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D W Branch

Publications and source records attributed to D W Branch.

At least 55 records · Page 3Linked to original sources
PubMed1997

Autoantibody screening for infertility: explaining the unexplained?

Several laboratories currently offer panels of serum autoantibody assays to screen women with unexplained infertility and those undergoing in vitro fertilization (IVF). Offering these tests implies that they have predictive value for the outcome of proposed infertility treatments such that the results of the testing would alter clinical management. Because screening for antiphospholipid antibodies adds expense to already costly procedures, it is an appropriate time to review the justification for the use of these panels.

Abortion, Habitual↗
PubMed1997

The factor V Leiden mutation is not a common cause of recurrent miscarriage.

Some investigators suggest that placental thrombosis and infarction can cause recurrent miscarriage. We have shown that the common missense mutation in the factor V gene, the Leiden mutation, which renders factor Va resistant to cleavage inactivation by activated protein C, predisposes to placental thrombosis and spontaneous miscarriage. Our objective was to determine the frequency of the Leiden mutation in a population with well-characterized idiopathic recurrent miscarriage. DNA was extracted from whole blood of 40 couples with a history of idiopathic recurrent miscarriage and 25 couples with a history of proven fertility (seven or more live births). The polymerase chain reaction was used to amplify exon 10 of the factor V gene followed by allele-specific restriction with Mnl1 for mutation detection. Results were analyzed with a chi 2 contingency table. None of the 40 women with idiopathic recurrent miscarriage carried the mutation and only one of their reproductive partners was heterozygous for the mutation. Similarly, none of the control women carried the mutation, and only one of the 25 control male partners was heterozygous for the mutation. In our referral population, the factor V Leiden mutation which predisposes to thrombosis is not a common cause of recurrent miscarriage.

Abortion, Habitual↗
PubMed1997

Immunosuppressive drugs and pregnancy.

Immunosuppressive therapy is a common practice in modern medicine. Typical uses of immunosuppressive drugs during pregnancy include the treatment of rheumatic diseases and transplant recipients. The purpose of this article is to assess and summarize current knowledge regarding the use of immunosuppressive drugs in pregnancy, focusing primarily on their effects on the mother and fetus.

Abnormalities, Drug-Induced↗
PubMed1997

Antiphospholipid syndrome in pregnancy. Obstetric concerns and treatment.

To be sure, antiphospholipid antibody syndrome is a protean disease with many manifestations, some of which are exacerbated during pregnancy, and some of which even lead to its initial diagnosis during pregnancy. Although the best treatment during pregnancy is uncertain at this point, and some of the treatments are even experimental, there does seem to be a benefit in at least identifying and probably treating those with risk factors. If treatment is not instituted with heparin, aspirin, or other medical management, at least monitoring for the known superimposed disease states, such as intrauterine growth retardation, preeclampsia, and fetal loss, should be judicious, with close antenatal surveillance.

Antiphospholipid Syndrome↗
PubMed1997

Antiphospholipid antibody: functional specificity for inhibition of prothrombin activation by the prothrombinase complex.

The antiphospholipid syndrome (APS) is associated with production of autoantibodies with lupus anticoagulant (LA) activity. These antibodies cause prolongation of in vitro clotting tests by inhibition of the conversion of prothrombin to thrombin in the presence of anionic phospholipid (PL). The extent to which this inhibition reflects antibody binding to, or functional inhibition of, phospholipids alone, prothrombin alone, or a prothrombin-phospholipid complex is pertinent to our understanding of the pathophysiology of this syndrome. Immunoglobulin fractions (IgG) from 18 patients with LA activity were tested for inhibitory activity against prothrombin activation by either factor Xa, in a purified prothrombinase system, or by purified fractions of snake venoms (E. carinatus, E. multisquamatus) which cleave prothrombin at the same initial site as the prothrombinase complex but do not require anionic phospholipid as a cofactor. Parallel testing of the same IgG samples for prothrombin binding by immunoassay was performed. Although all IgG samples inhibited the prothrombinase reaction, only three exhibited any inhibition of venom protease prothrombin activation in either the presence or absence of PL. Only one sample exhibited prothrombin binding by Western blot. These results suggest that lupus anticoagulant antibodies are heterogenous and that many, if not most, of the autoantibody populations responsible for LA activity impair prothrombin activation by interaction either with phospholipid alone or with a restricted range of prothrombin-phospholipid epitopes expressed by prothrombin only as part of the intact prothrombin-prothrombinase complex.

