Primary aldosteronism: Higher volume load, cardiac output and arterial stiffness than in essential hypertension.

BACKGROUND: The diagnostics of primary aldosteronism (PA) are usually carried out in patients taking antihypertensive medications. We compared haemodynamics between medicated PA, medicated essential hypertension (EH), never-medicated EH and normotensive controls (n = 130 in all groups). METHODS: The hypertensive groups were matched for age (53 years), sex (84 male/46 female) and body mass index (BMI) (30 kg m-2 ); normotensive controls had similar sex distribution (age 48 years, BMI 27 kg m-2 ). Haemodynamics were recorded using whole-body impedance cardiography and radial pulse wave analysis, and the results were adjusted as appropriate. Radial blood pressure recordings were calibrated by brachial blood pressure measurements from the contralateral arm. RESULTS: Radial and aortic systolic and diastolic blood pressure was similar in PA and never-medicated EH, and higher than in medicated EH and normotensive controls (P ≤ 0.001 for all comparisons). Extracellular water balance was ~ 4% higher in PA than in all other groups (P < 0.05 for all), whilst cardiac output was ~ 8% higher in PA than in medicated EH (P = 0.012). Systemic vascular resistance and augmentation index were similarly increased in PA and both EH groups when compared with controls. Pulse wave velocity was higher in PA and never-medicated EH than in medicated EH and normotensive controls (P ≤ 0.033 for all comparisons). CONCLUSIONS: Medicated PA patients presented with corresponding systemic vascular resistance and wave reflection, but higher extracellular water volume, cardiac output and arterial stiffness than medicated EH patients. Whether the systematic evaluation of these features would benefit the clinical diagnostics of PA remains to be studied in future.

Green areas around homes reduce atopic sensitization in children.

BACKGROUND: Western lifestyle is associated with high prevalence of allergy, asthma and other chronic inflammatory disorders. To explain this association, we tested the 'biodiversity hypothesis', which posits that reduced contact of children with environmental biodiversity, including environmental microbiota in natural habitats, has adverse consequences on the assembly of human commensal microbiota and its contribution to immune tolerance. METHODS: We analysed four study cohorts from Finland and Estonia (n = 1044) comprising children and adolescents aged 0.5-20 years. The prevalence of atopic sensitization was assessed by measuring serum IgE specific to inhalant allergens. We calculated the proportion of five land-use types--forest, agricultural land, built areas, wetlands and water bodies--in the landscape around the homes using the CORINE2006 classification. RESULTS: The cover of forest and agricultural land within 2-5 km from the home was inversely and significantly associated with atopic sensitization. This relationship was observed for children 6 years of age and older. Land-use pattern explained 20% of the variation in the relative abundance of Proteobacteria on the skin of healthy individuals, supporting the hypothesis of a strong environmental effect on the commensal microbiota. CONCLUSIONS: The amount of green environment (forest and agricultural land) around homes was inversely associated with the risk of atopic sensitization in children. The results indicate that early-life exposure to green environments is especially important. The environmental effect may be mediated via the effect of environmental microbiota on the commensal microbiota influencing immunotolerance.

Low serum level of 1,25(OH)2 D is associated with chronic periodontitis.

BACKGROUND AND OBJECTIVES: Vitamin D has been studied primarily for its involvement in calcium and phosphate absorption and bone metabolism. The active form of vitamin D-1,25(OH)2 D-has also been investigated for its immune modulatory properties. We explored associations between serum levels of 25(OH)D and 1,25(OH)2 D and periodontal health. SUBJECTS AND METHODS: This case-control study included 55 subjects with chronic periodontitis (cases) and 30 periodontally healthy subjects (controls). Their serum levels of 25(OH)D, 1,25(OH)2 D, ultrasensitive C-reactive protein and high-density lipoprotein cholesterol were determined. Associations between vitamin D and periodontal health status were studied using logistic regression analysis. RESULTS: A statistically significant association was found between serum 1,25(OH)2 D level and periodontal health status; in that subjects with a low 1,25(OH)2 D were more likely to belong to the periodontitis group (OR = 0.97, 95% CI = 0.95-1.00). There was practically no association between 25(OH)D level and periodontal health status. CONCLUSION: In this case-control study low serum 1,25(OH)2 D level appeared to be associated with periodontitis, which was in line with the previously reported associations between serum 1,25(OH)2 D levels and other inflammatory diseases. Whether this association is causal in nature, remains to be confirmed in future studies.

