Risk factors for chronic kidney disease progression over 20 years for primary prevention in Japanese individuals at a preventive medicine research center: Focus on the influence of plasma glucose levels.

AIMS/INTRODUCTION: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. MATERIALS AND METHODS: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis. RESULTS: During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). CONCLUSIONS: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

Prognostic analysis of pulmonary hypertension with lung parenchymal lesion: Comparison of mortality with and without connective tissue disease.

BACKGROUND: The prognosis of pulmonary hypertension (PH) associated with connective tissue diseases related to interstitial pneumonia (CTD-IP PH) is relatively good among patients with PH and lung disease. However, the impact of pulmonary vasodilator treatment on the prognosis of CTD-IP PH compared with that of PH-induced chronic lung disease (group-3 PH) remains unclear. METHODS: From 2012 to 2022, 50 patients with lung parenchymal lesions diagnosed with PH (mean pulmonary arterial pressure >20 mmHg) at Juntendo University Hospital were divided into two groups: CTD-IP PH (30 patients) and group 3-PH (20 patients). The impact of pulmonary vasodilator treatment and the use of long-term oxygen therapy (LTOT) on the prognosis of each group was examined retrospectively. RESULTS: The prognosis of CTD-IP PH was significantly better compared to group-3 PH. While the treatment with pulmonary vasodilators did not affect the prognosis in group 3-PH, the prognosis of the patients treated with vasodilators in the CTD-IP PH group was significantly better than that of the non-treated patients. Treatment with multi-pulmonary vasodilators did not affect the prognosis in CTD-IP PH. Although the prognosis for the patients with LTOT was poor in all registered patients in the present study, treatment with pulmonary vasodilators improved the prognosis even under the use of LTOT in CTD-IP PH (P = 0.002). In a multivariate analysis of the CTD-IP PH group, pulmonary vasodilator treatment was an independent factor for better prognosis. CONCLUSION: Treatment with a pulmonary vasodilator for CTD-IP PH may improve the prognosis, even in patients requiring LTOT.

Sex differences in predictive factors for onset of type 2 diabetes in Japanese individuals: A 15-year follow-up study.

AIMS/INTRODUCTION: The increase in the number of patients with type 2 diabetes mellitus is an important concern worldwide. The goal of this study was to investigate factors involved in the onset of type 2 diabetes mellitus, and sex differences in long-term follow up of people with normal glucose tolerance. MATERIALS AND METHODS: Of 1,309 individuals who underwent screening at our facility in 2004, 748 individuals without diabetes were enrolled. Correlations of metabolic markers including serum adiponectin (APN) with onset of type 2 diabetes mellitus were examined over 15 years in these individuals. RESULTS: The Kaplan-Meier curve for onset of type 2 diabetes mellitus for 15 years in the decreased APN group was examined. Hazard ratios for the APN concentration for onset of diabetes were 1.78 (95% confidence interval [CI] 1.20-2.63, P = 0.004) in all participants, 1.48 (95% CI 0.96-2.29, P = 0.078) for men and 3.01 (95% CI 1.37-6.59, P = 0.006) for women. During the follow-up period of 15 years, body mass index, estimated glomerular filtration rate, fatty liver, C-reactive protein and alanine aminotransferase in men were significant in univariate analysis, but only estimated glomerular filtration rate and fatty liver were significantly related to onset of type 2 diabetes mellitus in multivariate analysis. In women, body mass index, systolic blood pressure, triglyceride, fatty liver and APN were significant in univariate analysis, and APN was the only significant risk factor in multivariate analysis (P < 0.05). CONCLUSIONS: There are differences between men and women with regard to targets for intervention to prevent the onset of type 2 diabetes mellitus. Individuals requiring intensive intervention should be selected with this finding to maximize the use of limited social and economic resources.

A case of negative-pressure pulmonary oedema after first-time electroconvulsive therapy.

Electroconvulsive therapy (ECT) has been used for many years as an important treatment modality in patients with schizophrenia. Recently, many new oral medications have become available to treat schizophrenia. However, ECT remains a valuable therapy for patients who are resistant to oral medications. A 16-year-old girl with schizophrenia was admitted to our hospital with hypoxaemia due to negative-pressure pulmonary oedema (NPPE) after her first ECT. NPPE is an exceedingly rare complication after ECT. However, it can result in serious morbidity if not immediately recognized and treated. This case illustrates the importance of recognizing this rare complication.

Periostin-related progression of different types of experimental pulmonary hypertension: A role for M2 macrophage and FGF-2 signalling.

