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Biomedical subjects

M Ortner

Publications and source records attributed to M Ortner.

15 recordsLinked to original sources
PubMed2001

Photodynamic therapy for cholangiocarcinoma.

The prognosis of nonresectable cholangiocarcinoma is dismal, and in Bismuth type III and IV tumors relief of jaundice is seldom achieved, despite successful endoprosthesis insertion. Therefore, we evaluated additional photodynamic therapy in patients who failed to respond to endoprostheses insertion. All patients showed good clinical results in regard to jaundice, quality of life; and survival time (median, 439 days). Before initiating a randomized multicenter trial we wanted to evaluate these preliminary results in a greater number of patients. Twenty-one patients underwent photodynamic therapy in addition to endoscopic drainage. The hematoporphyrin derivative Photofrin was infused intravenously (2 mg/kg body weight), and intraluminal photoactivation was performed 2 days later. Bilirubin decreased from a mean level of 201.26 +/- 189.25 micromol/l after stenting alone to 68.87 +/- 78.27 micromol/l (P = 0.0051), and the Karnofsky index improved from 49.04% +/- 28.79% to 72.85 +/- 19.01 (P = 0.003). Thirteen patients have died and 8 patients are still alive, with a follow-up period of 82-739 days. The 6-month survival time is 95%. Similar results were obtained by another group, with 75% overall (stage M1 and M0) survival after 6 months and beyond 80% for stage M0. Other authors treated 7 patients and saw a remarkable reduction of bile duct stenosis and bilirubin decrease in all patients.

Adult↗
PubMed2001

Photodynamic therapy in the biliary tract.

Biliary tract cancers are rare malignancies usually characterized by slow growth and a low propensity for metastasis. Despite the relatively localized nature of these cancers, the only therapeutic measure with curative potential to date is surgical intervention. Because symptoms occur late, the diagnosis is rarely made at an early stage, and therefore only about half of the patients can have curative surgery. Patients with advanced disease face a dismal prognosis because palliative treatment options are limited. This review outlines recent advances in treatment of biliary cancer. Encouraging results from prospective, single-arm phase II trials of photodynamic therapy in nonresectable cholangiocarcinoma suggest considerable promise for this new palliative treatment modality. However, the apparent benefit of photodynamic therapy on survival, jaundice, and quality of life must be confirmed in a randomized multicenter trial.

Bile Ducts, Extrahepatic↗
PubMed2001

[Bile peritonitis in an alcoholic man after traumatic gallbladder perforation--differential ascitic decompensated liver cirrhosis diagnosis].

Traumatic rupture of the gallbladder is a very rare event associated with high mortality. Since clinical symptoms are nonspecific, diagnosis is difficult. We present an alcoholic with biliary ascites after traumatic perforation of the gallbladder. Initially, he was misdiagnosed to have ascites caused by liver cirrhosis. This case demonstrates, that the combination of patients history, clinical investigation and ultrasound allows the diagnosis of traumatic rupture of the gallbladder.

Adult↗
PubMed2000

Improved accuracy in the diagnosis of intrahepatic bile duct ectasia in Caroli's disease by combination of ultrasound and endoscopic retrograde cholangiography.

Caroli's disease is characterized by dilatation of the intrahepatic bile ducts. Cholangitis, liver cirrhosis and development of a cholangiocarcinoma are possible complications. For optimal therapy, a correct diagnosis of the extent of the disease is mandatory. The present report demonstrates that the combination of endoscopic retrograde cholangiography and ultrasound may lead to a more reliable diagnosis of the extent of Caroli's disease. It is therefore essential to perform ultrasound in all these patients.

Bile Duct Diseases↗
PubMed1999

Production of IL-12 in gastritis relates to infection with Helicobacter pylori.

