Microbial Biomarkers in Patients with Nonresponsive Celiac Disease.

BACKGROUND AND AIMS: In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD. METHODS: ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls. RESULTS: At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79). CONCLUSIONS: Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.

Presentation of Celiac Disease in Finnish Children Is No Longer Changing: A 50-Year Perspective.

OBJECTIVES: To chart trends in the presentation of celiac disease in a large cohort of Finnish children diagnosed over a period of 48 years. STUDY DESIGN: Clinical and serologic data, severity of small-bowel mucosal damage, and presence of associated conditions were gathered from 596 children diagnosed with celiac disease in 1966-2013. The children were divided into 4 groups based on the year of diagnosis (before 1980, 1980-1999, 2000-2009, and 2010-2013), and the variables were compared between the periods. The incidence of celiac disease autoimmunity in 2001-2013 was calculated based on the number of new antibody-positive cases in each year. RESULTS: Age at diagnosis rose from median 4.3 years before 1980 to between 7.6 and 9.0 years in the later periods. The severity of clinical presentation, in general, became milder and poor growth less common during the entire study period of 50 years. Percentages of children with classical gastrointestinal presentation decreased, and those with atypical or subclinical presentation increased after the 1990s, these changes leveling off in 2000-2013. Similarly, the severity of small-bowel mucosal damage was milder after the 1990s. The incidence of celiac disease autoimmunity increased in the early 2000s but then fluctuated without a clear trend. There were no significant secular changes in sex distribution, presence of anemia, levels of celiac antibodies, or celiac disease-associated conditions. CONCLUSIONS: The clinical and histologic presentation of celiac disease in children became milder, especially in the 1980s and 1990s. However, most of these changes have reached a plateau in recent years.

Faecal calprotectin in suspected paediatric inflammatory bowel disease.

OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data. METHODS: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator. RESULTS: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 µg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94). CONCLUSIONS: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.

Sleep and emotional and behavioral symptoms in adolescents with inflammatory bowel disease.

The current study assessed the associations between sleep and psychosocial symptoms in 157 Finnish adolescents with inflammatory bowel disease (IBD). Sleep trouble was self-rated in Sleep Self-Report (SSR) and in Youth Self-Report (YSR). Psychosocial symptoms of the adolescents were assessed by the YSR and Child Behavior Checklist (CBCL). Patients reporting sleep trouble had significantly more psychosocial symptoms than their counterparts without sleep trouble. This was shown in the CBCL and YSR scales of total problems (P < 0.01), anxious/depressed mood (P < 0.05), and aggressive behavior (P < 0.01). Additionally, SSR sleep problem subscale scores indicating lower sleep quality (bedtime, sleep behavior) associated significantly with attention problems (P < 0.05). These results point out that sleep trouble should be recognized and treated in adolescents with IBD to possibly avoid the emerging of psychosocial symptoms.

Increased expression of CXCL16, a bacterial scavenger receptor, in the colon of children with ulcerative colitis.

BACKGROUND AND AIMS: CXCL16 is a scavenger receptor which has been connected to phagocytosis of bacterial antigens in experimental colitis. It has also been shown to have a pivotal role in the development of experimental colitis in mice. The increased expression of CXCL16 has been demonstrated in inflamed lesions of patients with Crohn disease. Our aim was to study the expression of CXCL16 in the colon of patients with ulcerative colitis. METHODS: Relative quantitative reverse transcription-polymerase chain reaction was applied to explore the gene expressions of CXCL16, its receptor CXCR6, and interleukin 8, an inflammatory marker, in the colonic biopsies of children with active ulcerative colitis (n=19), children with ulcerative colitis in remission (n=9) and children with no inflammatory condition in colon (n=14). RESULTS: An increased expression of CXCL16 in the colonic biopsies of children with ulcerative colitis was found both in active disease (p=0.006) and in remission (p=0.033), when compared to children without inflammatory condition. The gene expressions of interleukin 8 and CXCL16 correlated with each other (rs=0.67, p=0.01). The expression of CXCR6 mRNA was comparable between the study groups (p=0.50). CONCLUSIONS: The gene expression of CXCL16 was increased in patients with ulcerative colitis both in active disease and in remission suggesting an important role of the molecule in the pathogenesis of the condition.

