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Rh immunoglobulin use with placenta previa and abruptio placentae.

Patients with obstetric hemorrhage from placenta previa or abruptio placentae may be at increased risk of Rh sensitization because they fail to receive Rh immunoglobulin (RhIG) or are given an inadequate dose. To evaluate the use of RhIG in this clinical situation, we studied 498 patients with hemorrhage from placenta previa or abruptio placentae treated at a large municipal hospital from 1975 to 1979. All 25 RhIG candidates received the product before their discharge from the hospital. This rate of RhIG use was equal to that for patients whose infants were delivered without these complications and significantly higher than that for patients with spontaneous abortion and ectopic pregnancy at the same hospital (P less than .05). Prompt administration of an adequate dose of RhIG to candidates with bleeding from placenta previa or abruptio placentae can further reduce Rh hemolytic disease.

Abortion, Spontaneous↗

The incidence of significant fetomaternal hemorrhage in patients undergoing cesarean section.

To determine the incidence of fetomaternal hemorrhage in patients undergoing cesarean section, Kleihauer-Betke tests were performed in the immediate postoperative period on 199 parturients. Some degree of hemorrhage was detected in 18.5% of patients, with 2.5% demonstrating greater than 30 ml of fetal blood. Comparison of groups on the basis of indication for cesarean delivery revealed no difference in rates of fetal hemorrhage. Because patients with greater than 30 ml of fetal blood would not be adequately protected from Rh sensitization by the standard 300 micrograms dose of Rh immune globulin, we recommend screening all Rh-negative patients undergoing cesarean section for the presence of significant fetomaternal hemorrhage.

Cesarean Section↗

[Hemosorption in the prevention of severe forms of hemolytic disease of the newborn in rhesus sensitization].

A total of 164 hemoperfusions were administered to 60 pregnant patients with Rh sensitization and a history of perinatal death of the newborns from hemolytic disease. Hemoperfusion was found to decelerate the progress of hemolytic disease of the newborns promoting delivery of babies with more benign forms of the disease. The method efficacy was 76%. Dynamic follow-up of fetal functional status over the course of hemosorption treatment by examinations of biophysical profiles and ultrasonic dopplerometry has shown no negative effects of this treatment modality on fetal status.

Adult↗

Hypothalamic, pituitary, testicular, and secondary organ functions and interactions during the sexual maturation of the male rat.

Puberty in the male rat is a complex process that involves maturational changes in the hypothalamus, pituitary, testes, and secondary sexual organs and in their interrelationships. During the course of sexual maturation the negative feedback control systems for the gonadotropins become less responsive to testosterone while the testes become more responsive to LH. In the immature rat testosterone can potentiate the effect of LH--RH on pituitary LH release; this response is lost with sexual maturation. LH--RH sensitizes the mature male pituitary glands for subsequent LH--RH administration; this self-priming effect is not present in the immature rat. The responsiveness of the secondary organs to testosterone is also altered with age, as is the relative proportion of testosterone and androstendione secreted by the testes. Experiments designed to prevent or mimic the transition in testicular steroid secretion suggest that it may be a critical component of sexual maturation in the male rat. An elevation in androstendione appears to be capable of delaying the maturation of the LH negative feedback system, the prostate gland, and the LH--RH self-priming effect.

Androstenedione↗

Prevention of Rh hemolytic disease of the newborn.

Rh(o)(D)-Immune Globulin was given to 322 Rh-negative women delivered of ABO-compatible, Rh-positive infants with no apparent failures to suppress Rh sensitization. In contrast, 32 of 305 mothers of a control group made Rh antibody during the six months following delivery. In subsequent pregnancies, 69 women administered RhoGAM had no evidence of isoimmunization after delivery while six of forty mothers of the control study produced anti-Rh. RhoGAM, given within 72 hours of delivery in the amounts employed, was effective for suppression of Rh immunization.

Erythroblastosis, Fetal↗

Radioimmunoassay for luteinizing hormone releasing hormone in plasma.

