RESUMEN
Hand osteoarthritis (HOA), characterized by an earlier onset age and reduced susceptibility to mechanical stress compared with knee and hip osteoarthritis, is considered a suitable disease for identifying predictive biomarkers of osteoarthritis. In particular, DNA methylation variants, expected to contribute to HOA susceptibility, hold potential as osteoarthritis biomarkers. In this study, leukocyte DNA methylation patterns were analyzed in blood samples from patients with HOA, aiming to identify disease-specific biomarkers for osteoarthritis. Using DNA methylation microarrays, we analyzed samples from three subjects with HOA and three age- and gender-matched healthy individuals. For validation, pyrosequencing analysis was conducted using samples from 16 to 9 subjects with and without HOA, respectively. From 735,026 probes in the DNA methylation array, the Top 100 CpG sites associated with HOA, based on low adjusted P-values, including those targeting bone morphogenetic protein 7 (BMP7), SBF2-AS1, PLOD2, ICOS, and CSF1R were identified. Validation analysis revealed significantly higher methylation levels in the BMP7-related site in the HOA group compared with the control group, even after adjusting for age, gender, and body mass index (p = 0.037). In contrast, no significant difference was observed in the other selected CpG sites between the HOA and control groups. This study highlights the significantly increased frequency of methylation at the specific BMP7 site in leukocytes of patients with HOA, suggesting its potential as a biomarker for HOA. Measurement of methylation levels at the CpG sites identified in this study offers a potential approach to prevent future osteoarthritis progression, providing valuable insights into disease management.
RESUMEN
INTRODUCTION/AIMS: T2 magnetic resonance imaging (MRI) mapping has been applied to carpal tunnel syndrome (CTS) for quantitative assessment of the median nerve. However, quantitative changes in the median nerve before and after surgery using T2 MRI mapping remain unclear. We aimed to investigate whether pathological changes could be identified by pre- and postoperative T2 MRI mapping of the median nerve in CTS patients after open carpal tunnel release. METHODS: This was a prospective study that measured median nerve T2 and cross-sectional area (CSA) values at the distal carpal tunnel, hamate bone, proximal carpal tunnel, and forearm levels pre- and postoperatively. Associations between T2, CSA, and nerve conduction latency were also evaluated. RESULTS: A total of 36 patients with CTS (mean age, 64.5 ± 11.7 years) who underwent surgery were studied. The mean preoperative T2 values significantly decreased from 56.3 to 46.9 ms at the proximal carpal tunnel levels (p = .001), and from 52.4 to 48.7 ms at the hamate levels postoperatively (p = .04). Although there was a moderate association between preoperative T2 values at the distal carpal tunnel levels and distal motor latency values (r = -.46), other T2 values at all four carpal tunnel levels were not significantly associated with CSA or nerve conduction latency pre- or postoperatively. DISCUSSION: T2 MRI mapping of the carpal tunnel suggested a decrease in nerve edema after surgery. T2 MRI mapping provides quantitative information on the median nerve before and after surgery.
Asunto(s)
Síndrome del Túnel Carpiano , Imagen por Resonancia Magnética , Nervio Mediano , Conducción Nerviosa , Humanos , Síndrome del Túnel Carpiano/cirugía , Síndrome del Túnel Carpiano/diagnóstico por imagen , Nervio Mediano/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Anciano , Conducción Nerviosa/fisiología , Estudios Prospectivos , AdultoRESUMEN
The prognosis for bile duct carcinoma in dogs is generally believed to be poor. However, only a few studies have evaluated the postoperative outcomes in such cases. The objective of this case series was to describe the postoperative outcomes of localized intrahepatic bile duct carcinoma in dogs. The electronic medical records of 16 dogs with bile duct carcinoma were reviewed, and 6 dogs were included in the study. All cases were diagnosed as bile duct carcinoma using postoperative pathology, and five of them had already been diagnosed using preoperative core biopsy. The tumors in all of the dogs were confirmed as completely resected on histopathological examination. Two dogs received toceranib following the surgery. The median follow-up time was 693 days (range, 420-1386 days), with a median survival time of 894 days (range, 420-1386 days). Local recurrence or distant metastases were detected in two of the six dogs (33%) on 354 and 398 days following surgery, respectively. The median progression-free survival was 492 days (range, 354-1386 days). In conclusion, dogs with localized intrahepatic bile duct carcinoma had a good prognosis following complete surgical resection.
