Ryuichiro Araki

Effect of Angiotensin Receptor Blockers on Cardiovascular Events in Patients Undergoing Hemodialysis: An Open-Label Randomized Controlled Trial

BACKGROUND Cardiovascular disease is the leading cause of mortality in patients with kidney failure treated with hemodialysis (HD). Although angiotensin receptor blockers (ARBs) reduce cardiovascular disease (CVD) events in patients with diabetes and chronic kidney disease, their effect in patients with kidney failure on HD therapy is not known. STUDY DESIGN Open-labeled randomized trial. SETTING & PARTICIPANTS Patients aged 30 to 80 years receiving HD 2 to 3 times weekly for 1 to 5 years at 5 university-affiliated dialysis centers. INTERVENTIONS Treatment with ARBs (valsartan, candesartan, and losartan) versus without ARBs after stratification by sex, age, systolic blood pressure, and diabetes. OUTCOMES The primary end point is the development of fatal and nonfatal CVD events, defined as the composite of CVD death, myocardial infarction, stroke, congestive heart failure, coronary artery bypass grafting, or percutaneous coronary intervention. The secondary end point is all-cause death. RESULTS 366 subjects initially were randomly assigned to an ARB or no ARB (control), but after a run-in phase, 180 were retained in each group. Mean age was 60 years, 59% were men, 51% had diabetes, and mean predialysis systolic blood pressure was 154 mm Hg. There were 93 fatal or nonfatal CVD events (52%); 34 (19%) in the ARB group and 59 (33%) in the non-ARB group. After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002). There were 63 deaths (35%); 25 (14%) in the ARB group and 38 (21%) in the non-ARB group. After adjustment, all-cause mortality differed between the 2 groups (hazard ratio, 0.64; 95% confidence interval, 0.39 to 1.06; P = 0.1). LIMITATIONS Because of the small sample size of this trial, the large effect may be a spurious finding. Use of an open-label design and 3 different agents in the ARB group might have influenced results. CONCLUSION Use of an ARB may be effective in reducing nonfatal CVD events in patients undergoing long-term HD. A larger study is required to confirm these results.

Implications of assisted reproductive technologies on term singleton birth weight: an analysis of 25,777 children in the national assisted reproduction registry of Japan

OBJECTIVE To evaluate the implications of assisted reproductive technologies (ART) on neonatal birth weight. DESIGN A retrospective study using analysis of covariance and multiple logistic regression analysis of the Japanese ART registry. SETTING Japanese institutions providing ART treatment. PATIENT(S) A total of 25,777 singleton neonates reaching term gestation following ART during the years 2007-2008, with 11,374 achieved through fresh embryo transfers (fresh ET) and 14,403 achieved through frozen-thawed embryo transfers (FET). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Birth weight. RESULT(S) The mean birth weight after FET was significantly higher compared with fresh ET and all Japanese births (3,100.7 ± 387.2 g, 3,009.8 ± 376.8 g, and 3,059.6 ± 369.6 g, respectively). The risk for low birth weight in FET was significantly lower compared with fresh ET. In fresh ET, ovarian stimulations were associated with about twofold risk of low birth weight compared with natural cycle. Regarding to the duration of embryonic culture, the risks resulting from a shorter culturing time were significantly higher compared with a longer culturing time in fresh ET. CONCLUSION(S) The best method of embryo transfer for fetal growth was FET after extended culturing until blastocyst stage. However, further investigations should be performed to understand the safety of ART treatment.

A practical prediction model for early hematoma expansion in spontaneous deep ganglionic intracerebral hemorrhage

OBJECTIVE Early hematoma expansion is a known cause of morbidity and mortality in patients with intracerebral hemorrhage (ICH). The goal of this study was to identify clinical predictors of ICH growth in the acute stage. MATERIALS AND METHODS We studied 201 patients with acute (<6 h) deep ganglionic ICH. Patients underwent CT scan at baseline and hematoma expansion (>33% or >12.5 ml increase) was determined on the second scan performed within 24 h. Fourteen clinical and neuroimaging variables (age, gender, GCS at admission, hypertension, diabetes mellitus, kidney disease, stroke, hemorrhagic, antiplatelet use, anticoagulant use, hematoma density heterogeneity, hematoma shape irregularity, hematoma volume and presence of IVH) were registered. Additionally, blood pressure was registered at initial systolic BP (i-SBP) and systolic BP 1.5 h after admission (1.5 h-SBP). The discriminant value of the hematoma volume and 1.5 h-SBP for hematoma expansion were determined by the receiver operating characteristic (ROC) curves. Factors associated with hematoma expansion were analyzed with multiple logistic regression. RESULTS Early hematoma expansion occurred in 15 patients (7.0%). The cut-off value of hematoma volume and 1.5 h-SBP were determined to be 16 ml and 160 mmHg, respectively. Hematoma volume above 16 ml (HV>16) ([OR]=5.05, 95% CI 1.32-21.36, p=0.018), hematoma heterogeneity (HH) ([OR]=7.81, 95% CI 1.91-40.23, p=0.004) and 1.5 h-SBP above 160 mmHg (1.5 h-SBP>160) ([OR]=8.77, 95% CI 2.33-44.56, p=0.001) independently predicted ICH expansion. If those three factors were present, the probability was estimated to be 59%. CONCLUSIONS The presented model (HV>16, HH, 1.5 h-SBP>160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome.