A sensitive and specific double antibody radioimmunoassay has been developed capable of measuring LH-RH in extracted human plasma. Thyrotropin releasing hormone, lysine vasopressin and most of LH-RH analogues did not appear to affect the assay. Hypothalamic extract and some of the LH-RH analogues produced displacement curves which were parallel to that obtained with the synthetic LH-RH. Sensitivity of the radioimmunoassay was about 3 pg per assay tube. The coefficient of variation of intraassay was 6.4%, while that of interassay was 9.6%. Exogenous LH-RH could be quantitatively extracted by acidic ethanol when varying amounts of synthetic LH-RH were added to plasma. Immunoreactivity of LH-RH was preserved in plasma until 2 hr in the cold and gradually reduced thereafter. The plasma levels in LH-RH were 20 pg/ml or less in normal adults and not detectable in children. The aged males over 60 yr and postmenopausal women showed a tendency to have higher levels of plasma LH-RH. Plasma LH-RH level was significantly higher in midcycle than in follicular and luteal stages. The disappearance rate of LH-RH from the circulation after intravenous injection could be represented as half times of 4-6 min. Between 0.2-0.4% of the injected dose was excreted into urine within 1 hr. These results indicate that the determination of LH-RH might be a useful tool for elucidating hypothalamic-pituitary-gonad interactions.

Adolescent↗

The effect of rheumatoid factors and of antigobulins of immune hemolysis in vivo.

Studies were undertaken in man and in the rat comparing the effects of rheumatoid factors and immune antiglobulins on red cells sensitized with incomplete antibodies. The interaction of immune antiglobulins with sensitized red cells produced (a) agglutination in vitro and (b) an accelerated sequestration of the sensitized cells in vivo. In contrast, rheumatoid macroglobulins, although capable of agglutinating Rh-sensitized red cells in vitro, did not modify their destruction in vivo. The failure of rheumatoid factors to function as antiglobulins in vivo appears to reflect their non-reactivity with sensitized cells in whole serum. It is suggested: (a) that the native (7S) gamma globulins of plasma competitively inhibit rheumatoid factors from reacting with fixed antibody in the blood stream; (b) that if these macroglobulins do indeed have pathogenetic activity, this may be limited to body fluids of low protein content.

Animals↗

Monocyte monolayer assay: an efficient noninvasive technique for predicting the severity of hemolytic disease of the newborn.

The authors performed monocyte monolayer assays (MMAs) with the use of normal donor monocytes, and homologous reagent red blood cells, sensitized in vitro, with antibodies in maternal sera. The sera were from 16 pregnant women with Rh antibodies, drawn at the time of amniotic fluid analysis. They compared the predictive value (PV) of the MMAs and the delta OD 450 of amniotic fluid in forecasting the need for transfusing the infant. The PV of the delta OD 450 result in Liley zone mid II-III was 100%, but in zones 0 to low II it was only 60% (13 samples from ten women were in these zones but four babies required transfusion). In contrast, the PV of a positive (greater than 20% reactivity) MMA was 91% (one false positive result) and the PV of a negative MMA was 100%. Thus, the MMA was more efficient than amniotic fluid analysis at predicting hemolytic disease of the newborn severe enough to require transfusion. The noninvasive MMA could be used as a screening test, reducing the number of amniocenteses or ultrasound evaluations performed on Rh-sensitized women.

Amniotic Fluid↗

In vitro effects of a synethetic enkephalin analogue (D-Met2,Pro5)-enkephalinamide on the hypothalamus-pituitary--testis function in rats.

The effects of (D-Met2,Pro5)-enkephalinamide, a synthetic analogue of the natural opioid pentapeptides, were investigated on the hypothalamus-pituitary-testis axis using in vitro tissue and isolated cell incubation systems. (D-Met2,Pro5)-enkephalinamide in a concentration range 10(-7)--10(-5) M did not alter the testosterone production and the troph-hormone sensitivity of the isolated Leydig cells, or the gonadotroph hormone release and the luteinizing-hormone--releasing hormone (LH-RH) sensitivity of the isolated anterior pituitary cells. However 10(-5)--10(-5) M synthetic enkephalin analogue induced a dose-dependent inhibition of LH-RH content and release of the mediobasal hypothalamus, which was prevented by equimolar concentrations of naloxone.

Animals↗

[Prenatal determination of fetal RHD in maternal plasma: two-years experience of routine clinical use].

OBJECTIVES: To evaluate the predictive value of RHD fetal genotype in maternal plasma of Rh D negative mothers after 10 weeks of gestation in a clinical use. MATERIAL AND METHOD: Prospective, comparative study between fetal RHD genotyping in maternal plasma, with amplification of exons 4,5,10 of the RHD gene, by real-time multiplex PCR, and Rh D serology at birth, in 218 pregnancy and their 223 babies, between November 2002 and 2004. RESULTS: Combining the amplification of three exons, the concordance rate of fetal Rh D genotyping in maternal plasma and baby phenotyping at delivery was 100%. Four women whose the babies were Rh D negative were positive for RHD exon 10 during pregnancy. This positivity was, in three cases, correlated with the presence of RHDpsi pseudogene and in last case, with a haplotype Cdes (r's). RHD genotyping was performed for five twin pregnancies. CONCLUSION: Multiplex PCR using maternal plasma provides perfect prenatal prediction of fetal RHD gene. These results confirm that this non invasive procedure is the preferred method for assessing Rh D fetal status in Rh negative mothers. Using this method for two years in routine practice has led us to modify our management scheme for sensitized Rh D-negative pregnant women.

