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Biomedical subjects

D W Branch

Publications and source records attributed to D W Branch.

118 records · Page 7Linked to original sources

Immunologic aspects of recurrent abortion and fetal death.

Although mechanisms that prevent rejection of the conceptus are incompletely understood, recent evidence suggests that maternal immunologic aberrations may cause repeated abortions. Autoimmune conditions associated with antiphospholipid antibodies sometimes produce vascular abnormalities in the decidua and placenta; successful pregnancies can be achieved in most of these women by treatment with corticosteroids and low-dose aspirin. Abnormal maternal immune responses to paternal or trophoblast alloantigens, with insufficient production of blocking antibodies or suppressor cells, have also been implicated. Immunization of these patients with paternal or third-party leukocytes has resulted in a number of live births. However, the mechanism of action, effectiveness, and safety of all treatment regimens remain controversial. Present recommendations for the evaluation of recurrent-abortion patients include diagnosis and appropriate treatment of traditional nonimmunologic and more recently recognized autoimmune factors. The remaining patients with no detectable cause for repetitive pregnancy loss are candidates for referral to research centers for further immunologic evaluation and experimental immunotherapy.

Abortion, Habitual↗

The demonstration of lupus anticoagulant by an enzyme-linked immunoadsorbent assay.

Lupus anticoagulant, an autoantibody associated with thromboembolic disease and pregnancy loss, is currently identified by its capability to prolong phospholipid-dependent coagulation tests, such as the activated partial thromboplastin time (APTT). The use of a coagulation assay for the detection of an antibody has several inherent disadvantages: fresh plasma is required for accurate testing, prolongation of coagulation test(s) is not specific for lupus anticoagulant, and coagulation assays are not easily manipulated for the characterization of antigen-antibody interactions. Using partial thromboplastin an the antigen, we have developed an enzyme-linked immunoadsorbent assay (ELISA) for the detection of lupus anticoagulant. Fifteen women with lupus anticoagulant (being evaluated for recurrent pregnancy loss or autoimmune disease) and 40 lupus anticoagulant-negative controls (including 20 with recurrent pregnancy loss, 12 parous women, and 8 with known autoimmune disease) were evaluated using the APTT and ELISA assays for lupus anticoagulant. All patients with lupus anticoagulant, as defined by the APTT, had significantly elevated IgG (sensitivity and specificity, 100%) or IgG + IgM (sensitivity 93%, specificity 95%) levels compared to controls.

Autoantibodies↗

Operations for cervical incompetence.

At present, cervical cerclage is indicated in those patients with a classic history of cervical incompetence. For the majority of these patients, a postconceptional cerclage procedure is better suited because it is done after the fetus has been evaluated ultrasonographically for obvious abnormalities and after the risk for spontaneous abortion is past. The greatest experience is with the Shirodkar and the McDonald procedures; allowing for operator differences, neither appears to have an important advantage. The transabdominal cervicoisthmic cerclage may be a useful postconceptional procedure in the selected patient whose cervix is either markedly foreshortened, deeply lacerated, or infected. Preconceptional cerclages are best reserved for those rare patients in whom a markedly foreshortened incompetent cervix is associated with early second-trimester pregnancy losses (preconceptional isthmic cerclage) or in whom the cervix has a single, identifiable scar or deep laceration extending through the internal os (Lash procedure).

Bibliographies as Topic↗

Obstetric complications associated with the lupus anticoagulant.

We identified eight patients with the lupus anticoagulant (an autoantibody acquired by some patients with systemic lupus erythematosus), by observation of an increased activated partial thromboplastin time and abnormal results on a tissue thromboplastin-inhibition test. The patients had experienced a total of 30 spontaneous abortions and fetal deaths in 31 previous pregnancies (96.8 per cent). During their next pregnancy, the patients were treated with 40 to 50 mg of prednisone per day and 81 mg of aspirin per day. The therapy shortened their activated partial thromboplastin times, produced normal values for tissue thromboplastin inhibition, and reduced the rate of pregnancy loss to 37.5 per cent. However, preeclampsia developed in the five patients who gave birth to live infants, and fetal growth retardation occurred in three cases. The corticosteroid and low-dose aspirin regimen appears to improve perinatal outcome in cases in which the mother has the lupus anticoagulant, but such practices as careful fetal surveillance and preterm delivery when appropriate are also important to successful obstetric management of such cases.

Abortion, Spontaneous↗

Physiologic adaptations of pregnancy.

Normal pregnancy changes include physiologic anemia, leukocytosis, and thrombocytopenia. Cardiac rate and stroke volume increase, vascular resistance falls, and creatinine clearance markedly rises. Thyroid binding globulin and cortisol binding globulin both increase, as do complement proteins and fibrinogen, the latter resulting in a normally high erythrocyte sedimentation rate. Estrogen and progesterone rise dramatically. Low back pain, hip and sacroiliac complaints are common. The cytolytic activity of natural killer (NK) cells is decreased, as are adhesion and chemotaxis of phagocytic cells. Antibody responses are normal. CD4 cells proportionately decrease. A large number of circulating proteins suppression lymphocyte proliferation, and T-cell interleukin-2 (IL-2) production may be suppressed. In studies of pregnant patients, controls must include normal pregnant women.

Female↗

Cyclosporin A attenuates increased prostaglandin and thromboxane production in response to various stimuli in human decidua.

PROBLEM: This study was undertaken to evaluate the effects of cyclosporin A on prostanoid (prostaglandin and thromboxane) production by human decidua. METHOD: Decidual 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 h with cyclosporin A (0.1-100 ng/ml) in the presence and absence of interleukin 1 beta (IL-1 beta, 10 ng/ml), phorbol 12-myristate 13-acetate (PMA, 10(-7) M) and ionomycin (0.5 micron). Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) were measured by radioimmunoassay, and cellular protein was determined. RESULTS: IL-1 beta, PMA, and ionomycin all stimulated decidual PGE2 and TXB2 production as expected. However, these stimulatory actions were attenuated by 20% when cells were coincubated with cyclosporin A (100 ng/ml). All concentrations of cyclosporin A tested were within the therapeutic range. CONCLUSIONS: Our results indicate that cyclosporin A does not stimulate decidual prostanoid production and is probably unrelated to preterm labor and delivery in allograft recipients.

Cells, Cultured↗

Human leukocyte antigen compatibility and failure to achieve a viable pregnancy with assisted reproductive technology.

Many couples fail to achieve a viable pregnancy with multiple attempts of Assisted Reproductive Technology (ART). Immunologic rejection of the embryo may be a factor in these couples. We evaluated shared human leukocyte antigen (HLA) antigenicity in 10 couples who failed multiple ART cycles and compared them with 10 couples who achieved a viable pregnancy with their first ART attempt. Study couples shared a statistically significant greater number of HLA antigens than control couples. Leukocyte immunotherapy is discussed. We conclude that couples who share multiple HLA antigens may have an immunologic basis for failing to achieve a viable pregnancy with multiple ART cycles.

Adult↗

Ceramide stimulates prostaglandin production by human amnion and decidual cells.

OBJECTIVE: To determine whether ceramide regulates prostaglandin (PG) production by cultured human amnion cells and decidual cells independently of interleukin-1 beta (IL-1 beta). METHODS: Cells were grown in monolayer culture and then incubated with varying concentrations of ceramide, IL-1 beta, ceramide in the presence and absence of IL-1, and control media. Production of PGE2 was determined using a specific radioimmunoassay. RESULTS: Ceramide induced a significant concentration-dependent increase in PGE2 production by amnion cells and decidual cells. However, PGE2 production induced by IL-1 beta was significantly more than with ceramide alone, and there was no potentiation of PGE2 production with coincubation of ceramide and IL-1 beta. CONCLUSION: We suggest that term human amnion cells and decidual cells are responsive to ceramide independent of IL-1 beta and that generation of these substances in response to an infection in the uterus may lead to increased PG production by human gestational tissues, indicating that there are several mechanisms leading to PG production by these cells.

Amnion↗