RESUMEN
BACKGROUND: PTEN is primarily known as a tumour suppressor gene. However, research describes higher rates of difficulties including intellectual disability and difficulties relating to autism spectrum conditions (ASCs) in people with germline PTEN mutations. Other psychological characteristics/experiences are less often reported and are explored in this study. METHODS: The parents of 20 children with PTEN mutations completed an online survey exploring adaptive behaviour, ASC-associated behaviours, anxiety, mood, hypermobility, behaviours that challenge, sensory experiences, quality of life and parental wellbeing. Published normative data and data from groups of individuals with other genetic neurodevelopmental conditions were used to contextualise findings. RESULTS: Overall levels of adaptive behaviour were below the 'typical' range, and no marked relative differences were noted between domains. Higher levels of ASC-related difficulties, including sensory experiences, were found in comparison with 'typically developing' children, with a possible peak in restrictive/repetitive behaviour; ASC and sensory processing atypicality also strongly correlated with reported joint hypermobility. A relative preservation of social motivation was noted. Anxiety levels were found to be elevated overall (and to relate to sensory processing and joint hypermobility), with the exception of social anxiety, which was comparable with normative data. Self-injurious behaviour was common. CONCLUSIONS: Results suggest a wide range of possible difficulties in children with PTEN mutations, including elevated anxiety. Despite elevated ASC phenomenology, social motivation may remain relatively strong. Firm conclusions are restricted by a small sample size and potential recruitment bias, and future research is required to further explore the relationships between such characteristics.
Asunto(s)
Trastorno del Espectro Autista , Fosfohidrolasa PTEN , Humanos , Masculino , Femenino , Fosfohidrolasa PTEN/genética , Niño , Trastorno del Espectro Autista/genética , Adolescente , Preescolar , Mutación de Línea Germinal , Ansiedad/genética , Adaptación Psicológica/fisiología , Discapacidad Intelectual/genéticaRESUMEN
Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis: The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination: Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/terapia , Ejercicio Físico/fisiología , Adulto , Metabolismo Basal/fisiología , Glucemia/metabolismo , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/prevención & control , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
O objetivo deste trabalho foi avaliar a utilização periódica de testes de diagnóstico mais sensíveis aliados às práticas de manejo, visando ao controle eficaz da artrite encefalite caprina (CAE). Foram realizadas oito coletas de sangue em matrizes e reprodutores. Da primeira à sétima análise, as coletas foram quadrimestrais, utilizando-se os testes de imunodifusão em gel de agarose (IDGA), ensaio imunoenzimático indireto (ELISA-i) e Western Blot (WB). A oitava coleta aconteceu seis meses após a sétima, utilizando-se o WB e a reação em cadeia de polimerase (PCR). A prevalência da CAE foi de 6,8%, 14,9% e 39,2% no IDGA, ELISA-i e WB, respectivamente. Na última análise, foram detectados 0,9% de animais positivos pelo WB e 10,8% pela PCR. Apesar de não erradicarem a CAE, as medidas adotadas, aliadas à utilização periódica dos testes sorológicos e à combinação com a PCR, foram importantes para reduzir significativamente os animais soropositivos no rebanho.(AU)
The aim of this study was to evaluate the periodic use of more sensitive diagnostic tests associated to management practices for the effective control of caprine arthritis-encephalitis (CAE). We carried out eight blood samples in does and bucks. From the first to the seventh analysis, the samples were quarterly, using Agarose Gel Immunodiffusion (AGID), Enzyme linked immunosorbent assay (i-ELISA) and Western Blot (WB) tests. The eighth collection was made six months after the seventh, using the WB and Polymerase Chain Reaction (PCR). The prevalence of CAE was 6.8%, 14.9% and 39.2% in the AGID, i-ELISA and WB respectively. The last analysis detected 0.9% of animals positive by WB and 10.8% by PCR. Although they do not eradicate CAE, steps taken together with the periodic use of serological tests and the combination with PCR were important to significantly reduce positive animals in the herd.(AU)
