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rat. Serum LH, FSH, and prolactin were measured during the first 8 days (a) of normal pregnancy and (b) lactating pregnancy with “short” and “long” delays in implantation. Of interest was the considerably lower average FSH secretion (506 ng/mI) and high prolactin (PL) (158 ng/ml) during the 8-day experimental period in animals with d.3lay of implantation when compared to the normal pregnant group (FSH = 876 ng/ml; PL = 32 ng/ml). LH concentrations were low throughout the experimental period and there were no significant differences in LH levels among the groups of animals studied. Utilizing highly sensitive methods for the production and detection of short periods of implantational delay, it was demonstrated that FSH and prolactin levels varied inversely with the delay of implantation. Administration of rat FSH (20 �cg NIH-FSH-B-1), rat PL (200 �cg NIH-PL-RP-1), or 20 �cg FSH + 200 ,tg PL on Day 3 of pregnancy to rats with both “short” and “long” delays in implantation confirmed the ability of FSH to stimulate implantation and PL to antagonize the FSH effect. Destruction of ovarian follicles by X-irradiation eliminated the stimulatory activity of FSH in Overcoming implantational delay. The results suggest that (a) FSH is required for induction of itoplantation, (b) the effectiveness of endogenous and exogenous FSH is dependent upon low serum PL concentrations, (c) the activity of FSH is mediated by the ovarian follicles, possibly due to enhanced estrogen secretion.

The content of lipids, cholesterol, and ascorbic acid was investigated in fetuses developing during normal pregnancy and in physiologically mature newborn rabbits, and also in fetuses developing during inhibition of the gestation dominant and in physiologically immature newborn rabbits. The results showed that in the first group the functional state of the adrenal cortex was activated, as shown by a low content of lipids, cholesterol, and ascorbic acid. In a state of increased adaptive motor responses the content of these substances was reduced still further. In the second group (physiological immaturity) their content was considerably increased. It is concluded that normal antenatal development is possible during exposure to natural physiological stress.

Die bei der normalen Schwangerschaft gefundenen Mittelwerte von Antithrombin III im Serum liegen zwischen 14,76 und 18,42 mg/100 ml; damit lassen sie eine deutliche Erniedrigung gegenuber den Normwerten nichtschwangerer Frauen erkennen.

Progesterone metabolism was studied in five pregnant women with intrahepatic cholestasis by determining several free and conjugated epimeric pregnanolones and pregnanediols and their 16α-and 21-hydroxylated derivatives in urine, bile and plasma. Comparison of the steroid profiles of these patients with those of healthy pregnant women showed the following features of intrahepatic cholestasis: (i) Biliary excretion of progesterone metabolites is impaired. 1. (ii) The conjugation of progesterone metabolites changes towards greater sulphate formation. 2. (iii) The metabolism of the steroid moiety of progesterone seems to differ from that occurring in normal pregnancy. These changes are in part attributable to the diminished enterohepatic circulation of steroids and in part to the increased steroid content of the liver cells.

After extraction, unconjugated estrone, estradiol, and estriol were separated with celite chromatography, with methanol-water as stationary phase, and measured by radioimmunoassay (RIA) using an anti-E 1 , 17β-hemisuccinate antibody. Separation of bound from free hormone was achieved by dextran-coated charcoal. The precision of the method is approximately 10 per cent for E 1 and E 3 and 15 per cent for E 2 . Ten women were followed throughout pregnancy. During the first trimester, plasma values of E 1 , E 2 , and E 3 were low; then there was a regular increase of plasma E 1 and E 2 to week 39; estriol showed a biphasic increase. This observation is confirmed by the changes in theE 2 E 3 ratio, which tended to decrease from week 20 to 40 of gestation.

An electron microscopic investigation has been carried out on spiral arteries in placental bed biopsies at the end of normal human pregnancy. The musculoelastic tissue is replaced to a greater or lesser extent by a fibrillar and granular material in which giant cells are found. These cells, by morphologic criteria, are identical to trophoblastic cells while part of the granular and fibrillar material shows the characteristics of fibrin. Furthermore, it is suggested that another part of this fibrinoid material is derived from the degeneration of trophoblastic cells in the spiral artery wall. These structural modifications to the arterial wall are probably the direct consequence of invasion of the wall by trophoblastic cells; they are more pronounced in the decidual than in the myometrial portions of the spiral arteries, but the mechanism of their production is presumably the same for both segments.

