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1.
Rinsho Ketsueki ; 64(11): 1415-1420, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-38072427

RESUMO

Here we describe two patients that required interruption of a busulfan (BU) containing conditioning regimen due to severe mental disorder before stem cell transplantation. The first patient was a 66-year-old man scheduled for unrelated peripheral blood stem cell transplantation with fludarabine/BU conditioning for myelodysplastic syndrome. He received 9.6 mg/kg BU and developed hallucinations that worsened the next day. BU was stopped on the final day, but the patient became comatose (grade 4). He recovered the next day. The second patient was a 69-year-old man scheduled for autologous peripheral blood stem cell transplantation with thiotepa (TT)/BU conditioning for cerebral nervous system relapse of mantle cell lymphoma. He received 12.8 mg/kg BU and developed hallucinations. His mental symptoms worsened on the next day, and thus administration was stopped on the second day of TT. His symptoms improved the next day. Both patients were over 65 years old, and their psychiatric symptoms worsened 1-2 days after the final dose of BU. Our findings suggest that BU may cause psychiatric disorders in elderly patients. When performing BU conditioning, it may be necessary to avoid azole antifungal medication and acetaminophen and to reduce the dose or perform therapeutic dose monitoring for elderly patients.


Assuntos
Bussulfano , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Idoso , Humanos , Masculino , Bussulfano/efeitos adversos , Ciclofosfamida , Alucinações/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva Local de Neoplasia , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina
2.
Palliat Med Rep ; 4(1): 71-78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36960234

RESUMO

Background: Patients with hematological malignancies (HMs) are reported to receive more aggressive care at the end of life (EOL) than patients with solid tumors. However, the reasons behind this occurrence are not fully understood. Objectives: To examine whether the care at EOL for HMs is mainly because of the disease characteristics or hematologists' attitudes and systems of care, we compared the EOL care of patients with acute myeloid leukemia (AML) and diffuse large B cell lymphoma (DLBCL). Design: We retrospectively analyzed the EOL care of patients with AML and DLBCL younger than 80 years who were receiving combination chemotherapy at a city hospital in Japan. Results: Fifty-nine patients with AML and 65 with DLBCL were included. Those with AML received chemotherapy more often within their last 30 days (48% vs. 19%, p < 0.001) and 14 days (37% vs. 1.5%, p < 0.001) of life, and consulted the palliative team less frequently (5.3% vs. 29%, p < 0.001). In the last 3 years, the mortality rate in hematological wards decreased from 74% to 29% in the DLBCL group, but only from 95% to 90% in the AML group. In multivariate analysis, AML (odds ratio [OR] 0.065) and death before 2018 (OR, 0.077) were significant factors associated with reduced referrals to specialized palliative teams. Conclusion: Patients with AML tend to have lesser access to specialized palliative care and fewer options for their place of death than those with DLBCL. Detailed EOL care plans are needed for these patients, considering the characteristics of the disease.

3.
Sci Rep ; 13(1): 1148, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670169

RESUMO

The pathophysiology underlying major depressive disorder (MDD) and schizophrenia is related to endocrine system functions and includes changes in the blood levels of cortisol and insulin-like growth factor 1 (IGF-1). However, these hormones have not been investigated simultaneously in patients with MDD and schizophrenia. We investigated the differences in serum cortisol and IGF-1 levels among patients with MDD and schizophrenia and controls. We included 129 patients with MDD, 71 patients with schizophrenia, and 71 healthy volunteers. Blood tests were performed between 6:00 am and 11:00 am after fasting. Serum cortisol levels were significantly higher in patients with schizophrenia than in patients with MDD and controls. Serum cortisol levels were significantly higher in patients with MDD than in controls. Serum IGF-1 levels were higher in both patient groups than in controls, whereas there was no significant difference between patients with MDD and schizophrenia. Both cortisol and IGF-1 levels were positively correlated with the Hamilton Rating Scale for Depression score in patients with MDD, whereas cortisol level was positively correlated and IGF-1 level was negatively correlated with the Brief Psychiatric Rating Scale score in patients with schizophrenia. The differences in the level of these hormones suggest pathophysiological differences between these disorders.


