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The effect of exercise habits on the increased incidence of lifestyle-related diseases among residents of the evacuation area in Fukushima Prefecture after the Great East Japan Earthquake is not well characterized. This study examined the influence of exercise habits on the frequency of new onset of lifestyle-related diseases in the aftermath of the earthquake using data from the Fukushima Health Management Survey (FHMS). Of the 32 289 individuals (14 004 men and 18 285 women) aged 40–90 years who underwent one or more health examinations in both 2011–12 and 2014–15, those who knew whether they had any lifestyle diseases and who responded to a questionnaire about their exercise and physical activity habits were included (dyslipidemia, 8017; hypertension, 7173; and diabetes mellitus, 13140 individuals). The association between the frequency of new onset of lifestyle-related diseases in 2014–15 and the presence or absence of persistent exercise and physical activity habits (active lifestyle) was examined using the FHMS data. The frequency of new onset of dyslipidemia was significantly lower in the active lifestyle group than in the sedentary lifestyle group (P = 0.008). On univariate and multivariate logistic regression analyses, the presence of active lifestyle, obesity and the experience of evacuation showed a significant association with new onset of dyslipidemia, independent of age, sex or follow-up period. Thus maintaining physical activity and exercise habits may help prevent the new onset of dyslipidemia among residents of the evacuation area in the Fukushima Prefecture after the earthquake.

Background and aims On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. This study assessed the association between evacuation and hyperuricemia based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. Methods and results This cross-sectional study included 22,812 residents (9391 men and 13,297 women) who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between hyperuricemia and lifestyle- and disaster-related factors including evacuation were estimated using a logistic and liner regression analysis. With hyperuricemia defined as uric acid levels >7.0 mg/dL for men and >6.0 mg/dL for women, significant associations were observed between evacuation and hyperuricemia in men (the multivariate-adjusted odds ratio 1.20, 95% confidence interval, 1.05–1.36, p = 0.005), but not in women. In the multivariate-adjusted multiple liner regression analysis, evacuation had significant and positive associations with uric acid levels both in men (β = 0.084, p = 0.002) and women (β = 0.060, p Conclusion Evacuation after a natural disaster is an independent factor associated with hyperuricemia.

Aim After the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. Methods We conducted a cohort study of residents aged 40–90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. Results Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03–1.86). Conclusion This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.

Aim The Fukushima Daiichi Nuclear Power Plant accident dramatically changed the lifestyle of residents who lived near the plant. We evaluated the association of metabolic syndrome (MetS) with specific lifestyle- and disaster-related factors in residents following the accident. Methods This cross-sectional study included 20,920 residents who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey from June 2011 to March 2012. Associations between MetS and lifestyle- and disaster-related factors, including psychological distress (post-traumatic stress disorder [PTSD]), were estimated using logistic regression analysis, adjusted for demographic and lifestyle factors, in 2019. Results MetS was present in 30.4% of men and 11.5% of women. There were significant differences in smoking, drinking status, and PTSD prevalence between subjects with and without MetS. Multivariable logistic regression analysis showed that age, quitting smoking, and low physical activity were significantly associated with MetS. Moreover, PTSD and light to moderate drinking were also significantly associated with MetS in women. Conclusions Lifestyle- and disaster-related factors, including PTSD, were associated with MetS among subjects who lived near the Fukushima Daiichi Nuclear Power Plant accident.

Objective Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. Design This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). Methods We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. Results Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. Conclusion Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.

BackgroundThe Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia.MethodsThe study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥ 40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 non-hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013-2015.ResultsWe found that the new onset of hyper-LDL cholesterolemia was significantly by 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index (BMI), smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise.ConclusionsThe findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.

Supplemental Digital Content is available in the text, We have been examining the Comprehensive Health Check of the Fukushima Health Management Survey of residents of 13 municipalities who were forced by the government to evacuate due to the 2011 Great East Japan Earthquake (GEJE). Our findings showed that evacuation is a risk factor for polycythemia and suggested that experiencing an unprecedented disaster and exposure to chronic stress due to evacuation might be a cause of polycythemia. We analyzed the relationship between the prevalence of polycythemia and the following factors observed in the Mental Health and Lifestyle Survey in an observational study with a cross-sectional design: traumatic symptoms, depression status, socioeconomic factors such as residential environment, and working situation after the GEJE. Target population of the survey included men and women who were at least 15 years of age and who lived in the evacuation zones specified by the government. Participants analyzed consisted of 29,474 persons (12,379 men and 16,888 women) who had participated in both the 2011 Comprehensive Health Check and Mental Health and Lifestyle Survey from June 2011 through March 2012. The prevalence of polycythemia was not associated with mental states associated with traumatic symptoms (Post-Traumatic Stress Disorder Checklist Scale ≥ 44) and depression status (Kessler 6-item Scale ≥ 13). Furthermore, multivariate analysis showed that there was a tendency for males to develop polycythemia, with characteristics such as being aged 65 years and older, highly educated, obese (body mass index ≥ 25), hypertensive, diabetic, having liver dysfunction, and a smoker being significantly related to the prevalence of polycythemia. Our findings conclusively demonstrated that polycythemia was not significantly related to psychological factors, but was significantly related to the onset of lifestyle-related disease after the GEJE.