Introduction of complementary foods in infancy and atopic sensitization at the age of 5 years: timing and food diversity in a Finnish birth cohort.

OBJECTIVE: To study the associations between timing and diversity of introduction of complementary foods during infancy and atopic sensitization in 5-year-old children. METHODS: In the Finnish DIPP (type 1 diabetes prediction and prevention) birth cohort (n = 3781), data on the timing of infant feeding were collected up to the age of 2 years and serum IgE antibodies toward four food and four inhalant allergens measured at the age of 5 years. Logistic regression was used for the analyses. RESULTS: Median duration of exclusive and total breastfeeding was 1.4 (interquartile range: 0.2-3.5) and 7.0 (4.0-11.0) months, respectively. When all the foods were studied together and adjusted for confounders, short duration of breastfeeding decreased the risk of sensitization to birch allergen; introduction of oats <5.1 months and barley <5.5 months decreased the risk of sensitization to wheat and egg allergens, and oats additionally associated with milk, timothy grass, and birch allergens. Introduction of rye <7.0 months decreased the risk of sensitization to birch allergen. Introduction of fish <6 months and egg ≤11 months decreased the risk of sensitization to all the specific allergens studied. The introduction of <3 food items at 3 months was associated with sensitization to wheat, timothy grass, and birch allergens; the introduction of 1-2 food items at 4 months and ≤4 food items at 6 months was associated with all endpoints, but house dust mite. These results were particularly evident among high-risk children when the results were stratified by atopic history, indicating the potential for reverse causality. CONCLUSIONS: The introduction of complementary foods was consecutively done, and with respect to the timing of each food, early introduction of complementary foods may protect against atopic sensitization in childhood, particularly among high-risk children. Less food diversity as already at 3 months of age may increase the risk of atopic sensitization.

Glomerular filtration rate and parathyroid hormone are associated with 1,25-dihydroxyvitamin D in men without chronic kidney disease.

BACKGROUND AND AIM: Vitamin D, estimated glomerular filtration rate (eGFR) and parathyroid hormone (PTH) are related to cardiovascular disease risk. We examined the associations between the levels of 25-hydroxyvitamin D (25-D) and 1,25-dihydroxyvitamin D (1,25-D) and both eGFR and PTH. DESIGN AND SETTING: Cross-sectional population-based study in Kuopio, Eastern Finland. SUBJECTS: A total of 909 men without known chronic kidney disease (CKD) and not receiving antidiabetic medication, aged from 45 to 73 years, were included in the study. Main outcome measures. Fasting levels of 25-D, 1,25-D, creatinine and PTH were measured, and an oral glucose tolerance test (OGTT) was performed. RESULTS: High levels of 25-D were associated with low levels of eGFR and PTH (ß = -0.17, P = 9 × 10(-7) and ß = -0.28, P = 6 × 10(-17) , respectively, adjusted for age, body mass index and levels of calcium, phosphorus and glucose in a 2-h OGTT, and also for either eGFR or PTH). By contrast, high 1,25-D levels were associated with high levels of eGFR and PTH (ß = 0.17, P = 2 × 10(-6) and ß = 0.19, P = 5 × 10(-8) , respectively, adjusted as mentioned earlier and additionally for 25-D). Eighteen per cent of men in the highest 25-D quartile were in the lowest 1,25-D quartile and also had a lower eGFR than men with high levels of both 25-D and 1,25-D (P = 4 × 10(-5) ). Finally, 15% of men in the lowest 25-D quartile were in the highest 1,25-D quartile and also had higher PTH levels than men with low levels of both 25-D and 1,25-D (P = 2 × 10(-3) ). CONCLUSION: Our findings suggest that both eGFR and PTH are significantly associated with vitamin D metabolism in men without known CKD.

