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Biomedical subjects

M Ortner

Publications and source records attributed to M Ortner.

At least 19 recordsLinked to original sources
PubMed2006

[Treatment of vitally endangered anorexia nervosa patients based on guardianship laws].

Anorexia nervosa is a psychiatric disorder occurring primarily in young women. Especially when chronic or the body mass index is less than 12 kg/m(2), it has a mortality of up to 20%. Often these patients are admitted to emergency units and treated internistically. If they accept psychiatric treatment, they are normally transferred to specialized psychosomatic units for further therapy. If patients are not able to accept necessary further therapy to overcome the danger to health and life, the question arises in terms of guardianship law of whether they are able to handle their personal concerns alone. After several vitally endangered anorexia nervosa patients had been admitted to our closed psychiatric ward, we developed a therapeutic concept for this subgroup of patients, taking the possibilities of guardianship law into account. This concept aims at restoring the body weight continuously and finally enable the patients to be transferred to less restrictive psychosomatic units. The chosen treatment is shown with the therapy courses of 25 patients treated according to this concept.

Adolescent↗
PubMed2003

Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions.

The clinical management of pancreatic disease is often hampered by a lack of tissue diagnosis. Endoscopic pancreatography offers the opportunity to investigate exfoliated cells. However, the significance of mere cytological investigation is compromised by an insufficient sensitivity. The evaluation of the molecular background of carcinogenesis hopefully is capable of providing more sensitive diagnostic markers. The p16INK4a-/retinoblastoma tumour-suppressive pathway has been shown to be involved in the development of near to all pancreatic neoplasms. p14ARF is another tumour suppressor located in the immediate neighbourhood of p16INK4a. Promoter methylation has been demonstrated to be a major inactivating mechanism of both genes. We sought to further evaluate the role of the gene locus INK4a methylation status in the endoscopic differentiation of chronic inflammatory and neoplastic pancreatic disease. Pancreatic fluid specimens of 61 patients with either pancreatic carcinoma (PCA: 39), chronic pancreatitis (CP: 16) or a normal pancreatogram (NAD: 6) were retrieved. In order to detect methylation of either the p14ARF or the p16INK4a promoter a methylation-specific PCR protocol was applied. While 19 out of 39 patients with PCA showed p16 promoter methylation (49%), none of the 16 patients with CP revealed p16 promoter methylation. p14ARF methylation was found in a lower percentage of PCA specimens and in none of the samples of patients with CP. These results suggest a specific significance of INK4a for the development of malignant pancreatic disease. Our data further indicate a potential role for INK4a methylation as a diagnostic marker in the endoscopic differentiation of benign and malignant pancreatic disease.

Adenocarcinoma↗
PubMed2003

Diagnostic yield of wireless capsule enteroscopy in comparison with computed tomography enteroclysis.

BACKGROUND AND STUDY AIMS: It is still difficult to visualize changes in the small intestine. Wireless capsule enteroscopy is a new method that promises to provide new insights into the small intestine. In a prospective study, the diagnostic yield of wireless enteroscopy was therefore compared with computed tomography (CT) enteroclysis. PATIENTS AND METHODS: Twenty-two patients with suspected small-bowel pathology underwent CT enteroclysis and wireless capsule enteroscopy examinations, conducted by two independent blinded investigators. The results of the two investigations (diagnoses and the number, extent, and location of lesions detected) were compared by a third investigator. RESULTS: The patients included in the study had obscure gastrointestinal bleeding (n = 8), Crohn's disease (n = 8), unexplained diarrhea (n = 5), or suspected carcinoid tumor (n = 1). Pathological lesions were detected using capsule enteroscopy in 13 patients (59 %) and using CT enteroclysis in eight (36 %; P = 0.12). In seven patients (one case each of colonic Crohn's disease, diverticulitis, Meckel's diverticulum, carcinoid tumor, mesothelioma, colonic polyps, and irritable bowel syndrome), no pathological changes were found in the small intestine using either method. The diagnosis was established by wireless capsule enteroscopy in four patients with obscure bleeding, whereas CT enteroclysis was positive in only one patient ( P = 0.1). Crohn's disease was found in two patients with unexplained diarrhea. Small-bowel lesions were identified in six patients with known Crohn's disease using capsule enteroscopy or CT enteroclysis. The only side effect of wireless capsule enteroscopy observed was abdominal pain in one patient with Crohn's disease. There were no serious side effects with CT enteroclysis. CONCLUSIONS: Wireless capsule enteroscopy detects more small-bowel lesions than CT enteroclysis in patients with obscure gastrointestinal bleeding and Crohn's disease.

Adolescent↗
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↗