Breathing Irregularity Is Independently Associated With the Severity of Obstructive Sleep Apnea in Patients With Multiple System Atrophy.

STUDY OBJECTIVES: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the combination of cerebellar ataxia, parkinsonism, and autonomic disturbance. Patients with MSA frequently have sleep-disordered breathing. In some patients with MSA, central sleep apnea manifests during the disease's natural course or as a treatment effect. Breathing instability may be involved in the development of obstructive sleep apnea (OSA); therefore, we investigated whether breathing instability affects the severity of OSA in patients with MSA. METHODS: Patients with MSA and a control group of individuals who were matched for age, body mass index (BMI), and supine apnea-hypopnea index (AHI) were recruited. Breathing instability was evaluated by using polysomnography to determine the irregular pattern with approximate entropy (ApEn) of chest respiratory movements during wakefulness before sleep onset. The ApEn values were compared between the groups. The severity of OSA was evaluated with background parameters and ApEn values by regression analysis. RESULTS: Twenty patients with MSA (9 men; mean age, 61 years; BMI, 24.1 kg/m2; supine AHI, 37.9 events/h) were compared to the control group. The ApEn values were higher in the patients with MSA than those in the control group (1.28 versus 1.11; P < .05). Multiple regression analysis showed that supine AHI was associated with ApEn values but not with BMI in patients with MSA and associated with BMI but not with ApEn values in the individuals in the control group. CONCLUSIONS: Patients with MSA had more breathing irregularity. In patients with MSA, breathing instability may be a more influential factor for OSA than BMI. COMMENTARY: A commentary on this article appears in this issue on page 1641.

Continuous Reduction of Protein-Bound Uraemic Toxins with Improved Oxidative Stress by Using the Oral Charcoal Adsorbent AST-120 in Haemodialysis Patients.

Accumulation of protein-bound uraemic toxins (PBUTs) is one of the reasons for the development of uraemia-related complications including cardiovascular disease; however, conventional haemodialysis is limited in its ability to remove PBUTs. We aimed to examine whether the oral charcoal adsorbent AST-120 has an additive effect on PBUT removal in haemodialysis patients. During the 4-week study, anuric patients undergoing haemodialysis received AST-120 (6 g/day) in the last 2 weeks (n = 10) or the first 2 weeks (n = 10). Serum levels of total and free PBUTs such as indoxyl sulfate, p-cresyl sulfate, and phenyl sulfate at the pre- and postdialysis sessions were measured before and after AST-120 use and after discontinuation. Levels of the oxidative stress markers oxidized albumin and 8-isoprostane were also measured. AST-120 use induced dramatic reduction of indoxyl sulfate (total, 45.7% [33.2-50.5%]; free, 70.4% [44.8-79.8%]), p-cresyl sulfate (total, 31.1% [25.0-48.0%]; free, 63.5% [49.3-70.9%]), and phenyl sulfate (free, 50.6% [32.3-71.2%]) levels; however, this effect disappeared after the discontinuation of AST-120. AST-120 use also induced substantial reduction of the oxidized albumin and 8-isoprostane levels. In conclusion, oral administration of AST-120 had additive effects on the continuous reduction of some PBUTs in anuric patients undergoing haemodialysis.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2012].

The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.

Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis.

BACKGROUND: We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. METHODS: We selected 394 individuals (169 males and 225 females) who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. RESULTS: The multivariate-adjusted model showed that age (odds ratio (OR), 1.034; 95% confidence interval (95%CI), 1.010 - 1.059), HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225), and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051) were significant variables that could independently predict the risk of new carotid artery atherosclerosis. CONCLUSION: The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

[Results of antifungal susceptibility testing of Candida species and trends of antifungal use in Niigata university medical and dental hospital].

The accuracy of antifungal susceptibility testing is important for the clinical management of patients with serious infections due to fungus. Our primary objective was to analyze the results of antifungal susceptibility testing of Candida species performed at Niigata University Medical and Dental Hospital and usage of antifungal agents. Antifungal susceptibility testing was performed by the CLSI M27-A2 method. Yeast-like fungi were isolated from 6% of 6,730 samples. All isolates were Candida species, i.e., C. albicans (50%), C. parapsilosis (28%), C. guilliermondii (9%), C. krusei (5%), C. glabrata (4%), and C. tropicalis (4%). The results of the minimum inhibitory concentration that inhibits 90% of the strain tested (MIC90) were 1 microg/mL for fluconazole, 0.5 microg/mL for miconazole, 0.06 microg/mL for itoraconazole, < or = 0.03 microg/mL for micafungin, respectively. The results of non-albicans species were 32 microg/mL for fluconazole, 8 microg/mL for miconazole, 0.5 microg/mL for itoraconazole, 1 microg/mL for micafungin, respectively. All Candida species were susceptible to the available antifungal agents, except C. krusei that was resistant to fluconazole. Thus, antifungal susceptibility varies greatly according to fungal species. The accuracy of identification of the fungus and antifungal susceptibility would contribute to the proper management of patients with serious fungal infections.

