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The paper deals with a viewpoint on the relationship between the drug industry and the medical world taking inspiration from the history of the discovery of Helicobacter pylori as a pathogenic agent in peptic disease.

Background and Aim: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are common conditions with some similarities, but different perceptual responses to somatic and visceral stimuli. The purpose of this study was to assess in a large group of IBS patients the somatic perception by transcutaneous electrical nerve stimulation (TENS) and its relation to the level of severity and presence of FMS., Methods: In 99 patients grouped by the validated functional bowel disorder severity index (FBDSI) in mild, moderate, and severe IBS and in 33 healthy controls (HC), we studied discomfort thresholds and perception of somatic stimuli at control (hands and elbows) and active (trapezius) sites by TENS and by using a specific questionnaire., Results: The use of TENS showed that IBS showed significant higher thresholds and lower perception cumulative score compared to HC. The severity of IBS is significantly associated with age and mean control site values for discomfort and borderline associated with gender in the ordinal model constructed for the ascending series protocol. The severity of IBS is also significantly associated with the active cumulative perception score in the long stimulus protocol. Due to limited sample size of IBS men with FMS, analyses of discomfort thresholds and cumulative perception score by FMS were done only for women. IBS women without FMS had significantly higher mean control site values for discomfort and significantly lower active cumulative perception score than HC. IBS women with FMS had significantly lower mean active site values for discomfort thresholds than IBS women without FMS (Dunn's test p < 0.05)., Conclusions: IBS patients showed somatic hypoalgesia to electrical stimuli. The severity of IBS and the presence of FMS influence the perception of somatic stimuli induced by TENS.

Background: The development of cranial proportions is the result of genetic, embriogenetic and environmental factors. Coeliac disease is a genetically inherited disease that is frequently diagnosed in adulthood in individuals, in whom the disease runs unidentified for years and can affect child growth from the moment of dietary gluten introduction up to the moment of gluten withdrawal following diagnosis. Data on the effects of gluten on craniofacial development in coeliac children are not available., Aim: The aim of the present study is to evaluate gluten-related effects on face development in patients with undiagnosed coeliac disease and their clinical relevance., Methods: The study was a prospective, multivariate analysis. Face photographs of adult patients with coeliac disease and healthy controls were marked at six reference points and distances and the ratios among distances were measured by computer program software., Results: The main finding of the study is that Caucasian Mediterranean adult coeliac individuals tend to have a peculiar aspect of the face characterised by a larger forehead when compared to general population controls., Conclusion: The craniofacial morphology of patients with coeliac disease reveals an altered pattern of craniofacial growth. This is the first report of alterations of craniofacial development in coeliac disease. This alteration is a clinical sign that should be included among the extraintestinal manifestation of coeliac disease. It has a frequency comparable to other signs or symptoms such as anaemia and short stature and is a better predictor of coeliac disease than other signs such as recurrent aphthous stomatitis, recurrent abortion and dental enamel hypoplasia. A large forehead is a sign easily evident visually or with very simple measurements; computer analysis is not required for the general practitioner. This sign along with the presence of other clinical signs and symptoms, should alert a physician to test a patient for coeliac disease.

Aim: To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re-exposed to gluten after only a few years and now on a gluten-containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten-free diet after childhood diagnosis., Methods: A total of 195 adults with a biopsy suggestive of coeliac disease in childhood, who either had adhered to a gluten-free diet for at least 1 year after diagnosis and now are either on gluten-free diet (n = 110) or on gluten-containing diet (n = 85), and adults with newly diagnosed coeliac disease (n = 165) underwent a medical check-up., Results: Body mass index and main laboratory indices were statistically different among groups (lowest in never on gluten-free diet, highest in gluten-free diet). The lowest average levels of bone mineral density were found among never on gluten-free diet patients. Prevalence of autoimmune disorders was increased in never on gluten-free diet when compared with the transient gluten-free diet and gluten-free diet groups. Histology revealed villous subatrophy in all patients of never on gluten-free diet group, in 39 of 110 patients of gluten-free diet and in 84 of 85 of transient gluten-free diet groups. Herpetiform dermatitis was found in three patients of gluten-free diet, three of transient gluten-free diet and three of never on gluten-free diet. Dental enamel defects were found in 15 patients of transient gluten-free diet, 43 of never on gluten-free diet and in zero of the gluten-free diet group. Pregnancy outcome was not significantly different between the two groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten-free diet group. Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten-free diet group when compared with the other two groups., Conclusion: Gluten withdrawal in childhood partly protects coeliac adults from clinical and behavioural effects of gluten sensitivity.

Objectives: Abdominal ultrasound can assess the extent and localization of Crohn's 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 Crohn's disease., Materials and Methods: From 1997 to 2000 we performed ultrasound in 174 consecutive patients with Crohn's 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 Crohn's disease may identify a subgroup that is at high risk for surgery. (Am J Gastroenterol 2004;99:1-7)

Background: Infection with Helicobacter pylori is recognised as a major risk factor for chronic gastritis, peptic ulcer disease and gastric cancer. The association between H. pylori infection and iron deficiency anaemia has been established. Multiple mechanisms have been advocated to explain the relationship between H. pylori and iron status and their association might reduce iron deposit., Aim: Aim of this study was to investigate whether H. pylori infection affects iron absorption., Methods: The study was designed on a prospective basis. Fifty-five subjects underwent upper gastrointestinal endoscopy and biopsy to investigate the presence of H. pylori and, when this was positive, also search of serum anti-CagA was performed. Tests included an oral iron absorption test with the administration of 1 mg/kg of Fe2+. Iron levels were measured before and 2 h after iron administration (delta iron). H. pylori-positive subjects were administered antibiotic therapy for 1 week and, 2 months later, the oral iron absorption test was repeated and urea-breath test was first performed., Results: H. pylori-positive subjects had lower serum level of ferritin and lower delta iron compared to H. pylori-negative subjects. That difference is significant in anaemic women and is independent of the presence of serum anti-CagA antibodies. After H. pylori eradication iron absorption test was similar to those of non-infected subjects., Conclusion: H. pylori infection impairs iron uptake. That mechanism, together with others, may contribute to the depletion of iron in infected patients.

