[Use of the S3 guidelines for early detection of prostate cancer in urological practices]. / Anwendung der S3-Leitlinie zur Prostatakrebsfrüherkennung in urologischen Praxen.

OBJECTIVES: The German S3 guideline on prostate cancer gives recommendations on early detection of prostate cancer. In this study we analyzed the adherence of urologists in private practice from the administrative district of Münster, Germany to this guideline. METHODS: Data were collected through a semistructured survey of 22 urologists based on the COREQ checklist (Consolidated criteria for reporting qualitative research) in four focus groups consisting of five or six urologists in private practice. We developed 23 questions relating to 12 recommendations of the paragraphs of the S3 guidelines dealing with early detection of prostate cancer and prostate biopsy. The recommendations of the guideline are subdivided in nine "strong", one "optional recommendation" and two "statements". The adherence to the guideline was investigated by using frequency and qualitative content analysis (Mayring) based on a mixed methods design. RESULTS: The urologists follow six of the nine "strong recommendations" of the guideline and deviate from three. Reasons for deviations from "strong recommendations" are the following: information about advantages and disadvantages of early detection for prostate cancer, recommendation of a prostate biopsy in case of PSA level ≥4 ng/ml, and indication for repeat biopsy. CONCLUSION: Most of the "strong recommendations" are followed by the interviewed urologists of the administrative district of Münster. Contextually relevant deviations from "strong recommendations" are justified, e. g., the only limited transferability of the PSA threshold of 4 ng/ml derived from population-based studies of asymptomatic men to men presenting in a urologist's office.

[Assessment of pruritus - current standards and implications for clinical practice : consensus paper of the Action Group Pruritus Parameter of the International Working Group on Pruritus Research (AGP)]. / Erfassung von Pruritus - aktuelle Standards und Implikationen für die Praxis : Konsensuspaper der Initiative Pruritusparameter der Arbeitsgemeinschaft Pruritusforschung (AGP).

With a prevalence of 20%, chronic pruritus is a symptom of many diseases with major impact on healthcare costs. The lack of specific therapeutic measures makes the development of new drugs and their testing in clinical trials urgent. It is not possible to measure pruritus in an objective way. For these reasons, it is necessary to have a series of standardized measures to characterize pruritus in a reliable way. Intensity scales such as the visual analog scale (VAS) are most frequently used to document the course of the symptoms. However, for assessing pruritus intensity, VAS is not an optimal instrument, although it cannot be dispensed with. The VAS should be combined with other scales in clinical studies in order to internally test the consistency of data. Other instruments for assessing intensity and course of pruritus are in the process of development. Presently scratch activity and scratch-associated lesions can be documented in a descriptive fashion. There are some studies that have employed devices to document scratch activity; however, methodological studies are not yet available. The patient-benefit index is an indispensable tool in clinical trials. A questionnaire for gathering data on the history and some pruritus-specific parameters has been developed and published. Questionnaires on patient quality of life, anxiety and depression are helpful in obtaining data on other cost-relevant parameters. A questionnaire on the quality of life, for instance, can provide important help in the assessment of the burden of the disease. The results of these questionnaires can be correlated with data on pruritus intensity scales. The relevant questionnaires have been partially digitalized so that they are available immediately as part of patient care. Additional methodological developments and studies are required in order to define a robust set of instruments for measuring pruritus in daily practice and in clinical studies.

Multilingual Medical Data Models in ODM Format: A Novel Form-based Approach to Semantic Interoperability between Routine Healthcare and Clinical Research.

