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Objective The orbital periosteum is considered to be a barrier to tumor spread; however, it is difficult to evaluate microscopic tumor spread during surgery. This study aimed to assess the impact of pathological status in orbital preservation surgery. Methods We retrospectively analyzed the 3-year local control rate and treatment outcomes of patients with malignant tumors invading the orbit who were treated between 2006 and 2012. Results In total, 27 patients were reviewed over a median follow-up period of 36 months. Pathologically, 19 had carcinomas and 8 had sarcomas. Treatment was by orbital exenteration in 6 patients and orbital preservation surgery in 21 patients. After orbital preservation surgery, poorer 3-year local control rates were significantly associated with positive surgical margins (negative vs. positive: 91% vs. 41%, P = 0.040) and microscopic orbital periosteum invasion (negative vs. positive: 90% vs. 39%, P = 0.010). These factors were independent risk factors in multivariate analysis. The locations of the positive margin were most common at the horizontal and vertical margins of the orbital periosteum and the posterior margin of the orbital apex. Moreover, in 24% of patients, invasion evaluation by preoperative imaging study was underestimated compared with postoperative microscopic evaluation. Conclusions The positive surgical margin and microscopic orbital periosteum invasion were the risk factors of orbital recurrence. It is difficult to determine the indications for orbital preservation surgery by preoperative imaging studies because of the unpredictable accurate pathological status before surgery and the limitations of preoperative imaging evaluation.

Adult rhabdomyosarcoma (RMS) is a highly aggressive tumor. Multidisciplinary treatment is important. However, the role of surgery is controversial. The purpose of this study was to reveal the role of a delayed primary excision (DPE) after induction chemotherapy (IC) in localized nonmetastatic adult head and neck RMS. We retrospectively reviewed 24 adult head and neck RMS. Treatment was classified into the following two groups: the DPE group, who received IC followed by surgery, postoperative radiotherapy, and adjuvant chemotherapy (17 patients); the chemoradiotherapy (CRT) group, who received IC followed by chemoradiotherapy (seven patients). We analyzed the efficacy of IC, local control rate (LCR), and overall survival (OS). In the DPE group, 10 patients (59%) underwent complete surgical resection. In the evaluation of the surgical specimens, 14 patients (82%) had residual viable tumors after IC. The response to IC was significantly associated with the 3‐year LCR (CR/PR vs. SD/PD: 100% vs. 33%, P = 0.0014). In patients with good response to chemotherapy, the DPE group had a significantly better 3‐year LCR compared with that of the CRT group (DPE group vs. CRT group, 100% vs. 44%, P = 0.018). However, the treatment modalities were not associated with OS (DPE group vs. CRT group, 65% vs. 57%: P = 0.98). The recurrence patterns differed according to treatments, and distant metastases were more frequent in the DPE group. DPE may impact local control of localized nonmetastatic adult head and neck RMS. Poor response to IC is a risk factor for local recurrence.

Two dinuclear complexes with novel coordination type, [Cu2(DPDIDT)2](PF6)2 (1) and [Ag2(DPDIDT)2](BF4)2 (2), plus a dinuclear complex of the usual coordination type, {Re(Cl)(CO)3}2(DPDIDT) (3) as a comparative complex were prepared from bis-(4-(2-pyridylmethyleneiminophenyl))disulfide (DPDIDT) and the relevant metal sources. Complexes (1) and (2) exist in solution as dimer structures of the square-pole type according to the interpretation of the ESI mass and 1H NMR spectra. The density functional theory calculations for the monomer and dimer models of the Cu(I) complex cations, [Cun(DPDIDT)n]n+ (n = 1, 2), demonstrated that the dimer form is structurally more stable than the monomer form. The UV–Vis absorption spectra of complexes (1) and (3) both exhibit a typical MLCT absorption band in the 400–700 nm region. The Re(I) complex (3) was revealed to possess a facial configuration with respect to the three carbonyl ligands by 1H NMR and IR data.

It is an important task of the pharmacist to triage appropriate over-the-counter (OTC) drugs for patients to achieve efficacy and safety.In this study,we investigated the present situation regarding the triage of OTC drugs for patients based on pharmacists interviewing patients in a fact-finding survey which determined how pharmacists in a drugstore communicate with patients during such interviews.We analyzed patterns of pharmacist communication with patients for the purpose of triaging OTC drugs in the drugstore and compared them with typical recommended communication patterns in the United States.In the drugstore,there were 3 patterns of initiating dialog with patients purchasing OTC drugs which were (1)“What are your symptoms?”2)“What is the name of the drug that you want?”and (3)“What disease do you have?” Using the first pattern we conducted a role play simulating the triaging of OTC drugs by pharmacists actually working in drug stores to standardized patients.In response to the patient’s description of his or her current symptoms,pharmacists used various speech patterns to explain the suitability of drugs selected and the cautions in use.In interviews conducted by inexperienced pharmacists,time was wasted in communication and there was no logical flow in them.Afterwards,some pharmacists said that they had not been able to obtain enough information from patients for triaging OTC drugs and others thought it was necessary to set algorithms for this purpose.These opinions suggest that pharmacy education in Japan should include training that makes pharmacists realize their responsibility in triaging OTC drugs for patients.

