Variables Associated with Severity of Bacterial Canker and Wilt Caused by Clavibacter michiganensis subsp. michiganensis in Tomato Greenhouses.

Clavibacter michiganensis subsp. michiganensis, the causal agent of bacterial canker and wilt of tomato, is considered to be one of the most important bacterial pathogens worldwide. In the year 2000 there was an increase in the number of infected greenhouses and in the severity of the disease in Israel. As part of the effort to cope with the disease, a comprehensive survey was conducted. Scouts recorded disease severity monthly in 681 production units. At the end of the season the scouts met with the growers and together recorded relevant details about the crop and cultural practices employed. The results suggested an absence of anisotropy pattern in the study region. Global Moran's I analysis showed that disease severity had significant spatial autocorrelation. The strongest spatial autocorrelation occurred within a 1,500 m neighborhood, which is comparable to the distance between production units maintained by one grower (Farm). Next, we tested three groups of variables including or excluding the Farm as a variable. When the Farm was included the explained variation increased in all the studied models. Overall, results of this study demonstrate that the most influential factor on bacterial canker severity was the Farm. This variable probably encompasses variation in experience, differences in agricultural practices between growers, and the quality of implementation of management practices.

Nasal-bone length in euploid fetuses at 16-24 weeks' gestation by three-dimensional ultrasound.

OBJECTIVE: To establish a normal range of nasal-bone length at 16-24 weeks' gestation by the use of three-dimensional (3D) ultrasound and to investigate the effect of deviations from the exact mid-sagittal plane on the measurement of nasal-bone length. METHODS: We acquired 3D volumes of the fetal profile from 135 normal fetuses at 16-24 weeks' gestation. The multiplanar mode was used to obtain the exact mid-sagittal plane and to produce parasagittal and oblique views of the fetal face. Nasal-bone length was measured in each plane and the sonographic landmarks of each profile view were examined. RESULTS: Nasal-bone length increased with gestational age from a mean of 4.1 mm at 16 weeks to 7.1 mm at 24 weeks. There was a tendency to underestimate nasal-bone length when the measurements were taken in parasagittal planes and to overestimate the measurements when they were taken in oblique views, compared to the exact mid-sagittal plane. The mean difference in nasal-bone length from the one in the mid-sagittal plane was 0.42 and 0.63 mm for parasagittal measurements at 1 and 2 mm, respectively, from the midline, -0.08 and -0.51 mm for oblique measurements at 10 degrees and 20 degrees rotation along the z-axis and -0.69 mm for rotation of 20 degrees along the z-axis and 10 degrees along the y-axis. The vomeral bone was the only sonographic landmark defining the exact mid-sagittal plane of the face that was not visible in the parasagittal and oblique planes. CONCLUSIONS: Parasagittal and oblique scanning planes may produce different degrees of under- or over-estimation of nasal-bone length compared to measurements systematically taken in the exact mid-sagittal plane. Inclusion of the vomeral bone in the definition of the exact mid-sagittal plane of the face could improve the reproducibility of measurements of nasal-bone length.

Aberrant right subclavian artery at 16 to 23 + 6 weeks of gestation: a marker for chromosomal abnormality.

