Arnold Klopper

The clinical significance of pre-operative serum CA 125 in ovarian cancer

In a prospective study of 52 patients with ovarian malignancy followed up for 3–18 months the clinical significance of pre‐operative serum CA 125 as a tumour marker was assessed. In 41 patients with epithelial ovarian cancer, the level of CA 125 correlated well with tumour load as indicated by FIGO stage. All epithelial histological types, including mucinous. released CA 125 although serous and undifferentiated tumours produced quantitatively more antigen. There was, however, no correlation between CA 125 concentration and histopathological grade, nor did CA 125 level appear to be of any prognostic value in epithelial ovarian cancer. Elevated CA 125 levels were also found in patients with sex cord/stromal tumours, Krukenberg tumours, an ovarian sarcoma and a serous carcinoma of low malignant potential.

Diagnosis of early pregnancy by assay of placental proteins

Summary. The plasma concentrations of Schwangerschaftsprotein 1 (SP1) and human chorionic gonadotrophin (hCG) were measured in 22 women before and after conception. In these pregnancies ovulation occurred spontaneously in seven subjects, or followed treatment with either clomiphene citrate (6 subjects), or human menopausal gonadotrophin (hMG) and hCG (6 subjects). The remaining three patients became pregnant after artificial insemination with donor semen. Seventeen of these pregnancies were normal and five were abnormal (3 abortions, 1 ectopic and 1 twin). SP1 could be detected 6–14 days after ovulation in all these patients. In contrast 40 non‐pregnant women gave a negative test for SP1.

ISOLATED HYPOGONADOTROPHIC HYPOGONADISM: A FAMILY WITH AUTOSOMAL DOMINANT INHERITANCE

A family is reported in which isolated hypogonadotrophic hypogonadism is inherited as air autosomal dominant condition with variable expression. In previous familial cases, inheritance was autosomal recessive. Comparison is made with the endocrine and genetic findings in Kallmanns syndrome, which should be considered a separate disorder. There is difficulty in drawing a sharp distinction between hypogonadotrophic hypogonadism and constitutional delay in puberty in this family

Estimation of gestational age by last menstrual period, by ultrasound scan and by SP1 concentration: comparisons with date of delivery

Summary. The date of delivery in 62 normal pregnant women was predicted by last menstrual period, by ultrasound scan and by the serum concentration of Schwangerschaftsprotein 1 (SP1). It was found that SP1 concentration in the first trimester gave as reliable an indication of when labour would occur as did the last menstrual period or ultrasound scan.

ENTEROHEPATIC CIRCULATION OF OESTRIOL: A STUDY OF THE EFFECTS OF AMPICILLIN ON PLASMA OESTRIOL LEVELS

Plasma total oestriol was measured daily before and during ampicillin therapy in five pregnant patients and in eight patients, four of whom were receiving ampicillin, for four days following delivery. Ampicillin caused a fall in plasma oestriol of 25 per cent during the first three days of treatment, thereafter the level remained stable with a lower day‐to‐day variability than in untreated patients. Ampicillin reduced the plasma half life of total oestriol by 60 per cent. This study illustrates how the re‐entry of oestriol from the gut leads to irregular fluctuations in plasma oestriol levels and helps to keep up the plasma concentration of the steroid when inflow from the fetoplacental unit is cut off.

Serum Concentration of Pregnancy Specific and Pregnancy-Associated Proteins in Early Gestation

SummaryPAPP-A, SP1, hCG and α2-PAG were determined in the serum of 17 patients at weekly intervals between 3 and 12 weeks from the last menstrual period; progesterone and 17β-oestradiol concentrations were also measured in the same samples. SP1 and hCG concentrations were consistently found to rise steeply from the first time the proteins were detected. PAPP-A, though detectable in early samples from 9 of the patients, started to rise sharply in all cases between 6 and 10 weeks after LMP. α2-PAG, which was detected in all serum samples, showed no consistent behaviour with advancing pregnancy. In 3 patients, α2-PAG was elevated as early as 3 weeks after LMP, while in others it remained at low levels during the entire interval observed. The correlation between these proteins (except between SP1and hCG) is therefore poor; and their synthesis or secretion seems to be independently controlled.

Observations on the source of pregnancy-associated plasma protein A (PAPP-A)

Summary. Pregnancy‐associated plasma protein A (PAPP‐A) was measured in 26 women before and after hysterectomy. The PAPP‐A concentration declined significantly in 24 of them. It is concluded that the uterus is a source of the protein.

Newly discovered pregnancy‐associated plasma proteins

Placental proteins, many of them secreted into the mother’s bloodstream, are multiplying like a well nourished rabbit. Two years ago the count stood at 10 (Bohn 1980); today it is twice that number. Only three, obscured by mysterious initials, are of immediate clinical interest: Schwangerschafts protein 1 (SP,), pregnancy-associated plasma protein-A (PAPP-A) and placental protein 5 (PP5). Pinning these down is like putting your finger on a blob of mercury. SP, turns out to be, not one but at least two, proteins (Teisner et al. 1978), and the work of the Geneva group now casts doubt on the exclusively placental origin of PAPP-A (Bischof et al. 1982; DuBerg e t al. 1982). The initial investigations on these three proteins have followed a well worn path: what do measurements of their concentration in maternal plasma tell about placental function? The answer is that they do not appear to be any better than assays of placental lactogen or oestriol but that they may give information of a different kind. SP, can be detected very early in pregnancy, within 14 days of ovulation (Grudzinskas et al. 1977). This puts it well into the running as a pregnancy test. Reports on the value of SP, assays for determining the prognosis in threatened abortion have been encouraging (Jandial ef al. 1978). It is likely that this will be the main clinical use for SP, assays, for measurements in a variety of late pregnancy diseases have, in spite of occasional optimistic reports to the contrary, not yielded much that could not be got by clinical common sense. Only in the case of retarded intrauterine growth is the evidence more convincing and even here SP, assays are unlikely to be a substantial improvement on the established parameters. With one curious exception PAPP-A assays are in no

Observations on the dating of pregnancy.

The relationship between the concentrations of placental proteins and the stage of gestation has been examined. Human chorionic gonadotrophin and Schwangerschaftsprotein 1 were measured in two groups of patients: one a group of 13 women studied daily from conception to 21 days after ovulation and the other 43 normal pregnancies studied from 5 to 16 wk gestation. The results of assessment of the stage of gestation as determined by placental protein assay were compared with the dating obtained from last menstrual period and ultrasonic scan. The measurement of placental proteins was at least as accurate as the last menstrual period or ultrasonic scan in determining the stage of gestation.

A study of maternal, retroplacental and umbilical cord estradiol levels in term infants delivered by caesarean section

Unconjugated estradiol (E2) levels were measured in 41 sets of blood from the umbilical cord vein and artery, retroplacental space and peripheral maternal blood at the time of caesarean section. Cord vein E2 levels were higher than the cord artery in the vast majority of cases, showing evidence of fetal abstraction. There was a good correlation between the cord vein and retroplacental levels but no other strong correlation was found between the parameters studied. No effect of parity or fetal sex was found.