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1.
Nature ; 595(7869): 661-666, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34321672

RESUMO

Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1-6, an inverse Hall angle that varies as temperature squared7-9 and a linear-in-field magnetoresistance10-13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple bandstructure. The prevailing consensus is that strange metallicity in the cuprates is tied to a quantum critical point at a doping p* inside the superconducting dome14,15. Here we study the high-field in-plane magnetoresistance of two superconducting cuprate families at doping levels beyond p*. At all dopings, the magnetoresistance exhibits quadrature scaling and becomes linear at high values of the ratio of the field and the temperature, indicating that the strange-metal regime extends well beyond p*. Moreover, the magnitude of the magnetoresistance is found to be much larger than predicted by conventional theory and is insensitive to both impurity scattering and magnetic field orientation. These observations, coupled with analysis of the zero-field and Hall resistivities, suggest that despite having a single band, the cuprate strange-metal region hosts two charge sectors, one containing coherent quasiparticles, the other scale-invariant 'Planckian' dissipators.

2.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684790

RESUMO

In this study, hydrogen boride films are fabricated by ion-exchange treatment on magnesium diboride (MgB2) films under ambient temperature and pressure. We prepared oriented MgB2 films on strontium titanate (SrTiO3) substrates using pulsed laser deposition (PLD). Subsequently, these films were treated with ion exchangers in acetonitrile solution. TOF-SIMS analysis evidenced that hydrogen species were introduced into the MgB2 films by using two types of ion exchangers: proton exchange resin and formic acid. According to the HAXPES analysis, negatively charged boron species were preserved in the films after the ion-exchange treatment. In addition, the FT-IR analysis suggested that B-H bonds were formed in the MgB2 films following the ion-exchange treatment. The ion-exchange treatment using formic acid was more efficient compared to the resin treatment; with respect to the amount of hydrogen species introduced into the MgB2 films. These ion-exchanged films exhibited photoinduced hydrogen release as observed in a powder sample. Based on the present study, we expect to be able to control the morphology and hydrogen content of hydrogen boride thin films by optimising the ion-exchange treatment process, which will be useful for further studies and device applications.

3.
Br J Surg ; 107(6): 632-635, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32246473

RESUMO

Probe electrospray ionization mass spectrometry (PESI-MS) is an ambient ionization-based mass spectrometry method that surpasses the original electrospray ionization technique in features such as the rapidity of analysis, simplicity of the equipment and procedure, and lower cost. This study found that the PESI-MS system with machine learning has the potential to establish a lipid-based diagnosis of breast cancer with higher accuracy, using a simpler approach. Rapid mass spectrometry for breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Mama/metabolismo , Metabolismo dos Lipídeos , Espectrometria de Massas por Ionização por Electrospray , Biópsia , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Sensibilidade e Especificidade
4.
J Infect Chemother ; 26(3): 294-297, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31735633

RESUMO

Corynebacterium simulans was first reported in 2000. Although it is a member of the normal skin flora, some cases of C. simulans infection have been reported. Other Corynebacterium spp. rarely cause chronic pyogenic spondylitis, and pyogenic spondylitis caused by C. simulans has not been reported at all. Here we report a case of acute pyogenic spondylitis due to C. simulans. A 78-year-old man with diabetes mellitus visited our hospital with a 3-day history of lower back pain and fever. Blood culture revealed C. simulans and magnetic resonance images of lumbar vertebrae showed pyogenic spondylitis. He recovered after treatment by vancomycin for 9 weeks and was discharged home. No recurrence has been observed for half a year. This is likely the first reported case of pyogenic spondylitis by C. simulans. In general, Corynebacterium spp. cause chronic pyogenic spondylitis, but this case showed an acute course.


Assuntos
Infecções por Corynebacterium , Corynebacterium , Espondilite , Doença Aguda , Idoso , Antibacterianos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Humanos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Vancomicina/uso terapêutico
5.
Eur J Neurol ; 26(3): 379-387, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30298540

RESUMO

The clinical outcomes of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (e.g. TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases, including PubMed, Scopus, Web of Science and Virtual Health Library, were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival were calculated using a random-effect model weighted by an inverse variance method. A total of 11 studies were finally selected from 2274 articles for meta-analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR, 1.96; 95% CI, 1.42-2.70), H3F3A mutation (HR, 3.21; 95% CI, 1.86-5.55) and EGFR amplification (HR, 1.67; 95% CI, 1.02-2.74). However, CDKN loss, ATRX mutation and coexisting gain of chromosome 7/loss of chromosome 10 showed no clinical significance in this glioma entity. Our study results demonstrated that IDH-wt LGGs are heterogeneous in clinical outcome and not all tumors have a poor prognosis. The presence of TERT promoter mutation, H3F3A mutation and EGFR amplification showed negative prognostic impacts in this tumor entity. These genetic events can be used to better stratify patient outcomes.


