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J Owen

Publications and source records attributed to J Owen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mutations in the HIV type 1 integrase of patients receiving long-term dideoxynucleoside therapy do not confer resistance to zidovudine.

Metabolites of AZT can inhibit HIV-1 integrase in vitro (Mazumder A, et al., Proc Natl Acad Sci USA 1994;91:5771-5775). To determine if long-term dideoxynucleoside therapy can lead to the emergence of HIV-1 AZT-resistant variants containing mutations in the integrase, we have sequenced the proviral DNA encoding the HIV-1 integrase of nine HIV-1-infected patients at different time points during treatment. Four of the nine patients developed mutations during the course of treatment. Although most mutations occurred at nonconserved amino acids, one patient developed a mutation at codon (R166T), a residue that is conserved among all integrases from known HIV-1 isolates. This mutation was introduced in the recombinant HIV-1 integrase protein to determine if it could confer resistance to AZT in vitro. We show that the R166T integrase mutant is still proficient at carrying 3'-processing and 3' end-joining but that the enzyme is not resistant to AZT-TP. Our results suggest that it is unlikely that integrase inhibition contributes to the antiviral activity of AZT.

Amino Acid Sequence↗
PubMed2000

Role of amniotic fluid homocysteine level and of fetal 5, 10-methylenetetrahydrafolate reductase genotype in the etiology of neural tube defects.

A mutation in the gene 5,10-methylenetetrahydrofolate reductase (MTHFR), leading to altered homocysteine metabolism, has been identified in parents and fetuses with fetal neural tube defects. We sought to determine which is of greater importance in fetal neural tube defect formation: the fetal MTHFR mutation or elevated amniotic fluid homocysteine level. We retrieved stored amniotic fluid from cases of isolated fetal neural tube defect diagnosed from 1988 to 1998 (n = 80), and from normal controls matched for race, month and year of amniocentesis, and maternal age. The presence or absence of the 677C-->T mutation of MTHFR was determined and homocysteine levels were measured; cases and controls were compared. Significantly more cases than controls were heterozygous or homozygous for the 677C-->T MTHFR mutation (44% vs 17%, P < or = 0.001). Cases were also significantly more likely than controls to have an amniotic fluid homocysteine level above the 90th centile (>1.85 micromol per liter); 27% vs 10%, P = 0.02. Thirty one cases and 12 controls had an abnormal genotype; however, amniotic fluid homocysteine levels were not significantly different between these two groups (6/31, or 19% of cases had an elevated homocysteine compared to 1/12, or 8% of controls; P = 0.65). In contrast, 40 cases and 60 controls had a normal genotype; the neural tube defect cases had significantly higher homocysteine levels (13/40, or 32% of cases had an elevated homocysteine level compared to only 6/60, or 10% of controls; P = 0.008). Although both abnormal fetal MTHFR genotype and abnormal amniotic fluid homocysteine concentration are significantly associated with neural tube defects, the association with amniotic fluid homocysteine concentration is significant regardless of the fetal MTHFR genotype. The relationship between maternal and fetal homocysteine metabolism is complex.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2000

Amniotic fluid homocysteine levels, 5,10-methylenetetrahydrafolate reductase genotypes, and neural tube closure sites.

A specific gene mutation leading to altered homocysteine metabolism has been identified in parents and fetuses with neural tube defects (NTDs). In addition, current animal and human data indicate that spine closure occurs simultaneously in five separate sites that then fuse. We sought to determine whether either this mutation or abnormal amniotic fluid homocysteine levels are associated with all five neural tube closure sites. We retrieved stored amniotic fluid from cases of isolated fetal neural tube defect diagnosed from 1988 to 1998 (n = 80) and from normal controls matched for race, month and year of amniocentesis, and maternal age. Cases were categorized according to defect site by using all available medical records. The presence or absence of the 677C-->T mutation of 5, 10-methylenetetrahydrafolate reductase (MTHFR) gene was determined, and homocysteine levels were measured; case and controls were compared. Significantly more cases than controls were heterozygous or homozygous for the 677C-->T MTHFR mutation (44% vs. 17%, P < or = 0. 001). Likewise, cases were significantly more likely than controls to have amniotic fluid homocysteine levels >90th centile (>1.85 micromol/L), 27% vs. 10%, P = 0.02. Most (83%) of control cases had both normal MTHFR alleles and normal amniotic fluid homocysteine levels (normal/normal), whereas only 56% of NTD case were normal/normal (P = 0.001). When evaluated by defect site, only defects involving the cervical-lumbar spine, lumbosacral spine, and occipital encephalocele were significantly less likely to be normal/normal than controls (P = 0.007, 0.0003, and 0.007, respectively), suggesting a strong association with the 677C-->T allele. In contrast, anencephaly, exencephaly, and defects confined to the sacrum included many cases that had both normal MTHFR alleles and normal homocysteine and were not significantly different from controls. The 677C-->T MTHFR mutation and elevated homocysteine levels appear to be disproportionately associated with defects spanning the cervical-lumbar spine, lumbosacral spine, and occipital encephalocele. In contrast, anencephaly, exencephaly, and defects confined to the sacrum may not be related to altered homocysteine metabolism.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2000

