Gait disturbance due to foot drop is refractory to treatment in nonsystemic vasculitic neuropathy.

BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is a vasculitis syndrome clinically restricted to the peripheral nervous system. Although treatment may improve prognosis, daily activities of such patients after treatment have not been well studied. METHODS: We evaluated clinical features, laboratory data, nerve conduction, and sural nerve biopsy findings for 16 unbiased consecutive patients with NSVN. RESULTS: Initial symptoms included neuropathic pain (31%) and lower limb sensory disturbance (19%). The mean duration between disease onset and initial treatment was 4.1 ± 4.8 months. Mean modified Rankin scale scores were 3.13 at hospital admission and 2.69 at final follow-up. The poor outcome group had significantly decreased compound muscle action potentials of peroneal nerves and significantly more patients presenting with foot drop compared with the good outcome group. No other significant differences were found. CONCLUSION: Pretreatment foot drop signaled poor outcome in daily activities of patients with NSVN, and earlier treatment may be critical for these patients.

Pharmacist medication instructions are associated with continued medication self-management in older adults: a retrospective observational study.

BACKGROUND: Various factors are related to self-management of medication. However, few reports comprehensively examine the factors related to patients, medication levels, and other factors related to the recuperative environment, such as family support. The aim of this study was to investigate factors affecting the continuation of medication self-management among hospitalized older adults receiving convalescent rehabilitation. METHODS: We conducted a retrospective observational study with 274 consecutive patients newly admitted to the convalescent rehabilitation wards at a single hospital in Japan between January 2017 and May 2018. Participants who were assessed for their ability to take their medication using the Japanese Regimen Adherence Capacity Tests, were deemed to be self-manageable, and were able to successfully continue to self-manage their medication from admission to discharge were categorized as the "continuation group," and those who were not able to continue were categorized as the "non-continuation group." We analyzed the groups' demographic data, laboratory data, and Functional Independence Measure. The primary outcome was the continuation of medication self-management from admission to discharge. RESULTS: After enrollment, 134 patients (median age 82 years; 62.7% women) were included in the final analysis. Some 60.4% of eligible patients were able to maintain medication self-management during their hospitalization. The multiple logistic regression analysis for the continuation of medication self-management during hospitalization after adjusting for confounding factors revealed that pharmacist medication instructions were independently and positively correlated with successful continuation of medication self-management (odds ratio: 1.378; 95% confidence interval 1.085-1.831; p = 0.0076). CONCLUSION: Successful continuation of medication self-management is associated with pharmacist medication instructions among hospitalized older adults undergoing rehabilitation. TRAIL REGISTRATION: The Ethics Committee's registration number is "TGE01216-066".

Factors affecting anxiety among administrative officers working within the urgent protective action planning zone of a nuclear power station.

The aim of this study was to clarify the factors affecting anxiety among administrative officers working within the urgent protective action planning zone of a nuclear power station to establish an effective education program on radiation and its health effects to help reduce anxiety in residents. We included 1,181 officers who worked at local authorities within the urgent protective action planning zone of Sendai Nuclear Power Station in Kagoshima Prefecture, Japan. Logistic regression analysis revealed that female sex (odds ratio = 2.33), working more than 21 years as an administrative officer (odds ratio = 1.49), lack of participation in training on nuclear disasters (odds ratio = 1.42), and not knowing the three principles of radiation protection (odds ratio = 1.36) were independently associated with anxiety among administrative officers working within the urgent protective action planning zone. It is important to establish an effective education program on radiation and its health effects for administrative officers working within the urgent protective action planning zone to reduce anxiety in residents.

Risk perceptions regarding radiation exposure among Japanese schoolteachers living around the Sendai Nuclear Power Plant after the Fukushima accident.

