Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland.

BACKGROUND: Screening for colorectal cancer (CRC) with guaiac-based faecal occult-blood test (FOBT) has been reported to reduce CRC mortality in randomised trials in the 1990s, but not in routine screening, so far. In Finland, a large randomised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004. We evaluate the effectiveness of screening as a public health policy in the largest population so far reported. METHODS: We randomly allocated (1:1) men and women aged 60-69 years to those invited for screening and those not invited (controls), between 2004 and 2012. This resulted in 180 210 subjects in the screening arm and 180 282 in the control arm. In 2012, the programme covered 43% of the target age population in Finland. RESULTS: The median follow-up time was 4.5 years (maximum 8.3 years), with a total of 1.6 million person-years. The CRC incidence rate ratio between the screening and control arm was 1.11 (95% CI 1.01 to 1.23). The mortality rate ratio from CRC between the screening and control arm was 1.04 (0.84 to 1.28), respectively. The CRC mortality risk ratio was 0.88 (0.66 to 1.16) and 1.33 (0.94 to 1.87) in males and females, respectively. CONCLUSIONS: We did not find any effect in a randomised health services study of FOBT screening on CRC mortality. The substantial effect difference between males and females is inconsistent with the evidence from randomised clinical trials and with the recommendations of several international organisations. Even if our findings are still inconclusive, they highlight the importance of randomised evaluation when new health policies are implemented. TRIAL REGISTRATION: 002_2010_august.

Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma.

This EORTC multicentre study analysed the efficacy and tolerability in patients with metastatic uveal melanoma of BOLD chemotherapy in combination with recombinant interferon alpha-2b. The dose of bleomycin was 15 mg on days 2 and 5, of vincristine 1 mg/m(2) on days 1 and 4, of lomustine 80 mg on day 1, and of dacarbazine (DTIC) 200 mg/m(2) on days 1-5, given every 4 weeks for a minimum of two cycles. Subcutaneous (s.c.) interferon alpha-2b at a dose of 3 x 10(6) IU was initiated on day 8 of the first cycle, and continued at a dose of 6 x 10(6) IU three times per week after 6 weeks. A median of two cycles were administered to 24 patients (median age 60.5 years). None achieved an objective response (0%; 95% Confidence Interval (CI): 0-14), 2 (8.3%) remained stable, 20 showed progression, and 2 (8.3%) were invaluable. The median progression-free survival was 1.9 months (95% CI: 1.8-3.4) and overall survival 10.6 months (95% CI: 6.9-16.4). Overall survival improved with increasingly favourable pretreatment characteristics (median, 14.7 versus 6.9 versus 6.0 months for Helsinki University Central Hospital (HUCH) Working Formulation stages IVBa, IVBb and IVBc, respectively; P=0.018). Grade 3 alopecia and neurotoxicity occurred in 13% of the patients. This multicentre study did not confirm earlier reports that BOLD with human leucocyte or recombinant interferon would induce at least 15% objective responses in metastatic uveal melanoma.

Serum adhesion molecules and interleukin-2 receptor as markers of tumour load and prognosis in advanced cutaneous melanoma.

Cell adhesion molecules are cell surface glycoproteins that may act as mediators in the metastatic process. Soluble interleukin-2 receptor (sIL-2R) is an immunological marker that may also serve as an indicator of tumour progression. Normal and neoplastic cells are capable of releasing these molecules into circulation. We evaluated the association between pretreatment serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sIL-2R and metastases and survival in 50 patients with advanced melanoma. The patients with liver and/or bone metastases had significantly higher sICAM-1 levels than those with soft tissue and/or lung involvement (P=0.002). In addition, there was a trend towards higher sIL-2R levels in patients with more metastatic sites (P=0.07). In univariate analysis, the number of metastatic sites (P=0.0001, odds ratio (OR) 3.0, 95% confidence interval (CI): 1.7-5.3), the metastatic site (P=0.01, OR 2.3, 95% CI: 1.2-4.4) and the levels of sICAM-1 (P=0.011, OR 2.5, 95% CI: 1.2-5.0), sVCAM-1 (P=0.036, OR 2.1, 95% CI: 1.0-4.3) and sIL-2R (P=0.0016, OR 3.0, 95% CI: 1.5-6.0) were found to be statistically significant prognostic factors for survival. In multivariate analysis, the number of metastatic sites was the dominant prognostic indicator. After it was excluded from the analysis, the sIL-2R level and the metastatic site were found to be significant. It can be concluded, that high sICAM-1 levels suggest liver metastases and sIL-2R seems to serve as a marker of tumour load in metastatic melanoma. Furthermore, the sIL-2R level appears to add to clinical data predicting the patient's outcome.

