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The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post‐hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo‐controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non‐deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.

Resumo Filmes de TiO2 dopados com Nb podem associar propriedades como TCO (transparent conductive oxide) e super-hidrofilicidade, quando ativados por luz UV. Filmes metálicos de Ti-Nb foram depositados sobre substrato de vidro via triodo magnétron sputtering e posteriormente os filmes foram oxidados em atmosfera ambiente a 600 °C durante 1,0 h em condições similares àquelas usadas no tratamento térmico de vidros. Medidas de rugosidade, cristalização, composição química e molhabilidade foram realizadas através das técnicas de microscopia de força atômica, difração de raios X, fluorescência de raios X e ângulo de contato, respectivamente. Os resultados mostraram que os filmes foram completamente oxidados, tornando-se visualmente transparentes à luz visível com cristalização da fase rutilo-TiO2. Após irradiação com luz UV, os filmes TiO2:Nb apresentaram rugosidade em escala nanométrica podendo ser classificados como super-hidrofílicos, com valores de ângulo de contato similares àqueles de filmes de TiO2 puros, preservando características de filmes autolimpantes.

In the present study metakaolin and clay brick waste (CBW) were used as a source of silica and alumina along with precursors aiming to obtain geopolymer cements, which were characterised via scanning electron microscopy (SEM) and X-ray diffraction (XRD). The CBW was obtained from rejected clay brick industrial manufacturing process. The precursors were activated by using of 5.0, 10.0 and 15.0 [mol.L-1] KOH solutions, which was added to K2SiO3 solution at 1:1 weight ratio. To obtain the geopolymer cements the weight ratio of precursor and activators were changed at levels of 0.6, 1.0 and 1.4. The samples were prepared and cured at room temperature for 7 days. The geopolymer cement obtained from metakaolin at 15 mol.L-1 level of KOH concentration and KOH/K2SiO3 ratio of 1:1.4 provided the best cement which can be estimated by the largest reduction and dissolution of crystalline phases in the activation reaction.

This study focuses in the synthesis of ceramic pigments based on the crystal structure of willemite (Zn2SiO4). The willemite obtained from the combination of commercial zinc oxide and rice husk ash is produced in a conventional ceramic process without the use of mineralizer agent and with the addition of cobalt oxide or nickel oxide as the source of chromophore ions. The synthesis temperature used was 1200°C. The characterization of pigments involves the use of X-ray diffraction and scanning electron microscopy. The pigments applied in matte enamel and sintered at 1100°C or 1200°C developed color between blue and beige. The construction of absorbance curves showed the color development behavior of each pigment. The results showed the possibility of obtaining willemite, from rice husk ash and the color development efficiency of the material, besides showing the interference of chromophore ion (Ni and Co) in color development.

A proper choice of inelastic parameters is one of the most important aspects for a successful simulation of metal forming processes. Several issues must be observed when choosing such parameters, amongst which the compatibility between the magnitude of the plastic deformation of the target forming operation and the mechanical test employed to obtain those parameters. Within this context, the present work addresses the suitability of selected phenomenological hardening models and identification of the corresponding inelastic parameters based on curve-fitting strategies (logarithmic-based equations) and optimization methods (non-logarithmic models) for the AISI 304 austenitic stainless steel. Tensile tests were performed using specimens of different sizes. Based on a combined assessment of all types of specimens, it was observed that the curve-fitting technique was able to describe with excellent accuracy deformations up to maximum load. In order to contemplate larger plastic deformations, an inverse problem strategy based on optimization methods was used to account for material response up to macroscopic failure of the specimens. Numerical simulation of the tensile tests shows that the latter technique associated with non-logarithmic hardening equations provided the best approximation to the experimental data.

The ongoing pursuit of quality improvement and cost reduction in metal forming operations has instigated intense research on both material modelling and identification of constitutive parameters. Metal forming applications involving large plastic deformations are subject to mechanical degradation and failure, thereby recommending use of damage models. Notwithstanding, accurate predictions require material parameters able to describe realistic stress–strain paths, especially when involving large inelastic deformations under non-uniform stress states. The present work addresses identification of material parameters for Gurson-type and Lemaitre-type constitutive models for a low alloy steel based on a hybrid global–local optimization technique. The simulations show that, in the featured examples, material degradation takes place under non-uniform stress states precluding application of classical calibration techniques. The material response to loading also shows that the Lemaitre-type material provides a somewhat better approximation to the experimental data than the Gurson-type model.