Background: Celiac disease is considered to arise from an inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people, whereas the T(H)2-type lymphocytes are mostly involved in IgE-mediated reactions. The matter of possible coexistence of T(H)1- and T(H)2-type diseases is still debated., Objective: This study was aimed to evaluate the allergy prevalence in a large series of adults with untreated celiac disease and their families at the moment of diagnosis. We also evaluated whether 1 year of gluten-free diet had any effect on allergy prevalence in our cohort., Methods: At the moment of celiac disease diagnosis a standardized questionnaire was administered for detailed information on presence and type of any allergy symptoms in 1044 adult patients with celiac disease, 2752 relatives, and 318 spouses. Those reporting any allergy underwent tests with dosage of serum levels of total IgE and search for serum specific IgE with a standard makeup of 20 antigens and PRICK tests in selected individuals. At follow-up visit patients with celiac disease were administered the same allergy questionnaire., Results: One hundred seventy-three patients with celiac disease (16.6%), 523 relative (19%), and 43 spouses (13.5%) had at least 1 allergy (P=not significant). Atopic dermatitis was more frequent in patients with celiac disease (3.8%) and their relatives (2.3%) than in spouses (1.3%). The presence of allergy in general and atopic dermatitis was not affected by presence of overt malabsorption or duration of undiagnosed disease. Follow-up data showed no change in allergy prevalence in the cohort examined., Conclusion: Allergy prevalence in a large series of patients with celiac disease is not different from that of their relatives and spouses. However, atopic dermatitis was about 3 times more frequent in patients with celiac disease and 2 times more frequent in their relatives than in spouses. One year of gluten-free diet did not change allergy prevalence in the celiac group under investigation.

Introduction: Untreated coeliac disease may induce malabsorption of many nutrients. It may also induce vitamin K deficiency, which causes prolongation of the prothrombin time. The aim of the present study was to evaluate the prevalence and associations of prolonged prothrombin time in a series of coeliac adults., Methods: We carried out a cross-sectional analysis of data collected on 390 adults with untreated coeliac disease diagnosed from January 1997 to December 2000. Prolonged prothrombin time was defined as INR > or = 1.4., Results: A prolonged prothrombin time was found in 72 coeliac patients (18.5%). Parenteral vitamin K therapy was required in 5.6% of patients. Patients with prolonged prothrombin time had significant lower values of haemoglobin, iron, proteins, cholesterol and serum aspartate transaminase, and significantly higher prevalence of diarrhoea, weight loss, abdominal pain and low bone mineral density in comparison with patients with normal prothrombin time. However, low bone density was present in 11.6% of patients with normal INR. A prolonged prothrombin time was only found in a few patients with subclinical coeliac disease (0.9%)., Conclusions: Data indicate that the prevalence of prolonged prothrombin time is about 20% in a large series of adult untreated coeliac patients. A prolonged prothrombin time was significantly related to all the markers of severe malabsorption, including low mineral density. Our suggestion is that vitamin K related proteins may also play a role in determining or worsening calcium homeostasis disorders in coeliac disease. The very low prevalence of coagulation disorders in subclinical coeliac disease indicates that there is no need to screen for coeliac disease in patients with isolated coagulation disorders.

Objective: Two common factors, cigarette smoking and appendectomy, have been found to play a role in ulcerative colitis (UC). Data on their role in the development of extraintestinal manifestations (EIM) are scarce., Methods: The relationship between cigarette smoking, appendectomy, and EIM was examined in a prospective study involving 535 (M/F = 319/216) consecutive UC patients followed up for 18 yr. We considered the major EIM: seronegative spondyloarthropathy, pyoderma gangrenosum/erythema nodosum, acute anterior uveitis, and primary sclerosing cholangitis. We excluded patients with a history of EIM or those colectomized before study entry, ex-smokers, and those who started to smoke during the course of UC., Results: In UC patients, seronegative spondyloarthropathy and dermatologic complications were found increased in smokers (p < 0.0001; p = 0.001) or in subjects with appendectomy (p = 0.0003; p = 0.02), while acute anterior uveitis and primary sclerosing cholangitis did not differ. The Kaplan-Meier analysis showed 18-yr rates for EIM of 71% in smokers and 45% in nonsmokers (log-rank test, p = 0.0001), and of 85% in patients with appendectomy and 48% in those without (p = 0.0001). Cox proportional-hazard model showed that cigarette smoking and appendectomy are independent factors promoting EIM. In smokers with appendectomy the adjusted hazard ratio (3.197, 95% CI 1.529-6.684) was higher than in patients with appendectomy alone (2.617, 95% CI 1.542-4.442) or smoking alone (1.947, 95% CI 1.317-2.879)., Conclusions: In UC patients, appendectomy and cigarette smoking are prognostic factors for the development of EIM. The unfavorable effect of cigarette smoking on EIM is additive to that of appendectomy.

Background: Small bowel bacterial overgrowth is common in Crohn's disease but its treatment is not clearly defined. Metronidazole and ciprofloxacin are effective antibiotics in active Crohn's disease., Aim: To investigate the efficacy of metronidazole and ciprofloxacin in the treatment of bacterial overgrowth in patients with Crohn's disease., Patients and Methods: We performed the lactulose breath test in 145 consecutive patients affected by Crohn's disease. Patients positive to the lactulose breath test underwent a glucose breath test to confirm the overgrowth. These patients were randomized in two treatment groups: metronidazole 250 mg t.d.s. (Group A) and ciprofloxacin 500 mg b.d. (Group B), both orally for 10 days. The glucose breath test was repeated at the end of treatment. The clinical outcome after therapy was also recorded., Results: Bacterial overgrowth was present in 29 patients (20%). Breath test normalization occurred in 13 out of 15 patients treated by metronidazole and in all 14 patients treated by ciprofloxacin (P = ns). In both groups antibiotic treatment induced an improvement of intestinal symptoms: bloating (Group A 85% and Group B 83%), stool softness (44% and 50%), and abdominal pain (50% and 43%)., Conclusions: Small bowel bacterial overgrowth is a frequent condition in Crohn's disease which can be effectively treated by metronidazole or ciprofloxacin.

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.

