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The environmental disturbances in a critical neurodevelopmental period exert organizational effects on brain intrinsic plasticity including excitatory and inhibitory (E/I) neurotransmission those can cause the onset of psychiatric illness. We previously reported that treatment of neural precursor cells with N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced reduction of GABAergic interneuron differentiation, and these changes recovered by atypical antipsychotic blonanserin treatment in vitro. However, it remains unclear how this treatment affects neural circuit changes in hippocampus and amygdala, which might contribute to the prevention of onset process of schizophrenia. To elucidate the pathogenic/preventive mechanisms underlying prenatal environmental adversity-induced schizophrenia in more detail, we administered poly (I:C) followed by antipsychotics and examined alterations in social/cognitive behaviors, GABA/glutamate-related gene expressions with cell density and E/I ratio, and brain-derived neurotrophic factor (Bdnf) transcript levels, particularly in limbic areas. Treatment with antipsychotic blonanserin ameliorated impaired social/cognitive behaviors and increased parvalbumin (PV)-positive (+) cell density and its mRNA levels as well as Bdnf with long 3'UTR mRNA levels, particularly in the dorsal hippocampus, in rats exposed to maternal immune activation (MIA). Low dose of blonanserin and haloperidol altered GABA and glutamate-related mRNA levels, the E/I ratio, and Bdnf long 3'UTR mRNA levels in the ventral hippocampus and amygdala, but did not attenuate behavioral impairments. These results strongly implicate changes in PV expression, PV(+) GABAergic interneuron density, and Bdnf long 3'UTR expression levels, particularly in the dorsal hippocampus, in the pathophysiology and treatment responses of MIA-induced schizophrenia and highlight the therapeutic potential of blonanserin for developmental stress-related schizophrenia.
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Antipsicóticos , Células-Madre Neurales , Femenino , Embarazo , Ratas , Animales , Antipsicóticos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Regiones no Traducidas 3' , Células-Madre Neurales/metabolismo , Interneuronas , Hipocampo/metabolismo , Amígdala del Cerebelo/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Glutamatos/farmacologíaRESUMEN
Long interspersed nuclear element-1 (LINE-1, L1) affects the transcriptome landscape in multiple ways. Promoter activity within its 5'UTR plays a critical role in regulating diverse L1 activities. However, the epigenetic status of L1 promoters in adult brain cells and their relationship with psychiatric disorders remain poorly understood. Here, we examined DNA methylation and hydroxymethylation of the full-length L1s in neurons and nonneurons and identified "epigenetically active" L1s. Notably, some of epigenetically active L1s were retrotransposition competent, which even had chimeric transcripts from the antisense promoters at their 5'UTRs. We also identified differentially methylated L1s in the prefrontal cortices of patients with psychiatric disorders. In nonneurons of bipolar disorder patients, one L1 was significantly hypomethylated and showed an inverse correlation with the expression level of the overlapping gene NREP. Finally, we observed that altered DNA methylation levels of L1 in patients with psychiatric disorders were not affected by the surrounding genomic regions but originated from the L1 sequences. These results suggested that altered epigenetic regulation of the L1 5'UTR in the brain was involved in the pathophysiology of psychiatric disorders.
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Epigénesis Genética , Trastornos Mentales , Humanos , Regiones no Traducidas 5' , Elementos de Nucleótido Esparcido Largo/genética , Encéfalo , Trastornos Mentales/genéticaRESUMEN
Aim: An assertive case management intervention program, ACTION-J, proved effective for preventing suicide attempters from reattempting suicide within 6 months. The ACTION-J randomized trial was conducted as part of the "National Strategic Research Projects." The program has been covered by the national medical payment system of Japan since 2016. The aim of the Post-ACTION-J Study (PACS) was to examine the current implementation status of assertive case management in a real-world clinical setting. Methods: PACS was a prospective, multicenter registry cohort study. The participants were suicide attempters admitted to the emergency departments of 10 participating medical facilities from October 2016 to September 2018. The assertive case management intervention developed by the ACTION-J Study was offered to all patients, and the primary outcome was the duration and frequency of use of the intervention at 6 months. Results: A total of 1159 patients were admitted to emergency departments after a suicide attempt during the study period, 144 of whom were included in our analysis. The proportion of participants who received the intervention for 6 months was 72.2% (104/144), and 63.9% (92/144) of the patients completed ≥7 case management interviews within 6 months. Conclusion: The findings of this study indicate successful implementation of an assertive case management intervention program based on the ACTION-J Study in a real-world clinical setting, following its integration with the national medical payment scheme in Japan. The study provided the useful information that could improve the implementation of assertive case management interventions in future.
