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1.
Jpn J Infect Dis ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32350218

RESUMO

We report the second case of deceased donor liver transplantation in a patient co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in Japan. A 48- year-old patient with hemophilia A was infected with HIV and HCV through a contaminated factor VIII concentrate in his childhood and developed cirrhosis and hepatocellular carcinoma. The patient was on the transplant list for a deceased donor liver. The patient had broad spectrum anti-HLA class I and II antibodies, which may have been due to repeated whole blood transfusions in the past. Catastrophic coagulopathy during the surgery was predicted because of the underlying hemophilic status and severe thrombocytopenia requiring HLA-matched platelet products, which are difficult to obtain quickly. To maintain adequate platelet counts(>5x104/ µl) while waiting liver transplantation, a thrombopoietin receptor agonist and rituximab were administered. During surgery, factor VIII concentrate was administered according to the previously planned protocol. Adequate hemostasis was obtained, and the operation was completed without uncontrollable coagulopathy. The postoperative course was uneventful, and the patient was discharged on postoperative day 41. Detailed planning is required for surgical patients with hemophilia and HIV/HCV cirrhosis, especially for those with a diverse spectrum of anti-HLA antibodies.

2.
Heart Vessels ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350637

RESUMO

Myocardial perfusion imaging (MPI) using Single Photon Emission Computed Tomography has been established as a standard noninvasive tool for risk stratification of coronary artery disease (CAD). We evaluated the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR) in comparison with MPI using invasive fractional flow reserve (invasive FFR) as a gold standard. We enrolled 97 patients with suspected CAD. Diagnostic performance of CT angiography (CTA), and CT-FFR was compared in 105 lesions of 97 patients. Invasive FFR ≤ 0.8 was detected in 38 (36%) lesions. Diagnostic performance of CT-FFR was improved compared with CTA (AUC 0.83 vs. 0.60, p < 0.0001). The lesions with both CTA and MPI findings (n = 47), invasive FFR ≤ 0.8 was detected in 19 (40.4) lesions. CT-FFR (AUC 0.81, 95% CI 0.72-0.94) significantly improved diagnostic performance compared with CTA-50% (AUC 0.59, p = 0.00019) and MPI (AUC 0.64, p = 0.0082). In lesions with ≥ 50% on CTA (n = 42), diagnostic accuracy of CT-FFR (AUC 0.81) was significantly superior to MPI (AUC 0.64, p = 0.0239). In conclusions, CT-FFR improved diagnostic accuracy to detect invasive FFR ≤ 0.8 compared with luminal stenosis on CTA and ischemia on MPI. Patients with ≥ 50% stenosis on CTA would be the candidates for CT-FFR.

3.
Int J Lab Hematol ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343486

RESUMO

INTRODUCTION: Bendamustine has been reported to be effective against low-grade B-cell lymphoma. We examined the effect of bendamustine on the lymphocyte-monocyte ratio (LMR) in low-grade B-cell lymphoma patients. METHODS: We retrospectively reviewed 127 cases of first line or relapse/refractory low-grade B-cell lymphoma in three individual institutions (Asahikawa Municipal Hospital, Aiiku Hospital, and Hakodate Municipal Hospital). Only patients who had received at least three courses of bendamustine therapy were selected; the LMR was evaluated at starting the initial course of bendamustine therapy. Time to next treatment (TTNT) was used to ascertain the efficacy of bendamustine therapy. RESULTS: Follicular lymphoma (FL), at 68.5% (87/127), is the most common histological subtype of low-grade B-cell lymphoma. The receiver operating characteristic (ROC) curve for the LMR showed a cutoff value of 2.0, and 33 cases (26.0%) had an LMR ≤2.0. Cases with LMR ≤2.0 had a significantly earlier progression than those with LMR > 2.0, based on the TTNT (P = .0007). Additionally, LMR ≤2.0 indicates earlier progression in TTNT when comparing only FL and low-grade B-cell lymphoma cases without FL (P = .007, 0.002). For multivariate analysis, the factors associated with an LMR ≤2.0 (HR, 2.741; 95% CI, 1.4330-5.245; P = .002) were considered as early progression factors with regard to the TTNT. CONCLUSION: Lymphocyte-monocyte ratio effectively predicts the efficacy of bendamustine therapy for low-grade B-cell lymphoma, particularly FL; its application may improve treatment strategies for this disease.

