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When artificial radionuclides are released into the atmospheric environment, one of the important processes by which they affect the human radiation dose is the direct deposition of the radionuclides onto crop surfaces. Because leafy vegetables are consumed while fresh and often raw, the mass interception coefficient [= concentration in food (Bq/kg dry mass (DM) or fresh mass)/total deposition (Bq/m

In the working population, bipolar disorder can have a significant negative effect on professional relationships, attendance, functioning, and loss of productivity. In Japan, workers who take a leave due to depressive episodes receive a work-focused intervention program called the "return to work program" during their leave. A 39-year-old Japanese woman with bipolar II disorder took a third sick leave of absence. We recommended her the return to work program of our university hospital. At the beginning of the program, she had a rigid thought process toward her perceptions of her duties in the workplace and at home. Through the program, mindfulness might identify rigidity, group cognitive-behavioral therapy might correct rigidity, and self-analysis might have regained flexibility. In conclusion, a variety of effects of our return to work program might have enabled her thought process to evolve from rigid to flexible, and she showed successful reinstatement.

Despite the unavailability of essential anti-dementia drugs, lithium may inhibit glycogen synthase kinase-3 (GSK-3) and decrease beta-amyloid and hyper-phosphorylated tau. In this review, we hypothesized that trace to standard levels of lithium (i.e., corresponding to the therapeutic levels for bipolar disorder) may be effective for dementia prevention. Excluding three insufficient level studies, we obtained two and one excellent clinical studies on standard and trace lithium levels, respectively, all of which supported the effects of lithium for dementia prevention. In addition, we identified good clinical and epidemiological studies (four each) on standard lithium levels, of which six studies supported the effects of lithium. Moreover, of three good epidemiological studies on trace lithium levels, two supported the aforementioned effects of lithium. The number of studies were substantially small, particularly those on trace lithium levels. Moreover, studies on standard lithium levels were insufficient to establish the efficacy of lithium for dementia prevention. This necessitates accumulating good or excellent clinical evidence for the effects of trace to standard lithium levels on dementia prevention.

Objectives Bright light therapy (BLT) was reported as an effective adjunctive treatment option for bipolar disorder. Previous meta‐analytic study showed that augmentation treatment with light therapy significantly decreased the severity of bipolar depression. However, most of included studies were case–control studies and several of them focused on BLT that was provided in combination with sleep deprivation therapy. Methods In this meta‐analysis, we used several electronic databases to search the studies and included only randomized controlled trial (RCT) studies to compare BLT with control experimental groups for treating bipolar depression with pharmacological treatment to clarify the adjunctive efficacy of BLT. We searched the databases of EMBASE, MEDLINE, Scopus, The Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and Clinicaltrials.gov for studies published in English until September 19, 2019. Two researchers conducted the literature screening, data extraction, and methodological quality assessment independently. The main outcome was the response rate and remission rate. We used the Review Manager 5.3 Software for the meta‐analysis. Results Four trials with a total of 190 participants (intervention: 94, control: 96) with bipolar depression were evaluated to gauge the effects of light therapy. The meta‐analysis showed risk ratios of 1.78 (95% CI 1.24–2.56, p = .002; I 2 = 17%) demonstrating a significant effect of light therapy in the response rate of bipolar disorder. The meta‐analysis shows risk ratios of 2.03 (95% CI 0.48–8.59, p = .34; I 2 = 67%) demonstrating no significant effect of light therapy in the remission rate of patients with bipolar disorder. None of the articles reported any serious adverse effects. Manic switch rate was 1.1% in the light therapy group and 1.2% in the control group. Conclusions Bright light therapy is an effective treatment for reducing depression symptoms among patients with bipolar depression., Bright light therapy is an effective treatment for reducing depression symptoms among patients with bipolar depression.

Objectives The aims of the present study thus were (a) to further investigate the association between lithium levels in drinking water and suicide rates by adjusting relevant factors using the so far largest available dataset in Japan, (b) to confirm sex differences, (c) to estimate the effects of long-term exposure to trace lithium, (d) to investigate the effects of drinking bottled instead of tap water, and (e) to exploratorily investigate which lithium levels may be associated with lower suicide rates. Methods Mean lithium levels in drinking water of all 808 cities and wards (ie, 785 cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to mean suicide standardized mortality ratios (SMRs) during the 7 years from 2010 to 2016. Multiple regression analyses adjusted for the size of each population were used to investigate the association of lithium levels with suicide SMRs with adjustments for relevant factors. Results The adjusted model showed significant inverse associations of lithium levels with total and male SMRs, but not with female SMRs. Neither the proportion of residents who continued to live in the same city nor the consumption of bottled water changed the association between lithium levels and suicide SMRs. Finally, it was 30 μg/L or more that was associated with lower suicide SMRs. Conclusions The present findings reconfirm the inverse association between lithium levels in drinking water and suicide rates particularly in the male population.