Extra-amniotic saline, laminaria, or prostaglandin E(2) gel for labor induction with unfavorable cervix: a randomized controlled trial.

OBJECTIVE: To determine which of three methods of cervical ripening resulted in the lowest cesarean rate in women with unfavorable cervices and indications for labor induction. METHODS: Consenting women with singleton gestations, vertex presentations, and unfavorable cervices (dilatation under 2 cm and effacement under 75%) were randomly assigned to laminaria and standard intravenous oxytocin, serial doses of intracervical prostaglandin (PG) E(2) gel (Prepidil, Pharmacia & Upjohn, Inc., Kalamazoo, MI) 0.5 microg every 6 hours for two doses followed by oxytocin if indicated, or extra-amniotic saline infusion and oxytocin. RESULTS: An interim analysis after recruitment of 321 subjects, 67% of the planned sample, found similar cesarean rates for the three groups (laminaria 36%; PGE(2) gel 33%; saline infusion 29%; P =.59); however, the mean randomization-to-delivery interval was significantly longer in the PGE(2) group. Stochastic curtailment, as part of the interim analysis, indicated a low likelihood of achieving a statistically significant difference in cesarean rates between PGE(2) gel and the other two groups. Therefore, we completed the study with saline infusion and laminaria. The saline infusion and laminaria groups had similar preinduction characteristics. The cesarean rates were similar (saline infusion 25.4% versus laminaria 30.3%; P =.32), but the mean interval from randomization to delivery was shorter in the saline infusion group (18.0 versus 21.5 hours, P =.002). There were no significant differences in selected maternal and neonatal morbidities. CONCLUSION: Cervical ripening with extra-amniotic saline infusion, PGE(2), or laminaria resulted in comparable cesarean rates in women with an unfavorable cervix and indications for labor induction. Extra-amniotic saline infusion had the shortest randomization-to-delivery interval without increasing maternal or neonatal morbidity.

Adult↗
PubMed2000

Criteria for failed labor induction: prospective evaluation of a standardized protocol.

OBJECTIVE: To assess the safety and efficacy of a protocol that mandated at least 12 hours of oxytocin administration after membrane rupture before cesarean delivery for failed labor induction in the latent phase. METHODS: Gravidas at or beyond 36 weeks' gestation undergoing indicated induction with cervical dilatation up to 2 cm were studied prospectively. Prior cesarean was an exclusion criterion. If the fetal heart rate pattern was reassuring, cesarean was not permitted before the active phase of labor (4-cm dilatation and at least 90% effacement or 5-cm dilatation regardless of effacement) unless the membranes had been ruptured and oxytocin administered for at least 12 hours. RESULTS: Five hundred nine women were treated according to protocol; 360 (71%) were nulliparas and 149 (29%) were parous. Twenty-five percent of nulliparas and 9% of parous women were delivered by cesarean. After 6 hours of ruptured membranes and oxytocin, 14% of nulliparas were still in the latent phase; 39% of whom delivered vaginally, compared with 7% still in the latent phase after 9 hours (vaginal delivery rate 28%), and 4% after 12 hours (vaginal delivery rate 13%). In contrast, after 6 hours of ruptured membranes and oxytocin, only five (3%) parous women were still in the latent phase. Among those, none remained in the latent phase for 12 hours and all were delivered vaginally. No women had serious complications. Severe neonatal morbidities were infrequent and not related to duration of the latent phase. CONCLUSION: By requiring a minimum of 12 hours of oxytocin after membrane rupture before failed labor induction could be diagnosed, many nulliparas who remained in the latent phase at 6 and 9 hours had safe vaginal deliveries, and failed labor induction was eliminated as an indication for cesarean in parous women.

