小谷 和彦

To foster work-ready general physicians, Jichi Medical University has developed various clinical teaching practices since its foundation. The educational courses for clinical laboratory medicine, being one of them, adopt practical trainings in ultrasonography, which is essential in practical medicine today. The aims and the specifics of the trainings adopted in the seminar of ultrasound and the required or the optional subjects of Bedside Learning (BSL) at Jichi Medical University are reported.

The clinical significance of the diameter of common carotid artery (CCA) measured ultrasonographically has not been sufficiently established. The object of this cross-sectional study was to investigate the relationship of the ultrasonic CCA diameter with coronary artery disease (CAD). In the male patients (n=169, mean age: 61 years) who had no apparent carotid arterial stenosis and cerebrovascular disease, a history of CAD, current smoking, body mass index, blood pressure, hemoglobin A1c, serum low-density-lipoprotein cholesterol, estimated glomerular filtration rate and ultrasonic measures of CCA diameter were analyzed. A total of 25 patients had a history of CAD (15%). The CCA diameters of patients with CAD were significantly higher than those of patients without CAD (7.9 +/- 1.0 mm and 7.4 +/- 0.9 mm; p = 0.01). Receiver operating characteristic curve of boundary value of CCA diameter revealed an area under the curve to identify the patients with CAD (0.63, p = 0.04). When the cut off value was considered 8.5 mm, the odds ratio was 4.50 (95% confidence interval = 1.71-11.84, p < 0.01), and the ratio were not largely altered in multivariate logistic regression analyses. The CCA diameter may therefore serve as a useful predictive marker for CAD in men.

Uncoupling protein 1 (UCP1) plays an important role in thermogenesis in brown adipose tissue. Previously, we reported an association between -3826 A/G single-nucleotide polymorphism (SNP) in the promoter of UCP1 gene and lower thermogenesis in young women, suggesting this SNP has an adverse effect on the regulation of energy balance. Based on the hypothesis that this SNP (G allele) may have resistance against diet-induced weight loss, we examined its effects on anthropometric and metabolic responses to short-term, controlled-energy diet in young women. Seventeen lean women (20.9 ± 0.2 years; body mass index, 22.1 ± 0.5 kg/m(2)) were fed a controlled-energy diet (5.0 MJ/d, 62% carbohydrate, 19% protein, and 19% fat) administered by dietitians for 2 weeks. Clinical measurements were determined at baseline and after the dietary intervention. The subjects' physical activity was obtained using pedometers and self-reporting. The thermoregulatory sympathetic nervous system was evaluated using heart rate variability power spectral analysis. Upon the completion of the intervention, subjects were genotyped using an allele-specific DNA primer assay and results compared with their clinical measurements focusing on with or without the G allele. After dietary intervention, G allele subjects (A/G + G/G, n = 10) showed significantly smaller changes in body weight, body mass index, and waist circumference compared with A/A genotype subjects (n = 7). Similar changes were observed in parameters regarding glucose or lipid metabolism in both groups. These results suggest that the UCP1 gene -3826 G allele may result in smaller weight loss after a short-term, controlled-energy diet in young, lean women.

BACKGROUND: A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized. METHODS: Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group. RESULTS: After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027). CONCLUSIONS: The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention. TRIAL REGISTRATION NUMBER: UMIN000003136.

Background/aim: Electrophoresis is useful for examining the lipoprotein fraction patterns. A simultaneous and cost-effective addition of cholesterol levels in each lipoprotein fraction to the lipoprotein patterns can more assist clinical decision-making. This study' aim was to develop the formulas for estimating the fractionated lipoproteins cholesterol levels in a recent system, the agarose gel Sebia HYDRAGEL LIPO+Lp(a) electrophoresis. Methods: Serum samples were analyzed by two Sebia electrophoresis, HYDRAGEL LIPO+Lp(a) and the quantitative HYDRAGEL LDL/HDL-CHOL Direct methods. The formulas for estimation of relative cholesterol (%) of individual lipoprotein fractions were developed using linear regression models. Thereafter, the calculated lipoproteins cholesterol values by multiplying the relative cholesterol with total cholesterol concentrations were compared with the standardized enzymatic assayed values. Results: The equations for calculating % relative cholesterol (y) from % relative lipoprotein (x) were y=x-8, x+21 and 0.75x-6.5 for high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) fractions, respectively. Regression statistics obtained between the calculated assays (y) and the standardized enzymatic assays (x') in samples with and without Lp(a) were y=1.07x'- 0.18 and 1.06x'-0.06, respectively for HDL-cholesterol, y=0.90x'+0.32 and 0.92x'+0.29 for LDL-cholesterol, and y=0.85x'-0.03 and 0.95x'+0.02 for VLDL-cholesterol. Conclusions: The proposed formulas can provide a reliable estimation of cholesterol levels in each major lipoprotein fraction by the HYDRAGEL LIPO+Lp(a) electrophoresis. Further studies with its application are needed.<br>

OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss. METHODS: Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system. RESULTS: Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P < 0.05). The AT₂R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P < 0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P < 0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P < 0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P < 0.05) than the C/C plus C/A genotypes. CONCLUSION: The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT₂R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.