Increased production of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-8, has been demonstrated in Helicobacter pylori-associated gastric mucosal inflammation. IL-12, a newly characterized cytokine, is thought to be a key mediator in host responses to bacterial infections. The aim of this study was to investigate differences in cytokine patterns between H. pylori-positive and -negative gastritis and normal mucosa. Secretion of IL-12, TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10 was measured in 176 patients with chronic gastritis in whole biopsy cultures. Gastritis was graded for chronic inflammation or acute inflammatory activity, respectively, according to the Sydney system. Biopsies with similar scores were matched for analysis from H. pylori-infected and non-infected patients. Secretion of IL-12 was significantly increased in H. pylori-associated gastritis in comparison with H. pylori-negative gastritis (P < 0.0001). In contrast, secretion of TNF-alpha, IL-1beta, IL-6, and IL-8 correlated with the degree of inflammation but was not different between H. pylori-positive and -negative patients. Moreover, IL-10 secretion was found to be higher in H. pylori-positive than in H. pylori-negative patients. IL-12 may play a specific role in H. pylori-associated gastric disease, whereas production of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6 and IL-8 does not seem to be restricted to H. pylori-induced inflammation. The contra-inflammatory cytokine IL-10 may be a contributor to the chronicity of H. pylori-associated gastritis by impairing clearance of the pathogen.

Adult↗
PubMed1998

Association between intraepithelial Escherichia coli and colorectal cancer.

BACKGROUND & AIMS: Although multiple studies have focused on Helicobacter pylori, little is known about the mucosa-associated flora of the colon. The aim of this study was to detect bacteria directly in colonic mucosa from patients screened for colorectal cancer. METHODS: Bacteria were quantified with the polymerase chain reaction and identified by comparative sequence analysis in colonoscopic biopsy specimens from 31 asymptomatic and 34 symptomatic controls with normal colonoscopic findings, 29 patients with colonic adenoma, and 31 patients with colorectal carcinoma. In 41 patients, intra- and extracellular location of bacteria was confirmed with the gentamicin protection assay. RESULTS: No bacteria were detected in biopsy specimens from 97% of asymptomatic and 69% of symptomatic controls. In contrast, bacterial concentrations of 10(3)-10(5) colony-forming units per microliter were detected in biopsy specimens from both malignant and macroscopically normal tissue in 90% and 93% of patients with adenoma and carcinoma, respectively. E. coli and coli-like bacteria were shown to colonize the colonic mucosa in 82% of these patients. The gentamicin protection assay indicated that E. coli was partially intracellular in 87% of patients with adenoma and carcinoma and in none of the controls. CONCLUSIONS: The colonic mucosa of patients with colorectal carcinoma but not normal colonic mucosa is colonized by intracellular E. coli.

Adenoma↗
PubMed1997

Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.

BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease.

Adult↗
PubMed1996

Molecular and structural analysis of a continuous birch profilin epitope defined by a monoclonal antibody.

The interaction of a mouse monoclonal antibody (4A6) and birch profilin, a structurally well conserved actin- and phosphoinositide-binding protein and cross-reactive allergen, was characterized. In contrast to serum IgE from allergic patients, which shows cross-reactivity with most plants, monoclonal antibody 4A6 selectively reacted with tree pollen profilins. Using synthetic overlapping peptides, a continuous hexapeptide epitope was identified. The exchange of a single amino acid (Gln-47 --> Glu) within the epitope was found to abolish the binding of monoclonal antibody 4A6 to other plant profilins. The NMR analyses of the birch and the nonreactive timothy grass profilin peptides showed that the loss of binding was not due to major structural differences. Both peptides adopted extended conformations similar to that observed for the epitope in the x-ray crystal structure of the native birch profilin. Binding studies with peptides and birch profilin mutants generated by in vitro mutagenesis demonstrated that the change of Gln-47 to acidic amino acids (e.g. Glu or Asp) led to electrostatic repulsion of monoclonal antibody 4A6. In conclusion the molecular and structural analyses of the interaction of a monoclonal antibody with a continuous peptide epitope, recognized in a conformation similar to that displayed on the native protein, are presented.

Allergens↗
PubMed1996

Helmholtz free energies of atom pair interactions in proteins.

