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PubMed1989

Update on molar pregnancy and choriocarcinoma.

The term gestational trophoblastic disease encompasses a wide spectrum of disorders ranging from the benign hydatidiform mole to the malignant choriocarcinoma and placental site trophoblastic tumor. Recent advances in cytogenetics and pathological criteria have brought to light the occurrence of the partial mole, which is probably more common than the complete mole. The World Health Organisation has proposed a classification to rectify the current confusion that exists with clinical and pathological terms. Evacuation of the uterus followed by meticulous followup with sensitive beta subunit Human Chorionic Gonadotropin assay remain the cornerstone of management of molar pregnancy. Prompt chemotherapy is the most important aspect in managing malignant sequelae. Newer chemotherapy regimes have helped to salvage failures from the usual drugs. Judicial use of surgery in metastatic trophoblastic disease can reduce the duration and toxicity of chemotherapy. All patients with gestational trophoblastic disease should be managed in a tertiary care centre with the expertise and facilities easily available to manage these cases.

Carbimazole↗

PubMed1985

Persistent ectopic pregnancy: complication of conservative surgery?

Conservative surgery with conservation of the affected tube is widely recommended as optimal therapy in the management of unruptured tubal gestation. Unfortunately it is not possible to guarantee complete removal of all trophoblastic tissue and there remains the possibility of continuing trophoblastic growth after the conservative operation, usually necessitating a second, more radical procedure. Four cases of this complication have been reported in the literature and we have recently encountered a fifth. It is our impression that the problem may be under-reported. We recommend routine serial beta-subunit human chorionic gonadotropin surveillance in the postoperative period following conservative surgery and feel that patients should be advised of the possibility of this complication whenever conservative surgery is contemplated. Furthermore, there may be a potential for management of this problem with cytotoxic agents in a manner analogous to that used for gestational trophoblastic disease.

Fallopian Tubes↗

PubMed1985

Early pregnancy interruption with a single PGF2 alpha 15-methyl-analogue vaginal suppository.

Pregnancy was interrupted successfully in 70% of 20 early pregnancies, 35-49 days in duration as dated from the first day of the last menstrual period, by administration of a single intravaginal suppository containing 3 mg of (15S)-15-methyl prostaglandin F2 alpha (PGF2 alpha). No correlation could be demonstrated with baseline beta-subunit human chorionic gonadotropin or serum levels of prostaglandin obtained within ten hours of treatment. Continued pregnancy was documented in 10%. The rate of failures and the frequency of gastrointestinal side effects were deemed too great to warrant adopting this agent for clinical usage.

Abortion, Induced↗

PubMed1982

Validation of the rosette inhibition test for the detection of early pregnancy in women.

The authors validated use of the rosette inhibition test for the detection of early pregnancy factor (EPF) in human pregnancy, first by optimizing conditions for the assay, using known pregnant and nonpregnant sera, and second, by examining the performance of this assay in three clinical situations: a "blind" study involving coded first-trimester sera showed 80% correlation with pregnancy status; serial assay of EPF activity in sera collected from normal women attempting to conceive, correlated with human chorionic gonadotropin beta-subunit (beta-hCG) levels and pregnancy status; a longitudinal study of serial serum samples through two normal pregnancies showing the continued presence of EPF until the early third trimester in each case. It was concluded that with the rosette inhibition assay, consistent demonstration of a pregnancy-associated substance (EPF) could be obtained.

Chaperonin 10↗

PubMed1983

The significance of measurement of several oncofetal antigens in diagnosis and management of epithelial ovarian tumors.

Association of serum alphafetoprotein (alpha FP), human chorionic gonadotropin beta-subunit (beta-HCG), carcinoembryonic antigen (CEA) and ferritin (FER) was studied in a group of 72 patients with epithelial ovarian cancer 15 days after surgery and at various times during 2 years. Only CEA and ferritin are able to reflect tumor burden in detecting evolutive disease; alpha FP and beta-HCG have a diagnostic significance in few cases, probably related to a particular, not evident, histological component of the tumor. Nevertheless the data indicate that the use of marker association can improve our capacity to detect, overall in the residual and evolutive disease, the real clinical burden of the patients.

Adenocarcinoma↗

PubMed1984

Evaluation of the beta-Neocept test for early pregnancy.

We tested the validity of the beta-Neocept test for early pregnancy against that of the plasma human chorionic gonadotropin beta-subunit radioimmunoassay (beta-HCG RIA). The beta-Neocept test had a sensitivity of 88%, a specificity of 93%, a positive predictive value of 95%, a negative predictive value of 84% and an accuracy of 90%. In view of these performance characteristics, its low cost and its ease of use, the beta-Neocept test could be used as the initial pregnancy test when there is a high probability of pregnancy, as there was in this study population, which consisted of 111 women attending endocrine infertility clinics. The more expensive beta-HCG RIA could be reserved for special indications and for patients in whom the results of the urinary hemagglutination inhibition tests are inconsistent with the clinical signs and symptoms.

