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D Ware Branch

Publications and source records attributed to D Ware Branch.

At least 19 recordsLinked to original sources
PubMed2025

A proteomic map of thromboinflammatory signatures in antiphospholipid syndrome: results from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) registry.

INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disease with thromboembolic and obstetric morbidity arising via a model of immunothrombosis. Individuals with APS may present with thrombotic (TAPS), obstetric (OAPS), or microvascular (MAPS) disease, while many have circulating antiphospholipid antibodies (aPL) without APS classification (NoAPS). Multiple pathophysiologic mechanisms have been proposed in APS, including activation by aPL of platelets, endothelial and immune cells, as well as complement and coagulation pathways; however, the pathophysiology of APS, particularly transition of clinical APS from aPL remains unclear. METHODS: Seeking to define the inflammatory signature of APS, we carried out an unbiased proteomic screen of persistently aPL-positive patients with different clinical phenotypes from the international APS Alliance for Clinical Trials and International Networking (ACTION) Registry and compared them to 10 healthy controls. 6398 unique proteins were estimated using an DNA aptamer-based assay. Subsequently, we validated our findings in 34 additional patients. RESULTS: Our data show that the mere presence of aPL confers a distinct thromboinflammatory signature characterized by the activation of coagulation, complement, innate and adaptive immune response pathways shared by all APS subtypes. Pathway enrichment analysis revealed increasing enrichment with rising statistical significance of thrombosis, complement, neutrophil and other innate and adaptive immune activation, as well as extracellular matrix (ECM) organization with increasing clinical severity, suggesting a model of progressive thromboinflammation in evolution of APS from NoAPS to TAPS and MAPS. CONCLUSIONS: Our findings provide novel insights into the pathogenesis of APS and identify potential novel targets for diagnostic and therapeutic intervention in APS across its entire spectrum.

Humans↗
PubMed2006

Factors associated with nonanomalous stillbirths: the Utah Stillbirth Database 1992-2002.

OBJECTIVE: This study was undertaken to characterize risk factors associated with nonanomalous stillborn (SB) infants and to ascribe the probability of fetal survival by gestational age among high-risk pregnancies. STUDY DESIGN: We compiled a database of all SB infants and an equivalent number of controls using information obtained from Utah Birth and Fetal Death Certificates during the years 1992 through 2002. Adjusted and unadjusted odds ratios for risk factors associated with SB were generated. Cox proportional hazard models were used to generate survival curves comparing pregnancies complicated by chronic hypertension or gestational hypertension with those of controls. RESULTS: Infants with major anomalies were eliminated from both cases and controls, to generate 1566 nonanomalous SBs and 2720 nonanomalous controls. In a logistic regression model controlling for multiple maternal and fetal factors, placental abruption, hydramnios, cord prolapse, and essential hypertension were associated with an increased risk of SB. In pregnancies complicated by essential hypertension, the survival curve diverged from that of controls at those gestational ages approaching term (hazard ratio 2.24; 95% CI 1.52-3.32). CONCLUSION: SB in nonanomalous infants in Utah is more common among pregnancies complicated by placental abruption, hydramnios, cord prolapse, and essential hypertension.

Databases, Factual↗
PubMed2006

Antiphospholipid syndrome and thrombosis.

The antiphospholipid syndrome is an autoimmune condition in which venous or arterial thrombosis is a primary clinical feature. The other primary clinical feature is adverse pregnancy outcome, specifically recurrent miscarriage, fetal death, or preterm delivery due to severe preeclampsia or placental insufficiency. The diagnostic autoantibodies for antiphospholipid syndrome are lupus anticoagulant, anticardiolipin, or anti-beta2-glycoprotein I.

Abortion, Spontaneous↗
PubMed2005

The use of cDNA microarray to identify differentially expressed labor-associated genes within the human myometrium during labor.

OBJECTIVE: Microarray technology was used to comprehensively analyze gene expression during human labor in the myometrium. STUDY DESIGN: cDNA micro-array was used to compare the transcriptomes of myometrium obtained from patients in spontaneous labor and those not in labor. Expression of four labor-specific genes was confirmed in the myometrium obtained from patients in spontaneous labor using RT-PCR, Northern blot analysis, and in-situ hybridization. RESULTS: Of the >6000 cDNAs evaluated, 56 were found to be differentially expressed during labor. The labor-specific expression of 4 genes was confirmed using RT-PCR and Northern blot analysis. The relative increased expression of thrombospondin-1 in myometrium obtained from patients in spontaneous labor was also confirmed using in-situ hybridization. CONCLUSION: cDNA microarray was used to identify 56 differentially expressed genes in myometrium obtained from patients in spontaneous labor. The up-regulation of four genes was confirmed by multiple methods. Elucidation of the role(s) of the genes identified by microarray should improve our understanding of normal labor physiology and may ultimately lead to more effective treatments for abnormal labor.