Early microbial markers of celiac disease.

BACKGROUND AND GOALS: Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) has been detected in celiac disease patients with small-bowel mucosal atrophy. Levels of these antibodies decrease during a gluten-free diet, but their functions and time of appearance in celiac disease are not known. We aimed to search for evidence of possible microbial targets of the immune responses in the early-stage celiac disease patients who showed normal small-bowel mucosal architecture at the time of the first investigations, but later on a gluten-containing diet developed mucosal atrophy. MATERIALS AND METHODS: Forty-four cases with proven early-stage celiac disease and normal mucosal morphology were enrolled. Patients' sera were tested for celiac disease antibodies against tissue transglutaminase (tTG-ab), endomysium, and for microbial antibodies against I2, OmpW, and ASCA IgG and IgA isotypes in both at the time of diagnosis and while on a gluten-free diet. RESULTS: Thirty-four (77%) of 44 patients with early-stage celiac disease had elevated serum antibodies to one or more of the antibodies ASCA, I2, and OmpW. Furthermore, 5 of 6 cases negative for both tTG-ab and endomysium showed positivity for the microbial markers. Seroreactivity to ASCA IgA, ASCA IgG, and OmpW decreased significantly during gluten-free diet. CONCLUSIONS: Seroreactivity to different microbial antigens is evident already in patients with early-stage celiac disease. ASCA antibodies seem to be gluten-dependent. The results indicate that the microbial targets might have a role in the early development of celiac disease.

[Nutrition of a diseased child]. / Sairaan lapsen ravitsemus.

The objective of nutritional therapy of a child patient is to secure the child's normal growth and development. In general, it is possible to achieve the goals by using enteral nutrition. Brief parenteral nutrition is often necessary, for example after surgical operations. Short-bowel syndrome is one of the diseases requiring prolonged parenteral nutrition and presenting exceptionally strong challenges for nutritional therapy. The planning and responsibility for implementation of nutritional therapy of a severely diseased child belong to specialized care. The nutrition team comprises a nutritional therapist, a pediatric nurse and a pediatrician specialized in nutrition.

Cow's milk allergy, asthma, and pediatric IBD.

We identified a total of 595 Finnish children born in 1994-2008 and diagnosed as having inflammatory bowel disease (IBD) by October 2010 from the National Reimbursement Register (based on certificates including the diagnostic criteria) to determine whether the presence of cow's milk allergy (CMA) or asthma is associated with the risk of contracting IBD (altogether 2380 matched controls). A diagnosis of CMA in infancy was associated with Crohn disease (odds ratio [OR] 1.92, confidence interval [CI] 1.09-3.36, P < 0.05) and ulcerative colitis (OR 1.71, CI 1.04-2.83, P < 0.05), but childhood asthma only with Crohn disease (OR 2.33, CI 1.41-3.86, P = 0.001). Thus, CMA in infants is a risk factor for contracting pediatric IBD and accordingly, asthma for Crohn disease.

Long-term outcomes after surgery on pediatric patients with Crohn disease.

