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Robert W Summers

Publications and source records attributed to Robert W Summers.

14 recordsLinked to original sources
PubMed2007

Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial.

BACKGROUND: Calcium supplementation has been shown to decrease the risk of recurrence of colorectal adenomas in randomized trials. However, the duration of this protective effect after cessation of active supplementation is not known. METHODS: In the Calcium Polyp Prevention Study, 930 subjects with a previous colorectal adenoma were randomly assigned from November 1988 through April 1992 to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium Follow-up Study was an observational phase of the trial that tracked adenoma occurrence for an average of 7 years after the end of randomized treatment and gathered information regarding the use of medications, vitamins, and supplements during that time. We obtained follow-up information for 822 subjects, 597 of whom underwent at least one colonoscopy after the end of study treatment and are included in this analysis. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of randomized calcium treatment on risk of adenoma recurrence during the first 5 years after study treatment ended and during the subsequent 5 years. Statistical tests were two-sided. RESULTS: During the first 5 years after randomized treatment ended, subjects in the calcium group still had a substantially and statistically significantly lower risk of any adenoma than those in the placebo group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005) and a smaller and not statistically significant reduction in risk of advanced adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the randomized treatment was not associated with the risk of any type of polyp during the next 5 years. The findings were broadly similar when the analysis was restricted to subjects who did not report use of any calcium supplements after the treatment phase of the trial ended. CONCLUSION: The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to 5 years after cessation of active treatment, even in the absence of continued supplementation.

Adenoma↗
PubMed2005

Role of helminths in regulating mucosal inflammation.

The rapid rise in prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in highly developed countries suggests that environmental change engenders risk for inflammatory bowel disease (IBD). Eradication of parasitic worms (helminths) through increased hygiene may be one such change that has led to increased prevalence of these diseases. Helminths alter host mucosal and systemic immunity, inhibiting dysregulated inflammatory responses. Animals exposed to helminths are protected from experimental colitis, encephalitis, and diabetes. Patients with CD or UC improve when exposed to whipworm. Lamina propria (LP) mononuclear cells from helminth-colonized mice make less interleukin (IL)-12 p40 and IFN-gamma, but more IL-4, IL-13, IL-10, TGF-beta, and PGE(2) compared to LP mononuclear cells from naive mice. Systemic immune responses show similar skewing toward Th2 and regulatory cytokine production in worm-colonized animal models and humans. Recent reports suggest that helminths induce regulatory T cell activity. These effects by once ubiquitous organisms may have protected individuals from many of the emerging immune-mediated illnesses like IBD, multiple sclerosis, type I diabetes, and asthma.

Animals↗
PubMed2005

Measurement of gastrointestinal transit.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.

Breath Tests↗
PubMed2005

Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial.

BACKGROUND & AIMS: Ulcerative colitis is most common in Western industrialized countries. Inflammatory bowel disease is uncommon in developing countries where helminths are frequent. People with helminths have an altered immunological response to antigens. In animal models, helminths prevent or improve colitis by the induction of regulatory T cells and modulatory cytokines. This study determined the efficacy and safety of the helminth Trichuris suis in therapy of ulcerative colitis. METHODS: This was a randomized, double blind, placebo-controlled trial conducted at the University of Iowa and select private practices. Trichuris suis ova were obtained from the US Department of Agriculture. The trial included 54 patients with active colitis, defined by an Ulcerative Colitis Disease Activity Index of > or =4. Patients were recruited from physician participants and were randomly assigned to receive placebo or ova treatment. Patients received 2500 Trichuris suis ova or placebo orally at 2-week intervals for 12 weeks. RESULTS: The primary efficacy variable was improvement of the Disease Activity Index to > or =4. After 12 weeks of therapy, improvement according to the intent-to-treat principle occurred in 13 of 30 patients (43.3%) with ova treatment compared with 4 of 24 patients (16.7%) given placebo (P = .04). Improvement was also found with the Simple Index that was significant by week 6. The difference in the proportion of patients who achieved an Ulcerative Colitis Disease Activity Index of 0-1 was not significant. Treatment induced no side effects. CONCLUSIONS: Ova therapy seems safe and effective in patients with active colitis.

Administration, Oral↗
PubMed2005

Colorectal cancer in patients under close colonoscopic surveillance.

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.

Adenoma↗
PubMed2005

Gastric emptying and intestinal absorption of a low-carbohydrate sport drink during exercise.

The purpose of this study was to determine if lowering carbohydrate (CHO) concentration in a sport drink influences gastric emptying, intestinal absorption, or performance during cycle ergometry (85 min, 60% VO(2peak)). Five subjects (25 +/- 1 y, 61.5 +/- 2.1 mL . kg(-1) . min(-1) VO(2peak)) ingested a 3% CHO, 6% CHO, or a water placebo (WP) beverage during exercise. Gastric emptying was determined by repeated double sampling and intestinal absorption by segmental perfusion. Total solute absorption and plasma glucose was greater for 6% CHO; however, neither gastric emptying, intestinal water absorption, or 3-mi time trial performance (7:58 +/- 0:33 min, 8:13 +/- 0:25 min, and 8:25 +/- 0:29 min, respectively, for 6% CHO, 3% CHO, and WP) differed among solutions. These results indicate lowering the CHO concentration of a sport drink from 6% CHO does not enhance gastric emptying, intestinal water absorption, or time trial performance, but reduces CHO and total solute absorption.

