G. Mazzacca

Long-Term Follow-Up of Celiac Adults on Gluten-Free Diet: Prevalence and Correlates of Intestinal Damage

Background and Aims: Celiac disease is the most common severe food intolerance in the Western world and is due to gluten ingestion in genetically susceptible children and adults. Intestinal biopsy is the golden standard for evaluation of mucosal damage associated with celiac disease. Gluten-free diet is the key treatment for celiac disease. Data on the long-term control of celiac disease are few and limited to small series of patients. The study reports data on the control of celiac disease and on its correlates in a large cohort of celiac adults during long-term treatment with gluten-free diet. Methods: The study cohort comprises 91 men and 299 women having undergone treatment with a gluten-free diet for at least 2 years and with complete records for visits at the time of diagnosis of celiac disease (baseline). Data collection included gender, age, education, weight, bowel habit, blood hemoglobin, plasma albumin and cholesterol, serum antiendomysium antibodies (EMA), dietary compliance to gluten-free diet (coded as good, low, or very low), and intestinal damage at biopsy (coded as absent, mild, or severe). Results: The duration of follow-up was 6.9 ± 7.5 years (mean ± SD, range 2–22 years). At follow-up visit, intestinal damage was absent in 170 patients (43.6%), mild in 127 (32.6%), and severe in 93 (23.8%). At follow-up, intestinal damage was significantly associated with dietary compliance, EMA, and plasma albumin (follow-up value and change value from baseline to follow-up). Baseline education significantly predicted dietary compliance and intestinal damage at follow-up. Conclusions: Celiac disease is often poorly controlled in the majority of patients on long-term treatment with a gluten-free diet as demonstrated by intestinal biopsy. Lack of adherence to strict gluten-free diet is the main reason of poorly controlled disease in adults. Laboratory and clinical information have a high positive predictive value and low negative predictive value for intestinal damage on long-term treatment. Dietary compliance as assessed by interview is the best marker of celiac disease control due to low cost, noninvasivity, and strong correlation with intestinal damage.

Gender and Clinical Presentation in Adult Celiac Disease

BACKGROUND Celiac disease may present in various forms. This study aimed to investigate whether gender affects the clinical presentation of the disease in adult celiac patients from the Mediterranean area. METHODS This study retrospectively analyzes data collected in all adult patients with celiac disease (n = 195) seen during the past 13 years at the Gastrointestinal Unit of the Federico II University of Naples, Italy. RESULTS In these series of patients the ratio of women to men was 3.33. Age at diagnosis was lower in women that in men (p < 0.05). Except for asthenia, all signs and symptoms were more frequent in women than in men. Hypochromic anemia was the most commonest finding in women and was 40% more frequent in women than in men (p < 0.001). Dyspepsia was twice as frequent in women as in men (p < 0.05); genital disorders were reported by 44% of women and by no men. Recent weight loss or low body mass index was the commonest finding in men. About 60% of men and women reported diarrhea; among patients without diarrhea, the prevalence of hypochromic anemia differed between sexes (p < 0.05), occurring in about 80% of women. CONCLUSION This study shows that the clinical presentation of celiac disease is not the same in men and women. The disease is not only more frequent in women than in men but is also more severe and more rapid. The data also suggest the need to look for celiac disease in patients with unexplained hypochromic anemia.

Clinical and neurological abnormalities in adult celiac disease

Abstract.We assessed the occurrence of neurological signs and symptoms in adult patients with celiac disease and evaluated the correlation between neurological features and diet. A total of 176 patients and 52 age-matched controls underwent a semistructural interview and a neurologic examination. The effect of gluten-free diet was evaluated by comparing the prevalence of signs and symptoms among patients adhering to a gluten-free diet and patients on an unrestricted diet. The occurrence of headache, dysthymia and signs of peripheral neuropathy was significantly higher in patients with celiac disease than in control subjects. Adherence to a strict gluten-free diet was associated with a significant reduction of headache, dysthymia, cramps and weakness, but did not modify the occurrence of paresthesia or hyporeflexia. Neurological signs and symptoms are associated with celiac disease and can be ameliorated by a gluten-free diet.