BACKGROUND AND OBJECTIVE: Remodelling of pulmonary arteries (PA) contributes to the progression of pulmonary hypertension (PH). Periostin, a matricellular protein, has been reported to be involved in the development of PH. We examined the role of periostin in the pathogenesis of PH using different types of experimental PH. METHODS: PH was induced by vascular endothelial growth factor receptor antagonist (Sugen5416) plus hypoxic exposure (SuHx) and venous injection of monocrotaline-pyrrole (MCT-P) in wild-type (WT) and periostin-/- mice. Pulmonary haemodynamics, PA remodelling, expression of chemokines and fibroblast growth factor (FGF)-2, accumulation of macrophages to small PA and the right ventricle (RV) were examined in PH-induced WT and periostin-/- mice. Additionally, the role of periostin in the migration of macrophages, human PA smooth muscle (HPASMCs) and endothelial cells (HPMVECs) was investigated. RESULTS: In PH induced by SuHx and MCT-P, PH and accumulation of M2 macrophage to small PA were attenuated in periostin-/- mice. PA remodelling post-SuHx treatment was also mild in periostin-/- mice compared to WT mice. Expression of macrophage-associated chemokines and FGF-2 in lung tissue, and accumulation of CD68-positive cells in the RV were less in SuHx periostin-/- than in SuHx WT mice. Periostin secretion in HPASMCs and HPMVECs was enhanced by transforming growth factor-ß. Periostin also augmented macrophage, HPASMCs and HPMVECs migration. Separately, serum periostin levels were significantly elevated in patients with PH compared to healthy controls. CONCLUSION: Periostin is involved in the development of different types of experimental PH, and may also contribute to the pathogenesis of human PH.

Hyperferritinemia Is a Predictor of Onset of Diabetes in Japanese Males Independently of Decreased Renal Function and Fatty Liver: A Fifteen-Year Follow-Up Study.

BACKGROUND: Type 2 diabetes is an important health concern worldwide. The disease etiology may depend on multiple environmental and genetic factors that cause insulin resistance, including dysregulation of iron storage. The goal of this study was to examine the relationship of the serum ferritin concentration with onset of diabetes over a long period. METHODS: Correlations of serum ferritin and metabolic markers with onset of diabetes mellitus were examined over 15 years in 150 males participating in a health screening program. RESULTS: HOMA-ß showed a gradual significant decrease in the first 4 years in subjects with ferritin > 190 ng/mL (group H) compared to those with ferritin ≤ 190 ng/mL, but there was no difference in HOMA-R between these groups. A significant number of cases with onset of diabetes was observed over 15 years (hazard ratio (HR): 3.97), and obesity, fasting blood glucose level, hemoglobin A1c (HbA1c), HOMA-R, fasting immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) were all significant in univariate comparison between non-diabetes and diabetes-onset groups. In multivariate analysis, ferritin in group H (HR: 3.25), fatty liver (HR: 3.38), estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m2 (HR: 3.48) and high-density lipoprotein (HDL) < 40 mg/dL (HR: 2.61) were significant predictive factors for onset of type 2 diabetes mellitus. CONCLUSIONS: These results suggest that the serum ferritin level is an important index for priority intervention in preventive medicine for reduction of onset of diabetes.

Improving contrast and spatial resolution in crystal analyzer-based x-ray dark-field imaging: Theoretical considerations and experimental demonstration.

PURPOSE: This paper describes and experimentally validates a methodology for improving contrast and spatial resolution of the x-ray dark-field imaging (XDFI) by cutting the monochromator-collimator asymmetrically and thinning the Laue angle analyzer. METHODS: We measure the spatial resolution of our XDFI setup using a test object consisting of wolfram tungsten meshes and compare it with the theoretical prediction. Using x-ray dark-field computed tomography of breast cancer specimens (lobular carcinoma in situ), we demonstrate that the resolution of XDFI is sufficient for histopathologic analysis. RESULTS: Our experimental results show that the overall spatial resolution of XDFI can be improved by approximately a factor of 2 when these modifications are implemented. The reconstructed images of breast cancer specimens provide sufficient details for radiologic histopathology. CONCLUSIONS: By cutting the monochromator-collimator and thinning the Laue angle analyzer, XDFI can achieve the resolution sufficient for radiologic histopathology.

Nintedanib ameliorates experimental pulmonary arterial hypertension via inhibition of endothelial mesenchymal transition and smooth muscle cell proliferation.

