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1.
Global Spine J ; 13(7): 1716-1727, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34672835

RESUMEN

STUDY DESIGN: This study is a retrospective review. OBJECTIVE: Central sensitization (CS) is a neurological phenomenon that involves hypersensitivity of the central nervous system. The central sensitization inventory (CSI) was developed as a screening tool to assess CS-related symptoms. The purpose of this study was to evaluate the association of preoperative CSI scores with patient-reported outcome measures (PROMs) including neurological symptoms for patients who underwent spine surgeries in a multicenter study. METHODS: A consecutive 673 patients who underwent spine surgery at 8 different institutions were included in this study. Preoperative CSI scores were assessed for all subjects. The participants completed the following PROMs: the Oswestry Disability Index (ODI), the Japanese Orthopaedic Association (JOA) back pain evaluation questionnaire (JOABPEQ) for lumbar spinal diseases, and the JOA cervical myelopathy evaluation questionnaire (JOACMEQ) for cervical spinal diseases. The association of CSI scores with PROMs was statistically evaluated. RESULTS: The average CSI score for the total subjects was 23.6 ± 13.5. The subjects with CS-related symptoms (CSI ≥ 40) were 13.2% (n = 89). The CSI score showed a significant and weak-to-moderate correlation with the PROMs including neurological symptoms that included all the domains of the JOACMEQ for cervical spinal diseases, and JOABPEQ and ODI for lumbar spinal diseases. Among these, psychological factors had the most influence on the correlation with CSI score. CONCLUSION: Central sensitization evaluated by the CSI is related to neurological symptoms and health-related quality of life in patients undergoing elective spine surgery.

2.
BMC Cancer ; 22(1): 1075, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36258189

RESUMEN

BACKGROUND: Coagulation and fibrinolysis are distinct processes that are highly correlated. Cells control coagulation and fibrinolysis by expression of tissue factor and urokinase-type plasminogen activator receptor on their surface. Tumor cells express these proteins, adjust their microenvironment and induce tumor exacerbation. We hypothesized that the expression of plasma markers for coagulation and fibrinolysis in patients with soft tissue sarcomas (STSs) was dependent on the level of tumor malignancy. To elucidate which markers are predictive of recurrence, metastasis and prognosis, coagulation or fibrinolysis, we analyzed the correlation between plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin (SF), plasmin-α2 plasmin inhibitor complex (PIC), D-dimer (DD) and clinical parameters in patients with STSs. METHODS: TAT, SF, PIC or DD were measured in pre-treatment blood samples from 64 patients with primary STSs and analyzed with clinicopathological parameters, and 5-year recurrence free survival (RFS), 5-year metastasis free survival (MFS) and 5-year overall survival (OS) were evaluated. RESULTS: The metastasis group had significantly higher DD (p = 0.0394), PIC (p = 0.00532) and SF (p = 0.00249) concentrations than the group without metastasis. The group that died of disease showed significantly higher DD (p = 0.00105), PIC (p = 0.000542), SF (p = 0.000126) and TAT (p = 0.0373) than surviving patients. By dividing the patients into low and high groups, the group with high DD, PIC, SF and TAT showed significantly lower 5-year MFS and 5-year OS than the corresponding low group. Furthermore, in multivariate COX proportional hazard analysis of continuous variables for 5-year MFS, only PIC was found to be a significant factor (HR: 2.14). CONCLUSION: Fibrinolysis was better than coagulation at reflecting the disease condition of patients with STS. Notably, PIC levels ≥ 1.1 can not only predict the risk of metastasis and poor prognosis, but also increasing PIC levels correspond to further increases in risks of metastasis and poor prognosis.


Asunto(s)
Antifibrinolíticos , Sarcoma , Humanos , Fibrinólisis , Fibrinolisina/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Tromboplastina , Péptido Hidrolasas , Biomarcadores , Microambiente Tumoral
3.
J Dermatol Sci ; 107(3): 151-159, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36150981