Objectives The aim of the present study was to clarify the clinicopathological characteristics, reconstruction methods after resection, and prognosis of cervical esophageal squamous cell carcinoma. Methods Seventy-four with squamous cell carcinomas of the cervical esophagus not previously treated who underwent cervical esophagectomy or total esophagectomy with or without laryngectomy were retrospectively analyzed. Results The operative morbidity and in-hospital mortality rates were 34% (25 patients) and 4% (3 patients), respectively. Alimentary continuity was achieved with free jejunal transfer (50 patients), gastric pull-up (19 patients), and other procedures (5 patients). The frequencies of postoperative complications and death did not differ between free jejunal transfer and gastric pull-up. The overall 3- and 5-year survival rates were 42% and 33%, respectively. The significant clinicopathological factors affecting survival were patient gender, high T factor, lymph node involvement, palpable cervical lymph nodes, vocal cord paralysis, lymphatic invasion, and extracapsular invasion. The pattern of first failure was most often locoregional (82%, 36 patients). Conclusion The choice of free jejunal transfer or gastric pull-up for reconstruction after surgical resection of cervical esophageal carcinoma depends on the degree of tumor extension. Adverse factors affecting survival should be considered when candidates for the surgery are selected. J. Surg. Oncol. 2007;96:166–172. © 2007 Wiley-Liss, Inc.

We experienced a case showing various psychotic symptoms following cessation of alcohol consumption. The symptoms included depressive state, delusion, confusion, psychomotor excitement and delirium, all of which disappeared in about two months. At first, we regarded all the symptoms as alcoholic hallucinosis, by a clinical standpoint, in spite of no auditory hallucination in this case. However, taking the overall clinical course into consideration, withdrawal syndrome could have been affected by some factors. One of the possibilities is that delusion might have been induced by aripiprazole. There still may be some other unknown influential factors on withdrawal, which are indicated by previous papers.

We report the first community epidemiological study of taijin kyofusho in Japan. A total of 132 inhabitants in a small community in the city of Kofu, Japan, was interviewed by trained interviewers using a semistructured interview, and completed self-report questionnaires. Of these respondents, nine (6.8%) reported ‘ taijin kyofu’ symptoms, eight of whom reported having specific concerns about strong body odor although the ‘ taijin kyofu’ symptoms were not serious enough to meet the criteria of a mental disorder. Although taijin kyofusho has traditionally been viewed as a disorder of young males, our cases were older and predominantly female. Although this sample was small and drawn from only one community, and we had no control group, our findings seem to support the view that some psychiatric symptoms are influenced by socio-cultural factors and that the symptoms of taijin kyofu are likely to be found in the general population of Japan.

現代医学的な血液生化学検査や精神症状評価などの結果より,「胸脇苦満」を分析しようと試みた。120例 (男性23例, 女性97例, 平均年齢42.4±16.2歳) を対象として, 胸脇苦満の程度と有無の評価, 血液生化学検査, Zung の Self Depression Scale (SDS), the Subjective Well-being Inventory (SUBI) を行った。93例 (77.5%) において, 左右いずれかもしくは左右ともに胸脇苦満を認めた。右側の胸脇苦満の「有」群と「無」群との間では, 血中クレアチニン値とSUBIの因子11 (人生に対する失望感) とで有意差を認めた。また, 左側の胸脇苦満の「有」群と「無」群との問では, SUBIの因子9 (身体的不健康感) と因子11とで有意差を認めた。以上の結果より, 強いストレッサー下にある症例ほど胸脇苦満を呈しやすいという結果が導き出された。

Interleukin-18 (IL-18) is a recently discovered proinflammatory cytokine which plays a pivotal role in T helper 1 (Th1) responses. IL-18 is produced by macrophage-like cells, and inappropriate IL-18 production has been known to be involved in immunological disturbances. Schizophrenia is a common disease whose pathogenesis is still unclear; however, an activation of the inflammatory response system, including the Th1 cytokine response, may be related to the pathophysiology of schizophrenia. We measured the serum IL-18 levels of 66 schizophrenics and age- and sex-matched control subjects by using an ELISA assay. We found significantly increased serum IL-18 levels in the schizophrenic patients (P=0.0002). This finding supports the hypothesis that immune activation is involved in the pathophysiology of schizophrenia.

