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Managing Functional Disturbances in Patients with Inflammatory Bowel Disease.

Functional disturbances occur in approximately 10% to 15% of the general population and in a similar percentage of patients with inflammatory bowel disease (IBD). Because overlapping irritable bowel syndrome (IBS) is so common, one of the most important interventions a clinician can make is recognizing its existence. This requires a thorough understanding of underlying pathophysiologic processes. Differentiating among the causes of symptoms is especially significant in a minority of patients mislabeled as having 'refractory IBD.' Escalating therapy directed at disease activity may have no effect on functional symptoms other than to reinforce their presence. Treatment of IBS in patients with IBD is similar to that of the general population. The cornerstone of treatment is establishing a constructive doctor-patient relationship. Initial therapy usually involves a conservative approach that includes patient education and diet and lifestyle modifications. Pharmacologic treatment is individualized and generally directed at the predominant symptoms. Options may broadly include antispasmodics, antidiarrheals, and antidepressants, either alone or in combination. Psychosocial therapies have shown to be beneficial in selected individuals.

Journal Article↗

Fecal incontinence.

Fecal incontinence is a multifactorial disorder that is often poorly understood and treated primarily by practicing physicians. Fecal impaction with overflow incontinence can be identified by patient history and physical examination and can be appropriately treated. For the remaining patients, diarrhea is a common aggravating factor that is frequently modulated by dietary changes, antidiarrheal agents, and occasionally by bile salt binders. When patients do not respond to conservative therapy, diagnostic studies to evaluate anorectal continence mechanisms are very helpful. Available therapies include biofeedback and pelvic floor retraining, surgery, and in the future, sacral nerve stimulation in carefully selected patients.

Journal Article↗

Treatment of functional diarrhea.

Functional diarrhea (FD), one of the functional gastrointestinal disorders, is characterized by chronic or recurrent diarrhea not explained by structural or biochemical abnormalities. The treatment of FD is intimately associated with establishing the correct diagnosis. First, FD needs to be distinguished from diarrhea-predominant irritable bowel syndrome (IBS), in which, unlike in FD, abdominal pain is a primary diagnostic criterion. Next, FD must be differentiated from the myriad organic causes of chronic diarrhea. Unlike IBS, in which a positive diagnosis can be made with an acceptable level of confidence using symptom-based criteria and minimal testing, the diagnosis of FD is still primarily a diagnosis of exclusion. Thus, the onus is on the physician to eliminate potential underlying causes, both common and uncommon, in the proper clinical setting. Once the diagnosis has been established, the clinician and patient should first focus on identifying, eliminating, and/or treating aggravating factors. These may include physiologic factors (eg, small bowel bacterial overgrowth), psychological factors (eg, stress and anxiety), and dietary factors (eg, carbohydrate malabsorption). Thereafter, appropriate treatment for functional diarrhea may be instituted. Treatment options include dietary and lifestyle modification, pharmacologic therapies, and alternative modalities. Although many of these strategies have been studied in IBS, almost none of them has been examined specifically in FD. Furthermore, given the poorly understood pathophysiologic basis of FD, these treatments primarily target a patient's symptoms and presumed altered physiology rather than underlying etiologic mechanisms. Therefore, we stress that treatment must be approached in an individualized manner and that dietary and pharmacologic therapies should be part of a comprehensive therapeutic approach in which education and reassurance form the foundation. In general, we attempt to remove dietary triggers and recommend increased fiber intake. We then add anticholinergic, antispasmodic, antimotility, and antidiarrheal agents as the first line of pharmacotherapy. Should a patient not respond to these, and for patients who have a significant degree of psychological dysfunction, central acting agents, including antidepressants and/or anxiolytics, may be beneficial. During the treatment period, we also recommend that physicians keep an open mind. If signs or symptoms that suggest an ongoing or previously unrecognized organic process develop, then a re-evaluation of the clinical picture is indicated.

Journal Article↗

Diarrhea in patients with AIDS.

