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R Hultcrantz

Publications and source records attributed to R Hultcrantz.

At least 19 recordsLinked to original sources
PubMed2005

Sporadic adenomatous polyp regression with exisulind is effective but toxic: a randomised, double blind, placebo controlled, dose-response study.

BACKGROUND AND AIMS: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. PATIENTS AND METHODS: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. RESULTS: A total of 281 patients were enrolled and randomised; 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p=0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p=0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. CONCLUSION: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.

Adenomatous Polyposis Coli↗
PubMed2005

Virtual reality colonoscopy simulation: a compulsory practice for the future colonoscopist?

BACKGROUND AND STUDY AIM: As for any manual procedure, the learning curves for medical interventions can have undesirable phases, occurring mostly in the early experience of applying a technique. There have been impressive advances in endoscopic procedures during recent years, and there is an emerging trend that the number of procedures is increasing in parallel with these. In addition, the introduction of screening programs for colorectal cancer will also increase the numbers of procedures needed. Recent developments in medical simulation seem promising with regard to the possibility of "training out" undesirable parts of the learning curve outside the operating room. The aim of this study was to investigate whether the use of the AccuTouch flexible endoscopy simulator improves the early part of the learning curve in colonoscopy training. METHOD: 12 endoscopy trainees, 10 surgeons and two medical gastroenterologists, all with experience in gastroscopy but with no specific colonoscopy experience, were randomly assigned to either simulator training or to a control group. They all received the same theoretical study package and the training group practiced with the AccuTouch colonoscopy simulator until a predefined expert level of performance was reached. All trainees performed their first ten individual colonoscopies described in detail in a separate protocol. RESULTS: Trainees in the simulator-trained group performed significantly better (P=0.0011) and managed to reach the cecum in 52% of their cases (vs. 19% in the control group), and were 4.53 times more likely to succeed compared with the controls. Additionally, there was a significantly shorter procedure time and less patient discomfort in the hands of the simulator-trained group. CONCLUSION: Skills acquired using the AccuTouch simulator transfer well into the clinical colonoscopy environment. The results of this trial clearly support the plan to integrate simulator training into endoscopic education curricula.

Adult↗
PubMed2004

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.

Adult↗
PubMed2003

Tumour necrosis factor alpha and its promoter polymorphisms' role in the phenotypic expression of hemochromatosis.

BACKGROUND: The majority of hemochromatosis patients are homozygous for the HFE-C282Y mutation. However, less than half of C282Y homozygous subjects identified by population screening studies actually develop the disease. The cytokine TNF-alpha is implicated in the regulation of iron metabolism at different levels. Our aim was to study the role of TNF-alpha and its promoter polymorphisms in the phenotypic expression of hemochromatosis in individuals with and without the C282Y mutation. METHODS: We studied 4 groups of 10 subjects each: (1) C282Y homozygotes without clinical hemochromatosis; (2) C282Y homozygotes with hemochromatosis; (3) secondary hemochromatosis (without C282Y mutation); and (4) controls. Groups were age-matched and sex-matched. Peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) and the release of TNF-alpha was measured. Additionally, the G/A polymorphisms at position -238 and -308 of the TNF-alpha, gene were determined by PCR and RFLP analysis in 178 hemochromatosis patients and 41 controls. RESULTS: TNF-alpha production from PBMC at 8 and 24 h after increasing concentrations of LPS stimulation were similar in the four groups. The prevalence of TNF-alpha polymorphisms was similar in patients and controls. The prevalences of cirrhosis, siderosis, median s-ferritin and median ALT values were similar in patients with and without the TNF-alpha polymorphisms. CONCLUSIONS: Neither TNF-alpha, released from PBMC nor the presence of TNF-alpha polymorphisms seem to be associated with disease manifestation in hemochromatosis.

Adult↗
PubMed2003

Psychological factors in irritable bowel syndrome: a population-based study of patients, non-patients and controls.