Adult↗

PubMed1995

Laparoscopic diagnosis and treatment of cornual pregnancy. A case report.

An early diagnosis of interstitial pregnancy was made by serial quantitative human chorionic gonadotropin beta-subunit evaluation, transvaginal ultrasound findings and laparoscopy. Cornual resection was performed using operative endoscopic techniques; the postoperative course was unremarkable.

Adult↗

PubMed1995

[Contemporary biopsy for diagnosis of abortion residues: preliminary experience].

The differential diagnosis between abortion and ectopic pregnancy has important clinical implications. In this report we have tested the accuracy of frozen sections in uterine curettings to identify intrauterine pregnancy. Uterine curettings with a diagnosis of products of gestation, from 104 patients were studied. In all of them plasmatic levels of B Gonadotrophin were measured. The curetting material was fixed and studied on frozen sections and on paraffin embedded tissue. A high positive relationship between frozen and embedded material was observed. The sensibility, specificity, positive and negative predictive value of the frozen section to detect chorionic villi were 90.6; 100; 100 and 74% for each of them.

Abortion, Incomplete↗

PubMed1996

[Fluorescence polarization immunoassay and microparticle enzyme immunoassay].

We describe a new clinical laboratory instrument, the Abbott AxSYM, which provides random- and continuous-access testing for immunoassays, 20 onboard reagents, primary tube sampling, and a throughput of 80 to 120 tests per hour. The AxSYM incorporates three separate analytical technologies for processing immunoassays: microparticle enzyme immunoassay, fluorescence polarization immunoassay, and a novel technology known as ion-capture immunoassay. The system incorporates both common and technology-specific subsystems controlled by a real-time software scheduling processor. Tests can be processed in one- or two-step sandwich or competitive formats, with variable pipetting steps, incubation periods, optical read formats, and wash sequences. Menu capabilities include test for hepatitis, retrovirus, tumor markers, fertility markers, thyroid functions, and therapeutic drugs. The time to first result is 15 approximately 25 min for most routine assay and < or = 15 min for stat assays (i.e., creatine kinase MB isoenzyme, human chorionic gonadotropin beta subunit, and therapeutic drugs). AxSYM assay performance for 23 assays was comparable with that of the Abbott IMx and TDx analyzers; specimen correlation data had correlation from 0.99 to 1.10. Within-run imprecision (CV) was 1.5% to 11.4%, with most assays (19 of 23) demonstrating CVs < or = 8.0%.

Fluorescence Polarization Immunoassay↗

PubMed1998

Prenatal screening in the first trimester of pregnancy.

Prenatal screening for fetal abnormalities in an accepted part of modern obstetric management. Improvements on current screening procedures need to address increased diagnostic efficacy and earlier diagnosis. This study evaluates diagnostic efficacy of PAPP-A and F beta-hCG in the detection of first trimester pregnancy abnormalities, including Down syndrome (DS). Of 731 pregnant volunteers, obtained from a mature age population undergoing chorionic villus sampling (CVS), 17 DS and 11 compromised (six numerical (excluding sex chromosome) aneuploidies, five spontaneously failed) pregnancies were detected. Application of an algorithm, which combines PAPP-A and F beta-hCG levels with material age, detected 66.6 per cent of DS pregnancies for a five per cent false positive rate. Similarly, for a 1-2 per cent recall rate, 72.2 per cent of compromised pregnancies were detected. This report supports the notion that prenatal screening at 9-12 weeks of pregnancy is achievable with PAPP-A and F beta hCG quantitation. Whereas mid-gestational screening targetted the detection of fetal abnormalities, screening earlier in pregnancy will detect other pregnancy-related abnormalities, in addition to aneuploidy.

Adult↗

PubMed1997

[Clinical significance of HCG in both maternal serum and placental tissue in normal term women and patients with pregnancy induced hypertension].

OBJECTIVE: To determine the maternal serum level of HCG beta and the hormones in normal term women and patients with pregnancy induced hypertension. METHOD: Semiquantitative immunohistochemistry of placental tissue was used in 193 normal term women and patients with pregnancy-induced hypertension (PIH). RESULTS: A strongly positive correlation between the maternal serum level of HCG and the immunostained positive syncytiotrophoblasts (ST) was found (correlated coefficient: 0.65, P < 0.01). Maternal serum HCG was produced mainly from placental ST. Serum HCG beta and HCG positive cells of the placenta were obviously higher in patients with PIH than those in normal term women (P < 0.01). An increase of HCG level was noted in maternal serum and the placental tissue with PIH. CONCLUSION: Abnormal higher HCG level may affect the pathogenesis of PIH.

