Package insert for rhesus immune globulin.
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Drug Labeling↗
Biomedical subjects
Kenneth J Moise
Publications and source records attributed to Kenneth J Moise.
Arginine flux and nitric oxide production during human pregnancy and postpartum.
OBJECTIVE: To compare second-trimester, third-trimester, and postpartum arginine flux and nitric oxide production using infusions of the stable isotope L-[(15)N(2)]-arginine in normal human gestation. METHODS: Kinetic measurements were made in pregnant volunteers with uncomplicated singleton gestations in mid gestation, late gestation, and more than 8 weeks postpartum. A bolus of 4.95 micromol/kg of labeled arginine was administered, followed by an infusion at 4.95 micromol/kg per hour for 6 hours. The isotopic enrichment of plasma arginine and nitrite or nitrate (NO(x)) was determined by gas chromatography, mass spectrometry, or both. We used the Kolmogorov-Smirnov test for normality, repeated-measures analysis of variance, and Newman-Keuls test. P <.05 denoted statistical significance. RESULTS: The rate of turnover of the intravascular NO(x) pool was significantly higher in mid gestation compared with late gestation and almost reached statistical significance when compared with postpartum values (6.2 +/- 0.9 versus 4.3 +/- 0.8 [P <.02] versus 3.7 +/- 2.1% pool/hour; P =.08). Arginine flux was significantly higher in early compared with late gestation and postpartum (107.8 +/- 13.9 versus 72.5 +/- 16.1 versus 82 +/- 8.8 micromol/kg per hour, respectively; P <.01). CONCLUSION: Arginine and nitric oxide production is higher in mid gestation. This suggests a role for nitric oxide in early cardiovascular adaptation in human gestations.
Adolescent↗
Maternal-fetal surgery for spina bifida: on the brink of a new era?
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Female↗
The role of fetal breathing motions compared with gasping motions in pulmonary airway uptake of intra-amniotic iron dextran.
OBJECTIVE: We hypothesized that normal fetal breathing, not acute asphyxial gasping, results in the movement of iron dextran from the amniotic cavity into the fetal lungs. In addition, the amount of iron dextran moving into the fetal lungs is cumulative with time. STUDY DESIGN: Twelve pregnant New Zealand White rabbits at 25 days of gestation were sedated and underwent ultrasound-guided injections of iron dextran into the amniotic cavities of the rabbit fetuses in both horns of each pregnant doe. Oxygen saturation was maintained at >90% in the pregnant does. The 12 does were then equally assigned to four groups on the basis of the duration of fetal exposure to the dextran (0, 8, 16, and 24 hours). At the end of each time point, one half of the fetuses received an intracardiac injection of potassium chloride to induce gasping just before necropsy. Gasping was confirmed by ultrasound scanning. At necropsy, the fetal lungs were evaluated grossly and underwent histomorphometry for iron distribution and quantification in the fetal airways. RESULTS: In the animals that received iron dextran, there was no significant difference in iron accumulation at any time point between those animals that did and did not receive potassium chloride, which suggests that acute gasping does not increase the accumulation of amniotic fluid substances in the lungs. The amount of iron in the fetal airways increased significantly with progressive length of exposure. CONCLUSION: We conclude that normal fetal breathing, not acute asphyxial gasping, resulted in the movement of intra-amniotic iron dextran into the fetal lungs and that the amount of substances that move into the fetal lungs accumulated with time.
Amniotic Fluid↗
Minimizing red blood cell contamination while isolating mononuclear cells from whole blood: the next step for the treatment of severe hemolytic disease of the fetus/newborn.
OBJECTIVE: We examined whether mononuclear cell purification of human blood could be done while minimizing contamination with RhD-positive red blood cells to treat hemolytic disease of the fetus/newborn that was caused by rhesus disease. STUDY DESIGN: Whole blood from 16 individuals who tested rhesus positive was diluted and centrifuged over a Ficoll gradient. The cell pellet was incubated with red blood cell lysis buffer, divided into three samples, and analyzed for cell count, mononuclear cell yield, and RhD-positive red cell contamination by flow cytometry. RESULTS: Mean RhD-positive red cell contamination was 0.24% (range, 0%-1.9%). The average yield of mononuclear cells was 11.5% (range, 1.8%-23.6%). Through regression analysis, 34 to 180 mL of paternal whole blood would be necessary to achieve an antigen load that is sufficient for an HLA antibody response. CONCLUSION: Purification of human blood is possible to produce reasonable mononuclear cell yields with minimal rhesus activity, which makes paternal leukocyte therapy a plausible treatment for severe rhesus alloimmunization.
Blood Component Removal↗
Management of rhesus alloimmunization in pregnancy.
