ABSTRACT
Lymphoedema-distichiasis is an inherited autosomal dominant disorder of the lymphatic system. Rarely, it is associated with fetal hydrops; the risk and severity of which increases with successive generations. The causative gene is a member of the forkhead transcription factor family (FOXC2). We describe a fetus presenting with early-onset, rapidly progressing body wall oedema, bilateral pleural effusions and a pericardial effusion in a mother with known FOXC2 mutation. First trimester chorionic villus sampling confirmed FOXC2 mutation in the fetus when there was only a large nuchal translucency. As the phenotype progressed, the couple consented to in utero ultrasound-guided insertion of sequential bilateral pleuro-amniotic chest drains (at 23 weeks) which successfully drained the pleural effusions. The fetus was delivered at 39 weeks gestation by elective caesarean section in good condition. The shunts were removed postnatally, and the baby was discharged after 7 days. This is the first case described of a fetus with severe early-onset fetal hydrops secondary to FOXC2 mutation successfully treated by the prenatal insertion of bilateral pleuro-amniotic shunts.
Subject(s)
Chest Tubes , Eyelashes/abnormalities , Fetus/surgery , Hydrops Fetalis/surgery , Lymphedema/surgery , Pleural Effusion/surgery , Thoracostomy/methods , Adult , Drainage , Edema/diagnostic imaging , Female , Forkhead Transcription Factors/genetics , Humans , Infant, Newborn , Lymphedema/genetics , Male , Pericardial Effusion/diagnostic imaging , Pleural Effusion/diagnostic imaging , Pregnancy , Pregnancy Trimester, Second , Skin , Surgery, Computer-Assisted , Ultrasonography, PrenatalABSTRACT
Uterine leiomyomas rarely present as gynaecological emergencies. We report a case of a 29-year-old nulliparous woman, with a negative pregnancy test, who presented with collapse and an admission haemoglobin count of 68 g/L. Urgent CT of the abdomen revealed a 14 × 19 × 10 cm uterine fibroid and intraperitoneal free fluid. Emergency laparotomy confirmed massive intraperitoneal haemorrhage from a large serosal vessel on top of a 19 cm subserosal fibroid. A myomectomy was performed, preserving this patient's fertility. Histopathology confirmed a benign leiomyoma with hydropic changes.
Subject(s)
Hemoperitoneum/diagnosis , Laparotomy , Leiomyoma/complications , Shock/etiology , Syncope/etiology , Uterine Myomectomy , Uterine Neoplasms/complications , Emergency Medical Services , Female , Fertility Preservation , Hemoperitoneum/etiology , Hemoperitoneum/surgery , Humans , Leiomyoma/diagnosis , Leiomyoma/surgery , Rupture, Spontaneous/complications , Rupture, Spontaneous/surgery , Treatment Outcome , Uterine Neoplasms/diagnosis , Uterine Neoplasms/surgery , Young AdultABSTRACT
The immunoglobulins (IgGs) for beta amyloid (Abeta) and receptors for the advanced glycation end products (RAGE) have previously been shown to be related to memory and language measures in a mixed neurological sample of older adults. In this study, we examined group differences in Abeta and RAGE IgGs, as well as the relationship between both IgGs and cognitive performance in nondiabetic older adults with normal cognition, mild cognitive impairment (MCI), and probable Alzheimer's disease (AD). We found RAGE and Abeta levels to be elevated in some AD participants, leading to significant AD-control group differences. While there was an overall correlation between both IgG levels and global cognition across all three groups, this relationship was largely attributable to group differences in cognition, highlighted by considerable variability within groups in the relationship between IgG levels and cognition. While findings do not support a consistent relationship between cognition and either IgG, further research with larger samples is needed to better characterize cognitive differences between AD participants with high versus low Abeta and RAGE titers.