Factors predicting interferon treatment response in patients with chronic hepatitis c: late viral clearance does not preclude a sustained response.

OBJECTIVES: Because of the suboptimal efficacy, cost, and adverse effects of interferon in chronic hepatitis C (HCV), predictors have been sought to detect patients with a good treatment response. Also, markers for determining a poor response early in the course of therapy, such as the lack of early viral clearance, have been proposed. METHODS: Ninety-seven patients with chronic hepatitis C were enrolled to receive leukocyte alpha-interferon according to a stepped-care management protocol. The final virological treatment response was evaluated in 74 patients after a 6-month post-treatment follow-up. The relationship between pretreatment and during-treatment variables and the long-term response was assessed. RESULTS: Non-1 viral genotype, higher pretreatment ALT levels, and lower gamma-glutamyl transferase (GGT)/ALT ratios and GGT as well as younger age were significantly associated with a sustained response; a trend was also detected for lower serum ferritin levels. Normalization of ALT by 3 months was also a significant predictor of a long-term response. Of the 27 patients carrying the HCV genotype 3a, seven (26%) were still HCV RNA positive at 6 months. Of these patients, however, five (19%) still achieved a sustained virological response after treatment for up to 12 months. CONCLUSIONS: In contrast to some previous reports, our results suggest that a late viral clearance after 6 months of interferon monotherapy may not preclude a favorable long-term response after a 12-month treatment, especially in patients carrying a non-1 HCV genotype. A low pretreatment GGT/ALT ratio is a predictor of a good treatment response.

The value of serum S-100beta and interleukins as tumour markers in advanced melanoma.

Recently serum S-100beta has shown promise as a tumour marker in melanoma; however, its use as a prognostic marker in the advanced stage needs to be confirmed. Interleukins (ILs) may mediate regression or progression of cancer. In order to study their relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of S-100beta, IL-6, IL-10 and IL-12 and metastatic site and survival in 50 patients with advanced melanoma who were to receive chemoimmunotherapy. Patients with liver and/or bone metastases had significantly higher median concentrations of S-100beta, IL-6 and IL-10 than those with only skin, nodal and/or lung involvement. The differences in IL-12 levels were unremarkable. Using univariate analysis, the S-100beta level and metastatic profile were found to be statistically significant prognostic factors for survival. Using multivariate analysis the S-100beta level was the most powerful prognostic indicator, while the metastatic profile was found to be significant after exclusion of S-100beta. The findings suggest that elevated serum levels of S-100beta, IL-6 and IL-10 reflect concurrent liver or bone metastases in melanoma. S-100beta is also an independent prognostic marker. Pretreatment IL levels were not associated with outcome.

Leukocyte interferon-alpha in the treatment of chronic hepatitis C in Finland.