RESUMEN

BACKGROUND: Given that ocular glands become infected secondarily to herpes simplex virus 1 (HSV-1) keratitis, resulting in the loss of tear production, sweat glands may also be susceptible to HSV-1 infection, resulting in sweating disturbance, which is observed frequently in atopic dermatitis. However, due to the lack of sweat glands on the hairy skin of mice, the role of sweating in the maintenance of skin hydration has not been elucidated. OBJECTIVE: To determine the relationship between HSV-1 infection of sweat glands and sweating disturbance-induced dry skin. METHODS: By using the impression mold technique, we examined the sweating response together with the detection of HSV-1 DNA in the sweat glands of footpads, the only area with sweat glands in mice, after local cutaneous HSV-1 inoculation of immunocompetent mice. RESULTS: The sweating response and skin surface hydration were significantly decreased at 7-14 days post-infection. Sweating disturbance and dry skin was markedly enhanced when HSV-1 inoculation was followed by hyperthermic stress. Both resolved spontaneously and became resistant to a second HSV-1 inoculation, associated with increased anti-HSV-IgG antibodies. HSV-1 DNA was detected in sweat glands and dorsal root ganglia. The sweating response remained decreased after subcutaneous injection with pilocarpine, correlating histologically with marked dilatation of sweat gland lumens. These findings indicate that sweating disturbance is unlikely to be the outcome of nerve damage by HSV-1 infection. CONCLUSION: Sweating disturbance could be due to HSV-induced dysfunction of sweat glands. We developed a sweating disturbance-induced dry skin mouse model by infection with HSV-1.


Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Animales , ADN , Inmunoglobulina G , Ratones , Pilocarpina , Glándulas Sudoríparas , Sudoración
4.
Exp Dermatol ; 31(12): 1891-1899, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36054736

RESUMEN

A long-standing paradox in dermatology is why skin dehydration in the fingers can be triggered by repeated water exposure despite the action of water to hydrate skin tissue. Potential clues might be provided by identifying a mechanism through which water is held in the skin of the fingers. We speculated that this mechanism would be impaired after repeated water exposure. Here, we investigated whether there might be glabrous skin-specific water-holding machinery and whether this machinery might be impaired in dry skin/hand eczema. We examined this by using an impression-mould technique, allowing for an accurate quantification of sweat gland/duct activity and optical coherence tomography. Unlike in hairy skin, sweat pores were rarely detected at the folds of the finger at baseline. Surprisingly, after water exposure, sweat pores at the folds opened and those at the ridges closed in healthy controls (HCs). Sweating in the dermal folds of the hands correlated with skin hydration, and decreased in dry skin/hand eczema, suggesting that its impairment may be one of the causes of dry skin. After repeated water exposure, basal sweating response at the folds was exhausted in patients with dry skin/hand eczema as well as HCs. This exhaustion was rescued by exposing individuals to high humidity. Basal sweating defects would be a target for dry skin/hand eczema. Maintaining basal sweating responses in the finger is the best preventive measures in achieving prevention of dry skin/hand eczema.


Asunto(s)
Eccema , Sudoración , Humanos , Piel , Glándulas Sudoríparas/fisiología , Agua
5.
Anticancer Res ; 42(9): 4319-4328, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36039444

RESUMEN

BACKGROUND/AIM: The development of new drugs is urgently needed for new treatment strategies that can improve the prognosis of osteosarcoma (OS). In this study, we attempted to identify combinations of new molecular-targeted agents for OS. MATERIALS AND METHODS: A library containing 324 compounds was used. For the first screening, MG-63 OS cells were treated with each of the compounds and cell viability was measured. After the best candidate compound was decided, the compound was included in a second screening. The combination of most effective compounds was decided. The antiproliferative effect of the combination was examined and the cell signaling mechanism was evaluated by western blot analysis. 143B OS-bearing mice were used for in vivo antitumor testing. RESULTS: In the first screening, bortezomib was chosen as the effective drug. In the second screening with bortezomib, everolimus was chosen. This combination showed a synergistic inhibitory effect on cell proliferation when compared to monotherapy with each of these drugs alone. Compared to monotherapy, the combination therapy enhanced the levels of cleaved poly (ADP-ribose) polymerase, caspase-3, caspase-8 and caspase-9, phospho-c-Jun N-terminal kinase, and P38. In contrast, the levels of c-MYC proto-oncogene bHLH transcription factor, survivin, and phospho-cyclin D1 were reduced. The combination effectively induced apoptosis and interfered with cell cycle progression. In the in vivo analysis, the combination therapy significantly inhibited tumor growth. CONCLUSION: The combination of everolimus and bortezomib demonstrated a synergistic effect against OS both in vitro and in vivo. These results indicate that this combination may be useful as a novel therapeutic strategy for OS.


