Treatment of senile maculopathy with etaretin

The results of parenteral treatment with Etaretin in 40 patients (79 eyes) suffering from senile maculopathy are reported. In 84% of the cases there was a degeneration of the dry type and in 16% a disciform exudative maculopathy. The cases of dry maculopathy responded well within a floow-up period of 8 to 18 months.     

Adeno-associated virus-mediated vascular endothelial growth factor gene therapy in skeletal muscle before transplantation promotes revascularization of regenerating muscle

Successful clinical transplantation of whole skeletal muscles can be limited by impaired muscle revascularization and regeneration. The aim of this study was to enhance the revascularization (and hence speed of regeneration) of transplanted whole muscles by transducing muscles with the vascular endothelial growth factor (VEGF) gene before transplantation, using a recombinant adeno-associated virus (rAAV). The rAAV encoding VEGF and green fluorescent protein (GFP) (rAAV.VEGF.GFP) was injected into the tibialis anterior muscles of adult BALB/c mice. One month after injection whole muscle autotransplantation was performed. Muscles were sampled 7 days after autografting. GFP expression was examined as an indicator of persistent transgene expression after grafting, and immunohistochemistry was used to identify VEGF, blood vessels, and newly formed myotubes. After grafting, GFP expression persisted only in a few surviving myofibers in the periphery of rAAV.VEGF.GFP-pretreated muscles, although abundant VEGF expression was seen in myogenic cells in all grafted muscles. Quantitative analysis demonstrated that, although only small numbers of rAAV.VEGF.GFP-transduced myofibers were present, whole muscle grafts preinjected with rAAV.VEGF.GFP were significantly more vascular than saline-injected and uninjected control muscle grafts. Furthermore, rAAV.VEGF.GFP-injected whole muscle transplants were further advanced in terms of regeneration (myotube formation) compared with the uninjected control muscle transplants. This study clearly shows that rAAV-mediated VEGF expression persists only in myofibers that survive the necrosis induced by muscle transplantation; however, this amount of VEGF results in significantly increased revascularization and regeneration of whole muscle transplants.     

Anästhesiologische Risikoevaluation und rechtssichere Aufklärung per Telemedizin – Sind wir bereit für einen Paradigmenwechsel?

Die Anaesthesiologie - In Deutschland werden pro Jahr 17 Millionen Narkosen und damit auch ungefähr so viele Narkosevorgespräche durchgeführt. Bis dato finden diese praktisch...     

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit. Antiarrhythmics Versus Implantable Defibrillator (AVID) Trial Investigators

OBJECTIVES: The goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD). BACKGROUND: Treatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD. METHODS: Data for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated. RESULTS: Factors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 +/- 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 +/- 0.07 (se) years (two-sided p = 0.05). CONCLUSIONS: Patients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.     

HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells

HIV infection is characterized by a brisk immune activation that plays an important role in the CD4 depletion and immune dysfunction of patients with AIDS. The mechanism underlying this activation is poorly understood. In the current study, we tested the hypothesis that this activation is the net product of two distinct pathways: the inflammatory response to HIV infection and the homeostatic response to CD4 T cell depletion. Using ex vivo BrdU incorporation of PBMCs from 284 patients with different stages of HIV infection, we found that CD4 proliferation was better predicted by the combination of CD4 depletion and HIV viral load (R² = 0.375, P < 0.001) than by either parameter alone (CD4 T cell counts, R² = 0.202, P < 0.001; HIV viremia, R² = 0.302, P < 0.001). Interestingly, CD8 T cell proliferation could be predicted by HIV RNA levels alone (R² = 0.334, P < 0.001) and this predictive value increased only slightly (R² = 0.346, P < 0.001) when CD4 T cell depletion was taken into account. Consistent with the hypothesis that CD4 T cell proliferation is driven by IL-7 as a homeostatic response to CD4 T cell depletion, levels of phosphorylated STAT-5 were found to be elevated in naive subsets of CD4 and CD8 T cells from patients with HIV infection and in the central memory subset of CD4 T cells. Taken together these data demonstrate that at least two different pathways lead to immune activation of T cells in patients with HIV infection and these pathways differentially influence CD4 and CD8 T cell subsets.