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Serum levels of smooth muscle heavy-chain myosin in patients with ectopic pregnancy.

STUDY OBJECTIVE: Previous studies have suggested that serum markers of smooth muscle destruction have utility in predicting ectopic pregnancy. Our goal was to determine whether a novel marker of muscle destruction, smooth muscle heavy-chain myosin (SMHC), is elevated in the serum of patients with ectopic pregnancy. METHODS: We conducted a prospective cohort study, with consecutive enrollment, of all women in the first trimester of pregnancy who presented to our urban emergency department with complaints of lower abdominal pain with or without vaginal bleeding. Patients were excluded if there was a history of recent surgery or major trauma. Means were compared using 2-tailed Student's t test with P values less than.05 set for significance. Data analysis included calculation of receiver operating characteristic (ROC), 95% confidence intervals (CIs), and a regression model. RESULTS: A total of 175 patients were enrolled; ectopic pregnancy was diagnosed in 29, and 146 had other diagnoses. Patients with ectopic pregnancy had a mean serum SMHC concentration of 2.53 ng/dL (95% CI 1.84 to 3.22), whereas those in the non-ectopic pregnancy group had a mean concentration of 1.41 ng/dL (95% CI 1.23 to 1.60; P <.0001). ROC analysis demonstrated an area under the curve of 0.72 (95% CI 0.65 to 0.79). Regression analysis to examine confounders in each group analyzed the effects of race, maternal age, estimated gestational age, and serum levels of human chorionic gonadotropin beta-subunit. Our analysis identified only a positive correlation between estimated gestational age and SMHC in the non-ectopic pregnancy group. CONCLUSION: There is a statistically significant elevation of serum SMHC levels in tubal pregnancy, although our data suggest that the assay has limited clinical utility as a lone marker for ectopic pregnancy. Further investigation is needed to determine whether the assay has a role as an adjunct in the evaluation of suspected ectopic pregnancy.

Abdominal Pain↗

Chemotherapy of metastatic testicular germ cell tumors: relationship of histologic response to size reduction and changes in tumor markers.

BACKGROUND: Although testicular germ cell tumor is one of the most curable cancers, approximately 20% of advanced cases remain incurable. In this study we investigate factors that may predict a poor response to standard chemotherapeutic regimens and thus allow earlier initiation of more aggressive measures. METHODS: We analyzed the records of 19 patients with metastatic testicular germ cell tumors (8 seminomas and 11 nonseminomas). Sixteen patients underwent surgical exploration for residual tumors following chemotherapy, and the histological findings on the resulting specimens were correlated with reductions in tumor size observed on computed tomography and with changes in tumor marker levels. RESULTS: Complete necrosis was obtained in 10 of 12 lesions that shrank by at least 80%, while continued existence of teratoma or cancer was confirmed in 9 of 11 lesions with smaller size reductions. An initial human chorionic gonadotropin-beta subunit (HCG-beta) level more than 100 times the upper limit of normal appeared to predict poor histological response (teratoma/cancer) to chemotherapy. Slow fall (prolonged half-life) of tumor markers during chemotherapy also correlated with poor histological response. CONCLUSION: Factors which predict poor histological response of tumors to chemotherapy include size reduction less than 80%, initial HCG-beta levels more than 100 times the upper limit of normal, and prolonged half-life of tumor markers (placental alkaline phosphatase, alpha-fetoprotein and HCG-beta).

Antineoplastic Combined Chemotherapy Protocols↗

Serum parameters and nuchal translucency in first trimester screening for fetal chromosomal abnormalities.