To investigate the prevalence rates and characteristics of poorly explained or unexplained somatic symptoms in the general population of Japan, questionnaires were administered to 132 people aged 18 years or older in a small community in the city of Kofu. The participants were then interviewed by trained interviewers using a semi-structured interview schedule. Of the 132 participants in our study, 55 (41%) reported somatic symptoms. Of these 55, nine (16%) were diagnosed with a specific DSM-IV somatoform disorder. Multiple regression analyses revealed that the number of poorly explained symptoms among women was related to the respondent’s score on Neuroticism. These data suggest that poorly explained or unexplained somatic symptoms are related to personality characteristics. Moreover, our analysis also revealed a gender difference in the pattern of these relationships. None of the respondents who reported medically unexplained somatic symptoms had sought psychiatric care.

The relationship between dimensions of personality characteristics and the perceived rearing attitude of parents in the Japanese population were investigated. The scores on a measure of perceived parental attitude of 153 normal female students, measured on the Parker Parental Bonding Instrument, were correlated with personality features from the Japanese version of the Cloninger Temperament and Character Inventory. Self-directedness, especially the subclasses of Responsibility vs Blaming and Congruent Second Nature vs Incongruent Habits, was significantly related to high scores on Maternal Care and low scores on Maternal Overprotection. The subscale of Self-acceptance vs Self-striving correlated only with low scores on Maternal Overprotection. Paternal Care was only related to the total scale scores on Self-directedness. Results suggest that some personality traits may be related to the perceived attitudes of parents, especially of the mother, during childhood.

We compared the subtype diagnoses of schizophrenia (ICD-10) of 58 Japanese and 61 European psychiatrists matched for clinical experience using 10 case summaries. As a result, there are marked differences between Japanese and European psychiatrists in the mode of subtype diagnoses of schizophrenia rather than in the clinical pictures of the patients themselves; the hebephrenic type (F20.1) was more likely to be diagnosed by Japanese psychiatrists, while the paranoid type (F20.0) was more frequently diagnosed by European psychiatrists. Japanese psychiatrists take into account the patient’s age at onset and the clinical course of the disease in identifying the subtype, while European psychiatrists tend to focus on the presenting symptoms, particularly paranoid symptoms.

BACKGROUND We examined interleukin-2 (IL-2) related immune pathways in depression to elucidate mechanisms underlying various immunological disturbances associated with depression. METHODS Subjects comprised 35 unmedicated patients with a major depressive episode without psychotic features and 36 age- and sex-matched healthy volunteers. The immune parameters examined included the numbers of B and T cells, IL-2 receptor-mediated blastoformation (IL-2R-mediated blastoformation), IL-2 production and expression of the IL-2 receptor alpha-subunit. RESULTS The patients with a severe episode showed significantly lower IL-2R-mediated blastoformation than the controls. There was a statistically significant negative correlation between IL-2R-mediated blastoformation and the severity of depression at the time of entry. CONCLUSION The reduced IL-2R-mediated blastoformation may partly explain several previously reported abnormal immune functions associated with depression.

遠隔記憶障害を検出する場合，想起された内容の真実性，再学習の有無，興味や関心の個人差，時間的傾斜の検出の可否が問題となる。社会的なことがらを利用した遠隔記憶検査では興味や関心の個人差が，自伝的なことがらを利用した遠隔記憶検査では想起された内容の真実性が特に問題となる。また，比較的やさしい課題で健常群の天井効果を認める場合，または，比較的難しい課題で健忘群の床効果を認める場合には，時間的傾斜の有無に関して確実なことがいえなくなる。流暢性ベースの遠隔記憶検査は，単位時間内に知人の名前や体験した出来事をできるだけたくさん想起する課題であり，検査の構造上，天井効果が起こりえないために時間的傾斜の問題を考える場合には好都合である。また，内容の異なる遠隔記憶でも流暢性ベースで質問することにより，記憶以外の条件を等しくできる利点もある。コルサコフ症候群において，自伝的記憶流暢性検査の成績は，従来までの自伝的記憶検査の成績と有意な相関を認めており，遠隔記憶検査として有用性が高いと思われた。

A 54-year-old Japanese businessman who was found to exhibit the ‘Alice in Wonderland’ syndrome and went on to develop a depressive disorder is described. Lengthening and shortening of time experience continued intermittently for about 3 months, and metamorphopsia, distortion of body image, and the quick-motion phenomenon (alteration in time sense) persisted for almost 2 days without interruption. There were no abnormal physical findings. The authors review studies on ‘Alice in Wonderland’ syndrome and suggest that depressive illness may be a causal factor.

Schizophrenic delusions of 324 inpatients in Tokyo, 101 in Vienna, and 150 in Tübingen (Germany) were compared according to the same classifications. Among the three areas, about 80% of the patients had equally ‘negative’ delusions (injury and/or belittlement), and about one-fourth had ‘positive’ delusions of grandeur. Transcultural influences were found in the detailed contents of the ‘negative’ delusions; specific and direct themes of persecutory delusion, i.e., delusions of poisoning, and religious themes of guilt/sin were conspicuous in Europe, while amorphous delusions of reference such as ‘being slandered’ were predominant in Japan. The latter may derive from the group-oriented self in Japanese ‘shame culture’.

