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Background: Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services., Methods/design: The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers' patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrollment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms' severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in 'real-world' clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction.

We report the case of a 35-year-old woman with a diagnosis of coeliac disease at the age of 32 due to a severe malabsorption and flat mucosa without endomysial and tissue transglutaminase antibodies. The lack of clinical and histological improvement after 1 year of a gluten-free diet led to a diagnosis of refractory sprue. She had a good clinical response to steroids that were stopped after 3 months when she became pregnant. After delivery, she again started to complain of malabsorption with arthritis. Positivity for enterocyte autoantibodies together with a flat mucosa persistence allowed to identify a condition of autoimmune enteropathy; moreover, a rheumatological assessment gave evidence of an associated rheumatoid arthritis. Treatment by steroids and methotrexate brought to the remission of intestinal and articular symptoms together with an improvement of duodenal histology. This is the first description of an autoimmune enteropathy associated with rheumatoid arthritis. Autoimmune enteropathy should be always ruled out in patients with a villous atrophy unresponsive to a gluten-free diet, autoimmune manifestations and negativity of coeliac disease markers.

Background: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia., Aims: To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet., Patients and Methods: Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay., Results: IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs., Conclusions: A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.

Background: Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively., Aim: To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage., Methods: One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence., Results: In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis., Conclusion: More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.

Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P < 0.0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease.

The presence of circulating autoantibodies to gut enterocytes has been very rarely described in adults and is considered a possible cause of refractory sprue. Our aims was to describe the case of an adult patient with serum anti-enterocyte autoantibodies associated with a clinical picture characterized by involvement of both the small intestine and colon. A female, age 50, had suffered from diarrhea with mucus and blood, abdominal pain, thinness, anemia, and leukopenia since the age of 20. She also suffered from HCV infection and had mild chronic hepatitis. Family history was positive for autoimmunity. Symptoms were reported to worsen after eating gluten-containing foods, but anti-transglutaminase and anti-endomysial antibodies were negative. Intestinal histology showed mild, patch villous atrophy with a high intraepithelial lymphocyte count, but a normal number of intraepithelial lymphocytes carrying the gamma/delta+ receptor. HLA was: A11, A31 (19), B52 (5), DR 15 (2), DR 14 (6), DR 51, DR 52, DQ1. Colonoscopy did not show ulcerations or erosions and colon histology showed a moderate inflammatory infiltrate without minor crypt distortion or granuloma. RAST tests were positive for lactalbumin, lactoglobulin, casein, egg, and gliadin. After commencement of an oligoantigenic diet, stool frequency initially decreased, but the presence of mucus in the stools persisted, with episodes of bloody diarrhea. After one year of diet, nutritional parameters were low and anemia associated with a low leukocyte count persisted. Upper and lower gastrointestinal endoscopy and histology of the small intestine and colon were virtually unchanged. Consequently, natural autoantibodies and enterocyte autoantibodies were assayed. The patient was positive for IgG class enterocyte autoantibodies at a titer of 1:34. No other organ-specific or non-organ-specific autoantibodies were positive. Prednisolone treatment was started and the symptoms improved. After one year of this treatment plus elimination diet she was reevaluated. Bowel movement frequency was normal, body weight increased, and the asthenia had completely regressed. IgG anti-enterocyte autoantibodies were absent. Histology of the distal duodenum showed a normal villus/crypt ratio and IEL infiltration was reduced. Colon histology showed a reduction in inflammatory infiltrate in the lamina propria. In conclusion, we report a case of generalized gut disorder in an adult patient, affecting both the small intestine and the colon and characterized by the presence of circulating anti-enterocyte autoantibodies. Systematic testing for enterocyte autoantibodies should be performed not only in patients with refractory sprue, but also in subjects with upper and lower intestinal symptoms who have not been definitively diagnosed.

Background: Little is known about the clinical and immunological features of coeliac disease patients with neurological disorders. In a large series of adult coeliac disease patients, we investigated the prevalence of neurological disorders and anti-neuronal antibodies, along with the clinical course., Methods: Neurological symptoms were investigated in 160 consecutive patients (120 F, 40 M) with biopsy-proven coeliac disease. Anti-neuronal antibodies to central/enteric nervous systems were investigated in all neurological patients, 20 unaffected ones and 20 controls., Results: Thirteen (8%) patients had neurological disorders, including epilepsy (n = 3), attention/memory impairment (n = 3), cerebellar ataxia (n = 2), peripheral neuropathy (n = 2), multiple sclerosis (n = 1), Moyamoya disease (n = 1) and Steinert's disease (n = 1). No significant demographic or clinical differences (gastrointestinal or other gluten-related signs) were found between patients with and without neurological involvement. In all but 2 of the 13 cases, the neurological disorder preceded diagnosis ofcoeliac disease. Neurological symptoms improved or disappeared in 7 patients who started a gluten-free diet within 6 months after neurological onset, and in none of 4 patients who began later. Prevalence of central nervous system anti-neuronal antibodies was significantly higher in neurological (61%) than in other patients (5%) (P = 0.0007) or controls (0%) (P = 0.00001)., Conclusions: Coeliac disease can sometimes present in the guise of a neurological disorder, which may greatly improve when a gluten-free diet is started promptly. Therefore, the possible presence of coeliac disease needs to be carefully considered in patients with cerebellar ataxia, epilepsy, attention/memory impairment or peripheral neuropathy.