Assuntos
Neoplasias Encefálicas/diagnóstico , Marcadores Genéticos , Glioma/diagnóstico , Isocitrato Desidrogenase , Neoplasias Encefálicas/genética , Glioma/genética , Humanos
6.
Public Health ; 174: 18-21, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301551

RESUMO

OBJECTIVES: To describe the health information preferences in middle-aged Japanese workers based on health literacy (HL) levels and presence of medications. STUDY DESIGN: A cross-sectional study. METHODS: We performed a web-based questionnaire survey with Japanese workers aged below 60 years. HL was assessed using the total score of communicative skills (five items) and critical skills (four items) from the 14-item Health Literacy Scale. Regarding their health information preferences, participants were asked about the health information they wanted (four items), could easily understand (six items), or easily use (two items) and answered on a 4-point scale (strongly agree/agree/disagree/strongly disagree). The percentages of the affirmative responses (strongly agree or agree) were compared among tertiles based on the HL score. RESULTS: We obtained data from a total of 3387 volunteers, of whom 510 participants were on either antihypertensive, lipid-lowering, or antidiabetic drugs. Compared with the high HL and middle HL groups, low HL had fewer affirmative responses to most health information items. Health information items received 70% of affirmative responses even in the low HL level. They were visually shown by figures or pictures, highlighted by colors for important points, could be read in 1-2 min, and were accessed on the Internet, regardless of the presence of medications. Additionally, the explanation for mechanisms of medications or lifestyle to prevent or improve diseases showed high affinity in all HL levels, only for those on medications. CONCLUSIONS: This result generates a hypothesis that low HL individuals have a low interest in health information. Our data showed several possible forms of health information with high affinity based on HL levels that would help plan future population approaches.


Assuntos
Comportamento do Consumidor/estatística & dados numéricos , Informação de Saúde ao Consumidor , Letramento em Saúde/estatística & dados numéricos , Adulto , Estudos Transversais , Emprego/estatística & dados numéricos , Feminino , Humanos , Internet , Japão , Masculino , Pessoa de Meia-Idade , Doenças não Transmissíveis/prevenção & controle , Inquéritos e Questionários
7.
Lupus ; 27(2): 273-282, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28683654

RESUMO

Background Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997). The treatment protocol was a starting dose of prednisolone of 0.6-1.0 mg/kg/day for 2 weeks and then tapered to a maintenance dose, intravenous cyclophosphamide (500 mg biweekly for 3 months) and tacrolimus (3.0 mg/day). Tacrolimus was continued as maintenance therapy. Complete remission was defined as a spot urine protein/creatinine ratio of < 0.5 g/gCr with no active urine casts and a serum creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with cyclophosphamide and prednisolone. Results At baseline, the mean patient age was 41.5 ± 14.6 years (male:female ratio 2:13), urine protein/creatinine ratio 3.9 ± 2.3 g/gCr and serum creatinine 84.6 ± 34.6 µmol/L. Lupus nephritis classifications included classes IV ( n = 8), III + V ( n = 1), IV + V ( n = 5) and unclassified ( n = 1). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of thrombotic microangiopathy. Conclusions Multitarget therapy with cyclophosphamide and tacrolimus can be a therapeutic option for lupus nephritis. Clinical trials registration Combination therapy of tacrolimus and intravenous cyclophosphamide for remission induction of lupus nephritis, UMIN: 000004893, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005830&language=E . Date of registration: 18 January 2011.