In response to the Fukushima Daiichi nuclear power plant disaster, the Nuclear Regulation Authority of Japan issued the new "Nuclear Emergency Response Guideline." However, there is a perception that scientific information about the health impact of radiation exposure has not been adequately shared among the local government staffs, including schoolteachers. We contacted schoolteachers at all 120 schools within the Urgent Protective Action Planning Zone of the Sendai Nuclear Power Plant, Kagoshima prefecture, in 2017. We invited them to take part in a written survey to clarify their concerns and risk perceptions regarding the effects of radiation exposure on health. Five hundred and fifty schoolteachers' replies were included in the analysis. The results revealed that 355 schoolteachers had concerns about the health effects of radiation exposure due to working within the Urgent Protective Action Planning Zone. A logistic regression analysis revealed that sex (OR = 2.26, 95% CI: 1.49-3.45, p < 0.001), age (OR = 3.39, 95% CI: 2.10-5.47, p < 0.001), reluctance to undergo a radiological examination at a hospital (OR = 1.91, 95% CI: 1.23-2.88, p = 0.004), place of work (OR = 2.18, 95% CI: 1.46-3.27, p < 0.001), and anxiety about having to address questions about radiation from students (OR = 4.66, 95% CI: 2.83-7.67, p < 0.001) were independently associated with schoolteachers' concerns about the health effects of radiation exposure due to working in the area around the nuclear power plant. Therefore, it is important to respond to these concerns in order to establish a meaningful education program for school children on radiation and its health effects.

[Approach to easing occupational stress for high-stress workers: applying the brief job stress questionnaire to workplace mental health promotion].

We investigated job stress among 442 employees from 19 divisions in a Japanese company using the Brief Job Stress Questionnaire. Job stress of the employees was estimated by the score for total health risk. Among the 19 divisions, two divisions showed over 120 points of mean total health risk score. Intervention with a stress-reduction program was carried out in these 2 divisions. First, to assess the job stress, health care staff interviewed all workers in the 2 divisions. Second, the results of the interviews were reported to the divisions' managers. Third, the managers applied the best remedy for job stress in their workplaces. In addition, occupational health staff conducted mental health education as well as individual interviews for the workers from the 2 divisions. At reevaluation one year later, both divisions showed a decreased general health risk (under 120 points). No sick leaves for depression occurred within the 2 divisions during the intervention. The results of the present study suggest that the intervention was effective in easing occupational stress for high-stress workers. The stress reduction program also seemed to have helped managers to change their recognition of occupational mental health and enabled close cooperation with occupational health staff, which may improve mental health in the workplace.

The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia.

The underlying pathophysiology of primary polydipsia in schizophrenia (SCZ) is poorly understood. Our previous study, however, suggested that this condition may have a genetic component [Shinkai et al 2003 Am J Med Genet 119B 7-12]. Orexins, also called hypocretins, play an important role in feeding and drinking behavior. Administration of orexin in rats has been shown to induce increased water intake with a longer-lasting effect than angiotensin II, which is also known as a potent dipsogen. Meerabux et al. [2005 Biol Psychiatry 58 401-407] reported an association between the 408Val allele of the orexin 1 receptor (HCRTR1) gene and polydipsia-hyponatremia in a sample of Japanese patients with SCZ. In the present study, we attempted to replicate the findings of Meerabux et al. in an independent Japanese case-control sample. Our sample included 312 patients with SCZ (DSM-IV) (65 with polydipsia and 247 without polydipsia). We also observed an association between the HCRTR1 Ile408Val polymorphism and polydipsia (genotype distribution: chi2 = 9.85, df = 2, P = 0.007). Meerabux et al. (2005) previously demonstrated an association between the 408Val allele of the HCRTR1 gene and polydipsia. In contrast with Meerabux et al. study, we found that the 408Ile allele was associated with polydipsia in our sample (chi2 = 8.00, df = 1, P = 0.0047; OR = 0.53; 95%CI = 0.34-0.83). How either allele contributes to the development of polydipsia in SCZ is unclear at this stage. It is possible that Ile408Val polymorphism is a non-functional marker that lies in linkage disequilibrium with an as-yet undetected functional variant. In any case, our results support the hypothesis that the HCRTR1 Ile408Val polymorphism may confer susceptibility to polydipsia in SCZ. Further studies examining the association between the orexin system and polydipsia in SCZ are warranted.

Association analyses of the DAOA/G30 and D-amino-acid oxidase genes in schizophrenia: further evidence for a role in schizophrenia.

