RESUMEN
Androst-5-ene-3beta, 17beta-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth in vitro and tumour growth in vivo. We report here the identification of a novel androstane steroid, HE3235 (17alpha-ethynyl-5alpha-androstan-3alpha, 17beta-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer.
Asunto(s)
Androstanoles/farmacología , Androstenodiol/farmacología , Antineoplásicos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones SCID , Neoplasias de la Próstata/patología , Receptores Androgénicos/genéticaRESUMEN
A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16alpha-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69+ CD25-) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p < 0.05). Gene expression in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before treatment, HIV-1-infected patients had significantly elevated transcripts for a number of inflammatory mediators (p < 0.012). After 50 mg or 100 mg HE2000, but not after placebo, there were significant sustained decreases in IL-1beta, TNF-alpha, IL-6 and Cox-2 transcripts (p < 0.05). There were no significant differences in CD4 cell numbers, although patients receiving 50-mg doses demonstrated a significant decrease in viral load (- 0.6 log; p < 0.01). Anti-HIV-1 T-cell responses were analysed serially using GAG-peptides to stimulate cytoplasmic IFN-gamma responses. After three courses, the 50-mg dose group demonstrated a significant increase in CD8 T-cell response against two distinct GAG peptide pools (p < 0.03). These findings suggest that immune-based therapies may be able to impact viral load by decreasing inflammation and/or stimulating CD8 T-cells.
Asunto(s)
Androsterona/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Adulto , Androsterona/administración & dosificación , Androsterona/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Recuento de Células , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Células Dendríticas/citología , Método Doble Ciego , Femenino , Citometría de Flujo , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Inyecciones Subcutáneas , Interleucina-1/genética , Interleucina-1/metabolismo , Subunidad alfa del Receptor de Interleucina-2/análisis , Interleucina-6/genética , Interleucina-6/metabolismo , Células Asesinas Naturales/inmunología , Lectinas Tipo C , Recuento de Leucocitos , Leucocitos Mononucleares/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , ARN Mensajero/análisis , Juego de Reactivos para Diagnóstico , Linfocitos T/inmunología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Carga ViralRESUMEN
INTRODUCTION: Basiliximab is a monoclonal antibody directed to the interleukin-2 receptor. Several studies have demonstrated both its efficacy and safety. Even with the use of polyclonal antibodies in renal pediatric transplant recipients, the local incidence of steroid-resistant rejections has been close to 10% of the total incidence of acute rejection episodes (AREs). An open, multicenter prospective study was performed to assess the safety tolerability, and efficacy of induction with basiliximab in renal pediatric transplant patients receiving cyclosporine, mycophenolate, and steroids. MATERIALS AND METHODS: Eighteen patients (8 boys) of mean age 11.9 +/- 4.5 years and body weight 32 +/- 15 kg received cadaveric (n = 7) or living (n = 11) donor grafts. Simulect was administered on days 0 and 4. Efficacy was assessed by the incidence of biopsy-proven acute rejection (BPAR). Safety assessment consisted of a description of the adverse events (AEs). RESULTS: Six BPAR (Banff I and II) occurred in 5, (27.7%) children all of which were steroid responsive. Creatinine levels at day 7 and months 3, 6, and 12 were 1.6 +/- 1.5 mg/dL, 1.0 +/- 0.4 mg/dL, 1.0 +/- 0.5 mg/dL, and 1.0 +/- 0.4 mg/dL, respectively. Schwartz calculation at 12 months was 71 +/- 15 mL/1.73 m2 AEs were hypertension (12), anemia (9), abdominal pain (8), metabolic acidosis (8), nausea (7), diarrhea (2), gingival hypertrophy (2), hirsutism (2), lymphocele (2), and infections (15). No deaths, graft losses, PTLDs, or malignancies were observed. CONCLUSIONS: No steroid-resistant AREs, were observed in this pediatric group using basiliximab. The Schwartz calculation at 12 months was 71 +/- 15 mL/min/1.73 m2.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Rechazo de Injerto/patología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Corticoesteroides/uso terapéutico , Basiliximab , Biopsia , Cadáver , Niño , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Prueba de Histocompatibilidad , Humanos , Donadores Vivos , Masculino , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Seguridad , Donantes de TejidosRESUMEN