Adult↗
PubMed2000

Ultrasound findings and multiple marker screening in trisomy 18.

OBJECTIVE: To compare detection of trisomy 18 in the second trimester by ultrasound and multiple-marker testing. METHODS: A computerized genetics database was used to identify fetuses of 14-22 weeks' gestation who had comprehensive ultrasound examinations, multiple-marker screening tests (alpha-fetoprotein [AFP]), hCG, unconjugated estriol [E3], and trisomy 18 karyotype. A positive trisomy 18 screen was defined as AFP up to 0.75 multiples of the median (MoM), hCG up to 0.55 MoM, and unconjugated E3 up to 0.60 MoM. A risk of at least 1:190 defined a positive Down syndrome screen. Ultrasound abnormalities were diagnosed prospectively and were confirmed later by retrospective review of sonographic images. RESULTS: From 1988-1997, 30 trisomy 18 fetuses who had comprehensive ultrasounds and multiple-marker testing were identified. Twenty-one (70%) had abnormalities detected by ultrasound, of which the most common isolated finding was choroid plexus cyst. Eleven fetuses (37%) had positive trisomy 18 screens, and two had positive Down syndrome screens, for a total of 13 of 30 (43%) fetuses with positive multiple-marker screening tests. CONCLUSION: We found that ultrasound was more likely to be abnormal than multiple-marker screening tests in fetuses with trisomy 18 (70%) (95% confidence interval [CI] 54, 86 versus 43% CI 25, 61). However, combining the two testing methods yielded the highest detection rate (80% [CI 66%, 94%]).

Adult↗
PubMed2000

Phase I open study of the effects of ascending doses of the cytotoxic immunoconjugate CMB-401 (hCTMO1-calicheamicin) in patients with epithelial ovarian cancer.

PURPOSE: We have performed a phase I study of the cytotoxic immunoconjugate CMB-401 in women with epithelial ovarian cancer (EOC). CMB-401 is a directed chemotherapy that comprises a genetically engineered human antibody against polymorphic epithelial mucin, to which is attached covalently two to three molecules, on average, of the cytotoxic antibiotic calicheamicin. The primary objectives of this two-centre study were to identify end-organ toxicities and to establish the maximum tolerated dose (MTD). PATIENTS AND METHODS: Thirty-four patients aged 37-75 years with progressive EOC not amenable to platinum/standard therapy, and with satisfactory WHO performance status (0-2) were recruited. Patients had received a mean of 3.2 previous chemotherapeutic regimens with a median interval since last chemotherapy of 182 days (range 34-1217). Patients received up to four cycles of a dual infusion of 35 mg/m2 hCTMO1 'predose' followed by doses of CMB-401 which were increased for each cohort--a regimen which minimises drug uptake in normal tissues whilst enhancing delivery to the ovarian tumour. CMB-401 dosing commenced at 2 mg/m2 and progressed via seven cohorts to 16 mg/m2. RESULTS: CMB-401 was generally well tolerated. However, transient fever and emesis occurred, necessitating routine prophylaxis, and increasingly significant malaise was reported as the dose increased. WHO grade 3-4 toxicities, irrespective of causality, included: anaemia 21%, granulocytopenia 9%, thrombocytopenia 9%, liver transaminases 3%, sepsis 3%, haemorrhage 6%, nausea/vomiting 76%; pulmonary 6%, and conscious state/somnolence 6%. The MTD was reached at 16 mg/m2. During the study four patients had a greater than 50% reduction in CA125, and three patients had radiological evidence of reduction in tumour bulk. CONCLUSIONS: CMB-401 appears to have an acceptable toxicity profile with demonstrable activity against EOC.

Adult↗
PubMed2000

A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma.

The purpose of this study was to compare the response rate, overall and 1-year survival in patients with advanced melanoma treated with a standard therapy, dacarbazine and interferon-alpha (DTIC/IFN), or combination chemotherapy, consisting of dacarbazine, BCNU, cisplatin and tamoxifen (DBCT). Treatment toxicity and time spent in hospital were secondary end points. One hundred and five patients (of whom 100 were eligible) were randomized to receive either DTIC/IFN or DBCT. The trial was designed to detect a 25% absolute difference in response rate or in 1-year survival with 80% power. There was no significant difference in response rate: this was 17.3% with DTIC/IFN and 26.4% with DBCT. Median overall survival was similar at 199 and 202 days respectively. One-year survival rate favoured standard treatment (30.6 vs 22.6%), but did not differ significantly between arms. DBCT was associated with significantly greater haematological toxicity, and a greater need for time spent in hospital (5.75 days/treatment cycle vs 2.29 with dacarbazine and interferon). DBCT combination therapy cannot be recommended as standard treatment for advanced melanoma. Dacarbazine remains the standard chemotherapy for this condition.