Asunto(s)
Antineoplásicos , Neoplasias Óseas , Osteosarcoma , Animales , Antineoplásicos/farmacología , Apoptosis , Neoplasias Óseas/tratamiento farmacológico , Bortezomib/farmacología , Bortezomib/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Combinación de Medicamentos , Everolimus/farmacología , Ratones , Osteosarcoma/patología , Inhibidores de Proteasoma/farmacología , Serina-Treonina Quinasas TOR/metabolismo
6.
BMC Cancer ; 21(1): 364, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827473

RESUMEN

BACKGROUND: The intimate relationship between coagulation and fibrinolysis in malignant tumors is a well-known phenomena, with the malignant phenotype enhancing coagulation and fibrinolysis. We hypothesized that soft tissue sarcoma (STS) affects the expression of coagulation and fibrinolysis markers, which could be used to distinguish STS from benign soft tissue tumors. We analyzed the correlations between plasma levels of D-dimer (DD), plasmin-α2 plasmin inhibitor complex (PIC), soluble fibrin (SF), and thrombin-antithrombin III complex (TAT) in benign soft tissue tumors and STS to elucidate whether these markers can be used to predict STS. METHODS: Plasma DD, PIC, SF and TAT levels in primary soft tissue tumors (benign 67, STS 68) were measured before biopsy or treatment. The marker levels were analyzed and compared to various clinicopathological parameters. RESULTS: In malignancy (STS), the average DD, PIC and SF levels were significantly higher than in benign tumors. Multivariate logistic analysis of continuous variables indicated that only PIC exhibited a significant difference (OR: 24.5, 95%CI: 3.55-170, p = 0.0012). Receiver operating characteristic curve analysis produced area under the curve values for DD: 0.691, PIC: 0.784, SF: 0.734 and TAT: 0.588. Youden's index was used to establish thresholds of 0.37 (DD), 0.80 (PIC), 0.90 (SF) and 0.82 (TAT). Threshold values for PIC and SF indicated high specificity (0.881, 0.791) and high positive predictive value (0.818, 0.745), respectively. The highest accuracy value among the markers was observed for PIC (0.704). Significant differences in multivariate analysis of binary variables were demonstrated by categorizing low and high groups based on their threshold, PIC (≥0.80) (OR: 3.36, 95%CI: 1.19-9.43, p = 0.0212) and SF (≥0.90) (OR: 2.63, 95%CI: 1.04-6.66, p = 0.0404) . CONCLUSIONS: Of the coagulation and fibrinolysis markers studied, increased PIC levels were related to STS and over 0.80 PIC was the most suitable for the prediction of STS, which, along with other diagnostic tools, represents a helpful subsidiary tool for the prediction of STS.


Asunto(s)
Biomarcadores/sangre , Coagulación Sanguínea/genética , Fibrinólisis/genética , Neoplasias de los Tejidos Blandos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
7.
Orthop Surg ; 12(6): 1726-1732, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33015987

RESUMEN

OBJECTIVE: To elucidate the correlation between expression of thrombomodulin (TM) mRNA from 83 benign soft tissue tumors or soft tissue sarcomas (STS) and clinicopathological parameters and to analyze the outcome of high-grade STS patients after 10 years. METHODS: Total RNA was extracted from 83 primary soft tissue tumors (15 benign tumors, 68 STS). TM mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase was measured with real-time quantitative polymerase chain reaction and compared to various clinicopathological parameters. The log-rank test and Cox proportional hazard analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival. RESULTS: Thrombomodulin mRNA levels were not significantly different between benign tumors and STS. In STS, TM mRNA levels were not significantly different between histologically high-grade (n = 57) and low-grade (n = 11) tumors. Following analysis of high-grade STS at the 10-year follow-up, 21 patients had experienced a recurrence, 22 patients had experienced metastasis, and 23 patients had died of disease (DOD). TM levels were significantly higher in patients with metastasis or DOD patients. Receiver operating characteristic analysis for identifying 5-year and 10-year DOD determined the threshold for best sensitivity and specificity as 0.283. We divided patients into those with high (<0.283) and low (≤0.283) TM mRNA levels. Based on Kaplan-Meier analysis, a significant difference between the two groups was seen for recurrence-free survival (5 years: low = 76.6%, high = 53.1%, 10 years: low: 67.0%, high 39.8%, P = 0.0122) and metastasis-free survival (5 years: low = 86.3%, high = 40.2%, 10 years: low: 73.3%, high: 35.2%, P = 0.00023). Furthermore, the high TM group showed significantly worse prognosis than the low TM group (5 years: low = 90.1%, high = 42.3%, 10 years: low: 76.4%, high 31.3%, P = 0.00031). Thus, high levels of TM mRNA are associated with highly recurrent and metastatic potential and lead to poor prognosis. In multivariate Cox proportional hazard analysis, only high TM showed a significant difference in metastasis-free survival (hazard ratio: 4.33, 95% confidence interval 1.61-11.6, P = 0.00359) and overall survival (hazard ratio: 3.69, 95% confidence interval 1.49-10.5, P = 0.00569). CONCLUSION: High levels of TM mRNA may be a significant predictor of recurrence, metastasis, and a poor outcome in STS patients after 10 years. TM is a candidate molecular marker and may be clinically useful for devising a therapeutic treatment strategy by prediction of prognosis.


