Biomedical subjects
Publications and source records attributed to G Adler.
A case of simultaneous appearance of bitemporal sterile abscesses of the upper eyelids and pyoderma gangrenosum in an 80-year-old woman with an acute flare of ulcerative colitis is described. Therapy with high-dose corticosteroids led to healing of the skin and upper eyelid lesions and induced remission of ulcerative colitis.
In spite of the improved MR-diagnosis of the abdomen, MRI is not used as a routine method for the diagnosis of inflammatory small bowel disease. The aim of this study was--after optimazation of the bowel opacification--the correlation of the findings obtained with enteroclysis and MRI in patients with known Crohns' disease. 60 patients between 17 and 72 years of age were investigated. First, an enteroclysis was performed in typical manner. The applicated methylcellulosis was blended with positive oral MR contrast media (Magnevist oral, Schering). After enteroclysis, MRI of the abdomen was performed using T1- and T2-weighted breathhold sequences (Flash 2D pre- and postcontrast and TSE) in axial and coronal planes. The length of the affected bowel and the stenosis seen with enteroclysis correlated well with the visible thickening of the small bowel wall and the stenosis seen in MRI. Using MRI, additional findings could be obtained in 28 patients, such as fistulas, abscesses or a hydronephrosis, or a better assessment of the stenosis was possible with MRI, because of the avoidance of overshadowing of the affected bowel loop with MRI. A brilliant MR-tomographic imaging of the small bowel is possible under the condition, that the small bowel contrast is optimal. The main prerequisite is a large filling volume of the small bowel to reach a homogeneous contrast and a good distension of the small bowel lumen.
The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.
BACKGROUND & AIMS: In transgenic mice overexpressing transforming growth factor (TGF)-alpha in the exocrine pancreas, progressive pancreatic fibrosis and a transdifferentiation of acinar cells to duct-like cells occurs. The present study was undertaken to analyze this transdifferentiation process. METHODS: Pancreatic specimens were characterized using light microscopy and immunohistochemistry. Expression of the epidermal growth factor receptor (EGFR) and TGF-alpha was evaluated with slot blot and Western analysis. To identify other generic events, K-ras mutations were screened with an enriched polymerase chain reaction approach and p53 expression was detected with immunohistochemistry. RESULTS: Morphological examination revealed an aggregation of interlobular fibroblasts and a decrease in acinar cell height starting at day 14 after birth. In older animals, these acinar cells change to duct-like cells, which form tubular structures and express ductal markers. Evidence for dysplastic changes was found in 12 of 21 TGF-alpha transgenic mice older than 1 year. We also observed four malignant pancreatic tumors, which were multicentric and originated from dysplastic tubular complexes. They displayed a mixed cystic-papillary phenotype strongly positive for carbonic anhydrase activity. EGFR expression progressively increased in the transition from acinar to duct-like and transformed cells. Activating K-ras mutations could not be detected; however, tubular complexes and tumors displayed increased immunoreactivity for nuclear p53. CONCLUSIONS: These data suggest an involvement of the TGF-alpha/EGFR pathway in conjunction with other yet unknown events in pancreatic tumor development. Furthermore, these observations are in favor of an acinar-ductal carcinoma sequence. Thus, these transgenic animals will be useful to define genetic alterations associated with a transition from acinar cells to a neoplastic ductal phenotype.
BACKGROUND & AIMS: Until now, the basic matrix-producing cell type responsible for pancreas fibrosis has not been identified. In this report, retinoid-containing pancreatic stellate cells (PSCs) in rat and human pancreas are described, and morphological and biochemical similarities to hepatic stellate cells are shown. METHODS: Electron and immunofluorescence microscopy (collagen types I and III, fibronectin, laminin, alpha-actin, and desmin) was performed using pancreatic tissue and cultured PSCs. Extracellular matrix synthesis was shown using quantitative immunoassay and Northern blot analysis. RESULTS: PSCs are located in interlobular areas and in interacinar regions. Early primary cultured PSCs contain retinol and fatty acid retinyl-esters. Addition of retinol to passaged cells resulted in retinol uptake and esterification. During primary culture, the cells changed from a quiescent fat-storing phenotype to a highly synthetic myofibroblast-like cell expressing iso-alpha-smooth muscle actin (>90%) and desmin (20%-40%) and showing strong positive staining with antibodies to collagen types I and III, fibronectin, and laminin. As determined on protein and messenger RNA level, serum growth factors stimulated the synthesis of collagen type I and fibronectin. CONCLUSIONS: The identification of PSCs, particularly in fibrotic areas, and the similarities of these cells to hepatic stellate cells suggest that PSCs participate in the development of pancreas fibrosis.