Background: The pathogenesis of inflammatory bowel disease is due, in part, to enhanced free-radical production and reduced antioxidant potential in mucosa cells., Aim: We evaluated in a rat model of trinitrobenzensulphonic acid (TNBS) colitis to see whether parenteral administration of glutathione is able to improve mucosal oxidative damage at onset (study A) and during chronic phases of colitis (study B)., Methods: In study A, the rats were injected with a single dose of glutathione (200 mg/kg, i.p.) or saline (0,2 ml, i.p.) 1 h before colitis induction and killed 1 h later. In study B, rats with induced colitis were treated with daily injection of glutathione (50 mg/kg, i.p.) or saline (0,2 ml, i.p.), and killed at 1, 2, 4 and 8 weeks. We evaluated on mucosal samples the macroscopic and histological damage and the oxidative stress assessed by the mucosal levels of lipoperoxides, malonyldialdehyde, glutathione and cysteine., Results: In study A, colitis induction caused a significant increase to the total histological score (p<0.05), lipoperoxide and malonyldialdehyde levels (p<0.001), but did not affect glutathione and cysteine content. Glutathione pre-treatment decreased both total histological score (p<0.05) and lipoperoxide and malonyldialdehyde values (p<0.001). In study B, the extensive macroscopic and histological colonic damage induced by TNBS was accompanied by a reduction of glutathione and cysteine mucosal levels (p<0.01) and increased lipid peroxidation. Glutathione supplementation significantly improved colonic damage (p<0.01), restored glutathione and cysteine levels, and decreased, and even, if not totally, abolished lipid peroxidation (p<0.001)., Conclusion: This paper further supports the pathogenic role of the imbalance in oxidant/antioxidant content in inducing mucosal colonic damage.

The trefoil factor family (TFF) encompasses small peptides of which intestinal trefoil factor (ITF) is expressed specifically in goblet cells of the small and large intestine. Previous studies have shown that ITF plays an important role in mucosal protection and repair. Coeliac disease represents a model of immune-mediated small intestinal inflammation and damage, with recovery on gluten-free diet. The aim of this study was to investigate the expression of ITF in the distal duodenal mucosa of subjects with coeliac disease, before and after treatment with a gluten-free diet. Expression of ITF and mucin in the distal duodenal biopsies from treated (n = 11) and untreated (n = 9) coeliac subjects and controls (n = 8) was investigated by immunohistochemistry and semiquantitative PCR. In untreated coeliac disease, there was reduction of ITF immunoreactivity in goblet cells but mucin expression was preserved. Mucosal recovery on gluten-free diet was associated with increased ITF immunoreactivity in goblet cells. There was also reduction in the expression of ITF transcripts, relative to MUC2 mRNA, in untreated coeliac duodenal samples, with recovery on gluten-free diet. Our study suggests that there is a selective reduction in the expression of the ITF gene in untreated coeliac disease. Recovery of ITF expression on a gluten-free diet suggests that the mucosal immune system regulates goblet cell differentiation and ITF expression in the human intestinal mucosa.

Background: 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.

Background: Allergic diseases and seronegative spondyloarthropathies are frequently observed in ulcerative colitis (UC). In this report we have investigated possible relationships between IgE-mediated allergic disease (AD), allergic contact dermatitis (ACD) and seronegative spondyloarthropathy (SpA) in UC patients at different grades and extensions of mucosa inflammation., Methods: Forty-five UC consecutive outpatients were graded according to clinical, endoscopic and histologic activity scores. SpA was diagnosed according to the European Spondyloarthropathy Study Group criteria. AD was detected by skin prick tests and confirmed by specific provocation tests, while ACD was diagnosed using the European standard series of patch tests. Thirty-seven patients' spouses or partners served as controls., Results: Fourteen patients and 1 control subject showed SpA (P = 0.001). Diagnosis of rhinitis, conjunctivitis or asthma was made in 19 patients and in 5 controls (P = 0.004), while ACD was found in 10 and in 4 (P = 0.17), respectively. In UC, AD coexisted with SpA in 2 cases (P = 0.01), AD with ACD in 1 case (P = 0.03) and ACD with SpA in 5 (P = 0.24)., Conclusions: Notwithstanding the high frequency of AD and SpA found in UC, the concurrence of AD with SpA or ACD is an unusual finding, while SpA and ACD may coexist. These data suggest that, in UC, atopy and seronegative arthritis, as well as atopy and delayed-type allergy, are strongly polarized conditions tending to mutual exclusion. In UC, the presence of AD without SpA or ACD, and of SpA or ACD without AD may indicate subgroups of patients in which T-helper-2 cell or T-helper-1 cell responses predominate.

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., (Copyright 2002 S. Karger AG, Basel)

The diagnosis of celiac disease patients may be delayed by misdiagnosis. Our aim was to evaluate in celiac patients the prevalence of surgery before diagnosis. Two hundred forty-four adult celiac patients and 232 controls were retrospectively investigated for surgery before diagnosis of celiac disease. The prevalence of surgery was increased in celiac patients versus controls (P = 0.001). Frequency of appendectomy (P = 0.0001), tonsillectomy (P = 0.009), and hernia repair (P = 0.05) were increased in celiac patients versus controls. Appendectomy was related to anemia (P = 0.006) and abdominal pain (P = 0.005); tonsillectomy was related to diarrhea (P = 0.02) and weight loss (P = 0,04). Appendectomy was elective in 73% of celiac patients and in 46% of controls. Cosmetic surgery was increased in celiac patients versus controls (P = 0.058). In conclusions, surgery before celiac disease diagnosis is increased in celiac patients compared to controls, as a result of doctors' misdiagnosis and/or poor health status, which increases the demand for medical intervention. The frequency of cosmetic surgery in celiac patients may berelated to impaired psychological profile of patients.

Fibromyalgia (FM) syndrome and irritable bowel syndrome (IBS) are functional disorders in which altered somatic and or visceral perception thresholds have been found. The aim of this study was to evaluate the prevalence of FM in a group of patients with IBS and the possible association of FM with patterns and severity of the intestinal disorder. One hundred thirty consecutive IBS patients were studied. The IBS was divided into four different patterns according to the predominant bowel symptom and into three levels of severity using a functional severity index. All patients underwent rheumatological evaluation for number of positive tender points, number of tender and swollen joints, markers of inflammation, and presence of headache and weakness. Moreover, patients' assessments of diffuse pain, mood and sleep disturbance, anxiety, and fatigue were also measured on a visual analogue scale. The diagnosis of FM was made based on American College of Rheumatology classification criteria. Nonparametric tests were used for statistical analysis. Fibromyalgia was found in 20% of IBS patients. No statistical association was found between the presence of FM and the type of IBS but a significant association was found between the presence of FM and severity of the intestinal disorder. The presence of FM in IBS patients seems to be associated only with the severity of IBS. This result confirms previous studies on the association between the two syndromes.

