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High-dose intravenous IgG for the treatment of severe rhesus alloimmunization.

The value of intravenous immunoglobulin (IVIG) in the treatment of 24 severely Rh-sensitized pregnant women was studied. IVIG was infused at a daily dose of 0.4 g/kg maternal body weight for 4-5 consecutive days, and was administered again 15-21 days later until delivery, depending on the evolution of the hemolytic disease. Our population was divided into 3 groups according to the time of onset of therapy: group 1 (n = 8), before 20 weeks' gestation; group 2 (n = 7), 20-28 weeks, and group 3 (n = 9), after 28 weeks. Initial mean anti-D level was significantly higher in group 1 (25.9 +/- 12.9 IU/ml) than in the other 2 groups, whose mean values were, however, higher than 10 IU/ml. Amniotic-fluid total bilirubin levels before the onset of therapy were pathologic, and in 55% of the cases they coincided with zone 3 of Liley's chart. Hydrops fetalis at the onset of treatment accounted for the only 3 fetal deaths in groups 1 and 2. None of the fetuses developed hydrops during treatment. Six of the 9 neonates in group 3 were depressed at birth (1-min Apgar below 7). However, at 5 min only 1 newborn showed an Apgar below 7. Mean birth weight was over 2,500 g in all the cases. Neonatal hematological condition in group 2 (50% of the babies required only phototherapy) was better than in the other 2 groups (transfusional therapy). There was a significant fall in maternal anti-D titers and intrauterine hemolysis after IVIG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Mid-trimester fetal ultrasound: diagnostic dilemmas.

Two cases are reported in which an unusual ultrasound finding preceded diagnostic amniocentesis and led to further work-up. In both cases a decision was made to terminate the pregnancy. One fetus in which a neck mass was detected by ultrasound was shown to be normal on post-mortem examination. The second fetus was aborted because of Rh sensitization and had the abnormality seen by ultrasound. However, this lesion, calcified intrahepatic plaques, had no presumed pathological significance. These cases suggest caution in the interpretation of results obtained with the new technologies used for prenatal diagnosis.

Abortion, Therapeutic↗

Nonstressed fetal heart rate monitoring in the antepartum period.

The role of nonstressed monitoring of the fetal heart rate (HR) in determining fetal well-being during the antepartum period was assessed in 125 high-risk patients. Observations on HR, variability, and HR response to fetal movement (FM) and uterine contractions (UC) over a 30 minute period were made with an external microphone and tocotransducer. A total of 625 tests were performed; the earliest gestation tested was 28 weeks, and the latest was 46 weeks. A reactive pattern (variability greater than 6 b.p.m. and accelerations with FM) appears to be a reliable indicator of fetal well-being. All the 51 fetuses exhibiting this pattern survived. This group also had the lowest incidence of neonatal complications. On the other hand, of the babies who failed to show variability greater than 6 b.p.m. or accelerations with FM (nonreactive pattern), 40% died in the perinatal period. Thirty-five patients showed features of both a reactive and nonreactive pattern (combined pattern). Poor outcome in this group was confined to those in whom the majority of the pattern was nonreactive. An undulating HR pattern with virtually absent variability (sinusoidal pattern) was found in 20 Rh-sensitized fetuses, 50% of whom died in the perinatal period. Bradycardia and tachycardia were not found to be reliable signs of fetal distress antepartum. Of the 12 fetuses who died during observation, six showed late decelerations with spontaneous UC but all showed diminished variability. The close correlation between nonstressed patterns and neonatal outcome demonstrated by this preliminary study warrants further use of this technique for fetal evaluation.

Female↗

Amniotic fluid phosphatidylglycerol in diabetic and control pregnant patients at different gestational lengths.