Aim We aimed to investigate the hypotheses that hyperthymic temperament may be positively associated with self-directedness and self-transcendence with adjustment for relevant factors. Methods Using the database of our previous studies, the data from 111 healthy subjects with scores for both the Temperament and Character Inventory and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire were secondarily used for the present study. Results Hyperthymic Temperament scores were significantly and positively associated with Self-Transcendence scores, but not with Self-Directedness scores, following adjustment for relevant factors. Despite the lack of association between self-transcendence and self-directedness, cooperativeness was significantly and positively associated with self-transcendence and self-directedness, but not with hyperthymic temperament. Moreover, despite the lack of association between hyperthymic temperament and self-directedness, harm avoidance was significantly and negatively associated with hyperthymic temperament and self-directedness, but not with self-transcendence. Conclusion The present findings suggest that hyperthymic temperament may be positively associated with self-transcendence, but not with self-directedness. Moreover, hyperthymic temperament may be, a selfish and reckless trait, self-transcendence may be altruistic and not reckless, and self-directedness may be altruistic but reckless.

Background Most studies have reported that suicide mortality rates are negatively associated with lithium levels in tap water; however, a few studies showed either no association or a positive association. Thus, the association between suicide mortality and lithium levels in tap water remains controversial. To clarify the association, our study evaluated the association between lithium levels in tap water and suicide mortality rates in Miyazaki Prefecture of Japan, after adjusting for confounding factors. Methods We measured lithium levels in tap water across the 26 municipalities of Miyazaki Prefecture in Japan. We examined the standardized mortality ratio (SMR) for suicide in each municipality and used the data as the average suicide SMRs over 5 years (2009–2013). Weighted least-squares regression analysis, adjusted for the size of each municipality’s population, was used to investigate the association between lithium levels in tap water and suicide SMRs. In addition to a crude model, in an adjusted model, potential confounding factors (proportion of elderly people, proportion of one-person households, annual marriage rate, annual mean income, unemployment rate, the density of medical doctors per 100,000 people, annual total rainfall, and proportion of people with a college education or higher) were added as covariates. Results We showed that male and female suicide SMRs were not associated with lithium levels in tap water in Miyazaki Prefecture. After adjusting for confounders, male suicide SMRs were significantly and positively associated with the proportion of elderly people in the population and annual total rainfall, and female suicide SMRs were associated with the proportion of elderly people in the population. Conclusions No association between lithium levels in tap water and suicide mortality rates was found in Miyazaki Prefecture.

Objective Previous studies have investigated the effects of omega-3, omega-6 and lithium on suicide-related behaviors separately. This study was performed to comprehensively investigate the effects of naturally absorbed EPA, DHA, arachidonic acid and lithium in relation to suicide attempt and deliberate self-harm, with adjustment for each other. Methods We analyzed plasma EPA, DHA, arachidonic acid levels and serum lithium levels of 197 patients including 33 patients with suicide attempts, 18 patients with deliberate self-harm, and 146 control patients. Results Multivariate logistic regression analysis with adjustment for age, gender, EPA, DHA, arachidonic acid and log-transformed lithium levels revealed that the negative associations with EPA levels (adjusted OR 0.972, 95% CI 0.947–0.997, p = 0.031) and log-transformed lithium levels (adjusted OR 0.156, 95% CI 0.038–0.644, p = 0.01) and the positive association with DHA levels (adjusted OR 1.026, 95% CI 1.010–1.043, p = 0.002) were significant in patients with suicide attempts than in control patients. The analysis also demonstrated that the positive association with arachidonic acid levels (adjusted OR 1.015, 95% CI 1.005–1.025, p = 0.004) was significant in patients with deliberate self-harm than in control patients. Limitations The limitations are relatively small number of patients and the effects of demographics of individual patients could not be adjusted for the analyses. Conclusions The present findings suggest that, as naturally absorbed nutrients, higher EPA and lithium levels may be associated with less suicide attempt, and that higher arachidonic acid levels may be associated with more deliberate self-harm.