A 53-year-old male presenting with a 3-month history of intermittent mild rectal bleeding was found, on double contrast barium enema, to have a large polyp on a long stalk in the sigmoid colon. Large bowel endoscopy confirmed the presence of a 2 cm pedunculated polyp which was removed using a diathermic snare, with slight bleeding following the procedure that did not require endoscopic haemostasis. Only after histologic examination was the polyp shown to be a colonic arteriovenous malformation. Endoscopically, arteriovenous malformations generally appear as flat or elevated bright red lesions. A pedunculated polypoid appearance is extremely uncommon. In this case, no gastrointestinal bleeding or polypoid recurrence was observed during the 12 months of clinical and endoscopic follow-up.

Gastrointestinal involvement is frequent in patients with systemic sclerosis (SSc); however, studies on the proximal stomach and its regulation are lacking. It has been hypothesized that the primary event in the pathogenesis of gastrointestinal involvement in SSc is an early neural lesion. This study investigates proximal stomach function and its relation to autonomic nerve function in SSc. Twenty SSc patients classified in to clinical subsets, underwent measurement of proximal stomach function with and without glucagon by electronic barostat and an assessment of autonomic nerve function. SSc patients were not significantly different from 11 controls for gastric compliance (59.5+/-5.0 vs 47.7+/-4.2 ml/mm Hg, P = 0.1). The pressure-volume curves in each participant with and without glucagon were significantly different (P < 0.001). A significant positive association was found between gastric compliance and autonomic nerve function (P < 0.05). The change in gastric compliance during glucagon administration was significant-associated with autonomic function (P < 0.05). The perception cumulative scores did not differ between SSc patients and control subjects (P = 0.2). In conclusion, proximal stomach function is associated with autonomic nerve function in SSc patients. This confirms the frequent association of motility disorders with autonomic dysfunction in SSc.

Factor XIIIa, a circulating form of transglutaminase, plays a key role in intestinal mucosal repair. We found that transglutaminase levels are decreased in serum of patients with inflammatory bowel diseases and demonstrated in a rat model of chronic colitis that serum transglutaminase is closely related to the severity of intestinal damage. We aimed, therefore, to correlate serum transglutaminase levels with standard endoscopic and histopathologic grading systems in patients affected by ulcerative colitis (UC). In 249 patients with UC, we assayed serum transglutaminase activity by a radioenzymatic method and measured clinical activity index (CAI) according to modified Rachmilewitz's criteria. In a subset of 82 patients undergoing colonoscopy, endoscopic and histologic indices were studied. Biopsy specimens were also taken from 28 patients to measure myeloperoxidase (MPO) as a marker of mucosa inflammation. Serum transglutaminase levels significantly correlated with the CAI scoring (r = -0.63; P < 0.01); likewise serum transglutaminase showed the best correlation with endoscopic (r = -0.71; P < 0.001) and histologic (r = -0.79; P < 0.001) scores. Myeloperoxidase activity was significantly higher in patients with active UC than those in remission (P < 0.01), showing a significant correlation with serum transglutaminase levels (r = -0.68; P < 0.01). Immunohistochemistry showed factor XIIIa localization in the extracellular matrix of damaged mucosa. In conclusion, these results suggest that transglutaminase assay can be useful in managing UC as a serological, noninvasive indicator of intestinal mucosal status.

Objective: In active ulcerative colitis (UC), magnetic resonance imaging (MRI) with ferumoxil, a superparamagnetic oral contrast agent, accurately evaluates, in our experience, the increased wall thickness and frequently shows a stronger perivisceral fat signal intensity (PFSI). The aim of our study was to evaluate the clinical significance of these MRI findings in active UC., Methods: Twenty-four consecutive patients affected by moderate pancolitis were enrolled. At entry, each patient underwent MRI with ferumoxil to evaluate wall thickness and PFSI. Two groups of patients were individuated: group A (increased PFSI) and group B (normal PFSI). After obtaining remission, the number of relapses and, at each flare-up, the clinical activity index (CAI) were evaluated in all patients in a 2-yr follow-up period. The mean CAI was calculated at the end of the follow-up in each patient. Where there was colectomy, a complete histological examination of the colon was performed., Results: PFSI was increased in 16 patients (group A) and was normal in the remainder (group B). There was a significant difference of wall thickness, number of relapses/yr, and mean CAI between the two groups of patients. No difference was observed with regard the duration of disease. Six patients of group A and no patient of group B underwent colectomy. The histological evaluation showed an increased thickness of the entire colonic wall with significant changes of the perivisceral fat structures., Conclusions: An increased

Background/aims: Tissue transglutaminase has been reported to be involved in the healing of experimental gastric ulcer; nevertheless, other type(s) of transglutaminase could be involved. The present experiments aimed at examining whether plasma transglutaminase (factor XIIIa) contributes to such healing and at evaluating whether factor XIII supplementation improves gastric mucosal lesions., Methods: The healing effect of 200 U/kg of factor XIII administered intravenously was examined using a water immersion restraint rat model of stress gastric damage. The rats were sacrified 0, 2, 4, and 12 h after stress. The gastric mucosa was examined macroscopically and microscopically, and the transglutaminase activities were assayed in serum and gastric mucosa. Factor XIIIa and tissue transglutaminase protein levels in the gastric mucosa were analyzed by immunoblot. Immunohistochemistry was used to identify the location of tissue transglutaminase, factor XIIIa, and fibronectin in the gastric mucosa., Results: The transglutaminase activity, reduced by stress in the gastric mucosa, increased up to 12 h after stress, peaking at 4 h, when the ulcer index significantly decreased. The serum transglutaminase level was low at all time points. Exogenous administration of factor XIII allowed a faster reduction of the ulcer index that was coincident with an increased transglutaminase activity in the mucosa. Both tissue transglutaminase and factor XIIIa protein levels were reduced by 6 h of stress and increased after factor XIII administration. Immunohistochemistry showed a colocalization of both factor XIIIa and tissue transglutaminase with fibronectin in the extracellular matrix of the damaged area., Conclusions: Two forms of transglutaminase are involved in the healing of stress-induced gastric erosions, and factor XIII administration allows faster gastric mucosa healing.