Diarrhea in patients with AIDS is a worldwide problem that can have a devastating impact on quality of life for the patient. Chronic diarrhea, usually defined as at least 4 weeks' duration, is more common in patients with low CD4-positive T-lymphocyte counts, signaling advanced immunosuppression. Some organisms, such as Microsporidia, usually cause diarrhea only in the immunosuppressed; others, such as Cryptosporidium, Salmonella, Shigella, and Campylobacter, which are capable of causing diarrhea in the immunocompetent population, produce more severe or prolonged infections in people living with AIDS. Familiarity with the most common pathogens in the clinician's region will help with diagnosis and treatment. Because treatment options vary widely depending upon the infectious agent, thorough microbiologic evaluation is warranted. A stepped diagnostic approach of stool cultures and specialized microscopy and stains for protozoa, followed by sigmoidoscopy or colonoscopy and duodenoscopy with biopsies for histopathological examination is recommended in all patients with persistent, disabling diarrhea who have a CD4 count of less than 200/mm3, and should be considered for those with higher counts on an individual basis. Treatment, tailored to the specific pathogen, may need to be prolonged in the most severely immunocompromised patients to prevent relapse or recrudescence. For patients taking antiretroviral therapy (especially protease inhibitors) in whom no infectious agent can be found, diarrhea may be due to the medications. Nonspecific antidiarrheal agents should be tried until one that suits the patient is found. The most essential component of any therapeutic strategy for a patient with AIDS-associated diarrhea is restoration of the underlying immunologic defect using highly active antiretroviral therapy.

Journal Article↗

Irritable Bowel Syndrome.

I believe there are four essential elements in the management of patients with irritable bowel syndrome (IBS): to establish a good physician-patient relationship; to educate patients about their condition; to emphasize the excellent prognosis and benign nature of the illness; and to employ therapeutic interventions centering on dietary modifications, pharmacotherapy, and behavioral strategies tailored to the individual. Initially, I establish the diagnosis, exclude organic causes, educate patients about the disease, establish realistic expectations and consistent limits, and involve patients in disease management. I find it critical to determine why the patient is seeking assistance (eg, cancer phobia, disability, interpersonal distress, or exacerbation of symptoms). Most patients can be treated by their primary care physician. However, specialty consultations may be needed to reinforce management strategies, perform additional diagnostic tests, or institute specialized treatment. Psychological co-morbidities do not cause symptoms but do affect how patients respond to them and influence health care-seeking behavior. I find that these issues are best explored over a series of visits when the physician-patient relationship has been established. It can be helpful to have patients fill out a self-administered test to identify psychological co-morbidities. I often use these tests as a basis for extended inquiries into this area, resulting in the initiation of appropriate therapies. I encourage patients to keep a 2-week diary of food intake and gastrointestinal symptoms. In this way, patients become actively involved in management of their disease, and I may be able to obtain information from the diary that will be valuable in making treatment decisions. I do not believe that diagnostic studies for food intolerances are cost-effective or particularly helpful; however, exclusion diets may be beneficial. I introduce fiber supplements gradually and monitor them for tolerance and palatability. Synthetic fiber is often better-tolerated than natural fiber, but must be individualized. In my experience, excessive fiber supplementation often is counterproductive, as abdominal cramps and bloating may worsen. Antidiarrheal agents are very effective when used correctly, preferably in divided doses. I use them in patients in anticipation of diarrhea and especially in those who fear symptoms when engaged in activities outside the home. I encourage patients to make decisions as to when and how much to use. However, almost always, a morning dose before breakfast is used (loperamide, 2 to 6 mg) and, perhaps again later in the day when symptoms of diarrhea are prominent. I prefer antispasmodics to be used intermittently in response to periods of increased abdominal pain, cramps, and urgency. For patients with daily symptoms, especially after meals, agents such as dicyclomine before meals are useful. For patients with infrequent but severe episodes of unpredictable pain, sublingual hyoscyamine often produces rapid relief and instills confidence. In general, I recommend that oral antispasmodics be used for a limited period of time rather than indefinitely, and generally for periods of time when symptoms are prominent. For chronic visceral pain syndromes, I recommend small doses of tricyclic antidepressants. These agents are especially effective in diarrhea-predominant patients with disturbed sleep patterns but may be unacceptable to patients with constipation. I educate patients that side effects occur early and benefits may not be apparent for 3 to 4 weeks. I consider using SSRIs in low doses in patients with constipation-predominant IBS; cisapride, 10 to 20 mg three times per day, also may be beneficial. When taken with drugs that inhibit cytochrome P450, cisapride has been associated with serious cardiac arrhythmias caused by QT prolongation, including ventricular arrhythmias and torsades de pointes. These drugs include the azole fungicides; erythromycin, clarithromycin, and troleandomycin; some antidepressants; HIV protease inhibitors; and others. In patients with IBS with mild to moderate co-morbid depression, I have found that the use of SSRIs such as paroxetine, fluoxetine, or sertraline may be beneficial. It is important to tell patients that anxiety and disturbed sleep may occur during the first 10 days and benefits may not occur for 3 to 4 weeks. I prescribe a small amount of a short-acting benzodiazepine such as alprazolam, 0.5 mg two times per day, to control these symptoms. For generalized anxiety without depression, buspirone or clonazepam may be useful. I have found that patients who also have associated panic disorder may benefit from a benzodiazepine, tricyclic antidepressant, or an SSRI. However, these patients are best managed in conjunction with a psychiatrist or psychologist. I consider the use of alternative therapies in patients who fail to respond to conventional measures and who are receptive to alternative strategies. These include general relaxation techniques such as biofeedback and hypnosis therapies.