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Objectives: To evaluate changes in radiographic findings and plantar pressure distribution after rheumatoid forefoot surgery.Methods: This study was performed on patients with rheumatoid arthritis (RA) who underwent Swanson implant arthroplasty for the 1st metatarsophalangeal (MTP) joint combined with shortening oblique osteotomy at the 2nd through 5th metatarsal necks (group Sw, 55 feet). The following two groups were used as controls: group NS, consisting of 75 feet in RA patients without scheduled forefoot surgery, and group HC, consisting of 24 feet in healthy female subjects. Plantar pressure distribution, and radiographic findings of hallux valgus angle, the angle between the metatarsal bones, talocalcaneal angle, calcaneal pitch angle and calcaneo-first metatarsal angle (CFMA) were measured pre- and one year postoperatively. Peak pressure was measured in nine sections.Results: Calcaneal pitch angle decreased and CFMA increased in group Sw. Peak pressure at the 1st interphalangeal joint (IP) and the 2nd and 3rd MTPs in group Sw decreased, while that at midfoot increased.Conclusion: While the clinical outcome in group Sw was favorable, postoperative longitudinal arch decreased. Postoperative peak pressure at the 2nd through 5th MTPs was comparable with that in group NS; however, it was significantly lower than that in group HC.
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Artritis Reumatoide/cirugía , Artroplastia/efectos adversos , Hallux Valgus/diagnóstico por imagen , Osteotomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Adulto , Anciano , Artroplastia/métodos , Femenino , Hallux Valgus/epidemiología , Humanos , Masculino , Huesos Metatarsianos/diagnóstico por imagen , Huesos Metatarsianos/cirugía , Articulación Metatarsofalángica/diagnóstico por imagen , Articulación Metatarsofalángica/cirugía , Persona de Mediana Edad , Osteotomía/métodos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: There has been number of studies suggesting experiences of adversity in early life interrelated subsequent brain development, however, neurobiological mechanisms confer risk for onset of psychiatric illness remains unclear. METHODS: In order to elucidate the pathogenic mechanisms underlying early life adversity-induced refractory depression in more detail, we administered corticosterone (CORT) to adolescent rats with or without prenatal ethanol exposure followed by an antidepressant or antipsychotic and examined alterations in depressive and social function behaviors and brain-derived neurotrophic factor (BDNF) levels in serum, the hippocampus, anterior cingulate cortex, and nucleus accumbens. RESULTS: The combined stress exposure of prenatal ethanol and adolescent CORT prolonged immobility times in the forced swim test (FST), and increased investigation times and numbers in the social interaction test (SIT). A treatment with escitalopram reversed depression-like behavior accompanied by reductions in BDNF levels in serum and the nucleus accumbens, while a treatment with blonanserin ameliorated abnormal social interaction behavior with reductions in serum BDNF levels. LIMITATIONS: Further studies are needed to clarify the clinical evinces responding to these results, and many questions remain regarding the mechanisms by which refractory depression and antidepressant/antipsychotic treatments cause changes in serum and brain regional BDNF levels. CONCLUSION: These results strongly implicate changes in BDNF levels in serum and the nucleus accumbens in the pathophysiology and treatment of early life combined stress-induced depression and highlight the therapeutic potential of escitalopram and new generation antipsychotic blonanserin for treatment-resistant refractory depression.