4.
Phys Rev Lett ; 124(13): 136404, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32302163

RESUMO

The chiral crystal is characterized by a lack of mirror symmetry and inversion center, resulting in the inequivalent right- and left-handed structures. In the noncentrosymmetric crystal structure, the spin and momentum of electrons are expected to be locked in the reciprocal space with the help of the spin-orbit interaction. To reveal the spin textures of chiral crystals, we investigate the spin and electronic structure in a p-type semiconductor, elemental tellurium, with the simplest chiral structure by using spin- and angle-resolved photoemission spectroscopy. Our data demonstrate that the highest valence band crossing the Fermi level has a spin component parallel to the electron momentum around the Brillouin zone corners. Significantly, we have also confirmed that the spin polarization is reversed in the crystal with the opposite chirality. The results indicate that the spin textures of the right- and left-handed chiral crystals are hedgehoglike, leading to unconventional magnetoelectric effects and nonreciprocal phenomena.

5.
Am J Forensic Med Pathol ; 41(1): 40-41, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31929320

RESUMO

The deceased was a 44-year-old male who was treated for a suspected Ebstein's anomaly observed using transthoracic echocardiogram. He was found dead in his bed at home. Autopsy revealed that the septal tricuspid leaflet was intact; however, a large anterior tricuspid leaflet cleft and right atrioventricular cavity dilation were observed. Pathological examination revealed a normal tricuspid valve, except for the presence of a cleft with local fibrosis of the left ventricle papillary muscle and hemosiderin-containing macrophages at both lungs. There were no other abnormalities that may have led to death. It was concluded that he died a cardiac death based on the right heart overload associated with the anterior tricuspid leaflet cleft. This case indicates the possibility that the anterior tricuspid leaflet cleft can cause death and also highlights the necessity of a detailed autopsy to accurately diagnose the cause of death.


Assuntos
Valva Tricúspide/anormalidades , Valva Tricúspide/patologia , Adulto , Proteína C-Reativa/análise , Diagnóstico Diferencial , Anomalia de Ebstein/diagnóstico , Fibrose , Patologia Legal , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/patologia , Hemossiderina/metabolismo , Humanos , Pulmão/metabolismo , Macrófagos/metabolismo , Masculino , Peptídeo Natriurético Encefálico/sangue , Músculos Papilares/patologia , Fragmentos de Peptídeos/sangue , Insuficiência da Valva Tricúspide/complicações
6.
Forensic Sci Int ; 307: 110136, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31896021

RESUMO

In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography-tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %-95 %; that of diazepam, paroxetine and triazolam was 10 %-45 %; and that of brotizolam, etizolam and levomepromazine was 1 %-5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes.


Assuntos
Estabilidade de Medicamentos , Toxicologia Forense/métodos , Fígado/química , Psicotrópicos/análise , Psicotrópicos/química , Animais , Cromatografia Líquida , Fixadores , Formaldeído , Preservação de Órgãos , Manejo de Espécimes , Suínos , Espectrometria de Massas em Tandem
7.
Int J Cardiovasc Imaging ; 36(2): 337-346, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31628575

