RESUMEN
OBJECTIVE: To determine the success rate of initial probing in children with congenital nasolacrimal duct obstruction at different ages, using nasal endoscopy. METHODS: Fifty eyes of 38 consecutive children with congenital nasolacrimal duct obstruction underwent endoscopic nasolacrimal duct probing under general anaesthesia. Patients were followed up for at least three months. Probing success was defined as complete remission of symptoms and a normal fluorescein dye disappearance test result. RESULTS: The age range of patients was 17-109 months. The success rates of probing were: 100 per cent (29 out of 29) for cases of stenosis at the lower nasolacrimal duct, 100 per cent (7 out of 7) for functional epiphora cases and 92.86 per cent (13 out of 14) for nasolacrimal atresia cases. Overall, there was only one child for whom the probing treatment for nasolacrimal duct obstruction was not successful; this child had Down's syndrome and a more complex developmental abnormality of the nasolacrimal duct. Age and site of obstruction were not found to significantly affect the outcome of probing. CONCLUSION: Probing of the nasolacrimal system using an endoscopic approach allows direct visualisation of the nasolacrimal duct. This can facilitate diagnosis of the anomaly and significantly increase the procedure success rate.
Asunto(s)
Dacriocistorrinostomía , Endoscopía/métodos , Obstrucción del Conducto Lagrimal/congénito , Cornetes Nasales/anomalías , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Enfermedades del Aparato Lagrimal , Obstrucción del Conducto Lagrimal/diagnóstico , Masculino , Pronóstico , Estudios Retrospectivos , Procedimientos Quirúrgicos Operativos , Resultado del Tratamiento , Cornetes Nasales/cirugíaRESUMEN
Type 3 von Willebrand disease (VWD) is a severe autosomal recessive inherited bleeding disorder. In affected individuals the underlying von Willebrand factor gene (VWF) mutations frequently remain uncharacterized. The aim of this study was to investigate the molecular basis of type 3 VWD in patients (11 Caucasians and 9 of Asian origin) attending the haemophilia centres at Central Manchester NHS Trust. A combination of DNA sequencing of VWF genomic and complementary DNA was performed to identify mutations in the patient cohort. Fifteen different VWF mutations were identified at the genomic DNA level: two gene conversion events, three nonsense, three frameshift, one missense, two splice site, one insertion-deletion and three deletion mutations. Homozygosity or compound heterozygosity for mutations was present in 15 of the 20 patients. In the remaining five individuals, heterozygosity for a single VWF mutation was identified in four cases and one patient had no detectable VWF mutation. Analysis of platelet-derived VWF RNA from these five individuals revealed heterozygosity for a deletion of exons 4 and 5 in four cases. The remaining patient was heterozygous for a three base deletion which had already been identified at the DNA level. Overall the observed VWF genotype explained the phenotype in 18 of the 20 patients investigated. In genetic studies in type 3 VWD, if VWF mutations are not detected at the DNA level, RNA analysis should be performed to search for intronic mutations, heterozygous deletions or aberrant splicing/post-transcriptional events. However, this may still not explain all cases of previously phenotypically diagnosed type 3 VWD.