One hundred and fifty-one non-insulin-dependent diabetic patients were assessed to detect sociodemographic, psychological and disease-related characteristics that were related to depressive state among diabetic patients. Depressive state in the patients was correlated with poor social support and low economic status, premorbid neurotic personality and the presence of complications, retinopathy in particular. However, depressive state did not correlate with age, gender, education, serum level of HbA1C or duration of diabetes. The severity of the depressive state in diabetic patients may vary with the cultural background of the patient and/or the country in which he or she is living. In treating diabetic patients, doctors need to pay special attention to these factors.

身体表現性障害に対する漢方治療の有効性を調べるための予備的な研究として, 漢方外来初診患者100名 (男性17名, 女性83名, 平均年齢39±16歳) を対象に, somatoform disorders schedule より作成した身体表現性障害チェックリスト, 主観的幸福感を調べる subjective well-being inventory (SUBI) を施行した。身体表現性障害の患者は全体の65%を占めた。身体表現性障害の患者は身体疾患患者に比べてSUBIの positive スコアが有意に低く (p=0.042), negative スコアが有意に高かった (p=0.001)。身体表現性障害群では, 身体表現性障害の症状数はSUBIの positive スコアと負の相関関係 (r=-0.267, p=0.032) を, negative スコアと正の相関関係 (r=0.337, p=0.006) を示した。

発病または急性増悪により入院し, 4～12週間のハロペリドールを中心とした抗精神病薬の治療により活動期症状が改善し, 精神症状が安定した後に抗精神病薬の投与量が最低2週間以上固定された精神分裂病圏の患者10名に対し, 黄連解毒湯を4週間追加投与した。黄連解毒湯の追加投与直前, 投与終了時, 投与終了4週後にそれぞれ Brief Psychiatric Rating Scale (BPRS) を用いて症状評価を行なった結果, BPRS 総得点は, 黄連解毒湯の追加投与直前と比較して投与終了時, 投与終了4週後ともに有意に減少した。症状別では,「罪業感」,「抑うつ気分」,「疑惑 (被害妄想)」,「興奮」に有意な改善がみられた。さらに, 血中ハロペリドール濃度には変化がみられなかったことより, 精神症状の改善がハロペリドールの血中濃度の変化によるものではないということが示唆された。また, 副作用はみられなかった。

Saiko-ka-ryukotsu-borei-to (TJ-12) is a Japanese kampo medicine used clinically for the treatment of hypertension and atherosclerosis. We investigated the effects of TJ-12 on the contraction of rat thoracic aorta induced by norepinephrine, 5-hydroxytryptamine and high potassium. TJ-12 relaxed endothelium-denuded rings, which had been precontracted with 1 microM norepinephrine, in a dose-dependent manner with an IC50 of 50 micrograms/mL. However, in the presence of TJ-12, endothelium-intact rings initially showed enhanced norepinephrine-induced contraction, followed by relaxation. Interestingly, TJ-12 dose-dependently reversed nitric oxide (2 microM)-induced relaxation of norepinephrine-induced precontraction ofendothelium-denuded rings, with an IC50 of 20 micrograms/mL. In serotonin-contracted rings, TJ-12 caused slight, though statistically significant, relaxation only at high doses (200 micrograms/mL). In constrat to these receptor-mediated contractions, TJ-12 failed to affect the tension produced by high potassium 40 mM). These results suggest that the antihypertensive effects of TJ-12 could be related to inhibition of norepinephrine-induced vasoconstriction. In addition, our in vitro experiments revealed an inhibitory effect on nitric oxide-induced relaxation.

In order to find a genetic marker for vulnerability to tardive dyskinesia (TD), we looked for an association between vulnerability to TD and polymorphic sites in the gene loci encoding the dopamine D2 receptor (Nco I site), the dopamine D3 receptor (Bal I site), and the dopamine transporter (40-bp, tandem repeat polymorphism). No significant difference was observed in the allele and genotype frequencies of any of the polymorphic sites examined, when comparing psychiatric patients who were specifically vulnerable to TD (n = 49) and those who were not (n = 56). These results suggest that the polymorphic gene loci examined in the present study are unlikely to be of major aetiologic importance in the development of TD. © 1997 John Wiley & Sons, Ltd.

