Sepsis erkennen im Rettungsdienst

Die Anaesthesiologie - Sepsis hat eine hohe Mortalität, die durch einen frühzeitigen Therapiebeginn reduziert werden kann. Da Patienten mit Sepsis häufig durch den Rettungsdienst in...     

Cerebellar Bottom-of-Fissure Dysplasia—a Novel Cerebellar Gray Matter Neuroimaging Pattern

We report on seven patients with a novel neuroimaging finding that involves exclusively the cerebellar gray matter at the bottom of several fissures of both hemispheres but spares the vermis. The abnormal fissures were predominantly located in the lower and lateral parts of the cerebellar hemispheres. The affected cerebellar cortex was hypointense on T1-weighted and hyperintense on T2-weighted and fluid attenuation inversion recovery sequences. In some patients, the involved cerebellar gray matter was mildly thickened and the affected fissures slightly widened. In three of seven patients, the neuroimaging findings were unchanged on follow-up studies up to 6 years. The seven patients had various indications for the brain magnetic resonance imaging studies, and none of them had cerebellar dysfunction. Based on the similarity of the neuroimaging pattern with the cerebral “bottom-of-sulcus dysplasia,” we coined the term “cerebellar bottom-of-fissure dysplasia” to refer to this novel neuroimaging finding. The neuroimaging characteristic as well as the unchanged findings on follow-up favors a stable “developmental” (malformative) nature. The lack of cerebellar dysfunction in the affected patients suggests that cerebellar bottom-of-fissure dysplasia represents most likely an incidental finding that does not require specific diagnostic investigation but allows a reassuring attitude.     

CRIM-negative infantile Pompe disease: 42-month treatment outcome

Pompe disease is a rare lysosomal glycogen storage disorder characterized by deficiency of acid α-glucosidase enzyme (GAA) and caused by mutations in the GAA gene. Infantile-type Pompe disease is a multiorgan disorder presenting with cardiomyopathy, hypotonia, and muscular weakness, which is usually fatal. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) has recently been shown to be effective and subsequently yielded promising results in cross-reactive immunologic material (CRIM)-positive patients. CRIM-negative patients showed a limited response to ERT and died or were ventilator dependant. Over a period of 44 months, we monitored cognitive and motor development, behavior, auditory function, and brain imaging of a CRIM-negative infantile Pompe disease patient on rhGAA and monoclonal anti-immunoglobulin E (anti-IgE) antibody (omalizumab) treatment due to severe allergic reaction. Cardiorespiratory and skeletal muscle response was significant, with almost normal motor development. Cognitive development—in particular, speech and language—deviated increasingly from normal age-appropriate development and was markedly delayed at 44 months, unexplained by moderate sensorineural hearing impairment. Brain magnetic resonance imaging (MRI) at 18, 30, and 44 months of age revealed symmetrical signal alteration of the deep white matter. Titer values of IgG antibodies to rhGAA always remained <1:800. The potential role of omalizumab in immune modulation remains to be elucidated; however, this is the first report presenting a ventilator-free survival of a CRIM-negative patient beyond the age of 36 months. The central nervous system (CNS) findings are hypothesized to be part of a yet not fully described CNS phenotype in treated patients with longer survival.     

Mode of delivery after previous obstetric anal sphincter injuries (OASIS)—a reappraisal?

Introduction and hypothesis  To prospectively evaluate anorectal symptoms, quality of life (QoL), sphincter integrity and function after subsequent childbirth following previous obstetric anal sphincter injuries (OASIS). Methods  A validated Manchester Health Questionnaire, endoanal sonography and manometry were performed during the third trimester and 13 weeks postpartum. Women without objective compromise of anal function were recommended a vaginal delivery and the others a caesarean section. Results  Seventy-three consecutive women with previous OASIS were seen during a subsequent pregnancy of whom 59 were reviewed 13 weeks following delivery. Anal manometry findings did not change significantly following a subsequent vaginal delivery or caesarean section. Only one new defect (internal sphincter) occurred after a vaginal delivery. There was no significant change in symptoms or QoL. Three (6.8%) sustained repeat OASIS. Conclusions  Women who have no antenatal evidence of objective compromise of anal sphincter function can be reassured that a vaginal delivery is not associated with any significant deterioration in function or QoL. This paper was presented at the 36th Annual meeting of the International Continence Society in Christchurch, New Zealand and a preliminary abstract is published in: Neurourology Urodynamics 2006;25(6):512–513.     