Journal Article↗

Lymphocytic and Collagenous Colitis: Medical Management.

When possible, patients taking nonsteroidal anti-inflammatory medications should discontinue them when the diagnosis of microscopic colitis is made. Although there is no direct evidence of its efficacy, a trial of elimination of caffeine or lactose or both should be undertaken. Nonspecific antidiarrheal agents (eg, loperamide, diphenoxylate) may be administered, but appear to be largely ineffective in this population. An aminosalicylate should be initiated at full therapeutic dose (2 to 4 g daily) as the first-line therapy. Because sulfasalazine appears to be associated with a high incidence of adverse effects in patients with microscopic colitis, other derivatives of 5-aminosalicylate (5-ASA) are preferred. Bile salt-binding agents such as cholestyramine or colestipol appear to be effective alternatives for patients who are either unresponsive to or intolerant of aminosalicylates. Systemic corticosteroids are an effective treatment for microscopic colitis, but may offer only transient improvement in symptoms. Given their potential adverse effects, corticosteroids should be reserved for patients with refractory disease in whom aminosalicylates and bile salt-binding agents have failed. Other agents that may be effective include antibiotics, bismuth subsalicylate, budesonide, pentoxifylline, octreotide, and methotrexate. Although these agents can be considered in unusual cases, the cumulative clinical experience with them in this setting is relatively limited. Surgical intervention, with either fecal stream diversion or subtotal colectomy, shows promise as an intervention of last resort. In refractory cases of microscopic colitis, strong consideration should be given to excluding a concomitant diagnosis of celiac disease, bacterial overgrowth, or chronic infection.

Journal Article↗

Mid-trimester abortion induced by intravaginal administration of prostaglandin E2 suppositories.

Mid-trimester abortion was successfully induced in 70 of 71 patients by administration of vaginal PGE2 suppositories. The one patient who failed to abort with this method was pregnant in the blind horn of a duplex uterus. The mean abortion time for the successful inductions was 11.88 hours. Multiparous patients aborted somewhat faster than nulliparous patients, but the difference was not significant. Among the 70 successful inductions 42 patients aborted in 12 hours or less and only one patient had an abortion time of more than 24 hours. The drug appeared effective throughout the stages of gestation included in this series--from 8 to 27 weeks. Eight patients were monitored throughout the abortion procedure and uterine activity was calculated and analyzed. The development of uterine activity was gradual without the sudden rise in frequency of contractions and intrauterine baseline tonus that characterized prostaglandin administered by other methods. The most frequently encountered side effect of vaginal PGE2 suppositories was a temperature elevation, which returned to normal within a few hours of the last dose of the drug. Gastrointestinal disturbances--vomiting and diarrhea--were also common, despite a low initial dose of PGE2 and premedication with antiemetic and antidiarrheal agents. These side effects were in general well tolerated by the patients and never required termination of therapy. The cardiovascular effects of PGE2 in this series could be considered minimal. In a single patient surgical intervention was required to remove the placenta. In seven patients the placenta was removed by sponge forceps and in five patients the placenta was removed manually. There was an estimated blood loss exceeding 250 ml. in 10 patients, but transfusion was not required. Although white blood cell count rose significantly during the abortion period there were no significant changes in hematocrit or platelet count. Mid-trimester abortion with intravaginal administration of PGE2 suppositories appears to offer a valid alternative to the presently available techniques, with a rapid abortion time, high success rate, and low incidence of complications.

Abortion, Induced↗

Management of intrauterine fetal death with prostaglandin E2 vaginal suppositories.

