Fifteen-year survival of resin-bonded vs full-coverage fixed dental prostheses.

PURPOSE: We clarified cumulative survival and event-free rates of resin-bonded fixed dental prostheses (RBFDPs) and compared them to those of fixed dental prostheses (FDPs) to refine risk factors for non-survival/event and use of tooth extraction after the period of non-survival/event. METHODS: Study subjects were selected among all patients who consecutively attended the Fixed Prosthodontic Clinic of Okayama University Hospital. Eligible patients were those who received 3-unit metal-framed 2-retainer (wing-wing) RBFDPs or conventional full-coverage FDPs (RBFDPs/FDPs: 129/177 prostheses). Data were analyzed by Kaplan-Meier analysis with the log-rank test, Mann-Whitney test, chi-square test, and Cox proportional hazards analysis. RESULTS: The 15-year cumulative survival rates were 66.5% for the RBFDP group and 61.6% for the FDP group, which were not significantly different (p = 0.59). The 15-year cumulative event-free rates were 53.4% for the RBFDP group and 59.2% for the FDP group, which were not significantly different (p = 0.52). No significant risk factors related to non-survival and event-free of RBFDPs/FDPs were identified in the analysis model using treatment method, sex, age, number of remaining teeth, and treatment site as explanatory variables. The number of cases in which RBFDPs/FDPs resulted in non-survival due to abutment tooth extraction was significantly lower in RBFDPs (p < 0.01). Further, the abutment tooth as a non-vital tooth was identified as a risk factor for RBFDPs/FDPs resulting in non-survival due to abutment tooth extraction. CONCLUSIONS: The present study is the first to indicate RBFDP as a prosthetic treatment option which should be selected for patients with slight or no abutment tooth decay.

Electrical measurement of antiferromagnetic moments in exchange-coupled IrMn/NiFe stacks.

We employ antiferromagnetic tunneling anisotropic magnetoresistance to study the behavior of antiferromagnetically ordered moments in IrMn exchange coupled to NiFe. Experiments performed by common laboratory tools for magnetization and electrical transport measurements allow us to directly link the broadening of the NiFe hysteresis loop and its shift (exchange bias) to the rotation and pinning of antiferromagnetic moments in IrMn. At higher temperatures, the broadened loops show zero shift, which correlates with the observation of fully rotating antiferromagnetic moments inside the IrMn film. The onset of exchange bias at lower temperatures is linked to a partial rotation between distinct metastable states and pinning of the IrMn antiferromagnetic moments in these states. The observation complements common pictures of exchange bias and reveals an electrically measurable memory effect in an antiferromagnet.

A spin-valve-like magnetoresistance of an antiferromagnet-based tunnel junction.

A spin valve is a microelectronic device in which high- and low-resistance states are realized by using both the charge and spin of carriers. Spin-valve structures used in modern hard-drive read heads and magnetic random access memoriescomprise two ferromagnetic electrodes whose relative magnetization orientations can be switched between parallel and antiparallel configurations, yielding the desired giant or tunnelling magnetoresistance effect. Here we demonstrate more than 100% spin-valve-like signal in a NiFe/IrMn/MgO/Pt stack with an antiferromagnet on one side and a non-magnetic metal on the other side of the tunnel barrier. Ferromagneticmoments in NiFe are reversed by external fields of approximately 50 mT or less, and the exchange-spring effect of NiFe on IrMn induces rotation of antiferromagnetic moments in IrMn, which is detected by the measured tunnelling anisotropic magnetoresistance. Our work demonstrates a spintronic element whose transport characteristics are governed by an antiferromagnet. It demonstrates that sensitivity to low magnetic fields can be combined with large, spin-orbit-coupling-induced magnetotransport anisotropy using a single magnetic electrode. The antiferromagnetic tunnelling anisotropic magnetoresistance provides a means to study magnetic characteristics of antiferromagnetic films by an electronic-transport measurement.

Poor applicability of estimation method for adults to calculate unbound serum concentrations of valproic acid in epileptic neonates and infants.