OBJECTIVES: This study was carried out to determine the feasibility of defining the position of the right subclavian artery (RSA) by fetal echocardiography between 16 and 23 weeks of gestation, and the association between an aberrant right subclavian artery (ARSA) and chromosomal and cardiac defects. METHODS: We examined the position of the RSA in all patients who attended our unit for a fetal cardiac scan. The assessment was carried out using a transverse view of the fetal chest sweeping up from the level of the aortic arch, using color flow mapping. An ARSA was diagnosed when this vessel was not seen in the normal position and an arterial vessel was seen crossing behind the trachea towards the right arm, arising as a fourth branch of the aortic arch, at a lower level than normal. RESULTS: The course of the RSA could be identified in more than 95% of the 2799 fetuses examined between 16 and 23 + 6 weeks of gestation. An ARSA was found in 43 fetuses. The incidence was 1.5% in normal fetuses, 28.6% in fetuses with trisomy 21, 18.2% in fetuses with trisomy 18 and 8% in fetuses with other chromosomal defects. There was an association between an ARSA and cardiac defects in seven of the 43 fetuses (16%), and three of these seven fetuses had a normal karyotype. CONCLUSIONS: Assessment of the RSA by a fetal cardiologist is possible in almost all cases. The finding of an ARSA is much more common in fetuses with chromosomal defects, in particular trisomy 21 (where the prevalence of an ARSA was 29%), compared with euploid fetuses. Moreover, the presence of an ARSA may be associated with an increased incidence of intracardiac malformations. Examination of the position of the RSA is likely to become a routine ultrasound marker for chromosomal abnormalities in the second trimester of pregnancy.

Depth of brain fissures in normal fetuses by prenatal ultrasound between 19 and 30 weeks of gestation.

OBJECTIVE: To establish normal reference ranges for the depth of the insula and Sylvian (SF), parieto-occipital (POF) and calcarine (CF) fissures on prenatal ultrasound between 19 and 30 weeks of gestation. METHODS: This was a prospective study of 15 consecutive normal fetuses per gestational week between 19 + 0 and 30 + 6 weeks. We measured the depth of the insula and SF in a standard transventricular axial plane of the fetal head; the depth of the POF in a plane above and parallel to that used for the insula; and the depth of the CF in a coronal view of the posterior fossa. All measurements were done transabdominally during the routine second- or third-trimester examination. Reproducibility for each of the parameters was assessed by two operators using stored images from 30 cases. RESULTS: The depth of the four structures increased with increasing gestational age. The insula and SF could be seen in all cases from 19 weeks onwards, while the POF and CF could be identified in 93.3% and 6.6% of cases, respectively, at 19 weeks. From 20 weeks onwards, the POF could be seen in all examinations, as could the CF from 24 weeks. Intra- and interobserver reproducibility analysis showed good results. CONCLUSIONS: Assessment of the insula, SF, POF and CF is feasible during prenatal ultrasound examination using standard views of the fetal head. Since the normal ranges increase with gestational age, they could be used to estimate brain development. It is possible that this assessment might be incorporated into the neurosonogram to identify fetuses at risk of maturation disorders or as a complement to other standard evaluations.

Learning curve in measurement of fetal frontomaxillary facial angle at 11-13 weeks of gestation.

OBJECTIVE: To determine the number of ultrasound examinations required to train sonographers to accurately measure the fetal frontomaxillary facial (FMF) angle at 11-13 weeks of gestation. METHODS: Eight sonographers accredited for nuchal translucency thickness (NT) measurement (and with different levels of experience) were trained to measure the fetal FMF angle using specially acquired three-dimensional (3D) volumes. Training was provided in cycles, and each cycle consisted of a training period on 20 randomly selected cases followed by an examination using 10 randomly selected cases. During training, the sonographer was informed of the true FMF angle value after each FMF angle measurement on a case-by-case basis. During examination, the difference between the measured and the true values of the FMF angle (i.e. the delta angle) was calculated. A measurement was considered accurate if the delta angle was less than 5 degrees . The sonographer was considered to be competent and the training finished if all 10 examination cases satisfied this criterion. Otherwise, the sonographer would undergo further cycles of training-examination, until he/she became competent. RESULTS: The number of training cases required for a sonographer to become competent was 40 for two sonographers, 60 for one, 80 for one, 100 for two, 120 for one and 140 for one, with a median of 90. The median number of failed cases reduced from 2.5 (out of 10) at the first cycle to 0 by the 7(th) cycle. As training cycles increased, the mean angle deviation and measurement time required both reduced significantly. The average delta angle of the passing examination cycle was 2.06 +/- 1.40 degrees . The number of training cases required to become competent in FMF angle measurement was 40 for the two most experienced trainees and 80, 120 and 140 for the three least experienced ones. CONCLUSIONS: We have demonstrated that competence in FMF angle measurement was achieved after a median number of 90 cases, with a range of up to 140. The number required was substantially lower, at 40 cases, among those with extensive experience of NT measurement.