Antibodies, Anticardiolipin↗
PubMed1997

Intravenous immune globulin in the management of severe Rh D hemolytic disease.

Although intrauterine fetal transfusion has improved dramatically perinatal outcome in Rh D alloimmunization, in some cases the fetus is affected before transfusion is possible. Immune globulin (IVIG) administration is being increasingly used to successfully treat a variety of immune-mediated diseases, such as pregnancies affected by platelet alloimmunization. Although only a limited number of pregnancies have been reported, favorable outcomes with IVIG treatment of severe Rh disease have been described. We present a case report, review the published experience with IVIG treatment in severe, early-onset anti-D sensitization, and propose that IVIG may have an adjunctive role in the treatment of severe Rh isoimmunization.

Adult↗
PubMed1997

Autoimmune disease in pregnancy. Systemic lupus erythematosus and antiphospholipid syndrome.

Autoimmune diseases occur most commonly in women of childbearing age. Over 70% of individuals with autoimmune diseases are women, though some conditions (e.g., ankylosing spondylitis) are more common in men. Many authorities have focused on sex hormones as an explanation for the relatively high proportion of females affected by autoimmune diseases. This article covers systemic lupus erythematosus, the prototypical autoimmune disease, and antiphospholipid syndrome, which is associated particularly with pregnancy loss.

Antibodies, Antiphospholipid↗
PubMed1996

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

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.

Animals↗
PubMed1996

Anticardiolipin antibodies: clinical consequences of "low titers".

OBJECTIVE: To clarify the implications of low levels of immunoglobulin (Ig)-G or IgM anticardiolipin antibodies. METHODS: Women who underwent clinically indicated testing for antiphospholipid antibodies were divided into four groups based on results: 1) high-positive (lupus anticoagulant or more than 19 IgG binding units of anticardiolipin antibodies; N = 131), 2) low-positive IgG (fewer than 20 IgG binding units; N 93), 3) IgM only (more than nine IgM binding units; N 97), and 4) negative (N = 153). The development of antiphospholipid antibody-related disorders was assessed for the time interval from initial antibody testing to patient interview. The median study interval for each group was at least 4 years. Forty-five percent of women had repeat testing at the time of interview. RESULTS: Women in the high-positive group were more likely to develop at least one new medical complication than those in the low-positive IgG (odds ratio [OR] 4.49, 95% confidence interval [CI] 2.01-10.03), IgM only (OR 6.00, 95% CI 2.65-13.59), and negative (OR 9.11, 95% CI 3.92-21.2) groups. In contrast, the low-positive IgG, IgM only, and negative groups had similar risks for the development of new disorders. Twelve of 129 (9.3%) women in the low-positive IgG, IgM only, or negative groups had lupus anticoagulant or more than 19 IgG binding units on retesting. Half of these women developed at least one new disorder. CONCLUSION: Women with IgM or low levels of IgG anticardiolipin antibodies comprise distinct populations from those with lupus anticoagulant or moderate to high levels of anticardiolipin antibodies. These women are not at risk for antiphospholipid antibody-related disorders beyond the risk conferred by their medical histories. However, repeat testing is warranted with new or recurrent clinical symptoms.

Adult↗
PubMed1996

Antiphospholipid antibodies and fetal death.