Diverse associations of 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D with dyslipidaemias.

BACKGROUND AND AIM: Previous studies have suggested a link between circulating levels of 25-hydroxyvitamin D (25-D) and dyslipidaemias. However, it is not known whether 25-D and the active hormone 1,25-dihydroxyvitamin D (1,25-D) have similar associations with dyslipidaemias. Therefore, we studied the associations between both 25-D and 1,25-D and total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides in a population-based study. DESIGN: Cross-sectional population-based study. SETTING: Kuopio, Eastern Finland. SUBJECTS: A total of 909 men, aged from 45 to 70 years, who were not receiving antidiabetic medication were enrolled. MAIN OUTCOME MEASURES: Fasting serum samples were obtained for measurement of 25-D, 1,25-D and lipid levels. An oral glucose tolerance test was performed, and insulin sensitivity was evaluated using the Matsuda insulin sensitivity index (Matsuda ISI). RESULTS: We found a significant inverse association between 25-D and total-C, LDL-C and triglycerides (ß = -0.15, -0.13 and -0.17, respectively, P < 0.001), but no association between 25-D and HDL-C was observed. By contrast, 1,25-D was associated with HDL-C (ß = 0.18, P < 0.001), whereas no relationship was found between 1,25-D and LDL-C or triglycerides. The associations remained significant after the exclusion of subjects receiving statin treatment and after adjustment for age, waist circumference, body mass index, alcohol consumption, smoking, renal function, glucose tolerance and Matsuda ISI. CONCLUSION: Low levels of active vitamin D (1,25-D) are associated with low HDL-C levels, whereas low levels of the storage form 25-D are associated with high levels of total-C, LDL-C and triglycerides. Our findings may provide new insights into the understanding of the link between vitamin D deficiency and cardiovascular disease.

Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption.

Acetaldehyde, the toxic product of ethanol metabolism in the liver, covalently binds to a variety of proteins. Recent studies indicate that such binding can stimulate the production of antibodies against the acetaldehyde adducts. We raised rabbit antibodies which recognized various protein-acetaldehyde conjugates but not the corresponding control proteins. Such antibodies were used in immunohistochemical studies to find out whether acetaldehyde-generated epitopes can be detected from liver specimens of 13 human subjects with different degrees of alcohol consumption. While the specimens obtained from alcohol abusers (n = 4) and alcoholics (n = 3) exhibited marked positive staining for acetaldehyde adducts inside the hepatocytes in a granular uneven pattern, the control samples (n = 6) were almost devoid of immunoreactivity. In the alcohol abusers with an early stage of alcohol-induced liver damage, staining was detected exclusively around the central veins. The data indicate that intracellular acetaldehyde adducts occur in the centrilobular region of the liver of individuals consuming excessive amounts of alcohol. Immunohistochemical detection of such adducts may prove to be of value in the early identification of alcohol abuse and in elucidating the mechanisms of alcohol-induced organ damage.

Experimental liver cirrhosis induced by alcohol and iron.

To determine if alcoholic liver fibrogenesis is exacerbated by dietary iron supplementation, carbonyl iron (0.25% wt/vol) was intragastrically infused with or without ethanol to rats for 16 wk. Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals. In both ethanol-fed and control rats, the supplementation produced a two- to threefold increase in the mean hepatic non-heme iron concentration but it remained within or near the range found in normal human subjects. As previously shown, the concentrations of liver malondialdehyde (MDA), liver 4-hydroxynonenal (4HNE), and serum aminotransferases (ALT, AST) were significantly elevated by ethanol infusion alone. The addition of iron supplementation to ethanol resulted in a further twofold increment in mean MDA, 4HNE, ALT, and AST. On histological examination, focal fibrosis was found < 30% of the rats fed ethanol alone. In animals given both ethanol and iron, fibrosis was present in all, with a diffuse central-central bridging pattern in 60%, and two animals (17%) developed micronodular cirrhosis. The iron-potentiated alcoholic liver fibrogenesis was closely associated with intense and diffuse immunostaining for MDA and 4HNE adduct epitopes in the livers. Furthermore, in these animals, accentuated increases in procollagen alpha 1(I) and TGF beta 1 mRNA levels were found in both liver tissues and freshly isolated hepatic stellate cells, perisinusoidal cells believed to be a major source of extracellular matrices in liver fibrosis. The dietary iron supplementation to intragastric ethanol infusion exacerbates hepatocyte damage, promotes liver fibrogenesis, and produces evident cirrhosis in some animals. These results provide evidence for a critical role of iron and iron-catalyzed oxidant stress in progression of alcoholic liver disease.