Asunto(s)
Sarcoma/genética , Neoplasias de los Tejidos Blandos/genética , Trombomodulina/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/metabolismo , Curva ROC , Adulto Joven
8.
Sci Rep ; 10(1): 9077, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493964

RESUMEN

The soluble form of PD-L1 (sPD-L1) is related to a poor prognosis in various cancers. Comparisons of sPD-L1 and PD-L1 expressed on tumor cells in soft tissue tumor patients have not been reported. The purpose of this study was to analyze serum sPD-L1 and PD-L1 levels in soft tissue tumor patients. A total of 135 patients with primary soft tissue tumors were enrolled in this study. The sPD-L1 level was quantitatively measured by enzyme immunoassay, and PD-L1 expression on high grade sarcoma cells was analyzed immunohistologically. There were no significant differences in sPD-L1 levels between benign (48) and soft tissue sarcoma (STS) patients (87). In STS, the high sPD-L1 (>44.26 pg/mL) group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low sPD-L1 group (≤44.26 pg/mL) at 5 years using the log-rank test. On multivariate Cox proportional hazard analysis, the high sPD-L1 group had significant differences in MS and OS compared to the low sPD-L1 group. Between positive and negative immunostaining groups, recurrence-free survival (RS), MS, and OS were not significantly different. No correlation was found between immunostaining and sPD-L1 with the Kappa coefficient. The sPD-L1 concentration could predict future metastasis and prognosis in STS patients. High sPD-L1 in STS patients may be a target for treatment with checkpoint inhibitors.


Asunto(s)
Antígeno B7-H1/metabolismo , Metástasis de la Neoplasia/patología , Sarcoma/metabolismo , Sarcoma/patología , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/patología , Anciano , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
9.
Cancer Biomark ; 26(2): 163-170, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31356193

RESUMEN

BACKGROUND: Thrombomodulin (TM) has multiple biological functions and modulates not only anti-coagulation, but also cell proliferation, adhesion, and anti-inflammation activities. The main function of TM is to activate the anticoagulant pathway of protein C. Soluble TM is related to metastasis by its inactivation of thrombin. OBJECTIVES: To clarify the correlation between serum TM levels and clinicopathological parameters. METHODS: The plasma TM levels (FU/ml) of 135 primary soft tissue tumors (benign, 67; soft tissue sarcoma (STS), 68) were measured before biopsy or treatment. TM levels were analyzed and compared to various clinicopathological parameters. Log-rank test and Cox proportional analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival. RESULTS: STS tumors had significantly higher TM values (15.9) than benign tumors (13.7) (p= 0.0138). 5-year MFS was 81.1% in low TM and 40.0% in high TM (p= 0.00671), and 5-year OS was 85.5% in low and 52.5% in high TM in grades 1-3 (p= 0.0673). In multivariate COX proportional analysis, high-TM showed a significant difference (MFS: HR 4.37, p= 0.0147; OS: HR 3.60, p= 0.0557) in grades 1-3. CONCLUSIONS: We demonstrated that a high level of soluble TM has the potential to be a significant predictor of metastasis and poor prognosis in STS patients. TM is a candidate molecular marker for high metastatic potential and can be clinically useful for guiding therapeutic strategy.