PURPOSE: To reveal the epidemiologic features of suicides in Tochigi Prefecture using police data, and to discuss critical points to improve suicide prevention and advantages and disadvantages of police data. METHODS: Individual data for suicides during a 2 year period of 2007 and 2008 provided by the Tochigi Police were analyzed. RESULTS: In the observed 2 years, there were 1166 cases of suicide (865 males and 301 females), a higher rate per population in Tochigi than that for the whole of Japan. The age-specific number was highest in the 50's among males, whereas the numbers were similar between the 30's and 70's among females. The age-specific number per population was higher than that for the whole of Japan for individuals in their 20's and 30's. The number was highest in early morning at around 10 o'clock in the weekdays. Of all cases, 58.1% committed suicides at home, and 58.0% were by hanging. As causes of suicides, selected as the 3 most common by the police, health problems were top (61.3%), followed by economic (22.7%) and familial (17.3%) difficulties. With health problems, physical and mental diseases each accounted for approximately half. Those committing suicides because of the economic problems were dominantly males aged 20-69 years, many of whom had multiple debts. One third of the deceased cases left testamentary letters, and 15.9% had experiences of attempted suicide in the past. According to these results, we consider that the following 6 points are important to prevent suicides in Tochigi (1) improvement of school and occupational health targeting males aged 20 to 39 years; (2) persons at high risk should be kept always under close observation by someone such as a family member; (3) those having experience of attempted suicides should be formally treated as high risk persons; (4) consultation systems for various problems, especially for multiple debts, should be prepared and appropriately advertised; (5) mental health care should be provided for patients with physical disorders; and (6) treatment and management for patients with mental illness should be comprehensive. In addition, we noted that the causes of suicides in the police data were based on inferences of police officers investigating the suicide cases so that the validity was poorer than that of psychological autopsy. However, the advantage of the police data was that there was less selection bias because police data covered all the suicides in the area. CONCLUSIONS: Using police data, the epidemiologic features of suicide in Tochigi Prefecture could here be demonstrated, and guidelines for prevention are indicated. Utility of police data for revealing the epidemiologic features of suicides to provide information for suicide prevention was confirmed.

Leptin may influence sweet taste sensitivity. However, there are no reports on an association between the sweet taste threshold and serum leptin levels during weight loss in humans. We investigated the changes in the sweet taste threshold and the serum leptin levels during a weight-loss program, in connection with a leptin receptor polymorphism (Lys109Arg) that may be related to insulin and glucose metabolism. The study included 20 obese, but otherwise healthy, females (mean age: 55 +/- 7 years, body mass index: 26.1 +/- 1.7 kg/m(2)). Participants completed a 12-week weight-loss program based on energy restriction through diet and exercise, which aimed at achieving their optimal weight. The sweet taste threshold was determined according to the whole-mouth gustatory method. Genetic analyses were performed using the allele-specific DNA assay. Serum leptin levels were decreased from 9.2 +/- 4.5 to 7.9 +/- 4.9 ng/ml (p = 0.014) after body weight loss. The sweet taste threshold also decreased significantly from 0.59 +/- 0.42 to 0.22 +/- 0.20% in a solution of sucrose (p = 0.004). In contrast, there were no differences in changes of the threshold between participants with and without the Lys109 allele. A multiple regression analysis revealed that the changes in serum leptin levels were significantly correlated with those in the sweet taste threshold, independent of the initial threshold levels and the Lys109 allele. In conclusion, the serum leptin levels are decreased significantly during a weight-loss program in obese females, which may be associated with the decrease in the sweet taste threshold.

BACKGROUND: Residents of rural communities are often more socially connected compared to urban dwellers. Using family and community support to motivate health behavior change may be useful in rural settings. The objective of this study was to pilot a salt reduction (SR) intervention for rural albuminuria patients using support from family and neighborhood residents compared to a usual care condition. The primary outcome was change in urine albumin-creatinine ratio (ACR). METHODS: All consecutive outpatients with an ACR >= 30 mg/gCr were recruited from the Koyadaira Clinic. Patients self-selected their participation in the intervention group (IG) or the control group (CG) because the rural population expressed concern about not being treated at the same time. In the IG, patients and their families were educated in SR for 30 minutes in their home by experienced dieticians. In addition, patients, families and neighborhood residents were also educated in SR for 2 hours at a public town meeting hall, with educational content encouraging reduction in salt intake through interactive activity. The CG received conventional treatment, and ACR and blood pressure (BP) were measured after 3 months. RESULTS: Of the 37 subjects recruited (20 male, 16 female, mean age; 72.8 +/- 9.2 years), 36 completed the 3-month follow up and were analyzed. In the IG, ACR decreased significantly from baseline (706 +/- 1,081 to 440 +/- 656; t = 2.28, p = 0.04) and was reduced compared to the CG (213 +/- 323 to 164 +/- 162; F = 3.50, p = 0.07), a treatment effect approaching significance. Systolic BP in the IG (145 +/- 14 to 131 +/- 13 mmHg; t = 3.83, p = 0.002) also decreased significantly compared to the CG (135 +/- 13 to 131 +/- 14; F = 4.40, p = 0.04). CONCLUSIONS: Simultaneous education of patients, their families and neighborhood residents may be important in rural areas for treatments and interventions requiring health behavior change. TRIAL REGISTRATION: UMIN000001972.

