Prenatal exposure to maternal cigarette smoking and structural properties of the human corpus callosum.

Alterations induced by prenatal exposure to nicotine have been observed in experimental (rodent) studies. While numerous developmental outcomes have been associated with prenatal exposure to maternal cigarette smoking (PEMCS) in humans, the possible relation with brain structure is less clear. Here we sought to elucidate the relation between PEMCS and structural properties of human corpus callosum in adolescence and early adulthood in a total of 1,747 youth. We deployed three community-based cohorts of 446 (age 25-27 years, 46% exposed), 934 (age 12-18 years, 47% exposed) and 367 individuals (age 18-21 years, 9% exposed). A mega-analysis revealed lower mean diffusivity in the callosal segments of exposed males. We speculate that prenatal exposure to maternal cigarette smoking disrupts the early programming of callosal structure and increases the relative portion of small-diameter fibres.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Dopaminergic function and intertemporal choice.

The discounting of delayed rewards, also known as temporal or delay discounting, is intrinsic to everyday decisions and can be impaired in pathological states such as addiction disorders. Preclinical and human studies suggest a role for dopaminergic function in temporal discounting but this relationship has not yet been verified using molecular imaging of the living human brain. Here, we evaluated dopaminergic function in temporal discounting using positron emission tomography (PET) with two different dopaminergic ligands assessing three populations in whom temporal discounting has been shown to be impaired. First, we show using [11C]raclopride PET that in pathological gamblers, greater temporal discounting correlates with decreased ventral striatal binding potential, convergent with translational findings of lower nucleus accumbens D2/D3 receptor density in high-impulsive rodents. Temporal discounting also correlates with lower ventral striatal dopamine release in response to high-reward magnitude suggesting that dopamine-mediated devaluation of larger delayed rewards may drive choice preferences. Second, we show using [18F]fluorodopa PET that in Parkinson's disease, temporal discounting correlates with greater left caudate dopaminergic terminal function. Finally, in subjects with Parkinson's disease and dopamine medication-induced behavioral addictions, temporal discounting is further correlated with greater dopaminergic terminal function in the anterior putamen. These findings provide insights into the relationship between striatal dopamine function and temporal discounting, and its potential role in pathological disorders and mechanisms underlying treatment interventions.

Childhood bullying behaviors at age eight and substance use at age 18 among males. A nationwide prospective study.

Childhood bullying behaviors (bullying and victimization) were studied as risk factors for substance use among Finnish males. The study design was a nationwide prospective general population study, where information was collected in 1989 and 1999. Bullying behaviors and childhood psychopathology at age eight were collected from teachers, parents and boys themselves. At age 18, self-reports of frequent drunkenness (once a week or more often), daily heavy smoking (10 cigarettes or more per day), and illicit drug use during the past six months were obtained from 78% of the boys attending the study at age eight (n=2946). Being frequently victimized at age eight predicted daily heavy smoking, and this was evident even after adjusting for childhood family background, psychopathology at age eight and at age 18, and other forms of substance use. In multivariate analysis, bullying others frequently predicted illicit drug use, while being a victim of bullying associated with a lower occurrence of illicit drug use. Bullying behaviors had no association with frequent drunkenness independent of other factors. Accordingly, being a victim of bullying predisposes in particular to subsequent smoking. Bullying others in childhood can be regarded as an early indicator to illicit drug use later in life. The screening and intervention possibilities in order to recognize the risk group for later health compromising behaviors are emphasized.

Brief report: validity of Finnish registry-based diagnoses of autism with the ADI-R.

AIMS: The aim of the study was to explore the validity of registry-based diagnoses of autism in Finland using the Autism Diagnostic Interview - Revised (ADI-R). This study was designed for the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A), an ongoing research project where registry-based diagnoses will be used for epidemiological studies. METHODS: In this small pilot study, a clinical sample of 95 subjects diagnosed with childhood autism or pervasive developmental disorder/pervasive developmental disorder - not otherwise specified (PDD/PDD-NOS) or Asperger's syndrome according to the Finnish Hospital Discharge Register (FHDR) was gathered nationwide. A small control group consisting of siblings without any registered diagnoses of those being examined was also included in the study. Diagnoses were further re-evaluated by interviewing parents with the ADI-R. RESULTS: The mean scores of autistic subjects clearly exceeded cut-off limits for autism on all three ADI-R domains and 96% of the subjects with registered diagnosis of childhood autism fulfilled the criteria based on the instrument as well. CONCLUSION: These results suggest that the validity of Finnish registry-based diagnoses of childhood autism can be considered good. Our findings lay important groundwork for further population- based studies of the aetiology of autism.

Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study.

BACKGROUND: Previous studies have documented associations between mental and physical health problems in cross-sectional studies, yet little is known about these relationships over time or the specificity of these associations. The aim of the current study was to examine the relationship between mental health problems in childhood at age 8 years and physical disorders in adulthood at ages 18-23 years. METHOD: Multiple logistic regression analyses were used to examine the relationship between childhood mental health problems, reported by child, parent and teacher, and physical disorders diagnosed by a physician in early adulthood. RESULTS: Significant linkages emerged between childhood mental health problems and obesity, atopic eczema, epilepsy and asthma in early adulthood. Specifically, conduct problems in childhood were associated with a significantly increased likelihood of obesity and atopic eczema; emotional problems were associated with an increased likelihood of epilepsy and asthma; and depression symptoms at age 8 were associated with an increased risk of asthma in early adulthood. CONCLUSIONS: Our findings provide the first evidence of an association between mental health problems during childhood and increased risk of specific physical health problems, mainly asthma and obesity, during early adulthood, in a representative sample of males over time. These data suggest that behavioral and emotional problems in childhood may signal vulnerability to chronic physical health problems during early adulthood.

Use of the ISO 9308-1 procedure for the detection of E. coil in water utilizing two incubation temperatures and two confirmation procedures and comparison with defined substrate technology.

Disinfected and non-disinfected samples have been used to determine the accuracy of the ISO procedure (ISO 9308-1) for detection of E. coli in drinking water. Samples were analysed using the ISO procedure at both 36 and 44 degrees C and using the defined substrate technology method Colilert-18/Quanti-Tray (Colilert-18). Utilizing the confirmation procedure described in ISO 9308-1, large numbers of false positive E. coli results were obtained using the ISO primary isolation procedure at 36 degrees C. However, when glucuronidase production was used as the confirmation procedure, the 'confirmed' count of E. coli was lowest with ISO 9308-1 performed at 36 degrees C. When TTC medium was incubated at 36 degrees C confirmation using production of indole at 44 degrees C resulted in 29% more 'E. coli' being recovered than when confirmation was performed using production of glucuronidase. When 44 degrees C was used as the primary isolation temperature the difference between the number of 'confirmed' E. coli identified using the two confirmation procedures was less than 1% and was not significant. Identification of isolates which 'confirmed' when using production of indole at 44 degrees C as the test method but which failed to produce beta-D-glucuronidase, showed that the majority of these isolates were Klebsiella oxytoca.

Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members.

BACKGROUND/AIMS: Sedation rates may vary among countries, depending on patients' and endoscopists' preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives' endoscopy units. RESULTS: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders' endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available 'in most of the endoscopy units' in 46% (13/28) of the countries. Though they were available in 91% of the national representatives' endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. CONCLUSIONS: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.

Innovation in multifunctional bioabsorbable osteoconductive drug-releasing hard tissue fixation devices.

We review in this paper the work performed by our group to develop multifunctional bioabsorbable ciprofloxacin releasing bone implants. Poly lactide-co-glycolide (PLGA 80/20 and polylactide (P(L/DL)LA 70/30) were used. Ciprofloxacin (CF) and bioactive glass (BaG) 13-93 were added. The mixture was then extruded and self-reinforced. CF release, mechanical strength, and the effect on S. epidermidis attachment and biofilm formation were evaluated. In rabbits, tissue reactions were assessed. Pull out strength was evaluated in cadaver bones. CF was released over 44 weeks (P(L/DL)LA) and 23-26 weeks (PLGA). Initial shear strength of the CF screws was 152 MPa (P(L/DL)LA) and 172 MPa (PLGA). Strength was retained for 12 weeks (P(L/DL)LA) and 9 weeks (PLGA). Histologically, CF releasing implants did not show much difference from control plain PLGA screws except for increased giant cells. CF miniscrews had lower pullout strength than the controls, but CF tacks had better values than controls. BaG led to a drop in pullout strength properties. Bacterial growth, attachment and biofilm formation on CF implants was significantly reduced when compared to controls. Accordingly, bioabsorbable multifunctional implants with appropriate CF release, mechanical, and biocompatibility properties are possible to develop and are considered appropriate to apply clinically.

