Background: The purpose of the present paper was to elucidate the influence of an elevated serum lipoprotein (a) (Lp(a)) concentration on the incidence of ischemic heart disease (IHD) and ...perforating artery occlusion‐type cerebral infarction (CI) in elderly patients with type‐2 diabetes.
Methods: The serum Lp(a) levels in type‐2 diabetic subjects aged ≥60 years (n = 158; 81 male, 77 female) were measured. At the commencement of the study, subjects were allocated on the basis of past history of CI to a CI– or CI+ group, and on the basis of past history of angina pectoris or myocardial infarction to an IHD– or IHD+ group. They were followed up prospectively for 4 years and the incidences of IHD and CI were monitored. Diagnoses of CI were confirmed by computed tomography (CT), and of myocardial infarction by electrocardiography and blood chemistry. Serum Lp(a) levels of ≥ 20 mg/dL were considered elevated, and < 20 mg/dL as normal. Kaplan–Meier survival analysis (log–rank test) was used to assess the time to event rate stratified by an Lp(a) cut‐off of 20 mg/dL. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis.
Results: The probability of IHD events was significantly higher in the elevated Lp(a) group than in the normal Lp(a) group without a history of IHD (P < 0.001; log–rank test), but was similar in the two subgroups of subjects with a history of IHD. No significant difference was seen between the elevated Lp(a) and normal Lp(a) groups in the probability of CI events, with or without a history of CI. On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of IHD were significant predictors of IHD, whereas hypertension, hyperlipidemia and a history of CI were significant predictors of CI.
Conclusion: These results indicate that an elevated serum Lp(a) concentration is an independent risk factor for IHD, but not for perforating artery occlusion‐type CI, in elderly patients with type‐2 diabetes.
Abstract To examine the relationship between the concentrations of urinary NAG and age, we measured ratios of urinary N-acetyl-β-D-glucosaminidase (NAG) to urinary creatinine (NAG index) in 137 ...healthy subjects, aged from 19 to 88 years. The study is also designed to evaluate the relationship between urinary NAG and blood pressure. The subjects were divided into 7 subgroups, according to their age (< 30, 30-39, 40-49, 50-59, 60-69, 70-79, 80 or more years). There was a positive correlation between NAG index and age (r=0.36 ; P<0.001). The regression equation relating NAG index (y) to age (x) was y=0.065x+0.97. The mean NAG indexes for the 7 subgroups divided by age were significantly different (P<0.01). There was a positive correlation between NAG index and systolic blood pressure (r=0.18 ; P<0.05), but was not between diastolic blood pressure and NAG index. In multiple regression analysis, age and BUN significantly correlated with NAG index (r=0.32 ; P<0.01, r=3.3 ; P=0.07, respectively), although there was no correlation between systolic blood pressure and NAG index. This cross-sectional study showed a clear elevation in NAG index with age. The rate of elevation was 0.65 per decade. Urinary excretion of NAG may be unrelated to blood pressure. (J Nippon Med Sch 1999;66:33-36)
Diabetic nephropathy is the major cause of death in diabetes mellitus. Once diabetic nephropathy is well established attempts to modify the relentless pro-gression of the disease have been ...essentially unsuc-cessful. Thus, indicators are needed to identify the early structural and functional changes of diabetic nepbropathy which may be reversed by strict blood glucose control. A growing body of evidence reveals that a persistent elevation of urinary albumin excretion (microalbuminuria) in diabetic patients without clinical proteinuria predicts future development of overt diabetic nephropathy1. N-acetyl-β-D-glucosaminidase (NAG) is a widely distributed lysosomal enzyme, located predominantly in the renal proximal tubules and is normally not filtered at the glomerulus2. NAG has been shown to be in-creased in the urine of patients with various renal dis-eases3 including diabetic nephropathy4. Some studies in diabetic patients have also shown that the elevation of urinary NAG is an early predictor of the development of diabetic nephropathy5-8. In addition, ratios of urinary NAG to urinary creatinine (NAG index) for random specimens provides a useful, convenient measurement of daily NAG excretion and avoids many of the problems of 24-hour collections . However, some crosssectional studies have demonstrated that urinary NAG activity may reflect metabolic control for patients with diabetes mellitus. The aim of the present study was to examine whether any correlation exists between the concen-trations of urinary NAG and control of longterm blood glucose in elderly type 2 diabetes mellitus.