Asunto(s)
Biomarcadores de Tumor/sangre , Sarcoma/secundario , Neoplasias de los Tejidos Blandos/patología , Trombomodulina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Sarcoma/sangre , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/sangre , Neoplasias de los Tejidos Blandos/cirugía , Tasa de Supervivencia , Adulto Joven
10.
Int J Oncol ; 49(6): 2275-2284, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27840900

RESUMEN

The development of clinical agents remains a costly and time-consuming process. Although identification of new uses of existing drugs has been recognized as a more efficient approach for drug discovery than development of novel drugs, little screening of drugs that might be used for a rare malignant tumor such as osteosarcoma (OS) has been performed. In this study, we attempted to identify new molecular targeted agents for OS by employing Screening Committee of Anticancer Drugs (SCADS) kits. To screen compounds for OS treatment, their effect on cell viability of the OS cell lines 143B, MG63, HOS, SAOS-2, and HUO9 were evaluated. Candidate drugs were narrowed down based on a global anti-proliferative effect against these five OS cell lines. After excluding cytotoxic compounds and compounds unsuitable for in vivo administration, cucurbitacin I was extracted. Cucurbitacin I has been found to have cytotoxic and anti-proliferative properties against several tumors through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Cucurbitacin I dose- and time-dependently inhibited the proliferation of all five OS cell lines. Following cucurbitacin I treatment, STAT3 was inactivated and analysis of Mcl-1, cleaved PARP and caspase-3 indicated apoptosis induction. Expression of cell cycle regulator proteins, such as phospho-cyclin D1, c-Myc and survivin, were suppressed. Finally, cucurbitacin I potently inhibited the tumor growth of human OS 143B cells in nude mice. Our in vitro and in vivo results suggest that STAT3 inhibition by cucurbitacin I will be an effective and new approach for the treatment of OS.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Triterpenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Neoplasias Óseas/patología , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ciclina D1/metabolismo , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Ratones , Ratones Desnudos , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Osteosarcoma/patología , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal/efectos de los fármacos , Survivin , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Cancer Biomark ; 16(3): 453-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27062702

RESUMEN

BACKGROUND: Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. OBJECTIVES: The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. METHODS: The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. RESULTS: According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). CONCLUSIONS: We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.


Asunto(s)
Fibrinógeno/metabolismo , Sarcoma/sangre , Sarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/sangre , Neoplasias de los Tejidos Blandos/diagnóstico , Proliferación Celular , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología
13.
Breast Cancer ; 20(3): 241-6, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22359194

RESUMEN

BACKGROUND: Breast cancer has the potential to metastasize to bone, causing debilitating symptoms. Although many tumor cells have thrombin-generating systems originating from tissue factor (TF), therapy in terms of the coagulation system is not well established. To elucidate the efficacy of the thrombin inhibitor, argatroban, on bone metastasis, we investigated TF activation and vascular endothelial growth factor (VEGF) secretion on treatment with thrombin and argatroban. METHODS: MDA-231 breast cancer cells were treated with thrombin in presence or absence of argatroban, and TF activity was measured in the form of activated factor X. Enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF concentrations in the medium. MDA-231 cells were injected into the left heart ventricle of mice, and then argatroban or saline was administered intraperitoneally for 28 days. After 28 days, incidence of bone metastasis was evaluated in the limbs by radiography. RESULTS: TF activity and VEGF secretion were upregulated by thrombin. Argatroban inhibited the enhancement of TF activity and VEGF secretion induced by thrombin. In vivo analysis revealed that the number of metastasized limbs in the argatroban group was significantly lower compared with the saline group (P < 0.05). CONCLUSIONS: Thrombin not only enhances VEGF secretion but also has a positive feedback mechanism to reexpress TF. These results indicate that inhibition of thrombin is of great value in suppression of tumor metastasis. Argatroban is a noteworthy and useful thrombin inhibitor because it has already been used in the clinical setting and has antimetastatic effects in vivo.