Assuntos
Ciclofosfamida/farmacologia , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/farmacologia , Tacrolimo/farmacologia , Administração Intravenosa , Adulto , Creatinina/sangue , Ciclofosfamida/administração & dosagem , Quimioterapia Combinada/métodos , Inibidores Enzimáticos/farmacologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/farmacologia , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Projetos Piloto , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Estudos Prospectivos , Indução de Remissão , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Resultado do Tratamento
8.
BMC Pulm Med ; 18(1): 23, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29378571

RESUMO

BACKGROUND: Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis. CASE PRESENTATION: We present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis. In our series, 20% of patients who were treated with nivolumab developed pneumonitis, all of which occurred approximately 2 weeks after the initiation of nivolumab treatment. Prompt recognition of the nivolumab-induced pneumonitis allowed for successful resolution. Computed tomography scan images of the patients demonstrated predominantly cryptogenic organizing pneumonia patterns. All patients were males, who had been heavily treated with antitumor drugs prior to nivolumab. CONCLUSIONS: Our case series showed that nivolumab had a high incidence of drug-induced pneumonitis with early onset, supporting the need for renewed attention to nivolumab-induced pneumonitis, particularly in patients with a history of heavy antitumor treatments.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Pneumonia/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/epidemiologia , Tomografia Computadorizada por Raios X
9.
Andrologia ; 50(7): e13024, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29665107

RESUMO

Klinefelter syndrome is a condition in which a male patient has one Y chromosome and one or more extra X chromosomes. It is the most common sex chromosome disorder. Klinefelter syndrome is distinguished by many clinical features, such as infertility, high gonadotropin and low testosterone levels, increased height, and sparse body and facial hair. We report the case of a 32-year-old man who visited our hospital complaining of male infertility. Semen analysis showed azoospermia, and chromosomal analysis revealed a 47,XY,i(X)(q10) karyotype, which is a rare variant of Klinefelter syndrome. No spermatozoon was found on microdissection testicular sperm extraction, and the testis biopsy histology showed only Sertoli cells and hyalinised seminiferous tubules. 47,XY, i(X)(q10) has an additional isochromosome made of the long arm of the X chromosome, which shares some features of classical Klinefelter syndrome in many aspects, but patients are usually shorter than average height and have normal intelligence. In addition, to the best of our knowledge, no successful sperm extractions from 47,XY, i(X)(q10) patients were reported in the literature. The reports of patients who have undergone microdissection testicular sperm extraction are very rare. Further reports and studies of this chromosomal abnormality are needed.


Assuntos
Azoospermia/genética , Aberrações Cromossômicas , Cromossomos Humanos Y/genética , Síndrome de Klinefelter/genética , Adulto , Azoospermia/diagnóstico , Azoospermia/patologia , Biópsia , Humanos , Cariótipo , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/patologia , Masculino , Testículo/patologia
10.
Nature ; 469(7329): 189-93, 2011 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-21228872

RESUMO

As silicon is the basis of conventional electronics, so strontium titanate (SrTiO(3)) is the foundation of the emerging field of oxide electronics. SrTiO(3) is the preferred template for the creation of exotic, two-dimensional (2D) phases of electron matter at oxide interfaces that have metal-insulator transitions, superconductivity or large negative magnetoresistance. However, the physical nature of the electronic structure underlying these 2D electron gases (2DEGs), which is crucial to understanding their remarkable properties, remains elusive. Here we show, using angle-resolved photoemission spectroscopy, that there is a highly metallic universal 2DEG at the vacuum-cleaved surface of SrTiO(3) (including the non-doped insulating material) independently of bulk carrier densities over more than seven decades. This 2DEG is confined within a region of about five unit cells and has a sheet carrier density of ∼0.33 electrons per square lattice parameter. The electronic structure consists of multiple subbands of heavy and light electrons. The similarity of this 2DEG to those reported in SrTiO(3)-based heterostructures and field-effect transistors suggests that different forms of electron confinement at the surface of SrTiO(3) lead to essentially the same 2DEG. Our discovery provides a model system for the study of the electronic structure of 2DEGs in SrTiO(3)-based devices and a novel means of generating 2DEGs at the surfaces of transition-metal oxides.

11.
Eur Heart J ; 37(11): 890-899, 2016 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-26746633

RESUMO

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.