Asunto(s)
Animales , Artritis/diagnóstico , Rumiantes/anomalías , Planificación Estratégica , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
This study aimed to isolate cells from the Wharton's jelly of umbilical cord (WJUC) of sheep collected during natural parturition using different culture media, in addition to reporting for the first time the permissiveness of these cells to in vitro infection by small ruminant lentiviruses. Ten umbilical cords were collected from healthy sheep. Each cord explants were grown in different media consisting of MEM, low glucose DMEM, M199, and RPMI-1640. The permissiveness of infection of sheep cells from WJUC was tested with CAEV-Cork and MVV-K1514 strains, inoculating 0.1 MOI of each viral strain. Four supernatants from each strain were obtained from WJUC sheep cell cultures infected in different media. The results demonstrated the presence of cytopathic effect after the in vitro infection by CAEV-Cork and MVV-K1514 with all of the tested culture media. Nested-PCR detected proviral DNA in all supernatants. Supernatants containing CAEV-Cork viruses had TCID 50/ml titres of 10 5.5 in MEM, 10 4.0 in low glucose DMEM, 105.0 in M199, and 10 5.7 in RPMI-1640. Supernatants containing the MVV-K1514 virus had TCID 50/ml titres of 10 4.3 in MEM, 10 3.5 in low-glucose DMEM, 10 4.7 in M199, and 10 3.5 in RPMI-1640. Sheep cells from WJUC are permissive to in vitro infection by small ruminant lentivirus.(AU)
O objetivo deste estudo foi isolar células da geleia de Wharton do cordão umbilical (GWCU) ovino coletado por ocasião do parto natural, utilizando-se diferentes meios de cultivo, além de relatar, pela primeira vez, sua permissividade à infecção in vitro por lentivírus de pequenos ruminantes (LVPRs). Dez cordões umbilicais foram coletados de ovelhas hígidas e soronegativas para LVPRs pelo teste de imunodifusão em gel de agarose (IDGA). De cada cordão, explantes foram cultivados em quatro meios distintos que consistiram em MEM, DMEM baixa glicose, meio 199 e RPMI-1640, todos acrescidos de 10% de soro fetal bovino em estufa com atmosfera úmida e 5% de CO2 a 37ºC. A permissividade de infecção das células GWCU ovino foi testada frente às cepas CAEV-Cork e MVV-K1514, inoculando-se 0,1 MOI de cada cepa viral e corando as monocamadas com May Grunwald Giemsa para visualização do efeito citopático. Foram obtidos quatro sobrenadantes CAEV-Cork e quatro MVV-K1514, provenientes do cultivo de células GWCU ovino infectadas por 21 dias em meios distintos, dos quais foram realizadas titulação em membrana sinovial caprina e extração do DNA pró-viral para realização de nested-PCR e eletroforese em gel de agarose a 2%. Os resultados demonstraram a presença de efeito citopático na infecção in vitro tanto por CAEV-Cork como por MVV-K1514 em todos os meios de cultivo, sendo visualizados sincícios e lise celular em microscópio invertido. A nested-PCR detectou o DNA pró-viral tanto do CAEV-Cork como do MVV-K1514 em todos os sobrenadantes. Os sobrenadantes contendo o vírus CAEV-Cork apresentaram títulos em TCID50/mL de 10 5,5 em MEM, 10 4,0 em DMEM baixa glicose, 10 5,0 em meio 199 e 10 5,7 em RPMI-1640. Os sobrenadantes contendo o vírus MVV-K1514 apresentaram título em TCID 50/mL de 10 4,3 em MEM, 10 3,5 em DMEM baixa glicose, 10 4,7 em meio 199 e 10 3,5 em RPMI-1640. Células GWCU ovino são permissivas à infecção in vitro pelos lentivírus de pequenos ruminantes CAEV-Cork e MVV-K1514.(AU)
Asunto(s)
Animales , Virus de la Artritis-Encefalitis Caprina , Técnicas In Vitro/veterinaria , Células Madre Mesenquimatosas/patología , Rumiantes , Infecciones/veterinaria , Lentivirus Ovinos-Caprinos , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
Wolcott-Rallison Syndrome is the commonest cause of neonatal diabetes in consanguineous families. It is associated with liver dysfunction, epiphyseal dysplasia, and developmental delay. It is caused by mutations in eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3).We report 4 children with WRS and Os Odontoideum resulting in significant neurological compromise. This cervical spine abnormality has not previously been described in this syndrome. This additional evidence broadens the clinical spectrum of this syndrome and confirms the role of EIF2AK3 in skeletal development. Furthermore, Os Odontoideum needs to be actively screened for in WRS patients to prevent neurological and respiratory compromise.