Blotting, Northern↗
PubMed2005

The factor V Leiden and the G20210A prothrombin gene mutations are rare in women with fetal death.

PROBLEM: To determine if there is an association between two commonly inherited thrombophilias, the factor V Leiden and the G20210A prothrombin mutations, and fetal death. METHOD OF STUDY: We used a case-control study design to compare the frequencies of these mutations in women with fetal death and controls. Fetal death was the intrauterine death of the conceptus > or =10 weeks gestation. Controls had one live birth, no miscarriages, and no fetal death. Results were compared using chi square analysis. RESULTS: One hundred and seventy-five cases and controls were identified. There were 4.6% of cases and 3.8% of controls heterozygous for the factor V Leiden mutation (NS), and 1.3% of cases and 1.7% of controls heterozygous for the prothrombin mutation (NS). CONCLUSION: In our population, neither the factor V Leiden nor the G20210A prothrombin mutations are associated with fetal death. Further evidence is required before routine screening for these mutations can be recommended.

Adolescent↗
PubMed2004

Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor.

OBJECTIVE: Microarray analysis was used to characterize the labor-selective transcriptome of the human myometrium during labor. One highly up-regulated transcript, monocyte chemotactic protein-1 (MCP-1), was further characterized. METHODS: Expression of MCP-1 was evaluated in the myometrium, the placenta, the gestational membranes (GM) and the amniotic fluid (AF) by real time RT-PCR, Northern blot analysis and ELISA. The level of immunoreactive (IR) MCP-1 content of primary myometrial cultures treated with inflammatory cytokines was quantified by ELISA. RESULTS: Up-regulation of the myometrial MCP-1 transcript in term laboring patients was demonstrated by microarray and confirmed by real time (RT)-PCR and Northern blot analysis. Increased MCP-1 transcripts were demonstrated in GM during term labor. The IR content of myometrial MCP-1 was increased during term labor and in the AF from patients experiencing preterm delivery. Levels of IR MCP-1 increased in myometrial cultures in response to interleukin 1-beta. CONCLUSION: The expression of myometrial MCP-1 was significantly increased during term labor and was similarly increased in vitro in response to interleukin 1-beta, a pro-inflammatory substance known to play a role in preterm birth. The increased IR content of MCP-1 within the AF preceding preterm delivery may render this protein a useful predictor of preterm birth.

Adult↗
PubMed2004

Homocysteine levels in women with antiphospholipid syndrome and normal fertile controls.

OBJECTIVE: Recent studies have identified hyperhomocysteinemia as a risk factor for both recurrent pregnancy loss and thrombosis. Antiphospholipid syndrome, an autoimmune disorder, is also characterized by recurrent pregnancy loss and thrombosis. Thus, our purpose was to determine if hyperhomocysteinemia is more common in patients with APS than normal fertile controls. METHODS: Plasma, sera and whole blood were obtained from two groups of women: (1) 22 with well-characterized antiphospholipid syndrome; and (2) 41 healthy fertile controls. Levels of fasting homocysteine, vitamin B16, vitamin B12, folate and the incidence of the C677/T mutation of the methylene tetrahydrofolate reductase genotype (C677T/MTHFR) were determined. RESULTS: The proportion of individuals with hyperhomocysteinemia and fasting plasma homocysteine levels were similar in women with APS and controls. Levels of vitamin B6, vitamin B12, folate and the incidence of C677/MTHFR were also similar in the two groups. CONCLUSION: Hyperhomocyteinemia and the C677T/MTHFR mutation are not common in women with antiphospholipid syndrome. Abnormal homocysteine metabolism is unlikely to play a major role in the pathogenesis of antiphospholipid syndrome.

Adult↗
PubMed2004

Poor obstetric outcome in subsequent pregnancies in women with prior fetal death.

OBJECTIVE: Patients with recurrent first-trimester spontaneous abortion have been the subject of intensive investigation. However, relatively little is known about second- and third-trimester pregnancy loss. Thus, it is difficult for clinicians to optimally counsel, evaluate, and manage women with previous unexplained fetal death. Our objective was to ascertain the outcome of subsequent pregnancies in patients with prior fetal death. METHODS: Subjects were identified from patients referred for evaluation of fetal death (occurring at >/= 10 weeks of gestation) and having at least one subsequent pregnancy. Patients with antiphospholipid antibodies were excluded. Logistic regression analysis was performed to determine the association of clinical variables with pregnancy outcome. RESULTS: Two hundred thirty subjects met inclusion criteria. Up through the time of their first fetal death, these women had a total of 721 pregnancies, resulting in 268 (37%) live births, 230 (32%) fetal deaths, and 200 (28%) spontaneous abortions. In total, these women had 839 subsequent pregnancies, resulting in 202 (24%) live births, 209 (25%) fetal deaths, and 372 (44%) spontaneous abortions. Univariate logistic regression analysis identified older age at pregnancy (P =.009, odds ratio 0.63, 95% confidence interval 0.42-1.03) and treatment with low-dose aspirin (P =.001, odds ratio 0.41, 95% confidence interval 0.25-0.68) to be associated with a decreased risk for subsequent pregnancy loss. CONCLUSION: Women with prior fetal death are at high risk for subsequent pregnancy loss and recurrent fetal death, with fewer than 25% of pregnancies resulting in surviving infants. These data underscore the need for additional research into the pathophysiology and prevention of recurrent fetal death.

Abortion, Spontaneous↗
PubMed2004

Recurrent fetal aneuploidy and recurrent miscarriage.

OBJECTIVE: Some investigators have found a high frequency of abortus aneuploidy in women with recurrent miscarriage, suggesting the possibility of recurrent aneuploidy as a cause of recurrent miscarriage. Others contend that aneuploidy is not a cause of recurrent miscarriage. The purpose of this study was to investigate the relationship between fetal aneuploidy and recurrent miscarriage by estimating whether fetal aneuploidy is more common in patients with recurrent miscarriage than in patients with sporadic miscarriage METHODS: Recurrent miscarriage cases (n = 135) included women who had a subsequent miscarriage in which an abortus karyotype was obtained. Controls (n = 150) were patients experiencing a sporadic miscarriage who had fetal karyotypes performed as part of a study to assess the utility of abortus tissue for transplantation. Karyotype analysis was performed using standard G-banding techniques. RESULTS: Abortuses from 122 cases and 133 controls were successfully karyotyped. Thirty-one (25.4%) abortuses from cases and 56 (42.1%) from controls were aneuploid (odds ratio 0.47, 95% confidence interval 0.27-0.80). Aneuploid abortuses occurred in 20% of cases and 25% of controls, aged 20-29 years, 19% of cases and 24% of controls, aged 30-34 years, 35% of cases and 47% of controls, aged 35-39 years, and 50% of both cases and controls, aged 40 years or older (not significant). Of 30 cases in whom 2 or more miscarriages were karyotyped, 3 (10%) had aneuploidy in each abortus. CONCLUSION: In our population of recurrent miscarriage patients, abortus aneuploidy occurred significantly less often than in sporadic miscarriages. The rate of aneuploidy in this study was considerably lower than reported in other studies. If recurrent aneuploidy contributes to recurrent miscarriage, it does so in only a small number of patients. LEVEL OF EVIDENCE: II-2

Abortion, Habitual↗
PubMed2003

Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss.

OBJECTIVE: To evaluate sperm chromosome aneuploidy and semen quality in 24 partners of women with unexplained recurrent pregnancy loss and to analyze the data in relation to sperm apoptosis data. METHODS: Semen quality parameters and sperm chromosome aneuploidy for chromosomes X, Y, 13, 18, and 21 were evaluated in the recurrent pregnancy loss patients, fertile controls, and a control group of men from the general population. RESULTS: The mean aneuploidy rate in the recurrent pregnancy loss group was 2.77 +/- 0.22, significantly higher (P <.005) than in either the general population (1.48 +/- 0.12) or in fertile (1.19 +/- 0.11) control groups. In the recurrent pregnancy loss patients, the percentage of aneuploid sperm was correlated to the percentage of apoptotic sperm (r =.62, P <.001). Normal morphology was diminished in the patient group, compared with the general population group (P <.01) and the donor group (P <.001). CONCLUSIONS: These data indicate that some recurrent pregnancy loss patients have a significant increase of sperm chromosome aneuploidy, apoptosis, and abnormal sperm morphology. This study demonstrates a new possible cause of recurrent pregnancy loss.

Abortion, Habitual↗
PubMed2003

Pregnancy outcome in recurrent miscarriage patients with skewed X chromosome inactivation.