Assuntos
Adaptação Psicológica/fisiologia , Doenças Cardiovasculares/mortalidade , Idoso , Doenças Cardiovasculares/psicologia , Feminino , Humanos , Incidência , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
12.
Skin Res Technol ; 22(2): 181-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26037969

RESUMO

BACKGROUND/ PURPOSE: A skin movement artifact is a major problem in three-dimensional motion analysis. Furthermore, skin tension lines are important in plastic surgery. Skin tension depends upon the body area and the direction of resistance. From the perspective of skin continuity and clinical observation, we hypothesized that the contralateral side of the skin of the extremities moves in the opposite direction. This study aimed to examine kinematics of thigh skin including movement direction during pelvic sway. METHODS: Fifteen healthy men participated in this study. Kinematic data were obtained using a three-dimensional motion analysis system. To detect opposite skin movement, 42 markers were attached to the front, back, lateral, and medial sides of the thigh and pelvis. Front and back markers in the sagittal plane and lateral and medial markers in the frontal plane were arranged in a line connecting the hip and ankle joint centers, respectively. Subjects performed maximal pelvic movements in the anterior-posterior and rightward-leftward directions. RESULTS: The results showed that the front skin of the thigh was transferred upward and that the back skin was transferred downward during pelvic anterior sway. Opposite skin movements were observed during posterior pelvic sway. We also found that the lateral skin was transferred upward and that the medial skin was transferred downward during hip adduction and vice-versa during hip abduction. CONCLUSION: These findings suggest that the skin moves according to certain physiological rules.


Assuntos
Pontos de Referência Anatômicos/anatomia & histologia , Pontos de Referência Anatômicos/fisiologia , Articulações/anatomia & histologia , Articulações/fisiologia , Movimento/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Artefatos , Marcadores Fiduciais , Humanos , Imageamento Tridimensional/métodos , Perna (Membro)/fisiologia , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Coxa da Perna/anatomia & histologia , Coxa da Perna/fisiologia
13.
Orthod Craniofac Res ; 19(2): 83-92, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26790630

RESUMO

OBJECTIVE: To investigate the effects of diabetes on orthodontic tooth movement and orthodontically induced root resorption in rats. SETTING AND SAMPLE POPULATION: Twenty-three 10-week-old male Sprague-Dawley rats divided into control (n = 7), diabetes (n = 9), and diabetes + insulin (n = 7) groups. MATERIALS AND METHODS: Diabetes was induced by administering a single intraperitoneal injection of streptozotocin. Rats with a blood glucose level exceeding 250 mg/dl were assigned to the diabetes group. Insulin was administered daily to the diabetes + insulin group. A nickel-titanium closed-coil spring of 10 g was applied for 2 weeks to the maxillary left first molar in all rats to induce mesial tooth movement. Tooth movement was measured using microcomputed tomography images. To determine the quantity of root resorption, the mesial surfaces of the mesial and distal roots of the first molar were analyzed using both scanning electron microscopy and scanning laser microscopy. RESULTS: After 2 weeks, the amount of tooth movement in the diabetic rats was lower than that in the control rats. Root resorption was also significantly lower in the diabetic rats. These responses of the rats caused by diabetes were mostly diminished by insulin administration. CONCLUSIONS: Diabetes significantly reduced orthodontic tooth movement and orthodontically induced root resorption in rats. The regulation of blood glucose level through insulin administration largely reduced these abnormal responses to orthodontic force application.


Assuntos
Reabsorção da Raiz/etiologia , Animais , Diabetes Mellitus Experimental , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Técnicas de Movimentação Dentária , Microtomografia por Raio-X/efeitos adversos
14.
Phys Rev Lett ; 114(19): 195002, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26024175

RESUMO

A novel direct core heating fusion process is introduced, in which a preimploded core is predominantly heated by energetic ions driven by LFEX, an extremely energetic ultrashort pulse laser. Consequently, we have observed the D(d,n)^{3}He-reacted neutrons (DD beam-fusion neutrons) with the yield of 5×10^{8} n/4π sr. Examination of the beam-fusion neutrons verified that the ions directly collide with the core plasma. While the hot electrons heat the whole core volume, the energetic ions deposit their energies locally in the core, forming hot spots for fuel ignition. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with the yield of 6×10^{7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. A one-dimensional hydrocode STAR 1D explains the shell implosion dynamics including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions. A two-dimensional collisional particle-in-cell code predicts the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions, which could be an additional heating source when they reach the core. Since the core density is limited to 2 g/cm^{3} in the current experiment, neither hot electrons nor fast ions can efficiently deposit their energy and the neutron yield remains low. In future work, we will achieve the higher core density (>10 g/cm^{3}); then hot electrons could contribute more to the core heating via drag heating. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high gain fusion.

15.
Transpl Infect Dis ; 17(6): 810-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26354293

RESUMO

BACKGROUND: Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. METHODS: We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. RESULTS: Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). CONCLUSIONS: Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.


