Elderly-onset vs adult-onset ulcerative colitis: a different natural history?

BACKGROUND: Incidence of ulcerative colitis (UC) in elderly population is increasing because of ageing and because of its minimal impact on life span. Data on natural history, outcomes and therapeutic strategies are limited. Our aim is to characterize UC in elderly-onset patients followed at our Inflammatory Bowel Disease outpatient clinic and compare with adult-onset UC. METHODS: From January 2000 to June 2019, 94 patients with UC diagnosed after the age of 65 years (elderly group, E-O) were identified and matched 1-1 according to gender and calendar year of diagnosis with patients diagnosed with UC at age between 40 and 64 years (adult age, A-O). RESULTS: Comorbidity Index (3.8 vs 1.6, p < 0.0005) was higher for elderly UC patients. Symptoms at presentation were similar between the two groups, although abdominal pain was more common in adults, and weight loss was more common in the elderly. At diagnosis, left colitis (61% vs 39%) and proctitis (14% vs 26%) (p = 0.011) were more frequent in the elderly. Therapy and clinical behaviour were similar. Surgery was more frequently performed in the elderly (20% vs 9%, p = 0.02), while biological therapy was less used (2.1% vs 22%, p < 0.0005). Complications were more frequent in the elderly. Extraintestinal manifestations were lower in elderly patients (9.6% vs 19.2%, p = 0.061). Time to first relapse was similar between the two groups. Mortality (p < 0.0005) was higher in elderly patients. CONCLUSIONS: Ulcerative Colitis has similar presentation and behaviour in elderly and adults patients. However, the elderly are more fragile because of comorbidities, increased risk of infections and disease-related complications.

Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet.

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12-18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696].

Subclinical cardiac involvement in Crohn's disease and ulcerative colitis: an echocardiographic case-control study.

BACKGROUND: Cardiovascular manifestations of inflammatory bowel disease (IBD) are considered rare. The aim of the present study was to assess cardiac structure and function by means of traditional Doppler echocardiography and tissue Doppler imaging in order to better appreciate myocardial subclinical alterations and their future implications for these kind of patients. METHODS: Twenty-seven patients affected by Crohn's disease (CD) and 43 suffering from ulcerative colitis (UC) were enrolled. They were selected without cardiovascular diseases nor risk factors. They were compared with 24 healthy subjects matched for sex and age. Everyone underwent transthoracic echocardiography. RESULTS: IBD patients had larger left atrial anterior-posterior dimension (34±7 vs. 31±2 mm; P=0.001) and volume (46±7 vs. 41±6; P=0.002), reduced left ventricular (LV) ejection fraction (59±6 vs. 63±5%; P=0.006) and higher pulmonary artery systolic pressure (26±6 vs. 22±2 mmHg; P<0.001) than healthy volunteers. Moreover, LV diastolic function was slightly altered in patients in respect of controls. Atrioventricular valve regurgitation was prevalent in IBD. Finally, we found that 18 (25.7%) patients had mitral valve prolapse, 35 (50.0%) mitral valve leaflets thickening and 3 (4.3%) pericardial effusion. We did not find differences in echocardiographic parameters between CD and UC. CONCLUSIONS: Our study suggests that subclinical cardiac involvement is frequent among IBD patients. The underlying mechanisms require further evaluation, but might be due to a systemic increase in cytokines and profibrotic factors.

Triticum monococcum in patients with celiac disease: a phase II open study on safety of prolonged daily administration.

BACKGROUND AND AIMS: To assess safety of prolonged daily administration of Triticum monococcum (Tm) using clinical, serological and histological criteria. Tm is an ancient wheat suitable for production of palatable baked goods that contains gluten devoid of strongly immunostimulatory epitopes and potentially safe for celiac disease (CD) patients as suggested by in vitro and ex vivo studies. METHODS: Protocol involved 60-day administration of 100 g/day Tm water biscuits to CD patients in remission on gluten-free diet. Symptoms Gastrointestinal Symptom Rating Scale questionnaire (GSRS) and CD-related serology were assessed at time (T) 0, T30 and T60 days, and duodenal biopsy was obtained at T0 and T60. RESULTS: Eight patients (F/M: 6/2, median age 26) were enrolled. One patient was excluded at T0 because of positive serology, and two patients dropped out because of symptoms recurrence. In the five patients completing the study, there was no difference in GSRS score at T0 to T60. All patients had Marsh II lesion at T0, four had Marsh III and one had recurrence of dermatitis herpetiformis at T60. CD-related antibodies converted from negative to positive at T60 in three patients. CONCLUSIONS: Our study shows that Tm is toxic for CD patients as judged on histological and serological criteria, but it was well tolerated by the majority of patients, suggesting that Tm is not a safe cereal for celiacs, but that it may be of value for patients with gluten sensitivity or for prevention of CD.