The recent Food and Drug Administration's approval of prostaglandin E2 (PGE2) vaginal suppositories provides the clinician with a technique for the immediate management of missed abortion and intrauterine fetal death (IUFD). During a 4-year period at our institution, 78 of 80 patients with gestations ranging from 13 to 42 weeks had pregnancy successfully terminated with PGE2 suppositories with a dose schedule of 20 mg every 2 hours. The mean interval from induction to delivery of the fetus was 8.9 hours. Fifty percent of the patients spontaneously expelled the placenta; active intervention to remove the placenta within 2 hours of delivery of the fetus is recommended to avoid excessive vaginal bleeding. The most frequently encountered side effect was a temperature elevation, which was managed by less frequent administration of the prostaglandin. Gastrointestinal side effects were minimized by premedication with antidiarrheal and antiemetic agents, which also were administered during the induction period when indicated by the patient's symptoms. A concomitant oxytocin infusion was utilized in 38 patients. In gestations of less than 24 weeks the oxytocin was administered via intravenous drip at a rate of 10 U/hour. In the case of a patient with IUFD and a gestation of 24 weeks or more, oxytocin should be administered only with a constant-rate infusion pump starting at a dose schedule of 1 mU/minute with careful titration of the dose against the monitored uterine activity. The availability of the vaginal PGE2 suppositories for missed abortion and IUFD makes it important for the clinician to fully acquaint himself with the drug, its administration, effects, and side effects.

Abortion, Therapeutic↗

Typhlitis: selective surgical management.

Typhlitis is a neutropenic enterocolitis of varying severity. Its incidence is increasing, particularly in patients with acute myelogenous leukemia undergoing high dose cytosine arabinoside chemotherapy. The onset is heralded by prodromal fever, watery or bloody diarrhea, abdominal distension, and nausea during the phase of severe neutropenia. The symptoms may then localize to the right lower quadrant with an associated increase in systemic toxicity. The diagnosis can be confirmed in these and other less specific cases by serial reexamination and abdominal radiographs, ultrasonography, computerized tomograms, or radionucleotide scans. The mainstay of management is complete bowel rest with nasogastric suction and total parenteral nutrition. Broad-spectrum combination antibiotics are essential, as is the avoidance of laxatives or antidiarrheal agents. Granulocyte support may be helpful. Patients with a history of nonspecific gastrointestinal complaints or of true typhlitis, successfully managed nonoperatively, should have prophylactic bowel rest and total parenteral nutrition instituted at the beginning of further chemotherapy. Patients with ongoing severe systemic sepsis who do not respond to chemotherapy and those with overt perforation, obstruction, massive hemorrhage, or abscess formation require surgical intervention. All necrotic material must be resected, usually by a right hemicolectomy, ileostomy, and mucous fistula. Divided ileostomy for less severe cases may be useful. Failure to remove the necrotic focus in these severely immunocompromised patients is fatal. With adequate recognition of typhlitis and its precipitating factors, the incidence of complications can be reduced through prevention and timely surgical intervention. Although typhlitis developed in a quarter of our acute myeloblastic leukemia patients, use of this combined approach was successful in all cases.

Adolescent↗

Inflammatory bowel disease. Part I: Nature and pathogenesis.

Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis; however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addresses the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focuses on microbial, immunologic, and genetic mechanisms and the inflammatory processes involved in the disease. In part II, which will be presented in next month's issue of Disease-a-Month, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease, the laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. The IBDs are mimicked by several enterocolonic infections and other conditions, making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodic preparations and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha 2/alpha 1-selectivity of test compounds: (1). Alpha-adrenoceptor antagonists.

Twenty one chemically dissimilar alpha-adrenoceptor antagonists were assessed in 7 different tests. The potencies of the compounds to protect rats from norepinephrine lethality were closely correlated with their potencies for inhibition of [3H]WB4101, but not of [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding to rat brain homogenates. The reverse was found for the potencies of the compounds to prevent the antidiarrheal effect of clonidine. The in vivo anti-norepinephrine/anti-clonidine potency ratios were highly correlated with the ratios between the in vitro potency to inhibit [3H]WB4101 binding on one hand and [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding on the other. The reliability of the above models for measuring alpha 1- and alpha 2-adrenoceptor antagonistic activity and selectivity is discussed.

Adrenergic alpha-Antagonists↗

Lidamidine inhibits intrinsic contractile patterns of the rat proximal colon.