Phosphatidylglycerol (PG) and lecithin/sphingomyelin (L/S) ratios were simultaneously determined in 1770 samples of amniotic fluid. PG was defined as "present" when it appeared in at least 2% of the total phospholipids. Comparison of the appearance of PG in samples of amniotic fluid obtained from diabetic and nondiabetic pregnant patients according to L/S ratios showed that samples from diabetic patients were less likely to have PG present than those from nondiabetic patients, particularly at L/S ratios between 3.1 and 4.0. Because of that, further studies compared the appearance of PG according to gestation in 186 diabetic patients with that in a group of 238 control patients that was composed only of those who underwent repeat cesarean section. Rh-sensitized patients were not included in the control group, since they had delayed appearance of PG. The results showed that the appearance of PG was delayed in patients with Classes B, C, and D-F-R diabetes. In patients with Class A diabetes, the appearance of PG was not significantly different from that in control patients over the entire gestational period, although the appearance of PG may be delayed during early gestation. In contrast, there were no significant differences in L/S ratios in various classes of diabetic pregnant patients and control patients at different gestations.

Adult↗

Utility of HLA and six erythrocyte antigen systems in excluding paternity among 500 disputed cases.

Six erythrocyte antigen systems and the HLA system were evaluated to establish their practical value in 500 cases of disputed paternity. The actual results were very close to predicted values. HLA testing is expected to detect 92% and red cell testing is expected to detect 67% of men falsely accused in paternity suits. The findings of this study show that HLA detected 94% and red cell testing detected 69% of 107 men falsely accused in 500 paternity cases. In order of sensitivity, Rh, MNSs, and ABO were the most useful erythrocyte marker systems. There were six out of 107 cases in which exclusions would have been undetected if red cell typing had not been performed. Five of the six cases involved "common" HLA haplotypes.

ABO Blood-Group System↗

Maternal-fetal conditions necessitating a medical intervention resulting in preterm birth.

OBJECTIVE: The objective of the study was to evaluate the extent to which maternal and fetal conditions necessitate medically indicated preterm birth. STUDY DESIGN: A population-based, retrospective, cohort study of women who delivered a singleton live birth at 20 weeks or longer in Missouri, 1989 to 1997 was performed (n = 684,711). Maternal-fetal conditions that necessitated iatrogenic preterm birth included preeclampsia, small-for-gestational-age birth, fetal distress, placental abruption, placenta previa, unexplained vaginal bleeding, pregestational and gestational diabetes, renal disease, Rh sensitization, and congenital malformations. We examined the association between each of the aforementioned conditions and risk of medically indicated preterm birth at less than 35 weeks. Medically indicated preterm birth was defined as a labor induction or a prelabor cesarean in the absence of premature rupture of membranes at preterm gestations. Adjusted relative risk with 95% confidence interval for preterm birth was derived from multivariable logistic regression models, and population attributable fractions were calculated. RESULTS: The preterm birth rate (less than 35 weeks) was 4.6% (n = 31,238), with 23.5% (n = 7,347) of such births being medically indicated. Preeclampsia, fetal distress, small-for-gestational-age, and placental abruption were the most common indications for a medical intervention resulting in preterm birth, with at least 1 of these conditions present in 53.2% of medically indicated preterm births and in 17.7% of term births (relative risk 4.9, 95% confidence interval 4.7, 5.2). CONCLUSION: Preeclampsia, fetal distress, small-for-gestational-age, and placental abruption, conditions that are associated with ischemic placental disease, are implicated in well over half of all medically indicated preterm births. Although the etiology of preterm birth is heterogeneous, it is reasonable that ischemic placental disease may serve as an important pathway to preterm birth.

Abruptio Placentae↗

Cholesteryl palmitate as a predictor of fetal lung maturity.

Cholesteryl palmitate was measured by thin-layer chromatography in 98 amniotic fluid samples obtained from pregnancies ranging from 15 to 40 weeks. Pregnancies complicated by diabetes mellitus or Rh sensitization were excluded. Cholesteryl palmitate concentration increased with gestational age from values less than 5 micrograms/ml at 15 weeks to maximum values of 384 micrograms/ml at term. Seventy-three patients were delivered of their infants within 24 hours of sampling. The mean concentration of cholesteryl palmitate for 55 infants without respiratory distress syndrome was 123.70 +/- 12.21 micrograms/ml (SD). For neonates that developed respiratory distress syndrome (n = 18), the mean concentration was 22.66 +/- 6.16 micrograms/ml (SD). This difference is significant (p less than 0.001). For all patients delivered, respiratory distress syndrome was not seen when the cholesteryl palmitate concentration was greater than 41 micrograms/ml (mean + 3 SD). All infants with a concentration below 38 micrograms/ml developed respiratory distress syndrome. We conclude that measurement of cholesteryl palmitate concentration in amniotic fluid might be another reliable method of assessing fetal lung maturity and may often improve specificity when compared with other tests of fetal lung maturity.