Asunto(s)
Diabetes Mellitus Tipo 1/diagnóstico , Epífisis/anomalías , Osteocondrodisplasias/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Diabetes Mellitus Tipo 1/genética , Epífisis/diagnóstico por imagen , Exones/genética , Femenino , Humanos , Lactante , Masculino , Mutación , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/genética , Radiografía , Adulto Joven , eIF-2 Quinasa/genéticaRESUMEN
A artrite-encefalite caprina (CAE) é diagnosticada rotineiramente pela técnica de imunodifusão em gel de agarose (IDGA), que é considerada pouco sensível. Objetivou-se com este estudo padronizar testes de Elisa-i e Western Blot (WB) para diagnóstico precoce de anticorpos em caprinos contra CAEV e comparar os resultados obtidos nesses testes com a prova de IDGA. Para a padronização dos testes Elisa-i e WB, utilizaram-se diferentes concentrações e diluições de antígeno, soros e conjugado. No Elisa-i, adotaram-se microplacas rígidas com 96 poços, sendo a combinação de concentração de 0,5µg/poço de antígeno e diluições de 1:100 de soro e 1:1500 de conjugado a que apresentou melhor resultado. No WB foram utilizadas membranas de nitrocelulose, definindo-se as diluições de 1:50 de soro e 1:15000 de conjugado. Para avaliar o desempenho das técnicas, 222 amostras de soro caprino foram testadas e os dados obtidos foram comparados com o IDGA. A sensibilidade e a especificidade do Elisa-i/IDGA, WB/IDGA e WB/Elisa-i foram de 70% e 91%, 100% e 72,6%, 84,6% e 76,5%, concomitantemente. O índice Kappa desses testes foi de 0,35, 0,2 e 0,36, respectivamente. As técnicas de Elisa-i e WB apresentaram-se mais sensíveis que a IDGA, podendo ser utilizadas como ferramentas para o diagnóstico precoce da CAE...
Caprine arthritis-encephalitis (CAE) is routinely diagnosed with the Agarose Gel Immunodiffusion (AGID) technique, which is considered to have low sensitivity. The objective of this study was to standardize testing i-Elisa and Western Blot for early detection of antibodies against CAEV in goats and compare the results obtained in these tests with proof of AGID. For standardization of i-Elisa and WB, different concentrations and dilutions of antigen, sera and conjugate were used. In the i-Elisa, rigid microplate with 96 wells was adopted, and the combination that showed the best result was a concentration of 0.5µg/ well of antigen and dilutions of the serum of 1:100 and conjugate of 1:1500. In the WB nitrocellulose membranes were used, and the dilutions of the serum were defined at 1:50 and conjugate at 1:15000. To evaluate the performance of the techniques, 222 goat serum samples were tested and the data were compared with the AGID. The sensitivity and specificity of Elisa-i/IDGA, WB/AGID and WB/Elisa-i were 70% and 91%, 100% and 72.6%, 84.6% and 76.5%, concomitantly. The Kappa index of these tests was 0.35, 0.2 and 0.36, respectively. The i-Elisa and WB techniques were more sensitive than the AGID and can be used as tools for early diagnosis of CAE...