Asunto(s)
Antitrombinas/farmacología , Neoplasias Óseas/prevención & control , Neoplasias de la Mama/prevención & control , Ácidos Pipecólicos/farmacología , Trombina/antagonistas & inhibidores , Animales , Arginina/análogos & derivados , Peso Corporal/efectos de los fármacos , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Ratones , Sulfonamidas , Tromboplastina/metabolismo , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismo
14.
Arthritis Res Ther ; 14(6): R241, 2012 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-23127251

RESUMEN

INTRODUCTION: Platelet-rich plasma (PRP) is a fraction of plasma in which several growth factors are concentrated at high levels. The active soluble releasate isolated following platelet activation of PRP (PRP-releasate) has been demonstrated to stimulate the metabolism of IVD cells in vitro. The in vivo effect of PRP-releasate on degenerated IVD remains unknown. The purpose of this study was to determine the reparative effects of autologous PRP-releasate on degenerated intervertebral discs (IVDs). METHODS: To induce disc degeneration, New Zealand white rabbits (n = 12) received anular puncture in two noncontiguous discs. Autologous PRP and PPP (platelet-poor plasma) were isolated from fresh blood using two centrifugation techniques. Four weeks after the initial puncture, releasate isolated from clotted PPP or PRP (PPP- or PRP-releasate), or phosphate-buffered saline (PBS; control) was injected into the punctured discs. Disc height, magnetic resonance imaging (MRI) T2-mapping and histology were assessed. RESULTS: Anular puncture produced a consistent disc narrowing within four weeks. PRP-releasate induced a statistically significant restoration of disc height (PRP vs. PPP and PBS, P<0.05). In T2-quantification, the mean T2-values of the nucleus pulposus (NP) and anulus fibrosus (AF) of the discs were not significantly different among the three treatment groups. Histologically, the number of chondrocyte-like cells was significantly higher in the discs injected with PRP-releasate compared to that with PBS. CONCLUSIONS: The administration of active PRP-releasate induced a reparative effect on rabbit degenerated IVDs. The results of this study suggest that the use of autologous PRP-releasate is safe and can lead to a clinical application for IVD degeneration.


Asunto(s)
Modelos Animales de Enfermedad , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Degeneración del Disco Intervertebral/terapia , Plasma Rico en Plaquetas/fisiología , Animales , Condrocitos/efectos de los fármacos , Condrocitos/fisiología , Femenino , Inyecciones , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/efectos de los fármacos , Disco Intervertebral/fisiopatología , Degeneración del Disco Intervertebral/etiología , Degeneración del Disco Intervertebral/fisiopatología , Imagen por Resonancia Magnética , Plasma Rico en Plaquetas/metabolismo , Punciones/efectos adversos , Conejos , Radiografía , Factores de Tiempo , Resultado del Tratamiento
15.
Orthopedics ; 34(9): e578-80, 2011 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-21902161

RESUMEN

Recurrent hemarthrosis after knee arthroplasty can be disabling, requiring adequate and immediate diagnosis and treatment for recovery of symptoms and joint function. The most commonly reported cause is impingement of proliferative synovium between prosthetic components. Although various procedures for hemarthrosis have been reported after knee arthroplasty for patients who do not respond to conservative treatment, the recommended first-line therapy is open surgery or embolization. Although hyperplastic synovium was observed during the first and second arthrotomy, in our case, tissue impingement was not detected. We describe a rare case of recurrent hemarthrosis after unicompartmental knee arthroplasty (UKA) and successful treatment by open synovectomy. A 66-year-old woman presented with spontaneous osteonecrosis of the medial femoral condyle in the right leg. She underwent UKA of the right knee of the medial condyle. Eighteen months after UKA, the patient developed recurrent hemarthrosis. Open arthrotomy was performed 22 months after UKA, revealing only hematoma with no obvious hemorrhage or loosening of the prosthesis. No history of trauma or use of anticoagulant medications was present. After a symptom-free period of 8 months, another 2 episodes of hemarthrosis occurred over the course of 8 months. A second open arthrotomy was performed. Hyperplastic synovium with fibrin and hemosiderin pigmentation was observed, again without hemorrhage or loosening. There were no pathological features of pigmented villonodular synovitis. Synovectomy was performed, and no hemarthrosis has recurred for 2 years.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Hemartrosis/etiología , Anciano , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Hemartrosis/cirugía , Humanos , Complicaciones Posoperatorias , Recurrencia , Sinovectomía
16.
Spine J ; 11(10): 927-32, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21925953