Adult↗

PubMedDate not supplied

Chromosomal abnormalities in ectopic pregnancy chorionic villi.

OBJECTIVE: To evaluate the incidence of chromosomal abnormalities in ectopic pregnancy chorionic villi. METHODS: A prospective study of patients with the diagnosis of ectopic pregnancy was conducted, with chorionic villi obtained at the time of surgical therapy cultured and analyzed for karyotype. Review of the patient's medical record and ultrasound evaluation was then completed and findings correlated with karyotype results. RESULTS: Twenty-two patients undergoing surgery for the diagnosis of ectopic pregnancy yielded chorionic villi for culture. Successful culture was performed in 21 patients, with 3 (14%) revealing abnormal karyotypes. Review of the medical record showed ultrasound results consistent with fetal development or a gestational sac in 15 of 18 patients with normal chromosomal analysis. Three of 6 patients without fetal development yielded abnormal chromosomal findings. CONCLUSION: Our results confirm that a high degree of success can be achieved in the karyotype analysis of ectopic pregnancy chorionic villi and that these conceptuses have a rate of abnormality similar to that reported for intrauterine gestations. Our data further suggest that when a gestational sac or fetal pole is identified by ultrasound, there is usually a normal karyotype.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed1976

The significance of measurement of human placental lactogen, human chorionic gonadotropin, and carcinoembryonic antigen in patients with ovarian carcinoma.

Human placental lactogen (HPL or HCS), the beta subunit of human chorionic gonadotropin (beta-HCG), and carcinoembryonic antigen (CEA) were measured by a specific radioimmunoassay in plasma of 65 patients with ovarian cancer. Fifty-one patients had epithelial tumors, while 14 had germ cell tumors. It was found that 47 patients (72 per cent) had high levels of plasma HPL, 29 patients (45 per cent) had high levels of plasma beta-HCG, and 34 patients (52 per cent) had high levels of plasma CEA, but there was no correlation between these protein marker levels in different patients. Twenty of these patients were studied before and after operation and during chemotherapy and/or radiotherpy. There was no consistent correlation between these marker levels and the course of the disease. These data suggest that measurement of HPL, beta-HCG, and CEA in sera of patients with ovarian cancer is not of value in assessing the clinical status of the patients or in determining the effect of therapy.

Adenocarcinoma↗

PubMed1996

NMR studies of the free alpha subunit of human chorionic gonadotropin. Structural influences of N-glycosylation and the beta subunit on the conformation of the alpha subunit.

Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone that is involved in the maintenance of the corpus luteum in early pregnancy. Glycosylation at Asn52 of its alpha subunit (alpha hCG) is essential for signal transduction, whereas the N-glycan at Asn78 stabilizes the structure of the protein. In this study, an almost complete 1H-NMR and a partial 13C-NMR spectral assignment for the amino acids and the N-glycans of alpha hCG and of an enzymatically deglycosylated form, which had a single GlcNAc residue at each of its two glycosylation sites, has been achieved. The secondary structure of alpha hCG is solution, which was determined based on NOE data, is partially similar to that of the alpha subunit in the crystal structure of hCG, but large structural differences are found for amino acid residues 33-58. In the crystal structure of hCG, residues 33-37 and 54-58 of the alpha subunit are part of an intersubunit seven-stranded beta-barrel and residues 41-47 constitute a 3(10)-helix. In contrast, in free alpha hCG in solution, amino acids 33-58 are part of a large disordered loop, indicating that in intact hCG interactions with the beta subunit of hCG stabilize the conformation of the alpha subunit. The NMR data of alpha hCG and its deglycosylated counterpart are very similar, indicating that removal of carbohydrate residues other than GlcNAc-1 does not notably affect the conformation of the protein part. However, numerous 1H-NOEs between the GlcNAc-1 residue at Asn78 and several amino acid residues show that this GlcNAc residue is tightly packed against the protein, being an integral part of the structure of the alpha subunit. 1H-NOEs across the glycosidic linkages of the glycan, resonance-line widths, and 1H and 13C chemical shifts of the other monosaccharides suggest that the remainder of the glycans at Asn78, and the glycans at Asn52 are largely extended in solution.

Amino Acid Sequence↗

PubMed1987

Radioimmunoscintigraphic detection of occult gestational choriocarcinoma.

Localized recurrent gestational choriocarcinoma, evidenced by a rising level of the beta-subunit of human chorionic gonadotropin, can be difficult to localize for surgical resection. We describe a patient with a rising level of the beta-subunit of human chorionic gonadotropin after extensive therapy for choriocarcinoma in which gamma scanning of the distribution of an intravenously administered iodine 131-labeled monoclonal antibody preparation (5F9.3) allowed localization of a focus of recurrent choriocarcinoma in the lung. Other imaging methods showed this only as a focus of stable scarring. The antibody scan guided surgical resection of this tumor focus, which on gamma counting had a tenfold excess of antibody activity compared with that of the normal lung. This approach may be useful in detecting occult foci of gestational choriocarcinoma for surgical resection in patients with rising levels of the beta-subunit of human chorionic gonadotropin and is under further evaluation.

Adult↗

PubMed1986

Eosinophilic globules in Kaposi's sarcoma. A histochemical, immunohistochemical, and ultrastructural study.

Of the 12 cases, 2 (17%) showed eosinophilic globules in the typical cutaneous type of Kaposi's sarcoma. The globules were stained with periodic acid-Schiff (PAS), periodic acid-Schiff reagent after diastase digestion, and phosphotungstic acid hematoxylin (PTAH), but were not stained with Mayer's mucicarmine, and alcian blue. As the results, these globules might be glycoprotein. The shape of the globules was very similar to glycoprotein globules of yolk sac tumor (endodermal sinus tumor) in the tissue of the ovary and testis. In the yolk sac tumor, similar globules are stained with alpha-fetoprotein, beta-subunit of human chorionic gonadotropin, and alpha-1-antitrypsin using immunohistochemical techniques. Immunoperoxidase investigations were done with antibodies to alpha-fetoprotein, beta-subunit of human chorionic gonadotropin, alpha-1-antitrypsin, and carcinoembryonic antigen in the eosinophilic globules of Kaposi's sarcoma, but these antigens were detected in the globules. The morphogenesis of the glycoprotein globules is not clear yet. A better understanding of the source of globules in Kaposi's sarcoma awaits further research.

Carcinoembryonic Antigen↗

PubMed1990

Localization of residues that confer antibody binding specificity using human chorionic gonadotropin/luteinizing hormone beta subunit chimeras and mutants.

The glycoprotein hormones are a family of conserved heterodimeric proteins which share a common alpha subunit but differ in their hormone-specific beta subunits. We used chimeras of human chorionic gonadotropin (hCG) and luteinizing hormone (hLH) beta subunits to identify residues which enable monoclonal antibodies (mAb) to distinguish the two hormones. The LH beta-CG beta chimeras appeared to fold similar to hCG beta, since they combined with hCG alpha and, depending on their sequences, were recognized by hCG-selective mAbs. Amino acid residues Arg8-Arg10,Gly47-Ala51, and Gln89-Leu92 form a major epitope region and appear to be adjacent to each other on the surface of hCG beta. Gly47-Ala51 and Gln89-Leu92 are recognized by dimer-specific mAbs while Arg8-Arg10 is recognized by mAbs which have highest affinity for the free beta subunit. These observations suggest that the conformation of this region of the beta subunit changes when the alpha and beta subunits combine. Residues which are C-terminal of Asp112 form a second epitope domain. mAbs to the third domain distinguish hCG beta and hLH beta by the presence of Asn77 in hCG beta and can be detected after hCG binds to receptors. These findings were used to develop a model of hCG beta which predicts the locations of these residues and their positions relative to the alpha subunit and receptor interfaces.

Amino Acid Sequence↗

PubMed1992

Amniotic fluid levels of human chorionic gonadotropin and its alpha and beta subunits in second-trimester chromosomally abnormal pregnancies.

Amniotic fluid from 135 pregnancies was assayed for human chorionic gonadotropin (hCG) and its free alpha (ahCG) and free beta (bhCG) subunits. Forty-six chromosomally abnormal pregnancies between 14 and 20 weeks' gestation were matched with 89 chromosomally normal samples. Compared with controls, trisomy 21 pregnancies exhibited significantly elevated levels of all three peptides, whereas trisomy 18 gestations gave rise only to significant elevation of ahCG. Female fetuses in both the trisomy 21 and trisomy 18 pregnancies provided significantly elevated levels of hCG and bhCG compared to their male counterparts. On converting the values to multiples of the median, it was determined that 6 of 7 trisomy 18 samples had abnormally elevated alpha/beta ratios, as did 6 of 21 Down's syndrome pregnancies. Further, 11 of 21 trisomy 21 gestations had abnormal amniotic fluid hCG levels. Using only ahCG, bhCG and their ratio, a 61 per cent sensitivity was found for these trisomies, with a 96 per cent specificity.

Amniocentesis↗