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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 235 records · Page 13Linked to original sources
PubMed1997

The influence of transforming growth factor beta 1 on the expression of genes coding for matrix metalloproteinases and tissue inhibitors of metalloproteinases during regeneration from cerulein-induced pancreatitis.

Enhanced synthesis and deposition of extracellular matrix (ECM) components is a characteristic feature during regeneration from acute cerulein-induced pancreatitis in rats. Transforming growth factor beta 1 (TGF beta 1) has been suggested to be an important modulator of the ECM by interfering with a number of essential processes such as the synthesis of ECM components. To study the involvement of the ECM degrading proteases (matrix metalloproteinases; MMPs) and their specific inhibitors in the process of pancreatic regeneration, we examined the expression of these genes on the transcript level and the activation of the corresponding enzymes by use of zymographies. Pancreatic RNA and protein were extracted from rats sacrificed 1, 2, 3, 5, and 7 days after induction of cerulein pancreatitis. To investigate the influence of TGF beta on gene expression of ECM proteases and their specific inhibitors, we blocked the activity of TGF beta 1 during regeneration from acute pancreatitis by use of neutralizing antibodies against TGF beta 1. Steady levels of 72-kD type IV collagenase (MMP-2), stromelysin (MMP-3), and tissue inhibitor of metalloproteinase 2 (TIMP-2) mRNA were significantly increased 2 days after induction of pancreatitis. MMP-9 and MMP-3 enzyme activity was elevated 12 h after induction of pancreatitis, whereas MMP-2 activity increased 12 h later. Inhibition of TGF beta 1 by neutralizing antibodies only reduced the amount of stromelysin transcripts throughout pancreatic regeneration. In summary, ECM degrading proteases, in particular stromelysin, appear to be involved in ECM remodeling during pancreatic regeneration. TGF beta 1 may be responsible for regulation of stromelysin transcription.

Animals↗
PubMed1997

Qualitative and semi-quantitative value of a modified 13C-urea breath test for identification of Helicobacter pylori infection.

OBJECTIVE: The 13C-urea breath test (13C-UBT) is the method of choice in evaluating the success of therapy for eradication of Helicobacter pylori infection. For reasons of cost efficiency and practicability, urea dose and measurement duration have been reduced and the DOB (delta over baseline) cutoff level with the highest predictive value determined. Further, the efficacy of the modified 13C-UBT as a semi-quantitative test method was evaluated by comparison with histologically determined bacterial infiltration. METHODS: In a prospective study, a modified 13C-UBT with reduced urea dose (75 mg) and shortened measurement duration (30 min) was administered to 145 patients. The DOB cutoff with the highest predictive value was determined using relative operating characteristic analysis. Reference methods included histology, bacterial culture and the rapid urease test. The DOB value was compared with the histologically determined grade of bacterial infiltration and the correlation evaluated using the Spearman ranking method. RESULTS: Reduction of the DOB cutoff level from 5.0 per thousand to 3.5 per thousand led to significant improvement in sensitivity (78.9% vs. 91.2%) and accuracy (88.6% vs. 90.2%) of the 13C-UBT. Only five of 57 infected patients were incorrectly reported as non-infected after modification of the DOB level. In two of three patients in whom histological findings were negative but the 13C-urease test positive, bacterial growth was observed at culture. The DOB level correlated significantly with histological grade of bacterial infection. CONCLUSION: The modified 13C-UBT proved to be a sensitive, practicable and cost-effective method for detecting H. pylori infection and permits a semi-quantitative estimation of bacterial infiltration.

Adolescent↗
PubMed1997

Combined treatment with C1 esterase inhibitor and antithrombin III improves survival in severe acute experimental pancreatitis.

BACKGROUND: Patients with severe acute pancreatitis die of complications closely related to the systemic activation of protease cascades. AIM: To examine the effects of human C1 esterase inhibitor (C1 INH) and antithrombin III (AT III) on two experimental models of acute pancreatitis. METHODS: Oedematous pancreatitis was induced by continuous intravenous infusion of caerulein and haemorrhagic pancreatitis by retrograde injection of sodium taurocholate into the biliopancreatic duct. C1 INH and AT III were given intravenously, either before or after the induction of pancreatitis. Treatment with C1 INH and AT III had no beneficial effect on oedematous pancreatitis. On the other hand, combined C1 INH and AT III therapy improved the survival in haemorrhagic pancreatitis compared with treatment with human serum albumin. This reduction in mortality was found regardless of whether the treatment was given prophylactically or therapeutically. CONCLUSIONS: Treatment with C1 INH and AT III represents a promising therapeutic concept for patients with severe haemorrhagic pancreatitis.