Asunto(s)
Genes Recesivos/genética , Mutación/genética , Enfermedad de von Willebrand Tipo 3/genética , Estudios de Cohortes , Inglaterra/epidemiología , Genotipo , Humanos , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Análisis de Secuencia de ARN , Enfermedad de von Willebrand Tipo 3/epidemiologíaAsunto(s)
Anestésicos Locales/uso terapéutico , Ciclopentolato/efectos adversos , Midriáticos/efectos adversos , Dolor/prevención & control , Propoxicaína/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Humanos , Isomerismo , Persona de Mediana Edad , Soluciones Oftálmicas , Dolor/inducido químicamente , Dimensión del DolorRESUMEN
We previously developed two models of human osteoblasts with distinct differentiation stages using cells derived from iliac crest trabecular bone explants cultured long term in the presence (HOB + DEX) and absence (HOB - DEX) of 10 nM dexamethasone (DEX) (Wong et al., J Bone Miner Res 1990;5:803). Using these models from 36 subjects aged 41-80 years, we examined the effects of 17 beta-estradiol (E2) on cell proliferation, osteocalcin (OC) production, alkaline phosphatase (ALP) and basal and parathyroid hormone (PTH)-stimulated adenylate cyclase activities, as well as the steady-state mRNA levels of ALP, collagen type I(COLL), OC, and receptors for E2 (ER) and PTH (PTHr). E2 alone had no effect on [3H]thymidine uptake in (HOB - DEX) cells but appeared to stimulate the uptake in (HOB + DEX) cells in a dose-dependent manner, with maximum effect at 10(-10)M (p < 0.05). However, in the presence of 10(-6)M PTH, E2 inhibited the uptake in (HOB - DEX) cells (ANOVA, KW = 18.95, p < 0.005) but stimulated the uptake in (HOB + DEX) cells (KW = 13.52, p < 0.025). E2 decreased the amount of osteocalcin in culture media from both (HOB - DEX) and (HOB + DEX) cells (p < 0.05). PTH alone or E2, alone or in combination with 10(-9)M PTH, had no effect on ALP activity in (HOB - DEX) cells. In contrast, in (HOB + DEX) cells, E2 + PTH but not E2 alone, had biphasic effects on ALP activity, with maximum stimulation observed at 10(-11) and 10(-10)M E2, and a return to basal levels at 10(-9)M E2. E2 decreased basal adenylate cyclase activities in a dose-dependent manner in (HOB + DEX) but not (HOB - DEX) cells (KW = 13.48, p < 0.05). In (HOB + DEX) cells, E2 had biphasic effects on PTH-stimulated adenylate cyclase activity, with significant stimulation observed at 10(-10)M (p < 0.05). While E2 had no significant effect on osteoblastic marker mRNA levels in (HOB - DEX) cells, it decreased osteocalcin and stimulated PTHr mRNA levels in (HOB + DEX) cells. Thus, in our human osteoblastic cell models, estrogen regulated metabolic function largely in the more differentiated cells, by modifying the effects of PTH.
Asunto(s)
Dexametasona/farmacología , Estradiol/farmacología , Glucocorticoides/farmacología , Osteoblastos/metabolismo , Hormona Paratiroidea/farmacología , Adenilil Ciclasas/genética , Adenilil Ciclasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Análisis de Varianza , Northern Blotting , División Celular/efectos de los fármacos , Células Cultivadas , ADN/biosíntesis , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteocalcina/biosíntesis , Osteocalcina/genética , ARN Mensajero/metabolismo , RadioinmunoensayoRESUMEN
We tested the effect of osteoblastic differentiation on the interactive effects of 17 beta-oestradiol (E2) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on alkaline phosphatase activity. As cell models we utilized the more differentiated human osteosarcoma (SaOS) cells that had been cultured for 6 days in medium containing 10 nM dexamethasone (Dex) (SaOS+Dex cells) and the less differentiated cells cultured in the absence of Dex (SaOS-Dex cells). The cells were challenged with 1,25(OH)2D3 in the presence or absence of Dex for 24 h and then with E2 for an additional 24 h. In SaOS-Dex cells, alkaline phosphatase activity remained constant over the 48-h period and was not significantly affected by E2, 1,25(OH)2D3 or 1,25(OH)2D3+E2 treatment. On the other hand, in SaOS+Dex cells, 1,25(OH)2D3 and E2+1,25(OH)2D3 stimulated alkaline phosphatase activity (ANOVA, F = 154.2, P < 0.0001) with the maximal response at 48 h (P < 0.01). In SaOS+Dex cells, 1,25(OH)2D3 had dose-dependent stimulatory effects which were strongly enhanced by 10 nM E2 (ANOVA, F = 46.0, P < 0.001). Studies on dose-dependent effects of E2, in the presence or absence of 100 nM 1,25(OH)2D3, revealed that in the presence of 1,25(OH)2D3, the E2 dose-response curve was biphasic in SaOS+Dex cells (ANOVA, F = 3.40, P < 0.005), with maximum stimulation at 10 nM E2 (P < 0.01). The specificity of E2 was verified using the inactive 17 alpha-oestradiol and the oestrogen antagonist, tamoxifen. These data indicate that E2 and 1,25(OH)2D3 have positive interactive effects on alkaline phosphatase activity in human osteoblasts, and suggest that the expression of this interaction is dependent on the stage of differentiation of the cells.