Background Given the reported inverse association between light and depressive mood, ambient light may also be associated with some of the brain regions in healthy subjects. The present study aims to investigate the effects of ambient light on glucose metabolism in the brain. We used the data of 28 healthy participants of the no intervention group from our previous randomized controlled trial and analyzed the association between ambient light and [18F]-FDG uptake in the brain. Results A whole brain analysis revealed a cluster of [18F]-FDG uptake that was significantly and inversely associated with log-transformed ambient light in the left culmen of the left cerebellum vermis. After adjustment for age, gender and serum melatonin levels, there remained a significant cluster of [18F]-FDG uptake with log-transformed ambient light in the left cerebellar vermis. Conclusions The present findings suggest that the uptake of [18F]-FDG is significantly and inversely associated with ambient light in the left cerebellar vermis in healthy subjects. The cerebellar vermis may be involved in mood suppression which may be alleviated by light exposure where glucose uptake and metabolism in this area are decreased. Trial Registration This study is a secondary analysis of the previous randomized study which was registered as UMIN000007537. Retrospectively registered (March 20th, 2012).

Cyclothymic temperament possesses a central dimension that includes rapid fluctuations in mood and emotional instability, and it is regarded as a prodromal state of bipolar disorder. The aim of the present study is to explore the neural correlates of cyclothymic temperament. We used the data of 55 healthy participants in our previous study and analyzed the association between cyclothymic temperament scores rated by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A) and the uptake of [18F]-FDG measured by positron emission tomography (PET). A whole brain analysis revealed a cluster of [18F]-FDG uptake significantly and positively associated with cyclothymic temperament scores, located in the right superior parietal lobule (SPL). Even after adjustment for relevant factors, there remained a significant cluster of [18F]-FDG uptake with cyclothymic temperament scores in the right SPL. In ROI analyses, there were similar significant peaks in the right SPL in association with cyclothymic temperament scores. These findings suggest that the right superior parietal lobule may be one of the neural correlates of cyclothymic temperament.

Several epidemiological studies have shown the inverse association of lithium levels in drinking water and suicide rates; however, it is necessary to perform a clinical study dealing with individual patients. We analyzed 199 patients including 31 patients with suicide attempts, 21 patients with self-harm, and 147 control patients. All were transferred to a university emergency department suffering from intoxication or injury, were aged 20 or more years, and were alive at the start of the study. The exclusion criteria consisted of suffering from schizophrenia and a past or present history of lithium therapy. These exclusions were applied because it is difficult to determine whether their suicide attempt was induced by the intent to end their life or by psychotic symptoms such as auditory hallucinations, and if the patient had received lithium therapy, the association between the small amount of lithium taken from drinking water and food and serum lithium levels cannot be detected. There was a significant difference (p = 0.043) between the three groups whereby patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.012) in males but not females. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059–0.883). The limitations of the present study are the nature of observational research which cannot reveal a causal relationship and the relatively small number of subjects. The present findings suggest that higher serum lithium levels may be protective against suicide attempts in lithium therapy-naive individuals.

Lithium therapy is generally accepted as a first-line treatment for bipolar disorder, and it is also identified as one of the best augmenting options for treatment-resistant depression. Furthermore, lithium has been investigated in association with suicide, dementia and aggressiveness. In this review, we examined articles about the effects of very small amounts of lithium in treating suicide, dementia, bipolar disorder and temperament, to assess the present state of trace lithium's effect on mental state. The results indicate that trace lithium may be effective for suicide prevention but randomized, placebo-controlled trials are required to draw a definite conclusion. Indications for using trace lithium in treating such conditions as dementia, bipolar disorder and temperament are supported by very limited evidence and such effects are yet to be determined.

In order to resolve the equivocal relationship between anxious temperament rated by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and harm avoidance rated by the Temperament and Character Inventory (TCI), the present study aimed to investigate whether the anxious temperament scale and the harm avoidance scale are significantly associated with adjustment of relevant factors. Our hypothesis was that anxious temperament might be associated with harm avoidance.From the database of our previous studies, the data of 111 healthy subjects who had both TCI and TEMPS-A scores were extracted for the present study. Two multiple regression analyses were performed: one to predict variance in anxious temperament scores without and with harm avoidance scores, and relevant factors; and another to predict variance in harm avoidance scores without and with anxious temperament scores, and relevant factors.Anxious temperament was significantly and positively associated with depressive temperament, irritable temperament, and Hamilton Rating Scale for Depression whereas harm avoidance was significantly and negatively associated with hyperthymic temperament, novelty seeking, persistence, and self-directedness, although both were significantly and positively associated with each other.These findings support our hypothesis and suggest that anxious temperament may have 'depressive proneness' whereas harm avoidance may have 'passive proneness.'

