Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. METHODS: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. RESULTS: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). CONCLUSIONS: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

Acute liver failure in Sweden: etiology and outcome.

OBJECTIVE: To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994-2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score with transplant-free deaths as a positive outcome. RESEARCH DESIGN AND METHODS: Adult patients in Sweden with international normalized ratio (INR) of >or=1.5 due to severe liver injury with and without encephalopathy at admission between 1994-2003 were included. RESULTS: A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive-predictive value (PPV) of 67%, negative-predictive value (NPV) of 84% in the acetaminophen group. Positive-predictive value and negative-predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score>30 had a positive-predictive value of 21%, negative-predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively. CONCLUSIONS: Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score<30 predicts a good prognosis in acetaminophen patients without transplantation.

Clinical and subclinical intestinal inflammation assessed by the mucosal patch technique: studies of mucosal neutrophil and eosinophil activation in inflammatory bowel diseases and irritable bowel syndrome.

BACKGROUND AND AIMS: There is a clear need for a rapid, simple, safe, and sensitive method of determining the type and intensity of inflammation in the gut mucosa in clinical practice. In this study, we have evaluated the potential of a new method, the mucosal patch technique, in patients with and without apparent gut inflammation, as assessed by conventional diagnostic procedures. SUBJECTS AND METHODS: The technique tested is based on the idea that inflammatory mediators released from the rectal mucosa can be absorbed by and then extracted from cellulose patches brought into contact with the mucosa by use of an instrument with an inflatable balloon. Measurements were performed in healthy controls (n = 16) and in patients with active (n = 19) and inactive ulcerative colitis (UC, n = 8), collagen colitis (CC, n = 12), coeliac disease (n = 13), and irritable bowel syndrome (IBS, n = 13). RESULTS: Inflammatory mediators from neutrophils (myeloperoxidase (MPO)) and eosinophils (eosinophil cationic protein (ECP)) were increased on average 300- and 10-fold, respectively, in patients with active UC compared with healthy controls and were correlated with the endoscopic score. Patients with inactive UC, CC, coeliac disease, and IBS exhibited no endoscopic signs of inflammation. These patient groups had significantly lower levels of MPO and ECP than the active UC group but showed on average a four- to sevenfold increase in MPO compared with healthy controls. CONCLUSION: The mucosal patch technique was well tolerated by patients and easily applied by the investigator. Pronounced neutrophil and eosinophil involvement in UC was demonstrated. With the high sensitivity of the technique, low degree mucosal neutrophil activation could also be quantified in patients with CC and UC in clinical remission. The finding of increased neutrophil involvement in patients with IBS contributes to the pathophysiological ideas of this disease.

An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis.

OBJECTIVES: The prevalence of osteoporosis amongst patients with primary biliary cirrhosis (PBC) is high and may be a serious clinical problem. Hormone replacement therapy (HRT) is effective in preventing bone loss but has not been evaluated in randomized trials in PBC. The primary aim was to study the effect of transdermal HRT in combination with daily vitamin D and calcium supplementation on bone loss compared with vitamin D and calcium supplementation only in postmenopausal women with PBC. The secondary aim was to study the safety of transdermal HRT. SUBJECTS/INTERVENTIONS: Eighteen females with PBC were randomized to receive 2 years therapy with either (i) transdermal oestradiol 50 microg 24 h(-1) two times per week + medroxyprogesterone 2.5 mg day(-1) + alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1) or (ii) alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1). Dual-energy X-ray absorptiometry for measurement of bone mineral density (BMD) and sampling of blood and serum for measurements of biochemical markers of liver function was performed before, during and at the end of treatment. RESULTS: BMD increased significantly at the lumbar spine (P < 0.05) and the femoral neck (P < 0.05) in the HRT group whereas no significant change was found in the control group. One oestrogen-treated patient was excluded after 1 year because of deteriorating, but reversible, aminotransferases. Dropout frequency because of nonliver-related causes was higher in the HRT group. Otherwise, no difference with respect to adverse liver reactions was found between the groups. CONCLUSION: Transdermal HRT increases BMD in PBC patients with few severe side effects related to the liver.