Factors that contribute to hypertransaminasemia in patients with celiac disease or functional gastrointestinal syndromes.

BACKGROUND & AIMS: Transaminasemia develops via different pathways in patients with celiac disease; no information is available on risk factors specifically attributable to celiac disease. METHODS: We analyzed data collected from consecutive patients referred from January 1997 through December 2009 to the celiac disease clinic at the Spedali Civili of Brescia, Italy. We assessed the factors affecting hypertransaminasemia in 683 patients with celiac disease (based on serologic and biopsy analysis, cohort A; 34 ± 14 years of age) and 304 with functional syndromes (cohort B; 37 ± 13 years of age). RESULTS: Hypertransaminasemia was detected in 138 patients in cohort A (20%). It was associated with malabsorption (odds ratio [OR], 2.22; P = .004), diarrhea (OR, 1.72; P = .005), and increasing severity of mucosal lesion (Marsh-Oberhuber class; OR, 1.46; P = .001) but not with body mass index (BMI) or the serum level of tissue-transglutaminase antibodies (tTG). Hypertransaminasemia was detected in 22 patients in cohort B (7%) and was associated with the World Health Organization's BMI categories (OR, 7.9; P < .001). In subsets of patients studied with the same analytical method (313 of cohort A and 188 of cohort B), the level of tTG was significantly higher in cohort A at baseline (25.2 ± 16.9 U/L aspartate aminotransferase [AST]) than in cohort B (20.6 ± 9.9 U/L AST, P < .0001) and was related to BMI in cohort B (P = .0012) but not cohort A. When patients were placed on gluten-free diets, the levels of AST decreased from 25.2 ± 16.9 U/L to 19.9 ± 6.6 U/L (P < .0001), independently of the changes of duodenal histology and tTG and correlated with BMI (P = .0007); the prevalence of hypertransaminasemia decreased from 13% to 4%. CONCLUSIONS: Patients with celiac disease have a higher prevalence of hypertransaminasemia than controls (patients with functional syndromes). Hypertransaminasemia is related to the severity of the duodenal lesion and malabsorption but not BMI. By contrast, there was a positive correlation between the levels of AST and BMI in controls; this relationship was restored when patients with celiac disease were placed on gluten-free diets.

Anti-TCR gamma antibody in celiac disease: the value of count on formalin-fixed paraffin-embedded biopsies.

Small bowel intraepithelial lymphocytosis (IL) may depend from different causes, including celiac disease (CD). Demonstration of increased number of duodenal T cell receptor gamma-delta (TCRγδ) positive intraepithelial lymphocytes (IELs) has been used to support CD diagnosis on frozen material. This work evaluates a new commercially available anti-TCRγ antibody on formalin-fixed paraffin embedded (FFPE) small bowel biopsies. Anti-CD3 and anti-TCR CγM1 (clone γ3.20) from Thermo Scientific were applied by immunohistochemistry on 59 FFPE biopsies from 18 cases of CD with mild/severe atrophy, 19 cases of IL in CD patients on gluten-free diet (IL-GFD), 14 cases of IL (6/14 with positive CD-related serology), and 8 controls (CTR) with mild duodenitis and negative CD serology and genotyping. IELs/100 epithelial cells were counted in at least six high power fields. CD3+ and TCRγ+ IELs were significantly higher in CD, IL-GFD, and IL compared with CTR, but in contrast to CD3+ IELs, TCRγ+ IELs were significantly increased in CD and IL-GFD compared with IL. Furthermore, TCRγ+ IELs discriminated between IL with negative and positive CD-related serology (p = 0.02). TCRγ+ IELs can be identified on FFPE samples and their evaluation adds useful information for the work-up of small bowel biopsies in CD diagnosis. In fact, TCRγ staining coupled with CD3, may represent an additional tool to recognize cases of latent/potential CD when serology and clinical data are not conclusive or when the histological diagnosis remains equivocal.

Celiac disease in elderly adults: clinical, serological, and histological characteristics and the effect of a gluten-free diet.

