Fast walking is a preventive factor against new-onset diabetes mellitus in a large cohort from a Japanese general population.

Based on questionnaires from 197,825 non-diabetic participants in a large Japanese cohort, we determined impact of (1) habit of exercise, (2) habit of active physical activity (PA) and (3) walking pace on new-onset of type 2 diabetes mellitus. Unadjusted and multivariable-adjusted logistic regression models were used to determine the odds ratio of new-onset diabetes mellitus incidence in a 3-year follow-up. There were two major findings. First, habits of exercise and active PA were positively associated with incidence of diabetes mellitus. Second, fast walking, even after adjusting for multiple covariates, was associated with low incidence of diabetes mellitus. In the subgroup analysis, the association was also observed in participants aged ≥ 65 years, in men, and in those with a body mass index ≥ 25. Results suggest that fast walking is a simple and independent preventive factor for new-onset of diabetes mellitus in the health check-up and guidance system in Japan. Future studies may be warranted to verify whether interventions involving walking pace can reduce the onset of diabetes in a nation-wide scale.

Walking Speed is the Sole Determinant Criterion of Sarcopenia of Mild Cognitive Impairment in Japanese Elderly Patients with Type 2 Diabetes Mellitus.

Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes mellitus (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, body mass index (BMI), duration of diabetes mellitus, hypertension, dyslipidemia, smoking, drinking, estimated glomerular filtration rate (eGFR), HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This study showed that slow walking speed is a sole determinant criterion of sarcopenia of MCI in patients with type 2 diabetes mellitus. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

[Coexisting Symptomatic Adrenocorticotropic Hormone- and Growth Hormone-producing Double Pituitary Adenomas with Difficulty in Tumor Localization:A Case Report].

Double functional pituitary adenomas are rare, and only a few cases of excessive clinical symptoms of both adrenocorticotropic hormone(ACTH)and growth hormone(GH)have been reported. We herein report a case of symptomatic ACTH-and GH-producing double pituitary adenomas, which were discretely located within the same pituitary gland. A 38-year-old woman presented with general malaise, facial and lower limb edema, unexplained weight gain, facial redness, acne, and nasal enlargement. Endocrinological findings matched with the diagnostic criteria for both acromegaly and Cushing's disease. Preoperative magnetic resonance imaging showed a 15-mm cyst-like lesion on the right side of the sellae surrounded by what was thought to be the normal contrast-enhancing pituitary gland. We assumed that the cyst-like lesion was an adenoma and performed endoscopic endonasal transsphenoidal surgery. However, the cyst-like lesion was a parenchymal tumor. Furthermore, the region we considered to be a normal pituitary gland was also found to be an adenoma. Both adenomas were completely resected. The postoperative blood analysis showed ACTH<1.0pg/dL, cortisol 1.8µg/dL, and insulin-like growth factor-1 60ng/mL, all of which were below reference levels. The histopathological examination confirmed the coexistence of two adenomas, a GH-producing adenoma and an ACTH-producing adenoma. We concluded that these adenomas were endocrinologically active within the pituitary gland. Thus, a diagnosis of double pituitary adenomas was made. When treating a patient with symptoms caused by hypersecretion of multiple anterior pituitary hormones, the possibility of coexisting multiple pituitary adenomas should be considered.

Assessment of myocardial ischemic memory using speckle tracking echocardiography.

