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1.
Int J Obes (Lond) ; 42(1): 115-118, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28871150

RESUMO

Intragastric Balloons are a temporary, reversible and safer option compared to bariatric surgery to promote significant weight loss, leading to improved metabolic outcomes. However, due to subsequent weight regain, alternative procedures are now preferred in adults. In adolescents, more amenable to lifestyle change, balloons may be an alternative to less reversible procedures. Our aim was to assess the tolerability and efficacy of the intragastric balloon in severely obese adolescents and the impact of associated weight loss on biomedical outcomes (glucose metabolism, blood pressure, lipid profiles) and bone density. A 2-year cohort study of 12 adolescents (BMI >3.5 s.d., Tanner stage >4) following 6 months intragastric balloon placement was carried out. Subjects underwent anthropometry, oral glucose tolerance test, and DEXA scans at 0, 6 and 24 months. The results showed clinically relevant improvements in blood pressure, insulin: glucose metabolism, liver function and sleep apnoea at 6 months. Changes were not sustained at 2 years though some parameters (Diastolic BP, HBA1c, insulin AUC) demonstrated longer-term improvement despite weight regain. Despite weight loss, bone mass accrual showed age appropriate increases. In conclusion, the intragastric balloon was safe, well tolerated and effective in supporting short-term weight loss and clinically relevant improvement in obesity-related complications, which resolved in some individuals. Benefits were not sustained in the majority at 2 years.


Assuntos
Balão Gástrico , Obesidade Mórbida , Adolescente , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/complicações , Masculino , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Redução de Peso
2.
BMC Endocr Disord ; 17(1): 33, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619024

RESUMO

BACKGROUND: Communication is complex in endocrine care, particularly during transition from paediatric to adult services. The aims of this study were to examine the feasibility of interventions to support young people to interact with clinicians. METHODS: Development and evaluation of a complex intervention in 2 phases: Pre-intervention observational study; Intervention feasibility study. Purposive sample of recordings of 62 consultations with 58 young people aged 11-25 years with long-term endocrine conditions in two paediatric and two adult endocrine clinics. Proportion of time talked during consultations, number and direction of questions asked; Paediatric Consultation Assessment Tool (PCAT); OPTION shared decision making tool; Medical Information Satisfaction Scale (MISS- 21). Young people were invited to use one or more of: a prompt sheet to help them influence consultation agendas and raise questions; a summary sheet to record key information; and the www.explain.me.uk website. RESULTS: Nearly two thirds of young people (63%) chose to use at least one communication intervention. Higher ratings for two PCAT items (95% CI 0.0 to 1.1 and 0.1 to 1.7) suggest interventions can support consultation skills. A higher proportion of accompanying persons (83%) than young people (64%) directed questions to clinicians. The proportion of young people asking questions was higher (84%) in the intervention phase than in the observation phase (71%). CONCLUSIONS: Interventions were acceptable and feasible. The Intervention phase was associated with YP asking more questions, which implies that the availability of interventions could promote interactivity.


Assuntos
Serviços de Saúde do Adolescente , Comunicação , Participação do Paciente , Adolescente , Criança , Tomada de Decisões , Endocrinologia/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino
3.
Arch Dis Child ; 102(6): 503-508, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27998884

RESUMO

BACKGROUND: Many infants born prematurely experience growth failure following delivery, with subsequent catch-up growth. Traditionally catch-up was thought to be complete in the first few years of life. Most studies have focused on groups of infants defined by birth weight, for example <1500 g, resulting in disproportionate numbers of small for gestational age infants. This study aimed to determine whether appropriate weight for gestation (AGA) preterm born children reach their expected adult height when compared with term controls. METHODOLOGY: This UK based prospective longitudinal cohort study recruited 204 preterm children born at a tertiary neonatal unit during 1994 and 50 matched controls. Growth parameters have been assessed annually until the completion of growth. RESULTS: There was no significant difference in the final height SD score (SDS) of children born at term (n=30) and those born prematurely and AGA (n=70) (0.45 term vs 0.22 preterm). Catch-up growth however, continued throughout the whole of childhood. When the difference between final height SDS and mid-parental height SDS were compared, there were again no significant differences (0.13 term vs 0.03 preterm). CONCLUSIONS: Those born prematurely with an AGA achieve a comparable adult height to children born at term, however, catch-up growth continues for much longer than traditionally thought.