BACKGROUND: It has been suggested that psychopathology in irritable bowel syndrome (IBS) patients is a function of patient status rather than of the disease. Although there are many studies comparing IBS patients, IBS non-patients, and controls with each other, no previous study has recruited all three groups from a representative community sample and had all subjects diagnosed by a physician. In the present study we aimed to compare psychological factors in IBS patients, IBS non-patients, and normal controls in a sample recruited from the population. METHODS: Subjects aged 18-45 years were recruited from a random sample of the normal population. Seventeen (2 M and 15 F) IBS patients were matched by sex and age with IBS non-patients and normals. Measures of personality traits, interpersonal distress, and temporary psychological distress were used. A physician diagnosed all 51 subjects in order to exclude possible gastrointestinal diagnoses other than IBS. RESULTS: Controls often differed from IBS non-patients and patients on the personality, interpersonal, and psychological distress measures, while IBS non-patients and patients very rarely differed from each other. All three groups were non-alexithymic. CONCLUSIONS: The results indicate that there are psychopathological differences between normals and IBS persons (patients and non-patients), but they could not confirm that psychopathology was a function of patient status. Whether this psychopathology is a vulnerability factor for IBS, or a consequence of it, remains to be studied.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

Acquired platelet dysfunction may be an aetiologic factor in Heyde's syndrome--normalization of bleeding time after aortic valve replacement.

BACKGROUND: There is a well-documented relationship, with unknown aetiology, between aortic valve stenosis and occult gastrointestinal bleeding in elderly patients. Despite several studies attempting to determine the prevalence and to discuss the aetiology, there are still many unanswered questions. METHODS: A total of 288 consecutive patients with valvular aortic stenosis--mean age 73 +/- 9 years aortic stenosis group (ASG)--were compared with 129 pacemaker-treated patients, mean age 73 +/- 9 years control group (CG). Screening for occult blood in stools was performed in both groups. Those with a positive Hemocult test or a history of gastrointestinal bleeding were scheduled for further examination including upper endoscopy and colonoscopy. Template bleeding time was performed on patients in both groups and in patients with a prolonged bleeding time with an extended coagulation evaluation was carried out. Patients referred to aortic valve replacement and with a preoperatively prolonged bleeding time were re-examined after surgery. RESULTS: There was a significant difference in the number of subjects with prolonged bleeding time between groups (ASG 19; CG 2; P = 0.028). Re-examination of the bleeding time after aortic valve surgery revealed normalized values in nine of 12 (P = 0.0003). The number of patients with positive Hemocult test did not differ between groups (ASG 29; CG 12; NS). Comparison of the pressure gradient over the aortic valve demonstrated a significantly higher maximal gradient amongst patients with a preoperatively prolonged bleeding time (113 mm HG vs. 90 mmHG; P = 0.005). CONCLUSION: Prolonged bleeding time is related to valvular aortic stenosis and seems to be caused by acquired platelet dysfunction. The normalization of the bleeding time after valve surgery supports the hypothesis that the calcified cusps may interact with the platelet function.

Aged↗
PubMed2002

Iron overload decreases the protective effect of tumour necrosis factor-alpha on rat hepatocytes exposed to oxidative stress.

BACKGROUND: Intracellular iron can participate in the formation of free radicals, leading to liver cell damage. This may be prevented by the ability of ferritin to oxidize and store iron. Tumour necrosis factor alpha (TNF-alpha) has been shown to increase the ferritin synthesis. In the liver, cytokines are secreted by activated Kupffer cells and T-lymphocytes. The aim of this study was to investigate the effects of TNF-alpha on normal and iron-loaded rat hepatocytes exposed to oxidative stress. METHODS: Primary cultures of hepatocytes from rats fed a normal rat chow or a carbonyl iron-enriched diet were incubated with TNF-alpha before incubation with tert-butyl hydroperoxide. Malondialdehyde concentrations, activities of lactate dehydrogenase, ferritin H and manganese superoxide dismutase mRNA and ferritin H protein were analysed. The total amounts of glutathione and chelatable iron were measured. RESULTS: TNF-alpha diminished the concentrations of malondialdehyde and activities of lactate dehydrogenase in hepatocytes exposed to tert-butyl hydroperoxide. This was seen in hepatocytes from normal but not iron-loaded animals. The transcription of manganese-superoxide dismutase mRNA was increased in both cell types, whereas total glutathione contents of cells were unaffected. The transcription and translation of ferritin H was induced in cells from normal but not from iron-loaded animals. The amount of chelatable iron was significantly lowered only in hepatocytes from normal rats. CONCLUSIONS: TNF-alpha protects rat hepatocytes from normal but not iron-loaded rats from oxidative stress. The protection may be due to an induction of the ferritin synthesis.