Objectives The aim of this study was to investigate the impact of adrenal venous sampling (AVS) lateralization cutoffs on surgical outcomes. Patients and Methods Cosyntropin-stimulated AVS was used to guide surgical management of 377 patients with primary aldosteronism (PA) who were evaluated 6 months after surgery. Main Outcome Measures The proportion of patients that achieved clinical benefit and complete biochemical success based on the AVS aldosterone lateralization index (LI) was determined. Results Clinical benefit was achieved in 29 of 47 patients with an LI between 2 and 4, in 66 of 101 with an LI between 4 and 10, and in 158 of 203 with an LI > 10 (P < 0.01 for trend). Complete biochemical success was achieved in 27 of 42 with an LI between 2 and 4, in 60 of 76 with an LI between 4 and 10, and in 127 of 155 with an LI > 10 (P = 0.024 for trend). After adjustment for confounders and using those patients with an LI between 2 and 4 as a reference, a clinical benefit was associated only with those with an LI > 10 (OR, 2.30; 95% CI, 1.03 to 5.16), whereas complete biochemical success was associated with those with an LI between 4 and 10 (OR, 2.83; 95% CI, 1.14 to 7.01) or LI > 10 (OR, 3.55; 95% CI, 1.47 to 8.55). Conclusions Difference of clinical outcome was relatively small when strict LI diagnostic threshold was used; biochemical cure was sufficiently achieved when an LI > 4 was used. Our study by standardized outcome measures validated that an LI > 4 may be appropriate for determining unilateral disease in PA., We investigated the impact of AVS lateralization cutoffs on surgical outcome by standardized measures and validated that an LI > 4 is appropriate to determine unilateral disease in PA.

There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K + ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations

Although the incidence of hepatobiliary enzyme abnormality increased immediately after the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident, longer-term trends remain unclear. The aims of this study were to determine longer-term trends in hepatobiliary enzyme abnormality and to elucidate lifestyle factors associated with such changes among residents of a nuclear-disaster-affected area. This longitudinal survey enrolled 20,395 adults living in the vicinity of Fukushima Daiichi Nuclear Power Plant. Data were obtained from the records of annual health checkups of adults aged ≥40 years between 2011 and 2012. Follow-up examinations were conducted from June 2013 to March 2014. Associations were assessed between changes in hepatobiliary enzyme abnormality immediately and 3–4 years after the disaster and lifestyle factors. The overall prevalence of hepatobiliary enzyme abnormality significantly decreased over the study period, from 29.9% to 27.1%. Multivariate logistic regression analysis revealed significant associations between improved hepatobiliary enzyme abnormality and improvements in daily physical activity and frequency of breakfast consumption. The results suggest that improvements in daily physical activity and frequency of breakfast consumption significantly reduced the incidence of hepatobiliary enzyme abnormality 3–4 years after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident.

Background About 146,000 people were forced into long-term evacuation due to the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. Disaster is known to induce hypertension in survivors for a certain period, but it is unclear whether prolonged disaster stress influences chronic kidney disease (CKD). We conducted an observational cohort study to elucidate the effects of evacuation stress on CKD incidence. Methods Participants were individuals living in communities near the Fukushima nuclear power plant, aged 40–74 years without CKD as of their 2011 general health checkup (non-evacuees: n = 9780, evacuees: n = 4712). We followed new-onset CKD [estimated glomerular filtration rate (eGFR)

We previously reported that the lifestyle of evacuees significantly increased the prevalence of polycythemia compared with non-evacuees at an average of 1.6 years (2011–2012) from the previous annual health checkup before the Great East Japan Earthquake (GEJE). Here we analyzed how the prolonged evacuation affected the prevalence of polycythemia an average of 2.5 years (2013–2014) after the previous data. Subjects were individuals aged 40–90 years living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima Prefecture who had attended the annual health checkups since 2008. The prevalence of polycythemia and changes in its defining factors of red blood cell count (RBC), hemoglobin (Hb) level, hematocrit (Ht) level were compared between before and after the GEJE in 7713 individuals (3349 men and 4364 women) receiving follow-up examinations both 2011–2012 and 2013–2014. RBC, Hb levels and Ht levels in 2011–2012 were higher among evacuees than non-evacuees in both men and women. However, all levels in 2013–2014 were on the decline from those in 2011–2012. On the other hand, among evacuees, Hb and Ht levels continued to be higher than before the GEJE in both men and women evacuees. The prevalence of polycythemia, which was diagnosed if one of the defining factors was beyond the standard value, was significantly higher among evacuees than non-evacuees regardless of the presence or the absence of overweight/obesity, smoking, and hypertension. Therefore, prolonged evacuation is a cause of polycythemia even 3 to 4 years after the GEJE and regular health management of evacuees is important., Highlights • Evacuation after the Great East Japan Earthquake (GEJE) causes polycythemia. • Evacuation is an independent factor of polycythemia. • Prevalence of polycythemia among evacuees persists even after 4 years of the GEJE.

