Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
J Cardiol Cases ; 26(1): 62-65, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35923528

RESUMO

A 42-year-old man with a history of acute myocarditis after streptococcal pharyngitis developed recurrent fulminant myocarditis. Endomyocardial biopsy revealed myocyte degeneration, interstitial edema, and neutrophil infiltration. The patient's cardiac function deteriorated rapidly, and he died despite mechanical circulatory support. Autopsy revealed neutrophil infiltration, interstitial edema, and micro-abscesses containing masses of streptococci and neutrophilic phagocytosis within the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence. Learning objective: We report a rare case of recurrent fulminant non-rheumatic streptococcal myocarditis. Endomyocardial biopsy and autopsy revealed neutrophil infiltration and micro-abscesses containing bacterial masses of streptococci and neutrophilic phagocytosis in the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence.

2.
ESC Heart Fail ; 9(2): 1304-1313, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35112500

RESUMO

AIMS: Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non-ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM. METHODS AND RESULTS: We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high-ATX group and low-ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6-689.5) pg/mL vs. 96.5 (40.8-191.5) pg/mL, P = 0.010] were higher in the high-ATX group than low-ATX group, whereas high-sensitivity C-reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan-Meier survival analysis revealed that the event-free survival rate was significantly lower in the high-ATX group than low-ATX group (log-rank; P = 0.007). Cox proportional hazard analysis revealed that high-ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high-sensitivity C-reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048). CONCLUSION: High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.


Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Insuficiência Cardíaca , Cardiomiopatias/complicações , Cardiomiopatia Dilatada/complicações , Feminino , Coração , Insuficiência Cardíaca/complicações , Humanos , Masculino , Prognóstico
3.
CJC Open ; 4(5): 501-505, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35187464

RESUMO

A 48-year-old woman suffered from cardiogenic shock with fulminant myocarditis following the second dose of COVID-19 vaccine (mRNA-1273). Venoarterial extracorporeal membrane oxygenation and Impella support were essential in achieving hemodynamic stability. Endomyocardial biopsy revealed lymphocytic infiltration with predominant immunostaining for CD8- and CD68-positive cells. The left ventricular ejection fraction improved significantly after treatment with mechanical circulatory support. Myocarditis following COVID-19 mRNA vaccination may also occur in middle-aged women; it may be fulminant and require mechanical circulatory support. Although our results suggest the involvement of cytotoxic T lymphocytes and macrophages, further investigation is needed before these can be established as pathogenetic mechanisms.


Une femme de 48 ans a souffert d'un choc cardiogène accompagné d'une myocardite fulminante après avoir reçu la deuxième dose du vaccin contre la COVID-19 (ARNm-1273). L'oxygénation par membrane extracorporelle veino-artérielle et l'assistance par Impella ont joué un rôle essentiel pour atteindre la stabilité hémodynamique. Une biopsie endomyocardique a révélé la présence d'infiltrats lymphocytaires avec une immunocoloration prédominante pour les cellules exprimant CD8 et CD68. La fraction d'éjection ventriculaire gauche s'est améliorée considérablement après un traitement par assistance circulatoire mécanique. Des cas de myocardite peuvent également survenir chez des femmes d'âge moyen après l'administration d'un vaccin à ARNm contre la COVID-19; ils peuvent être fulminants et nécessiter une assistance circulatoire mécanique. Bien que nos résultats laissent croire à une participation des lymphocytes T cytotoxiques et des macrophages, une étude approfondie s'impose avant de pouvoir cerner les mécanismes pathogènes.

