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Biomedical subjects

D W Branch

Publications and source records attributed to D W Branch.

At least 109 records · Page 6Linked to original sources
PubMed1990

Pathophysiology of antiphospholipid antibodies: absence of prostaglandin-mediated effects on cultured endothelium.

Antiphospholipid antibodies are associated with recurrent pregnancy loss and thrombosis. Studies suggest that antiphospholipid antibodies may inhibit the production of prostacyclin by vascular tissues. We incubated sera from women with moderate to high levels of antiphospholipid antibodies with primary human umbilical vein endothelial cell cultures. Intact confluent, subconfluent, hydrogen peroxide-damaged, and mechanically damaged endothelial cell monolayers were evaluated for the production of the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in the presence of sera that were positive and negative for antiphospholipid antibodies. All sera were assayed for baseline concentrations of 6-keto-prostaglandin F1 alpha before incubation with endothelial monolayers. Additionally, the extent of binding of antiphospholipid antibodies to intact and damaged endothelium was studied by immunofluorescent techniques and enzyme-linked immunosorbent assay. Our results indicate that prostacyclin production is not impaired by sera containing antiphospholipid antibodies, regardless of the condition of the endothelium. Further, we were unable to demonstrate binding of immunoglobulin from sera containing antiphospholipid antibodies to intact or damaged endothelium. However, the baseline concentration of 6-keto-prostaglandin F1 alpha was nearly fourfold higher in sera containing antiphospholipid antibodies. The finding of elevated baseline serum concentrations of prostacyclin metabolite in patients with antiphospholipid antibodies suggests a condition of long-term stimulation or altered metabolism of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

IgG1 and IgG2 are the predominant subclasses of antiphospholipid antibody in women with the lupus anticoagulant.

We studied the sera of 36 patients with lupus anticoagulant and IgG antibodies against both phosphatidylserine and cardiolipin. Most sera also had IgG antibodies against other phospholipids: 97% against phosphatidylinositol, 91% against phosphatidylglycerol, and 82% against phosphatidylethanolamine. IgG2 was the predominant subclass against cardiolipin and phosphatidylserine; 35 of 36 patients (98%) had IgG2 against both phospholipids. Most patients also had the IgG1 subclass; 32 of 36 (89%) against cardiolipin and 25 of 36 (69%) against phosphatidylserine. IgG3 and IgG4 subclasses were present at very low concentrations and in only a minority of the sera. The antibody response against phosphatidylserine was characterized by significantly less IgG1 than was the response against cardiolipin (P less than 0.01), although the IgG2 responses against each phospholipid were not different. IgG subclasses were unrelated to any other aspect of the patients' history, including a history of thrombocytopenia or thrombosis, a positive antinuclear antibody test, or a diagnosis of systemic lupus erythematosus.

Blood Coagulation Factors↗
PubMed1990

Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss.

We determined whether purified immunoglobulin G from patients with antiphospholipid antibodies causes fetal loss in pregnant mice. Sera were obtained from nonpregnant parous women (group 1) and nonpregnant women with antiphospholipid antibodies and a history of fetal loss (group 2). Pregnant BALB/c mice were given an intraperitoneal injection of 15 mg of IgG on day 8 of pregnancy. Typically, mice treated with IgG from antiphospholipid antibodies aborted within 48 hours. When animals were sacrificed on days 9 to 15, the uterus of each animal was inspected for the presence of live, dead, or resorbing fetuses. In contrast to mice injected with control IgG or saline solution, each mouse injected with IgG from antiphospholipid antibodies aborted and no live fetuses were found (p less than 0.05). Histologic examination of the uteroplacental interface showed decidual necrosis in the mice treated with IgG containing antiphospholipid antibodies, and immunofluorescent studies also showed prominent intravascular decidual IgG and fibrin deposition. We conclude that IgG from antiphospholipid antibodies of women with fetal loss causes fetal loss in BALB/c mice. It appears that the fetal loss is mediated by IgG binding in the maternal decidual vasculature.

Animals↗
PubMed1990

Pregnancy in the patient with rheumatic disease: the obstetrician's perspective.

Patients with rheumatic diseases who become pregnant are justifiably categorized as having high-risk pregnancies. Utilizing a multidisciplinary approach, including perinatologists, rheumatologists and anaesthetists, successful pregnancies have become the rule rather than the exception. However, women with rheumatic disease are particularly prone to develop serious obstetric problems which often result in early hospitalization and delivery. Although vigilant obstetric care improves perinatal outcome, prematurity will continue to be a major problem complicating pregnancies in women with rheumatic disease.

