Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients.

SUMMARY: Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism. INTRODUCTION: Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism. METHODS: Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined. RESULTS: ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = -0.303, p < 0.0001), hemoglobin A1C (ρ = -0.214, p < 0.01), and glycated albumin (ρ = -0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH]. CONCLUSION: Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Serum adiponectin and bone mineral density in male hemodialysis patients.

SUMMARY: Bone mineral density of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin. There was a significant positive correlation between serum adiponectin and serum NTX. Thus, adiponectin may play a role in mineral and bone disorder in chronic kidney disease stage 5 dialysis (CKD 5D) patients. INTRODUCTION: Serum adiponectin, an adipocyte-produced hormone, has been reported to correlate negatively with bone mineral density (BMD) in the general population. However, little is known about the association between adiponectin and BMD in patients with CKD. METHODS: BMD of the 1/3 distal and ultra-distal radius, which are enriched with cortical and cancellous bone, respectively, and the lumbar spine was measured by dual X-ray absorptiometry in 114 Japanese male hemodialysis patients (age 61.0 ± 11.1 years; hemodialysis duration 6.6 ± 3.0 years; 43.9% diabetics). Serum total adiponectin, bone formation marker (bone alkaline phosphatase, BAP), and bone resorption marker (cross-linked N-telopeptide of type I collagen (NTX)) were measured. RESULTS: The BMD of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin level (r = -0.229, p = 0.014; r = -0.286, p = 0.002; r = -0.227, p = 0.013, respectively). In multiple linear regression analyses, serum adiponectin was significantly and independently associated with the BMD of the 1/3 distal radius (R(2) = 0.173, p < 0.001) and ultra-distal radius (R(2) = 0.278, p < 0.001) after adjustment of age, hemodialysis duration, body weight, %fat mass, and log [intact PTH], although it was not with the BMD of the lumbar spine. There was a significant positive correlation between serum adiponectin and serum NTX (r = 0.321, p < 0.001), although there was no significant correlation between serum adiponectin and serum BAP. CONCLUSION: Increased levels of serum adiponectin were associated with decrease in BMD in male hemodialysis patients. Adiponectin may play a role in mineral and bone disorder, possibly in bone resorption, of patients with CKD 5D.

Distinct effects of pitavastatin and atorvastatin on lipoprotein subclasses in patients with Type 2 diabetes mellitus.

AIMS: Effects of pitavastatin and atorvastatin on the lipid profile and lipoprotein subclasses were compared in patients with Type 2 diabetes with dyslipidaemia. METHODS: Patients with Type 2 diabetes with hypercholesterolaemia and/or hypertriglyceridaemia were randomized to receive pitavastatin 2 mg (n = 16) or atorvastatin 10 mg (n = 15) for 6 months, and blood lipid and lipoprotein profiles and cholesterol and triglyceride contents of 20 lipoprotein subclasses, determined by high-performance liquid chromatography, were compared. RESULTS: At baseline, cholesterol in VLDL and LDL subclasses were increased equally in two groups of patients with diabetes as compared with normolipidaemic control subjects. As compared with baseline, serum levels of total cholesterol, LDL cholesterol, non-HDL cholesterol, LDL cholesterol:HDL cholesterol ratio and apolipoprotein B were decreased after 1, 3 and 6 months of treatment with atorvastatin and pitavastatin. Serum triglyceride levels were decreased after 1, 3 and 6 months of atorvastatin, but only at 3 months of pitavastatin. Serum HDL cholesterol was increased after 1, 3 and 6 months of pitavastatin, whereas HDL cholesterol was even decreased after 6 months of atorvastatin. Cholesterol levels of most VLDL and LDL subclasses were decreased equally in both groups. However, only pitavastatin increased cholesterol of medium HDL subclass. Serum triglyceride and triglyceride contents in VLDL and LDL subclasses were decreased only by atorvastatin. CONCLUSIONS: The impact on lipoprotein subclass profiles was different between pitavastatin and atorvastatin. It may be beneficial to determine lipoprotein subclass profile and select the appropriate statin for each profile in patients with diabetes with an additional cardiovascular risk such as low HDL cholesterol or hypertriglyceridaemia.

Acute encephalopathy in a patient with Dravet syndrome.