Background The Japanese archipelago stretches over 4000 km from north to south and has four large islands: Hokkaido, Honshu, Shikoku, and Kyushu. Previously, using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A), we compared the hyperthymic scores of residents in Sapporo, Obihiro, Takaoka, Koshigaya, and Oita cities (which are located at latitudes of 43°N, 42°N, 36°N, 36°N and 33°N with various combinations of ambient temperament and sunshine in Japan, respectively). We found that latitude predicted significant variance in hyperthymic temperament, and that ambient temperature, but not sunshine, significantly affected hyperthymic temperament scores. However, the analysis failed to consider the effects of naturally occurring low-dose lithium on temperament. Methods In addition to the TEMPS-A data previously collected, we measured lithium levels of the five cities. The effect of temperature, sunshine, and lithium levels on hyperthymic temperament was analyzed for the five cities. Results A stepwise multiple regression analysis revealed that lithium levels as well as latitude, but not temperature or sunshine, predicted significant variance in hyperthymic temperament scores. Hyperthymic temperament scores were significantly and positively associated with lithium levels whereas they were significantly and negatively associated with latitude. Limitations The light, temperature, lithium exposure that residents actually received was not measured. The number of regions studied was limited. The findings might not be generalized to residents across Japan or other countries. Conclusions The present findings suggest that lithium in drinking water may positively maintain hyperthymic temperament, and that latitude may negatively maintain it.

Introduction: Lamotrigine is one of several mood stabilizers and its effects for the treatment and prevention of depressive episodes, particularly in bipolar disorder, are generally accepted. Although the findings about a therapeutic window of lamotrigine are yet to be determined, it seems important to obtain information on individual pharmacokinetic peculiarities. This study was conducted to formulate the predictive model of plasma lamotrigine levels. Methods: Using the data of 47 patients whose lamotrigine levels, liver function, and renal function were measured, predictive models of lamotrigine levels were formulated by stepwise multiple regression analyses. The predictive power of the models was compared using another dataset of 25 patients. Results: Two models were created using stepwise multiple regression. The first model was: plasma lamotrigine level (μg/mL)=2.308+0.019×lamotrigine dose (mg/day). The second model was: plasma lamotrigine level (μg/mL)=0.08+0.024×lamotrigine dose (mg/day)+4.088×valproate combination (no=0, yes=1). The predictive power of the second model was better than that of the first model. Discussion: The present study proposes a prompt and relatively accurate equation to predict lamotrigine levels.

Some studies for radiological protection of the environment have been made at the National Institute of Radiological Sciences (NIRS). Transfer of radionuclides and related elements has been investigated for dose estimation of non-human biota. A parameter database and radionuclide transfer models have been also developed for the Japanese environments. Dose (rate)-effect relationships for survival, growth and reproduction have been investigated in conifers, Arabidopsis, fungi, earthworms, springtails, algae, duckweeds, daphnia and medaka. Also genome-wide gene expression analysis has been carried out by high coverage expression profiling (HiCEP). Effects on aquatic microbial communities have been studied in experimental ecosystem models, i.e., microcosms. Some effects were detected at a dose rate of 1 Gy day(-1) and were likely to arise from interspecies interactions. The results obtained at NIRS have been used in development of frameworks for environmental protection by some international bodies, and will contribute to environmental protection in Japan and other Asian countries.

