RESUMEN
Aims: The aim of this study was to investigate the clinical and radiographic outcomes of microendoscopic laminotomy in patients with lumbar stenosis and concurrent degenerative spondylolisthesis (DS), and to determine the effect of this procedure on spinal stability. Patients and Methods: A total of 304 consecutive patients with single-level lumbar DS with concomitant stenosis underwent microendoscopic laminotomy without fusion between January 2004 and December 2010. Patients were divided into two groups, those with and without advanced DS based on the degree of spondylolisthesis and dynamic instability. A total of 242 patients met the inclusion criteria. There were 101 men and 141 women. Their mean age was 68.1 years (46 to 85). Outcome was assessed using the Japanese Orthopaedic Association and Roland Morris Disability Questionnaire scores, a visual analogue score for pain and the Short Form Health-36 score. The radiographic outcome was assessed by measuring the slip and the disc height. The clinical and radiographic parameters were evaluated at a mean follow-up of 4.6 years (3 to 7.5). Results: There were no significant differences in the preoperative measurements between the group and no significant differences between the clinical parameters at the final follow-up. The mean percentage slip was 17.1% preoperatively and 17.7% at the final follow-up (p = 0.35). Progressive instability was noted in 13 patients (8.2%) with DS and 6 patients (7.0%) with advanced DS, respectively (p = 0.81). There was radiological evidence of restabilization of the spine in 30 patients (35%) with preoperative instability. The success rate of microendoscopic laminotomy was good/excellent in 166 (69%), fair in 49 (20%) and poor in 27 patients (11%) in both groups. Conclusion: Microendoscopic laminotomy is an effective form of surgical treatment for patients with DS and stenosis. Preservation of the stabilizing structures using this technique prevents postoperative instability. Cite this article: Bone Joint J 2018;100-B:499-506.
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Endoscopía/métodos , Laminectomía/métodos , Vértebras Lumbares/cirugía , Estenosis Espinal/cirugía , Espondilolistesis/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/etiología , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Estenosis Espinal/complicaciones , Estenosis Espinal/diagnóstico por imagen , Espondilolistesis/complicaciones , Espondilolistesis/diagnóstico por imagenRESUMEN
Hot Jupiters are giant Jupiter-like exoplanets that orbit their host stars 100 times more closely than Jupiter orbits the Sun. These planets presumably form in the outer part of the primordial disk from which both the central star and surrounding planets are born, then migrate inwards and yet avoid falling into their host star. It is, however, unclear whether this occurs early in the lives of hot Jupiters, when they are still embedded within protoplanetary disks, or later, once multiple planets are formed and interact. Although numerous hot Jupiters have been detected around mature Sun-like stars, their existence has not yet been firmly demonstrated for young stars, whose magnetic activity is so intense that it overshadows the radial velocity signal that close-in giant planets can induce. Here we report that the radial velocities of the young star V830 Tau exhibit a sine wave of period 4.93 days and semi-amplitude 75 metres per second, detected with a false-alarm probability of less than 0.03 per cent, after filtering out the magnetic activity plaguing the spectra. We find that this signal is unrelated to the 2.741-day rotation period of V830 Tau and we attribute it to the presence of a planet of mass 0.77 times that of Jupiter, orbiting at a distance of 0.057 astronomical units from the host star. Our result demonstrates that hot Jupiters can migrate inwards in less than two million years, probably as a result of planetdisk interactions.
RESUMEN
Dental preparation sometimes causes transient congestion, edema, and necrosis of the pulp. We hypothesized that nitric oxide (NO) is involved in the pathophysiological changes in pulp after preparation. The mRNA and protein expression of the inducible isoform of NO synthase (iNOS) was examined in murine pulp after dental preparation. The effects of NO on the proliferation, mineralization, and apoptosis of pulp cells were also studied in vitro. We found that not only iNOS, but also mRNAs for alkaline phosphatase and plasma membrane glycoprotein-1, were expressed in the pulp after preparation. NOC-18, an NO donor, suppressed the proliferation of pulp cells without inducing cell death, whereas it promoted the mineralization of cells cultured in the presence of beta-glycerophosphate, ascorbic acid, dexamethasone, and KH(2)PO(4). Under these conditions, NOC-18 induced the apoptosis of pulp cells. These results suggest that NO regulates the growth, apoptosis, and mineralization of pulp cells.
