RESUMEN
To continuously and noninvasively monitor the cerebral tissue oxygen saturation (StO2) and hemoglobin concentration (gasHb) in cardiac surgery patients, a method combining the use of a cerebral tissue oximeter using near infrared time-resolved spectroscopy (tNIRS-1) and the bispectral index (BIS) was developed in this study. Moreover, the correlation between the estimated hemoglobin concentration (estHb), measured via tNIRS-1, and the hemoglobin concentration (gasHb), analyzed using a blood gas analyzer, were compared. The relationship between the BIS and gasHb was also examined. Through the comparison of BIS and StO2 (r1), and estHb and gasHb (r2), the correlation between the two was clarified with maximum r1 and r2 values of 0.617 and 0.946, respectively. The relationship between BIS and gasHb (r3), showed that there was a favorable correlation with a maximum r3 value of 0.969. There was also a continuous correlation between BIS and StO2 in patients undergoing cardiac surgery. In addition, a strong correlation was found between estHb and gasHb, and between BIS and gasHb. It was therefore concluded that the combined use of BIS and tNIRS-1 is useful to evaluate cerebral hypoxia, allowing for quick response to cerebral hypoxia and reduction of hemoglobin concentration during the operation.
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Encéfalo/metabolismo , Procedimientos Quirúrgicos Cardíacos , Monitores de Conciencia , Hemoglobinas/metabolismo , Hipoxia Encefálica/diagnóstico , Hipoxia Encefálica/prevención & control , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/prevención & control , Monitoreo Intraoperatorio/métodos , Oximetría/métodos , Consumo de Oxígeno , Biomarcadores/metabolismo , Análisis de los Gases de la Sangre/métodos , Humanos , Espectroscopía Infrarroja CortaRESUMEN
Sensing-actuation systems can assist a bladder with lost sensation and weak muscle control. Here, we advance the relevant technology by integrating a soft and thin capacitive sensor with a shape memory alloy-based actuator to achieve a high-performance closed-loop configuration. In our design, sensors capable of continuous bladder volume detection and actuators with strong emptying force have been used. This integration has previously hindered performance due to large bladder volume changes. Our solution integrates sensing-actuation elements that are bladder compatible but do not interfere with one another, achieving real-time bladder management. The system attains a highly desirable voiding target of 71 to 100% of a rat's bladder with a volume sensitivity of 0.7 µF/liter. Our system represents an efficient voiding solution that avoids overfilling and represents a technological solution to bladder impairment treatment, serving as a model for similar soft sensor-actuator integration with other organs.
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Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.
Asunto(s)
Trastorno Bipolar/genética , Adulto , Proteínas de Ciclo Celular/genética , Citocinas/genética , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Japón/epidemiología , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Herencia Multifactorial/genética , Factores de Transcripción NFI/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.
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Esquizofrenia/genética , Adulto , Estudios de Casos y Controles , Hibridación Genómica Comparativa/métodos , Variaciones en el Número de Copia de ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Japón , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
The topology of pure Bi is controversial because of its very small (â¼10 meV) band gap. Here we perform high-resolution angle-resolved photoelectron spectroscopy measurements systematically on 14-202 bilayer Bi films. Using high-quality films, we succeed in observing quantized bulk bands with energy separations down to â¼10 meV. Detailed analyses on the phase shift of the confined wave functions precisely determine the surface and bulk electronic structures, which unambiguously show nontrivial topology. The present results not only prove the fundamental property of Bi but also introduce a capability of the quantum-confinement approach.
RESUMEN
Ultrafast magnetization reversal of a ferrimagnetic metallic alloy GdFeCo was investigated by time-resolved resonant magneto-optical Kerr effect measurements using a seeded free electron laser. The GdFeCo alloy was pumped by a linearly polarized optical laser pulse, and the following temporal evolution of the magnetization of Fe in GdFeCo was element-selectively traced by a probe free electron laser pulse with a photon energy tuned to the Fe M-edge. The results have been measured using rotating analyzer ellipsometry method and confirmed magnetization switching caused by ultrafast heating.
RESUMEN
Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT.
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Corazón/fisiopatología , Polimorfismo Genético/genética , Risperidona/efectos adversos , Risperidona/metabolismo , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Adulto , Antipsicóticos/efectos adversos , Antipsicóticos/metabolismo , Antipsicóticos/uso terapéutico , Electrocardiografía , Femenino , Humanos , Masculino , Análisis de Regresión , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismoAsunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Proteínas Proto-Oncogénicas/genética , Receptores Notch/genética , Esquizofrenia/genética , Adulto , Anciano , Pueblo Asiatico/genética , Femenino , Estudios de Seguimiento , Estudios de Asociación Genética , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Receptor Notch4RESUMEN
We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-resistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 × 10(-6), odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD.