SUMMARY Experimental hydrocephalus was induced by the infusion of a non-inflammatory silicone oil into the cisterna magna of adult rabbits and infant dogs. In an histological and electron-microscopical study, the brain tissue damage in these animals was compared with that in cerebral biopsies from hydrocephalic human infants. The main features of ependymal disruption, with nerve fibre destruction and clear-fluid (probably csf) extracellular oedema of the periventricular white matter, were present to varying degrees in all the severe hydrocephalic brains. Very much less disruption occurs in the unmyelinated infant brain than in the partially or fully myelinated animal brains. It appears that the extent of the tissue damage bears some relationship to the degree of white matter myelination. RESUME Une hydrocephalie experimentale a ete provoqutee par l'injection d'huile de silicone non inflammatoire dans la grande citerne de lapins adultes et de chiots. Une etude histo-logique et electromicroscopique a permis de comparer les lesions cerebrales chez ces animaux avec les biopsies cerebrales provenant de jeunes hydrocephales humains. Les principales caracteristiques de l'epanchement ependymaire, avec destruction des fibres nerveuses et oedeme de liquide clair (probablement LCR) de la substance blanche periventriculaire, ont ete observees a des degres varies dans tous les cas d'hydrocephalies severes. Un epanchement beaucoup moindre se produit dans le cas du cerveau non myelinise du jeune enfant que dans les cerveaux animaux, partiellement ou totalement myilinises. II apparait donc une relation entre l'etendue des lesions tissulaires cerebrales et le degre de myelinisation de la substance blanche. ZUSAMMENFASSUNG Ein experimenteller Hydrocephalus wurde durch die Infusion von nicht entzundendem Siliconol in die Cysterna magna von erwachsenen Kaninchen und jungen Hunden hervorge-rufen. In einer histologischen und elektronenmikroskopischen Untersuchung wurde die Schadigung des Gehirngewebes verglichen mit der in cerebralen Biopsien von hydro-cephalischen Kindern beobachteten Schadigung. Die hauptsachlichen Merkmale der ependymalen Zerreiβung mit Zerstorung von Nervenfasern und einem klarussigen (wahrscheinlich CSF) extrazellularen Oedem der periventrikularen weiβen Substanz fanden sich in unterschiedlichem Ausmaβ in allen schwer hydrocephalischen Gehirnen. In den nicht myelinisierten kindlichen Gehirnen kommt sehr viel weniger Zerreiβung vor als in den teilweise oder ganz myelinisierten Gehirnen der Tiere. Es scheint so, daβ das Ausmaβ der Gewebeschadigung in einem gewissen Verhaltnis zur Myelinisierung der weiβen Substanz steht. RESUMEN Se produjo una hidrocefalia experimental por la infusion de un aceite siliconico ininflam-able en la cisterna magna de conejos adultos y de perrillos lactantes. En un estudio histologico y electromicroscopico, se comparo el dano a los tejidos cerebrales en estos animales con el dano revelado por biopsias cerebrales en lactantes humanos con hidrocefalia. Las caracteristicas mas importantes de disrupcion ependimaria, con destruccion de las fibras nerviosas y edema extracelular de liquido claro (probablemente liquido cefalorra-quideo) de la substancia blanca periventricular se hallaban a un grado variable en todos los cerebros hidrocefalos mas graves. Mucho menos disrupcion ocurre en el cerebro no mieli-nico del lactante que en los cerebros animales parcial o completamente mielinicos. Parece que la extension del dano a los tejidos tiene relacion con el grado de mielinizacion de la substancia blanca.

Purpose: Second cancers are among the most serious sequelae for cancer survivors who receive radiotherapy. This article aims to review current knowledge regarding how the risk of radiotherapy-associated second cancer can be minimized by biological measures and to discuss relevant research needs. Results: The risk of second cancer can be reduced not only by physical measures to decrease the radiation dose to normal tissues but also by biological means that interfere with the critical determinants of radiation-induced carcinogenesis. Requirements for such biological means include the targeting of tumor types relevant to radiotherapy-associated risk, concrete safety and efficacy evidence and feasibility and minimal invasiveness. Mechanistic insights into the process of radiation carcinogenesis provide rational approaches to minimize the risk. Five mechanism-based strategies are proposed herein based on the current state of knowledge. Epidemiological studies on the joint effects of radiation and lifestyle or other factors can provide evidence for factors that modify radiation-associated risks if deliberately controlled. Conclusions: Mechanistic and epidemiological evidence indicates that it is possible to develop interventional measures to minimize the second cancer risk associated with radiotherapy. Research is needed regarding the critical determinants of radiation-induced carcinogenesis available for intervention and joint effects of radiation and controllable factors.

Background Previously, we showed the inverse association between lithium in drinking water and male suicide in Kyushu Island. The narrow variation in meteorological factors of Kyushu Island and a considerable amount of evidence regarding the role of the factors on suicide provoked the necessities of adjusting the association by the wide variation in sunshine, temperature, rain fall, and snow fall. Methods To keep the wide variation in meteorological factors, we combined the data of Kyushu (the southernmost city is Itoman, 26°) and Hokkaido (the northernmost city is Wakkanai, 45°). Multiple regression analyses were used to predict suicide SMRs (total, male and female) by lithium levels in drinking water and meteorological factors. Results After adjustment of meteorological factors, lithium levels were significantly and inversely associated with male suicide SMRs, but not with total or female suicide SMRs, across the 153 cities of Hokkaido and Kyushu Islands. Moreover, annual total sunshine and annual mean temperature were significantly and inversely associated with male suicide SMRs whereas annual total rainfall was significantly and directly associated with male suicide SMRs. Limitations The limitations of the present study include the lack of data relevant to lithium levels in food and the proportion of the population who drank tap water and their consumption habits. Conclusions The present findings suggest that trace lithium is inversely associated with male but not female suicide after adjustment of meteorological factors.