OBJECTIVE: It was the aim of this study to investigate whether there is any relationship between oxidative stress, as assessed by the diacron reactive oxygen metabolite (d-ROM) test, and carotid atherosclerosis among hypercholesterolemic patients. SUBJECTS AND METHODS: A well-defined group of patients with type II hypercholesterolemia (n = 81, mean age 59 years) was studied to observe the correlation between the levels of serum d-ROMs and carotid artery intima-media thickness (IMT) using B-mode ultrasound, in relation to the traditional atherosclerotic risk factors (age, sex, smoking, body mass index, blood pressure, glucose and lipid panels). RESULTS: The mean level in low-density lipoprotein cholesterol (LDL-C) in this population was 4.45 mmol/l, d-ROMs were 323.2 Carr U, and IMT was 0.91 mm. A multiple regression analysis revealed a positive and significant correlation between IMT and d-ROMs (β = 0.27, p < 0.05), along with age and LDL-C. CONCLUSION: These results indicate that the increased oxidative stress levels using the d-ROM test, independent of aging and increased LDL-C levels, may be associated with carotid atherosclerosis even in hypercholesterolemic patients.

Hypertension (HT) and C-reactive protein (CRP) are risk factors of cardiovascular diseases (CVD). The current study's purpose was to investigate the relationship between serum CRP levels and daily lifestyles, including physical activity, in Japanese HT patients. Lifestyle factors, blood pressure (BP), blood cholesterol, glucose, and CRP were measured in a total of 312 HT patients (153 men/159 women, mean age: 62.6 y). Women with physical activity of ≥ 1 time/week showed significantly lower CRP levels than those without it (p < 0.05). The data suggest that regular physical activity could reduce the CRP levels in HT patients, thereby maybe preventing CVD.

The uncoupling protein-1 (UCP1) gene is of major importance for regulation of body weight and lipid/lipoprotein metabolism. Our cross-sectional study has shown that subjects with the G/G genotype of the -3826 A/G polymorphism in the UCP-1 gene have higher levels of serum high-density lipoprotein cholesterol (HDL-C) than those with other genotypes. Low circulating HDL-C level has been regarded as a major atherosclerotic risk factor. We therefore investigated whether the -3826 A/G polymorphism affects the obesity- and lipid-related parameters during a low-calorie diet (LCD) intervention. In 32 obese women (49.9 +/- 8.4 years of age), anthropometric, physiological and biochemical characteristics were measured before and after a 2-month LCD treatment, which restricted each subject to the same energy intakes, such as 5,120 kJ/day. The -3826 A/G polymorphism was detected using a PCR-restriction fragment-length polymorphism method. There were 6 subjects with the A/A genotype, 15 with the A/G genotype and 11 with the G/G genotype. The LCD intervention decreased weight (P < 0.001) and serum HDL-C levels (P < 0.05) in all subjects. There was no difference in the levels of change in weight, nutrient intake, physiological measurements in energy expenditure, and fat oxidation between subjects with and without the G allele. In contrast, the degree of the reduction in the HDL-C levels was significantly smaller in subjects with the G allele than those without the G allele. These results suggest that the G allele at -3826 in the UCP1 gene may ameliorate the reduction in serum HDL-C levels in obese women during LCD.

BACKGROUND: Lifestyle modification improves the pathophysiology of lipid disorder, leading to the development of cardiovascular disease (CVD). While oxidized low-density lipoprotein (oxLDL) may be involved in this mechanism, various oxLDL measurements have recently been developed and therefore further detailed studies are called for in this area. Our aim was to investigate the effects of lifestyle modification on serum amyloid A-LDL (SAA-LDL), a new oxLDL, in subjects with primary lipid disorder. METHODS: A total of 141 asymptomatic subjects (women/men=100/41, mean age 57.6 years) with>or=1 lipid abnormality (circulating high levels of low-density lipoprotein cholesterol [LDL-C] and triglyceride [TG] or low levels of high-density lipoprotein cholesterol [HDL-C]), who completed a 6-month lifestyle modification program in combination with diet and exercise, were analyzed. In the pre- and post-intervention, the metabolic variables including SAA-LDL were assessed. RESULTS: During our intervention, the body mass index, blood pressure, LDL-C, TG, glucose and SAA-LDL significantly decreased, while HDL-C significantly increased. Multiple regression analysis revealed that the change levels of TG (positive) and HDL-C (inverse) were significantly and independently correlated to those of SAA-LDL. CONCLUSIONS: These results suggest that SAA-LDL may contribute to the link between lipid disorder and the development of CVD, and that the application of SAA-LDL measurements may be useful for the assessment of the risk of CVD as a biochemical marker.