Neointimal lesion and medial wall thickness of pulmonary arteries (PAs) are common pathological findings in pulmonary arterial hypertension (PAH). Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling contribute to intimal and medial vascular remodeling in PAH. Nintedanib is a tyrosine kinase inhibitor whose targets include PDGF and FGF receptors. Although the beneficial effects of nintedanib were demonstrated for human idiopathic pulmonary fibrosis, its efficacy for PAH is still unclear. Thus, we hypothesized that nintedanib is a novel treatment for PAH to inhibit the progression of vascular remodeling in PAs. We evaluated the inhibitory effects of nintedanib both in endothelial mesenchymal transition (EndMT)-induced human pulmonary microvascular endothelial cells (HPMVECs) and human pulmonary arterial smooth muscle cells (HPASMCs) stimulated by growth factors. We also tested the effect of chronic nintedanib administration on a PAH rat model induced by Sugen5416 (a VEGF receptor inhibitor) combined with chronic hypoxia. Nintedanib was administered from weeks 3 to 5 after Sugen5416 injection, and we evaluated pulmonary hemodynamics and PAs pathology. Nintedanib attenuated the expression of mesenchymal markers in EndMT-induced HPMVECs and HPASMCs proliferation. Phosphorylation of PDGF and FGF receptors was augmented in both intimal and medial lesions of PAs. Nintedanib blocked these phosphorylation, improved hemodynamics and reduced vascular remodeling involving neointimal lesions and medial wall thickening in PAs. Additionally, expressions Twist1, transcription factors associated with EndMT, in lung tissue was significantly reduced by nintedanib. These results suggest that nintedanib may be a novel treatment for PAH with anti-vascular remodeling effects.

Dementia Cafés as Hubs to Promote Community-Integrated Care for Dementia through Enhancement of the Competence of Citizen Volunteer Staff Using a New Assessment Tool.

INTRODUCTION: Dementia cafés have recently been attracting attention. The increased involvement of citizen volunteers and the competence of dementia café staff could enhance the potential of dementia cafés. The aim of the present study was to examine enhancement of the competence of citizen volunteers using a new assessment tool. METHODS: This cross-sectional analysis included 433 dementia café staff members, including medical and care professionals and citizen volunteers. A 20-item dementia café staff self-assessment (DCSA) instrument was newly developed. After confirmation of the reliability and validity of the instrument, DCSA scores among citizen volunteers were evaluated. RESULTS: DCSA showed very good psychometric properties. The mean (±SD) DCSA score was significantly higher for café staff with a medical and care professional background (n = 267) than for citizen volunteers (n = 166) (2.2±0.5 vs. 1.7±0.7, respectively; p < 0.001). The DCSA scores of citizen volunteers became significantly higher with increasing attendance (minimum: n = 24; 1.3±0.7; intermediate: n = 65; 1.6±0.6; and frequent: n = 77; 1.8±0.7; p < 0.01). CONCLUSION: Assessment of the competence of dementia café staff using the DCSA revealed the potential of citizen volunteers. This tool could also enhance the potential of dementia cafés.

Dark-Field Imaging: Recent developments and potential clinical applications.

This paper describes an X-ray phase contrast imaging technique using analyzer-based optics called X-ray Dark-Field Imaging that has been under development for the past 10years. We describe the theory behind XDFI, the X-ray optics required for implementing it in practice, and algorithms used for 2D, 2.5D, and 3D image reconstruction. The XDFI optical chain consists of an asymmetrically cut, Bragg-type monochromator-collimator that provides a planar monochromatic X-ray beam, a positioning stage for the specimens, a Laue-case angle analyzer, and one or two cameras to capture the dark and bright field images. We demonstrate the soft-tissue discrimination capabilities of XDFI by reconstructing images with absorption and phase contrast. By using a variety of specimens such as breast tissue with cancer, joints with articular cartilage, ex-vivo human eye specimen, and others, we show that refraction-based contrast derived from XDFI is more effective in characterizing anatomical features, articular pathology, and neoplastic disease than conventional absorption-based images. For example, XDFI of breast tissue can discriminate between the normal and diseased terminal duct lobular unit, and between invasive and in-situ cancer. The final section of this paper is devoted to potential future developments to enable clinical and histo-pathological applications of this technique.

Association of morning fasting blood glucose variability with insulin antibodies and clinical factors in type 1 diabetes.