PATH study group., In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre‐randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow‐up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post‐study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal., Editorial support was provided by Meridian HealthComms Ltd, funded by CSL Behring.

The pursuit to reduce manufacturing costs and increase product quality has led industries to use commercial codes and appropriate material models to simulate a wide range of metal forming operations. This scenario has prompted a healthy discussion on the strategies to obtaining constitutive parameters able to yield accurate numerical predictions. Optimization-based parameter identification techniques have opened completely new routes to determine material parameters for this class of forming problems. Notwithstanding, the most appropriate optimization strategy (or development of new ones) for the trinomial forming operation – constitutive model – constitutive parameters is still open to debate. This work highlights the important role that optimization strategies play to determine parameters of constitutive models. A brief description of gradient-based, gradient-free and hybrid optimization approaches is presented within the framework of parameter identification. Comparative studies and applications to classical and damaged material models are also discussed. Die Anstrengungen zur Reduktion der Herstellungskosten und zur Erhohung der Produktqualitat fuhren dazu, dass Firmen kommerzielle Berechnungsprogramme und entsprechenden Materialmodelle verwenden, um eine breite Palette von Metallumformvorgangen zu simulieren. Dies hat die Diskussion uber die Strategien zur Bestimmung konstitutiver Parameter zur Erlangung genauer numerischer Vorhersagen angeregt. Optimierungsbasierte Parameteridentifikationstechniken eroffneten hierbei vollig neue Wege, um Materialparameter fur diese Klasse von Umformproblemen zu bestimmen. Ungeachtet dessen wird die am besten geeignete Optimierungsstrategie (oder deren Neuentwicklung) fur das dreistufige Problem Umformvorgang – konstitutives Modell – konstitutive Parameter immer noch diskutiert. Diese Arbeit unterstreicht die wichtige Rolle, die Optimierungsstrategien bei der Parameterbestimmung von Stoffgesetzen spielen. Eine kurze Beschreibung der gradientenbasierten, gradientenfreien und hybriden Optimierungsansatze wird im Rahmen der Parameteridentifikation dargestellt. Vergleichende Untersuchungen zur Anwendungen klassischer und Schadigungsmaterialmodelle werden ebenfalls diskutiert.

Mika Saarela työryhmän jäsenenä. Background Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Methods Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0.2 g/kg or 0.4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1: 1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials. gov, number NCT01545076. Findings In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50-74]) patients on placebo, 22 (39% [27-52]) on low-dose SCIg, and 19 (33% [22-46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0.0007). Absolute risk reductions were 25% (95% CI 6-41) for low-dose versus placebo (p=0.007), 30% (12-46) for high-dose versus placebo (p=0.001), and 6% (-11 to 23) for high-dose versus low-dose (p=0.32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. Interpretation This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP.

In the ceramic coating industry, color and its stability influence the visual appearance of the product. These features account for the growing interest in obtaining pigments that are stable and may optimize the process. There are different synthesis routes to obtain pigments. Obtaining glass and its subsequent crystallization is an alternative proposed in the literature. This study focuses on the possible use the glass of the Li2O-ZrO2-SiO2 system as base glass and hematite as chromophore source. Different contents of hematite (1%, 2%, 3%), from the beneficiation process of metal sheets were used. The choice of composition aimed at facilitating the devitrification process for the formation of zirconia, which is often used as an encapsulating matrix in inorganic pigments. Results showed that glass synthesis is feasible and the effect of crystallization in the presence of hematite is favored, so an effective pigmenting effect is expected.

We made three kinds of measurements at E p = 13 MeV ; i) D ( p , p p ) n experiment at pp FSI, ii) D ( p , p ) p n experiment at θ p = 10 ° – 60 ° , and iii) D ( p , p p ) n experiment at many angle pairs around the space star. For an easy estimate of Coulomb effects in pd breakup reaction, we proposed Watson- Migdal & Faddeev calculation which was found to give nearly the same results as the pd calculation by Deltuva et al. . Cross sections of i) and ii) are well reproduced by the pd calculation, however, 10-15% discrepancy has been found between the cross section of iii) and the calculation.