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Antidepresivos/farmacología , Citalopram/farmacología , Depresión/tratamiento farmacológico , Piperazinas/farmacología , Piperidinas/farmacología , Animales , Conducta Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corticosterona , Depresión/inducido químicamente , Depresión/metabolismo , Modelos Animales de Enfermedad , Femenino , Hipocampo/metabolismo , Masculino , Núcleo Accumbens/metabolismo , Embarazo , Ratas , Conducta Social , NataciónRESUMEN
INTRODUCTION: Suicide attempt is the most important risk factor for later suicide. A randomised-controlled, multicentre trial of postsuicide attempt case management for the prevention of further suicide attempts in Japan, named ACTION-J, has established effective interventions for prevention of suicide reattempts. The ACTION-J assertive case management intervention programme was adopted by the Japanese Ministry of Health, Labour and Welfare in 2016, when medical fees were revised. This nationwide programme is provided to patients who attempt suicide and who are admitted to emergency departments in Japan.The aim of the present study is to examine the current implementation status of the ACTION-J programme. The present study also aims to clarify which patients' and hospitals' factors affect the implementation of the programme. METHODS AND ANALYSIS: This is a prospective, multicentre, patient registry cohort study. Participants will be suicide attempters admitted to the emergency departments of medical facilities with both psychiatry and emergency departments. The assertive case management programme will be delivered to participants by a case manager for up to 24 weeks, based on psychiatric diagnoses, social risks and patient needs. The core feature of the programme is to encourage patients to participate in psychiatric treatment.The primary outcome will be the proportion of patients still participating in the case management intervention at 24 weeks after registration. The secondary outcomes will include measures of the fidelity of the case management intervention. The fidelity will be evaluated using a fidelity assessment manual developed by the study group. ETHICS AND DISSEMINATION: This observational study has been approved by the ethics board of Sapporo Medical University. Enrolment began in October 2016 and will continue until December 2018. Dissemination plans include presentations at scientific conferences and scientific publications. TRIAL REGISTRATION: UMIN000024474.
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Manejo de Caso , Trastornos Mentales/terapia , Sistema de Registros , Prevención del Suicidio , Intento de Suicidio/prevención & control , Servicio de Urgencia en Hospital , Humanos , Japón , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Desarrollo de Programa , Estudios Prospectivos , Proyectos de InvestigaciónRESUMEN
Many patients with mental disorders visit emergency departments (EDs). However, the majority of these patients do not receive psychiatric assessment. In the present study, we investigated the detailed proportion of patients with mental disorders visiting an urban ED in the largest northern city in Japan. A retrospective chart review study was performed at a University Hospital from January 2012 to December 2015. The reasons for psychiatric consultations made by ED staff, and the primary psychiatric diagnoses were investigated. Among all living patients, 20% of them received consultations. The most common reason for consultation was suicide attempt followed by agitation or insomnia. Of all diagnoses, organic mental disorder was the most frequent and the mean age was significantly higher than the other diagnostic groups. Our study indicated that the frequency of psychiatric consultation was high. This indicates the high demand for mental health services at the ED. A thorough psychiatric assessment can provide adequate psychiatric services to acute patients; thereby possibly preventing suicide attempters from later actually dying by suicide.
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AIM: Somatic mutations in the human brain are hypothesized to contribute to the functional diversity of brain cells as well as the pathophysiology of neuropsychiatric diseases. However, there are still few reports on somatic mutations in non-neoplastic human brain tissues. This study attempted to unveil the landscape of somatic mutations in the human brain. METHODS: We explored the landscape of somatic mutations in human brain tissues derived from three individuals with no neuropsychiatric diseases by whole-genome deep sequencing at a depth of around 100. The candidate mutations underwent multi-layered filtering, and were validated by ultra-deep target amplicon sequencing at a depth of around 200 000. RESULTS: Thirty-one somatic mutations were identified in the human brain, demonstrating the utility of whole-genome sequencing of bulk brain tissue. The mutations were enriched in neuron-expressed genes, and two-thirds of the identified somatic single nucleotide variants in the brain tissues were cytosine-to-thymine transitions, half of which were in CpG dinucleotides. CONCLUSION: Our developed filtering and validation approaches will be useful to identify somatic mutations in the human brain. The vulnerability of neuron-expressed genes to mutational events suggests their potential relevance to neuropsychiatric diseases.
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Encéfalo/metabolismo , Análisis Mutacional de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación/genética , Neuronas/metabolismo , Secuenciación Completa del Genoma/métodos , Anciano , Anciano de 80 o más Años , Autopsia , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801. We herein demonstrated that antipsychotics promoted or restored changes in the oligodendrocyte/GABAergic interneuron differentiation functions of NG2(+) cells induced by the exposure to MK-801, which was considered to be one of the drug-induced schizophrenia model. We also demonstrated that antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with differentiation impairment. The antipsychotics olanzapine, aripiprazole, and blonanserin, but not haloperidol increased HSP90 levels, which were reduced by the exposure to MK-801. Our results showed that antipsychotics, particularly those recently synthesized, exerted similar GABAergic interneuron genesis effects on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing cellular HSP production, and also suggest that HSP90 may play a crucial role in the pathophysiology of schizophrenia and is a key target for next drug development.
