Event-related potentials in people at risk for vascular dementia.

This study examined the relationship between the integrity of cerebrovascular microcirculation, neuropsychological testing and event-related potential indices of cognitive functioning in a nonclinical group of participants being at risk for vascular dementia. Sonographic measures, magnetic resonance (MR) scans and ERPs were recorded in 30 participants treated for arterial hypertension, with no report of neurological or psychiatric disorders. As a sonographic measure of cerebral microcirculation, the arteriorvenous cerebral transit time (cTT) was recorded. While neuropsychological measures of memory functions and general mental ability functions did not show systematic correlations with the cTT and other measures of vascular pathology, a pronounced correlation was obtained between P3a latency and cTT. Participants with long cTT showed a delayed P3a. These findings suggest that the P3a is a sensitive measure for reduced cognitive functions even at early stages of cerebrovascular pathology and by this may be a valuable tool for the early identification of cognitive deficits in individuals being at risk for vascular dementia.     

Oxygenation of Spontaneous Canine Tumors During Fractionated Radiation Therapy*

BACKGROUND AND PURPOSE: Tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. MATERIAL AND METHODS: Tumor oxygen partial pressure (pO(2)) measurements were performed with the Eppendorf-pO(2)-Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO(2) was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). RESULTS: 15/26 tumors had a pretreatment median pO(2) < or = 10 mmHg. The pO(2) values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO(2) of initially hypoxic tumors (pretreatment median pO(2) < or = 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO(2) decreased. CONCLUSION: Hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were < or = 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic.     

111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model.

Transplantation of progenitor cells (PCs) has been shown to improve neovascularization and left ventricular function after myocardial ischemia. The fate of transplanted PCs has been monitored by fluorescence labeling or by genetic modifications introducing reporter genes. However, these techniques are limited by the need to kill the experimental animal. The aim of this study was to radiolabel CD34(+) hematopoietic PCs (HPCs) with (111)In-oxine and to evaluate the feasibility of this in vivo method for monitoring myocardial homing of transplanted cells in a rat myocardial infarction model. METHODS: Human HPCs were isolated from mobilized peripheral blood and labeled with (111)In-oxine. Labeled HPCs were injected into the cavity of the left ventricle in nude rats 24 h after induction of myocardial infarction (n = 4) or sham operation (n = 4). Scintigraphic images were acquired up to 96 h after HPC injection. After animals were killed, tissue samples of various organs were harvested to calculate tissue-specific activity and for immunostaining. RESULTS: Labeling efficiency of HPCs was 32% +/- 11%. According to trypan-blue staining, viability of radiolabeled HPCs was impaired by 30% after 48 and 96 h in comparison with unlabeled cells, whereas proliferation and differentiation of HPCs was nullified after 7 d, as assessed by colony-forming assays. After injection of HPCs, the specific activity ratio of heart to peripheral muscle tissue increased from 1.10 +/- 0.32 in sham-operated rats to 2.47 +/- 0.92 (P = 0.020) in infarcted rats. However, the overall radioactivity detected in the heart was only about 1%. A transient high lung uptake of 17% +/- 6% was observed within the first hour after infusion of HPCs. At 24 h after injection, the initial lung activity had shifted toward liver, kidneys, and spleen, resulting in an increase of radioactivity in these organs from 37% +/- 6% to 57% +/- 5%. CONCLUSION: Radiolabeling with (111)In-oxine is a feasible in vivo method for monitoring transplanted HPCs in a rat myocardial infarction model. The potential to detect differences in myocardial homing between infarcted and normal hearts suggests that this method may provide a noninvasive imaging approach for clinical trials using transplanted HPCs in patients. Our findings, however, also demonstrated a negative effect of (111)In-oxine on cellular function, which resulted in complete impairment of HPC proliferation and differentiation. For future trials in stem cell imaging with (111)In-oxine, therefore, it will be mandatory to carefully check for radiation-induced cell damage.     

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.     

Digital droplet PCR-based absolute quantification of pre-transplant <Emphasis Type="Italic">NPM1</Emphasis> mutation burden predicts relapse in acute myeloid leukemia patients

Allogeneic hematopoietic stem cell transplantation is an established consolidation therapy for patients with acute myeloid leukemia. However, relapse after transplantation remains a major clinical problem resulting in poor prognosis. Thus, detection of measurable (“minimal”) residual disease to identify patients at high risk of relapse is essential. A feasible method to determine measurable residual disease may be digital droplet PCR (ddPCR) that allows absolute quantification with high sensitivity and specificity without the necessity of standard curves. Using ddPCR, we analyzed pre-transplant peripheral blood and bone marrow of 51 NPM1-mutated acute myeloid leukemia patients transplanted in complete remission or complete remission with incomplete recovery. Mutated NPM1 measurable residual disease-positive patients had higher cumulative incidence of relapse (P?<?0.001) and shorter overall survival (P?=?0.014). Restricting the analyses to patients receiving non-myeloablative conditioning, mutated NPM1 measurable residual disease positivity is associated with higher cumulative incidence of relapse (P?<?0.001) and shorter overall survival (P?=?0.006). Positive mutated NPM1 measurable residual disease status determined by ddPCR before allogeneic stem cell transplantation is associated with worse prognosis independent of other known prognostic markers—also for those receiving non-myeloablative conditioning. In the future, mutated NPM1 measurable residual disease status determined by ddPCR might guide treatment and improve patients’ outcomes.     

Exploring Perceived Barriers and Facilitators of PrEP Uptake among Young People in Uganda,Zimbabwe, and South Africa

Archives of Sexual Behavior - Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. Few studies have explored adolescents and young people’s perspectives toward PrEP. We...