Aim After the Great East Japan Earthquake, over 160,000 residents near the Fukushima Daiichi Nuclear Power Plant were forced to evacuate due to a nuclear accident. Health problems in these evacuees have since become major issues. We examined the association between evacuation and incidence of metabolic syndrome (METS) among residents in Fukushima. Methods We conducted a cohort study among residents aged 40-74 years without METS at the time of the disaster in Fukushima. Among 20,269 residents who met the inclusion criteria before the disaster, 8,547 residents (3,697 men and 4,850 women; follow-up proportion: 42.2%) remained available for follow-up examinations after the disaster by the end of March 2013. The main outcome was incidence of METS, defined by guidelines from the Japanese committee, using data from the Comprehensive Health Check before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of METS, adjusting for potential confounders, age, gender, waist circumference, exercise habit, and alcohol consumption. Results Incidence of METS was higher in evacuees (men 19.2%, women 6.6%) than in non-evacuees (men 11.0%, women 4.6%). Evacuees had higher body mass index, waist circumference, triglycerides, and fasting plasma glucose after the disaster than non-evacuees. We found a significant association between evacuation and incidence of METS (adjusted odds ratio 1.72, 95% confidence interval; 1.46-2.02). Conclusion This is the first study to demonstrate that evacuation after a disaster is associated with increased incidence of METS.

Context Adrenal tumors (ATs), even those diagnosed as nonfunctioning, may cause metabolic disorders. Some primary aldosteronism (PA) patients with ATs are diagnosed with bilateral PA based on adrenal venous sampling (AVS), and their ATs are apparently nonfunctioning. Objective To clarify the influence of apparently nonfunctioning ATs, we compared hormone levels and clinical complications between bilateral PA cases with and without ATs. Design, setting, and participants After retrospectively assessing 2814 patients with PA in the multicenter Japan PA study, bilateral PA cases on AVS were divided into cases with and without ATs by computed tomography findings. Importantly, patients with cortisol levels >1.8 µg/dL after the 1-mg dexamethasone suppression test (DST) were excluded. Clinical characteristics and biochemical data were compared between them. The correlation between AT size and hormone levels was also analyzed. Main outcome measures Analyzed were 196 bilateral PA patients with ATs and 331 those without ATs. Although basal cortisol and aldosterone levels were similar between them, cortisol levels after the 1-mg DST and the prevalences of diabetes mellitus and proteinuria were significantly higher and ACTH levels and plasma renin activity were significantly lower in cases with ATs than in those without. After adjusting for patients’ backgrounds, cortisol levels after the 1-mg DST and plasma renin activity remained significantly different between them. Moreover, cortisol levels after the 1-mg DST and ACTH levels correlated with AT size. Conclusions Apparently nonfunctioning ATs in bilateral PA cases may cause latent autonomous cortisol secretion, inducing diabetes and proteinuria.

OBJECTIVE To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia ( RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30–69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mardi 7 novembre 2017

SummaryContext Chronic kidney disease (CKD) is sometimes unmasked after unilateral adrenalectomy in patients with primary aldosteronism (PA) without expectation. Objective Our study aim was to elucidate factors responsible for developing postoperative CKD and to provide a simple scoring system to predict postoperative CKD in PA. Design and Patients Forty-five patients with PA treated with unilateral adrenalectomy and followed for at least 1 month postsurgery were studied. Thirty-one patients with non-PA adrenal disease who underwent unilateral adrenalectomy were also studied as control. Patients with pre-operative estimated glomerular filtration rate (eGFR)

On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. This study assessed the hypothesis that evacuation may have increased the risk of hypertension among residents in Fukushima. A longitudinal study examined data collected from 31 252 Japanese participants aged 40 to 74 years sourced from general health checkups conducted in 13 communities between 2008 and 2010. Follow-up examinations were conducted from 2011 through 2013. A total of 21 989 participants (follow-up proportion, 70.4%) received follow-up examinations. Mean blood pressure significantly increased in both evacuees and nonevacuees after the disaster, with greater changes in blood pressure among the former. The changes in systolic and diastolic blood pressure among the evacuees and nonevacuees were +5.8/3.4 versus +4.6/2.1 mm Hg ( P P P =0.33/ P P P =0.37) for women, respectively. For men, after adjustment for confounding variables, the hazard ratio slightly decreased to 1.20, but the association was essentially unchanged. Blood pressure increased among residents, especially evacuees, in the evacuation zone of Fukushima prefecture after the Great East Japan Earthquake. Evacuation may be associated with an increased risk of hypertension among men in the 2 years after the disaster.

