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Biomedical subjects

Michael Scheurlen

Publications and source records attributed to Michael Scheurlen.

12 recordsLinked to original sources
PubMed2007

High recurrence rate of Barrett's epithelium during long-term follow-up after argon plasma coagulation.

OBJECTIVE: Several studies have shown that argon plasma coagulation (APC) combined with proton-pump inhibitor (PPI) therapy is a suitable procedure to eradicate Barrett's epithelium for a short-term follow-up. The real impact of this kind of management with respect to cancer risk and durability of squamous regeneration remains unclear. We present the follow-up data for up to 51 months after eradication of Barrett's mucosa. MATERIAL AND METHODS: In 1998-2001, 25 patients with Barrett's esophagus were included in a prospective study. After baseline documentation, Barrett's epithelium was treated with repeated APC until complete squamous restoration was reached. Thereafter, all patients were continuously treated with high-dose PPIs. RESULTS: Each patient underwent a median of four APC sessions. Twenty-one (84%) of the patients had complete squamous regeneration at the end of treatment. During a follow-up of up to 51 months, Barrett's epithelium was found to have recurred in 14/21 (66%) patients. Including the patients with initially incomplete squamous restoration, a long-lasting and complete effect was achieved in only 7 patients (28%) after a mean follow-up period of 30 months. CONCLUSIONS: So far, it is still not proven whether coagulation-induced squamous regeneration reduces the risk of Barrett's carcinoma. Furthermore, the high relapse rate, the procedure-related risk, and the high costs incurred preclude the routine use of APC for the treatment of non-dysplastic Barrett's esophagus. The different recurrence rates between published studies may be due to technical differences and PPI schedule. We suggest that optimal conditions for the procedure must be defined before further studies are undertaken.

Adult↗
PubMed2005

Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C.

AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon. METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98 patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 mug peginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R). RESULTS: Therapy with pegylated interferon alfa-2b produces comparable scores for depression (ANOVA: P = 0.875) as compared to conventional interferon. Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups. CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.

Adolescent↗
PubMed2005

Neurocognitive changes in patients with hepatitis C receiving interferon alfa-2b and ribavirin.

BACKGROUND: During antiviral therapy of chronic hepatitis C, patients frequently report impairment of concentration or memory. Therefore we prospectively investigated neurocognitive performance in patients receiving interferon alfa and ribavirin. METHODS: Repeated computer-based testing of neurocognitive function was performed in 70 patients with chronic hepatitis C receiving interferon alfa-2b (pegylated or conventional) and ribavirin. In addition, depression scores were obtained (Hospital Anxiety and Depression Scale). RESULTS: Reaction times were significantly increased during treatment (mean reaction time increase after 3 months of therapy: alertness, 46.76 ms [95% confidence interval (CI)], 26.86-66.66 ms), P < .001; divided attention, 47.04 ms [95% CI, 26.44-67.64 ms], P < .001; vigilance, 60.78 ms [95% CI, 29.24-92.32 ms], P < .001; and working memory, 38.53 ms [95% CI, 1.22-75.83], P = .34). Accuracy measures (number of false reactions) were affected for the working-memory task exclusively. Cognitive performance returned to pretreatment values after the end of therapy. Cognitive impairment was not significantly correlated with the degree of concomitant depression (0.04 < r [absolute value] < 0.10, P > .390). CONCLUSIONS: Interferon-based combination therapy of chronic hepatitis C causes significant but reversible impairment of neurocognitive performance. Consequences for the requirements of an active life in patients with chronic hepatitis C receiving antiviral therapy need to be assessed.

Adult↗
PubMed2005

Physician-patient relationship and disclosure behaviour in chronic hepatitis C in a group of German outpatients.

OBJECTIVES: In chronic hepatitis C infection, the doctor-patient relationship can be burdened for various reasons. Factors associated with the doctor-patient relationship and self-disclosure of hepatitis C virus (HCV) status have not so far been investigated systematically. The goal of the study was to examine self-disclosure of HCV positivity, perceived stigmatization, and potential predictor variables in a German outpatient group. METHODS: In a cross-sectional single-centre study, we included a volunteer sample of 103 HCV outpatients. Patient recruitment was between March 2003 and September 2004. Data were obtained from a fully standardized face-to-face interview [HCV disclosure behaviour (main interview variable), stigmatization, doctor-patient relationship] and psychometric self-assessment questionnaires [Hospital Anxiety and Depression Scale, German version; Symptom Checklist-90 Revised (global severity index); Inventory of Interpersonal Problems (total score)]. RESULTS: The overall general disclosure rate was 44.7% (with respect to all physicians). However, 75% stated revealing their positive serostatus in future physician appointments (P < 0.05). With respect to family/friends, disclosure rates were clearly higher (permanent partner, 99%; average, 76.7%). Patients' disclosure behaviour could not be predicted by sociodemographic variables or personality factors (binary logistic regression, P > 0.05). Similarly, the Hospital Anxiety and Depression Scale and Symptom Checklist-90 subscales were not substantially associated with HCV disclosure. Experiences of stigmatization (rate 38.8%) were more frequent in women (P = 0.014) and patients with higher depression scores (P = 0.029). CONCLUSIONS: There is a need for education in the field of chronic hepatitis C in order to improve the physician-patient relationship. HCV disclosure rates might thus be increased and the frequency of problematic contacts reduced. Importantly, the data show that physicians should explicitly ask for the patients' HCV status because unrequested disclosure cannot be taken for granted.