RESUMO

Fractional flow reserve (FFR) is an established method for diagnosing physiological coronary artery stenosis. A method for computing FFR using coronary computed tomography (CT) images was recently developed. However, its calculation requires off-site supercomputer analysis. Here, we report the preliminary result of a method using simple estimation of boundary conditions. The lumen boundaries of the coronary arteries were semi-automatically delineated using full width at half maximum of CT number profiles. The computational fluid dynamics (CFD) of the blood flow was performed using the boundary conditions of a fixed pressure at the coronary ostium and flow rates at each outlet. The total inflow at the coronary ostium was estimated based on the uniform wall shear stress hypothesis and corrected using a hyperemic multiplier to gain a hyperemic flow rate. The flow distribution from a parent vessel to the downstream daughter vessels was determined according to Murray's law. FFR estimated by CFD was calculated as FFRCFD = Pd/Pa. We collected patients who underwent coronary CT and coronary angiography followed by invasively measured FFR and compared FFRCFD with FFR. Sensitivity, specificity, and correlations were assessed. A total of 48 patients and 72 arteries were assessed. The correlation coefficient of FFRCFD with FFR was 0.56. The cut-off value was ≤ 0.80, sensitivity was 59.1%, and specificity was 94.0%. CFD-based FFR using simple boundary conditions for on-site clinical computation provided FFRCFD values that were moderately correlated with invasively measured FFR.

8.
Intern Med ; 59(5): 757-758, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31666463
9.
Artigo em Inglês | MEDLINE | ID: mdl-31877431

RESUMO

Therapeutic drug monitoring is important in patients taking BCR-ABL and Bruton's tyrosine kinase inhibitors (TKIs). Some TKI active metabolites with long elimination half-lives, such as dihydrodiol ibrutinib (DHI), N-desmethyl imatinib (N-DI), and N-desmethyl ponatinib (N-DP), have been characterized, indicating that these active metabolites should be monitored along with the parent compounds. However, there are currently no methods for the simultaneous quantification of BCR-ABL and Bruton's TKIs and their three active metabolites. The present study aimed to develop and validate a method for the simultaneous quantification of nine pharmacologically active compounds (bosutinib, dasatinib, DHI, ibrutinib, imatinib, N-DI, N-DP, nilotinib, and ponatinib) using high-performance liquid chromatography-tandem mass spectrometry. A 150-µL sample of plasma was analyzed after purification with supported liquid extraction. The method has a run time of 7 min and was successfully validated over the following calibration ranges: 0.25-75 ng/mL for N-DP, 0.5-150 ng/mL for dasatinib and ponatinib, 10-3000 ng/mL for imatinib and nilotinib, and 1-300 ng/mL for the other analytes. Stability of the analytes after short- and long-term storage in the presence of plasma matrix was examined, and all analytes were found to be stable under all tested conditions. The recovery was ≥83%, and the relative standard deviation of internal-standard normalized matrix effects ranged from 3.9 to 13.9%. Dilution integrity up to 4-fold was ensured. The applicability of the method for all analytes was demonstrated using patient samples.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Monitoramento de Medicamentos/métodos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Inibidores de Proteínas Quinases/sangue , Adolescente , Compostos de Anilina/sangue , Compostos de Anilina/química , Compostos de Anilina/farmacocinética , Antineoplásicos/sangue , Antineoplásicos/química , Antineoplásicos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Dasatinibe/sangue , Dasatinibe/química , Dasatinibe/farmacocinética , Humanos , Limite de Detecção , Modelos Lineares , Nitrilos/sangue , Nitrilos/química , Nitrilos/farmacocinética , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Quinolinas/sangue , Quinolinas/química , Quinolinas/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
10.
J Autoimmun ; 108: 102390, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31883830

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing vasculitis with the presence of pathogenic ANCA. ANCA can potentially cause neutrophil activation and induce neutrophil extracellular traps (NETs), resulting in endothelial damage as well as activation of autoreactive B cells and alternative complement pathway. Recombinant thrombomodulin (rTM) protects the endothelium from vascular injury during disseminated intravascular coagulation, thus we hypothesized that rTM ameliorates necrotizing vasculitis in AAV. In this study, rTM was administered in an experimental AAV rat model. Treatment of experimental AAV rats with rTM improved pulmonary hemorrhage and glomerulonephritis, with a suppression of ANCA production and NETs formation. In addition, in vitro experiments showed that rTM bound to neutrophils via Mac-1 (macrophage-1 antigen) and inhibited ANCA-induced NETs formation accompanied by a suppression of histone citrullination, leading to a protection of the endothelium from NETs toxicity. Additionally, rTM affected lymphocytes leading to the inhibition of pro-inflammatory cytokine/chemokin in PBMC during the antibody production process, which might indirectly be involved in the reduction of pathogenic ANCA. Our data revealed that the rTM could ameliorate autoimmune vasculitis through a combination of different biological mechanisms.