Hypertension is a major risk factor for future atherosclerotic changes in the Japanese population.

BACKGROUND: Great differences in age-standardized mortality rates by cardiovascular disease exist among countries. We prospectively assessed determinants of future cardiovascular changes in a Japanese cohort. METHODS: In 1996, 1011 men and 1153 women from a Japanese community participated in a study on cardiovascular risk factors at a local health centre. Of these, the 896 subjects who visited the centre both in 1996 and 2001 were selected for the analysis. The presence of cardiovascular changes was defined as the appearance of one or more of the following in five years: positive electrocardiographic findings, intima-media thickness of the carotid artery >or=0.8 mm and retinal vascular changes >or=Keith-Wegener-Barker classification stage I. RESULTS: Of the 607 subjects who had no history of cardiovascular disease in 1996, 421 showed changes in 2001. Both the age-adjusted and multivariate models showed that the risk of the cardiovascular changes increased as systolic blood pressure (SBP) increased to >or=135 mmHg (multivariate odds ratio = 1.739, 95% confidence interval = 1.076-2.810, P < 0.05) compared with those with an SBP of 110-134 mmHg. When we made the analyses only for laboratory test results by excluding SBP, body mass index, alcohol intake and current smoking from the regression model, high-density lipoprotein cholesterol and fasting plasma glucose were significant variables. CONCLUSION: The risk of future cardiovascular changes is significantly greater with higher SBP in the Japanese population.

[Antioxidant reactions and activities of teas and wines by the cumene hydroperoxide/hemoglobin * methylene blue method].

BACKGROUND: We reported a new method using cumene hydroperoxide to determine the antioxidant activity of polyphenols. METHODS: We measured antioxidant activities of a variety of different teas and wines by the cumene hydroperoxide/hemoglobin * methylene blue method. The activities of teas were observed by adding 100 ml of boiling water to 2g of tea leaves. The wine samples were mainly diluted 10 times. RESULTS: The average level of antioxidant activity of teas was as follows: wild plants (n = 6) were 59 micromol/l, heated green (n = 3) was 400 micromol/l, green (n = 8) was 550 micromol/l, powdered green (n = 2) was 960 micromol/l, and black (n = 11) was 405 micromol/l. The antioxidant activity of wines was as follows: red (n = 7) was 1,920 micromol/l, white (n = 7) was 1,010 micromol/l, additive-free red (n = 6) was 658 micromol/l, and additive-free white (n = 6) was 118 micromol/l. The correlation between the concentration of teas or wines and antioxidant activity was not a linear type. For this reason, the tea and wine were measured under comparable conditions. The concentration of free sulfur dioxide contained within red wine was 20 mg/l and, white wine was 55 mg/l. The apparent-antioxidant activity of these concentrations of free sulfur dioxide was 234 micromol/l and 651 micromol/l. CONCLUSIONS: Tea is the national drink of Japan, green tea and heated green tea are particularly favored. The antioxidant activities of these teas were lower than that of red wine. However larger quantities of tea than wine are consumed every day. Therefore, we concluded that the total antioxidant activity of tea is the same or higher than that of red wine.

[Report on a training course for clinical research coordinators].

Recently, nurses and pharmacists have become to play important roles in clinical trials as clinical research coordinators (CRC). However, clinical laboratory personnel have a very few chances to contribute to such tasks. CRCs have responsibility to protect the human rights, to assure the safety of volunteers during studies, and to keep quality of data. One of the authors had a chance to participate in a training course for CRC that was held in Tokyo, 2004. In this paper, we report about the training course and roles of CRC. We also discuss how laboratory personnel should contribute to clinical trials.

[Consultation for the prevention of atherosclerotic diseases].

We have conducted a population-based, long-term trial with the purpose of investigating risk factors for atherosclerotic diseases in a Japanese population, from 1996 (Niigata Study). Through the trial, we have learned what is going on at the initial phase of atherosclerotic diseases. This experience plays an important role in contributing to clinical decision-making. We are engaging ourselves in improving not only diagnoses but also therapies and research relating to atherosclerotic diseases. We are specialized in performing laboratory tests for lipid analysis such as the two-dimensional nondenaturing electrophoresis of lipoproteins, which is exclusively conducted in our laboratory. Three children with the oculocerebrorenal syndrome of Lowe, for example, were confirmed by these lipid analyses and also by gene analyses performed by us. Our potential goal is a regenerative or cellular therapy for patients with vascular insufficiency. We are now conducting basic research for angiogenesis.

