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Biomedical subjects

Gerhard Treiber

Publications and source records attributed to Gerhard Treiber.

At least 19 recordsLinked to original sources
PubMed2006

Budesonide induces complete remission in autoimmune hepatitis.

AIM: Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis (AIH). However, only 65% of the patients enter complete histological remission. Recently, budesonide (BUD) was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH. METHODS: Eighteen patients (12 women, 6 men; mean age 45.4+/-21 years)with AIH were treated with BUD (Budenofalk) 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis (n=5) or primary sclerosing cholangitis (n=2). Advanced liver fibrosis or cirrhosis was present in 6 patients. RESULTS: Fifteen (83%) patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis,were given BUD as first-line therapy, of which seven enter remission. Three patients, two with liver cirrhosis, did not improve.All patients with second-line therapy experienced long-term remission. A histological remission was also seen in three patients. Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis (n=4). CONCLUSION: BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

Adult↗
PubMed2006

Impact of the operator's experience on value of high-resolution transabdominal ultrasound in the diagnosis of choledocholithiasis: a prospective comparison using endoscopic retrograde cholangiography as the gold standard.

OBJECTIVE: Transabdominal ultrasound (US) is the most frequently used imaging method for the diagnosis of choledocholithiasis. The aim of this prospective study was to evaluate the diagnostic accuracy of high-resolution US in the diagnosis of common bile duct stones depending on the operator's experience and in comparison with endoscopic retrograde cholangiography (ERC) as the gold standard. MATERIAL AND METHODS: From April 2003 through November 2004, 126 patients referred because of clinically and biochemically suspected common bile duct stones were included in the study. Two patients were excluded because they refused to undergo ERC. Consequently, the study comprised 124 patients (86 F, 38 M, mean age 63.2 years, range 21-91 years). High-resolution US was performed (2-5 MHz sector scanner; Siemens Elegra, Erlangen, Germany) by operators who were unaware of the results of other imaging procedures. The definitive diagnosis was established by means of ERC. RESULTS: Thirty-five out of 124 patients were investigated by experienced examiners. Twenty-seven of 35 patients (77%) were found to have stones at ERC. Bile duct stones were correctly found by US in 22 out of 27 patients (sensitivity 82%, 95% CI: 63-92). Of the 8 patients without stones at ERC, one false-positive diagnosis was made with US (specificity 88%, 95% CI: 53-98). Correct diagnoses were made in 29 out of 35 (accuracy 83%, 95% CI: 67-92) patients investigated by experienced examiners. Eighty-nine out of 124 patients were investigated by less-experienced examiners. Fifty-four of 89 patients (61%) were found to have stones at ERC. Choledocholithiasis was found correctly in only 25 out of 54 patients (sensitivity 46%, 95% CI: 34-59). Of the 35 patients without stones at ERC, three false-positive diagnoses were made with US (specificity 91%, 95% CI: 78-97). In conclusion, correct diagnoses were observed in 57 of 89 patients (accuracy 64%, 95% CI: 54-73) investigated by less-experienced examiners (p<0.05 in comparison with the results of experienced examiners). CONCLUSIONS: High-resolution US carried out by experienced examiners has a high diagnostic accuracy in the diagnosis of choledocholithiasis. Therefore, good training and continued experience are prerequisites for successful sonographic detection of bile duct stones using US. Under these conditions, further expensive and invasive methods such as ERC, magnetic resonance cholangiopancreatography and endoscopic ultrasonography may not be necessary in cases with a clear sonographic diagnosis.

Adult↗
PubMed2006

Helicobacter pylori infection, but not low-dose aspirin, results in a local reduction of the secretory leukocyte protease inhibitor in gastroduodenal mucosa.