主訴に睡眠障害 (入眠困難) を含む, 未投薬の精神分裂病および他の精神病性障害患者18名を無作為に2群に分け, 一群には黄連解毒湯と抗精神病薬 (ハロペリドール) を, 他群には抗精神病薬のみを投与し, 4週間の精神症状の推移と睡眠薬の頓服使用状況を評価した。精神症状においては, 黄連解毒湯追加投与群では非追加投与群と比較して, 思考障害 (思考解体, 誇大性, 幻覚, 思考内容の異常) において, 改善 (P=0.06) がみられた。また, 睡眠薬 (ニトラゼパム) の頓服回数においても, 非追加投与群では平均7.7回であったのに対し, 黄連解毒湯追加投与群では平均1.9回と, 同様に改善 (P=0.06) がみられた。黄連解毒湯の追加投与が, 睡眠障害を伴う精神分裂病および他の精神病性障害の急性期の治療に有効であることが示唆された。

The aim of this study was to investigate the childhood abuse histories of bulimic patients in order to characterize the effect of these histories, on their later social adjustment, psychiatric distress, and bulimic severity. Fifty Japanese female bulimic outpatients filled out a 28-item version of the General Health Questionnaire, the Dissociative Disorders Interview Schedule, the Bulimic Inventory Test, and a clinical database questionnaire. Among 50 bulimic patients, 16 reported a history of physical abuse, and 20 a history of sexual abuse. The nature of the sexual abuse reported was relatively mild compared to Western reports. Although the age of onset of dieting, anorexia, binge eating, vomiting, and severity of bulimia had no relationship to abuse history, the patients with sexual abuse histories had more absenteeism in junior high school and reported more sexual activity than those without such histories. The patients who reported physical abuse histories scored higher on the somatic symptom section of the General Health Questionnaire. The findings of this study suggest that, while abuse experiences themselves do not seem to be a cause of bulimia, these experiences may affect the style and level of adaptive functioning in later life, and the type of abuse may influence the nature of future psychological difficulties. Differences in the severity of child abuse between Japan and Western countries requires further study.

This paper discusses the characteristics of avoidant personality disorder in a cultural context based on the Japanese concept of taijin kyoufu as well as that of DSM-III-R and DSM-IV social phobia. Sixty-six patients were given the International Personality Disorder Examination and questionnaires including the Beck Anxiety Inventory. Among the 23 DSM-III-R personality disorder patients, 8 patients were diagnosed as having avoidant personality disorder. Six of them were suffering from taijin kyoufu symptoms. Among 27 ICD personality disorder patients, 22 patients were diagnosed as having ICD anxious personality disorder. All DSM avoidant patients were included in the ICD anxious group. These findings suggest that patients with avoidant personality disorder have had a long history of difficulties and share common personality problems with a milder form of taijin kyoufu, which is conceptually different from social phobia.

In order to investigate the biological characteristics of deficit syndrome in schizophrenia (Carpenter et al 1988), we examined cerebroventricular ratios (CVRs) and plasma concentrations of homovanillic acid (HVA) in a group of schizophrenic inpatients with deficit syndrome ( n = 20) and in a control group of age- and sex-matched schizophrenic inpatients without deficit syndrome ( n = 20). Symptoms and intelligence levels were measured using the Brief Psychiatric Rating Scale (BPRS) and the Wechsler Adult Intelligence Scale (WAIS), respectively. Patients in the deficit group had significantly higher CVRs as well as significantly elevated plasma HVA concentrations when compared with patients in the nondeficit group. We also found that the mean total WAIS score in the deficit group was significantly lower than that in the nondeficit group. These findings suggest the biological heterogeneity of schizophrenia. Increased central dopaminergic turnover, as indicated by higher plasma HVA concentrations may partially account for the pathogenesis of deficit syndrome.

We investigated whether interleukin-1 (IL-1) activity in the rat hypothalamus was increased by immobilization stress (IS), and whether pretreatment with an interleukin-1 receptor antagonist (IL-1Ra) is capable of inhibiting IS-induced elevations of hypothalamic norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and the levels of their metabolites as well as of plasma adrenocorticotropic hormone (ACTH). IL-1 activity was estimated with a bioassay using mouse thymocyte proliferation in the presence of concanavalin A. IL-1Ra was administered directly into the anterior hypothalamus, and monoamines were determined using a microdialysis technique and an HPLC system. First, we found that levels of IL-1 activity in the rat hypothalamus reached a maximum at 60 min after starting IS. Second, IL-1Ra (2 micrograms) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1Ra (2 micrograms) also inhibited the IS- induced elevation of plasma ACTH levels. Third, timing effects of IL- 1Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 micrograms) administered at 5 or 60 min before the start of IS, but not at 5 or 60 min after IS had been started, exerted inhibitory effects on these responses, indicating that the effects of IL-1 occurred within 5 min after the initiation of IS. In summary, these results suggest that IS enhances biologically active IL-1 in the hypothalamus, and that hypothalamic IL-1 plays a role in the regulation of IS-induced responses including elevated monoamine release in the hypothalamus and activation of the hypothalamo-pituitary-adrenal axis. Moreover, since 5 min is too short a time for IS to induce production of IL-1, IS may augment the effects of preexisting IL-1 in the hypothalamus.