4.
BMC Res Notes ; 15(1): 40, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35144676

RESUMO

OBJECTIVE: Spleen volume increases in patients with advanced heart failure (HF) after left ventricular assist device (LVAD) implantation. However, the relationship between spleen volume and exercise tolerance (peak oxygen consumption [VO2]) in these patients remains unknown. In this exploratory study, we enrolled 27 patients with HF using a LVAD (median age: 46 years). Patients underwent blood testing, echocardiography, right heart catheterization, computed tomography (CT), and cardiopulmonary exercise testing. Spleen size was measured using CT volumetry, and the correlations/causal relationships of factors affecting peak VO2 were identified using structural equation modeling. RESULTS: The median spleen volume was 190.0 mL, and peak VO2 was 13.2 mL/kg/min. The factors affecting peak VO2 were peak heart rate (HR; ß = 0.402, P = .015), pulmonary capillary wedge pressure (PCWP; ß = - 0.698, P = .014), right ventricular stroke work index (ß = 0.533, P = .001), blood hemoglobin concentration (ß = 0.359, P = .007), and spleen volume (ß = 0.215, P = .041). Spleen volume correlated with peak HR, PCWP, and hemoglobin concentration, reflecting sympathetic activity, cardiac preload, and oxygen-carrying capacity, respectively, and was thus related to peak VO2. These results suggest an association between spleen volume and exercise tolerance in advanced HF.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Teste de Esforço , Tolerância ao Exercício , Insuficiência Cardíaca/terapia , Humanos , Pessoa de Meia-Idade , Consumo de Oxigênio , Baço/diagnóstico por imagem , Volume Sistólico
5.
Heart Vessels ; 37(8): 1344-1355, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35092456

RESUMO

The spleen is an important immune organ that releases erythrocytes and monocytes and destroys aged platelets. It also reserves 20-30% of the total blood volume, and its size decreases in hypovolemic shock. However, the clinical significance of splenic size in patients with heart failure (HF) remains unclear. We retrospectively analyzed the data of 206 patients with clinically stable HF gathered between January 2001 and August 2020 and recorded in a single-center registry. All patients underwent right heart catheterization and computed tomography (CT). Splenic size was measured using CT volumetry. The primary outcomes were composite cardiac events occurring for the first time during follow-up, namely, cardiac death and hospitalization for worsening HF. The median splenic volume and splenic volume index (SVI) were 118.0 mL and 68.9 mL/m2, respectively. SVI was positively correlated with cardiac output (r = 0.269, P < 0.001) and stroke volume (r = 0.228, P = 0.002), and negatively correlated with systemic vascular resistance (r = - 0.302, P < 0.001). Seventy cardiac events occurred, and the optimal receiver operating characteristic curve SVI cutoff value for predicting cardiac events was 68.9 mL/m2. The median blood adrenaline concentration was higher in the low-SVI group than the high-SVI group (0.039 ng/mL vs. 0.026 ng/mL, respectively; P = 0.004), and the low-SVI group experienced more cardiac events (log-rank test, P < 0.001). Multivariate Cox proportional hazards regression revealed that a low SVI was an independent predictor of cardiac events, even when adjusted for the validated HF risk score, blood-brain natriuretic peptide concentration, blood catecholamine concentrations, and hemodynamic parameters. Splenic size reflects hemodynamics, including systemic circulating blood volume status and sympathetic nerve activity, and is associated with HF prognosis.


Assuntos
Insuficiência Cardíaca , Baço , Idoso , Insuficiência Cardíaca/diagnóstico , Hemodinâmica , Humanos , Prognóstico , Estudos Retrospectivos , Baço/diagnóstico por imagem , Volume Sistólico/fisiologia
6.
Cardiooncology ; 7(1): 26, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229760