Assuntos
Estatura/fisiologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Adulto , Envelhecimento/fisiologia , Antropometria/métodos , Estudos de Casos e Controles , Desenvolvimento Infantil/fisiologia , Feminino , Idade Gestacional , Crescimento/fisiologia , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Valores de Referência , Caracteres Sexuais , Nascimento a Termo
4.
Int J Obes (Lond) ; 41(4): 591-597, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27795553

RESUMO

BACKGROUND: Severe adolescent obesity (body mass index (BMI) >99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment. Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. OBJECTIVES: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included weight loss, waist and hip measurements, psychosocial outcomes including health-related quality of life (HRQoL) and physical self perceptions, physical activity and cardiorespiratory fitness. METHOD: Non-randomised pilot study. RESULTS: Twelve severely obese adolescents (5 males, 7 females; mean age 15 years; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146). At 24 months (n=10), there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. CONCLUSION: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well-tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months.


Assuntos
Aptidão Cardiorrespiratória/fisiologia , Exercício Físico/fisiologia , Balão Gástrico , Obesidade Mórbida/terapia , Obesidade Infantil/terapia , Comportamento de Redução do Risco , Redução de Peso/fisiologia , Adolescente , Aptidão Cardiorrespiratória/psicologia , Inglaterra , Exercício Físico/psicologia , Feminino , Seguimentos , Humanos , Masculino , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/psicologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/fisiopatologia , Obesidade Infantil/psicologia , Projetos Piloto , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
5.
Diabet Med ; 33(2): 192-203, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26248789

RESUMO

AIM: To assess the effect of a 5-day structured education course (Kids in Control of Food; KICk-OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes. METHODS: This was a cluster-randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk-OFF courses, whereas control centres delivered usual care. Participants were 11-16 years of age and had Type 1 diabetes for at least one year. The KICk-OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self-efficacy. RESULTS: Three hundred and ninety-six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75-81) vs. 76 mmol/mol (74-79) [9.3% (9-9.6%) vs. 9.1% (8.9-9.4%); 24 months: 77 mmol/mol (74-79) vs. 78 mmol/mol (75-81) (9.2% (8.9-9.4%) vs. 9.3% (9-9.6%)], adjusted mean difference, -2.0 mmol/mol (6.5-2.5) [2.3% (-2.7% to 2.4%)], P = 0.38. CONCLUSIONS: Attending a KICk-OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c , was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268).


Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Diabetes Mellitus Tipo 1/terapia , Dieta para Diabéticos , Ajustamento Emocional , Cooperação do Paciente , Educação de Pacientes como Assunto , Estresse Psicológico/prevenção & controle , Adolescente , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Análise por Conglomerados , Estudos de Coortes , Terapia Combinada , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Feminino , Seguimentos , Processos Grupais , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Masculino , Qualidade de Vida , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Reino Unido
6.
J Clin Endocrinol Metab ; 100(10): E1362-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26259131