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Antipsicóticos/efectos adversos , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Discinesia Inducida por Medicamentos/genética , Proteínas del Tejido Nervioso/genética , Canales de Potasio/genética , Alelos , Animales , Antipsicóticos/uso terapéutico , Pueblo Asiatico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Discinesia Inducida por Medicamentos/metabolismo , Femenino , Expresión Génica , Genotipo , Humanos , Intrones , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , Polimorfismo de Nucleótido Simple , Canales de Potasio/metabolismo , Esquizofrenia/tratamiento farmacológicoRESUMEN
Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10(-5), odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10(-4)). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.
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Estudio de Asociación del Genoma Completo , Trastorno de Pánico/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Herencia Multifactorial , Polimorfismo de Nucleótido SimpleRESUMEN
Several studies have shown increased rates of hyperglycemia and diabetes in schizophrenic patients treated with olanzapine. However, the underlying mechanism is poorly understood. Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic ß cells. Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). We assessed the influence of this GIPR gene polymorphism on glucose metabolism in 60 schizophrenic patients treated with olanzapine and 103 healthy controls. The GIPR gene polymorphism was determined using TaqMan methods. We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. Our findings suggest that schizophrenic patients with the A allele of GIPR rs10423928 are at risk of developing hyperinsulinemia when treated with antipsychotics.
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Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Insulina/sangre , Polimorfismo Genético , Receptores de la Hormona Gastrointestinal/genética , Esquizofrenia/tratamiento farmacológico , Adulto , Área Bajo la Curva , Péptido C/sangre , Femenino , Genotipo , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Olanzapina , Esquizofrenia/genética , Esquizofrenia/metabolismoRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. CASE SUMMARY: We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. WHAT IS NEW AND CONCLUSION: There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.
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Acatisia Inducida por Medicamentos/prevención & control , Antipsicóticos/efectos adversos , Dibenzotiazepinas/uso terapéutico , Monitoreo de Drogas , Piperazinas/efectos adversos , Quinolonas/efectos adversos , Adulto , Factores de Edad , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Aripiprazol , Dibenzotiazepinas/administración & dosificación , Antagonistas de los Receptores de Dopamina D2 , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Fumarato de Quetiapina , Quinolonas/administración & dosificación , Quinolonas/uso terapéutico , Factores de Riesgo , Esquizofrenia/tratamiento farmacológico , Caracteres Sexuales , Resultado del Tratamiento , Adulto JovenRESUMEN
We report a 64-year-old male patient with papillary fibroelastoma of the tricuspid valve associated with moderate mitral regurgitation. Echocardiography had revealed a 10 x 10 mm tumor attaching to the anterior tricuspid leaflet 3 years before. Because the tumor was enlarged to 19 x 15 mm, we excised it with a part of the anterior tricuspid leaflet, and performed tricuspid and mitral valvoplasty. The histological findings suggested papillary fibroelastoma. The postoperative course was uneventful.
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Fibroma/cirugía , Neoplasias Cardíacas/cirugía , Insuficiencia de la Válvula Mitral/etiología , Válvula Tricúspide , Fibroma/complicaciones , Neoplasias Cardíacas/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A multivariate analysis [4] revealed that the presence of crescent formation on initial biopsy irrespective of type of membranoproliferative glomerulonephritis (MPGN) was independently associated not only with end-stage renal disease but also with post-transplantation recurrence. In this study, we reported on a 4-year-old male pediatric patient requiring hemodialysis due to rapidly progressive idiopathic MPGN Type 1 with severe nephrotic syndrome and extensive cellular crescent formation on initial biopsy. The patient had been treated intravenously (i.v.) with 9 pulses of methylprednisolone, followed by daily prednisolone, resulting in the withdrawal of dialysis within 1 month. However, since active lesions in the second renal biopsy such as cellular crescents still remained and nephrotic range proteinuria had persisted for more than 2 months, the patient received additional 3 i.v. pulses of methylprednisolone, followed by combinations of alternate-day prednisolone, mizoribine, dipyridamole and warfarin, which lead to complete remission in a short-period of time. The patient has been off the combination therapy for 10 months because the third biopsy prior to the termination of this regimen showed decreased inflammatory activity. There is currently no established protocol for children with crescentic MPGN due to a rarity of its clinicopathological presentation. This case report indicates that early treatment with multiple pulses of methylprednisolone followed by the short-term combination therapy may be of benefit for children with rapidly progressive idiopathic MPGN Type 1, even when both diffuse crescentic changes and nephrotic syndrome are present at onset.