Die Konzentration der Immunglobuline IGG, IGM und IGA wurde mittels der einfachen radialen Immunodiffusionsmethode nach Mancini bei Frauen mit normaler Schwangerschaft ab der 13. Woche gepruft. Durch insgesamt 743 Untersuchungen wurde eruiert: die Konzentration von IGG zeigt mit fortschreitender Schwangerschaft eine signifikante Erniedrigung; die Konzentration von IGM liegt am hochsten in der 17.–20. Woche und ist gegenuber diesen Werten zu Ende der Schwangerschaft signifikant erniedrigt. Der Spiegel von IGA zeigt erniedrigte Werte am 5% Niveau zu Ende der Gestation gegenuber der Fruhschwangerschaft.

Presentation of Case A 12-month-old girl was admitted to the hospital because of a thoracoabdominal mass. She was born of a normal pregnancy, labor and delivery and was well until three months before admission, when she began to have diarrhea after each feeding. Elimination of cow's milk and other potential allergens had no effect, and she became increasingly fussy. Three weeks before entry abdominal distention was observed, and the child vomited several times. One week later she was admitted to another hospital. A film of the chest and abdomen (Fig. 1) disclosed a large fusiform mass that appeared to extend . . .

Bei insgesamt 112 Nichtschwangeren, Schwangeren, Kreisenden und Frauen unter Tokolyse wegen vorzeitiger Wehentatigkeit wurde die neuromuskulare Erregbarkeit amMusculus tibialis anterior gemessen, um daraus moglicherweise Ruckschlusse auf die uterine Erregbarkeit ziehen zu konnen.

Summary The clinical value of maternal serum HPL concentrations determined by radio-immunoassay in complicated early pregnancy was studied between the 6th and 20th weeks of pregnancy. The subjects were 203 normally pregnant women and 188 whose pregnancy was complicated by uterine bleeding. In threatened abortion where the pregnancy continued successfully (102 patients) the HPL level was generally similar to that in normal pregnancy and showed a pattern of increase in serial determinations. In complicated pregnancies with an unsuccessful outcome (blighted ovum 19, incomplete abortion 42, and missed abortion 25) HPL values were low and decreased in serial samples. A single HPL determination seemed to be a sufficiently reliable index of viable pregnancy from the 14th week onwards, but before that serial HPL samples would seem to be needed.

Summary Twenty-one healthy pregnant women took part in a serial study in which their 24-hour urinary excretion of glucose was measured during the final weeks of pregnancy, on every day of the first week after delivery where possible, and again at eight weeks post partum. In addition, for the whole of several weeks before delivery and continuously after delivery, every urine sample passed was tested with “Clinistix”. Every woman showed a raised excretion of glucose in pregnancy compared to that at eight weeks after delivery, and the pattern was characteristically intermittent. After delivery there was almost always a rapid fall in glucose excretion which reached non-pregnant levels in all subjects within a week of delivery. The pattern of return to normal throws no light on the phenomenon of pregnancy glycosuria.

Human chorionic somatomammotrophic (HCS) concentrations were measured in the maternal serum and amniotic fluid by means of radioimmunoassay. The HCS ratio of the concentration in the amniotic fluid and maternal serum decreases continuously from the 11th to the 40th week of gestation. This decrease is statistically highly significant. Several hypotheses are discussed to explain this decreasing ratio between the maternal compartment and the amniotic fluid.

The role of circulating maternal free fatty acids (FFA) in regulating serum levels of human chorionic somatomammotropin (HCS) has been studied in normal pregnancy. Depression of FFA levels, induced by nicotinic acid (200 mg.) administration, and elevation of FFA levels, induced by either 10 per cent intralipid or 10 per cent intralipid and heparin, produced no consistent change of HCS concentrations. It is concluded that acute changes in circulating FFA levels are probably not important in the regulation of HCS concentration.

