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PubMed2002

Treatment of ectopic pregnancy with a single intramuscular dose of methotrexate.

This study evaluates the outcome of unruptured ectopic pregnancies treated with single-dose intramuscular methotrexate injection. There were 77 women with unruptured non-laparoscopically diagnosed ectopic pregnancies who were prospectively followed after receiving a single dose of 50 mg/m2 intramuscular methotrexate. Diagnosis required transvaginal ultrasound and serial quantification of beta subunit of human chorionic gonadotropin (betahCG). A repeat dose was given if the weekly drop of betahCG was less than 30%. Therapy was considered successful if complete resolution of betahCG to a level below 25 IU/L was achieved without surgical intervention. Treatment in 73 (95%) cases was successful. The mean pre-treatment level of betahCG was 2592 +/- 3771 IU/L (177-15000 IU/L), the mean diameter of ectopic mass was 2.4 +/- 1.0 cm (1.7-3.5 cm). The average resolution period was 3.2 +/- 1.0 weeks (1-6 weeks) and this significantly correlated with the pre-treatment betahCG level. With strict criteria of inclusion and follow-up, single-dose intramuscular methotrexate is a successful method for the treatment of selected cases of ectopic pregnancy.

Abortifacient Agents, Nonsteroidal↗

PubMed2003

Placental villotrophoblastic pulmonary emboli after elective abortion: immunohistochemical diagnosis and comparison with ten control cases.

Although pulmonary trophoblastic embolism is now considered a physiologic phenomenon of normal pregnancy, this phenomenon has not been demonstrated in a living asymptomatic patient. Recently we encountered a 26-year-old woman suspected of pulmonary embolism of villotrophoblastic tissues after therapeutic abortion. Although her serum beta-hCG was low, a computed tomography scan showed multiple nodules in both lungs. Histological examination of a nodule in a lung-biopsy specimen showed granulation tissue surrounding a hemorrhagic mass within which were structures resembling degenerating chorionic villi. Immunohistochemical study on the patient's lung nodule, and a second endometrial-curettage specimen, six control endometrial and tubal specimens containing degenerating chorionic villi, and four endometrial specimens containing viable chorionic villi were performed. The patterns of immunostaining for cytokeratin, human chorionic gonadotropin, human placental lactogen, placental alkaline phosphatase, and inhibin-alpha of the chorionic villus-like structures in the lung nodule were almost identical to those in the degenerating chorionic villi, but different from those of viable villi. This is a unique case of embolism of chorionic villi and trophoblast to the lung in a living patient after therapeutic abortion.

Abortion, Induced↗

PubMed1994

Emergency department screening for ectopic pregnancy: a prospective US study.

PURPOSE: To determine the effectiveness of pelvic sonography as a screening test for ectopic pregnancy. MATERIALS AND METHODS: Pelvic sonograms were prospectively analyzed in 1,427 consecutive patients with a serum level of the beta subunit of human chorionic gonadotropin of over 1,500 IU/L. RESULTS: Sonograms were diagnostic in 1,158 patients and indeterminate in 269. When indeterminate studies were considered falsely negative, the diagnostic accuracy was 81%. Twenty-four percent of patients with indeterminate studies were subsequently proved to have ectopic pregnancy. In ectopic pregnancy (n = 103), the most common finding was a complex adnexal mass (specificity = 92% [P < .001]). The sensitivity and specificity of screening sonography for ectopic pregnancy were 99% and 84%, respectively. CONCLUSION: Pelvic sonography is an effective screening test for ectopic pregnancy. Having a one in four chance of harboring an ectopic pregnancy, patients with indeterminate studies require close follow-up. The presence of a complex adnexal mass is a strong predictor of ectopic pregnancy.

Adult↗

PubMed1989

Placental protein distribution in maternal diabetes mellitus: an immunocytochemical study.

Placentas associated with maternal diabetes are generally characterized by features of villous immaturity. We correlated the villous histology with the immunocytochemical distribution of four trophoblastic proteins: beta human chorionic gonadotropin (beta HCG), placental alkaline phosphatase (PLAP), pregnancy specific beta-1-glycoprotein (SP1), and human placental lactogen (HPL) in 14 third-trimester placentas associated with diabetes mellitus. Staining was increased for beta HCG and decreased for PLAP, SP1, and HPL in the diabetic placentas compared to control placentas of similar gestational age. This pattern was most prominent in areas of marked architectural villous immaturity within individual placentas and suggests concomitant functional immaturity.

Alkaline Phosphatase↗

PubMed1982

Tumor marker production in human bronchial carcinoma xenografts.