OBJECTIVES: To compare celiac disease (CD) in older and younger adults and to assess the effects of a gluten-free diet (GFD). DESIGN: Retrospective retrieval of information prospectively entered into a structured database. SETTING: CD clinic, University and Spedali Civili, Brescia, Italy. PARTICIPANTS: Two cohorts were identified (older, Group A, n = 59, >65; younger, Group B, n = 1,166, 18-64), and Group B was subgrouped (B1, n = 600, 18-34; B2, n = 440, 35-49; and B3, n = 26, 50-64). MEASUREMENTS: Clinical, serological, and histological characteristics of individuals with CD studied before and during a GFD. RESULTS: At presentation, weight loss (37% vs 21%, P = .005) and dyspepsia (22% vs 12%, P = .04) were more frequent in older than younger participants. Incidence at diagnosis of non-Hodgkin's lymphoma (NHL) was much higher in older (5%) than younger participants (0.3%, P = .003). Prevalence of osteoporosis was 67% in older and 14% in younger male participants and 70% in older and 9% in younger female participants ( P < .001). During treatment, adherence to a GFD was 90%, normal villous structure was reconstituted, and t-transglutaminase antibodies were negative in 80% of older and younger participants. Lumbar-sacral and femoral T scores increased significantly during a GFD in pooled results of 48 older and younger participants studied before and during GFD. CONCLUSION: NHL is already present at CD diagnosis in most cases in individuals aged 50 and older, emphasizing the importance of early diagnosis. Older and younger individuals are equally adherent and equally benefit from a GFD, indicating that older age is not a barrier to dietary treatment.

Abnormal anandamide metabolism in celiac disease.

The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase-polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.

High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease.

BACKGROUND: Duodenal biopsy may be unnecessary to confirm celiac disease in patients with high tissue-transglutaminase antibody level. AIMS: To define a cut-off value of tissue-transglutaminase antibody with high positive likelihood ratio for duodenal atrophy in patients with suspected celiac disease. METHODS: We retrospectively identified 945 patients with suspected celiac disease and classified according to the method used for tissue-transglutaminase antibody assay: Group A (n=393, Eu-tTG® Eurospital), Group B (n=263; Eu-tTG® Eurospital) and Group C (n=289; Celikey® Phadia). Duodenal histology was graded according to Marsh. Sensitivity, specificity, and positive likelihood ratio were used to evaluate cut-off points of tissue-transglutaminase antibody as predictor of villous atrophy. RESULTS: 100% specificity and ∞ positive likelihood ratio for duodenal atrophy was observed at a cut-off value of tissue-transglutaminase antibody 5 times higher than the upper limit of normal. CD diagnosis was confirmed by concordance with antiendomysial antibodies, and by reduction of t-TG titre in all patients and improvement of duodenal histology in 80% during gluten-free diet. CONCLUSIONS: Tissue-transglutaminase antibody level 5-folds the upper limit of normal is 100% specific for duodenal atrophy and using this cut-off biopsy could by avoided in 1/3 of patients. Diagnostic criteria of celiac disease in adults need revision.

Bio-physical characteristics of gastrointestinal mucosa of celiac patients: comparison with control subjects and effect of gluten free diet-.

BACKGROUND: Intestinal mucosa is leaky in celiac disease (CD), and this alteration may involve changes in hydrophobicity of the mucus surface barrier in addition to alteration of the epithelial barrier. The aims of our study were i) to compare duodenal hydrophobicity as an index of mucus barrier integrity in CD patients studied before (n = 38) and during gluten- free diet (GFD, n = 68), and in control subjects (n = 90), and ii) to check for regional differences of hydrophobicity in the gastro-intestinal tract. METHODS: Hydrophobicity was assessed by measurement of contact angle (CA) (Rame Hart 100/10 goniometer) generated by a drop of water placed on intestinal mucosal biopsies. RESULTS: CA (mean ± SD) of distal duodenum was significantly lower in CD patients (56° ± 10°)) than in control subjects (69° ± 9°, p < 0.0001), and persisted abnormal in patients studied during gluten free diet (56° ± 9°; p < 0.005). CA was significantly higher (62° ± 9°) in histologically normal duodenal biopsies than in biopsies with Marsh 1-2 (58° ± 10°; p < 0.02) and Marsh 3 lesions (57° ± 10°; p < 0.02) in pooled results of all patients and controls studied. The order of hydrofobicity along the gastrointestinal tract in control subjects follows the pattern: gastric antrum > corpus > rectum > duodenum > oesophagus > ileum. CONCLUSIONS: We conclude that the hydrophobicity of duodenal mucous layer is reduced in CD patients, and that the resulting decreased capacity to repel luminal contents may contribute to the increased intestinal permeability of CD. This alteration mirrors the severity of the mucosal lesions and is not completely reverted by gluten-free diet. Intestinal hydrophobicity exhibits regional differences in the human intestinal tract.