BACKGROUND: To evaluate the efficacy of leukocyte interferon in previously untreated patients with chronic hepatitis C, 97 patients were enrolled in a prospective study in Finland with a stepped-care management protocol. METHODS: The treatment was initiated with 3 million units of interferon-alpha subcutaneously three times a week. At 3 months, if the serum alanine aminotransferase was still abnormal, the dose was doubled. If serum hepatitis C virus (HCV) RNA had turned negative at 6 months, the treatment was stopped; if it was still positive, treatment was continued for up to 12 months. All patients were followed up after treatment for 6 months. Altogether, 74 patients completed the treatment and follow-up periods. RESULTS: Of all the originally enrolled patients 36% (35 of 97) achieved sustained virologic response, defined as HCV RNA negativity 6 months after the end of treatment. The commonest HCV genotype among these patients was 3a, and as many as 52% of such patients achieved sustained virologic response. Thirty-two per cent of the patients had HCV genotype 1a, 1b, or a mixture of these; a sustained response was achieved in only 6% of such patients but in 50% of patients with a non-1 genotype. Adverse effects caused treatment cessation for 10% of the patients and IFN dose reduction for 20%. CONCLUSIONS: Monotherapy with human leukocyte interferon resulted in sustained virologic response in 36% of patients with chronic hepatitis C. In those infected with a HCV genotype other than 1, the sustained virologic response rate was 50%.

Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine.

BACKGROUND: Cholesterol metabolic studies are simplified in colectomized patients because of rapid intestinal passage and reduced bacterial action. OBJECTIVE: Our objective was to study the effect on cholesterol and plant sterol metabolism of feeding a margarine containing stanol ester to 11 colectomized patients. DESIGN: A margarine containing 2 g stanol was consumed for 7-18 d. Serum, biliary, and fecal lipids were measured before and during consumption of the margarine. RESULTS: Serum cholesterol concentrations and the ratio of plant sterol to cholesterol decreased after 1 d of consumption of stanol esters (P < 0.05). After 7 d, serum cholesterol decreased by 16% (P < 0.01), cholesterol absorption efficiency decreased by approximately 40%, and fecal output of cholesterol as neutral sterols (but not as bile acids) increased by 36%. Biliary bile acid composition and the molar percentage of biliary cholesterol were unchanged. Increased ratios of cholesterol precursor sterols in serum and bile indicated enhanced cholesterol synthesis during consumption of stanol esters; the percentage absorption of plant sterols and the ratios of plant sterols to cholesterol decreased, whereas serum and biliary plant stanols and their biliary secretion gradually increased. In feces, 95% of cholesterol and 90% of plant stanols were in unesterified form. CONCLUSIONS: In colectomized patients, effective inhibition of cholesterol absorption and lowering of serum cholesterol concentrations and plant sterol ratios occurs within 1 d of the start of consumption of stanol esters. The composition of major bile lipids is unchanged, indicating that gallstone formation is unlikely. Small amounts of plant stanols are recovered in serum and bile during consumption of stanol esters but effectively are secreted through bile, thereby balancing the intake-induced increase in their absorption.

Serum matrix metalloproteinase-2 as a prognostic marker in advanced cutaneous melanoma.

The association was studied between serum concentration of matrix metalloproteinase-2 (MMP-2) and metastatic site, survival and disease progression in patients with advanced cutaneous melanoma. The patient population consisted of 50 patients who were treated with chemoimmunotherapy. The median baseline serum concentration of MMP-2 was 724 ng/ml (range 500-2,297 ng/ml). There were no significant differences in MMP-2 levels according to metastatic site. Baseline MMP-2 concentration did not have a prognostic value. The patients with levels below 800 ng/ml survived for 8.8 months and those with higher levels for 9.7 months. On serial measurements, median serum MMP-2 concentration at disease progression in 25 patients was significantly higher than before treatment. Only five samples at response were available, and the levels were not significantly different from baseline levels. In conclusion, serum MMP-2 is not a prognostic marker in advanced melanoma. It also appears to be of limited clinical value in monitoring.

Serum dolichols in chronic cholestatic liver diseases.

