Diagnostic reliability of vaginal ultrasound in ectopic pregnancy

The therapeutic approach to ectopic pregnancy (EP) has changed over the last decade. A prerequisite for a differentiated management is an early diagnosis of EP. This can be achieved by transvaginal sonography (TVS). The purpose of this study was to evaluate the accuracy of TVS in the diagnosis of EP. 184 patients with clinically suspected ectopic pregnancy were examined by TVS. In 103 cases suspicion of EP was confirmed, in 81 cases it was ruled out. All cases were evaluated by laparoscopy, D&C, serial HCG determinations or sonographic follow-up in case of an intrauterine pregnancy. Sensitivity of TVS in the diagnosis of EP was 96%, specificity 88%, the positive predictive value was 89%, the negative predictive value was 95%. Four cases with a false negative result at TVS were very early in pregnancy and were subjected to laparoscopy because of persistent high HCG values without demonstration of an intrauterine pregnancy. Five cases of sonographically confirmed ectopic pregnancies were missed by the first laparoscopy. These cases required intervention because of clinical symptoms and had low levels of HCG. TVS has a high diagnostic accuracy in the diagnosis of ectopic pregnancy.     

A prospective study of early pregnancy loss

The New York State Early Pregnancy Detection Study was a prospective study of early pregnancy loss, between implantation and menses, in 217 women attempting to become pregnant during 1989-1992. Women collected urine samples on three consecutive mornings during the late luteal phase of their menstrual cycle, for up to 12 cycles, contributing samples for 1253 menstrual cycles. Urinary human chorionic gonadotrophin (HCG), measured using an immunoradiometric assay, was the biomarker for pregnancy. We observed a range of early pregnancy loss (EPL) rates, from a low estimate of 11.0% to a high estimate of 26.9%, depending on the definition used and the subgroup analysed. Based on a definition of 3 days of HCG concentration > or = 4.00 pmol/l, 2 days > or = 5.33 pmol/l or the last day of HCG > or = 6.67 pmol/l, we identified 115 positive cycles; 95 cycles were clinically confirmed pregnancies and 20 cycles were EPL, giving an EPL rate of 17.4% [95% confidence interval (CI) 11.0-25.6]. In addition, we observed an EPL rate of 19.5% (95% CI 11.3-30.1) for samples collected within a 15 day window around menses, and a rate of 20.3% (95% CI 11.3-32.2) for samples limited to the first three menstrual cycles. Because studies use urine collection schemes other than daily sampling, the definition of pregnancy will be crucial in defining EPL.     

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.     

Lupus anticoagulants in patients with systemic lupus erythematosus

Lupus anticoagulants (LA) and anticardiolipin antibodies (aCL) are known as thrombosis-related antiphospholipid antibodies. LA is not as well characterized as aCL, and the relation between LA and aCL is not clarified. Since standardized method for the detection of LA has not been established, we measured LA activities in outpatients with SLE by using two different methods (KCT and dRVVT), and analyzed the characteristics of LA in SLE. LA was detected in 29.8% of all samples (14.3% in both methods, 15.5% in one method). IgG-aCL and IgM-aCL was detected in 38% and 20%, respectively, of all LA positive samples. Though a good correlation was observed between LA activities and IgG-aCL levels, a considerable number of LA positive samples were negative for aCL. This indicated the presence of factors with LA activity other than aCL. On the contrary there was also a high percentage of LA negative samples with positive aCL (42.4% in IgG-aCL, 47.4% in IgM-aCL), suggesting the presence of aCL with poor or low LA activity. These findings showed the heterogeneity of antiphospholipid antibodies both in LA and in aCL. The platelet function tests showed increased platelet adhesiveness and normal platelet aggregation in LA positive patients with SLE even in the inactive phase. The serum levels of factors such as protein C, protein S, antithrombin III and thrombomodulin were within normal range. Clinical features such as hemolytic anemia, thrombosis and abortion were more frequently observed in LA positive population than in LA negative population. The clinical features tend to be different between patients with dRVVT-LA and those with KCT-LA, though not significant. Because of the heterogeneity in LA, a combination of more than two different methods including dRVVT was recommended for the detection and the evaluation of LA.     