RESUMO

CONTEXT: GLIS3 (GLI-similar 3) is a member of the GLI-similar zinc finger protein family encoding for a nuclear protein with 5 C2H2-type zinc finger domains. The protein is expressed early in embryogenesis and plays a critical role as both a repressor and activator of transcription. Human GLIS3 mutations are extremely rare. OBJECTIVE: The purpose of this article was determine the phenotypic presentation of 12 patients with a variety of GLIS3 mutations. METHODS: GLIS3 gene mutations were sought by PCR amplification and sequence analysis of exons 1 to 11. Clinical information was provided by the referring clinicians and subsequently using a questionnaire circulated to gain further information. RESULTS: We report the first case of a patient with a compound heterozygous mutation in GLIS3 who did not present with congenital hypothyroidism. All patients presented with neonatal diabetes with a range of insulin sensitivities. Thyroid disease varied among patients. Hepatic and renal disease was common with liver dysfunction ranging from hepatitis to cirrhosis; cystic dysplasia was the most common renal manifestation. We describe new presenting features in patients with GLIS3 mutations, including craniosynostosis, hiatus hernia, atrial septal defect, splenic cyst, and choanal atresia and confirm further cases with sensorineural deafness and exocrine pancreatic insufficiency. CONCLUSION: We report new findings within the GLIS3 phenotype, further extending the spectrum of abnormalities associated with GLIS3 mutations and providing novel insights into the role of GLIS3 in human physiological development. All but 2 of the patients within our cohort are still alive, and we describe the first patient to live to adulthood with a GLIS3 mutation, suggesting that even patients with a severe GLIS3 phenotype may have a longer life expectancy than originally described.


Assuntos
Doenças Ósseas/genética , Hipotireoidismo Congênito/genética , Deficiências do Desenvolvimento/genética , Diabetes Mellitus/genética , Resistência à Insulina/genética , Hepatopatias/genética , Fenótipo , Fatores de Transcrição/genética , Doenças Ósseas/congênito , Proteínas de Ligação a DNA , Diabetes Mellitus/congênito , Feminino , Humanos , Lactente , Recém-Nascido , Hepatopatias/congênito , Masculino , Proteínas Repressoras , Transativadores
8.
J Clin Endocrinol Metab ; 98(1): 322-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23175691

RESUMO

CONTEXT: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the evidence in obese children and young people is inconclusive. OBJECTIVE: The objective of the study was to assess the effect of metformin on body mass index sd score (BMI-SDS), metabolic risk factors, and adipokines. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at six pediatric endocrine centers in the United Kingdom. PARTICIPANTS: One hundred fifty-one obese children and young people with hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6% postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants. The age range was 8-18 yr, the mean age was 13.7 (SD 2.3) yr, and the mean BMI-SDS was +3.4 (SD 0.5). INTERVENTIONS: The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months. MAIN OUTCOME MEASURE: The main outcome measure was a reduction in BMI-SDS at 6 months. Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio (ALR) at 3 and 6 months. RESULTS: Metformin was associated with a significant reduction in BMI-SDS compared with placebo at 6 months [mean difference -0.1 SD (95% confidence interval -0.18 to -0.02), P = 0.02]. Significant improvements at 3 months were found in the metformin group: fasting glucose, -0.16 mmol/liter (-0.31 to -0.00), P = 0.047; ALT, 19% (5-36%), P = 0.008; and ALR, 32% (4-67%), P = 0.02. CONCLUSIONS: Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.


Assuntos
Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Adolescente , Idade de Início , Criança , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Masculino , Adesão à Medicação/estatística & dados numéricos , Metformina/efeitos adversos , Obesidade/complicações , Obesidade/epidemiologia , Placebos , Resultado do Tratamento
9.
Arch Dis Child Educ Pract Ed ; 97(3): 98-105, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22611124

RESUMO

This expert opinion provides detailed guidance on assessing obesity in secondary paediatric practice. This guidance builds on existing recommendations from National Institute of Health and Clinical Excellence in the UK, and is evidence based where possible. Guidance is provided on which obese children and young people are appropriate to be seen in secondary care and relevant history and investigations, and guidance on when further investigation of causes and obesity-related comorbidity is appropriate.