Asunto(s)
Preparación de la Cavidad Dental/efectos adversos , Pulpa Dental/metabolismo , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Óxido Nítrico/fisiología , Fosfatasa Alcalina/biosíntesis , Animales , Apoptosis , Diferenciación Celular , Procesos de Crecimiento Celular/efectos de los fármacos , Procesos de Crecimiento Celular/fisiología , Células Cultivadas , Pulpa Dental/citología , Pulpa Dental/fisiopatología , Inducción Enzimática , Masculino , Ratones , Ratones Endogámicos C57BL , Donantes de Óxido Nítrico/farmacología , Compuestos Nitrosos/farmacología , Hidrolasas Diéster Fosfóricas/biosíntesis , Pulpitis/etiología , Pirofosfatasas/biosíntesis , Calcificación de DientesRESUMEN
Bone-resorbing osteoclasts exhibit polarized morphological structures such as actin rings, clear zones, and ruffled borders. To gain insight into the mechanism of bone-resorbing activity of osteoclast and to discover new types of anti-resorptive agents, we have screened for natural compounds that inhibit the bone-resorbing activity of osteoclast-like multinucleated cells (OCLs). Destruxin B (DestB) and E (DestE), cyclodepsipeptides, were found to inhibit pit formation without affecting osteoclast differentiation and survival. Destruxins reversibly induced morphological changes in OCLs in a dose-dependent manner (DestB, 0.2-1 microM; DestE, 0.01-0.05 microM) and inhibited pit formation. Destruxin-induced morphological changes were accompanied by disruption of the actin rings in OCLs. The formation of actin rings in OCLs after adhesion was also inhibited by destruxins. Electron microscopical analysis revealed that destruxin-treated OCLs on dentine slices have no prominent clear zones and ruffled borders. The effective concentrations of destruxins on the morphological changes were almost the same as those that inhibited bone resorption in organ culture system. These results suggest that the anti-resorptive effects of destruxins result from induction of a disorder of the morphological structures in polarized OCLs.
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Actinas/metabolismo , Resorción Ósea/inducido químicamente , Depsipéptidos , Proteínas Fúngicas , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Péptidos Cíclicos/farmacología , Fosfatasa Ácida/análisis , Animales , Resorción Ósea/metabolismo , Radioisótopos de Calcio , Diferenciación Celular/efectos de los fármacos , Fusión Celular , Polaridad Celular/efectos de los fármacos , Células Cultivadas , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Citoesqueleto/ultraestructura , Dentina , Células Gigantes/efectos de los fármacos , Isoenzimas/análisis , Masculino , Ratones , Microscopía Electrónica , Técnicas de Cultivo de Órganos , Osteoclastos/ultraestructura , Péptidos Cíclicos/química , Plásticos , Fosfatasa Ácida TartratorresistenteRESUMEN
Although osteoclasts incorporate bisphosphonates during bone resorption, the mechanism of this incorporation by osteoclasts is not known. We previously reported that bisphosphonates disrupt the actin rings (clear zones) formed in normal osteoclasts, but did not disrupt actin rings in osteoclasts derived from osteosclerotic oc/oc mice, which have a defect in the gene encoding vacuolar H(+)-ATPase (V-ATPase). The present study showed that V-ATPase is directly involved in the incorporation of risedronate, a nitrogen containing bisphosphonate, into osteoclasts. Treatment of osteoclasts with risedronate disrupted actin rings and inhibited pit formation by osteoclasts on dentine slices. Bafilomycin A(1), a V-ATPase inhibitor, inhibited the pit-forming activity of osteoclasts but did not disrupt actin rings. Risedronate failed to disrupt actin rings in the presence of bafilomycin A(1). E-64, a lysosomal cysteine proteinase inhibitor, showed no inhibitory effect on the demineralization of dentine by osteoclasts but inhibited the digestion of dentine matrix proteins without disrupting actin rings. Risedronate disrupted actin rings even in the presence of E-64. Treatment of osteoclasts placed on plastic plates with risedronate also disrupted actin rings. Bafilomycin A(1) but not E64 prevented the disruption of actin rings in osteoclasts treated with risedronate on plastic plates. Inhibition of V-ATPase with bafilomycin A(1) also prevented disruption of actin rings by etidronate, a non-nitrogen-containing bisphosphonate. These results suggest that V-ATPase induced acidification beneath the ruffled borders of osteoclasts and subsequent bone demineralization triggers the incorporation of both nitrogen-containing and non-nitrogen-containing bisphosphonates into osteoclasts.