BACKGROUND/AIMS: Dolichols are long-chain polyisoprenoid alcohols. It has been suggested that they modify membrane fluidity, stability and permeability. Some lysosomal diseases are associated with elevated serum dolichol levels. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol, however, is not known. METHODS: We therefore studied the effect of early or intermediate primary biliary cirrhosis, primary sclerosing cholangitis and alcoholic liver cirrhosis on serum dolichol concentration. Furthermore, serum dolichol content was measured in patients with end-stage primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis, waiting to be transplanted. RESULTS: As compared to age-adjusted controls, serum dolichol was significantly increased in early and intermediate primary biliary cirrhosis (451+/-56 ng/ml vs. 225+/-13 ng/ml, p<0.0001) and primary sclerosing cholangitis (315+/-16 ng/ml vs. 224+/-7 ng/ml, p<0.0001). However, in alcoholic liver cirrhosis serum dolichol was unaffected. Serum dolichol content was also significantly elevated in patients with end-stage primary biliary cirrhosis (844+/-210 ng/ml vs. 225+/-13, p<0.001) and chronic active hepatitis (594+/-198 vs. 224+/-7 ng/ml, p<0.02). Furthermore, in patients with liver diseases serum dolichol concentration correlated positively with serum high density lipoprotein (HDL)-cholesterol (r = +0.50, p<0.0001). CONCLUSIONS: Serum dolichol levels are elevated in all stages of chronic cholestatic liver diseases but not in alcoholic liver cirrhosis. Impaired biliary excretion of dolichols appears to be the primary explanation for this finding.

Characterization of recombinant human type IX collagen. Association of alpha chains into homotrimeric and heterotrimeric molecules.

As type IX collagen is a minor cartilage component, it is difficult to purify sufficient amounts of it from tissues or cultured cells to study its structure and function. Also, the conventional pepsin digestion used for fibrillar collagens cannot be utilized for purifying type IX collagen, because it contains several interruptions in its collagenous triple helix. A baculovirus expression system was used here to produce recombinant human type IX collagen by coinfecting insect cells with three viruses containing full-length cDNAs for the alpha1(IX), alpha2(IX), and alpha3(IX) collagen chains together with a double promoter virus for the alpha and beta subunits of human prolyl 4-hydroxylase. Correctly folded recombinant type IX collagen was secreted, consisting of the three alpha chains in a 1:1:1 ratio and showing the expected biphasic thermal melting profile. When the individual alpha chains were expressed, disulfide-bonded homotrimers and homodimers of the alpha chains were observed. When the cells were coinfected with the viruses for all three alpha chains, heterotrimers of alpha1(IX), alpha2(IX), and alpha3(IX) were detected in cell culture medium, and the other possible combinations were less prominent. When any two of the alpha chains were co-expressed, in addition to the homodimers and homotrimers, only alpha1(IX) and alpha3(IX) chains were disulfide-bonded. The results thus suggest that the most favored molecular species is an alpha1(IX)alpha2(IX)alpha3(IX) heterotrimer, but the chains are also able to form disulfide-bonded heterotrimers of alpha1(IX) and alpha3(IX) chains and (alpha1(IX))(3), (alpha2(IX))(3), and (alpha3(IX))(3) homotrimers.

Antibodies to pyruvate dehydrogenase in primary biliary cirrhosis: correlation with histology.

Antimitochondrial antibodies to pyruvate dehydrogenase are the hallmark of primary biliary cirrhosis. Their pathogenic role has not been proven, although antibodies to pyruvate dehydrogenase are bound to biliary epithelium. The aim of this study was to characterize serum IgA antibodies to pyruvate dehydrogenase and to evaluate their response to different treatment regimens. We also compared the level of antibodies with severity of histological lesions and the data of biochemical liver tests. Serum samples were collected at baseline and after 24 months from 61 primary biliary cirrhosis patients, whereas 23 patients were treated with ursodeoxycholic acid, 20 with colchicine, and 18 with placebo. ELISA was used to detect antibodies to pyruvate dehydrogenase. IgA and IgG were separated with jacalin and protein-A, respectively. Capacity of immunoglobulins to inhibit enzymatic activity was detected by spectrophotometric observation of the rate of enzyme reaction. 49 (80.3%) of the 61 patients possessed IgA antibodies to pyruvate dehydrogenase. Significant decrease in IgA antibodies was observed only in the ursodeoxycholic acid group (p<0.05). 15 of 18 IgA preparations and all 24 IgG preparations of patients' sera were inhibitory towards pyruvate dehydrogenase (mean inhibitory percent +/-SD: 42+/-33.4% and 79+/-22.4%, respectively, at a protein concentration of 100 microg/ml). The level of serum antibodies to pyruvate dehydrogenase correlated with several histological parameters (fibrosis, inflammatory infiltrate), but not with biochemical parameters. Our data reveal that IgA antibodies to pyruvate dehydrogenase inhibit enzyme function. The correlation between antibodies to pyruvate dehydrogenase and histological parameters might suggest the pathogenic role of these antibodies.