OBJECTIVE: Of pediatric patients with Crohn disease, 20% to 30% undergo surgery within 10 years. Although disease relapses and reoperations are common, long-term functional outcomes and quality of life (QoL) are unclear. METHODS: In 2010, we reviewed the hospital records of all pediatric patients with CD who had undergone intestinal resections during childhood in 2 major tertiary care hospitals between 1985 and 2008 and mailed out questionnaires that asked about health outcomes and QoL. We compared the QoL of the patients and a group of matched controls randomly chosen from the Population Register Centre. RESULTS: In total, 36 children had undergone bowel resection a median of 10 years earlier and had at least 2 years of follow-up. Disease activation (verified at endoscopy) requiring medical or surgical treatment occurred in 94% (median 1.8 years after primary resection). At least 1 surgical complication occurred in 77%, and 54% underwent re-resection. The patients reported a median stool frequency of 3 stools during the day and zero at night, with 33% being totally continent. Overall, 96% were completely or moderately satisfied with the outcome of the surgery. The QoL was comparable between the patients and controls, but school or work absences diminished the QoL of the patients. CONCLUSIONS: Surgery for pediatric-onset CD is risky even under expert care. Disease relapses and bowel re-resections are common during the first decade after primary surgery. In the long term, however, bowel function is acceptable and the QoL is comparable between patients and their peers.

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis.

AIM: To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC). METHODS: In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs. RESULTS: Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 µg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression. CONCLUSION: The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.

Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation.

AIM: To investigate the association between serum antibody levels and a subsequent celiac disease diagnosis in a large series of children and adults. METHODS: Besides subjects with classical gastrointestinal presentation of celiac disease, the study cohort included a substantial number of individuals with extraintestinal symptoms and those found by screening in at-risk groups. Altogether 405 patients underwent clinical, serological and histological evaluations. After collection of data, the antibody values were further graded as low [endomysial (EmA) 1:5-200, transglutaminase 2 antibodies (TG2-ab) 5.0-30.0 U/L] and high (EmA 1: ≥ 500, TG2-ab ≥ 30.0 U/L), and the serological results were compared with the small intestinal mucosal histology and clinical presentation. RESULTS: In total, 79% of the subjects with low and 94% of those with high serum EmA titers showed small-bowel mucosal villous atrophy. Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a gluten-containing diet, or responded positively to a gluten-free diet. CONCLUSION: Irrespective of the initial serum titers or clinical presentation, EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis.

Incidence trends of pediatric inflammatory bowel disease in Finland, 1987-2003, a nationwide study.

BACKGROUND: The present study aimed to characterize the incidence of pediatric inflammatory bowel disease (IBD) in Finland and determine its temporal trends. METHODS: The patients' data were based on the database of the Social Insurance Institution. New cases diagnosed with IBD at the age <18 years in Finland between years 1987-2003 were included. Annual incidence rates were calculated per 100,000 pediatric populations (with 95% confidence intervals [CI]). The country is divided into 21 hospital districts and regional differences were evaluated accordingly. RESULTS: The incidence of pediatric IBD increased from 5 per 100,000 in 1987 to 15 per 100,000 in 2003. The average rate of increase was 6.5% per year (95% CI 5.4%-7.5%). The trends were comparable for boys and girls, also by age group. Information on disease subtype was available from 1992 and during this 12-year period the incidence of Crohn's disease (CD) increased from 2-5 per 100,000 and that of ulcerative colitis (UC) from 4-9 per 100,000. CONCLUSIONS: Our results demonstrate a very high incidence rate for childhood IBD and in particular UC in Finland. Furthermore, a rapid increase took place nationwide in the incidence of both CD and UC during the past two decades.

Parent and self-report of sleep-problems and daytime tiredness among adolescents with inflammatory bowel disease and their population-based controls.