Gestational sac volume: comparison between SonoAVC and VOCAL measurements at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVES: To assess the novel three-dimensional (3D) tool, Sonography-based Automated Volume Count (SonoAVC) in the calculation of gestational sac volume at 11 + 0 to 13 + 6 weeks of gestation, to correlate the measurements with those obtained using Virtual Organ Computed-aided AnaLysis (VOCAL) and to study the reproducibility of SonoAVC volume calculation of this irregularly shaped structure. METHODS: We acquired 3D volumes of the uterus in 65 pregnancies at 11 + 0 to 13 + 6 weeks of gestation. We performed volume calculation of the gestational sac, excluding the fetus and the placenta, using VOCAL with 15 degrees 12-step rotation. We then repeated the calculation with three different SonoAVC settings and compared both techniques. In 30 cases we assessed the reproducibility of the SonoAVC volume calculations. RESULTS: In 95% of cases it was possible to calculate the gestational sac volume with SonoAVC. This volume increased with advancing gestation and the volumes were expressed as delta values to compare the measurements made with VOCAL and the three different SonoAVC settings. There was no difference between delta values of gestational sac volume calculated using VOCAL and SonoAVC with high and medium growth settings. Reproducibility analysis showed good results. CONCLUSION: Gestational sac volume calculation is feasible with SonoAVC in most cases and does not differ from that performed using VOCAL. High and medium growth SonoAVC settings seem to be more accurate for gestational sac volume calculation, although larger studies are required for standardization of the technique. The reproducibility analysis showed similar results to those previously published.

Marcadores ecográficos para la detección del síndrome de Down en las semanas 11-13 + 6 / Sonographic markers for Down´s Syndrome screening at 11-13 + 6 weeks

Objetivo. Presentar nuestra experiencia en la valoraciónde todos los marcadores ecográficos validados para el cribadodel síndrome de Down en la semana 11-13 + 6.Métodos. Capacitamos seis médicos para evaluar elhueso nasal (HN), flujo tricuspídeo (FT) y flujo en el ductusvenoso (DV) durante una exploración de 20 min en las semanas11-13 + 6. Comparamos los resultados con los obtenidospor el médico capacitador, en dos mitades. En un subgrupode tres médicos valoramos además la realización delángulo facial. Utilizamos como guía los parámetros de la FetalMedicine Foundation, Londres.Resultados. El número total de exploraciones fue de939. El grupo de seis médicos realizó 356 exploraciones enla primera mitad, y 355 en la segunda mitad; las valoracionessatisfactorias fueron para traslucencia nucal (TN) 85,4 y89 %, HN 82,7 y 82,7 %, FT 82,7 y 86,8 %, DV 89 y 86,6%respectivamente. El capacitador obtuvo en 228 exploracionesresultados satisfactorios en 100% TN, 94,7 % HN,99,6 % FT, 97,3 % DV y 73,5 % ángulo facial (AF). El AF fuevalorado satisfactoriamente por el subgrupo de tres médicosen el 69 % de los casos.Conclusiones. Es posible valorar todos los marcadoresecográficos de aneuploidía en la mayoría de los casos en semanaslas 11-13 + 6. La TN fue el marcador con resultadosmás satisfactorios. El entrenamiento continuo y la auditoriason indispensables para mejorar el estándar del cribado parael síndrome de Down en las semanas 11-13 + 6 (AU)