Liver is a main organ to regulate energy metabolism, nutrients production, storage and supply to the whole body. Glucose is the essential energy source for the whole body organs, especially for brain which has no ability to synthesize glucose and store glycogen or utilize non-glucose nutrients. Liver plays pivotal role to regulate glucose metabolism by precise regulation of glycogenolysis and gluconeogenesis, which are controlled not only by endocrine system, insulin and its counterregulatory hormones, but also by neuronal network, autonomic nervous system and brain. Recent development of molecular biology and gene analysis has revealed the precise molecular mechanism of hepatic carbohydrate metabolism and regulatory system by endocrine system, insulin or glucagon signaling pathway and those hormone-induced transcription of effector molecules, CREB, FoxO1, ChREBP, SREBPs, PGC1 or several kinds of enzymes. Recent studies also revealed that organ-to-organ network medicated autonomic neural system plays important roles in hepatic glucose metabolism.

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.

A 23-year-old female with polycystic ovary syndrome (PCOS) and a growth-hormone (GH)-producing pituitary adenoma is described. A reduction in the elevated GH levels to normal levels following the administration of dopaminergic agents decreased plasma insulin-like growth factor (IGF)-1 and ovarian dysfunction. Menstrual cycles were therefore restored and the number of ovarian cysts reduced, suggesting that insulin and/or IGF-1, stimulators of theca cell proliferation, may be pathogenetic factors in PCOS.

To evaluate effects of metformin on endocrine, metabolic parameters and endometrial androgen receptor (AR) expression in polycystic ovary syndrome (PCOS).Prospective observational study.We analyzed blood samples from 10 PCOS patients, of whom endometrium was also analyzed in five patients. Before and after three months of metformin treatment, endocrine, glucose metabolic parameters and the endometrial AR expressions were assessed. The relative expression levels of AR were examined by immunohistochemistry.The group post-treatment mean of homeostasis model assessment insulin resistance (HOMA-IR) for all patients was significantly lower than the pretreatment. Ovulation was restored in five out of 10 patients. The group post-treatment means of luteinizing hormone (LH) and HOMA-IR for the five ovulatory patients were significantly lower. The relative expression levels of endometrial AR were decreased in four out of the five patients as compared with pretreatment. In the four patients, one or more of the parameters, HOMA-IR, LH or free testosterone, decreased compared with pretreatment.Metformin was effective in decreasing HOMA-IR, LH, free testosterone and the relative expression levels of AR. Furthermore, metformin might improve the systemic and local environment of the uterus caused by hyperandrogenemia in PCOS patients with insulin resistance.

OBJECTIVE Several recent studies have indicated that patients with adrenal incidentaloma often have disturbed glucose tolerance or/and hypertension. It is unclear whether these metabolic conditions could be caused by adrenal incidentaloma. We investigated the prevalence of disturbed glucose tolerance, hypertension and insulin resistance in the patients with non-functioning adrenal incidentaloma and evaluated the changes of the parameters such as glucose tolerance, blood pressure and insulin sensitivity after adrenalectomy. PATIENTS AND METHODS Among 15 patients with incidentally discovered adrenal tumours in our department from 1996 to 1999, 4 patients were diagnosed as having pre-clinical Cushing's syndrome and the other 11 as having non-functioning tumours based on detailed endocrinological examinations including dexamethasone suppression testing. Four tumours with pre-clinical Cushing's syndrome and 8 tumours out of 11 patients with non-functioning tumours were diagnosed histopathologically as adrenocortical adenomas and the other 3 as of non-adrenal origin including a myelolipoma, an adrenal vascular cyst and an endothelioma. The prevalence of disturbed glucose tolerance was determined with an oral glucose tolerance test, and insulin sensitivity was evaluated by the method of steady state of plasma glucose (SSPG). RESULTS All 12 patients with adrenocortical adenoma exhibited insulin resistance based on the SSPG (6·9–13·2 mmol/l). Before surgical removal of the tumours, the SSPG titre was relatively higher in the patients with pre-clinical Cushing's syndrome than in those with non-functioning with adrenocortical adenoma (mean value 11·65 vs. 8·99 mmol/l), whereas 2 of the 3 patients with non-adrenocortical tumours did not have insulin resistance. Among the 12 patients with adrenocortical adenoma, 7 (58%) and 9 (75%) patients exhibited hypertension and disturbed glucose tolerance, respectively. After removal of the tumours, SSPG of the patients with adrenocortical adenoma, but not that of the other 3 patients with non-cortical tumours, was significantly decreased compared to pre-adrenalectomy values. There are no significant differences in the changes of SSPG titres between in pre-clinical Cushing's syndrome and in non-functioning adrenocortical adenoma. Systolic blood pressure, but not diastolic blood pressure, was also significantly decreased in the patients with adrenocortical adenoma. CONCLUSION High prevalences of disturbed glucose tolerance, insulin resistance and hypertension were found among the patients with non-functioning adrenocortical tumours. Adrenocortical adenoma may be one of the risk factors for insulin resistance that is believed to induce disturbed glucose tolerance and/or hypertension. Therefore, it is useful to evaluate insulin resistance for the patients with adrenal incidentalomas since results are likely to be helpful in deciding whether to remove the tumour by surgery.