Assuntos
Obesidade/etiologia , Obesidade/terapia , Encaminhamento e Consulta , Glicemia/análise , Índice de Massa Corporal , Criança , Jejum , Humanos , Insulina/análise , Lipídeos/sangue , Testes de Função Hepática , Anamnese , Síndrome Metabólica/diagnóstico , Exame Físico , Sono , Apneia Obstrutiva do Sono/diagnóstico
10.
Clin Exp Allergy ; 42(2): 284-92, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22181034

RESUMO

BACKGROUND: Although adrenaline is recommended as first line treatment for anaphylaxis, it is often not utilized. There has been a debate about when adrenaline autoinjectors should be prescribed and how many should be dispensed. OBJECTIVES: To see how many adrenaline autoinjectors were used during anaphylactic reactions and to determine why they were not used in situations where they were clinically indicated. METHODS: Patients were recruited prospectively at 14 paediatric allergy clinics throughout UK. Participants completed a questionnaire covering demographic data, atopic status and details of allergic reactions in the previous year and reasons for using more than one device. RESULTS: A total of 969 patients were recruited of whom 466 (48.1%, 95% CI: 37.9-58.2) had had at least one reaction in the previous year; 245 (25.3%, 95% CI: 16.2-34.4) of these reactions were anaphylaxis. An adrenaline autoinjector was used by 41 (16.7%, 95% CI: 11.7-21.3) participants experiencing anaphylaxis. Thirteen participants received more than one dose of adrenaline, for nine of these a health professional gave at least one. The commonest reasons for using more than one were severe breathing difficulties (40%), lack of improvement with first dose (20%) and miss-firing (13.3%). The commonest reasons for not using adrenaline in anaphylaxis were 'thought adrenaline unnecessary' (54.4%) and 'unsure adrenaline necessary' (19.1%). Many with wheeze did not use their autoinjector. CONCLUSIONS AND CLINICAL RELEVANCE: Adrenaline is used by only a minority of patients experiencing anaphylaxis in the community. Thirteen of the 41 patients with anaphylaxis who used their autoinjector needed another dose of adrenaline. Further research is needed to consider how to best encourage the usage of adrenaline when clinically indicated in anaphylaxis.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Anafilaxia/prevenção & controle , Epinefrina/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Injeções Subcutâneas/instrumentação , Injeções Subcutâneas/métodos , Masculino , Estudos Prospectivos , Reino Unido
11.
Clin Endocrinol (Oxf) ; 75(4): 443-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21635277

RESUMO

CONTEXT: Increasing numbers of very low birth weight (VLBW) infants are surviving into adulthood because of improvements in neonatal intensive care. Adverse events in early life can have long-term effects through reprogramming of metabolic systems. OBJECTIVE: To determine whether young adult VLBW survivors have abnormalities of skeletal development or endocrine function. DESIGN: Cross-sectional, observational, case-control study. PARTICIPANTS: Thirty-seven VLBW subjects and 27 healthy controls at peak bone mass (mean age 23). MEASUREMENTS: Differences between cases and controls in body size, body composition, bone mass and bone geometry [assessed by dual-energy X-ray absorptiometry (DXA), hip structure analysis and peripheral quantitative computed tomography (pQCT)], bone turnover [urine N-terminal telopeptide of type I collagen (NTX), serum C-terminal telopeptide of type I collagen (CTX)], aminoterminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase), hormones (sex steroids, IGF-1, PTH and 25-OH vitamin D) and insulin sensitivity (HOMA-IR and oral glucose tolerance testing). RESULTS: VLBW subjects had lower bone density at the lumbar spine (5.7%) and femoral neck (8.6%), which persisted after correction for bone size by the estimation of volumetric density (bone mineral apparent density). Urine NTX was higher in VLBW subjects than in controls, but there were no significant differences in other bone turnover markers. VLBW survivors had lower insulin sensitivity (mean INS-30 controls = 57.0, VLBW subjects = 94.3, P < 0.01), but there were no differences in whole body fat mass or truncal fat mass between VLBW subjects and controls. CONCLUSIONS: Young adult VLBW survivors have reduced bone density for their bone size and reduced insulin sensitivity, which may have significant implications for their risk of fracture and diabetes in later life.