Adult↗
PubMed2005

Helminths and the modulation of mucosal inflammation.

PURPOSE OF REVIEW: Inflammatory bowel disease is an emerging illness associated with socioeconomic development. The current epidemic of immune-mediated diseases may result from our loss of exposure to parasitic worms (helminths). This review summarizes some of the recent findings showing that helminths induce regulatory circuits that could prevent and treat inflammatory bowel disease. RECENT FINDINGS: Inflammatory bowel disease appears to result from a dysregulated immune response. Although genes influence the risk of inflammatory bowel disease, it seems that critical changes in our environment have permitted its expression. One such change is the eradication of helminths. Helminths can impede interleukin-12, interferon gamma, and tumor necrosis factor alpha release and promote interleukin-10, transforming growth factor beta, and regulatory T-cell production. Helminths can prevent and reverse intestinal inflammation in animal models of inflammatory bowel disease. In clinical studies of patients with inflammatory bowel disease, exposure to the helminth Trichuris suis reduces disease activity. SUMMARY: If harboring helminths protects against immune-mediated disease, then these animals must be viewed in a new light. Are there "good" helminths in addition to bad? Instead of being detestable objects marked for eradication, helminths should be viewed as useful animals that may produce important compounds helpful for therapy of human disease.

Animals↗
PubMed2003

A randomized trial of aspirin to prevent colorectal adenomas.

BACKGROUND: Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel. METHODS: We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals. RESULTS: Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23). CONCLUSIONS: Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel.

Adenoma↗
PubMed2003

Fructose intolerance: an under-recognized problem.

OBJECTIVES: Although the role of lactose intolerance in the pathogenesis of abdominal symptoms is well known, the role of fructose intolerance is unclear. Our aims were 1) to examine the prevalence of fructose intolerance in patients with unexplained abdominal symptoms, and 2) to explore whether fructose concentration influences fructose breath test. METHODS: Over 2 yr, patients with unexplained symptoms answered questionnaires and underwent fructose breath tests. Patients received 50 g fructose in 150 ml water (33% solution). Breath samples were collected for hydrogen and methane. In a second study, breath test was performed after giving either 10%, 20%, or 33% fructose solution. Data were analyzed retrospectively. RESULTS: A total of 183 patients (50 male, 133 female) had breath tests, of whom 134 (73%) were positive. Among these, 119 (89%) had elevated H(2), and 15 (11%) had elevated CH(4) or both gases. Questionnaires showed that flatus (83%), pain (80%), bloating (78%), belching (70%), and altered bowel habit (65%) were the most common symptoms. Breath test reproduced symptoms in 101 patients (75%). In the second study, 14/36 (39%) tested positive with a 10% solution, 23/33 (70%) with a 20% solution, and 16/20 (80%) with a 33% solution (10% versus 20% or 33%, p < 0.01). CONCLUSIONS: Fructose intolerance may cause unexplained GI symptoms. The higher yield of positive tests in our initial study may be due to referral bias or testing conditions; lower test dose produced a lower yield. Nonetheless, recognition and treatment of fructose intolerance may help many patients.

Adult↗
PubMed2003

Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD), especially Crohn's disease (CD), probably results from failure to downregulate a chronic Th1 intestinal inflammatory process. Induction of a Th2 immune response by intestinal helminths diminishes Th1 responsiveness. This study evaluates the safety and effectiveness of helminthic ova in the treatment of active IBD. METHODS: We studied four patients with active CD and three with ulcerative colitis (UC). In an initial treatment and observation period, a single dose of 2500 live Trichuris suis eggs was given orally, and patients were followed every 2 wk for 12 wk. Baseline medications were continued at the same dose throughout the study. Safety was monitored by following the patients' clinical status and laboratory studies at regular intervals. Patients also were monitored regularly using the Crohn's Disease Activity Index, Simple Clinical Colitis Activity Index (SCCAI), and the Inflammatory Bowel Disease Quality of Life Index (IBDQ). To assess safety and efficacy with repetitive doses, two patients with CD and two with UC were given 2500 ova at 3-wk intervals as maintenance treatment using the same evaluation parameters. RESULTS: During the treatment and observation period, all patients improved clinically without any adverse clinical events or laboratory abnormalities. Three of the four patients with CD entered remission according to the Crohn's Disease Activity Index; the fourth patient experienced a clinical response (reduction of 151) but did not achieve remission. Patients with UC experienced a reduction of the Clinical Colitis Activity Index to 57% of baseline. According to the IBD Quality of Life Index, six of seven patients (86%) achieved remission. The benefit derived from the initial dose was temporary. In the maintenance period, multiple doses again caused no adverse effects and sustained clinical improvement in all patients treated every 3 wk for >28 wk. CONCLUSIONS: This open trial demonstrates that it is safe to administer eggs from the porcine whipworm, Trichuris suis, to patients with CD and UC. It also demonstrates improvement in the common clinical indices used to describe disease activity. The benefit was temporary in some patients with a single dose, but it could be prolonged with maintenance therapy every 3 wk. The study suggests that it is possible to downregulate aberrant intestinal inflammation in humans with helminths.

Administration, Oral↗