Recent studies have shown that the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' is associated with poor cardiovascular prognosis. We assessed the hypothesis that this phenomenon may specifically influence left ventricular (LV) structure in treated hypertensive patients. A total of 272 outpatients (mean age, 65 years) with chronically treated essential hypertension and without remarkable white-coat effect were enrolled. Patients were classified into two groups according to office and daytime ambulatory systolic blood pressure (SBP); that is subjects without (Group 1: office SBPor =daytime SBP, n=149) and with reverse white-coat effect (Group 2: office SBPdaytime SBP, n=123). LV mass index and relative wall thickness were echocardiographically determined. In all subjects, LV mass index and relative wall thickness were positively correlated with daytime and 24-h SBP, but not with office SBP. In addition, these two indices were inversely correlated with office--daytime SBP difference. LV mass index (136+/-31 and 115+/-28 g/m(2), mean+/-s.d.) and relative wall thickness (0.49+/-0.09 and 0.46+/-0.07) were significantly greater in Group 2 than in Group 1. As for LV geometric patterns, Group 2 had a significantly higher rate of concentric hypertrophy compared with Group 1 (48 and 28%). Multivariate analyses revealed that the presence of reverse white-coat effect was a predictor for LV concentric hypertrophy, independent of age, sex, hypertension duration, antihypertensive treatment and ambulatory blood pressure levels. Our findings demonstrate that reverse white-coat effect is an independent risk factor for LV hypertrophy, especially concentric hypertrophy, in treated hypertensive patients.

Carotid intima-media thickness (IMT) assessed by ultrasonography is regarded as an early predictor of general arteriosclerosis in patients with essential hypertension. However, the methods of measuring IMT have not been globally standardized, and it remains unclear whether conventional measurement of IMT represents the prevalence of hypertensive target organ damage. In this study, we verified the association between several commonly used carotid ultrasonographical parameters and the severity of hypertensive target organ damage (retinal arteriosclerosis, microalbuminuria, left ventricular hypertrophy (LVH)). Carotid ultrasonography, echocardiography, urinalysis, and funduscopy were performed in 184 patients (64 +/- 12 years, 96 males and 88 females) with various stages of essential hypertension. Carotid arteriosclerosis was assessed using four methodologically different methods: conventional-IMT, maximum-IMT (Max-IMT), Mean-IMT, and Plaque Score (the sum of all plaque thicknesses). Age and all carotid ultrasonographical parameters were significantly associated with albuminuria, retinal arteriosclerosis, and left ventricular mass index. High-sensitivity CRP was significantly correlated with retinopathy and LVH. Carotid parameters in patients with histories of cardiovascular events were significantly greater in those without events. Among all carotid parameters, Max-IMT showed the highest correlation coefficient of the severity of target organ damage, and showed significant association with CRP. Stepwise regression analysis revealed that Max-IMT was the independent factor for predicting target organ damage. Max-IMT is suggested to be the most reliable and simplest parameter for predicting hypertensive target organ damage including microangiopathy in patients with essential hypertension.

A model correctly predicting the observed atmospheric γ radiation from radon progeny adsorbed onto the surface of rain and snow enables monitoring of precipitation rates to better than 0.3 mm/h. This model predicts that the surface (volume) deposition of radon progeny yields γ-ray flux rates proportional to the 2/5 (3/5) power of rain rates, respectively. The γ-ray rates observed were proportional to the 0.45 power for rain, but for snow which does not form spherical droplets a linear relationship was observed with proportionality constant dependent upon snow type. Atmospheric γ radiation was measured at one site in Mitaka, Japan since 1999 and more recently at another site a distance 220 m from the first using 12.9 cm3 NaI detectors. Correlation coefficients ranging from 0.85 to 0.95 and improving with elevation were obtained when data were fit with predominantly surface adsorption model and an age correction factor for the 30 min half-life of dominant radon progeny. Measurement of atmospheric γ radiation from radon progeny naturally adsorbed by rain at 20 m above ground (moderate building height) may serve as a reliable, live monitor of precipitation rates limited only by counting statistics. The regional applicability of this technique has been confirmed and will most likely have global and remote applicability.

Data taken at 6–20 m above ground from March through June of 2002 was used to confirm that the background subtracted atmospheric γ radiation (GRR) was directly related to precipitation rates. An anomalous increase in GRR (AGR) shortly after lightning strokes several times that expected from only the observed precipitation was concurrently observed at two sites separated by a distance of 220 m. The increase in activity in the detector environment subsequently decayed with a half-life of about 50 min. A model, which assumes the presence of an ensemble of radioisotopes produced by proton and photon-induced nuclear reactions in the atmosphere, fits the observed 50 min (33 min) decay half-life without (with) rain with correlation coefficients of 0.98. The possibilities that energetic protons and to a lesser extent brehmsstrahlung resulting from ions accelerated in electric fields during positive lightning produce this delayed activity and that AGR may be used as a remote monitor of lightning as well as the rel...