Cyclosporine for microemulsion has been widely used in the treatment of rheumatoid arthritis (RA) with remarkably good results over progression of joint damage, as reported by the GRISAR Study. A local group in Argentina, performed a prospective, open label study (Neo-Ra-02), consisting of 12 centres which recruited 50 RA patients, who were followed during 6 months in order to assess efficacy, tolerability and safety of cyclosporine microemulsion in the treatment of RA. Efficacy parameters were: morning stiffness, functional evaluation (HAQ, Lee and Ritchie index) and laboratory and radiological (Larsen score) assessments. Safety parameters were: blood pressure and renal, liver and hematological laboratory data. Patients criteria for participation were: presence of active RA (as defined by the ACR), Steinbrocker anatomic and functional grade I to III, disease evolution no longer than 5 years, no previous history of hypertension, renal or liver disease and absence of DMARDs use during the previous 2 months. There was a statistically significant decrease in morning stiffness and in pain evolution. Improvement became evident after 4 weeks of treatment. Reduction of Ritchie index was significant also at 4 weeks and the same observation was made with tenderness and swollen joint scores. Regarding evolution of CRP and RF, a statistically significant reduction was observed only in positive RF. Safety parameters showed no significant increase in serum creatinine or uric acid: 6/50 patients developed mild hypertension with only a significant increase in systolic blood pressure in comparison with baseline. Cyclosporine microemulsion demonstrated efficacy with minimal adverse events (12% mild hypertension) when appropriately monitored and administered in low doses (3 mg/kg/day).
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Ciclosporina/uso terapéutico , Adolescente , Adulto , Anciano , Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Creatinina/análisis , Ciclosporina/efectos adversos , Emulsiones , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Ácido Úrico/análisisRESUMEN
Cyclosporine for microemulsion has been widely used in the treatment of rheumatoid arthritis (RA) with remarkably good results over progression of joint damage, as reported by the GRISAR Study. A local group in Argentina, performed a prospective, open label study (Neo-Ra-02), consisting of 12 centres which recruited 50 RA patients, who were followed during 6 months in order to assess efficacy, tolerability and safety of cyclosporine microemulsion in the treatment of RA. Efficacy parameters were: morning stiffness, functional evaluation (HAQ, Lee and Ritchie index) and laboratory and radiological (Larsen score) assessments. Safety parameters were: blood pressure and renal, liver and hematological laboratory data. Patients criteria for participation were: presence of active RA (as defined by the ACR), Steinbrocker anatomic and functional grade I to III, disease evolution no longer than 5 years, no previous history of hypertension, renal or liver disease and absence of DMARDs use during the previous 2 months. There was a statistically significant decrease in morning stiffness and in pain evolution. Improvement became evident after 4 weeks of treatment. Reduction of Ritchie index was significant also at 4 weeks and the same observation was made with tenderness and swollen joint scores. Regarding evolution of CRP and RF, a statistically significant reduction was observed only in positive RF. Safety parameters showed no significant increase in serum creatinine or uric acid: 6/50 patients developed mild hypertension with only a significant increase in systolic blood pressure in comparison with baseline. Cyclosporine microemulsion demonstrated efficacy with minimal adverse events (12
mild hypertension) when appropriately monitored and administered in low doses (3 mg/kg/day).
RESUMEN
OBJECTIVE: To compare the therapeutic efficacy and safety of ivermectin and lindane for the treatment of human scabies. DESIGN: Randomized, prospective, controlled, double-blind, "double-dummy," and parallel clinical study. SETTING: A single department of dermatology at a hospital in Buenos Aires, Argentina. PATIENTS: Patients were outpatients, hospitalized patients, and those referred to our hospital from nursing homes and asylums. Fifty-three patients had clinical signs and symptoms compatible with scabies. INTERVENTION: Patients received either a single oral dose of ivermectin (150-200 microg/kg of body weight) or a topical application of 1% lindane solution. Treatment was repeated after 15 days if clinical cure had not occurred. MAIN OUTCOME MEASURES: Clinical healing and adverse effects. RESULTS: Of 53 patients, 43 (81%) completed the study, 19 in the group treated with ivermectin and 24 in the group treated with lindane. At day 15, 14 patients (74%; 95% confidence interval, 48.8%-90.8%) in the group receiving ivermectin showed healing of their scabies and 13 patients (54%; 95% confidence interval, 32.8%-74.4%) in the group treated with lindane were healed. At 29 days, both treatments resulted in statistically equivalent therapeutic efficacy: 18 patients (95%; 95% confidence interval, 74.0%-99.9%) were healed with ivermectin and 23 patients (96%; 95% confidence interval, 78.9%, 99.9%) were healed with lindane (P<.02). Adverse effects from the treatments were few, mild, and transient. Results from laboratory tests showed no major abnormalities and no difference between treatments. CONCLUSIONS: Ivermectin is as effective as lindane for the treatment of scabies. Ivermectin is simpler to use and, therefore, is a promising tool to improve compliance and to control infestations.