OBJECTIVES: The aim of this study was to evaluate which regional myocardial parameters derived from speckle tracking echocardiography could demonstrate myocardial ischemic memory in a brief ischemia-reperfusion dog model. BACKGROUND: Myocardial ischemic memory imaging, denoting the visualization of abnormalities provoked by ischemia and sustained even after restoration of perfusion, can convey important clinical information. We previously reported that post-systolic shortening (PSS) remains in the risk area after recovery from brief ischemia. However, it is still unclear whether abnormalities in other regional deformation parameters persist after relief from brief ischemia. METHODS: Echocardiographic data were chronologically acquired from 11 dogs during 2 min of coronary occlusion followed by reperfusion. Regional systolic and diastolic deformation parameters, including parameters related to PSS, were measured from radial and circumferential strain and from strain rate analyzed in the risk and normal areas. Strain imaging diastolic index (SI-DI), which had been proposed as a parameter for assessing ischemic memory, was also calculated. RESULTS: Peak systolic strain, end-systolic strain, and peak systolic strain rate decreased in the risk area during occlusion but recovered to the baseline level immediately after reperfusion. Strain rate during early diastole decreased during occlusion; however, the decrease did not persist after reperfusion. Post-systolic strain index (PSI) and time-to-peak strain index, which are parameters of PSS, increased during occlusion. These increases persisted until 10 to 20 min after reperfusion (circumferential PSI: 0.02 ± 0.04 [baseline] vs. 0.08 ± 0.04 [20 min], p < 0.05). SI-DI did not show a significant change during occlusion because of a large variation. CONCLUSIONS: Although abnormalities of PSS-related parameters alone persisted after recovery from 2-min occlusion, abnormalities of other deformation parameters, such as strain rate during early diastole, did not. These data suggest that assessment of PSS by speckle tracking echocardiography is useful for detecting myocardial ischemic memory.

Effects of mechanical limitation of apical rotation on left ventricular relaxation and end-diastolic pressure.

Left ventricular (LV) twist is thought to play an important role in cardiac function. However, how twist affects systolic or diastolic function is not understood in detail. We acquired apical and basal short-axis images of dogs undergoing open-chest procedures (n = 15) using a GE Vivid 7 at baseline and during the use of an apical suction device (Starfish) to limit apical rotation. We measured LV pressure and stroke volume using a micromanometer-tipped catheter and an ultrasonic flow probe, respectively. Peak radial strain, peak rotation, peak twist, peak systolic twisting rate (TR), peak untwisting rate during isovolumic relaxation period (UR(IVR)), and peak early diastolic untwisting rate after mitral valve opening (UR(E)) were determined using speckle tracking echocardiography. Immobilizing the apex with gentle suction significantly decreased apical rotation (-50 ± 27%) and slightly increased basal rotation, resulting in a significant decrease in twist. The time constant of LV relaxation (τ) was prolonged, and LV end-diastolic pressure increased. TR and UR(IVR) decreased. LV systolic pressure, peak positive and negative first derivative of LV pressure (±dP/dt), stroke volume, radial strain, and UR(E) were not changed. The correlation between τ and UR(IVR) (r = 0.63, P = 0.0006) was stronger than that between peak +dP/dt and TR (r = 0.46, P = 0.01). Diastolic function was impaired with reduced apical rotation and UR(IVR) when the apex of the heart was immobilized using an apical suction device.

Problems of positive list system revealed by survey of pesticide residue in food.

The positive list system became effective from May 29, 2006 to improve the regulation of residual agricultural chemicals (pesticides, feed additives and veterinary drugs) in foods. In accordance with the system, we investigated pesticide residues in 50 agricultural products purchased in Morioka city from March to November 2006. Analyses were performed according to the "Multiresidue Method for Agricultural Chemicals by GC/MS", the Notice of the Ministry of Health, Labour and Welfare. Five pesticides and two non-agricultural chemicals were detected from 16 samples. Ortho-phenylphenol (OPP) was detected from 8 samples: immature pea, snap bean, kiwi, plain-boiled bamboo shoot, mango, white asparagus, lemon and domestic shiitake mushroom. Maximum residue limits (MRLs) have not been established for these products, and they exceeded the uniform level of 0.01 ppm. DDT was detected from Philippines banana (0.30 ppm) and Korean paprika (0.45 ppm). The residual level in Philippines banana was lower than the MRL, but Korean paprika exceeded its MRL. Chlorpyrifos, Thiabendazole and Imazaril were detected from citrus imported from the U.S.A., but their residue levels were lower than the respective MRLs. Aniline and 2-pyrrolidone were detected from several imported products. These two may not be regulated by the positive list system because they are not agricultural chemicals, although their derivatives are used as pesticides or veterinary drugs. Three problems have been revealed from this survey: 1) application of the uniform level to minor agricultural products, 2) residues of non-agricultural chemicals whose toxicity is uncertain, 3) metabolites of agricultural chemicals, which are also regulated by the positive list system, have not been clearly defined.