Letnbe a non-zero positive integer and Λ(n) the set of all partitions ofn. There is a one-to-one correspondence between Λ(n) and the set of the conjugacy classes ofSn, the symmetric group of degreen. Let X(Sn)= (Sn, {R*λ}λ∈Λ(n)) be the group association scheme ofSnand X=(X, {Rλ}λ∈Λ(n)) be an association scheme having intersection numbers identical to those of X(Sn). Suppose there exists no set of four vertices {x1,x2,x3,x4} withx1,x2,x3,x4∈Xsatisfying (x1,x2), (x2,x3), (x3,x4), (x4,x1) ∈R(2), (x1,x3) ∈R(3)and (x2,x4) ∈R(2,2). Then X is shown to be isomorphic to X (Sn). (In [17], the authors show that ifn≥ 5, X does not possess four vertices of this type.)

Selection criteria for performance test of yearling bulls commonly include indicators of important traits, such as withers height (WH), chest girth (CG) and body length (BL). Estimations of (co)variance component and genetic parameter of WH, CG and BL of Bali cattle are rarely reported or have not been reported. Therefore, the objective of this study was to estimate (co)variance components and genetic parameter among the indicator traits WH, CG and BL. Records for WH (n = 140), CG (n = 133), and BL (n = 130) were obtained from the Bali Breeding Center which consisted of 23 sires and 134 dams represented in the data. (Co)variance components were estimated using animal model, and average information REML was used to obtain estimates of heritability and genetic correlations. Fixed effects included sex, age, and calving season. The random effect of the animal was included to estimate additive genetic effects. Generally heritability estimates of 0.41±0.08, 0.40±0.09, and 0.39±0.08 were obtained for WH, CG and BL on the underlying scale, respectively. The genetic correlation between WH and CG (0.05) was close to zero, as were the estimated genetic correlations between WH and BL (0.05) and CG and BL (0.05). Genetic and phenotypic trends did not show improvement due to selection. However, these results suggest that concomitant selection for increased withers height, chest girth and body length would not be antagonistic.

The objective of this study was to estimate genetic parameters for growth and body composition traits at 60 d of age and at finish in a population of Berkshire pigs and to evaluate the effectiveness of selection at 60 d of age for meat productivity. A total of 4,548 purebred Berkshire (2,344 males and 2,204 females) pigs born between December 1994 and January 2005 were used in this study. The traits analyzed were BW at 60 d of age; daily BW gain from birth to finish, from weaning to 60 d, from weaning to finish, and from 60 d to finish; age at finish; backfat thickness at 60 d of age and at finish; loin eye area at 60 d of age (LEA60) and at finish; and the number of teats. The heritability estimates for BW at 60 d of age, daily BW gain from weaning to 60 d, backfat thickness at 60 d of age, and LEA60 were 0.22, 0.25, 0.49, and 0.22, respectively. The estimated common environmental effect for BW at 60 d of age, daily BW gain from weaning to 60 d, backfat thickness at 60 d of age, and LEA60 were 0.12, 0.13, 0.18, and 0.21, respectively. Therefore, the common environmental effect should be included in the model to analyze traits at 60 d of age. The positive genetic correlation between LEA60 and loin eye area at finish and the negative genetic correlation between LEA60 and backfat thickness at finish indicated that improvement of the ultrasonic loin eye area at 60 d of age may result in favorable correlated responses to the traits at finish, an increase in loin eye area, and a decrease in backfat thickness. In addition, genetic correlations of backfat thickness at 60 d of age with backfat thickness at finish and loin eye area at finish were found to be favorable, indicating that improvement of ultrasonic backfat thickness at 60 d of age may result in greater correlated responses to the traits at finish: an increase in loin eye area and a decrease in backfat thickness. Therefore, constructing a selection scheme that includes body composition traits at 60 d and traits at finish is practical for gaining a greater selection response.

