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Background: Cancer antigen CA15-3 antigen is known as a valuable marker for the management of breast cancer. Methods: The analytical and clinical performance of the Access® BR Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA15-3 on the Elecsys® System (Roche Diagnostics). Results: Total imprecision (%CV) of the BR Monitor ranged between 5.5% and 11.7%, and inter-laboratory reproducibility between 3.4% and 5.1%. Linearity upon dilution showed a mean recovery of 98.5% (SD±9.1%). Endogenous interferents had no influence on BR Monitor levels (mean recoveries: hemoglobin 112%, bilirubin 111%, triglycerides 108%). There was no high-dose hook effect up to 13,540 kU/L. Clinical performance investigated in sera from 1811 individuals showed a general correlation between the Access BR Monitor and Elecsys CA15-3 (R=0.797), with a slope of 1.383. CA15-3 serum levels, as measured by the BR Monitor, were low in healthy individuals (n=267, median=11.9 kU/L, 95th percentile=23.5 kU/L), higher in individuals with various benign diseases (n=549, medians=11.3–15.6 kU/L, 95th percentiles=21.6–54.6 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=11.2–22.8 kU/L, 95th percentiles=30.0–429.7 kU/L). Best diagnostic accuracy for cancer detection against the relevant benign control group by the BR Monitor was found for locoregional and metastatic breast cancer, as well as for ovarian cancer [area under the curve (AUC) 0.619, 0.897 and 0.774]. Results for the reference CA15-3 assay were comparable (AUC 0.611, 0.887 and 0.818). Conclusions: The Access BR Monitor provides accurate methodological characteristics and demonstrates an analytical and clinical correlation with Elecsys CA15-3. Best diagnostic accuracy for the BR Monitor was found in breast and ovarian cancer. Our results also suggest a clinical value of the BR Monitor in other cancers. Clin Chem Lab Med 2008;46:612–22. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access® GI Monitor assay (Beckman Coulter) was evaluated on the UniCel® DxI 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access® GI Monitor and Elecsys CA19-9 (R=0.959, slope=1.004, intercept=+0.17). GI Monitor serum levels were low in healthy individuals (n=267, median=6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n=550, medians=5.8–13.4 kU/L, 95th percentiles=30.1–195.5kU/L) and even higher in individuals suffering from various cancers (n=995, medians=8.4–233.8 kU/L, 95th percentiles=53.7–13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer [area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access® GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers. Clin Chem Lab Med 2008;46:600–11. [ABSTRACT FROM AUTHOR]

Background: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. Methods: The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD+8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycerides 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R=0.982, slope=0.921, intercept=+1.951). OV Monitor serum levels were low in healthy individuals (n=267, median=9.7 kU/L, 95th percentile=30.8 kU/L), higher in individuals with various benign diseases (n=549, medians=10.9–16.4 kU/L, 95th percentiles=44.2–355 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=12.4–445 kU/L; 95th percentiles=53.4–4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer [area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). Conclusions: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers. Clin Chem Lab Med 2008;46:588–99. [ABSTRACT FROM AUTHOR]

The role of attention in generating motor memories remains controversial principally because it is difficult to separate the effects of attention from changes in kinematics of motor performance. We attempted to disentangle attention from performance effects by varying attention while plasticity was induced in human primary motor cortex by external stimulation in the absence of voluntary movement. A paired associative stimulation (PAS) protocol was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single-pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the right abductor pollicis brevis muscle (APB) to generate near-synchronous events in the left primary motor cortex. In experiment 1, the spatial location of attention was varied. PAS failed to induce plasticity when the subject's attention was directed to their left hand, away from the right target hand the cortical representation of which was being stimulated by PAS. In experiment 2, the grade of attention to the target hand was manipulated. PAS-induced plasticity was maximal when the subject viewed their target hand, and its magnitude was slightly reduced when the subject could only feel their hand. Conversely, plasticity was completely blocked when the subject's attention was diverted from the target hand by a competing cognitive task. A similar modulation by attention was observed for PAS-induced changes in the duration of the silent period evoked by TMS in voluntarily contracted muscle. Associative plasticity in the human motor cortex depends decisively on attention. [ABSTRACT FROM AUTHOR]

β-Amyloid deposits, hallmarks of Alzheimer’s disease, contain both sugar-derived ‘advanced glycation end products’ (AGEs) and copper and iron ions. Our in vitro experiments using synthetic β-amyloid peptide and glucose or fructose show that formation of covalently cross-linked high-molecular-mass β-amyloid peptide oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions. Formation of these covalent AGE cross-links can be inhibited by capping agents of amino groups, redox-inactive metal chelators and antioxidants, suggesting that these drugs may be able to slow down the formation of insoluble β-amyloid deposits in vivo and possibly the progression of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Paired associative stimulation (PAS) refers to a paradigm consisting of slow-rate repetitive low-frequency median nerve stimulation combined with transcranial magnetic stimulation (TMS) over the contralateral motor cortex. This protocol has been shown to induce plastic changes of excitability in the human motor cortex. Its principles of design were shaped after associative long-term potentiation (LTP) in experimental animals, a cellular mechanism likely to be relevant for learning and memory. PAS-induced changes of cortical excitability share a number of physiological properties with LTP. Of particular importance is the fact that the sign of PAS-induced changes of the size of amplitudes of the motor evoked potentials (MEPs) depends on the exact interval between the afferent and the magnetic pulse during the intervention. A number of observations suggest that PAS-induced excitability changes may have functional significance. PAS-induced plasticity may contribute to elucidating the pathogenesis of neurological disorders where neuroplasticity is thought to have a pathogenetic role. Finally, PAS-induced plasticity may itself have therapeutic potential.