Objectives: In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy., Methods: Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis., Results: Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease., Conclusions: The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

Background: Unexplained hypertransaminasaemia can be regarded as an extraintestinal presentation of coeliac disease., Aim: To evaluate the reliability of immunoglobulin A anti tissue transglutaminase antibodies for identifying coeliac disease in those patients with raised transaminases of unknown origin., Patients: Of 1,120 consecutive patients referred to the outpatient clinic for liver disease due to raised transaminases from September 1995 to December 1999, 110 were classified as having cryptogenic hypertransaminasaemia after the exclusion of every known cause of liver disease., Methods: These 110 patients were tested for immunoglobulin A anti tissue transglutaminase and antiendomysial antibodies by enzyme-linked immunosorbent assay and indirect immunofluorescence, respectively., Results: Ten patients resulted positive for both antibodies; in all of them duodenal biopsy showed a subtotal villous atrophy consistent with coeliac disease. They did not complain of any gastrointestinal symptom. Liver biopsy, performed in five, showed a histological picture of non-specific reactive hepatitis., Conclusions: Due to the high proportion (9.15%) of patients with cryptogenic hypertransaminasaemia affected by symptomless coeliac disease, serological screening for gluten-sensitive enteropathy must be included in the work-up of these patients. In this respect, anti tissue transglutaminase antibodies represent a valid alternative to antiendomysial antibodies with the advantage of being feasible everywhere thanks to the worldwide availability of enzyme-linked immunosorbent assay.

Background and Aims: The close association between coeliac disease and autoimmunity prompted us to perform an antibody screening for gluten-sensitive enteropathy in patients with autoimmune thyroid dysfunction., Methods: Sera from 220 patients with autoimmune thyroiditis, 50 euthyroid subjects with thyroid nodules and 250 blood donors were tested for IgA anti-tissue transglutaminase (anti-tTG) and antiendomysial antibodies (EmA)., Results: IgA anti-tTG was positive in 7 patients with autoimmune thyroiditis, whereas IgA EmA was found only in 6 of them. Duodenal biopsy confirmed coeliac disease diagnosis disclosing marked and mild villous atrophy in 6 and 1 of them, respectively. All but 2 of the 7 coeliacs did not show any sign of malabsorption. All euthyroid controls were negative for IgA antibodies, whereas 1 blood donor, positive for both IgA anti-tTG and EmA, was found to be coeliac. The prevalence of coeliac disease in patients with autoimmune thyroiditis (3.2%) was significantly higher than that found in blood donors (0.4%) (p = 0.022, Fisher's exact test)., Conclusions: Antibody screening for coeliac disease should be included in the work-up of patients with autoimmune thyroiditis. Either IgA anti-tTG or EmA may be used, even though the former seems to be slightly more sensitive than the latter., (Copyright 2001 S. Karger AG, Basel)

The "campus" represents a good instrument to improve the independence of the child and adolescent with diabetes. What are the expectation of children taking part in it? For them, will it be a vacation or a period of hospitalization? To evaluate these aspects we have studied, in addition to the theoretical and practical knowledge, the emotional life of 53 young diabetics (31 males and 22 females, age 8.1-15.7 years, duration of disease 2 months 10 years, and HbA1c 6.5-12.6%). We observed that 80% of the patients improved the injection technique; we also found an increase of correct answers (from 60% to 73%, x = 3.8, p < 0.05) to a list of questions on different aspects of diabetes asked at the beginning and at the end of the campus. From the drawings collected at the end of the stay, we observed that 78% of the children lived the experience in a playful way, 11% in a medical and 11% in a educational way. It must be pointed out that the children who perceived the educational aspect of the stay were older than the others (11.5 +/- 2 vs. 13.9 +/- 1; p < 0.05). Consequently, we believe that educational programs on diabetes, like the "campus", should be reserved to children older than 12 years of age.

This study was undertaken in order to evaluate the prevalence of headache and its subtypes (migraine, muscle tension headache, cluster and psychogenic headache) in a population of 160 depressed patients. Headache was present in 83 subjects (51.9%); 36 (22.5%) were affected by migraine, 39 (24.4%) by muscle tension headache, six (3.7%) by psychogenic headache and two (1.2%) by cluster headache. No significant differences in the prevalence of migraine and muscle tension headache were observed among patients with major depression, bipolar depressive disorder and dysthymic disorder. These data speak against a specific correlation among subtypes of headache and depressive disorders.