STUDY OBJECTIVES: to evaluate the frequency of sleep problems and daytime tiredness among adolescents with inflammatory bowel disease (IBD) in comparison with their healthy peers. DESIGN: Parent and self-reports of sleep problems and daytime tiredness. SETTING: questionnaire-based postal survey. INTERVENTION: N/A. PARTICIPANTS: one hundred sixty Finnish adolescents with IBD; 236 adolescents matched for age, sex, and place of residence; and the parents of both groups. MEASUREMENTS AND RESULTS: Sleep Self-Report and sleep questions of the Child Behavior Check-List, and Youth Self-Report. The parents of adolescents with IBD reported in their index child more trouble sleeping (P < 0.01), more nightmares (P < 0.01), sleeping more than most children during the day/night (P < 0.001), and overtiredness (P < 0.001) than did the parents of control subjects. In contrast, adolescents with IBD themselves did not report more problems than their peers. However, in the group of patients with self-reported severe IBD symptoms, both the parents and the adolescents reported trouble sleeping and overtiredness more often (P values < 0.01) than in the group with mild symptoms or control subjects. Adolescents with severe IBD reported more often that their symptoms affected the quality of their sleep (P < 0.001) than did adolescents with mild disease. CONCLUSIONS: adolescents with severe IBD symptoms have disturbed sleep and are overtired more often than are adolescents with mild IBD symptoms or control subjects. Thus, in adolescents with severe IBD symptoms, evaluating sleep is important in characterizing the disease burden. Both parent and adolescent reports are needed for comprehensive assessment of sleep in the young.

Celiac disease without villous atrophy in children: a prospective study.

OBJECTIVE: To establish whether children who are endomysial antibody (EmA) positive and have normal small-bowel mucosal villous morphology are truly gluten-sensitive and may benefit from early treatment with a gluten-free diet. STUDY DESIGN: Children who were EmA positive with normal small-bowel mucosal villi were compared with children who were seropositive with villous atrophy by using several markers of untreated celiac disease. Thereafter, children with normal villous structure either continued on a normal diet or were placed on a gluten-free diet and re-investigated after 1 year. Seventeen children who were seronegative served as control subjects for baseline investigations. RESULTS: Normal villous morphology was noted in 17 children who were EmA positive, and villous atrophy was noted in 42 children who were EmA positive. These children were comparable in all measured variables regardless of the degree of enteropathy, but differed significantly from the seronegative control subjects. During the dietary intervention, in children who were EmA positive with normal villi, the disease was exacerbated in children who continued gluten consumption, whereas in all children who started the gluten-free diet, both the gastrointestinal symptoms and abnormal antibodies disappeared. CONCLUSIONS: The study provided evidence that children who are EmA positive have a celiac-type disorder and benefit from early treatment despite normal mucosal structure, indicating that the diagnostic criteria for celiac disease should be re-evaluated.

Fecal calprotectin mirrors inflammation of the distal ileum and bowel function after restorative proctocolectomy for pediatric-onset ulcerative colitis.

BACKGROUND: The goal was to cross-sectionally assess fecal calprotectin after restorative proctocolectomy for pediatric-onset ulcerative colitis (UC). METHODS: Fecal calprotectin, histology of the distal ileum, inflammation biochemistry, episodes of pouchitis, and bowel function were cross-sectionally determined at early adulthood in 32 patients who had undergone proctocolectomy with ileoanal anastomosis for UC at a mean (SD) age of 12.0 +/- 4.1 years. RESULTS: A total of 15 (47%) patients showed increased (>100 microg/g) fecal calprotectin (669 +/- 866 microg/g), although their serum C-reactive protein (5.2 +/- 3.8 mg/L), erythrocyte sedimentation rate (13 +/- 13 mm/h), and white blood cell count (6.7 +/- 1.7 E9/L) were normal or slightly elevated. Calprotectin correlated positively with the histological neutrophil count of the distal ileum (r = 0.715; P < 0.001), the frequency of pouchitis (r = 0.468; P < 0.01), and with the maximum daily frequency of bowel actions (r = 0.610; P < 0.001). Mean fecal calprotectin was 71 +/- 50 microg/g among patients with no history of pouchitis (n = 10), 290 +/- 131 microg/g among patients with a single episode of pouchitis (n = 15), and 832 +/- 422 microg/g among those with recurrent pouchitis (P = 0.019 between recurrent pouchitis and no pouchitis). Sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin concentration over 300 microg/g to detect recurrent pouchitis were 57%, 92%, 67%, and 89%, respectively. CONCLUSIONS: Neutrophilic inflammation of the distal ileum, as reflected by fecal calprotectin, is common after restorative proctocolectomy for pediatric-onset UC.