OBJECTIVE: To determine the type of recurrent pregnancy loss associated with antiphospholipid antibodies. METHODS: This was a retrospective analysis of women who had two or more pregnancy losses and who were tested for antiphospholipid antibodies. The specific type of pregnancy losses were determined in patients with and without antiphospholipid antibodies. RESULTS: In our highly selected referral population, 76 of 366 women (21%) tested positive for lupus anticoagulant or anticardiolipin antibodies of 20 or more immunoglobulin-G phospholipid antibody units. Pregnancy loss occurred in 280 of 333 (84%) prior pregnancies in women with and 1240 of 1479 (84%) without antiphospholipid antibodies. However, 50% of pregnancy losses in women with antiphospholipid antibodies were fetal deaths, compared with less than 15% in women who were antiphospholipid antibody-negative. More than 80% of women with antiphospholipid antibodies had at least one fetal death, compared with less than 25% of women without (P < .001). The specificity of fetal death for the presence of antiphospholipid antibodies in patients with recurrent pregnancy loss was 76%. In contrast, two or more early first-trimester losses without fetal death had a specificity of only 6% for antiphospholipid antibodies. CONCLUSION: Fetal death is more characteristic of the type of loss experienced by patients with recurrent pregnancy loss than early first-trimester pregnancy loss in women with antiphospholipid antibodies.

Abortion, Habitual↗
PubMed1996

Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy.

BACKGROUND: The purpose of this study was to determine which low dose of low dose aspirin (LDA) optimized the urinary prostacyclin (PGI2)/thromboxane (TXA2) ratio and minimized evidence of platelet aggregation during normal late pregnancy. METHODS: Twelve women with uncomplicated singleton pregnancies between 28 and 34 weeks gestation participated in a randomized blinded study. Blood samples for salicylate levels were obtained pretreatment, 4 hours and 7 days after administration of placebo, 20mg, 40mg or 80mg of aspirin. Twenty-four hour urine specimens collected at the same intervals were assayed for PGI2 and TXA2 metabolites. In addition, bleeding time and platelet aggregation studies were performed prior to and after 7 days of LDA or placebo. RESULTS: A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA, but not with the 20 mg dose or placebo. Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI2/TXA2 ratio increased with aspirin doses as low as 20mg, with a decrease in TXA2 metabolites but not in PGI2 metabolites. Serum salicylate was not detectable in any sample from any patient. CONCLUSION: There are dose-related changes in platelet aggregation and bleeding times with progressively increasing doses of LDA. A lower dose of LDA, such as 20-40 mg per day, may be as efficacious as higher doses in the prophylaxis of pre-eclampsia in high risk populations.

Adolescent↗
PubMed1996

5-Hydroxyeicosatetraenoic acid and human parturition.

5-Hydroxyeicosatetraenoic acid (5-HETE) is an arachidonic acid (AA) metabolite derived from the lipoxygenase pathway which is capable of inducing uterine contractions. The purpose of this study was to determine a). whether 5-HETE concentrations in amniotic fluid increase before or after the onset of labor and b). whether acetylsalicylic acid (ASA) could modulate the production of 5-HETE by human amnion cells. 5-HETE concentrations are increased in amniotic fluid before the onset of labor. Furthermore, ASA treatment as expected inhibited PGE2, but also significantly increased 5-HETE production by amnion cells. 5-HETE concentrations on average increased by greater than 2.5 fold (p < 0.001) in amniotic fluid prior to spontaneous labor when compared with samples obtained from the same patients earlier in gestation and therefore may be important in mechanisms regulating the onset of labor. ASA provokes an increase in 5-HETE biosynthesis by amnion cells: control media 2.60 +/- 1.5, ASA treatment alone 5.17 +/- 0.20, IL-1 beta alone 6.39 +/- 2.1, and ASA + IL-1 beta 8.95 +/- 1.2 (mean +/- SEM) picograms per microgram protein per 16 hours. These findings may explain in part why cyclooxygenase inhibitors are not always successful in treating women with preterm labor.