Abortion, Spontaneous↗
PubMed1990

Interpretation of blocking activity in maternal serum depends on the equation used for calculation of mixed lymphocyte culture results.

Immunosuppressive blocking factors in maternal serum are usually determined by inhibition of mixed lymphocyte cultures (MLC), but reports on the importance of these factors for successful pregnancy are conflicting. Here we measured serum blocking activity in men, non-pregnant nulliparous women, non-pregnant multiparous women, women with normal pregnancies, and in women who had had recurrent spontaneous abortions and were treated with leucocyte immunizations. Three different equations were used for calculation of blocking activity: blocking effect index (BEI); stimulation index (SI); and blocking index (BI). By all three methods of calculation, significantly lower levels of blocking activity were noted for men and women compared with pregnant women and multiparae. In the patients with a history of recurrent spontaneous abortions blocking activity as determined by BEI and BI increased into the positive range after treatment with infusions of third-party donor leucocytes in a statistically significant number of women (P less than 0.05). However, blocking activity as determined by BEI had a higher predictive value for successful pregnancy than did that determined by BI or SI. Our data suggest that the equation used for calculating BEI is superior to other methods for the determination of blocking activity when monitoring the response to leucocyte immunization in women with recurrent spontaneous abortion. However, these results also cast doubt on the importance of blocking antibodies in histories of recurrent abortion, since pregnancies occurred in the absence and spontaneous abortions occurred in the presence of blocking activity.

Abortion, Habitual↗
PubMed1990

Antiphospholipid antibodies and pregnancy: maternal implications.

Antiphospholipid antibodies are associated with a spectrum of serious medical conditions. Several of these are of special concern to the obstetrician because they have a tendency to occur during pregnancy. Untreated pregnant women with aPLA appear to be especially prone to thrombotic events, including stroke. Atypically early-onset preeclampsia occurs in a large proportion of women with aPLA and a history of pregnancy loss. Conversely, a modest proportion of women with early-onset preeclampsia have aPLA. Although rare, a syndrome of postpartum pleuropulmonary disease and thrombosis is associated with aPLA. Finally, certain neurologic conditions, such as TIAs and chorea gravidarum, appear to be related to aPLA. It is important to recognize pregnant women with aPLA so they can be appropriately managed in an effort to avoid fetal loss and thromboembolic events.

Autoantibodies↗
PubMed1989

Amaurosis fugax associated with antiphospholipid antibodies.

In more than 50% of amaurosis fugax patients under 45 years of age no cause for the episodes of visual loss is identifiable. We have encountered 6 young adults (4 women and 2 men) with episodes of amaurosis fugax associated with elevated levels of antiphospholipid antibodies. Splinter hemorrhages of the nail beds were present in most patients. Treatment with antiplatelet medications and anticoagulants appeared to reduce the frequency of episodes and might prevent central retinal artery occlusions or stroke.

Adult↗
PubMed1989

The association of antiphospholipid antibodies with severe preeclampsia.

Over a 3-year period, we studied 43 women who presented with severe preeclampsia prior to 34 weeks' gestation. Seven (16%) had significant levels of antiphospholipid antibodies, whereas none of the normotensive controls of similar gestational age had antiphospholipid antibodies (P less than .001). Three of the seven women with antiphospholipid antibodies suffered the following complications during the peripartum period: 1) cerebral infarction and episodes of transient monocular blindness; 2) pulmonary embolism, deep venous thrombosis, and an autoimmune flare in the postpartum period; and 3) transient monocular blindness and amnesia after delivery. Our experience suggests that antiphospholipid antibodies are found in a substantial proportion of cases of early-onset severe preeclampsia and have important clinical implications. We suggest that patients with early-onset severe preeclampsia be screened for antiphospholipid antibodies; if antibodies are detected, these women should be considered for prophylactic anticoagulation therapy.

Autoantibodies↗
PubMed1989

Elevated anti-D titer after the administration of Rh immune globulin. A case report.

An anti-D titer of 1:16 was detected in a woman who had received 300 micrograms of Rh immune globulin as antepartum prophylaxis. It has been generally accepted that antibody titers following the administration of Rh immune globulin are less than 1:2. Although Rh immunization is always a potential cause of a titer greater than 1:4, a conservative approach is warranted in managing the patient with elevated anti-D antibody titers detected following the administration of Rh immune globulin.

Adult↗
PubMed1988

Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies and Rh immunization.