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Animales , Cabras/inmunología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunodifusión/veterinaria , Virus de la Artritis-Encefalitis Caprina/aislamiento & purificación , Western Blotting/veterinariaRESUMEN
AIMS: We prospectively evaluated the effect of insulin intensification on glycaemic control and lipid levels in children and young persons with Type 1 diabetes in relation to ethnicity. METHODS: In the first 2 years of a 3-year observation period, as part of routine clinical care, 231 children and young persons (40% white, 28% South Asian, 32% black) from a single clinic were offered intensive insulin therapy. After 2 years, 222 were on intensive therapy and their data were compared between ethnic groups at the end of year 3. RESULTS: We observed ethnic differences in HbA(1c) levels during the study [study beginning and end: white children and young persons 77 and 70 mmol/mol (9.2 and 8.6%) vs. South Asian 72 and 68 mmol/mol (8.7 and 8.4%) vs. black 83 and 79 mmol/mol (9.7 and 9.4%), P-value for ANCOVA = 0.007]. By study end, South Asians had the lowest HDL cholesterol (2.0 vs. 1.4 vs. 1.6 mmol/l, P-value = 0.03) and highest triglyceride levels (0.9 vs. 1.8 vs. 1.0 mmol/l, P-value = 0.001). In linear mixed modelling, after adjustment for socio-economic deprivation and other covariates: (1) black ethnicity was associated with poorer glycaemic control (P < 0.001) and (2) South Asian ethnicity was associated with higher triglyceride levels (P < 0.001), independent of HbA(1c). CONCLUSIONS: The effect of insulin intensification on glycaemic control and lipid profile in children and young persons with Type 1 diabetes differs in relation to ethnic group.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulinas/administración & dosificación , Adolescente , Análisis de Varianza , Asia Occidental/etnología , Población Negra/etnología , Glucemia/metabolismo , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/etnología , Femenino , Hemoglobina Glucada/metabolismo , Disparidades en el Estado de Salud , Humanos , Inyecciones , Sistemas de Infusión de Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Londres/epidemiología , Masculino , Estudios ProspectivosRESUMEN
Avaliou-se a influência do vírus da CAE nas características físico-químicas de amostras de leite de 54 cabras, sem predileção racial, distribuindo-as em dois grupos: cabras positivas e negativas para o teste de imunodifusão em gel de agarose. As amostras de leite foram submetidas à análise ultrassônica para obtenção de parâmetros físico-químicos - gordura, extrato seco, proteínas, lactose e densidade; realização de microbiologia - bactérias mesófilas (UCF/mL). Foram coletadas amostras de tecido mamário para exame histopatológico e imunohistoquímica. Não houve diferença significativa das características avaliadas entre os dois grupos; no microbiológico, não houve relação direta da presença de mesófilas associada à infecção pelo CAEV. Na histopatologia, observaram-se áreas com infiltração celular de monócitos, polimorfonucleares, plasmócitos, fibrose, ausência de morfologia normal do parênquima mamário, denotando processo inflamatório crônico; e foi confirmada a presença do vírus na glândula pela imunohistoquímica. Os resultados não mostraram relação direta da incidência da CAE como fator negativo no desenvolvimento do rebanho.
Aiming to evaluate the influence of CAE viruses in the chemical and physical characteristics of milk, the samples were collected from 54 goats, without racial predilection, these were divided into two groups: goats positive and negative according results of test Agarose Gel Immunodiffusion. Milk samples were ultrasonic analyzed to obtain physicochemical parameters (fat, solids, protein, lactose and density); performance microbiology (mesophilic bacteria - CFU/mL) and mammary gland samples were collected for evaluation histopathology and immunohistochemistry. The results of physical-chemical analysis showed no significant difference between the milk samples of two groups. In the microbiological analysis showed the presence of aerobic mesophilic bacteria, but this change is not associated with the presence of CAEV infection. On histopathology, there were areas with infiltration of mononuclear-leukocyte and polymorph nuclear, plasma cells, fibrosis and absence of normal morphology of the mammary tissue, indicating a chronic inflammatory process; and confirmed the presence of virus, in the gland, by immunohistochemistry. The results showed no direct relationship between incidence of CAE in the herd as a negative factor for its development, however it is known that the disease in its chronic nature, causes reduction in the productivity of the herd.