Psychosocial symptoms and competence among adolescents with inflammatory bowel disease and their peers.

BACKGROUND: The aim was to evaluate psychosocial symptoms and competence as reported by the parents and the adolescents themselves among patients with inflammatory bowel disease (IBD) in relation to population-based controls. METHODS: Standardized Achenbach questionnaires-Child Behavior Checklist (CBCL) for the parents and Youth Self-Report (YSR) for the adolescents-were sent to Finnish families of adolescents with IBD (age 10-18 years), and their controls matched for age, gender, and place of residence. The final study group comprised 160 adolescents with IBD and 236 controls with their parents, respectively. RESULTS: According to parent reports, adolescents with IBD had more symptoms of anxious/depressed mood (P < 0.001), withdrawn/depressed mood (P < 0.05), social problems (P < 0.05), thought problems (P < 0.001), somatic complaints (P < 0.001), and lower competence (P < 0.05) than population-based controls. Unexpectedly, there was no group difference in the amount of self-reported psychosocial symptoms, somatic complaints, or competence between adolescents with IBD and their peers. However, adolescents with severe IBD reported significantly more emotional problems (P < 0.001) than those with mild symptoms or controls. CONCLUSIONS: According to parents, adolescents with IBD have more emotional problems, social problems, thought problems, and lower competence than their population-based peers. Self-perceived severity of the IBD symptoms is associated with a larger amount of parent and self-reported emotional symptoms. Complementary methods should be used while assessing the psychosocial well-being of adolescents with IBD as questionnaires alone may be insufficient.

[Chronic inflammatory bowel diseases in children and adolescents]. / Krooniset tulehdukselliset suolistosairaudet lapsilla ja nuorilla.

Chronic inflammatory bowel diseases in children and adolescents Inflammatory bowel disease (IBD) is further increasing in children and adolescents in most Western countries including Finland. The etiologic factors of IBD and possible triggers have remained unclear. The clinical picture in paediatric IBD is more aggressive than in adults and operative intervention is common. Medical therapy is basically in line with the therapy used in adult patients. Optimal treatment is crucial in order to support normal growth and pubertal development. New serological and fecal analyses enhance the diagnostic accuracy and help the screening of the disease. The impact of IBD into the quality of life and psychosocial health has to be considered especially in severe cases.

Sexual functions in adulthood after restorative proctocolectomy for paediatric onset ulcerative colitis.

BACKGROUND AND AIM: Proctocolectomy with straight or J-pouch ileoanal anastomosis is the standard surgical treatment (ST) for ulcerative colitis (UC) also in children. Pelvic dissection may damage structures essential for sexual functions (SF). We compared SF in adults with ST during childhood or adolescence with adults with medical treatment (MT). MATERIALS AND METHODS: Sixty-three sexually active patients (ST 25, males 8; MT 38, males 19) median age of 27 years (range 17-41) (ST) and 29 years (20-40) (MT) (P = NS) were included. UC was diagnosed 15 years (5.1-26) (ST) and 7.5 years (2-20) (MT) (P < 0.05) before. Median ages at and follow-up after ST was 13 years (5.0-19) and 13 years (4.4-22), respectively. In ST and MT groups the daily stooling frequency and the incidence of soiling were 6 (2-17) and 2 (1-12), and 13/25 (52%) and 3/38 (8%), respectively (P < 0.05). SF were assessed with a structured form. RESULTS: In ST and MT groups, 21/25 (84%) and 31/38 (82%) reported satisfactory SF and 17/25 (68%) and 28/38 (74%) enjoyable sex life (P = NS). Urinary and faecal incontinence disturbed SF in both ST and MT groups in 2/25 (8%) and 3/38 (8%) and 13/25 (52%) and 15/38 (39%) (P = NS in each). Faecal incontinence inversely correlated with sexual satisfaction in all patients (R range; 0.36-0.68, P < 0.05). No erectile problems occurred. One patient (MT) reported ejaculatory problems. In females, dysorgasmia and dyspareunia were reported by 1/17 (6%) and 6/17 (35%) (ST) and 1/19 (5%) and 11/19 (58%) (MT) (P = NS). With intention to conceive 2/5 females in ST and 2/3 in MT group became pregnant within 1 year (P = NS). Only 2/25 (8%) (ST) and 7/38 (18%) (MT) had received information of the effect of treatment on SF. CONCLUSION: Compared with adult CU patients with MT, SF in patients with ST for CU in childhood or adolescence were similar. ST at a young age does not seem to affect SF in adulthood. Faecal incontinency disturbed SF in MT and ST groups.