Hemolytic disease of the newborn secondary to rhesus alloimmunization was once a major contributor to perinatal morbidity and mortality. Today, rhesus immune globulin has markedly decreased the prevalence of this disease so that only one to six cases occur in every 1000 live births. The rarity of this condition warrants consideration of consultation or referral to a maternal-fetal medicine specialist. Once sensitization occurs, rhesus immune globulin is no longer effective. Evaluation for the presence of maternal anti-D antibody should be undertaken at the first prenatal visit. First-time sensitized pregnancies are followed with serial maternal titers and, when necessary, serial amniocenteses to detect fetal bilirubin by DeltaOD(450). In cases of a heterozygous paternal genotype, new deoxyribonucleic acid techniques now make it possible to diagnose the fetal blood type through amniocentesis or even from plasma/serum deoxyribonucleic acid analysis. When there is a history of an affected fetus or infant, maternal titers are no longer diagnostic as a screening test. Serial peak middle cerebral artery velocities using Doppler ultrasound can be used in these pregnancies to detect fetal anemia. In some situations, intrauterine transfusion is necessary through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. Perinatal survival rates of more than 90% have been reported; hydrops fetalis reduces the chance for a viable outcome by up to 25%. Immediate neonatal outcome is complicated by the need for repeated transfusions secondary to suppressed erythropoiesis. Long-term studies have revealed normal neurologic outcomes in more than 90% of cases. Future therapy will involve selective modulation of the maternal immune system making the need for intrauterine transfusions a rarity.
Amniocentesis↗
Paternal leukocyte alloimmunization as a treatment for hemolytic disease of the newborn in a rabbit model.
OBJECTIVE: The purpose of this study was to evaluate maternal alloimmunization to paternal leukocytes as a treatment for hemolytic disease of the fetus/newborn in a rabbit model. STUDY DESIGN: Twelve does and paired red blood cell-incompatible bucks underwent the experimental protocol. Fetal hematologic parameters that were obtained by ultrasound-guided intracardiac sampling were compared from unaffected, compatible litters; from affected, incompatible litters (after alloimmunization to red blood cell antigens); and from affected, incompatible litters after alloimmunization to paternal leukocytes. Generalized estimation equations were used for statistical analysis. A probability value of <.05 was considered significant. RESULTS: Six of 12 does had at least one affected litter after alloimmunization to paternal leukocytes. After an adjustment for the mating cycle, the fetuses of does that underwent white blood cell immunization exhibited higher hemoglobin and hematocrit levels (beta = 4.6, P <.001, and beta = 11.6, P =.006, respectively) compared with the fetuses of does that were immunized only to red blood cells. CONCLUSION: Maternal alloimmunization to paternal leukocytes decreases the severity of hemolytic disease and may play a role in the treatment of severe hemolytic disease of the newborn in humans.
Animals↗
Longitudinal assessment of the middle cerebral artery peak systolic velocity in healthy fetuses and in fetuses at risk for anemia.
OBJECTIVE: Our purpose was to assess the feasibility of longitudinal assessment of the middle cerebral artery peak systolic velocity (MCA-PSV) to predict fetuses who will have severe anemia. STUDY DESIGN: Doppler measurement of MCA-PSV was serially performed in 15 healthy fetuses (99 measurements; range: 4-9 per fetus), 8 fetuses who were mildly anemic (41 measurements; range: 3-10 per fetus), and 11 who were severely anemic (50 measurements; range: 2-7 per fetus) at their first cordocenteses. Linear models were fitted to the data from individual fetuses and the slopes were determined. The average rate of change (slope) of MCA-PSV as a function of gestational age in the 3 groups was calculated from these data. Estimated average slopes were computed using restricted maximum likelihood. F tests were used for hypothesis tests, with the degrees of freedom based on the Kenward and Roger approximation. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). A P <.05 indicated statistical significance. RESULTS: Gestational age at the time of the Doppler studies ranged from 15.1 to 41 weeks in the healthy fetuses. It was between 15 and 33.4 weeks in the fetuses who became anemic. The estimated average slopes increased with the degree of anemia (P =.03). The difference in mean slope between the severely anemic sample and the healthy sample was statistically significant (estimated difference = 2.2, SE =.65, P =.01). The difference in mean slope between the mildly anemic and healthy samples was not statistically significant (estimated difference = 1.1, SE =.06; P =.08). CONCLUSIONS: We have demonstrated that the MCA-PSV slope is an excellent tool for identifying those fetuses who will become severely anemic and, therefore, need to be followed up more closely during the pregnancy. Our findings expand the clinical applications to which Doppler ultrasonography can be applied in monitoring pregnancies at risk for fetal anemia.
Anemia↗