Adult↗
PubMed2000

Cardiovascular effects of intravaginal misoprostol in the mid trimester of pregnancy.

OBJECTIVE: Our aim was to evaluate the cardiovascular effects of high-dose intravaginal misoprostol administration by means of transthoracic electrical bioimpedance monitoring. STUDY DESIGN: Healthy women undergoing mid trimester pregnancy interruption with intravaginal misoprostol were eligible for this prospective observational study. Baseline blood pressure was obtained for 1 hour and transthoracic electrical bioimpedance monitoring was performed before misoprostol administration, 600 microg vaginally. Posttreatment assessments were made every 15 minutes for a total of 4 hours, with patients in a left lateral recumbent position. Heart rate, mean arterial pressure, cardiac index, stroke index, systemic vascular resistance index, and end-diastolic volume index were determined. Measurements were averaged for 30-minute intervals and reported as mean +/- SD. Statistical analyses included the paired t test and repeated-measures analysis of variance. RESULTS: Nine women consented to have transthoracic electrical bioimpedance monitoring, and no statistically significant changes in any of the measured cardiac parameters for the 4-hour monitoring interval were noted. Direct comparisons between the pretreatment and 2-hour posttreatment intervals (reported time peak of blood misoprostol levels) also revealed no significant differences in the cardiovascular index values. CONCLUSION: High-dose intravaginal misoprostol in the mid trimester does not alter maternal cardiac function as measured by transthoracic electrical bioimpedance.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Ignorance is not bliss. Doctors, managers and development.

Current government policy places great emphasis on increased collaboration between disciplines and professions within health care, as in public services across the board. To date, analyses of doctor-manager relations have tended to focus on equipping doctors with management skills, once they have reached consultant level. In contrast, this paper evaluates a new management development initiative, designed to involve doctors and managers at an earlier career stage, and on an inter-disciplinary basis. Interview and questionnaire responses indicate that specialist registrars and young managers share common values; however, they also acknowledge a high degree of mutual ignorance. Evaluation suggests that inter-disciplinary programmes can provide a starting-point for closer collaboration in practice; in conclusion, some options for sustaining this in the long term are identified.

Attitude of Health Personnel↗
PubMed2000

Danaparoid sodium.

Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan antithrombotic agent approved for the prophylaxis of post-operative deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. Danaparoid is a low molecular weight heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic activity has been well established. Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT). It has excellent bioavailability following s.c. injection. Danaparoid has little effect on routine coagulation tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]). Patients with elevated serum creatinine should be monitored carefully. For its FDA approved indication (DVT prophylaxis during hip replacement surgery), its cost per day is approximately eight times more than LMWH. Even though monitoring is not routinely necessary according to the manufacturer for its approved indication, monitoring is frequently necessary when it is used in other clinical scenarios. Its higher cost than comparable therapies for DVT prophylaxis and the low availability of the FXa assay in most non-tertiary care hospitals has limited the widespread use of danaparoid. Danaparoid has been found to be effective in the treatment of HIT although this is an off label use, despite being the most frequent reason why danaparoid is used.

Anticoagulants↗
PubMed1999

Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants.

Human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes of 105 hMIP-1alpha variants generated by systematic mutagenesis and expression in yeast were determined. hMIP-1alpha residues Asp26 and Glu66 were critical to the self-association process. Substitution at either residue resulted in the formation of essentially homogenous tetramers at 0.5 mg/ml. Substitution of identical or analogous residues in homologous positions in both hMIP-1beta and RANTES demonstrated that they were also critical to aggregation. Our analysis suggests that a single charged residue at either position 26 or 66 is insufficient to support extensive aggregation and that two charged residues must be present. Solution of the three-dimensional NMR structure of hMIP-1alpha has enabled comparison of these residues in hMIP-1beta and RANTES. Aggregated and disaggregated forms of hMIP-1alpha, hMIP-1beta, and RANTES generally have equivalent G-protein-coupled receptor-mediated biological potencies. We have therefore generated novel reagents to evaluate the role of hMIP-1alpha, hMIP-1beta, and RANTES aggregation in vitro and in vivo. The disaggregated chemokines retained their human immunodeficiency virus (HIV) inhibitory activities. Surprisingly, high concentrations of RANTES, but not disaggregated RANTES variants, enhanced infection of cells by both M- and T-tropic HIV isolates/strains. This observation has important implications for potential therapeutic uses of chemokines implying that disaggregated forms may be necessary for safe clinical investigation.