BACKGROUND/AIMS: A causative role of hepatitis C virus infection (HCV) has been discussed in the pathogenesis of mixed cryoglobulinaemia and in B-cell non-Hodgkin's lymphoma. No data are available concerning the newly discovered hepatitis G virus (HGV) and extrahepatic manifestations such as haematological malignancies. But, HCV and HGV most probably belong to the same family of Flavivirus. Consequently, we looked for the prevalence of HCV, HGV and cryoglobulins in patients with B-cell non-Hodgkin's lymphoma. METHODS: Serum samples from 69 patients with non-Hodgkin's lymphoma were studied. Diagnosis of non-Hodgkin's lymphoma was established according to the Kiel classification. Active HCV- and HGV infections were investigated using polymerase chain reaction for detection of viral RNA. Cryoglobulins were detected from serum and monoclonal immunoglobulin components were analysed with immunofixation electrophoresis. In addition, we assessed the clinical course of HCV- and HGV-infected patients under chemotherapy. RESULTS: Three of 69 (4.3%) patients with B-cell non-Hodgkin's lymphoma were HCV-infected and nine non-Hodgkin's lymphoma patients (13.0%) were positive for hepatitis G virus RNA. All HGV infected patients were suffering from low-grade non-Hodgkin's lymphoma. No HGV-infected patient was co-infected by HCV and neither HCV- nor HGV-infected patients showed clinical signs of chronic liver disease before, during or after chemotherapy. Serum samples from all patients were devoid of cryoglobulins. CONCLUSIONS: HCV seems to have no significance for the pathogenesis of non-Hodgkin's lymphoma in Germany. The increased prevalence of hepatitis G (16.3%) in patients with low-grade non-Hodgkin's lymphoma could suggest a pathological consequence of HGV infection outside of the liver. Evidence of clinically relevant hepatic disease in HGV infected patients was not obtained. Further, chemotherapy does not seem to affect the subsequent clinical course of HGV infection.
BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial. METHODS: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients. RESULTS: Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients. CONCLUSION: Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.
We investigated the association of commonly prescribed antibiotics with the prevalence of current Helicobacter pylori infection among children. All children who were screened in 1996 for school fitness by physicians of the Public Health Service in Ulm, a city in the south of Germany, were invited to participate in the study. Infection status was determined by 13C-urea breath test. In addition, the parents of the children were asked to fill out a standardized questionnaire. Nine hundred forty-five out of the 1201 eligible children participated in the study (response rate = 79%). The children were aged 5 to 8 years. Seventeen children who were receiving antibiotics at the day of the breath test were excluded from the analysis. Overall, for 683 children (73.6%) a prior usage of antibiotics was reported. Prevalence of H. pylori infection was significantly lower in children with reported antibiotic usage (odds ratio = 0.46; 95% CI, 0.27-0.76 after adjustment for confounders). Our results suggest that information on prior usage of antibiotics should always be considered in studies evaluating prevalence and risk factors of H. pylori infection in children.
The study objective was to investigate prevalence and determinants of current Helicobacter pylori infection in an asymptomatic population of middle-aged to elderly people. A cross-sectional study was conducted among 337 participants of a general education programme of the University of Ulm aged 50-85 years. Prevalence of infection as determined by means of the [13C]urea breath test was 34.8% (95% CI 29.6-40.3%); overall, 33.8% (95% CI 23.0-46.0) in the age group 50-59 years, 32.4% (95% CI 25.4-39.9) in the age group 60-69 years and 41.0% (95% CI 30.0-52.7) in the age group 70-85 years. Duration of school education of the father, sharing a bed with parents or siblings during childhood, and the area in which participants had grown up were independent determinants of current infection status in a multivariable analysis. We conclude that the prevalence of current H. pylori infection in healthy elderly subjects may not be as high as seroprevalence studies have suggested. Socioeconomic characteristics of childhood living conditions appear to be important determinants of infection status even at older age.
