July 1, 2005 • www.internalmedicinenews.com 71

T HE E FFECTIVE P HYSICIAN ‘Prebiotic’ May Hold Gastroparesis Promise for Crohn’s BY WILLIAM E. GOLDEN, M.D., AND ROBERT H. HOPKINS, M.D. Background medulla oblongata. Serotonin (5-HT3) receptor Patients with gastroparesis present numerous antagonists may act on the area postrema and BY ANN C. LOGUE Crohn’s disease was achieved by challenges to the practicing internist. The the afferent branches of the . Al- Contributing Writer 40% of the patients. There was a American Gastroenterological Association re- though 5-HT3 agents are effective in other caus- 6.8% increase in the volume of Bi- cently released recommendations on the diag- es of and , no studies document C HICAGO — Ten patients with fidobacteria found in dried fecal nosis and treatment of this condition. the efficacy of these drugs for gastroparesis. moderate Crohn’s disease took sup- samples between the start and end Ǡ There is little evidence that antihistamines plements of fructooligosaccharide, of the study. In addition, the num- Conclusions are effective for symptom control of gastro- a substance found in artichokes and ber of interleukin-10 dentridic cells Gastroparesis is a symptomatic, chronic dis- . Transdermal hyoscine (the scopolamine asparagus, and showed an increase increased, as did the number of order of delayed gastric emptying, without patch) may actually delay gastric emptying. in fecal Bifidobacteria and produc- cells expressing Toll-like receptors. mechanical obstruction. Patients typically have Ǡ Prokinetic agents can increase antral con- tion of mucosal dendritic cells, Patients in the study, 60% of nausea and vomiting, early satiety, , tractility, improve gastric muscle function, and James Lindsay, Ph.D. reported at whom were completely compli- and upper . Common causes improve antroduodenal coordination. Some the Digestive Disease Week. ant with the study regimen, toler- include , postsurgical changes, and agents, such as and domperi- Although the findings are pre- ated the supplement well. The idiopathic presentations. In diabetes, gastro- done, have antiemetic properties. Response to liminary, this is the first known most common complaints were paresis can reflect neuropathy of the vagus these medications is judged clinically, rather study of “prebiotic” dietary thera- rumbling and flatulence. nerve or impaired motility secondary to hy- than with follow-up gastric emptying tests. pies for Crohn’s, and the strategy “Traditional therapies tend to perglycemia. As many as 20%-40% of diabet- Ǡ Metoclopramide, used for 35 years to treat may offer a way to supplement increase effector pathways. The al- ic patients eventually develop symptoms of gastroparesis, has prokinetic and antiemetic ac- traditional treatments or to man- ternative is to increase regulatory gastroparesis. tions. The dosage can be increased to 20 mg be- age patients who do not respond to pathways,” said Dr. Lindsay, con- Gastroparesis can occur as a af- fore meals and at bedtime, especially for pa- them, he said. sultant gastroenterologist at St ter laparoscopic fundoplication for gastro- tients with severe symptoms. A small subset of Fructooligosaccharide is a car- Bartholomew’s Hospital and the esophageal reflux disease. It is also seen with patients can have acute dystonic reactions. bohydrate that selectively alters the Royal London Hospital. vagal denervation of the after py- Prolonged use of metoclopramide can produce colonic microbiota, Dr. Lindsay ex- Balfour Sartor, M.D., a professor loroplasty. Gastrojejunostomy with distal gas- parkinsonian-like symptoms, which usually plained. It is a prebiotic that may of medicine, microbiology, and tric resection can result in severe gastric stasis subside 2-3 months after discontinuation. Tar- provide a substrate upon which immunology at University of and/or delayed small bowel transit in the den- dive dyskinesia is seen in up to 15% of patients healthy bacteria can grow, as op- North Carolina at Chapel Hill, is ervated efferent loop. Idiopathic gastroparesis on higher doses for at least 3 months. posed to probiotics, which are the familiar with the work of Dr. Lind- is seen mostly in women. Some evidence sug- Ǡ doesn’t cross the blood-brain healthy bacteria themselves. say and his colleagues because it gests a viral etiology in a subset of these pa- barrier and has fewer extrapyramidal effects The supplement given to the 10 overlaps with his own. He said tients, who typically have a slow resolution of than metoclopramide. In one study, its effect patients in the open-label study that Dr. Lindsay’s study is not in symptoms over several years. on solid-phase emptying was lost after 6 weeks. was prepared by Nestlé UK, which the mainstream of Crohn’s re- Gastroparesis should be distinguished from Ǡ can stimulate gastric emptying provided financial support for the search, but that it is a legitimate the cyclical vomiting syndrome, which is char- in diabetic gastroparesis, idiopathic gastropare- research. The