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Biomedical subjects

Markus Stein

Publications and source records attributed to Markus Stein.

4 recordsLinked to original sources

Reliability of diagnoses coding with ICD-10.

OBJECTIVE: Reliability of diagnoses coding is essential for the use of routine data in a national health care system. The present investigation compares reliability of diagnoses coding with ICD-10 between three groups of coding subjects. METHOD: One hundred and eighteen students coded 15 diagnoses lists, 27 medical managers from hospitals 34 discharge letters, and 13 coding specialists 12 discharge letters. Agreement in principal diagnosis was assessed using Cohen's Kappa and the fraction of coincidences over the number of pairs, agreement for the full set of diagnoses with a previously developed measure p(om). RESULTS: Kappa values were fair (managers) or moderate (coders) for terminal codes with 0.27 and 0.42 (agreement 29.2% versus 46.8%), substantial for the chapter level with 0.71 and 0.72 (agreement 78.3% versus 80.8%). p(om) was lower for the full set of diagnoses than for principal diagnoses, for example in case of managers with 0.21 versus 0.29 for terminal codes. Best results were achieved by students coding diagnoses lists. In summary, the results are remarkably lower than in earlier publications. CONCLUSION: The refinement of the ICD-10 accompanied by innumerous coding rules has established a complex environment that leads to significant uncertainties even for experts. Use of coded data for quality management, health care financing, and health care policy requires a remarkable simplification of ICD-10 to receive a valid image of health care reality.

Diagnosis-Related Groups↗

Interaction with CagF is required for translocation of CagA into the host via the Helicobacter pylori type IV secretion system.

Development of severe gastric diseases is strongly associated with those strains of Helicobacter pylori that contain the cag pathogenicity island (PAI) inserted into the chromosome. The cag PAI encodes a type IV secretion system that translocates the major disease-associated virulence protein, CagA, into the host epithelial cell. CagA then affects host signaling pathways, leading to cell elongations and inflammation. Since the precise mechanism by which the CagA toxin is translocated by the type IV secretion system remained elusive, we used fusion proteins and immunoprecipitation studies to identify CagA-interacting secretion components. Here we demonstrate that CagA, in addition to other yet-unidentified proteins, interacts with CagF, presumably at the inner bacterial membrane. This interaction is required for CagA translocation, since an isogenic nonpolar cagF mutant was translocation deficient. Our results suggest that CagF may be a protein with unique chaperone-like function that is involved in the early steps of CagA recognition and delivery into the type IV secretion channel.

Antigens, Bacterial↗

Canadian Helicobacter Study Group Consensus Conference: Update on the approach to Helicobacter pylori infection in children and adolescents--an evidence-based evaluation.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H. pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H. pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H. pylori infection; recurrent abdominal pain of childhood is not an indication to test for H. pylori infection; H. pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H. pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H. pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H. pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H. pylori infection; serological antibody tests are not recommended as diagnostic tools for H. pylori infection in children; first-line therapy for H. pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H. pylori infection in children is 14 days; and H. pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.

Adolescent↗

c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs.

The human pathogen Helicobacter pylori colonizes the mucous layer of the stomach. During parasitic infection, freely swimming bacteria adhere to the gastric epithelial cells and trigger intracellular signalling pathways. This process requires the translocation of the effector protein CagA into the host cell through a specialized type IV secretion system encoded in the cag pathogenicity island. Following transfer, CagA is phosphorylated on tyrosine residues by a host cell kinase. Here, we describe how the tyrosine phosphorylation of CagA is restricted to a previously identified repeated sequence called D1. This sequence is located in the C-terminal half of the protein and contains the five-amino-acid motif EPIYA, which is amplified by duplications in a large fraction of clinical isolates. Tyrosine phosphorylation of CagA is essential for the activation process that leads to dramatic changes in the morphology of cells growing in culture. In addition, we observed that two members of the src kinases family, c-Src and Lyn, account for most of the CagA-specific kinase activity in host cell lysates. Thus, CagA translocation followed by tyrosine phosphorylation at the EPIYA motifs promotes a growth factor-like response with intense cytoskeletal rearrangements, cell elongation effects and increased cellular motility.

Amino Acid Motifs↗