The fasting blood glucose concentration in type 1 diabetes may vary without being much affected by diet and exercise. This study aimed to identify association of morning fasting blood glucose concentration variability with insulin antibodies and clinical factors. The subjects in this study were 54 patients with type 1 diabetes who had high variation of fasting blood glucose. The insulin antibody level was measured, and correlations of glycemic variability with antibody levels, binding rates, and other clinical factors were investigated. The standard deviation (SD) of the 30-day morning self-monitored fasting blood glucose concentration (FBG SD) was evaluated as an index of glycemic variability. The mean glucose level was 159.8±42.1 mg/dL and the FBG SD was 47.5±22.0 mg/dL. Glycemic variability (FBG SD) was positively correlated with insulin antibody level, but not with insulin antibody binding rate, and had a negative correlation with C-peptide immunoreactivity/plasma glucose (CPR/PG) and positive correlations with diabetes duration, basal insulin dose and bolus insulin dose. Glycemic variability was not correlated with BMI, HbA1c or age. In multiple regression analysis of glycemic variability, CPR/PG was the only significant related factor. The results showed that glycemic variability was mainly influenced by endogenous insulin secretion capacity and was high in patients with high insulin antibody levels. In some patients with a high insulin antibody titer, the antibody may have an effect on the variability of the fasting glucose concentration in type 1 diabetes.

Intrahepatic and extrahepatic aminotransferase elevation associated with clinical-therapeutic events in a schizophrenic patient.

A schizophrenic patient showed rhabdomyolysis with idiopathic transaminitis. The intermixed pattern of intrahepatic and extrahepatic alanine aminotransferase (ALT) elevation is associated with respective clinical-therapeutic events. Aminotransferases play a role as surrogate biomarkers of "liver metabolic functioning" beyond the obsolete classical concept associating ALT elevation only with liver cellular damage.

Long-term changes of aortic 18F-FDG uptake and calcification in health-screening subjects.

BACKGROUND: We investigated long-term changes in aortic (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and calcification in health-screening subjects and their relation with atherogenic risk factors. METHODS AND RESULTS: A total of 94 consecutive subjects (72 men, 22 women; age 47-85 years, mean 57.9 years) participating in a health-screening protocol were evaluated retrospectively. All subjects had follow-up PET/CT scans 3.0-5.8 years (mean 4.1 years) later. We measured (18)F-FDG uptake (maximum SUV) and calcium score (Agatston score) of the ascending, descending thoracic and infrarenal abdominal aorta on PET/CT images. (18)F-FDG uptake and calcium score of the whole aorta (FUWA and CSWA) increased significantly in the follow-up study compared with the initial study (p = 0.02 and p < 0.0001, respectively). Multiple regression analysis showed that the change in FUWA per year was significantly associated with visceral fat area, while the change of CSWA per year was significantly associated with age and smoking habit. The degrees of (18)F-FDG uptake and calcium score increases were significantly greater in the abdominal aorta than in the thoracic aorta (p = 0.05 and p < 0.0001, respectively). CONCLUSIONS: Our data demonstrated the longitudinal progressions of vascular inflammation and calcification of health-screening subjects. Inflammation and calcification were observed to progress significantly faster in the abdominal aorta than in the thoracic aorta. The progressions of vascular inflammation and calcification may be associated with different atherogenic risk factors.

High-throughput screening identified disease-causing mutants and functional variants of α-galactosidase A gene in Japanese male hemodialysis patients.

Fabry disease is a genetic disorder caused by deficient activity of lysosomal enzyme α-galactosidase A (GLA) and end-stage renal disease (ESRD) will be present after accumulation of glycosphingolipids within the kidney. Undiagnosed atypical variants of Fabry disease, which are limited to renal involvement, were found in several ESRD patient populations. On the other hand, unexpectedly high frequencies of male subjects having the c.196G>C nucleotide change (p.E66Q) showing low α-GLA activity have been reported on Japanese and Korean screening for Fabry disease. However, several evidences indicate the c.196G>C is not a pathogenic mutation but is a functional polymorphism. In the present study, high-throughput screening of serum GLA could successfully indentify two Fabry disease patients in a cohort consisted of 1080 male hemodialysis patients. Moreover, our serum assay was able to distinguish two patients with disease-causing genetic mutations (p.G195V and p.M296I) from eight functional variants that showed relatively decreased enzyme activity (p.E66Q). In conclusion, high-throughput serum enzyme assay distinctly identified disease-causing mutants and functional variants of GLA gene in Japanese male hemodialysis patients. In addition, our results underscore the high prevalence of not only undiagnosed Fabry patients but functional variants of p.E66Q among the ESRD population.

[Case of rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibody in the course of MPO-ANCA-associated pachymeningitis].