Lidamidine is a clinically effective antidiarrheal agent that inhibits intestinal secretion, reduces intestinal transit, and inhibits smooth muscle contraction. Yet, its specific effects upon colonic motility have not been thoroughly examined. The purpose of our studies was to examine lidamidine's inhibitory effects upon colonic contractile patterns in the rat and identify the responsible receptor mechanism. Fasted male rats were anesthetised and equipped with an intraluminal cannula positioned at the proximal end of a 10 cm fluid-filled segment of the ascending colon (basal pressure, 10 cm H2O). Intraluminal pressure was monitored by a transducer attached to a closed fluid-filled system. All drugs were administered intravenously by slow infusion. A regular pattern of distinct contractile complexes was observed over a 70 min period. These contractions increased intraluminal pressure to 39 +/- 1.2 cm H2O (mean +/- S.E.), occurred at a frequency of 0.3 per min and lasted from 1 to 2.5 min. Inhibition of these contractile patterns was observed with either atropine (0.1 mg/kg) or lidamidine (3.0 mg/kg). A 20 min pretreatment with idazoxan (3.0 mg/kg) antagonized lidamidine's but not atropine's effect. Trimazosin (1 mg/kg) or propranolol (0.3 mg/kg) pretreatment did not antagonize the lidamidine-generated inhibition. These results indicate that lidamidine inhibits an intrinsically generated, cholinergically controlled pattern of colonic contractions primarily by an alpha 2-receptor-mediated mechanism.

Adrenergic beta-Agonists↗

Inhibition by loperamide of mucus secretion in the rat colon in vivo.

The effect of loperamide on mucus secretion and the net transport of fluid, sodium and potassium was investigated in the perfused rat colon in vivo. Prostaglandin E2 (PGE2, 1 mg/kg per h intraarterially) and deoxycholic acid (2 mM intraluminally) were used as secretagogues. Mucus secretion was determined as the total amount of protein-bound hexose in the effluent. Under basal conditions, loperamide (6 mg/kg subcutaneously) slightly decreased mucus secretion and increased the absorption of fluid and sodium. PGE2 and deoxycholic acid stimulated mucus secretion about 4- and 9-fold, respectively. Loperamide abolished the mucus secretory response to PGE2 and reduced the response to deoxycholic acid by 50%. It also reduced the fluid secretion following PGE2 but did not affect the diminished fluid absorption following deoxycholic acid. Potassium secretion was not significantly influenced by loperamide and therefore was independent of the secretion of mucus. The data suggest that loperamide is a potent inhibitor of colonic mucus secretion, a property that possibly contributes to the antidiarrheal effect of this opiate analogue.

Animals↗

Naloxone-insensitive transport effects of loperamide in guinea-pig gallbladder epithelium.

The effects of the antidiarrheal drug, loperamide, on HCO3 and Na transport across guinea-pig gallbladder epithelium were investigated using Ussing-chamber methods. Under basal conditions, mucosal loperamide (10(-4) mol/l) moderately lowered both the absorptive (JHCO3ms) and the secretory HCO3 flux (JHCO3sm) (pH-stat method), most likely by changing paracellular HCO3 flow. Exposure to serosal prostaglandin E1 (10(-6) mol/l) abolished Na absorption and turned HCO3 secretion electrogenic. The associated short-circuit current (Isc) was inhibited by loperamide in a concentration-dependent manner; mucosal addition (threshold at 3 x 10(-6) mol/l) of the drug was more effective. Inhibition of Isc was related to a decrease in JHCO3sm, but exceeded the drop in JHCO3net. The effects on JHCO3sm and Isc were mimicked by [Met5]enkephalin. Naloxone (10(-6) mol/l) was unable to influence the effects of loperamide and [Met5]enkephalin on Isc. There were no pro-absorptive effects of loperamide on unidirectional Na fluxes. We conclude that antisecretory properties of loperamide are solely due to inhibition of electrogenic HCO3 secretion, an effect unrelated to opiate receptor binding.

Alprostadil↗

Studies on the mechanism of bowel disturbance in ulcerative colitis.

The transit of a radiolabeled meal through the gastrointestinal tract and stool output were measured in 62 patients with ulcerative colitis, subdivided according to the activity and extent of their disease. The results were compared with those from 20 sex-matched normal subjects. Mouth-to-cecum transit was significantly slower than normal in all patient groups although gastric emptying was normal. Whole gut transit was not accelerated in any group of patients. An abdominal x-ray taken 48 h after ingesting the meal showed that patients with active colitis had proximal colonic stasis, whereas transit through the rectosigmoid region was rapid. Stool weights and frequencies were higher in patients with active colitis than in patients with quiescent disease. Patients with active colitis also passed smaller amounts of stool during each bowel movement, suggesting that they experienced a desire to defecate at lower rectal volumes. These results indicate that (a) diarrhea in ulcerative colitis is associated with rectosigmoid irritability rather than rapid transit and (b) caution should be used when treating active colitis with antidiarrheal drugs that could further retard proximal colonic transit.

Colitis, Ulcerative↗

Effect of berberine on myoelectric activity and transit of the small intestine in rats.

The motility of the small intestine in unanesthetized rats receiving berberine sulfate (0.2, 2.0, and 20.0 mg/kg i.p.) was investigated. Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na51CrO4). The 20.0-mg/kg dose caused a marked inhibition of spike activity for 21.8 +/- 7.0 min and disrupted activity fronts of the migrating myoelectric complex for 212.3 min. Berberine, 2.0 mg/kg i.p., disrupted migrating myoelectric complexes for 64.6 min but spike inhibition was not observed. Transit of the small intestine was significantly (p less than 0.001) delayed at 15 and 100 min after the highest dose of berberine. Naloxone blocked the spike inhibition noted with 20.0 mg/kg of berberine but failed to improve transit. Phentolamine blocked spike inhibition and was associated with a significantly earlier return of activity fronts of the migrating myoelectric complex. Animals pretreated with this antagonist tended toward a higher geometric center in transit studies than those injected with berberine alone. Berberine was also administered by various routes (intraperitoneal injection, intravenous injection, orogastric gavage, and intraluminal injection). An intraperitoneal injection was 10-fold more potent than an intravenous injection. Orogastric gavage and intraluminal administration of berberine did not alter intestinal motility. In summary, berberine sulfate significantly inhibits myoelectric activity and transit of the small intestine. This appears to be partially mediated by opioid and alpha-adrenergic receptors. The antidiarrheal properties of berberine may be mediated, at least in part, by its ability to delay small intestinal transit.

Administration, Oral↗

Cessation of Cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum.

Cryptosporidium is a parasite of the human gastrointestinal tract that can cause life-threatening diarrhea in immunodeficient patients. Although more than 80 agents have been tried with occasional anecdotal success, treatment remains primarily limited to hydration. A 38-yr-old homosexual man with antibody to human immunodeficiency virus and Cryptosporidium-related diarrhea is described. The patient excreted 6-12 L of stool per day for at least 3 mo, 2 of them spent in the hospital. Trials with more than 6 antidiarrheal medications were ineffective. The patient received bovine colostrum hyperimmune to Cryptosporidium by direct duodenal infusion. During infusion, the patient's fecal output decreased to less than 2 L per day, and 48 h after treatment, stools were formed and oocysts to Cryptosporidium were absent. The patient remained asymptomatic for 3 mo. Hyperimmune bovine colostrum offers an exciting new therapy for cryptosporidiosis; controlled trials to establish efficacy should be undertaken and the active factor(s) characterized.

Acquired Immunodeficiency Syndrome↗

Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea.

BACKGROUND/AIMS: Diarrhea is a significant problem in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine octreotide effectiveness in refractory AIDS-associated diarrhea. METHODS: In a 3-week protocol, 129 patients with a stool weight of > 500 g/day despite standard antidiarrheal therapy were randomized to receive octreotide or placebo (3:2 ratio). Octreotide dose was increased 100 micrograms weekly to a maximum of 300 micrograms three times a day based on weekly 72-hour stool collections. Subsequently, patients received open-label octreotide at doses of up to 500 micrograms three times a day. RESULTS: A 30% decrease in stool weight defined response. After 3 weeks, 48% of octreotide- and 39% of placebo-treated patients had responded (P = 0.43). At 300 micrograms three times a day, 50% of octreotide- and 30.1% of placebo-treated patients responded (P = 0.12). At a baseline stool weight of 1000-2000 g/day, 57% of octreotide- and 25% of placebo-treated patients responded (P = 0.06). Response rates based on CD4 counts, diarrhea duration, body weight, human immunodeficiency virus risk factor, and presence or absence of pathogens showed no benefit of octreotide. Adverse events were more frequent in the octreotide-treated group. CONCLUSION: In the doses studied, octreotide was not more effective than placebo in patients with refractory AIDS-associated diarrhea. This lack of effectiveness may be attributable to inadequate sample size, doses, and duration of study treatment.

Acquired Immunodeficiency Syndrome↗