Fibrotic process and drug metabolism in alcoholic liver disease.

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.

Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury.

Generation of oxygen free radicals and reactive aldehydes as a result of excessive ethanol consumption has been well established. Recent studies in human alcoholics and in experimental animal models have indicated that acetaldehyde, the first metabolite of ethanol, and the aldehydic products of lipid peroxidation can bind to proteins in tissues forming stable adducts. The demonstration of such adducts in zone 3 hepatocytes in alcoholics with an early phase of histological liver damage indicates that adduct formation may have an important role in the sequence of events leading to alcoholic liver disease. There may be interference with cellular functions, stimulation of fibrogenesis, and immunological responses. Autoantibodies towards distinct types of adducts have been shown to be associated with the severity of liver disease in alcoholic patients. High fat diet and/or iron supplementation combined with ethanol may increase the amount of aldehyde-derived epitopes and promote fibrogenesis in the liver. Recently, ethanol-derived protein modifications have also been found from other tissues exposed to ethanol and acetaldehyde, including rat brain after lifelong ethanol administration, pancreas, and rat muscle. Elevated adduct levels also occur in erythrocytes of alcoholics, which may be related to ethanol-induced morphological aberrations in hematopoiesis.

Aldehyde-protein adducts in the liver as a result of ethanol-induced oxidative stress.

A number of systems that generate oxygen free radicals and reactive aldehydic species are activated by excessive ethanol consumption. Recent studies from human alcoholics and from experimental animals have indicated that acetaldehyde and aldehydic products of lipid peroxidation, which are generated in such processes, can bind to proteins forming stable adducts. Adduct formation may lead to several adverse consequences, such as interference with protein function, stimulation of fibrogenesis, and induction of immune responses. The presence of protein adducts in the centrilobular region of the liver in alcohol abusers with an early phase of histological liver damage indicates that adduct formation is one of the key events in the pathogenesis of alcoholic liver disease. Dietary supplementation with fat and/or iron strikingly increases the amount of aldehyde-derived epitopes in the liver together with promotion of fibrogenesis.

High-activity carbonic anhydrase isoenzyme (CA II) in human gallbladder epithelium.

Acidification of bile is one of the factors that prevents calcium precipitation and thereby gallstone formation. Carbonic anhydrase II (CA II) has previously been shown to be one of the key factors in the human alimentary tract that regulates the acid-base balance. We demonstrated CA II expression in the human gallbladder epithelium using immunohistochemical techniques, elucidated the CA II content of the epithelium by digital image analysis of the immunohistochemically stained enzyme in samples from 16 patients undergoing cholecystectomy, and correlated the results with the calcium content of the gallstones. Nine patients had symptomatic gallstone disease and seven an acalculous, histologically normal gallbladder. The patients were classified into two groups on the basis of the calcium content of their gallstones: no gallstones or gallstones containing no calcium (Group 1) and gallstones with 2-87% calcium by weight (Group 2). The immunohistochemical techniques showed distinct epithelial CA II-positive staining in most of the gallbladder samples, but digital image analysis revealed distinct variations in staining intensity among them. The median staining intensity index was significantly higher in Group 1 (0.4463) than in Group 2 (0.2376; p = 0.0262). The results suggest that CA II is abundantly expressed in the normal gallbladder epithelium and that decreased expression may be associated with the formation of calcified gallstones. These findings are relevant to the pathogenesis of gallstone disease.

Heterogeneity of the antigens related to the aminoterminal propeptide of type III procollagen in human serum.

Inhibition curves that are considerably less steep than the reference peptide curve are a constant finding when human serum samples are studied with the radioimmunoassay for the aminoterminal propeptide Col 1-3 of type III procollagen. This is due to the presence in the serum of three main peptide forms which differ in their antigenic properties and can be separated by gel filtration. Their molecular sizes are, respectively, larger than, equal to and smaller than the peptide Col 1-3. The proportions of these forms were different in a number of serum samples tested. An elevated value in the Col 1-3 radioimmunoassay need not reflect increased deposition of type III collagen in the liver, but could also be due to increased degradation of a newly-synthesized type III procollagen or degradation of a tissue form still containing the aminoterminal propeptide. This should be considered when interpreting elevated serum values.

Serum IgG and IgE antibodies against mold-derived antigens in patients with symptoms of hypersensitivity.

BACKGROUND: Exposure to mold in water-damaged buildings has been suggested to be responsible for various health problems such as hypersensitivity and upper respiratory tract diseases. However, only little information is available on possible diagnostic tools for examining mold-associated health problems. METHODS: We used recently developed immunofluorometric IgG and IgE assays (UniCAP) to examine serum IgG and IgE antibodies against mold-derived allergens from 70 mold-exposed individuals with (n = 55) or without (n = 15) symptoms of sensitization. Controls were healthy individuals (n = 31) without any history of such exposure. RESULTS: The IgG titers exceeded the upper normal limits of control individuals (mean +/- 2 S.D.) in 35% of symptomatic men and in 25% of women. The IgG titers were usually higher in women than in men (P < 0.05) showing no significant association with the severity of symptoms. During follow-up of eight mold-exposed subjects for 9-12 months the IgG titers remained relatively constant. Elevated anti-mold IgEs were found in six (11%) of the exposed subjects who were all symptomatic. CONCLUSIONS: Measurements of anti-mold IgGs may help to confirm exposure in patients with hypersensitivity symptoms and evidence of mold growth in living or working environment. Some exposed symptomatic patients present IgE-mediated responses. Combined measurements of IgGs and IgEs may prove to be of value in the comprehensive assessment and treatment of such patients.

Impairment of histone H1 DNA binding by adduct formation with acetaldehyde.

Incubation of histone H1 with pharmacologically relevant concentrations of acetaldehyde resulted in the formation of spontaneously stable acetaldehyde-protein linkages. The reaction of acetaldehyde and H1 purified from rat liver either by a DNA recognition site affinity chromatography or by perchloric acid extraction occurred primarily at the lysine residues in the carboxyterminal tail of H1, which is crucial for its function as a eukaryotic repressor. It was further shown using an H1-lacZ fusion protein produced in E. coli and the protein isolated from rat liver that the formation of acetaldehyde adducts with H1 impair its DNA binding properties. We propose that such a reaction may occur in vivo and lead to an inability to repress genes in the liver upon excessive alcohol consumption. This mechanism may play a role in acetaldehyde-induced collagen synthesis in alcoholics.

Improved method for detecting knee replacement infections based on extended combined 99mTc-white blood cell/bone imaging.

The purpose of this study was to evaluate whether an extension of the imaging time to 24 h post-injection improves the diagnostic accuracy of technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) leucocyte imaging in detecting knee replacement infections. Thirty patients were studied, with infection confirmed in eight (27%) and excluded in 22 on the basis of clinical and microbiological findings. Leucocyte imaging was carried out at 2-4 h (routine images) and at 24 h (late images) post-injection. For comparison, bone imaging with technetium-99m-hydroxydiphosphonate (99mTc-HDP) was carried out at arterial, soft tissue and metabolic phases. Late leucocyte imaging was found to be more sensitive (100% vs. 87.5%) and more specific (82% vs. 77%) than routine leucocyte imaging in detecting infections. All the bone imaging methods showed a sensitivity of 100%, whereas the specificity varied from only 5% to 23%. All procedures had high negative predictive values (NPVs) (94 to 100%) for excluding infection. However, the positive predictive value (PPV) was only 28 to 32% for bone imaging and 58% for routine leucocyte imaging, whereas late leucocyte imaging showed a PPV of 67% and a diagnostic accuracy of 87%. The data indicate that late leucocyte imaging may be superior to routine leucocyte imaging for examining patients with symptomatic knee replacements.