RESUMO

BACKGROUND: The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in cancer treatment as the use of these drugs has become more frequent and for a longer duration. As a result of T-cell-mediated inflammation at the programmed cell death-1, programmed death-ligand-1, and cytotoxic T-lymphocyte antigen-4 pathways, immune-related adverse events (irAEs) occur in various organs and can cause a rare but potentially induced cardiotoxicity. Although irAEs are associated with the efficacy of ICI therapy and better prognosis, there is limited information about the correlation between irAEs and cardiotoxicity and whether the benefits of irAEs apply to patients with underlying cardiovascular disease. This study aimed to investigate the association of irAEs and treatment efficacy in patients undergoing ICI therapy with and without a cardiovascular history. METHODS: We performed a retrospective review of the medical records of 409 consecutive patients who received ICI therapy from September 2014 to October 2019. RESULTS: Median patient age was 69 years (29.6% were female). The median follow-up period was 278 days. In total, 69 (16.9%) patients had a history of any cardiovascular disease and 14 (3.4%) patients experienced cardiovascular irAEs after ICI administration. The rate of cardiovascular irAEs was higher in patients with prior non-cardiovascular irAEs than without. The prognosis of patients with irAEs ( +) was significantly better than that of the patients without irAEs (P < 0.001); additionally, this tendency did not depend on the presence or absence of a cardiovascular history. Furthermore, the Cox proportional hazards analysis revealed that irAEs were an independent predictor of mortality. CONCLUSIONS: Although cardiovascular irAEs may be related to prior non-cardiovascular irAEs under ICI therapy, the occurrence of irAEs had a better prognostic impact and this tendency was not affected by cardiovascular history.

7.
ESC Heart Fail ; 8(2): 1359-1368, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33471966

RESUMO

AIMS: Left ventricular reverse remodelling (LVRR) is a well-established predictor of a good prognosis in patients with dilated cardiomyopathy (DCM). The prediction of LVRR is important when developing a long-term treatment strategy. This study aimed to assess the clinical predictors of LVRR and establish a scoring system for predicting LVRR in patients with DCM that can be used at any institution. METHODS AND RESULTS: We consecutively enrolled 131 patients with DCM and assessed the clinical predictors of LVRR. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, accompanied by a decrease in left ventricular end-diastolic dimension (LVEDD) ≥ 10% on echocardiography at 1 ± 0.5 years after a diagnosis of DCM. The mean patient age was 50.1 ± 11.9 years. The mean LVEF was 32.2 ± 9.5%, and the mean LVEDD was 64.1 ± 12.5 mm at diagnosis. LVRR was observed in 45 patients (34%) at 1 ± 0.5 years. In a multivariate analysis, hypertension [odds ratio (OR): 6.86; P = 0.002], no family history of DCM (OR: 10.45; P = 0.037), symptom duration <90 days (OR: 6.72; P < 0.001), LVEF <35% (OR: 13.66; P < 0.0001), and QRS duration <116 ms (OR: 5.94; P = 0.005) were found to be independent predictors of LVRR. We scored the five independent predictors according to the ORs (1 point, 2 points, 1 point, 2 points, and 1 point, respectively), and the total LVRR predicting score was calculated by adding these scores. The LVRR rate was stratified by the LVRR predicting score (0-2 points: 0%; 3 points: 6.7%; 4 points: 17.4%; 5 points: 48.2%; 6 points: 79.2%; and 7 points: 100%). The cut-off value of the LVRR predicting score was >5 in receiver-operating characteristic curve analysis (area under the curve: 0.89; P < 0.0001; sensitivity: 87%; specificity: 78%). An LVRR predicting score of >5 was an independent predictor compared with the presence of late gadolinium enhancement on cardiovascular magnetic resonance or the severity of fibrosis on endomyocardial biopsy (OR: 11.79; 95% confidence interval: 2.40-58.00; P = 0.002). CONCLUSIONS: The LVRR predicting score using five predictors including hypertension, no family history of DCM, symptom duration <90 days, LVEF <35%, and QRS duration <116 ms can stratify the LVRR rate in patients with DCM. The LVRR predicting score may be a useful clinical tool that can be used easily at any institution.