Assuntos
Transtorno Depressivo Maior , Esquizofrenia , Humanos , Hidrocortisona , Fator de Crescimento Insulin-Like I/metabolismo , Jejum
4.
Intern Med ; 62(3): 465-468, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35793964

RESUMO

Recent studies have reported that autoantibodies against glial fibrillary acidic protein (GFAP), a major cytoskeletal protein expressed in astrocytes, can lead to GFAP astrocytopathy, an autoimmune central nervous system inflammatory disease. We herein report the unique case of a 59-year-old Japanese woman with GFAP astrocytopathy who presented with characteristic symptoms, including signs of meningeal irritation, cerebellar ataxia, and bladder/rectal dysfunction, in the absence of specific findings on initial brain magnetic resonance imaging (MRI). The patient exhibited new abnormal changes mainly in the brainstem on follow-up MRI, illustrating the need to recognize that MRI abnormalities may appear later in GFAP astrocytopathy.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalopatias , Doenças do Sistema Nervoso Central , Feminino , Humanos , Pessoa de Meia-Idade , Proteína Glial Fibrilar Ácida , Encéfalo , Imageamento por Ressonância Magnética , Autoanticorpos
5.
Cancer Immunol Immunother ; 72(6): 1493-1504, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36477623

RESUMO

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors.


Assuntos
Proteína HMGB1 , Hipertermia Induzida , Melanoma Experimental , Animais , Camundongos , Proteína HMGB1/metabolismo , Fator de Necrose Tumoral alfa , Ácido Glicirrízico/uso terapêutico , Adjuvantes Imunológicos , Fenômenos Magnéticos , Camundongos Endogâmicos C57BL , Imunoterapia , Microambiente Tumoral
6.
Int J Hematol ; 117(4): 618-621, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36309629

RESUMO

COVID-19 mRNA vaccines manufactured by Pfizer-BioNTech and Moderna have been approved in many countries, and have been administered since 2020. Recent reports of mRNA vaccination exacerbating autoimmune hematologic disorders, such as immune thrombocytopenia or autoimmune hemolytic anemia, have caught the attention of the general public, resulting in alarm over the risks of serious consequences. Meanwhile, in very rare cases, vaccination was reported to trigger new onset of hemolytic anemia. However, it remains unknown whether this was a transient reaction or a persistent event, because all cases reported to date were immediately treated with corticosteroids or rituximab. Here, we present a case of newly diagnosed cold agglutinin disease after a third COVID-19 mRNA vaccination. The patient was followed for 4 months without treatment and continued to exhibit high levels of cold agglutinin and aggregation of red blood cells. The present case indicates that the disease can become chronic, and provides insights into the pathogenesis and treatment strategies.


Assuntos
Anemia Hemolítica Autoimune , COVID-19 , Púrpura Trombocitopênica Idiopática , Humanos , Anemia Hemolítica Autoimune/etiologia , COVID-19/prevenção & controle , Eritrócitos , RNA Mensageiro , Vacinação/efeitos adversos
7.
Am J Case Rep ; 23: e937215, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36203333

RESUMO

BACKGROUND Peripherally inserted central catheters (PICCs) are commonly used by clinicians in daily practice as a safe and reliable alternative to central venous catheters. While there are advantages to the use of PICCs, such as a low insertion-related complication rate and cost-effectiveness, using PICCs may expose patients to life-threatening severe complications such as a central line-associated bloodstream infection and deep venous thrombosis (DVT). There have been no reports of infectious myositis associated with PICC insertion. CASE REPORT We report a case of infectious myositis related to PICC insertion complicated by brachial DVT in a 43-year-old immunocompromised patient with myelodysplastic syndrome. Despite the administration of broad-spectrum antibiotics, the patient's condition did not improve. He developed septic shock and required emergency excision of the infected and necrotic muscles. Although the pathogen responsible for the infection was unknown, infectious myositis and myonecrosis were observed intraoperatively. Furthermore, histopathological examination revealed evidence of infectious myositis in the biceps brachii and brachial muscles. The septic shock resolved with treatment and the patient survived with residual elbow joint dysfunction. CONCLUSIONS We present a case of infectious myositis related to PICC insertion. We believe that urgent resection of infected and necrotic tissues, rather than broad-spectrum antimicrobial therapy alone, was essential to save the patient's life.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Miosite , Choque Séptico , Adulto , Antibacterianos , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Humanos , Masculino , Miosite/etiologia , Miosite/terapia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Choque Séptico/etiologia
8.
Rice (N Y) ; 15(1): 54, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36315339

