metabolism of ingested carbohydrates in the intestinal lumen results in the production of hydrogen gas that is absorbed and expired. For these studies (performed only in the patients with scleroderma), the patients ate meals low in nonabsorbable carbohydrates, such as bread or pasta, for 24 hours before breath testing,22 and any medication that might alter gastrointestinal motility, including octreotide, was discontinued 72 hours before testing. After a 12-hour fast, two basal breath samples were collected 15 minutes apart. For this sampling, the patients were instructed to expire at the end of a normal inspiration. At the end of the expiration, they were asked to expire maximally into a 50-ml gas-impermeable syringe with a three-way stopcock. They then drank 250 ml of water containing 50 g of glucose in 2 minutes, and breath samples were collected at 15-minute intervals for 2 hours. The samples were analyzed for hydrogen within 30 minutes by gas chromatography (Model 12 Microlyzer, Quintron Instrument, Milwaukee). The results were expressed as parts per million. Using this technique, we have noted little variation in breath-test results in individual subjects after glucose ingestion (data not shown). Breath hydrogen tests were performed before and after three weeks of therapy with octreotide, given subcutaneously at bedtime in a dose of 50 μg. For studies of the breath-test response to octreotide and for the assessments of symptoms described below, no changes were made in the patients' other medications during the three weeks of octreotide therapy. All the patients had had no response in trials of other prokinetic agents, and none were taking such medications at the time of the study. No patient received antibiotic therapy before or during the administration of octreotide.
Scoring of Gastrointestinal Symptoms
The patients with scleroderma were evaluated for their symptomatic response during the three-week period of octreotide therapy. Symptoms of nausea, bloating, and abdominal pain were assessed on a scale of 0 to 3 (0 indicating no symptoms, 1 mild symptoms not interfering with daily activities, 2 moderate symptoms interfering with but not preventing daily activities, and 3 severe symptoms preventing the performance of desired daily activities). Daily symptom scores were summed for the seven days before octreotide therapy began and for the last seven days of therapy, and the mean daily pretreatment and treatment symptom scores were calculated. The patients' weights were recorded before and at the end of therapy. The number of episodes of emesis and the number of bowel movements during each of the two seven-day periods were counted.
Statistical Analysis
The results are expressed as means ±SD. The motility results and plasma motilin concentrations were compared with use of Student's t-test for paired and unpaired observations. The breath hydrogen results and symptom scores were compared with use of Student's t-test for paired observations. A P value of 0.05 indicates statistical significance. All t-tests were two-tailed.
Results
Gastrointestinal Manometric Results
The manometric recordings in the normal subjects showed propagative intestinal patterns during fasting, with 1.5 ±1.0 phase 3 complexes occurring every three hours (Fig. 1Figure 1
Intestinal Manometric Tracings in a Normal Subject and a Patient with Scleroderma.). In contrast, none of the patients with scleroderma who had pseudoobstruction and bacterial overgrowth had any spontaneous duodenal phase 3 activity (Fig. 1). Two of the five patients with scleroderma had no spontaneous duodenal contractions, one had intermittent bursts of intense nonpropagative phasic contractions, and two had intermediate motor patterns consisting of intermittent low-amplitude bursts of uncoordinated contractile activity. Octreotide induced propagative phase 3 activity that originated in the duodenum in all the normal subjects (Fig. 1), whereas gastric phase 3 activity was suppressed. In all five patients with scleroderma, octreotide also evoked intestinal phase 3 complexes that were qualitatively similar to the complexes evoked by octreotide in the normal subjects (Fig. 1). There was no spontaneous gastric phase 3 activity in the patients with scleroderma. In the patient with intense uncoordinated intestinal motility, gastric recording revealed rare nonpropagated contractions that were inhibited by octreotide. In the other four patients, gastric activity was minimal and was not modified by octreotide.Duodenal phase 3 complexes evoked by octreotide were more frequent than spontaneous complexes (Table 2Table 2