Objective: To evaluate Helicobacter pylori (HP) and peptic disease prevalence in coeliac disease patients and in a control group., Design: In the retrospective study, data collected on 690 upper endoscopies in coeliac patients, carried out between 1990 and 1997, were analysed. In the prospective study 263 consecutive adult patients were studied for follow-up of coeliac disease or suspected malabsorption/coeliac disease. Tests included routine blood tests; serum dosage of EMA; IgG anti-HP and, in a subgroup of participants, anti-CagA antibodies; upper endoscopy with multiple gastric and duodenal biopsies; histological examination of gastric and duodenal specimens with staining providing evidence for the presence of HP., Setting: A centre for the treatment of malabsorptive diseases, University Federico II of Naples, Italy., Participants: Adults with coeliac disease at the time of diagnosis and follow-up., Results: In the retrospective study, peptic disease had a prevalence of 0.72% in the endoscopy series of coeliac patients examined. In the prospective study, the prevalence of HP infection was significantly lower in untreated coeliac patients when compared with treated patients and controls (20.7%, 32.4% and 55.3%, respectively; P = 0.001, chi2). The prevalence of HP was related to both gender and age. It was found more frequently in men and the frequency increased with age in all groups. The study confirmed the low prevalence of peptic disease in coeliac patients compared with controls (0.9% vs 3.8%, P = 0.001)., Conclusion: Patients with coeliac disease show a significantly lower prevalence of HP infection and peptic disease when compared to controls. Gluten free diet-induced changes in the intestinal environment and/or the host immuno-response may explain the increased HP prevalence in treated coeliac patients.

Azathioprine-related side-effects occur in about 15% of treated patients. Liver toxicity is a rare complication of this drug, but is considered, in most cases, a contraindication to the continuation of treatment. However, abnormal liver tests may occur in patients under azathioprine treatment also due to infections. The distinction between toxic and infective causes of abnormal liver tests is important in order to identify patients that can be rechallenged with the drug. Cytomegalovirus infection is common in immunosuppressed transplant recipients, while the incidence is lower in patients with inflammatory bowel disease treated with immunosuppressive drugs. To our knowledge, only 2 cases of cytomegalovirus hepatitis occurring during azathioprine treatment for Crohn's disease had been reported so far. Here, we describe two patients who experienced mild hepatitis associated with the onset of cytomegalovirus infection during azathioprine treatment. The infection was documented by the appearance of IgM anti cytomegalovirus. Both cases were self-limiting. In one of the 2 patients, azathioprine was given again after resolution of the hepatitis with good control of Crohn's disease and without other complications. We also retrospectively evaluated the incidence of liver abnormalities assessed by blood tests in 58 consecutive patients with Crohn's disease treated with azathioprine at our institution. Abnormal results were obtained in 8 out of these 58 patients, requiring discontinuation of the drug in 3 patients, two of whom were the cytomegalovirus cases described above.

Bacterial overgrowth is frequent in patients with Crohn's 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.

Background: Data on allergy in ulcerative colitis (UC) have led to conflicting conclusions without proving any causal association. In this report we have investigated the presence of allergy and its possible relation with chronic colonic inflammation in patients with UC., Methods: Fifty UC patients underwent clinical, endoscopic, and histologic evaluations. The allergologic study included family/personal history; prick/patch exposition to airborne, food, and contact allergens; total serum IgE; and quantification of eosinophils in peripheral blood and intestinal mucosa. Diagnosis of rhinitis, conjunctivitis, and asthma was confirmed by specific provocation tests. Fifty healthy subjects were studied as control group., Results: A higher prevalence of allergic symptoms was found in patients (56%) and their first-degree relatives (52%) than in controls (18% and 26%) (P < 0.0001; P = 0.008). In patients skin tests showed increased rates of immediate (54%) and delayed-type (20%) hypersensitivity compared with controls (30% and 6%) (P= 0.01; P= 0.03). Diagnosis of allergic IgE-mediated disease was made in 19 cases and 6 controls (P= 0.01), and allergic contact dermatitis in 10 and 3, respectively (P= 0.03). IgE levels were higher in UC patients than in controls (P=0.02). No dose-response relationship was found between degree of colonic tissue eosinophilia and clinical. endoscopic, and histologic disease severity. The degree of colonic tissue eosinophilia was higher in the presence of skin reactivity to food allergens., Conclusions: UC patients frequently show several markers of allergy. In particular, our data suggest an association between ulcerative colitis, tissue eosinophilia, and type-I allergy.

Factor XIII (FXIII) is the plasma-borne transglutaminase involved in fibrin clot stabilization and wound healing. FXIII levels in the plasma of patients with inflammatory bowel diseases are lower than normal and there is a significant inverse correlation of FXIII levels with clinical severity. Moreover, uncontrolled studies report beneficial effects of FXIII supplementation in patients resistant to conventional therapies. We investigated the effects of intravenous recombinant FXIII (rFXIII) treatment in experimentally induced rat colitis to verify that FXIII was the active agent in plasma FXIII concentrates and to better understand the potential therapeutic use of this protein. Colitis was induced by instillation of 12% 2.4,6-trinitrobenzenesulfonic acid (TNBS) in 50% ethanol into the colon of male Wistar rats. Rats were treated with 0.65 mg/kg rFXIII or vehicle (intravenously) daily for 10 days. Treatment was started either immediately after TNBS/EtOH instillation (to evaluate effects on developing lesions) or seven days later (to evaluate effects on established lesions). In both cases rats were killed either immediately after the end of treatment (to evaluate immediate effects) or 17 days later (to evaluate long-lasting effects). The effects of rFXIII were compared to positive (5-amino-2-hydroxybenzoic acid) control over a 35-day time course. The severity of lesions was determined by colon weight and macroscopic and histologic scores. Transglutaminase activity was measured in both colon tissue and serum. rFXIII treatment reduced lesion severity significantly not only in developing but also in established lesions. Improvements in healing persisted at least 18 days after treatment was discontinued. Serum and tissue transglutaminase levels were restored by rFXIII treatment. In conclusion, pure rFXIII is as effective as plasma FXIII concentrates in a rat model of experimental colitis. In addition, rFXIII significantly improves the healing of preexisting lesions, a characteristic useful in treatment of human inflammatory bowel diseases.