Long-term outcomes of restorative proctocolectomy in children with ulcerative colitis.

OBJECTIVE: Long-term outcomes of restorative proctocolectomy for pediatric-onset ulcerative colitis are unclear. METHODS: Questionnaires on health outcomes and quality of life were mailed to patients with childhood-onset ulcerative colitis who had undergone proctocolectomy with ileoanal anastomosis in 2 university hospitals between 1985 and 2005. Investigators not involved in the surgical management of the patients approached participants. Matched control children were randomly chosen from the Population Register Centre of Finland. RESULTS: Fifty-two (66%) patients and 117 (37%) controls responded. After a mean follow-up of 10 years, at least 1 surgical complication had occurred in 39 (75%) patients, and 28 (54%) had undergone reoperation. Only 1 failure of ileoanal anastomosis occurred. Ulcerative colitis had been reclassified as Crohn disease in 6 (12%) patients. Pouchitis occurred in 37 (73%) patients. The median stool frequency was 5 for day and 1 for night, but 46% used medication to control stool frequency. Nighttime soiling was reported by 56% of the patients. The mean overall quality-of-life score, the mean BMI (22 kg/m(2) for both), and the number of subjects (aged >20 years) with offspring (14% vs 15%) was similar to the population-based controls. CONCLUSIONS: Stool frequency after restorative proctocolectomy in children with ulcerative colitis is stable and comparable to those of adult patients. Although nighttime incontinence is common, general health status and overall quality of life are comparable to the normal population.

Enhanced expression of transcription factor GATA-4 in inflammatory bowel disease and its possible regulation by TGF-beta1.

BACKGROUND: Transforming growth factor beta 1 (TGF-beta1) promotes epithelial healing in inflammatory bowel disease. We hypothesized that GATA-4, a transcription factor cooperating with TGF-beta signaling pathway, is upregulated by TGF-beta1 in the inflamed intestinal epithelium. METHODS: Normal and inflamed intestinal samples were subjected to immunohistochemistry for GATA-4/6 and the TGF-beta signaling pathway components Smad2/3/4. Proliferation and apoptosis were analyzed using Ki-67 and in situ DNA 3'-end labeling assays and Bax and Bcl-2 immunohistochemistry. Furthermore, GATA-4 was assessed in intestinal Caco-2 cells stimulated with TGF-beta1, or interleukin-6 and tumor necrosis factor alpha. RESULTS: GATA-4 was detected in only 20% of normal intestinal samples, but was upregulated in corresponding inflamed regions. GATA-6 expression remained unchanged during inflammation. TGF-beta1 and Smad3/4, but not Smad2, were expressed concomitantly with GATA-4 in inflamed bowel mucosa. In intestinal Caco-2 cells, TGF-beta1 upregulated GATA-4 and Smad2/3/4, whereas treatment with control cytokines had no effect. Inflammation was associated with increased epithelial cell apoptosis and the enhancement of Bcl-2, but not Bax. CONCLUSIONS: We surmise GATA-4 expression is upregulated in inflamed intestine correlating with the activation of TGF-beta signaling pathway. We speculate that TGF-beta1 drives GATA-4 expression during intestinal inflammation, these two components cooperating to promote epithelial healing.