A total of 37 human bronchial carcinomas (15 small cell, 10 squamous, six large cell and six adenocarcinomas) have been successfully heterotransplanted into immune-suppressed mice. Monolayer tissue cultures have been established from 23 of the xenograft lines. After contact with tumour cells, supernatant culture medium was analysed by radioimmunoassay for adrenocorticotrophin (ACTH), calcitonin, human chorionic gonadotropin beta subunit (beta HCG) and carcinoembryonic antigen (CEA). Calcitonin production was associated with three (13%) xenograft lines (two small cell, one adenocarcinoma). beta HCG was found in three (13%) lines (one small cell, two large cell anaplastic). CEA was produced in 13 (56.5%) lines (seven small cell, two squamous, one large cell, three adenocarcinomas). ACTH was present in 18 (78.2%) lines (11 small cell, two squamous, two large cell, three adenocarcinomas), but evidence indicates that this hormone is not in all cases produced and secreted by the tumour.

Adenocarcinoma↗

PubMed1993

Protein folding and assembly in vitro parallel intracellular folding and assembly. Catalysis of folding and assembly of the human chorionic gonadotropin alpha beta dimer by protein disulfide isomerase.

Although purified proteins will refold and assemble in vitro, it is not known if cellular factors change the mechanisms of these processes. Based on the gel migration of folding intermediates, the kinetic relationships between these intermediates, and on the order of formation of six disulfide bonds, we have found that the in vitro folding pathway of the human chorionic gonadotropin beta subunit (hCG-beta) is indistinguishable from the intracellular folding pathway. The same rate-limiting event was found in both folding environments; however, the t1/2 for this step in a cell is 4 min, whereas in vitro the t1/2 was > or = 80 min. Protein disulfide isomerase (PDI) increased the in vitro rate of this event (t1/2 = 25 min) without changing the order of disulfide bond formation. PDI also catalyzed the in vitro rate of assembly of hCG subunits. In intact cells, assembly of the alpha beta heterodimer occurs before all of the intramolecular disulfide bonds of beta are formed. In vitro, assembly was increased after reduction of two of the carboxyl-terminal disulfide bonds of hCG-beta by PDI. These results strongly suggest that both in intact cells and in vitro, partially unfolded hCG-beta is more assembly-competent than is fully folded hCG-beta. The comparison of in vitro and intracellular hCG-beta folding and hCG subunit assembly which is shown in this report indicates that the assisted folding and assembly pathway that occurs in cells, where proteins such as PDI play a role, differs only in rate but not in the order of disulfide bond formation or in the precursor-product relationships among the folding intermediates.

Animals↗

PubMed2006

Syncytiotrophoblastic vesicles in placental intervillous space.

OBJECTIVE: This study was undertaken to investigate the origin and function of vesicles found in the intervillous space. STUDY DESIGN: A retrospective study was performed by using placental sections of different gestational ages. The number of vesicles was counted in each section of gestational age groups. Immunohistochemical staining for beta-human chorionic gonadotropin (beta-hCG) and human placental lactogen (hPL) was conducted to confirm the origin of vesicles. RESULTS: Staining for beta-hCG and hPL was prominent in vesicles separating from syncytiotrophoblast into the intervillous space. The numbers of vesicles were not significantly different in gestational age groups of 42 to 30 weeks and all vesicles disappeared in 9- to 5-week groups. Large vesicles tended to show degeneration and disintegration in the intervillous space. CONCLUSION: The vesicles containing beta-hCG and hPL suggest a different secretory mechanism of syncytiotrophoblast.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMedDate not supplied

Two unusual recurrences of intracranial germinoma.

Two recurrent cases of intracranial suprasellar germinoma, with relapses at 55 and 16 months, respectively, after the end of primary therapy strongly effective against pure germinoma, are presented. Human chorionic gonadotropin beta subunit was elevated in the cerebrospinal fluid and in the serum in both patients at the time of recurrence but not before. This and resulting treatment failures suggest that there were also other, more resistant elements within the primary tumor, which have not been identified in biopsy specimens. The problem of adequate diagnosis and its impact on patients' survival are discussed.

Antineoplastic Agents↗

PubMed1995

[Double cancers of renal cell carcinoma and testicular seminoma: a case report].

A case of metachronous presentation of renal cell carcinoma and testicular seminoma is reported. A 48-year-old man underwent left radical nephrectomy for a renal tumor on September 4, 1991. Pathological examination revealed clear cell carcinoma with no capsular penetration. There was no evidence of distant metastases. During postoperative follow-up, he noticed a painless left testicular induration in July, 1994. Serum human chorionic gonadotropin beta subunit as a tumor marker was elevated. Left radical orchiectomy was performed on October 17, 1994. Pathological examination revealed an anaplastic seminoma localized within the testis. Chest X-ray was normal and CT of the abdomen demonstrated no evidence of retroperitoneal lymphadenopathy. The patient was diagnosed as clinical stage I left testicular seminoma. He was free of disease 8 months postoperatively. Including our case, 15 cases of clinically detected double cancers of renal cell carcinoma and testicular germ cell tumor have been reported worldwide. This is the first case of a metachronous presentation of these two cancer types preceded by renal cell carcinoma.