OBJECTIVE: To characterize the relationship between total and unbound concentrations of valproic acid (VPA) in epileptic neonates and infants, the clinical examination records of those patients archived via therapeutic drug monitoring (TDM) activities were retrospectively analyzed. METHODS: The screening encompassed 249 records of 114 epileptic patients aged 0-19 years old, who were treated with VPA monotherapy and whose total and unbound VPA concentrations were determined. These data were divided into groups according to the patients' age. In each group, the relationship between total and unbound VPA concentrations was compared to a reference profile, and the deviation from the reference was evaluated. The reference profile was calculated using the Langmuir equation, in which two parameters Kd and Bm were set to 7.8 and 130 microg/mL, respectively, according to our previous findings. RESULTS: The relationship between total and unbound VPA concentrations of patients of 0 years old considerably deviated from the reference, and their unbound VPA concentrations were generally higher compared to the corresponding reference values. It is suggested that the large deviation is related to the fact that the serum albumin concentrations of patients younger than 1 year old tend to be lower than those of patients in other age groups. CONCLUSION: Since the relationship between the VPA concentrations of epileptic neonates and infants is noticeably different from the reference, the unbound serum VPA concentrations of these patients are not adequately estimated using the same method as that for grown-ups. The unbound VPA concentrations of neonates and infants should be explicitly determined via TDM activities.

A simple and sensitive method for detection of Bacillus anthracis by loop-mediated isothermal amplification.

AIMS: To develop a rapid and simple system for detection of Bacillus anthracis using a loop-mediated isothermal amplification (LAMP) method and determine the suitability of LAMP for rapid identification of B. anthracis infection. METHODS AND RESULTS: A specific LAMP assay targeting unique gene sequences in the bacterial chromosome and two virulence plasmids, pXO1 and pXO2, was designed. With this assay, it was possible to detect more than 10 fg of bacterial DNA per reaction and obtain results within 30-40 min under isothermal conditions at 63 degrees C. No cross-reactivity was observed among Bacillus cereus group and other Bacillus species. Furthermore, in tests using blood specimens from mice inoculated intranasally with B. anthracis spores, the sensitivity of the LAMP assay following DNA extraction methods using a Qiagen DNeasy kit or boiling protocol was examined. Samples prepared by both methods showed almost equivalent sensitivities in LAMP assay. The detection limit was 3.6 CFU per test. CONCLUSIONS: The LAMP assay is a simple, rapid and sensitive method for detecting B. anthracis. SIGNIFICANCE AND IMPACT OF THE STUDY: The LAMP assay combined with boiling extraction could be used as a simple diagnostic method for identification of B. anthracis infection.

Rapid and simple detection of Clostridium botulinum types A and B by loop-mediated isothermal amplification.

AIMS: To develop a convenient and rapid detection method for toxigenic Clostridium botulinum types A and B using a loop-mediated isothermal amplification (LAMP) method. METHODS AND RESULTS: The LAMP primer sets for the type A or B botulinum neurotoxin gene, BoNT/A or BoNT/B, were designed. To determine the specificity of the LAMP assay, a total of 14 C. botulinum strains and 17 other Clostridium strains were tested. The assays for the BoNT/A or BoNT/B gene detected only type A or B C. botulinum strains, respectively, but not other types of C. botulinum or strains of other Clostridium species. Using purified chromosomal DNA, the sensitivity of LAMP for the BoNT/A or BoNT/B gene was 1 pg or 10 pg of DNA per assay, respectively. The assay times needed to detect 1 ng of DNA were only 23 and 22 min for types A and B, respectively. In food samples, the detection limit per reaction was one cell for type A and 10 cells for type B. CONCLUSIONS: The LAMP is a sensitive, specific and rapid detection method for C. botulinum types A and B. SIGNIFICANCE AND IMPACT OF THE STUDY: The LAMP assay would be useful for detection of C. botulinum in environmental samples.

Characterization of non-linear relationship between total and unbound serum concentrations of valproic acid in epileptic children.

OBJECTIVE: To establish a regression equation to properly estimate the unbound serum concentration of valproic acid (VPA) from its total serum concentration; the relationship between total and unbound serum VPA concentrations was retrospectively characterized. METHODS: Data were obtained from the clinical examination records that were routinely archived during therapeutic drug monitoring. The screening encompassed 342 records of 108 paediatric patients whose total and unbound VPA concentrations had been determined. The relationship between total and unbound VPA concentrations was characterized according to the Langmuir equation by taking account of inter-individual variability with the nonmem program. RESULTS: The total VPA concentration (C(t)) in the screened patients ranged from 5.5 to 179.8 microg/mL, and the unbound VPA concentration (C(f)) increased in a non-linear manner as the total VPA concentration increased. Taking account of the effects of antiepileptics concurrently administered, the VPA dissociation constant (K(d)) and maximum binding site concentration (B(m)) were 7.8 +/- 0.7 and 130 +/- 4.5 microg/mL respectively, for the regression equation, C(t) = C(f) + B(m) x C(f)/(K(d) + C(f)). An alteration in the unbound concentration was seen in patients who were treated with the combination of VPA and ethosuximide and in those who received two additional antiepileptics. CONCLUSIONS: A regression equation for estimation of the unbound VPA concentration, based on total VPA concentration collected during routine therapeutic drug monitoring was established. Use of two additional antiepileptics and ethosuximide treatment was considered as potential factors affecting unbound VPA concentration.