Glucose tolerance is known to decrease with advancing age. Spence1 in 1920 was the first to document that the glucose metabolism was impaired in subjects over the age of 60 yr. Since this initial ...obser-vation, numerous reports have appeared showing that glucose tolerance declines as a function of age. The decline begins in the third or fourth decade of life and continues through the entire adult life span2. This age-related decline in the glucose metabolism appears to have only a small effect on the fasting plasma glucose concentration, which rises by 1 mg dl per decade. On the other hand, following oral glucose ingestion, the lh plasma glucose response has been shown to increase by 4～14 mg dl (mean=9 mg) per decade and the 2h plasma glucose value by 1～11 mg dl (mean=5 mg dl) per decade3. Therefore, two-thirds of elderly dia-betic patients have postchallenge hypergylcemia during oral glucose tolerance tests without fasting hyper-glycemia. Some investigators say that elderly type 2 diabetic patients with fasting hyperglycemia also have increased postprandial hyperglycemia relative to their younger counterparts4. But, whether or not this is true remains to be proven. Daily blood glucose profiles were measured in 98 type 2 diabetic patients treated with diet alone. The subjects were divided into two groups according to whether they were<65 years old (middle-aged group, mean age; 54.7 ± 8.3 y old) or≧65 years old (elderly group, mean age; 72.8 ± 5.7 y old). They were consid-ered to have overt diabetes only if their fasting plasma glucose concentrations were greater than 126 mg dl on 2 separate occasions5. All patients were admitted to our hospital and were prescribed a weight-maintaining diet (25 ～ 30 kcal/kg standard body weight).
Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of the immune system. We describe a new mouse model of spontaneous autoimmune disease. Activation-induced cytidine ...deaminase-linked autoimmunity (aida) mice harbor a loss-of-function mutation in the gene encoding lymphocyte activation gene 3 (LAG-3), an inhibitory co-receptor. Although LAG-3 deficiency alone did not induce autoimmunity in nonautoimmune-prone mouse strains, it induced lethal myocarditis in BALB/c mice deficient for the gene encoding the inhibitory co-receptor programmed cell death 1 (PD-1). In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.
The accurate and prompt diagnosis of SARS-CoV-2 infection is required for the control and treatment of the coronavirus infection disease 2019 (COVID-19). In this study, we aimed to investigate the ...time courses of the anti-severe acute corona respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM and IgG titers and to evaluate the sensitivity and specificity of such tests according to the specific day after the onset of COVID-19 among a patient population in Japan. We measured the titers of SARS-CoV-2 IgM and IgG in sera from 105 subjects, including 26 symptomatic COVID-19 patients, using chemiluminescent immunoassay (CLIA) methods utilizing magnetic beads coated with SARS-CoV-2 nucleocapsid protein and spike protein. The results of a ROC analysis suggested the possibility that the cutoff values in Japan might be lower than the manufacturer's reported cutoff (10 AU/mL): 1 AU/mL for IgM and 5 AU/mL for IgG. The sensitivity of the test before Day 8 after symptom onset was less than 50%; at Days 9-10, however, we obtained a much higher sensitivity of 81.8% for both IgM and IgG. At 15 days or later after symptom onset, the SARS-CoV-2 IgG test had a sensitivity of 100%. These results suggest that if the number of days since disease onset is taken into consideration, these antibody tests could be very useful for the diagnosis of COVID-19 and similar diseases.
Difficult-to-treat infections caused by rapidly growing mycobacteria (RGM) are increasingly observed in clinical settings. However, studies on antimicrobial susceptibilities and effective treatments ...against RGM in Japan are limited.