Nanostructured materials have been largely studied in the last few years because they have a great potential to applications in different fields like physics, chemistry, biology, mechanic and medicine. Synthesis and characterization of nanostructured materials is a subject of great interest involving science, market, politicians, government and society. The nanostructured materials are in demand in biomedical area, mainly the bioceramics composed of calcium phosphates (Ca/P), which have an excellent biocompatibility and mineralogical characteristics similar to those of bones. The aim of this work was to optimize the method of powder synthesis of nanostructured calcium phosphate and of nanocomposites composed of calcium phosphate//SiO2n, containing 5, 10 and 15% (in volume) of nanometric silica (SiO2n). The results are expressed according to the method of synthesis, mineralogical and morphological characterization, and thermal behavior for the different compositions of the nanostructured powder synthesized. Os materiais nanoestruturados são promissores e vêm tomando espaço em diferentes áreas de aplicação termomecânica, aeroespacial, nuclear e biomédica. Na área biomédica, as biocerâmicas na composição (Ca/P), os fosfatos de cálcio têm se destacado, em razão das características mineralógicas destes biomateriais serem semelhantes a da apatita estrutura óssea do esqueleto humano e por apresentarem boa biocompatíbilidade. A síntese de pós cerâmicos nanoestruturados de fosfato de cálcio e materiais nanocompósitos são promissores em aplicações cirúrgicas médico-odontológicas na fixação de próteses, enchimento ósseo, em revestimentos, na estabilização de implantes e como elemento matricial na reconstituição da estrutura óssea. Este trabalho teve como objetivo a otimização do método síntese de pós biocerâmicos nanoestruturados em fosfato de cálcio e nanocompósito fosfato de cálcio/SiO2n, nas composições percentuais de sílica nanométrica (SiO2n) de 5%, 10% e 15% em volume. Foram sintetizadas quatro composições, a matriz fosfato de cálcio e nanocompósitos fosfato de cálcio/SiO2n. Os resultados apresentados estão relacionados ao método de síntese, da caracterização mineralógica, morfológica e do comportamento térmico para as diferentes composições de pós nanoestruturados sintetizados.

In order to determine whether L-DOPA-derived extracellular dopamine (DA) in the striatum with dopaminergic denervation is affected by activation of serotonin autoreceptors (5-HT(1A) and 5-HT(1B) receptors), we applied in vivo brain microdialysis technique to 6-hydroxydopamine-lesioned rats and examined the effects of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the selective 5-HT(1B) receptor agonist CGS-12066 A on L-DOPA-derived extracellular DA levels. Single L-DOPA injection (50 mg/kg i.p.) caused a rapid increase and a following decrease of extracellular DA, with a peak value at 100 min after L-DOPA injection. Pretreatment with both 0.3 mg/kg and 1 mg/kg 8-OH-DPAT (i.p.) significantly attenuated an increase in L-DOPA-derived extracellular DA and the times of peak DA levels were prolonged to 150 min and 225 min after L-DOPA injection, respectively. These 8-OH-DPAT-induced changes in L-DOPA-derived extracellular DA were antagonized by further pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. In contrast, intrastriatal perfusion with the 5-HT(1B) agonist CGS-12066 A (10 nM and 100 nM) did not induce any changes in L-DOPA-derived extracellular DA. Thus, stimulation of 5-HT(1A) but not 5-HT(1B) receptors attenuated an increase in extracellular DA derived from exogenous L-DOPA. These results support the hypothesis that serotonergic neurons are primarily responsible for the storage and release of DA derived from exogenous L-DOPA in the absence of dopaminergic neurons.

To discriminate patients with severe mental disorders from those complaining of menopausal symptoms, psychological tests were performed on patients who visited the menopausal clinic. The effectiveness of hormone replacement therapy (HRT) in patients with slight mental disorders was also evaluated.Patients with menopausal symptoms (n = 150, 41-59 yr. old) were interviewed by a psychiatrist (according to DSM-III-R) and classified as the climacteric syndrome group (C) and the mental disorder group (P). The patients were also evaluated by the Menopausal index (MI), Maudsley Personality Inventory (MPI) and Self-rating depression Scale (SDS). The patients with severe mental disorders were eliminated and the remaining patients with menopausal symptoms were treated with conjugated equine estrogen (0.625 mg/day) and medroxyprogesterone acetate (2.5mg/day) for 24 weeks.1) Thirty six patients were diagnosed as P (24%) and seven of them were diagnosed as having major depression (4.7% of the all patients). 2) MPI-N (neurosis scale) in C was 16.2 +/- 10, and in P was 30.5 +/- 9.0, and SDS in C and P were 39.0 +/- 8.0, and 51.4 +/- 8.9, respectively. In both psychological test, P shows a significantly higher value than C (p0.01). 3) Ninety point six % of the patients responded. HRT was not effective in 63.2% of P, but when psychotropic drugs were combined, significant improvement (p0.05) was observed.One fourth of the patients were suspected of having mental disorders in the menopausal clinic, and 5% of the patients needed the care of the psychiatrist. And the application of MPI and SDS was useful in helping the gynecologist to differentiate and classify the mental disorders to some extent. The applicability and effectiveness of HRT for patients with mild mental disorders were suggested.