Risk of hypoglycemia associated with thyroid agents is increased in patients with liver impairment.

OBJECTIVE: To determine the risk of developing hypoglycemia from drugs that affect glucose homeostasis and evaluate the elevation of that risk by liver impairment as judged by a decrease of liver reserve or the severity of abnormal values in liver function tests. METHODS: A hospital-based case-control study was carried out. The base population consisted of all patients aged 20 years and older attending a university hospital in Japan from 2002 - 2004 who had received drugs and serum glucose measurements. Cases were defined as having had at least one episode of hypoglycemia as determined by a serum glucose concentration below 70 mg/dl. Up to 5 controls for each case were matched for the year of serum glucose measurement, out- or inpatient status, clinical departments visited, and age difference within 5 years, taken randomly from the base population without hypoglycemia. The odds ratio for developing hypoglycemia was estimated using conditional logistic regression analysis. RESULTS: From a base population of 10,011, 245 cases and 1,194 controls were enrolled. Of the drugs investigated, levothyroxine use was associated with an increased risk of hypoglycemia in patients with liver impairment (adjusted odds ratio; non-use with normal liver (reference), non-use with liver impairment 0.91 (95% CI 0.62, 1.33), use with normal liver 4.50 (0.58, 34.76), use with liver impairment 14.68 (1.57, 137.4), p for trend 0.007). The risk elevation likely depended on the lowering of liver reserve. CONCLUSION: Clinicians and pharmacists should carefully monitor serum glucose concentrations in levothyroxine users with liver impairment, especially those with lower liver reserve.

Superconducting state of the organic conductor (TMTSF)2ClO4.

(TMTSF)2ClO4 is a quasi-one-dimensional organic conductor and superconductor with Tc=1.4 K, and one of at least two Bechgaard salts observed to have upper critical fields far exceeding the paramagnetic limit. Nevertheless, the 77Se NMR Knight shift at low fields reveals a decrease in spin susceptibility chi(s) consistent with singlet spin pairing. The field dependence of the spin-lattice relaxation rate at 100 mK exhibits a sharp crossover (or phase transition) at a field Hs approximately 15 kOe, to a regime where chi(s) is close to the normal state value, even though Hc2>> Hs.

Mott transition from a spin liquid to a Fermi liquid in the spin-frustrated organic conductor kappa-(ET)2Cu2(CN)3.

The pressure-temperature phase diagram of the organic Mott insulator kappa-(ET)2Cu2(CN)3, a model system of the spin liquid on triangular lattice, has been investigated by 1H NMR and resistivity measurements. The spin-liquid phase is persistent before the Mott transition to the metal or superconducting phase under pressure. At the Mott transition, the spin fluctuations are rapidly suppressed and the Fermi-liquid features are observed in the temperature dependence of the spin-lattice relaxation rate and resistivity. The characteristic curvature of the Mott boundary in the phase diagram highlights a crucial effect of the spin frustration on the Mott transition.

Spontaneous subacute intratumoral hemorrhage of hepatic cavernous hemangioma.

We report a case of giant hepatic cavernous hemangioma associated with spontaneous subacute intratumoral hemorrhage. Magnetic resonance imaging showed an oval, homogeneous, high-intensity lesion with a low-intensity rim in the original high-intensity tumor on T2-weighted images. On T1-weighted images, this oval lesion showed heterogeneous high intensity with peripheral higher intensity. The histologic specimen confirmed hepatic hemangioma with intratumoral hemorrhage.

Diffusion-weighted MR imaging of Carmofur-induced leukoencephalopathy.