Asunto(s)
Animales , Cabras , Glándulas Mamarias Animales/anomalías , Inmunohistoquímica/veterinaria , Lentivirus , Fenómenos Químicos , Técnicas Histológicas/veterinariaRESUMEN
Este estudo teve como objetivo produzir um antígeno (Ag) a partir de cultura de células de membrana sinovial caprina (MSC) infectadas com o vírus de artrite encefalite caprina (CAEV), pela técnica de microfiltração seriada, substituindo a ultracentrifugação em colchão de sacarose (UCCS) para utilização em ELISA indireto (ELISA-i). Amostras de 188 soros caprinos, que previamente foram testados pelo Western blot (WB) com Ag UCCS, foram submetidas à análise pelo ELISA-i com o novo antígeno produzido, que mostrou concordância de 92% em relação ao antígeno UCCS. A sensibilidade e a especificidade do ELISA em relação ao WB foram de 95,6% e 88,5%, respectivamente. A nova técnica, criada a partir de microfiltrações, mostrou-se efetiva e de baixo custo para o diagnóstico sorológico de anticorpos para CAEV em comparação ao antígeno ultracentrifugado, e constitui uma alternativa viável para produção de antígeno purificado de lentivírus de pequenos ruminantes.
This study aimed to produce an antigen (Ag) from the culture of goat synovial membrane cells (MSC) infected by CAEV through serial microfiltering technique replacing ultra ultracentrifugation in sacarosis Mattress (UCCS) for the indirect diagnosis ELISA tests (i ELISA). Samples of 188 sera from goats previously examined by Western Blot (WB) with Ag UCCS were submitted to analysis by i ELISA with new antigen produced, demonstrating an accordance of 92% in relation to UCCS antigen. The specificity and sensitivity relating to WB were of 95,65% and 88, 5% respectively. The new technique created from the microfiltering is effective and with low cost for the serological antibodies diagnosis of CAEV comparing to the ultracentrifuged one, presenting, therefore, as a viable alternative for purified antigen of lentivirus in small ruminants.
Asunto(s)
Animales , Antígenos/análisis , Encefalitis , Proteínas Oncogénicas v-sis/biosíntesis , Artritis/veterinaria , Lentivirus Ovinos-Caprinos , Técnicas para Inmunoenzimas/veterinariaRESUMEN
O objetivo do presente estudo foi determinar a susceptibilidade dos folículos ovarianos, espermatozoides e embriões caprinos ao Vírus da Artrite Encefalite Caprina (CAEV). Para isto, foram analisados espermatozoides e folículos ovarianos pelas técnicas de imunohistoquímica e microscopia eletrônica de transmissão, antes e após protocolos de infecção in vitro com o CAEV. Foram submetidos à análise ultraestrutural, embriões caprinos produzidos in vivo, oriundos de cabras negativas e positivas para o CAEV. Nas amostras seminais, provenientes de animais tanto com infecção natural quanto dos artificialmente infectados, foi observada imunomarcação positiva dos espermatozoides, assim como alterações degenerativas na sua análise ultraestrutural. Já nas amostras de tecido ovariano, a imunomarcação foi mais discreta e identificada na região do estroma. No tocante à análise ultraestrutural, folículos e embriões se apresentaram íntegros. De acordo com esses resultados, pode-se concluir que os espermatozoides caprinos apresentaramse infectados, assinalando a susceptibilidade dessas células ao vírus, bem como a potencialidade do CAEV ser carreado ao cerne do oócito, originando embriões infectados.
The aim of this study was to determine the susceptibility of goat ovarian follicles, spermatozoa and embryos to caprine arthritis-encephalitis virus (CAEV). Spermatozoa and ovarian follicles were analyzed, before and after in vitro infection with CAEV, through immunohistochemistry and transmission electron microscopy techniques. Goat embryos, produced in vivo from infected and non-infected goats, were submitted to ultrastructural analysis. Immunohistochemical examination of seminal samples from goats naturally and artificially infected with CAEV revealed viral antigens in spermatozoa, while the ultrastructural analysis showed degenerative changes in these cells. Ovarian tissue samples presented a more discreet immunohistochemical positive reaction situated in the stroma region. Ultrastructural analysis revealed that the embryos and ovarian follicles were intact. These results indicate that the spermatozoa were infected, confirming the susceptibility of these cells to the virus, as well as the potential of CAEV entering the oocyte, giving rise to infected embryos.