Carcinoma, Renal Cell↗

PubMed1988

Immunohistochemistry of germ cell and trophoblastic neoplasms.

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.

Alkaline Phosphatase↗

PubMed2000

[Pathology of gestational trophoblastic tumors].

Gestational trophoblastic tumours result from an abnormal proliferation of different types of trophoblasts. The morphological pattern, together with the immunohistochemical aspect, the cytogenetic data and the clinical profile, helps identify each pathological entity. Hydatiform moles represent malformed placentas caused by genetic aberrations of the villous trophoblast. A complete hydatiform mole displays an hydropic degeneration of all the chorionic villi with a more or less marked proliferation of trophoblasts. A partial hydatiform mole is made up of molar vesicles interspersed with normal chorionic villi. In an invasive hydatiform mole or chorioma destruens, molar vesicles penetrate the myometrium giving rise to a mass distorting the uterine wall. A choriocarcinoma is a malignant proliferation of atypical villous trophoblasts without villi formation. Necrosis, haemorrhage, vascular invasion and distant metastases strongly compromise its outcome. A trophoblastic implantation site tumor, clearly less frequent, results from a proliferation of extravillous trophoblasts, particular for their secretion of human placental lactogen hormone (hPL). This tumour, exceptionally malignant, should be differentiated from the exaggerated placental site and its variants. Except for the placental site trophoblastic tumour, and whatever the outcome (benign or malignant), all gestational trophoblastic tumours secrete the beta-subunit of the chorionic gonadotropic hormone (beta-hCG) more or less abundantly. The serum or urinary level of this unit is proportional to the tumour volume and represents a fundamental basis for the follow-up of these tumours. Multidisciplinary care of high-risk cases allows us to cure the disease, and helps the patient recover her reproductive uterine function.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed2001

Preoperative serum concentration of hCGbeta as a prognostic factor in ovarian cancer.

In spite of a gradual improvement, survival in epithelial ovarian cancer is disappointingly low. New therapeutic regimens are emerging, and it would be important to be able to predict the prognosis and to stratify patients for clinical trials before therapy. We have evaluated the prognostic value of the pretreatment serum concentrations of 3 tumor markers. The free beta subunit of human chorionic gonadotropin (hCGbeta), CA125 and tumor-associated trypsin inhibitor (TATI) were measured in pretreatment serum samples from 146 patients treated for ovarian cancer between 1990-1995. The patients were followed up until 1998. Elevated concentrations of hCGbeta, CA125 and TATI were observed in 29%, 79% and 33%, respectively. When tested as single variables in Cox's proportional hazards model, stage, grade, size of residual tumor and hCGbeta (all p < 0.001) and CA125 (p = 0.004) correlated with prognosis. However, when fitted as multiple variables together with stage, grade and age in the same model, hCGbeta (RR = 3.42) stage (RR = 2.77) and grade (RR = 3.80) were the only significant variables. When serum hCGbeta was normal, 5-year survival was 80%, but it was only 22% when hCGbeta was elevated. In patients with stage III or IV and minimal residual disease, 5-year survival was 75% if hCGbeta was normal compared with 0% if hCGbeta was elevated. hCGbeta in serum is a strong independent prognostic factor in epithelial ovarian cancer, and its prognostic value is similar to that of grade and stage. The availability of this marker before surgery could facilitate selection of treatment modalities.

Adult↗

PubMed1998

Midtrimester N-terminal proatrial natriuretic peptide, free beta hCG, and alpha-fetoprotein in predicting preeclampsia.

OBJECTIVE: To determine whether maternal midtrimester serum N-terminal peptide of proatrial natriuretic peptide, free beta subunit of human chorionic gonadotropin (hCGbeta), or alpha-fetoprotein (AFP) levels can predict preeclampsia. METHODS: A population-based cohort included 1037 nulliparous women, of whom 637 (61%) participated in a maternal serum Down syndrome screening program. Measurements of hCGbeta, AFP, and N-terminal peptide of proatrial natriuretic peptide were made from maternal serum collected at 15-19 weeks' gestation. Sensitivity, specificity, and predictive values were calculated for elevated AFP (at least 2.0 multiples of the median [MoM]) and hCGbeta (at least 2.0 MoM) values. RESULTS: No difference was found in the concentrations of the N-terminal peptide of proatrial natriuretic peptide among the 30 women in whom preeclampsia developed later (median 270 [range 142-604] pmol/L) compared with 536 women who remained normotensive (274 [51-2626] pmol/L). The sensitivity and specificity of elevated AFP in predicting preeclampsia were 3% and 98% and those of elevated hCGbeta were 20% and 84%, respectively. When a stepwise multiple logistic regression model was used, only mean arterial pressure was an independent risk factor in predicting preeclampsia. CONCLUSION: Determinations of the proposed new marker N-terminal peptide of proatrial natriuretic peptide, as well as serum hCGbeta or AFP, are not helpful in predicting preeclampsia.

