RESUMEN
The induction of tolerance has been proposed as a therapeutic strategy for arthritis aiming to decrease progression of the pathology, probably by promoting suppressor mechanisms of the autoimmune response. This work aimed to confirm whether the treatment with vitamin D3 could synergize oral tolerance induced by hydrolyzed collagen peptides, in our experimental model of antigen induced arthritis in New Zealand rabbits. Clinical observation of the phenomenon indicates that simultaneous treatment with hydrolyzed collagen peptides and vitamin D3 was beneficial when compared with no treatment, for arthritic animals, and for arthritic animals that received treatment with only hydrolyzed collagen peptides or vitamin D3. Treatment with hydrolyzed collagen peptides caused diminished proinflammatory cytokine levels, an effect synergized significantly by the simultaneous treatment with vitamin D3. The anatomical-pathological studies of the animals that received both treatments simultaneously showed synovial tissues without lymphocytic and plasma cell infiltrates, and without vascular proliferation. Some of the synovial tissue of the animals of these groups showed a slight decrease in Galectin-3 expression. We propose that simultaneous oral treatment with vitamin D3 and hydrolyzed collagen peptides could increase the immunoregulatory effect on the process of previously triggered arthritis. We used articular cartilage hydrolysate and not collagen II because peptides best expose antigenic determinants that could induce oral tolerance. Oral tolerance may be considered in the design of novel alternative therapies for autoimmune disease and we have herein presented novel evidence that the simultaneous treatment with vitamin D3 may synergize this beneficial effect.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Colecalciferol/administración & dosificación , Péptidos/administración & dosificación , Administración Oral , Animales , Colágeno/química , Citocinas/inmunología , Femenino , Humanos , Conejos , Membrana Sinovial/inmunologíaRESUMEN
Estudiar los niveles de topotecan total y lactona en el vitreo luego de la administración periocular en un modelo animal. Material y métodos: Se administró 1 mg de topotecan periocular en ambos ojos a 9 conejos sin retinoblastoma y se midieron niveles en el vitreo a las 0.25, 0.5, 1, 2, 4 y 24 horas. Se midieron niveles plasmáticos en 2 animales a las 2 horas. Se midió topotecan total y lactona por HPLC. Todos los animales fueron enucleados al completar el experimento y los ojos fueron examinados patológicamente para evalur toxicidad. Resultados: Tanto el topotecan total como la lactona alcanzaron niveles en el vitreo, mostrando un pico a los 30 minutos de la administración periocular. Los niveles medios en el pico fueron de 158 ng/ml para el topotecan total y 122 ng/ml para el topotecan lactona decayendo con una vida media de 2.44 hs. y 2.8 hs. para el topotecan total y lactona respectivamente. Se encontraron bajos niveles plasmáticos en los 2 animales estudiados a las 2 hs. de la administración de topotecan periocular ((32.0 ng7ml). No se evidencio toxicidad significativa. Conclusiones: En este estudio preliminar, el topotecan mostro lograr pernetrar al vitreo luego de la administración periocular a concentraciones potencialmente tumoricidas. Nuestro grupo proseguirá con estudios más detallados para evaluar su comportamiento famacocinético con el fin de utilizarlo potencialmente en paciente con retinoblastoma.
