Lucy A. Bayer-Zwirello

Transplantation of unrelated cord blood cells

A 43-year-old woman with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in acute phase received high-dose chemotherapy followed by transfusion of 12 randomly selected units of umbilical cord blood. HLA analysis showed cells of one donor from day +10 to day +43 post-transfusion. This unit was HLA class II identical with that of the patient.

Preclinical regulatory validation of a 3-stage amniotic mesenchymal stem cell manufacturing protocol

PURPOSEnBecause of the 4 to 6-month interval between a diagnostic amniocentesis and birth, clinical application of amniotic mesenchymal stem cell (AMSC)-based therapies demands a 3-stage cell manufacturing process, including isolation/primary expansion, cryopreservation, and thawing/secondary expansion. We sought to determine the feasibility and cell yield of such a staged cell manufacturing process, within regulatory guidelines.nnnMETHODSnHuman AMSCs isolated from diagnostic amniocentesis samples (n = 11) were processed under Food and Drug Administration-accredited good manufacturing practice. Expanded cells were characterized by flow cytometry and cryopreserved for 3 to 5 months. Cell release criteria included more than 90% CD29+, CD73+, and CD44+; less than 5% CD34+ and CD45+; negative mycoplasma quantitative polymerase chain reaction (QPCR) and endotoxin assay; and at least 70% viability.nnnRESULTSnIsolation and ample expansion of AMSCs was achieved in 54.5% (6/11) of the samples. Early processing and at least a 2-mL sample were necessary for reliable cell manufacturing. Cell yield before cryopreservation was 223.2 +/- 65.4 x 10(6) cells (44.6-fold expansion), plus a 14.7 x 10(6)-cell backup, after 36.3 +/- 7.8 days. Cell viability postthaw was 88%. Expanded cells maintained a multipotent mesenchymal progenitor profile.nnnCONCLUSIONSnHuman amniotic mesenchymal stem cells can be manufactured in large numbers from diagnostic amniocentesis, by an accredited staged processing, under definite procurement guidelines. These data further support the viability of clinical trials of amniotic mesenchymal stem cell-based therapies.

Successful treatment of dermatomyositis during pregnancy with intravenous immunoglobulin monotherapy.

BACKGROUND: Dermatomyositis is rare during pregnancy and, if untreated, is associated with poor fetal outcome. Corticosteroids are a standard treatment for dermatomyositis in pregnancy, but they have adverse effects. Intravenous immune globulin is an effective therapy for this condition and may have few adverse effects. CASE: A young, white primigravida presented with dermatomyositis at 4 5/7 weeks of gestation (creatine kinase 2,762 units/L). Intravenous immune globulin was administered monthly at a dose of 1 g/(kg·d) for 2 consecutive days. The patient’s symptoms resolved and no complications were experienced during therapy. At term, creatine kinase was 29 units/L and a healthy 3,657.5-g (8-lb, 1-oz) neonate was born. CONCLUSION: Pregnant patients with dermatomyositis can be treated with intravenous immune globulin, resulting in good fetal outcome, thus avoiding the deleterious effects of corticosteroid therapy on pregnancy.

The MisoPROM study: A multicenter randomized comparison of oral misoprostol and oxytocin for premature rupture of membranes at term ☆

OBJECTIVEnThis study was undertaken to determine whether induction of labor with oral misoprostol will result in fewer cesarean deliveries than intravenous oxytocin in nulliparous women with premature rupture of membranes at term.nnnSTUDY DESIGNnThree hundred five women at 10 centers were randomly assigned to receive oral misoprostol, 100 microg every 6 hours to a maximum of two doses or intravenous oxytocin. The primary outcome measure was cesarean deliveries. Secondary outcomes were time from induction to vaginal delivery and measures of maternal and neonatal safety.nnnRESULTSnThe study was stopped prematurely because of recruitment difficulties. We present the results for the 305 enrolled women. There was no difference in the proportion of women who underwent cesarean delivery (20.1% in the misoprostol group, 19.9% in the oxytocin group). The time interval from induction to vaginal delivery was also similar (11.9 hours for the misoprostol group, and 11.8 hours for the oxytocin group). Maternal and neonatal safety outcomes were similar for the two treatments. More infants born to women in the misoprostol group received intravenous antibiotics in the neonatal period (16.4% vs 6.9%, P=.01), although there were no differences in chorioamnionitis or in proven neonatal infections. Women receiving misoprostol were less likely to have postpartum hemorrhage than those receiving oxytocin (1.9% vs 6.2%, P=.05).nnnCONCLUSIONnOral misoprostol does not offer any advantage in time from induction to vaginal delivery or risk of cesarean section.