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Resorción Ósea/metabolismo , Difosfonatos/farmacología , Ácido Etidrónico/análogos & derivados , Ácido Etidrónico/farmacología , Osteoclastos/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Actinas/efectos de los fármacos , Animales , Células Cultivadas , Difosfonatos/metabolismo , Inhibidores Enzimáticos/farmacología , Ácido Etidrónico/metabolismo , Líquido Extracelular/química , Masculino , Ratones , Microscopía Inmunoelectrónica , Osteoclastos/efectos de los fármacos , Ácido RisedrónicoRESUMEN
Eighteen elbows in 17 patients with cubital tunnel syndrome were treated by simple decompression using only a 1.5-2.5 cm skin incision with no endoscopic assistance. According to McGowan's criteria, three elbows were classified preoperatively as grade I, six as grade II and nine as grade III. The mean follow-up period was 14 months (range 3-25). Clinical results were evaluated as excellent for four elbows, good for ten and fair for four. Improvement of symptoms occurred in all patients and dislocation of the ulnar nerve was not observed. Simple decompression through a small skin incision can be recommended for the treatment of cubital tunnel syndrome, if the indication is appropriate.
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Síndrome del Túnel Cubital/cirugía , Descompresión Quirúrgica/métodos , Procedimientos Ortopédicos/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Fibroblast growth factor receptor 3 (FGFR3) is one of the four distinct membrane-spanning tyrosine kinase receptors for fibroblast growth factors. The FGFR3 is a negative regulator of endochondral ossification and mutations in the FGFR3 gene have been found in patients of human hereditary diseases with chondrodysplastic phenotypes. Recently, we mapped the locus responsible for hereditary chondrodysplastic dwarfism in Japanese brown cattle to the distal region of bovine chromosome 6 close to the FGFR3 gene, suggesting that FGFR3 was a positional candidate gene for this disorder. In the present study, we isolated complementary DNA (cDNA) clones containing the entire coding region of the bovine FGFR3 gene. Comparison of the nucleotide sequence between affected and normal animals revealed no disease-specific differences in the deduced amino acid sequences. We further refined the localization of FGFR3 by radiation hybrid mapping, which is distinct from that of the disease locus. Therefore we conclude that bovine chondrodysplastic dwarfism in Japanese brown cattle is not caused by mutation in the FGFR3 gene.