Asunto(s)
Conejos , Cuerpo Vítreo , Retinoblastoma , Topotecan/farmacocinética , Topotecan/toxicidad , Topotecan/uso terapéuticoRESUMEN
AIMS: To describe the outcome of patients with non-metastatic unilateral retinoblastoma with high risk histopathological features after primary enucleation, and to clarify the need and results of adjuvant therapy. PATIENTS AND METHODS: From 1980 to 2001 adjuvant therapy was recommended only to patients with scleral involvement, post-laminar optic nerve involvement (PLONI) with either a positive margin or associated choroidal involvement, or (before 1994) isolated PLONI. RESULTS: 108 of 224 patients had at least one high risk feature (choroidal, scleral, anterior chamber, and/or PLONI). Patients with isolated choroidal (n = 55) or anterior chamber (n = 2) invasion, and most with PLONI without other risk factors (n = 21) were not treated; three relapsed but are long term survivors after intensive therapy. Four with isolated PLONI received adjuvant chemotherapy and none relapsed. Three of 11 with PLONI and concomitant choroidal or scleral involvement who received adjuvant therapy relapsed, versus two of four not treated. Two of five with scleral disease relapsed. All 12 with cut end involvement received adjuvant treatment and none relapsed. In the total group, all four patients who relapsed after adjuvant therapy died. CONCLUSIONS: Relapsing patients can be rescued with intensive therapy. Those with isolated choroidal or PLONI have a good prognosis without adjuvant therapy. Patients with PLONI with a positive margin have a good prognosis if treated with combined therapy. Those with scleral involvement or PLONI with concomitant choroid disease may benefit from adjuvant therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enucleación del Ojo/métodos , Neoplasias de la Retina/cirugía , Retinoblastoma/cirugía , Cámara Anterior , Niño , Preescolar , Neoplasias de la Coroides/patología , Terapia Combinada/métodos , Femenino , Humanos , Lactante , Masculino , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia , Neoplasias del Nervio Óptico/patología , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/radioterapia , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/radioterapia , Estudios Retrospectivos , Factores de Riesgo , Enfermedades de la Esclerótica/patología , Resultado del TratamientoAsunto(s)
Humanos , Femenino , Embarazo , Recién Nacido , Adulto , Embarazo , Complicaciones del Embarazo , Riesgo , Ultrasonografía DopplerRESUMEN
A retrospective chart review was performed on the charts of 1265 patients with retinoblastoma who were on file at New York Hospital and whose conditions had been diagnosed between the years 1960 and 1990. The mean follow-up was 90 months, ranging from 0 to 409 months. Thirty-two distinct presenting signs of retinoblastoma were identified, the most common of which were leukocoria (56.2%), strabismus (23.6%), poor vision (7.7%), and family history (6.8%). No correlation was found between any of the presenting signs and laterality, sex, race, or survival. Leukocoria correlated to Reese-Ellsworth Group Va or Vb, whereas strabismus was invariably associated with either macular tumors or macular retinal detachments. Eighty-three (96.5%) patients presenting with a family history did so before the age of 24 months. The presenting sign leading to a diagnosis of retinoblastoma was correlated with degree of advancement and tumor location. Leukocoria and strabismus are the most common presenting signs, with leukocoria correlated to more advanced disease and strabismus always associated with macular involvement. Vitreous hemorrhage (1 case, 0.1%), microphthalmos (4 cases, 0.3%), and orbital cellulitis (3 cases, 0.2%) are extremely rare presenting findings in retinoblastoma.
Asunto(s)
Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias de la Retina/genética , Neoplasias de la Retina/fisiopatología , Retinoblastoma/genética , Retinoblastoma/fisiopatología , Estudios RetrospectivosRESUMEN
A retrospective review of 297 cases of enucleated and histologically proven unilateral retinoblastoma with a minimum of 5-year follow-up was analyzed to see if there were any clinical or prognostic differences between endophytic and exophytic type retinoblastoma. Endophytic retinoblastoma (181 cases) was found more often than exophytic (116 cases). The following features were not associated with the clinical appearance of either endophytic or exophytic tumors: sex of patient, right vs left eye, propensity for bilateral development, initial sign or symptom, presence of rubeosis, preoperative metastasis, optic nerve invasion, orbital recurrence, survival of the patient, length of follow-up, or age at diagnosis. Three features were found that correlated with type: a disproportionately higher percentage of patients with endophytic retinoblastoma had a positive family history; a disproportionately high percentage of patients with exophytic retinoblastoma developed glaucoma; and choroidal invasion occurred significantly more often in patients who had exophytic retinoblastoma than in those who had endophytic retinoblastoma.