Amniocentesis↗
PubMed1996

Cyclosporin A inhibits prostaglandin E2 production by fetal amnion cells in response to various stimuli.

Use of cyclosporin A as part of an immunosuppressive regimen in pregnant transplant patients is not uncommon. Although successful pregnancies have been reported with the use of various immunosuppressive agents including cyclosporin A, the concern for fetal outcome still remains. Our purpose was to evaluate the effects of immunosuppressive cyclosporin A on prostaglandin E2 (PGE2) production by human fetal amnion. Amnion cells were isolated from term placentae obtained at elective cesarean section before the onset of labor. Cells were grown to confluence and then incubated for 16 hours with cyclosporin A (1-1000 ng/ml) in the presence and absence of interleukin 1 beta (IL-1 beta, 1 ng/ml), phorbol 12-myristate 13-acetate (PMA, 10(-7) M) and ionomycin (0.5 microM). PGE2 was measured by radioimmunoassay and cellular protein determined. IL-1 beta, PMA and ionomycin all stimulated amnion cell PGE2 production as expected. However, these stimulatory actions were attenuated by at least 50% when cells were co-incubated with cyclosporin A (1000 ng/ml). Concentrations of cyclosporin A tested included the therapeutic range (250-1000 ng/ml). Our results indicate that cyclosporin A does not stimulate amnion cell PGE2 production and is probably unrelated to preterm labor and delivery in allograft recipients.

Amnion↗
PubMed1996

Studies on the interaction of placental anticoagulant protein I, beta 2 glycoprotein 1, and antiphospholipid antibodies in the prothrombinase reaction and in the solid phase anticardiolipin assays.

Recently it has been suggested that antiphospholipid antibodies may not be specific for phospholipids but directed to beta2glycoprotein 1 (beta2GP1), phospholipid-beta2GP1 complexes, prothrombin, or prothrombin-phospholipid complexes. To explore this issue further, we examined the influence of two phospholipid binding proteins, annexin V (placental anticoagulant protein I (PAP I)) and beta2GP1, on the activity of immunoglobulin G (IgG) fractions from patients with antiphospholipid syndrome (APS), both in the prothrombin-thrombin conversion assay and in the anticardiolipin enzyme-linked immunosorbent assay (ELISA). Results showed that each of eight IgG-APS; fractions, as well as PAP I and beta2GP1, individually inhibited the prothrombinase reaction. When IgG-APS samples were combined with PAP I or beta2GP1, or both PAP I and beta2GP1, inhibition of the prothrombinase reaction was additive. In the anticardiolipin ELISA, PAP I inhibited IgG-APS binding to cardiolipin, but beta2GP1 enhanced IgG-APS binding to cardiolipin. The "enhancing" effect of beta2GP1 in the ELISA system was neutralized by PAP I, an effect partially overcome by increasing the concentration of beta2GP1. Similar results were observed when affinity-purified anticardiolipin antibodies were used in place of whole IgG-APS preparations. These data indicate that IgG preparations obtained from the 8 patients with APS recognize similar epitopes; on anionic phospholipids in the anticardiolipin test and in the prothrombin-thrombin conversion assay. These data do not exclude the possibility that the IgG preparations may bind prothrombin-phospholipid or beta2GP1-phospholipid complexes.

Annexin A5↗
PubMed1996

Induction of preterm birth in mice by RU486.