Evaluation of diagnostic procedures to detect Mycoplasma synoviae in commercial multiplier-breeder farms and commercial hatcheries in Florida

Sera from 5325 chickens representing 71 commercial poultry flocks were tested for Mycoplasma synoviae (MS) using standard National Poultry Improvement Program (NPIP) testing guidelines. Based on the NPIP guidelines, only sera (N = 195) from flocks that test positive by specific plate agglutination (SPA) were submitted for additional confirmatory tests. Flocks from three multihouse farms were identified as seropositive for MS and confirmed by culture and polymerase chain reaction (PCR). Serum samples (N = 195) from these seropositive flocks were compared by SPA, enzyme-linked immunoassay (ELISA), and hemagglutination-inhibition (HI). Of the 195 sera tested for MS from these flocks, 145 (74%) sera were positive by SPA. Of the 145 SPA-positive sera, the HI test was positive for 127 samples (90.2%), whereas the ELISA was positive for 141 samples (98.6%). This difference between the two tests was significant (P = 0.0006). Significant differences (P = 0.0002) in titer were obtained from paired serum samples that were submitted to three different laboratories for HI analysis. Both the SPA and HI tests failed to detect early infection in newly introduced flocks following depopulation of MS-positive facilities. Both ELISA and PCR detected new infections on these farms. In the MS outbreak described in this study, SPA was not adequate as the sole screening test and HI was not adequate for confirmation of flock infection status. Continued reliance on the same or a similar type of testing could result in missed infections. Confirmation of infection by PCR was preferable to HI and also may be used in place of culture. The findings of this study suggest that ELISA should be considered as a serologic screen in lieu of SPA, screening with SPA may miss MS-infected flocks, and PCR should be considered as a confirmatory test.     

Carpal fractures in children

This study addresses the likelihood of false negative urine pregnancy test results, due to physiological urine dilution as described in some anecdotal reports. In this prospective study 320 pregnancy tests were performed on urine samples of varying concentrations obtained from 40 women, with suspected complications of early pregnancy, who had presented for ultrasound scans. Four different pregnancy tests were used and serum betahCG levels were measured quantitatively. Despite a mean fivefold increase in urine dilution, the pregnancy tests with low betahCG detection limits maintained maximal sensitivity. The detection of betahCG in dilute urine was adversely affected by using pregnancy tests with higher betahCG detection limits and these tests should be used with caution when assessing gynaecological emergencies.     

Endometrial and placental protein markers and ovarian steroids in serum during in-vitro fertilization cycles

The objective of this study was to find the earliest time at which it was possible to detect clinical pregnancy in an in-vitro fertilization (IVF) treatment cycle supported with human chorionic gonadotrophin (HCG), and also retrospectively to diagnose abnormal ovarian- or endometrium-related situations in failure cycles. Serum samples were taken in 41 IVF cycles at frequent intervals from the beginning of ovarian stimulation until menstrual bleeding occurred or a pregnancy was established. Concentrations of oestradiol, progesterone, placental protein 14 (PP14), pregnancy-specific beta 1-glycoprotein (SP1), and pregnancy-associated plasma protein A (PAPP-A) were determined in the serum samples using commercially available (steroid) or purpose-developed (protein) immunoassays. The cycles were retrospectively distributed into four outcome groups: (i) fertilization failure (FF, n = 8); (ii) implantation failure (IF, n = 10); (iii) 'interaction' (embryo-endometrium) cycle (IC, n = 14), and (iv) clinical pregnancy (CP, n = 9). The embryo-endometrium interaction was detected by a rise in SP1 in 23 cycles (70% of embryo transfers) at a time when endogenous HCG was still masked by external support. Early ('false') positive SP1 concentrations were observed in two out of eight and five out of 14 cases in groups FF and IC respectively, but never amongst the ongoing pregnancies (CP). PAPP-A did not distinguish pregnancy from the other outcomes. The PP14/progesterone ratio was lower, later in the cycle, in CP than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ectopic pregnancy--changing trends