Recently, the central roles of interleukin-1 (IL-1) in physical stress responses have been attracting attention. Stress responses have been characterized as central neurohormonal changes, as well as behavioral and physiological changes. Administration of IL-1 has been shown to induce effects comparable to stress-induced changes. IL-1 acts on the brain, especially the hypothalamus, to enhance release of monoamines, such as norepinephrine, dopamine, and serotonin, as well as secretion of corticotropin-releasing hormone (CRH). IL-1-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis in vivo depends on secretion of CRH, an intact pituitary, and the ventral noradrenergic bundle that innervates the CRH-containing neurons in the paraventricular nucleus of the hypothalamus. Recent studies have shown that IL-1 is present within neurons in the brain, suggesting that IL-1 functions in neuronal transmission. We showed that IL-1 in the brain is involved in the stress response, and that stress-induced activation of monoamine release and the HPA axis were inhibited by IL-1 receptor antagonist (IL-1Ra) administration directly into the rat hypothalamus. IL-1Ra has been known to exert a blocking effect on IL-1 by competitively inhibiting the binding of IL-1 to IL-1 receptors. In the latter part of this review, we will attempt to describe the relationship between central nervous system diseases, including psychological disorders, and the functions of IL-1 as a putative neurotransmitter.

To investigate the possible effect of polymorphism at the BalI site of the dopamine D3 receptor gene (DRD3) on the phenotype in human subjects, allele and genotype frequencies for this polymorphic site were examined in 113 schizophrenic patients, including six subgroups, and 48 normal controls. The schizophrenic subgroups included patients with early onset, those with a family history, and those who suffered from one of the following psychiatric symptoms at their first episode: (1) delusion and hallucination; (2) disorganization; (3) bizarre behavior; and (4) negative symptoms. No significant differences were observed in genotype, allele and homozygosity frequencies between the whole group or any subgroup of schizophrenic patients and the controls. The present results indicate that polymorphism at the BalI site of the DRD3 is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.

A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatricy symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia.

We investigated the effects of lithium ion (Li+) on muscarinic receptor-mediated nitric oxide (NO) generation, and guanylate cyclase (GCase) activation using the mouse neuroblastoma clone, N1E-115. The levels of released NO were determined by measuring the levels of nitrite/nitrate in the incubation medium, and the activity of GCase was measured with an assay for cellular cyclic [3H] GMP levels. We determined that Li+ had no effects on muscarinic receptor-activated elevation of nitrite/nitrate levels, which were significantly inhibited by 100 microM L-NG-monomethylarginine, although it has been reported that Li+ inhibits muscarinic receptor-activated cyclic GMP formation in the cells. In addition, Li+ inhibited the cyclic GMP formation induced by an NO donor, sodium nitroprusside (SNP), in both intact cells and a crude cellular homogenate; thus, the inhibition by Li+ of muscarinic receptor-mediated cyclic GMP synthesis appeared to be at the level of GCase, but not NO synthase.

We investigated the effects of interleukin-1 beta (IL-1 beta), administered directly into the rat anterior hypothalamus (AHY), on monoamine release in the same region by using a brain microdialysis technique and an HPLC-electrochemical detection system. First, to study the local effects of IL-1 beta, we used a microdialysis probe equipped with a microinjection tube for administering IL-1 beta in the same region into which the probe had been inserted. IL-1 beta (1 ng) injected directly into the AHY elicited release of norepinephrine (NE), dopamine (DA), and 5-HT, as well as increases in their metabolites, 4- hydroxy-3-methoxyphenylglycol, 3,4-dihydroxyphenylacetic acid, 4- hydroxy-3-methoxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid, in the AHY. Vehicle alone exerted no effect on monoamine release. Although the elevated levels of NE and DA persisted for more than 6 hr after injection of IL-1 beta, the elevated levels of 5-HT were transient. Second, in order to investigate whether this effect of IL-1 beta is a direct action in the AHY, we performed in vitro experiments using hypothalamus slices. IL-1 beta (0.1 and 1 nM) increased the levels of each monoamine released from hypothalamic slices in a dose- dependent manner. These findings suggest that IL-1 beta acts directly on the hypothalamus to induce release of NE, DA, and 5-HT. Third, the roles of prostaglandins (PGs) in NE release in the AHY elicited by direct injection of IL-1 beta were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