Lipid analyses for the management of vascular diseases.

Despite a long history of studies on lipid abnormalities, numerous problems in laboratory technologies and techniques remain unresolved. One of the most commonly tested molecules is low-density lipoprotein (LDL) cholesterol, and a homogenous assay technique for measurement of this molecule has recently been introduced. Although the method represents remarkable technological breakthroughs with great potential for improving lipoprotein analysis, some discrepancies exist among assay protocols. Even for direct measurement of high-density lipoprotein (HDL) cholesterol, which has widely been accepted, there are still large discrepancies among data obtained by different protocols. Oxidatively modified LDL is an independent factor that is considered to directly contribute to the pathogenesis of early atherosclerosis. Lipid peroxidation products, surface charge, and spectrophotometric patterns are all applicable to the evaluation of in vitro oxidation. Only enzyme-linked immunosorbent assays using monoclonal antibodies have a potential for clinical use, but such methods are not yet standardized. There is also increasing evidence for the presence of anti-oxidized LDL autoantibodies in human sera, but the diagnostic utility remains controversial. In addition, small dense LDL has recently attracted much attention as an independent risk factor. Although this is a potential target of oxidization, a robust and simple analytical method does not yet exist. This review presents the current state of laboratory technologies for testing lipid abnormalities.

A new method of measuring the antioxidant activity of polyphenols using cumene hydroperoxide.

BACKGROUND: It is well known that polyphenols lower the risk of chronic diseases such as heart disease and cancer. We describe a new method using cumene hydroperoxide (CHP) to determine the antioxidant activity of polyphenols. CHP is considered to be a model reactive lipid peroxidation product. METHODS: The method was based on two reactions: the reduction of a known concentration of CHP by polyphenols and the reaction of the remaining CHP with a methylene blue derivative (10-N-methylcarbamoyl-3,7 dimethylamino-10H-phenothiazine) in the presence of haemoglobin. Methylene blue was formed as a result of the two reactions and then measured by absorbance at 675 nm. We named this assay the 'cumene hydroperoxide/haemoglobin.methylene blue (CHP/Hb.MB) method'. We examined 13 polyphenols and nine compounds known to be antioxidants. RESULTS: Among the 13 polyphenols, milicetin, with the largest number of hydroxyl groups, had the highest antioxidant activity, followed by cyanidin, pelargonidin and quercetin. It is suggested that the increase in the number of hydroxyl groups induced a higher antioxidant activity. Within-run coefficients of variation were 3.6% and 3.5% at the mean antioxidant activity of 50 micromol/L and 151 micromol/L, respectively. CONCLUSION: We conclude that this CHP/Hb.MB assay is capable of measuring the antioxidant activity of polyphenols.

[Antioxidant activities of green and black teas determined by the cumene hydroperoxide/hemoglobin.methylene blue method].

Antioxidant activity in tea was measured by the new cumene hydroperoxide/hemoglobin.methylene blue(CHP/Hb.MB) method developed in our laboratory. Using the CHP/Hb.MB method, we investigated the activities of polyphenols(11 varieties) in order to determine their reactivity on CHP. According to the CHP/Hb.MB method, an increase in the number of hydroxyl groups in polyphenols induced high antioxidant activity. We found that this method was capable of measuring the antioxidant activity of polyphenols. Consequently, we were able to measure the antioxidant activities of heated, green, powdered and black teas by this method. The average of antioxidant activities of heated green tea was 207 nmol/ml, while that of green tea was 280 nmol/ml, powdered green tea was 481 nmol/ml and black tea was 215 nmol/ml respectively.

An integrated medical image database and retrieval system using a web application server.

We developed an Integrated Medical Image Database and Retrieval System (INIS) for easy access by medical staff. The INIS mainly consisted of four parts: specific servers to save medical images from multi-vendor modalities of CT, MRI, CR, ECG and endoscopy; an integrated image database (DB) server to save various kinds of images in a DICOM format; a Web application server to connect clients to the integrated image DB and the Web browser terminals connected to an HIS system. The INIS provided a common screen design to retrieve CT, MRI, CR, endoscopic and ECG images, and radiological reports, which would allow doctors to retrieve radiological images and corresponding reports, or ECG images of a patient simultaneously on a screen. Doctors working in internal medicine on average accessed information 492 times a month. Doctors working in cardiological and gastroenterological accessed information 308 times a month. Using the INIS, medical staff could browse all or parts of a patient's medical images and reports.