Carmofur (1-hexylcarbamyl-5-fluorouracil), a derivative of 5-fluorouracil (5-FU), has been widely used in Japan as a postoperative adjuvant chemotherapy agent for colorectal and breast cancer. Periventricular hyperintensity on T2-weighted MR images in carmofur-induced leukoencephalopathy confront the physician with a broad range of differential diagnoses. We describe two cases of carmofur-induced leukoencephalopathy in which diffusion-weighted MR imaging revealed periventricular hyperintensity. We compared their findings with those of age-related periventricular hyperintensity in five patients and found discrepancies in signal intensity of periventricular areas. Our results suggest that diffusion-weighted MR imaging may be useful to differentiate carmofur-induced leukoencephalopathy from age-related periventricular hyperintensity.

Age-Related decrease in calcitonin gene-related peptide mRNA in the dorsal root ganglia of spontaneously hypertensive rats.

Age-related changes in levels of calcitonin gene-related peptide (CGRP) mRNA of the dorsal root ganglia was studied in 8-, 12- and 15-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). CGRP mRNA levels in SHR but not in WKY decreased with age. The contents of CGRP-like immunoreactivities in the atrium and mesenteric artery of 15-week-old SHR were greater than those in age-matched WKY. These results suggest that the outflow of CGRP-containing nerves from the spinal cord and CGRP release from CGRP nerve terminals decreases in SHR.

Adrenergic nerves mediate acetylcholine-induced endothelium-independent vasodilation in the rat mesenteric resistance artery.

Mechanisms underlying acetylcholine-induced endothelium-independent vasodilation were studied in the rat mesenteric vascular bed isolated from Wistar rats. In preparations without endothelium, and contracted by perfusion with Krebs solution containing methoxamine (2-7 microM), perfusion of acetylcholine (1-100 microM) for 1 min produced a concentration-dependent vasodilation. Denervation of denuded preparations by cold storage (4 degrees C for 72 h) abolished the acetylcholine-induced vasodilation; 10 and 100 nM atropine abolished 1 and 10 microM acetylcholine-induced vasodilation, but it inhibited only 20% of vasodilation by 100 microM acetylcholine. The acetylcholine-induced atropine-resistant vasodilation was inhibited by 10 and 100 microM hexamethonium, 5 microM guanethidine, 50 microM bretylium, in vitro 6-hydroxydopamine (2 mM for 20 min, twice), 1 microM capsaicin and 0.5 microM calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist). These findings suggest that the acetylcholine-induced endothelium-independent nicotinic vasodilation requires the presence of intact adrenergic nerves, and is mediated by endogenous CGRP released from CGRP-containing nerves.

Effects of 4-hydroxyantipyrine and its 4-O-sulfate on antipyrine as biodistribution promoter.

The effects of 4-hydroxyantipyrine (4-OH), a major metabolite of antipyrine, and its 4-O-sulfate (4-S) on the pharmacokinetics of antipyrine were investigated in rats. Plasma elimination of intravenously administered antipyrine was significantly decelerated under a steady-state concentration of 4-OH but not under that of 4-S. Tissue-to-plasma concentration ratio (Kp) of antipyrine under its steady-state concentration was significantly increased in the brain and heart by the concomitant use of 4-OH, while similar use of 4-S had no effect. The enhancement of the blood-brain barrier (BBB) permeability of antipyrine caused by the concomitant use of 4-OH was believed to be concerned with the increase of the Kp value of antipyrine in the brain. These results suggested that 4-OH could be used as a biodistribution promoter.

Papillonodular type of cystic partially differentiated nephroblastoma: a case report.

We report a case of the papillonodular type of cystic partially differentiated nephroblastoma (CPDN), an extremely rare renal neoplasm that occurs in newborns and infants. The papillonodular type of CPDN is a variant of the conventional form of CPDN. MRI clearly demonstrated the gross pathologic features, distinguishing it from other renal multilocular cystic tumors.

Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter.

The effects of 4-hydroxyantipyrine (4-OH), a major metabolite of antipyrine and its sulfate, 4-hydroxyantipyrine O-sulfate (4-S), on the pharmacokinetics of citicoline and thiopental sodium were investigated in rats. The concomitant use of 4-OH increased significantly the tissue-to-plasma concentration ratio (Kp) of citicoline in the brain and liver and that of thiopental sodium in the brain, liver, and heart, while 4-S did not affect them. The permeability clearance of blood-brain barrier (BBB) (Kin) and the total distribution volume (Vdbr) of citicoline were not affected by either 4-OH or 4-S. However, those of thiopental sodium were significantly increased by not only 4-OH but also by 4-S. On the other hand, the plasma concentration of antipyrine was significantly decreased by the intravenous bolus coadministration of N-acetyl-p-aminophenyl O-sulfate (APAPS) at steady-state plasma concentration of antipyrine. A similar reduction was not observed with the intravenous coadministration of acetaminophen (APAP). The Kp value of antipyrine was significantly increased in the brain by the coadministration of APAPS, but was not affected by APAP. The increment in the drug distribution to the brain with the concomitant use of 4-OH (or APAPS) observed in this study is useful information for the application of drug combinations as biodistribution promoters.

