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D W Branch

Publications and source records attributed to D W Branch.

At least 73 records · Page 4Linked to original sources
PubMed1995

Maternal thrombocytopenia in pregnancy: time for a reassessment.

Antiplatelet autoantibodies in women with autoimmune thrombocytopenic purpura can cause fetal thrombocytopenia and serious bleeding problems. Obstetricians have used fetal scalp sampling, cordocentesis, and cesarean delivery in this disorder to avoid fetal complications such as intracranial hemorrhage. Accumulating evidence indicates that the fetal risk of intracranial hemorrhage is much lower than initially reported. Moreover, these invasive tests and treatments are costly, cause morbidity, and have little effect in preventing neonatal bleeding complications. Therefore we suggest these interventions should no longer be used in the management of maternal thrombocytopenia.

Cerebral Hemorrhage↗
PubMed1995

Induction of high levels of anticardiolipin antibodies in mice by immunization with beta 2-glycoprotein I does not cause fetal death.

OBJECTIVE: Our purpose was to determine whether anticardiolipin antibodies induced by immunization with beta 2-glycoprotein I cause fetal death in mice. STUDY DESIGN: Female BALB/c mice were immunized with beta 2-glycoprotein I in a carbohydrate adjuvant or with carbohydrate adjuvant alone. The mice were mated with BALB/c males and killed on day 11 to 13 of pregnancy, and the fetal status was determined. Posttreatment blood samples were obtained for measurement of anticardiolipin and anti-beta 2-glycoprotein I antibodies and platelet counts. RESULTS: Anticardiolipin and anti-beta 2-glycoprotein I antibodies developed in all mice immunized with beta 2-glycoprotein I. Fetal death occurred in 17 of 145 gestational sacs (12%) in 18 mice immunized with beta 2-glycoprotein I compared with 24 of 177 (14%) sacs in 21 control mice. There were no morphometric or histologic differences between gestational tissues, and platelet counts were similar for each group. CONCLUSIONS: The induction of high levels of anticardiolipin antibodies in BALB/c mice by beta 2-glycoprotein I immunizations did not result in fetal death or thrombocytopenia. These nonpathogenic beta 2-glycoprotein I-induced anticardiolipin antibodies should prove useful in the characterization of clinically relevant epitopes for antiphospholipid syndrome.

Animals↗
PubMed1995

The regulation of arachidonate lipoxygenase metabolite formation in cells derived from intrauterine tissues.

Products of arachidonic acid (AA) metabolism via the lipoxygenase pathways may have key roles in the maintenance of pregnancy and the onset of labor. We have determined whether calcium ionophores can modulate the rate of biosynthesis within the uterus of five important arachidonate lipoxygenase metabolites, i.e. leukotriene B4 (LTB4), LTC4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE. Amnion, chorion, and decidual cells were isolated, grown to confluence and incubated with ionomycin. The production of LTB4, LTC4, 5-HETE, 12-HETE, and 15-HETE was determined using specific radioimmunoassays. Cell-specific, concentration-related stimulatory actions of ionomycin on 5-HETE, 12-HETE, 15-HETE, and LTC4 but not LTB4 production were found. A23187 had effects similar to ionomycin. Hence elevation of intracellular calcium levels can result in enhanced intrauterine production of arachidonate lipoxygenase metabolites that may affect pregnancy outcome.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1995

Human leukocyte antigen DQ alpha sharing is not increased in couples with recurrent miscarriage.