Acute Disease↗
PubMed1997

Liposome mediated gene transfer into the rat oesophagus.

BACKGROUND: Cancer of the oesophagus has so far eluded every attempt at pharmacological treatment. The recent advent of somatic gene therapy offers a new therapeutic approach to malignant tumours. AIM: To investigate whether and how gene transfer into the oesophagus can be achieved. METHODS: A LacZ reporter gene was used as marker and transferred into the oesophagus of rats using cationic liposomes. Gene transfer was achieved by either luminal instillation into a closed segment using a double balloon catheter, or by intramural injection through a needle. Expression of beta-galactosidase was monitored in the oesophagus and various control tissues by histochemistry, polymerase chain reaction (PCR), reverse transcriptase PCR, and Southern blotting. RESULTS: Up to 100 days after in vivo gene transfer beta-galactosidase activity could be demonstrated in the oesophagus. Following luminal application, the transgene was expressed in epithelial cells whereas intramural injection induced preferential expression in fibroblasts. CONCLUSION: In vivo gene transfer into the esophagus is feasible and safe, and the route of administration largely determines cell type specificity. This novel approach will enable in vivo studies of growth, differentiation, and malignant transformation in the oesophagus, and may open new avenues to the confinement of oesophageal malignancies.

Animals↗
PubMed1997

Protein tyrosine phosphorylation in pancreatic acini: differential effects of VIP and CCK.

Cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) stimulate enzyme secretion from pancreatic acini by binding to heptahelical receptors without intrinsic tyrosine kinase activity. Signal transduction by the CCK receptor involves activation of phospholipase C by Gq proteins and activation of tyrosine kinases, whereas occupation of VIP receptors stimulates adenylyl cyclase through binding to Gs proteins. Here, we use electrophoretic separation of cellular proteins and antiphosphotyrosine immunoblotting to demonstrate a VIP-stimulated rapid and dose-dependent increase in tyrosine phosphorylation of proteins migrating at 130, 115, and 93 kDa in freshly isolated rat pancreatic acini. Phosphorylation of these proteins was increased after direct stimulation of adenylyl cyclase or the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase with forskolin or dibutyryl cAMP and was inhibited by the tyrosine kinase inhibitors genistein or tyrphostin 23. Compared with VIP, CCK stimulated tyrosine phosphorylation of additional proteins migrating at 60, 66, and 72/78 kDa. Using two-dimensional electrophoretic separation or immunoprecipitation, the 72/78-kDa phosphoprotein was identified as paxillin. We propose that paxillin might be involved in CCK-but not in VIP-induced exocytosis.

Animals↗
PubMed1997

Failure of a prolyl 4-hydroxylase inhibitor to alter extracellular matrix deposition during experimental pancreatitis.

In chronic pancreatitis the exocrine pancreatic tissue is replaced by extracellular matrix deposits from fibroblasts. We have stimulated fibrogenesis in the pancreas by inducing a single episode of cerulein pancreatitis (10 microg/kg/h for 12 h). We have used a spectrophotometrical assay to measure the tissue hydroxyproline content and immunohistochemistry to study the transient deposition of extracellular matrix in the pancreas. We have investigated whether a potent prolyl 4-hydroxylase inhibitor (HOE-077) can influence the deposition of extracellular matrix in the pancreas. Three days after the induction of the pancreatitis we found the maximum increase in pancreatic hydroxyproline content (by 63%), the maximum decrease in total protein content and amylase activity (by -39 and -86%, respectively), as well as a significant increase in DNA content and the deposition of interstitial collagen fibers on electron microscopy. By immunohistochemistry the largest expansion of extracellular matrix components was found for fibronectin. HOE 077, regardless of the concentration administered, failed to affect any of these parameters. We conclude that the induction of a single episode of cerulein pancreatitis and the serial determination of pancreatic hydroxyproline content represents a simple method to induce and monitor experimental fibrogenesis in the pancreas. Prolyl 4-hydroxylase inhibition did not affect the course of extracellular matrix deposition in the pancreas.

Acute Disease↗
PubMed1997

Proximal gastric motility functions are normal in severe obesity.

The role of altered gastric motor functions for the development of obesity is still unclear. In this study, we investigated whether severe obesity is related to gastric dysfunctions or to abnormal perception in response to distension. 31 obese patients and 20 healthy volunteers were studied using an electronic barostat. Basal gastric tone, gastric accommodation, and perception in response to distension were not altered in obese patients. The median minimal distending pressure, reflecting the intra-abdominal pressure, was significantly elevated in obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude that the proximal gastric motility, including perception and accommodation in response to intragastric distension, is not impaired in severe obesity. Whether disturbances of gastric reflex relaxation in response to a meal are involved in the pathogenesis of obesity remains to be established.

Adult↗
PubMed1997

Smoking in nursing homes: conflicts and challenges.

Nursing home social workers were surveyed to determine nursing home smoking policies and the effect these policies may have on resident and staff interaction. Data analyses suggest that in the past five years there has been a trend toward facilities becoming smoke-free. Facilities that permit smoking face greater conflicts between residents and staff. Social workers are expected to be resident advocates as well as mediators in such areas of conflict. This difficult position is further complicated by the social workers' personal views regarding smoking and "guest" standing in medical settings.

Adult↗
PubMed1997

Use of commonly prescribed antibiotics is not associated with prevalence of Helicobacter pylori infection in adults.

BACKGROUND: The aim of the study was to investigate the association of the use of commonly prescribed antibiotics with prevalence of Helicobacter pylori infection in a population of adult outpatients. METHODS: All patients aged 15-79 years who visited the practice of a general practitioner (GP) between June and September 1996 in a suburban community near Ulm, a city in southern Germany, were asked to participate in the study. Infection status was determined with a 13C-urea breath test. In addition, the patients were asked to fill out a self-administered questionnaire. RESULTS: Overall, 475 outpatients were included in the study (response, 94.1%). A total of 266 patients (56.0%) reported a history of antibiotic treatment within the past 5 years, whereas 147 patients (30.9%) did not (62 patients (13.1%) did not know). Prevalence of infection in patients with a history of antibiotic medication during the past 5 years was 23.3%, whereas the prevalence of infection was 20.4% in subjects without antibiotic treatment (P = 0.283 after stratification for age). Control for other potential confounders by multivariable analysis did not materially alter the results. CONCLUSION: Coincidental antibiotic treatment is not associated with H. pylori prevalence in adults.

Adolescent↗
PubMed1997

Gallstone prevalence in relation to smoking, alcohol, coffee consumption, and nutrition. The Ulm Gallstone Study.

BACKGROUND: Besides considering well-known risk factors for the development of gallbladder stones, such as age, sex, fecundity, and hereditary predisposition, efforts at prevention have focused increasingly on other factors, such as nicotine, alcohol, and caffeine consumption, as well as general nutrition, which may be modified. METHODS: A total of 1116 blood donors were examined between April 1994 and February 1995 in the central blood bank of the German Red Cross in Ulm, Germany. Each subject received a questionnaire and underwent to an upper abdominal ultrasound examination. RESULTS: Gallbladder stone disease (current cholecystolithiasis and history of cholecystectomy) was detailed in 5.8% of the men and 6.3% of the women. Neither regularity nor number of daily meals correlated with the frequency of gallstone disease. Vegetarians (n = 48), as a group, were not found to have gallstones. In relation to the consumption of alcohol, tobacco, or caffeine higher prevalence of cholecystolithiasis was found only in heavy drinkers of coffee (P = 0.051; odds ratio (OR), 1.083; 95% confidence interval (CI), 0.999, 1.174). CONCLUSION: Results of the present study do not show a definite relationship between nutritional factors and the consumption of alcohol, tobacco, or caffeine and an increased prevalence of gallbladder stone disease.

Adult↗
PubMed1997

Evaluation of the 13C-methacetin breath test for quantitative liver function testing.

