A common haplotype of carnitine palmitoyltransferase 1b is associated with the metabolic syndrome.

The carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into mitochondria to provide substrates for ß-oxidation. We performed an analysis including three coding SNP in the muscle isoform of the CPT1b gene (rs3213445, rs2269383 and rs470117) and one coding SNP in the CPT2 gene (rs1799821) to find associations with traits of the metabolic syndrome (MetS). Male participants (n 755) from the Metabolic Intervention Cohort Kiel were genotyped and phenotyped for features of the MetS. Participants underwent a glucose tolerance test and a postprandial assessment of metabolic variables after a standardised mixed meal. Carriers of the rare CPT1b 66V (rs3213445) allele had significantly higher γ-glutamyl transpeptidase (GGT), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) activities (P< 0·0001, P= 0·03 and P= 0·048, respectively) and a higher fatty liver index (FLI, P= 0·026). Fasting and postprandial TAG (P= 0·007 and P= 0·009, respectively) and fasting glucose (P= 0·012) were significantly higher in 66V-allele carriers. The insulin sensitivity index determined after a glucose load was lower in those subjects (P= 0·005). Total cholesterol (P= 0·051) and LDL-cholesterol (P= 0·062) tended to be higher in 66V-allele carriers when compared with I66I homozygotes. Homozygosity of the rare K531E allele presented with lower GGT and GOT activities (P= 0·011 and P= 0·027, respectively). E531E homozygotes tended to have lower GPT and FLI (P= 0·078 and P= 0·052, respectively). CPT2 V368I (rs1799821) genotypic groups did not differ in the investigated anthropometric and metabolic parameters. The present results confirm the association of CPT1b coding polymorphisms with the MetS, with a deleterious effect of the CPT1b I66V and a protective impact of the CPT1b K531E SNP, whereas haplotype analysis indicates a relevance of the E531K polymorphism only.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.

[Not Available]. / Die deutsche Agentur für Health Technology Assessment (HTA) beim DIMDI (DAHTA@DIMDI).

With the Health Reform Act 2000 the assessment of medical procedures (Health Technology Assessment, HTA) was first applied to quality assurance in German public health. Since taking this step Germany belongs to the group of countries (Great Britain, Sweden, Australia, etc.) that employ HTA as an objective instrument to determine scientific grounds for political health decisions, for instance for decisions concerning absorption of costs or the development of a benefit catalogue. The German Agency for Health Technology Assessment was founded in September 2000 at the German Institute for Medical Documentation and Information (DAHTA@DIMDI) to fulfil the legal requirements. DAHTA set up and operates a databank-supported information system to supply HTA- relevant information. Additionally research assignments are commissioned for this area and quality standards determined. The goal is to create an up to date and objective information base for health politics and also for medical qualified personnel and consumers that considers the social, ethical, economical and legal results besides the efficacy and effectiveness of medical procedures.

[Not Available]. / HTA-Berichte auf dem Prüfstand Standardverfahren zur Erstellung und Beurteilung von HTA-Berichten : Standardverfahren zur Erstellung und Beurteilung von HTA-Berichten.

Quality-oriented medicine, which has the goal of healing or improving the patients quality of life as highest imperative, also has the obligation to fulfil the required standards itself. Standards, defined for the implementation of this goal, are supported thereby by standard operating procedures (SOPs), the structured and systematic descriptions of the necessary working processes. Both (Standards and SOPs) are part of the integrated quality management of the Total Quality Management (TQM).The quality demands of the German agency for Health Technology Assessment (DAHTA@DIMDI) apply to the processes of product creation as well as to the product itself. The quality management used by DAHTA@DIMDI orients itself on internationally recognized quality assurance standards (e.g. DIN EN ISO 9000:2000FF). The DAHTA@DIMDI pursues the goal, that the development processes and the contents of the evaluation of medical procedures (Health Technology Assessment - HTA) attains the highest acceptance possible in all target groups.

[The concept of "evidence-based medicine" in psychiatry. A path to a more rational psychiatry?]. / Das Konzept der "Evidence-based Medicine" in der Psychiatrie. Ein Weg zu einer rationaleren Psychiatrie?