patients took 15 g area of investigation. acterized by episodes of relentless nausea and sis, and postvagotomy conditions. It may be per day for 3 weeks. Dr. Lindsay emphasized the pre- vomiting lasting hours to days and sometimes most potent when used intravenously. Oral ad- Patients and doctors noted an liminary nature of the findings. associated with migraine . ministration should start at low doses, such as improvement on the Harvey Brad- “One would have to be quite cau- 125-250 mg three to four times daily; liquid sus- shaw index, with the mean falling tious in interpreting the results un- Diagnosis pensions can improve absorption. Intravenous from 9.8 at the start of the study til we have performed a controlled Ǡ Scintigraphy is the gold standard for diag- erythromycin, 100 mg every 8 hours, is used for to 6.9 at the end. Remission of trial,” he said. ■ nosis. Such studies require assessment of the patients hospitalized with severe conditions. emptying of solids; emptying of liquids may be Ǡ Three-quarters of patients with refractory normal even in severe gastroparesis. The radio- gastroparesis in one study responded to a pro- label must be cooked into a test meal to ensure kinetic agent, but up to one-quarter were re- In Japan, Crohn’s Disease Rises binding to the solid phase. Scintigraphy should fractory to all interventions. If all pharma- be extended to at least 2-4 hours. cotherapy fails, consider placement of a feeding As Rice Consumption Falls Ǡ The upper GI barium series is insensitive for jejunostomy and/or venting gastrostomy. measuring gastric emptying, as barium is not Ǡ New therapies under evaluation include in- C HICAGO — The increasing that the rising prevalence of a physiologic test meal. jection of botulinum toxin into the pyloric re- prevalence of Crohn’s disease in Crohn’s disease closely paralleled Ǡ Patients should stop drugs that could affect gion and gastric electric stimulation. Japan correlates closely with the the decreasing intake of fiber and gastric emptying for at least 48-72 hours prior decreasing consumption of rice, rice and the increasing intake of to a study. Opiate analgesics and anticholiner- Reference Ryosuke Shoda, M.D., said at the fiber from wheat and grains, Dr. gic agents can delay emptying. Serotonin re- Parkman H.P., et al. American Gastroentero- annual Digestive Disease Week. Shoda said. ceptor antagonists, such as , do not logical Association Technical Review on the Di- Crohn’s disease was once almost Of nine sources of fiber studied, affect emptying and can be continued. Other agnosis and Treatment of Gastroparesis. Gas- unknown in Japan, Dr. Shoda said rice was the only one that was in- drugs that can delay gastric emptying include troenterology 2004;127:1592-622. in a poster presentation. In the dependently correlated with the tricyclic antidepressants, calcium channel block- early 1960s and before, rice was the prevalence of Crohn’s disease. ers, progesterone, proton pump inhibitors, main source of dietary fiber in When changes in the consumption diphenhydramine, and L-dopa, as can alcohol. Japan, providing the average citi- of animal fat were included in the zen with about 28 g of fiber per analysis, rice remained the only Treatment day. Today, the average intake of independent factor. Ǡ Treatment should focus on correcting fluid fiber from rice is 12-15 g/day. Breakfast is the meal that has and electrolyte abnormalities, improving un- Meanwhile, the prevalence of changed the most in Japan and is derlying conditions, and reducing symptoms. Crohn’s disease went from virtu- probably the most responsible for Ǡ Dietary recommendations include eating ally nothing in the 1960s to 2.9 per the decline in rice consumption, small, frequent meals; increasing fluids; and re- 100,000 persons in the mid-1980s Dr. Shoda said in an interview. ducing fat and fiber intake. Carbonated bever- and about 14 per 100,000 today, Many people in Japan now eat bread ages can aggravate gastric distention. Alcohol said Dr. Shoda, chief of the de- rather than rice with breakfast. and tobacco products impair gastric function. DR. GOLDEN is professor of medicine and public partment of general internal med- Dr. Shoda declined to speculate Ǡ Maintaining euglycemia in patients with di- health and DR. HOPKINS is associate director of icine at the International Medical on what might explain the associ- abetes can improve gastric motor function as the medicine/pediatrics residency program at the Center of Japan, Tokyo. ation. “This is just statistics,” he well as the effects of prokinetic agents. University of Arkansas, Little Rock. Write to Dr. Data on fiber consumption and told this newspaper. “No one Ǡ Antiemetic agents are a primary therapy. Phe- Hopkins and Dr. Golden at our editorial offices or Crohn’s disease from the Japanese knows about this for certain. There nothiazines act on the area postrema of the [email protected]. Ministry of Health, Welfare, and must be other factors.” Labor from 1966 to 1993 show —Timothy F. Kirn