Objective:To study the feasibility of multimodal neuroimaging in mild to moderate Alzheimer disease (AD) and to estimate the size of possible treatment effects of memantine on potential functional, structural and metabolic biomarkers of disease progression.Methods:In this randomised, double-blind, placebo-controlled pilot study, 36 patients with moderate AD received 52 weeks of memantine (20 mg/day) or placebo. Patients were re-evaluated after 26 and 52 weeks to measure the change from baseline in several outcome measures including global and regional glucose metabolism, total brain and hippocampal volumes, as well as chemical shift imaging-derived global and regional N-acetylaspartate and myoinositol concentrations.Results:In the total population, global glucose metabolism decreased by 2.3% (p<0.01), total brain volume by 2.1% (p<0.001) and hippocampal volume by 2.7% (p<0.01) after 52 weeks. Chemical shift imaging (CSI) spectra were severely affected by patient-induced artefacts and highly variable. Patients receiving memantine showed less decline in glucose metabolism in all brain areas than patients on placebo. Their loss of hippocampal volume was substantially smaller (2.4% vs 4.0%). No between-group differences were seen for changes in total brain volume.Conclusions:The results support the use of multimodal imaging including MRI and positron emission tomography (PET) to monitor the progression of moderate AD. CSI yielded unreliable longitudinal results. The data suggest that memantine has potentially protective effects in AD and they can be used for planning larger confirmatory studies on the cerebral effects of memantine.
Specific clinical symptoms such as spontaneous awakening night pain, cervical pain and tenderness of the SIJs on clinical examination appear useful in screening younger patients with back pain for early SpA.
These results suggest that there are differences between rabbit ATG products. The superior prevention of rejection with thymoglobuline may be the reason for the lower rate of graft arteriosclerosis.
(P < 0AE01) compared with the BM group. The numbers of proven bacterial and viral infections were equally distributed between the three groups. In conclusion, recipients of allogeneic highly purified CD34 + PBSC or unmanipulated BM have higher lymphocyte subset counts at 6 months after transplantation than recipients of autologous CD34-selected PBSC. Infection rates and outcome, however, were not significantly different.Keywords: immune reconstitution, transplantation, purified blood stem cells, bone marrow, children. Lang et al, 2004). T-cell depletion of the graft, however, is known to impair T-cell reconstitution in the recipient, causing post-engraftment immunodeficiency and increased non-relapse mortality (Ochs et al, 1995;Davison et al, 2000).The aim of the present prospective study was to analyse and compare laboratory data of immunity in children receiving unmanipulated allogeneic BM or CD34-selected autologous or allogeneic PBSC.
Patients and methods
Patient characteristicsOver a 7-year period, 61 children were enrolled in this study after informed consent was obtained from parents. Eighteen patients died early after HSCT and could not be evaluated. Seven patients were lost to follow-up. Patients receiving autologous unselected PBSC (n ¼ 2), autologous PBSC + autologous BM (n ¼ 1) and unmanipulated UCB (n ¼ 2) were excluded. The remaining 31 patients (female: n ¼ 9, male: n ¼ 22) were diagnosed with severe aplastic anaemia . These patients underwent a total of 31 single HSCT and were studied with respect to immunological reconstitution. All 31 transplantations were grouped according to the different stem cell source used: autologous CD34-selected PBSC (group 1; n ¼ 10), allogeneic CD34-selected PBSC (group 2; n ¼ 12), and allogeneic unmanipulated BM (group 3; n ¼ 9) for statistical analysis.
Transplantation characteristicsTransplantation characteristics are depicted in Table I. As conditioning regimen patients received busulfan-based (n ¼ 13), total body irradiation (TBI)-based (n ¼ 4) or other high dose chemotherapy-based regimens (n ¼ 13). In one patient, a reduced intensity immunoablative conditioning regimen was used.
Graft manipulationAutologous PBSC were mobilised and harvested according to treatment protocols used. Allogeneic PBSC were mobilised by subcutaneous injection of granulocyte colony-stimulating factor (G-CSF, 5-10 lg/kg body weight/d) once daily for 5 consecutive days. Allogeneic and autologous PBSC were CD34-selected using the CD34 + Progenitor Cell Isolation Kit (Miltenyi Biotec, Bergisch Gladbach, Germany) applying a magnetic cell separation (MACS) technique using the Clini-MACS sorting device (Miltenyi Biotec) according to the manufacturer's instructions. The purity and recovery of the isolated CD34 + cells and the contamination with T-lymphocytes were assessed by flow cytometry. Autologous PBSC were frozen after dilution with a dimethylsulfoxide (DMSO) containing freezing solution using a computerised nitrogen freezer and stored at )193°C in the liquid phase of nitrogen until tran...
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