14 research outputs found
Osteoprotegerin antibodies in the pathogenesis of osteoporosis
Osteoporosis is a common complication of many autoimmune diseases that is
typically attributed to disease specific factors rather than a direct autoimmune
process. This thesis arises from the investigation of a patient with severe high bone
turnover osteoporosis who was identified as having autoimmune disease but whose
osteoporosis deteriorated despite appropriate treatment. This presentation led to the
hypothesis that neutralising autoantibodies to the bone protective cytokine
osteoprotegerin (OPG) may have developed.
Serum from the index patient, but not healthy controls, was able to
immunoprecipitate recombinant OPG protein, demonstrating that OPG had become
the target of an autoimmune response. Purified immunoglobulins from the index case
were able to inhibit the function of OPG in vitro, by suppressing OPG-mediated
inhibition of a luciferase reporter cell line. This represents the first description of
disease associated with neutralising antibodies to OPG. Whilst the
immunoprecipitation assay did identify OPG antibodies in further patients these
results were difficult to quantify. A more robust enzyme linked immunosorbent
assay for OPG antibodies was developed using OPG as a capture antigen, which
allowed the screening of patient cohorts. Presence of OPG antibodies was defined as
a titre greater than the mean plus three standard deviations of 101 healthy volunteers.
A low prevalence of 14/864 (1.6%) was seen in a general population cohort and no
association with bone density or turnover was seen. An association with higher
vascular calcification score in this cohort requires replication. A prevalence of
37/315 (11.7%) was seen in an osteoporosis cohort though no association was seen
with bone density or response to treatment. In a coeliac cohort OPG antibodies were
identified in 14/282 (5.0%) patients and presence of antibody was independently
associated with reduced spine bone density. Functional inhibition of OPG was shown
in vitro in 3/14 (21.4%) of the positive cases. Case finding of osteoporosis in the
coeliac cohort was not improved by identification of OPG antibodies. These results
are consistent with OPG antibodies being pathological in a small number of patients
with osteoporosis but a clinical utility of measuring OPG antibodies has not been
established
A História da Alimentação: balizas historiográficas
Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema
967 Cervical Dysplasia and Inflammatory Bowel Disease: No Effect of Disease Status or Immunosuppressants On Analysis of 2,199 Smear Records
S1192 A Retrospective Analysis of Small Bowel MRI in Evaluation of Disease Activity in Ileal Crohn's Disease
1128 A Trial With Mercaptopurine Following Azathioprine Intolerance is a Safe Treatment Strategy for the Majority of Patients With IBD
1043 The Efficacy of Corticosteroid Therapy: Analysis of 10-Year Inflammatory Bowel Disease Inception Cohort (1998-2007)
Tu1251 Implications of Evolving Anti-Tumour Necrosis Factor (Anti-TNF) Treatment Patterns in a Tertiary Referral Centre: Results of 1457 Patient-Years Follow-up
S1175 Elevated Faecal Calprotectin Levels Are Associated with the Need for Colectomy in Acute Severe Ulcerative Colitis
Maternal intramuscular dexamethasone versus betamethasone before preterm birth (ASTEROID): a multicentre, double-blind, randomised controlled trial
Background: Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, whether dexamethasone or betamethasone have better maternal, neonatal, and childhood health outcomes remains unclear. We therefore aimed to assess whether administration of antenatal dexamethasone to women at risk of preterm birth reduced the risk of death or neurosensory disability in their children at age 2 years compared with betamethasone. We also aimed to assess whether dexamethasone reduced neonatal morbidity, had benefits for the mother, or affected childhood body size, blood pressure, behaviour, or general health compared with betamethasone. Methods: In this multicentre, double-blind, randomised controlled trial, we recruited pregnant women from 14 maternity hospitals in Australia and New Zealand that could provide care to preterm babies. Women were eligible for study inclusion if they were at risk of preterm birth before 34 weeks of gestation, had a singleton or twin pregnancy, and had no contraindications to antenatal corticosteroids. We randomly assigned women (1:1) to receive two intramuscular injections of either 12 mg dexamethasone (dexamethasone sodium phosphate) or 11·4 mg betamethasone (Celestone Chronodose), 24 h apart. The randomisation schedule used balanced, variable blocks that were stratified by hospital, gestational age, and number of fetuses (singleton or twins). We masked all participants, staff, and assessors to treatment groups. Analyses were by intention to treat. The primary outcome was death or neurosensory disability at age 2 years (corrected for prematurity). This study is registered with ANZCTR, ACTRN12608000631303. Findings: Between Jan 28, 2009, and Feb 1, 2013, we randomly assigned 1346 (78%) women who were pregnant with 1509 fetuses to groups: 679 (50%) women were assigned to receive dexamethasone and 667 (50%) women were assigned to receive betamethasone. 27 (4%) fetuses, infants, or children in the dexamethasone group and 28 (4%) fetuses, infants, or children in the betamethasone group died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was determined for 603 (79%) of 763 fetuses whose mothers received dexamethasone and 591 (79%) of 746 fetuses whose mothers received betamethasone. We found a similar incidence of death or neurosensory disability in the dexamethasone (198 [33%] of 603 infants) and betamethasone groups (192 [32%] of 591 infants; adjusted relative risk [adjRR] 0·97, 95% CI 0·83 to 1·13; p=0·66). 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group reported side-effects. Discomfort at the injection site, the most frequent side-effect, was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02). Interpretation: The incidence of survival without neurosensory disability at age 2 years did not differ between dexamethasone and betamethasone treatment. Our findings indicate that either antenatal corticosteroid can be given to women before preterm birth to improve infant and child health. Funding: National Health and Medical Research Council (Australia)