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Antipsicóticos/farmacología , Encéfalo/citología , Encéfalo/fisiología , Neuronas GABAérgicas/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/metabolismo , Neurogénesis/efectos de los fármacos , Animales , Antígenos/metabolismo , Encéfalo/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Maleato de Dizocilpina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Glutamato Descarboxilasa/metabolismo , Técnicas In Vitro , Ventrículos Laterales/citología , Ventrículos Laterales/efectos de los fármacos , Masculino , Nestina/metabolismo , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Técnicas de Cultivo de Órganos , Embarazo , Proteoglicanos/metabolismo , Ratas , Ratas Wistar , Estadísticas no Paramétricas , Células Madre/efectos de los fármacos , Tubulina (Proteína)/metabolismoRESUMEN
OBJECTIVES: The objective of this study is to clarify the surgical indication for rheumatoid forefoot deformity according to background characteristics and plantar pressure. METHODS: Patients with rheumatoid arthritis were divided into a non-surgical group (group N) and a surgical group (group S). The former consisted of 225 ft, and the latter consisted of 88 ft. DAS28, Japanese Society for Surgery of the Foot rheumatoid arthritis foot and ankle scale (JSSF scale) and hallux valgus angle (HVA) were evaluated as background characteristics. Distribution of peak pressure as plantar pressure was measured in nine sections. RESULTS: In groups N and S, the mean DAS28 was 3.6 and 3.0, the mean JSSF scale was 81.1 and 63.0, and the mean HVA was 19.9° and 35.3°, respectively. The mean peak pressure of group S at the first and third metatarsophalangeal joints was significantly higher compared with group N. Significant differences between the two groups were also seen in Δ pressure (the difference between the maximum and minimum peak pressure values). The cut-off values were 75.0 for JSSF scale, 24.9° for HVA and 3.94 kg/cm2 for Δ pressure. CONCLUSIONS: The combined assessment of HVA and Δ pressure was found to be useful as an indication for surgical treatment of the forefoot.
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Artritis Reumatoide/cirugía , Artroplastia/efectos adversos , Deformidades Adquiridas del Pie/cirugía , Hallux Valgus/cirugía , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Artroplastia/métodos , Femenino , Deformidades Adquiridas del Pie/etiología , Deformidades Adquiridas del Pie/patología , Humanos , Masculino , Articulación Metatarsofalángica/cirugía , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , PresiónRESUMEN
Suicide is one of the common severe accidents occurring in hospitals. This study aimed to investigate inpatient suicides simultaneously in medical and psychiatric settings in a large number of hospitals and to examine the prevalence of common suicide risk factors, related symptoms in inpatients who had died by suicide and the differences in inpatient suicides between both settings. We conducted a survey of hospitals in Japan that belonged to the nationwide standard-setting and accrediting body. The questionnaire covered the: 1) presence or absence of inpatient suicides in each hospital from 2012 to 2015; 2) number of inpatient suicides; 3) method, location, and timing of inpatient suicides; and 4) characteristics of inpatients who died by suicide. In total, 529 hospitals reported 262 inpatient suicides during the 3-year period: 131 were in medical settings and 131 were in psychiatric settings. The prevalence of common suicide risk factors was frequent in inpatient suicides. Inpatients had characteristics and suicide risk factors specific to those settings such as worsening of physical health in medical settings. Therefore, recognizing common suicide risk factors and understanding differences in inpatient suicides between both settings are important to prevent inpatient suicides.
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Hospitales Psiquiátricos/estadística & datos numéricos , Pacientes Internos/psicología , Suicidio/psicología , Hospitales , Humanos , Pacientes Internos/estadística & datos numéricos , Japón , Factores de Riesgo , Suicidio/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), 123 I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT-SPECT. Taking finances and patient burden into consideration, we compared the tests to determine priority. METHODS: Thirty-four patients with probable DLB (75.0 ± 8.3 years old; 14 men, 20 women) underwent bp-SPECT, MIBG scintigraphy, and DAT-SPECT. RESULTS: Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine-transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp-SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group. CONCLUSIONS: In terms of stand-alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT-SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp-SPECT, MIBG scintigraphy, and DAT-SPECT increased the accuracy of the clinical diagnosis of DLB.