Assuntos
Cardiomiopatia Dilatada , Adulto , Cardiomiopatia Dilatada/diagnóstico , Meios de Contraste , Gadolínio , Humanos , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda
8.
Cardiovasc Interv Ther ; 35(4): 353-360, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31939067

RESUMO

Reducing radiation exposure is a very important issue in interventional cardiology techniques such as percutaneous coronary intervention. Although novel techniques to reduce radiation exposure are valuable, we should also reconsider older techniques. Digital zoom has been available in Japan from 2005. Digital zoom enlarges an 8-inch field of view (FOV) by 1.2 times, allowing visualization of a 6.7-inch FOV without FOV switching. We identified 2101 suitable cases of percutaneous intervention (PCI) and divided them into two groups according to the use of digital zoom; 1195 patients were included in the digital zoom group and 906 patients in the conventional group. We collected data regarding the reference air kerma (RAK) and dose-area product (DAP). We calculated RAK and DAP per minute fluoroscope time (RAK/min, DAP/min, respectively). There were intergroup differences in RAK, DAP, RAK/min, and DAP/min (digital zoom group vs conventional group; RAK, 1590 mGy [990-2410] vs 1850 [1220-2720], p < 0.01, RAK/min; 54.7 mGy/min [38.5-73.2] vs 71.2 [51.5-93.0], p < 0.01; DAP, 16,000 cGy × cm2 [10,300-24,400] vs 20,700 [13,400-29,500], p < 0.001; DAP/min, 557 cGy × cm2/min [392-737] vs 782 [571-1010], p < 0.01, respectively). Because of baseline differences between the two groups, we performed propensity score matching. Even after score matching, there were intergroup differences in DAP, DAP/min, RAK, and RAK/min. Furthermore, the least squares method showed that digital zoom is a significant predictor of RAK (ß = 0.14, p < 0.01) and DAP (ß = 0.20, p < 0.01). Digital zoom is an older cost-effective technique that can significantly reduce radiation exposure in PCI.


Assuntos
Intervenção Coronária Percutânea/métodos , Doses de Radiação , Exposição à Radiação/prevenção & controle , Ampliação Radiográfica/métodos , Idoso , Angiografia Coronária/métodos , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Ampliação Radiográfica/economia , Estudos Retrospectivos , Fatores de Risco
9.
Case Rep Orthop ; 2019: 9103412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565457

RESUMO

Atypical fractures commonly arise in the subtrochanteric region or the femoral shaft, whereas those of the upper extremities are rare. Only 15 fractures in 13 patients have been described in the English literature. The management of such fractures has not been established. We describe a patient with an atypical fracture of the ulnar diaphysis, which required revision surgery to achieve the union of the fracture site. Teriparatide together with low-intensity pulsed ultrasound contributed to bone healing. Further studies are needed to determine the optimal strategy for treating atypical fractures of the ulna.

10.
Mol Cancer Ther ; 18(7): 1205-1216, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31092565

RESUMO

NEDD8-activating enzyme (NAE) is an essential E1 enzyme of the NEDD8 conjugation (neddylation) pathway, which controls cancer cell growth and survival through activation of cullin-RING ubiquitin ligase complexes (CRL). In this study, we describe the preclinical profile of a novel, highly potent, and selective NAE inhibitor, TAS4464. TAS4464 selectively inhibited NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibited cullin neddylation and subsequently induced the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IκBα in human cancer cell lines. TAS4464 showed greater inhibitory effects than those of the known NAE inhibitor MLN4924 both in enzyme assay and in cells. Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines, but also patient-derived tumor cells. TAS4464 showed prolonged target inhibition in human tumor xenograft mouse models; weekly or twice a week TAS4464 administration led to prominent antitumor activity in multiple human tumor xenograft mouse models including both hematologic and solid tumors without marked weight loss. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.