Dravet syndrome (severe myoclonic epilepsy in infancy) is an epileptic syndrome with various types of seizures that begin in the first year of life and may result in intellectual impairment. Mutations of the SCN1A gene are the most prevalent genetic cause of Dravet syndrome. In this study, we report a 12-year-old girl with Dravet syndrome carrying an SCN1A mutation, c.2785Cdel (L929del fsX934). She had an episode of status epilepticus and persistent lethargy after 48 h of acute febrile illness that was preceded by an annual flu vaccination. Low voltage activities detected by electroencephalogram and elevated neuron-specific enolase/interleukin-6 concentrations in the cerebrospinal fluid suggested acute encephalopathy. MRI showed abnormalities in the bilateral thalami, cerebellum and brainstem. These abnormalities were protracted over a month. The biochemical and MRI characteristics of this case are different from any known type of encephalopathy, and may suggest a vulnerability of neurons expressing mutant SCN1A in the brain.

Effect of cinacalcet on bone mineral density of the radius in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND/AIM: Cinacalcet, an allosteric modulator of the calcium sensing receptor, effectively reduces serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. It is not well known whether bone mineral density (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered after cinacalcet treatment. METHODS: The BMD in the distal 1/3 of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the start, and 1 year after cinacalcet treatment, in 61 patients. RESULTS: The BMD of both the distal 1/3 and ultradistal radius decreased significantly in the year prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not change significantly in the year after cinacalcet treatment. The annual changes in the BMD of the distal 1/3 radius increased significantly from -0.023 ± 0.029 g/cm2/year to -0.002 ± 0.033 g/cm2/year, prior to and after cinacalcet treatment, respectively; however, the annual changes in the BMD of the ultradistal radius did not change significantly prior to and after cinacalcet treatment. CONCLUSION: There was a significant association between cinacalcet treatment and reduction in BMD loss in patients with secondary hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly affected by cinacalcet treatment.

Rotationally correlated reactivity in the CH (v = 0, J, F(i)) + O2 → OH (A) + CO reaction.

The rotational-state-selected CH (v = 0, J, F(i)) beam has been prepared by using an electric hexapole and applied to the crossed beam reaction of CH (v = 0, J, F(i)) + O(2) → OH (A) + CO at different O(2) beam conditions. The rotational state selected reactive cross sections of CH (RSSRCS-CH) turn out to depend remarkably on the rotational state distribution of O(2) molecules at a collision energy of ∼ 0.19 eV. The reactivity of CH molecules in the N = 1 rotational states (namely ∣J = 1∕2, F(2)> and ∣J = 3∕2, F(1)> states, N designates the angular momentum excluding spin) becomes strongly enhanced upon a lowering of the rotational temperature of the O(2) beam. The RSSRCS-CH in these two rotational states correlate linearly with the population of O(2) molecule in the specific K(O(2)) frame rotation number states: CH(|J = 1/2,F(2)>) with O(2)(|K(O(2)) = 1>);CH(|J = 3/2,F(1)>) with O(2)(|K(O(2)) = 3>). These linear correlations mean that the rotational-state-selected CH molecules are selectively reactive upon the incoming O(2) molecules in a specific rotational state; here, we use the term "rotationally correlated reactivity" to such specific reactivity depending on the combination of the rotational states between two molecular reactants. In addition, the steric asymmetry in the oriented CH (∣J = 1∕2, F(2), M = 1∕2>) + O(2) (|K(O(2)) = 1>) reaction turns out to be negligible (< ±1%). This observation supports the reaction mechanism as theoretically predicted by Huang et al. [J. Phys. Chem. A 106, 5490 (2002)] that the first step is an intermediate formation with no energy barrier in which C-atom of CH molecule attacks on one O-atom of O(2) molecule at a sideways configuration.

Controlling the phase matching conditions of optical parametric chirped-pulse amplification using partially deuterated KDP.

Using a partially deuterated KDP crystal for an optical parametric amplifier, we demonstrated ultrabroadband optical parametric chirped-pulse amplification of more than 250 nm bandwidth at a center wavelength of 1050 nm. We numerically show how to control the broadband phase matching conditions at different wavelengths to match center wavelengths of suitable broadband seed sources by adjusting the deuteration level in partially deuterated KDP.

Diagnostic accuracy of cardiac metaiodobenzylguanidine scintigraphy in Parkinson disease.