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3-Yodobencilguanidina , Encéfalo/diagnóstico por imagen , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Imagen de Perfusión Miocárdica/métodos , Imagen de Perfusión/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Anciano de 80 o más Años , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/metabolismo , Masculino , Valor Predictivo de las Pruebas , Radiofármacos , Sensibilidad y EspecificidadRESUMEN
Recent reports suggest a lifetime suicide risk for schizophrenia patients of approximately 5%. This figure is significantly higher than the general population suicide risk consequently, detection of those at risk is clinically important. This study was undertaken to define the characteristics of suicide attempts by schizophrenia patients compared with attempts by patients with mood disorders. All patients were diagnosed using the ICD-10 criteria. The study population comprised 65 patients with F2 disorders (schizophrenia, schizotypal and delusional disorders), i.e., "the F2 group", and 94 patients with F3 disorders (mood disorders), i.e., "the F3 group", who presented in the clinical setting of consultation-liaison psychiatry. The F2 group had a significantly younger mean age and significantly higher ratios of 'past/present psychiatric treatment' and 'more than 3 months interruption of psychiatric treatment'. In contrast, the ratios of 'physical disorder comorbidity', 'alcohol intake at suicide attempt' and 'suicide note left behind' were significantly higher in the F3 group. The F2 group attempted suicide by significantly more serious methods. Furthermore, 'hallucination-delusion' was the most prevalent motive in the F2 group and was the only factor that showed a significant association with the seriousness of the method of suicide attempt (ORâ=â3.36, 95% CI: 1.05-11.33).
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Deluciones/psicología , Trastornos del Humor/psicología , Psicología del Esquizofrénico , Intento de Suicidio/psicología , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
To better understand the relationship of repeated exposure to adversity during early development as a risk factor for refractory depression, we exposed pregnant female rats to ethanol and the resulting pups to corticosterone during adolescence. A stressful forced swim test was then used to induce depression-like behavior. The adolescent rat brains were examined for the possible therapeutic benefit of a combination of sertraline, an antidepressant, and neural stem cells (NSCs) complexed with atelocollagen in relation to the level of GABAergic interneuron and synaptic protein density in different brain regions. The combined exposures of prenatal and adolescent stress resulted in a reduction in parvalbumin (PV)-positive phenotype of GABAergic interneurons and reduced postsynaptic density protein 95 (PSD-95) levels in the anterior cingulate cortex, amygdala, and hippocampus. Treatments with sertraline and NSCs reversed the reductions in PV-positive cells and PSD-95 levels. Furthermore, the combined treatment of sertraline and NSCs resulted in reduced depressive-like behaviors. These experiments underscore a potentially important role for synaptic remodeling and GABAergic interneuron genesis in the treatment of refractory depression and highlight the therapeutic potential of stem cell and pharmacological combination treatments for refractory depression.
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Trastorno Depresivo Resistente al Tratamiento/terapia , Células-Madre Neurales/trasplante , Trasplante de Células Madre/métodos , Animales , Antidepresivos/farmacología , Encéfalo/fisiopatología , Terapia Combinada , Trastorno Depresivo Resistente al Tratamiento/fisiopatología , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large , Neuronas GABAérgicas/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Células-Madre Neurales/fisiología , Parvalbúminas/metabolismo , Ratas Wistar , Sertralina/farmacologíaRESUMEN
Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.
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Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Colágeno/farmacología , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Animales , Encéfalo/citología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Ratas , Ratas Wistar , Trasplante de Células Madre/métodosRESUMEN
Fondaparinux and enoxaparin are useful for preventing venous thromboembolism after total knee arthroplasty (TKA), but both drugs have associated complications. The purpose of this study was to clarify the risks associated with use of these drugs in Japanese patients who underwent TKA.A total of 575 patients (935 knees) underwent TKA and were retrospectively reviewed; 277 patients (454 knees) were treated with fondaparinux and 298 patients (481 knees) were treated with enoxaparin. The authors investigated the incidences of deep venous thrombosis of the lower limbs and pulmonary embolism to evaluate venous thromboembolism, knee enlargement compared with the preoperative size, incidence of subcutaneous knee hematoma, and other complications. No significant differences were observed between the 2 drugs regarding the incidences of deep venous thrombosis and pulmonary embolism. However, fondaparinux use resulted in knee enlargement (P<.0005) and subcutaneous hematoma of the knee (P=.035) significantly more often than enoxaparin use. Conversely, enoxaparin use significantly caused the elevation of alanine aminotransferase (one of the liver enzymes) at a higher rate than fondaparinux (30.1% vs 8.3%, respectively; P<.0001). However, the increased alanine aminotransferase levels were transient, and no patient exhibited symptoms of abnormal liver function, such as jaundice or cutaneous pruritus.Fondaparinux and enoxaparin were both effective in preventing venous thromboembolism in Japanese patients undergoing elective TKA. However, both drugs had some adverse effects. It is important to be aware of these potential risks when prescribing these drugs.