Background This study aims to comprehensively investigate the causal relationship between suicide and its risk factors in a longitudinal design. Methods A model was derived in which suicide rate in 2008 was longitudinally and comprehensively predicted by potential risk factors recorded one year before (2007) which included personal and interpersonal factors, medical factors, economic factors, climate factors, alcoholic factors, and ω-3 fatty-acid factors. Results In males, elderly population rate and complete unemployment rate predicted SMR of suicide significantly and positively whereas marriage rate and annual postal savings per person predicted SMR of suicide significantly and negatively. Also in females, complete unemployment rate predicted SMR of suicide significantly and positively whereas annual mean temperature predicted SMR of suicide significantly and negatively. Limitations The limitations of this study are that predictions are based on the data of only the recent two years, that these epidemiological data cannot be always extrapolated to individuals, and that other factors should be taken into consideration to female suicide. Conclusions The present findings suggest that male suicide may be accounted for by older age, more complete employment rate, less marriage rate and less annual postal savings whereas female suicide may be accounted for by more complete employment rate and lower annual mean temperature.

A 73-year-old woman outpatient with mild cognitive impairment, parasomnia and depressive state with musical hallucinations failed to respond to 400 mg/day of valproate. Once she was admitted to a university hospital, her musical hallucinations partially responded to 1 mg/day of clonazepam and sufficiently improved on 100 mg/day of carbamazepine. Two months after discharge, however, her musical hallucinations recurred probably as a consequence of psychological stress. The increase of carbamazepine from 100 to 200 mg/day completely remitted her musical hallucinations. This case suggests that musical hallucinations respond in a dose-dependent manner to increasing carbamazepine, and that gradual titration from small doses of carbamazepine is required because optimal doses appear to be smaller than those required for epilepsy and bipolar disorder. Further studies are warranted to determine the therapeutic levels of carbamazepine for musical hallucinations.

Objective Recently, several epidemiologic studies reported that lithium in drinking water may be associated with lower rates of suicide mortality at the population level, but other studies failed to confirm the association. The objective of the present study is to determine whether lithium in drinking water is associated with lower suicide rate after adjustment of potential confounding factors. Method From 2010 to 2013, 274 mean lithium levels of 434 lithium samples in drinking water were examined in relation to suicide standardized mortality ratios (SMRs) in 274 municipalities of Kyushu Island in Japan. Weighted least squares regression analysis adjusted for the size of each population was used to investigate the association of lithium levels with suicide SMRs. The associations of lithium levels in drinking water with suicide SMRs (total, male, and female) were investigated adjusting for proportion of elderly people, proportion of 1-person households, proportion of people with college education or more, and proportion of people engaging in primary industry (adjusted model 1), and further adjustment was performed with overall unemployment rate, annual marriage rate, annual mean temperature, and annual postal savings per person (adjusted model 2). Results Lithium levels in drinking water were significantly (β = -.169, P = .019) and inversely associated with male suicide SMRs but not total or female SMRs in the adjusted model 2. Conclusions The present findings suggest that lithium in drinking water may be associated with the low risk of male suicide in the general population. Further studies are required to confirm these findings and investigate gender differences.

A 69-year-old man with alcohol dependence and mild cognitive impairment (MCI) suffered from repeated tonic–clonic seizures. The seizures typically occurred several hours after his last alcohol intake at home (early withdrawal seizure) and 22 days after his last intake of alcohol (14 days after the last dose of diazepam substituting for alcohol: late withdrawal seizure) on the ward. Psychiatrists in charge of this patient found it difficult to attribute his seizures to alcohol withdrawal syndrome (AWS) because of the atypical onset. The patient responded to diazepam resumption and valproate combination. This case highlights the need to always consider AWS as a possible cause of seizures and to gradually decrease diazepam as a substitute for alcohol. Moreover, in this patient, MCI may have induced vulnerability in the brain for AWS and the patients’ older age might have decreased liver function leading to delayed onset of the seizures after diazepam withdrawal.