Gastroesophageal reflux disease and Barrett's esophagus.

Gastroesophageal reflux disease is the most common gastrointestinal diagnosis recorded during visits to outpatient clinics. The spectrum of injury includes esophagitis, stricture, the development of columnar metaplasia in place of the normal squamous epithelium (Barrett's esophagus), and adenocarcinoma. Barrett's esophagus is a premalignant lesion detected in the majority of patients with esophageal and gastroesophageal adenocarcinoma. The incidence of these cancers has been increasing in the United States and they are associated with a low rate of survival (5-year survival rate, 15-20%). When symptoms of gastroesophageal reflux disease are typical and the patient responds to therapy, no diagnostic tests are necessary to verify the diagnosis. Endoscopy is the primary test in patients whose condition is resistant to empirical therapy but its yield in this setting is low because of the poor correlation between symptoms attributed to the condition and endoscopic features of the disease. Clinical experience suggests that lifestyle modifications may be beneficial for gastroesophageal reflux disease although trials of the clinical efficacy of dietary or behavioral changes are lacking. Abundant data from randomized trials show benefits of inhibiting gastric acid secretion and suggest that proton-pump inhibitors are superior to H2-blockers and that both are superior to placebo. In patients with Barrett's esophagus, antireflux interventions are intended to control symptoms of reflux and promote healing of the esophageal mucosa. If a patient has symptoms refractory to proton-pump inhibitors or cannot tolerate such therapy, antireflux surgery, most commonly Nissen fundoplication, may be an alternative management approach. In patients with high-grade dysplasia, endoscopic therapies or surgical resection must be considered.

[Extraintestinal manifestations in Crohn's disease: risk factors and influence of intestinal surgery]. / Manifestazioni extraintestinali della malattia di Crohn. Fattori di rischio e impatto della chirurgia digestiva.

BACKGROUND: Extraintestinal manifestations significantly affect the quality of life of patients with Crohn's disease. The aim of the present study is to define the risk factors for extraintestinal manifestations and the relative influence of intestinal surgery. PATIENTS AND METHODS: In a cohort of 223 patients with Crohn's disease we analyzed the association between demographic/clinico-pathological factors and extraintestinal manifestations. In addition, we evaluated their association with the timing of appearance of the extraintestinal manifestations with respect to the intestinal surgery. RESULTS: Fifty-seven patients (25.6%) developed 91 extraintestinal manifestations. Demographic and clinico-pathological variables significantly associated with extraintestinal manifestations were: female gender (OR 2.84, 95% CI: 1.37-5.90) and colonic involvement (OR 2.68, 95% CI: 1.06-6.76). In patients not undergoing surgery and in patients with extraintestinal manifestations present only before surgery, the latency period between the onset of Crohn'S disease and extraintestinal manifestations were 3.7 +/-8.2 and 2.1 +/- 6.3 years, respectively. In patients developed extraintestinal manifestations only after surgery, the latency between surgery and extraintestinal manifestations was 12.0 +/-10.0 years. In 5 patients with early onset of extraintestinal manifestations, these did not regress or recur after surgery. CONCLUSION: Female gender and colonic involvement are confirmed as risk factors for the development of extraintestinal manifestations in Crohn's disease. Surgical treatment of the intestinal disease represents a therapeutic option for patients with extraintestinal manifestations, as it seems to prevent or delay these manifestations in most cases.

How to proceed in Helicobacter pylori-positive chronic gastritis refractory to first- and second-line eradication therapy.

Helicobacter pylori is a widespread disease causing most of the peptic ulcer diseases and low-grade mucosa-associated lymphoreticular tissue (MALT) lymphoma. Moreover, H. pylori is a proven environmental risk factor for gastric carcinoma and it has been recognized as a type 1 carcinogen factor. A combination of drugs has been proposed, using a proton pump inhibitor (PPI), amoxicillin, clarithromycin, metronidazole and tetracycline to treat the infection. Since 1996, according to the European guidelines, the first-line approach using PPI, amoxicillin and clarithromycin or metronidazole has been suggested. Seven days of quadruple therapy with PPI (or ranitidine), tetracycline, bismuth salts and metronidazole has been reserved as second-line treatment. To improve the eradication rate of the triple therapy, a different combination of the available antibiotics has been proposed, consisting of a 10-day sequential regimen. A second-line levofloxacin-amoxicillin-based triple therapy given for 10 days has been proposed, obtaining a high eradication rate, suggesting this regimen to be a suitable retreatment option in eradication failure. A third-line treatment with rifabutin-based regimen has been proposed.