1962年より1990年までの間に, 国立がんセンター中央病院において根治的目的の放射線治療が施行された50歳未満の頭頸部扁平上皮癌患者のうち, 喉頭, 中・下咽頭癌症例の治療成績を検討した。対象症例は喉頭癌59例, 中咽頭癌32例, 下咽頭癌15例で, 根治的放射線治療の施行された全症例のそれぞれ12, 20, 10%を占めた。対象の年齢は26～49歳で中央値は45歳であった。5年生存率は喉頭癌, 中咽頭癌, 下咽頭癌それぞれ88, 62, 40%であった。また, 5年局所制御率はそれぞれ, 72, 71, 52%であった。生存率, 局所制御率共に全年齢層のそれと有意な差はなかった。一方, 異時性重複癌が8例に, また放射線治療後5年以降の再発が喉頭癌において5例認められた。若年者頭頸部癌患者に放射線治療を適応しても治療成績が劣ることはないが, 重複癌発生と晩期再発の両方の観点から長期の経過観察が重要と思われた。

SummaryDepressive conditions such as treatment-resistant depression, persistent depression and chronic mild depression have recently been the subject of much interest in Japan. The term “atypical depression” is not in common use, however depressive states falling outside the “typical” categories of the major depressive disorders (MDD) can be discussed in terms of symptomatology, etiology, and response to treatment. The term “neurasthenia” which refers to a hypochondriacal disorder with or without physical illness, as well as to a subtype of neurosis (ICD-9, 300.5), is no longer extensively used. “Dysthymia” is classically employed to signify either a dysphoric state accompanied by mild depression and irritability, as defined by the German school, or a mild depressive personality disorder; it is currently used as an alternative to “neurotic depression” (ICD-9 300.4), or “dysthymic disorder” (DSM III-R). Recurrent brief depression is not yet a prevalent concept in Japan. Despite the observation of depression with hyperphagia and/or hypersomnia, these phenomena have not received a specific designation. Therapeutic approaches to depression include both non-drug modalities (psychotherapy, environmental modification, etc) and the standard drug regimens (antidepressants, anxiolytics, etc); clinical trials are currently underway with selective serotonin reuptake inhibitors which we expect to be effective in treatment-resistant depression. Plant-based traditional remedies are still widely employed in Japan, and several of these are described. Finally, we discuss the Morita therapy, a specifically Japanese modality for treatment of mild depression with obsessive-compulsive symptoms based upon the Zen philosophy. This approach involves an initial period of absolute bed-rest, followed by gradual resumption of work and social activities with support and counseling.

A study of electric-pulse-induced crystallization of Ge2Sb2Te5 (GST) was conducted by in situ scanning electron microscopy observation and resistance measurement. A lateral phase-change memory with a top GST channel connected by two separate underlying electrodes was adopted in this study to easily observe the crystallization process. At a low voltage pulse, randomly distributed nuclei were initiated. At the first growth stage, these nuclei grew fast with the pulse amplitude at a rate of around 60 nm/V and then growth rate slowed down to around 14 nm/V when the grain diameter was closed to film thickness. Device resistance during crystallization dropped by around one order of magnitude, which should be due to amorphous to face-centered-cubic transition.

In this paper, characterizations of sputtered undoped and nitrogen-doped Sb2Te3 (ST and STN) films by X-ray diffraction (XRD) and resistance measurements are described and their application of lateral phase-change memory (PCM) is presented. Nitrogen concentration of the films was controlled by changing the flow rate ratio of N2/Ar during sputtering. Resitivity of STN films drops by 3-4 orders of magnitude due to crystallization. Resistivity increase of the STN film (N2/Ar=0.15) at above 270°C results from phase precipitation of SbN. Experimental results reveal that the temperature of crystallization to face-centered cubic (fcc) significantly increases from below 100°C to 160–220°C with increasing the ratio of N2/Ar (in the range of 0–0.15) and crystal structure further transforms from fcc to hexagonal. At high flow rate ratio of N2/Ar (>0.15), hexagonal Te phase firstly appears at 160°C and then orthorhombic SbN appears at 290°C.

In order to distinguish the trigger and the factors maintaining bulimia nervosa (BN), TCI temperamental scores were compared among BN patients, normal controls without diet experiences (N-N), and normal controls with diet experiences (N-D). On the novelty-seeking (NS) scale, the BN patients scored significantly higher than the N-N subjects, but there was no significant difference between the BN patients and the N-D subjects, and the N-D subjects scored higher than the N-N subjects. These findings suggest that high NS scores are related to diet experiences rather than chronic bulimic symptoms.

We have studied a possibility to read small pits in electron beam (EB) resist layer using a near-field optical probe for ultrahigh density optical storage. For the reading, we used small near-field optical probe in prototype atomic force cantilevered SNOM, which has an ability to obtain both atomic force microscope (AFM) and scanning near-field microscope (SNOM) images simultaneously. We formed 20-nm sized pit arrays with a pitch of 60 nm using a conventional EB writing system based on a scanning electron microscope (SEM). Using the arrays and the prototype ANOM system, we have demonstrated the possibility to read-out 20-nm-sized pits using near-field optical probe

We investigated a genetic association between mood disorders (bipolar and unipolar) and the alleles of monoamine oxidase (MAO) A and B (MAOA and MAOB). One hundred and twelve unrelated Japanese patients (60 bipolar, 52 unipolar) and 100 controls were genotyped for three markers of MAOA and for one marker of MAOB. No statistically significant difference in the distribution of the alleles existed between cases and controls. Therefore, our results did not support the involvement of the alleles at MAOA and MAOB in the etiology of mood disorder.