Asunto(s)
Animales , Cabras/embriología , Virus de la Artritis-Encefalitis Caprina/aislamiento & purificación , Embrión de Mamíferos/virología , Células Germinativas/virología , Inmunohistoquímica/veterinariaRESUMEN
Inibidores da enzima transcriptase reversa e da protease foram avaliados quanto ao seu efeito inibitório na replicação do Vírus da Artrite Encefalite Caprina (CAEV) cepa CAEV Cork e do vírus Maedi-Visna (MVV) cepa K1514 cultivados em células fibroblásticas de caprinos. Os fármacos utilizados foram: lamivudina, didanosina, estavudina, zidovudina, efavirenz, atazanavir e lopinavir/ritonavir. A maior concentração utilizada para lamivudina, estavudina, zidovudina e efavirenz foi 500 ?M, para atazanavir foi 50 ?M e 5,0 ?M para lopinavir/r e didanosina. A atividade antiviral in vitro foi pesquisada por meio da avaliação da viabilidade celular através da redução do MTT e pela pesquisa de inibição dos efeitos citopáticos (CPE) dos vírus. A replicação dos vírus só não foi completamente bloqueada pelos inibidores de protease (IP) atazanavir e lopinavir/r enquanto os demais apresentaram eficácia antiviral significativa em diferentes concentrações. Os IP juntamente com o efavirenz, não mostraram atividade antiviral quando foram avaliados pela técnica de redução do MTT. Esses dados indicam que os fármacos inibidores da transcriptase reversa lamivudina, didanosina, estavudina e zidovudina são eficazes na inibição in vitro dos lentivírus de pequenos ruminantes.
Inhibitors of the reverse transcriptase and protease enzymes were evaluated for their inhibitory effect on the replication of caprine arthritis encephalitis virus (CAEV) strain CAEV Cork and of the Maedi-Visna virus (MVV) strain K1514 cultured in fibroblastic cells. The drugs lamivudine, didanosine, stavudine, zidovudine, efavirenz, atazanavir and lopinavir/ritonavir were used. The highest concentration used for lamivudine, stavudine, zidovudine and efavirenz was 500 ?M, for atazanavir it was 50 ?M and 5.0 ?M for lopinavir/r and didanosine. The in vitro antiviral activity was investigated by evaluating the cell viability by the MTT method and testing for inhibition of cytopathic effects (CPE) of the virus. The replication of the virus was not completely inhibited by the protease inhibitors atazanavir and lopinavir/r in the test for CPE, while the others drugs showed significant antiviral efficacy in different concentrations. The protease inhibitors together with the efavirenz did not show antiviral activity when they were assessed by the reduced MTT technique. These data showed that the reverse transcriptase inhibitor drugs lamivudine, didanosine, stavudine and zidovudine were effective in the in vitro inhibition of small ruminant lentivirus.
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Animales , Cabras/virología , Virus Visna-Maedi/aislamiento & purificación , Lentivirus Ovinos-Caprinos/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/análisis , Inhibidores de Proteasa Viral/análisisRESUMEN
OBJECTIVES: Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients. STUDY DESIGN/METHODS: Retrospective patient case note review. RESULTS: Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae and hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to i.v. CRH (mean increase 113%). Pituitary imaging performed in all the patients showed poor concordance with findings at surgery (31%). In contrast bilateral simultaneous inferior petrosal sinus sampling (BSIPSS), performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS, the cure rate was 64%. Of the 16 patients, 9 patients who were not cured by TSS received external pituitary radiotherapy. CONCLUSIONS: Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to i.v. CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.