Clinical significance and outcome of gastric mucosal erosions: a long-term follow-up study.

Our purpose was to evaluate the long-term clinical significance of gastric erosions. A series of 117 patients with gastric erosions without peptic ulcer disease, and matched controls were studied in 1974-1979. All available subjects were reinvestigated 17 years later, including detailed clinical history and laboratory analysis. At follow-up, erosions were still more prevalent (39%; 20/50) in the erosion group than in the controls (11; 7/66). In Helicobacter pylori-positive participants, peptic ulcer or a scar was more common in the erosion group (17%; 9/52) than in controls (5%; 3/66). Overall malignancy rate was higher in controls (15%; 17/117) than in erosion group (5%; 6/117; P = .025), but no other differences were seen between the groups or related with current erosion. We conclude that a significant proportion of gastric erosions are chronic or recurrent but mostly without serious complications. However, H. pylori-positive patients with erosions have significant risk to develop a peptic ulcer.

Clinical characteristics of collagenous and lymphocytic colitis.

BACKGROUND: Microscopic colitides (MC), collagenous colitis (CC) and lymphocytic colitis (LC) share clinical features, but their mutual relationship is unclear, and clinical comparative studies are rare. We aimed to examine the clinical features in CC and LC by focusing on concomitant diseases. METHODS: Patients with MC (30 with CC, 54 with LC) were identified in the pathology databases and by reviewing biopsies. Controls included 84 age- and sex-matched persons. The clinical data collected from patient records were prospectively completed by interviews. RESULTS: The female:male ratio was 2:1 in CC and 5.75:1 in LC. Mean age at diagnosis was 53 in CC and 55.4 years in LC. There were no differences in the pattern of symptoms. Concomitant autoimmune diseases were more common in CC (53.3%) than in LC (25.9%; P = 0.017). Celiac disease was common in both CC (20%) and LC (14.8%). Bronchial asthma was associated with LC (25.9%), but not with CC (6.7%; P = 0.042). Colon diverticulosis was rare in MC (16%) compared with the controls (39%; P = 0.001). Hypolactasia was common in MC (45%; 76% in CC, 54% in LC) compared to its prevalence in the Finnish general population (17%). CONCLUSIONS: CC and LC are largely similar clinically, but the differences in the occurrence of autoimmune conditions and bronchial asthma suggest that they differ in immunopathogenesis. MC is associated with reduced lactose tolerance and shows a negative association with diverticular disease, possibly related to the small intestinal pathology and abnormal stool consistency.

Primary Helicobacter pylori resistance to metronidazole and clarithromycin in the Finnish population.

AIM: To systematically determine Helicobacter pylori primary antimicrobial resistance in Finland and the associated demographic and clinical features. METHODS: A total of 342 adult patients referred for gastroscopy at 23 centres in different parts of Finland and positive for the rapid biopsy urease test were recruited. Clinical and demographic data were collected via a structured questionnaire. Patients with positive H. pylori culture and successful antibiotic sensitivity determination by the E-test method (n = 292) were included in the present analysis. RESULTS: The study population consisted of 134 men and 158 women, mean age 56 years (95% CI, 55-58 years). Resistance to metronidazole was 38% (110 of 292) and to clarithromycin 2% (seven of 292). Resistance to metronidazole was higher in women than in men (48% vs. 25%, P < 0.001). Previous use of antibiotics for gynaecological infections predicted metronidazole resistance (P = 0.01), and previous use of antibiotics for respiratory (P = 0.02) and dental infections (P = 0.02) the clarithromycin resistance. We observed no major geographical variations in metronidazole resistance. CONCLUSIONS: The primary metronidazole resistance of H. pylori was 38% and was common in women previously treated for gynaecological infections. Primary clarithromycin resistance was uncommon (2%) and may associate with previous dental and respiratory infections.