The cerebrovascular and renal actions of antihypertensive agents are important clinically. The aim of the present study was to assess the effects of felodipine on cerebral blood flow (CBF) and renal blood flow (RBF) by a simple, noninvasive method for quantitative radionuclide angiography with 99m technetium (Tc)- dl -hexamethyl propylenamine oxime and 99m Tc-diethylenetriamine pentaacetic acid in patients with essential hypertension. Five patients with untreated mild-to-moderate essential hypertension were given felodipine twice daily (10 mg/d) for 4 weeks. The antihypertensive effect and the effects on CBF, RBF, and blood viscosity were tested before and on completion of the active treatment. The CBF and RBF were measured by radionuclide angiography coupled with single-photon emission computed tomography after intravenous administration of the radioactive agents. After administration of felodipine, systolic and diastolic blood pressures decreased significantly ( P P P

The role of beta 2-adrenoceptor on the pathogenesis of insulin resistance in essential hypertension (EH) was explored. After the measurement of blood pressure in 15 EH patients and 8 control subjects, EH patients were divided into two groups by the elevation of plasma NE (delta NE) 5 min after standing: 7 normoadrenergic EH (delta NE or = 140 pg/ml). On the morning after a 12-h overnight fast, regular insulin (0.1 U/kg) was injected intravenously, and glucose disappearance rate (GDR) was measured and used as an index of insulin sensitivity. On the following day, the test was reinvestigated following the administration of mabuterol, a beta 2 agonist. Plasma growth hormone (GH), cortisol, norepinephrine (NE) and epinephrine (Epi) were measured before and after the mabuterol administration. Although there were no significant differences of basal GDR among these three groups, mabuterol induced a considerable decrease in GDR in EH patients but not in control subjects. There was no significant difference in the decrease of GDR between normo- and hyperadrenergic EH. The decrease in GDR tended to correlate with the mean blood pressure at rest in EH but not in normal subjects. Plasma glucose and serum insulin in EH patients were increased more than in normal subjects. Plasma GH, cortisol and Epi were not elevated by mabuterol, but plasma NE increased in each group, significantly in hyperadrenergic EH. There was no correlationship between the increase in plasma NE and the decrease in GDR after mabuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

The blood of two patients were investigated for immune hemolytic anemia after administration of the following antibiotic drugs: Aspoxicillin (Asp. Doyle®) in the first case, Sodium Sulbactam/Sodium Cefoperazone (SBT/CPZ, Sulperazon®) in the second case.Anti-Asp antibodies of the IgG1 subclass were found in the patient's sera and in the eluates of direct antiglobulin test (DAT) positive red blood cells in the first case, therefore we suggested that hemolysis was caused by anti-Asp antibodies reacting by a well-known ‘hapten-type’ drug absorption mechanism.The other, the autologous red blood cells in the second case was positive by DAT, but only with anti-C3d reagents, and when the patient's serum was incubated (2 hrs at 37°C) with enzyme-treated red blood cells in the presence of the drugs (SBT-CPZ) and complement, hemagglutination was obserbed by indirect antiglobulin test (IAT). It was interesting that, at the time of these findings, the patient's serum reacted weakly with SBT-coated red blood cells but not with CPZ-coated red blood cells by the flow cytometric analysis. These would suggest that so-call ‘immune complex’ mechanism and another mechanism (perhaps drug absorption mechanism) were involved. It is probable that one or both of these mechanisms were responsible for the patient's immune hemolytic anemia in the second case.

