The determination of human placental lactogen (HPL) for hormonal supervision in late pregnancy

In the serum of 145 women between the 34th and 42nd weeks of pregnancy, 209 radioimmunological determinations of human placental lactogen were made, using the Pharmacia, Uppsala, Sweden, HCS Phadebas Test. Following the determination of normal HPL levels in late pregnancy, the HPL values of high-risk pregnancies were investigated in relation to normal values and compared with the clinical pattern. A satisfactory relation was found between low HPL levels and fetal growth retardation. To some extent the HPL data can also be used in monitoring severe EPH-gestosis and postmaturity. Light cases of gestosis and pregnancies involving Rh-incompatibility do not affect HPL production. The clinical findings regarding HPL levels should not be overestimated in attempting to diagnose placental insufficiency.     

Immunoperoxidase localisation of human placental lactogen: a marker for the placental origin of the giant cells in ''syncytial endometritis'' of pregnancy

Various common C4 gene products were isolated from serum by immunoprecipitation. After reduction the C4 alpha-, beta-, and gamma-polypeptide chains were studied by two-dimensional electrophoresis. Isoelectrofocusing was performed in the first dimension and sodium dodecyl sulphate polyacrylamide gradient gel electrophoresis in the second. The charge differences behind the electrophoretic C4 polymorphism were shown to reside in the 95,000-u (atomic mass units) alpha-chain. Charge variation closely mirroring the alpha-chain differences were also found in a 49,000-u fragment of the alpha-chain, most probably C4d. The basic beta-chain could not be studied in detail, but no differences were observed with regard to molecular weight or charge of the gamma-chains of the different C4 gene products.     

The diagnostic and prognostic value of immunophenotyping in acute leukemia

Immunophenotyping with monoclonal antibodies to leucocyte differentiation antigens has an established diagnostic role in the laboratory investigation of acute leukemia. In the vast majority of cases, a hemopoietic lineage can be confidently assigned; namely, acute myeloid leukemia (AML), or the precursor-B and precursor-T variants of acute lymphoblastic leukemia (ALL). The areas of greatest practical importance are in morphologically difficult or undifferentiated cases, and in distinguishing between the major variants of precursor-B and T-ALL. Cases with aberrant patterns of marker expression (acute mixed lineage leukemia, lineage infidelity) are frequently encountered in both ALL and AML, and can lead to diagnostic confusion. However, correlation with morphology and other clinicopathologic features, and careful consideration of the weight of phenotyping evidence almost always allows the correct lineage to be identified. The prognostic value of phenotypic information in acute leukemia is generally limited. Recognition of the major variants of ALL is still of clinical importance, but the significance of myeloid antigen positivity in ALL is controversial, and may not have prognostic value. Patterns of myeloid antigen expression in AML have limited prognostic significance, while the relationship between lymphoid antigen expression and treatment response in AML remains highly controversial. Careful evaluation of the predictive power of immunophenotype in large controlled clinical trials in acute leukemia is still required.     

Effect of ionic environment on the release of human placental lactogen in vitro

The in vivo and in vitro metabolism of (3H)-5alpha-androstane-3lapha,17beta-diol by the male rat anterior pituitary was studied. A rapid and intensive conversion of 5alpha-androstane-3alpha, 17beta-diol into 5alpha-dihydrotestosterone was demonstrated, since following a 30 min. incubation time, 73% of the recovered radioactivity were constituted by 5alpha-dihydrotestosterone. Studies on the subcellular distribution of steroids showed that 5alpha-dihydrotestosterone was the main steroid recovered except from the 105,000 X g pellet. From in vivo and in vitro experiments it was concluded that the transformation of 5alpha-dihydrotestosterone into 5alpha-androstane-3alpha, 17beta-diol was a reversible process, and that this last steroid could exert its biological action mainly via 5alpha-dihydrotestosterone.     

Circulating thyroid hormone concentrations and placental thyroid hormone receptor expression in normal human pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR)

Thyroid hormones are critical to growth and development of the human fetus. Abnormal placental development, a major cause of intrauterine growth restriction (IUGR), is associated with a high perinatal mortality and morbidity. Thyroid status has been postulated to play a role in the pathogenesis of such morbidity. In the present study, we have investigated fetal thyroid function and placental expression of thyroid hormone receptor (TR) alpha and beta variants during normal human pregnancy and in pregnancy associated with IUGR. Measurement of free thyroid hormones and TSH concentrations revealed significant rises in free T4 and free T3 between the second and third trimesters of normal pregnancy. Serum concentrations of free T4 and free T3 were lower in fetuses affected by IUGR, although serum TSH levels were not significantly different. Immunocytochemistry demonstrated the presence of TR alpha1, alpha2, and beta1 proteins within the nuclei of trophoblast and stromal placental cells. Immunostaining for these TR variants increased with increasing gestation in normal placenta. Comparison of IUGR placental samples with normal samples revealed greater immunostaining for TR alpha1, alpha2, and beta1 variants in IUGR. Examination of pretranslational expression of TR alpha1, alpha2, beta1, and beta2 variants by semiquantitative RT-PCR revealed increasing expression of TR alpha1, alpha2, and beta2 messenger RNAs with increasing gestation in normal pregnancy, which "mirrored" post-translational expression. However, and in contrast, there were no significant differences in expression of TR messenger RNAs in normal and IUGR placenta. The present findings of reduction in serum free thyroid hormones and increased expression of TR alpha and beta proteins in association with IUGR highlight the potential importance of thyroid status in influencing long-term fetal outcome in this condition.     