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Anticoagulantes/efectos adversos , Artroplastia de Reemplazo de Rodilla , Enoxaparina/efectos adversos , Artropatías/cirugía , Polisacáridos/efectos adversos , Tromboembolia Venosa/prevención & control , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Enoxaparina/uso terapéutico , Femenino , Fondaparinux , Humanos , Masculino , Polisacáridos/uso terapéutico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: The type of osteoarthritis and the degree of severity which causes restriction of knee range of motion (ROM) is still largely unknown. The objective of this study was to analyse the location and the degree of cartilage degeneration that affect knee range of motion and the connection, if any, between femorotibial angle (FTA) and knee ROM restriction. METHODS: Four hundreds and fifty-six knees in 230 subjects with knee osteoarthritis undergoing knee arthroplasty were included. Articular surface was divided into eight sections, and cartilage degeneration was evaluated macroscopically during the operation. Cartilage degeneration was classified into four grades based on the degree of exposure of subchondral bone. A Pearson correlation was conducted between FTA and knee flexion angle to determine whether high a degree of FTA caused knee flexion restriction. A logistic regression analysis was also conducted to detect the locations and levels of cartilage degeneration causing knee flexion restriction. RESULTS: No correlation was found between FTA and flexion angle (r = -0.08). Flexion angle was not restricted with increasing FTA. Logistic regression analysis showed significant correlation between restricted knee ROM and levels of knee cartilage degeneration in the patella (odds ratio (OR) = 1.77; P = 0.01), the lateral femoral condyle (OR = 1.62; P = 0.03) and the posterior medial femoral condyle (OR = 1.80; P = 0.03). CONCLUSION: For clinical relevance, soft tissue release and osteophyte resection around the patella, lateral femoral condyle and posterior medial femoral condyle might be indicated to obtain a higher degree of knee flexion angle.
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Osteoartritis de la Rodilla/fisiopatología , Anciano , Anciano de 80 o más Años , Cartílago/patología , Estudios de Casos y Controles , Femenino , Humanos , Articulación de la Rodilla/patología , Masculino , Osteoartritis de la Rodilla/cirugía , Rango del Movimiento ArticularRESUMEN
BACKGROUND: Knee size and body size differ in Asians compared with Caucasians. Nevertheless, many total knee arthroplasty (TKA) prostheses used worldwide are made for Western Caucasian subjects. As a result, an Asian's knee might not fit these prostheses. We studied the Flexible Nichidai Knee (FNK) system, a new model of TKA for Asian patients. The purpose of this report is to investigate the outcomes of this prosthesis retrospectively. METHODS: We investigated 1055 primary TKAs in 595 patients who underwent FNK for osteoarthritis (OA) in Japan and were followed for > 5 years. The knee score and function score were used for clinical evaluation. We examined the range of motion (ROM) preoperatively and at final follow-up and radiographic assessments. In addition, postoperative complications were investigated. A survivorship analysis was also conducted using two endpoints: revision for any reason and aseptic failure. RESULTS: 890 knees in 502 patients were available for study (follow-up rate of 96.0%). The mean follow-up term was 8.3 years (range, 5.0-14.1 years). The knee and function score significantly improved from 41.3 to 90.3 and from 39.1 to 76.2 points, respectively (p < 0.001). The mean ROM in FNK posterior cruciate retaining (CR) type and FNK posterior-stabilized (PS) type ameliorated significantly from 107.8° and 95.6° to 110.7° and 110.4°, respectively (p < 0.01). Ten knees underwent revision surgery (infection in 3 cases, instability in 2, loosening in 2, and non-union of femoral supracondylar fracture, severe pain, and recurrent hemarthrosis in 1 each). The survivorship rate was 99.4% (95% CI, 99.0-99.8) at 5 years (n = 952 patients at risk) and 96.2% (95% CI, 91.9-100) at 12.5 years (n = 49 patients at risk). CONCLUSION: The FNK prosthesis for Asians achieved excellent mid- to long-term survivorship and clinical results.