Objective: To evaluate colonic mucosa of patients with both active psoriasis and psoriatic arthritis (PsA) without bowel symptoms., Methods: Fifteen persons (9 men, 6 women) who had both active psoriasis and PsA without bowel symptoms underwent colonoscopy with multiple biopsies of bowel mucosa. Ten nonhospitalized healthy subjects in followup colonoscopy after resection of benign polyps (8 men, 2 women) took part as a control group., Results: Six psoriatic patients (40%) showed macroscopically normal colonic mucosa. In the remaining 9 reddening was frequently recorded (6 cases). while edema and granular changes appeared less commonly (3 cases each, respectively). Friability was markedly rare (only one case) and bleeding and ulcerations were absent. All 15 patients showed microscopic changes. Increase in lamina propria cellularity (consisting of plasma cells and lymphocytes) and lymphoid aggregates were found in all cases. Active inflammation, evident as neutrophilic polymorph infiltration occurred in 9 patients. Glandular atrophy was found in 3 cases; mucosal surface changes and crypt abnormalities occurred in one case each. No control had macroscopic or microscopic inflammatory changes of bowel mucosa., Conclusion: Bowel mucosa of patients with PsA without bowel symptoms show microscopic lesions even when mucosa appeared macroscopically normal. This result may support a pathogenetic link between skin, joints, and gut in psoriatic patients with arthritis even in the absence of bowel symptoms.

Objective: The introduction of new oral contrast agents that enhance image quality has increased the importance of magnetic resonance imaging (MRI) in the management of ulcerative colitis. The aim of our study was to investigate the usefulness of a new negative superparamagnetic oral contrast (ferumoxil) alone or in association with gadolinium i.v. in the assessment of the disease., Methods: Twenty-eight patients with clinically active ulcerative colitis and 10 control subjects entered the study. In each patient a clinical, endoscopic, histological, and MRI evaluation was performed. In particular, in 14 patients affected by ulcerative colitis (group A) and in five controls, magnetic resonance images were acquired 1 h after the oral administration of 900 ml of ferumoxil, while the remaining 14 patients (group B) and five controls were submitted to double-contrast MRI (ferumoxil and gadolinium). In both groups, wall thickness, length of affected bowel segments, and, in group B, also percent contrast enhancement were calculated., Results: The comparison of endoscopic and MRI extent of disease was statistically significant. Wall thickness and, in group B, also percent contrast enhancement were significantly correlated with clinical and endoscopic activities. In each group wall thickness was significantly different in the activity phases of the disease., Conclusions: MRI with negative superparamagnetic oral contrast is comparable to endoscopy in the assessment of ulcerative colitis. The double-contrast imaging does not provide more information than single oral contrast, so we concluded that the latter is preferable in the follow-up of the disease and in patients unable or with a poor compliance to undergo endoscopy.

The aim of this study was to evaluate the accuracy of enteroclysis in the diagnosis of Crohn's disease of the small bowel in a group of consecutive patients. From January 1992 to December 1995, 165 patients with suspected Crohn's disease of the small bowel presented to our institution for enteroclysis. In 14 patients up to three enteroclysis exams were performed. Most patients (78%) underwent colonoscopy and retrograde ileoscopy. In the remaining patients clinical follow-up was used as gold standard. In 79 patients no radiographic abnormalities were found. Sixty-one patients (40 men and 21 women; mean age 34.2 years) had a radiological diagnosis of Crohn's disease. This involved the terminal ileum in 39 patients (64%) either alone (n = 25) or in association with the pelvic ileum (n = 14). In 12 of these patients retrograde ileoscopy was not feasible. Twenty-one patients underwent surgery. In 4 patients pathology revealed diseases other than Crohn's. These patients had all ileocecal diseases (tuberculosis = 2; non-Hodgkin's lymphoma = 1; adenocarcinoma = 1). One false-negative result was observed. Overall, enteroclysis showed a sensitivity of 98.2% and a positive predictive value of 93.4%. Enteroclysis is a sensitive technique in evaluating both the extent and the severity of small bowel involvement in Crohn's disease, although the overlap of radiographic findings may hamper its accuracy when the disease is confined to the ileocecal area.

Objective: Hypochromic anemia is at times attributable to nondiagnosed celiac disease. The aim of this study was to define the correlates of celiac disease in anemic adults without overt malabsorption., Methods: One hundred patients with hypochromic anemia and without diarrhea underwent a complete diagnostic work-up, including screening for celiac disease, i.e., upper endoscopy with duodenal biopsy and search of antiendomysium antibodies., Results: Patients with hypochromic anemia were from two different Divisions and were analyzed as a single group because they were not significantly different for any variable. Hypochromic anemia was attributable to celiac disease in 10 patients. Compared to anemic patients without celiac disease, anemic patients with celiac disease had significant or borderline significant differences for plasma cholesterol (-17.9%), albumin (-9.4%), and body mass index (-11.8%), but not for gender distribution, age, weight, height, blood hemoglobin, mean corpuscolar volume, plasma iron, and ferritin. All anemic patients with celiac disease had plasma cholesterol < 156 mg/100 ml. Within the entire cohort of anemic patients, plasma cholesterol inversely related to prevalence of celiac disease (p < 0.001); also plasma albumin and body mass index inversely related to celiac disease, but coefficients were borderline significant (p = 0.056 and 0.052, respectively)., Conclusions: The data suggest that among patients with hypochromic anemia, plasma cholesterol in the high-to-normal range could be used to exclude the presence of celiac disease. Other nutritional markers are less sensitive as indices of risk of celiac disease. Hematological indices are not of help to define the risk of celiac disease in anemic patients without signs of malabsorption.

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.

Background: The identification of cirrhotic patients with low life expectancy is an open clinical problem. Hypocholesterolemia is frequently found in severe chronic hepatic insufficiency because the liver is the most active site of cholesterol metabolism, but poor information is available on its precise prognostic value. We evaluated the prognostic role of hypocholesterolemia in patients with advanced liver cirrhosis., Methods: Serial serum cholesterol concentrations of 34 patients with virus-induced cirrhosis, from the first appearance of Child-Pugh class C to death, were considered. To compare survival functions, we established three base-line cholesterol cut-off points (150, 125, and 100 mg/dl) and stratified patients into groups A and B, with base-line cholesterol levels lower and higher than each cut-off value, respectively., Results: Cholesterolemia decreased progressively in all patients. At the 100 mg/dl cut-off point all group-A patients died within 17 months, whereas 75% of group-B patients were alive at 24 months (P < 0.0001). Moreover, cholesterolemia was significantly correlated with cholinesterase, indirect bilirubin, and total bilirubin at entry time and immediately before death. No correlation was observed between cholesterol and these variables when stratified for the Child-Pugh score., Conclusions: Base-line serum cholesterol levels lower than 100 mg/dl identify a subgroup of Child-C cirrhotic patients with high mortality risk within a 2-year follow-up. The prognostic importance of cholesterolemia may also be deduced by the significant correlation with other well-established indicators of survival.