Among cases of infantile acute pharyngolaryngitis with cough as a chief complaint, 21 cases that the involvement of bacterial infections has been demonstrated were given minocycline (MINO) and the effectiveness and safety of MINO were investigated. 1. Regarding the clinical effectiveness, the number of cases assessed as markedly effective was 9 (43%) and that as effective was 8 (38%), so that the effectiveness rate was 81%, and particularly, in the infections caused by Haemophilus influenzae, MINO showed a high effectiveness. 2. Five strains of Streptococcus pneumoniae, 2 strains of Streptococcus pyogenes and 16 strains of H. influenzae, a total of 23 strains of pathogenic bacteria were isolated, and MINO showed high activities against not less than 80% of these strains. 3. The bacteriological effect in terms of the rate of eradication was 71%, and that of H. influenzae was as high as 88%, while S. pneumoniae remained in 3 of 5 cases. 4. Adverse reactions were observed in 2 cases (10%), 1 case each of abdominal pain and stomatitis, and both of them were improved after the treatment termination. 5. Regarding the usefulness, which was comprehensively assessed using clinical effectiveness and safety as criteria, the number of cases evaluated satisfactorily useful was 8 (38%) and that as useful was 8 (38%), so that the overall usefulness rate was 76%. From the above results, it was confirmed that MINO is a drug having high efficacy and safety against infantile acute pharyngolaryngitis with cough as a chief complaint caused by H. influenzae.(ABSTRACT TRUNCATED AT 250 WORDS)

To objectively evaluate the clinical efficacy and safety in acute tonsillitis, flomoxef (FMOX) was examined for the distribution of sensitivity of clinical strains to it and for its clinical usefulness. 1. The 80% minimum inhibitory concentration of 11 clinical strains of Gram-positive bacteria, 6 of Gram-negative bacteria and 5 of anaerobic bacteria was 0.39 microgram/ml. FMOX showed the strongest, most comprehensive antibacterial action among the drugs tested. 2. Thirty patients received FMOX. Clinical effectiveness was evaluated in 28 patients, and clinical usefulness and safety in 30. 3. The clinical efficacy rate ('excellent' and 'good') was 75% (21/28). 4. As for bacteriological response, bacterial elimination rates were 67% for Gram-positive bacteria, 100% for Gram-negative bacteria, 100% for anaerobic bacteria and 100% for mixed infections. 5. Side effects occurred in 2 (6%) patients: drug eruption and diarrhea in 1 patient each. These symptoms improved rapidly after discontinuation of the drug. 6. Although abnormal clinical test results were found in 7 (23%) patients, i.e., increases in GOT and GPT in 2, in GPT in 4 and in BUN in 1, they were transient. 7. The usefulness of FMOX was assessed in light of its efficacy and safety. It was highly satisfactory in 14 patients, satisfactory in 11, relatively satisfactory in 1, unsatisfactory in 2 and highly unsatisfactory in 2, and rate of usefulness was 83%. FMOX is considered to be highly useful for the treatment of severe acute tonsillitis.

Clinical, electrophysiological and histopathological findings in 6 children with steroid-responsive acquired demyelinating neuropathy are presented. The clinical features and nerve conduction findings are basically similar to those of chronic inflammatory demyelinating neuropathy (CIDP) in adults, although early-onset cases had prominent pes cavus deformity and thickened nerves, which are rare findings in acquired neuropathies in adults. The diagnostic criteria of adult CIDP can be adopted for most of the cases, however, repeated electrophysiological tests may be required to identify multifocality of the nerve lesion, especially when conduction block is not apparent before treatment. The biopsied sural nerves showed many thinly-myelinated fibers, subperineurial and endoneurial edema, and cellular infiltrations. Varied fascicular involvements were common. Two cases with almost complete or considerable loss of myelinated fibers in the biopsied sural nerve revealed good clinical response to steroid therapy. The degree of nerve degeneration in the sural nerve thus, may not be helpful to estimate the prognosis and the responsiveness to treatment. Therapeutic trials should be employed when the main conduction findings are those of demyelinating neuropathies, even if genetically-determined neuropathy is suggested from the clinical pictures.