A New Method of Bone Tissue Measurement Based upon Light Scattering

In recent years, time‐resolved spectroscopy systems using near infrared pulsed laser have been applied to develop optical computed tomography. We applied this technique to measure the optical properties of osseous tissue. First, we gradually demineralized 10 mm blocks of bovine trabecular bone with EDTA, maintaining the absorption characteristics and structure but varying the hydroxyapatite content, thus creating specimens differing only in light scattering properties. We used computer densitograms to assess light penetration, and analyzed the correlation with bone mineral density (BMD) as with dual‐energy X‐ray absorptiometry scans. The light penetration increased with decreasing BMD. Second, using the above‐mentioned pulsed laser time‐resolved spectroscopy system, we investigated the correlation between the BMD and the time response waveforms of 10‐mm blocks of bovine cortical bone, trabecular bone, and surrounding tissue as well as human trabecular bone. The human lumbar vertebral bone also displayed an inverse correlation between BMD and maximum light penetration and a positive correlation between BMD and peak time delay. This is the first demonstration of a correlation between BMD and light scattering properties showing that BMD can indeed be measured with light. Our results show the possibility of obtaining information on internal bone structure and composition in vivo through assessment of the waveforms obtained by a time‐resolution system in the near infrared region.

Characteristics and prognostic value of acute catecholamine surge in patients with aneurysmal subarachnoid hemorrhage

Abstract Objectives: The characteristics of serum catecholamine concentration at the hyper-acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship between patient outcome and delayed vasospasm were investigated. Methods: Patients with aneurysmal SAH (170) were prospectively studied between August 2008 and June 2011. Baseline demographic data and physiological parameters, including plasma concentrations of adrenaline (AD), noradrenaline (NA), and dopamine (DP) were evaluated for all patients. Results: On admission, plasma AD, NA, and DP levels were significantly higher in patients with a poor clinical grade on admission (Hunt and Kosnik grade: IV–V), compared to those with a good clinical grade on admission (Hunt and Kosnik grade: I–III). AD showed a markedly high concentration immediately after the onset of SAH and then rapidly decreased. NA levels peaked within 6 hours after onset, then significantly decreased. The increase of DP with time was not significant, but showed a similar trend to that of NA. The level of each catecholamine showed significant mutual correlation. Our multivariate model demonstrated that age, poor clinical grade at admission, plasma AD and NA levels were good predictors of poor patient outcome [receiver operating characteristic (ROC) area: 0·83]. And that poor clinical grade at admission, Fisher scale, blood sugar level and plasma AD level were good predictors of the development of delayed vasospasm (ROC area: 0·81) (1·3). Conclusions: The present findings suggest that sympathetic activation in patients in the acute phase of SAH reflects the severity of SAH, and is closely related to the development of delayed vasospasm, leading to the subsequent immune response and inflammatory reactions. Strategies for suppressing catecholamine at the hyper-acute phase may contribute to vasospasm prevention and improve patient outcome.

The effect of hyperbaric oxygen on cerebral hemoglobin oxygenation and dissociation rate of carboxyhemoglobin in anesthetized rats: spectroscopic approach.

By measuring near-infrared transmittance spectra, we examined the effect of HBO on cerebral Hb oxygenation in normal and ischemic brain in the anesthetized rat. The oxygenation state of Hb was around 80% in the rat brain under 1 ATA air breathing. HBO did not induce further cerebral Hb oxygenation above 2 ATA in control animals but improved tissue oxygenation in the ischemic brains. The oxidation-reduction state of cyt. aa3 in the normal brain was not affected by HBO. In the ischemic brain, however, HBO prevented ischemia-induced reduction of cyt. aa3. Non-invasive optical monitoring of COHb with visible reflectance spectrophotometry was also examined. HBO markedly accelerated dissociation of COHb. Tight correlation was found between the optical signal and COHb content determined from blood samples. These results demonstrated the usefulness of optical monitoring in vivo under hyperbaric conditions.