Lithium has been used as a mood-stabilizing drug in people with mood disorders. Previous studies have shown that natural levels of lithium in drinking water may protect against suicide. This study evaluated the association between lithium levels in tap water and the suicide standardized mortality ratio (SMR) in 40 municipalities of Aomori prefecture, which has the highest levels of suicide mortality rate in Japan. Lithium levels in the tap water supplies of each municipality were measured using inductively coupled plasma-mass spectrometry. After adjusting for confounders, a statistical trend toward significance was found for the relationship between lithium levels and the average SMR among females. These findings indicate that natural levels of lithium in drinking water might have a protective effect on the risk of suicide among females. Future research is warranted to confirm this association.

A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations. Furthermore, even after risperidone was decreased and discontinued, her auditory hallucinations did not recur. These findings suggest that trazodone may induce auditory hallucinations in some susceptible patients.

SummaryAlthough lithium is known to prevent suicide in people with mood disorders, it is uncertain whether lithium in drinking water could also help lower the risk in the general population. To investigate this, we examined lithium levels in tap water in the 18 municipalities of Oita prefecture in Japan in relation to the suicide standardised mortality ratio (SMR) in each municipality. We found that lithium levels were significantly and negatively associated with SMR averages for 2002–2006. These findings suggest that even very low levels of lithium in drinking water may play a role in reducing suicide risk within the general population.

A seventy-one year-old Japanese man suffering from carcinoma of the com mon bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior commu nicating artery.

Since it is very rare that cardiac tamponade due to myocardial rupture caused by infective endocarditis, occurs we are reporting this case. A 62 year old man, who had underlying diseases of pneumoconiosis and hypertensive heart disease, visited Chikuho Rosai Hospital complaining of chest oppression and general fatigue on Feb. 7, 1987. He was diagnosed as having ischemic heart disease by electrocardiogram. Two days later, he suddenly had chills and a fever, and the laboratory data showed leukocytosis and a positive C-reactive protein (CRP). The echo cardiogram showed mitral regurgitation (MR) and aortic regurgitation (AR), but neither vegetation nor pericardial effusion was observed. On Feb. 16, he was admitted with shock, and he died the next day. The blood cultures grew gram-positive cocci, respectively. From the clinical symptoms, chest roentgenogram and electrocardiogram, we suspected a cardiac tamponade. On autopsy findings, though coronary arteries were intact, the aortic valves had severe valvular adhesions, calcifications and hypertrophies. The rupture hole was observed in the left ventricles, which was just under the aortic valve through the pericardiac space. It seemed that he died of a cardiac tamponade due to the outflow of blood from this hole. On histopathologic findings of the cardiac wall, gram-positive cocci and many of neutrophils were observed.

Eight cases of pellagra, diagnosed on the grounds of neuropathological findings and retrospective study of clinical data, were found among 106 necropsy cases of tuberculosis. Although these eight patients had shown various mental, neurological and gastrointestinal symptoms, as well as skin lesions, the diagnosis of pellagra had not been made clinically. In all the patients, pellagra symptoms appeared during isoniazid therapy. Death occurred 4 to 16 weeks later. Isoniazid inhibits the conversion of tryptophan to niacin and may induce pellagra, particularly in poorly nourished patients. Pellagra should be suspected whenever tuberculous patients under treatment with isoniazid develop mental, neurological or gastrointestinal symptoms, even in the absence of typical pellagra dermatitis.

Two siblings with intrahepatic cholestatic cirrhosis and their brother, who had a potentially related disease at the time of accidental death, are presented. The onset of disease occurred during adolescence in all 3 cases. The initial sign was mild jaundice or portal hypertension. There was no abnormality in the countenance, cardiovascular system, or vertebral column. Except for the brother who died from an accident, jaundice gradually increased. Death followed due to cirrhosis. Liver biopsy specimens of these 2 patients showed diminution of interlobular bile ducts with no significant cholangitis. At autopsy, the livers of the 2 patients showed biliary cirrhosis without extrahepatic biliary obstruction. In both cases there was an accessory lobe on the right hepatic lobe. Histologically, septal bile ducts showed pronounced papillary proliferations of the epithelium; there was also a decrease in the number of small interlobular bile ducts. Excess copper accumulation in the liver was ascertained. It is suggested that the disease in the 2 autopsied cases is intrahepatic cholestatic cirrhosis due to hypoplasia of the intrahepatic biliary trees.