RESUMO

Iron is an essential micronutrient for living organisms, but its solubility is extremely low under alkaline conditions. Plants often suffer from iron deficiency chlorosis in calcareous soils, which consist of approximately 30% of the world's cultivated area, severely limiting plant productivity. Iron deficiency anemia is also a widespread problem in humans, especially in Asian and African people who take up iron mainly from staple foods containing low iron concentrations. Transgenic manipulation of genes involved in plant iron uptake, translocation, and storage has made improvements in enhancing iron deficiency tolerance or iron accumulation in edible parts, but these two properties have been characterized separately. We previously produced transgenic rice lines, with concomitant improvement of iron deficiency tolerance and grain iron accumulation by knocking-down OsHRZ ubiquitin ligases, which negatively regulate iron deficiency response and iron accumulation in rice. In the present report, we aimed to further improve the iron deficiency tolerance and grain iron accumulation of OsHRZ knockdown rice by the simultaneous introduction of the engineered ferric-chelate reductase gene Refre1/372 under the control of the OsIRT1 promoter for further enhancement of iron uptake. We obtained several transgenic rice lines with repressed OsHRZ expression and induced Refre1/372 expression. These lines showed a variable degree of iron deficiency tolerance in calcareous soils, with increased iron accumulation in brown seeds under both iron-deficient and iron-sufficient soil cultures. Selected OsHRZ knockdown plus Refre1/372 lines showed similar or better growth compared with that of singly introduced OsHRZ knockdown or Refre1/372 lines in calcareous soils under both non-submerged and submerged conditions. After submerged calcareous soil cultivation, these OsHRZ knockdown plus Refre1/372 lines accumulated 2.5-4.3 times and 17-23 times more iron concentrations than that of non-transformants in brown rice and straw, respectively, which was comparable or superior to a single OsHRZ knockdown line. Our results indicate that the combined introduction of OsHRZ knockdown and OsIRT1 promoter-Refre1/372 is highly effective in further improving the iron deficiency tolerance without compromising the iron accumulation of the OsHRZ knockdown effects.

9.
Jpn J Clin Oncol ; 52(9): 1001-1007, 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-35661218

RESUMO

BACKGROUND: The aim of the study was to investigate a prevalence of sarcopenia in patients with gynecological cancer in accordance with current diagnostic criteria of sarcopenia. METHODS: A series of 513 patients with gynecological cancer who were intended to newly receive initial or salvage treatment were recruited in a prospective study. Eligible patients were examined with dual energy X-ray absorptiometry and underwent handgrip strength test and the Short Physical Performance Battery before treatment. Sarcopenia was defined as both low skeletal muscle mass (skeletal muscle mass index) and low muscle strength (handgrip strength of <18.0 kg) or both low skeletal muscle mass index and low physical performance (Short Physical Performance Battery score of ≤9). RESULTS: A total of 475 patients (92.6%) were completely assessed in this study. Eligible patients' median age was 60 years (range: 29-89 years). Frequencies of patients with low skeletal muscle mass index, low hand grip strength and low Short Physical Performance Battery were 118 (24.8%), 70 (14.7%) and 80 (16.8%), respectively. Sarcopenia was finally identified in 45 patients (9.5%), which accounted for 38.1% of patients with low skeletal muscle mass index, 64.3% of the patients with low hand grip strength and 56.3% of the patients with low physical performance, respectively. CONCLUSIONS: The prevalence of sarcopenia of 9.5% in patients with gynecological malignancy who were scheduled to newly receive an initial or a salvage treatment. A large-scale, nation-wide study might be planned to elucidate an accurate prevalence of sarcopenia among gynecologic cancer patients.