This study is an attempt to have an overall view of the changing trends in the clinical presentation, diagnostic modalities and management of ectopic pregnancy over a period of three and a half decades. The incidence of ectopic pregnancy was one in 368 during the 15-year period from 1959-1973 (group A) and has increased to one in 160 during the latter part of the study period from 1988-1993 (group B). Medical termination of pregnancy, abortion, intra-uterine contraceptive device and previous tubal ligation were the important risk factors recently (group B). Unruptured tubal pregnancy was diagnosed in 9.8% (group B) as compared to only 3% in group A. However, as most of the patients came to the hospital with disturbed pregnancy, the use of ultrasonography and urine gravindex test was helpful in only 14% in the latter part of the study. The characteristic clinical features like pain abdomen with amenorrhoea, vaginal bleeding and positive culdocentesis were the most reliable diagnostic criteria in both the groups. There is an increasing trend towards conserving the tubes and methotrexate use recently.     

Hormone therapy of spontaneous abortion. Our experience with treatment with Gravibinan

The results of the treatment of 151 pregnancies with threatened and/or habitual abortions by using high hormonal dosages (Gravibinan "Alkaloid") are presented. Eight pregnancies were in primigravidas, the remaining 143 patients having previously had 47 interruptions of pregnancy, 66 deliveries, and 313 spontaneous abortions. Disregarding artificial abortions in 379 previous pregnancies there were 313 or 82.5 per cent spontaneous abortions. The treatment was performed by i. m. applications of Gravibinan, during the first week every two days, during the following two weeks every three days, and until the accomplished 16 weeks of pregnancy every five days. Besides hormonal therapy, all patients were on bed rest; in the following course of pregnancy tocolysis and in the case of opened cervix the cerclage cervicis were performed. The vitality of the ovum and the fetus, as well as the efficacy of the treatment were evaluated by clinical findings, HCG and estriol urinary eliminations, and by ultrasonography. Out of 151 treated pregnancies, 21 (13.91%) resulted in early abotion, 17 (11.26%) in mid-trimester abortion, 6 (3.97%) in pre-term, and 107 (70.86%) in term deliveries. There were two (1.77%) perinatally dead premature infants. HCG urinary eliminations were significantly lower in pregnancies resulting is missed abortion or first-trimenon miscarriage, whereas no difference was established between pregnancies resulting in delivery or mid-trimester abortion. The authors recommend hormonal treatment in early threatening and/or habitual abortions by administering high dosages of estrogens and gestagens. Such a treatment stimulates secretory transformation of the endometrium at the beginning of pregnancy, and this allows early placentation and the uterine growth with a simultaneous quiescence of the myometrium, which, in turn, makes the growth of the ovum possible. The authors stress the importance of a complex procedure in the establishment of the etiology and in the treatment of spontaneous and/or habiutal abortion.     

Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility

Methotrexate treatment was compared to laparoscopic salpingotomy for conservative management of ectopic pregnancy in a prospective randomized study. One hundred patients were randomized into two groups using random numbers. Inclusion criteria were an ectopic pregnancy visualized by ultrasound with a pre-therapeutic score <13 as assessed by the following six criteria, graded from 1 to 3: gestational age, human chorionic gonadotrophin (HCG) concentration, progesterone concentration, abdominal pain, haemoperitoneal volume and diameter of the haematosalpinx. The treatments were either 1 mg/kg of methotrexate injected transvaginally into the ectopic pregnancy without anaesthesia or administered i.m. when the pregnancy could not safely or easily be punctured (group 1), or laparoscopic salpingotomy (group 2). Success was defined as the return to normal (<10 mIU/ml) of HCG concentrations. Treatment was successful for 45 of 51 patients in group 1 (88.2%) and 47 of 49 in group 2 (95.9%). Medical treatment was significantly (P < 0.05) associated with shorter postoperative stay (24 compared with 46 h), but HCG returned to normal more quickly after laparoscopic treatment (13 compared with 29 days). Spontaneous reproductive performance was similar in both groups, but overall intrauterine pregnancy was higher, and repeat ectopic pregnancy lower, after methotrexate treatment. In selected cases of ectopic pregnancy, with a pre-therapeutic score <13, methotrexate treatment appeared as safe and efficient as conservative treatment by laparoscopy and was associated with improved subsequent fertility.     

Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients

The performance of two Aspergillus antigenemia systems, the sandwich enzyme-linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive aspergillosis were compared by testing 364 serum samples from 22 bone marrow transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were 60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients found positive with both methods, the ELISA test became positive earlier than the LA test or remained positive after the LA test had become negative. These results encourage further evaluation of the Platelia Aspergillus test, to assess its role in the management of invasive aspergillosis in BMT patients.     

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype

OBJECTIVE: To assess the relation between maternal serum pregnancy associated plasma protein A (PAPP-A) in the first trimester and the outcome of pregnancy by karyotype. DESIGN: A retrospective study of PAPP-A levels in blood samples collected prior to chorionic villus sampling. SETTING: Milan, Italy. SUBJECTS: Five hundred twenty-two women aged 20 to 47, at 7 to 11 weeks gestation, prior to undergoing chorionic villus sampling. Four hundred forty-five women had a pregnancy with a normal karyotype; in 30 pregnancies the karyotype was abnormal (including 14 cases of Down's syndrome and 7 of trisomy 18). MAIN OUTCOME MEASURES: Normal or abnormal fetal karyotype. Serum PAPP-A at 6 to 11 weeks gestation measured by radioimmunoassay. RESULTS: The median value of PAPP-A in the abnormal group was 0.27 multiples of the normal median (MoM). This is significantly lower than the median value in the normal group (1.01 MoM) (95% CI for the difference 0.46-0.84 MoM; P < 0.00001 Mann-Whitney test). CONCLUSIONS: There is an association between low levels of PAPP-A in the first trimester with chromosome anomalies. Screening by measurement of PAPP-A might detect 60% of cases of Down's syndrome in the first trimester with a false positive rate of 5%.     

Detection of hydatid antigen in urine by countercurrent immunoelectrophoresis

Hydatid antigen was demonstrated for the first time in the urine of patients with hydatid disease by countercurrent immunoelectrophoresis (CIEP). The antigen was detected in the concentrated urine of 7 of 16 (43.75% positive) patients with surgically confirmed hydatid disease, 4 of 10 (40% positive) patients with ultrasound-proven hydatid disease (daughter cysts or prominent septation and hydatid sands demonstrated by ultrasound), and 8 of 14 (57.14% positive) patients with clinically diagnosed (presumptive) hydatid disease. No antigen was detected in the concentrated urine from 24 patients with parasitic diseases other than hydatid disease. However, antigen was detected in 2 (8% false positive) of 25 concentrated urine samples collected from healthy control subjects (blood donors and students). These result suggest that the detection of hydatid antigen in the urine by CIEP is a simple, rapid, and noninvasive method of diagnosis of hydatid disease.     