PROBLEM: The results regarding human leukocyte antigen (HLA) DQ alpha allele sharing in recurrent miscarriage couples are conflicting. The purpose of this study was to determine the frequency of HLA DQ alpha allele sharing in our unexplained recurrent spontaneous abortion (RSA) patients using modern DNA analytical techniques. METHODS: DNA was extracted from whole blood samples of 1) 51 couples with at least three miscarriages, and 2) 43 fertile couples (with at least seven children and no known history of recurrent miscarriage). The polymerase chain reaction (PCR) was used to amplify the second exon of the HLA DQ alpha locus on chromosome 6. Genotypes were identified by allele specific hybridization with 12 sequence-specific oligonucleotide probes. RESULTS: 47% of recurrent miscarriage couples and 35% of fertile couples shared no alleles. 47% of recurrent miscarriage couples compared to 58% of fertile couples shared one allele, and 6% of recurrent miscarriage couples and 7% of fertile couples shared two alleles. CONCLUSIONS: Reproductive partners with unexplained recurrent pregnancy loss have no increased frequency of HLA DQ alpha allele sharing. It is unlikely that HLA DQ alpha genotyping will be helpful in the management of patients with RSA.

Abortion, Habitual↗
PubMed1995

Fetal outcome in murine Lyme disease.

Lyme disease is an inflammatory syndrome caused by infection with Borrelia burgdorferi. Although this syndrome has important implications for human pregnancy, little is known about gestational infection with B. burgdorferi. Fetal death occurred in 33 of 280 gestational sacs (12%) in 39 C3H/HeN female mice infected by intradermal injection of B. burgdorferi 4 days after mating (acute infection), compared with 0 of 191 sacs in 25 control mice (P = 0.0001). Forty-six percent of acutely infected mice suffered at least one fetal death, compared with none of the control animals (P = 0.0002). There were no fetal deaths in 18 C3H/HeN mice infected 3 weeks prior to mating (chronic infection). A sensitive PCR technique detected B. burgdorferi DNA in the uteri of acutely infected mice but did not detect DNA in the uteri of controls or chronically infected mice. Spirochete DNA was only rarely detected in fetal tissues, and its presence was not required for fetal death. The inclusion of an internal competitive PCR target indicated that the lack of B. burgdorferi sequences in fetal DNA was not due to the presence of a PCR inhibitor. Histologic analysis of gestational tissues from infected animals demonstrated nonspecific pathology consistent with fetal death. These findings indicate an association between murine fetal death and acute infection with B. burgdorferi early in gestation but not with chronic infection. Our data suggest that fetal death is due to a maternal response to infection rather than fetal infection. These findings could provide an explanation for observations in humans in which sporadic cases of fetal death in women infected with B. burgdorferi during pregnancy have been reported, while previous infection has not been associated with fetal death.

Animals↗
PubMed1995

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

Maternal infection is a cause of spontaneous abortion and preterm labor in humans, but the pathophysiology is unclear. We hypothesized that eicosanoids play an important role in infection-driven pregnancy loss. To investigate this hypothesis, we administered lipopolysaccharide (LPS) to pregnant C3H/HeN mice and found that LPS administration caused fetal death in a dose-dependent fashion. Pretreatment with indomethacin significantly decreased the proportion of fetal death from 83% to < 25% in mice injected with 10 micrograms of LPS. Also, decidual explants from LPS-treated mice produced significantly more inflammatory eicosanoids, including prostaglandins E2 and F2 alpha and thromboxane B2, than controls. We investigated the regulatory mechanisms responsible for increased decidual prostanoid production in response to LPS. Western and Northern blots demonstrated that decidual protein and mRNA levels of a recently recognized highly inducible form of cyclooxygenase, COX-2, were substantially increased in mice treated with LPS. Induction of COX-2 was rapid: mRNA was detected 30 min after LPS injection. In contrast, another form of cyclooxygenase, COX-1, was only minimally induced in response to LPS. Our data indicate that LPS induces decidual prostanoid production via increased COX-2 expression. Since LPS-mediated fetal death is markedly diminished by pretreatment with indomethacin, COX-2-mediated eicosanoid production is likely a key pathophysiologic event in LPS-mediated fetal death.

Abortion, Spontaneous↗
PubMed1995

The factor V Leiden mutation which predisposes to thrombosis is not common in patients with antiphospholipid syndrome.