The Ulm Gallbladder Stone Study is the first ultrasound-based epidemiologic survey of cholecystolithiasis in the former West Germany. A study population of 1116 blood donors (656 men, age 38.0 +/- 12.0 years; 460 women, age 34.1 +/- 11.2 years) at the Central Blood Bank of the German Red Cross in Ulm was examined between April 1994 and February 1995. Based on age, subjects were assigned to one of four groups (18-30, 31-40, 41-50, and 51-65 years). Following a structured interview of each study subject, an ultrasound examination was carried out and a blood sample obtained for laboratory study. Overall, 6.0% (95% (95% CI: 4.8%-7.6%) of all study subjects (5.8% of the men and 6.3% of the women) exhibited evidence of current or past gallbladder disease (cholelithiasis or history of cholecystectomy). The prevalence of gallbladder disease correlated positively with age, reaching a maximum of 13.7% (9.5-20.0) in the 51- to 65-year-old age group, and also correlated as with body mass index (BMI). Female subjects with previous full-term pregnancies showed a higher prevalence of cholelithiasis, but this difference was not statistically significant for age-adjusted analysis. Subjects with a family history of cholelithiasis were found to suffer from gallstones in 11.5% (8.0-16.7) of cases compared with 4.6% (3.4%-6.3%) of subjects without such family history. Autopsy studies conducted in Germany have shown the prevalence of gallstones to be about 13.1% in men and 33.8% in women. Our sonographic data are relatively low in comparison. This may be due, in part, to the specific selection characteristics inherent in retrospective autopsy studies, such as age distribution and the presence of other pathologic factors associated with increased risk for cholelithiasis. The Ulm data rank in the lower third of the prevalence range reported for European sonographic studies to date. Age, positive family history, and increased BMI all correlated positively with the prevalence of gallbladder disease (P < 0.05). For the study population as a whole, there was no gender-specific increased risk for the development of gallstones.
BACKGROUND: Low-dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known. AIM: To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole. METHODS: One hundred and sixty-three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.). metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the 13C-urea breath test. RESULTS: One-hundred and thirty-nine patients completed the study. Based on a per protocol analysis. successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention-to-treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%). CONCLUSIONS: Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.
BACKGROUND: In patients suffering from chronic pancreatitis the risk for the development of pancreatic cancer ranges from 4 to 6 per cent. Various mutations are associated with pancreatic cancer, especially of p53 and K-ras. The incidence of these mutations in resected chronic pancreatitic tissue was investigated. METHODS: In the present study DNA from 80 samples of tissue from patients with chronic pancreatitis was isolated and subjected to single-strand conformation polymorphism (SSCP) analysis of p53 exons 5-9 and restriction fragment length polymorphism analysis of K-ras (codon 12). RESULTS: No mutations in the K-ras gene were detected. On SSCP analysis, eight of 80 cases of chronic pancreatitis showed alterations (two in exon 5, four in exon 6, two in exon 7). DNA sequence analysis revealed one deletion of 21 amino acids (exon 5), four polymorphisms in exon 6 with no change in the amino acid sequence, one point mutation in exon 5, and two point mutations located in the intron between exons 6 and 7. CONCLUSION: These data show that in some cases of chronic pancreatitis mutations in the p53 gene occur without morphological evidence of pancreatic cancer.