BACKGROUND Tardive dyskinesia (TD) is a therapy-resistant adverse effect of neuroleptics. Although the exact pathophysiology of TD is unknown, oxygen radicals have been speculated to play a role in TD based on several lines of evidence. Superoxide dismutase (SOD) is a key enzyme which scavenges oxygen radicals. The authors investigated the association between erythrocyte SOD activity and TD. METHODS Erythrocyte SOD activities were measured, blinded as to the presence or absence of TD. In 30 patients with schizophrenia who had been on typical neuroleptics for more than 10 years. TD severity was independently assessed, using the abnormal involuntary movement scale (AIMS), by two raters. RESULTS There was a significant decrease in erythrocyte SOD activity in the definite TD group (N = 10) as compared with the no TD (N = 8) and questionable TD (N = 12) groups. Erythrocyte Cu,Zn-SOD activities correlated with AIMS scores. CONCLUSIONS Patients with TD had low SOD activities as compared to those without TD. As a causal link between SOD activity and TD was not established in this study, larger prospective studies are warranted to determine whether patients with low SOD activity are susceptible to neuroleptic-induced TD.

We investigated the efficacy of nilvadipine, a calcium channel inhibitor, for psychiatric symptoms and tardive dyskinesia in 30 patients with chronic schizophrenia in a placebo-controlled double-blind crossover study. The total scores of the Brief Psychiatric Rating Scale decreased significantly when the patients were on nilvadipine compared with placebo. Improvement was particularly significant in emotional withdrawal and uncooperativeness. Nilvadipine was not effective, however, for tardive dyskinesia. No adverse effects, such as hypotension, occurred.

To investigate the possible role of the dopamine transporter (DAT) gene in determining the phenotype in human subjects, allele frequencies for the 40-bp variable number of tandem repeats (VNTR) polymorphism at this site were compared between 117 Japanese normal controls and 118 schizophrenic patients, including six subgroups: early-onset, those with a family history, and those suffering from one of the following psychiatric symptoms at their first episode: delusion and hallucination; disorganization; bizarre behavior; and negative symptoms. No significant differences were observed between the group as a whole or any subgroup of schizophrenic patients and controls. The results indicate that VNTR polymorphism in the DAT gene is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects. 12 refs., 1 fig., 2 tabs.

The efficacy of paroxetine in the treatment of obsessive-compulsive disorder in Western populations is well established. The present study compares the efficacy and safety of paroxetine with placebo in the treatment of obsessive-compulsive disorder in Japanese patients. Patients aged 16 years or older who met Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for obsessive-compulsive disorder and had a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of >/=16 were randomized to receive 12 weeks' therapy in a double-blind manner. Paroxetine 20-50 mg/day or placebo was administered following a 1 week, placebo run-in phase. One hundred and ninety-one patients were randomized to either paroxetine or placebo, 188 patients were assessed as the full analysis set (FAS) and 144 patients completed the 12 week study. After adjustment for the Y-BOCS total score at baseline, reductions in obsessive-compulsive total score at week 6 and at the end of therapy were significantly greater in the paroxetine group than the placebo group. Most of the adverse events that occurred during the study were of mild to moderate intensity. Paroxetine is effective and well tolerated in Japanese adult patients with obsessive-compulsive disorder.

Neuroleptic noncompliance is a major reason for relapse in outpatients with schizophrenia. In a 2-year follow-up study, we used the Japanese version of the Rating of Medication Influences Scale (ROMI-J) to investigate the reasons for compliance and noncompliance in outpatients with schizophrenia. Ninety outpatients who were confirmed by interview to have had good compliance for more than 3 months completed the initial interview, which included the Clinical Global Impressions Scale (CGI), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale (GAF), the UKU Side Effect Rating Scale, and the ROMI-J. All the outpatients were followed up for 2 years. At the initial interview, the most frequent reason for compliance was "relapse prevention," while the most frequent reason for noncompliance was "distressed by side effects." Fifteen outpatients who proved to be noncompliant in the follow-up period had higher baseline BPRS "agitation" scores and ROMI-J "no perceived daily benefit" ratings than compliant patients. Sixty-four outpatients who maintained compliance during the follow-up had higher baseline ROMI-J ratings of "fulfillment of life goals" than their noncompliant counterparts. It is important to understand the attitudes of patients with schizophrenia toward drug therapy in order to predict better compliance and provide psychoeducation designed to forestall relapses.