A 59-year-old woman with chronic renal failure due to type 2 diabetes mellitus (DM) is presented. Her father and a brother had a history of brain tumor. Her blood urea nitrogen and serum creatinine levels were 102 mg/dl and 4.5 mg/dl, respectively. Her serum Ca(2+) and Pi were within the normal range (9.4 mg/dl and 5.4 mg/dl, respectively). Her intact parathyroid hormone (PTH) level was 1 730 000 pg/ml. A (99m)Tc-methoxy-isobutylisonitrile scintigraphy showed high uptake in three parathyroid glands. A magnetic resonance image showed microadenoma in the pituitary gland. The serum gastrin level was high. Genetic examination revealed a mutation of the MEN1 gene (894-9 G --A). From these findings, she was diagnosed with multiple endocrine neoplasia (MEN) type 1. Subsequently, a parathyroidectomy was performed successfully, a parathyroid gland was transplanted to her right forearm, and her serum Ca(2+) level was controlled at 8.5-9.0 mg/dl. It is very important to identify MEN1 if an end-stage renal disease (ESRD) patient has hyperparathyroidism with multigland involvement. Examination of the MEN1 gene may be valuable to make an accurate diagnosis and choose the appropriate therapy in some ESRD patients with hyperparathyroidism.

This study was aimed to evaluate the significance and mechanism of vascular endothelial dysfunction in diabetic patients. Thirty-eight patients with type 2 diabetes mellitus were categorized to 3 groups according to the grade of retinopathy and treated for 4 weeks randomly with glibenclamide (n = 14) or troglitazone (n = 24). While plasma tissue plasminogen activator (tPA) (23.9 vs. 8.9 ng/ml; P< 0.05) and plasminogen activator inhibitor-1 (PAI-1) (23.6 vs. 11.8 pg/ml; P< 0.05) levels were significantly elevated in type 2 diabetes patients compared to the control subjects, the PAI-1 titer, but not tPA, was correlated with the severity of retinopathy. Four weeks-treatment by troglitazone was associated with significant reduction of PAI-1 level (20.1 from 26.8 pg/ml, P< 0.05), but not that of tPA, which was correlated with reduction of the steady state plasma glucose (SSPG) titer, but not with that of fasting plasma glucose. Immunoreactive PAI-1 or endothelin-1 (ET-1) were measured by ELISA in culture medium of human umbilical vein endothelial cells (HuVEC) or bovine vascular endothelial cells (bVEC), respectively, in the presence or absence of test agents (insulin, thiazolidinediones, 15-deoxy-delta 12, 14-prostaglandin J2 (15d-PGJ2), bezafibrate). Thiazolidinediones inhibited tumor necrosis factor α (TNF- α )-stimulated PAI-1 secretion and mRNA expression in a dosedependent fashion. Thiazolidinediones and 15d-PGJ2, but not bezafibrate, inhibited basal and insulin-stimulated ET-1 secretion and mRNA expression in a dose-dependent fashion.

P-402 Key Words: Losartan, Angiotensin Receptor (AT1) Antagonist, Cognitive Function, PWV

In order to clarify the role of the kallikrein-kinin system in the hypotensive mechanisms of converting-enzyme inhibition, captopril was administered in a single oral dose of 50 mg to 17 hypertensive patients, of whom 14 had essential hypertension, one had chronic renal failure, one had primary aldosteronism, and one had glucocorticoid responsive hyperaldosteronism. Captopril lowered blood pressure remarkably in either low-renin or normal-, and high-renin hypertensives, however, there was no significant relationship between the fall in blood pressure and pretreatment levels of plasma renin activity (PRA) in any of the patients any time after the administration. PRA was significantly increased in normal- and high-renin hypertensives but not in low-renin patients. Plasma aldosterone concentration (PAC) was decreased significantly in normal- and high-renin patients, while no significant change in PAC was observed in patients with low-renin activity. Captopril elevated plasma bradykinin concentration (PBK) from a control value of 12.5 +/- 4.1 (mean +/- s.d.) to 20.3 +/- 7.7 pg/ml (p less than 0.001) at 30 min, and there was a significant correlation between changes in PBK and changes in mean blood pressure 120 min after the administration in all the patients (r = 0.741, p less than 0.01, n = 17). In one patient with primary aldosteronism, PBK increased from a baseline of 10.0 to a maximum value of 19.0 pg/ml, corresponding to the rapid fall in blood pressure. Also, in one patient with glucocorticoid responsive hyperaldosteronism, captopril increased PBK from a control of 14.1 to 27.9 pg/ml at 30 min, corresponding to the marked fall in blood pressure from 170/106 to 136/90 mmHg. From these findings, it is suggested that the accumulation of kinins following captopril administration plays a major role in the short-term reduction of blood pressure in hypertensive patients, especially in those with low renin-angiotensin activity.