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Artroplastia de Reemplazo de Rodilla/efectos adversos , Pueblo Asiatico , Prótesis de la Rodilla/tendencias , Complicaciones Posoperatorias/mortalidad , Falla de Prótesis/efectos adversos , Falla de Prótesis/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/mortalidad , Tamaño Corporal/fisiología , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
This article reports a case of bilateral fatigue fracture of the femoral components in a cruciate-retaining uncemented total knee arthroplasty (TKA). A 75-year-old woman (height, 158 cm; weight, 72 kg; body mass index, 29.2) had undergone one-stage bilateral TKA for osteoarthritis 11 years previously at the author's institution. Surgery was performed using an uncemented Flexible Nichidai Knee. Equal tension of the collateral ligaments and normal mechanical axis were achieved during the primary procedure. The patient was an ardent lover of the game of badminton and had higher activity levels with daily playing. At 8 years postoperatively, she started complaining of mild pain in both knees. The pain gradually increased, and at 11 years postoperatively, she had difficulty walking. Anteroposterior radiographs showed narrowing of the medial joint space, indicating wear of the polyethylene insert. Lateral radiographs showed signs of broken implants in both knees. There were no signs of gross implant loosening or osteolysis. One-stage revision surgery was performed, and the knees were converted to cemented posterior-stabilized TKAs. At revision, the bilateral femoral components were found to be fractured at the junction between the trochlear flange and the medial condyle, anteriorly to the medial peg. The polyethylene insert showed mild wear at the medial middle portion. In the majority of case reports, stress fractures of the femoral component have predominantly affected the medial condyle, following uncemented implantation of fixed-bearing knees. In this case, failure of bone ingrowth in uncemented components, higher body mass index, and a higher athletic activity led to fatigue fracture of the femoral components.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Cementos para Huesos , Fracturas del Fémur/complicaciones , Fracturas por Estrés/complicaciones , Prótesis de la Rodilla , Falla de Prótesis , Anciano , Cementación , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/cirugía , Estado de Salud , Humanos , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Oseointegración , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/cirugía , Ligamento Cruzado Posterior , Radiografía , Rango del Movimiento Articular , Recuperación de la Función , ReoperaciónRESUMEN
PURPOSE: Total knee arthroplasty (TKA) has been proven to be the most effective treatment for patients with severe joint disease. Although infection is not a frequent complication, it is certainly one of the most dreaded. The purpose of this study was to identify factors associated with infection after TKA. METHODS: Between 1995 and 2006, 2,022 primary TKAs in 1,146 patients were evaluated. Flexible Nichidai Knee (FNK) was used as a prothesis in all subjects. Twenty-four patient-specific data items were collected via chart review for each patient. Revision arthroplasty procedures and infected knees were excluded. The medical records were reviewed to extract the following information: age, gender, body mass index (BMI), preoperative C-reactive protein (CRP), preoperative erythrocyte sedimentation rate (ESR), preoperative total protein (TP), duration of surgery, operative blood loss, total blood loss, duration of surgical drain, duration of antibiotic prophylaxis, primary diagnoses, smoking, diabetes mellitus, steroid or disease modifying anti-rheumatic drugs (DMARDs) therapy, previous operation around the knee joint, previous arthroscopic surgery, previous non-arthroscopic surgery, previous high tibial osteotomy (HTO) or open reduction internal fixation (ORIF), remnants of previous internal fixation material, bone graft, patella replacement, and bone cement. RESULTS: The median age of the patients at the time of primary TKA was 72 (range, 26-91) years. The median follow-up period after primary TKA was 42 (range, 6-145) months. During the study period, 17 infected knee arthroplasties in 17 patients were identified. Previous history of ORIF, male gender, remnants of previous internal fixation material, and BMI showed significant correlation with postoperative infection. CONCLUSION: This study identified previous history of fracture and remnants of internal fixation as major risk factors of infection after TKA. For clinical relevance, surgeons should be aware of potential infection when performing TKA in patients with these risk factors and patients should be informed of the potential risks.