A clinical study with 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA) was performed in 10 patients with hepatobiliary disease. In this study, scintigraphic data and images with 99mTc-GSA were compared with several serological liver function tests, the hepatic blood perfusion index and image quality using 99mTc-DTPA-human serum albumin (99mTc-HSA). Dynamic and serial hepatic images were obtained over a 20 min period after 99mTc-GSA injection, and time activity curves from the heart and liver were generated. The blood clearance index (HH15), and the hepatic uptake index (LHL15) were calculated from each curve of the heart and liver, respectively. In addition, using two compartment fitting, the blood clearance (KH1, KH2) index was calculated, and using exponential fitting, the hepatic uptake index (KL) was calculated. The mean HH15 in LC group and non-LC group was 0.81 +/- 0.05, 0.64 +/- 0.10, respectively. The mean LHL15 in LC group and non-LC group was 0.79 +/- 0.04, 0.91 +/- 0.06, respectively. There were significant differences between non-LC group and LC group in HH15, and LHL15, KH1 and KL. There were also significant correlations of KH1 with HH15, and KL with LHL15. Parameters of 99mTc-GSA showed significant correlations with various liver functions. 99mTc-GSA scintigraphy showed clearer liver images in hepatobiliary diseases than 99mTc-HSA. These results suggest that 99mTc-GSA scintigraphy is useful in estimating preserved liver function and hepatic morphology.

We treated two patients with chronic inflammatory demyelinating polyneuropathy (CIDP) with high-dose intravenous immunoglobulin (HIG). The patients received 400 mg/kg of immunoglobulin a day for five days. One patient, who had failed to respond to prednisolone before, was treated with HIG, 18 months after the onset. His motor symptoms resolved immediately after the commencement of HIG. Electrophysiologically, the compound muscle action potentials increased in amplitude in all nerves examined and F wave reappeared in the left median nerve. The electrophysiological changes were compatible with improvement of conduction blocks. This patient had headache and exanthema during the HIG therapy, but they settled after cessation of the infusion. The other patient was administered HIG as an initial treatment, four months after the onset. HIG was of no effect in this case, but he showed remarkable recovery during the following prednisolone therapy. Although corticosteroid therapy is the first choice for CIDP, there are CIDP patients who do not respond to steroid or can not complete the steroid therapy because of adverse effects. HIG is an expectative and recommendable treatment for the steroid resistant CIDP patients.

Event-related potentials (ERPs) during a two-tone discrimination task were recorded in 85 normal subjects and 110 schizophrenic subjects. We divided ERPs into 4 interpeak components. We named them A, A', B and B'. A is the component from the stimulus point to n100 peak. A' is the one from n100 peak to p200 peak. B is the one from p200 peak to n200 peak. B' is the one from n200 peak to p300 peak. Their latency was named Al, A'l, Bl, and B'l respectively. Their amplitude was also named Aa, A'a, Ba and B'a respectively. Bl and A'l of the schizophrenic group were both significantly longer than those of the normal group. B'a of the schizophrenic group was significantly smaller than that of the normal group. Interrelations between interpeak components of the normal group were examined statistically. Regarding latency, a significant negative correlation was seen between Al and A'l, and also between Bl and B'l. Regarding amplitude, a significant positive one was seen between Aa and A'a, and also between Ba and B'a. Interrelations between Al and A'l, Bl and B'l, Aa and A'a, and Ba and B'a of the schizophrenic group were the same as those of the normal group. These negative correlations in latency suggest that n100 peaks and n200 peaks have 'jitter'. A combination of interpeak components is supposed to reflect a higher function of the brain. There was a significant negative correlation between (A + A')l and (B + B')l in the normal group, but there was not a significant one between them in the schizophrenic group. The schizophrenic group is supposed to have a certain abnormality in a higher function of the brain. Our result suggests that we may possibly be able to associate an abnormal focus around p200 peak with some symptoms and signs of schizophrenia.