A number of linkage studies have previously implicated the region of chromosome 13q34 in schizophrenia. Chumakov and colleagues (2002) identified a gene complex called G72 (now termed D-amino acid oxidase activator: DAOA)/G30 in this region and performed association analyses of the DAOA/G30 as well as the D-amino-acid oxidase (DAAO) gene with schizophrenia. DAAO oxidizes D-serine, a potent activator of the N-methyl-D-aspartate (NMDA) type glutamate receptor in the human brain whereas the DAOA protein is considered an activator of DAAO. The interaction of these two genes has thus been implicated in the NMDA receptor regulation pathway in schizophrenia. To date, several studies have shown a relatively consistent positive association between schizophrenia and DAOA/G30, but not with DAAO. The aim of our study was to further evaluate the contributions of these genes to the susceptibility to schizophrenia using two different sample sets. Our sample consisted of 168 matched case-control pairs as well as a family-based sample (n=113) for transmission disequilibrium test. Significant associations between the DAOA/G30 M-7 and M-18 polymorphisms and schizophrenia were observed in our case-control sample whereas no associations were observed for DAAO markers. We also observed significant or suggestive transmission disequilibrium for DAOA/G30 M-7, M-23, and M-24 to probands with schizophrenia in our family-based sample. Subsequent analysis of haplotypes made up of four DAOA/G30 markers, one marker selected from each of two linkage disequilibrium blocks that were observed in our sample as well as both ends (M-7 and M-25), were also associated with schizophrenia. Our data provide further evidence that the DAOA/G30 locus may play a role in the pathophysiology of schizophrenia. Although no direct link to genetic polymorphism in these genes and NMDA receptor function has been revealed, the present findings support previous reports implicating DAOA/G30 as susceptibility genes for schizophrenia. Further research is warranted to determine the functional variation underlying these findings and to relate this to the pathophysiology of schizophrenia.

No association between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and schizophrenia in Asian populations: Evidence from a case-control study and meta-analysis.

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that plays an important role in the development and maintenance of adult neurons and is important regulator of synaptic plasticity in human brain. It has been reported that there are alterations in BDNF levels in the brains of patients with schizophrenia. It has also been reported that transneuronal transfer of BDNF is dependent on neuronal activity, suggesting that BDNF plays an important role in neurotransmission. A single nucleotide polymorphism (SNP) in the BDNF gene that causes a valine to methionine substitution at codon 66 (Val66Met) has been demonstrated to affect human memory and hippocampal function. A possible positive association between the BDNF Val66Met polymorphism and schizophrenia has also been shown in Scottish and Spanish populations. Furthermore, the BDNF Val66Met polymorphism has been implicated in the age of onset of schizophrenia. In the present study, we attempted to replicate these findings in a Japanese case-control sample (211 patients with schizophrenia and 205 controls). We did not find an association between the BDNF Val66Met polymorphism and schizophrenia. An association between the Val66Met polymorphism and age of onset was not observed either. Furthermore, a meta-analysis including the present and previous Asian studies comparing 2059 patients with schizophrenia and 2765 controls also revealed no significant association between the BDNF Val66Met polymorphism and schizophrenia. Our results do not support a significant role for the BDNF Val66Met polymorphism in the development of schizophrenia in Asian populations.

The usefulness of sleep apnea syndrome screening using a portable pulse oximeter in the workplace.