99m Tc-ciprofloxacin (Infecton) imaging in the diagnosis of knee prosthesis infections.

The purpose of this study was to evaluate the usefulness of 99mTc labelled ciprofloxacin imaging in detecting the presence of infection in patients with symptomatic knee prostheses. Among 16 randomly selected patients of whom seven had infection based on clinical and microbiological findings and nine did not, 99mTc-ciprofloxacin images were obtained at 1, 4 and 24h after the injection of the tracer. While there was some diffuse non-specific accumulation of 99mTc-ciprofloxacin in large synovial joints and in prosthetic knee joints, the infected knee prostheses were found to show more intensive focal uptake, which also extended outside the synovial cavity. The infection related uptake remained visible in the 24h images, whereas non-specific uptake had a fading tendency at this time point. 99mTc-ciprofloxacin imaging showed diagnostic sensitivity of 86% and a specificity of 78% for correctly classifying the presence of infection. The data indicate that 99mTc-ciprofloxacin imaging may be used in the diagnosis of knee prosthesis infections. Infection-related uptake remains visible in the 24h images and is typically found also outside the synovial cavity, which should be noted in the evaluation of the images.

Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with extended imaging time.

The purpose of this study was to compare the utility of 99mTc labelled ciprofloxacin (Infecton) imaging with the 99mTc white blood cell and three-phase bone imaging procedures for identifying hip prosthesis infection. We studied 30 symptomatic patients in whom infection was confirmed in eight and excluded in 22 cases based on clinical and microbiological findings. 99mTc ciprofloxacin images were obtained at 1, 4 and 24 h after the injection of the tracer, and the data were compared to those obtained from 99mTc leukocyte and three-phase bone imaging. The 99mTc ciprofloxacin imaging correctly identified all true infections. In 13 (59%) of the non-infected patients, non-specific uptake of 99mTc ciprofloxacin was found in the 1-h and 4-h images, which disappeared, however, in the 24-h images. When the early and late 99mTc ciprofloxacin images were compared, the specificity was found to improve from 41% to 95%, positive predictive value from 38% to 89%, and the diagnostic accuracy from 57% to 97%. The accuracy of the conventional 99mTc leukocyte imaging was 90%. Dynamic bone imaging also yielded abnormal findings in all the infected patients although also in 23% of the non-infected patients. Current data indicate that 99mTc ciprofloxacin is a useful method for confirming hip prosthesis infection. The diagnostic efficiency of this method is improved when the imaging time is extended to 24 h post-injection of the tracer.

Characteristics of symptomatic gallbladder disease in patients with either solitary or multiple cholesterol gallstones.

Recent studies have indicated that solitary or multiple gallstones may differ with respect to the conditions favoring their formation, such as nucleation time. We examined the clinical, histological and laboratory characteristics of symptomatic gallstone disease in a series of 125 consecutive patients with either solitary (n = 33) or multiple (n = 92) cholesterol gallstones undergoing cholecystectomy. The nature of biliary pain was found to differ in the two groups. Histological diagnoses of acute cholecystitis and gallbladder cancer was more frequent in the patients with multiple stones, and cholesterolosis in those with solitary stones. Furthermore, the stone cholesterol content was higher in the solitary stone group than in the multiple stone group. Morbid complications such as cholangitis and pancreatitis were rare and occurred only in the multiple stone group. The results support the view that gallbladder disease presents histological evidence of biliary complications more often in patients with multiple cholesterol stones than in those with solitary stones.

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.