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With maternal serum alpha-fetoprotein testing, large numbers of previously "low-risk" patients are now considered high risk and are offered genetic testing. Anecdotally, these patients have been perceived as more highly anxious than other second-trimester patients referred for genetic testing because of advanced maternal age. Thus we have studied patient demographics, true genetic risks, the perceptions of risk, and state (situational) and trait (constitutional) anxiety for these patients and their partners. Significantly increased state anxiety was noted for mothers as compared with fathers both in the group of women referred for testing because of maternal serum alpha-fetoprotein levels and in those referred due to advanced maternal age. State anxiety was increased in the women referred for maternal serum alpha-fetoprotein levels as compared with women referred for advanced maternal age. True genetic risks were comparable between the groups. Some critics have argued that maternal serum alpha-fetoprotein screening engenders unnecessary anxiety. Our data show that patients undergoing genetic testing due to maternal serum alpha-fetoprotein levels have higher state anxiety than women undergoing testing because of advanced maternal age, but that indication is much less a factor than are partner differences. Therefore, increased anxiety after abnormal maternal serum alpha-fetoprotein testing results cannot be reasonably used as an argument against such testing.

We report a prospective study aimed at assessing the value of serum marker determinations in a supposedly healthy population to detect cancer and to identify individuals at high risk. We analyzed a group of 1,611 supposedly healthy subjects attending a cancer detection center, over a 1-5 year period and a control group of 100 cancer patients. Repeated determinations of the following markers were made: CEA, AFP, HCG, beta-HCG, beta 2-M, ferritin, beta 1-SP, all by radioimmunoassay. In the literature, marker determinations are considered not to be useful for cancer screening; in spite of this, we determined "normal" and "suspicious" levels for each marker and were able to define a group "at risk" that may harbor an early cancer (representing 23.6% of the total) and a "normal" group. The cancer detection rate was 45 0/00 (17/378) in the risk group and 3.2 0/00 in the "normal" one (4/1233). Our data show that markers could play a role in cancer screening.

The blood levels of tumour markers (alpha-foetoprotein and human chorionic gonadotropin) were determined and serial chest X-rays were obtained from 11 patients with germ cell tumours to study the growth of the tumours. Assuming an exponential growth pattern, the tumour marker levels and diameters of lung metastases were analysed. The use of a simple model made it possible to describe the time course of the change of tumour marker levels in blood before and during treatment. The analysis provided estimates of doubling times for marker-positive subpopulations, which were generally in accordance with the doubling times for lung metastases. The estimated doubling times had a log-normal mean value of 21.3 days, in agreement with the 19.5 days for embryonic tumours obtained in other studies.

Assays of maternal serum alpha-fetoprotein are subject to the phenomenon of assay drift, which may be defined as incorrect increase or decrease of alpha-fetoprotein values from their true values. Low maternal serum alpha-fetoprotein weekly volume (for example, fewer than 500 specimens per week) will result in a greater than 47% probability that 10% assay drift will not be recognized. Further, laboratory reports to clinicians may lead to either misdirecting 43% more pregnant women (with positive drift) into further (possibly invasive) diagnostic procedures or the offer of further diagnostic services to 32% fewer gravidas at increased risk (with negative drift) than should be so managed. We address the problem outlined above and present the reasons for establishment of regional maternal serum alpha-fetoprotein screening programs operating at sufficient volume to permit the identification and control of assay drift.

Between 1979 and 1982, 69 men with metastatic malignant teratoma completed sequential combination chemotherapy (POMB/ACE). Although two-thirds of these patients initially had advanced and bulky disease, life-table analysis projects a survival of 83%. Multivariate analysis indicates that the strongest predictor of survivals is not the clinical and radiological extent of disease but the initial serum concentration of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP). In patients presenting with HCG levels below 50 000 IU/l and AFP levels below 500 kU/l the survival in 47 patients was 96%. This contrasts with the survival projected at 56% in 22 patients presenting with tumour markers at higher concentrations.