BACKGROUND: The secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein with mucosa-protective features. Helicobacter pylori and the usage of low-dose aspirin are two independent risk factors for the development of gastrointestinal diseases. Therefore, the effect of low-dose aspirin on gastrointestinal SLPI expression was analyzed in the context of H. pylori infection. MATERIAL AND METHODS: The study included 20 volunteers (H. pylori positive and negative: n = 10) who received 2 x 50 mg aspirin/day for 7 days. H. pylori-positive subjects underwent eradication therapy and repeated the protocol. Gastroduodenoscopy was performed at day 0, 1, 3, and 7, and biopsies were obtained each from antrum, corpus, and duodenal bulb. SLPI expression was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: A reduction of antral SLPI levels, ranging between 582 (day 0) and 941 pg/10 microg protein (day 7), was determined in H. pylori-positive compared to H. pylori-negative and -eradicated subjects (1600-2050 pg/10 microg protein, ANOVA: p = .001-.045). No differences concerning aspirin were observed within the groups. SLPI levels in corpus and duodenal mucosa were neither affected by H. pylori nor low-dose aspirin. There was an inverse correlation between SLPI and H. pylori-induced inflammation (activity: r = -0.575, -0.69 to -0.43, p < .0001; chronicity: r = -0.54, -0.66 to -0.39, p < .0001) in antral mucosa only, whereas other locations as well as the usage of low-dose aspirin did not show an association between SLPI and inflammation. CONCLUSIONS: H. pylori infection, but not the usage of low-dose aspirin, has a role in the down-regulation of antral SLPI levels.

Adult↗
PubMed2006

Helicobacter pylori-induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for H. pylori-mediated diseases.

The secretory leukocyte protease inhibitor (SLPI) exerts antiproteolytic activity towards serine proteases, as well as anti-microbial and anti-inflammatory effects. To investigate its role in H. pylori-mediated diseases, SLPI expression was analyzed by RT-PCR, ELISA and immunohistochemistry in clinical samples and gastric tumor cell lines. Determination of the mucosal SLPI levels in 126 patients confirmed the previously reported downregulation of SLPI in H. pylori-infected patients. The lower SLPI levels in antral biopsies of H. pylori-positive subjects were associated with a 30-fold increase (p<0.01) in neutrophil elastase activity, and a significant negative correlation was demonstrated for both parameters (R=-0.63, p=0.0002). Eradication of the bacterium in a long-term study (5-7 years) led to a recovery of mucosal SLPI expression. In vitro experiments using four gastric tumor cell lines (AGS, MKN-28, MKN-45, NCI-N87) generally confirmed the clinical findings. While the co-incubation of these cell lines with H. pylori resulted in lower or unchanged SLPI protein levels, the corresponding SLPI mRNA amounts were upregulated by up to five-fold (p=0.006) in all cell lines. Taken together, these results indicate that the reduction in antral SLPI levels in H. pylori-infected subjects has a functional relevance for gastric mucosa and the H. pylori-induced decrease in SLPI is primarily regulated at the posttranslational level.

Base Sequence↗
PubMed2005

Acute exacerbation of autoimmune hepatitis induced by Twinrix.

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix. In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid, and led to complete normalization of the pathological liver function tests. We believe that Twinrix led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

Adult↗
PubMed2005

Breath and string test: a diagnostic package for the identification of treatment failure and antibiotic resistance of Helicobacter pylori without the necessity of upper gastrointestinal endoscopy.

AIM: Helicobacter pylori (H pylori) resistance after failed eradication has a major impact on the outcome of a further treatment regimen. The aim of this study was to assess the validity of a non-invasive strategy using the 13C-urea breath test (UBT) and the gastric string test in identifying post-treatment resistance of H pylori. METHODS: The UBT was routinely performed 4 to 6 wk after H pylori eradication therapy. Forty-two patients (24 females, 18 males, mean age 48 years) with a positive UBT were included in the study. A gastric string test using a capsule containing a 90 cm-long nylon fiber was performed. Before the capsule was swallowed, the free end of the string was taped to the cheek. After one hour in the stomach, the string was withdrawn. The distal 20 cm of the string was inoculated onto an agar plate and processed under micro-aerophilic conditions. Following the string test, upper gastrointestinal endoscopy was performed to obtain gastric biopsies for conventional culture. RESULTS: H pylori was successfully cultured from the gastric string in 34 patients (81%), but not in 5 patients due to contamination with oropharyngeal flora. H pylori was cultured from the gastric biopsies obtained at endoscopy in 39 patients (93%). CONCLUSION: The UBT followed by the gastric string test in the case of treatment failure is a valid diagnostic strategy with the aim of determining the post-therapeutic antibiotic resistance of H pylori with little inconvenience to the patient. Upper GI-endoscopy can be avoided in several cases by applying consequently this diagnostic package.

Anti-Bacterial Agents↗
PubMed2005

Protective role of heat shock protein 27 in gastric mucosal injury.