A population-based audit for diagnosing colorectal cancer.

BACKGROUND: Knowledge of the diagnostic work-up of colorectal cancer is a prerequisite to improve its quality. Family history is one of few known risk factors of the disease and it is therefore important to investigate to what extent this factor is used in routine management. METHODS: Copies of records from all health-care suppliers visited during diagnostic work-up were requested for 227/235 (97%) patients with recently diagnosed colorectal cancer in the county of Västmanland during 1998-99. A first consultation was identified and records and all diagnostic measures related to the initial consultation were scrutinized. A family history of colorectal cancer was known for 179 patients. RESULTS: Most of the patients, 107 (66%) colon and 57 (86%) rectal cancer patients, had consulted with a general practitioner. The median diagnostic work-up time was 42 days (IQ 12-110) for colon and 23 days (IQ 0-49) for rectal cancer. A double-contrast barium enema was the most commonly used diagnostic method for colon cancer. Family history was documented at the first consultation in 2/179 (1%) cases. In patients with right-sided cancer, median diagnostic work-up time was 53 days in patients with a positive result of faecal occult blood test (FOBT) as compared with 448 in patients with a negative result (P < 0.01). CONCLUSION: Primary care is the key actor in diagnosing rectal cancer. The restricted capacity for X-ray is one of the main obstacles in detection of colon cancer. Family history is rarely documented during diagnostic work-up of colorectal cancer. The benefit of using FOBT in symptomatic patients is questioned.

A group-based patient education programme for high-anxiety patients with Crohn disease or ulcerative colitis.

BACKGROUND: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn disease (CD) affect a person's health-related quality of life (HRQOL). IBD patients report high levels of anxiety, which correlates with the degree of perceived dissatisfaction with the information on disease-related themes provided in routine health care. The aim of this study was to evaluate changes in anxiety after participation in a group-based educational intervention for IBD patients screened for high anxiety. METHODS: The programme consisted of 8 sessions, and 49 patients participated. Anxiety was assessed using the Hospital Anxiety and Depression (HAD) Scale at baseline and 6 months after intervention. HRQOL was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ) and the SF-36 health survey. Participant satisfaction with education was measured using a study-specific questionnaire. RESULTS: No significant change on the HAD anxiety score was found at the 6-month follow-up for those who participated in the education programme despite the fact that the participants reported they had gained better knowledge of disease-related items. Furthermore, there were no significant changes over time regarding bowel symptoms, systemic symptoms, emotional functioning and social functioning of the IBDQ or generic HRQOL (SF-36). CONCLUSIONS: IBD patients with a high anxiety level reported improved satisfaction with information about disease-related items, but did not indicate any benefits in terms of reduced anxiety or improved HRQOL after participating in the education programme, not at least in the short-term perspective. In this selected group of patients, psychosocial problems other than disease-related concerns were found that warrant other approaches.

Longitudinal bone loss in postmenopausal women with primary biliary cirrhosis and well-preserved liver function.

OBJECTIVES/DESIGN: Increased rate of bone loss has been reported in women with primary biliary cirrhosis (PBC) and varying degree of liver dysfunction. Whether bone loss is increased in patients without liver dysfunction is unclear. The aim of this study was to estimate retrospectively the rate of bone loss in postmenopausal women with PBC and well-preserved liver function. SUBJECTS/INTERVENTIONS: Forty-three women with PBC, and classified as Child-Pugh class A, were included. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at the lumbar spine and the femoral neck. RESULTS: Median time between measurements of BMD was 26 months (range, 12-48 months). Twenty women were not receiving any bone protective treatment, i.e. hormone replacement therapy (HRT), bisphosphonates or vitamin D/calcium supplementation, whilst 23 women received such treatment. Mean annual bone loss in the former group was 0.38 +/- 2.56% and 0.42 +/- 2.29% at the lumbar spine and the femoral neck, respectively. Women receiving treatment, however, increased their BMD by 1.92 +/- 3.76% and 0.15 +/- 2.75% at the lumbar spine and the femoral neck, respectively. At the lumbar spine the difference with regard to changes in BMD between untreated and treated women was statistically significant (P = 0.02). Women who received HRT (n = 11) increased their BMD at the lumbar spine by 2.95 +/- 3.91%, P = 0.03 when compared with untreated women. CONCLUSION: Bone loss in postmenopausal women with PBC and well-preserved liver function is not increased above normal. Treatment with bone protective treatment, mainly HRT, improves BMD at the lumbar spine.