Amino Acid Sequence↗
PubMed1999

Patterns of radiotherapy practice for patients with squamous carcinoma of the uterine cervix: patterns of care study.

PURPOSE: To determine the impact of research findings and evolving technology on the patterns of radiotherapy practice for patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Sixty-two radiation therapy facilities participated in the study after having been selected from a random sample, proportionally stratified according to practice type, of all United States facilities. Each facility submitted a list of patients treated during 1992-1994 with radiation for squamous carcinoma of the cervix. Cases for review were randomly selected from each institution after excluding those of patients who had distant metastases or initial hysterectomy. A total of 471 patients' records were reviewed in the treating institutions to obtain information about patients' characteristics, diagnostic evaluation, tumor extent, treatment approach, and radiotherapy techniques. RESULTS: Of the 61 facilities that treated eligible cases of intact cervical cancer during the 3-year survey period, 35 (57%) treated fewer than three eligible patients per year. Thirty-four (83%) of 41 non-academic facilities vs. 1 (5%) of 20 academic facilities treated fewer than three patients per year. FIGO stages were I, II, III, and IV in 32%, 40%, 24%, and 3% of patients, respectively. Computed tomography (CT) was the most common method of lymph node evaluation, but surgical evaluation, which was performed in 76 (16%) patients, had increased from previous surveys. Fields were designed using a dedicated simulator in 95% of patients; a dedicated CT unit was used for treatment planning in 119 (30%) cases. External beam irradiation was most often given using a four-field technique at 180 cGy per day on a 10-20 MV linear accelerator. The average daily fraction size had decreased from previous surveys, and 13% of patients were treated with daily doses of 170 cGy or less. Most patients were treated with a combination of external beam and low dose-rate (LDR) intracavitary irradiation. Of 425 patients who had treatment with curative intent that included brachytherapy, 362 (85%) had LDR brachytherapy, 45 (11%) had high dose-rate (HDR) brachytherapy, 3 had a combination of HDR and LDR, and 15 had incomplete information about the brachytherapy dose-rate. Forty-six (23%) of 197 patients with Stages I-IIA disease were treated with radiation followed by extrafascial hysterectomy. Of 111 patients treated with curative intent for Stage III-IV disease, 72 (65%) had a combination of external beam and intracavitary radiation therapy, 22 (20%) had external beam plus interstitial brachytherapy, and 17 (15%) were treated with external beam irradiation only. For patients who completed treatment with curative intent and did not have adjuvant hysterectomy or HDR brachytherapy, the median total dose at point A was 82.5 Gy. For all patients who completed treatment with radiation alone, the median total duration of treatment was 63 days; more than 70 days were taken to complete treatment in 33% of cases. Twenty-nine percent of patients received chemotherapy, usually concurrent with their radiation therapy. Only 27% of these patients were on investigational protocols. CONCLUSIONS: Greater participation in well-designed prospective trials might help clinicians address important clinical questions and reduce current inconsistencies in the use of adjuvant treatments. Radiation oncologists should take steps to avoid unnecessary treatment protraction and to improve patient compliance. Future studies will be needed to determine whether the small number of cases being treated in most nonacademic facilities will influence the outcome for patients with invasive cervical carcinoma.

Adult↗
PubMed1999

Indicated versus spontaneous preterm delivery: An evaluation of neonatal morbidity among infants weighing </=1000 grams at birth.