Heat shock protein 27 (HSP27) mediates cytoprotective effects through its function as a molecular chaperone and through the phosphorylation-dependent stabilization of actin filaments. The role of HSP27 in gastric ulcer formation and healing is, however, unknown. The expression of HSP27 was studied in human gastric tissue specimens obtained from patients with gastric ulcers and from healthy Helicobacter pylori-negative individuals, who received low-dose aspirin, rofecoxib, and the combination in a prospective study. The susceptibility of the gastric mucosa to indomethacin-induced lesions was further studied in transgenic mice overexpressing human HSP27 (Tg(huHSP27)) and compared with wild-type mice (Wt). The expression of HSP27, COX-1, and COX-2 was investigated in Tg(huHSP27) mice and Wt mice by immunohistochemistry and western blot analysis. While no specific changes in HSP27 expression were found following exposure of healthy human gastric mucosa to oral administration of aspirin or refocoxib, chronic gastric ulcers showed strong HSP27 expression at the ulcer base and margins. Here it was expressed by granulation tissue and regenerating surface epithelium. In Tg(huHSP27) mice, overexpression of HSP27 led to a significant decrease of indomethacin-induced erosions and ulcers compared with Wt mice. COX-1 and COX-2 levels did not change. HSP27 is involved in chronic gastric ulcer repair mechanisms in humans, while overexpression of human HSP27 in gastric epithelial cells in mice reduces the susceptibility to non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulceration. This indicates that HSP27 expression is critical for mucosal protection in the stomach.

Aged↗
PubMed2005

Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data.

BACKGROUND: The clinical outcome of acid-related disorders treated by proton pump inhibitors (PPIs) might be dependent on the polymorphically expressed cytochrome P450 (CYP) 2C19, which is involved in PPI metabolism. We tested whether esomeprazole-induced healing of gastroesophageal reflux disease (GERD) is related to CYP2C19 genotype. METHODS: Two hundred five patients with GERD (Los Angeles classification grade A or B) were included in a case-control study according to endoscopic outcome (healed versus unhealed group, matched for confounders) after treatment with 40 mg esomeprazole daily for 4 weeks. The frequency of CYP2C19 genotypes was determined as the primary outcome measure for both groups. In a second trial plasma levels of esomeprazole and corresponding CYP2C19 and CYP3A4 metabolites (5-hydroxyomeprazole and omeprazole sulfone) were monitored in 10 CYP2C19 wild-type patients with GERD after the first and last doses (day 7) of 40 mg esomeprazole daily to calculate metabolic ratios. RESULTS: CYP2C19 wild-type (n = 148) and heterozygous (n = 51) or homozygous variant (n = 6) patients did not differ with respect to baseline characteristics. The frequency distribution of CYP2C19 genotypes was not different between patients with complete (75/100) and incomplete (73/105) healing (P = .65). When a single esomeprazole dose and multiple dosing were compared, the low contribution of CYP2C19 to the elimination of esomeprazole decreased further by 50%. In contrast, the CYP3A4-dependent formation of omeprazole sulfone increased by 40%, and consequently, the metabolic ratio of omeprazole sulfone to 5-hydroxyomeprazole was elevated from 7.9 to 19.3 (P = .0004). CONCLUSION: In contrast to other PPIs, esomeprazole-induced healing of GERD is unrelated to the CYP2C19 genotype, which can be explained by the metabolic shift toward the CYP3A4-mediated pathway.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

The pathophysiology of portal hypertension.

Portal hypertension is defined by an elevation in blood pressure in the portal system. Different causes are known and include a pre-, intra-, or posthepatic block. Portal hypertension is also classified according to the sinusoidal system. Portal pressure becomes elevated by either an increase in blood flow (Q), an increase in resistance (R), or both. Regulation of the vascular tone in the splanchnic system includes intrinsic and extrinsic aspects. A variety of metabolic end-products (e.g. adenosine), endothelium-derived substances (e.g. nitric oxide), and certain neurotransmitters (e.g. acetylcholine) are known to relax the tone and thus produce vasodilation. Important vasoconstrictor influences on splanchnic arterioles include circulating agents (e.g. angiotensin), endothelium-derived substances (e.g. endothelin), and again neurotransmitters (norepinephrine). Besides vascular tone, structural changes (thrombosis, fibrosis, shear stress, and cell regeneration) add to overall hepatic resistance. Further consequences of portal hypertension include an increase in blood flow which leads to a hyperdynamic state with fluid retention, leading to secondary involvement of other organs, such as cirrhotic cardiomyopathy, hepatopulmonary syndrome and hepatorenal syndrome. Finally, portal hypertension will end up in the formation of collateral vessels. Varices can involve the whole gastrointestinal tract and are a frequent source of bleeding.