Asunto(s)
Hexaclorociclohexano/uso terapéutico , Insecticidas/uso terapéutico , Ivermectina/uso terapéutico , Escabiosis/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
The most satisfactory solution to the problem of modeling a family of regressions with repeated measures in the experimental units is multivariate in nature. However, multivariate methods are difficult to follow and implement. Furthermore, by keeping the focus on the experimental unit, a family of simple univariate linear models will often parallel both the investigator's intuitive grasp of the statistical task at hand. We present two examples based on data from a study of the suckling stimulus during breastfeeding in newborn infants. We show how a family of regression lines can provide useful, if approximate, answers to the questions of interest. One example involves a regression setting proper and the other a typical case of correlation. We discuss alternative univariate models that may be useful for this type of problems.
Asunto(s)
Modelos Biológicos , Análisis de Regresión , Análisis de Varianza , Humanos , Lactante , Modelos Lineales , Modelos Logísticos , Conducta en la Lactancia , Factores de TiempoRESUMEN
The most satisfactory solution to the problem of modeling a family of regressions with repeated measures in the experimental units is multivariate in nature. However, multivariate methods are difficult to follow and implement. Furthermore, by keeping the focus on the experimental unit, a family of simple univariate linear models will often parallel both the investigators intuitive grasp of the statistical task at hand. We present two examples based on data from a study of the suckling stimulus during breastfeeding in newborn infants. We show how a family of regression lines can provide useful, if approximate, answers to the questions of interest. One example involves a regression setting proper and the other a typical case of correlation. We discuss alternative univariate models that may be useful for this type of problems.
RESUMEN
Introducción: Las necesidades dermatológicas de un número importante de pacientes son cubiertas por médicos no especializados en dermatología. El aumento creciente de la incidencia del cáncer de piel, requiere estrategias adecuadas de asistencia y educación sanitaria tendientes al diagnóstico precoz. Objetivo: Determinar el índice de sospecha de malignidad del médico no dermatólogo. Motivar al personal médico del hospital a ser participe de la Campaña Nacional de Prevención del Cáncer de Piel. Material y método: Médicos no dermatólogos completaron una grilla con las opciones: lesión benigna, lesión maligna o lesión sospechosa de malignidad, en respuesta a 39 diapositivas con patología dermatológica benigna tumoral o no tumoral y tumores malignos. Se determinaron los siguientes índices: índice de certeza diagnóstica de patología neoplásica, índice de sospecha de malignidad, índice de derivación y de capacidad diagnóstica del médico no dermatólogo. Resultados: Fueron encuestados 85 médicos no dermatólogos: 63,50 por ciento de sexo masculino, 36,50 por ciento femenino. Treinta y tres médicos tenían menos de 5 años de egresados, 15 entre 5 y 10 años de egreso; y 37 con más de diez. El 65,90 por ciento tenían orientación clínica y el 34,10 por ciento orientación quirúrgica. La media fue de 11 respuestas correctas. El índice de certeza de patología neoplásica fue de 21,81 por ciento, de sospecha de malignidad de 34,43 por ciento, de derivación de 56,24 por ciento y de capacidad diagnóstica de 28,99 por ciento. La erosión, ulceración y el aspecto verrugoso de la lesión eran asociados con malignidad, mientras que la ausencia de esas características y la falta de relieve sobre la superficie de la piel inducían diagnóstico de benignidad. Conclusión: Con los bajos índices de certeza diagnóstica, de sospecha de malignidad y de capacidad diagnóstica hallados, se puede inferir que estamos frente a un grave problema de salud pública. Los errores diagnósticos y las demoras en el tratamiento pueden generar aumento en la morbimortalidad. Un adecuado entrenamiento de los médicos de cabecera y la derivación oportuna al médico especialista pueden mejorar el manejo del paciente con cáncer de piel (AU)
Asunto(s)
Humanos , Masculino , Femenino , Neoplasias Cutáneas/diagnóstico , Conocimientos, Actitudes y Práctica en Salud , Errores Médicos/estadística & datos numéricos , Recolección de Datos/estadística & datos numéricos , Dermatología/educación , Médicos/estadística & datos numéricosRESUMEN