Assuntos
Antivirais/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Transplante de Células-Tronco/efeitos adversos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Relação Dose-Resposta a Droga , Ganciclovir/administração & dosagem , Ganciclovir/efeitos adversos , Ganciclovir/uso terapêutico , Humanos , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Valganciclovir
17.
Br J Cancer ; 111(4): 763-71, 2014 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-24937671

RESUMO

BACKGROUND: Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. METHODS: Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. RESULTS: Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. CONCLUSIONS: Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.


Assuntos
Fibroblastos/metabolismo , Interleucinas/metabolismo , Sistema de Sinalização das MAP Quinases , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Técnicas de Cocultura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Fosforilação , Processamento de Proteína Pós-Traducional , Receptores de Interleucina/metabolismo , Neoplasias Gástricas/patologia , Interleucina 22
18.
Transpl Infect Dis ; 16(5): 797-801, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25154638

RESUMO

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection, reverse seroconversion (RS), is a serious complication after allogeneic stem cell transplantation (alloHSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV-RS. This report is an update of the hepatitis B vaccine study. METHODS: In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. RESULTS: None of the 21 patients in the vaccine group developed HBV-RS and 12 controls developed HBV-RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody (HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. CONCLUSION: These results demonstrated the long-term effects of HBV vaccine for preventing HBV-RS after alloHSCT. Of note, no HBV-RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Transplante de Células-Tronco , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Feminino , Seguimentos , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
19.
Clin Radiol ; 69(3): e140-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24355660

RESUMO

AIM: To examine the sonographic features of shunt vessels derived from the splenic vein at splenic hilum (SS), and explore the relationship between the SS pattern and clinical presentations. MATERIALS AND METHODS: This prospective study in cirrhotic patients consisted of study I (n = 15), which compared the anatomical features of SS at ultrasonography versus angiography, and study II (n = 233), which examined the incidence/haemodynamics of SS and SS-related presentations. RESULTS: Study I showed that SS1 (running toward the upper pole of the spleen) corresponded to short gastric veins, and SS2 (running toward the lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111), SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence of gastric cardia varices was significantly higher in patients with SS2 (6/19) than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric fundal varices was significantly higher in patients with SS1 (44/86) than in those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no difference in the incidence of oesophageal varices among the three SS groups. The Child-Pugh score and grade of ascites was significantly worse in patients with SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001) compared to SS1. CONCLUSION: The SS pattern facilitates estimation of the possible manifestations, indicating the direction of clinical management of cirrhosis patients. Potential poor liver function is noted in patients with SS3.


Assuntos
Circulação Colateral , Cirrose Hepática/diagnóstico por imagem , Veia Esplênica/diagnóstico por imagem , Idoso , Endoscopia Gastrointestinal , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Ultrassonografia
20.
Pharmacopsychiatry ; 47(3): 101-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24764200

RESUMO

INTRODUCTION: The effects of escitalopram (10 mg/d) coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 13 Japanese psychiatric patients and compared with those of paroxetine (10 mg/d) coadministration. METHODS: The patients had received 6-24 mg/d of aripiprazole for at least 2 weeks. Patients were randomly allocated to one of 2 treatment sequences: paroxetine-escitalopram (n=6) or escitalopram-paroxetine (n=7). Each sequence consisted of two 2-week phases. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. RESULTS: Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during paroxetine coadministration were 1.7-fold (95% confidence intervals [CI], 1.3-2.1, p<0.001) and 1.5-fold (95% CI 1.2-1.9, p<0.01) higher than those values before the coadministration. These values were not influenced by escitalopram coadministration (1.3-fold, 95% CI 1.1-1.5 and 1.3-fold, 95% CI 1.0-1.5). Plasma dehydroaripiprazole concentrations remained constant during the study. CONCLUSION: The present study suggests that low doses of escitalopram can be safely coadministered with aripiprazole, at least from a pharmacokinetic point of view.


Assuntos
Citalopram/sangue , Transtornos Mentais/sangue , Piperazinas/sangue , Quinolonas/sangue , Adulto , Aripiprazol , Povo Asiático , Citalopram/uso terapêutico , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Quimioterapia Combinada , Eletrocardiografia , Eletroencefalografia , Feminino , Genótipo , Humanos , Masculino , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Pessoa de Meia-Idade , Paroxetina/sangue , Paroxetina/uso terapêutico , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico
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