Assuntos
Densidade Óssea/fisiologia , Recém-Nascido de muito Baixo Peso/sangue , Recém-Nascido de muito Baixo Peso/metabolismo , Resistência à Insulina/fisiologia , Absorciometria de Fóton , Adulto , Estudos de Casos e Controles , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/metabolismo , Humanos , Recém-Nascido , Masculino , Peptídeos/sangue , Adulto Jovem
12.
Eur J Endocrinol ; 164(3): 437-43, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21139041

RESUMO

INTRODUCTION: Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with six affected cases from three families reported to date. Additional features, described previously, include congenital glaucoma, hepatic fibrosis, polycystic kidneys, developmental delay and facial dysmorphism. SUBJECTS: We report two new cases from unrelated families with distinct novel homozygous partial GLIS3 deletions. Both patients presented with neonatal diabetes mellitus, severe resistant hypothyroidism in the presence of elevated thyroglobulin and normal thyroid anatomy, degenerative liver disease, cystic renal dysplasia, recurrent infections and facial dysmorphism. These novel mutations have also resulted in osteopenia, bilateral sensorineural deafness and pancreatic exocrine insufficiency, features that have not previously been associated with GLIS3 mutations. Gene dosage analysis showed that the parents were carriers of a deletion encompassing exons 1-2 (case 1) or exons 1-4 (case 2) of the 11 exon gene. Genome-wide SNP analysis did not reveal a common ancestral GLIS3 haplotype in patient 2. CONCLUSIONS: Our results confirm partial gene deletions as the most common type of GLIS3 mutations, accounting for four of five families identified to date. We propose that mutations in GLIS3 lead to a wider clinical phenotype than previously recognised. We also report the first case of a recessive GLIS3 mutation causing neonatal diabetes and congenital hypothyroidism in a child from a non-consanguineous pedigree, highlighting the importance of molecular genetic testing in any patient with this phenotype.


Assuntos
Mutação , Fenótipo , Fatores de Transcrição/genética , Hipotireoidismo Congênito/genética , Proteínas de Ligação a DNA , Diabetes Mellitus/genética , Éxons/genética , Feminino , Dosagem de Genes/genética , Haplótipos/genética , Humanos , Recém-Nascido , Masculino , Proteínas Repressoras , Transativadores
13.
Bone ; 48(2): 189-96, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20932948

RESUMO

UNLABELLED: Obese children, particularly those who have fractured, have reduced body size-adjusted total body and regional bone mass. We performed an observational cross-sectional cohort study to determine the relationship between adipokines (leptin and adiponectin), bone-derived cytokines and bone turnover in children which may explain this observation. Participants aged 5-16 years were recruited into obese (BMI SDS 3.3±0.6) and lean (BMI SDS 0.2±1.0) groups and further subdivided into groups by fracture history. Free leptin (leptin/leptin soluble receptor) and adiponectin; RANK-ligand (RANKL), osteoprotegerin (OPG); Dickkopf-1 (DKK1); and the bone turnover markers procollagen type I amino propeptide (P1NP) and carboxy-terminal telopeptide of type I collagen (CTx). Total body and truncal fat mass were measured by DXA. RESULTS: Free leptin (p>0.0001) and adiponectin (p=0.0002) were higher and lower in obese children respectively. OPG was lower in obese children (p=0.01), being inversely related to free leptin (p=0.009), total body and truncal fat mass (both p=0.01). RANKL was inversely related to free leptin in children with prior fracture (p=0.03). CTx was higher in obese children (p=0.003). Free leptin was positively associated with both CTx (p=0.03) and P1NP (p=0.02). DKK1 was inversely related to adiponectin (p=0.02). CONCLUSION: Bone formation relative to resorption was reduced in obese children; this difference was accentuated in those with prior fracture. Adipokines may regulate these changes. Osteoprotegerin may play a fundamental role in the failure of obese children to accrue bone mass appropriately.