11.
Sci Rep ; 9(1): 17846, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31780797

RESUMO

Herein, a conductive boron-doped nanodiamond (BDND) particle is prepared as an electrode material for an aqueous electric double-layer capacitor with high power and energy densities. The BDND is obtained by depositing a boron-doped diamond (BDD) on a nanodiamond particle substrate with a primary particle size of 4.7 nm via microwave plasma-assisted chemical vapor deposition, followed by heat treatment in air. The BDND comprises BDD and sp2 carbon components, and exhibits a conductivity above 10-2 S cm-1 and a specific surface area of 650 m2 g-1. Cyclic voltammetry measurements recorded in 1 M H2SO4 at a BDND electrode in a two-electrode system shows a capacitance of 15.1 F g-1 and a wide potential window (cell voltage) of 1.8 V, which is much larger than that obtained at an activated carbon electrode, i.e., 0.8 V. Furthermore, the cell voltage of the BDND electrode reaches 2.8 V when using saturated NaClO4 as electrolyte. The energy and power densities per unit weight of the BDND for charging-discharging in 1 M H2SO4 at the BDND electrode cell are 10 Wh kg-1 and 104 W kg-1, respectively, and the energy and power densities per unit volume of the BDND layer are 3-4 mWh cm-3 and 10 W cm-3, respectively. Therefore, the BDND is a promising candidate for the development of a compact aqueous EDLC device with high energy and power densities.

12.
Cell Struct Funct ; 44(2): 195-204, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31735741

RESUMO

The oncogenic tyrosine kinase BCR-ABL activates a variety of signaling pathways and plays a causative role in the pathogenesis of chronic myelogenous leukemia (CML); however, the subcellular distribution of this chimeric protein remains controversial. Here, we report that BCR-ABL is localized to stress granules and that its granular localization contributes to BCR-ABL-dependent leukemogenesis. BCR-ABL-positive granules were not colocalized with any markers for membrane-bound organelles but were colocalized with HSP90a, a component of RNA granules. The number of such granules increased with thapsigargin treatment, confirming that the granules were stress granules. Given that treatment with the ABL kinase inhibitor imatinib and elimination of the N-terminal region of BCR-ABL abolished granule formation, kinase activity and the coiled-coil domain are required for granule formation. Whereas wild-type BCR-ABL rescued the growth defect in IL-3-depleted Ba/F3 cells, mutant BCR-ABL lacking the N-terminal region failed to do so. Moreover, forced tetramerization of the N-terminus-deleted mutant could not restore the growth defect, indicating that granule formation, but not tetramerization, through its N-terminus is critical for BCR-ABL-dependent oncogenicity. Our findings together provide new insights into the pathogenesis of CML by BCR-ABL and open a window for developing novel therapeutic strategies for this disease.Key words: BCR-ABL, subcellular localization, stress granule.

13.
Nagoya J Med Sci ; 81(3): 519-528, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31579342

RESUMO

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant Staphylococcus aureus sepsis, gastrointestinal bleeding, peritonitis caused by Stenotrophomonas maltophilia, gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients' clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.