Effects of Octreotide on Intestinal Motility and Plasma Motilin Concentrations in Normal Subjects and Patients with Scleroderma.). The normal subjects had 1.5±1.0 phase 3 complexes during the 3 hours of basal recording and 4.1 ± 1.1 complexes during the 3 hours after the administration of octreotide, or approximately 1 complex every 40 minutes (P = 0.012). The octreotide-evoked motor patterns consisted of alternating phase 1 and phase 3 activity, with marked reductions in phase 2 activity; the duration of phase 2 activity decreased from 77±39 to 3±2 minutes per complete cycle between consecutive phase 3 complexes (P = 0.001). The responses in the patients with scleroderma were similar: octreotide increased the number of phase 3 complexes from 0 to 3.6±2.3 per 3 hours, which is not different from that in the five normal subjects after octreotide therapy (Table 2). The cycling induced by octreotide in the patients with scleroderma consisted of alternating phase 1 and phase 3 activity, with only 1.5± 1.4 minutes of phase 2 activity between consecutive phase 3 complexes.The durations and amplitudes of the spontaneous and octreotide-induced phase 3 complexes were similar in the normal subjects. To determine the amplitude of an individual phase 3 complex, we calculated a motility index by measuring the area under the phase 3 pressure curve. The motility indexes of individual spontaneous and octreotide-evoked phase 3 complexes were similar in the normal subjects (9.3±1.2 vs. 12.1±5.4 mm Hg · min (Table 2). The complexes evoked by octreotide in the patients with scleroderma were qualitatively similar to those in the normal subjects, although the amplitudes (as indicated by the phase 3 motility index) and frequencies of occurrence varied among patients (Table 3Table 3
Effects of Octreotide on Duodenal Motility in Patients with Scleroderma.). The mean motility index of the octreotide-evoked phase 3 complexes in the patients with scleroderma was 5.9±3.0 mm Hg · min, which was half the value for octreotide-evoked complexes (P = 0.005) and two thirds of the value for spontaneous complexes in the normal subjects (P = 0.026). Octreotide evoked phase 3 complexes with mean motility indexes of 1.4 and 3.7 mm Hg · min in the two patients with scleroderma who had no basal duodenal activity (Patients 4 and 5) (Table 3). In contrast, the patient with intense uncoordinated basal duodenal activity (Patient 1) had intense phase 3 complexes after receiving octreotide, with a mean motility index of 13.2 mm Hg · min.Octreotide also decreased the propagation velocity of phase 3 complexes (the time taken for a phase 3 complex to migrate from the proximal to the distal duodenal recording site) in normal subjects from 11±1 to 7±1 cm per minute. In the patients with scleroderma, the rate of propagation of octreotideevoked phase 3 complexes was 11 ± 1 cm per minute, which is similar to the rate of spontaneous complexes in the normal subjects.
Plasma Motilin Concentrations
The complexes evoked by octreotide were associated with decreased plasma motilin concentrations (Table 2). In the normal subjects, plasma motilin cycled in phase with the migrating motor complex; the mean concentration was 92±27 pmol per liter in phase 1 and 112±37 pmol per liter in phase 3 (P = 0.05). The phase 3 complexes evoked by octreotide were associated with a decrease in the plasma motilin concentration to 57± 16 pmol per liter (P = 0.006 for the comparison with phase 1). The plasma motilin concentration was persistently elevated in the patients with scleroderma (229±74 pmol per liter, P = 0.002). As in the normal subjects, the plasma motilin concentration decreased to 141 ±76 pmol per liter in the patients with scleroderma after the administration of octreotide, suggesting that the cycling of motilin is not needed for octreotide-induced complexes.