Assuntos
Adipocinas/sangue , Obesidade/sangue , Obesidade/metabolismo , Adipocinas/metabolismo , Adiponectina/sangue , Adiponectina/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leptina/sangue , Leptina/metabolismo , Masculino , Osteoprotegerina/sangue , Osteoprotegerina/metabolismo , Ligante RANK/sangue , Ligante RANK/metabolismo
14.
Scand J Immunol ; 71(6): 393-402, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20500691

RESUMO

Dendritic cells (DC) are an essential link between the innate and adaptive immune response. To become effective antigen-presenting cells DC need to undergo maturation, during which they up-regulate co-stimulatory molecules and produce cytokines. There is great interest in utilizing DC in vaccination regimes. Over recent years, Toll-like receptor (TLR) signalling has been recognized to be one of the major inducers of DC maturation. This study describes a mutant version of the TLR adaptor molecule MyD88 (termed MyD88lpr) as a novel adjuvant for vaccination regimes. MyD88lpr specifically activates DC by disrupting a DC intrinsic inhibitory mechanism, which is dependent on single immunoglobulin IL-1R-related. Moreover, MyD88lpr was able to induce an IgG2a-dominated response to a co-expressed antigen, suggesting Th1 immunity. However, when used as a vaccine adjuvant for Influenza nucleoprotein there was no significant difference in the lung viral titres during the infection. This study describes MyD88lpr as a potential adjuvant for vaccinations, which would be able to target DC specifically.


Assuntos
Células Dendríticas/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Receptores de Interleucina-1/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais/sangue , Células Dendríticas/efeitos dos fármacos , Feminino , Humanos , Imunidade Inata/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/farmacologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/farmacologia , Organismos Livres de Patógenos Específicos , Células Th1/imunologia , Vacinação/métodos
16.
J Pediatr Endocrinol Metab ; 21(12): 1129-32, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19189685

RESUMO

BACKGROUND: There are few data in the paediatric literature on the normal cortisol response to stimulation during the low dose synacthen test (LDST) (1 microg). AIM: To examine the cortisol responses in children, subsequently presumed to be normal, who had an LDST during anterior pituitary function tests (APFTs). METHODS: A retrospective review of results in children with short stature and normal growth hormone levels. RESULTS: Of 33 children tested, seven had suboptimal cortisol responses based on accepted criteria (peak <500 nmol/l)--a false positive rate of 21%. Only three of these children had a repeat LDST, which was normal in all cases. The peak cortisol response (median 633, range, 417-1052 nmol/l) was inversely correlated with age (r = -0.44, p < 0.05). CONCLUSION: One in five tests did not meet normal criteria. This false positive rate (21%) should be borne in mind when interpreting synacthen tests to prevent overdiagnosis of adrenal insufficiency.


Assuntos
Insuficiência Adrenal/diagnóstico , Cosintropina , Hidrocortisona/sangue , Testes de Função Hipofisária/métodos , Adeno-Hipófise/fisiologia , Adolescente , Insuficiência Adrenal/sangue , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Reações Falso-Positivas , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos
17.
Biochem Soc Trans ; 35(Pt 6): 1501-3, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18031253

RESUMO

PRR (pattern-recognition receptor) signalling is involved early in the immune response and therefore would be attractive to target during vaccination. The use of PRR ligands has shown some success; however, toxicity and non-specificity are issues with this strategy. The targeting of PRR intracellular signalling networks would allow for greater specificity and reduced systemic toxicity. The present review examines the successes seen with overexpression or repression of PRR signalling molecules.