A patient with antiphospholipid antibodies and nine consecutive fetal deaths and a severely Rh-immunized woman with one previous live birth and seven fetal/neonatal deaths achieved live births after antepartum administration of intravenous immunoglobulin. This agent shows promise as a new treatment for patients with previous repetitive fetal deaths from immunologic causes.

Adult↗
PubMed1988

Occult placental abruption after maternal trauma.

Three cases of occult abruption after maternal trauma are presented. In each instance, there was no vaginal bleeding, and abdominal findings were subtle. By maintaining a high index of suspicion and monitoring the fetus continuously, the obstetrician may minimize the fetal complications of placental abruption in traumatized pregnant patients.

Abdominal Injuries↗
PubMed1987

Association of lupus anticoagulant with antibody against phosphatidylserine.

Lupus anticoagulant (LAC) is an antiphospholipid autoantibody identified by prolongation of in vitro phospholipid-dependent coagulation tests. Its presence is associated with thromboembolic disease and recurrent pregnancy loss in patients with or without clinical autoimmune disease. The purpose of this study was to identify the specific phospholipid(s) against which LAC is directed. The sera of 15 patients with LAC and of 41 LAC-negative controls were evaluated. Specific phospholipids were used to inhibit IgG binding in a partial thromboplastin ELISA, and serologic reactivity was measured with ELISAs which used specific phospholipids in the solid phase. Both phosphatidylserine and cardiolipin significantly inhibited IgG binding in the partial thromboplastin ELISA (76 and 75%, respectively); however, the serum of one patient who was strongly positive for LAC in coagulation assays was not inhibited by cardiolipin. In the specific phospholipid ELISAs, LAC-positive sera contained IgG (15 of 15 sera) and frequently IgM (9 of 15 sera; 60%) to phosphatidylserine. Most LAC-positive sera also contained IgG antibodies against other phospholipids: cardiolipin (10 of 11 sera; 91%), phosphatidylcholine (1 of 15 sera; 7%), phosphatidylethanolamine (12 of 15 sera; 80%), phosphatidylglycerol (12 of 15 sera; 80%), and phosphatidylinositol (10 of 15 sera; 67%). None of the LAC-negative controls had measurable IgG against any of these phospholipids. We conclude that LAC-positive sera contain antibody specificities against multiple phospholipids; however, anticoagulant activity is always associated with the presence of antibodies against phosphatidylserine.

Abortion, Habitual↗
PubMed1987

Platelet-binding immunoglobulins in pregnancy-induced hypertension. I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?

Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and r = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and r = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.

Autoantibodies↗
PubMed1987

Immunologic disease and fetal death.

Both maternal isoimmunization and maternal autoimmune disease are associated with fetal death. For isoimmunization the immunologic nature of fetal death (hydrops fetalis) is beyond question, but many of the details are poorly understood. It would be extremely helpful to know what immunologic factors are responsible for the wide variation in the degree of fetal hemolysis. This information would surely lead to improved management of isoimmunized pregnancies and create new and more successful therapies for fetuses at risk for hemolysis. The immunology of autoimmune-associated fetal death is, for the most part, an enigma. For the fetal deaths associated with SLE and the antiphospholipid antibodies, demise appears to be a consequence of uteroplacental vascular damage. But the observable pathology is nonspecific, and the evidence for a direct immunologic mechanism is sparse. The similarity between the uteroplacental vascular lesions found with these autoimmune conditions and those seen in preeclampsia demands more intensive investigation. For the fetal deaths caused by complete congenital heart block associated with maternal autoantibodies, the evidence for a direct immunologic mechanism is now being established. As with isoimmunization, a more complete understanding of autoimmune-associated fetal death will open new avenues of management and therapy.

Autoantibodies↗
PubMed1987

A new postpartum syndrome associated with antiphospholipid antibodies.

Three women with antiphospholipid antibodies and a postpartum syndrome of pleuropulmonary disease, fever, and cardiac manifestations are presented. Each patient had either lupus anticoagulant or anticardiolipin antibodies or both, but did not have antinuclear antibodies or fulfill the criteria for the diagnosis of systemic lupus erythematosus. No infection or embolus was detected that could explain the pulmonary findings. All three patients had electrocardiographic abnormalities, and one patient developed a cardiomyopathy with extensive immunoglobulin G (IgG), IgM, IgA, and C3 deposition in the myocardium. In addition to the reported association between antiphospholipid antibodies and fetal loss, fetal growth retardation, and preeclampsia, we suggest that patients with antiphospholipid antibodies are at risk for a previously unreported and serious autoimmune postpartum syndrome.

Adult↗