Asunto(s)
Carcinoma , Enfermedades de los Perros , Animales , Conductos Biliares , Carcinoma/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/cirugía , Perros , Hígado , PirrolesRESUMEN
Canine hemangiosarcoma (HSA) has an extremely poor prognosis, making it necessary to develop new systemic treatment methods. MicroRNA-214 (miR-214) is one of many microRNAs (miRNA) that can induce apoptosis in HSA cell lines. Synthetic miR-214 (miR-214/5AE), which showed higher cytotoxicity and greater nuclease resistance than mature miR-214, has been developed for clinical application. In this study, we evaluated the effects of miR-214/5AE on stage 2 HSA in a mouse model. Mice intraperitoneally administered with miR-214/5AE (5AE group) had significantly fewer intraperitoneal dissemination tumor foci (median number: 72.5 vs. 237.5; p < 0.05) and a lower median foci weight (0.26 g vs. 0.61 g; p < 0.05). Mice in the 5AE group had increased expression of p53 and cleaved caspase-3, and a significantly lower proportion of Ki-67-positive cells, than those in the non-specific miR group. Notably, no significant side effects were observed. These results indicate that intraperitoneal administration of miR-214/5AE exhibits antitumor effects in an intraperitoneal dissemination mouse model of HSA by inducing apoptosis and suppressing cell proliferation. These results provide a basis for future studies on the antitumor effect of miR-214/5AE for HSA.
Asunto(s)
Enfermedades de los Perros , Hemangiosarcoma , MicroARNs , Enfermedades de los Roedores , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Perros , Regulación Neoplásica de la Expresión Génica , Hemangiosarcoma/tratamiento farmacológico , Hemangiosarcoma/genética , Hemangiosarcoma/veterinaria , Ratones , MicroARNs/genética , Enfermedades de los Roedores/genéticaRESUMEN
OBJECTIVES: This study aimed to compare the pre- and postoperative morphology of the median nerve using three-dimensional (3-D) MRI in patients with carpal tunnel syndrome (CTS). METHODS: We assessed 31 patients with CTS who underwent open carpal tunnel release and T2*-weighted MRI of the wrist preoperatively and at 6 months postoperatively. The median nerve morphology was evaluated on the basis of the cross-sectional areas (CSAs) and cross-sectional volumes (CSVs). The association between these MRI findings and nerve conduction studies was also evaluated. RESULTS: The mean preoperative CSA and CSV values at the proximal carpal tunnel level significantly decreased from 22.2 mm2 and 24.4 mm3 to 16.5 mm2 and 18.1 mm3, respectively, postoperatively. Median nerve swelling at the proximal carpal tunnel level was observed in 29 (94%) and 23 (74%) patients before and after surgery, respectively. The mean preoperative CSA and CSV values at the hamate level significantly increased from 9.9 to 12.3 mm2 and from 10.9 to 13.5 mm3 after surgery, respectively. Nerve narrowing at the hamate bone level was preoperatively observed in 28 (90%) patients and postoperatively in 21 (68%) patients. Preoperative CSA and CSV values at the proximal carpal tunnel were significantly associated with preoperative distal motor and sensory latency. CONCLUSIONS: Visual confirmation of the median nerve morphology using 3-D MRI is useful when considering postoperative recovery and explaining the nerve condition to the patients. KEY POINTS: ⢠The 3-D morphology of the median nerve after carpal tunnel release can be delineated using 3-D MRI. ⢠Preoperative swelling of the median nerve in the 2-D and 3-D planes reflects the severity of carpal tunnel syndrome. ⢠Visual confirmation of the median nerve morphology is useful when considering median nerve recovery after carpal tunnel release and for explaining the condition of the nerve to patients.
Asunto(s)
Síndrome del Túnel Carpiano , Nervio Mediano , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Nervio Mediano/patología , Muñeca/diagnóstico por imagen , Articulación de la MuñecaRESUMEN
INTRODUCTION: We investigated the changes in MRI T2 mapping values in subjects with carpal tunnel syndrome (CTS) compared to healthy controls. METHODS: We enrolled 71 patients with CTS and 26 healthy controls. Median nerve T2 values were measured at the distal carpal tunnel, hamate bone, proximal carpal tunnel, and forearm levels. These were compared between patients and controls and correlated with median nerve cross-sectional area (CSA) and nerve conduction measurements. RESULTS: The mean T2 values at the proximal carpal tunnel levels were higher in the CTS group (56.7 ms) than in the control group (51.2 ms, P = .02) and also were higher than at the distal carpal tunnel (51.0 ms, P < .001) and forearm levels (47.6 ms, P < .001). T2 values were not significantly associated with CSA or nerve conduction measurements. DISCUSSION: T2 mapping of the carpal tunnel provides qualitative information on median nerve pathology but does not reflect CTS severity.