OBJECTIVE: To assess the relation between serum parameters and nuchal translucency in pregnancies affected by fetal aneuploidy in the first trimester. DESIGN: Retrospective study of different serum parameters collected prior to chorionic villus sampling and measurement of nuchal translucency in relation to fetal aneuploidy. SETTING: Switzerland (German and Italian sector) and Bregenz, Austria. POPULATION: One thousand one hundred and fifty-one women aged 25 to 44 years at 10 to 13 weeks of gestation undergoing chorionic villus sampling, mostly for advanced maternal age. Fetal aneuploidy was found in 23 pregnancies including four cases of trisomy 21, five of trisomy 18 and one case of trisomy 13. MAIN OUTCOME MEASURE: Fetal karyotype, serum levels of free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and alpha-fetoprotein and the measurement of nuchal translucency. RESULTS: Serum PAPP-A was decreased in all common chromosomal abnormalities. Free beta-hCG levels were increased in trisomy 21 but decreased in trisomy 18, whereas alpha-fetoprotein was low in trisomy 21, 18 and other chromosomal abnormalities. Nine of twenty-three abnormal embryos had evidence of an increased nuchal translucency. Nuchal translucency, however, did not seem to be associated with any alteration in the levels of the biochemical parameters in either chromosomally normal or abnormal embryos. A low serum PAPP-A or an increased nuchal translucency was seen in two-thirds of all pregnancies with chromosomal abnormalities. CONCLUSION: A nuchal translucency > or = 3 mm and depressed serum PAPP-A levels have a good predictive value in the detection of fetal aneuploidy at 10 to 13 weeks of pregnancy. Serum free beta-hCG and alpha-fetoprotein levels may give additional information. An increased nuchal translucency was not associated with altered serum parameters. This would allow these different markers to be used in combination.

Adult↗

Measurement of mRNA of trophoblast-specific genes in cellular and plasma components of maternal blood.

BACKGROUND: Placental mRNA in maternal plasma is suitable for quantitative analysis regardless of fetal gender and genetic polymorphism status. METHODS: We obtained 155 blood samples from pregnant women to compare human placental lactogen (hPL) and beta-subunit of human chorionic gonadotropin (beta hCG) mRNA and protein levels between the cellular and plasma components of maternal blood. To assess clearance of hPL mRNA expression, we obtained blood samples from nine women immediately before and after delivery by caesarean section. mRNA was extracted from the cellular and plasma components of all samples, and hPL and beta hCG mRNA expression was analysed by reverse transcription-PCR assay. RESULTS: The concentration of beta hCG mRNA in the cellular component positively correlated with the plasma concentration of beta hCG protein and beta hCG mRNA (p = 0.001 for both). The concentration of hPL protein in the plasma correlated with the hPL mRNA concentration of the cellular component (p<0.05). For both hPL and beta hCG, the mRNA concentration of the cellular component was greater than that of the plasma component (22.9-fold higher for hPL and 4.3-fold higher for beta hCG). The half life of hPL mRNA clearance was significantly longer for the cellular fraction (mean half life = 203.8 min, range 150-3465 min) than for the plasma fraction (mean half life = 32.2 min, range 15-385 min) (p = 0.008). CONCLUSION: The present findings indicate that the concentration of hPL and beta hCG mRNA is significantly higher in the cellular component of maternal blood samples than in the plasma component. Cellular mRNA in maternal blood is useful for non-invasive evaluation of placental function.

Chorionic Gonadotropin↗

Gestational trophoblastic neoplasm of the uterus: MR assessment.

Magnetic resonance (MR) imaging characteristics of uterine gestational trophoblastic neoplasia were prospectively studied in nine women (aged 21-58 years). MR imaging was done at the time of initial clinical diagnosis, after each of the first two cycles of chemotherapy, and 6-9 months after initiation of chemotherapy. Sagittal and transverse MR images of the pelvis were generated with a 0.35-T superconducting magnet and the double spin-echo technique with short and long repetition times (TRs). The neoplasm distorted the MR appearance of uterine zonal structures (myometrium, endometrium, and junctional zone) and demonstrated hypervascular masses of heterogeneous signal intensity. Favorable response to chemotherapy was determined by a decrease in serum beta-subunit human chorionic gonadotropin (HCG) concentrations, and was accompanied by MR findings of regression of vascular abnormalities, development of intralesional hemorrhage, and return of normal appearance of uterine zones. The return of uterine zonal anatomy on MR images antedated definitive decrease in uterine volume. All eight patients imaged 6-9 months after initial imaging showed normal uterine volume and zonal anatomy.

