scispace - formally typeset
Search or ask a question
Author

D W Branch

Other affiliations: Intermountain Healthcare
Bio: D W Branch is an academic researcher from University of Utah. The author has contributed to research in topics: Antiphospholipid syndrome & Pregnancy. The author has an hindex of 25, co-authored 51 publications receiving 7968 citations. Previous affiliations of D W Branch include Intermountain Healthcare.


Papers
More filters
Journal Article
TL;DR: Pregnancy in women with antiphospholipid syndrome appears to be improved by treatment, but fetal loss may occur despite treatment, and thrombosis prophylaxis should be considered in these patients.

420 citations

Journal ArticleDOI
TL;DR: It is demonstrated that many aPL are directed at neoepitopes of oxidized phospholipids, and suggest that oxidative events may be important in the pathophysiology of APS.
Abstract: The optimal clinical management of patients with antiphospholipid antibody syndrome (APS) is uncertain because of a lack of an underlying hypothesis to explain why antiphospholipid autoantibodies (aPL) form to such ubiquitous compounds as phospholipids (PL). In this paper, we demonstrate that many, if not most, aPL are actually directed at neoepitopes of oxidized PL, or neoepitopes generated by adduct formation between breakdown products of oxidized PL and associated proteins. Each cardiolipin (CL) molecule contains four unsaturated fatty acids and is highly susceptible to oxidation, particularly upon exposure to air. Yet, standard anticardiolipin antibodies (aCL) immunoassays routinely bind CL to microtiter wells by evaporation of the ethanol solvent overnight at 4 degrees C. Using a variety of techniques, we demonstrated that rapid oxidation occurs when CL is plated and exposed to air. Sera from apo E-deficient mice, which have high autoantibody titers to oxidized low density lipoprotein, showed a striking time-dependent increase in binding to CL that was exposed to air for increasing periods of time. Monoclonal antibodies to oxidized LDL, cloned from the apo E-deficient mice, also bound to oxidized CL. Both sera and affinity-purified aCL-IgG from APS patients bound to CL progressively as it was oxidized. However, the monoclonal antibodies from apo E-deficient mice, or sera or aCL-IgG from APS patients did not bind to a reduced CL analog that was unable to undergo peroxidation. These data demonstrate that many aPL are directed at neoepitopes of oxidized phospholipids, and suggest that oxidative events may be important in the pathophysiology of APS. In turn, this suggests new therapeutic strategies, possibly including intensive antioxidant therapy.

362 citations

Journal ArticleDOI
TL;DR: A 32-year-old woman presents for evaluation after three consecutive miscarriages, one of which was identified by ultrasonographic testing as a dead embryo measuring 7.5 weeks’ size.
Abstract: Copyright © 2010 Massachusetts Medical Society. A 32-year-old woman presents for evaluation after three consecutive miscarriages. Before these miscarriages, she had one successful pregnancy. The patient reports no medical problems or previous surgeries. In her first miscarriage, uterine bleeding and cramping started in the 7th week of gestation, and an ultrasonographic evaluation showed an empty gestational sac of 6 weeks’ size. In her next pregnancy, she presented with a miscarriage in the 8th week. The third miscarriage was identified by ultrasonographic testing as a dead embryo measuring 7.5 weeks’ size. How should her case be evaluated and managed?

288 citations

Journal ArticleDOI
TL;DR: The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.
Abstract: HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.

167 citations


Cited by
More filters
Journal ArticleDOI
01 Jan 2011-Stroke
TL;DR: In this paper, the authors provided evidence-based recommendations for the prevention of future stroke among survivors of ischemic stroke or transient ischemi-chemic attack, including the control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke.
Abstract: The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

4,545 citations

Journal ArticleDOI
TL;DR: This review examines how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors.
Abstract: ▪ Abstract The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.

2,780 citations

Journal ArticleDOI
TL;DR: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications, and higher antICOagulation targets than in usual critically ill patients should therefore probably be suggested.
Abstract: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.

2,147 citations