The effect of processing and cryopreservation on nucleated umbilical cord blood cells

Abstract Recovery of nucleated cord blood cells after storage in liquid nitrogen was evaluated. Red cells were depleted using Ficoll-Paque™ or Puregene® red cell lyses. Freeze Medium contained 10% dimethylsulfoxide and 20% serum for cryoprotection. Recovery of the original cell population remaining serviceable for fluorescence activated cell sorting (FACS) was 12 ± 10% (average ± standard deviation), with a range of 1% to 55%. Viability measured by FACS analysis after freezing was significantly lower than that of the same specimens prior to freezing, 62 ± 20% compared to 91 ± 11% (p < 0.001). Percentage CD45+34+ cells were the same for fresh and frozen cells. Gestational age at which specimens were collected had no effect on the percent cells carrying the CD45+34+ markers. We conclude that better cryoprotective supplements are needed to insure consistent high recovery of viable nucleated umbilical cord blood cells after preservation in liquid nitrogen.

De novo translocation (8;12) and frontofacionasal dysplasia in a newborn boy

We describe a newborn boy one of triplets, whose karyotype was 46,XY, t(8;12)(q22;q21). Prenatal diagnosis of multiple craniofacial anomalies had been made. Following delivery, the patient was thought to exhibit findings consistent with a diagnosis of frontofacionasal dysostosis. We hypothesize that one of the break points of this translocation may involve a gene essential to craniofacial development.

Acog’s 1999 VBAC guidelines: a survey of western massachusetts obstetric services

Abstract Objective: ACOG Practice Bulletins provide management standards for obstetric and gynecologic services. The recent ACOG guidelines for vaginal birth after cesarean (VBAC) (Number 5, July 1999) are controversial concerning hospital VBAC policy. We surveyed all western Massachusetts obstetric services regarding their VBAC policy. Methods: A survey regarding procedure rates and VBAC policy was presented to chiefs of western Massachusetts obstetric services and the data summarized. Results: All services completed the survey. Of the approximately 8,000 annual deliveries performed in western Massachusetts, 18.5% are cesarean. From 1994, all services reported a decline in overall cesarean rate and an increase in VBAC rate. All institutions reported an unchanged primary cesarean rate, except for the only level 3 center surveyed, where it rose slightly. Regarding recent ACOG VBAC guidelines, five of six services were aware of the new guidelines. Fifty percent describe “immediately available” as cesarean delivery initiated within 30 minutes and 50% as within 15 minutes. Sixty-seven percent describe “physician availability for cesarean delivery” as anesthesia coverage in-hospital and 33% as anesthesia coverage on labor and delivery. The only service mandating an obstetrician’s attending presence during VBAC trials is the tertiary care center due to residency training. Five of six services have anesthesia availability in hospital, but not specific to labor and delivery. Conclusions: The recent ACOG VBAC guidelines were inconsistently interpreted among the services surveyed. At these institutions, declines in cesarean deliveries are due to the increase in VBAC trials. While failure to incorporate guidelines could increase liability for institutions, strict implementation may discourage VBAC trials and increase cesarean deliveries by as much as 50%. In our opinion, closer review of data regarding VBAC complication rates is necessary to develop workable guidelines applicable to institutions of all levels.

Beckwith-Wiedemann Syndrome: Prenatal Ultrasonic Diagnosis and Clinical Implications

The Beckwith-Wiedemann syndrome (BWS) is a complex congenital disorder with omphalocele, macroglossia, and gigantism as its most common neonatal features. However, in individual cases, the phenotypic expression of this condition is variable. Antenatal diagnosis in previously unsuspected cases depends upon the identification of a number of specific ultrasonic findings. We report a case in which the antenatal diagnosis of BWS was made, and review the previously described cases, noting the specific ultrasonic findings that suggest the correct in utero diagnosis.

Chorioangioma: An Atypical Ultrasonic Presentation

Chorioangiomas are common, benign placental tumors that rarely result in perinatal compli- cations unless large or strategically located. A characteristic ultrasonic appearance usually permits easy diagnosis. In the current case, an atypical chorioangioma was observed in close proximity to the cord insertion, leading to diagnostic difficulties. The clinical implications of chorioangiomas and their differen- tial ultrasonic diagnosis are discussed.