OBJECTIVE: The aim of the study was to determine whether infants weighing </=1000 g after birth who are born to women who undergo indicated preterm delivery have different neonatal outcomes than do those born as a result of either spontaneous preterm labor or preterm premature rupture of membranes. STUDY DESIGN: In a 1-year observational study (1992-1993) the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network collected outcome data for 799 infants whose birth weights were </=1000 g. Only singleton infants with gestational age >20 weeks who were not produced as the result of an induced abortion were included. Our analysis was further limited to infants without major congenital anomalies who survived >2 days, were deemed potentially viable by the obstetrician, and would have undergone a cesarean delivery for fetal indications (N = 411). The primary reason for delivery was categorized as indicated delivery, spontaneous preterm labor, or spontaneous preterm premature rupture of membranes. Selected neonatal outcomes were evaluated among infants born to women in each of these groups. Logistic regression analyses were used to control for the effects of other potentially confounding variables. RESULTS: A total of 156 of the 411 infants were born to women who underwent an indicated preterm delivery, whereas 160 were born after spontaneous preterm labor and 95 were delivered after preterm premature rupture of membranes. Univariate analyses revealed significantly lower incidences of grade III or IV intraventricular hemorrhage, grade III or IV retinopathy of prematurity, and seizure activity among infants born in an indicated preterm delivery than among those born after spontaneous preterm labor or preterm premature rupture of membranes. However, infants of women who underwent indicated preterm delivery had a more advanced mean gestational age at birth than did those born after spontaneous preterm labor or preterm premature rupture of membranes (28 +/- 2 weeks, 26 +/- 2 weeks, and 26 +/- 1 weeks, respectively, P <.001). Multiple logistic regression analysis was therefore used to control for the disparity in gestational age. Multivariate analyses did not confirm the apparent improvement in neonatal outcome in the indicated delivery group. CONCLUSION: In this population of infants weighing </=1000 g, selected neonatal outcomes did not differ according to birth by indicated preterm delivery, spontaneous preterm labor, or preterm premature rupture of membranes.

Adult↗
PubMed1999

Transperineal versus endovaginal ultrasonographic examination of the cervix in the midtrimester: a blinded comparison.

OBJECTIVE: Shortening of the cervix that occurs early in gestation as determined by ultrasonography has been correlated with subsequent spontaneous preterm birth. Because previous studies have compared transperineal and endovaginal ultrasonographic assessment of the cervix over a wide gestational age range, we compared these methods in the midtrimester. STUDY DESIGN: We performed a prospective, blinded comparison of endovaginal and transperineal cervical ultrasonographic assessment. Unselected gravid women at 15-23 weeks' gestation were sequentially examined by 2 experienced sonographers using an endovaginal probe and a curvilinear probe. For each patient the initial sonographer and examination method were randomly assigned. The sonographer who performed the second examination was blinded to the results and images from the first examination. RESULTS: One hundred two women were studied at a mean of 19.6 weeks' gestation. The overall intermethod correlation was poor (R = 0.38). In 12 cases a transperineal measurement could not be obtained because of poor visualization of the required landmarks. In 33% of cases the intermethod difference in cervical length was >/=20%. There was no correlation in the identification of funneling at the internal os and very small correlation for the identification of a poorly developed lower uterine segment. CONCLUSION: Transperineal ultrasonographic imaging of the cervix is an unsatisfactory alternative to an endovaginal assessment in the midtrimester.

Adult↗
PubMed1999

Prospective evaluation of free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for aneuploidy detection.

OBJECTIVE: Our goal was to prospectively evaluate the use of the free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for the detection of fetal Down syndrome and other aneuploidies. STUDY DESIGN: Women who had a second-trimester multiple-marker screening test (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) and genetic amniocentesis from August 1996 to August 1998 were included. Serum was also analyzed for inhibin and the free beta-subunit of human chorionic gonadotropin. Detection and false-positive rates for 4 analyte combinations at 5 different screening risk cutoff points for Down syndrome were determined and compared. RESULTS: We evaluated 1256 patients, including 23 with aneuploidy (13 with Down syndrome, 10 others). The maternal age was 35.9 +/- 4.6 years (mean +/- SD). At the optimal risk cutoff point for Down syndrome detection (1:190; false-positive rate, 19%), the multiple-marker screening test plus inhibin was superior, detecting 85% of Down syndrome cases, in comparison with 69% when the multiple-marker screening test alone was used and 62% when the other 2 combinations were used. The multiple-marker screening test plus inhibin also detected 60% of the other aneuploidies. CONCLUSIONS: When evaluated prospectively in a high-risk population, the multiple-marker screening test plus inhibin was superior to the traditional multiple-marker screening test and 2 other analyte combinations, with a lower false-positive rate and increased detection of all aneuploidies in a high-risk population.

Amniocentesis↗