Increased serum gamma-glutamyl-transpeptidase concentration is associated with nonalcoholic steatosis and not with cholestasis in patients with chronic hepatitis C.

BACKGROUND AND AIM: Increased pretreatment gamma-glutamyl-transpeptidase (gammaGT) is common in patients with chronic hepatitis C and with little or no alcohol consumption. The mechanism involved in this phenomenon is unclear, and the aim of this study was to investigate factors associated with increased gammaGT levels, specifically looking at the role of cholestasis that frequently accompanies hepatitis C. METHODS: Fifty patients with chronic hepatitis C enrolled in two trials of antiviral treatment, 25 with normal and 25 with elevated pretreatment gammaGT levels, were retrospectively selected. In addition to the common liver function and virological tests, other values measured were serum bile acid concentration and composition by gas-chromatography as a sensitive index of cholestasis, and liver biopsy scores for cholestasis and steatosis in addition to siderosis, fibrosis and inflammation. RESULTS: Total mean serum bile acid concentration was 11.6 +/- 1.4 micromol/L and 8.5 +/- 1.2 micromol/L (not significant) in patients with elevated and with normal gammaGT, respectively, and individual bile acid composition was similar in the two groups. By univariate analysis, serum gammaGT level was linearly related to total serum bile acid (P < 0.05) and to cholestasis score (P < 0.001) among other variables, but steatosis score (P < 0.001) and Knodell score (P < 0.04) were the only variables independently associated with elevated serum gammaGT level by multivariate analysis. CONCLUSIONS: Increased serum gammaGT level in patients with chronic hepatitis C is associated with liver steatosis and fibrosis, and indicates more advanced liver disease rather than reflecting the cholestasis that often accompanies this condition.

Is TCRgamma clonality assay useful to detect early celiac disease?

BACKGROUND: Although histology is considered the gold standard for the diagnosis of celiac disease, the early stages (latent or potential) of this disease are difficult to diagnose, because of the negativity of laboratory tests and the lack of villous atrophy. Thus, markers of early disease are needed. AIMS: We investigated the possibility to detect latent or potential celiac disease by means of TCRgamma clonality assay in intraepithelial T cells in patients with suspected disease, negative laboratory tests, and an increased number of intraepithelial lymphocytes. PATIENTS AND METHODS: Duodenal biopsies were obtained from 35 patients with nonspecific duodenitis (controls), 13 latent or potential celiac disease subjects, 28 well-defined celiac patients, and 8 celiac patients in gluten-free diet. Histologic and immunohistochemical quantification of intraepithelial lymphocytes, as well as TCRgamma clonality assay, were carried out in all subjects by means of standard techniques. RESULTS: Intraepithelial lymphocytes and TCRgamma clonality were significantly increased in potential and defined celiac patients with respect to the controls, even though the increase in TCRgamma clonality was lesser with respect to that of intraepithelial lymphocytes. No significant differences were found concerning this variable between the potential and defined celiac subjects. CONCLUSIONS: TCRgamma clonality does not represent a marker of early disease. However, it might be useful to help in distinguishing celiac disease from other causes of nonspecific duodenitis.

Helicobacter pylori infection in patients with celiac disease.

BACKGROUND AND AIMS: Patients with Helicobacter pylori gastritis are more likely to have increased duodenal intraepithelial lymphocytes (IEL); this can be reversed by H. pylori eradication. We hypothesized that: (1) H. pylori-infected celiac disease (CD) patients could have different clinicopathological features from noninfected subjects; and (2) the histopathological responses to a gluten-free diet could be different in H. pylori-infected and noninfected patients. METHODS: Duodenal and gastric biopsies obtained from 80 adults with histologically and serologically confirmed CD before and after 12-18 months of a gluten-free diet were retrospectively evaluated. Gastritis was classified and scored according to the Updated Sydney System; duodenal biopsies were classified using both the Marsh-Oberhuber and a simplified classification proposed by our group. RESULTS: At baseline, 30 patients had H. pylori infection and 50 did not; at follow-up five new infections were detected. Fifteen patients (3 H. pylori-positive and 12 negative) had lymphocytic gastritis. At baseline, a greater proportion of H. pylori-negative patients had severe villous atrophy (p < 0.01), but milder forms were more prevalent in H. pylori-positive patients (p < 0.01). After a gluten-free diet, significant improvement occurred in all duodenal features (p < 0.001), irrespective of H. pylori status; gastric variables did not change, except for lymphocytic, which resolved in 2 infected and 10 noninfected patients. CONCLUSIONS: The clinical features of CD patients are unrelated to H. pylori gastritis, and a gluten-free diet is equally effective in infected as in uninfected patients. The higher prevalence of milder duodenal lesions in CD patients with H. pylori infection suggests that lymphocytosis induced by H. pylori gastric infection becomes less obvious as profound inflammatory and structural changes alter the mucosal architecture. This study also provides further support for a pathogenetic relationship between CD and lymphocytic gastritis.