The study was designed to explore the mechanism of dopamine secretion related to blood pressure in patients with essential hypertension. The 19 patients with essential hypertension were administered to first 153 mEq of sodium and 70 mEq of potassium diet, next 51 mEq of sodium and finally 340 mEq of sodium for every one week. The patients whose mean blood pressure elevated 10 mmHg or more on the high-sodium loading and depleted 10 mmHg or more on the low-sodium loading were classified as A-, and depleted 10 mmHg or more on the high-sodium loading and elevated 10 mmHg or more on the low-sodium loading as B- and the other patients as C-group. The hypertensive patients were also classified to low- (below 1.0 ng/ml/h), normal- (from 1.0 to 6.0 ng/ml/h) and high- (above 6.0 ng/ml/h) renin groups from the results of plasma renin activity (PRA) obtained after an intravenous injection of furosemide (1 mg/kg) followed by 2-hour ambulation. PRA, plasma aldosterone concentration (PAC), plasma epinephrine concentration (PE), plasma norepinephrine concentration (PNE), plasma dopamine concentration (PDC), circulating plasma volume, body weight, hematocrit and pulse rate were measured at 8 a.m. after sodium loading for 8-days. The patients with essential hypertension were classified into 6 of A- and 2 of B- and 11 of C-groups with the maneuver of sodium loading. The A-group contained 5 patients with low-renin. The circulating plasma volume was relatively large (44.7 +/- 4.8 ml/kg) and markedly increased on the high-sodium loading in 6 patients of A-group. The increment of body weight was higher in A-group than the other groups on the high-sodium loading. In the 2 patients of B-group, hematocrit and pulse rate increased on the low-sodium and decreased on the high-sodium loading, and the variability were larger than the other groups. In the A-group, PRA was significantly low (0.5 +/- 0.4 ng/ml/h) and increased on the low-sodium loading and decreased on the high-sodium loading, and the variability of PRA was lesser than the other groups. In the A-group, PAC was within normal range (5.4 +/- 2.8 ng/dl) and the variation of PAC paralleled with the change of PRA, but the variability of PAC was remarkably low. PE and PNE were unchanged in the A- and the C-groups, but the significant high values were observed in the B-group on the high-sodium loading.

A 17-year-old female weighing 37 kg and 140 cm in height was referred to our hospital for evaluation of dwarfism and primary amenorrhea. She was delivered with 3350 g in weight and 50 cm in height after a ten month pregnancy without complications. No abnormal findings were revealed in physical appearance except critomegaly. Episodes of nausea, vomiting and dehydration were rare throughout her childhood, but she had a tendency to salt craving. At the age of 14, her height was 140 cm. On admission, her physical development was markedly retarded for her age, except external genitalia. Diffuse pigmentations on the trunk and extremities were observed. Her blood pressure was normal (112/62 mm Hg). Serum potassium concentration was 2.9 mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Both of renin activity (PRA) and aldosterone concentration (PAC) in plasma at rest were markedly elevated to 15.5 ng/ml/h and 107.1 ng/dl, respectively. The plasma concentrations of pregnenolone (1449 ng/dl), progesterone (178 ng/dl), 17-OH-pregnenolone (1613 ng/dl), 17-OH-progesterone (180 ng/dl), dehydroepiandrosterone (3706 ng/dl), androstendione (824.6 ng/dl) and testosterone (900 ng/dl) were high, whereas deoxycorticosterone (15.7 ng/dl), corticosterone (0.65 microgram/dl) and cortisol (6.8 micrograms/dl) were within normal limits. Urinary 17-KS excretion showed high levels between 65.7 and 109.4 mg/day, while urinary 17-OHCS excretion was normal (5.7-7.0 mg/day). Vascular response to angiotensin II (A-II) was attenuated. Distal fractional chloride reabsorption was decreased (CH2O/CH2O+CCl = 0.62, normal: 0.92 +/- 0.04). Moderate hyperplasia of the juxtaglomerular cells was demonstrated in biopsy specimen of the kidney. Cytogenetic studies showed a 46, XX chromosome constitution with translocation of the long arm of chromosome 6 to the short arm of chromosome 9. Her mother as well as younger brother and sister, whose electrolytes and arterial-blood gas analysis showed normal values, had chromosomes with the same translocation. Treatment with dexamethasone (2 mg/day) reduced every adrenal steroids to normal range, but PRA and PAC remained high levels. Furthermore, neither hypokalemic alkalosis nor vasoreactivity to exogenous A-II was improved. Indomethacin (75 mg/day) decreased urinary excretion of prostaglandin E2 from a high level of 738.4 ng/day to 433.4 ng/day and normalized metabolic alkalosis. Vascular response to A-II was moderately improved. However, serum potassium remained low.(ABSTRACT TRUNCATED AT 400 WORDS)

1. There is increasing evidence which suggests that the adrenal gland contains the renin–angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin. 2. Sizable quantities of renin-like activity (32.0 ± 7.7 ng of angiotensin I generated h−1 mg−1 of protein, mean ± SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D. 3. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36000, 37000, 44000 and 48000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00). 4. These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme.