Assuntos
Neoplasias , Sarcopenia , Feminino , Força da Mão , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Neoplasias/patologia , Prevalência , Estudos Prospectivos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/etiologia
10.
Materials (Basel) ; 15(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35591417

RESUMO

The influence of cold-rolling directions on the recrystallization texture evolution of pure iron was examined. As-received pure iron sheets were cold-rolled under two different conditions (specimens A and B). Specimen A was cold-rolled in the vertical direction against the cold-rolling direction of the as-received sheet. Specimen B was cold-rolled in the vertical direction against the cold-rolling direction of the as-received sheet, and then in the cold-rolling direction of the as-received sheet. Cold-rolled specimens were heated to each desired temperature before being quenched in water to room temperature (298 ± 2 K). Both cold-rolled specimens showed the development of γ-fiber and {100}<011> orientation. Additionally, γ-fiber formed comparatively more in cold-rolled specimen A, while α-fiber developed comparatively more in cold-rolled specimen B. Strain distribution in cold-rolled specimen A was presumably inhomogeneous, whereas that in cold-rolled specimen B was rather uniform at the macro-scale. The formation of γ-fiber was confirmed in annealed specimen A. In annealed specimen B, however, the recrystallization texture tended to be random, and the formation of α-fiber was observed. Furthermore, the formation of Goss orientation in both annealed specimens was established. Recrystallized ferrite grains with Goss orientation nucleated in high strain regions of cold-rolled specimen. These findings show that by devising the cold-rolling direction, it is possible to discover new types of recrystallization textures.

11.
Cureus ; 14(3): e23374, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35475058

RESUMO

We herein report a case of genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein (PrP) gene diagnosed at a preserved cognitive function stage. Although neuropsychological tests revealed normal cognitive functions, increased signal intensity in the cerebral cortices with swelling on diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI) prompted genetic testing for the PrP gene. This case suggests that cortical hyperintensity on DWI with swelling may be a useful finding of brain MRI for the diagnosis of V180I genetic CJD even at an extremely early stage, such as at the preserved cognitive function stage.

12.
Exp Hematol ; 109: 45-54, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35245608

RESUMO

Somatic mutation of DNMT3A (DNA methyltransferase 3 alpha) is implicated in the development of a wide range of hematological disorders, including clonal hematopoiesis of indeterminate potential. To elucidate the functional roles of endogenous levels of a DNMT3A R882 mutant, we generated a novel Dnmt3a R878C conditional knock-in mouse model. In contrast to viable heterozygotes, mice homozygous for the Dnmt3a R878C mutation in the hematopoietic system were not viable (Dnmt3a R878C is homologous to human DNMT3A R882C). Hematopoietic cell-specific heterozygous expression of Dnmt3a R878C led to significant expansion of adult quiescent hematopoietic stem cells (HSCs); however, these mice had no hematological malignancies. The expanding HSC population in heterozygous Dnmt3a R878C knock-in mice had an accumulation of G0-phase cells. In contrast to aberrantly enhanced self-renewal capacity in vitro, heterozygous Dnmt3a R878C knock-in HSCs had no competitive repopulating advantage in vivo over wild-type HSCs. Considering the capacity of the heterozygous Dnmt3a R878C mutant for HSC pool expansion, our Dnmt3a R878C knock-in mouse line is a useful platform on which to dissect the pathophysiology of clonal hematopoiesis. This mouse line can also help to elucidate the biological and molecular actions of DNMT3A mutations in the malignant transformation of normal HSCs.


