Schmerztherapie

Ohne Zusammenfassung     

Wegener-Granulomatose im Kindes- und Jugendalter

Wegener’s granulomatosis (WG) is a necrotising granulomatous small vessel vasculitis with a clinical predilection for the involvement of the upper airways, lungs and kidneys. It occurs at all ages. The pathogenesis of WG is determined by the pathological activation of phagocytes during transmigration through the vessel. Whereas most aspects of WG are similar at all ages, some features appear to be significantly different. WG in childhood is more frequently complicated by subglottic stenosis and nasal deformity, while treatment related morbidity is less common compared to adults. The introduction of combined treatment with cyclophosphamide and glucocorticoids has resulted in a dramatic improvement in patient outcome; however, commonly occurring disease relapses and the risk of chronic organ damage at all ages make long-term follow-up of all patients necessary.     

Suprakondyläre Humeruspseudarthrosen

The standard surgical protocol presented, with resection of the bone that has not healed. stable osteosynthesis with locking plates, and autologous bone graft augmentation, is an established and successful method of treating atrophic nonunion of the distal humerus. Bone healing was observed in all patients, and a single surgical operation was sufficient. In addition, elbow joint arthrolysis was performed to resect joint fibrosis and ossification and release tissue contractures. With this combined approach bony healing and improvement in range of motion and function of the elbow joint were achieved.     

Schlaf bei neurodegenerativen Erkrankungen

Zusammenfassung Die neurodegenerativen Erkrankungen bestehen aus einer Gruppe heterogener, progredient verlaufender Erkrankungen unterschiedlicher Ätiologie, die ein oder mehrere Systeme beeinträchtigen. Sie treten überwiegend im höheren Lebensalter auf, in dem sich zusätzlich sowohl die Art wie auch das Ausmaß des Schlafes ändern. Die neurodegenerativen Prozesse verursachen strukturelle Veränderungen der Schlaf-Wach-Generatoren im Hirnstamm, die Schlafstörungen wie Tagesschläfrigkeit, Insomnie, nächtliche bewegungs- und schlafbezogene Atmungsstörungen sowie Störungen des zirkadianen Schlaf-Wach-Rhythmus zur Folge haben können. Bei manchen neurodegenerativen Erkrankungen sind im Vorfeld der Krankheitsmanifestation auftretende Schlafstörungen bereits Krankheitsprädiktoren. Polysomnographisch finden sich Schlaffragmentierung, tonische oder phasische Beinbewegungen, Störungen der Atemmuskulatur, verminderter Tiefschlaf, Abwesenheit von REM-Schlaf oder REM-Schlaf ohne Muskelatonie, vermehrte Arousal- und Weckreaktionen, epileptiforme EEG-Aktivität oder schlafbezogene Atmungsstörungen. Sehr häufig sind REM-Schlaf-Verhaltensstörungen assoziiert mit neurodegenerativen Erkrankungen. In dieser Übersichtsarbeit werden Symptomatik, Pathophysiologie und polysomnographische Befunde von Schlafstörungen häufiger neurodegenerativer Erkrankungen vorgestellt.     

Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers

Summary The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele.In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs.Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted.Overall, the DNA analysis result matched the in vivo phenotype in 97.5 % of individuals.     

Characterization of the major 68 kDa heat shock protein in a rat transformed astroglial cell line.

The heat shock response in a transformed astrocyte line was compared with nontransformed astrocytes. The synthesis of HSP 68, the major inducible heat shock protein (HSP 68) was induced by a non-lethal 45 degrees C, 10 min heat shock. Although the incorporation of [35S]methionine into HSP 68 suggested that similar amounts of protein were being synthesized after heat shock, Western immunoblotting demonstrated striking differences in the HSP immunostaining between the two cell types. By one- and 'two-dimensional gel electrophoresis the major 68 kDa heat shock protein (HSP 68) was similar in both cell types. However, HSP 68 from heat shocked, transformed astrocytes did not immunostain with the monoclonal antibody, C-92, which is specific for the major inducible heat shock protein of HeLa cells. In contrast HSP 68 from heat shocked, nontransformed astrocytes immunostained quite well. A polyclonal antibody raised against the inducible 72 kDa heat shock protein of HeLa cells immunostained the HSP 68 from both astrocytes and transformed astrocytes. Analysis of the mRNA from the two cell types after heat shock revealed two bands of approximately 2.5 and 2.8 kb in astrocytes but only a single 2.5 kb band in the heat shocked transformed astroglia. These results suggest that structural differences in the HSP 68 may be present in the transformed astrocytes compared to the normal astrocytes.     

