Onco-developmental protein concentrations in the sera of patients with ovarian cancer prior to treatment.

Eight onco-developmental proteins have been measured in the serum of women prior to their operation and treatment for ovarian cancer. Alpha-foetoprotein, CEA, hCG and PAPP-A were not often elevated whereas CPAP, SP1, CanAg 50 and CA 125 were. Many of our findings differed from those of previous workers, possibly due to differences in clinical material and analytical technique. We conclude that large profiles of tumour markers are no longer of use in the investigation of ovarian cancer. At the present time we think that CA 125 could prove the most useful marker in the investigation of ovarian cancer.

Preliminary observations on the application of carcino-placental alkaline phosphatase to the investigation of patients with seminoma of the testes.

Suitable tumour markers for monitoring the treatment of seminoma of the testis have not yet been established in clinical practice. Carcino-placental alkaline phosphatase (CPAP) has been suggested for this purpose but it is difficult to detect and specifically analyse this enzyme. We have devised an immunoenzymatic method of analysis in which cross-reactions with liver type and intestinal alkaline phosphatase are minimal and we have applied this test to seven patients with histologically proven seminoma. CPAP was raised in 4 patients prior to treatment and chorionic gonadotrophin in two of these. Alpha-fetoprotein was normal in all cases. We conclude that the use of CPAP in monitoring treatment of testicular seminoma is worthy of further attention.

Lack of comparability between CEA analyses using three different methods.

Three different methods for the assay of carcinoembryonic antigen were investigated--radioimmunoassay, enzyme-linked immunoassay, and a commercial immunoradiometric assay. Two standard preparations of CEA were used: the 1st British Standard (73/601) and a commercial preparation obtained as a component of the IRMA kit. Serum samples were assayed by each method against each standard material. Significant differences between results were obtained when the different methods were compared. When using the two standards in the same assay system no significant differences were found between results. A possible explanation and the implications of these findings for the routine assay of CEA are discussed.

Obstetric aspects of the use in pregnancy-associated hypertension of the beta-adrenoceptor antagonist atenolol.

The obstetric implications of the use of the beta-adrenoceptor antagonist atenolol have been evaluated in a prospective, randomized, double-blind, and placebo-controlled study involving 120 women with pregnancy-associated hypertension. The clinical interpretation of antenatal and intrapartum cardiotocographs was uninfluenced by atenolol. Human placental lactogen concentration fell in the atenolol group, but this was not an indicator of subsequent fetal distress. Other obstetric indices, such as urinary estriol excretion, were the same in both groups. Spontaneous premature labor occurred in five women receiving placebo but in none who received atenolol. Together with previously reported findings on pregnancy outcome, our study leads us to conclude that beta-blockers such as atenolol can appropriately be used in the management of hypertension during pregnancy.

The predictive value of three pregnancy-associated proteins in the detection of the light-for-dates baby.

Three pregnancy-associated proteins, human placental lactogen, pregnancy-specific beta 1-glycoprotein and pregnancy-associated plasma protein-A have been measured in two groups of pregnant women. One group subsequently gave birth to children of normal birthweight, the other group were all delivered of a child with a birthweight less than the 10th centile. From the results obtained the values of the tests in predicting intrauterine growth retardation have been calculated. Human placental lactogen proved to be the most useful of the tests compared in predicting intrauterine growth retardation in the individual patient.

An ELISA for pregnancy-associated plasma protein A.

An enzyme-linked immunoassay for pregnancy-associated plasma protein A is described. The assay is sensitive (7.6 IU/l) and precise (overall CV varied between 8.9% and 10.8%). Recovery was 100% over the working range. Parallel behaviour was observed between the International Reference Preparation 78/610 and pregnancy serum, thus allowing calibration of a laboratory standard pool against IRP 78/610.

The effect of excess antigen on the enzyme-linked immunosorbent assay of onco-placental proteins.

The time course of the antigen-antibody reaction between human chorionic gonadotrophin, pregnancy specific beta 1 glycoprotein and pregnancy associated plasma protein A and their respective immobilised antibodies has been investigated. All 3 antigens showed enhanced binding with increasing length of incubation up to a maximum value, followed by a decrease. It is suggested that the diminution in binding at high antigen concentration is caused by the solubilisation of the immobilised antigen-antibody complex and that this is promoted by the high concentration of antigen.

Human placental lactogen and pregnancy-specific beta 1-glycoprotein in pregnant diabetic women.