Background: Sexual behaviour is often altered in chronic illness., Aim: To evaluate sexual behaviour in coeliac patients before and after treatment with a gluten-free diet., Patients: Fifty-five adults with coeliac disease and 51 age- and sex-matched healthy controls., Methods: Routine clinical and laboratory work-up was used for diagnosis of coeliac disease. Age of first sexual intercourse, prevalence of individuals who were sexually active, frequency of intercourse, reduction in sexual desire, difficulty in attaining orgasm, pain during intercourse, and prevalence of individuals defining themselves as satisfied with their sexual life were investigated by an anonymous, self-administered questionnaire administered before and after one year's treatment with a gluten-free diet in coeliac patients, and only once in controls. Analyses included clinical conditions, demographic and socio-economic data., Results: Compared with controls, untreated coeliac patients had a significantly lower frequency of intercourse and a lower prevalence of individuals satisfied with their sexual life. Patients with overt and subclinical coeliac disease did not show significant differences for any indices of sexual behaviour. Compared with untreated conditions, coeliac patients after one year of treatment had improved values for all indices of sexual behaviour: differences were significant for frequency of intercourse and prevalence of individuals satisfied with their sexual life., Conclusion: Untreated coeliac disease, even in its subclinical presentation, is associated with disorders in sexual behaviour which are improved by the dietary treatment.

Objective: A high prevalence of reflux esophagitis in celiac children and gut motor disorders in adult patients have been described. The aim of this study is to investigate the prevalence of esophageal symptoms and the esophageal motility pattern in adult celiac patients before and after gluten-free diet., Methods: In 22 consecutive adult celiac patients, before and after gluten-free diet, and in controls we calculated an esophageal symptom score regarding heartburn, regurgitation, dysphagia, and chest pain, and performed esophageal manometry using a constantly perfused multilumen catheter., Results: Patients were divided into two groups: with and without steatorrhea. Before gluten-free diet, the prevalence of esophageal symptoms was 45.5 % in all patients, but was significantly higher in patients with steatorrhea than in those without and in 44 control subjects (80% vs 16.7% and 27%, p < 0.05). Lower esophageal sphincter pressure was 17.5+/-5.3 in all patients, but was significantly lower in patients with steatorrhea than in patients without steatorrhea and 11 controls subjects (13.1+/-4.1 vs 21.0+/-2.9 and 20.7+/-3.7 mm Hg (mean+/-SD, p < 0.05). After the diet, the prevalence of esophageal symptoms diminished in all patients (9% vs 45.4%, p < 0.05) and lower esophageal sphincter pressure, measured in 13 patients, increased (19.0+/-3.7 vs 15.7+/-5.3 mm Hg, p < 0.05)., Conclusion: Adult celiac patients with steatorrhea present a higher prevalence of esophageal symptoms and a lowered lower esophageal sphincter pressure compared with celiac patients without steatorrhea and control subjects, but these phenomena can be reverted to control levels by gluten-free diet.

Background/aims: Beclomethasone dipropionate is one of the topical corticosteroids which appear to have minimal systemic effects. We evaluated whether combined therapy with Beclomethasone dipropionate enemas and oral 5-aminosalicylic acid could be effective in patients suffering from ulcerative colitis not responsive to oral 5-aminosalicylic acid as monotherapy., Patients: In twenty patients, non responders to 5-aminosalicylic acid treatment (2.4-3.6 g/day) given for at least 6 weeks, Beclomethasone dipropionate enemas (3 mg/60 ml/day) were added for 4 weeks., Methods: Efficacy of the combination was evaluated before and at the end of the treatment using a clinical, endoscopic and histological score., Results: After a four-week treatment period, a significant clinical improvement in stool frequency (p < 0.01), stool consistency (p < 0.001), blood (p < 0.001) and mucus in stools (p < 0.05), was observed. Endoscopy and biopsy confirmed an improvement in the activity score at the end of the treatment (p < 0.001). Six patients (30%) achieved remission, ten patients showed an improvement (50%) and four (20%) showed no benefits. No adverse event was observed., Conclusions: Beclomethasone dipropionate enemas combined with oral 5-aminosalicylic acid may be a safe and useful therapeutic approach in the treatment of ulcerative colitis not responsive to oral 5-aminosalicylic acid alone.

Background: Psychic symptoms and depression have been reported in coeliac disease (CD). The aim of this study was to explore depression in a large cohort of adult CD patients., Methods: Depressive symptoms were evaluated in 92 adult coeliacs, 100 normal controls (NC), and 48 chronic persistent hepatitis (CPH) patients by means of a modified version of the Zung Self-Rating Depression Scale (M-SDS). CD patients were evaluated for the level of knowledge about CD and the compliance with diet., Results: The M-SDS score differentiated CD patients from NC. Age at diagnosis and duration of and compliance with diet did not correlate with depression. Three main factors could be identified with the M-SDS: 'reactiveness', 'pessimism', and 'anhedonic-asthenic'., Conclusion: Depressive symptoms are a feature of CD; they are present to a similar extent in patients with childhood- and adulthood-diagnosed CD. The results underline the relevance of personal psychologic resources, which play a fundamental role in determining and sustaining depression.

Objective: Conflicting evidence is reported about the effect of treatment on bone mineral density (BMD) in adults with celiac disease (CD). This study analyzed the effects on BMD induced by treatment with a calcium-rich, gluten-free diet in adults with nonsilent CD., Methods: In 30 women and 11 men with newly diagnosed CD, BMD was measured at the right femur (femoral neck and right Ward's triangle) and the lumbar spine by dual-energy x-ray absorptiometry under untreated conditions (pretreatment) and after 1-yr treatment with a calcium-rich, gluten-free diet., Results: On average, posttreatment BMD was greater than pretreatment BMD at the lumbar spine (mean +/- SE: 0.907 +/- 0.028 and 0.795 +/- 0.028 g/cm2, respectively; p < 0.001), the femoral neck (0.818 +/- 0.023 and 0.741 +/- 0.030 g/cm2, respectively; p = 0.002), and the Ward's triangle (0.703 +/- 0.025 and 0.654 +/- 0.025 g/cm2, respectively; p < 0.001). The greatest BMD change (percent of baseline) was observed at the lumbar spine (+14.1%), the smallest at the Ward's triangle (+7.5%). In the absence of appropriate controls, the BMD change expected in the patients under untreated conditions was estimated by regressing pretreatment BMD over duration of CD with control for gender and age at which CD became clinically evident. The regression coefficient of this analysis indicated that 1 yr of untreated CD was associated with a BMD decrease at the lumbar spine by 0.00570 g/cm2 (95% confidence interval -0.0103 to -0.0011 g/cm2). The 95% confidence interval of the treatment-induced change in BMD at the lumbar spine (+0.060 to +0.160 g/cm2) did not overlap the 95% confidence interval of the BMD change expected under untreated conditions. A large interindividual variability was observed in the BMD response to the treatment: in univariate and multivariate analyses, the treatment-induced change in BMD was significantly related to gender (greater in women than in men) and to pretreatment age and BMD., Conclusions: The data show that BMD is increased by dietary treatment of CD in most but not all adult patients; pretreatment BMD, gender, and pretreatment age predict the bone response after a 1-yr treatment.