Amniotic Fluid↗

Leukocyte esterase activity in amniotic fluid: normal values during pregnancy.

Chorioamnionitis during pregnancy is a common diagnostic dilemma for the obstetrician. Fast and accurate diagnosis poses the most significant problem. Since leukocytes are known to be released in response to infections, examination of amniotic fluid for their presence is an important part of the evaluation for chorioamnionitis. These neutrophils contain several esterases that are not present in serum, urine, or vaginal secretions. The esterases are not influenced by bacteria or by commonly used drugs. We have previously described the reliability of leukocyte esterase (LE) activity for the detection of chorioamnionitis in term pregnancies uncomplicated by other diseases. A prospective study was performed to assess the presence or absence of LE activity to establish normal values in amniotic fluid at various gestational ages prior to term before its use as a possible predictor for chorioamnionitis. Sterile amniotic fluid specimens were obtained from 13 patients undergoing second trimester genetic amniocentesis (with gestational ages varying from 15 to 19 weeks) and from 11 patients with a wide variety of medical problems, undergoing amniocentesis for Rh sensitization or lung maturation studies (with gestational ages ranging from 25 to 27 weeks). All patients with ruptured membranes or preterm labor were excluded. Each amniotic fluid sample was divided into two parts, one of which was transported to the laboratory for aerobic and anaerobic cultures and the other used for LE activity detection as measured by dipstick. The LE results were retrospectively compared with the results of the cultures. LE activity was always found to be negative when the culture results were negative. negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

Percutaneous umbilical blood sampling in the management of Kell isoimmunization.

As the use of Rhesus immune globulin has decreased the incidence of Rh sensitization, other red blood cell antigen systems have become relatively more common. The most common of these is the Kell antigen, which often produces unexpectedly severe fetal disease. High-resolution ultrasound was used to guide in the sampling of fetal blood directly from the umbilical cord as an aid in the management of these patients.

Adult↗

Leucocyte alkaline phosphatase activity during high risk pregnancies.

142 determinations of leucocyte alkaline phosphatase (LAP) activity have been done in 103 cases of high risk pregnancy. A statistically significant elevation of LAP score has been found in high risk pregnancies due to diabetes mellitus, toxaemia, renal diseases and third trimester haemorrhage, but not in pregnancies complicated by cardiac disease, chronic hypertension, Rh sensitization or anaemia.

Alkaline Phosphatase↗

Male-female differences in the cytotoxic activity of human monocytes in vitro.

The cytotoxic activity of human monocytes towards anti-D-sensitized Rh(D)-positive red cells in vitro was studied in relation to the age and sex of healthy monocyte donors. It was found that cytotoxic activity of monocytes from young females (age range 18-40 years) was significantly less than that of monocytes from age-matched males, irrespective of the use of oral contraceptives. No such difference was found between monocytes from older males and females (age range 43-63 years). The cytotoxic activity of monocytes from the two latter groups of donors was similar to that of young males. In the presence of cytochalasin B, which enhances the cytotoxic activity of monocytes, no male-female difference was detected, indicating that the maximal cytotoxic capacity of monocytes from young females is similar to that of monocytes from young males. We have previously presented evidence that the cytotoxic activity of monocytes is mediated by lysosomal enzymes released by these cells. These present data suggest that the reduction in cytotoxic activity of monocytes from young females might be a result of a reduced lysosomal enzyme release which is possibly related to the in vivo action of female sex hormones. However, we were not able to detect an inhibitory effect of oestrogens and progestagens on cytotoxic activity of monocytes from males in vitro.