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Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Preescolar , Quimioterapia Combinada , Glomerulonefritis Membranoproliferativa/patología , Humanos , Masculino , Metilprednisolona/administración & dosificación , Prednisolona/administración & dosificaciónRESUMEN
Neuregulin-1 (NRG1) gene is implicated in the etiology or neuropathology of schizophrenia, although its biological contribution to this illness is not fully understood. We have established an enzyme-linked immunosorbent assay (ELISA), which recognizes the NRG1beta1 immunoglobulin-like (Ig) domain, and measured soluble Ig-NRG1 immunoreactivity in the sera of chronic schizophrenia patients (n = 40) and healthy volunteers (n = 59). ELISA detected remarkably high concentrations of Ig-NRG1 immunoreactivity in human serum (mean 5.97 +/- 0.40 ng/mL, ~213 +/- 14 pM). Gender and diagnosis exhibited significant effects on serum Ig-NRG1 immunoreactivity. Mean Ig-NRG1 immunoreactivity in the schizophrenia group was 63.2% of that measured in the control group. Ig-NRG1 immunoreactivity in women was 147.1% of that seen in men. We also attempted to correlate six SNPs of NRG1 genome with serum Ig-NRG1 immunoreactivity. Analysis of covariance with compensation for gender identified a significant interaction between diagnosis and SNP8NRG243177 allele. The T allele of this SNP significantly contributed to the disease-associated decrease in Ig-NRG1 immunoreactivity. Although we hypothesized a chronic influence of antipsychotic medications, there was no significant effect of chronic haloperidol treatment on serum Ig-NRG1 immunoreactivity in monkeys. These findings suggest that serum NRG1 levels are decreased in patients with chronic schizophrenia and influenced by their SNP8NRG243177 alleles.
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Neurregulina-1/sangre , Neurregulina-1/genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/sangre , Esquizofrenia/genética , Adulto , Alelos , Análisis de Varianza , Animales , Antipsicóticos/administración & dosificación , Antipsicóticos/farmacología , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Haloperidol/administración & dosificación , Haloperidol/farmacología , Humanos , Macaca fascicularis , Masculino , Esquizofrenia/tratamiento farmacológico , Factores SexualesRESUMEN
In order to elucidate the spatial distribution of brominated flame retardants (BFRs) in the Japanese coastal environment, hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs) and organochlorines (OCs: PCBs, DDTs, CHLs, HCHs, HCB) were determined in bivalves (oysters and mussels) collected from Japanese coastal waters. HBCDs and PBDEs were detected in all samples analyzed. Concentration ranges of HBCDs were 12-5200 ng g(-1) lipid wt., followed by PCBs (20-3100 ng g(-1))>PBDEs (3.1-86 ng g(-1) lipid wt.). The highest concentration of HBCDs was found in the Osaka region. This result indicates that HBCDs are ubiquitous and predominant compounds in bivalves from the Japanese coastal waters. Since no species differences between oysters and mussels were observed for the bioaccumulation properties of HBCDs and PBDEs, oysters could be utilized for BFR contamination monitoring worldwide as an alternative to mussels. Global comparisons between oysters and mussels showed that HBCD concentrations in Japan are among the highest levels reported from Asia and Europe. Estimated dietary exposures of HBCDs and PBDEs through seafood were 0.45-34 ng kg body weight(-1)d(-1), and 0.054-6.8 ng kg body weight(-1)d(-1), respectively. These exposure levels were more than 1000 times lower than the lowest observable effects or no observable adverse effects levels for HBCDs and PBDEs, respectively.