Assuntos
Proteína NEDD8/genética , Neoplasias/tratamento farmacológico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos SCID , Pirimidinas/farmacologia , Pirróis/farmacologia
11.
J Med Chem ; 62(2): 531-551, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30525599

RESUMO

The molecular chaperone heat shock protein 90 (HSP90) is a promising target for cancer therapy, as it assists in the stabilization of cancer-related proteins, promoting cancer cell growth, and survival. A novel series of HSP90 inhibitors were discovered by structure-activity relationship (SAR)-based optimization of an initial hit compound 11a having a 4-(4-(quinolin-3-yl)-1 H-indol-1-yl)benzamide structure. The pyrazolo[3,4- b]pyridine derivative, 16e (TAS-116), is a selective inhibitor of HSP90α and HSP90ß among the HSP90 family proteins and exhibits oral availability in mice. The X-ray cocrystal structure of the 16e analogue 16d demonstrated a unique binding mode at the N-terminal ATP binding site. Oral administration of 16e demonstrated potent antitumor effects in an NCI-H1975 xenograft mouse model without significant body weight loss.


Assuntos
Benzamidas/química , Desenho de Fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Pirazóis/química , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Benzamidas/metabolismo , Benzamidas/uso terapêutico , Sítios de Ligação , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Camundongos , Camundongos Nus , Conformação Molecular , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pirazóis/metabolismo , Pirazóis/uso terapêutico , Quinolinas/química , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Solubilidade , Relação Estrutura-Atividade
13.
Pain Pract ; 18(5): 625-630, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29080243

RESUMO

PURPOSE: We aimed to evaluate the incidence of (and risk factors for) postoperative pregabalin and/or limaprost to treat persistent numbness and/or pain of the lower extremities after lumbar spinal stenosis (LSS) surgery. METHODS: Medical records of 329 patients (168 men, 161 women; average age 70 years) were retrospectively reviewed for data on the duration of LSS diagnosis; LSS disease; preoperative medication (limaprost, pregabalin, or combined limaprost/pregabalin; duration); symptoms; preoperative/postoperative intermittent claudication (IC); operation type; and postoperative medication and period. RESULTS: Limaprost, pregabalin, and combined limaprost/pregabalin were prescribed preoperatively for 43%, 7%, and 5% of patients, respectively. At an average of 21 months postoperatively, limaprost, pregabalin, and combined therapy were prescribed in 11%, 8%, 4% of patients, respectively. Medication requirement was significantly lower postoperatively than preoperatively (P < 0.0001). Significant risk factors for required postoperative medication were required preoperative medication (odds ratio [OR] 3.088, 95% confidence interval [CI] 1.679 to 5.681]; postoperative period (OR 1.063, 95% CI 1.031 to 1.096); and postoperative IC (OR 3.868, 95% CI 1.481 to 10.103). A negative impact from postoperative medication was seen in patients who had undergone decompression surgery (OR 0.589, 95% CI 0.377 to 0.918). CONCLUSIONS: Overall, 23% of LSS patients required medication for pain and/or numbness at 21 months postoperatively. Significant factors portending required postoperative medication were preoperative medication, longer postoperative period, and postoperative IC. A negative influence from postoperative medication was seen in patients who had undergone decompression surgery without fusion.


Assuntos
Alprostadil/análogos & derivados , Dor/tratamento farmacológico , Pregabalina/uso terapêutico , Estenose Espinal/tratamento farmacológico , Idoso , Alprostadil/uso terapêutico , Descompressão Cirúrgica , Feminino , Humanos , Hipestesia/tratamento farmacológico , Hipestesia/etiologia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Estenose Espinal/complicações , Estenose Espinal/cirurgia
14.
Eur Spine J ; 26(12): 3156-3161, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27832364