BACKGROUND: Semantic interoperability between routine healthcare and clinical research is an unsolved issue, as information systems in the healthcare domain still use proprietary and site-specific data models. However, information exchange and data harmonization are essential for physicians and scientists if they want to collect and analyze data from different hospitals in order to build up registries and perform multicenter clinical trials. Consequently, there is a need for a standardized metadata exchange based on common data models. Currently this is mainly done by informatics experts instead of medical experts. OBJECTIVES: We propose to enable physicians to exchange, rate, comment and discuss their own medical data models in a collaborative web-based repository of medical forms in a standardized format. METHODS: Based on a comprehensive requirement analysis, a web-based portal for medical data models was specified. In this context, a data model is the technical specification (attributes, data types, value lists) of a medical form without any layout information. The CDISC Operational Data Model (ODM) was chosen as the appropriate format for the standardized representation of data models. The system was implemented with Ruby on Rails and applies web 2.0 technologies to provide a community based solution. Forms from different source systems - both routine care and clinical research - were converted into ODM format and uploaded into the portal. RESULTS: A portal for medical data models based on ODM-files was implemented (http://www.medical-data-models.org). Physicians are able to upload, comment, rate and download medical data models. More than 250 forms with approximately 8000 items are provided in different views (overview and detailed presentation) and in multiple languages. For instance, the portal contains forms from clinical and research information systems. CONCLUSION: The portal provides a system-independent repository for multilingual data models in ODM format which can be used by physicians. It serves as a platform for discussion and enables the exchange of multilingual medical data models in a standardized way.

A newly discovered gene, tfuA, involved in the production of the ribosomally synthesized peptide antibiotic trifolitoxin.

Trifolitoxin (TFX) is a gene-encoded, posttranslationally modified peptide antibiotic. Previously, we have shown that tfxABCDEFG from Rhizobium leguminosarum bv. trifolii T24 is sufficient to confer TFX production and resistance to nonproducing strains within a distinct taxonomic group of the alpha-proteobacteria (E. W. Triplett, B. T. Breil, and G. A. Splitter, Appl. Environ. Microbiol. 60:4163-4166, 1994). Here we describe strain Tn5-2, a Tn5 mutant of T24 defective in the production of TFX, whose insertion maps outside of the tfx cluster. It is not altered in growth compared with T24, nor does it inactivate TFX in its proximity. The wild-type analog of the mutated region of Tn5-2 was cloned. Sequencing, transcriptional fusion mutagenesis, and subcloning were used to identify tfuA, a gene involved in TFX production. On the basis of computer analysis, the putative TfuA protein has a mass of 72.9 kDa and includes a peroxidase motif but no transmembrane domains. TFX production studies show that extra copies of the tfxABCDEFG fragment increase TFX production in a T24 background while additional copies of tfuA do not. Lysate ribonuclease protection assays suggest that tfuA does not regulate transcription of tfxA. Upstream of tfuA are two open reading frames (ORFs). The putative product of ORF1 shows high similarity to the LysR family of transcriptional regulators. The putative product of ORF2 shows high similarity to the cytosine deaminase (CodA) of Escherichia coli.

Expression of tfx and sensitivity to the rhizobial peptide antibiotic trifolitoxin in a taxonomically distinct group of alpha-proteobacteria including the animal pathogen Brucella abortus.

Three phylogenetically distinct groups within the alpha-proteobacteria which differ in trifolitoxin sensitivity are described. Trifolitoxin sensitivity was found in strains of Agrobacterium, Brucella, Mycoplana, Ochrobactrum, Phyllobacterium, Rhodobacter, Rhodopseudomonas, Rhodospirillum, and Rhizobium. Strains of Agrobacterium, Brucella, Phyllobacterium, Rhizobium, and Rhodospirillum were capable of producing trifolitoxin upon conjugal transfer of tfxABCDEFG.

DNA sequence of the common nodulation genes of Bradyrhizobium elkanii and their phylogenetic relationship to those of other nodulating bacteria.