In 1983, a comprehensive programme was introduced to halt the spread of hepatitis B virus (HBV) infection and to reduce mortality from hepatocellular carcinoma (HCC) in Alaskan Natives, in whom the incidence of HBV infection was high. This programme includes: serological screening of all Alaskan Natives; immunisation of susceptible persons, including all newborn babies, with hepatitis B vaccine; and testing HBsAg-positive carriers twice a year for alpha-fetoprotein (AFP) to detect HCC at an early stage. By October, 1986, over 53,000 Alaskan Natives (84% of the total Native population) had been tested for HBV serological markers and 80% of the identified susceptibles had been or were being vaccinated against HBV. After complete immunisation of 90% of the susceptibles in the area with the highest infection rates in Alaska, the annual incidence of acute symptomatic HBV infection decreased from 215 to 14 cases per 100,000 population. After the introduction of AFP screening, the 1-year-case-fatality rate for HCC fell, from 100%, to 50%.

Low maternal serum alpha-fetoprotein values during the second trimester of pregnancy are associated with an increased risk of Down syndrome in the fetus. In this study a sensitive, monoclonal-based radioimmunoassay for alpha-fetoprotein was used to determine whether such an association also applies to the first trimester and if maternal serum alpha-fetoprotein screening could successfully detect a significant number of pregnancies in which the fetus had a trisomy or other chromosome disorder. Sera were obtained prospectively from 540 women just before chorionic villus sampling for prenatal diagnosis of chromosome defects (largely because of advanced maternal age) at 8 to 12 weeks' fetal age and assayed for alpha-fetoprotein under code without knowledge of the cytogenetic results. Eight of 27 (29.6%) of all serious chromosome defects were associated with low maternal serum alpha-fetoprotein values (less than or equal to 0.6 multiples of the median). Overall, 59 of 540 patients (10.9%) had maternal serum alpha-fetoprotein values less than or equal to 0.6 multiples of the median, eight of whom had a fetus with a serious chromosome defect. Women whose maternal serum alpha-fetoprotein value was less than or equal to 0.6 multiples of the median had one in eight odds of carrying a fetus with a trisomy and one in seven odds of the fetus having any serious chromosome defect. From this study of a group of women at higher risk, we conclude that first-trimester maternal serum alpha-fetoprotein screening for chromosome defects is feasible. A prospective study to determine detection efficiency is now required of a consecutive routine pregnancy population in whom gestational age is determined by menstrual dates as is usually the case in clinical practice.

Plasma alpha-feto protein (AFP) levels were measured by radioimmunoassay in 73 women using oral contraceptive pills for varying durations of time. The levels were significantly higher at 6 months of pill use and tended to return to normal after 12 months. In none of the women was plasma AFP higher than 25 ng/ml which is considered to be indicative of liver damage.

Experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE) are animal models of organ-specific autoimmune disease. In this study, BALB/cByJ and BALB/cAnNCr mice were susceptible to both autoimmune diseases whereas BALB/cJ subline mice were resistant. Disease resistance in BALB/cJ mice did not appear to be a reflection of either (i) a nonspecific generalized impairment of cellular immunity or (ii) an alteration in the phenotypic expression of Bordetella pertussis-induced histamine sensitization, a phenotype which has been shown to be associated with susceptibility to both diseases. Susceptibility to both EAE and EAO was inherited as a dominant trait in F1 hybrid animals. Segregation analysis in a (BALB/cByJ X BALB/cJ) X BALB/cJ backcross population suggested that disease resistance may be associated with a single genotypic difference in a common regulatory gene affecting susceptibility to both diseases. Linkage analysis of the backcross population failed to demonstrate an association of disease resistance with the mutant raf-1b allele carried by BALB/cJ mice. The results of these studies support previous observations that multiple genotypic differences may in fact exist in mice of the BALB/cJ subline and that such differences play a significant role in the genetic control of susceptibility to EAE and EAO.