Humans↗
PubMed2004

Identification of a novel isoform predominantly expressed in gastric tissue and a triple-base pair polymorphism of the cathepsin W gene.

In order to investigate the prevalence of potential polymorphisms of the cathepsin W gene, the complete cDNA of 50 dyspeptic patients was analyzed. From those 37 (74%) revealed the wildtype sequence, 6 samples (12%) contained independent single base pair changes including 4 silent and 2 with amino acid changes. Furthermore, a triple-base pair polymorphism was found in 7 samples (14%, 4x heterozygous, 3x homozygous) leading to the following changes: F(217)S, H(248)Y, and I(250)T. Furthermore, a novel alternative splice variant concerning intron 10 was identified in 6 samples (12%). Notably, this novel isoform was only found in samples of gastric mucosa lymphocytes, whereas peripheral NK cells expressed cathepsin W wildtype only. Taken together, this study demonstrated for the fist time that a genetic variant and a novel isoform of cathepsin W are present in about 14% and 12%, respectively, within the Caucasian population.

Alternative Splicing↗
PubMed2004

CYP2C19 polymorphism is a major predictor of treatment failure in white patients by use of lansoprazole-based quadruple therapy for eradication of Helicobacter pylori.

OBJECTIVE: Proton pump inhibitors, metabolized by the polymorphic enzyme cytochrome P450 (CYP) 2C19, are essential drugs for Helicobacter pylori eradication. It was reported that patients with CYP2C19 wild type in Asia had lower eradication rates. This study tests the hypothesis that CYP2C19 wild type ( wt/wt ) in white patients is also associated with a higher probability of treatment failure. METHODS: This was a cohort study involving 131 H pylori -positive white (German) patients treated by quadruple therapy including lansoprazole (30 mg twice daily for 5 days). Eradication success, as well as lansoprazole trough steady-state serum concentrations, was determined according to different CYP2C19 genotypes. RESULTS: We found 3 homozygous variant patients (2.3%) ( mt/mt, CYP2C19*2/*2 ), 42 heterozygous patients (32.1%) ( wt/mt, CYP2C19*1/*2 ), and 86 wild-type individuals (65.6%). Significant differences in eradication success could be found between wt/wt patients (80.2%) versus combined mt/mt (100%) and wt/mt patients (97.8%) ( P <.01; odds ratio, 10.8 [confidence interval, 1.4-84]), which were associated with corresponding changes in the serum levels of lansoprazole (median, 753 ng/mL for mt/mt, 59 ng/mL for wt/mt, and 21 ng/mL for wt/wt; P <.001). Apart from antibiotic resistance, CYP2C19 polymorphism was the most important influencing factor for eradication success on multivariate analysis ( P <.0001). CONCLUSION: Eradication rates of H pylori highly depend on CYP2C19 in white patients if standard doses of lansoprazole (30 mg twice daily) are administered within a quadruple regimen. Because wt/wt individuals have lower eradication rates and lower serum concentrations of lansoprazole, these patients might benefit from a higher proton pump inhibitor dosage.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

CYP2C19 polymorphism and proton pump inhibitors.

Proton pump inhibitors such as omeprazole (esomeprazole), lansoprazole, pantoprazole and rabeprazole are eliminated by the hepatic route and the polymorphic CYP2C19 is mainly involved in their metabolism. In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5-12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors.

Anti-Ulcer Agents↗
PubMed2004

Helicobacter pylori-mediated gastritis induces local downregulation of secretory leukocyte protease inhibitor in the antrum.

Helicobacter pylori-infected subjects exhibited a strong decline in antral secretory leukocyte protease inhibitor (SLPI) levels compared to H. pylori-negative subjects and subjects from whom H. pylori had been eradicated (P = 0.002). This reduction was specific for the antrum, whereas SLPI expression in corpus and duodenum was not affected. Antral SLPI levels were inversely correlated with inflammatory scores of antrum-predominant gastritis.

Adult↗
PubMed2003

Clinical implications of alpha-fetoprotein expression in gastric adenocarcinoma.