BACKGROUND: Pancreatic cancer represents a malignancy with very poor clinical prognosis and limited therapeutic potential. Recent developments of gene transfer technology offer new therapeutic avenues by delivering recombinant genes directly into normal or neoplastic tissue in vivo. METHODS: Here we show that the LacZ marker gene, complexed to cationic liposomes, can be introduced into the pancreas by either intraductal or intra-arterial injection. Expression of the beta-galactosidase gene product was monitored by polymerase chain reaction and histochemistry. RESULTS: Up to 28 days after in vivo gene transfer, beta-galactosidase activity could be demonstrated in the pancreas. Intraductal application induced gene expression in lining duct cells preferentially. Twenty-four hours after intraductal injection of liposomes, a dose-dependent, transient increase in serum amylase levels was detected. Nevertheless, no histological signs of pancreatitis were evident. Intra-arterial injection resulted in beta-galactosidase expression in endothelial cells of intrapancreatic arteries, as well as in the spleen, lymph nodes and liver, but not in ductal cells of the pancreas. Only occasionally were acinar cells positive for blue staining by either type of treatment. CONCLUSION: These experiments demonstrate that in vivo gene transfer into the pancreas is feasible using DNA-liposome complexes. Furthermore, the route of administration largely determines cell type specificity and side-effects. This technique might have an impact for the development of gene therapy strategies for pancreatic diseases.
BACKGROUND: The 13C-urea breath (13C-UBT) test value is (semi-)quantitatively related to Helicobacter pylori density in the gastric antrum, and the value correlates with the grade of gastritis. The aim of this study was to assess variation of the 13C-urea breath test value by sociodemographic factors in H. pylori-positive children. METHODS: The analysis was performed on 127 asymptomatic children (aged 5-7 years) who were identified as H. pylori-positive with the 13C-UBT test in a large population-based epidemiologic study in the city of Ulm (southern Germany). The parents of the children were asked to fill out a standardized questionnaire about sociodemographic data. RESULTS: Forty-two infected children (33.1%) were of German nationality, 47 children (37.0%) were of Turkish and 38 children (29.9%) were of another nationality. Turkish children had a significantly higher 13C-UBT value (geometric mean = 27.2%) than German children (16.7%) or children with another nationality (19.3%) (P < 0.001). Girls had a trend towards higher values than boys (P = 0.058 after adjustment for nationality). Body mass index, education of the parents, and prior use of antibiotics were unrelated to the extent of the 13C-UBT. CONCLUSIONS: This study identified significant variation in the extent of the 13C value by nationality among H. pylori-infected children. Further studies are needed to elucidate the causes and potential consequences of these variations.
Family history of peptic ulcer and infection with Helicobacter pylori have been identified as major risk factors for peptic ulcer disease. It is unclear, however, to what degree their impacts are independent of each other. This question was addressed in a cross-sectional study among 299 consecutive out-patients (25-54 years old) of a general practitioner. Adjusted odds ratios (95% confidence intervals) for gastroscopically verified peptic ulcer disease were 3.8 (1.4-10.1) for persons with H. pylori infection, 8.4 (2.9-24.1) for persons with a family history of ulcer, and 29.5 (6.1-143.9) for persons with both risk factors compared with persons without these risk factors. These results suggest strong, multiplicative contributions of both factors to the risk for peptic ulcer disease.
Dexfenfluramine has been shown to reduce body weight and lower blood pressure in obese individuals. However. it is not clear whether the blood pressure-lowering effect is due to dexfenfluramine or to the loss of weight. This project was designed to study the effect of a 5-d treatment of dexfenfluramine on blood pressure changes in obese postmenopausal women. Twenty women aged 51-60 y matched for body mass index [BMI (in kg/m2) of 34.5-50.1] were assigned to either the dexfenfluramine group (15 mg orally twice a day for 5 d) or the control group. All subjects were instructed about an isoenergetic diet. Twenty-four-hour ambulatory blood pressure, plasma catecholamines, glucose, insulin, and lipids were measured at the beginning and repeated at the conclusion of the study. On day 5 the mean systolic (SBP) and mean diastolic blood pressures (DBP) in the dexfenfluramine group were lower than those of the control group (SBP: 114+/-7 mm Hg in the dexfenfluramine group compared with 124+/-12 mm Hg in the control group, P < 0.05; DBP: 70+/-9 mm Hg in the dexfenfluramine group compared with 76+/-10 mm Hg in the control group, P < 0.05). The mean plasma norepinephrine concentration was lower in the dexfenfluramine group than in the control group (1.60+/-0.5 compared with 2.41+/-0.5 nmol/L, respectively, P < 0.05). No differences were noted in epinephrine, glucose, insulin. and lipid concentrations between the two groups. We showed that a 5-d treatment of dexfenfluramine decreases blood pressure and reduces heart rate in obese postmenopausal women. Our data suggest that these effects are results of the direct action of dexfenfluramine.