The acute antihypertensive effect of a new long-acting oral angiotensin I-converting enzyme (ACE) inhibitor, enalapril maleate, was assessed in 20 hypertensive patients, of whom 14 had essential hypertension, 4 had renovascular hypertension, one had hypertension associated with chronic renal failure, and one had primary aldosteronism. Enalapril maleate significantly lowered the blood pressure in either low-renin or normal- and high-renin hypertensives. There was a significant correlation for all patients as a group between the pretreatment levels of serum ACE activity and the reduction in mean blood pressure (r = -0.454, p less than 0.05, n = 20) 2 h after drug administration. The serum ACE activity decreased maximally 3 to 4 hours after drug administration and did not return to baseline levels within 24 h. There was a significant correlation between the reduction in mean blood pressure and changes in ACE activity 90 min and 2 h after drug administration, respectively, for all patients as a group (r = 0.495, p less than 0.05, n = 20, at 90 min; r = 0.508, p less than 0.05, n = 20, at 2 h). The plasma renin activity (PRA) significantly increased in normal- and high-renin hypertensives but not in low-renin hypertensives. There was a close correlation between the reduction in mean blood pressure and the PRA 8 h after drug administration in normal- and high-renin patients (r = -0.623, p less than 0.05, n = 13), while no such relationship was observed in low-renin patients. The plasma aldosterone concentration (PAC) significantly decreased within 3 h, the lowest values occurring at 8 h after drug administration, and it returned to baseline levels within 24 h in all patients. No relationship was found between the reduction in mean blood pressure and changes in PAC after drug administration in either low-renin or normal- and high-renin hypertensives. The plasma bradykinin concentration (PBC) increased within 1 h, the highest values occurring at 3 h after drug administration, and returned to baseline levels within 24 h in low-renin hypertensives, while the PBC was significantly increased at 4 h and had not returned to baseline levels within 24 h in normal- and high-renin hypertensives. There was a significant correlation between percentage changes in mean blood pressure and those in PBC 90 min after drug administration in normal- and high-renin hypertensives (r = -0.556, p less than 0.05, n = 13), while no relationship was observed between them in low-renin hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)

To assess the interaction between dopamine and aldosterone secretion in primary aldosteronism, the dopamine antagonist, metoclopramide (methoxy-2-chloro-5-procainamide), was given as an i.v. bolus (10 mg) to 5 patients with primary aldosteronism and 5 normal subjects treated with dexamethasone (2 mg/day) to eliminate an influence of ACTH. Metoclopramide increased plasma aldosterone concentration (PAC) in primary aldosteronism from 39.1 +/- 15.5 to 42.5 +/- 15.9 ng/100 ml (p less than 0.05) and also from 12.9 +/- 2.3 to 23.6 +/- 3.4 ng/100 ml (p less than 0.01) in normal subjects at 15 min. Plasma renin activity (PRA), and plasma concentrations of cortisol, potassium, and sodium did not significantly change with metoclopramide in either primary aldosteronism or normal subjects. Plasma prolactin increased by 12- and 20-fold in primary aldosteronism and in normal subjects, respectively, but there was no significant positive correlation between changes in PAC and in plasma prolactin in either primary aldosteronism or normal subjects. It is suggested that dopamine inhibits the secretion of aldosterone in primary aldosteronism as well as in normal subjects. It seems unlikely that dopamine affects the release of renin in primary aldosteronism.

High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr=46, 000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin pI=4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.

症例, 30才,女.生下時より全身の脂肪萎縮著明. 27才時糖尿病を指摘. 29才時右結膜仮性リンパ腫にて放射線療法施行. 1982年6月全身の脂肪萎縮の精査のため当科入院.検査所見:血沈亢進,白血球減少, RAテスト陽性,高γグロブリン血症.血清脂質正常. GTTにて糖尿病型, IRIは遅延反応.インスリン感受性低下.尿中diabetogenic peptide陽性. HGH, LHおよびFSHはそれぞれアルギニン, LH-RH負荷に対し遅延反応.以上より本症例を脂肪萎縮性糖尿病と診断した. 1984年5月ごろより口内乾燥感・両側膝関節痛出現, Sjoren症候群を合併すると診断した.現在までかかる症例の報告はなく,本疾患の発症・維持に免疫機構の異常を示唆した点で興味深い.

High activity of renin was demonstrated in human neuroblastoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 122.8 ng of angiotensin I generated mg of protein-1 h-1. It shared some biochemical features with well-known kidney renin, such as molecular weight, optimum pH, the presence of trypsin-activatable inactive renin, and glycoprotein nature. Furthermore, angiotensin-converting enzyme (ACE) activity (2.64 nmol mg of protein-1 min-1) was found in the tissue. This activity was inhibited by captopril, a specific ACE inhibitor, or by omission of chloride ion. These results suggest that true renin in addition to ACE exists in human neuroblastoma tissue.