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Enfermedades de los Bovinos/genética , Enanismo/veterinaria , Osteocondrodisplasias/veterinaria , Proteínas Tirosina Quinasas , Receptores de Factores de Crecimiento de Fibroblastos/genética , Animales , Secuencia de Bases , Bovinos , Mapeo Cromosómico , ADN Complementario/genética , Enanismo/genética , Humanos , Mutación , Osteocondrodisplasias/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Especificidad de la EspecieRESUMEN
Microvolt T-wave alternans (TWA) and QT interval dispersion (QTD), which reflect temporal and spatial repolarization abnormalities, respectively, have been proposed as useful indices to identify patients at risk for ventricular tachyarrhythmias (VTs). The purpose of this study was to clarify which repolarization abnormality marker is more useful in predicting arrhythmic events in patients with dilated cardiomyopathy (DCM). Forty-two consecutive nonischemic DCM patients underwent the assessment of TWA and QTD. Patients undergoing antiarrhythmic pharmacotherapy, except beta-blockers and those with irregular basic rhythms, were excluded from entry. Eight patients were also excluded because of indeterminate test results. Therefore, 34 DCM patients were prospectively assessed. The end point of the study was the documentation of VT defined as > or = 5 consecutive ectopic beats during the follow-up period. TWA and QTD (> or = 65 msec) were positive in 24 (80%) and 11 (37%) of 30 patients with available follow-up data, respectively. There was no relationship between TWA and QTD. During a follow-up of 13+/-11 months, VTs occurred in 13 patients (43%). In Cox regression analysis, TWA was a significant risk stratifier (p=0.02), whereas QTD was not. The sensitivity, specificity, and positive and negative predictive values of TWA in predicting VTs were 100%, 35%, 54%, and 100%, respectively. TWA could be a useful noninvasive index to identify patients at risk for VTs in the setting of DCM. This study may suggest that temporal repolarization abnormality is associated more with arrhythmogenesis than with spatial repolarization abnormality in DCM patients.
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Cardiomiopatía Dilatada/complicaciones , Electrocardiografía , Taquicardia Ventricular/diagnóstico , Adulto , Anciano , Antiarrítmicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Riesgo , Sensibilidad y EspecificidadRESUMEN
Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.
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Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Taquicardia Ventricular/diagnóstico , Adulto , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Taquicardia Ventricular/fisiopatologíaRESUMEN
A 55-year-old woman presented with fever and a stiff neck due to an intracranial poorly differentiated carcinoma at the right cerebellopontine angle. The patient suffered from typical trigeminal pain and had undergone a removal of the right cerebellopontine angle epidermoid 13 years before at another hospital. On admission, MRI imaging showed a lesion at the right cerebellopontine angle with marked contrast enhancement. Partial removal of the tumor was achieved. A histological examination of the tumor showed a poorly differentiated carcinoma accompanied by typical desquamated tissue of the epidermoid. The patient died 3 months after the operation because of aggressive meningeal carcinomatosis.
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Carcinoma de Células Escamosas/patología , Neoplasias Cerebelosas/patología , Ángulo Pontocerebeloso/patología , Carcinoma de Células Escamosas/cirugía , Transformación Celular Neoplásica , Neoplasias Cerebelosas/cirugía , Angiografía Cerebral , Resultado Fatal , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
BACKGROUND: Microvolt T-wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. METHODS: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow-up period. RESULTS: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow-up of 13 +/- 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow-up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan-Meier event-free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. CONCLUSIONS: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias.