Adult↗
PubMed2004

[Differential diagnosis in cholestatic liver diseases].

Causes of cholestasis include disturbed bile flow out of the hepatocyte into the biliary capillaries, or obstruction (stone, tumor, inflammation) of small or larger intrahepatic or extrahepatic. In the event of acute or subacute onset, Cholestatic liver disease becomes manifest by its clinical presentation; in the case of a chronic course it tends to be an incidental finding based on liver parameters. For the differential diagnosis, the history (duration of symptoms, general symptoms, family history, drug history), clinical picture, laboratory investigations (alkaline phosphatase, g-GT, possibly specific autoantibodies) and imaging procedures (in particular ultrasonography and ERCP) point in the right direction. The present article provides an overview of the major differential diagnoses of intrahepatic and extrahepatic cholestasis. A diagnostic algorithm is presented.

Algorithms↗
PubMed2004

Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis.

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.

Adult↗
PubMed2003

Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett's esophagus.

The development of an oesophageal adenocarcinoma arising in Barrett's mucosa is associated with a multistep process of genetic lesions that may be triggered by persistent oxidative damage. The glutathione peroxidase isoforms pGPx and GI-GPx, which were identified recently in the mucosa of the esophagus, may play a role as defense factors to prevent such oxidative injury. To determine alterations of the expression of pGPx and GI-GPx in Barrett's mucosa as compared to primary and regenerative squamous epithelium. Biopsy samples of oesophageal mucosa of patients with Barrett's esophagus (n = 12), patients with squamous restoration after thermal ablation (n = 10), and healthy controls (n = 5) were analyzed for pGPx and GI-GPx mRNA expression by Northern blot and for glutathione peroxidase activity by enzymatic assay. Squamous regeneration was induced by argon plasma coagulation (APC) combined with proton pump inhibitor therapy. In Barrett's epithelium mRNA levels of pGPx (the secreted isoform) were significantly reduced and of GI-GPx (the intracellular isoform) significantly increased as compared to normal squamous mucosa. In squamous mucosa that had regenerated after APC, no significant differences compared to the expression pattern of primary squamous mucosa were found. Compared to squamous mucosa, Barrett's metaplasia shows a different mRNA expression of pGPx and GI-GPx that may be associated with increased susceptibility to oxidative damage.

Antioxidants↗
PubMed2003

Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenomas.

Selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR), and selenoprotein P (SePP) contain molecular selenium in form of selenocysteines within their active center. They are involved in the defense of reactive oxygen species, which otherwise may cause DNA damage and alterations of protein function. Selenium intake has been linked to colon carcinogenesis in epidemiological and interventional studies. In a double-blinded, placebo-controlled trial, we demonstrate that carriers of colon adenomas present with low basal serum levels of selenium and plasma glutathione peroxidase (pGPx) activity before treatment, but both parameters can be normalized by interventional selenium supplementation. GPx activity in colon mucosa was enhanced in the verum group, albeit this had only borderline significance. No change of activity was observed for mucosal TrxR activity on selenium supplementation. In summary, our results confirm the existence of low selenium levels in patients prone to colon adenomas and show that by selenium supplementation this can be normalized. If prospective trials confirm that selenium supplementation reduces colon cancer incidence rates, it may be concluded that selenium supplementation should be recommended for patients at risk.

Adenoma↗
PubMed2003

Psychiatric symptoms in patients with chronic hepatitis C receiving interferon alfa-2b therapy.