Several studies have reported that high sodium (Na) intake increases not only urinary Na but also urinary calcium (Ca), suggesting that high Na intake could be involved in the pathogenesis of hypercalciuria. No research data are available on the relationship of Na intake to the prevalence of hypercalciuria within the general population. Moreover, it is not clear if Na intake relates only to urinary Ca or also to other indices of Ca homeostasis, including intestinal Ca absorption. In the present paper, two distinct studies addressed these points using 24-hour urinary Na as an index of salt intake in individuals on their habitual unrestricted free diet. Study 1 analyzed the relationship between 24-hour urinary Na and hypercalciuria (24-hour urinary Ca > or = 7.5 mmol in men, > or = 6.25 mmol in women) in a population sample of 203 men and women, aged 20-59 years. Study 2 analyzed the relationship between 24-hour urinary Na and intestinal strontium (Sr) absorption, used as an index of intestinal Ca absorption, urinary (24-hour and fasting) and plasma Ca, and plasma parathyroid hormone in 36 healthy men and women, aged 18-65 years. Within the population sample (study 1), 24-hour urinary Na was directly and significantly correlated with prevalence of hypercalciuria when controlling for gender, age, weight, and urinary creatinine: the relationship was continuous and linear for urinary Na ranging between 40 and 200 mmol/24 h. In the 36 volunteers (study 2), 24-hour urinary Na was related to 24-hour and fasting urinary Ca (p < 0.001) but not to intestinal Sr absorption: the relationship between 24-hour urinary Na and urinary Ca (both 24 h and fasting) was also significant, controlling for other variables. The results indicate that in adults on their habitual diet, urinary Na, which reflects dietary salt intake, correlates with the prevalence of hypercalciuria independently of intestinal Ca absorption and mainly via renal mechanisms.

Arthritis has often been alluded to as an extra-intestinal clinical manifestation of coeliac disease, but definitive data regarding its prevalence are still lacking. We therefore evaluated the overall prevalence of articular involvement in 200 consecutive adult coeliac patients attending routine gastroenterology follow-up and in 40 controls, and determined whether the prevalence and pattern of articular involvement varied according to the dietary status. An arthritis was present in 26% of patients and in 7.5% of controls, prevalences ranging from 41% in patients on a regular diet to 21.6% in patients on a gluten-free diet (P < 0.005). Arthritis was peripheral in 19 patients, axial in 15 and an overlap of both in 18 subjects. These data suggest that arthritis is much more common than previous reports have indicated, particularly in patients receiving an appropriate dietary regimen, and support the need for combined gastrointestinal and rheumatological follow-up in coeliac patients.

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42 +/- 15 years, mean +/- SD), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8 +/- 2.3 vs placebo: 2.8 +/- 1.6; P < 0.002) and a significant decrease in straining at defecation (P < 0.01), stool consistency (P < 0.02), and use of laxatives (P < 0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Abnormalities in gastrointestinal motility have been reported in a substantial proportion of patients with functional dyspepsia, supporting the use of prokinetic drugs for treatment of dyspeptic symptoms. To evaluate efficacy and safety of levosulpiride in short-term treatment, 1298 patients were enrolled in a double-blind multicentric study carried out in 45 Italian Gastroenterology Departments. Patients were randomly assigned to either levosulpiride (25 mg tid), domperidone (10 mg tid), metoclopramide (10 mg tid) or placebo (1 tablet tid) for 4 weeks. Patients were selected on the basis of: a) occurrence in the last 4 weeks of at least 5/10 selected symptoms (anorexia, nausea, vomiting, upper abdominal pain, postprandial bloating, abdominal fullness, early satiety, belching, heartburn, regurgitation), severity of which should reach/exceed a total score of 8, as assessed by a specific scale ranging from 0 (absent) to 3 (severe); b) normal results of routine biochemical, ultrasound and endoscopic examinations. In addition, each patient subjectively evaluated efficacy of treatment by a visual analogue scale. Significant improvement was recorded for all symptoms at days 10 and 28 in all groups (p < 0.001), but levosulpiride was significantly (p < 0.01) superior to domperidone, metoclopramide and placebo both in the overall clinical improvement scale as well as in a subgroup of symptoms (postprandial bloating, epigastric pain, heartburn). Active treatments and placebo were comparable as far as concerns occurrence of side-effects (12-20%) including galactorrhoea, breast tenderness and menstrual changes.

Background & Aims: Butyrate is effective in experimental colitis by increasing transglutaminase activity. Because ulcerative colitis increases the risk of colonic neoplasia, the aim of this study was to investigate whether butyrate treatment reduces mucosal sensitivity to colon cancer development in rats with experimental colitis., Methods: Colon cancer was induced by azoxymethane injections in 10 rats with trinitrobenzensulfonic acid-induced colitis and 10 rats without colitis. Three additional groups of rats with colitis were treated with butyrate, mesalamine, and saline enemas, respectively, twice daily for 8 weeks; 1 week after colitis induction, tumors were induced. Biopsy specimens for assessment of proliferation pattern and transglutaminase activity were obtained during the latent period of cancer development. Characteristics of tumors were recorded 27 weeks after the first exposure to azoxymethane., Results: Experimental colitis enhanced carcinogenesis; butyrate therapy reduced both incidence and size of tumors and also affected colonic proliferation pattern. Transglutaminase levels were restored by butyrate treatment in rats with colitis., Conclusions: The protective effect of butyrate against large bowel cancer in experimental colitis suggests its usefulness in long-term therapy to decrease disease relapses and to reduce colon cancer risk in ulcerative colitis.

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.