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Antiarrítmicos/farmacología , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/tratamiento farmacológico , Ecocardiografía/efectos de los fármacos , Taquicardia Ventricular/complicaciones , Taquicardia Ventricular/tratamiento farmacológico , Adulto , Anciano , Prueba de Esfuerzo/métodos , Femenino , Estudios de Seguimiento , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Volumen Sistólico/efectos de los fármacos , Fibrilación Ventricular/complicacionesRESUMEN
Ventricular tachyarrhythmia (VT) is an independent risk factor for an increased overall mortality in patients with impaired left ventricular (LV) function, but there is not an established noninvasive tool to detect such patients. The present study aimed to clarify the most useful noninvasive approach for identification of patients with moderately or severely impaired LV function complicated by VT. Sixty-seven patients in New York Heart Association (NYHA) classes I-III with an LV ejection fraction (LVEF) less than 40% and an LV end-diastolic dimension (LVDD) of at least 55 mm on echocardiography were enrolled. Impaired LV function was caused by either ischemic (n=30) or nonischemic dilated cardiomyopathy (n=37). T-wave alternans (TWA), QT dispersion (QTD), and late potentials (LP) on signal-averaged electrocardiography were sequentially determined without using antiarrhythmic drugs. VT was defined as more than 6 consecutive ventricular ectopic beats. The mean NYHA class was 1.9+/-0.7, mean LVEF was 31+/-8%, and mean LVDD was 65+/-10mm. A history of VT was present in 26 of the patients (39%). Univariate and multivariate logistic analysis showed that TWA and LP were closely related to VT, whereas NYHA> or =III, LVEF<30%, LVDD> or =70mm, and QTD> or =90ms were not. The combination of TWA and LP had the most significant value (p=0.0004, odds ratio=8.44) by univariate analysis, and only this combination had significant value in multivariate analysis (p=0.04). Therefore, the combination of TWA and LP could be a useful index for identifying those patients with impaired LV function who are at risk for VT.
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Electrocardiografía/normas , Taquicardia Ventricular/diagnóstico , Disfunción Ventricular Izquierda/complicaciones , Potenciales de Acción , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Sensibilidad y Especificidad , Volumen Sistólico , Taquicardia Ventricular/etiología , Taquicardia Ventricular/fisiopatología , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
OBJECTIVES: The aim of this study was to compare the use of various noninvasive markers for detecting risk of life-threatening arrhythmic events in patients with Brugada syndrome. BACKGROUND: The role of conduction disturbance in arrhythmogenesis of the syndrome is controversial, whereas it is well established that repolarization abnormalities are responsible for arrhythmias. The value of noninvasive markers reflecting conduction or repolarization abnormalities in identifying patients at risk for significant arrhythmias has not been shown. METHODS: We assessed late potentials (LP) using signal-averaged electrocardiography (ECG), microvolt T-wave alternans (TWA), and corrected QT-interval dispersion (QTD) in 44 consecutive patients who had ECGs showing a pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 but structurally normal hearts. The patients were compared with 30 normal individuals. RESULTS: Eleven patients were excluded from data analysis because of an absence of ECG manifestations of Brugada syndrome at the time of the tests. A history of life-threatening events defined as syncope and aborted sudden death was present in 19 of 33 patients (58%); in 15 of the 19 patients, stimulation induced ventricular fibrillation or polymorphic ventricular tachycardia. The LP were present in 24 of 33 patients (73%); TWA were present in 5 of 31 patients (16%); and a QTD >50 ms was present in 9 of 33 patients (27%). The incidence of LP in Brugada patients was significantly (p < 0.0001) higher than in the controls, whereas incidences of TWA and QTD were not significantly different. Multivariate logistic regression analysis revealed that the presence of LP had the most significant correlation to the occurrence of life-threatening events (p = 0.006). CONCLUSIONS: Late potentials are a noninvasive risk stratifier in patients with Brugada syndrome. These results may support the idea that conduction disturbance per se is arrhythmogenic.