HLA class II markers and clinical heterogeneity in Swedish patients with primary biliary cirrhosis.

Genetic susceptibility to PBC can, at least in part, be ascribed to the major histocompatibility complex. The relevance of immunogenetic markers for the clinical presentation and course, however, is unclear. Thus, the aim of this study was to investigate the contribution of HLA class II genes to susceptibility, clinical presentation and course of disease in PBC patients. HLA genotyping for HLA-DRB1, -DQB1 and -DPB1 was carried out in a total of 99 Swedish PBC patients and 158 controls. Clinical parameters including epidemiologic variables, signs and symptoms of PBC-related liver disease and histologic data were collected and analyzed in 92 patients at study entry and at follow-up five years later. Significant clinical heterogeneity was seen among PBC patients upon study entry. Although a significant disease association was seen for HLA DRB1*08 and DQB1*0402, immunogenetic markers identified neither a particular subset of patients nor an association with the clinical course of the disease. HLA-DRB1*08 and DQB1*0402 provide the strongest immunogenetic influence in PBC. However, this association is not restricted to any particular, clinically defined subgroup of patients and it is not predictive for the course of the disease.

Health-related quality of life and psychological distress in a population-based sample of Swedish patients with inflammatory bowel disease.

BACKGROUND: The chronicity of inflammatory bowel disease (IBD) and effects of medical and surgical treatments probably affect the daily lives of patients and may thus impair their health-related quality of life and psychological well-being. METHODS: Health-related quality of life and psychological distress were investigated in a population-based Swedish sample of patients with IBD. A total of 492 patients, 331 with ulcerative colitis (UC) and 161 with Crohn disease (CD), filled out the Short Form-36 (SF-36), the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Hospital Anxiety and Depression (HAD) scale. RESULTS: Patients with UC reported higher (superior) levels in all dimensions of health-related and disease-specific quality of life than did patients with CD. CONCLUSIONS: Having an ileostomy does not seem to affect patients' quality of life, while having ileoanal anastomosis appears to reduce patients' quality of life in several of the dimensions assessed. CD patients reported more anxiety and depression than did patients with UC. The higher psychological distress in the CD group could be explained by more severe symptoms of the disease. Having ileoanal anastomosis may lead to more anxiety and depression, while having an ileostomy does not.

Independent patterns of cytochrome P450 gene expression in liver and blood in patients with suspected liver disease.

OBJECTIVE: Assessment of liver metabolism using blood samples was tested by comparison of cytochrome P450 (CYP) gene expression in paired liver and blood samples from 13 individuals. METHODS: Total RNA was isolated from percutaneous needle biopsies and blood collected simultaneously. Gene expression for CYP1A2, CYP1B1, CYP2E1 and CYP3A4 was studied using a real-time reverse-transcription polymerase chain reaction (RT-PCR) method. RESULTS: All CYP mRNA species were expressed in all liver biopsies but at varying levels. The highest and lowest levels of expression were observed for CYP2E1 and CYP1B1, respectively. The expression patterns differed between blood and liver. CYP1B1 was expressed in all blood samples at a 20% higher level than in the liver. CYP1A2, CYP2E1 and CYP3A4 were expressed in blood at 35- to 5,000-fold lower levels than in liver. None of the transcripts in blood showed any correlation with the expression in liver. CONCLUSION: We conclude that blood cannot serve as a surrogate organ for assessment of the expression of the studied CYP genes in liver.

IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinal mucosa in ulcerative colitis.

