Hämodynamisches Monitoring bei Einlungenventilation

One-lung ventilation causes adverse effects in pulmonary gas exchange and cardiocirculatory function. These adverse effects become particularly important for patients with underlying cardiopulmonary comorbidities. Alterations in pulmonary gas exchange have been investigated in several experimental and clinical trials. However, the hemodynamic consequences of one-lung ventilation are to a great extent unknown. Furthermore, no conclusive recommendations exist as to which kind of hemodynamic monitoring should be preferred in the situation of one-lung ventilation. Many issues regarding hemodynamic monitoring in one-lung ventilation remain unacknowledged. This article will review the current literature on hemodynamic monitoring in one-lung ventilation in order to derive recommendations for the application of hemodynamic monitoring in this specific peri-operative situation.     

Targeting vascular endothelial growth factor (VEGF)-receptor-signaling in renal cell carcinoma

Metastatic renal cell carcinoma (RCC) is resistant to conventional chemotherapy. Combined data for a variety of immunotherapies resulted in an overall chance of partial (PR) or complete remission (CR) of only 12.9%. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of RCC disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. Von Hippel-Lindau (VHL) gene inactivation is observed in most clear cell renal carcinoma, resulting in vascular endothelial growth factor (VEGF) over-expression and driving the malignant phenotype. This review discusses the efficacy of novel therapies targeting the VEGF receptor (VEGFR) (e.g. anti-VEGF antibodies, VEGFR tyrosine kinase inhibitors, mTOR inhibitors), some of which were recently approved by the Food and Drug Administration/European Medicines Evaluation Agency (FDA/EMEA) and represent the new treatment standards in RCC patients.     

Urachal carcinoma: contemporary surgical outcomes

PURPOSE: We determined surgical outcomes in a contemporary series of patients who underwent surgery for urachal carcinoma. MATERIALS AND METHODS: A cohort of 50 patients with clinically staged localized urachal carcinoma underwent extended partial cystectomy, including the urachal tumor mass and entire urachus. The patients were followed a median of 5+ years for cancer-free survival. RESULTS: Of the 50 patients 93% (26 of 28) with tumor confined to the urachus and bladder survived compared to 69% (9 of 13) with extravesical or peri-urachal tumor invasion and none (9 patients) with tumor invasion into the peritoneal cavity. Local recurrence was noted in 9 patients (18%) and 2 had salvage therapy. The most significant predictors of survival were pathological tumor stage and negative surgical margins. CONCLUSIONS: Wide resection of the tumor mass and entire urachus resulting in negative soft tissue and bladder margins cures the majority of nonmetastatic urachal cancers.     

Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians

BACKGROUND: CNS histamine has been shown to have an inhibitory effect on reward and it is implicated in the etiology of addiction and stress. Histamine N-methyltransferase (HNMT) is believed to be the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common, functional polymorphism, a C314T transition in the HNMT gene, results in a Thr105Ile substitution of the protein encoded. A recent study has shown that the frequency of the Ile105 allele was significantly lower in alcoholics compared to that in non-alcoholics in Finns and Plains American Indians. Following up these results, we tested whether the Thr105Ile polymorphism was associated with alcoholism in German Caucasians. METHODS: Thr105Ile was genotyped in n=366 psychiatrically interviewed German Caucasian ICD-10 lifetime alcoholics, along with n=200 ethnically matched controls. RESULTS: No significant difference was found in the frequency of the Ile105 allele between alcoholics (0.11) and controls (0.10) (chi(2)=0.21, d.f.=1, p=0.647). Likewise, genotype distributions did not differ significantly. However, the frequency of the Ile105 allele was significantly lower in male alcoholics with a family history of alcoholism compared to that in male alcoholics without a family history of alcoholism (chi(2)=4.07, d.f.=1, p=0.044). CONCLUSIONS: In German Caucasians the association of the HNMT Thr105Ile polymorphism with alcoholism was not replicated per se, but a congruent association was found between the Ile105 allele and family history of alcoholism supporting the protective role of the Ile105 allele against alcoholism.     

Avian bornaviruses escape recognition by the innate immune system

Like other pathogens that readily persist in animal hosts, members of the Bornaviridae family have evolved effective mechanisms to evade the innate immune response. The prototype of this virus family, Borna disease virus employs an unusual replication strategy that removes the triphosphates from the 5' termini of the viral RNA genome. This strategy allows the virus to avoid activation of RIG-I and other innate immune response receptors in infected cells. Here we determined whether the newly discovered avian bornaviruses (ABV) might use a similar strategy to evade the interferon response. We found that de novo infection of QM7 and CEC32 quail cells with two different ABV strains was efficiently inhibited by exogenous chicken IFN-α. IFN-α also reduced the viral load in QM7 and CEC32 cells persistently infected with both ABV strains, suggesting that ABV is highly sensitive to type I IFN. Although quail cells persistently infected with ABV contained high levels of viral RNA, the supernatants of infected cultures did not contain detectable levels of biologically active type I IFN. RNA from cells infected with ABV failed to induce IFN-β synthesis if transfected into human cells. Furthermore, genomic RNA of ABV was susceptible to 5'-monophosphate-specific RNase, suggesting that it lacks 5'-triphospates like BDV. These results indicate that bornaviruses of mammals and birds use similar strategies to evade the host immune response.     

An epistasis effect of functional variants on the BDNF and DRD2 genes modulates gray matter volume of the anterior cingulate cortex in healthy humans

Recent evidence suggests that mesolimbic dopaminergic pathways are regulated by the brain derived neurotrophic factor (BDNF). The present study shows that the prominent single nucleotide polymorphisms (SNPs) BDNF Val66Met and DRD2 Taq Ia/ANKK1 exert an epistasis effect on the anterior cingulate cortex (ACC) in 161 healthy Caucasian participants. Carriers with at least one 66Met allele (Val66Met and Met66Met) of the BDNF SNP and one A1 allele (A1/A1 and A1/A2) of the DRD2 SNP are associated with the lowest gray matter volume of the ACC in the current sample. As the smaller gray matter volume of the ACC has been associated with addiction before, this study yields evidence that especially carriers of both allele variants that have been associated with addiction and other psychopathological disorders before might have an increased risk to develop psychiatric symptoms under adverse environmental conditions.