Noninvasive 13C-breath tests are used for the assessment of hepatocellular dysfunction. 13C-methacetin is metabolized in the liver by O-demethylation to 13CO2 and acetaminophen. The aim of the study was to evaluate the 13C-methacetin breath test in comparison to the Child-Pugh score and other quantitative liver function tests (MEGX-test and indocyanin green-clearance). 2 mg/kg 13C-methacetin were orally given to 31 patients with histologically proven liver cirrhosis of different etiology and severity (nine Child A, 13 Child B, nine Child C), ten patients with chronic viral hepatitis and ten healthy volunteers. The increase of exhaled 13CO2 was expressed as delta over baseline (DOB; delta /1000). Different DOB-values were compared as parameters for assessing hepatocellular dysfunction. All breath test parameters analyzed provided an excellent discrimination between cirrhotic and noncirrhotic individuals. The DOB-value at 20 min showed a superior correlation with the Child-Pugh score (r = 0.67) than did MEGX-test or indocyanine green clearance results (r = 0.39 and r = 0.43, respectively). With a cut-off value of < or = 25 delta /1000 at 20 min, sensitivity and specificity to discriminate between cirrhotic and noncirrhotic individuals was 93.5% and 95%, respectively. The 13C-methacetin breath test is a safe and precise quantitative liver function test. Using one single breath sample 20 min after substrate administration, the test discriminates well between cirrhotic and noncirrhotic patients. Its prognostic value remains to be established.

Acetamides↗
PubMed1997

Portal vein thrombosis and multiple liver abscesses in Crohn's disease--an example for successful conservative treatment.

We report about a 27-year-old patient with Crohn's disease presenting with two complications; Portal vein thrombosis and multiple liver abscesses. Conservative treatment with antibiotics and percutaneous catheter drainage was successful, the liver abscesses disappeared. 18 months later the patient presented in best condition. Ultrasound showed cavernous transformation of the portal vein system and splenomegaly, discrete esophageal varices were seen by esophagogastroscopy. This is an example for an excellent course under conservative therapy of liver abscesses, on the other hand it is the first reported case of a patient with a combination of portal vein thrombosis and multiple liver abscesses in Crohn's disease.

Adult↗
PubMed1997

Driving and dementia: dilemmas and decisions.

Dementia may compromise the competence and safety of an older driver. Persons with dementing diseases frequently experience disturbances in memory, language, orientation, visual spatial skills, and the ability to perform complex tasks. Safety cannot be increased by training or modifications to the vehicle, nor can those afflicted be expected to exercise sound judgment. Individuals may become lost on familiar streets, fail to follow directional signs, and drive at inappropriate speeds. This paper will provide an overview of state licensing provisions, physician responsibilities, and a clinical approach to address and manage the driver with dementia.

Aged↗
PubMed1997

[Mutation T-->C of nucleotide 2238 in the gene of atrial natriuretic peptide (ANP) precursor and heterogeneity of sodium-sensitive hypertension. Preliminary report].

Atrial natriuretic peptide (ANP) is involved in the pathogenesis of sodium-sensitive hypertension. The loss of Sca I restriction site in the ANP precursor gene abolishes the regular stop codon. The aim of our study was the analysis of the Sca I gene polymorphism in 23 patients with sodium-sensitive hypertension, the molecular characteristic of the mutation and the comparison of the blood pressure values, plasma renin activity, plasma ANP and aldosterone concentration between patients with or without mutation. Applying the polymerase chain reaction (PCR), followed by digestion with Sca I, the heterozygous mutation has been found in 9 (39%) patients. The sequencing of PCR products indicated that the loss of Sca I restriction site is caused by T2238-->C transition leading to the translation of ANP with two additional arginines. The higher concentration of ANP in plasma has been found in T2238-->C transition patients on normal and high sodium diet as compared with patients without mutation. These preliminary results suggest that the heterogeneity of sodium-sensitive hypertension is associated with the T2238-->C mutation of the ANP precursor gene.

Adult↗
PubMed1996

A pancreatic cancer-specific expression profile.