14.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 75(10): 1141-1149, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31631107

RESUMO

PURPOSE: Ichihara et al. (Fujita Med J 2015; 1(1): 9-14) developed a method to simultaneously obtain both coronary computed tomography (CT) angiography and CT myocardial perfusion (CTP) using 64-multi detector CT (MDCT). An input-function (time enhancement curve, TEC) of the ascending aorta (Ao) and myocardial CT density are necessary to calculate absolute myocardial blood flow (ml/g/min) using a two-compartment model. Helical scan starting timing is important to capture the peak (P) of Ao time enhancement curve (TEC). The purpose is to search the optimal timing of starting helical scan to capture the P. METHODS: We performed 14 CTPs using Definition AS+ (SIEMENS). A dynamic scan at the Ao level was started at 7 s after contrast injection and helical scan was started at various trigger on bolus tracking. Definition AS+ needs 2 s (other scanner may need 4 s) for changing from a dynamic to helical scan mode. We created TECs of pulmonary artery (PA) and Ao using the fifth function fitting. We measured the time from trigger point to the P (t200, t250, t300 and tCP). RESULTS: Mean t200, t250, t300 and tCP were 9.1±1.9, 7.9±2.0, 6.6±1.9 and 3.9±1.2 s, respectively. In additional other 16 CTP studies using the cross point method, we can capture the P in all (100%) examinations. CONCLUSION: Scan starting at the cross point is best for Definition AS+, and the Ao=300 HU may be best for other scanner that needs 4 s for changing scan mode to obtain a fine input function for calculating absolute myocardial blood flow.


Assuntos
Angiografia por Tomografia Computadorizada , Meios de Contraste , Angiografia Coronária , Tomografia Computadorizada Espiral , Tomografia Computadorizada Multidetectores , Cintilografia , Fatores de Tempo , Tomografia Computadorizada por Raios X
15.
Chemistry ; 25(68): 15580-15585, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31550386

RESUMO

Oxidation of 5,15-dithiaporphyrin with meta-chloroperbenzoic acid afforded the corresponding S,S-tetraoxide in good yield. The resultant 5,5,15,15-tetraoxo-5,15-dithiaporphyrin exhibited the highly electron-deficient nature as elucidated by the electrochemical analysis and theoretical calculations. Treatment of tetraoxodithiaporphyrin with zinc(II) acetate and nickel(II) acetate provided the corresponding metal complexes efficiently. Owing to its enhanced Lewis acidity of the metal center by the electron-deficient ligand, the nickel complex underwent facile axial ligation to form pentacoordinate and hexacoordinate high-spin (S=1) complexes in solution and solid, respectively. The binding constant of pyridine to the NiII center was significantly higher than those of conventional porphyrin NiII complexes. Temperature-dependent magnetic susceptibility measurements of the high-spin NiII complex revealed the presence of weak ferromagnetic interactions.

16.
World J Clin Cases ; 7(15): 2049-2057, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31423437

RESUMO

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is a type of T-cell lymphoma that can be divided into two categories: anaplastic lymphoma kinase-positive (ALK+) and ALK-negative. Gastrointestinal ALK+ ALCL is rare. Multiple lymphomatous polyposis (MLP) is thought to be a representative form of gastrointestinal lesion in mantle cell lymphoma, and T-cell lymphomas seldom show this feature. Here, we report the first known case of ALK+ ALCL with gastroduodenal involvement to present with MLP. CASE SUMMARY: The patient was a 43-year-old man who was complained of a mass in the left inguinal area and was performed open biopsy. ALK+ ALCL was diagnosed pathologically. Computed tomography scan demonstrated multiple lymph node lesions in the abdomen - pelvis/inguinal region, and scattered nodular lesions in both lung fields. He did not complain of gastrointestinal symptoms. While, esophagogastroduodenoscopy identified MLP lesions from the antrum of the stomach to the descending portion of the duodenum and mild thickened folds on the corpus of the stomach, and biopsy showed invasion of ALK+ ALCL. We treated this patient with six cycles of CHOEP (Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, and Prednisone) chemotherapy. At the conclusion of treatment, there was complete remission. Numerous white scars were found on the stomach, endoscopically consistent with a remission image of lymphoma. The endoscopic features of this case were thought to be similar to those of MCL. CONCLUSION: The macroscopic/endoscopic features of gastrointestinal ALK+ ALCL may be more similar to those of B-cell lymphomas rather than T-cell lymphomas.