Asunto(s)
Síndrome del Túnel Carpiano/diagnóstico por imagen , Nervio Mediano/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
This retrospective cohort study was designed to validate the reliability of measurement of the lateral capitellohumeral angle (LCHA), an index of sagittal angulation of the elbow, in healthy children. The results were compared to the Baumann angle (BA), which is a similar concept to LCHA.Sixty-two radiographs of the elbow in healthy children (range, 2-11 years) were reviewed by 6 examiners at 2 sessions. The mean value and reliability of the measurement of LCHA and BA were assessed. Intraobserver reliability and interobserver reliability were calculated using intraclass correlation coefficients (ICCs).The mean LCHA value was 45° (range, 22° to 70°) and the mean BA was 71° (range, 56° to 86°). The ICCs for intraobserver reliability of the LCHA measurements were almost perfect for 2 examiners, substantial for 3 examiners, and moderate for 1 examiner with a mean value of 0.77 (range, 0.57-0.95). For BA measurements, the ICCs were almost perfect for 1 examiner and substantial for 5 examiners with a mean value of 0.74 (range, 0.66-0.83). The ICCs for interobserver reliability between the first and second measurements were both moderate for LCHA (0.56 and 0.51) and for BA (0.52 and 0.50).LCHA showed almost the same reliability in measurement as BA, which is the gold standard assessment for coronal alignment of the elbow. LCHA showed moderate-to-good reliability in the evaluation of sagittal plane elbow alignment.
Asunto(s)
Articulación del Codo/diagnóstico por imagen , Húmero/diagnóstico por imagen , Niño , Preescolar , Femenino , Voluntarios Sanos , Humanos , Masculino , Variaciones Dependientes del Observador , Radiografía , Valores de Referencia , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
OBJECTIVE: We examined the surgical outcomes of the Sauvé-Kapandji (S-K) procedure using a headless compression screw and a metal cancellous screw in patients with rheumatoid arthritis (RA). METHODS: This retrospective study included 41 RA patients who underwent the S-K procedure for distal radioulnar joint disorders with two screws: headless compression screws (HCS group, n = 20) and cannulated cancellous screws (CCS group, n = 21). Clinical and radiographic outcomes were assessed 1 year after surgery. Radiographic outcomes included bony union of the distal radioulnar joint (DRUJ), bone resorption around the screw, a screw back-out, and use of additional K-wire. We investigated any complications related to the screw head. RESULTS: All 20 patients in the HCS group showed bone fusion of the DRUJ. In the CCS group, an asymptomatic non-union was observed in one patient and additional K-wire was needed to stabilize the DRUJ in three patients. No patients complained of any complications related to the screw head in the HCS group, while the CCS group demonstrated the hardware protrusion in two patients who complained of tenderness or discomfort at the screw head. CONCLUSIONS: The use of a headless compression screw in the S-K procedure is useful in patients with RA.