We present an approach making use of technology established in the context of the genome project to describe a pancreatic cancer-specific expression profile and to identify new potential disease genes or disease-associated-genes. By use of gridded arrays of pancreatic cancer cDNA libraries and differential hybridizations we show that 4% the gridded cDNA library clones contain sequences preferentially expressed in pancreatic cancer. EST-sequencing of 369 distinct (408 total), differentially expressed sequences identified novel genes (32.5%) or homologs to EST-sequences with unknown function (26.3%). Homologies to known genes allow to determine a pancreatic cancer-specific expression profile, which provides for the first time evidence for complex primary and secondary alterations of gene expression responsible for the development of the phenotype of pancreatic cancer cells. In addition this has led to the identification of novel differentially expressed genes, which represent potential oncogenes or disease-associated markers and may be helpful for the development of therapeutic or diagnostic modalities.

Animals↗
PubMed1996

[Multicentric gastric carcinoid in autoimmune gastritis].

HISTORY AND FINDINGS: A now 54-year-old woman was 32 years ago found to have immune thrombocytopenia and 3 years ago ANA-positive and HBsAg-negative hepatitis with cirrhotic metaplasia. Numerous small asymptomatic carcinoids with marked hypergastrinaemia (1626 ng/l) were also first found 3 years ago. No gastrinoma could be found. Severe arthralgia was the main symptom on admission. INVESTIGATIONS: Gastroscopy revealed a polypoid carcinoid, 1 cm in diameter. There was total achlorhydria. No pernicious anaemia or carcinoid syndrome was found. TREATMENT AND COURSE: Total gastrectomy with construction of a jejunal substitute stomach was performed. Histology showed typical chronic-atrophic gastritis type A, all stages of an argyrophilic endocrine cell hyperplasia, as well as microcarcinoidosis and multicentric carcinoid, in part with submucosal infiltration and lymph node metastases. Immunohistology revealed immune reaction for the global endocrine marker. No specific hormones were demonstrable in the carcinoid cells. The postoperative course was without complications. Serum gastrin levels have since been normal. CONCLUSIONS: The case confirms the possibility of an achlorhydria-hypergastrinaemia-carcinoid sequence. Now new stage-related therapeutic guidelines for this disease are needed.

Achlorhydria↗
PubMed1996

Gallstone recurrence after successful dissolution therapy.

After successful dissolution therapy of cholesterol gallbladder stones bile again becomes supersaturated and recurrent gallstones may develop. Three different postdissolution treatments [500 mg ursodeoxycholic acid (UDCA) per day (N = 14, group I), 100 mg aspirin per day (N = 14, group II) and diet (N = 15, group III) versus a control group (no treatment, N = 15, group IV) aimed at preventing recurrence of gallstones were investigated in a prospective, randomized study in 58 gallstone patients (33 female, 25 male) after complete stone clearance. Bile samples (prior to dissolution therapy and at stone recurrence) were investigated for biliary cholesterol (C), phospholipids (PL), total bile acid concentration (BA), cholesterol saturation index (CSI), total lipid concentration (TLC), total biliary protein concentration (TP), and nucleation time (NT). In group IV multiple gallstones tended to recur more often than solitary stones (66.7% vs 16.7%) whereas in groups I-III only solitary stones recurred. Recurrent gallbladder stones were detectable in 10 patients (eight patients in group IV and one each in groups I and II, respectively) within one year after dissolution and in two patients (one each in groups III and IV, respectively) after 15 months. Furthermore, the probability of stone recurrence was significantly higher in untreated patients as compared to treated patients. In nine (group IV) of 12 patients with recurrent stones NT, C, CSI, PL, BA, TLC, TP, and bile acid spectrum remained nearly unchanged as compared to their pretreatment values, whereas in three (groups I-III) of 12 cases a decrease in C, CSI, and TP was observed during therapy. However, in each of these three patients, initial and after-treatment TP was significantly higher and NT shorter as compared to groups I-IV. Furthermore, in these cases (N = 3) NT was prolonged, whereas no significant changes were found in PL, BA, TLC, and bile acid spectrum. Recurrence of gallstones, which seems to occur more likely in patients with multiple stones as compared to solitary stones, will happen in the early stage after stone clearance, again causing biliary pain. UDCA, aspirin or diet will reduce the probability for recurrent stones after complete gallstone dissolution.

Adult↗