Human chorionic somatomammotropin (hCS) is important in the hormonal monitoring of human pregnancies. Presented is the case of a clinically normal pregnancy in which a very low plasma level of hCS was detected. The concentration of messenger ribonucleic acid (mRNA) coding for hCS was evaluated to determine the level on which the deficiency occurred.

In general ataxia telangiectasia is a disease of childhood leading to severe ataxia in the first decade and death in adolescence. We present a brother and a sister with the characteristic features of ataxia telangiectasia at the age of 43 and 44. They are still in reasonable good health, despite their relative old age. This unusual manifestation of ataxia telangiectasia will be discussed with emphasis on clinical and genetic aspects.

Traditionally diagnosis of tumors is made by histopathology, because tumor markers are not sufficiently specific, and only low rates of positive cases have been observed. To induce free release of tumor markers into the blood, the IM injection of vitamin A and infrared-ray hyperthermia was used in 203 cancer patients. Blood samples were collected periodically to determine the levels of CEA, ferritin (FT), alpha-fetoprotein, sialic acid, and the ratio of ferritin to serum iron (FT/Fe). The analysis of each released tumor marker led to an increase in the rate of positive interpretations, indicating a linear correlation between tumor marker and tumor size. As a result of the evaluation of a combination assay of tumor markers using release induction, the rates of positive cases for any three of five markers were increased to 53, 65, and 94% in correlation with an increase in tumor size.

Fetoplacental function and maternal nutritional condition were assessed in order to clarify the mechanism of retarded fetal growth in pregnant women who smoked. Dehydroepiandrosterone sulfate (DHA-S) loading tests and measurements of cotinine, which is a major metabolite of nicotine, were also made. In heavy smokers, urinary estriol and serum levels of human placental lactogen (hPL) were lower than those in nonsmokers. There was no difference in maternal nutrition between smokers and nonsmokers. Heavy smokers demonstrated a lower conversion of DHA-S to estradiol than did nonsmokers. Levels of cotinine in maternal blood and umbilical cord blood of heavy smokers were remarkably higher than those in nonsmokers. Microscopic examination showed atrophic and hypovascular changes in placental villi from mothers who smoked. These results suggest that retarded fetal growth in heavy smokers is due to impairment of uteroplacental circulation as a result of the vasoconstricting effect of nicotine.

Measuring maternal serum alpha-fetoprotein (AFP) levels in the second trimester is an effective screening test for identifying pregnancies at increased risk for neural tube defects. In the absence of a neural tube defect there are many nonpathologic and pathologic causes for elevated AFP including underestimated gestational age, twin gestation, impending fetal death, and rare fetal malformations. In this series, intraplacental sonolucent spaces were detected in a significant percentage of second trimester pregnancies with elevated serum AFP in the absence of any other cause for the elevation. It is postulated that these cystic spaces are a conduit for the transfer of fetal blood into the maternal circulation, thus accounting for the nonpathologic AFP elevation in the maternal serum.

Ultrasound records were examined retrospectively in the cases of 70 fetuses with open spina bifida diagnosed by ultrasonography at 16-23 weeks' gestation. Biparietal diameter was below the 5th centile for gestation in 61% and head circumference measurements in 26%. The anterior horn of the lateral cerebral ventricle to hemisphere ratio was above the 95th centile in 77%, and ventriculomegaly of the posterior horn of the lateral venricle was observed in 86%. In the 54 fetuses for which pictures were taken at the level of the biparietal diameter a scalloping of the frontal bones (the lemon sign) was seen. In 12 of 21 fetuses for which a suboccipital bregmatic view of the cranium had been obtained, the cerebellar hemispheres were curved anteriorly with simultaneous obliteration of the cisterna magna (the banana sign); in a further 8 cases the cerebellum was not displayed. None of these changes was seen in 100 patients presenting consecutively for routine ultrasound examination in the second trimester.