BACKGROUND: Proteins fold to unique three-dimensional structures, but how they achieve this transition and how they maintain their native folds is controversial. Information on the functional form of molecular interactions is required to address these issues. The basic building blocks are the free energies of atom pair interactions in dense protein solvent systems. In a dense medium, entropic effects often dominate over internal energies but free energy estimates are notoriously difficult to obtain. A prominent example is the peptide hydrogen bond (H-bond). It is still unclear to what extent H-bonds contribute to protein folding and stability of native structures. RESULTS: Radial distribution functions of atom pair interactions are compiled from a database of known protein folds. The functions are transformed to Helmholtz free energies using a recipe from the statistical mechanics of dense interacting systems. In particular we concentrate on the features of the free energy functions of peptide H-bonds. Differences in Helmholtz free energies correspond to the reversible work required or gained when the distance between two particles is changed. Consequently, the functions directly display the energetic features of the respective thermodynamic process, such as H-bond formation or disruption. CONCLUSIONS: In the H-bond potential, a high barrier isolates a deep narrow minimum at H-bond contact from large distances, but the free energy difference between H-bond contact and large distances is close to zero. The energy barrier plays an intriguing role in H-bond formation and disruption: both processes require activation energy in the order of 2kT. H-bond formation opposes folding to compact states, but once formed, H-bonds act as molecular locks and a network of such bonds keeps polypeptide chains in a precise spatial configuration. On the other hand, peptide H-bonds do not contribute to the thermodynamic stability of native folds, because the energy balance of H-bond formation is close to zero.

Drug Stability↗
PubMed1996

Multiple fistulas and tracheobronchial stenoses require extensive stenting of the central airways and esophagus in squamous-cell carcinoma.

We report here on two cases of double airway and esophageal stenting in patients with multiple esophagotracheal fistulas and stenoses of the airways and esophagus due to squamous-cell carcinoma. Dumon stents and a Strecker device were used for tracheobronchial stenting. Covered Gianturco Z-stents were implanted into the esophagus. In one case, extrinsic compression of the trachea and tumor progression required recanalization by Nd:YAG laser. Clinical improvement led to discharge of the patients within two weeks after the procedure. The results show that simultaneous implantation of stents in the central airways and covered Gianturco Z-stents in the esophagus is an effective therapeutic strategy in patients with tracheal and esophageal obstructions and esophagorespiratory fistulas. Further systematic studies evaluating double stenting are warranted.

Aged↗
PubMed1995

Progress in fold recognition.

The prediction experiment reveals that fold recognition has become a powerful tool in structural biology. We applied our fold recognition technique to 13 target sequences. In two cases, replication terminating protein and prosequence of subtilisin, the predicted structures are very similar to the experimentally determined folds. For the first time, in a public blind test, the unknown structures of proteins have been predicted ahead of experiment to an accuracy approaching molecular detail. In two other cases the approximate folds have been predicted correctly. According to the assessors there were 12 recognizable folds among the target proteins. In our postprediction analysis we find that in 7 cases our fold recognition technique is successful. In several of the remaining cases the predicted folds have interesting features in common with the experimental results. We present our procedure, discuss the results, and comment on several fundamental and technical problems encountered in fold recognition.

Algorithms↗
PubMed1994

A respirometer for investigating oxidative cell metabolism: toward optimization of respiratory studies.

Oxygen flux measurements are critical at low rates of. respiration and at oxygen tensions below air saturation. Difficulties are primarily due to increased oxygen diffusion and consumption processes which may occur in conventional closed respirometric chambers. To avoid measurement errors encountered with standard equipment, a new type of oxygraph was developed. This instrument provides reliable quantification of oxygen flux in small organisms, tissue samples, cells, isolated mitochondria, and chloroplasts. The instrument is available commercially or can be rebuilt in a well-equipped laboratory workshop.

Cells↗
PubMed1991

Reversibility of oxygen switch-off effect on Bacillus polymyxa nitrogenase.

The objective of this study was to analyse in vivo the effect of oxygen on the nitrogenase of Bacillus polymyxa. The culture technique employed in this study prevented spore formation by B. polymyxa during the entire period of exposure to acetylene. Under these conditions the acetylene-reduction assay allowed quantification of nitrogenase activity over long incubation periods (44 h). Nitrogenase activity was highest in cells harvested in the late logarithmic phase. At PO2 of 0.19 and 0.37 kPa, acetylene reduction was inhibited by 80 and 100%, respectively. This switch-off effect could be reversed through oxygen exhaustion, either by flushing the culture with N2 or by cellular respiration, suggesting a respiratory protection mechanism for the nitrogenase complex in B. polymyxa. Oxygen consumption measured by a closed-chamber respirometer showed a linear increase up to a PO2 of 0.2 kPa. Above 0.3 kPa a saturation in oxygen consumption was observed. Exposure to high oxygen pressures resulted in an irreversible loss of nitrogenase activity. The oxygen inhibition pattern was shown to be similar to that in other microaerophilic and anaerobic nitrogen-fixing microorganisms.

Bacillus↗