"Silent" lacunar stroke, often found in the elderly, has been proposed as a predisposing condition for clinically overt stroke. However, the risk factors related to this condition have not been studied thoroughly. We conducted brain magnetic resonance imaging and measured the levels of fibrinogen, molecular markers of coagulation activation [prothrombin fragment 1 + 2 (F1 + 2)] and endothelial cell damage [von Willebrand factor (vWF) and thrombomodulin], and lipid profiles including lipoprotein (a) [Lp(a)] in 178 asymptomatic, high-risk, Japanese subjects aged 44 to 93 years. We also studied 32 symptomatic patients with lacunar stroke (symptomatic lacunar group). The prevalence of silent lacunar stroke increased with age up to 85 years but decreased with age in those 85 years old and older. Of the 160 elderly subjects ( > or = 60 years) 84 (53%) had > or = 1 lacunar infarcts (silent lacunar group) and the remaining 76 were considered as the nonlacunar group. Fibrinogen and F1 + 2 levels in the silent lacunar group were significantly higher than those in the nonlacunar group (P < .01). Mean Lp(a) levels and the prevalence of subjects with an Lp(a) level > 30 mg/dL were significantly higher in the symptomatic lacunar group than the nonlacunar group (P < .05), whereas these levels in the silent lacunar group were intermediate to those of the other two groups. When we further classified the silent lacunar group into three subgroups based on the number of lacunes (few lacunes, 1 or 2; moderate number of lacunes, 3 or 4; and numerous lacunes, > or = 5), levels of Lp(a), F1 + 2, vWF, and thrombomodulin were significantly higher and Lp(a) levels > 30 mg/dL more common in the numerous-lacune than in the few-lacune subgroup. We conclude that silent lacunar stroke is often found in asymptomatic, high-risk, elderly Japanese patients and that silent multiple lacunar stroke is associated with hypercoagulability, endothelial cell damage, and high Lp(a) levels.

To investigate the etiology of the age-related decrease in hemoglobin (Hb) concentration, we measured serum erythropoietin (EPO), serum iron, total iron binding capacity, and serum ferritin levels in 247 elderly subjects aged 60-99 years. EPO levels were determined by radioimmunoassay. An age-related increase in the serum EPO concentration (r = 0.220; P < 0.01) and a significant inverse relationship between EPO and Hb concentrations were found in normal elderly subjects without anemia (r = -0.302; P < 0.001), but not in 111 younger controls. Serum EPO levels were slightly higher in elderly subjects with pre-anemic iron deficiency than in the normal elderly subjects (P < 0.05). These results suggest that the EPO secretion is accelerated in the elderly even though the Hb remains above 12.0 g/dl, probably as a compensatory mechanism for peripheral tissue hypoxia. An inverse relationship between the EPO and Hb concentrations was found in the elderly subjects with iron deficiency anemia, but not in those with unexplained senile anemia. The changes of EPO levels were also assessed in 20 elderly subjects who had developed anemia when reviewed after 12 months. Serum EPO levels increased in relation to the decrease in Hb concentration in those with iron deficiency anemia, but not in those with unexplained senile anemia. Reduced EPO secretion thus seems to play a role in the progression of unexplained senile anemia, and recombinant human EPO may possibly be effective for treating this type of anemia by mobilizing excess iron.

SummaryTo study the mechanism underlying the high lipoprotein (a) [Lp(a)] level in uremic patients on chronic hemodialysis, we investigated the levels of Lp(a), acute phase reactants (C-reactive protein and sialic acid), and interleukin-6 (IL-6) in 54 dialysis patients. The mean [95% Cl] Lp(a) level was increased in the hemodialysis patients compared with the 30 controls (30 [25-36] vs. 18 [14-23] mg/dl, p <0.005). Among dialysis patients, 46% had an Lp(a) level >30 mg/dl, which was significantly higher than the percentage in the control group (17%). The levels of C-reactive protein, sialic acid, and IL-6 were also increased in dialysis subjects compared with controls (200 [134-299] vs. 37 [24-58] μg/dl, p <0.0001; 63 [59-66] vs. 54 [52-56] mg/dl, p <0.002; and 9.2 [7.8-11] vs. 5.5 [5.0-6.1]pg/ml, p <0.0005, respectively). The Lp(a) level was positively correlated with that of C-reactive protein (r = 0.415, p <0.002), sialic acid (r = 0.426, p <0.002), and IL-6 (r = 0.298, p<0.05) in the hemodialysis patients, but not in the controls or non-dialysis uremic patients. The Lp(a) level in the dialysis patients was also positively correlated with activation markers of coagulation (thrombin-antithrombin III complex and plasmin-α2-plasmin inhibitor complex, p <0.005). These results indicate that the Lp(a) level is closely related to the acute phase reaction and hypercoagulability in chronic hemodialysis patients.

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In order to elucidate the mechanisms of fluoroquinolone resistance in Enterococcus faecium, spontaneous mutants isolated from Ent. faecium ATCC 19434 by stepwise selection with sparfloxacin (SPX) or norfloxacin (NOR) and 13 clinical isolates of Ent. faecium were characterized by analysing quinolone-resistance-determining regions (QRDRs) of the gyrA, gyrB, parC and parE genes and examining changes in MICs of SPX and NOR in the presence of efflux pump inhibitors. The SPX-selected first-step mutant had a point mutation only in gyrA, and the mutants QR7-18 and QR7-39, and clinical isolates that had point mutations in parC, showed NOR resistance. These results indicate that the primary targets of SPX and NOR are DNA gyrase and topoisomerase IV, respectively, and therefore that the primary target of fluoroquinolones in Ent. faecium differs depending on the structure of the compound used. The characterization of the spontaneous mutants and the clinical isolates demonstrates that in addition to the previously reported alterations in GyrA and ParC, an alteration in GyrB, a NorA-like pump, an unknown efflux pump, which excretes both SPX and NOR from bacterial cells, and probably other unknown mechanism(s) all contribute to fluoroquinolone resistance in Ent. faecium.