Confirmation of Escherichia coli and its distinction from Klebsiella species by gas and indole formation at 44 and 44.5 degrees C.

AIMS: In the enumeration of coliform bacteria, confirmation of Escherichia coli has been based upon gas and indole production at the elevated incubation temperature. The test for gas production has recently been questioned. The aim of this study was to investigate the impact of gas production test on the reliability of confirmation of E. coli. METHODS AND RESULTS: The impact of several media on growth, gas and/or indole formation was tested at 44 and 44.5 degrees C using 547 environmental isolates. These were mainly E. coli, Klebsiella pneumoniae, K. oxytoca and Enterobacter cloacae strains. Another set of 250 faecal and environmental klebsiellae were tested for their maximum temperature for growth (Tmax) and for gas formation. Escherichia coli and even K. pneumoniae grew well in all the media, but gas production was more dependent on the medium used. Growth of the mainly gas negative Ent. cloacae and K. oxytoca strains was still more sensitive to the medium and incubation conditions. Tryptophan salt broth was the most productive medium for the indole test, followed by lauryl tryptose mannitole and tryptone mannitol ricinoleate broth (TRM). Tmax of K. oxytoca was clearly lower than Tmax of K. pneumoniae but a rather high fraction of its isolates produced indole at 44.5 degrees C. CONCLUSIONS: False-positive E. coli confirmation is possible if gas production is not tested for and the confirmation is based on indole test only. SIGNIFICANCE AND IMPACT OF THE STUDY: Erroneous positive results on routine analysis for E. coli can occur.

A comparison of the International Standards Organisation reference method for the detection of coliforms and Escherichia coli in water with a defined substrate procedure.

AIMS: This study investigated the use of the International Standards Organisation (ISO) procedure for the comparison of microbiological methods. Using this procedure the ISO reference procedure for the detection of coliforms and Escherichia coli in water was compared with a defined substrate method (ColilertTM). METHODS AND RESULTS: A total of 20 laboratories from 13 European countries compared the use of Colilert/Quanti-TrayTM, a quantitative defined substrate test (DST) for the presence of coliforms and E. coli with the ISO reference procedure, which utilizes tergitol-TTC medium. Results of the study showed that DST detected significantly more coliforms and E. coli than did the reference procedure. In the case of E. coli the recoveries were also higher when using DST and the difference seen was statistically significant. The confirmation rate obtained when using the DST product suggested that no confirmation of wells positive for E. coli was necessary during routine use. CONCLUSIONS: Colilert is a suitable alternative to the ISO reference procedure for the detection of coliforms and E. coli in water. The methods used during the comparison study indicated that confirmation of all colonies/positive wells led to the most accurate information and it is recommended that for future comparison studies this should become standard practice. Confirmation of a small proportion of colonies led to misleading conclusions and should be avoided when comparing microbiological methods. SIGNIFICANCE AND IMPACT OF STUDY: It has been demonstrated that the ISO reference procedure fails to detect a significant proportion of coliforms and E. coli in drinking water. Colilert/QuantiTrayTM is a more suitable alternative.

IL-1 RN 2/2 genotype and simultaneous carriage of genotypes IL-1 RN 2/2 and IL-1beta-511 T/T associated with oesophagitis in Helicobacter pylori-negative patients.