Breath Hydrogen Excretion after Long-Term Administration of Octreotide
Breath hydrogen excretion was determined in the patients with scleroderma before and after three weeks of treatment with octreotide (50 μg subcutaneously at bedtime), to provide an objective measurement of the presence and extent of bacterial overgrowth. The patients with scleroderma had a basal hydrogen excretion of 25±5 ppm while fasting (Table 4Table 4
Effects of Octreotide on Breath Hydrogen Excretion in Patients with Scleroderma.), which decreased to 4±2 ppm after three weeks of treatment with octreotide (P = 0.001 ). After the ingestion of 50 g of glucose, mean breath hydrogen excretion increased to 46 ±24 ppm (Table 4) before the administration of octreotide. The increase in breath hydrogen after the ingestion of glucose was much smaller (8±7 ppm, P = 0.015) after the three-week treatment period. After octreotide treatment, none of the patients had elevated breath hydrogen excretion while fasting, and only one of the five had a breath hydrogen increase of more than 15 ppm at that time. There was no difference in the time to peak breath hydrogen excretion after the ingestion of glucose at either time (111±8 minutes before octreotide treatment vs. 90±18 minutes after treatment). These results suggest substantial improvement in bacterial overgrowth in all patients.Gastrointestinal Symptoms after Long-Term Administration of Octreotide
Symptoms consistent with bacterial overgrowth and pseudoobstruction were compared before and during the last seven days of the three-week period of treatment with octreotide. The mean daily symptom scores for abdominal pain decreased from 2.0±0.6 to 0.5±0.5 (P = 0.002) during treatment (Fig. 2Figure 2
Effect of Three Weeks of Treatment with Octreotide (50 μg Every Evening) in Patients with Scleroderma.A). Similarly, the symptom scores for nausea decreased from 1.7±1.1 to 0.2±0.2 (P = 0.05), and for bloating from 2.6±0.6 to 0.5±0.4 (P = 0.003). The number of episodes of emesis declined from 3.7±2.9 to 0.1 ±0.2 per week (P = 0.05) (Fig. 2B). There was great variability in stool frequency before and during octreotide therapy. Before treatment, the frequency averaged 5.2±5.4 bowel movements per week; it was 14.2± 10.1 per week during the last week of treatment (P = 0.09). Finally, there was no change in the patients' weight before and during octreotide therapy (51±8 vs. 52±8 kg). This improvement in some of the abdominal symptoms in the patients with scleroderma suggests that octreotide may have therapeutic potential in such patients.Discussion
Pseudoobstruction is a debilitating complication of scleroderma. Manometry in patients with scleroderma reveals abnormal cycling of the migrating motor complex that corresponds to the severity of symptoms of gastrointestinal dysfunction.10 , 11 Therapy with lowresidue diets or antibiotics for bacterial overgrowth is usually unsatisfactory. Prokinetic agents such as metoclopramide evoke only low-amplitude motor activity.10 Cisapride enhances gastric emptying in scleroderma and enhances intestinal transit acutely in idiopathic pseudoobstruction.23 24 25 There are no reports, however, that cisapride has prolonged efficacy against pseudoobstruction in scleroderma.
We found that octreotide evoked alternating phase 1 and phase 3 activity in normal subjects and patients with scleroderma. The octreotide-evoked complexes originated in the duodenum, and gastric activity was inhibited, confirming previous studies of the motor effects of somatostatin.12 , 14 , 26 None of the patients with scleroderma had any spontaneous phase 3 activity during four hours of recording. Octreotide had qualitatively similar effects on motor activity in the patients with scleroderma and the normal subjects. The octreotide response, as measured by the phase 3 motility index, was only slightly smaller in the patients than in the normal subjects, suggesting a potent prokinetic effect. Plasma motilin concentrations decreased after the administration of octreotide in both groups, confirming earlier studies.26 The patients had higher plasma motilin concentrations while fasting, suggesting that the lack of phase 3 activity may interrupt the normal feedback inhibition of motilin release.10