A 6.6-kb BamHI fragment containing the common nodulation genes of Bradyrhizobium elkanii USDA94 was identified by southern hybridization using the common nod genes of B. japonicum as a probe. This fragment was cloned and sequenced. Analysis of the sequence showed open reading frames highly homologous to nolA, nodD2, nodD1, and nodKABC from other bradyrhizobial sources. The sequence showed higher homology to the common nod genes of Bradyrhizobium sp. (Parasponia) than to those from B. japonicum. The open reading frame identified between nodD1 and nodA in the B. elkanii sequence was far more similar to nodK from Bradyrhizobium sp. (Parasponia) than to nodY from B. japonicum. The molecular phylogeny of nodD and nodAB from many sources was analyzed. The genetic distance between the nod genes is far greater than the distance between the 16S rRNA and nifH genes. The differences between the nod genes among the species of Rhizobium is as great as that between Bradyrhizobium and Rhizobium. The host range of the microsymbiont was found to be a better predictor of the similarities of the common nod genes than the 16S rRNA or nifH genes. We propose two groups of nod genes among the rhizobia and bradyrhizobia, based on molecular phylogenetic analysis: those which nodulate legumes of temperate origin in the tribes Vicieae or Trifolieae and those which nodulate legumes of tropical origin in the tribe Phaseoleae.

DNA sequence and mutational analysis of genes involved in the production and resistance of the antibiotic peptide trifolitoxin.

The 7.1-kb fragment of Rhizobium leguminosarum bv. trifolii T24 DNA which confers trifolitoxin production and resistance to nonproducing, sensitive Rhizobium strains (E. W. Triplett, M. J. Schink, and K. L. Noeldner, Mol. Plant-Microbe Interact. 2:202-208, 1989) was subcloned, sequenced, and mutagenized with a transcriptional fusion cassette. The sequence of this fragment revealed seven complete open reading frames, tfxABCDEFG, all transcribed in the same direction. TfxA has an 11-amino-acid carboxy terminus identical to the known amino acid sequence of the trifolitoxin backbone, DIGGSRXGCVA, where X is an UV-absorbing chromophore. This is evidence that trifolitoxin is synthesized ribosomally as a prepeptide that is posttranslationally modified to yield the active peptide. TfxB shows 27.6% identity with McbC, a protein required for the production of the ribosomally synthesized antibiotic microcin B17. Tn3GUS transcriptional fusion insertions in tfxA, tfxB, tfxD, or tfxF caused a nonproducing, trifolitoxin-resistant phenotype and confirmed the direction of transcription of these frames. No insertion mutations were found in tfxE or tfxG. Sequence analysis along with insertion and deletion mutation analysis suggest that (i) trifolitoxin is synthesized ribosomally from tfxA; (ii) tfxA, tfxE, and tfxG have their own promoters; (iii) TfxG is required for immunity; (iv) TfxB, TfxD, and TfxF are required for trifolitoxin production; and (v) the UV-absorbing chromophore is derived from glutamine.

[Osteogenesis imperfecta and aortic incompetence. One case with pathological findings. Review of the literature (author's transl)]. / Ostéogenèse imparfaite et insuffisance aortique. Une observation avec documents anatomiques. Revue de la littérature.

Cardiovascular manifestations of Lobstein's disease are rare, probably unrecognized, and determining factors for the final prognosis, the most frequent lesion being aortic incompetence. The eleventh case to be reported with pathological findings in the literature is described. This complication is usually found in men, blood regurgitation being large in amount, symptomatic, and progressive. Its mechanism is related less to dilatation of the aorta and its ring than to valvular changes, they being frequently bicuspid and dysplasic. Histological findings, not however pathognomonic, are myxoid degeneration in the valves and parietal cystic necrosis in the aortic wall. Apart from the absence of an aneurysm and aortic dissection, macro- and microscopic lesions are similar to those observed in Marfan's syndrome and osteogenesis imperfecta. Operative therapy was employed in all eleven cases, with three postoperative deaths and three later deaths. Certain complications arise from uncontrollable severe hemorrhage, which justifies the use of valve heterografts not requiring antivitamin K administration.