Animals↗
PubMed2001

Outcome of primary and secondary ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis.

PURPOSE: The aim of this study was to present Swedish experiences of the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis from the introduction in 1984. The study also compared the surgical and functional outcome of different anal continence preserving procedures: ileal pouch-anal anastomosis as primary surgery, ileal pouch-anal anastomosis as secondary surgery after colectomy and ileorectal anastomosis, and ileorectal anastomosis alone. METHODS: The material comprises all 120 patients with familial adenomatous polyposis reported to the Swedish Polyposis Registry who had undergone prophylactic colorectal surgery, including those operated on because of colorectal cancer from 1984 until the end of 1996. Anal continence preserving surgery was performed on 102 patients: 20 had ileal pouch-anal anastomosis as primary surgery at a median age of 24.5 years, 39 had ileal pouch-anal anastomosis as secondary surgery at a median age of 34 years, and 43 had ileorectal anastomosis alone, at a median age of 26 years, because 6 of the initially ileorectal anastomosis-operated patients were converted to ileal pouch-anal anastomosis as secondary surgery. Surgical outcome was assessed on the basis of hospital records. A questionnaire was used to evaluate the functional outcome. Fisher's exact probability test was used for statistical analysis. RESULTS: Complications occurred in 51 percent of the patients after ileal pouch-anal anastomosis: 40 percent after ileal pouch-anal anastomosis as primary surgery and 56 percent after ileal pouch-anal anastomosis as secondary surgery. When the previous ileorectal anastomosis was taken into account 67 percent of the patients suffered complications which was significantly more compared with ileal pouch-anal anastomosis as primary surgery. After ileorectal anastomosis, 26 percent had complications which was significantly less compared with all other procedures but ileal pouch-anal anastomosis as primary surgery. No cancer occurred after ileal pouch-anal anastomosis, either in the ileal pouch or in retained rectal mucosa, but two of the patients who had an ileorectal anastomosis developed rectal cancer. One pouch excision was performed compared with ten rectal excisions. Functional outcome did not differ between ileal pouch-anal anastomosis as primary surgery and ileal pouch-anal anastomosis as secondary surgery. However, ileorectal anastomosis-operated patients had significantly better bowel function with regard to nighttime stool frequency, continence and perianal soreness. CONCLUSION: These findings indicate that major advantages of ileal pouch-anal anastomosis are the low excision rate and, so far, no cancer in the ileal pouch. Moreover, the surgical outcome of ileal pouch-anal anastomosis as primary surgery is not significantly different from that of ileorectal anastomosis. However, the good surgical and functional outcome of ileorectal anastomosis, despite the long-range prognosis including rectal cancer and excision risks, has to be taken into consideration when selecting patients with familial adenomatous polyposis for primary surgery.

Adenomatous Polyposis Coli↗
PubMed2001

Hepatic damage in C282Y homozygotes relates to low numbers of CD8+ cells in the liver lobuli.

BACKGROUND: Although most Caucasian patients with hereditary haemochromatosis (HH) show the same mutation in the HFE gene, the phenotypic expression of the disease varies greatly. We have previously shown that patients with HH who have high iron stores have low numbers of circulating CD8+ T lymphocytes. PATIENTS AND METHODS: Liver and peripheral blood were studied in 37 C282Y homozygous HH patients; nine normal livers and 11 livers from patients with cirrhosis due to hepatitis C virus or alcoholic liver disease were also investigated. Eleven jejunal biopsies from HH patients and 17 normal biopsies were studied. The numbers of CD8+ cells were determined in peripheral blood by fluorescence-activated cell sorting analysis, and in the liver or small intestine by immunohistochemistry. RESULTS: In HH patients the number of CD8+ T lymphocytes in peripheral blood correlated significantly with the number of CD8+ cells in the liver lobuli but not with that in the small intestine. Body iron stores correlated negatively with the number of CD8+ T lymphocytes in peripheral blood and in the liver, but not with the number in the small intestine. HH patients with cirrhosis had the lowest CD8+ cell count in liver sections, in contrast with other forms of cirrhosis. CONCLUSION: The results indicate that HH patients with the HFE C282Y mutation and low numbers of CD8+ cells in the liver lobuli have higher iron stores and are more prone to develop liver cirrhosis.