Female↗

Underutilization of Rh prophylaxis in the emergency department: a retrospective survey.

STUDY OBJECTIVE: To determine the practice of emergency physicians with regard to the issue of Rh isoimmunization. DESIGN: A retrospective chart review. SETTING: A university-affiliated tertiary care hospital emergency department. TYPE OF PARTICIPANTS: Pregnant women presenting with a risk factor for Rh sensitization. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-eight patient encounters were analyzed descriptively as to whether they were candidates for Rh immune prophylaxis, and if so, whether it was given. Most (68%) were hospitalized. Of those, all were Rh typed, but two patients were not given Rh immune globulin (RhIG) when indicated. Of those discharged from the ED, most (86%) were not Rh typed, and none was administered RhIG. CONCLUSION: This study demonstrates a need for increased attention to the potential for Rh isoimmunization in patients presenting to the ED.

Abortion, Spontaneous↗

Antenatal prophylaxis of Rh immunization with 250 micrograms anti-D immunoglobulin.

Anti-D immunoglobulin (250 micrograms) was given i.m. to 830 Rh-negative primigravidae and multigravidae round the 32nd to 34th week of gestation. The multigravidae had previously been treated with anti-D immunoglobulin post partum or after abortion and had been followed up serologically after 8 months. Five hundred and twenty-nine of the women delivered Rh-positive infants and received another injection of anti-D immunoglobulin (250 micrograms) within 72 hours of delivery. At the serological follow-up 8 months after delivery 2 women (0.4%) had weak anti-D antibodies by the papain technique. No anti-D could be detected in these 2 women 14 and 20 months, respectively, after delivery. In a previously performed postnatal clinical study with 250 micrograms anti-D immunoglobulin the failure rate was 1.6% (10 out of 645 women). Thus, antenatal prophylaxis significantly (p less than 0.05) reduced the incidence of Rh immunization. The haemoglobin and bilirubin levels in cord blood and capillary blood did not differ in the Rh-positive and Rh-negative infants. Three primiparae (0.2%) had anti-D antibodies at the time of the antenatal injection before delivery. Thus, the antenatal regimen of gestation did not give full protection from Rh immunization. It is suggested that an antenatal injection at the 28th week of gestation would have been more effective, as Rh sensitization during pregnancy has been reported to be more frequent from the 29th week of pregnancy. Since the introduction of postnatal anti-D prophylaxis the Rh immunization occurring during pregnancy accounts for most of the observed failures (2, 4, 5, 14, 20). The efficacy and safety of antenatal injection of anti-D immunoglobulin has therefore been investigated (5, 6, 7). At the Växjö Hospital in Sweden, where the incidence of anti-D antibodies was 1.6% (15), 250 micrograms of anti-D immunoglobulin were given at about 32-34 weeks of gestation from March, 1973, to December, 1977. The results are presented here.

Antibodies↗

Mitochondria in platinum resistant cells.

Based on the previous report showing that mitochondrial (MT) alteration is associated with platinum (Pt) resistance, we have determined how the alternative MT function is involved in Pt cell cytotoxicity particularly in relation to the apoptosis. MT membrane potential (delta psi m) semi-quantitatively assessed by rhodamin 123 (Rh) sensitivity was significantly elevated in acquired Pt-resistant 2008/C13*5.25 cells (C13) established from its parental 2008 cells or known intrinsic Pt-resistant JHOC cells established from ovarian clear cell adenocarcinoma. Laser confocal microscopy of these cells stained with Rh revealed that MT in Pt-resistant cells were distributed in whole cytoplasm with relatively higher fluorescent intensity whereas MT in Pt-sensitive cells were localized in perinuclear space with lower fluorescent intensity. Electron microscopy showed the predominantly condensed MT in which crestal structure was not observed clearly in Pt-resistant cells. Western blot analysis using murine monoclonal anti-Bcl-2 antibody showed more than 5-fold Bcl-2 overexpression in Pt-resistant cells in response to cisplatin treatment. Cytochrome C (CytC) in MT was released from MT into cytoplasm in response to cisplatin treatment in Pt-sensitive cells, whereas up-regulation of CytC level in MT rather than CytC release from MT was observed in Pt-resistant cells. These data are strongly suggesting that changes at MT level would impact on the relative resistance of malignant cells to undergo drug-induced apoptosis.