Adult↗

Sonographic, cytogenetic and DNA analysis in four 69,XXX fetuses diagnosed in the second trimester.

OBJECTIVE: To describe the ultrasound findings and its relationship with the cytogenetic study and the origin of the extra haploid chromosome set in four 69,XXX cases. METHODS: Four pregnant women were referred because of abnormal 2nd trimester ultrasound. Karytoypes, FISH and DNA analysis were performed. RESULTS: All cases presented asymmetrical intrauterine growth retardation, marked oligohydramnios and placental alterations and showed a 69,XXX karyotype. In three cases, DNA analysis allowed to establish the origin of the extra haploid chromosome set. CONCLUSIONS: At least three fetuses had a maternal extra haploid chromosome set. Thus, it has been possible to establish the main ultrasonographic markers and to observe the survival of the fetus until the second trimester when they have a maternal origin.

Adult↗

Maternal serum screening for chromosome defects: human chorionic gonadotropin versus its free-beta subunit.

The addition of maternal serum intact hCG (MShCG) to routine maternal serum alpha-fetoprotein screening for Down's syndrome is expected to yield a detection efficiency around 60% for an amniocentesis rate approximating 5%. We compared the detection rate using intact MShCG and free-beta hCG in 480 normal pregnancies and 48 with chromosome defects (Down's syndrome 31, other chromosome defects 17). No significant difference in detection efficiency was determined. However, since the false-positive rate with free-beta hCG was almost twice that found with intact hCG, and the detection rate for other chromosome defects was more than double, the intact MShCG assay is currently preferred. Free-beta hCG earlier in gestation may, however, ultimately prove superior in maternal screening for chromosome defects.

Adult↗

Intensive chemotherapy in poor-prognosis nonseminomatous germ cell tumors of the testis.

Forty-one patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) of the testis were treated between 1980 and 1989. This group was defined by the presence of one of the following features: multiple large lung metastases, bone, liver or brain metastases, abdominal mass greater than 10 cm, abdominal mass greater than 5 cm with high serum concentration of the tumor markers [alpha-fetoprotein (alpha FP) greater than 500 kU/l or beta-subunit of human chorionic gonadotropin (beta HCG) greater than 1,000 IU/l) or very high serum tumor marker concentrations (alpha FP greater than 5,000 kU/l or beta HCG greater than 10,000 IU/l). The first 21 patients were treated with cisplatin, vinblastine, bleomycin (PVB) chemotherapy and the following 20 with an intense, alternating 6-drug chemotherapy consisting of cisplatin, bleomycin, vincristine, methotrexate, etoposide and ifosfamide (BOMP/EPI). Surgery of residual masses was performed when tumor markers were negative. Fifteen patients (71.4%) in the PVB group and 18 patients (85%) in the BOMP/EPI group remained disease-free at a median follow-up of 67 and 41 months, respectively. None of the resected masses in the BOMP/EPI group contained malignant disease whereas viable carcinoma was found in 5 of 14 (26.4%) patients in the PVB group. The toxicity of the BOMP/EPI regimen was severe but tolerable. Intensive chemotherapy regimen seems to be useful in this subset of patients, but randomised prospective trials comparing these with standard chemotherapy are necessary.

Adolescent↗

Reversible increase in serum alpha-fetoprotein content associated with hepatic dysfunction during chemotherapy for seminoma.

Serial monitoring of the serum content of the beta subunit of human chorionic gonadotropin (beta hCG) and alpha-fetoprotein (alpha FP) is useful in the initial staging of germ cell tumors and assessing the response to treatment. An increase in either marker during or following treatment almost always heralds disease progression and indicates the need for additional therapy. We report two patients in whom substantial increases in the serum content of AFP occurred during chemotherapy for advanced seminoma. Hepatic dysfunction was present in both patients; in one patient, a chronic carrier of hepatitis B virus, the liver dysfunction was associated with reactivation of hepatitis B manifested by anicteric hepatitis and hepatitis B e antigen positivity. Marked tumor regression had occurred in both patients, and chemotherapy was discontinued in spite of the elevated alpha FP level. The alpha FP content in the serum gradually returned to normal, and hepatic dysfunction resolved. Both patients remain free of disease 15 and 17 months following the last chemotherapy treatment. These cases illustrate that hepatic dysfunction and alpha FP production may occur during chemotherapy and that increases in serum alpha FP content must be interpreted with caution since the elevated alpha FP level does not always indicate progression of germ cell tumors.