Abnormal esophageal acid exposure is common in morbidly obese patients and improves after a successful Lap-band system implantation

AbstractsBackground: The relation between gastro-esophageal reflux disease (GERD) and obesity is controversial. The laparoscopic adjustable gastric band (LAGB) procedure is effective for morbid obesity. Its indication in the presence of GERD, however, is still debated. This study aimed to investigate esophageal symptoms, motility patterns, and acid exposure in morbidly obese patients before and after LAGB placement. Method: For this study, 43 consecutive obese patients were investigated by a standardized symptoms questionnaire, stationary manometry and 24-h ambulatory pH-metry, and 16 patients with abnormal esophageal acid exposure were reevaluated 18 months after LAGB placement. Results: Symptom scores and abnormal esophageal acid exposure were found to be significantly higher, Lower Esophageal Sphincter (LOS) pressure was significantly lower in obese patients than in control subjects. After LAGB, esophageal acid exposure was significantly reduced in all but two patients, who presented with proximal of gastric pouch dilation. Conclusions: There is a high prevalence of GERD in the obese population. Uncomplicated LAGB placement reduces the amount of acid in these patients with abnormal esophageal acid exposure.

Direct evidence of oxidative damage in acute and chronic phases of experimental colitis in rats

During inflammatory colitis in man and experimental animals, the production of free radicals increases. This study evaluated the histological pattern and biochemical parameters of oxidative damage during acute and chronic colitis induced by 2,4,-trinitrobenzenesulfonic acid + ethanol in rats. On the samples of scraped mucosa of six groups of rats, one not treated, one killed after 1 hr, and those killed one, two, four, and eight weeks after the induced-damage, we determined the histological and superoxide dismutase activity and the concentration of lipoperoxides, malonyldialdheyde, and reduced glutathione. After 1 hr, the mucosal damage and superoxide dismutase activity were slight; glutathione, lipoperoxides, and malonyldialdheyde were significantly increased. At one week, the histological damage was severe, decreasing progressively, and significantly correlated to superoxide dismutase activity. Lipoperoxides and malonyldialdheyde were high throughout the study. Glutathione was significantly increased at one and two weeks and dramatically decreased thereafter. Therefore, in experimental colitis the cascade of free-radical production induces a constant self-maintaining lipoperoxidation and consumes the cellular antioxidant capability.

Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn's disease

Background : Small bowel bacterial overgrowth is common in Crohns disease but its treatment is not clearly defined. Metronidazole and ciprofloxacin are effective antibiotics in active Crohns disease.

Butyrate, mesalamine, and factor XIII in experimental colitis in the rat: Effects on transglutaminase activity

BACKGROUND/AIMS Butyrate and factor XIII may improve ulcerative colitis; they also affect tissue and serum transglutaminase levels. We investigated the therapeutic potential of sodium butyrate and factor XIII and the role of transglutaminase during mucosal repair in experimental colitis. METHODS Rats with induced colitis were treated with sodium butyrate, mesalamine, sodium butyrate plus mesalamine, or saline enemas. Thromboxane B2 was monitored as index of inflammation. In a fifth group, the effectiveness of intravenous Factor XIII was assessed. RESULTS Sodium butyrate, alone or plus mesalamine, reduced histological activity from 13.7 +/- 1.7 (saline) to 2.5 +/- 1.3 and 2.3 +/- 1.1 (P < 0.01), respectively. Transglutaminase, reduced in the colons of the saline group (783 +/- 157 vs. normal 1800 +/- 192 mU/g; P < 0.01), returned toward normal values in the sodium butyrate or sodium butyrate plus mesalamine groups (1390 +/- 228 and 1226 +/- 172 mU/g, respectively; P < 0.01 vs. saline). Furthermore, sodium butyrate plus mesalamine reduced thromboxane B2 levels by day 5 (0.92 +/- 0.16 vs. saline 1.85 +/- 0.34 ng/mL; P < 0.05). Factor XIII therapy improved the histological picture (2.7 +/- 2.1 vs. saline 13.8 +/- 1.7; P < 0.01) and increased transglutaminase levels both in serum (2.81 +/- 0.11 vs. saline 1.45 +/- 0.09 mU/mL; P < 0.01) and in colon (1503 +/- 127 vs. saline 747 +/- 103). CONCLUSIONS Sodium butyrate and factor XIII improve colitis, sodium butyrate plus mesalamine reduce early thromboxane B2 synthesis, and transglutaminase(s) plays a role in ulcer healing.

Orocecal transit time and bacterial overgrowth in patients with Crohn's disease.