Adenocarcinoma, Clear Cell↗

Fetal DNA in maternal plasma: emerging clinical applications.

OBJECTIVE: To review the potential clinical diagnostic applications of fetal DNA analysis in maternal plasma or serum for noninvasive prenatal diagnosis and screening. DATA SOURCES: We conducted a MEDLINE search of articles published between January 1970 and March 2000 using the key terms "fetal DNA," "plasma," and "serum." METHODS OF STUDY SELECTION: All 369 articles describing the detection of fetal DNA in maternal plasma were reviewed. RESULTS: The diagnostic use of circulating fetal DNA in maternal plasma is currently limited to genes that are present in the fetus but not in the mother. From a clinical perspective, the most advanced application is for noninvasive detection of fetal rhesus D (Rh[D]) genotype. The results of studies performed by four different groups showed that prenatal diagnosis of fetal Rh(D) status by molecular analysis of maternal plasma or serum is routinely possible beginning in the second trimester. Noninvasive fetal genotyping should be useful for the treatment of sensitized Rh(D)-negative women whose partners are heterozygous for the Rh(D) gene because no further diagnostic or therapeutic procedures are necessary if the fetus is Rh(D) negative. Future clinical applications of fetal DNA may be in its use as a screening test for Down syndrome, preeclampsia, or preterm labor. However, these applications currently rely on the detection of Y chromosomal sequences and consequently are limited presently to male fetuses. CONCLUSION: The recent discovery of high concentrations of fetal DNA in maternal plasma represents a promising noninvasive approach to prenatal diagnosis. Compared with the analysis of the cellular fraction of maternal blood, the analysis of fetal DNA extracted from maternal plasma has the advantage of being rapid, robust, and easy to perform. The fetal DNA detected is limited to the current pregnancy. However, universal fetal gene sequences must be identified that allow analysis of genetic material from both male and female fetuses. Study of fetal DNA in maternal plasma can improve our understanding of fetomaternal biology and physiology. The long-term effects of maternal exposure to relatively high amounts of foreign DNA are unknown but represent an exciting area for future inquiry.

DNA↗

[Monoclonal anti-D antibodies: obtaining and use].

The principles of obtaining monoclonal antibodies against D-antigen of the rhesus system are overviewed. The lines secreting anti-D antibodies are characterized. The strategies for selecting the anti-D producers secreting the antibodies are substantiated, which are useful for developing rhesus-typing diagnostics and preparations to prevent Rh-sensitization.

Animals↗

INDUCTION OF LABOUR FOR PREVENTION OF STILLBIRTH FROM RH HEMOLYTIC DISEASE.

The fate of 80 infants delivered after induction of labour in 72 Rh-sensitized mothers was studied to determine whether the stillbirth rate could be reduced. Labour was induced at 32 to 39 weeks of gestation; the criteria for induction were based on the history of previously affected infants, and a maternal Rh-antibody titre of 1/40 or greater, using an indirect antiglobulin technique. Nine mothers were delivered by Cesarean section. It was estimated that 26 infants were so severely affected as to be unlikely to have survived to term. However, only seven died, and one was stillborn. Two of these would normally have survived, one being Rh-negative. These two cases demonstrated the main danger in this method of management. There was a probable saving of 18 infants. In 22 mothers there was no history of previous delivery of an affected infant; in all 22 the infants survived, though six probably would not have survived to term. In 15 pregnancies in which the mothers had had a previous stillbirth, 12 infants survived. Sixty-seven infants required a total of 116 exchange transfusions. Despite the hazards it is concluded that early induction has an important place in management of Rh hemolytic disease.

Bilirubin↗

High-dose intravenous gamma globulin: does it have a role in the treatment of severe erythroblastosis fetalis?

The role of high-dose intravenous (IV) gamma globulin in the treatment of erythroblastosis fetalis was assessed in five pregnancies with severe Rh (four) or Kell (one) isoimmunization. These women were treated with IV gamma globulin (1.0 g/kg body weight) once a week. In addition, fetal blood transfusions were performed when indicated. In four patients with Rh sensitization, high-dose IV gamma globulin treatment had no apparent effect on the total number of intrauterine transfusions required, the interval between transfusions, or the volume of blood required at each transfusion. The treatment did not prevent fetal hydrops and had no effect on maternal antibody titers. In one patient with Kell sensitization, however, the course of the disease was less severe than anticipated, suggesting that IV gamma globulin treatment may have modified the severity of the disease. We conclude that high-dose IV gamma globulin does not appear to be useful in the treatment of severe Rh disease. Its role in Kell and other types of red-cell isoimmunization deserves further evaluation.

Adult↗