Adrenomedullin inhibits neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in rat mesenteric resistance arteries.

We have reported that the rat mesenteric resistance artery has innervation of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRPergic nerves). We also demonstrated that adrenomedullin (AM) causes mesenteric vasodilation through activation of CGRP receptors. The present study was designed to examine the effect of AM on neurotransmission of CGRPergic nerves in rat mesenteric arteries. In preconstricted preparations without endothelium, periarterial nerve stimulation (PNS, 1 and 2 Hz) induced a frequency-dependent vasodilation. A bolus injection of CGRP (10 pmol) into the perfusate also caused a vasodilation. AM (0.1 to 10 nM) concentration-dependently caused 40% to 60% inhibition of the PNS-induced vasodilation, but AM did not attenuate vasodilation induced by exogenous CGRP injection. The inhibitory effect of AM (10 nM) on PNS-induced vasodilation was further potentiated by CGRP [8-37] (CGRP receptor antagonist, 50 nM), which attenuated the vasodilator response to the CGRP injection. Combined perfusion of AM [22-52] (AM receptor antagonist, 10 to 100 nM) resulted in further inhibition of PNS-induced neurogenic vasodilation without affecting the vasodilator response to the CGRP injection. CGRP [8-37] but not AM [22-52] antagonized vasodilation induced by AM perfusion. These findings suggest that AM presynaptically inhibits neurotransmission of CGRPergic nerves, probably decreasing CGRP release, via receptors different from CGRP receptors.

Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat.

The vascular effects of bradykinin were studied in rat perfused mesenteric vascular beds with active tone. Bolus injections of bradykinin (1-1000 pmol) but not des-Arg(9)-bradykinin (bradykinin B(1) receptor agonist) induced triphasic vascular responses: the initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. The triphasic vascular responses to bradykinin were abolished by FR 172357 (3-bromo-8-[2,6-dichloro-3-[N-[(E)-4-(N,N-dimethylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-metylimidazo[1,2-a]pyridine) (bradykinin B(2) receptor antagonist, 0.1 microM). Endothelium removal with sodium deoxycholate and N(w)-nitro-L-arginine (300 microM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 microM) and seratrodast (thromboxane A(2) receptor antagonist, 0.5 and 5 microM) abolished the bradykinin-induced second vasoconstriction. The bradykinin-induced third vasodilation was abolished by capsaicin (1 microM) and calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist, 0.5 microM). These findings suggest that the bradykinin-induced initial sharp vasodilation is endothelium dependent, that endogenous thromboxane A(2) is involved in the second vasoconstriction, and that the third slow vasodilation is produced by activation of capsaicin-sensitive CGRP-containing nerves.

Decreased depressor response mediated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves to spinal cord stimulation and levels of CGRP mRNA of the dorsal root ganglia in spontaneously hypertensive rats.

The depressor response to electrical stimulation of the spinal cord and the level of calcitonin gene-related peptide (CGRP) mRNA in the dorsal root ganglion (DRG) in the spontaneously hypertensive rat (SHR) was compared with the normotensive Wistar Kyoto rat (WKY) and Wistar rat (WR). The animals were pithed by inserting a stainless-steel rod into the spinal cord. Pithed rats were treated with hexamethonium (2 mg/kg/min i.v.) to block autonomic outflow, and mean arterial blood pressure (MBP) was maintained at approximately 100 mmHg with continuous infusion of methoxamine (10 to 15 microg/kg/min i.v.). Electrical stimulation (2 and 4 Hz for 30 s) of the lower thoracic spinal cord (T9-12) via the pithing rod caused a frequency-dependent depressor response without a change in heart rate. The depressor response to spinal cord stimulation was significantly smaller in SHR than in WKY and WR. Long-term treatment of 8 week-old SHR with captopril (0.1% in drinking water) for 7 weeks restored the reduced depressor response to spinal cord stimulation. The level of CGRP mRNA in DRG of SHR was significantly lower than that in WKY. These results suggest that the function of CGRP-containing nerves from the spinal cord decreases in SHR and captopril treatment prevents its reduction.