White matter lesions and intra-arterial thrombolysis

The aim of the study was to assess the influence of white matter lesions in patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). From September 2003 to January 2010, we treated 400 patients with IAT at our institution. Of these patients, 292 were evaluated with MRI scans and included in this observational study. Clinical data were collected prospectively. Outcome after 3 months was measured with the modified Rankin Scale (mRS); mRS 0-1 was considered as favorable outcome. White matter lesions were scored visually by two observers using the semiquantitative Scheltens and Fazekas scores. Logistic regression analysis was used to identify the association of white matter lesions and clinical outcome, recanalization, and cerebral hemorrhage. The severity of white matter lesions was inversely correlated with favorable outcome, survival and successful recanalization. White matter lesions were an independent predictor of outcome (OR 0.569, p = 0.007) and survival (OR 0.550, p = 0.018) and a weak but independent predictor for recanalization (OR 0.949, p = 0.038). Asymptomatic intracerebral bleeding after IAT was associated with white matter lesions in the basal ganglia in the univariate analysis (p = 0.036), but not after multivariable analysis. The severity of white matter lesions independently predicts clinical outcome and survival in patients treated with IAT. White matter lesions are also a weak but independent predictor for recanalization. Symptomatic intracranial bleeding after IAT are not associated with white matter lesions. Therefore, white matter lesions should not be considered as a contraindication against IAT.

Microvascular response to shock wave application in striated skin muscle

This study aims to quantify by intravital microscopy the microhemodynamic response after extracorporeal shock wave application (ESWA) to the physiologic microcirculation of the mouse dorsal skinfold chamber.

Hemodynamic effects of exercise training in heart failure

Exercise performance improvement after training in heart failure (HF) can be due to central or peripheral changes.

A comparison of initial antiretroviral therapy in the Swiss HIV Cohort Study and the recommendations of the International AIDS Society-USA

In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS).

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MR imaging (DETECT Trial)

To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol.

Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection

Human systemic antibody responses to commensal microbiota are not well characterised during health and disease. Of particular interest is the analysis of their potential modulation caused by chronic HIV-1 infection which is associated with sustained enteropathy and systemic B cell disturbances reflected by impaired B cell responses and chronic B cell hyperactivity. The mechanisms underlying B cell hyperactivation and the specificities of the resulting hypergammaglobulinaemia are only poorly understood.

Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin

New theories on the regeneration of ischemic vasculature have emerged indicating a pivotal role of adult stem cells. The aim of this study was to investigate homing and hemodynamic effects of circulating bone marrow-derived mesenchymal stem cells (MSCs) in a critically ischemic murine skin flap model. Bone marrow-derived mesenchymal stem cells (Lin(-)CD105(+)) were harvested from GFP(+)-donor mice and transferred to wildtype C57BL/6 mice. Animals receiving GFP(+)-fibroblasts served as a control group. Laser scanning confocal microscopy and intravital fluorescence microscopy were used for morphological analysis, monitoring and quantitative assessment of the stem cell homing and microhemodynamics over two weeks. Immunohistochemical staining was performed for GFP, eNOS, iNOS, VEGF. Tissue viability was analyzed by TUNEL-assay. We were able to visualize perivascular homing of MSCs in vivo. After 4 days, MSCs aligned along the vascular wall without undergoing endothelial or smooth muscle cell differentiation during the observation period. The gradual increase in arterial vascular resistance observed in the control group was abolished after MSC administration (P<0.01). At capillary level, a strong angiogenic response was found from day 7 onwards. Functional capillary density was raised in the MSC group to 197% compared to 132% in the control group (P<0.01). Paracrine expression of VEGF and iNOS, but not eNOS could be shown in the MSC group but not in the controls. In conclusion, we demonstrated that circulating bone marrow-derived MSCs home to perivascular sites in critically ischemic tissue, exhibits paracrine function and augment microhemodynamics. These effects were mediated through arteriogenesis and angiogenesis, which contributed to vascular regeneration.

The role of migration and domestic transmission in the spread of HIV-1 non-B subtypes in Switzerland

By analyzing human immunodeficiency virus type 1 (HIV-1) pol sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the prevalence of non-B subtypes reflects domestic transmission or migration patterns.

Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations

Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence.

Ageing with HIV: medication use and risk for potential drug-drug interactions

To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥ 50 years or <50 years.

No longitudinal mitochondrial DNA sequence changes in HIV-infected individuals with and without lipoatrophy

The potential for mitochondrial (mt) DNA mutation accumulation during antiretroviral therapy (ART), and preferential accumulation in patients with lipoatrophy compared with control participants, remains controversial. We sequenced the entire mitochondrial genome, both before ART and after ART exposure, in 29 human immunodeficiency virus (HIV)-infected Swiss HIV Cohort Study participants initiating a first-line thymidine analogue-containing ART regimen. No accumulation of mtDNA mutations or deletions was detected in 13 participants who developed lipoatrophy or in 16 control participants after significant and comparable ART exposure (median duration, 3.3 and 3.7 years, respectively). In HIV-infected persons, the development of lipoatrophy is unlikely to be associated with accumulation of mtDNA mutations detectable in peripheral blood.

Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death

A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.

Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption

Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B

Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important.

Effect of early antiretroviral therapy during primary HIV-1 infection on cell-associated HIV-1 DNA and plasma HIV-1 RNA

Early initiation of combination antiretroviral therapy (ART) during primary HIV-1 infection may prevent the establishment of large viral reservoirs, possibly resulting in improved control of plasma viraemia rebound after ART cessation.