Adult↗

Circulating placental RNA in maternal plasma is associated with a preponderance of 5' mRNA fragments: implications for noninvasive prenatal diagnosis and monitoring.

BACKGROUND: The molecular characteristics of placental RNA circulating in maternal plasma are unknown. We investigated the integrity of circulating placental RNA in maternal plasma and tested the relevance of plasma RNA integrity for noninvasive prenatal diagnosis. METHODS: Six different placental transcripts and mRNA of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were quantified for the 5' and 3' regions in maternal plasma by 1-step real-time reverse transcription-PCR (RT-PCR) assays. This quantitative strategy was validated by 2-step RT-PCR and serial dilution experiments. The rates of detection by the 5' and 3' assays for the beta-subunit of human chorionic gonadotropin (beta hCG) were assessed in maternal plasma samples collected from different gestational periods. RESULTS: For 5 of the 7 genes, the plasma mRNA concentrations measured by the 5' amplicons were significantly higher than those measured by the corresponding 3' amplicons. Every transcript under study demonstrated a higher rate of detection in the 5' assay than in the 3' assay in maternal plasma. In particular, the detection rate of beta hCG mRNA in maternal plasma was increased throughout gestation when the 5' assay was used. CONCLUSIONS: Circulating placental RNA is associated with a preponderance of 5' mRNA fragments in maternal plasma. Apart from its intrinsic biological interest, this information could have important implications for the development of new assays targeting fetal RNA markers for noninvasive prenatal diagnosis and monitoring.

Chorionic Gonadotropin↗

[Molecular staging of testicular cancer using polymerase chain reaction of the testicular cancer-specific genes].

Most testicular germ cell tumors have serological tumor markers such as alpha-fetoprotein (AFP) and human chorionic gonadotropin beta-subunit (beta-HCG). On the other hand, molecular staging of these tumors has not been well established compared to other urogenital malignancies like prostate cancer. Recently, melanoma antigen (MAGE) which is one of the tumor-associated antigens recognized by cytotoxic T lymphocytes (CTL) has been found to be present in a variety of malignant tumor types and normal testis. In addition, Wilms' tumor-associated gene WT1 has been found to be expressed in some testicular cancers. Thus, we examined the expression of these genes in testicular cancer tissues and peripheral blood of cancer-bearing patients using reverse transcription-polymerase chain reaction (RT-PCR). The expression of the MAGE1-3 genes was examined in 34 testicular germ cell tumors (24 seminomas and 10 nonseminomas). Of the seminomas and nonseminomas, 87.5% and 40% were positive for MAGE1, 91.7% and 60% for MAGE2, and 83.3% and 30% for MAGE3, respectively. The expression of the MAGE genes was not correlated with the tumor stage. The expression of the WT1 gene was quantified in 26 testicular germ cell tumors. WT1 was highly expressed in 5 of the 7 high stage cases, but in only 4 of the 19 low stage cases (p < 0.01). The mRNA of these genes could not be detected from the peripheral blood of patients with high stage tumors. These results suggest that MAGE genes may be useful tumor markers for molecular staging of testicular cancer, especially seminoma, and that the WT1 gene may be a tumor marker for high stage testicular germ cell tumors. However, these genes cannot yet be used for molecular staging of testicular germ cell tumors.

Antigens, Neoplasm↗

Primary hepatic choriocarcinoma--a case report.

A 65-year-old man experienced anorexia and abdominal enlargement and died suddenly 45 days after admission. Multiple necrotic and hemorrhagic tumors were present in the liver (6 kg). The fragile tumor ruptured and a large amount of blood accumulated in the peritoneal cavity. The tumor was composed of cytotrophoblast and syncytiotrophoblast cells. Neoplastic cells were positive for human chorionic gonadotropin and negative for alpha-fetoprotein and carcinoembryonic antigen. The huge tumor directly invaded the entire antrum of stomach. Neoplastic trophoblastic cells proliferated mainly in the serosa and propria muscular layer of the stomach, and tiny cancer nests were observed in many vessels of the submucosa and propria mucosa. The serum alpha and beta human chorionic gonadotropin subunits showed a very high level; 51 ng/mL and 820 ng/mL, respectively. No tumor, cyst or scar was observed in the testes, mediastinum and retroperitoneum, macroscopically and microscopically. Based on these autopsy findings, we diagnosed this patient as having primary hepatic choriocarcinoma.

Aged↗

[Biosynthesis of a single peptide chain containing human chorionic gonadotropin beta and ovine common alpha subunits tandem].

hCG beta-oLH alpha chimeric cDNA was constructed by using overlapping PCR to contact the codons of C-terminal end of hCG beta with the codons of N-terminal end of oLH alpha, then it was subcloned into nuclear polyhedrosis virus (AcNPV) expression vector pVL1393 to construct expression vector pVL1393-hCG beta-oLH alpha. The insect cells (Sf9) were cotransfected by the expression vector pVL1393-hCG beta-oLH alpha and BaculoGold AcNPV linearized genomic DNA, and recombinant viruses AcNPV-hCG beta-oLH alpha were screened out by plaque assay. Further the insect cells were infected by the recombinant viruses, the recombinant hCG beta-oLH alpha was purified by immunoaffinity chromatography column coupling anti-hCG beta monoclonal antibody from the conditioned media of infected cells. The results of SDS-PAGE silver staining and western blotting showed that hCG beta-oLH alpha single peptide chain had apparent molecular weights of 40.5 kD and 38.0 kD under non-reducing and reducing conditions respectively, indicating the occurrence of disulfide bonds and significant tertiary structure in the single peptide chain. From the results of competitive inhibition of 125I-hCG beta binding we can conclude that the anti-hCG beta antibody-binding activity of hCG beta-oLH alpha chimera is lower than that of native hCG, but higher than that of native hCG beta. Therefore, we assume that the hCG beta-oLH alpha chimera should have potential application as a target antigen of anti-hCG fertility regulatory vaccine.

Animals↗

[Effect of mifepristone on the expression of chorionic gonadotropin beta subunit and collagen type IV in female rhesus monkey decidua and villus at early gestation].

OBJECTIVE: To study the effect of mifepristone on the expression of chorionic gonadotropin beta subunit (beta-CG) and collagen type IV in female Rhesus monkey decidua and villus during the first trimester of pregnancy. METHODS: Eighteen sexually mature female Rhesus monkeys were allowed to cohabitate with their male counterparts and diagnosed as being pregnant by B-ultrasound at days 38-45 of the menstrual cycle. They were randomly divided into mifepristone treatment group (15 mg/ml.kg.day, 3 days), control group(no treatment) and CMC-Na treatment group(0.5% CMC-Na, 1 ml/kg.day, 3 days). The content and distribution of chorionic gonadotropin beta subunit and collagen type IV in the female Rhesus monkeys were examined by immunohistochemical technique. RESULTS: Compared with the control group, the immunohistochemical reaction intensity of chorionic gonadotropin beta subunit in the plasm of stroma cells, glandular epithelial cells and decidual cells of decidua, and synctial trophoblast cells of villus significantly decreased in the mifepristone treatment group. The positive staining of collagen type IV surrounding the epithelial glandular basal membrane, decidual cells and blood vessels in decidua and surrounding the synctial trophoblast cells in villus were significantly reduced. CONCLUSION: Mifepristone may have a strong effect in decreasing the bioactivity of beta-CG in decidua and the synthesis of beta-CG in villus, and in accelerating the degradation of collagen type IV in decidua and villus.