BACKGROUND: Interleukin-1 receptor antagonist genotype 2/2 is associated with a prolonged and enhanced inflammatory response. It is suspected of being a risk factor for atrophic gastritis and gastric cancer and for some autoimmune diseases. No specific genetic risk factors for oesophagitis have been identified so far and there are no reports of IL-1 polymorphism in relation to oesophageal disease. METHODS: We studied the IL-1RN, IL-1beta-511 and IL-1beta + 3953 polymorphisms in an unselected series of 142 adult patients scheduled for gastrointestinal endoscopy because of dyspepsia. The control group consisted of university staff and students (n = 179). Helicobacter pylori status was determined by antibody testing and bacterial detection. RESULTS: Endoscopic oesophagitis was noted in 40 patients. The IL-1RN 2/2 genotype was significantly more prevalent in the patients with H. pylori-negative oesophagitis than in the control subjects (27% versus 9%; OR 3.574, CI 1.23-10.35, P = 0.034) or in the dyspeptic patients (27% versus 7%; OR 5.089. CI 1.51-17.11, P = 0.009). IL-1beta-511 T/T genotype tended to be more frequent in the H. pylori-negative patients with oesophagitis than in the control subjects (P = 0.071). The strongest association was between the simultaneous carriage of genotypes IL-1RN 2/2 and IL-1beta -511 T/T and H. pylori-negative oesophagitis. where the combined genotype was more prevalent than in the control subjects (23% versus 6%; OR 4.492, CI 1.40-14.46, P = 0.012) or the dyspeptic patients without oesophagitis (23% versus 3%: OR 9.706. CI 2.12-44.42, P = 0.003). CONCLUSIONS: The results indicate that the IL-1RN 2/2 genotype and the carriage of combined genotypes IL-1RN 2/2 + IL-1beta-511 T/T are associated with H. pylori-negative oesophagitis. This is the first report on the association between IL-1 gene polymorphism and oesophagitis.

The role of Herpes simplex and Helicobacter pylori infection in the etiology of persistent or recurrent gastric erosions: a follow-up study.

The etiology of chronic gastric erosions is unknown. We have evaluated the significance of Helicobacter pylori and herpes simplex virus (HSV) infections, the use of nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, and smoking in a prospective long term follow-up study. A prospective series of 117 patients with gastric erosions and 117 controls were studied in 1974-1981, and invited for reendoscopy in 1996. At both visits, H. pylori infection was diagnosed by histology, serum HSV antibodies were measured, and the use of NSAIDs, alcohol, and smoking was evaluated by interview. Biopsies from erosions from the latter visit were studied for HSV by immunohistochemistry and polymerase chain reaction (PCR). In the follow-up visit, 16 of 42 patients had still gastric erosions while six of 47 controls had developed erosions. No HSV antigen or DNA could be detected in biopsy specimens. However, only high antibody titers (> or = 32) against HSV at the first visit predicted persistence of erosions (P = 0.000), while H. pylori infection, use of NSAIDs, alcohol, or smoking were not associated with chronic erosions. High HSV titers at the follow-up visit were also significantly associated with concurrent erosions in the patient group. In conclusion, the results suggest that a significant proportion of chronic gastric erosions are related to HSV infection.

Effect of CD14 promoter polymorphism and H. pylori infection and its clinical outcomes on circulating CD14.

CD14 is a pattern recognition receptor on the membranes of monocytes and macrophages for several microbial products, of which lipopolysaccharide (LPS) is the best known. A shed form of CD14 is present in serum. As the CD14 gene promoter polymorphism -159C/T and some bacterial infections may affect the sCD14 levels, we compared the impact of both the CD14 promoter polymorphism and Helicobacter pylori infection on serum sCD14 levels in 201 dyspeptic patients (group 1) who had undergone gastroscopy, and 127 staff members (group 2) with no endoscopy. sCD14 was measured from the sera by a commercial enzyme immunoassay (EIA), and CD14 genotyping was carried out with PCR. Helicobacter pylori infection was detected by serology and/or culture or PCR. sCD14 levels were elevated in the subjects carrying the T allele (CT or TT genotype) in both groups when compared with subjects with the CC genotype. Overall, H. pylori-positive subjects tended to have higher sCD14 levels compared with H. pylori-negative subjects. In group 1 consisting of dyspeptic patients, those with gastric ulcer, gastric erosion or duodenal ulcer had significantly elevated levels of sCD14 compared with the patients with normal endoscopic findings or macroscopic gastritis. The recent use of NSAIDs was also associated with enhanced sCD14. Thus, we were able to show several factors, one genetic and the other environmental (H. pylori infection and mucosal lesion), to have an impact on sCD14.

Elevated serum PIIINP and laminin in inflammatory bowel disease indicate hepatobiliary and pancreatic dysfunction.

BACKGROUND/AIMS: Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables. METHODOLOGY: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound. RESULTS: S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity. CONCLUSIONS: In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.