We hypothesized that treatment of pregnant mice with the progesterone receptor antagonist RU486 might cause preterm labor and result in the delivery of live pups. We also hypothesized that RU486 administration would alter prostaglandin production by decidual explants taken from these pregnancies. C3H/HeN females mated with C57BI/6 males were injected with a single s.c. dose of RU486 on Days 12-14 of gestation. Three doses were tested (50 micrograms, 150 micrograms, and 250 micrograms), and the mice were observed for evidence of delivery. The time course of delivery was determined in a second experiment using 150 micrograms of RU486, and care was taken to observe the condition of the delivered pups. In a third experiment, mice were killed when delivery commenced after injection with 150 micrograms of RU486, and decidual explants were prepared. Controls that had received injections of vehicle were killed at the same time, and decidual explants were established. Media were removed after 24 h and analyzed for prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) by RIA and for interleukin 6 (IL-6) by ELISA. Two of 3 mice given 50 micrograms of RU486 delivered 16 pups prematurely. All 3 mice given 150 micrograms of RU486 delivered 22 pups prematurely, and 2 of 3 given 250 micrograms of RU486 delivered 12 pups prematurely. Of mice treated with 150 micrograms of RU486, none delivered within 12 h; 2 of 7 delivered within 15 h; and 6 of 7 delivered within 22 h. All pups appeared to be healthy, with no evidence of placental infarction or death. PGE2, PGF2 alpha, and IL-6 production by decidual explants was significantly greater in tissues taken from RU486-treated mice (n = 6) than in controls (n = 3). In summary, RU486 reliably induced preterm birth of the mice within 24 h after s.c. injection. This was associated with increased decidual prostaglandin and cytokine production and thus may mediate preterm labor. Inducing preterm birth with RU486 in a mouse model may be useful in investigations of the mechanism(s) of preterm labor.

Abortifacient Agents, Steroidal↗
PubMed1996

Sensitivity of the activated partial thromboplastin time, the dilute Russell's viper venom time, and the kaolin clotting time for the detection of the lupus anticoagulant: a direct comparison using plasma dilutions.

Increasing dilutions of lupus anticoagulant (LA) plasmas from twelve patients were used to directly compare the sensitivity of four tests for LA. The tests evaluated were the modified Bell and Alton activated partial thromboplastin time (APTT), an APTT using a commercially prepared partial thromboplastin (Platelin LS APTT), a modified dilute Russell's viper venom time (DRVVT), and a modified kaolin clotting time (KCT). LAs were detected in all twelve plasmas by each of three tests and eleven of twelve plasmas in a fourth test when undiluted patient plasma was used. Repeating the tests after diluting the LA plasmas with normal platelet-free plasma (PFP) showed that the KCT was the most sensitive test for LA, detecting eleven of twelve LAs at a dilution of 10% patient plasma and ten of twelve LAs at a dilution of 5% patient plasma. The modified Bell and Alton APTT and the modified DRVVT had similar sensitivities at a patient plasma concentration of 10%, detecting seven of twelve and eight of twelve LAs, respectively. The Platelin LS APTT detected only four of twelve LAs at a patient plasma concentration of 10%. Our results indicate that the modified KCT is a sensitive method for the detection of LAs. The modified Bell and Alton APTT and the DRVVT were less sensitive.

Humans↗
PubMed1995

Suitability of fetal tissues from spontaneous abortions and from ectopic pregnancies for transplantation. Human Fetal Tissue Working Group.

OBJECTIVE: To assess the potential availability and utility of fetal tissues obtained from spontaneous abortions and from ectopic pregnancies for human transplantation therapy. DESIGN: Tissue collection and analysis by personnel skilled in tissue banking. SETTING: Procurement programs in five tissue banks located in diverse geographical areas that are funded by the National Institutes of Health. PATIENTS: All women entering obstetric clinics during 1993 who consented to participate in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Evaluation of the products of conception by standard developmental, histological, microbiological, and cytogenetic criteria. RESULTS: From 22,235 obstetric admissions, 1250 spontaneously aborted embryos and 247 products of ectopic pregnancies were obtained. Of these, seven embryos (0.5%) were potentially useful for human transplantation therapy. CONCLUSION: Fetal tissues from spontaneous abortions and from ectopic pregnancies are quite limited as feasible sources for human transplantation therapy.

Aborted Fetus↗