BACKGROUND AND PURPOSE: To estimate the diagnostic accuracy of cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigram for detection of Parkinson disease. METHODS: A cross-sectional study with index test of MIBG scintigram and reference standard of U.K. Parkinson's Disease Brain Bank Criteria was performed in 403 patients. Ratio of cardiac-to-mediastinum MIBG accumulation was determined at 20 min (early H/M) and 4 h (late H/M). Area under the receiver-operator characteristic (ROC) curve, sensitivity and specificity in detecting Parkinson disease were analyzed. Accuracy was analyzed in a subgroup of patients with disease duration of 3 years or less. RESULTS: Area under the ROC curve was 0.89 using either early or late H/M as a diagnostic marker (95% CI 0.85-0.92 for early H/M and 0.86-0.93 for late H/M). Sensitivity and specificity were 81.3% (76.1-85.8%) and 85.0% (77.7-90.6%) for early H/M and 84.3% (79.3-88.4%) and 89.5% (83.01-94.1%) for late H/M. In the subgroup with duration of 3 years or less, the ROC curve area, sensitivity, and specificity were 0.86 (0.79-0.92), 76.0% (64.8-85.1%), and 83.9% (71.7-92.4%) for early H/M and 0.85 (0.78-0.92), 73.3% (61.9-82.9%), and 87.5% (75.9-94.8%) for late H/M. CONCLUSION: Although diagnostic accuracy of cardiac MIBG scintigram is high, it is limited because of insufficient sensitivity in patients with short duration.

Collision energy dependence of the rotational-state-resolved cross section in the CH (v = 0, J, F(i)) + O(2) --> OH(A) + CO reaction.

A velocity variable rotational-state-selected CH (v = 0, J, F(i)) beam has been prepared by using an electric hexapole and applied to the CH (v = 0, J, F(i)) + O(2) --> OH(A) + CO reaction. The CH rotational-state-resolved reaction cross sections have been determined under the beam-cell condition at the collision energy range of 0.06-0.18 eV. The N = 2 rotational states are 2-3 times more reactive than the other states (N = 1, 3). In addition, we observed a noticeable difference in the collision energy dependence of the cross section between the CH rotational states. The reaction cross section for the N = 2 states has a gentle negative dependence on collision energy, while, the reaction cross section for the N = 1 states has a positive dependence on collision energy.

Comparability and reproducibility of the carotid-femoral pulse wave velocity measurements using a multi-element carotid tonometry sensor.

To evaluate the comparability and reproducibility of the carotid-femoral pulse wave velocity (PWV) measured by the newly developed device compared to that measured by the standard device and the validity of brachial-ankle PWV as a substitute of carotid-femoral PWV. We measured aortic PWV twice in 21 normotensive males by using the standard devices and the newly developed device. We also measured brachial-ankle PWV in the same subjects. There was a strong, significant correlation between aortic (carotid-femoral) PWV measured by using two different devices (r = 0.741, P = 0.00012). Interquartile range of the differences of carotid-femoral PWV measured by Form (0.75 m/s (-0.36, 0.39)) was smaller than that by Complior (1.67 m/s (-1.03, 0.63)). There was no correlation between carotid-femoral PWV, measured by either device, and brachial ankle PWV. Our present results suggest that carotid-femoral PWV measured by using Form was comparable to, and may be more reproducible than, that measured by Complior that has been widely used as a predictable marker for cardiovascular events. Our results also suggest brachial-ankle PWV may not be a substitute for carotid-femoral PWV.

Optimal patient selection for anticoagulant therapy in sepsis: an evidence-based proposal from Japan.

Selecting an appropriate target population is essential to maximize survival benefits of anticoagulant therapy against sepsis. Our meta-analysis of three populations with sepsis and nationwide observational study in Japan showed that anticoagulants improved mortality only in sepsis-induced disseminated intravascular coagulation (DIC) but not in non-DIC. This divergent effect was physiologically explained by host-protective immune responses of local thrombosis, which are mandatory in the early stage of sepsis. Meanwhile, the lack of definitive evidence for survival benefit provided by several trials of sepsis-induced DIC indicated that this condition was probably not the best target of anticoagulants. Our multicenter cohort study including only patients with sepsis-induced DIC showed a survival benefit from recombinant thrombomodulin only in patients with high disease severity. Thus, we believe that the population with sepsis and DIC and high disease severity is the optimal target for anticoagulant therapy. Anticoagulant therapy without appropriate target selection should be avoided because of the increased risk of bleeding with no survival benefit.

Multi-millijoule, diode-pumped, cryogenically-cooled Yb:KY(WO(4))(2) chirped-pulse regenerative amplifier.

A diode-pumped, cryogenically-cooled Yb:KYW regenerative amplifier utilizing chirped-pulse amplification and regenerative pulse shaping has been developed. An amplified pulse with an energy of 5.5 mJ and a broad bandwidth of 3.4 nm is achieved.

Ultra-broadband optical parametric chirped-pulse amplification using an Yb: LiYF(4) chirped-pulse amplification pump laser.