Since attention has such a close correlation with arousal level, the influence of sleep on the waveforms of event related potential (= ERP) must be studied in advance for evaluating attentiveness of human mental activity. ERP, which odd-ball paradigm was used to elicit, was examined in 9 adult and healthy subjects from arousal to sleep. And ERP during a whole night was also examined in 5 of them to study the relation of the waveforms of ERP and sleep stages including a stage of rapid eye movement. As a result, there were some clear differences between the waveforms of the rare and frequent stimuli, and with change of sleep stages the differences also changed. Remarkable increase of amplitude and prolongation of latency of P200 and N200 were found in the waves of target stimuli in stage I. Activities of both components were connected with each other like a complexed component and preceded by the change of P300 activities. The waveforms of target stimuli in stage II had same kind of components with those of arousal stage. There were increased P200, N200, P300 activities and subsequent large negative activity which we called N3. These components were not clear in the waveforms of non-target stimuli. But P300 and N3 components were disappeared gradually during stage III. The averaged waveforms in stage III accompanied with 14-16 Hz fast wave suggested that they were identical with K-complex of sleep EEG. Add to this result, the habituation usually observed on P200 and N200 of nontarget stimuli in arousal let us to think that they are also identical with orienting reflex by rare and novel stimuli of external events (Sokolov). According to the result of examination changing the probability of target stimuli (20%----50%----80%), the waves of target stimuli in stage II were dependent on the probability of rare stimuli as well as in arousal stage. The dependence on probability was thought to reflect an automatic processing of selecting stimuli by orienting reflex in sleep. Another 3 subjects were examined of auditory evoked response in sleep with the same stimuli and without a task of counting numbers of rare stimuli. In stage II, however, they showed the waveforms by rare stimuli just like those by rare and target stimuli of 9 subjects. Then, it was supposed that attentiveness for external stimuli might be existent in sleep and changeable with sleep stages.

The hydB gene of Escherichia coli, which is related with the expression of hydrogenase activity, was cloned into the plasmid (pES1). Using the maxicell protein-labeling method, the molecular weight of hydB gene product was estimated. Comparing between the gene products from the mutant strains and that of the hydB genes cloned strains, the molecular weight of the gene product was 35,000 Mr. Similarly, the molecular weight of the gene product of hydA, which had been previously cloned, was determined by maxicell analysis. The molecular weight of hydA gene product was estimated to be 80,000 Mr. Using deletion analysis and Tn1000 insertional inactivation of hydA's function, the hydA coding region was estimated between 2.2 kb and 2.8 kb in a 3.1 kb EcoRI-MluI fragment on the recombinant plasmid pEH3.

The occurrence, distribution and abundance of larvae and juveniles of a Japanese flounder, Paralichthys olivaceus , were investigated in Shijiki Bay, south-western Japan, from 1982 through 1987, with special reference to immigration, settlement and mortality in this nursery ground. Sampling for pelagic larvae and settling and settled juveniles revealed that immigration and settlement occur during the late phase of metamorphosis, when flounders immigrate from coastal waters and settle in the near-shore sandy nursery area. Immigration of metamorphosing larvae begins in early April and continues until early June. The recruitment of flounders into the nursery ground was found to occur in several distinct phases, coinciding with spring tides. The semi-lunar periodicity found in the immigration of flounders may be due to the combination of landward tidal currents during spring tides and the tide-related vertical movements of metamorphosing flounders. Population size appeared to decrease rapidly during the first week after settlement, when lengths ranged from 11 to 14 mm. Field evidence demonstrated that heavy mortality may occur during the early phases of settlement, the extent depending on annual flounder densities and food abundance. Cannibalism of early-settled larger flounders on late-settled smaller flounders seemed to occur frequently in the nursery ground, and was more likely to occur under conditions of food deficiency and higher population densities. Thus, predation related t starvation could be one of the most important future research targets in determining recruitment dynamics in nursery areas.

The polymer support method for the oligonucleotide synthesis has been developed and used for the chemical synthesis of a 27-desamidosecretin gene. The gene carrying Pst I recognition sites at both ends was built from 16 fragments and each of them was synthesized by a stepwise addition of protected nucleotides on a polymer support. The coupling yield of each step was almost 90% and after partial deblocking, oligonucleotides carrying trityl groups were purified by chromatography on a reverse phase column. The recombinant DNA containing this synthetic gene was expressed in bacterial cells.