17.
Arterioscler Thromb Vasc Biol ; 39(9): 1802-1816, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31366219

RESUMO

OBJECTIVE: n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on atherosclerosis. Although specific salutary actions have been reported, the detailed distribution of n-3 polyunsaturated fatty acids in plaque and their relevance in disease progression are unclear. Our aim was to assess the pharmacodynamics of EPA and DHA and their metabolites in atherosclerotic plaques. Approach and Results: Apolipoprotein E-deficient (Apoe-/-) mice were fed a Western diet supplemented with EPA (1%, w/w) or DHA (1%, w/w) for 3 weeks. Imaging mass spectrometry analyses were performed in the aortic root and arch of the Apoe-/- mice to evaluate the distribution of EPA, DHA, their metabolites and the lipids containing EPA or DHA in the plaques. Liquid chromatography-mass spectrometry and histological analysis were also performed. The intima-media thickness of atherosclerotic plaque decreased in plaques containing free EPA and EPAs attached with several lipids. EPA was distributed more densely in the thin-cap plaques than in the thick-cap plaques, while DHA was more evenly distributed. In the aortic root, the distribution of total EPA level and cholesteryl esters containing EPA followed a concentration gradient from the vascular endothelium to the media. In the aortic arch, free EPA and 12-hydroxy-EPA colocalized with M2 macrophage. CONCLUSIONS: Administered EPA tends to be incorporated from the vascular lumen side and preferentially taken into the thin-cap plaque.

18.
CMAJ ; 191(22): E614, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160498
19.
Case Rep Oncol ; 12(2): 376-383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182954

RESUMO

Gastrosplenic fistula (GSF) is a rare condition arising from gastric or splenic lymphomas. Surgical resection is the most common treatment, as described in previous reports. We report two cases of GSF in diffuse large B-cell lymphoma (DLBCL) patients that were successfully treated with chemotherapy and irradiation without surgical resection. Case 1 was of a 63-year-old man who had primary gastric DLBCL with a large lesion outside the stomach wall, leading to a spontaneous fistula in the spleen. Case 2 was of a 59-year-old man who had primary splenic DLBCL, which proliferated and infiltrated directly into the stomach. In both cases, chemotherapy comprising rituximab + dose-adjusted EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) was administered. Case 1 had significant bleeding from the lesion of the stomach during the treatment cycle; however, endoscopic hemostasis was achieved. Case 2 developed a fistula between the stomach and the spleen following therapeutic chemotherapy; however, no complications related to the fistula were observed thereafter. In both cases, irradiation was administered, and complete remission was achieved.

20.
Int J Hematol ; 110(4): 482-489, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240558

RESUMO

Nilotinib is widely used for primary treatment of patients with chronic myelogenous leukemia (CML). We previously reported that use of an FRET-based drug sensitivity test at diagnosis efficiently predicts the response to treatment with imatinib or dasatinib. Here, we conducted a phase-II study to evaluate the efficacy and safety of nilotinib treatment and identify useful biomarkers, including results of the FRET-based drug sensitivity test, for predicting treatment response. Data from 42 patients were used in the analysis. Major molecular response (MMR), MR4, and MR4.5 rates at 12 months were 64.3, 42.9, and 28.6%, respectively. Grade 3/4 non-hematologic adverse events occurred in 11 patients (26.2%). The dose intensity of nilotinib (> 76.44%) and halving time (HT, < 13.312 days) were identified as significant factors for MMR at 12 months. However, when we focused on patients whose dose intensity of nilotinib was > 76.44%, the FRET-based drug sensitivity test became a predictive factor of MR4 achievement at 12 months. Our study reconfirmed the efficacy and safety of nilotinib treatment in CML patients. Moreover, our results suggest that the FRET-based drug sensitivity test is an independent predictor for achievement of MR4 in patients treated with a sufficient dose intensity of nilotinib.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Transferência Ressonante de Energia de Fluorescência/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Adulto Jovem
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