Adult↗

PubMed1985

ELISA solid phase: stability and binding characteristics.

Stability of solid-phase antibody (SP-Ab) was investigated using polystyrene surface coated, by simple physical adsorption, with a rabbit antibody against the beta subunit of human chorionic gonadotropin. SP-Ab stored wet in 0.1 M Tris-HCl buffer, pH 7.2, or in 10% ammonium sulphate solution in the Tris buffer did not lose any activity upto the entire period of the study, i.e., 95 days at 6 degrees C and room temperature and 53 days at 40 degrees C. However, SP-Ab lost some activity upon drying and decrease in activity continued when air-dried SP-Ab was stored at any of these temperatures. Secondary coating of SP-Ab with sucrose or lactose before drying offered only partial protection to the activity of SP-Ab. Using radiolabeled antibody it was found that the loss of activity was not caused by desorption of the antibody; rather it could be the result of surface denaturation of the molecules. Binding of the antibody to polystyrene was so strong that week-long storage of SP-Ab in 6 M urea or 0.1% acetic acid could not bring about desorption by more than 1.8%. It is recommended that SP-Ab should be stored in a buffer and should not be allowed to dry.

Adsorption↗

PubMed1986

Multiple markers for lung cancer diagnosis: validation of models for advanced lung cancer.

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.

Aged↗

PubMedDate not supplied

Combination of HCGbeta, CA 19-9 and CEA with logistic regression improves accuracy in gastrointestinal malignancies.

BACKGROUND: Earlier studies suggest that the free beta-subunit of human chorionic gonadotropin (hCGbeta) may be a useful tumour marker for gastrointestinal cancers. Our aim was to investigate hCGbeta in serum in gastrointestinal diseases in comparison with CA 19-9 and carcinoembryonic antigen (CEA). PATIENTS AND METHODS: The serum concentrations of hCGbeta, CA 19-9 and CEA were measured from 142 patients with malignant and 178 with benign gastrointestinal diseases. The diagnostic accuracies of the markers were compared and a diagnostic algorithm was established with logistic regression (LR) analysis. RESULTS: The hCGbeta serum level was elevated most frequently in bile duct (56%), pancreatic (45%) and gastric cancer (41%). In benign diseases, hCGbeta concentration was elevated in 10% of the patients. In an LR model each marker provided independent diagnostic information and the probability of cancer was calculated. It was applied as a diagnostic algorithm providing better accuracy than the markers alone. In receiver operating characteristic (ROC) curve analysis the area under the curve (AUC) value of the algorithm was significantly higher than the AUC values of CA 19-9, CEA, or hCGbeta (p=0.009-0.049). CONCLUSION: Serum hCGbeta, CA 19-9 and CEA provide additive diagnostic information in gastrointestinal malignancies and the use of an algorithm established by LR analysis improves diagnostic accuracy.

Adult↗

PubMed1994

Serum PAPP-A and free beta-hCG are first-trimester screening markers for Down syndrome.

Serum measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta-human chorionic gonadotrophin (hCG) subunit were made in 13 women with Down syndrome (DS) pregnancies and six other women with fetal aneuploidy ascertained at chorionic villus sampling (CVS), as well as 89 women with contemporaneous normal control pregnancies. Median serum PAPP-A measurements (0.31 MOM, 95 per cent confidence interval (CI) 0.22-0.65 vs. normal 1.06, 95 per cent CI 0.89-1.20) were lower and free beta-hCG subunit measurements (1.13 MOM, 95 per cent CI 0.93-2.63 vs. normal 0.91, 95 per cent CI 0.79-1.03) were higher at statistically significant levels. Receiver operator characteristics (ROC) curves showed that the highest sensitivity for detection, 71.2 per cent (95 per cent CI 54.7-87.6 per cent), was for depressed PAPP-A levels; the combination of low serum PAPP-A levels, maternal age, and elevated free beta-hCG levels yielded a detection rate of 78.9 per cent (95 per cent CI 64.9-92.8 per cent) of the affected pregnancies at 8-12 weeks' gestation.

Adult↗

PubMed2005

First-trimester or second-trimester screening, or both, for Down's syndrome.

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates.

Adult↗