Plasma oestradiol and progesterone levels in peripheral blood have been studied before and during premature labour of unknown aetiology. Hormones were measured by radio-immunoassay using specific antisera. Levels in patients who delivered prematurely were compared with levels measured serially in 33 primigravidae during normal pregnancy and labour.In 19 out of 25 patients admitted in progressive premature labour the plasma oestradiol level was two standard deviations or more above the mean for the control patients of similar gestational age. The mean (+/- S.E. of mean) plasma oestradiol in premature labour was 19.1 +/- 1.1 ng/ml, similar to levels found in labour at term (18.5 +/- 1.4 ng/ml). In contrast, in over 50% of cases levels of plasma progesterone during premature labour lay below the mean for gestation though within the normal range. In six patients studied serially oestradiol levels rose dramatically, high values being detected one to 10 days before the onset of premature labour. Serial progesterone levels gave no consistent trend though one patient showed steadily decreasing values.These studies suggest that the onset of premature labour is preceded by a marked increase in peripheral plasma oestradiol levels, which may be of value not only in the prediction of premature labour but also in its prevention by suppression of the premature oestradiol surge.

Levels of prostaglandin F 2α (PGF 2α ) in the amniotic fluid were determined by radioimmunoassay. Concentrations of the prostaglandin were relatively constant between 15 and 35 weeks' gestation, but an increase was observed after 36 weeks. The rise was continued up to 44 weeks. A still greater elevation of PGF 2α levels was recorded during labour, when the levels were related to the amount of cervical dilatation. Amniotic fluid PGF 2α levels in toxaemia of pregnancy did not significantly differ from those found in normal pregnancy.

One hundred and seventy-two plasma progesterone determinations were performed in normal pregnancy, labor, and the puerperium. One hundred and nineteen of the assays were done on isolated samples; 53 of the assays were done in 11 serial studies. While the concentration of progresterone in peripheral blood increased progressively with advancing pregnancy, no apparent decrease in the hormone level occurred at or near the onset of labor or during its progress. A significant decrease in plasma progesterone one hour after the delivery of the placenta continued to decline to menstrual cycle levels by 72 hours post partum.

Induced maternal hypoxia, using 15 per cent oxygen in nitrogen as a stimulus, causes a predictable pattern of response of the fetal heart rate. In clinically normal pregnancy, the fetal heart rate changes little, if at all, during the stimulation or poststimulation periods. In abnormal pregnancy, the stimulus is augmented by impaired placental function and causes a severe fetal response, clearly reflecting the secondary hypoxic status of the fetal environment. The theoretical basis for the stimulus-effect relationship is discussed. The correlation between test results and subsequent development of fetal distress is presented with the proposal for using this test in the prospective management or investigation of abnormal pregnancies.

Serial plasma estriol determinations were conducted in the third trimester of human pregnancy on 22 normal, 25 diabetic, and 16 toxemic patients. In addition, 10 cases of suspected fetal death were evaluated. In normal pregnancy the levels rise in a generally regular fashion as pregnancy proceeds, increasing about fivefold in the last trimester. However, the individual curves vary considerably. The average plasma estriol level at term is about 27 μg per 100 ml. with a range between 10 and 55. The plasma estriol levels of the diabetic patients (Classes A, B, and C) in good control, were not statistically different from those of the normal patients. The toxemic patients could be classified into three groups according to their estriol levels. Those with severe symptoms and small fetuses had correspondingly low levels. The patients under good control had normal values while three patients with renal involvement superimposed on toxemia had surprisingly high levels. The values for patients with dead fetuses were extremely low. Although a larger number of cases involving fetal jeopardy must be studied before the contribution of plasma estriol determinations toward the improvement of fetal salvage rates can be assessed, the potential advantages of plasma assays over urine assays in this regard are discussed.

1. 1. The fifth reported case of pregnancy occurring in a cretin is presented. 2. 2. Thyroid therapy beginning in childhood is postulated as an explanation for the phenomena of a reasonably normal ovarian function, conception, and eventual delivery of a normal, term, living male infant. 3. 3. It is noted that cretins, ipso facto, are not infertile, and that this fact should be kept in mind by those responsible for the care of these unfortunate people.

Presentation of Case An 18-month-old girl was admitted to the hospital because of a bone lesion. The child was the product of a normal pregnancy and delivery of a mother aged 35 years. The birth weight was 3.3 kg. The child was well until four weeks before admission, when she fell from her crib, without sustaining obvious injury. One week later her mother observed that she limped and took her to a physician, who made a diagnosis of otitis and prescribed ampicillin. Diarrhea developed, and ampicillin was omitted after four days. Two weeks before entry the child became listless and . . .