We studied 30 necropsy cases of vascular dementia with a lacunar state. Manifestations included dementia, lack of volition, emotional lability, small-stepped gait, dysarthria, urinary incontinence, grasp reflex, pyramidal signs, paraplegia in flexion, and akinetic mutism. Pathologically, there was diffuse incomplete softening of white matter in all cases. Both lacunes and diffuse softening were found predominantly in the frontal lobes. The prominent clinical features were therefore frontal lobe symptoms, with good correlation between the symptoms and the distribution of pathologic lesions.

Twelve cases of pancreatoblastoma, 7 males and 5 females, were 5 years of age in average and showed an organoid structure consisting of acinar differentiation with squamoid corpuscles. Seven cases died, but 5 lived after surgery. On the contrary, 17 cases of papillary cystic tumor, ductuloacinar adenoma of the pancreas, one male and 16 females, were 21 years of age in average and disclosed a monomorphous pseudopapillary pattern of ductuloacinar type of tumor cells with some degenerative and granulomatous changes. All of the cases had suffered no recurrence after resection. Immunohistochemically, strong positivity for alpha 1-antitrypsin may be associated with the autodigestive process and limited growth of this tumor. Electron microscopically, both tumors showed centroacinar and acinar types of tumor cells. Both tumor cells frequently contained well-developed RER, zymogen-like granules, and annulate lamellae. The ductular or acinar lumina were clear in pancreatoblastoma, but not in ductuloacinar adenoma due to degeneration. Though both tumors disclosed contiguous histogenesis, pancreatoblastoma should be differentiated from ductuloacinar adenoma, based upon the young age, almost equal sex ratio, unfavorable prognosis, high serum AFP level in three measured cases, an organoid structure containing frequent mitotic figures, and the invasive growing margin.

An unusual nodular transformation of the liver was found in a 53-year-old man with meningoencephalitis who died of brain stem herniation. Postmortem examination revealed marked neuronal ischemic changes and bronchopneumonia as well as meningoencephalitis. The liver showed no significant lesions macroscopically. Histologically, there were many small nodules, less than 1 mm in diameter and composed of clear hepatocytes, throughout the liver. The liver cells in these nodules showed mild hyperplastic changes. Many fine granules, stained by orcein and Victoria blue, were found exclusively in the hepatocytes of these nodules. We describe the peculiar histopathology of this case with reference to some related lesions. ACTA PATHOL JPN 38: 83–88, 1988.

A 45-year-old woman with a meningioma growing in the parapharyngeal space is reported. Her initial symptom was a stuffy feeling in the right ear and swelling of the right parapharynx. The parapharyngeal mass was biopsied, and a frozen section diagnosis suggested a paraganglioma. On electron microscopy, however, the tumor cells failed to show secretory granules, and represented a prominent interdigitation of the cytoplasm with occasional desmosomal attachments. Based on these features the tumor was diagnosed as a meningioma. Thereafter a mass lesion in the temporal lobe of the brain was detected by computerized tomography of the brain. The extracranial extension of the meningioma may occur in some occasions, but such cases in which the infiltrative portion in the parapharyngeal space was initially discovered have been rarely reported.

A 42 year old man with variant angina occasionally associated with syncopal attacks died of acute myocardial infarction 17 months after the onset of angina. Prior to the onset of variant angina, he had Raynaud's phenomenon of the tongue for 2 years. Both Valsalva maneuver and hyperventilation could repeatedly provoke chest pain and ST segment elevation in leads II, III and aVF. The infusion of prostaglandin E1 at a rate of 0.05 microgram/kg/min, was able to prevent the attack of variant angina induced by these maneuvers. Although coronary angiography performed 15 months prior to death revealed no organic lesions except for complete spastic occlusion at segment 1 following intravenous ergonovine, autopsy revealed marked intimal proliferation and accumulation of abundant glycosaminoglycans in three coronary vessels, as well as in small and muscular arteries of other organs. This suggests that a rapid systemic progression of narrowing due to proliferation of the intima might occur in some cases of variant angina.

In three adult cabinet finishers weakness and sensory loss developed as a result of prolonged and intense exposure to an industrial solvent. After leaving this employment, they improved. Analysis of the immediate environment and solvent revealed that each worker had an oral, respiratory and dermal contact with toxic levels of n-hexane. Adequate ventilation and direct contact precautions are essential in the future use of this common industrial solvent.