Octreotide stimulated intestinal motor complexes of variable intensity in the patients with scleroderma. The responses in the patient with intense uncoordinated activity under basal conditions were larger than the mean response in the normal subjects, whereas the two patients with no basal activity had responses that were less than one third of those in the normal subjects. These findings agree with those of a previous study that described two patterns of motility in scleroderma.11 The intense uncoordinated activity was thought to result from a neuropathic form of scleroderma, whereas hypomotility was more consistent with a myopathy. Although we studied only a small number of patients, our results suggest that the neuropathic pattern may be associated with a larger response to octreotide than the myopathic pattern. Although the hypothesis is controversial, gut involvement in scleroderma has been postulated to progress from an early neuropathic form to a later myopathic form. Cohen and others found impaired gastroesophageal-sphincter responses to neural stimuli such as gastrin and the cholinesterase inhibitor edrophonium, but normal responses to the direct muscle stimulant methacholine, in patients who had had scleroderma for an average of 4 years, whereas patients who had had the disease for an average of 10 years had impaired responses to methacholine as well.27 DiMarino and colleagues reported that patients with long-standing scleroderma had impaired duodenal myoelectric responses to hormonal stimuli, whereas those with disease of shorter duration had normal responses to hormonal stimuli but abnormal responses to the neural stimulus of duodenal distention.28
Although octreotide has potent motor effects, its effects on transit are unclear. In normal subjects, octreotide slows duodenal phase 3 propagation, a finding in agreement with studies showing a delay in transit with somatostatin.29 30 31 This may not be relevant in patients with scleroderma and intestinal pseudoobstruction, since radiography may show barium retention for up to 24 hours.9 , 32 33 34 Combined manometric and flow studies show the most rapid transit in phase 3, with somewhat slower transit in phase 2.18 , 35 Patients with scleroderma probably have slowed transit because of their lack of organized phase 2 or phase 3 activity. Octreotide evoked phase 3 complexes in our patients that propagated at the same velocity as spontaneous complexes in the normal subjects. Octreotide thus probably accelerates rather than slows transit in patients with pseudoobstruction.
We treated the study patients with octreotide for three weeks to examine its potential role as a prokinetic agent in scleroderma. Octreotide was not given before meals because somatostatin impairs motor responses to feeding,12 and we gave a low dose at bedtime because multiple large daily doses cause steatorrhea that is due to impaired pancreatic secretion and mucosal absorption.36 With bedtime dosing, we expected the drug's effects on meal-related phenomena to be minimal. Breath hydrogen testing after the ingestion of glucose detects intestinal bacterial overgrowth in 62 to 93 percent of patients in whom the results of jejunal culture are positive.21 , 37 38 39 Breath hydrogen excretion is thus a useful screening test for bacterial overgrowth.21 The patients with scleroderma had elevated breath hydrogen excretion during fasting, as well as marked increases in hydrogen excretion after the ingestion of glucose, findings indicative of bacterial carbohydrate metabolism, and both were reversed after three weeks of treatment with octreotide. We presume that the motor effects of octreotide reduced intestinal stasis, thereby allowing bacterial clearance.
The assessment of symptoms before and during octreotide treatment provided a second measure of drug efficacy. During the treatment period nausea, vomiting, bloating, and pain lessened. Disturbances in bowel pattern were a smaller problem in our study than in others.40 The increase in stool frequency from 5 to 14 bowel movements per week during treatment with octreotide was not perceived as diarrheal by our patients. We do not know what the effect of octreotide would be in patients with diarrhea, but we suspect that the symptom would improve with the reduction in bacterial overgrowth, which is the principal cause of diarrhea in scleroderma.
In conclusion, octreotide stimulated propagative intestinal phase 3—like activity in patients with scleroderma through motilin-independent pathways, and the administration of octreotide for three weeks reversed abnormal breath hydrogen excretion and improved symptoms in patients with bacterial overgrowth. These results suggest that a long-term trial of octreotide therapy as a prokinetic agent is warranted in patients with scleroderma and pseudoobstruction.
Supported in part by grants (RO1 DK35783 and P30 DK34933) from the National Institutes of Health and by a grant (5MOI-RR-42) from the General Clinical Research Program.
Source Information
From the Department of Internal Medicine, Gastroenterology Research Unit, University of Michigan Medical Center, 3912 Taubman Ctr., Box 0362, 1500 E. Medical Center Dr., Ann Arbor, MI 48109, where reprint requests should be addressed to Dr. Owyang.
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