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Interstitial and intracavitary ultrasound applicators had been developed and studied for minimally invasive treatments (MIT). However, the acoustic outputs are limited by the small-size PZT. We therefore studied the acoustic waveguide (AW) applicator which enables the use of a large-size PZT, and we aimed to advance AW applicators towards thermal ablation applications.Double parabolic reflectors wave-guided ultrasonic transducer (DPLUS) was introduced which has two parabolic reflectors for enhancing the acoustic output. Theoretical modeling was conducted for optimizing the DPLUS thin waveguide.Modeling results showed that optimal [Formula: see text] (thin waveguide radius/wavelength) can be found and the optimal [Formula: see text] depends on the excitable vibration amplitude in the thin waveguide. A local optimal [Formula: see text]=0.2392 was considered the best choice, which results in the optimal frequency of 2.2 MHz at the radius [Formula: see text] of 0.6 mm. To verify this optimal frequency, experiments under two working frequencies of 1.0282 MHz and 2.2579 MHz were conducted. Temperature rise curves in the chicken breast tissue showed good agreements between experiments and modeling results, which proved the effectiveness of the modeling. In addition, experiments showed an ablated area with a diameter of 1.03±0.12 mm under continuous excitation of 2.2579 MHz and 5 s.The developed DPLUS advanced the AW applicators towards thermal ablation applications.This study provides the evidence for recognizing AW applicators as a technique for thermal ablation.

To realize compact and portable hemolysis devices, an ultrasonic transducer with a blood channel is proposed in this study. Ultrasound waves are focused by a parabolic reflector to generate high sound pressure inside the channel for hemolysis. The hemolysis performance of the transducer is evaluated using simulations and experiments. Experiments are performed with various voltages and flow rates to verify the feasibility of hemolysis. The hemolysis rate is more than 93% at an applied voltage of 80 Vp-p, a flow rate of 0.25 mL/min, and a driving frequency of 1.28 MHz.

For high-power piezoelectric devices, nonlinear vibrations and related increases in temperature are critical problems produced by large internal stress and strain. Such nonlinear vibrations have been studied by some researchers; however, the related increase in temperature has not been taken into consideration, because it is a complicated phenomenon. In this study, the mechanism underlying the interaction between nonlinear vibration and temperature increase in a piezoelectric transducer under high-power conditions was clarified. For this purpose, cubic terms of the mechanical strain, the nonlinear transfer matrix method, and the heat conduction equation were combined. Additionally, it is necessary to utilize the distributed parameter model because the temperature increase is not uniform. The calculation results obtained using the measured temperature dependence of material constants verified that the temperature increase significantly degrades the piezoelectric vibration. It is expected that the proposed model will prove indispensable in the development of piezoelectric materials for high-power piezoelectric devices.

This study verifies the effectiveness of a dynamic resonant frequency control system for transducers. This system enables the resonant frequency of the transducer to match the driving frequency. In general, the resonant frequency of an ultrasonic transducer is fixed based on its design and material properties. Therefore, it is difficult to actively control the frequency when driving the transducer. However, for high-power piezoelectric actuators, it is important to control the ratio of the fundamental and higher-order resonant frequency of the longitudinal vibration precisely at 1:2. A high-power and high mechanical quality factor (high-Q) ultrasonic transducer requires precise control of its resonant frequency. However, the resonant frequency may shift due to changes in boundary conditions or non-linear phenomena in piezoelectric vibration while driving the ultrasonic transducer. To maintain the resonant frequency ratio of the ultrasonic transducer at 1:2, we propose to dynamically control the resonant frequency ratio constant. In this study, we made two main proposals to our dynamic resonant frequency control system. One is the stepped structure of the transducer, and the other is the completely automatic control. In the stepped structure, a Langevin transducer was designed to have a resonant frequency ratio of almost 1:2 for the first and third longitudinal mode in the initial condition. Additionally, this structure could achieve control of only one of two resonant frequencies of the transducer. For the utterly automatic control system, piezoelectric elements were introduced for controlling the resonant frequency ratio precisely. For this propose, switching the electrical boundary conditions of these piezoelectric elements was carried out by MOSFETs connected to the ultrasonic transducer and control its optimum duty ratio automatically by our feedback system. This system realized dynamic control of the resonant frequency. As a result, the resonant frequency of the transducer matched the driving frequency in the frequency band from 23.23 kHz to 23.93 kHz. It was also confirmed that the shape of the excited non-sinusoidal waveform could be controlled by using resonant frequency control.