There is an increased influx of activated eosinophils to the intestinal mucosa in active ulcerative colitis, and an increased release of eosinophil-derived proteins, such as ECP, has also been observed. These findings indicate that eosinophils may contribute to tissue damage and intestinal inflammation in this disease. The relative importance of different chemotactic factors and the impact of steroid treatment on their effect in active ulcerative colitis are not known. We measured the eosinophil chemotactic activity in perfusion fluids from 11 patients with ulcerative colitis before and after steroid treatment and from 7 control patients. The effect of neutralizing antibodies to IL-5 and -8, RANTES, eotaxin, MCP-3, TNF-alpha, GM-CSF was investigated. The chemotactic activity was higher in perfusion fluids from patients than from controls (P = 0.0043). Anti-IL-5 (P = 0.005) and -TNF-alpha (P = 0.017) inhibited the activity in perfusion fluids obtained before treatment. Steroid treatment prevented the effect of all antibodies but had no significant effect on the chemotactic activity. The chemotactic activity correlated with the levels of eosinophil granule proteins in the perfusion fluids. In conclusion, in ulcerative colitis, eosinophils are attracted to the intestinal tissue by chemotactic factors, of which IL-5 and TNF-alpha may be the most prominent steroid-sensitive ones. The steroid-insensitive chemotactic activities remain unidentified.

Evidence of local eosinophil activation and altered mucosal permeability in collagenous colitis.

The local release of the inflammatory mediators eosinophil cationic protein and myeloperoxidase and the permeability marker albumin was studied in collagenous colitis using a new technique for segmental perfusion of the rectum and descending colon. Perfusion of both segments was successful in 19/25 (76%) of patients with collagenous colitis and controls with noninflammatory conditions. The concentration of myeloperoxidase was increased in the perfusion fluids from both segments in only one patient with collagenous colitis and in none of the controls. On the other hand, concentrations of eosinophil cationic protein and albumin in the perfusate from the rectum were significantly increased in collagenous colitis compared with controls, and similar trends were seen in the perfusates from the descending colon. Furthermore, there was a significant correlation between the increased concentrations of eosinophil cationic protein and albumin, indicating a possible relation between eosinophil activation and disturbed mucosal permeability in collagenous colitis.

Neutrophil and eosinophil granule proteins as markers of response to local prednisolone treatment in distal ulcerative colitis and proctitis.

OBJECTIVE: The pathophysiological role of neutrophil and eosinophil granulocytes in relation to steroid enema treatment was studied in patients with distal ulcerative colitis and proctitis. METHODS: The rectal release of the neutrophil (myeloperoxidase, MPO), and eosinophil (eosinophilic cationic protein, ECP and eosinophil peroxidase, EPO) granule constituents were measured in 11 patients using intraluminal segmental perfusion of the rectum. The released amounts of MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays before and during prednisolone enema treatment and related to clinical, endoscopical, and histopathological data in addition to treatment outcome. RESULTS: Clinical activity and particularly endoscopic activity correlated well with intraluminal MPO concentrations both before and during treatment. At the end of the study, eight of 11 patients fulfilled predefined response criteria; all responding patients had significant decrease of MPO concentrations (p < 0.01). This decline of MPO concentration was seen after 7 days of treatment (p < 0.05) in the response group and often occurred before clinical improvement. There was a nonsignificant trend toward a decrease in the concentrations of ECP and EPO at the end of treatment in responders.

Circulating levels of insulin-like growth factors and their binding proteins in patients with chronic liver disease: lack of correlation with bone mineral density.