RESUMEN

BACKGROUND CONTEXT: Detection of ossification of the posterior longitudinal ligament (OPLL) of lesions by lateral radiography is sometimes difficult because the lesions are small. Three-dimensional computed tomography (3D CT) imaging has made it possible to detect lesions not been seen by lateral radiography. PURPOSE: To evaluate the use of 3D CT in visualizing and classifying OPLL, and the added value of magnetic resonance imaging (MRI) in determining spinal cord compression. STUDY DESIGN: Prospective case study in an academic department of orthopedic surgery. PATIENT SAMPLE: Patients with OPLL diagnosed by lateral radiography of the cervical spine from April 2006 to March 2007 were identified. METHODS: Ossification of the posterior longitudinal ligament visualized lateral radiography was classified according to the existing scheme as continuous, segmental, mixed, or other type. Ossification of the posterior longitudinal ligament visualized by 3D CT was organized into a classification system comprising flat, irregular, or localized types and were compared with the lateral radiographic images. Magnetic resonance imaging was done to determine the extent of spinal cord compression. RESULTS: All 55 patients (35 men and 20 women; median age, 66 years) with OPLL were enrolled. Of these, 41 (75%) had a type of OPLL as visualized by 3D CT that corresponded with only one type of OPLL as visualized by lateral radiography. In 39 (71%) of 55, the areas of the ossified lesions visualized by 3D CT were the same as those visualized by lateral radiography. In the other 16, the lesions were either too small or too unclear to be visualized by lateral radiography. In all cases, 3D CT imaging showed that the transverse width of OPLL was within the bilateral Luschka joints, which was not noted by lateral radiography. In 13 of the 14 subjects who underwent MRI, spinal cord compression was noted at the superior or inferior edges of the ossified lesions that had been seen by 3D CT. CONCLUSIONS: Three-dimensional computed tomography visualization of OPLL provided the basis of a classification system, superior to lateral radiography, and provided new information about OPLL. Combining 3D CT with MRI might be useful to provide details about spinal cord compression in OPLL.


Asunto(s)
Osificación del Ligamento Longitudinal Posterior/diagnóstico , Compresión de la Médula Espinal/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osificación del Ligamento Longitudinal Posterior/diagnóstico por imagen , Osificación del Ligamento Longitudinal Posterior/patología , Estudios Prospectivos , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/patología , Tomografía Computarizada por Rayos X
18.
Asian Spine J ; 5(1): 68-72, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21386949

RESUMEN

Ependymomas are uncommon tumors that arise in the brain, spinal cord or cauda equina. Myxopapillary ependymomas is located exclusively in the conus medullaris or cauda equina, or film terminale region. In most myxopapillary ependymomas, the histological examination reveals low mitotic activity that is associated with a low MIB-1 labeling index (LI). The prognosis is generally favorable, when the appropriate treatment, including a total resection, is performed. The authors encountered a 39-year-old man with multifocal type of myxopapillary ependymomas compressing the cauda equina from the L2 to L3 level and L5-S1 level. A subtotal resection of the tumor was carried out. The histological examination revealed extremely high mitotic activity with a MIB-1 LI of 9.1%. Therefore, cranio-spinal radiation was added after surgery. The postoperative course was uneventful over the 3.5 year follow-up period.

19.
J Anesth ; 25(1): 120-2, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21188427

RESUMEN

Upper airway obstruction resulting from overflexion fixation of the cervical spine is a rare but life-threatening complication after cervical spine surgery. There are few reports of dyspnea after a posterior cervical fusion. We present the case of a 63-year-old woman with rheumatoid arthritis who developed an upper airway obstruction immediately after an O-C4 fusion. She was reintubated with a fiberoptic scope. Revision surgery allowing the angle to return to the neutral position was performed to ameliorate the overflexion of the cervical spine fixation and the consequent upper airway obstruction. After revision surgery, the upper airway obstruction disappeared. Our experience suggests that intraoperative use of fluoroscopy and extubation with a tube exchanger are recommended to avoid this complication, especially in patients at high risk of upper airway obstruction.


Asunto(s)
Obstrucción de las Vías Aéreas/etiología , Vértebras Cervicales/fisiología , Vértebras Cervicales/cirugía , Complicaciones Intraoperatorias/etiología , Hueso Occipital/cirugía , Fusión Vertebral/métodos , Obstrucción de las Vías Aéreas/terapia , Anestesia General , Vértebras Cervicales/diagnóstico por imagen , Femenino , Fluoroscopía , Humanos , Complicaciones Intraoperatorias/terapia , Intubación Intratraqueal , Persona de Mediana Edad , Hueso Occipital/diagnóstico por imagen , Postura
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