In this study, we aimed to improve the backdrivability and torque control of a traveling wave ultrasonic motor (TWUSM). Because of its operating principle, a TWUSM has strong holding torque. While this feature is useful for maintaining the rotor in a fixed position in many applications, it can be problematic for applications that require backdrivability, such as assistive exoskeletons or haptic devices. We used the theoretical contact model, which considers tangential elasticity, to calculate the torque–speed characteristics of a TWUSM. To evaluate backdrivability, we simulated not only the case in which the TWUSM drives the output shaft actively, but also the case in which the output torque opposes the rotation direction and the TWUSM is driven by an external torque passively. According to the analysis of the contact force distribution, the holding torque was reduced because the sticking contact area was decreased by stator vibration. To verify the simulation results, we built an experimental setup to measure the actual torque characteristics, and the obtained results agreed with the simulation. Furthermore, using the same experimental setup, we compared two torque control methods, driving frequency control and phase difference control. As the theoretical model predicted, the latter method resulted in higher control accuracy.

二次性副甲状腺機能亢進症治療薬シナカルセト塩酸塩（以下シナカルセト）の有害事象として上部消化管症状が頻繁に認められる．これは消化管に存在するカルシウム受容体（以下CaSR）の影響が考えられる．上部消化管機能を胃酸分泌能（胃内pH・血中ガストリン濃度・血中ペプシノーゲン濃度）と胃排出能（アセトアミノフェン法）にて評価した．シナカルセト使用後に血中ガストリン濃度の上昇はみられたが胃酸分泌に明らかな変化はみられなかった．シナカルセト非使用時とくらべ使用時には胃排出能の遅延が認められた．シナカルセトによる胃排出能抑制の強い症例に上部消化管症状がよくみられた．シナカルセトを服用することで消化管に存在するCaSRに擬似的なCa2+負荷が加わり，アセチルコリン遊離が抑制され副交感神経系の抑制による症状が起こることが示唆された．この上部消化管症状に対する対策としては，胃の内容物ができるだけ少ない時間帯や胃排出能が亢進している透析後にシナカルセトを服用し，胃排出能を促進するような健胃消化剤・アセチルコリン作動薬・プロスタグランディン製剤などを使用することが有効であった．制酸剤の効果は定かでなかったが，シナカルセトを使用する前に上部消化管内視鏡を行い，胃疾患・胃内酸状況・胃粘膜状態・胃の運動機能を把握することが望ましい．これらの工夫によってシナカルセト服用のコンプライアンスは向上し，今後の二次性副甲状腺機能亢進症の治療に有用になることが期待された．

1歳3カ月より難治性の全身性強直性痙攣が出現し、5歳より欠神と思われる発作もみられた。5歳5カ月、発熱と全身強直性間代性痙攣重積で入院し、右弛緩性片麻痺に気づかれた。入院後右半身または上肢痙攣が断続的に9日間続いた。入院時脳波で左半球徐波化、頭部CTで左大脳半球の浮腫、頭部MRI T2強調像で左大脳半球灰白質の肥厚と高輝度、SPECTで左半球の血流増加を認めたが1カ月後には左大脳半球萎縮と血流低下を認めた。経過中血清グルタミン酸受容体e2抗体は陽性だった。意識の回復後も右半身麻痺は続き、入院8カ月後より欠神発作が再発し、脳波上右半球優位の広汎性3 c/s棘徐波複合がみられた。発作はESMにより抑制された。左大脳皮質優位の病変にもかかわらず欠神発作が再発した事は欠神発作の出現に中心脳系の働きが重要と考えられた。

