Cellular immunity of patients with malignant glioma: prerequisites for dendritic cell vaccination immunotherapy

OBJECT: Vaccination therapy that uses dendritic cells (DCs) is a promising immunotherapeutic approach. However, it relies on intact cellular immunity and efficient generation of mature DCs, both of which can be impaired in patients with glioma. Therefore, the immune status and ex vivo generation of DC in such patients were studied. METHODS: The frequencies of white blood cell subsets and monocyte-derived, mature DCs in patients with high-grade gliomas and healthy control volunteers were analyzed using flow cytometry. In the patients, frequencies of lymphocytes, T cells, and B cells were reduced in comparison with the volunteers in the control group, whereas frequencies of neutrophils and monocytes were increased. There were no differences between the two groups in terms of white blood cell counts or the frequency of NK cells and the major T-cell subsets. The responsiveness of T cells to lectin stimulation was normal. For monocytes, lower frequencies of CD80+ and CD86+ cells but not of CD40+ and HLA-DR+ cells were observed in patients. Ex vivo DC generation in a two-step culture protocol in autologous plasma-supplemented medium or in serum-free medium showed only minor differences in CD80 and HLA-DR expression between the patient and control groups. Frequencies of CD83+, CD1a+, CD14-, CD40+, and CD86+ cells were comparable. Overall, the serum-free medium was superior to the plasma-supplemented medium and allowed efficient ex vivo generation of CD83+, CD1a+, and CD14- mature DCs. CONCLUSIONS: Only minor defects in the immune status of patients with glioma were observed, which probably would not hamper immunotherapy. Mature DCs can be generated successfully in normal numbers and with typical immunophenotypes from monocytes of patients with glioma, particularly under serum-free conditions.     

Doppler echocardiography description of diastolic function disorder in terminal renal failure--new characterization of uremic cardiomyopathy

In order to characterize left ventricular diastolic filling abnormalities in uremic cardiomyopathy in 50 patients on hemodialysis, the ratio VE/VA of peak early (VE) and late (VA) filling velocity was calculated using CW-Doppler echocardiography. Compared with normal subjects of identical age, VE/VA was found to be significantly lower in patients younger than 40 years, but without, however, significant differences in patients aged 40-60 years and older than 60. Thus, the incidence of diminished VE/VA-ratios fell from 64% in patients younger than 40 years to 5% in patients older than 60. Whereas duration of dialysis, extent of renal anemia and interdialytic volumeload showed no influence, diastolic malfunction was correlated to renal hypertension. Therefore, an actualized characterization of uremic cardiomyopathy can be achieved by CW-Doppler echocardiography, describing diastolic malfunction in most patients with terminal renal failure. In elderly patients, however, a distinction from physiologic alteration of diastolic filling is not possible. Clinical significance of diastolic malfunction is characterized by reduced tolerance of interdialytic volume-expansion, as well as intradialytic volume-depletion.     

Evidence for direct impairment of neuronal function by subarachnoid metabolites following SAH

Dysfunction of neuronal signal processing and transmission occurs after subarachnoid hemorrhage (SAH) and contributes to the high morbidity and mortality of this pathology. The underlying mechanisms include early brain injury due to elevation of the intracranial pressure, disruption of the blood–brain barrier, brain edema, reduction of cerebral blood flow, and neuronal cell death. Direct influence of subarachnoid blood metabolites on neuronal signaling should be considered. After SAH, some metabolites were shown to directly induce disruption of neuronal integrity and neuronal signaling, whereas the effects of other metabolites on neurotoxicity and neuronal signaling have not yet been investigated. Therefore, this mini-review will discuss recent evidence for a direct influence of subarachnoid blood and its metabolites on neuronal function.