Adult↗
PubMed2001

Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations.

BACKGROUND & AIMS: Patients with familial adenomatous polyposis (FAP) have a high prevalence of duodenal adenomas, and the region of the ampulla of Vater is the predilection site for duodenal adenocarcinomas. This study assessed the risk of stage IV periampullary adenomas according to the Spigelman classification and periampullary adenocarcinomas in Swedish FAP patients screened by esophagogastroduodenoscopy (EGD). The genotype of patients with stage IV periampullary adenomas and periampullary adenocarcinomas was also investigated. METHODS: A retrospective study of 180 patients screened by EGD in 1982-1999 was undertaken. Kaplan-Meier analysis was performed to evaluate cumulative risk. Mutation analysis was carried out in patients with periampullary adenocarcinomas diagnosed outside the screening program, in addition to patients in the screening group with stage IV periampullary adenomas and adenocarcinomas. RESULTS: Periampullary adenoma stage IV was diagnosed in 14 patients (7.8%), with a cumulative risk of 20% at age 60 years. Periampullary adenocarcinoma was diagnosed in 5 patients (2.8%), with a cumulative risk of 10% at age 60. Three of the adenocarcinomas occurred in patients with stage IV periampullary adenomas compared with 2 in patients with less severe periampullary adenomatosis at screening (odds ratio, 31; 95% confidence interval, 4.6-215). Fifteen (88%) of the APC gene mutations were detected; 12 of these were located downstream from codon 1051 in exon 15. CONCLUSIONS: The life time risk of severe periampullary lesions in FAP patients is high, and an association between stage IV periampullary adenomas and a malignant course of the periampullary adenomatosis is strongly suggestive. Mutations downstream from codon 1051 seem to be associated with severe periampullary lesions.

Adenocarcinoma↗
PubMed2001

Dynamic 99Tcm-HIDA SPET: non-invasive measuring of intrahepatic bile flow. Description of the method and a study in primary sclerosing cholangitis.

In this study dynamic 99Tcm-HIDA single photon emission tomography (SPET) was performed in patients with primary sclerosing cholangitis and normal test subjects. The method offers the possibility of functional analysis of individual liver segments. After injection of 120 MBq of 99Tcm-HIDA, 12 consecutive SPET examinations were performed at 6-min intervals. The segmental borders of liver segments as seen on computed tomography or magnetic resonance examinations were superimposed on the scintigraphic images allowing placement of regions of interest (ROIs) in specific liver segments. Sampling from the same ROIs in consecutive SPET images enabled creation of time-activity curves for individual liver segments. A range of normal values was created by quantitative analysis of normal volunteer studies. Results of the studies in patients correlated well with cholangiographic extent of disease, liver function tests and histological stage. The technique may have particular value in diseases that affect the liver in a nonhomogenous or segmental fashion. Giving an indication of bile clearance from individual liver segments, it can quantify the functional importance of radiologically detected strictures. Percutaneous liver biopsy can be directed to the worst affected parts of the liver, making biopsy more representative. Sequential studies may allow monitoring of disease progression, aiding in selection and timing of therapeutic procedures.

Adult↗
PubMed2000

PDGF-mediated chemoattraction of hepatic stellate cells by bile duct segments in cholestatic liver injury.

