There is no universally acceptable inclusive laboratory biomarker for the diagnosis and staging of neurodegenerative diseases, for example, Alzheimer's. There is an abnormal increase of oxidative stress in the central nervous system (CNS) of Alzheimer's patients that causes oxidation of proteins, lipids and DNA. We have published that the antiphospholipid (aPL) autoantibodies that are members of the redox-reactive autoantibody (R-RAA) family, are significantly decreased or absent in the cerebrospinal fluids of autopsy-confirmed Alzheimer's disease (AD) patients. Because of the known elevation of oxidation-induced damage in the CNS and the abnormal enrichment of redox reactive metals in postmortem AD brains, we questioned if the R-RAA in the blood of AD patients might also show a departure from the normal aPL levels. We compared 16 AD serum samples to 17 serum samples, from age-matched volunteer blood donors. Each serum was tested before and after oxidation for four aPL specificities by using an in-house ELISA. Comparisons between the AD and normal populations revealed highly significant differences. In-sample Fisher's linear discriminate analysis found a sensitivity of 88% and a specificity of 94%. In-sample Classification and Regression Tree analysis (CART) found a sensitivity of 84% and a specificity of 100%. This study is the first to indicate that blood tests for R-RAA may be used as a laboratory criterion for an Alzheimer's diagnosis.
Our results demonstrated FtLI was likely at early gestation (<28 weeks) and FtLM was probable beyond 35 weeks. Discordance for FtLM was likely at 32 weeks; therefore, clinicians should guard against complacency that this gestational mark assures an uncomplicated respiratory course for all infants within the set.
There are no reports indicating the effect of prophylactic transabdominal cerclage (TAC) on the prolongation of multifetal pregnancies. We report the use of TAC in triplets, which evolved over 20 years in one practice. A retrospective cohort study of triplet pregnancies was conducted. Obstetric and neonatal outcomes were compared among women who underwent a prophylactic TAC or transvaginal cerclage and no cerclage. Of the 141 women who delivered triplets, prophylactic TAC was associated with reduced incidence of extreme prematurity and improved incidence of neonatal/postnatal survival. With the exception of mode of conception, prepregnancy weight, and the use of home monitoring uterine activity monitor, procardia and terbutaline, no major differences were found in terms of patient characteristics and pregnancy and delivery management among the three groups. It was concluded that in triplet pregnancies, prophylactic placement of a TAC appears to lower the incidence of delivery before 28 weeks.
A robust blood biomarker is urgently needed to facilitate early prognosis for those at risk for Alzheimer’s disease (AD). Redox reactive autoantibodies (R-RAAs) represent a novel family of antibodies detectable only after exposure of cerebrospinal fluid (CSF), serum, plasma or immunoglobulin fractions to oxidizing agents. We have previously reported that R-RAA antiphospholipid antibodies (aPLs) are significantly decreased in the CSF and serum of AD patients compared to healthy controls (HCs). These studies were extended to measure R-RAA aPL in serum samples obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI). Serum samples from the ADNI-1 diagnostic groups from participants with mild cognitive impairment (MCI), AD and HCs were blinded for diagnosis and analyzed for R-RAA aPL by ELISA. Demographics, cognitive data at baseline and yearly follow-up were subsequently provided by ADNI after posting assay data. As observed in CSF, R-RAA aPL in sera from the AD diagnostic group were significantly reduced compared to HC. However, the sera from the MCI population contained significantly elevated R-RAA aPL activity relative to AD patient and/or HC sera. The data presented in this study indicate that R-RAA aPL show promise as a blood biomarker for detection of early AD, and warrant replication in a larger sample. Longitudinal testing of an individual for increases in R-RAA aPL over a previously established baseline may serve as a useful early sero-epidemiologic blood biomarker for individuals at risk for developing dementia of the Alzheimer’s type.
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