要旨：致死的経過を辿った治療抵抗性頻回熱性痙攣の2症例を報告した。いずれも女児で家族に痙攣素因はなく、生後6カ月より熱性痙攣として発症し治療抵抗性で頻回再発し、10歳で痙攣重積を生じ死亡した。総熱性痙攣回数はそれぞれ24、56回だった。経過中の脳波ではてんかん波に乏しく血液生化学、髄液、画像所見などに異常なかった。そこで一般の熱性痙攣頻回例を検討したところ、1歳発症の男児に多く、痙攣素因の家族歴は40.4％を占めた。最終熱性痙攣月齢は57.5±23.4カ月（平均±SD)、総熱性痙攣回数は7.3±2.5回、3歳までの累積痙攣回数は5.6±3.1回だった。1歳未満発症例あるいは女児例で有意に発作が早く終了していた。無熱性痙攣は男児7例にみられた。以上より痙攣素因のない1歳未満の女児が単純型熱性痙攣で発症するも、難治で3歳までの累積発作回数が12回以上なら、今回報告したような例も存在するため注意深い経過観察が必要である。

We report the mutation analysis of a Japanese patient diagnosed with infantile-type Alexander disease. The genetic analysis revealed a new missense mutation, an A to G transition at nucleotide position 1026 in exon 6, leading to the substitution of glycine for glutamic acid at amino acid position 371(E371G). This mutation was not detected in 50 Japanese controls using denaturing high-performance liquid chromatography.

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.

A 72-year-old man with refractory anemia with an excess of blasts developed overt leukemia with leukothrombocytosis. Hematological and physical findings closely resembled those of an accelerated or blastic phase of chronic myelocytic leukemia. The cytogenetic anomaly of i(17q) was observed during the course. The present case is suggestive of the diversities of myelodysplastic syndromes (MDS), including relationships between MDS and myeloproliferative disorders (MPD) and acute leukemia.

Chromosomes were studied in 9 individuals with pigmentary dysplasias of the skin and other abnormalities. Of the 9 individuals, 5 were chromosomal mosaics in both blood lymphocytes and skin fibroblasts (46,XY/47,XY, + 13;46,XX/47,XX, + 14;46,XY/47,XY, + 18;46,XX/47,XX, + 18;46, XX/47,XX, + mar), while the other 4 individuals were chromosomally normal in both tissues studied. The pigmentary dysplasias involved hypo- or hyperpigmented patches/flecks or lines/whorls. The latter ran along Blachko lines on the back, abdomen and the limbs. These patterns varied not only between individuals but also between different regions of an individual. The possibility of chimerism was studied but ruled out (1/32 to 1/256) in 7 individuals, using chromosomal heteromorphisms in the patients and their parents as markers.

A physical disruption of the Prader-Willi syndrome (PWS) chromosome region is thought to cause PWS. We describe 2 girls with PWS phenotype, who had unique chromosome 15 abnormalities. The first patient showed mosaicism: 45,XX,t(15;15)(qter----p11.1::q11.200----qter)/46,XX,t(15;15)(qter----p1 1.1::q 11.200----qter), +mar. The band 15q11.2 apparently remained intact in the t(15;15) chromosome, and the mar chromosome was considered as r(15) (p11.1q11.1). The second patient had a karyotype of 47,XX,del(15)(q11.200----q11.207), +idic (15)(pter----q11.1::q11.1----pter). The complex breakage and reunion involving the 15q11.2 regions of the father's homologous chromosomes 15 at meiosis appeared to have resulted in the idic(15) and the del(15) chromosomes. These cytogenetic findings suggest that the PWS chromosome region may be localized on the very proximal portion of band 15q11.2.

Summary Purpose: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis. Methods: Ninety-six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groups—the Dravet syndrome group (n = 46) and the non-Dravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p-value. Results: An age of onset of febrile seizure ≤ 7 months, a total number of seizures ≥ 5, and prolonged seizures lasting more than 10 min. were regarded as significant risk factors for Dravet syndrome. Other factors highly predictive of this syndrome were hemiconvulsions, partial seizures, myoclonic seizures, and hot water–induced seizures. A total clinical score of six or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A missense and truncated mutations were detected significantly more often in the Dravet syndrome group than in the non-Dravet syndrome group. Discussion: This simple screening test was designed to be used by general pediatricians. It could help to predict Dravet syndrome before one year of age. If the sum of the clinical risk score is ≥ 6, then the performance of an SCN1A mutation analysis is recommended.