A 56-year-old female developed rapidly progressive glomerulonephritis in the course of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated pachymeningitis that had been found four years previously. On admission, her serum creatinine increased from 0.8 mg dL to 1.84 mg dL and to 3.66 mg dL every 3 to 4 weeks. Urinalysis revealed that urinary protein excretion was 1.25 g day and 3+ hematuria. MPO-ANCA titer was found to be 50 EU and anti-glomerular basement membrane (GBM) antibody was also elevated to as high as 174 EU. Renal pathology revealed cellular to fibrocellular crescents in 21 out of 23 glomeruli with interstitial inflammation and fibrosis. Immunohistochemistry with anti IgG antibody showed linear staining along the glomerular capillary walls. Following plasma exchange and methylprednisolone pulse therapy, oral prednisolone at a dose of 50 mg day was instituted, but without significant effect. Subsequent cyclophosphamide pulse therapy was effective, resulting in the stabilization of serum creatinine at 2 mg dL and disappearance of urine abnormalities. In addition, the MPO-ANCA titer and anti-GBM antibody titer of the patient decreased to within the normal range in one month and three months, respectively. Pulmonary lesions were not found throughout the course. Recently the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA-associated vasculitis has increasingly been reported. Accumulation of such cases may unravel the pathogenesis of these diseases. one month and three months, respectively. Pulmonary lesions were not found throughout the course. Recently the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA-associated vasculitis has increasingly been reported. Accumulation of such cases may unravel the pathogenesis of these diseases.

[Clinical evaluation of serum albumin reductivity in patients with renal dysfunction: a comparison between conservative renal failure patients and hemodialysis patients].

We examined the relationship between change in the redox state of the plasma albumin molecule and the metabolic disorder of sulfur amino acid observed being accompanied by reduction of renal function. Thirty-seven cases of pre-dialysis renal failure with conservative treatment and thirteen cases of chronic hemodialysis were selected as the subjects of this examination. The fraction of plasma albumin and the concentration of plasma cysteine and homocysteine were respectively measured by the HPLC and GC/MS (gas chromatography/mass spectrometry) methods. In the case of pre-dialysis renal failure with conservative treatment, the reduction rate of plasma albumin significantly decreased in correspondence with reduction of the glomerular filtration rate (GFR). It is well known that the reduction rate of plasma albumin also decreases with the aging process. However, in regard to chronic hemodialysis, a correlation with aging was not found, where the transient reduction rate of plasma albu- min increased after the hemodialysis session. However, in correspondence with the decrease in renal function, the concentration of plasma cysteine and homocysteine increased. This shows that there was a negative correlation with GFR in cases of pre-dialysis renal failure with conservative treatment. In cases of chronic hemodialysis, the concentration of free cysteine and free homocysteine rapidly decreased after a hemodialysis session. Therefore, a negative correlation was recognized between the reduction rate of plasma albumin and the concentration of plasma cysteine and homocysteine. The result of this examination shows the following mechanisms: plasma albumin plays an important role in the reaction of oxidation/reduction in blood plasma, and sulfur amino acid in blood plasma, especially the abnormality of cysteine concentration, plays an important role in changing the redox state of the blood plasma observed in the decrease in renal function.

Regulation of Src homology 2-containing protein tyrosine phosphatase by advanced glycation end products: the role on atherosclerosis in diabetes.

Advanced glycation end products (AGEs), among the most important causes of atherosclerosis in diabetes mellitus, stimulate the proliferation of smooth muscle cells (SMCs). Smooth muscle cells are central in the formation of atherosclerotic lesions, where they show both increased migration and accelerated proliferation. In investigating how AGEs stimulate SMC proliferation, we focused on protein tyrosine phosphatase, especially Src homology 2-containing protein tyrosine phosphatase (SHP2), which is considered important in regulating cell proliferation. Advanced glycation end products increased activity of SHP2 in the membrane fraction of rat aortic SMCs compared with control bovine serum albumin (P < .05). Upon characterizing the genomic and promoter structure of SHP2, we detected nuclear factor-kappaB (NF-kappaB) binding sites in the promoter area. Advanced glycation end product stimulation increased luciferase activity in cells transfected with SHP2 promoter region including NF-kappaB binding sites (P < .05) and increased SHP2 expression (P < .05). These data indicate that AGE stimulation appears to activate NF-kappaB. Activated NF-kappaB binds to sites on the SHP2 promoter, resulting in increased SHP2 expression, SHP2 activity, and, ultimately, SMC proliferation. It suggests that AGE stimulation induces SMC proliferation via SHP2, underscoring the importance of control of AGE for suppressing macroangiopathy in diabetes mellitus.

Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy.

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p