Summary We are attempting to establish standards as a basis for a quantitative Friedman test. Using these standards, a differential diagnosis between normal pregnancy and hydatidiform mole was attempted in four cases. In two of the moles, definite evidence of a markedly excessive excretion of the substance responsible for the reaction was found. In the other two, such findings were not present. These latter moles did not present the typical pathologic picture; they probably had ceased to grow, or were actually undergoing degeneration. It is our impression, at the present, that the quantitative test, herein described, will be of real value in aiding the diagnosis of an active hydatidiform mole, but that it will be of questionable value in ruling out a mole that has ceased to grow or is undergoing degeneration. The single case of chorionepithelioma does not allow an expression of opinion. The data presented on vomiting of pregnancy would seem to open a new avenue of approach to a possible etiologic explanation of the condition. The presence of an excessive amount of the substance responsible for the reaction in the urine of vomiting, eases has been consistent and has been quite constant as to contrast with the findings in normal pregnancy. The factor of concentration of the urine due to dehydration must, of course, be ruled out. We feel that we are able to eliminate this factor, at least as far as relationship to specific gravity of the urine is concerned. As another link in the chain, we are at present repeating the work as outlined above on blood serum. While there is insufficient evidence to advance a hormonal explanation of the cause of vomiting of pregnancy, the evidence, to date, would seem important enough to warrant continued investigation.

Reported cases of avascular necrosis of the head of the femur associated with pregnancy are rare. Two further cases are presented, and a review of the previously reported cases suggests that other known predisposing causes of avascular necrosis may be incriminated in the aetiology. The possibility that a normal pregnancy may very rarely be associated with avascular necrosis is suggested by one of our patients and receives some support from the previously reported cases.

A versatile radioimmunoassay for serum oestriol in pregnancy has been developed which requires 10 μ| of serum (for total) or 50 μ| (for unconjugated). Selection of the optimum conditions for the hydrolysis of serum oestriol conjugates, the isolation of free oestriol, the displacement of tritiated oestriol by cold oestriol and the separation of the free and bound fractions is described. Total oestriol levels doubled between weeks 34 and 38 of normal pregnancy, very little change occurring in the mean level after the 38th week of gestation. In a random series of pregnancy sera there was a significant correlation between total and unconjugated oestriol.

Presentation of Case* A six-month-old boy was admitted to the hospital because of fever and dyspnea. The child was the product of a normal pregnancy and delivery and weighed 7 pounds, 14 ounces, at...

1. 1. Sixty-six Rh-negative mothers with homozygous Rh-positive husbands or two or more Rh-positive children have been studied in relation to the incidence of obstetric procedures. None of these women had been immunized. Twenty-nine, or 44 per cent, had a history of obstetric incidents other than routine delivery. 2. 2. Twenty-four Rh-negative immunized mothers were likewise studied in relation to the incidence of obstetric procedures. All but one of these mothers had given birth to an erythroblastotic infant. Seventeen per cent of these patients had experienced obstetric procedures other than routine delivery. 3. 3. Rh antiserum titers were found to be misleading in prognosticating the outcome of the present or future pregnancies. 4. 4. Isoimmunization occurs during normal pregnancy in some women and obstetric factors do not seem to influence this process.

SummaryGrowth of the mammary gland of the rat during normal pseudopregnancy was only 18% of the growth found at day 18 of normal pregnancy as measured by DNA. This suggests that the corpora lutea of pseudopregnancy function at approximately one-fifth the level of those in pregnancy. Hysterectomy, which resulted in a 6-day extension of pseudopregnancy, was without effect in the enhancement of mammary gland growth over normal pseudopregnancy. However, the ratio of RNA to DNA in the mammary glands of these animals was raised significantly. The production of deciduomata concomitant with pseudopregnancy resulted in a 9-day extension of pseudopregnancy and a slight increase in mammary gland growth over that of normal pseudopregnancy. It was only 30% of that at day 18 of pregnancy and 76% of that at day 12 of pregnancy when DNA was standardized to body weight.