BACKGROUND: Alpha-fetoprotein (AFP)-producing gastric adenocarcinoma has an extremely poor prognosis. Few cases have been reported in Germany until now. Here we report on a patient with an AFP-producing gastric cancer and a subsequent analysis of AFP expression in a more extended series of gastric cancer patients. MATERIAL AND METHODS: A 62-year-old man was referred to our hospital with suspected gastric cancer. Gastroscopy, ultrasound, and CT scans of the abdomen showed a gastric tumour. Serological and histopathological investigations led to the diagnosis of a poorly differentiated adenocarcinoma expressing AFP. Following diagnosis, a short-term response was achieved by palliative chemotherapy. Expression of AFP and albumin was then investigated on an extended series of 25 patients with gastric cancer and four gastric cancer cell lines using immunohistochemistry and RT-PCR. No patient had suffered from hepatocellular carcinoma or germ cell tumor. RESULTS: Using paraffin-embedded gastric cancer specimens, we found AFP immunohistochemically in 2 of 25 (8%) patients. AFP-mRNA was expressed in 3 (12%) patients and a single gastric cancer cell line (AGS). Albumin-mRNA was not found in any gastric cancer sample or gastric cancer cell line. CONCLUSIONS: Our study shows that AFP-producing gastric adenocarcinomas are an important clinical entity with a frequency that has been underestimated in the past. In the absence of a primary liver tumor, clinicians have to consider a primary gastric cancer, which has a poor prognosis, and merits a more aggressive therapy.

Adenocarcinoma↗
PubMed2003

A two-step method for the extraction of high-quality RNA from endoscopic biopsies.

The use of molecular techniques such as quantitative RT-PCR depends on the quality of cellular RNA. In particular, RNA extraction from endoscopic biopsies is difficult with respect to yield, and especially integrity. Endoscopic biopsies taken from the gastric antrum, corpus and duodenum were subjected to various RNA extraction protocols, and the RNA was used for quantitative RT-PCR. The subsequent use of two methods, (i) a phenol/chloroform extraction and (ii) a column-based extraction method, resulted in a yield of 4.5 microg total RNA per biopsy with reliable quality in 80% of samples. The quantitative RT-PCR analysis revealed that only RNA samples that clearly show both 18S- and 28S-RNA bands in agarose gel electrophoresis were suitable for quantitative RT-PCR as shown by expression of corpus-specific pepsinogen C-mRNA and the duodenum-specific multi-drug resistance protein-1 (mdr-1)-mRNA. In partially degraded RNA, pepsinogen C, mdr-1, or beta-actin mRNAs were still detectable, but the quantitative determination gave inconsistent data. The two-step method described here is a suitable option for extracting high-quality RNA from endoscopic biopsies when other standard protocols fail.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study).

BACKGROUND: Short-term therapies for eradicating Helicobacter pylori in selected patients might offer advantages in terms of costs, compliance, and adverse effects in contrast to standard 1-week triple therapy. METHODS: To determine eradication success and influencing factors in a new short-term quadruple therapy, a total of 243 patients positive for H pylori were randomly assigned to 1 of 3 regimens according to age, smoking status, and diagnosis: a 5-day treatment with 3 antibiotics (amoxicillin, 1 g twice daily [bid]; clarithromycin, 250 mg bid; and metronidazole, 400 mg bid) and lansoprazole (30 mg bid [L5; reference treatment]) or ranitidine hydrochloride (300 mg bid [R5]), or the same 3-day antibiotic-lansoprazole combination (L3) with a 2-day pretreatment with lansoprazole. RESULTS: A total of 234 patients completed the study. On an intention-to-treat basis, overall eradication of H pylori was confirmed in 86.4%: 89.2% in the L5 group vs 81.2% in the L3 group vs 88.8% in the R5 group; differences were not significant. Multiple logistic regression analysis showed that younger age (<55 years; P =.03), history of peptic ulcer disease (P =.04), smoking (P =.03), metronidazole resistance (P =.003), low ranitidine trough serum concentrations (P =.005), cytotoxin-associated gene A-negative strains in peptic ulcer disease (P =.04), and outer inflammatory protein A-positive strains (P =.02) were associated with eradication failure. CONCLUSIONS: This new quadruple H pylori eradication regimen is efficacious, safe, well tolerated, and cost saving, and may be a treatment option for patients older than 55 years with no history of peptic ulcer disease. Furthermore, strains that are sensitive to all antibiotics, cytotoxin-associated gene A-positive, and outer inflammatory protein A-negative could be suitable for short-term quadruple therapy. Patients with an unfavorable combination of characteristics should be treated for a minimum of 7 days.

2-Pyridinylmethylsulfinylbenzimidazoles↗