Adolescent↗

Rheumatoid vasculitis.

Today, we cannot conclude comments on the treatment of immune-complex disease without paying our respects to therapeutic plasmapheresis and leukapheresis. Numerous centers are beginning to examine the value of removing either plasma or lymphocytes from patients with many rheumatic diseases. Efficacy appears to be established in hyperviscosity diseases (Waldenstrom's), myasthenia gravis, Goodpasture's syndrome, RH sensitized pregnant mothers, and thrombotic thrombocytopenic purpura. In active rheumatoid arthritis, it is a useful short-term tool but hardly cost effective. Although it would appear to be an advance from the medieval concept of purging out the "evil humors," pheresis for rheumatoid vasculitis must be considered a limited research tool, which may teach us something about mechanism of action. The mechanical removal of immune complexes by pheresis probably requires additional remittive or immunosuppressive therapy to prevent rebound in immune complex production. Effort now need to be directed to the agents that initiate production of immune complexes. Once the host's antibody system is so stimulated, we often find ourselves trying to close the barn door after the horse is long gone.

Adrenal Cortex Hormones↗

Inhibition of immune phagocytosis by human sera with HLA A, B, C and DR but not with DQ or EM type reactivity.

613 sera from pregnant women were investigated for inhibition of immune phagocytosis (IPI) by monocytes exposed to anti-D (Rh)-sensitized human red blood cells. IPI was detected in 42 (26%) of 165 and in 78 (17%) of 448 sera assessed against monocytes from 15 or 5 panel donors, respectively. All IPI-positive sera reacted in an allotypic pattern. Eight IPI-positive sera tested with autologous monocytes were found to be nonreactive. Upon comparative analysis of 448 sera, a significant correlation was found between the specific patterns of IPI and lymphocytotoxicity by HLA antibodies. In addition, 13 sera (4%) were positive for IPI, but not for lymphocytotoxicity. Twenty IPI-positive sera were tested by indirect immunofluorescence against platelets and T lymphocytes and revealed IgG antibodies in 16 and 11 sera, respectively. IPI activity could be removed from 8 out of 10 positive sera by platelet pool absorption. While virtually all sera exhibiting HLA, A, B or C-like activity (cytotoxicity with all cells) or HLA DR-like activity (exclusive cytotoxicity with B lymphocytes and monocytes) were IPI-positive, IPI was infrequently observed with sera containing HLA DQ-like activity (cytotoxicity with B lymphocytes only). IPI was also rarely seen with sera cytotoxic only to monocytes and not at all with sera containing antibodies against endothelial/monocyte antigens. We conclude that IPI is caused by cytotoxic as well as noncytotoxic HLA A, B, C, DR-specific antibodies. This effect may bear significance for the maternal immune response against fetal antigens and may be useful for pretransplant histocompatibility testing.

Adult↗

Sinusoidal heart rate pattern: Reappraisal of its definition and clinical significance.