Assuntos
DNA (Citosina-5-)-Metiltransferases , Hematopoese , Animais , Hematopoiese Clonal , DNA (Citosina-5-)-Metiltransferases/genética , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Heterozigoto , Camundongos
13.
Intern Med ; 61(9): 1345-1352, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34670884

RESUMO

Objective Few reports have described the real-world outcomes of rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) plus response-adapted whole-brain radiotherapy (WBRT) for elderly patients with primary central nervous system lymphoma (PCNSL). We evaluated the outcome of this regimen. Methods We evaluated >60-year-old patients with newly diagnosed PCNSL who received R-MPV plus WBRT from January 2010 to December 2019 at Toyohashi Municipal Hospital. The patients' characteristics, regimen enforcement, response rate, survival, and toxicity were analyzed. Patients Ten patients were consecutively enrolled. Their median age was 69 years old, and 60% had a performance status of 3 or 4 before induction therapy. Results Seven patients achieved a complete response after induction, and all 10 patients achieved a complete response after consolidation. Seven received reduced-dose WBRT at 23.4 Gy, and 2 received WBRT at 45 Gy. The median follow-up was 44.4 months; the 3-year progression-free survival and overall survival rates were 60% and 80%, respectively; and the cumulative incidence of relapse was 40%. The incidence of symptomatic delayed neurotoxicity was 70%. Of the 7 patients who received reduced-dose WBRT, 4 (57%) developed delayed neurotoxicity, including 1 severely affected patient. Only one patient survived without relapse and delayed neurotoxicity. The ratio of patients who developed relapse or delayed neurotoxicity that impaired daily life was 33% and 100% in the MTX high- and low-intensity groups, respectively. Conclusion This regimen in elderly patients is unsatisfactory because of delayed neurotoxicity. We should consider maintaining an adequate MTX intensity, postponing or minimizing WBRT, and choosing high-dose consolidation therapy for select patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encéfalo/patologia , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/radioterapia , Terapia Combinada , Humanos , Linfoma/tratamento farmacológico , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
14.
PCN Rep ; 1(3): e28, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38868699

RESUMO

Aim: There is little evidence on the effects of antipsychotic polypharmacy on metabolic parameters in patients with schizophrenia. Thus, this cross-sectional study explored the associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia. Methods: We obtained metabolic parameter data from 19,675 patients with schizophrenia. Of these, 1380 (7.0%), 8422 (42.8%), 6326 (32.2%), and 3547 (18.0%) were treated with none, one, two, and three or more antipsychotics, respectively. We compared eight metabolic parameters among the four groups using univariate analyses. We then performed multiple regression analysis to assess the effect of the number of antipsychotics prescribed on metabolic parameters after controlling for the effects of age, sex, type of care (outpatient/inpatient), chlorpromazine-equivalent dose, and antipsychotic type (aripiprazole, olanzapine, and risperidone). Results: There were significant differences in body mass index (BMI), systolic and diastolic blood pressure (dBP), total cholesterol, low-density lipoprotein cholesterol, and triglycerides among the four groups. The multiple regression analysis showed that the number of antipsychotics prescribed was significantly correlated with BMI and dBP (standardized regression coefficient = 0.031 and 0.026, respectively). Conclusion: Our results suggested that the number of antipsychotics prescribed adversely affects BMI and dBP. Clinicians should avoid inappropriate antipsychotic polypharmacy, especially polypharmacy involving three or more antipsychotics.

15.
Front Hum Neurosci ; 15: 755025, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899218

RESUMO

Objective: We conducted this non-randomized prospective interventional study to clarify the relationship between improved attention-deficit hyperactivity disorder (ADHD) symptoms and regional brain activity. Methods: Thirty-one adult patients underwent near-infrared spectroscopy examinations during a go/no-go task, both before and 8 weeks after atomoxetine administration. Results: Clinical symptoms, neuropsychological results of the go/no-go task, and bilateral lateral prefrontal activity significantly changed. A positive correlation was observed between right dorsolateral prefrontal cortex activity and Conners' Adult ADHD Rating Scales scores. Before atomoxetine administration, no correlations between prefrontal cortex activity and clinical symptoms were observed in all cases. When participants were divided into atomoxetine-responder and non-responder groups, a positive correlation was observed between prefrontal cortex activity and clinical symptoms in the non-responder group before treatment but not in the responder group, suggesting that non-responders can activate the prefrontal cortex without atomoxetine. Conclusions: Individuals with increased ADHD symptoms appear to recruit the right dorsolateral prefrontal cortex more strongly to perform the same task than those with fewer symptoms. In clinical settings, individuals with severe symptoms are often observed to perform more difficultly when performing the tasks which individuals with mild symptoms can perform easily. The atomoxetine-responder group was unable to properly activate the right dorsolateral prefrontal cortex when necessary, and the oral administration of atomoxetine enabled these patients to activate this region. In brain imaging studies of heterogeneous syndromes such as ADHD, the analytical strategy used in this study, involving drug-responsivity grouping, may effectively increase the signal-to-noise ratio.