We report a 3-year-old girl with idiopathic hypereosinophilic syndrome. She was admitted to our hospital because of fever, cough, significant eosinophilia (16,500/microliter) and an elevated serum IgE level (114,685 u/ml). After wheezes continued for several days, paraplegia, dysuria and dyschezia developed. CSF, chest roentgenogram and spinal MRI were normal, as well as motor and sensory conduction velocities of the median and tibial nerves. Flaum's hematologic score was 4. Treatment with prednisolone resulted in remission of neurological symptoms and a rapidly normalization of the eosinophil count. During the following months, eosinophilia reappeared with tapering the medication, but there was no recurrence of neurological signs. Glucocorticoid therapy was discontinued after 21 months.

This study aims to (i) investigate longitudinally developmental changes of diurnal variations of body temperature and sleepiness in preschool and school-age children and (ii) investigate the effect of acute 2 h sleep reduction on daytime sleepiness over a 3 year period. Three subjects were evaluated over three consecutive days: two control days and one 2 h sleep reduction day. A sleep latency test was conducted five times each day at 2 h intervals from 10.00 h, and oral temperature measured every hour. The results showed that (i) daytime sleepiness was high and decreased with increasing age, (ii) an afternoon dip occurred with pubertal development, (iii) effects of sleep loss generally increased daytime sleepiness, in particular at 10.00 h, and (iv) temperature acrophase was delayed with age.

In a Japanese patient with familial LPL deficiency, a new null allelic mutation, one base pair deletion at nucleotide position 916 was identified in exon 5 of one allele. In exon 3 of the other allele, we found the same nonsense mutation as we described previously in other Japanese kindreds. For the deletional mutant allele, we developed a simple detection method and constructed the DNA haplotype.

Case Report The patient was a 5 year and 5 month-old boy. A brother had a history of febrile convulsions. The patient was born after 38 weeks of pregnancy, birth weight 3,260 g. The neonatal period was uneventful. His development was normal until 1 year and 3 months of age, after which he suffered generalized tonic seizures 2–3 times per year. Episodes of unconsciousness as often as ten times per day began at 5 years of age. Brain MRI, performed at 2 years of age, was normal. EEG revealed spikes from the right mid-temporel and right central regions and diffuse irregular spike and waves at 4 years of age. Cryptogenic localization-related epilepsy was diagnosed and treated with phenobarbital, carhamazepine, valproic acid, and acetazolamide without control of his convulsions. After 5 years of age, he began losing consciousness approximately 10 times per day. At 5 years and 5 months of age, he had fever, cough, rhinorrhea, and 2 generalized tonic-clonic convulsions for about 2 minutes and subsequently generalized tonicclonic convulsive status epilepticus for 30 minutes. He was admitted to Kagawa Prefectural Central Hospital. At admission, his consciousness score was 200 points (JCS) and he had intermittent clonic convulsions of the right hand and face. He also exhibited right hemiplegia. Partial seizures continued for about 2 weeks, Blood examination revealed CRP of 1.4 mg/dl, with negative antibody titers for herpes simplex and EB virus. CSF findings were normal. At 6 days of admission, T2-weighted brain MRI studies revealed high density i n the gray matter in the left hemisphere. After 2 months of hospitalization, MRI revealed remarkable left hemispheric atrophy. Two SPECT studies done at an interval of 2 months disclosed hyperperfusion of the left hemisphere. These findings were considered compatible with Rasmussen syndrome. At admission, the EEG revealed left high-voltage slow wave activity and frequent spikes in the left anterior temporal region. After 4 months of hospitalization, tonic-clonic convulsions occurred once per month. After 8 months of hospitalization, episodes of unconsciousness occurred 10 times per day. The ictal EEG revealed diffuse right hemisphere dominant 3isecond spike and wave bursts, which were induced by hyperventilation. Ethosuximide completely controlled these episodes and also improved EEG findings. Conclusion: The clinical findings suggested that this patient had RdS- mussen syndrome during the course of a cryptogenic localizationrelated epilepsy and subsequently experienced absence seizures. Despite his organic brain damage, his ictal 3/second spike and wave bursts exhibited no preceding focal spikes or slow waves, and ethosuximide markedly improved these absence seizures and EEG abnormalities. The mechanism of these absence seizures was thus not secondary bilateral synchrony and appeared to be the same as that of the primary generalized seizures.