OBJECTIVES: To address the clinical significance of sinusoidal heart rate (SHR) pattern and review its occurrence, define its characteristics, and explain its physiopathology. BACKGROUND: In 1972, Manseau et al. and Kubli et al. described an undulating wave form alternating with a flat or smooth baseline fetal heart rate (FHR) in severely affected, Rh-sensitized and dying fetuses. This FHR pattern was called 'sinusoidal' because of its sine waveform. Subsequently, Modanlou et al. described SHR pattern associated with fetal to maternal hemorrhage causing severe fetal anemia and hydrops fetalis. Both Manseau et al. and Kubli et al. stated that this particular FHR pattern, whatever its pathogenesis, was an extremely significant finding that implied severe fetal jeopardy and impending fetal death. UNDULATING FHR PATTERN: Undulating FHR pattern may be due to the following: (1) true SHR pattern; (2) drugs; (3) pre-mortem FHR pattern; (4) pseudo-SHR pattern; and (5) equivocal FHR patterns. FETAL CONDITIONS ASSOCIATED WITH SHR PATTERN: SHR pattern has been reported with the following fetal conditions: (1) severe fetal anemia of several etiologies; (2) effects of drugs, particularly narcotics; (3) fetal asphyxia/hypoxia; (4) fetal infection; (5) fetal cardiac anomalies; (6) fetal sleep cycles; and (7) sucking and rhythmic movements of fetal mouth. DEFINITION OF TRUE SHR PATTERN: Modanlou and Freeman proposed the following definition for the interpretation of true SHR pattern: (a) stable baseline FHR of 120-160 bpm; (b) amplitude of 5-15 bpm, rarely greater; (c) frequency of 2-5 cycles per minute; (d) fixed or flat short-term variability; (e) oscillation of the sinusoidal wave from above and below a baseline; and (f) no areas of normal FHR variability or reactivity. PHYSIOPATHOLOGY: Since its early recognition, the physiopathology of SHR became a matter of debate. Murata et al. noted a rise of arginine vasopressin levels in the blood of posthemorrhagic/anemic fetal lamb. Further works by the same authors revealed that with chemical or surgical vagotomy, arginine vasopressin infusion produced SHR pattern, thus providing the role of autonomic nervous system dysfunction combined with the increase in arginine vasopressin as the etiology. CONCLUSION: SHR is a rare occurrence. A true SHR is an ominous sign of fetal jeopardy needing immediate intervention. The correct diagnosis of true SHR pattern should also include fetal biophysical profile and the absence of drugs such as narcotics.

Arrhythmias, Cardiac↗

Timing of cord clamping revisited.

Although cord cutting has been performed since the beginning of mankind, the timing and advantages of early versus delayed cord clamping are still controversial. Early cord clamping (within the first 30 s after birth) is usually justified for potential prevention of postpartum hemorrhage and for immediate treatment of the newborn, but at the same time, may increase Rh-sensitization. Delayed cord clamping is performed after a period of 30 s during which 'placental transfusion' of approximately 80 mL of blood occurs. This amount seems to protect the baby from childhood anemia without increasing hypervolemia-related risks. In preterm infants, delayed clamping appears to reduce the risk of intraventricular hemorrhage and the need for neonatal transfusion. Obtaining cord blood for future autologous transplantation of stem cells needs early clamping and seems to conflict with the infant's best interest. Although a tailored approach is required in the case of cord clamping, the balance of available data suggests that delayed cord clamping should be the method of choice.

Anemia, Iron-Deficiency↗

HCS, estriol and oxytocinase in maternal serum and neonatal condition in high risk pregnancies.

In order to find a reliable index of fetal wellbeing, maternal estriol, hCS and oxytocinase levels were related with condition of the neonate. Fifty six high risk pregnancies were studied. Estriol and hCS were determined by specific radioimmunoassay and oxytocinase with a colorimetric method. The condition of the newborn was evaluated by the APGAR score. Neonates were divided into two groups, depressed (APGAR score 0-6) and vigorous (APGAR score 7-10). When the mean birthweights of both groups were statistically different, maternal estriol levels were corrected to avoid the influencing factor of newborn weight. Mean maternal estriol level corresponding to vigorous newborns was 46.73 ng/ml. This value was statistically higher than that corresponding to the group of depressed newborns, which was 26.25 ng/ml (Fig. 1). The mean birthweight of depressed infants (2,382.75 g) was statistically lower than that of the vigorous group (3,044.75 g). The corrected mean maternal estriol values of vigorous neonates (45.44 ng/ml) was different from that of depressed ones (25.14 ng/ml) (Fig. 2). When patients were divided according to maternal diseases (diabetes, vascular pathology, Rh sensitization) serum estriol levels of the mother were statistically different according to the Apgar score of the newborns. There was no significant difference between serum hCS and oxytocinase levels of mothers with depressed and vigorous newborns. Discarding fetal weight as an influencing factor in maternal hormone level, our results indicate the suitability of maternal serum estriol determinations to predict condition of the newborns in high risk pregnancies.

Aminopeptidases↗

Disease versus disease: how one disease may ameliorate another.