Lovastatin induces the expression of bradykinin type 2 receptors in cultured human coronary artery endothelial cells

Cardioprotective bradykinin type-2 receptors (BK-2Rs) are downregulated in the myocardial endothelium of both human and rat failing hearts. Statins are cardioprotective drugs that reduce the level of plasma cholesterol but also exert cholesterol-independent pleiotropic effects. Here we examined the effect of lovastatin on BK-2R expression in cultured human coronary artery endothelial cells. The effect of lovastatin on the expression of BK receptors in human coronary artery endothelial cells (HCAECs) was examined by real-time PCR, Western blot analysis and immunocytochemistry. Lovastatin induced a time- and concentration-dependent increase in both BK-2R and BK-1R mRNA expression in the cultured HCAECs. Also, the number of functional BK-2Rs capable of inducing BK-mediated NO production and cGMP signaling was increased in the lovastatin-treated HCAECs. Mevalonate, the direct metabolite of HMG-CoA reductase, reversed the effect of lovastatin. Furthermore, lovastatin inhibited Rho activation and a selective inhibitor of Rho-associated kinases, Y-27632, induced a similar increase in BK-2R expression as lovastatin. In contrast, a specific inhibitor of COX-2, NS398, significantly inhibited the lovastatin-induced expression of BK-2Rs. Here we show for the first time that lovastatin induces the expression of BK-2Rs in cultured human coronary artery endothelial cells through a novel cholesterol-independent pleiotropic mechanism that involves RhoA kinase inhibition and COX-2 activation. Thus, reported beneficial effects of statins in cardiovascular diseases may be partly mediated by an increased expression of cardioprotective BK-2Rs in the endothelial cells of the coronary tree. Moreover, the use of COX-2 inhibitors may affect the level of endothelial BK-2Rs in a negative fashion.     

Reversibility and time-dependency of contrast medium induced inhibition of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) conversion in renal proximal tubular cells in vitro: comparison of a monomeric and a dimeric nonionic iodinated contrast medium

OBJECTIVES: To evaluate the time-course and reversibility of toxicity of a low-osmolar and an iso-osmolar radiographic contrast medium on renal tubular cell cultures. MATERIALS AND METHODS: LLC-PK1-cells were incubated with iomeprol, iodixanol, and mannitol (4.7-75 mg I/mL, 2-24 hours). Metabolic activity was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-(MTT) assay. RESULTS: Iomeprol and iodixanol induced a time- and dose-dependent inhibition of MTT conversion (75%-19% and 70%-23% of control for iomeprol and iodixanol, respectively, at concentrations ranging from 4.7 to 75 mg I/mL after an incubation time of 2 hours and 64%-14% and 65%-12% of control after 24 hours). The mannitol induced inhibition of the MTT conversion was significantly weaker than that induced by iomeprol (99%-47% of control at concentrations corresponding to 4.7-75 mg I/mL after an incubation time of 24 hours, P < 0.001). After 24 hours incubation with iomeprol, iodixanol, or mannitol and a recovery time of 2 hours after removal of the test-solutions, there was only a small inhibition of MTT-conversion (89%, 88%, and 95% of control at 75 mg I/mL). CONCLUSIONS: Contrast medium induced cytotoxicity consisted of a reversible part and an irreversible part. There was no difference in cytotoxicity between iomeprol and iodixanol over a broad range of concentrations and incubation-times.     

The rs1990760 polymorphism within the IFIH1 locus is not associated with Graves' disease, Hashimoto's thyroiditis and Addison's disease

Background  

Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD).