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Biomedical subjects

A M Peaceman

Publications and source records attributed to A M Peaceman.

At least 37 records · Page 2Linked to original sources

The effect of aspirin and indomethacin on prostacyclin and thromboxane production by placental tissue incubated with immunoglobulin G fractions from patients with lupus anticoagulant.

OBJECTIVE: We investigated the hypothesis that nonsteroidal antiinflammatory agents can influence the abnormal prostanoid production associated with antiphospholipid antibodies. We specifically assessed whether aspirin or indomethacin could eliminate the increased placental thromboxane production previously observed with immunoglobulin G fractions from patients with lupus anticoagulant without adversely affecting prostacyclin production. STUDY DESIGN: Immunoglobulin G fractions were prepared from the plasma of eight nonpregnant patients with antiphospholipid antibody syndrome and demonstrable lupus anticoagulant. Samples from each patient were then placed in incubation wells containing explants from normal term pregnancies and 10(-4) mol/L aspirin, 10(-7) mol/L indomethacin, or no added drug. Aliquots were removed at intervals up to 48 hours of incubation and assessed for placental prostacyclin and thromboxane production by radioimmunoassay of the stable metabolites prostaglandin F1 alpha and thromboxane B2. RESULTS: The addition of aspirin to wells containing immunoglobulin G from patients with lupus anticoagulant was associated with a significant decrease in thromboxane production compared with wells without added drug, but prostacyclin production was unaffected. In contrast, the addition of indomethacin also decreased thromboxane production significantly, but prostacyclin production was also diminished, so the ratio of thromboxane to prostacyclin was unaffected. CONCLUSION: These results support a role for the use of aspirin for antiphospholipid antibody-related pregnancy loss through a mechanism similar to that postulated for preeclampsia, namely, selective inhibition of thromboxane production.

Antibodies, Antiphospholipid↗

Understanding prostaglandin metabolites and platelet-activating factor in the pathophysiology and treatment of the antiphospholipid syndrome.

As clinicians include an immunologic evaluation in their assessment of recurrent fetal loss among otherwise asymptomatic women, the diagnosis of PAPS will be uncovered with greater frequency. Our understanding of the underlying pathophysiology of PAPS is critical if we are to propose safe and rational therapies for these patients. It appears as though prostaglandin metabolites are implicated directly in the processes that culminate in this unique, localized vasculopathy; and research is actively progressing with this focus in mind. For the present, we should look critically at the available treatments to be sure that the rationale for use is consistent with current evidence and that the margin of fetal and maternal safety justifies their use. To date, only low-dose aspirin appears to alter prostaglandin metabolites favorably and is thus, emerging as our safest and most efficacious treatment.

Abortion, Habitual↗

Immunoreactive tumor necrosis factor-alpha is elevated in maternal plasma but undetected in amniotic fluid in the second trimester.

OBJECTIVE: We investigated the participation of the cellular arm of the immune system in adaptation to pregnancy by assessing plasma and amniotic fluid levels of the cytokine tumor necrosis factor-alpha. STUDY DESIGN: Fifty-five healthy pregnant women who underwent second-trimester genetic amniocentesis at a mean gestational age of 17.0 +/- 1.4 weeks composed study group A. Blood was drawn from each patient before amniocentesis, and an aliquot of amniotic fluid was obtained for this study. Twenty-one healthy patients at a mean gestational age of 35.5 +/- 4.8 weeks composed study group B, and blood was obtained from each patient at an outpatient prenatal visit. Twenty-two healthy, nonpregnant women of reproductive age composed the control group (C). All specimens were stored at -70 degrees C and collectively assayed for tumor necrosis factor-alpha by a specific enzyme-linked immunoassay. RESULTS: All patients in group A had a normal karyotype and all patients in groups A and B had uneventful pregnancies. Tumor necrosis factor-alpha was detected in the plasma of 43 of 55 (78.2%) patients in group A compared with 7 of 21 (33.3%) patients in group B (p < 0.001); tumor necrosis factor-alpha was not detected in any of the 22 women in group C. The median plasma tumor necrosis factor-alpha level for group A was 135 pg/ml (range 0 to 625 pg/ml) compared with 0 pg/ml (range 0 to 110 pg/ml) in group B (p < 0.001). Tumor necrosis factor-alpha was not detected in any of the amniotic fluid specimens studied. CONCLUSIONS: Levels of tumor necrosis factor-alpha were elevated in the plasma but not detected in the amniotic fluid of normal pregnant patients in the second trimester. These findings suggest involvement of the cellular branch of the immune system and its products, the cytokines, in the normal adaptation of the mother to the fetal allograft, with a possible role in regulating trophoblast growth and invasion.

Adult↗

Severe postpartum pulmonary, cardiac, and renal syndrome associated with antiphospholipid antibodies.

BACKGROUND: The antiphospholipid antibody syndrome has been associated with thromboembolic events, thrombocytopenia, fetal death, fetal growth retardation, and early-onset severe preeclampsia. CASE: A postpartum woman developed fever, pulmonary infiltrates, cardiac conduction defects, and renal insufficiency following severe preeclampsia. She tested positive for lupus anticoagulant and anticardiolipin antibody, and responded to steroid therapy and plasmapheresis. CONCLUSION: The postpartum multi-system involvement suggests that a variety of clinical presentations may be associated with antiphospholipid antibodies. Treatment with plasmapheresis or corticosteroids may be of value in similar cases.

Acute Kidney Injury↗

Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia.

OBJECTIVE: Our purpose was to investigate whether markers for activation of the immune system are present in patients with preeclampsia by assessing maternal plasma and amniotic fluid for tumor necrosis factor-alpha and interleukin-1 beta. STUDY DESIGN: Twenty-one patients with severe preeclampsia composed the study group (group A). An antepartum comparison group was composed of healthy nulliparous patients not in labor and matched for gestational age (group B). Another control group consisted of term nulliparous patients in labor with uneventful pregnancies (group C). Maternal plasma samples were collected from all patients at recruitment and from patients in groups A and C immediately after delivery and again 20 to 24 hours post partum. Amniotic fluid was also collected from patients in groups A and C during labor. All samples were collectively assayed for tumor necrosis factor-alpha and interleukin-1 beta by specific enzyme-linked immunoassays. RESULTS: Before labor tumor necrosis factor-alpha was detected more frequently in the plasma of preeclamptic patients than in the plasma of patients in group B (12/16 vs 5/16, p < 0.05) and in higher concentrations (median 35 pg/ml vs median 0 pg/ml, p < 0.05). Although tumor necrosis factor-alpha was frequently detected in the plasma of patients in group C in early labor (16/20), concentrations were higher in the four preeclamptic patients first sampled in early labor (210 pg/ml vs 65 pg/ml, p < 0.05). Similarly, amniotic fluid levels of tumor necrosis factor-alpha were increased in preeclamptic patients compared with control patients. At delivery tumor necrosis factor-alpha was more likely to be identified in the plasma of preeclamptic patients and was found in higher concentrations, but by 20 to 24 hours post partum measurements in the preeclamptic and control patients were similar. There were no differences in the frequency with which interleukin-1 beta was detected or the concentration of interleukin-1 beta in any of the samples. CONCLUSIONS: Tumor necrosis factor-alpha is increased in the plasma and amniotic fluid of patients with severe preeclampsia. These data are suggestive of a role for abnormal immune activation in the pathophysiologic mechanisms of preeclampsia.

Adult↗

Factors contributing to the increased cesarean birth rate in older parturient women.

OBJECTIVE: Our purpose was to determine factors contributing to the increased use of cesarean section in patients > or = 35 years old. STUDY DESIGN: Data were collected prospectively on nulliparous patients in spontaneous labor with term, singleton pregnancies and vertex presentations. Criteria for the diagnosis of labor were standardized: regular, painful uterine contractions at least once every 5 minutes in the presence of either complete cervical effacement or spontaneous rupture of membranes. The labors of women > or = 35 years old (n = 74) were compared with those of women 20 to 29 years old (n = 275). RESULTS: The cesarean section rate was significantly greater for patients > or = 35 years old (21.6% vs 10.2%, odds ratio 2.4, 95% confidence interval 1.2 to 5.1). Mean birth weights were similar in the two groups, but when birth weight was > or = 3600 gm patients > or = 35 years old were more likely to be delivered by cesarean section (36.7% vs 12.2%, odds ratio 4.0, 95% confidence interval 1.4 to 11.9). There were no differences between the two age groups in physician factors that could explain the disparate rates of cesarean delivery. Indeed, of patients delivered vaginally the older parturients received oxytocin for longer duration (6.4 +/- 2.6 vs 5.0 +/- 3.1 hours, p < 0.05) and at higher maximum doses (12.4 +/- 6.1 vs 9.8 +/- 6.2 mU, p < 0.05). After controlling for potentially confounding variables with multiple logistic regression analysis, maternal age (R = 0.125, p < 0.005), birth weight (R = 0.196, p < 0.001), the need for oxytocin (R = 0.210, p < 0.001), and epidural anesthesia (R = 0.195, p < 0.001) were found to be independently associated with the increased rate of cesarean section. CONCLUSION: We could not identify any controllable physician factors affecting the rate of cesarean section in patients > or = 35 years old. The increased oxytocin requirements and the incidence of dystocia with birth weight > or = 3600 gm suggest that maternal and fetal characteristics contribute to the increased frequency of cesarean section in older parturients.

Adult↗

Factors that influence route of delivery--active versus traditional labor management.

OBJECTIVE: Our purpose was to compare maternal and fetal factors that influence the route of delivery with active management of labor and a traditional labor management protocol. STUDY DESIGN: Data were collected prospectively on 346 consecutive patients receiving active management of labor and 354 patients who were managed traditionally. Within each group demographic and labor characteristics of patients undergoing cesarean section were compared with those of patients having vaginal deliveries by means of the Student t test, chi 2 analysis, and stepwise logistic regression. RESULTS: With both active management of labor and traditional labor management success in achieving vaginal delivery was related to the station of the fetal vertex at admission, the need for oxytocin augmentation of labor, the uterine response to oxytocin, the use of epidural anesthesia, and the development of chorioamnionitis. By means of multiple logistic regression analysis maternal age, height, payor status, and birth weight were also identified as risk factors for cesarean section with traditional labor management but not with active management of labor. CONCLUSIONS: Differences were identified in risk factors for cesarean section between active management and traditional labor management. Active management of labor may diminish or eliminate some patient characteristics as risk factors for cesarean birth.

Adult↗

The effect of immunoglobulin G fractions from patients with lupus anticoagulant on placental prostacyclin and thromboxane production.

OBJECTIVE: We evaluated whether the production of prostacyclin and thromboxane by normal human placental tissue is consistently altered by incubation with immunoglobulin G fractions prepared from plasma of patients with lupus anticoagulant. STUDY DESIGN: The immunoglobulin G fractions were prepared from eight patients with lupus anticoagulant and eight control patients. Doses of these fractions (3 mg, 7.5 mg, and 12 mg) were incubated with placental explants obtained from normal pregnancies, and prostacyclin and thromboxane production was assessed over 48 hours. RESULTS: Prostacyclin production was similar for placental tissue incubated with immunoglobulin fractions from control and lupus anticoagulant patients at all of the doses tested. Placental production of thromboxane was significantly increased with immunoglobulin fractions from lupus anticoagulant patients for all three doses (p = 0.02). CONCLUSIONS: The immunoglobulin G fraction from patients with lupus anticoagulant consistently alters placental thromboxane production without affecting prostacyclin production. Increases in placental thromboxane production may contribute to antiphospholipid antibody-mediated pregnancy loss.

Epoprostenol↗

Reducing cesarean births at a primarily private university hospital.

OBJECTIVE: The rise in cesarean birth at Northwestern Memorial Hospital in 1986 to 27.3% prompted implementation of three initiatives to reverse the escalating cesarean section rate. STUDY DESIGN: First, vaginal birth after cesarean section was more strongly encouraged. Second, after the 1988 calendar year the cesarean section rate of every obstetrician was circulated annually to each attending physician. Third, on completion of a prospective, randomized trial of the active management of labor in early 1991, this protocol was recommended as the preferred method of labor management for term nulliparous patients. RESULTS: The total, primary, and repeat cesarean section rates declined from 27.3%, 18.2%, and 9.1% in 1986 to 16.9%, 10.6%, and 6.4%, respectively, in 1991. At the same time the perinatal mortality dropped from 19.5 to 10.3. Significant reductions in abdominal deliveries occurred for both private patients (30.3% to 19.1%, p < 0.0001) and clinic patients (20.8% to 11.5%, p < 0.0001). A decline in operative deliveries for dystocia and an increase in vaginal birth after prior cesarean section were the principal factors contributing to the lower cesarean section rates. However, in 1991 individual private physicians still had wide variations in primary cesarean section rates (4.6% to 21.1%) and use of vaginal birth after prior cesarean section (5.3% to 90%). CONCLUSION: The cesarean section rate has been significantly reduced for both private and clinic patients. Differences in population demographics and individual physician practice patterns contributed to a higher incidence of cesarean birth on the private service.

Birth Weight↗

A controlled trial of a program for the active management of labor.

BACKGROUND: Over the past two decades, the rate of cesarean section in the United States has risen from 5 percent to 25 percent of deliveries, primarily because of the increased frequency of dystocia (arrest of labor). One strategy that has been proposed for increasing the rate of vaginal delivery is a program of active management of labor that encourages early amniotomy, early diagnosis of slow progress in labor, and the use of higher than usual doses of oxytocin; the efficacy and safety of this approach are uncertain, however. METHODS: We conducted a randomized trial in which nulliparous women in spontaneous labor at term were randomly assigned to either active management of labor or traditional management. With active management, amniotomy was performed within one hour of the diagnosis of labor, and when the rate of cervical dilation was less than 1 cm per hour, oxytocin was infused at an initial rate of 6 mU per minute. The dose was increased by 6 mU per minute every 15 minutes (to a maximum of 36 mU per minute) until there were seven contractions every 15 minutes. RESULTS: For the women assigned to active management (n = 351), the cesarean-section rate was 10.5 percent, as compared with 14.1 percent for those assigned to traditional management (n = 354, P = 0.18). The 26 percent reduction in the cesarean-section rate was due primarily to a decrease in dystocia. After we controlled for potential confounding variables, the reduction in the rate of delivery by cesarean section was statistically significant (odds ratio for women given active as compared with traditional management, 0.57; 95 percent confidence interval, 0.36 to 0.95). With active management, the average length of labor was shortened by 1.66 hours, principally because of earlier amniotomy and earlier use of oxytocin. There was no increase in maternal or neonatal morbidity, and there were significantly fewer infectious complications in the mothers. CONCLUSIONS: The program we studied for the active management of labor reduces the incidence of dystocia and increases the rate of vaginal delivery without increasing maternal or neonatal morbidity.

Adult↗

Interlaboratory variation in antiphospholipid antibody testing.

OBJECTIVE: Because of the widespread use of antiphospholipid antibody testing in the evaluation of patients with recurrent pregnancy loss, we evaluated the consistency of results among laboratories testing for anticardiolipin antibody and the lupus anticoagulant. STUDY DESIGN: A questionnaire regarding methods used and samples of blood from 20 patients were sent to five university-based and five commercial facilities for antiphospholipid antibody testing. RESULTS: The responses of the participating laboratories to the questionnaires revealed significant differences in methods, standardization, and units of reporting. For anticardiolipin antibody, the number of specimens found to be positive for any isotype (immunoglobulin G, M, or A) varied considerably among laboratories, with a range of 5 to 13. All laboratories were in agreement (i.e., at least one isotype was present or all were absent) for only 5 of 20 specimens (25%). In contrast, lupus anticoagulant results were more reproducible, although one facility reported results markedly discordant from the other four laboratories. CONCLUSION: These observations suggest that significant interlaboratory variation exists in antiphospholipid antibody, and particularly anticardiolipin antibody, testing and might lead to unnecessary therapeutic interventions.

Antibodies↗

The immunoglobulin G fraction from plasma containing antiphospholipid antibodies causes increased placental thromboxane production.

OBJECTIVE: Our objective was to evaluate whether the immunoglobulin G fraction from plasma containing high levels of antiphospholipid antibodies alters the production of prostacyclin or thromboxane when incubated with normal human placental tissue. STUDY DESIGN: The immunoglobulin G fraction was prepared from the pooled plasma of five volunteers with normal obstetric histories and no antiphospholipid antibodies. The immunoglobulin G fraction was prepared similarly from a patient with the antiphospholipid antibody syndrome. Doses of these immunoglobulin G fractions ranging from 0.3 to 3.0 mg were incubated with placental explants obtained from eight normal pregnancies, and prostacyclin and thromboxane production was assessed over 48 hours. RESULTS: Placental prostacyclin production was unaltered by incubation with either immunoglobulin G fraction at any of the doses tested. Placental thromboxane production tripled by 32 hours with the addition of 0.6, 1.5, and 3.0 mg of the antiphospholipid antibody fraction (p < 0.05) compared with baseline production but was unaltered by the addition of the normal pooled plasma fraction at any dose. The increase in thromboxane production with antiphospholipid antibody immunoglobulin G appeared to be dose related. CONCLUSION: The immunoglobulin G fraction prepared from plasma containing antiphospholipid antibodies caused increased placental thromboxane production without altering prostacyclin production.

Antibodies, Antiphospholipid↗

Antepartum management of triplet gestations.

OBJECTIVE: We evaluated an alternative approach to the management of triplet gestations that did not include home uterine monitoring, prophylactic tocolysis, or routine antepartum hospitalization. STUDY DESIGN: Fifteen patients were managed over a 42-month period by an antepartum protocol that emphasized patient education regarding signs and symptoms of preterm labor, weekly prenatal visits after 24 weeks' gestation with cervical examination, and increased rest in an outpatient setting. Tocolytic therapy was only used for regular uterine contractions when cervical change was documented. RESULTS: Nine of 15 (60%) patients with management in this uniform manner were delivered at > or = 35 weeks' gestation, and six patients (40%) completed 37 weeks of pregnancy. Only five patients (33%) received tocolytic therapy. The mean birth weight was 1957 +/- 488 gm, and only 19 of 45 neonates (42%) were admitted to the intensive care nursery. CONCLUSION: This management scheme was effective in reducing preterm delivery and thereby optimizing perinatal outcome.

Birth Weight↗

Sexually transmitted viral disease in women.

During the past decade, the incidence of sexually transmitted viral diseases has increased dramatically. In many cases, diagnosis is difficult, consequences are severe, and curative therapy is not available at present. In this article, Drs Peaceman and Gonik review current evidence about sexual transmission of viruses and discuss the latest methods of diagnosis, management, and prevention.

Female↗

Epidural analgesia and cesarean section for dystocia: risk factors in nulliparas.

A retrospective study assessing the effect of epidural analgesia in labor on the incidence of cesarean section was performed. The first 500 consecutive nulliparas meeting the following criteria were included in this study: term (37 weeks or longer) and singleton gestation, cephalic presentation, spontaneous onset of labor, and 5 cm or less of cervical dilation on admission. Patients were grouped according to their rate of cervical dilation in early labor (greater than or equal to 1 cm/hr, and less than 1 cm/hr) and the timing of epidural placement (none, early, or late). There was no effect of epidural analgesia on the incidence of cesarean section for fetal distress. The incidence of cesarean section for dystocia was significantly greater (p greater than 0.000001) in the epidural group (15.6%) than in the nonepidural group (2.4%). The greatest effect of epidural analgesia on the incidence of cesarean section for dystocia was observed in nulliparas who dilated at slower rates (less than 1 cm/hr) in early labor and who had epidural analgesia placed at 5 cm or less of cervical dilation (20.6% versus 3.4%, relative risk of 6, p less than 0.0005). The increase of cesarean section for dystocia associated with epidural analgesia could not be accounted for when other possibly confounding variables were studied. Both the dilation rate prior to epidural placement and the cervical dilation at epidural placement were significantly correlated to frequency of cesarean section for dystocia (p less than 0.01). This study suggests that epidural analgesia in labor may increase the incidence of cesarean section for dystocia in nulliparas.

Adolescent↗

Abdominal gunshot wounds in pregnancy.

The incidence of gunshot wounds in the civilian population is increasing. Likewise, pregnant women are more frequently sustaining wounds of the abdomen. We report on three women who sustained abdominal gunshot wounds during pregnancy. Guidelines for management are suggested. Select patients may be observed if the following conditions are present: mother's condition is stable, the entrance wound is below the fundus of the uterus, the missile can be radiographically demonstrated to be in the uterine cavity, there is a negative abdominal examination, and there is no blood in the urine or gastrointestinal tract.

Abdominal Injuries↗

The effect of magnesium sulfate tocolysis on the fetal biophysical profile.

The biophysical profile has proved to be a valuable tool for the assessment of fetal well-being, independent of gestational age. Magnesium sulfate is commonly used as a tocolytic agent, yet relatively little is known about its effects on the biophysical activities of the fetus. To investigate the effects of magnesium sulfate on the biophysical profile, we performed serial studies on patients who received tocolytic therapy with this agent because of preterm labor. A total of 16 women with 22 fetuses at 26 to 34 weeks' gestation in spontaneous preterm labor were studied. An initial biophysical profile was performed at the time of admission, and a second examination was performed when maternal serum magnesium levels reached 6 to 8 mg/dl. On admission all fetuses had reactive nonstress test results and 21 of 22 (95%) demonstrated sustained fetal breathing movements. With magnesium sulfate tocolysis, 50% of fetuses had nonreactive nonstress test results, and only 4 of 22 (18%) demonstrated sustained fetal breathing movements. Fetal tone, gross body movements, and amniotic fluid volume were found to be unaffected by magnesium sulfate tocolysis.

Adult↗

Bernard-Soulier syndrome complicating pregnancy: a case report.

The pregnancy of a patient with Bernard-Soulier syndrome is described. Coagulation abnormalities were encountered, as well as isoimmunization from previous transfusions. Immune suppression was achieved with steroids and intravenous gamma globulin, and plasmapheresis was performed to allow platelet transfusion.

Adult↗