Fragmentation of cell-free fetal DNA in plasma and urine of pregnant women.

OBJECTIVES: We assessed the effect of freezing on fragmentation of fetal DNA in maternal plasma and differences in DNA fragmentation between plasma and urine from pregnant women. METHODS: 1. We prepared seven kinds of real-time PCR assays to amplify different-sized amplicons targeting the SRY gene. Fragmentation of fetal DNA in maternal plasma was compared between new (n=10) and 4-year-old samples (n=10). 2. To investigate differences in fragmentation of fetal DNA between plasma and urine from pregnant women, we amplified three different-sized amplicons and compared DNA fragmentation between plasma and urine (n=7). RESULTS: 1. Relative concentrations of fetal DNA compared to a 63-bp amplicon in new samples were 53.1, 42.0, 9.2 and 2.0% (median) for PCR amplicons of 107, 137, 193 and 313 bp, respectively. Concentrations in 4-year-old samples were 70.4, 40.9, 11.9 and 2.3%, respectively. 2. Although fetal DNA in urine was not detected for 107- and 137-bp amplicons of the SRY sequence, fetal DNA using a 63-bp amplicon was detectable in five of seven cases (71.4%). CONCLUSION: Cell-free fetal DNA in maternal plasma is stable under cryopreservation at -20 degrees C for at least 4 years. Approximately, 60% of fetal DNA in maternal plasma was fragmented to <100-bp long, and fetal DNA in urine was further fragmented. Maternal urine may be usable for detection of fetal DNA, although smaller target size is more important for PCR amplification of fetal DNA in urine than in the analysis of plasma from pregnant women.

Total cell-free DNA (beta-globin gene) distribution in maternal plasma at the second trimester: a new prospective for preeclampsia screening.

OBJECTIVES: Levels of cell-free foetal DNA (f-DNA) in maternal plasma are higher in those asymptomatic subjects who will eventually develop preeclampsia. f-DNA is, however, informative only for those women bearing a male foetus, by amplification of Y-specific sequences and represents a small fraction of total circulating DNA that can be dosed by using ubiquitous genes as well as beta-globin. In this study, we examined the quantitative distribution of total DNA by amplification of beta-globin gene, in asymptomatic women matched with controls to evaluate its possible role in predicting preeclampsia. METHODS: Forty-eight low-risk women (8 asymptomatic cases matched for gestational age at the second trimester with 40 controls) were enrolled in the present study. beta-globin concentrations were converted into multiples of the median of the controls (MoM), in order to assess the possible different distribution of beta-globin MoM in cases and controls. RESULTS: MoM values were as follows: controls, 1.00 +/- 0.59; asymptomatic cases, 1.99 +/- 1.95. After Gaussian conversion of data, at a false-positive rate (FPR) of 5%, the detection rate (DR) was 46%. CONCLUSION: beta-globin (total DNA) levels are higher in those patients who subsequently developed preeclampsia and can potentially be used in screening for early detection of the disease. These findings represent a step forward in the study of cell-free DNA in maternal blood as a screening variable, because it overcomes the gender limitations of foetal DNA screening.

beta-globin DNA in maternal plasma as a molecular marker of pre-eclampsia.

OBJECTIVES: Levels of cell-free foetal DNA in maternal plasma are higher in the presence of clinical features of pre-eclampsia (PE). However, currently, this method is informative only in women bearing a male foetus, by amplification of Y-specific sequences. In the present study, we overcame this limitation by examining quantitative distribution of beta-globin, a foetal gender-independent DNA marker. METHODS: We quantified beta-globin concentrations in the plasma of 207 pregnant women: control group, 164 subjects; affected group, 43 women affected by PE (n = 43). beta-globin concentrations were converted into multiples of the median of the controls (MoM), in order to assess the possible different distribution of beta-globin MoM in cases and controls. RESULTS: Adjusted MoM values were as follows: controls, 1.00 +/- 0.71; affected group 4.03 +/- 3.77 (p-value < 0.001). Among the PE affected cases, MoM beta-globin values of cases with foetal growth restriction (FGR) were almost twice as great as those cases without FGR (p-value = 0.003). CONCLUSION: beta-globin levels are higher in the plasma of pregnant women with PE, especially in those cases complicated with FGR, and do not depend on foetal gender. Such a molecular marker can potentially be used in evaluating the pathophysiological severity of PE.