The implications of an "inconclusive" acetylcholinesterase test (a faint but true band) in amniotic fluid were studied over a 2 1/2-year period in our laboratory. One thousand one hundred fifty-four amniotic fluid samples were tested for acetylcholinesterase and alpha-fetoprotein; the rate of an inconclusive acetylcholinesterase result was 3.3% (38 of 1154). Fourteen such results were found in patients with a high amniotic fluid alpha-fetoprotein level (23.3%), and 24 results were associated with normal amniotic fluid alpha-fetoprotein levels (2.19%). The rates of congenital fetal malformation associated with an inconclusive acetylcholinesterase result in the two groups were 57.14% and 37.5%, respectively. In amniotic fluid samples obtained before 15 weeks' gestation, there was a higher rate of inconclusive acetylcholinesterase tests (9.29%), but a lower percentage of malformed fetuses were found compared with later in pregnancy (2.46% and 56%, respectively). Thus we suggest the terminology "equivocal" for early specimens and "suspicious" for later specimens. If obtained in early second trimester and the ultrasound scan is normal, such findings implicate the need for a careful search for fetal malformations. A positive pregnancy outcome may be expected in most cases.

Malignant ovarian tumors only account for 3 per cent of all malignancies under 15 years of age, and more than two third of them are of germ cell origin. Abdominal mass and/or pains are the usual revealing symptoms and abnormal sexual prematurity is infrequently encountered. Diagnostic ultrasonography is currently the most useful imaging investigation. Alpha-foeto-protein (alpha-FP) serum determination is mandatory before surgery to indicate the presence of endodermal sinus tumor cells. Surgical procedure is in childhood usually restricted to unilateral salpingo-oophorectomy, if allowed by tumoral spreading which is carefully searched in the abdominal cavity. Thus will be defined, along with the post-operative lymphangiography, the extension of the tumor, according to the staging system of Wollner (Memorial Hospital NY) more than the FIGO. Malignant teratomas are the most frequent malignant germ cell ovarian tumors in young females. They may realize pure or mixed pathological types of immature teratoma, embryonal carcinoma, endodermal sinus tumor and very seldom choriocarcinoma. Serial assays of serum alpha-FP are of utmost value to follow therapeutic progress or detect recurrences. Since new sequential multidrug protocol including, vincristine, actinomycin D, cyclophosphamide, adriamycin, méthotrexate and cis-platinum, protracted survivals are to be expected in a higher number of patients with localized stages and even in some with advanced disease. Value of extended pelvi-abdominal and/or lymph node radiotherapy is still under evaluation. Ovarian dysgerminomas are radiosensitive tumors in which chemotherapy is as a rule not indicated. Relapses may be most often prevented by a prophylactic irradiation of iliac ipsilateral, lumboaortic, mediastinal and supraclavicular nodes. Among functional ovarian tumors, mainly granulosa cell types with isosexual precocity, malignant tumors are so rarely encountered that no complementary treatment has to be performed after a complete resection. Cystadenocarcinoma or borderline ovarian epithelial tumors occur after puberty and require the same treatment as in adult though keeping a conservative view. Ovarian deposits of Burkitt's tumor may account in some exposed african areas for most ovarians malignancies in childhood. Gonadoblastomas with both stromal and germ cell elements are exclusively to be found in dysgenetic gonads.

Human alpha-fetoprotein (AFP) was isolated from cord serum on an immunoadsorbent column obtained by covalently linking rabbit anti AFP to cyanogen bromide activated Sepharose. Bound AFP was eluted with 8 M urea with better than 50% recovery. The purified AFP was iodinated prior to its use in a double antibody radioimmunoassay. The purification and radioimmunoassay employ commercially available materials. A standard inhibition curve was obtained which allowed determination of AFP levels between 50 and 100 ng/ml in human serum. The assay was verified by measureing AFP levels in normal female serum, pregnancy serum, cord serum, hepatoma ascitic fluid and a standardized AFP solution.