Assuntos
Adjuvantes Imunológicos , Receptores de Reconhecimento de Padrão/imunologia , Transdução de Sinais/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Humanos , Sistema Imunitário/imunologia , Ligantes , Receptores de Reconhecimento de Padrão/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Vacinação , Vacinas de DNA/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos
18.
Eur J Endocrinol ; 157 Suppl 1: S61-5, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17785700

RESUMO

BACKGROUND: Phytosterolaemia (sitosterolaemia) is a rare autosomal recessive condition caused by mutations on the ABCG5 and ABCG8 gut transporter proteins. This leads to accumulation of plant-derived cholesterol-like molecules in blood and tissues. CASE: We describe a family of Bangladesh origin, where three siblings (two males and one female) have homozygous mutations for phytosterolaemia, and exhibit short stature and adrenal failure with the female having ovarian failure. FINDINGS: The index case (18-year-old female) and her sibling (16 years) have adrenal insufficiency with hyperpigmentation and raised levels of ACTH, at 367 and 690 ng/l respectively. The youngest child at 7 years has normal adrenal function. In addition, the index case has ovarian failure and sibling 2 has partial growth hormone deficiency. CONCLUSION: Although short stature is a recognised phenomenon, no previous association has been made between phytosterolaemia and other endocrine abnormalities. We postulate that the elevated plant sterol levels in phytosterolaemia may interfere with endocrine hormone synthesis; in particular, we present evidence that adrenal cholesterol metabolism may be preferentially affected, accounting for the adrenal insufficiency.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Insuficiência Adrenal/etiologia , Genes Recessivos , Lipoproteínas/genética , Mutação , Fitosteróis/sangue , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adolescente , Insuficiência Adrenal/sangue , Hormônio Adrenocorticotrópico/sangue , Estatura , Criança , Feminino , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/deficiência , Homozigoto , Humanos , Hiperpigmentação/etiologia , Masculino , Linhagem , Insuficiência Ovariana Primária/etiologia
20.
Proc Natl Acad Sci U S A ; 103(39): 14459-64, 2006 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-16971487

RESUMO

There is a pressing need for adjuvants that will enhance the effectiveness of genetic vaccines. This is particularly important in cancer and infectious disease such as HIV and malaria for which successful vaccines are desperately needed. Here, we describe an approach to enhance immunogenicity that involves the activation of NF-kappaB by the transgenic expression of an intracellular signaling molecule, NF-kappaB-inducing kinase (NIK). In vitro, NIK increases dendritic cell antigen presentation in allogeneic and antigen-specific T cell proliferation assays by potently activating NF-kappaB and consequently up-regulating the expression of cytokines (TNF-alpha, IL-6, IL-12, IL-15, and IL-18), chemokines [IL-8, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3], MHC antigen-presenting molecules (class I and II), and costimulatory molecules (CD80 and CD86). In vivo, NIK enhances immune responses against a vector-encoded antigen and shifts them toward a T helper 1 immune response with increased IgG2a levels, T cell proliferation, IFN-gamma production, and cytotoxic T lymphocyte responses more potently than complete Freund's adjuvant, a very efficacious T helper 1-inducing adjuvant. These findings define NIK, and possibly other inducers of NF-kappaB activation, as a potent adjuvant strategy that offers great potential for genetic vaccine development.


Assuntos
Adjuvantes Imunológicos/metabolismo , Expressão Gênica , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Vacinas/imunologia , Animais , Anticorpos/sangue , Formação de Anticorpos/imunologia , Apresentação de Antígeno/imunologia , Proliferação de Células , Quimiocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/imunologia , Vetores Genéticos , Antígenos de Histocompatibilidade/imunologia , Humanos , Imunização Secundária , Camundongos , Proteínas Recombinantes de Fusão/metabolismo , Linfócitos T Citotóxicos/imunologia , Células Th1/citologia , Células Th1/imunologia , Fatores de Tempo , Regulação para Cima/genética , Quinase Induzida por NF-kappaB
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