Objective. To report our experience in the assessmentof all the available ultrasound markers for Down´sSyndrome screening at 11-13 + 6 weeks of gestation.Methods. We trained six doctors to evaluate the nasalbone (NB), tricuspid regurgitation (TR), and a-wave inthe ductus venosus (DV), during a routine 20 minutescan. We compared the results in two halves, with thoseobtained by the trainer. In a subgroup of three doctors,we assessed the facial angle (FA) with the same methodology.The audit of the stored images was performed bya doctor with experience in first trimester markers. Wefollowed guidelines from the Fetal Medicine Foundation,London for the assessment of the markers.Results. We examined 939 patients. The group of sixdoctors performed 356 and 355 scans in each half of thestudy respectively. The assessment was satisfactory foreach marker: nuchal translucency thickness (NT) 85.4%and 89%, NB 82.7% and 82.7%, TR 82.7% and 86.8%,DV 89% and 86.6% respectively. The trainer performed228 scans and the results were satisfactory in 100% TN,94.7% NB, 99.6% TR, 97.3% DV and 73.5% facial angle.In the subgroup with 3 doctors, the facial angle was satisfactorymeasured in 69% of the cases.Conclusions. It is feasible to assess all the ultrasoundmarkers for chromosomal abnormality in a 20 minutescan in a high proportion of cases. NT assessmentwas the most successful. The continuous training andaudit process are critically important to rise the standardof the 11-13 + 6 weeks Down’s Syndrome screening (AU)

Prenasal thickness in trisomy-21 fetuses at 16-24 weeks of gestation.

OBJECTIVE: To construct a reference range for fetal prenasal thickness between 16 and 24 weeks of gestation and to evaluate the thickness in fetuses with trisomy 21. METHODS: We acquired three-dimensional (3D) volumes of the fetal profile from 135 normal fetuses and 26 fetuses with trisomy 21 at 16-24 weeks' gestation. We used the multiplanar mode to obtain the exact mid-sagittal plane and measured the prenasal thickness as the shortest distance between the anterior edge of the lowest part of the frontal bone (at the junction with the nasal bone when present) and the skin anteriorly. RESULTS: In the normal group prenasal thickness increased with gestation from a mean of 2.4 mm at 16 weeks to 4.6 mm at 24 weeks. Repeatability studies demonstrated that in 95% of the cases the difference between two measurements of prenasal thickness by the same operator and by different operators was less than 1 mm. In the trisomy-21 fetuses the mean prenasal thickness was significantly larger than in normal fetuses and in 19 (73.1%) cases it was above the 95(th) centile of the normal range. There was no significant difference in prenasal thickness between the trisomic fetuses with and without ventriculomegaly, nuchal edema, absent nasal bone or a cardiac defect. CONCLUSIONS: The fetal profile is routinely examined during the second-trimester scan and therefore the skill needed to obtain the view necessary for the measurement of prenasal thickness is widely available. If the finding of our study--that in more than 70% of fetuses with trisomy 21 prenasal thickness is above the 95(th) centile--is confirmed in prospective screening studies this measurement alone could prove a highly sensitive method of second-trimester screening for trisomy 21.