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Bivalvos/metabolismo , Éteres Difenilos Halogenados/metabolismo , Hidrocarburos Bromados/metabolismo , Hidrocarburos Clorados/metabolismo , Contaminantes Químicos del Agua/metabolismo , Animales , Monitoreo del Ambiente , Retardadores de Llama/metabolismo , Geografía , Japón , Océano Pacífico , Agua de Mar/químicaRESUMEN
BACKGROUND: Mycophenolate mofetil (MMF) is being used increasingly in children with steroid-dependent nephrotic syndrome (SDNS). However, there is limited information on the optimal therapeutic range for mycophenolic acid (MPA), the active metabolite of MMF, in these patients. METHODS: 26 patients with SDNS (mean age 13.1 years, 19 with minimal change disease and 7 with focal segmental glomerulosclerosis) who had received MMF for at least 6 months after longterm cyclosporine (CsA, mean 56 months) at Saitama Children's Medical Center between September 2002 and August 2008 were analyzed. MMF was introduced at an initial dose of 250 mg/12 h, adjusted to maintain target predose MPA at greater than 2 microg/ml (maximum 1 g twice daily) gradually over 4 weeks. After the introduction of MMF, the dosages of both CsA and prednisolone (PSL) were tapered off if possible. RESULTS: The mean MMF dose required was 34 +/- 6 mg/kg, which maintained the mean predose MPA levels of 3.1 mg/ml. In 26 patients, treatment with MMF for a mean follow-up period of 19 months (range 7 - 42), resulted in a reduction of the mean PSL dose from 0.33 +/- 0.23 to 0.17 +/- 0.11 mg/kg per day (p < 0.01) and mean CsA dose from 3.2 +/- 1.7 to 1.3 +/- 1.8 mg/kg per day (p < 0.01). The mean 12-monthly relapse rates decreased from 2.5 +/- 1.4 to 0.8 +/- 1.2 episodes (p < 0.01). In 20 patients treated with MMF (77%), the dose of PSL and/or CsA was successfully tapered with a reduction in the relapse rates. In 6 patients, however, CsA therapy was reintroduced or its dose was increased because of treatment failure. The patients whose average predose MPA levels were less than 3 microg/ml were significantly likely to have treatment failure (p < 0.05). 2 patients reduced the MMF dosage because of anemia or herpes labialis. However, no severe gastrointestinal discomfort was seen in any patients. Despite long-term CsA therapy, marked tubulointerstitial fibrosis developed during MMF therapy in surveillance biopsies of only one of these five patients. CONCLUSIONS: Therapy with MMF based on the predose MPA levels can be a less toxic alternative to CsA or in some cases a useful additional medication to allow for a reduction in the CsA and/or PSL dosage.
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Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Síndrome Nefrótico/tratamiento farmacológico , Adolescente , Edad de Inicio , Niño , Preescolar , Femenino , Glucocorticoides/uso terapéutico , Humanos , Lactante , Masculino , Ácido Micofenólico/uso terapéutico , Prednisolona/uso terapéutico , Estudios Prospectivos , Estadísticas no Paramétricas , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
An impact of serum hepatitis B virus (HBV) DNA on hepatocarcinogenesis has not been investigated in a cohort of patients with non-B, non-C cirrhosis. Eighty-two consecutive Japanese patients with cirrhosis, who showed negative hepatitis B surface antigen and negative anti-hepatitis C virus, were observed for a median of 5.8 years. Hepatitis B virus core (HBc) region and HBx region were assayed with nested polymerase chain reaction. Both of HBc and HBx DNA were positive in 9 patients (11.0%) and both were negative in 73. Carcinogenesis rates in the whole patients were 13.5% at the end of the 5th year and 24.6% at the 10th year. The carcinogenesis rates in the patients with positive DNA group and negative DNA group were 27.0% and 11.8% at the end of the 5th year, and 100% and 17.6% at the 10th year, respectively (P = 0.0078). Multivariate analysis showed that men (P = 0.04), presence of HBc and HBx DNA (hazard ratio: 8.25, P = 0.003), less total alcohol intake (P = 0.010), older age (P = 0.010), and association of diabetes (P = 0.005) were independently associated with hepatocellular carcinogenesis. Existence of serum HBV DNA predicted a high hepatocellular carcinogenesis rate in a cohort of patients with non-B, non-C cirrhosis.
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Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , ADN Viral/sangre , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/complicaciones , Cirrosis Hepática/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Antígenos del Núcleo de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Humanos , Japón/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Transactivadores/genética , Proteínas Reguladoras y Accesorias Virales/genéticaRESUMEN
Chromosome 1p13 is linked with schizophrenia in Japanese families, and one of the candidate genes in this region is the netrin G1 (NTNG1) gene at 1p13.3. Associations of 56 tag single-nucleotide polymorphisms (SNPs) with schizophrenia were explored by transmission disequilibrium analysis in 160 Japanese trios and by case-control analysis in 2,174 Japanese cases and 2,054 Japanese controls. An association between SNP rs628117 and schizophrenia was identified by case-control comparison (nominal allelic p=0.0009; corrected p=0.006). The associated polymorphism is located in intron 9 and in the haplotype block encompassing the alternatively spliced exons of the gene. Allelic association of a different SNP in the same haplotype block in Japanese families was previously reported. These findings support that the NTNG1 gene is associated with schizophrenia in the Japanese.