Asunto(s)
Artritis Reumatoide/cirugía , Artrodesis/métodos , Tornillos Óseos , Articulación de la Muñeca/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Resultado del Tratamiento , Articulación de la Muñeca/diagnóstico por imagen , Adulto JovenRESUMEN
This article was updated on May 4, 2017, because of a previous error. The proximal line drawn in Figure 1 was different from the line described in the Materials and Methods section, which reads "The proximal line was drawn at the level of the radial tuberosity, and the distal line was made at the level of the top of the radial bowing (Fig. 1)." The correct figure is presented in this version of the article. An erratum has been published: JBJS Open Access. 2017 May 26;2(2):e0012ER. BACKGROUND: We conducted a retrospective cohort study to evaluate the normal value, range, reliability, and validity of measurement of the humerus-elbow-wrist angle, an index of valgus-varus angulation of the elbow, in healthy children. This measurement has been used to assess postoperative radiographic results. METHODS: Radiographs of the elbow in 62 healthy children ranging from 2 to 11 years of age were reviewed by 6 examiners at 2 sessions. The mean value and the reliability of measurement of the humerus-elbow-wrist angle, the carrying angle, and the Baumann angle were assessed. Intraobserver and interobserver reliability were calculated with use of intraclass correlation coefficients (ICCs). To determine concurrent validity, the association between the humerus-elbow-wrist angle and carrying angle measurements was examined with use of Pearson correlation coefficients. RESULTS: The mean humerus-elbow-wrist angle value was 12.0° (range, 1° to 24°), and the mean carrying angle was 14.6° (range, 4° to 28°). The ICCs for intraobserver measurements of the humerus-elbow-wrist angle were almost perfect for 4 examiners and were substantial for 2 examiners, with a mean value of 0.85 (range, 0.73 to 0.94). The ICCs for interobserver reliability with regard to the first and second measurements of the humerus-elbow-wrist angle were both substantial (0.76 and 0.78). A significant association between the humerus-elbow-wrist angle and the carrying angle was observed, with the Pearson correlation coefficients ranging from 0.74 to 0.90 (p < 0.001). CONCLUSIONS: Measurement of the humerus-elbow-wrist angle demonstrated good reliability and validity. The humerus-elbow-wrist angle is a reliable radiographic measure of coronal alignment of the humerus and forearm.
RESUMEN
The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus.
Asunto(s)
Dióxido de Carbono/química , Química Farmacéutica/métodos , Polímeros/química , Polímeros/metabolismo , Agua/química , Agua/metabolismo , Administración Oral , Solubilidad , ComprimidosRESUMEN
Oral oil formulations have been reported to deliver drugs into the lymph. Lymphatic delivery of immunomodulatory drugs can more efficiently expose the drugs to T-cells in lymph, consequently induce higher efficacy and lower side effects. In this study, effects of tacrolimus oral oil formulations on drug blood exposure, and on inhibition of T-cell's interleukin-2 (IL-2) production were investigated in rats. Oil formulations (sunflower oil, cacao butter, medium chain triglyceride, and palm oil) dissolving tacrolimus showed lower drug blood concentration than a solid dispersion formulation (SDF). The sunflower oil, and cacao butter formulations suppressed drug blood exposure to 50% of the SDF, and inhibited T-cell's IL-2 production similar to the SDF. In vitro digestion tests indicated that slower digestion of the oils might reduce amount and rate of tacrolimus blood absorption. The cacao butter formulations showed 3.0 times more rapid tacrolimus absorption to lymphatic fluid than the SDF. Ratio of the rate constants of absorption into lymph to that into blood was higher in oil formulations (15 times in cacao butter, 15 times sunflower oil, and 3.5 times palm oil) than in the SDF. These results indicated that the oral oil formulations might be suitable for reduced tacrolimus blood concentration for low systemic side effects, and keep high lymph concentration for high efficacy in organ transplantation patients.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Interleucina-2/antagonistas & inhibidores , Ganglios Linfáticos/efectos de los fármacos , Aceites de Plantas/administración & dosificación , Linfocitos T/efectos de los fármacos , Tacrolimus/administración & dosificación , Animales , Química Farmacéutica , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/farmacocinética , Relación Dosis-Respuesta a Droga , Interleucina-2/biosíntesis , Ganglios Linfáticos/metabolismo , Masculino , Aceite de Palma , Aceites de Plantas/química , Aceites de Plantas/farmacocinética , Ratas , Ratas Endogámicas Lew , Aceite de Girasol , Linfocitos T/metabolismo , Tacrolimus/química , Tacrolimus/farmacocinéticaRESUMEN
PURPOSE: Sepantronium bromide (YM155) is administered by 168-hour continuous infusions in clinical studies due to its time-dependent pharmacological efficacy and rapid elimination from plasma. To enable more convenient administration, i.e., bolus injections with low frequency, we prepared liposomal formulations of YM155 and evaluated their antitumor activities. METHODS: A kinetic simulation model of liposomal YM155 to predict the free drug concentration in both tumor and plasma was developed. A liposomal formulation with the target drug release rate was prepared based on the simulation. Antitumor activities of the formulation were examined in various tumor xenograft mouse models. In addition, antitumor activities of liposomal formulations with different drug release rates were compared in order to confirm the validity of the simulation-based prediction. RESULTS: Liposomal YM155 with the release half-life of 48 h was prepared as a promising formulation. This formulation showed significantly potent antitumor activities in tumor xenograft models by weekly bolus injections. Further studies demonstrated that this release rate was optimal for YM155 in terms of both efficacy and safety. CONCLUSIONS: We successfully developed a liposomal formulation of YM155 that could substitute for long-term continuous infusion of the drug solution in clinical settings by being given as weekly bolus injections.