We conducted susceptibility testing of potential antimicrobial agents, including tigecycline and tebipenem, against RGM. Clinical RGM isolates were collected from a university hospital in Japan between December 2010 and August 2013. They were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the sequencing of 16S rRNA, rpoB, and hsp65 genes. The samples were utilized for susceptibility testing using 16 antimicrobials, with frozen broth microdilution panels.
Forty-two isolates were obtained: 13, Mycobacterium abscessus complex; 12, Mycobacterium chelonae; 9, Mycobacterium fortuitum; and 8, M. fortuitum group species other than M. fortuitum. Different antimicrobial susceptibility patterns were observed between RGM species. Clarithromycin-susceptible strain rates were determined to be 0, 62, and 100% for M. fortuitum, M. abscessus complex, and M. chelonae, respectively. M. abscessus complex (100%) and >80% M. chelonae isolates were non-susceptible, while 100% M. fortuitum group isolates were susceptible to moxifloxacin. Linezolid showed good activity against 77% M. abscessus complex, 89% M. fortuitum, and 100% M. chelonae isolates. Regardless of species, all tested isolates were inhibited by tigecycline at very low minimal inhibitory concentrations (MICs) of ≤0.5 μg/mL. MICs of tebipenem, an oral carbapenem, were ≤4 μg/mL against all M. fortuitum group isolates.
Our study demonstrates the importance of correct identification and antimicrobial susceptibility testing, including the testing of potential new agents, in the management of RGM infections.
Vancomycin is a widely used clinical drug to treat for infection by methicillin-resistant Staphylococcus aureus. Some patients show a weak response to vancomycin treatment. We previously reported ...that β-lactams increase the susceptibility to vancomycin by vancomycin-highly resistant S. aureus (VRSA) strains obtained following repeated in vitro mutagenesis and vancomycin selection. Here we found that the susceptibility of the VRSA strains to vancomycin was remarkably increased by combined treatment with D-cycloserine. On the other hand, VRSA did not show increased susceptibility to vancomycin in combination with bacitracin, fosfomycin, erythromycin, lincomycin, gentamicin, levofloxacin or nisin. Furthermore, in an in vivo infection model with silkworms, combined treatment with vancomycin and D-cycloserine exhibited therapeutic effects, whereas treatment with each compound alone did not. These findings suggest that combined treatment with vancomycin and D-cycloserine could be therapeutically effective against infectious diseases caused by VRSA.
Bacillus cereus is one of the pathogens causing nosocomial bloodstream infections (BSIs). However, few reports have documented the antimicrobial susceptibility and clinical characteristics of ...Bacillus cereus BSI and the importance of empirical therapy. The aim of this study was to investigate the clinical characteristics and antimicrobial susceptibility of B. cereus isolates from patients with BSI and to analyze the impact of appropriate empirical therapy on the outcome of patients with B. cereus BSI.
All adult cases of bacteremia between April 2003 and March 2012 in a teaching hospital in Tokyo, Japan were reviewed retrospectively. Clinical data were collected from the patients' medical records and charts. Antimicrobial susceptibility testing was performed by broth microdilution method. The patients with B. cereus BSI were divided into an appropriate empirical therapy group and an inappropriate empirical therapy group. The primary outcome was all-cause mortality at 4 weeks after the start of BSI. The secondary outcome was early defervescence within 2 days after starting empirical therapy.
There were 29 B. cereus bloodstream infection cases. No vancomycin, gentamicin, and imipenem-resistant isolates were found. However, 65.5 % were resistant to clindamycin and 10.3 % were resistant to levofloxacin. The main etiology was venous catheter-related (69 %). All-cause mortality at 4 weeks was not significantly different between the appropriate empirical therapy group (9 cases) and the inappropriate group (20 cases) in this study. However, early defervescence within 2 days after starting empirical therapy was significantly different (p = 0.032).
The BSI of B. cereus is mostly caused by venous catheter-related infections. Appropriate empirical therapy is important to achieve early clinical resolution in B. cereus BSI. Vancomycin is one of the appropriate selections of empirical therapy for B. cereus BSI.
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