BACKGROUND: Helicobacter pylori is among the most common infections in humans and has been recognized as major cause of various gastroduodenal diseases. There is limited knowledge, however, on the prevalence and determinants of this infection in children. We addressed these issues in a population-based cross-sectional study in Southern Germany. METHODS: Study subjects were all preschool children in Ulm, a city in the South of Germany, who were screened for school fitness by physicians of the public health service in 1996. Infection status was determined by 13C-urea breath test. In addition, the parents of the children were asked to fill out a standardized questionnaire. RESULTS: In total, 945 out of the 1201 eligible preschool children participated in the study (response rate = 79%). The children were aged 5-8 years. The majority were of German nationality (72.6%). Overall, 127 children (13.4%) were infected with H. pylori. Nationality, place of residence in the first year of life and duration of living in Germany were strongly associated with H. pylori infection status. The prevalence varied from 4.8% (95% confidence interval [CI]: 3.3-6.8%) in children with German nationality who were born in Germany or had lived in Germany since their first year of life to 66.7% (95% CI: 29.9-92.5%) in the children with Turkish nationality who came to Germany after the first year of life. CONCLUSION: Our results showed a large variation in prevalence of H. pylori infection in children living in the same geographical area according to nationality. They indicate an association between living conditions in early childhood and H. pylori infection and indicate that H. pylori associated morbidity may evolve very differently in population subgroups living in the same area.
OBJECTIVE: To analyze the expression of the antiapoptotic gene bcl-xL in human pancreatic cancer and to correlate the results with clinical patient parameters. SUMMARY BACKGROUND DATA: Bcl-xL belongs to the bcl-2-related gene family and acts as a broad antiapoptotic factor to extend both normal and tumor cell survival. Recent findings indicate that tumor cell death induced by chemotherapy and radiotherapy is mediated by the activation of apoptosis. The fact that pancreatic cancer has an extremely malignant potential and that it is resistant to most anticancer treatment modalities suggests that mechanisms are activated that increase the viability of pancreatic cancer cells. METHODS: Seventy-four pancreatic cancer tissue samples were obtained from 32 female and 42 male patients undergoing surgery for exocrine pancreatic cancer. Normal human pancreatic tissue samples were available from 11 organ donors and 4 patients without pancreatic disease. The levels of bcl-xL mRNA expression were analyzed by Northern blot analysis. The exact site of bcl-xL mRNA transcription was determined by nonradioactive in situ hybridization. In addition, immunohistochemistry using specific polyclonal antibodies was used to localize the protein. RESULTS: Northern blot analysis indicated that, in comparison with the normal pancreas, bcl-xL mRNA was markedly overexpressed in 54% of the pancreatic cancer samples. Densitometric analysis revealed that pancreatic adenocarcinomas exhibited a mean 3.4-fold increase (p < 0.01) in bcl-xL mRNA levels in comparison with normal controls. With in situ hybridization, bcl-xL mRNA was found to be highly expressed in the cancer cells of tumor samples that exhibited increased mRNA expression by Northern blot analysis. Immunohistochemical analysis revealed bcl-x immunostaining in 88% of the cancer samples. Correlation of the molecular data with clinical patient parameters revealed that patients whose tumors exhibited no, faint, or weak bcl-xL expression lived significantly longer after tumor resection (median 12 months) than patients whose tumors exhibited moderate bcl-xL mRNA expression (median 5 months) (p < 0.05). However, 5 patients whose tumors exhibited intense bcl-xL mRNA expression tended to live longer (median 14 months). CONCLUSION: Enhanced expression of the antiapoptotic gene bcl-xL in pancreatic cancer and its association with shorter patient survival suggests that this factor may enhance the viability of pancreatic cancer cells in vivo. Inhibition of apoptotic pathways might be one of the reasons why pancreatic cancer shows only limited sensitivity to anticancer treatment.