Sleep Apnea Syndrome (SAS) is a condition characterized by sleep-disordered breathing resulting in health impairment and sleep problems. From the viewpoints of the prevention of health impairment, accidents at work and traffic accidents, active implementation of screening for SAS in workplaces is necessary. Using a portable pulse oximeter, we conducted SAS screening for workers, who applied for the screening or who were instructed to participate by occupational physicians based on their symptoms at the time of medical check-up, in order to evaluate the effectiveness of a portable pulse oximeter as a screening device in the workplace. During the 2-yr study period from April 2002 to March 2004, 380 workers underwent overnight pulse oximetry at home; data on 367 of them were considered valid and included in the analysis. We deemed screening-positive as oxygen desaturation of the peripheral artery of 4% or greater if 10 or more events were observed per hour (ODI4> or =10); or oxygen desaturation of the peripheral artery of 3% or greater if 15 or more events were observed per hour (ODI3> or =15). Eighty-three subjects were identified as screening-positive and 54 of them underwent polysomnography. All of them were diagnosed as having SAS with an apnea hypopnea index (AHI)> or =5, of which continuous positive airway pressure (CPAP) therapy was indicated in 48 cases (88.9%) with AHI> or =20. On the other hand, 11 of the 284 screening-negative subjects with mild sleep disordered breathing underwent polysomnography and all of them were diagnosed as having SAS with AHI> or =5. However, CPAP therapy was indicated only for 5 with AHI> or =20 of the 11. Therefore, in total, 65 subjects were diagnosed with SAS in this study and for 53 of them CPAP therapy was indicated. The simplicity of the SAS screening by pulse oximetry makes it easy to use for screening of workers, and this method was highly effective in detecting individuals with severe SAS for whom CPAP therapy was indicated.

The effects of the Kumamoto earthquake on the clinical symptoms of patients with Parkinson's disease.

Our hospital is the designated treatment base for intractable neurological diseases in the Kumamoto Prefecture. It is located in the center of the prefecture where the major 7.3-magnitude Kumamoto earthquake was recorded in 2016. In order to examine whether this earthquake affected the clinical symptoms of patients with Parkinson's disease in this hospital, we investigated outpatients examined up to 4 weeks after the earthquake. The subjects were 26 consecutive patients without any changes in anti-Parkinson's disease treatment or their attending physician during the examination period. All of the items in Part III of the Unified Parkinson's Disease Rating Scale (UPDRS), which is a clinician-scored scale for monitoring and evaluating motor function, were confirmed with the subjects before and after the earthquakes. After the earthquakes, worsened symptoms were found in 7 patients and 7 patients felt better. On the UPDRS, worsened symptoms were most commonly found among the items examining "muscle rigidity" and "slowness of movement and decreased movement" among the 7 patients with exacerbated symptoms. After the earthquake, clinical symptoms worsened significantly in women (P = 0.0188), patients with mild symptoms (P = 0.0111), and those who suffered a high degree of personal loss, such as those whose homes were damaged, who were forced to take refuge, or who had to sleep in their car (P = 0.0184). The mental and emotional burden due to the earthquake might be particularly high in the group of patients with worsened symptoms, suggestive of a relationship between stress and the exacerbation of parkinsonian symptoms.

No association between a functional NAD(P)H: quinone oxidoreductase gene polymorphism (Pro187Ser) and tardive dyskinesia.

Several lines of evidence have indicated that free radicals may play a role in the pathophysiology of tardive dyskinesia (TD) (reviewed in Andreassen and Jorgensen, 2000). NAD(P)H: quinone oxidoreductase (NQO1) is an important enzyme in the human body that counteracts the oxidative stress-induced neuronal injury caused by the toxic free radicals such as dopamine-semiquinones. Taking the possible genetic predisposition to TD into account (Yassa and Ananth, 1981), the NQO1 gene is a good candidate gene that may confer increased susceptibility to TD. Based on this hypothesis, Pae et al. (2004) reported a significant association between the Pro187Ser polymorphism in the NQO1 gene and TD. In the present study, we attempted to replicate the findings of Pae et al. (2004) with the same polymorphism in 222 Japanese patients with schizophrenia. No significant difference was detected between patients with and without TD in the allelic distribution (chi2 = 0.070, d.f. = 1, p = 0.795) and in the genotypic distribution (chi2 = 0.910, d.f. = 2, p = 0.657). In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups (p = 0.49). Our results suggest that the NQO1 gene polymorphism does not confer an increased risk of TD.

Association study between functional polymorphisms in the cytochrome P450 1A2 and 2D6 genes and polydipsia in schizophrenia.