RESUMO

PURPOSE: Malnutrition is one of the important risk factors for postoperative complications. Transferrin, prealbumin, and retinol-binding protein, so-called rapid turnover proteins (RTPs), may be the better indicators for early detection of nutritional deficits. However, few studies have described the impact of serum RTP levels on postoperative surgical site infection (SSI) in spine surgery. The purpose of this study was to investigate the relationship between preoperative serum RTPs and postoperative SSI. METHODS: The data of 105 patients (64 male, 41 female; average age 64.4 years; age range 20-88 years) who underwent spine surgery in a single institution between 2014 and 2015 were retrospectively analyzed. Preoperative total lymphocyte count, serum albumin, transferrin, prealbumin, retinol-binding protein, pre-and postopeartive C-reactive protein (CRP), white blood cell count (WBC), and total lymphocyte count were evaluated. Postoperative CRP, WBC, and total lymphocyte count were repeated two or three times/week until hospital discharge. A broad spectrum penicillin or second generation cephalosporin was administered as a prophylactic antibiotic to each patient. When repeated CRP elevation or lymphopenia (no more than 10% or 1000/µL) after postoperative day 3 or 4 was observed, possible SSI was diagnosed. Variables between possible SSI group and non-SSI group were compared using Mann-Whitney U or Chi square test. All variables on univariate analysis were included in multiple logistic regression analysis to identify risk factors for possible postoperative SSI. RESULTS: Thirty-five patients were diagnosed with possible SSI. The mean operative time of possible SSI group was significantly longer (p = 0.036), preoperative total lymphocyte count and serum prealbumin level of possible SSI group were significantly lower (p = 0.002, p = 0.048, respectively) than that of non-SSI group. On univariate analysis, operative time (p = 0.012), preoperative total lymphocyte count (p = 0.041), serum albumin level (p = 0.038), and serum prealbumin level (p = 0.044) were significant contributors to possible SSI, and multiple logistic regression analysis revealed that operative time was the significant contributor to possible SSI (odds ratio 1.008, 95% confidence interval (CI) 1.001-1.015, p = 0.024). CONCLUSIONS: A low prealbumin level is a possible risk factor for early-stage SSI in spine surgery, though it was not statistically significant; operative time was the most important indicator of SSI on multivariate analysis.


Assuntos
Proteínas Sanguíneas/análise , Procedimentos Ortopédicos , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/estatística & dados numéricos , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/sangue , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/epidemiologia , Adulto Jovem
15.
Case Rep Med ; 2012: 513707, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22431934

RESUMO

Spermatic cord lymphoma is a rare lethal disease. It has a poor prognosis even in stage I or II disease when treated locally, therefore, multidisciplinary treatment for early stage is recommended. On the other hand, the treatment of choice for stage III or IV spermatic cord lymphoma remains to be determined. It is said that spermatic cord lymphoma is clinicopathologically similar to primary testicular lymphoma, therefore the treatment of spermatic cord lymphoma has often been determined by reference to the recommended treatment for primary testicular lymphoma. Here we report a new case of spermatic cord lymphoma, which was found in stage IV disease. We also review thirty-three cases which have been reported as spermatic cord lymphoma to date, and discuss treatment options.

16.
Hinyokika Kiyo ; 57(9): 521-4, 2011 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-22075616

RESUMO

An 85-year-old male visited our hospital with a complaint of painless swelling of the right testis. Right high orchiectomy was performed under the diagnosis of the right testicular tumor. Histopathological diagnosis was Leydig cell tumor. We reviewed 86 cases of this tumor previously reported in Japan. To our knowledge, our patient is the oldest one treated in Japan.


Assuntos
Tumor de Células de Leydig , Neoplasias Testiculares , Idoso de 80 Anos ou mais , Humanos , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/cirurgia , Masculino , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia
17.
J Med Chem ; 52(22): 7289-300, 2009 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-19883081

RESUMO

A series of benzoxazinones was synthesized and evaluated as novel long chain fatty acid elongase 6 (ELOVL6) inhibitors. Exploration of the SAR of the UHTS lead 1a led to the identification of (S)-1y that possesses a unique chiral quarternary center and a pyrazole ring as critical pharmacophore elements. Compound (S)-1y showed potent and selective inhibitory activity toward human ELOVL6 while displaying potent inhibitory activity toward both mouse ELOVL3 and 6 enzymes. Compound (S)-1y showed acceptable pharmacokinetic profiles after oral dosing in mice. Furthermore, (S)-1y significantly suppressed the elongation of target fatty acids in mouse liver at 30 mg/kg oral dosing.