Introducción: Las necesidades dermatológicas de un número importante de pacientes son cubiertas por médicos no especializados en dermatología. El aumento creciente de la incidencia del cáncer de piel, requiere estrategias adecuadas de asistencia y educación sanitaria tendientes al diagnóstico precoz. Objetivo: Determinar el índice de sospecha de malignidad del médico no dermatólogo. Motivar al personal médico del hospital a ser participe de la Campaña Nacional de Prevención del Cáncer de Piel. Material y método: Médicos no dermatólogos completaron una grilla con las opciones: lesión benigna, lesión maligna o lesión sospechosa de malignidad, en respuesta a 39 diapositivas con patología dermatológica benigna tumoral o no tumoral y tumores malignos. Se determinaron los siguientes índices: índice de certeza diagnóstica de patología neoplásica, índice de sospecha de malignidad, índice de derivación y de capacidad diagnóstica del médico no dermatólogo. Resultados: Fueron encuestados 85 médicos no dermatólogos: 63,50 por ciento de sexo masculino, 36,50 por ciento femenino. Treinta y tres médicos tenían menos de 5 años de egresados, 15 entre 5 y 10 años de egreso; y 37 con más de diez. El 65,90 por ciento tenían orientación clínica y el 34,10 por ciento orientación quirúrgica. La media fue de 11 respuestas correctas. El índice de certeza de patología neoplásica fue de 21,81 por ciento, de sospecha de malignidad de 34,43 por ciento, de derivación de 56,24 por ciento y de capacidad diagnóstica de 28,99 por ciento. La erosión, ulceración y el aspecto verrugoso de la lesión eran asociados con malignidad, mientras que la ausencia de esas características y la falta de relieve sobre la superficie de la piel inducían diagnóstico de benignidad. Conclusión: Con los bajos índices de certeza diagnóstica, de sospecha de malignidad y de capacidad diagnóstica hallados, se puede inferir que estamos frente a un grave problema de salud pública. Los errores diagnósticos y las demoras en el tratamiento pueden generar aumento en la morbimortalidad. Un adecuado entrenamiento de los médicos de cabecera y la derivación oportuna al médico especialista pueden mejorar el manejo del paciente con cáncer de piel
Asunto(s)
Humanos , Masculino , Femenino , Errores Médicos/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Neoplasias Cutáneas/diagnóstico , Dermatología/educación , Médicos/estadística & datos numéricos , Recolección de Datos/estadística & datos numéricosRESUMEN
We determined intraocular pressure (IOP) in 55 premature infants (122 determinations) with stage V retinopathy of prematurity (ROP) by applanation and indentation tonometry corrected for scleral rigidity and found a modest correlation of r = 0.52 between readings. Chronologic age and the scleral rigidity coefficient were the most significant factors affecting the closeness in readings. Our findings suggest that the applanation method of obtaining IOP values is preferable in infants with ROP because this method is less affected by technical error and the variable nature of premature infant sclera. Frequent examination may be necessary to detect an early IOP increase, especially in infants who have had successful retinal reattachment through vitreoretinal techniques.
Asunto(s)
Presión Intraocular , Retinopatía de la Prematuridad/fisiopatología , Tonometría Ocular/métodos , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
To understand the natural history of retinal pigment epithelial (RPE) detachments (PEDs) associated with drusen, we retrospectively reviewed 125 PEDs that had not undergone laser treatment over an average follow-up period of 28 months. We identified six types of RPE detachments: pseudo-vitelliform, confluent drusen, serous, vascular, and hemorrhagic lesions as well as PEDs associated with a retinal vascular abnormality. We correlated the type of detachment with visual acuity and anatomic outcome. The poorest results were obtained for PEDs associated with neovascularization (vascular, hemorrhagic, and retinal vascular abnormality types). Eyes presenting with pseudo-vitelliform lesions or confluent drusen had the best visual prognosis and anatomic results. Obvious subretinal new vessels developed in 16 (34%) of the serous PEDs over an average follow-up period of 25 months. Subretinal neovascularization was rare in the pseudo-vitelliform and confluent drusen groups. The proposed classification system may be useful in predicting the natural course of PEDs.