16.
Medicine (Baltimore) ; 100(27): e26552, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232195

RESUMO

BACKGROUND: Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy. METHODS: Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography. RESULTS: The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ±â€Š.04 mg/kg [mean ±â€Šstandard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ±â€Š.31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ±â€Š32.3 ng/mL in 7 responders and was significantly higher than 29.5 ±â€Š23.9 ng/mL (P < .01) for the 29 non-responders. CONCLUSIONS: These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.


Assuntos
Cloridrato de Atomoxetina/farmacocinética , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Inibidores da Captação Adrenérgica/farmacocinética , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
17.
Int J Comput Assist Radiol Surg ; 16(3): 349-361, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33655468

RESUMO

PURPOSE: In recent years, fully convolutional networks (FCNs) have been applied to various medical image segmentation tasks. However, it is difficult to generate a large amount of high-quality annotation data to train FCNs for medical image segmentation. Thus, it is desired to achieve high segmentation performances even from incomplete training data. We aim to evaluate performance of FCNs to clean noises and interpolate labels from noisy and sparsely given label images. METHODS: To evaluate the label cleaning and propagation performance of FCNs, we used 2D and 3D FCNs to perform volumetric brain segmentation from magnetic resonance image volumes, based on network training on incomplete training datasets from noisy and sparse annotation. RESULTS: The experimental results using pseudo-incomplete training data showed that both 2D and 3D FCNs could provide improved segmentation results from the incomplete training data, especially by using three orthogonal annotation images for network training. CONCLUSION: This paper presented a validation for label cleaning and propagation based on FCNs. FCNs might have the potential to achieve improved segmentation performances even from sparse annotation data including possible noises by manual annotation, which can be an important clue to more efficient annotation.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Humanos , Imageamento Tridimensional/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
BMC Psychiatry ; 21(1): 157, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731067

RESUMO

BACKGROUND: Hormones of the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA), and hypothalamic-pituitary-somatotropic (HPS) axes are potentially involved in major depressive disorder (MDD), but these hormones have not been simultaneously investigated in male patients with MDD. We investigated the association between male MDD symptoms and estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF1). METHODS: Serum estradiol, testosterone, cortisol, DHEAS, and IGF1 levels were measured in 54 male patients with MDD and 37 male controls and were compared with clinical factors. We investigated the associations between hormone levels and Hamilton Depression Rating Scale (HAM-D) scores. The correlations among hormones were also investigated. RESULTS: Patients had significantly lower estradiol levels than controls (22.4 ± 8.4 pg/mL vs. 26.1 ± 8.5 pg/mL, P = 0.040). Serum estradiol levels were negatively correlated with HAM-D scores (P = 0.000094) and positively correlated with Global Assessment of Functioning scores (P = 0.000299). IGF1 levels and the cortisol:DHEAS ratio were higher in patients than in controls (IGF1: 171.5 ± 61.8 ng/mL vs. 144.1 ± 39.2 ng/mL, P = 0.011; cortisol:DHEAS ratio: 0.07 ± 0.05 vs. 0.04 ± 0.02, P = 0.001). DHEAS levels were lower in patients than in controls (227.9 ± 108.4 µg/dL vs. 307.4 ± 131.2 µg/dL, P = 0.002). IGF1, cortisol:DHEAS ratio, and DHEAS were not significantly correlated with HAM-D scores. Cortisol and testosterone levels were not significantly different between patients and controls. Serum estradiol levels were positively correlated with DHEAS levels (P = 0.00062) in patients, but were not significantly correlated with DHEAS levels in controls. CONCLUSION: Estradiol may affect the pathogenesis and severity of patients with MDD in men, and other hormones, such as those in the HPA and HPS axes, may also be involved in male MDD. Additionally, a correlation between estradiol and DHEAS may affect the pathology of MDD in men.