Subject(s)
Alzheimer Disease/immunology , Amyloid beta-Peptides/immunology , Cognition Disorders/immunology , Immunoglobulin G/blood , Peptide Fragments/immunology , Receptor for Advanced Glycation End Products/immunology , Aged , Aged, 80 and over , Alzheimer Disease/blood , Analysis of Variance , Cognition Disorders/blood , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Neuropsychological Tests , Psychiatric Status Rating Scales , Statistics as TopicABSTRACT
BACKGROUND: Blood-based immunoglobulins (IgGs) may mark the presence of amyloid plaques characterizing the progression of Alzheimer's disease (AD). Previous studies suggest that anti-RAGE and anti-Abeta IgGs increase proportionately with accumulation of amyloid-beta (Abeta) peptides at receptor sites for advanced glycation end products (RAGE), within cortical areas of brain tissue. We assessed the relationship between these potential markers and an AD-type cognitive profile. We hypothesized that these specific IgG levels would be positively correlated with Clinical Dementia Rating (CDR) scores as well as index scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in domains associated with cortical function. METHODS: Participants were 118 older adults (mean age = 74, standard deviation = 10.5) drawn from the community and local physician referrals. Participants were reassigned into five groups based on CDR. Blood IgG levels were determined through an affinity purification process. RESULTS: Analysis of covariance analyses revealed that CDR scores were significantly related to anti-RAGE, F(4,106) = 12.93, p < .001, and anti-Abeta, F(4,106) = 17.08, p < .001, after controlling for age and total IgG levels. Regression analyses indicated significant variance accounted for by anti-RAGE and anti-Abeta above and beyond total IgG effects. Additional regression identified specific RBANS domains accounting for significant variance in anti-RAGE levels including language (t = -3.74, p < .001) and delayed memory (t = -2.31, p < .05), whereas language accounted for a significant amount of variance in anti-Abeta levels (t = -3.96, p < .001). CONCLUSIONS: Anti-RAGE and anti-Abeta IgGs correlate strongly with global scores of dementia. Furthermore, they are associated with a profile of deficiency in domains associated with specific cortical function. Results suggest potential for anti-Abeta and anti-RAGE IgGs as blood biomarkers for AD.
Subject(s)
Aging/blood , Amyloid beta-Peptides/metabolism , Cognition Disorders/immunology , Dementia/immunology , Immunoglobulin G/blood , Receptors, Immunologic/blood , Age Factors , Aged , Aged, 80 and over , Aging/physiology , Amyloid beta-Peptides/blood , Biomarkers/blood , Cognition Disorders/blood , Cognition Disorders/diagnosis , Cohort Studies , Dementia/blood , Dementia/diagnosis , Disease Progression , Female , Humans , Immunoglobulin G/metabolism , Logistic Models , Male , Multivariate Analysis , Probability , Prognosis , Receptor for Advanced Glycation End Products , Receptors, Immunologic/antagonists & inhibitors , Receptors, Immunologic/metabolism , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Severity of Illness Index , Sex FactorsABSTRACT
Features of autoimmunity have been associated with both Alzheimer's disease (AD) and with diabetes. In both diseases high levels of advanced glycation end products (AGEs) and their receptor (RAGE) have been detected in tissues and in the circulation. In addition high titers of antibodies directed against a RAGE-like peptide occur in the circulation. In this study we report the presence of auto-antibodies directed against RAGE and the cytotoxic amyloid peptide Abeta42 in plasma samples derived from four study groups. Anti-RAGE IgG titers were greatest in the AD-diabetic cohort. They were followed in decreasing order by the AD-non-diabetic cohort, the elderly diabetic cohort, and lastly by the control non-diabetic elderly cohort. The same profile of IgG differences was evident for the anti-Abeta42 titers. When all of the data were combined, there was a strong linear correlation between the RAGE and Abeta42 titers suggesting that the two peptides exist as a tight complex in plasma. Plasma IgG titers were not correlated with cognitive status except that AD and AD-diabetic participants were significantly cognitively impaired relative to the two non-AD groups. There also was no significant correlation between IgG titers and subject age, except that there was a trend for a negative slope for the AD participants and a positive slope for the control participants. In keeping with the human data, we also report that chemically-induced diabetes in rats was associated with high levels of AGEs, anti-RAGE-like IgGs, and anti-Abeta42-like IgGs. For non-diabetic rats, there was a clear age-dependency regarding the magnitude of the IgG levels. These data support the concept of an interrelationship between diabetes and AD. For both diseases one underlying contributing factor to cytotoxicity could be the development of an autoimmune response triggered by the presence of AGEs and amyloid peptides.