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Adenoma/terapia , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/terapia , Neoplasias Hipofisarias/terapia , Adenoma/complicaciones , Adenoma/diagnóstico , Adolescente , Niño , Preescolar , Terapia Combinada , Hormona Liberadora de Corticotropina , Femenino , Humanos , Hidrocortisona/sangre , Hipertensión/etiología , Inmunoensayo , Imagen por Resonancia Magnética , Masculino , Sobrepeso/etiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Hipófisis/fisiopatología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Virilismo/etiologíaRESUMEN
BACKGROUND: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin-angiotensin-aldosterone axis have been reported in a subset of patients at presentation. Anecdotally, some patients with FGD have been initially diagnosed as having Addison's disease (AD), with implications for treatment and genetic counselling. Currently, mutations in three genes: the ACTH receptor (MC2R); the melanocortin 2 receptor accessory protein (MRAP); and the steroidogenic acute regulatory protein (STAR) are known to give rise to FGD types 1-3. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes. METHODS: Forty patients with known AD without evidence of autoimmune disease were screened for mutations in MC2R, MRAP and STAR. In addition, patients were genotyped for the MC2R promoter polymorphism previously associated with reduced responsiveness to ACTH. RESULTS: No mutations in MC2R, MRAP or STAR were identified in any patient. The frequencies of the MC2R promoter polymorphism were similar to those reported in healthy controls. CONCLUSIONS: FGD does not appear to be underdiagnosed in the AD population. However, in approximately 50% of patients with FGD, no genetic cause has yet been identified and it is possible that the other, as yet unidentified, genes giving rise to FGD may be implicated in AD.
Asunto(s)
Enfermedad de Addison/genética , Glucocorticoides/deficiencia , Proteínas de la Membrana/genética , Fosfoproteínas/genética , Receptor de Melanocortina Tipo 2/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Genotipo , Glucocorticoides/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Adulto JovenRESUMEN
Este estudo examinou correlatos de adaptação psicossocial, demográficos e clínicos entre 120 mulheres em tratamento de câncer de mama. As análises indicaram que a existência de filhos adultos morando em casa, maior escolaridade e melhor renda familiar estavam relacionados a uma melhor adaptação psicossocial das mulheres entrevistadas, enquanto que mudanças no trabalho devido à doença e ao Estádio III C do tumor associaram-se mais a problemas psicológicos e sociais. Os achados oferecem importante fundamentação para o entendimento de variáveis associadas à adaptação ao tratamento do câncer de mama.
This study examines psychosocial, demographic, and clinical adjustment correlates in 120 women treated for breast cancer. Analysis suggests that the presence of grown-up children living at home, higher education, and higher family income was related to increased psychosocial adjustment levels. Changes at work due to the disease and tumor stage IIIC were associated with psychological and social problems. The findings offer an important basis to understand variables associated with adaptation to breast cancer treatment.
El presente estudio analizó relatos de adaptación psicosocial, demográficos y clínicos entre 120 mujeres en tratamiento de cáncer de mama. Los análisis indicaron que la presencia de hijos adultos viviendo en el hogar, mayor escolaridad y mejor ingreso familiar son factores que se relacionan con una mejor adaptación psicosocial de las mujeres entrevistadas. Por otro lado, las alteraciones laborales a causa de la enfermedad y del estadio III C del tumor se asocian más a problemas psicológicos y sociales. Los hallazgos ofrecen bases importantes para entender las variables asociadas a la adaptación al tratamiento de cáncer de mama.
Asunto(s)
Humanos , Femenino , Adulto , Persona de Mediana Edad , Adaptación Psicológica , Neoplasias de la Mama/psicología , Factores SocioeconómicosRESUMEN
We describe an 8-year-old boy who presented with severe facial swelling. This progressed rapidly and 17 months later he died of gastrointestinal and pulmonary infections. The diagnosis was initially brown tumour associated with hyperparathyroidism, but this was revised in the light of laboratory investigations that were within the reference ranges, and normal appearance of the parathyroids on exploration to that of an extreme case of cherubism that behaved in a locally aggressive manner.