BACKGROUND/AIMS: Insulin-like growth factor-I (IGF-I) levels are low in patients with chronic liver disease (CLD) and have been found to correlate with measurements of bone mineral density (BMD) in men with viral cirrhosis. The aim of this study was to investigate the relationship between circulating IGF-I levels and BMD in patients with CLD of other causes. METHODS: Fifty-eight patients with CLD were included. Age- and sex-matched normal individuals served as controls. Serum levels of IGF-I and IGF-II and their binding proteins (IGFBP-1-3) were measured by radioimmunoassay. BMD was measured by dual energy X-ray absorptiometry. RESULTS: IGF-I levels were 57+/-33 and 136+/-48 ng/ml; p<0.0001 in patients and controls, respectively. IGF-II and IGFBP-3 levels were lower (p<0.0001) and IGFBP-1 and IGFBP-2 levels were higher in patients compared with controls (p<0.0005 and p<0.0001, respectively). All growth factors, except for IGFBP-2, correlated with parameters of liver function. In a multiple regression analysis, adjusting for age, no correlation was found between IGF-I, IGF-II, IGFBP-1-3 and BMD in either patients or controls. CONCLUSION: Patients with CLD have low levels of IGF-I, IGF-II and IGFBP-3 that correlate with liver function. No relationship was found between low levels of growth factors and BMD.

[Therapeutic program for ascites. Recommendations from the Swedish Society of Gastroenterology and Gastrointestinal Endoscopy]. / Behandlingsprogram vid ascites. Rekommendationer från Svensk förening för gastroenterologi och gastrointestinal endoskopi.

As ascites is related to liver cirrhosis in 80% of the patients, the present therapeutic guidelines are focused on ascites in liver cirrhosis. A combination of spironolactone and furosemide is recommended as first line therapy in patients with mild to moderate ascites and is effective in 90% of patients. In patients with pronounced or tense ascites, first line treatment is total paracentesis with intravenous infusion of human albumin as colloid replacement. Maintenance therapy for the prevention of recurrent ascites is based on spironolactone with or without furosemide. The indications for peritoneovenous shunt, or transjugular intrahepatic stent-shunt (TIPSS), are limited and only recommended in strictly selected patients with refractory ascites. Ascites in liver cirrhosis is a symptom of advanced liver disease, and liver transplantation should always be considered in eligible patients.

Inverse relationship between circulating levels of leptin and bone mineral density in chronic liver disease.

BACKGROUND AND AIM: The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease. METHODS: Fifty-eight patients, 39 females and 19 males, and age- and gender-matched controls were included. Bone mineral density was measured by using dual energy X-ray absorptiometry. Serum leptin was measured by using a radioimmunoassay. RESULTS: The mean serum leptin concentration was 10.4 +/- 11.3 and 15.2 +/- 17.9 ng/mL; P=0.11, in the patients and controls, respectively. Leptin correlated positively with body mass index in patients (r=0.40; P=0.003) and in controls (r=0.55; P < 0.0001). In patients classified as Child-Pugh grade B and C, serum leptin correlated negatively with bone mineral density in females at both the lumbar spine and the femoral neck (r=-0.78; P=0.04 and r=-0.86; P=0.03, respectively). In male patients, the correlation was only significant at the lumbar spine (r=-0.99; P=0.002 and r=-0.86; P=0.06, at the lumbar spine and femoral neck, respectively). No correlation was found between serum leptin and bone mineral density in the controls. CONCLUSION: An inverse relationship between serum leptin and bone mineral density was found in patients with advanced chronic liver disease. The reasons for these findings are uncertain, but a pathophysiological role of circulating leptin in osteoporosis in chronic liver disease is possible.

Allopurinol in addition to 5-aminosalicylic acid based drugs for the maintenance treatment of ulcerative colitis.

BACKGROUND: To investigate the value of combined treatment with allopurinol and 5-aminosalicylic (5-ASA) based drugs as maintenance treatment for ulcerative colitis (UC). METHODS: 199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5-ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months. RESULTS: Intention-to-treat analysis after 6 and 12 months showed similar results in both groups. A log-rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar. CONCLUSIONS: It appears possible that allopurinol in combination with 5-ASA is better than 5-ASA alone for a 6-month, but not a 12-month period. This has to be verified in further dose-ranging studies.

[11C]Hyaluronan uptake with positron emission tomography in liver disease.

BACKGROUND: A hyaluronan-loading test has been developed for assessment of hyaluronan kinetics and applied in patients with liver and joint diseases. This test describes the metabolic process of hyaluronan but cannot define the specific contribution of different organs. A method for labelling of hyaluronan with the short-lived positron-emitting radionuclide 11C has been published and in this study applied in healthy subjects and liver diseases. MATERIALS AND METHODS: Positron emission tomography (PET) was used for the regional assessment and quantification of [11C]hyaluronan uptake in three healthy subjects, four patients with alcoholic liver cirrhosis, one with alcoholic hepatitis and one with liver steatosis. After intravenous administration of 60 MBq of 11C-labelled hyaluronan, a 55-min PET scan was performed over the liver and plasma radioactivity was analysed. Rate constants describing the transport of the [11C]hyaluronan tracer from plasma to the liver were calculated. RESULTS: High uptake was observed in the liver combined with a rapid elimination of tracer from plasma. The liver uptake rate (k1) was significantly lower in patients (0.018 min-1) than in healthy subjects (0.043 min-1, P = 0.002). The rate constants seem to be related to the severity of the disease as defined by the Child-Pugh score. CONCLUSIONS: The study suggests that PET with [11C]hyaluronan could be an accurate method by which to assess liver dysfunction, in conditions where endothelial cell function is impaired. The possibility of quantification over extended portions of the body also opens up possibilities to explore regional differences in liver function and to assess other elimination routes of hyaluronan.

Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet.

In a previous screening study, 16% of patients with psoriasis had IgA and/or IgG antibodies to gliadin (AGA). The aim of the present study was to evaluate the effect of a gluten-free diet (GFD) in 33 AGA-positive and six AGA-negative psoriasis patients. Of the 33 AGA-positive patients, two had IgA antibodies to endomysium (EmA) and 15 an increased number of lymphocytes in the duodenal epithelium, but in some this increase was slight. Two patients had villous atrophy. A 3-month period on a GFD was followed by 3 months on the patient's ordinary diet. The severity of psoriasis was evaluated with the psoriasis area and severity index (PASI). The examining dermatologists were unaware of the EmA and duodenal biopsy results throughout the study. Thirty of the 33 patients with AGA completed the GFD period, after which they showed a highly significant decrease in mean PASI. This included a significant decrease in the 16 AGA-positive patients with normal routine histology in duodenal biopsy specimens. The AGA-negative patients were not improved. After GFD, the AGA values were lower in 82% of those who improved. There was a highly significant decrease in serum eosinophil cationic protein in patients with elevated AGA. When the ordinary diet was resumed, the psoriasis deteriorated in 18 of the 30 patients with AGA who had completed the GFD period. In conclusion, psoriasis patients with raised AGA might improve on a GFD even if they have no EmA or if the increase in duodenal intraepithelial lymphocytes is slight or seemingly absent.

Quantitation of cytochrome P450 mRNAs in patients with suspected liver diseases as assessed by reverse transcriptase-polymerase chain reaction.

The cytochrome P450 system (CYP) is vital for the oxidation and detoxification of numerous drugs and other xenobiotics in the liver. Many of the CYP enzymes are polymorphically expressed and may be induced or inhibited by xenobiotics including drugs and alcohol. The measurement of gene expression is thus important in studies of the mechanisms of interaction with and function of the CYP system. We have developed a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method for the study of the mRNA expression of three CYP enzymes--2E1, 1A2, and 3A4--in snap-frozen percutaneous liver biopsy samples. The method was made quantitative by the introduction of a recombinant RNA internal standard that contains a transcript of the beta-globin gene and sequences specific for the studied CYP enzymes. The method allows the analysis of mRNA expression of several enzymes in as little as 5 mg of liver tissue. Liver tissue specimens from 19 patients with suspected liver disease were analyzed for CYP-specific mRNA expression. The mean mRNA concentrations for CYP1A2, 2E1, and 3A4 were 0.16, 0.74, and 0.32 amol of specific mRNA per nanogram of poly (A+) mRNA, respectively, but a large interindividual variation was observed. CYP3A7 primers were included in the internal standard. However, because of low expression it was not possible to quantitate the enzyme. This quantitative RT-PCR method is of value for studies of the mechanisms of variation and interactions with the members of the CYP enzyme family in healthy and diseased liver and other organs.