Asunto(s)
Epitelio Pigmentado Ocular/patología , Desprendimiento de Retina/clasificación , Drusas Retinianas/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Terapia por Láser , Persona de Mediana Edad , Pronóstico , Desprendimiento de Retina/etiología , Desprendimiento de Retina/patología , Drusas Retinianas/patología , Estudios Retrospectivos , Agudeza VisualRESUMEN
The cyclooxygenase and lipoxygenase enzyme systems can metabolize a number of C20 polyunsaturated fatty acids. Although arachidonic acid is the usual substrate for these pathways, the eicosanoid precursor pool can be nutritionally manipulated by supplementation with alternative precursors, often generating less active or down-regulatory metabolic products. Prefeeding with gamma-linolenic acid, eicosapentaenoic acid, or a combination of both failed to influence the lagphase, epithelial migration rate, or epithelial wound healing kinetics after either 1N or 4N NaOH alkali burning of the rabbit cornea. Initial epithelial wound healing probably does not involve eicosanoid-mediated processes. Essentially linear epithelial healing kinetics continued to closure without a late decrease in wound edge velocity.
Asunto(s)
Quemaduras Químicas/fisiopatología , Córnea/fisiopatología , Ácido Eicosapentaenoico/farmacología , Quemaduras Oculares/fisiopatología , Ácidos Linolénicos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Álcalis , Animales , Quemaduras Químicas/patología , Ciclo Celular , Córnea/patología , Lesiones de la Cornea , Epitelio/lesiones , Epitelio/fisiopatología , Quemaduras Oculares/patología , Masculino , Conejos , Ácido gammalinolénicoRESUMEN
The effects of altering the eicosanoid precursor pool on several aspects of the nonimmunologically mediated inflammatory and angiogenic processes that follow 1N and 4N NaOH alkali burning of the rabbit cornea were compared with controls. Diets were supplemented with several dosages of oils containing either gamma-linolenic acid (GLA) (borage oil), eicosapentaenoic acid (EPA) (sardine oil), or a combination of the two in a dose-response protocol. Significant changes in serum fatty acid composition were demonstrated. Gamma-linolenic acid proved consistently superior to EPA in modulating the neovascular response judged by three neovascular indices. At 14 days, GLA significantly reduced the polymorphonuclear leukocyte and macrophage inflammatory infiltrate and EPA reduced the macrophage component, both with high dose; EPA also reduced keratocyte proliferation. Wound-healing parameters were unaffected. Evidence for GLA-EPA synergism was modest. Prolonged neovascular responses and chronic inflammation occurring in the clinically relevant context of severe structural damage can be modulated by nutritional alteration of the eicosanoid precursor pool.
Asunto(s)
Quemaduras Químicas/patología , Grasas de la Dieta/farmacología , Quemaduras Oculares/patología , Ácidos Grasos Insaturados/farmacología , Neovascularización Patológica/patología , Animales , Eicosanoides/metabolismo , Quemaduras Oculares/inducido químicamente , Ácidos Grasos no Esterificados/sangre , Inflamación , Masculino , Conejos , Hidróxido de SodioRESUMEN
We examined the impact of aging on the numbers of photoreceptors and retinal pigment epithelium (RPE) cells, and the number of photoreceptors per RPE cell profile, in selected regions of 30 human eyes. The mean ratio of photoreceptors to RPE cell was higher in the macula than in the paramacula (P less than 0.01) or the equatorial area (P less than 0.001). We found evidence for an age-related loss of RPE in both whites (P less than 0.02) and blacks (P less than 0.0006), although the rate of loss in whites was significantly slower than in blacks. Photoreceptor loss in blacks was inversely correlated with age (P less than 0.04). In whites, however, photoreceptor loss was very significantly and directly correlated with lipofuscin concentration in the opposing RPE (P less than 0.0001) and unrelated to age. The disparity in the rates of photoreceptor and RPE cell loss produced, in older eyes, a higher ratio of photoreceptors per RPE cell profile. In the macula, the ratio for whites over 50 years of age was significantly higher (P less than 0.05) than that in blacks over 50. Our data suggest that the increased phagocytic and metabolic load on the RPE, which ultimately the macula causes a preferential age-related accumulation of lipofuscin in the RPE, which ultimately leads to photoreceptor death. This may prove a useful model of age-related macular degeneration and Stargardt's disease.