Epidemiological, clinical and histopathologic characteristics of celiac disease: results of a case-finding population-based program in an Italian community.

OBJECTIVE: Celiac disease (CD) is underdiagnosed mainly because of lack of awareness of its heterogeneous clinical presentation. The Center for Surveillance and Control of Celiac Disease (CCD) was set up in June 2000 in the province of Brescia, Northern Italy (1,016,426) inhabitants to enhance case-finding, to standardize diagnostic criteria and to collect epidemiological data. MATERIAL AND METHODS: The CCD has prompted an educational "celiac awareness program" in the primary-care setting focusing on selective serological screening of high-risk groups, and has reviewed by standardized criteria all diagnoses made in the province since 1984. RESULTS: A total of 1437 CD patients have been identified by the CCD, 508 of them diagnosed after June 2000 during the 3 years of activity of the Center (M:F 2:1). Annual incidence was 0.11/1000 before and increased to 0.17/1000 during CCD activity, and this increase was greater for adult (from 0.07/1000 to 0.12/1000) than for pediatric CD (from 0.04/1000 to 0.05/1000). Mean age at diagnosis also increased from 20.2+/-17.7 years to 27.2+/-19.3 years (p<0.0001) as did the proportion of asymptomatic patients (8% versus 15%) before and during CCD activity. There was a linear trend towards increasing proportions of symptomatic patients with increasing severity of histopathologic lesions (p<0.03). CONCLUSIONS: Our results indicate that educational programs promoting serological screening of CD in high-risk groups are effective for case-finding in large communities, particularly among the adult population, and suggest that primary-care doctors caring for adults should be particularly targeted by "celiac awareness programs".

Ursodeoxycholic acid does not affect ethinylestradiol bioavailability in women taking oral contraceptives.

OBJECTIVE: Contraception is recommended for female patients during ursodeoxycholic acid (UDCA) treatment for the potential teratogenic effect of this bile acid, and the aim of our study was to determine whether this treatment affects the bioavailability of ethinylestradiol (EE2). METHODS: In this double-blind, randomised study, we measured EE2 pharmacokinetics in eight healthy volunteers randomly allocated to receive oral contraceptive (30 microg EE2 and 75 microg gestodene) plus either UDCA (8-10 mg/kg per day) or placebo for 21 days during the first of three consecutive menstrual cycles. After a washout period during the second cycle, the subjects received the alternative treatment during the third menstrual cycle. Serum EE2 and UDCA were measured using radioimmunoassay and gas chromatography-mass spectrometry, respectively. RESULTS: The profile for serum EE2 concentration was similar during UDCA (mean maximum serum concentration 177 pg/ml, SEM 59) and during placebo treatment (153 pg/ml, SEM 62), and mean area under the curve (AUC) was 1374 pg/h per ml (SEM 580) and 1320 pg/h per ml (SEM 551) during the two regimens, respectively. The point estimates and 90% confidence intervals of UDCA/placebo ratios for EE2 AUC and for maximum serum concentration were 1.1 (0.8-1.5) and 1.2 (1.0-1.4), respectively. Mean serum triglycerides concentration increased from 58.3 mg/dl (SEM 6.8) at enrolment to 91.4 mg/dl (SEM 10.7) during placebo (P < 0.01) and to 88.6 mg/dl (SEM 13.7) during UDCA treatment (P < 0.05). During UDCA treatment, serum enrichment with this bile acid and with the metabolite iso-UDCA was 29% (16%) and 3% (2%), respectively. CONCLUSION: Co-administration with UDCA does not affect the bioavailability of EE2 in healthy volunteers, indicating that contraceptive efficacy is not affected.