Assuntos
Acetiltransferases/antagonistas & inibidores , Benzoxazinas/administração & dosagem , Benzoxazinas/farmacologia , Descoberta de Drogas , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Acetiltransferases/metabolismo , Administração Oral , Animais , Benzoxazinas/síntese química , Benzoxazinas/química , Linhagem Celular Tumoral , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Elongases de Ácidos Graxos , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Relação Estrutura-Atividade
18.
Bioorg Med Chem Lett ; 19(15): 4232-6, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19520574

RESUMO

A series of novel dihydrobenzoxathiin derivatives was synthesized and evaluated as potent human histamine H(3) receptor inverse agonists. After systematic modification of lead 1a, the potent and selective histamine H(3) inverse agonist 1-(3-{4-[(2S,3S)-8-methoxy-3-methyl-4,4-dioxido-2,3-dihydro-1,4-benzoxathiin-2-yl]phenoxy}propyl)pyrrolidine (5k) was identified. Compound 5k showed good pharmacokinetic profiles and brain penetrability in laboratory animals. After 3mg/kg oral administration of 5k, significant elevation of brain histamine levels was observed in rats where the brain H(3) receptor was fully occupied.


Assuntos
Química Farmacêutica/métodos , Oxati-Inas/química , Receptores Histamínicos H3/química , Administração Oral , Animais , Encéfalo/metabolismo , Desenho de Fármacos , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Concentração Inibidora 50 , Modelos Químicos , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Relação Estrutura-Atividade
19.
Bioorg Med Chem Lett ; 18(23): 6041-5, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18952421

RESUMO

Novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives were identified as potent human H(3) receptor inverse agonists. After systematic modification of lead 5a, the potent and selective analog 5r was identified. Elimination of hERG K(+) channel and human alpha(1A)-adrenoceptor activities is the main focus of the present study.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Agonistas dos Receptores Histamínicos/farmacologia , Quinazolinonas/farmacologia , Administração Oral , Encéfalo/efeitos dos fármacos , Técnicas de Química Combinatória , Relação Dose-Resposta a Droga , Canal de Potássio ERG1 , Humanos , Estrutura Molecular , Quinazolinonas/química , Relação Estrutura-Atividade
20.
Gan To Kagaku Ryoho ; 35(7): 1193-5, 2008 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-18633261

RESUMO

A 75-year-old man with advanced gastric cancer underwent distal gastrectomy with lymph node dissection(D1)and Roux-en Y reconstruction. Pathological staging was Stage IV (T3N3P1CY1M1), and curability was Cur C. He started adjuvant chemotherapy with oral administration of S-1(100 mg/body weight), but experienced grade 3 anorexia for one month. Abdominal computed tomography(CT)2 months postoperatively showed multiple liver metastases and ascites. We then conducted tailored S-1/CPT-11 as second-line chemotherapy(S-1 80 mg/body weight on days 1-5 and 8-12, CPT-11 60 mg/body weight on days 1 and 8). After 5 courses of this therapy, CT showed that the liver metastases and ascites had disappeared, leading to a complete response(CR). The only adverse event was general grade 1 fatigue. He continues to undergo oral administration of S-1(80 mg/body weight)as maintenance therapy, and maintained CR for 12 months since undergoing chemotherapy. Adverse events in tailored S-1/CPT-11 combination therapy are mild and tolerable, making this regimen a potential therapeutic strategy for patients with advanced or recurrent gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Hepáticas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Tegafur/uso terapêutico , Idoso , Biomarcadores Tumorais/sangue , Camptotecina/uso terapêutico , Combinação de Medicamentos , Gastroscopia , Humanos , Irinotecano , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Estadiamento de Neoplasias , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA