Lawrence Schiller
Texas A&M University, Internal Medicine, Faculty Member
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Diarrhea, defined as loose stools, occurs when the intestine does not complete absorption of electrolytes and water from luminal contents. This can happen when a nonabsorbable, osmotically active substance is ingested ("osmotic... more
Diarrhea, defined as loose stools, occurs when the intestine does not complete absorption of electrolytes and water from luminal contents. This can happen when a nonabsorbable, osmotically active substance is ingested ("osmotic diarrhea") or when electrolyte absorption is impaired ("secretory diarrhea"). Most cases of acute and chronic diarrhea are due to the latter mechanism. Secretory diarrhea can result from bacterial toxins, reduced absorptive surface area caused by disease or resection, luminal secretagogues (such as bile acids or laxatives), circulating secretagogues (such as various hormones, drugs, and poisons), and medical problems that compromise regulation of intestinal function. Evaluation of patients with secretory diarrhea must be tailored to find the likely causes of this problem. Specific and nonspecific treatment can be valuable.
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The association between upper gastrointestinal (GI) motility disorders and respiratory problems is reviewed. Upper GI motility disorders, such as gastroesophageal reflux disease, gastroparesis, and achalasia, have been associated with... more
The association between upper gastrointestinal (GI) motility disorders and respiratory problems is reviewed. Upper GI motility disorders, such as gastroesophageal reflux disease, gastroparesis, and achalasia, have been associated with respiratory problems, including aspiration, airway obstruction, asthma, bronchospasm, chronic cough, and laryngitis. These associations, which had been based solely on clinical observation, have recently been supported by physiologic studies and treatment trials. The association of reflux disease with asthma has the most support. Up to 80% of persons with asthma have evidence of pathologic gastroesophageal reflux, and in several studies antireflux therapy with prokinetic agents, antisecretory drugs, or fundoplication surgery has been found to reduce asthma symptoms and the need for medication in some patients. Reflux has also been associated with chronic cough and laryngitis, and antireflux therapy can reduce respiratory symptoms. Gastroesophageal reflux, gastroparesis, and achalasia are all associated with aspiration. In addition, in rare instances, the megaesophagus associated with achalasia can produce mechanical airway obstruction. Effective therapy for these GI motility disorders can eliminate complicating respiratory problems.
Research Interests: Gastroenterology, Asthma, Medicine, Humans, Child, and 14 moreInternal Medicine, Chronic Disease, Female, Male, Adult, Gastrointestinal motility, Cough, Achalasia, Gastroesophageal Reflux, Laryngitis, Gastroparesis, Pharmacology and pharmaceutical sciences, esophageal motility disorders, and Respiratory Tract Diseases
Point sources of Brainerd diarrhea are rarely identified, though cases of sporadic illness indistinguishable from Brainerd diarrhea have been reported in many states2,4. The recognition of point-source outbreaks of Brainerd diarrhea is... more
Point sources of Brainerd diarrhea are rarely identified, though cases of sporadic illness indistinguishable from Brainerd diarrhea have been reported in many states2,4. The recognition of point-source outbreaks of Brainerd diarrhea is complicated by the low rate of attack2 and a long and ...
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For some time, diarrhea caused by Clostridium difficile has been a serious problem in hospitals. Recently, more virulent strains of this pathogen have started to show up in hospitals.
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Adapted and reproduced from Drugs 2006; 66 (6): 873-81[1-3] New pharmacological treatments for chronic constipation are needed that are based on an understanding of the underlying pathophysiology. Lubiprostone (AmitizaTM)1 is an oral... more
Adapted and reproduced from Drugs 2006; 66 (6): 873-81[1-3] New pharmacological treatments for chronic constipation are needed that are based on an understanding of the underlying pathophysiology. Lubiprostone (AmitizaTM)1 is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the gastrointestinal epithelium.[4] An increase in the secretion of chloride-rich intestinal fluid increases intestinal motility and facilitates the passage of softened stool through the intestines and relieves the symptoms of constipation.[5] In two pivotal, randomised, double-blind, multicentre phase III studies in patients with chronic idiopathic constipation, the frequency of spontaneous bowel movements was significantly greater in patients receiving lubiprostone 24μg twice daily than in those receiving Features and properties of lubiprostone (AmitizaTM)[1]
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Research Interests: Gastroenterology, Educational Measurement, Informed Consent, Airway Management, Hepatology, and 15 moreEndoscopy, Curriculum, Continuing Medical Education, Humans, Female, Male, Benzodiazepines, Clinical Sciences, General Anesthesia, Gastrointestinal Endoscopy, Clinical Competence, Competency Based Education, Gastroenterology Nursing, Conscious Sedation, and Deep sedation
Research Interests: Research Design, Gastroenterology, Treatment Outcome, Medicine, Endoscopy, and 12 moreDiarrhea, Literature Review, Clinical Practice, Humans, Chronic Disease, United States, Clinical Sciences, Physical examination, Iron Deficiency Anemia, Neurosciences, Gastrointestinal bleeding, and Paediatrics and reproductive medicine
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Neurotrophin-3 (NT-3) is a neurotrophic factor involved in the growth, development, and function of the nervous system. In preliminary studies, s.c. recombinant methionyl-human NT-3 enhanced transit throughout the GI tract and increased... more
Neurotrophin-3 (NT-3) is a neurotrophic factor involved in the growth, development, and function of the nervous system. In preliminary studies, s.c. recombinant methionyl-human NT-3 enhanced transit throughout the GI tract and increased stool frequency in normal and constipated subjects. Our aim was to assess 1) the dose-related effects of NT-3 on bowel function, colon transit, and symptoms of chronic constipation, and 2) its safety. This was a double-blind, randomized, placebo-controlled phase II study. A total of 107 patients with a diagnosis of functional constipation (Rome II criteria) were randomized to receive 4 wk of double blind, s.c. injections of either placebo, 3 mg, or 9 mg NT-3 once per week (qW) or three times per week (TTW); or 9 mg NT-3 TTW for 1 wk, then qW. The primary endpoint was the change in number of spontaneous, complete bowel movements per week. Colon transit was assessed before and at end of treatment. Compared with placebo, patients who received 9 mg NT-3 TTW showed significant increases in frequency of spontaneous, complete bowel movements and total bowel movements, as well as dose-related softening of stool and improved ease of passage. The number of days per week without a bowel movement also decreased, colon transit improved, as did constipation-related symptoms. Weekly dosing was ineffective. Transient injection-site reactions, seen in one third of patients receiving NT-3 TTW, were the most frequent adverse event. NT-3, administered TTW, increased stool frequency, enhanced colon transit, and improved symptoms of chronic constipation. NT-3 seems to be a novel, safe, and effective agent for the treatment of functional constipation.
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Microscopic colitis syndrome consists of chronic watery diarrhea, a normal or near-normal gross appearance of the colonic mucosa, and a specific histologic picture described as either lymphocytic colitis or collagenous colitis. The cause... more
Microscopic colitis syndrome consists of chronic watery diarrhea, a normal or near-normal gross appearance of the colonic mucosa, and a specific histologic picture described as either lymphocytic colitis or collagenous colitis. The cause of microscopic colitis is unknown, but recent work suggests some immunologic similarities to celiac disease, suggesting that luminal antigens may be important in its pathogenesis. Diarrhea in microscopic colitis seems to be directly related to the extent of inflammation, suggesting that inflammatory mediators are responsible for reduced water absorption by the colon. Microscopic colitis is a frequent diagnosis in patients with chronic diarrhea seen at referral centers. It is often associated with other immune-mediated conditions and frequently is complicated by fecal incontinence. The differential diagnosis is broad, comprising all causes of watery diarrhea. Evaluation is straightforward with the key aspect being review of colon biopsy specimens by an experienced pathologist. Treatment is still being defined: symptomatic management with antidiarrheal agents, 5-aminosalicylate drugs, corticosteroids, especially budesonide, bile acid-binding resins, and bismuth subsalicylate all can be effective. The prognosis is good with no evidence of conversion to classic inflammatory bowel disease or of development of neoplasia over time.
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Diet often is blamed for digestive symptoms, particularly diarrhea, and patients with diarrhea and malabsorption usually request guidance about what to eat. Food-induced symptoms are very common. Although many recommendations have been... more
Diet often is blamed for digestive symptoms, particularly diarrhea, and patients with diarrhea and malabsorption usually request guidance about what to eat. Food-induced symptoms are very common. Although many recommendations have been made for dietary management in diarrheal diseases, there is little supportive evidence for efficacy for any of them. Knowledge of gastrointestinal physiology and the physiologic effects of foods can be used to design a dietary program for individual patients. Coordination of diet with drug therapy is an important part of a comprehensive treatment plan for these patients.
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One of the surprises of the flood of placebocontrolled, endoscopic, double-blind studies of duodenal ulcer healing in the last 10 yr has been the realization that placebo therapy results in healing in up to 50% of patients treated for 4-6... more
One of the surprises of the flood of placebocontrolled, endoscopic, double-blind studies of duodenal ulcer healing in the last 10 yr has been the realization that placebo therapy results in healing in up to 50% of patients treated for 4-6 wk and may approach the rate of healing noted with active therapy* after this time (;1,2). For example, in a large American multicenter double-blind study of cimetidine versus placebo for duodenal ulcer (3), a significant difference in healing rates was evident only at 2 wk but not at 4 or 6 wk. Even more striking is the similarity in symptom relief between placebo and active agents: no statistically significant differences are demonstrable in most studies (4-6). These observations have led some to conclude that ulcer therapy with currently available drugs such as antacids, antisecretory agents, or sucralfate may not be truly efficacious (7) and others to conclude that placebo treatment for peptic ulcer might be the ideal therapy: safe, cheap, and effective (8). These conclusions, however, may be wrong. Because of the relatively small size of each individual study, the good overall results with placebo might mask rare but important complications or problems that might be avoided by using active agents. To evaluate this, we examined the results of 48 double-
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In people with constipation, it is not known if decreased frequency of defecation is associated with abnormalities in the weight or in the consistency of stools or if the weight or the consistency of stools correlates with the severity of... more
In people with constipation, it is not known if decreased frequency of defecation is associated with abnormalities in the weight or in the consistency of stools or if the weight or the consistency of stools correlates with the severity of various discomforts associated with bowel movements. In neither normal nor constipated subjects has the consistency of stools been carefully correlated
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Acute diarrhea often runs a self-limited course and little by way of treatment is needed except for oral rehydration therapy. Chronic diarrhea poses a longer-term problem. If not treatable with specific therapy aimed at the underlying... more
Acute diarrhea often runs a self-limited course and little by way of treatment is needed except for oral rehydration therapy. Chronic diarrhea poses a longer-term problem. If not treatable with specific therapy aimed at the underlying pathophysiology, chronic diarrhea often needs long-term symptomatic therapy. This paper aims to examine the options for symptomatic, nonspecific treatment of diarrhea. The most frequently used therapies are opiate antidiarrheal drugs. These drugs are effective for a wide variety of diarrheal conditions and generally can be used safely if monitored closely. They work by slowing motility and allowing more time for absorption. They vary in potency and in addictive liability. In recent years, a variety of other drugs have been developed, which provide more targeted therapy that can mitigate diarrhea in specific situations. These drugs work on other regulatory pathways in the gut or on mucosal absorptive mechanisms. There is evidence for efficacy for both traditional and newer agents used for the symptomatic management of diarrhea. Opiates are used most often for this indication. Other agents may benefit individuals, but further research is needed to establish indications and best practices.
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Little is known about the clinical presentation and natural history of previously healthy patients in whom chronic idiopathic diarrhea develops. We reviewed the case records of 152 patients with chronic diarrhea who had no history of... more
Little is known about the clinical presentation and natural history of previously healthy patients in whom chronic idiopathic diarrhea develops. We reviewed the case records of 152 patients with chronic diarrhea who had no history of gastrointestinal surgery and who were evaluated in detail as part of a chronic-diarrhea protocol from 1985 to 1990. Patients were considered to have chronic idiopathic diarrhea if they had persistently loose stools for more than four weeks, no systemic illness, and no identifiable cause of diarrhea. Seventeen patients (10 men and 7 women) ranging in age from 33 to 72 years met the criteria for chronic idiopathic diarrhea. Each patient had a history of a relatively abrupt onset of symptoms, often soon after returning home from a trip, starting two to seven months before evaluation. Their diarrhea did not occur during a local outbreak of diarrhea, and other family members did not become ill. Stool frequency ranged from 5 to 25 movements per day, stool weights ranged from 417 to 1480 g per day, and fecal electrolyte and osmolality values were consistent with a diagnosis of secretory diarrhea. The results of biopsies of the small intestine and colon were normal, as were small-bowel roentgenograms. Extensive studies for infectious causes of diarrhea were negative, and no patient responded to antibiotic therapy. In every patient the diarrhea stopped without specific therapy after 7 to 31 months (mean, 15) and did not recur during a follow-up period averaging 38 months. Sporadic idiopathic chronic diarrhea is a recognizable syndrome that can last many months, but is self-limited.
Research Interests: Nursing, Diarrhea, Travel, Humans, Chronic Disease, and 12 moreFemale, Male, Aged, Middle Aged, Adult, New England, Public health systems and services research, Feces, New England Journalof Medicine, Occupational and environmental medicine, Medical and Health Sciences, and Paediatrics and reproductive medicine
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Chronic constipation remains a therapeutic challenge for today's physicians. Traditional approaches include use of fiber, osmotic laxatives, stimulant laxatives, prokinetic agents, biofeedback training, and... more
Chronic constipation remains a therapeutic challenge for today's physicians. Traditional approaches include use of fiber, osmotic laxatives, stimulant laxatives, prokinetic agents, biofeedback training, and surgery. These often are tried sequentially and episodically and have little evidence of long-term efficacy. Patients often report inadequate relief of symptoms. There is room for improvement, therefore, in the therapy of chronic constipation. Future advances largely will be based on insights into the enteric nervous system (ENS), the structure and function of which is being revealed in great detail. Manipulating the ENS pharmacologically offers the opportunity to reprogram this key control system to improve bowel function. For example, interneurons in the ENS display 5-HT4 receptors, activation of which enhances the peristaltic reflex. Prokinetic agents that stimulate those receptors, such as tegaserod and prucalopride, have demonstrated efficacy as investigational agents for the treatment of chronic constipation in large studies. Less well studied investigational drugs with presumed activity in the ENS include opiate antagonists and the nerve growth factor neurotrophin-3. Both of these types of agents have been shown to be effective in small groups of patients with constipation. Another approach under development is to stimulate colonic fluid secretion by opening chloride channels in the epithelium pharmacologically. Existing non-pharmacological treatments that can be improved include biofeedback training for pelvic floor dysfunction and surgery. Future developments include investigation of electrical stimulation of the colon and use of stem cells to repopulate degenerated populations of neurons, interstitial cells of Cajal, or smooth muscle cells.
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Constipation is a common symptom that may be idiopathic or due to various identifiable disease processes. Laxatives are agents that add bulk to intestinal contents, that retain water within the bowel lumen by virtue of osmotic effects, or... more
Constipation is a common symptom that may be idiopathic or due to various identifiable disease processes. Laxatives are agents that add bulk to intestinal contents, that retain water within the bowel lumen by virtue of osmotic effects, or that stimulate intestinal secretion or motility, thereby increasing the frequency and ease of defecation. Drugs which improve constipation by stimulating gastrointestinal motility by direct actions on the enteric nervous system are under development. Other modalities used to treat constipation include biofeedback and surgery. Laxatives and lavage solutions are also used for colon preparation and evacuation of the bowels after toxic ingestions.