Fetal DNA in maternal plasma as a screening variable for preeclampsia. A preliminary nonparametric analysis of detection rate in low-risk nonsymptomatic patients.

OBJECTIVE: Our objective was to examine whether plasma fetal DNA can be used as a screening variable in those women who developed preeclampsia but without any clinical symptom at the time of blood draw. METHODS: Fetal DNA was extracted from 1.5-mL plasma samples, and the DYS14 gene was analyzed by real-time quantitative polymerase chain reaction. Plasma collected and frozen from six women were each paired with five matched control samples of identical specimen type from gravid women carrying a presumed normal male fetus. Matched rank-sum analysis and nonparametric receiver operating characteristic (ROC) curves analysis of estimated multiples of median (MoM) were used for calculating detection rate (DR) and false-positive rate (FPR). RESULTS: The mean observed rank of 5.08 in the cases was significantly higher than the expected 3.18 (p-value = 0.013). Pregnancies that will develop a preeclampsia exhibit 2.39-fold higher levels of maternal plasma cell-free fetal DNA compared to matched controls. DR was 33 and 50% at an FPR of 5 and 10% respectively. CONCLUSIONS: The estimated DR allows to consider fetal DNA as a potential variable to predict preeclampsia in a low-risk population. Further studies will be addressed to calculate a parametric statistical algorithm and to estimate a proper posterior risk of the disease by means of fetal DNA alone or combined with other markers.

Evaluation of bidirectional transfer of plasma DNA through placenta.

To clarify the origin of cell-free fetal DNA in maternal plasma, we analyzed bidirectional transfer of plasma DNA between fetus and mother. We analyzed maternal and fetal plasma DNA obtained from 15 pregnant women at the time of Cesarean section. The subjects were five patients with preeclampsia and 10 gestational-age-matched normal controls. DNA was extracted from 1.5-ml plasma samples and the cellular fraction of maternal and umbilical blood. Seven polymorphic marker genes were analyzed. The relative concentration of fetal DNA in maternal plasma and maternal DNA in cord blood were evaluated. The relative concentration of maternal DNA in fetal circulation (median, 0.9%; range, 0.2-8.4%) was significantly lower than that of fetal DNA in maternal blood (14.3%, 2.3-64%), with P=0.007. The relative concentration of maternal DNA in fetal blood was not affected by preeclampsia. These findings indicate that cell-free DNA is unequally transferred through the placenta. The structural characteristics of the placenta suggest that the majority of cell-free fetal DNA in maternal plasma is derived from villous trophoblasts.

Cell-free fetal DNA in the plasma of pregnant women with severe fetal growth restriction.

OBJECTIVE: Although there have been reports of increased fetal nucleated erythrocytes in the blood of pregnant women who are carrying growth-restricted fetuses, there have been no reports of quantification of fetal DNA concentration in the plasma of women with fetal growth restriction. We quantified fetal DNA concentration in the plasma of pregnant women with preeclampsia and/or fetal growth restriction. STUDY DESIGN: We examined maternal plasma from 9 pregnant women with fetal growth restriction and 9 with preeclampsia and from 20 women who were gestational age-matched normal control subjects. All women carried a male fetus. DNA was extracted from 1.5-mL plasma samples, and the DYS14 and beta-globin gene were analyzed by real-time quantitative polymerase chain reaction. RESULTS: The concentration of fetal DNA was significantly higher in subjects with preeclampsia than in fetal growth restriction subjects and normal control subjects. Fetal DNA concentrations in fetal growth restriction subjects were similar to those of normal control subjects. The concentration of total DNA (beta-globin) was significantly higher in subjects with preeclampsia when compared with healthy control subjects. CONCLUSION: We demonstrated that there was no increase in fetal DNA in the plasma of pregnant women with fetal growth restriction and that most fetal DNA in maternal plasma originates from trophoblasts.