Bacterial overgrowth is frequent in patients with Crohns disease (CD) and can contribute to symptoms. Motility abnormalities can predispose to bacterial overgrowth. The hydrogen (H2) and methane (CH4) breath test is a sensitive and simple tool for the diagnosis of bacterial overgrowth and for the evaluation of orocecal transit time (OCTT). In this study, we investigated the prevalence of OCTT modifications and bacterial overgrowth in a series of consecutive adult patients with CD. In 43 healthy subjects and 67 patients with CD. we performed the lactulose breath test using a gas analyzer that offers the opportunity of measuring both H2 and CH4. Of the patients, 24 had undergone an ileocolic resection before the test with ablation of the ileocecal valve. At the time of the test 15 patients had active disease, whereas in 52 subjects the disease was quiescent. Fifty-seven patients and forty controls were evaluable for OCTT and bacterial overgrowth. In 10 patients and in 3 controls, no H2 or CH4 peak was recorded during the 8-hour test. Out of 57 patients, 13 (23%) were affected by bacterial overgrowth. The prevalence of bacterial overgrowth was higher in patients with previous surgery (30%) than in nonoperated patients (18%). In all patients with bacterial overgrowth, an antibiotic treatment induced a normalization of the test and an improvement of the symptoms. We observed a longer OCTT in the patients compared to controls, although this difference was not statistically significant (154 +/- 45 vs. 136 +/- 45 minutes). OCTT was significantly longer compared to controls in the 14 CD patients with previous ileocolic resection ( 180 +/- 53 vs. 136 + 45 minutes; p < 0.004). In conclusion, we found that a significant proportion of unselected patients with CD has bacterial overgrowth and prolongation of OCTT. We suggest that the modifications in OCTT in patients with CD can predispose to bacterial overgrowth. The lactulose breath test is a simple method that can be more widely used in patients with CD.

Short-Chain Fatty Acid in the Human Colon

Short chain fatty acids (SCFAs) are the end products of anaerobic bacteria break down of carbohydrates in the large bowel. This process, namely fermentation, is an important function of the large bowel; SCFAs, mainly acetate, propionate and butyrate account for approximately 80% of the colonic anion concentration and are produced in nearly constant molar ratio 60:25:15. Among their various properties, SCFAs are readily absorbed by intestinal mucosa, are relatively high in caloric content, are metabolized by colonocytes and epatocytes, stimulate sodium and water absorption in the colon and are trophic to the intestinal mucosa. While the fermentative production of SCFAs has been acknowledged as a principal mechanism of intestinal digestion in ruminants, the interest in the effects of SCFAs production on the human organism has been raising in the last ten years. SCFAs are of major importance in understanding the physiological function of dietary fibers and their possible role in intestinal neoplasia. SCFAs production and absorption are closely related to the nourishment of colonic mucosa, its production from dietary carbohydrates is a mechanism whereby considerable amounts of calories can be produced in short-bowel patients with remaining colonic function and kept on an appropriate dietary regimen. SCFAs enemas or oral probiotics are a new and promising treatment for ulcerative colitis. The effects have been attributed to the oxidation of SCFAs in the colonocytes and to the ability of butyrate to induce enzymes (i.e. transglutaminase) promoting mucosal restitution. Evidence is mounting regarding the effects of butyrate on various cell functions the significance of which needs further considerations. Up until now, attention has been related especially to cancer prophylaxis and treatment. This article briefly reviews the role of SCFAs, particularly butyrate, in intestinal mucosal growth and potential clinical applications in inflammatory and neoplastic processes of the large bowel.

Bowel Wall Thickness at Abdominal Ultrasound and the One-Year-Risk of Surgery in Patients with Crohn's Disease

OBJECTIVES:Abdominal ultrasound can assess the extent and localization of Crohns disease, and an increased bowel wall thickness is the most common finding. Our aim was to correlate bowel wall thickness at ultrasound, with the risk of short-term surgical outcome in patients with Crohns disease.MATERIALS AND METHODS:From 1997 to 2000 we performed ultrasound in 174 consecutive patients with Crohns disease. Surgical operations were recorded over a 1-yr follow-up. Logistic regression analysis was performed to identify clinical and ultrasound risk factors for surgery.RESULTS:Fifty-two patients underwent surgery within 1 yr. Indication for surgery was strictures in most of the cases. Median bowel wall thickness was higher in patients with surgery (8 mm) than those without surgery (6 mm) (p < 0.0001). A receiver operating characteristic (ROC) curve was constructed taking into account bowel wall thickness for selecting patients with a high risk of surgery. The optimized cut-off for equally important sensitivity and specificity was calculated at 7.008 mm. The binary regression analysis showed that CDAI > 150, absence of previous surgery, stricturing–penetrating pattern, the presence of intestinal complications, and intestinal wall thickness >7 mm were associated with an increased risk of surgery. Patients with intestinal wall thickness >7 mm at ultrasound had the highest risk (OR: 19.521, 95% CI: 5.362–71.065).CONCLUSIONS:Data suggest that bowel wall thickness >7 mm at ultrasound is a risk factor for intestinal resection over a short period of time. Routine use of abdominal ultrasound during evaluation of patients with Crohns disease may identify a subgroup that is at high risk for surgery.