We demonstrate ultra-broadband optical parametric chirpedpulse amplification of 300-nm bandwidth pumped by a broadband pulse delivered from a diode-pumped, cryogenically-cooled Yb:YLF chirped- pulse amplification laser.

Different real-time PCR assays could lead to a different result of detection of varicella-zoster virus in facial palsy.

Real-time PCR is a useful tool for rapid detection of viral genomic DNA. However, there are many types of real-time PCR, and this variation may induce different results. The sensitivity of two different real-time PCR assays was evaluated for the detection of the varicella-zoster virus (VZV) genome: LightCycler PCR and TaqMan PCR. Auricular skin cells and saliva were sampled from 201 patients with facial nerve paralysis. A hundred and seventy-one of these patients were diagnosed clinically with Bell's palsy, and the remaining 30 with Ramsay Hunt syndrome. In 30 specimens obtained from Ramsay Hunt syndrome patients, VZV DNA was detected in 26 skin and 3 saliva specimens using the LightCycler PCR, while 28 skin and 9 saliva specimens were positive using the TaqMan PCR. None of the patients with Bell's palsy were positive for VZV by the LightCycler PCR, whereas five of these patients were positive by the TaqMan PCR. The TaqMan PCR assay has a better sensitivity compared to the LightCycler PCR for the detection of VZV genome from patients with facial palsy. Further study is required to develop a more sensitive real-time PCR.

Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.

BACKGROUND: Lafora's progressive myoclonic epilepsy (Lafora's disease) is an autosomal recessive neurodegenerative disorder characterised by the presence of polyglucosan intracellular inclusions called Lafora bodies. Mutations in two genes, EPM2A and NHLRC1, have been shown to cause the disease. A previous study showed mutations in the EPM2A gene in 14 Lafora's disease families and excluded the involvement of this gene in five other families who were biopsy proven to have the disease. OBJECTIVE: To relate the genetic findings to the clinical course of the disease. METHODS: As part of an ongoing mutational study of the Lafora's disease genes, five new families with the disease were recruited and the genetic analysis was extended to screen the entire coding region of the NHLRC1 gene. Genotype-phenotype correlations were carried out. RESULTS: Seven NHLRC1 mutations were identified, including five novel mutations (E91K, D195N, P218S, F216_D233del, and V359fs32), in eight families with Lafora's disease. On relating the genetic findings to the clinical course of the disease it was shown that patients with NHLRC1 mutations had a slower rate of disease progression (p<0.0001) and thus appeared to live longer than those with EPM2A mutations. A simple DNA based test is described to detect the missense mutation C26S (c.76T-->A) in the NHLRC1 gene, which is prevalent among French Canadians. CONCLUSIONS: Patients with NHLRC1 mutations have a slower rate of disease progression than those with EPM2A mutations.

Phenotypes and genotypes in epilepsy with febrile seizures plus.

In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes.

Spectroscopic characterization of an ultrashort-pulse-laser-driven Ar cluster target incorporating both Boltzmann and particle-in-cell models.

A model that solves simultaneously both the electron and atomic kinetics was used to generate a synthetic He alpha and satellite x-ray spectra to characterize a high intensity ultrashort laser driven Ar cluster target experiment. In particular, level populations were obtained from a detailed collisional-radiative model where collisional rates were computed from a time varying electron distribution function obtained from the solution of the zero-dimensional Boltzmann equation. In addition, a particle-in-cell simulation was used to model the laser interaction with the cluster target and provided the initial electron energy distribution function (EEDF) for the Boltzmann solver. This study suggests that a high density average, high, of 3.2 x 10(20) cm(-3) was held by the system for a time, delta tau, of 5.7 ps, and during this time the plasma was in a highly nonequilibrium state in both the EEDF and the ion level populations.

Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and adenocarcinoma of the lung.

We examined loss of heterozygosity in 49 adenocarcinomas and 18 squamous cell carcinomas of the lung with 19 RFLP markers on the short arm of chromosome 3. Although no interstitial deletions were observed in any squamous cell carcinomas, interstitial or partial deletions were detected in 23 adenocarcinomas. Identification of two common regions of deletion in adenocarcinomas, at 3p21.3 and 3p14.1-21.1, suggested the presence of at least two tumor suppressor genes on 3p within the same regions commonly deleted in renal cell carcinomas. Correlation between the frequency of loss of heterozygosity on 3p and histopathological grade of adenocarcinoma also was observed. These results imply an etiological difference between two major types of non-small cell lung cancers, adenocarcinoma and squamous cell carcinoma.