Asunto(s)
Envejecimiento/fisiología , Lipofuscina/metabolismo , Degeneración Macular/metabolismo , Pigmentos Biológicos/metabolismo , Retina/fisiología , Adolescente , Adulto , Anciano , Envejecimiento/metabolismo , Recuento de Células , Supervivencia Celular , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Fagocitosis , Células Fotorreceptoras/metabolismo , Epitelio Pigmentado Ocular/metabolismo , Retina/metabolismo , Estadística como AsuntoRESUMEN
A precise definition of epithelial healing kinetics following chemical injury is necessary to aid the investigation of control mechanisms, potential therapeutic intervention and ophthalmic drug toxicity. Wound healing was studied photographically at frequent intervals in rabbits following 1N or 4N alkali burns. Planar wound areas were determined by computerized planimetry and transformed mathematically to curved surface data. The decrease in equivalent wound radius with time was computer-modelled using two linear and three nonlinear regressions. A periodic function was also investigated. Serial photographs showed that intermittent attrition of small areas of the migrating wound edge was a common confounding variable. Although excellent coefficients of determination were found for all models, the addition of nonlinear factors gave a small advantage. A mean lag phase of 3.96 and 6.52 hr occurred after 1N and 4N alkali burns, respectively; wound edge attrition was notably prevalent in early healing. Epithelial healing in the rabbit had a fundamental linear component, with mean epithelial migration rates of 76 and 80 microns/hr after 1N and 4N alkali burns, respectively, and which continued to closure. A quadratic nonlinear component was also suggested. No significant circadian component was detected.
Asunto(s)
Álcalis/efectos adversos , Quemaduras Químicas/patología , Lesiones de la Cornea , Quemaduras Oculares/inducido químicamente , Cicatrización de Heridas , Animales , Movimiento Celular , Córnea/patología , Células Epiteliales , Quemaduras Oculares/patología , Matemática , Modelos Estadísticos , Fotograbar , ConejosRESUMEN
The estimation of corneal endothelium mean cell area (and, hence, mean cell density) is an important problem in clinical ophthalmology. Mitotic division of these cells is not known to occur, and cell deaths are followed by the enlargement of adjacent cells. As a consequence, cell-area distributions change drastically as functions of age and disease. Changes in cell-area distributions, in particular multimodality and skewness due to aging, are observed, and give rise to some difficult sampling problems. In this paper, sample quantiles are investigated as an alternative to the use of the sample mean. Asymptotic approximations are provided for the sample sizes required to estimate population quantiles with a desired precision. Asymptotic sample sizes are then compared with those obtained from tolerance limits. Empirical sample quantiles that can be used as benchmarks to compare corneas of normal individuals against corneas with unknown cell-area distributions are also presented. Aspects that merit further investigation are noted.
Asunto(s)
Córnea/citología , Endotelio/citología , Adolescente , Adulto , Anciano , Envejecimiento , Niño , Técnicas Citológicas , Humanos , Matemática , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
A number of equations was developed to predict skeletal mass in living beagles, utilizing data from 92 dogs aged 0-3103 days. Twenty eight independent variables were utilized are predictors. These included sex, age, body weight, four external measurements and 21 measurements taken on eight individual bones. The derived predictive equations were ordered as to complexity, i.e., using minimal to maximal information. Skeletal mass could be best predicted when the beagles were divided into four age groups. The use of criteria other than the adjusted coefficient of determination (Ra(2)) was helpful in selecting the single best predictive equation from a subset offered by the computer. Average relative predictive errors could be reduced to 4--8% with maximal information as compared to 11% or more when only minimal information was (hypothetically) available. A single ratio of skeletal to body weight was shown to give poor results when used as the sole criterion for estimating skeletal weight.