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Bloqueo de Rama/diagnóstico , Bloqueo de Rama/genética , Electrocardiografía/métodos , Canales Iónicos/genética , Función Ventricular Derecha , Potenciales de Acción , Adulto , Anciano , Biomarcadores , Bloqueo de Rama/complicaciones , Bloqueo de Rama/fisiopatología , Estudios de Casos y Controles , Muerte Súbita Cardíaca/etiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Procesamiento de Señales Asistido por Computador , Síncope/etiología , SíndromeRESUMEN
Activated neutrophils display an array of physiological responses, including initiation of the oxidative burst, phagocytosis, and cell migration, that are associated with cellular adhesion. Under conditions that lead to cellular adhesion, we observed rapid tyrosine phosphorylation of an intracellular protein with an approximate relative molecular mass of 92 kDa (p92). Phosphorylation of p92 was inducible when Mac-1 was activated by phorbol 12-myristate 13-acetate, the beta(2)-specific activating antibody CBR LFA-1/2, or interleukin-8 (77 amino acids). In addition, tyrosine phosphorylation of p92 was dependent on engagement of Mac-1 with ligand. Several observations suggest that this event may be an important step in the signaling pathway initiated by Mac-1 binding. p92 phosphorylation was specifically blocked with antibodies to CD11b, the alpha-subunit of Mac-1, and was rapidly reversible on disengagement of the integrin ligand interaction. Integrin-stimulated phosphorylation of p92 created binding sites that were recognized in vitro by the SH2 domains of c-CrkII and Src. Our observations suggest that neutrophil adhesion mediated through the binding of the beta(2)-integrin Mac-1 initiates a signaling cascade that involves the activation of protein tyrosine kinases and leads to the regulation of protein-protein interactions via SH2 domains, a key process shared with growth factor signaling pathways.
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Adhesión Celular/fisiología , Antígeno de Macrófago-1/fisiología , Activación Neutrófila/fisiología , Neutrófilos/fisiología , Anticuerpos Monoclonales/farmacología , Citocalasina B/farmacología , Inhibidores Enzimáticos/farmacología , Fibrinógeno/fisiología , Genisteína/farmacología , Glutatión Transferasa/química , Glutatión Transferasa/metabolismo , Humanos , Técnicas In Vitro , Interleucina-8/farmacología , Cinética , Antígeno de Macrófago-1/efectos de los fármacos , Antígeno de Macrófago-1/inmunología , Activación Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Fosforilación , Fosfotirosina/sangre , Inhibidores de Proteínas Quinasas , Proteínas Quinasas/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Estaurosporina/farmacología , Acetato de Tetradecanoilforbol/farmacología , Vanadatos/farmacología , Dominios Homologos srcRESUMEN
OBJECTIVES: To assess patient compliance and efficacy of a combination chemotherapy consisting of weekly administration of paclitaxel and carboplatin for gynecologic malignancy in Japanese women. METHODS: Fourteen ovarian and three uterine cancer patients received 80 mg/m2 of paclitaxel (paclitaxel) and AUC 1.5 to 2.0 of carboplatin weekly. The toxicity was evaluated and patients' QOL was tested. RESULTS: Neutropenia higher than grade 3 were observed in 29.4%. Four patients received G-CSF support. Grade 1 neurotoxicity was seen in 76.5% of patients. Evaluation of QOL by EORTC-QLQC30 showed significantly better tolerance of a weekly than monthly regimen. Three out of four patients with lung metastasis showed complete disappearance of the lesions. One patient with stage IIIb cervical cancer underwent postchemotherapy-hysterectomy and a complete pathological response was confirmed. The overall response rate was 64.7% including patients previously treated with platinum based multidrug regimens. CONCLUSIONS: A weekly paclitaxel and carboplatin regimen was well tolerated by Japanese women. The regimen was active in over 60% of cases and it also appeared active in multidrug resistant cases.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Cooperación del Paciente , Calidad de Vida , Anciano , Carboplatino/administración & dosificación , Esquema de Medicación , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Ováricas/psicología , Paclitaxel/administración & dosificaciónRESUMEN
Prognostic value of clinicopathologic factors and biologic markers was analyzed in 185 patients who received a curative resection and adjuvant chemotherapy of pathologically confirmed stage II or III gastric cancer. No difference was found between the chemotherapeutic regimens according to the frequency of recurrence, but tumor type, histology, depth of invasion, nodal metastasis, and lymphatic and venous invasion were significantly different between recurrent (n=62) and non-recurrent (n=123) patients. However, the degree of lymphatic dissection and the patterns of biological markers (DNA ploidy, p53 staining and PCNA labeling) were not different. Hepatic metastasis and venous invasion were more frequent on patients recurring within one year, compared to those who recurred later. Multivariate analyses showed that depth of invasion, level 2 lymph node metastasis and tumor histology were risk factors for recurrence. Pathologic factors were more important for predicting recurrence than biological markers.