BACKGROUND: Psychiatric side effects of interferon alfa are frequently observed in the therapy of patients with chronic hepatitis C infection. The goal of the present study was to assess prospectively the incidence, spectrum, and extent of psychiatric symptoms of patients receiving interferon alfa therapy as compared with an untreated reference group. METHOD: 104 patients with chronic hepatitis C were consecutively enrolled in a prospective longitudinal study. The treatment group (N = 84) received interferon alfa-2b for up to 12 months, and the reference group (N = 20) received no treatment. Patients who began treatment between November 1996 and August 1998 (N = 44) received interferon alfa-2b, 5 million units 3 times per week. Patients who began treatment in September 1998 or later (N = 40) received a combination of interferon alfa-2b, 3 to 5 million units 3 times per week, and ribavirin, 1000-1200 mg/day. Diagnostic scores for depression and anxiety were obtained by means of the psychometric instrument Hospital Anxiety and Depression Scale, and scores for anger/hostility were obtained with the Symptom Checklist-90 Revised. RESULTS: In contrast to the untreated reference group, we found significantly increased scores for depression (p <.001) and anger/hostility (p <.001) during interferon alfa therapy in the treatment group. Even before therapy, scores of those in the treatment group were above the respective cutoff values for clinically relevant symptoms of depression in 15.5% of the patients, anxiety in 13.1% of the patients, and anger/hostility in 11.3% of the patients. These proportions rose to 35.0% (depression), 25.6% (anxiety), and 24.5% (anger/hostility). The cumulative frequency of clinically relevant emotional distress (depression, anxiety, or anger/hostility) during interferon alfa therapy was 57.7%, as compared with 22.5% before therapy. However, interferon alfa therapy had to be stopped prematurely because of untreatable psychiatric symptoms in only 8.3% of patients. CONCLUSION: In view of the high frequency and extent of psychiatric symptoms with interferon alfa therapy, we recommend a close follow-up of patients receiving this therapy with respect to potential limiting mood changes.

Adolescent↗
PubMed2002

[Gilbert disease and type I and II Crigler-Najjar syndrome due to mutations in the same UGT1A1 gene locus].

BACKGROUND: Gilbert syndrome and the Crigler-Najjar syndromes Type I and II are disorders of bilirubin conjugation with consecutive indirect hyperbilirubinemia of different severity. Morbus Gilbert is a mild hyperbilirubinemia, which is only of significance in case of drug therapy or differential diagnosis. Crigler-Najjar syndrome II leads to a more serious kind of hyperbilirubinemia. In case of Crigler-Najjar syndrome I patients are suffering from a very severe hyperbilirubinemia, which often causes death during the first months of life. MOLECULAR GENETICS: The molecular defects of these three syndromes have been characterized during the last decade. They are caused by mutations in the UGT1A1 gene locus. This locus codes for the enzyme bilirubin uridine 5'-diphosphate-(UDP-) glucuronosyltransferase (UGT1A1). In the case of Gilbert syndrome two bases are inserted into the promoter of the gene. In Crigler-Najjar syndrome type I and II mutations lead to the exchange of amino acids, changes of the reading frame or to stop codons. CONCLUSION: All three forms of indirect hyperbilirubinemia are caused by mutations in the UGT1A1 gene locus, which codes for the enzyme UDP-glucuronosyltransferase.

Amino Acid Substitution↗
PubMed2002

A complex DNA-repeat structure within the Selenoprotein P promoter contains a functionally relevant polymorphism and is genetically unstable under conditions of mismatch repair deficiency.

Epidemiological data, animal studies and interventional studies provide evidence for a potential chemopreventive effect of selenium during development of colorectal cancer. The human glycoprotein Selenoprotein P (SeP) contains up to 50% of plasma selenium content. SeP is expressed in the gastrointestinal tract and the liver, where its expression is downregulated by various proinflammatory cytokines (Il1beta, TGFbeta, IFNgamma). Previously, we have demonstrated dramatically reduced SeP expression in human colon adenomas. Here, we have identified a complex (A)4-C-(A)4-GG-(A)8-GCT-(TC)5-(T)17 (bp -429 to bp - 477) repeat structure within the SeP promoter and we have analysed this regulatory DNA sequence with respect to polymorphisms, genomic instability and functional relevance to promoter activity. As opposed to the (TC)5 variant we identified a novel (TC)3 polymorphism within this repeat in the general population, which conferred significantly reduced basal promoter activity to reporter gene constructs in HepG2 cells. Allelic distribution of this (TC)(n) element was similar in colon carcinoma patients and healthy controls. Additionally, we observed genetic instability within the (T)17 repeat motif in colon cancers of the mutator phenotype. This instability of the (T)17 repeat had no effect on basal promoter activity in reporter gene assays. In conclusion, we characterised a complex repeat structure within the SeP promoter that may be of functional relevance to SeP gene expression. Further studies on the effect of different SeP promoter genotypes on SeP protein expression and disease susceptibility are needed.

Base Pair Mismatch↗