A children's version of the Morningness-Eveningness Questionnaire was administered to approximately 1150 pupils of primary school and 500 pupils of junior high school. Analysis showed that the mean morningness-eveningness scores significantly changed to eveningness from Grade 4 of primary school to the Grade 1 junior high school and suggested that circadian phase might be established by the older age (grade).

We present, here, a few thoughts on the mechanisms involved in the development ofsymptoms in rheumatoid arthritis (RA) following a study of cellular and humoral parameters.The PPD skin reaction was used as an in vivo index and was markedly decreased in 11 out of 58 cases tested. The DNCB skin test, however, was positive in 40 of a total58 cases, 12 of these showing hyper-reactivity. T-lymphocytes causing rosette formation of sheep erythrocytes were used as an in vitro index, and were present in decreased numbers, 44.3±15.7 (control 50.6±13.6) . Despite this, there was a slightly increased reaction to PHA.B-lymphocytes indicative of surface immunoglobulin were found in increased numbers (35.9±20.8 ; control 24.6±9.8). There was no correlation between the numbers of B-lymphocytesand RF, but patients with an increased sedimentation rate had an increase in B-lymphocytes.Inhibition of migration was demonstrated with MIT and LIT using both antigenic material from synovial tissue and also heat-denatured IgG. Moreover, it was possible to show thatsensitization to these antigens was present in the patients with RA. There was no correlationbetween LIT, the antigenic material of heat-denatured IgG, and RF. The followingpoints were suggested by our findings : 1. Both qualitative and quantitative abnormalitiesof T- and B-lymphocytes were present in RA ; 2. The abnormalities of cellular immunityhad occurred in response to antigens of synovial tissue and heat-denatured IgG ; 3. Therewas no sighificant correlation between cellular and hormonal indices.

The energy allocation patterns to reproductive structures (RA) and the propagule output (PN) of five annual weedy or ruderal fox-tail species (Gramineae)-Setaria viridis (2x) (including var. pachystachys (2x)), S. X pycnocoma (2x), S. faberi (4x), S. glauca (4x, 8x), and S. pallide-fusca (8x)-were studied in relation to their biomass on the materials from ten different wild populations in Toyama and Fukui Prefectures, Japan. In addition, the relationship between the RA and PN was also critically examined.For all five fox-tail species, proportional partitioning of dry matter into total reproductive structures (caryopses, bristles, inflorescence axis and other persistent floral organs at the fruiting stage) (RA) shows considerable overlaps, but more or less constant within each taxon and independent of the biomass. On the other hand, the number of propagules produced per plant (PN) is remarkably dependent on the size of plants and thus a function of the biomass. This high efficiency of energy allocation to propagules is evidently determined by the breeding system (i.e., predominant inbreeding) of these weedy annual species. However, the relationship between the RA and PN showed no conspicuous trend, and thus the reproductive output is also independent of RA. The reproductive strategy found in Setaria is perhaps typical in such weedy annuals which grow chiefly in frequently disturbed, unpredictable environments. Another notable discovery was that, in spite of differences in ploidy levels (from 2x to 8x), all five species showed a very similar reproductive strategy, although slight but clear decrease was noted in the RA in response to the increase in ploidy levels, ranging from 49.52% (in diploids) to 27.53% (in tetraploids and octoploids). Seed weight (per gram), on the contrary, clearly increases in response to the increase in ploidy levels, i.e., ranging from 7.09×10-4 g (in diploids) to 41.87×10-4g (in octoploids).

In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became "seizure free" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.

On the prevalence day, 2,378 epileptic children were identified. Therefore, the prevalence rate for epilepsy was 8.2 per 1,000. The lowest prevalence rate was 1.2 in children under one year of age, and the highest was 11.0 at five years of age. The rate was higher for males than females. The annual incidence rate for epilepsy was estimated at 145.0 per 100,000 for 1975. The onset of seizures was high in the first three years, totaling 1,795 cases (77.7%), and this decreased after four years of age. Primary generalized epilepsy was found in 577 cases (31.7%), secondary generalized epilepsy in 167 (9.2%), partial epilepsy with elementary symptomatology in 205 (11.3%), with complex symptomatology in 61 (3.3%) and partial seizures secondarily generalized in 801 (44.5%). The study on such a number of cases had hitherto never been reported in the world.