Antiphospholipid syndrome is associated with venous, arterial, and placental thrombosis, possibly through autoantibody impairment of phospholipid-dependent protein C activation. Recently, a missense mutation in the factor V gene (1691 G-->A) has been identified that results in an abnormal factor V product (1). This mutation, known as the Leiden mutation, causes an amino acid substitution of glutamine for arginine at position 506 in the factor V molecule and renders the protein resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis (2, 3). We hypothesized that some individuals with antiphospholipid syndrome may also carry the Leiden mutation, and thus have a "second hit" predisposition to thrombosis. To test this hypothesis, allele-specific hybridization and allele-specific restriction analysis were used to test for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10 of whom had a history of thrombosis. None of the women were heterozygous or homozygous for the factor V mutation. We conclude that the presence of the factor V Leiden mutation is not a prerequisite for the thrombotic events in patients with antiphospholipid syndrome, due to the occurrence of thrombosis seen in patients lacking the factor V mutation.

Alleles↗
PubMed1994

Pre-eclampsia and serum antibodies to oxidised low-density lipoprotein.

Oxidised low-density lipoprotein (Ox-LDL) has been associated with arterial foam-cell formation, and autoantibodies to Ox-LDL are present in human serum. Lipid peroxidation is enhanced in pre-eclampsia. We assessed whether the titre of IgG autoantibody to an epitope of Ox-LDL, malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), was increased in the sera of pre-eclamptic patients. 16 such patients had significantly higher mean titres of autoantibodies to MDA-LDL than healthy pregnant women (p = 0.028). In a multiple regression model, pre-eclamptic patients still had a significantly higher mean titre (p = 0.048). Enhanced lipid peroxidation may be involved in the foam-cell formation of decidua and in the pathogenesis of pre-eclampsia.

Adult↗
PubMed1994

Lipopolysaccharide-induced fetal death: the role of tumor-necrosis factor alpha.

Lipopolysaccharide (LPS) administration has been known to cause murine fetal death for over 50 years, but the responsible mechanism(s) remains unclear. We used the LPS-hyporesponsive murine strain, C3H/HeJ, to 1) establish whether LPS-induced fetal death is due to a maternal or fetal response to LPS and 2) to investigate the involvement of tumor necrosis factor alpha (TNF alpha) in fetal death caused by LPS. C3H/HeJ (LPS-hyporesponsive) or C3H/HeN (LPS-responsive) females were mated with C57B1/6 or C3H/HeN males (both LPS-responsive). Administration of 10 micrograms LPS caused fetal death in C3H/HeN mothers. However, up to 1000 micrograms LPS did not result in the death of LPS-responsive fetuses when administered to C3H/HeJ mothers. Systemic administration of TNF alpha was able to cause fetal death in both C3H/HeN and C3H/HeJ strains of mice. Pretreatment of pregnant C3H/HeN mice with anti-TNF alpha antibodies significantly reduced fetal death caused by LPS administration. The administration of a sublethal dose of TNF alpha plus 10 micrograms LPS to pregnant C3H/HeJ mice restored abortifacient activity. These results indicate that LPS-induced fetal death is due to a maternal response as opposed to a direct fetal response to LPS and that TNF alpha appears to be an important mediator of fetal death caused by LPS.

Animals↗
PubMed1994

Potential alloimmune factors and immunotherapy in recurrent miscarriage.

It is difficult to determine whether alloimmune factors are responsible for some cases of recurrent miscarriage. No diagnostic tests have been found to be clinically useful. It appears that paternal cell immunization may increase the live birth rate slightly, but the results of large prospective, randomized studies presently being conducted are necessary to confirm this therapeutic effect. Finally, there are few published reports on the neonatal, childhood, or long-term effects of immunotherapy on the offspring. Therefore, we recommend that physicians adopt a cautious approach to the diagnosis and treatment of potential alloimmune RPL. Patients who strongly desire to pursue immunotherapy after appropriate counseling should be referred to a research center with an interest in this area.

Abortion, Habitual↗
PubMed1994

Inhibition of prothrombin activation by antiphospholipid antibodies and beta 2-glycoprotein 1.

Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal plasma protein beta 2-glycoprotein 1 (beta 2GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta 2GP1. Using a purified system for measurement of prothrombin activation to thrombin, we demonstrated significant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta 2GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by equivalent concentrations of patient IgG correlated well with the extent of prolongation of the plasma clotting time in lupus anticoagulant assays of whole patient plasma. Additional studies with eight patient IgG preparations indicated that the addition of beta 2GP1 to patient IgG-phospholipid vesicle mixtures resulted in either independently additive inhibition by the two protein species (six cases) or potential inhibition of beta 2GP1 of the IgG inhibitory activity demonstrable in the absence of beta 2 GP1 (two cases). In addition, beta 2GP1-independent inhibition of prothrombin activation also occurred with three patient IgG preparations obtained by affinity binding to cardiolipin.

Antibodies, Anticardiolipin↗
PubMed1994

Thoughts on the mechanism of pregnancy loss associated with the antiphospholipid syndrome.

Although far from conclusive, the available clinical and histopathological information are consistent with an hypoxic cause for aPL-related fetal loss. In turn, this is due to impairment of the maternal spiral arterial blood flow. To date, there is only one case report of detailed placental and uteroplacental vascular histopathological examination by a recognized expert in this field of pathology. This and the findings provided by the only study to take placental bed biopsies suggest that spiral arterial vasculopathy resulting in placental and fetal hypoxia is the immediate cause of fetal loss in women with aPL syndrome. Data from the large study by Out et al. are consistent with this. The absence of spiral arterial vasculopathy in several studies could be attributed to the fact that the vessels examined were those adherent to the separated placenta, too superficial to necessarily demonstrate the pathological changes. Our future efforts at defining the 'cause' of aPL-related fetal loss must include: (1) meticulous clinical details regarding the timing and nature of pregnancy loss, (2) thorough evaluation of the abortus, (3) examination of the placenta by a pathologist well versed in placental pathology, (4) examination of the placental bed biopsies whenever possible, (5) the cellular biology and biochemistry of maternal-fetal junction, with particular focus on how the cytotrophoblast invades the spiral arteries, and (6) the cellular biology and biochemistry of spiral arterial vasculopathy.

Abortion, Spontaneous↗
PubMed1994

Unexplained elevations of maternal serum alpha-fetoprotein in women with antiphospholipid antibodies: a harbinger of fetal death.

OBJECTIVE: To determine whether unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) in women with antiphospholipid antibodies are associated with adverse pregnancy outcomes. METHODS: A retrospective cohort study was used to compare pregnancy outcomes between women with second-trimester MSAFP values equal to or greater than 2.5 multiples of the median (MoM) and less than 2.5 MoM. The cohort included 60 pregnancies in 47 women with medium to high positive levels of immunoglobulin (Ig) G anticardiolipin antibodies, lupus anticoagulant, or both. RESULTS: Thirteen pregnancies (22%) had elevated MSAFP values (median 3.6 MoM, range 2.5-12.6). Of these, amniotic fluid AFP was normal in seven and elevated in one. None of the elevated MSAFP levels were explained by fetal anomalies, current fetal death, multiple gestation, incorrect dates, or vaginal bleeding. Pregnancies with elevated MSAFP values had a significantly higher incidence of fetal death (eight of 13, 62%, versus three of 47, 6%) and perinatal loss (ten of 13, 77%, versus seven of 47, 15%) than those with normal MSAFP (P < .001, Fisher exact test). In these women, the sensitivity and specificity of an unexplained elevated MSAFP level in ascertaining fetal death were 73 and 90%, respectively. For perinatal loss, the sensitivity was 59% and the specificity was 93%. Of the placentas studied, infarction occurred in eight of nine (89%) among the women with elevated MSAFP. CONCLUSIONS: Unexplained second-trimester elevations of MSAFP are common in women with antiphospholipid antibodies and are significantly associated with fetal loss. Abnormalities in the fetoplacental barrier are implicated as part of the pathophysiology of antiphospholipid antibody-mediated pregnancy loss.