Asunto(s)
Adenocarcinoma/cirugía , Biomarcadores de Tumor/análisis , Quimioterapia Adyuvante , ADN de Neoplasias/análisis , Gastrectomía , Proteínas de Neoplasias/análisis , Recurrencia Local de Neoplasia/epidemiología , Antígeno Nuclear de Célula en Proliferación/análisis , Neoplasias Gástricas/cirugía , Proteína p53 Supresora de Tumor/análisis , Adenocarcinoma/química , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Aneuploidia , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Invasividad Neoplásica , Estadificación de Neoplasias , Periodo Posoperatorio , Pronóstico , Factores de Riesgo , Neoplasias Gástricas/química , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) produced by osteoblasts/stromal cells are involved as positive and negative regulators in osteoclast formation. Three independent signals have been proposed to induce RANKL expression in osteoblasts/stromal cells: vitamin D receptor-, cAMP-, and gp130-mediated signals. We previously reported that intracellular calcium-elevating compounds such as ionomycin, cyclopiazonic acid, and thapsigargin induced osteoclast formation in cocultures of mouse bone marrow cells and primary osteoblasts. Increases in calcium concentration in culture medium also induced osteoclast formation in cocultures. Treatment of primary osteoblasts with these compounds or with high calcium medium stimulated the expression of both RANKL and OPG messenger RNAs (mRNAs). 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)-tetra(acetoxymethyl)ester, an intracellular calcium chelator, suppressed both ionomycin-induced osteoclast formation in cocultures and expression of RANKL and OPG mRNAs in primary osteoblasts. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, also stimulated osteoclast formation in these cocultures and the expression of RANKL and OPG mRNAs in primary osteoblasts. Protein kinase C inhibitors such as calphostin and staurosporin suppressed ionomycin- and PMA-induced osteoclast formation in cocultures and expression of RANKL and OPG mRNAs in primary osteoblasts. Ionomycin stimulated RANKL mRNA expression in ST2 and MC3T3-G2/PA6 cells, but not in MC3T3-E1 or NIH-3T3 cells. These effects were closely correlated with osteoclast formation in response to ionomycin in cocultures with these stromal cell lines. OPG strongly inhibited osteoclast formation induced by calcium-elevating compounds and PMA in cocultures, suggesting that RANKL expression in osteoblasts is a rate-limiting step for osteoclast induction. Forskolin, an activator of cAMP signals, also stimulated osteoclast formation in cocultures. Forskolin enhanced RANKL mRNA expression but suppressed OPG mRNA expression in primary osteoblasts. These results suggest that the calcium/protein kinase C signal in osteoblasts/stromal cells is the fourth signal for inducing RANKL mRNA expression, which, in turn, stimulates osteoclast formation.