OBJECTIVE: To analyze X inactivation in women with recurrent miscarriage to estimate whether skewed X inactivation is associated with recurrent miscarriage and whether it predicts next pregnancy outcomes. METHODS: A multicenter study was performed. A power calculation determined that 101 patients were needed to detect a difference in skewed X inactivation between patients and controls. Patients were entered into a prospective trial of mononuclear-cell immunotherapy and subsequently tested for skewed X inactivation. Age-matched controls had one live birth and no prior miscarriages. Results from our X inactivation assay were compared with those from an independent genetics laboratory. RESULTS: Greater than 75% skewing was seen in 22.6% of patients and 26.5% controls (P =.52). Greater than 90% skewing was seen in 6.6% of patients and 3.9% of controls (P =.77). There were 19.8% of primary aborters and 32% of secondary aborters with greater than 75% skewed X inactivation (P =.38). There were 4.9% of primary aborters and 12.0% of secondary aborters with greater than 90% skewed X inactivation (P =.27) Neither greater than 75% nor greater than 90% skewed X inactivation impacted next pregnancy outcomes (odds ratios = 0.87 [95% confidence interval (CI) 0.34, 2.3] and 1.4 [95% CI 0.27, 7.5], respectively). Results of the exchange of samples with an independent laboratory were highly correlated (alpha = 0.987, P <.001, coefficient of variation = 5.5%). CONCLUSION: Skewed X chromosome inactivation is not associated with recurrent miscarriage. A patient's X chromosome inactivation status does not predict next pregnancy outcome. Our assay correlates with another experienced laboratory.

Abortion, Habitual↗
PubMed2003

Antiphospholipid syndrome: obstetric diagnosis, management, and controversies.

Antiphospholipid syndrome, a condition characterized by one or more thrombotic or pregnancy-related clinical features in association with medium to high levels of antiphospholipid antibodies, has emerged as an important diagnostic consideration in several medical fields. Antiphospholipid syndrome is one of the few treatable causes of pregnancy loss, and successful pregnancy rates of 70% or more can be achieved with appropriate treatment. Heparin, usually combined with low-dose aspirin, is used in patients at risk for thrombosis. Pregnancy in these women is associated with increased rates of preeclampsia, placental insufficiency, and preterm delivery, so that attentive clinical care is required for best outcomes. Recent studies indicate that women at low risk for thrombosis may be treated with low-dose aspirin. However, remaining controversies and unanswered questions in the field of antiphospholipid syndrome are a source of clinical confusion. This review highlights the most important controversies, taking into account the results of recent obstetric treatment trials and our own clinical experience.

Algorithms↗
PubMed2003

Anticardiolipin and anti-beta2-glycoprotein-I antibodies in preeclampsia.

OBJECTIVE: To estimate whether antiphospholipid antibodies, specifically anticardiolipin and anti-beta(2)-glycoprotein-I antibodies, are associated with preeclampsia. METHODS: Plasma was prospectively obtained from four groups of pregnant women: those with 1) mild preeclampsia (n = 109); 2) severe preeclampsia (n = 134); 3) hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 57); and 4) normotensive controls (n = 100). Anticardiolipin and anti-beta(2)-glycoprotein-I levels were determined by enzyme-linked immunoassay. RESULTS: Subjects with mild preeclampsia, severe preeclampsia, and HELLP syndrome did not have significantly elevated levels of immunoglobulin G (IgG) and IgM anticardiolipin and anti-beta(2)-glycoprotein-I antibodies compared with normotensive controls (P >.05, Kruskal-Wallis). Similarly, subjects with mild preeclampsia, severe preeclampsia, and HELLP syndrome did not have a significantly higher proportion of women testing positive for each autoantibody compared with normotensive controls (chi(2)). The proportion of patients testing positive for anticardiolipin and anti-beta(2)-glycoprotein-I antibodies were similar in patients with preeclampsia developing before and after 34 weeks' gestation (chi(2)). CONCLUSION: Circulating levels of both anticardiolipin and anti-beta(2)-glycoprotein-I antibodies were not increased in patients with mild preeclampsia, severe preeclampsia, or HELLP syndrome compared with normotensive controls. Our data do not support routine testing for anticardiolipin and anti-beta(2)-glycoprotein-I antibodies in women with preeclampsia.

Adult↗
PubMed2003

The inherited thrombophilias: genetics, epidemiology, and laboratory evaluation.

It is now possible to identify a predisposing thrombophilic condition for venous thrombosis in well over half of the cases. Certain thrombophilia diagnoses have a major impact on anticoagulant therapy, and hence it is incumbent upon physicians to understand how to diagnose and manage these conditions. This chapter covers the genetics and epidemiology of the inherited thrombophilias and provides a useful, common-sense approach to the laboratory evaluation of a patient with venous thrombosis.

Antithrombin III Deficiency↗