Near-infrared imaging in vivo: imaging of Hb oxygenation in living tissues

1 ) To enhance spatial resolution of near-infrared (NIR) imaging in vivo, we performed computer-aided refocusing of NIR-projection images of human forearm. Simple inverse, constrained least squares, and Wiener filters were tested as refocusing algorithms. Wiener filter gave the best result in terms of image quality and computation time. By applying Wiener filter, we obtained enhanced spatial resolution. 2) We also examined 2-dimensional visualization of Hb oxygenation state using NIR-projection images of human forearm. Forearm occlusion caused increase in 2-dimensional O.D. at 700 nm, while slight decrease was observed at 800 nm. On the basis of in vitro experiments using RBC suspension and test phantoms, we calculated 2-dimensional changes in Hb oxygenation in the human forearm caused by ischemia. 3) To confirm whether NIR-CT can detect changes in Hb quantity in the living tissues, we reconstructed CT images from NIR-projection data of mouse abdomen measured at 700 and 800 nm. Infusion of physiological saline into the liver caused decrease in gray level in the location of the liver in the CT images (700-800 nm), although uncertain artifacts were observed in the other areas. Although more detailed considerations are required for practical application of this technique, we have obtained NIR-projection and CT images which indicate regional changes in the state of Hb in the living tissues.

Interaction of 1,1,1-trichloroethane with the mixed-function oxidation system in rat liver microsomes

1. The action of 1,1,1-trichloroethane (1,1,1-TCE) on cytochrome P-450-dependent mixed-function oxidation by rat liver microsomes was studied by determination of the rates of O2 consumption, H2O2 production, and 1,1,1-TCE metabolism, and from the spectral change in cytochrome P-450. 2. 1,1,1-TCE caused increases in the rate of O2 consumption, and H2O2 production although metabolism of 1,1,1-TCE was minimal. The stoichiometry of the rate of metabolism of 1,1,1-TCE to the increase in the rate of O2 consumption was about 0.011. The increase in O2 consumption and the production of H2O2 did not occur in microsomes treated with SK&F 525-A. 3. Spectral studies indicated that 1,1,1-TCE bound to cytochrome P-450 and showed a type I spectral change. 4. The addition of NADH with NADPH in the reaction medium enhanced the increase in O2 consumption caused by 1,1,1-TCE, whereas it did not change the rate of H2O2 production. 5. There was no increase in the formation of thiobarbituric acid substances in the reaction medium incubated with 1,1,1-TCE. 6. It was concluded that 1,1,1-TCE had an uncoupling effect on the cytochrome P-450-dependent mixed-function oxidation system.

Multicomponent Analysis of Near-Infrared Spectra of Anesthetized Rat Head: (II) Quantitative Multivariate Analysis of Hemoglobin and Cytochrome Oxidase by Non-Negative Least Squares Method

We developed a method for quantitating absolute value of Hb oxygenation and that of redox state of cyt. aa3 on the basis of multiple regression analysis of near-infrared spectrophotometric data. Flattening of the spectrum of Hb in both RBC suspension and the brain in situ was observed. This phenomenon was explained by localization of Hb within RBC for in vitro flattening, and by localization of RBC within the vessels as well as deformation of RBC in the microcirculation in vivo. Under resting air-breathing conditions, So2 and redox state of cyt. aa3 were estimated to be 50-70% and over 90%, respectively. Increase in FIO2 up to 3 ATA O2 caused stepwise increase in So2, whereas cyt. aa3 was fully oxidized when the animal inspired O2 under 1 ATA. Problems which must be solved for more accurate estimation of absolute values of So2 and redox state of cyt. aa3 were described and discussed.

Near-Infrared Imaging in vivo (I): Image Restoration Technique Applicable to the NIR Projection Images

To enhance spatial resolution of NIR projection images in vivo, we performed refocusing of NIR projection images of human forearm of about 50 mm thickness. A volunteers forearm was illuminated by parallel light beam-flux, and then projection images at 750 nm was measured with a Pertier-cooled CCD video camera and digitized. For refocusing computation, PSF of the light transmitted through the tissue was calculated by general equation proposed by van der Zee and Delpy (1988). Simple inverse, constrained least squares, and Wiener filters were tested as refocusing algorithms. Wiener filter gave the best result in terms of image quality and computation time. By applying Wiener filter to the image refocusing of NIR projection images of human forearm, we obtained enhanced spatial resolution.