Serum placental lactogen (hPL) and pregnancy-specific beta 1-glycoprotein (SP1) concentrations were measured in 16 insulin-dependent pregnant diabetic women and in 16 non-diabetic control subjects matched for placental weight. hPL concentrations were found to be significantly higher in diabetics with placental weight greater than 90th centile compared with those in (i) non-diabetic controls with placental weight greater than 90th centile and (ii) diabetics with placental weights less than 90th centile. SP1 concentrations were higher in both diabetic groups compared with those in their respective non-diabetic controls, but no difference existed between the two diabetic groups. In the control subjects infant birthweights were lower in the women with small placentae, but no such difference was observed between the two diabetic groups.

Kernicterus at low levels of serum bilirubin: the impact of bilirubin albumin-binding capacity. A 10-year retrospective survey.

A retrospective survey of neonatal post-mortems over a 10-year period was made to establish the incidence of kernicterus and the associated laboratory abnormalities. Cases with evidence of kernicterus without hyperbilirubinaemia were found to have significantly lower reserve albumin-binding capacity (RABC) than the control group. The results suggest that RABC estimation is a necessary adjunct in the assessment of the jaundiced, low birthweight neonate.

Pregnancy specific beta 1 glycoprotein: a comparison of analysis by radioimmunoassay and enzyme linked immunosorbent assay observations on patients with malignant teratoma of testis.

A comparison of serum pregnancy specific beta 1 glycoprotein analysis by enzyme linked immunosorbent assay and radioimmunoassay has been made. Excellent correlation was obtained between the two methods but radioimmunoassay was found to be more precise and to have a lower detection limit than enzyme linked immunosorbent assay. Using the more sensitive radioimmunoassay system, 2 out of 10 control male sera were found to contain detectable levels of pregnancy specific beta 1 glycoprotein. Sequential results are presented on patients with diagnosed malignant teratoma of testis who were undergoing chemotherapy.

Enzyme-linked immunoassay for placental lactogen in human serum.

We describe an enzyme-linked immunoassay for measuring human placental lactogen (HPL) in serum. After suitable dilution, sera are pipetted into the wells of polyvinyl microtitre plates previously coated with anti-HPL. After incubation the sera are decanted, and replaced by a conjugate of horseradish peroxidase and anti-HPL. An amount of enzyme proportional to the concentration of HPL in the serum is bound to the wells via an antibody--HPL--antibody bridge. Peroxidase activity is measured by oxidation of o-phenylenediamine, the resulting color being related to the concentration of HPL. Results correlate well with those by radioimmunoassay (r = 0.96). Our between-assay coefficient of variation was 13%; no discernible effect of protein was observed. This 4-h assay can be used to monitor placental function in pregnancy.

Serum enzymes in colorectal cancer.

A study of the value of serum enzymes in 184 patients with colorectal cancer has been performed. The enzymes studied were gamma glutamyltransferase (gammaGT), alkaline phosphatase (AP), lactate dehydrogenase (LDH), 5'-nucleotidase (5'-NT), glutathione reductase (GR), alanine and aspartate transaminases. In patients without liver metastases, elevated enzyme levels were found in 11-55% preoperatively. 5'-NT showed the least number of elevated activities, while gammaGT activities were increased in 29% and LDH in 55%. The percentage of elevated enzyme levels rose significantly in the early postoperative period. Patients with liver metastases showed increased enzyme activities in 40-60% preoperatively: gammaGT was the most sensitive indicator. Increased enzyme activity was related to the degree of liver involvement with secondary tumor. With extensive liver metastases, gammaGT levels were increased in 82%. It is concluded that serum enzymes are of limited value in the preoperative detection of liver metastases, and particularly when tumor involvement of the liver is small.

The quantitation of pregnancy specific beta 1-glycoprotein by enzyme linked immunoassay.

A rapid enzyme linked immunoassay for pregnancy specific beta 1-glycoprotein is described. The method is sensitive and precise (within batch C.V. = 6.5-7.4%) and should be suitable for the biochemical monitoring of pregnancy and the investigation of patients suffering from various malignancies.

Enzyme multiplied immunoassay of phenobarbital by LKB reaction Rate Analyser: a comparison with analysis by gas-liquid chromatography.

A procedure for the enzyme multiplied immunoassay of phenobarbital using the LKB Reaction Rate Analyser is described. The temperature optimum, linearity, specificity, and precision of the assay are reported. A highly significant correlation coefficient is obtained when the technique is compared with gas-liquid chromatography by analysing human sera containing a range of phenobarbital levels.