Many of the diagnostic and therapeutic procedures in psychiatry and psychotherapy are based on opinion rather than evidence. The concept of evidence-based medicine aims to bridge the gap between clinical research and clinical decision-making by integrating the best available external evidence with personal expertise. In this article, we demonstrate several examples of the non-evidence-based medicine paradigm. Then we show the usefulness and practicability of the new evidence-based medicine paradigm by using a clinical example. Finally, we discuss the consequences, chances, and limitations of this new model. We also examine the role of the individual clinician's viewpoint as well as the need of institutional re-engineering and the possible restructuring of the entire health care system towards evidence-based methods.

Purification and biochemical characterization of a hydroxyneurosporene desaturase involved in the biosynthetic pathway of the carotenoid spheroidene in Rhodobacter sphaeroides.

Hydroxyneurosporene desaturase is involved in the carotenoid biosynthetic pathway of Rhodobacter species. The gene encoding this enzyme was expressed in Escherichia coli, purified, and biochemically characterized. The resulting protein contained an N-terminal six-histidine extension which derived from the cloning vector; this allowed for a one-step purification of the enzyme to homogeneity after solubilization with Nonidet P-40. The hydrogen acceptor in the C-3,4 desaturation reaction was molecular oxygen. NAD+, NADP+, and flavin adenine dinucleotide had no influence on enzymatic activity. Different acyclic 1-hydroxycarotenoids were tested as substrates. Very good conversion was achieved with 1-hydroxyneurosporene and 1-hydroxylycopene, whereas 1-hydroxy-gamma-carotene and 1,1'-dihydroxylycopene were much less effective. From 1'-hydroxy-3,4-didehydrolycopene only trace amounts of product were obtained, and 1-methoxyneurosporene was not converted by purified hydroxyneurosporene desaturase. A Km of 13.4 microM was determined for 1-hydroxyneurosporene.

Production of zeaxanthin in Escherichia coli transformed with different carotenogenic plasmids.

Carotenoids are of great commercial interest and attempts are made to produce different carotenoids in transgenic bacteria and yeasts. Development of appropriate systems and optimization of carotenoid yield involves transformation with several new genes on suitable plasmids. Therefore, the non-carotenogenic bacterium Escherichia coli JM101 was transformed in our study with several genes that mediated the biosynthetic production of the carotenoid zeaxanthin in this host. Selection of plasmids for the introduction of five essential genes for zeaxanthin formation showed that a pACYC-derived plasmid was the best. Multiplasmid transformation generally decreased production of zeaxanthin. By cotransformation with different plasmids, limitations in the biosynthetic pathway were found at the level of geranylgeranyl-pyrophosphate synthase and beta-carotene hydroxylase. In our study a maximum zeaxanthin content of 289 micrograms/g dry weight was obtained. This involved the construction of a plasmid that mediate high-level expression of beta-carotene hydroxylase. The level of expression was demonstrated on protein gels and solubilization by the mild detergent Brij 78 revealed that a significant portion of the expressed enzyme is located in the E. coli membranes where it can exert its catalytic function. Based on the results obtained, new strategies for vector construction and strain selection were proposed which could increase the present concentrations drastically. Optimal growth conditions of the transformed E. coli strains for carotenoid formation were found at a temperature of 28 degrees C and a cultivation period of 2 days.

Blockage of longitudinal flow in endolymphatic hydrops.

The external shunt operation on the endolymphatic sac is based on the concept that it will drain excess endolymph and thus arrest the progression of endolymphatic hydrops. We performed histological studies on 46 temporal bones from 13 cases of bilateral and 20 cases of unilateral Meniere's disease to evaluate the status of the pathways of longitudinal flow of endolymph to the sac. The endolymphatic ducts were blocked in 8 specimens (17%), the endolymphatic sinuses in 9 (19.5%), the utricular ducts in 12 (26%), the saccular ducts in 7 (15%), and the ductus reuniens in 27 (59%). These blockages arrested longitudinal flow from both the pars superior and inferior in 21 cases (46%), the pars superior only in 3 (6.5%), and the pars inferior only in 16 (35%). In the 6 ears with all pathways open, 2 were found to have fistulae between the saccules and the perilymphatic spaces, which theoretically results in internal shunting, thus alleviating the need for the external shunt procedure. In the aggregate, therefore, 42 (91%) of 46 ears showed either areas of blockage of longitudinal flow or internal shunts that would theoretically negate the value of external endolymphatic shunt procedures. These temporal bones, however, are from an autopsy population and the severity of pathological changes is probably greater than it would have been at an earlier age when external shunt surgery might have been a therapeutic consideration.