Assuntos
Transtorno Depressivo Maior , Sulfato de Desidroepiandrosterona , Humanos , Hidrocortisona , Fator de Crescimento Insulin-Like I , Masculino , Testosterona
19.
Neuropsychiatr Dis Treat ; 16: 2229-2236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061393

RESUMO

BACKGROUND: Reliable and easy screening for metabolic syndrome (MetS) is important for patients with schizophrenia. The aim of this study was to assess the predictive utility of body mass index (BMI) for MetS among patients with schizophrenia in Japan. METHODS: In total, 8468 patients (4705 males, 3763 females) with schizophrenia or schizoaffective disorders based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), or the International Classification of Diseases, tenth revision (ICD-10), were assessed for MetS using the criteria of the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A). We applied a stratum-specific likelihood ratio (SSLR) analysis, which is independent of the prevalence of the target disease. RESULTS: The mean (± standard deviation) age of these patients was 57.4 ± 13.5 years. The prevalence of MetS was 20.4%. Among males, the SSLRs predicting MetS were 0.03 (95% CI 0.02-0.06), 0.54 (95% CI 0.48-0.60), 2.77 (95% CI 2.44-3.14) and 8.75 (95% CI 7.40-10.36) for BMI <20 kg/m2, 20 kg/m2 ≤ BMI < 25 kg/m2, 25 kg/m2≤ BMI < 28 kg/m2, and 28 kg/m2≤BMI, respectively. For females, the SSLRs predicting MetS were 0.08 (95% CI 0.05-0.12), 0.73 (95% CI 0.66-0.82), 2.50 (95% CI 2.16-2.90) and 4.83 (95% CI 4.12-5.67) for the same BMI categories, respectively. CONCLUSION: The predictive utility of BMI is confirmed, and BMI has more predictive value in males than in females. Patients with a BMI of 28 kg/m2 or greater had a significantly higher SSLR than those with a BMI less than 28 kg/m2.

20.
Int J Comput Assist Radiol Surg ; 15(10): 1653-1664, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32734313

RESUMO

PURPOSE: Noninvasiveness and stability are significant issues in laparoscopic liver resection. Inappropriate grasping force can cause damage or serious bleeding to the liver. In addition, instability of grasping can result unsafe operations or wavered cutting. We propose a surgical device to improve stability of liver manipulation. METHODS: A proposed device adheres to the liver surface with suction fixation, then tunes its stiffness to being hard and shapes like as a bulge on the liver surface to be grasped with laparoscopic forceps. It consists of two soft beams, a chamber sponge, membrane covering the device upper, suburb extrusion wing membrane, a vacuuming tube and to-be-grasped bars. The beams are designed as being non-stretchable and easy to bend. The device is connected to a medical vacuuming pump to vacuum air in the device and then gets hard to transfer forceps operation well. This stiffness tuning mechanism by pneumatic control features the device for achieving good liver shape followability and forceps operation propagation less invasively. The proposed device was tested with rubber phantoms and porcine livers on shape followability, stiffness transition, liver invasiveness and operational usability in the experiments. RESULTS: Performance of the proposed device was assessed in experiments. The device showed good object-shape followability. It held the liver with 2.43-N force for vertical lifting and 4.90-N shear force with - 80 kPa vacuuming pressure. Invasiveness was reduced to acceptable level of liver damage. In usability test, the device grasped the liver stably and transferred surgical forceps operations to the liver surface well. CONCLUSION: The proposed device showed effective performance to improve laparoscopic liver manipulation. It held the liver stably and less invasively and transferred forceps operation force to the liver surface well.


Assuntos
Desenho de Equipamento , Laparoscopia/instrumentação , Fígado/cirurgia , Sucção/instrumentação , Instrumentos Cirúrgicos , Animais , Microcirurgia/instrumentação , Suínos
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