Systemic disease, either genetic or acquired, may prevent or decrease the severity of another disease. These observations have led to important therapeutic advances. The best-known examples are Edward Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's 1942 observation that erythrocyte disorders such as thalassemia and sickle cell disease modify the severity of malaria. Patients with and carriers of cystic fibrosis may have genetic resistance to tuberculosis and/or secretory diarrhea. The beneficial effects of undernutrition have led to therapeutic diets for seizures, celiac disease, type 2 diabetes, and inflammatory bowel disease. Finasteride for prostatic hypertrophy was developed after the observation that patients with male pseudohermaphrodism resulting from 5-alpha-reductase mutations do not develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic disease prevention followed the observation that ABO incompatibility prevented Rh sensitization. The natural immunosuppression of measles may cause remission of nephrosis, and that of leprosy prevents psoriasis. Patients with one form of agammaglobulinemia (X-linked) never get Epstein-Barr virus infection, and patients with another form (common variable) are seemingly cured by HIV infection. HIV/AIDS is prevented or modified by co-receptor mutations (notably the CCRDelta32 chemokine mutation), HIV-2, or GB virus C infection. Additional exploration of these genetic, infectious, and metabolic influences on disease severity may provide new therapeutic approaches to HIV and other diseases.

Disease↗

[The identification of high-risk pregnancy, using a simplified antepartum risk-scoring system].

This study was carried out to assess the problems with the pregnant women, and check out the risk-factors in the high-risk pregnancies, using a simplified antepartum risk-scoring system, which was revised from Edwards' scoring system to be suitable for Korean situation. This instrument was included 4 categories, demographic, obstetric, medical and miscellaneous factors. This survey was based on the 1300 pregnant women who were admitted, from Jan. 1, 1988, to May 31, 1990, Chung Ang Medical Center. Data were collected from June 25, 1990 to July 7, 1990. Data was analyzed by x2-test, F-test, Pearsons correction, using statistical package SAS in NAS computer system, KIST. The results of the study were as follows; 1. 1313 infants were deliveried of these 560 infants (42.7%) were born to mothers with risk-scores greater than 7, and 753 infants (57.3%) were born to mothers risk-scores less than 7. 2. Maternal age, parity, education level, of the demographic factors were significant relation statistically to identify the high risk pregnancies (X2 = 20.88, 42.87, 15.60 P less than 0.01). 3. C-section, post term, incompetent cervix, uterine anomaly, polyhydramnios, congenital anomaly, sensitized RH negative, abortion, preeclampsia, excessive size infant, premature, low birth weight infant, abnormal presentation, perinatal loss, multiple pregnancy, of the obstetric factors were significant relation statistically to identify the high risk-pregnancies. (chi 2 = 175.96, 87.5, 16.28, 21.78, 9.46, 8.10, 6.75, 22.9, 64.84, 6.93, 361.43, 185.55, 78.65, 45.52, P less than 0.01). 4. Abnormal nutrition, anemia, UTI, other medical condition (pulmonary disease, severe influenza), heart disease, V.D., of the miscellaneous and medical factors, were significant relation statistically to identify the high risk-pregnancies. 5. Premature, low birth weight infant, contracted pelvis, abnormal presentation, of the risk factors were significantly related with Apgar score at 1 & 5 minute after birth and neonatal body weight. 6. Apgar score at 1 & 5 minute after birth and neonatal body weight were significantly negative correlated with risk-score. 7. There were statistically significant difference between risk-score and Apgar score at 1 & 5 minute after birth, 3 group (0-3, 4-6, above 7), and neonatal body weight, 2 group (below 2.5 kg, the other group) (F = 104.65, 96.61, 284.92, P less than 0.01). 8. Apgar score at 1 & 5 minute after birth (below 7), and neonatal body weight (below 2.5 kg), were significant relation statistically with risk score. (chi 2 = 65.99, 60.88, 177.07, P less than 0.01) were 60.8%, 60%.(ABSTRACT TRUNCATED AT 400 WORDS)

Apgar Score↗