Asunto(s)
Antineoplásicos/farmacocinética , Portadores de Fármacos/química , Imidazoles/farmacocinética , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Modelos Biológicos , Naftoquinonas/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Química Farmacéutica , Simulación por Computador , Preparaciones de Acción Retardada , Esquema de Medicación , Diseño de Fármacos , Liberación de Fármacos , Humanos , Imidazoles/administración & dosificación , Imidazoles/química , Imidazoles/farmacología , Liposomas , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Naftoquinonas/administración & dosificación , Naftoquinonas/química , Naftoquinonas/farmacología , Survivin , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We report a case of primary lung cancer with ossification. A 69-year-old woman was referred to our hospital due to an abnormal shadow on a chest roentgenogram. Chest computed tomography demonstrated an irregular mass with scattered high-density areas in the left lower lung. Excisional biopsy of the mass revealed lung adenocarcinoma, and we performed left lower lobectomy. Histologic examination revealed the tumor to be a papillary adenocarcinoma with ossification. We confirmed that bone morphogenetic protein(BMP)-2 developed from the tumor by a western blot analysis.
Asunto(s)
Adenocarcinoma/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Neoplasias Pulmonares/metabolismo , Osificación Heterotópica/metabolismo , Adenocarcinoma/complicaciones , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma del Pulmón , Anciano , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Estadificación de Neoplasias , Osificación Heterotópica/etiología , Tomografía Computarizada por Rayos XRESUMEN
A 69-year-old woman was referred to our hospital due to an abnormal shadow on a chest roentgenogram. Computed tomographic scanning revealed a complete atelectasis of the left lower lobe. Though the definitive diagnosis was not obtained preoperatively, we performed a left lower lobe excision because atelectasis existed for more than one year. Immunohistochemical staining showed that tumor cells were positive for vimentin, CD34, bcl-2, CD99, and negative for S-100, α-smooth muscle actin. The tumor was diagnosed as a solitary fibrous tumor of the bronchus, which has been rarely reported to date.
Asunto(s)
Neoplasias de los Bronquios/cirugía , Tumores Fibrosos Solitarios/cirugía , Anciano , Neoplasias de los Bronquios/patología , Femenino , Humanos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
A 35-year-old man was referred to our hospital, because of recurrent pneumonia. His chest X-ray film and computed tomography showed mass-like consolidation with a cavity in the right upper lobe. He underwent a bronchoscopic examination, but no diagnosis was established. Therefore a surgical biopsy was performed, but the pathological findings revealed that it was only an inflammatory change without any malignant component. For a while, antibiotic and the steroid treatment was continued resulting in the aggravation of clinical findings. Finally, an upper lobe excision was performed for the complete excision of the lesion. As a result of pathology, pulmonary actinomycosis was diagnosed.
Asunto(s)
Actinomicosis/diagnóstico , Enfermedades Pulmonares/diagnóstico , Actinomicosis/cirugía , Adulto , Biopsia , Humanos , Enfermedades Pulmonares/cirugía , Masculino , Neumonectomía , Tomografía Computarizada por Rayos XRESUMEN
Sepantronium bromide (YM155) exhibits time-dependent antitumor activity, although the plasma half-life of YM155 after a bolus intravenous (i.v.) administration is very short. Therefore, greater antitumor efficacy is obtained by continuous infusion than by bolus i.v. administration. In the present study, we attempted to liposomalize YM155 to obtain a longer circulation time than that achieved by bolus i.v. administration and yet retain sufficient antitumor activity. Encapsulation of YM155 in polyethylene glycol-coated liposomes extended the half-life of the drug, and high tumor accumulation of the drug was observed. Bolus i.v. administration of liposomal YM155 by a weekly administration regimen showed antitumor activity comparable to that obtained by the continuous infusion without severe toxicity in a murine xenograft model. Therefore, this liposomal formulation can be a new dosage form of YM155 that achieves sufficient efficacy and safety and is a more convenient administration regimen for users. It should be noted that liposomal YM155 showed unexpectedly high accumulation in the kidneys. This is a specific finding for liposomal YM155, offering important information for the consideration of the potential toxicity of liposomal YM155.