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study.

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.

Human COL9A1 and COL9A2 genes. Two genes of 90 and 15 kb code for similar polypeptides of the same collagen molecule.

Here we report the complete structure for the human COL9A1 and the complete sequence for the human COL9A2 genes. The COL9A1 gene is about 90 kb and consists of 38 exons. The COL9A2 gene is only about 15 kb, and it contains 32 exons. Sequence analysis of the promoter regions for the human COL9A2, the mouse Col9a2 and the human COL2A1 genes identified a conserved 14 bp sequence. The data also indicated that the alternative exon 1* found in intron 6 of the COL9A1 gene is separated from exon 7 only by a short intron in the chick, human, mouse and rat genes probably explaining why transcripts from exon 1* are spliced directly to exon 8.

Cholesterol metabolism and serum and biliary noncholesterol sterols in gallstone patients during simvastatin and ursodeoxycholic acid treatments.

Effects of long-term high-dose ursodeoxycholic acid (UDCA) and simvastatin treatments on cholesterol metabolism and biliary lipid compositions were compared in patients with cholesterol gallstones. Absorption and synthesis of cholesterol, serum and biliary noncholesterol sterols and lipids were determined in 14 patients randomized to UDCA (23-25 mg/kg/d) or simvastatin (40 mg/d) for 1 year. Simvastatin reduced serum low-density lipoprotein cholesterol by 55%, and UDCA, by 9%. Cholesterol absorption was decreased (35%) by UDCA, but nonsignificantly increased by simvastatin (P < .05 for difference of changes caused by the two drugs). Whole-body synthesis and biliary output of cholesterol were both significantly decreased only by UDCA. In addition, UDCA inconsistently increased the proportions of serum and biliary precursor sterols of cholesterol, known to reflect cholesterol synthesis, but did not affect their biliary secretions. Simvastatin, however, dramatically reduced serum and also biliary cholesterol precursor sterol proportions and their biliary secretions and increased proportions of serum and biliary plant sterols and cholestanol, known to reflect cholesterol absorption, but had no effect on their biliary secretion. Only UDCA significantly decreased the molar percentage of cholesterol, the lithogenic index, and the cholesterol/phospholipid (CH/ PL) ratio in bile, whereas both treatments inconsistently decreased the vesicular CH/PL ratio (P < .07 in both groups). It is concluded that both drugs decreased serum cholesterol and inhibited cholesterol synthesis, but had a differing influence on precursor sterols and the absorption of cholesterol. UDCA had more beneficial effects than simvastatin on the antilithogenic properties of bile.

The sedimentable sterols in gallstone patients before and during ursodeoxycholic acid and simvastatin treatments.