Asunto(s)
Fosfatasa Alcalina/metabolismo , Calcitriol/farmacología , Estradiol/farmacología , Osteoblastos/efectos de los fármacos , Osteosarcoma/enzimología , Diferenciación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Osteoblastos/enzimología , Estimulación Química , Tamoxifeno/farmacología , Células Tumorales CultivadasRESUMEN
We have previously shown that osteoblasts derived from trabecular bone explants and cultured long term in 10 nM dexamethasone ((HOB + DEX) cells) exhibited properties consistent with a more differentiated phenotype compared with those grown in the absence of dexamethasone ((HOB-DEX) cells). To characterize these two cell models further, we measured the steady-state mRNA levels of the phenotypic markers alkaline phosphatase (ALP), collagen type I (COLL) and osteocalcin (OC), OC production, and the activities of ALP and parathyroid hormone (PTH)-stimulated adenylate cyclase. These findings were then correlated with the age and sex of the bone donors. Long-term culture in dexamethasone significantly increased ALP and OC mRNA levels and the activities of ALP and PTH-stimulated adenylate cyclase but not OC production, in (HOB + DEX) compared with (HOB-DEX) cells (p < 0.05). When the data were examined with respect to the age of the bone donor, age-dependent differences in the expression and responses to dexamethasone were apparent. ALP and PTH-stimulated adenylate cyclase activities decreased with increasing age of the bone donor in (HOB-DEX) and (HOB + DEX) cells (p < 0.05). There were no significant correlations between phenotypic marker mRNA levels and bone donor age in (HOB-DEX) and ((HOB + DEX) cells. All age-dependent decreases in ALP and PTH-stimulated cyclase activities were enhanced in the (HOB + DEX) cells. However, when the data were examined according to the sex of the bone donor, there were no differences in mRNA levels, OC production, or ALP and cyclase activities between cells from male and female donors. These results indicate an age dependence in the expression of osteoblastic markers in human bone cells at different stages of differentiation: thus osteoblastic cultures derived from older donors are likely to contain fewer osteoprogenitor cells, lower levels of glucocorticoid receptors or represent more differentiated osteoblasts compared with those derived from younger donors.
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Fosfatasa Alcalina/metabolismo , Dexametasona/farmacología , Osteoblastos/metabolismo , Adenilil Ciclasas/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , División Celular/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Proteínas/metabolismo , ARN Mensajero/análisisRESUMEN
We studied the effects of 17 beta-estradiol (E2) and PTH on alkaline phosphatase activity in SaOS-2 cells that had been passaged and grown continually in the presence (SaOS + Dex) or absence (SaOS - Dex) of 10(-8) M dexamethasone (Dex). We showed that the more differentiated SaOS + Dex cells had higher alkaline phosphatase activity and PTH-responsive adenylate cyclase than the less differentiated SaOS - Dex cells. In SaOS - Dex cells, E2 or PTH (1 x 10(-11)-1 x 10(-6) M) had no effect on alkaline phosphatase activity. On the other hand, in SaOS + Dex cells, PTH and E2 each had small but very significant stimulatory effects on alkaline phosphatase activity. The combined effects of PTH and E2 resulted in potentiation which was dose dependent for PTH and E2. 17 alpha-estradiol and tamoxifen (1 x 10(-11)-1 x 10(-6) M) had no effect on PTH-stimulated alkaline phosphatase activity in SaOS + Dex cells, but the latter inhibited the E2 effect, clearly demonstrating its specificity. In conclusion, we have shown that in more differentiated osteoblastic cells, E2 and PTH have interactive effects on alkaline phosphatase activity.
Asunto(s)
Fosfatasa Alcalina/metabolismo , Diferenciación Celular/fisiología , Estradiol/farmacología , Hormona Paratiroidea/farmacología , Adenilil Ciclasas/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Clonales , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Humanos , Osteoblastos , Osteosarcoma , Tamoxifeno/farmacología , Células Tumorales CultivadasRESUMEN
Procedures proposed to present a methodology for planning relevant health education curriculum included having students write out questions they felt their peers had about health in the specific content areas of community health, consumer health, diseases, drugs, alcohol, and tobacco, ecology, family life, nutrition, mental health, personal health and safety and first aid. A sample survey was presented where 80 junior high school students wrote a total of 981 questions and 74 senior high school students wrote 786 questions. Implications for the health education curriculum would be as follows: (1) Curriculum can be made relevant if the specific content covered is directly related to problems of daily living: (2) Provide needed cognitive information to meet real or potential problems of students; and (3) Provide guidance for the health educator in planning the kind and the amount of emphasis within the total health education program.