Pharmacological profile of the novel P2T-purinoceptor antagonist, FPL 67085 in vitro and in the anaesthetized rat in vivo.

1. We measured the ratio of ETA and ETB sub-types in the media (containing mainly smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary), internal mammary arteries and saphenous veins. 2. In saturation experiments, [125I]-endothelin-1 ([125I]-ET-1) bound with high affinity to the media of each vessel (n = 3 individuals or homogenate preparations +/- s.e. mean): coronary artery, KD = 0.14 +/- 0.02 nM, Bmax = 71.0 +/- 21.0 fmol mg-1 protein; pulmonary artery, KD = 0.85 +/- 0.25 nM, Bmax = 15.2 +/- 10.3 fmol mg-1 protein; aorta, KD = 0.51 +/- 0.02 nM, Bmax = 9.4 +/- 4.4 fmol mg-1 protein; internal mammary artery. KD = 0.34 +/- 0.31 nM, Bmax = 2.0 +/- 0.5 fmol mg-1 protein and saphenous vein, KD = 0.28 +/- 0.05 nM, Bmax = 52.8 +/- 1.0 fmol mg-1 protein. In each vessel, over the concentration-range tested, Hill slopes were close to unity and a one site fit was preferred to a two site model. 3. In competition binding assays, the ETA selective ligand, BQ123 inhibited the binding of 0.1 nM [125I]-ET-1 to the media in a biphasic manner. In each case, a two site fit was preferred to a one or three site model: coronary artery, KDETA = 0.85 +/- 0.03 nM, KDETB = 7.58 +/- 2.27 microM, ratio = 89:11%; pulmonary artery, KDETA = 0.27 +/- 0.05 nM, KDETB = 24.60 +/- 5.34 microM, ratio = 92:8%; aorta, KDETA = 0.80 +/- 0.40 nM, KDETB = 2.67 +/- 2.60 microM ratio = 89:11%; saphenous vein, KDETA = 0.55 +/- 0.17 nM, KDETB = 14.4 +/- 0.26 microM, 85:15% (n = 3 individuals or homogenate preparations +/- s.e. mean). BQ123 showed up to 18000 fold selectivity for the ETA over the ETB sub-type. The ETA-selective ligand, [125I]-PD151242 labelled 85% of the receptors detected by a fixed concentration of [125I]-ET-1 in media of internal mammary artery, measured by quantitative autoradiography. In contrast, the density of ETB receptors detected with [125I]-BQ3020 was 7.0 +/- 1.5 amol mm-2, representing about 8% of [125I]-ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ein Beitrag zur aktuellen Antidementivadiskussion in Deutschland

In Germany, the role of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease (AD) has become a topic of recent discussion. The present article addresses issues which, in the opinion of the authors, have not received sufficient attention. These include the distinction between statistical and clinical significance, outcome parameters, the duration of clinical trials, variability in treatment response and the definition of treatment responders. The authors argue that these issues need to be considered in an in-depth evaluation of acetylcholinesterase inhibitors in the treatment of AD.     

Inzidentalome der Nebenniere

Adrenal incidentalomas are clinically inapparent masses detected incidentally with imaging studies conducted for other reasons. They are relatively common and require structured diagnostic workup. In many cases surveillance is warranted. The diagnostic workflow has to reveal whether the mass is hormonally functioning and/or if there is evidence of malignancy. If the tumor is functionally silent and not larger than 4 cm, surveillance is warranted. Functioning tumors and masses larger than 6 cm have to be resected. Fine-needle aspiration biopsy is indicated in very rare cases, but pheochromocytoma has to be ruled out first.