The underlying pathophysiology of polydipsia in schizophrenia is poorly understood. Several studies, however, have suggested that there might be a genetic predisposition to polydipsia. In the present study, using a case-control sample that is independent from the previous family sample, we examined a possible association between polydipsia and functional polymorphisms in the genes of cytochrome P450 (CYP) 1A2 and 2D6, primarily important enzymes to the pharmacokinetics of antipsychotic drugs. Japanese patients with schizophrenia (63 polydipsics and 78 nonpolydipsics) were genotyped for two functional polymorphisms, the 734C/A polymorphism in the CYP1A2 gene and the 2D6*10 allele of the CYP2D6 gene. Neither of the polymorphisms was found to be associated with polydipsia nor was any evidence found that the two polymorphisms have an additive effect on the liability to polydipsia. Our results suggest that the CYP1A2 and CYP2D6 polymorphisms are not likely to play a major role in the development of polydipsia in schizophrenia, although further studies testing other alleles of CYP1A2 and CYP2D6 using different ethnic populations are warranted.

Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia.

A possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A., Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61, 525-541.]). Long-term administration of neuroleptics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a possible functional polymorphism of the human glutathione peroxidase (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment-refractory patients with schizophrenia. A proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No significant difference in total Abnormal Involuntary Movements Scale (AIMS) scores was observed among patients in the three genotype groups. Moreover, no significant differences in genotype or allele frequencies were observed between subjects with and without TD. Our results suggest that the GPX1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia.

A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (chi(2)=1.47, d.f.=2, p=0.48). Moreover, no significant differences in genotype (chi(2)=0.05, d.f.=2, p=0.98) or allele frequencies (chi(2)=0.00, d.f.=1, p=1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Genetic association analysis of neuronal nitric oxide synthase gene polymorphism with tardive dyskinesia.

Possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has been proposed. Long-term administration of neuroleptics alters dopaminergic turnover, yielding the increase of the formation of reactive oxygen species (ROS), which may lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a polymorphism of the neuronal nitric oxide synthase (NOS1) gene whose reaction product, nitric oxide (NO), is involved in oxidative stress was studied in 171 Japanese patients with schizophrenia, including 41 patients meeting TD criteria. The C/T polymorphism in exon 29 of the NOS1 gene was genotyped using polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion. No significant difference in genotype frequencies was detected between subjects with and without TD (chi2 = 1.54, df = 2, p = 0.46). In addition, there was no difference in allele frequencies (chi2 = 0.42, df = 1, p = 0.51). These results suggest that the NOS1 gene polymorphism may not confer increased susceptibility to TD, although more investigations on other populations are warranted.

Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia.

OBJECTIVE: Recent studies have revealed positive associations between tardive dyskinesia (TD) and genetic polymorphisms of several cytochrome P450 (CYP) subfamilies that are involved in pharmacokinetic process of antipsychotic drugs. In the present study, we analyzed the relationship between TD and two polymorphisms of the CYP1A2 gene, 734C/A and -2964G/A, in a sample of Japanese patients with schizophrenia. METHODS: We studied 199 Japanese patients with schizophrenia. We used the Abnormal Involuntary Movement Scale to evaluate TD. Two polymorphisms of the CYP1A2 gene, 734C/A and -2964 G/A were genotyped by means of polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Neither the 734C/A nor the -2964G/A polymorphism was associated with TD [734C/A genotype: chi2=0.02, degrees of freedom (df)=2, P=1.00; allele: chi2=0.02, df=1, P=0.89; -2964G/A genotype: chi2=0.21, df=2, P=0.90; allele: chi2=0.15, df=1, P=0.70]. In addition, CYP1A2 haplotype was associated with TD (chi2=0.24, df=3, P=0.97). Furthermore, in both the subgroup of smokers and the subgroup of patients receiving high-dosage antipsychotics (chlorpromazine equivalent >1000 mg), neither the 734C/A nor the -2964G/A polymorphism was associated with TD. CONCLUSIONS: We did not find significant associations between the 734C/A and -2964G/A polymorphisms of CYP1A2 gene and TD in Japanese patients with schizophrenia. Our results suggest that these CYP1A2 gene polymorphisms may not contribute to TD susceptibility.

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia.

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.