Antiphospholipid Syndrome↗
PubMed1994

Clinical consequences of antiphospholipid antibodies: an historic cohort study.

OBJECTIVE: To determine the risk of antiphospholipid antibody-related disorders in women with elevated levels of these antibodies. METHODS: We used an historic cohort study design. Surveys of medical and obstetric histories for the interval from initial antibody testing to the time of patient interview were used to calculate age-adjusted rates for the development of medical disorders associated with antiphospholipid antibodies. The cohort included 130 women with lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. RESULTS: The median interval of study was 3.2 years (range 0.7-9.5, mean 3.7). Sixty-three subjects (48%) developed at least one new disorder during the study interval. The age-adjusted rates (per 1000 patient-years; +/- standard error) for the development of the disorders studied were as follows: thrombosis (156.8 +/- 30.0), cerebrovascular accident (93.8 +/- 25.1), amaurosis fugax (57.1 +/- 23.2), transient ischemic attack (170.4 +/- 27.6), systemic lupus erythematosus (9.8 +/- 3.8), and autoimmune thrombocytopenia (56.0 +/- 22.2). Of the 34 thrombotic events that occurred during the study interval, eight were associated with pregnancy and eight occurred while the patients were taking anticoagulant medications. CONCLUSIONS: Our subjects developed complications associated with antiphospholipid antibodies at a substantial rate, and almost half suffered at least one new event during the study interval. The high rate of thrombosis in individuals with antiphospholipid antibodies, especially associated with pregnancy, underscores the need to evaluate long-term anticoagulation in these patients.

Adult↗
PubMed1993

5-Hydroxyeicosatetraenoic acid biosynthesis by gestational tissues: effects of inflammatory cytokines.

OBJECTIVE: Our purpose was to determine whether inflammatory cytokines can modulate the production of arachidonate lipoxygenase metabolites by gestational tissues. STUDY DESIGN: Primary cultures of amnion, chorion, and decidual cells were incubated in the presence and absence of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6. Supernatants were assayed for leukotriene B4, leukotriene C4, 5-, 12- and 15-hydroxyeicosatetraenoic acid by means of specific radioimmunoassays. Cellular proteins were determined. RESULTS: 5-Hydroxyeicosatetraenoic acid production was significantly increased by interleukin-1 beta and interleukin-6 treatment in amnion, chorion, and decidual cells. Tumor necrosis factor-alpha elicited a modest increase, which was not statistically significant, in mean 5-hydroxyeicosatetraenoic acid production by these cells. Production rates of leukotrienes B4 and C4 and 12 and 15-hydroxyeicosatetraenoic acid were not affected by treatment with interleukin-1 beta. CONCLUSIONS: Inflammatory cytokines generated in response to intrauterine infection may modulate uterine activity by stimulation of 5-hydroxyeicosatetraenoic acid biosynthesis.

Amnion↗
PubMed1993

First-trimester ultrasonography findings in women with a history of recurrent pregnancy loss.

OBJECTIVE: We tabulated first-trimester ultrasonography findings in women with recurrent pregnancy loss and determined the rate of subsequent pregnancy loss and live births after demonstration of a live embryo. STUDY DESIGN: Sixty-seven women with three or more recurrent miscarriages underwent first-trimester ultrasonography and were prospectively followed through 101 pregnancies. RESULTS: First-trimester ultrasonography showed a dead embryo in seven pregnancies. Two of gestational sac in 12, and an empty uterus in four. A live embryo was seen in 78 pregnancies. Two of these pregnancies were terminated because of fetal chromosomal abnormalities. Of the remaining 76 pregnancies, 13 (17%) ended in a fetal loss (spontaneous abortion or fetal death) and 63 (83%) resulted in viable live births. CONCLUSIONS: Among women with recurrent pregnancy loss the presence of a live embryo detected by first-trimester ultrasonography is not as encouraging as in normal pregnant women. These findings are useful in counseling patients with recurrent pregnancy loss.

Abortion, Habitual↗