The accumulation of myofibroblasts and fibrosis around proliferating bile ducts in cholestatic liver disease has been attributed to the proliferation and phenotypic modulation of portal fibroblasts, whereas the contribution of hepatic stellate cells remains uncertain. There is increasing evidence to indicate that bile ducts may stimulate chemoattraction of hepatic stellate cells (HSC). In the present study, we undertook dynamic tests to examine such a possibility and to investigate the role of two potential mediators: platelet-derived growth factor-BB (PDGF-BB) and endothelin-1. Cholestasis was induced by bile duct ligation in rats. HSC were isolated from normal rats and culture activated into myofibroblasts expressing PDGF-beta receptors. Migration of myofibroblastic HSC was investigated in a Transwell chemotaxis filter assay. As compared with basal conditions, PDGF-BB (100 microg/l) and endothelin-1 (10(-8) M) induced a 3-fold and 1.7-fold increase in HSC migration, respectively. Bile duct segments isolated from cholestatic rats triggered a 3-fold increase in migration. This stimulation was significantly more potent than that observed in the presence of normal bile ducts. It was inhibited by neutralizing anti-PDGF antibodies and by STI571 PDGF receptor tyrosine kinase inhibitor, by 60% and 85%, respectively, whereas Bosentan, an endothelin receptor antagonist, had no significant inhibiting effect. In bile duct segments from cholestatic rats PDGF-B chain mRNA was detected at higher levels than in controls, whereas PDGF-BB was immunolocalized in bile duct epithelial cells. The results indicate that chemotaxis of HSC towards bile duct structures may contribute to the development of periductular fibrosis in cholestatic disorders, and that PDGF-BB is the major mediator in this process. In addition, anti-liver fibrogenic properties of STI571 are suggested by potent inhibition of myofibroblastic HSC function.

Animals↗
PubMed2000

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.

Adult↗
PubMed2000

Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosis.

The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the DeltaF508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of DeltaF508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease.

Adolescent↗
PubMed2000

In situ expression of transforming growth factor-beta1-3, latent transforming growth factor-beta binding protein and tumor necrosis factor-alpha in liver tissue from patients with chronic hepatitis C.

BACKGROUND: The mechanisms determining liver damage in chronic hepatitis C remain unclear. The aim was to evaluate the in situ expression of transforming growth factor beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), two key cytokines implicated as important pathogenic mediators in the development of liver fibrosis. METHODS: In situ expression of TNF-alpha and of TGF-beta isoforms 1-3, and its transport protein latent TGF-beta binding protein (LTBP), was determined by immunohistochemistry in 9 untreated patients with chronic hepatitis C infection and in 6 controls without liver disease. In addition, TGF-beta1 expression was analyzed in 10 HCV patients before and after treatment with interferon-alpha alone, or in combination with ribavirin. RESULTS: Liver biopsies from HCV patients showed positive staining for TGF-beta1-3 isoforms and LTBP, and to a lesser degree for TNF-alpha, in areas with inflammation and fibrosis. Normal control liver showed no positive staining. TGF-beta1 expression before treatment, quantified by morphometric analysis, did not differ between non-responders and sustained responders. In patients responding to therapy, TGF-beta1 expression decreased in parallel with histological improvement, while no difference in TGF-beta1 expression was seen before and after treatment in non-responders. CONCLUSION: These results suggest that TNF-alpha and all three isoforms of TGF-beta are involved in the pathogenesis of HCV related liver disease, and that treatment leading to eradication of the virus affects the expression of TGF-beta1.

Adult↗
PubMed2000

A population study on irritable bowel syndrome and mental health.

BACKGROUND: Irritable bowel syndrome (IBS) is commonly thought to be associated with psychologic distress. However, in some studies only persons who had sought medical care for IBS (IBS patients) showed an increased frequency of psychiatric symptoms, and nonpatients did not differ significantly from normal subjects. Our aims were 1) to estimate the prevalence of IBS in the population aged 18-45 years, 2) to find the proportion seeking medical care for IBS, and 3) to compare IBS subjects with normals, and IBS patients with IBS nonpatients with regard to mental health. METHODS: Questionnaires on IBS symptoms and the General Health Questionnaire (GHQ) were mailed to 5000 randomly sampled persons aged 18-45 years. The response rate was 58%. RESULTS: IBS was found in 7.4% of the men and 13.3% of the women. Those who had sought medical attention had more severe symptoms. The Likert mean score on the GHQ was 4.7 (95% confidence interval, 4.4-5.0) points higher for the IBS group than for normals (P < 0.001). There was no difference in GHQ scores between IBS patients and nonpatients. CONCLUSIONS: The results indicate that IBS per se is associated with more psychiatric distress, regardless of medical care-seeking. Seeking medical care is associated with more severe IBS symptoms.

Adult↗