Animals↗

[Study on the indication of surgical resection of pulmonary metastasis of malignant trophoblastic tumor].

OBJECTIVE: To investigate the indication of lung lobectomy in patients of malignant trophoblastic tumor with lung metastasis. METHODS: Data on a total of 629 cases of malignant trophoblastic tumor of stage III-IV in Peking Union Medical College Hospital from 1990 to 2003 were reviewed. Ninety-five cases including those that underwent lung lobectomy and cases with normal level of serum human chorionic gonadotropin-beta subunit (beta-hCG, < 2 IU/L) and residual pulmonary nodules after chemotherapy were selected and studied. RESULTS: Lung lobectomies were performed on six cases of invasive mole with lung metastasis and the pathological results were all necrotic nodules;another 35 cases of invasive mole with normal level of serum beta-hCG but residual pulmonary nodules after chemotherapy have been followed up for 6 months to 11 years and all were stable of diseases (SD). Lung lobectomies were performed on 29 cases of choriocarcinoma with lung metastasis. Among them, there were 17 cases whose pathological results were hemorrhage and necrotic tissue without trophoblastic cells (negative pathological results), while trophoblastic cells could still be detected in 12 cases of resected lung specimens (positive pathological results). Twenty-five cases of choriocarcinoma with normal serum beta-hCG but residual pulmonary nodules after chemotherapy were followed up, five cases had progress of disease (PD) and 20 were SD. There were no significant differences of age, stage and the last pregnancy between the positive and negative pathological results, SD and PD groups, respectively. However, the number of chemotherapeutic courses for decreasing beta-hCG from 10 IU/L to 2 IU/L and the total courses in the group of positive pathological results and PD group were significantly more than that of negative pathological results group and SD group (P = 0.01, P = 0.001). CONCLUSIONS: For invasive mole, lung metastasis can be successfully treated by chemotherapy alone. Patients with residual pulmonary nodules but normal serum beta-hCG after chemotherapy can be followed up and spared lung lobectomy. For choriocarcinoma, slowly decreasing of beta-hCG from 10 IU/L to 2 IU/L is a high risk for chemoresistance, and it is an indication for thoracotomy. Progression of disease after multiple chemotherapy courses should be treated with lung lobectomy.

Adult↗

Does cyclic human chorionic gonadotropin secretion indicate embryo loss in in vitro fertilization?

The human chorionic gonadotropin (hCG) beta subunit curve of normal singleton in vitro fertilization (IVF) pregnancies shows cyclic peaks during the first 56 days after embryo transfer (ET). This phenomenon is not demonstrable in normal spontaneous conceptions. The hCG curves of 151 singleton IVF pregnancies achieved by transfer of two, three, and four embryos therefore were compared statistically with the hCG curves of singleton IVF pregnancies achieved by transfer of only one embryo. The hCG levels of singleton IVF pregnancies achieved by transfer of more than one embryo had statistically higher hCG levels at 7 and 8, 19 and 20, and 37 and 38 days after ET. In a separate evaluation it was observed that declines in hCG levels of normal singleton IVF pregnancies preceded four of five first-trimester abortion incidence peaks of singleton IVF pregnancies. The observed cyclic hCG secretion may be indicative of early embryo deaths. This observation supports the contention that multiple ET results in significantly more multiple implantations than previously appreciated. Thus embryo survival in utero may represent another major contributory factor to success or failure of IVF.

Chorionic Gonadotropin↗

Pitfall in the diagnosis of ectopic pregnancy: immunocytochemical evaluation in a patient with false-negative serum beta-hCG levels.

Tubal pregnancy specimens from a patient with undetectable serum beta-hCG levels and a control case with a low beta-hCG titer by radioimmunoassay were analyzed using peroxidase-antiperoxidase immunocytochemical localization of placental proteins. The results indicated that deficient production of beta-hCG by ectopic trophoblast was responsible for false-negative pregnancy tests in one patient.

Adult↗