Clinical significance of changes of urinary enzymes in pregnancy induced hypertension

OBJECTIVE: To study the clinical significance of changes of N-acetyl-beta-D-glucosaminidase (NAG) and lysozyme in random urine sample in pregnancy induced hypertension (PIH). METHODS: The concentration of NAG was measured by oronitrophenol spectrophotometric methods, and the concentration of lysozyme by agar plate diffusion method. Random urine samples from 266 pregnant women were examined, 110 cases were normal pregnant women, 156 cases were PIH patients. RESULTS: (1) The level of NAG and lysozyme in moderate and severe PIH patients were significantly higher than that in mild PIH patients and normal pregnant women (P < 0.01) and it increased with the severity of disease. (2) There was a positive correlation between NAG and protein/creatinine (Pr/Cr) ratio in random urine. (3) There was a positive correlation between urinary lysozyme and serum beta 2-microglobulin (r = 0.874, P < 0.05). CONCLUSION: Determination of urinary NAG and lysozyme levels will differentiate various states of PIH.     

Multiplex AMPLICOR PCR screening for Chlamydia trachomatis and Neisseria gonorrhoeae in women attenting non-sexually transmitted disease clinics. The European Chlamydia Epidemiology Group

A new PCR kit (AMPLICOR CT/NG; Roche Diagnostic Systems, Inc., Branchburg, N.J.) was used as a screening tool for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in first-void urine (FVU) specimens from 3,340 asymptomatic women attending European health care units for contraceptive advice or pregnancy termination. All samples were kept frozen (-20 degrees C) prior to testing. Chlamydia-positive samples were retested once by the plasmid-based PCR kit and also by a major outer membrane protein (MOMP) primer-based PCR. Discrepancies were resolved by using the direct immunofluorescence test (DIF) with the centrifuged sediment of the FVU specimens. Samples positive for N. gonorrhoeae were retested by chromosomal primer-based PCR and verified by a 16S RNA PCR. Of the samples tested, 1.8% were considered inhibitory by using the internal amplification control. Of 81 samples positive for C. trachomatis, 74 samples were positive by both plasmid- and MOMP-based PCRs, 6 samples were positive by plasmid-based PCR and DIF, and one sample was positive by both MOMP-based PCR and DIF. Nine samples (0.3%) were positive for N. gonorrhoeae by the chromosomal primer-based PCR; however, none of the results could be confirmed. The test offers the unique ability to identify inhibition of amplification with the optional internal control.     

Cytologic diagnosis of transitional cell carcinoma of the urinary bladder. Comparison with endoscopical and pathological findings on 538 cases

There were investigated 583 cases with tumors of the urinary bladder and 612 patients with non-malignant diseases of the urinary tract. Samples of voided urine were taken from all cases and direct smears fixed by drying were stained by rapid blue polychrome-tanin Dr?gan method Cytological results were compared with endoscopical and pathological findings. The overall rate of real positive results was 91.7% and false negative results were noticed in 8.3% of cases. A direct relationship between real positive results and histological "G" was found. Causes for false negative results were: tumor developed in a bladder diverticulum, calcified tumor, irradiated tumor, insufficient quantity of voided urine, chronic urinary infections and underestimation of cytological criteria of cellular malignancy. There were 9 false positive results in patients with nonmalignant diseases, due to lithiasis, chronic renal failure and chronic urinary infections. The cytological grade of differentiation was performed by the method purposed by Friedman and Ash, and concordance with the standard histological finding was 76.4%. Urine cytology is thought to be a useful method in the primary diagnosis and recurrences of transitional cell carcinoma of the urinary bladder, in all patients with hematuria, recurrent infections of the urinary tract and neglected lithiasis.     

Haematological aspects of antenatal diagnosis for thalassaemia in Britain

The results are described of 200 antenatal diagnostic tests for haemoglobinopathies performed on samples of fetal blood obtained during the second trimester of pregnancy. Haemoglobin A synthesis in the fetus was measured by incorporation of tritiated leucine in vitro and separation of the globin chains on CM23 columns. The range of HbA synthesis detected was 3.5-8.0% in normal fetuses, 2.0-5.0% in fetuses with thalassaemia trait, and less than 1.6% in fetuses with thalassaemia major. There were eight cases in which other haemoglobinopathies were diagnosed. 29% of the pregnancies were terminated because thalassaemia major was diagnosed, and 9.5% of the remaining healthy fetuses were lost for obstetric reasons. Follow up has been possible for 96% of the 124 surviving babies and three misdiagnoses have come to light; one false positive (0.5%) and two false negatives (1%). These figures represent a first effort at antenatal diagnosis for haemoglobinopathies and it is likely that they will improve with the passage of time.     