The lecithin/spingomyelin quotient as determined using a modified method and human placental lactogen in the amniotic fluid

Thirty amniotic fluid samples in late gestational age were analysed for HPL-values and the L/S-ratio. The pregnant women used in this study were healthy except three patients who developed a rh-incompatibility. The amniotic fluid was only obtained by abdominal amniocentesis. We found a decreasing tendency of the HPL-values in late pregnancy. The L/S-ratio increased. A significant correlation of both values could not be observed. In all three cases of rh-incompatibility the decrease of HPL and the increase of the L/S-ratio occurred obviously earlier and steeper. Further studies will prove the significance of these results.     

The maternal and fetal levels of human chorionic gonadotropin, human placental lactogen and prolactin during the perinatal period (author's transl)

The levels of human chorionic gonadotropin (HCG), human placental lactogen (human choriosomatomamotropin HCS) and prolactin (PRL) were determined in the serum of 72 maternity patients and the serum of the newborn infants. The determinations were done with radioimmunologic tests (RIA). These three protein hormones were also determined in the amniotic fluid and in the maternal serum from 4-6 days prior to the delivery of the infant. The concentration of HCG or HCS in the serum of the newborn infants was a mean 0.43 or 0.37% of the level in the maternal serum. The concentration of PRL in the serum of the newborn was 118% and slightly higher than in the serum of the mothers. The concentration in the amniotic fluid was 1.5% for HCG, 5.8% for HCS, and 252% for PRL, compared to the corresponding levels in the maternal serum. The fact that the hormone concentrations in the amniotic fluid are significantly higher than in the serum of the newborn suggests excretion of the hormones from the fetal circulation via the fetal liver and the fetal kidney. The high levels of PRL in the maternal and the newborn serum may be caused by the high concentrations of estrogen or progesterone. Increased during the course of the pregnancy there was a significant sex linked difference in the level of HCG in the maternal serum correlated to the sex of the newborn infant.     

The diagnostic value of serum lysozyme activity in inflammatory bowel disease

The inferior alveolar nerve was cut or the vessels entering the mandibular canal were damaged in 39 guinea pigs at 10 days of age. Possible changes in the incisors were recorded during a 100-day observation period whereafter the animals were killed and the skulls freed of soft tissues; at this time, 35 skulls were found suitable for further examination. The changes in the mandibular incisors on the operated side became observable 30-40 days post-operatively as discolourization, a 'trauma line' around the tooth, narrowing of the tooth or total loss of it's visible part. In the guinea pigs with the nerve cut (group A), such signs of maldevelopment were seen in 5 out of 19 animals, whereas the corresponding figure for the animals with the damaged vessels (group B) was 14/16. All incisors in group A and 13 out of 14 in group B recovered from the state of maldevelopment; one animal in group B showed complete loss of the incisor. The molar region was examined only from the cleaned skulls. In group A, the first molar was deformed in two animals; in group B, seven animals displayed either maldevelopment of the first molar or the first and second molar or complete loss of the first molar. No malformation of the third molar was observed. With two exceptions, the deformation or loss of molars occurred in combination with incisor maldevelopment. The malformations were considered to result from a disturbed blood supply. In group A, the dental changes may perhaps be ascribed to a short-term interference with the blood supply during the operation. The variable results in group B seem to imply that the mandibular teeth receive at least part of their blood supply from vessels besides those entering the mandibular canal. The innervation appears to have a subordinate role in the restoring of the morphology of continuously erupting teeth.     

Plasma levels of oestriol-17 beta, oestriol and human placental lactogen during bed rest

Plasma unconjugated oestradiol-17 beta, total oestriol and human placental lactogen levels were measured in twelve healthy volunteers admitted for bed rest in the last trimester of pregnancy. No significant alteration in levels was observed.     

Ionized and total serum calcium and parathyroid hormone in hyperthyroidism

Total and ionized calcium concentrations as well as parathyroid hormone levels were measured in a group of hyperthyroid persons. Ionized and total calcium levels were elevated in 21 of 45 (47%) and in 12 of 45 (27%) thyrotoxic patients, respectively. Mean ionized and total calcium levels were higher in these 45 patients than in normal persons. Using two different radioimmunoassay systems for a total of 44 determinations, mean parathyroid hormone levels were lower in thyrotoxic patients than in subjects with proved hyperparathyroidism. These data suggest that [1] elevations of both ionized and total calcium concentrations occur frequently in thyrotoxic patients; [2] ionized calcium concentrations may be elevated in a higher percentage of hyperthyroid subjects than are total calcium concentrations; and [3] the hypercalcemia associated with thyrotoxicosis is not associated with elevated parathyroid hormone levels.     