Asunto(s)
Calcio/metabolismo , Proteínas Portadoras/genética , Regulación de la Expresión Génica , Glicoproteínas/genética , Glicoproteínas de Membrana/genética , Osteoblastos/metabolismo , Proteína Quinasa C/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Células 3T3 , Animales , Animales Recién Nacidos , Northern Blotting , Células de la Médula Ósea/metabolismo , Línea Celular , Técnicas de Cocultivo , Colforsina/farmacología , AMP Cíclico/metabolismo , Inhibidores Enzimáticos/farmacología , Ionomicina/farmacología , Masculino , Ratones , Ratones Endogámicos , Osteoclastos/fisiología , Osteoprotegerina , Proteína Quinasa C/antagonistas & inhibidores , Ligando RANK , ARN Mensajero/análisis , Receptor Activador del Factor Nuclear kappa-B , Receptores del Factor de Necrosis Tumoral , Transducción de Señal , Células del Estroma , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
We assessed 23 patients who underwent surgical therapy of hepatectomy or microwave coagulation therapy (MCT) for bilobular multiple hepatic metastatic foci following curative resection of the primary lesion of colorectal cancer. Hepatectomy was the first surgical therapy for 10 patients, and 6 of them received combined intra-arterial chemotherapy. All 13 patients in the MCT group received intra-arterial chemotherapy, and 8 of them underwent combined hepatectomy. The two-year survival rate of the hepatectomy group, classified according to the first surgical therapy, was 40% against 52% in the MCT group. In comparison with the H2 (2-5 foci) patients in the hepatectomy group, there were 7 H2 patients in the MCT group, and the two-year survival rate of these 7 patients was 50%. No significant difference was observed between hepatectomy and the MCT as the first surgical therapy. The survival rates of the 5 patients who received treatment for recurrence after the first surgery and of the 18 patients without any recurrence treatment were 80% and 40%, respectively. No significant difference existed between the two groups, but a p value of 0.06 was noted. MCT was considered to be useful local therapy for cancer as the first therapy and as a therapy following recurrence.
Asunto(s)
Neoplasias Colorrectales/patología , Fotocoagulación , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Microondas/uso terapéutico , Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/mortalidad , Terapia Combinada , Hepatectomía , Humanos , Bombas de Infusión , Neoplasias Hepáticas/mortalidad , Tasa de SupervivenciaRESUMEN
Among the locoregional therapies for hepatic malignant tumor, percutaneous microwave coagulation therapy (PMCT) has spread widely as a minimally invasive therapy. We performed PMCT on 40 patients under hepatic blood flow interruption with the aim of improving the radical treatment and expanding the coagulation area by single microwave delivery. A patient with a 2.5 cm lesion in S5 of the liver under PMCT transdiaphragmatically, but he developed a postoperative biliary fistula with consequent development of an intra-thoracic abscess through the diaphragm. Biliary fisture and liver abscess disappeared with open drainage under thoracotomy and laparotomy. Liver abscess has occasionally been reported as a PMCT complication, whereas there have been no reports, to the authors' knowledge, about intra-thoracic abscess as a PMCT complication, as in our case. It should be kept in mind that the penetration of the diaphragm as a route for PMCT may result in a biliary fistula flowing into the thorax, leading to a very serious condition.
Asunto(s)
Absceso/etiología , Fístula Biliar/etiología , Electrocoagulación/efectos adversos , Microondas/efectos adversos , Enfermedades Torácicas/etiología , Anciano , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/cirugía , MasculinoRESUMEN
Transcatheter arterial chemo-embolization (TACE) using degradable starch microspheres (DSM) was performed for multiple recurrence after hepatectomy in a patient with cholangiocarcinoma. The patient was a 68-year-man. He received treatment for hepatitis type C starting in 1996 at a nearby hospital. In November 1997, an increased AFP level was noted and a CT scan of the abdomen revealed an abnormal shadow in the liver. On May 21, 1998, imaging results led to the diagnosis of cholangiocarcinoma or a mixed type of hepatocellular carcinoma with cholangioma. Hepatic S7 sub-sequential resection was performed. The lesion was found to be a tumor-forming type, measuring 2.2 x 2.0 cm in diameter, diagnosed histopathologically as cholangiocarcinoma, tw (-), but Stage III since a nodule suggesting intrahepatic metastasis was noted in the cut surface of the resected liver. CT scan after a month revealed multiple metastatic lesions in the liver. TACE was performed by administering 450 mg of DSM, 10 mg of MMC and 30 mg of FARM, given in three divided doses on October 30, 1998, and February 9, 1999, according to Seldinger's method. A CT scan on January 31, 2000 revealed nearly complete remission of the hepatic SOL. Accordingly, TACE was considered to be useful therapy in combination with DSM, MMC and FARM for intrahepatic recurrence of cholangiocarcinoma.