BACKGROUND: The insoluble material in supersaturated bile is prerequisite for the formation of gallstones. We therefore studied the biliary precipitable and soluble cholesterol and noncholesterol sterols, including the cholesterol precursor sterols (including lanosterol and lathosterols), and the plant sterols campesterol and sitosterol, and cholestanol, which usually reflect cholesterol synthesis and absorption, respectively, before and after a 6-month treatment with ursodeoxycholic acid (UCDA), 15.4 +/- 4 mg/kg/day (standard error of the mean) or simvastatin (40 mg/day) in 21 patients with cholesterol gallstones, to obtain further information about the factors contributing to the formation of gallstones. METHODS: The sediment and supernatant fractions of duodenal bile samples were separated by ultracentrifugation and analyzed with gas-liquid chromatography. RESULTS: At the base line (n = 21) 50% +/- 3% of biliary cholesterol and a variable amount of the noncholesterol sterols (from 14% of lanosterol to 62% of cholestanol) were in the sediment fraction. The pattern of the noncholesterol sterols in the sediment resembled that of gallstones described previously. At base line body mass index was positively related to the percentage of precipitable cholesterol in bile (r = 0.46, P < 0.05), and the serum sitosterol proportion negatively related to the molar percentage of biliary cholesterol and positively to that of bile acids (r = -0.46 and r = 0.50, P < 0.05 for both). UDCA decreased the precipitable percentage of cholesterol from 46% to 31% (P < 0.03) and simvastatin from 57% to 42% (P = 0.05). Both drugs also decreased the precipitable percentages of lathosterols and cholestanol while increasing that of lanosterol. In relation to cholesterol, the sediment to supernatant ratios of all methylsterols were increased, whereas those of polar lathosterols tended to decrease during UDCA treatment. CONCLUSIONS: Patients with high body mass index have more precipitable cholesterol in their bile. Although both UDCA and simvastatin decreased the precipitable cholesterol, the bile still contained one-third of its cholesterol in the sedimentable form.

Expression and therapeutic response related to apolipoprotein E polymorphism in primary biliary cirrhosis.

BACKGROUND/AIMS/METHODS: Apolipoprotein E polymorphism, affecting intestinal absorption and biliary secretion of bile acids, might also contribute to the variable course and response to drug treatment of primary biliary cirrhosis. To test this possibility, we studied the apo E gene frequency, and the expression and response to drug therapy in different apo E isoforms of 88 patients with primary biliary cirrhosis, randomized to ursodeoxycholic acid, colchicine or placebo treatments for 2 years. RESULTS: The frequency of the epsilon2 allele was 2.4 times higher (p<0.01) in the patients with primary biliary cirrhosis compared with the Finnish population. At entry the patients with the epsilon4 allele were significantly younger (p<0.01) than those with other epsilon alleles, while the severity of primary biliary cirrhosis was similar in the three apolipoprotein E phenotypes. Liver enzymes, acute hepatic inflammation, serum total and low density lipoprotein cholesterol were decreased by ursodeoxycholic acid only in the patients with the epsilon4 and homozygous epsilon3 alleles, but not in those with the epsilon2 allele. Improvements of liver enzyme tests by ursodeoxycholic acid were more marked in the patients with the epsilon4 than other epsilon alleles. CONCLUSIONS: The present data show that in primary biliary cirrhosis the epsilon2 allele is overrepresented, and suggest that the expression of primary biliary cirrhosis and response of the disease to ursodeoxycholic acid treatment are closely related to the apo E polymorphism.

Cholesterol metabolism and non-cholesterol sterols in patients with ileal pouch anastomosis.

BACKGROUND: Previous studies suggest only minor changes in bile acid metabolism after panproctocolectomy with ileal pouch construction. AIMS/METHODS: To investigate these changes further, we studied cholesterol absorption and serum, biliary and fecal non-cholesterol sterols and lipids in 12 ileal pouch patients and 10 controls. RESULTS: In patients, cholesterol absorption was markedly reduced and was associated with low serum total and LDL cholesterol and LDL triglyceride levels, but surprisingly, cholesterol synthesis, as indicated by sterol-balance data or serum cholesterol precursor levels, was within low normal limits. The high proportions of serum plant sterol to cholesterol, particularly that of campesterol, were not related to cholesterol absorption, but were attributable to a markedly reduced biliary cholesterol secretion. Interestingly, in these patients the fractional absorption of campesterol was normal, whereas that of sitosterol, like cholesterol, was reduced and was positively related to the intestinal influx of cholesterol. The patients' serum cholestanol proportion was normal, but the proportion of the cholestanol formed during intestinal passage was significantly reduced (17.9% vs 65.2% in controls). CONCLUSIONS: Thus ileal pouch patients are characterized by sterol malabsorption, lowered serum total and LDL-cholesterol levels, but unexpectedly without any increase in cholesterol synthesis. The lack of high serum cholestanol, shown earlier frequently in unoperated patients with ulcerative colitis, may indicate reversible cholestasis, a finding deserving further exploration.