Undetectable maternal serum unconjugated estriol levels in the second trimester: risk of perinatal complications associated with placental sulfatase deficiency

OBJECTIVE: Our purpose was to determine the prevalence of undetectably low second-trimester maternal serum unconjugated estriol levels and the association with increased perinatal morbidity or mortality in pregnancies at risk for placental sulfatase deficiency. STUDY DESIGN: Nine centers in New England identified singleton pregnancies with undetectably low unconjugated estriol levels. Each unexplained case was matched with four controls; pregnancy outcome information was sought. RESULTS: Among 130,295 pregnancies surveyed, undetectably low unconjugated estriol levels were identified in 167 (13/10,000). Explanations included fetal death (53), overestimated gestational age (50), nonpregnancy (12), and chromosome abnormalities (5). The 41 unexplained cases were compared with 163 matched controls. Male offspring were more frequent (85%) among cases than among controls (55%). Although rates of perinatal complications were not significantly different, primary cesarean sections occurred about twice as often among cases. No perinatal deaths occurred. CONCLUSIONS: Neither severity of symptoms nor perinatal morbidity or mortality currently warrant routine interpretation of unexplained undetectably low unconjugated estriol levels as a marker for placental sulfatase deficiency.     

Left ventricular hypertrophy; differences in the diagnostic and prognostic value of electrocardiography and echocardiography

OBJECTIVE: To compare the electrocardiogram (ECG) and the echocardiogram for demonstration of left ventricular hypertrophy (LVH) and the prognostic values of these methods. DESIGN: Literature study. SETTING: Department of General Practice, Social and Nursing Home Medicine, R.C. University of Nijmegen, the Netherlands. METHOD: Using articles retrieved by means of a search action in Medline (1962-January 1996), a study was made of the differences between determination of LVH by ECG and by echocardiography with regard to the sensitivities and specificities for measuring anatomical LVH, and their predictive values concerning cardiovascular morbidity and mortality. RESULTS: The sensitivity of echocardiography for the prediction of anatomical LVH (88-93%) exceeded that of ECG (21-54%), while both methods had a high specificity (77-97%). ECG-LVH seemed a better predictor of cardiovascular complications than echo-LVH. CONCLUSION: Echocardiography is the better instrument for screening for LVH, but ECG should keep its place in the diagnostics of LVH in view of its high predictive value for morbidity and mortality and its availability to primary health care. In regard to LVH, echocardiography measures only morphological disorders, while ECG also detects functional disorders.     

Culture of first-trimester and full-term human chorionic villus explants: role of human chorionic gonadotropin and human placental lactogen as a viability index

In long-term cultures of human chorionic villus explants, the viability of the tissue must be controlled to ensure the reliability of functional studies. Ionic levels (pH), gas concentrations (pO2, pCO2) and metabolic markers (glucose, lactate) in the culture medium are often utilized. Analyses of hormone, enzyme and protein levels are also frequently used to estimate viability. The purpose of this study was to evaluate whether in vitro release and immunoreactivity of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) were correlated with the viability of first-trimester and full-term chorionic villus explants as determined by histopathology. Villus explants of first-trimester and full-term pregnancies were incubated in 6-well plates of RPMI medium which was supplemented with 10% fetal calf serum. Incubations were performed for 10 days, and the plates were kept at 37 degrees C under a water-saturated atmosphere containing 5% CO2 and 95% O2. The medium was replaced every day and samples of supernatant were frozen for later testing of hCG (first trimester) or hPL (full term), glucose consumption and lactate production. The tissue was also fixed and embedded for light-microscopic examination and immunocytochemistry. The hCG release remained stable during 6-7 days at a high level before decreasing, whereas hPL release decreased during the first 5-6 days then stabilized at a relatively low level. Only hCG kinetics were significantly different between tissue incubated with and without cycloheximide or iodoacetic acid. Both hCG and hPL immunoreactivity were not significantly different between tissue cultures with, and without, addition of cycloheximide or iodoacetic acid and even with morphological evidence of trophoblast and endothelial necrosis. The immunoreactivity for both hormones remains highly positive when the significant release has stopped, and does not reflect the tissue viability.     

Changes in estriol excretion in the urine and kidney function during Partusisten infusion

In a random controlled trial the effects of a betamimetic infusion (Fenoterol 2 micrograms/min) on the estriol excretion and the renal function were analysed in 30 patients in the 28.-34. weeks of pregnancy. It was stated that the estriol excretion in urine during the Partusisten infusion significant decreases (from 663 micrograms/2 h to 376 micrograms/2 h, i.e. to 56%). The diuresis and the creatinine-clearance showed a significant diminishing too (from 218 ml/2 h to 154 ml/2 h and from 131 ml/min to 88 ml/min). The decrease of estriol excretion is caused on the one hand by the diminution of GFR, on the other by a direct effect of betamimetics on the kidney. From the results obtained in this study the following consequences can be drawn: 1. The determination of urinary estriol during tocolytic treatment is not a suitable method for the monitoring the fetoplacental unit. 2. Applying the tocolysis in an infusion a possible reduction of water intake and a strict control of water balance is of great importance. 3. The betamimetic therapy in patients having an impaired renal function can be applied only with great precaution.