Susumu Satô

BACKGROUND: Data from the human motor cortex suggest that, depending on polarity, direct current (DC) brain polarization can depress or activate cortical neurons. Activating effects on the frontal lobe might be beneficial for patients with frontal lobe disorders. This phase 1 study tested the safety of frontal DC, including its effects on frontal and other brain functions. METHODS: The authors applied 20 minutes of anodal, cathodal, or sham DC to the left prefrontal cortex in three groups of right-handed subjects and looked for effects on global measures of processing and psychomotor speed, emotion, and verbal fluency, a measure of local cortical function. In one experiment (n = 30), the authors tested before and after 1 mA DC and monitored EEG in 9 subjects. In two other experiments using 1 mA (n = 43) and 2 mA (n = 30), the authors tested before and then starting 5 minutes after the onset of DC. RESULTS: All subjects tolerated DC well. There were no significant effects on performance with 1 mA DC. At 2 mA, verbal fluency improved significantly with anodal and decreased mildly with cathodal DC. There were no clinically significant effects on the other measures. CONCLUSIONS: Limited exposure to direct current polarization of the prefrontal cortex is safe and can enhance verbal fluency selectively in healthy subjects. As such, it deserves consideration as a procedure to improve frontal lobe function in patients.

Abstract The fluorescence yield of europium chelates in several solutions varies, through its maximum value, with the increase in the energy difference between the triplet state of a ligand and the emitting level of an europium ion. The time-resolved spectroscopic measurements show that the excitation energy is transferred from the triplet state to the lower and nearest resonance level of the europium ion. The intramolecular energy transfer mechanisms for europium chelates and terbium chelates are proposed, taking the resonance exchange interaction and the thermal deactivation processes from the emitting levels of rare earth ions into consideration. Steady-state rate equations are made, and the equation of the fluorescence yield is obtained. Thus, the relations between the fluorescence yield and the triplet state energy are estimated and the fluorescence properties of rare earth β-diketone chelates may be qualitatively described.

In this study, we analyzed the relationships of exercise capacity and health status to mortality in patients with chronic obstructive pulmonary disease (COPD). We recruited 150 male outpatients with stable COPD with a mean postbronchodilator FEV1 at 47.4% of predicted. Their pulmonary function, progressive cycle ergometry, and health status using the Chronic Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire (SGRQ), and the Breathing Problems Questionnaire were measured at entry. Among 144 patients who were available for the 5-year follow-up, 31 had died. Univariate Cox proportional hazards analysis revealed that the SGRQ total score and the Breathing Problems Questionnaire were significantly correlated with mortality; however, with the Chronic Respiratory Disease Questionnaire, the total score was not significantly correlated. Multivariate Cox proportional hazards analysis revealed that the peak oxygen uptake and the SGRQ total score were both predictive of mortality, independent of FEV1 and age. Stepwise Cox proportional hazards analysis revealed that the peak oxygen uptake was the most significant predictor of mortality. We found that exercise capacity and health status were significantly correlated with mortality, although different health status measures had different abilities to predict mortality. These results will have a potentially great impact on the multidimensional evaluation of disease severity in COPD.

BACKGROUND: Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations in a copper-transport gene, ATP7A. Early treatment with copper injections may prevent death and illness, but presymptomatic detection is hindered by the inadequate sensitivity and specificity of diagnostic tests. Exploiting the deficiency of a copper enzyme, dopamine-beta-hydroxylase, we prospectively evaluated the diagnostic usefulness of plasma neurochemical levels, assessed the clinical effect of early detection, and investigated the molecular bases for treatment outcomes. METHODS: Between May 1997 and July 2005, we measured plasma dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol in 81 infants at risk. In 12 newborns who met the eligibility criteria and began copper-replacement therapy within 22 days after birth, we tracked survival and neurodevelopment longitudinally for 1.5 to 8 years. We characterized ATP7A mutations using yeast complementation, reverse-transcriptase-polymerase-chain-reaction analysis, and immunohistochemical analysis. RESULTS: Of 81 infants at risk, 46 had abnormal neurochemical findings indicating low dopamine-beta-hydroxylase activity. On the basis of longitudinal follow-up, patients were classified as affected or unaffected by Menkes disease, and the neurochemical profiles were shown to have high sensitivity and specificity for detecting disease. Among 12 newborns with positive screening tests who were treated early with copper, survival at a median follow-up of 4.6 years was 92%, as compared with 13% at a median follow-up of 1.8 years for a historical control group of 15 late-diagnosis and late-treatment patients. Two of the 12 patients had normal neurodevelopment and brain myelination; 1 of these patients had a mutation that complemented a Saccharomyces cerevisiae copper-transport mutation, indicating partial ATPase activity, and the other had a mutation that allowed some correct ATP7A splicing. CONCLUSIONS: Neonatal diagnosis of Menkes disease by plasma neurochemical measurements and early treatment with copper may improve clinical outcomes. Affected newborns who have mutations that do not completely abrogate ATP7A function may be especially responsive to early copper treatment. (ClinicalTrials.gov number, NCT00001262.)