Intestinal Chlamydia in finishing pigs

Gut and blood samples from 119 finishing pigs derived from 11 farms were collected during routine slaughter at an abattoir. Sections of formalin-fixed, paraffin-embedded tissues were labeled immunohistochemically using genus-specific, mouse monoclonal antibody against chlamydial lipopolysaccharide; goat polyclonal antiserum against the major outer membrane protein of Chlamydia trachomatis; and mouse monoclonal antibody against the ovine abortion subtype of C. psittaci. Gut samples from 33 of 111 (29.7%) individual pigs stained positive with the genus-specific monoclonal antibody, and of these 30 of 32 (93.7%) also reacted with the C. trachomatis-specific antiserum. Labeled inclusions were restricted to mature enterocytes of the large intestine in 33 of 111 cases. Infection of small intestinal enterocytes was noted in only one of 82 ileal samples. The blood samples were tested for antichlamydial antibodies by enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT). With ELISA, 95 of the 115 sera tested (82.6%) yielded positive antichlamydial reactions. With CFT, 34 of the 119 sera tested (28.6%) were unequivocally positive (> or = 1:10, 100% binding), and 10 (7.6%) yielded doubtful positive reactions (1:10, 50-75% binding). Positive ELISA and CFT titers showed poor agreement (kappa = 0.112), whereas the agreement between positive findings by immunohistochemical labeling and CFT was fair (kappa = 0.205).     

Advanced laboratory techniques for diagnosing Toxoplasma gondii encephalitis in AIDS patients: significance of intrathecal production and comparison with PCR and ECL-western blotting

The aim of this study was to determine the influence of neonatal focal cerebral hypoxia-ischemia (HI) on sleep-waking pattern, electrocorticogram (ECoG) power spectra and locomotor activity (LA) in adult Wistar rats. Seven-day old pups were subjected to permanent unilateral ligation of the common carotid artery and transient hypoxia (8% O2). At 10 weeks of age, the extent of brain damages was evaluated by magnetic resonance imaging (MRI) and homogenous injured animals were selected before chronic implantation of radiotelemetry device. Using a single ECoG recording channel method, waking (W), paradoxical sleep (PS) and slow wave sleep (SWS) were continuously recorded for 72 h and they were semi-automatically analyzed off-line. We observed that neonatal HI triggers a cascade of events leading, in adult rats, to brain dysfunction characterized by an increase in SWS (55.0 vs. 40.2% in sham-operated rats, p<0.05) and a marked decrease in W phases duration (43.4 vs. 51.5%, p<0.05) while PS was almost suppressed in HI rats (1.6 vs. 8.3%, p<0.05). In addition, power spectral analysis of ECoG revealed significant (p<0.05) alteration in PS power density with a shift of the dominant frequency peak (5.0 to 7.5 Hz for HI and sham-operated rats, respectively). During the light period, we found that HI induced a pronounced reduction of LA (-30%, p<0.05). These results indicate that Wistar rats exposed to a neonatal unilateral cerebral HI present significant ECoG activity, sleep-waking pattern and behavioral disturbances when adults. However, it remains to establish whether such alterations can be prevented by neuroprotective agents.     

The 'LH/HCG test', a valuable aid in the diagnosis of tubal pregnancy

174 patients with suspected tubal pregnancy were thoroughly examined. The diagnosis was confirmed in 102 women. As the usual noninvasive and invasive examination methods proved to be rather inaccurate, a new procedure, the 'LH/HCG test', was evaluated. Results were positive in all our cases. It was therefore concluded that this assay should receive primary consideration when tubal pregnancy is in question.