Frontomaxillary facial angle in screening for trisomy 21 at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: Trisomy 21 is associated with a flat face, which can now be quantified by measurement of the frontomaxillary facial (FMF) angle. The aim of this study was to examine whether in trisomy 21 fetuses fetal nuchal translucency (NT) thickness and maternal serum free ss-human chorionic gonadotropin (ss-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are independent of the FMF angle, and to estimate the performance of a first-trimester screening test for trisomy 21 that includes measurement of the FMF angle. METHODS: This was a prospective study in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation in which three-dimensional volumes of the fetal head were obtained and measurement of the FMF angle performed immediately before fetal karyotyping by chorionic villus sampling (CVS). The women chose to have CVS after risk assessment by a combination of maternal age, fetal NT thickness and maternal serum free ss-hCG and PAPP-A. Regression analysis was used to examine the significance of the association within the euploid and within the trisomy 21 fetuses between the deviation from the normal median in FMF angle and the deviation in NT, free ss-hCG and PAPP-A. We estimated the detection rate (DR) and false positive rate (FPR) of first-trimester screening for trisomy 21 by measuring the FMF angle in all cases and of an alternative policy in which first-stage screening is by fetal NT and maternal serum biochemistry in all patients, followed by second-stage assessment of FMF angle only in those with an intermediate risk (1 in 51 to 1 in 1000) after the first stage. RESULTS: The FMF angle was measured in 782 euploid and 108 trisomy 21 fetuses. In the euploid fetuses the mean FMF angle decreased linearly with CRL from 83.5 degrees at a crown-rump length (CRL) of 45 mm to 76.4 degrees at a CRL of 84 mm. In the euploid fetuses the mean delta FMF angle was 0.0 (SD, 4.264) degrees and the respective values in the trisomy 21 fetuses were 7.172 (SD, 4.092) degrees . Incorporating the FMF angle in first-trimester combined screening increased the estimated DR from 90 to 94% at an FPR of 5% and from 85 to 92% at an FPR of 3%. In two-stage screening it would be necessary to measure the FMF angle in 12% of cases and the DRs would be 93 and 91% at FPRs of 5 and 3%, respectively. CONCLUSIONS: Measurement of the FMF angle improves the performance of first-trimester screening for trisomy 21.

Frontomaxillary facial angle in trisomy 21 fetuses at 16-24 weeks of gestation.

OBJECTIVES: To establish a normal range for the frontomaxillary facial (FMF) angle by three-dimensional (3D) ultrasound imaging and to examine the FMF angle in trisomy 21 fetuses at 16-24 weeks of gestation. METHODS: We measured the FMF angle using 3D volumes of the fetal profile obtained with the transducer parallel to the long axis of the nose and at 45 degrees to the palate, which had been acquired from 150 normal fetuses and 23 fetuses with trisomy 21. RESULTS: In the normal group there was no significant association between the FMF angle and gestational age; the mean FMF angle was 83.9 degrees (range, 76.9-90.2 degrees ) and the 95(th) centile was 88.5 degrees . In 15 (65.2%) of the fetuses with trisomy 21 the FMF angle was greater than 88.5 degrees . Repeatability studies demonstrated that in 95% of cases the difference between two measurements of FMF angle by the same operator and different operators was less than 5 degrees . CONCLUSIONS: In the majority of second-trimester fetuses with trisomy 21 the FMF angle is increased.

Aberrant right subclavian artery at 11 + 0 to 13 + 6 weeks of gestation in chromosomally normal and abnormal fetuses.

OBJECTIVES: To establish the feasibility of examining the subclavian artery at 11 + 0 to 13 + 6 weeks of gestation, and to determine the prevalence of aberrant right subclavian artery (ARSA) in chromosomally normal and chromosomally abnormal fetuses. METHODS: Fetal echocardiography was performed prospectively in 516 patients before chorionic villus sampling at 11 + 0 to 13 + 6 weeks of gestation. Transabdominal sonography was carried out, and color flow mapping was used to identify the right subclavian artery and determine whether this was normal or aberrant (ARSA). Second-trimester fetal echocardiography was also carried out in a subgroup of 183 fetuses. RESULTS: The median gestational age was 12 weeks and the median crown-rump length was 68 mm. Successful assessment of the right subclavian artery was achieved in 425/516 (82.4%) cases and the rate of failure to do so was significantly associated with decreasing fetal crown-rump length (r = 0.174, P < 0.001) and increasing maternal body mass index (r = 0.275, P < 0.001). An ARSA was observed in 2/353 (0.6%) fetuses with a normal karyotype, in 4/51 (7.8%) cases with trisomy 21 and in 2/20 (10.0%) with other chromosomal defects. In a subgroup of 183 fetuses examined in both the first and second trimester there were three cases of ARSA observed at both scans and an additional case in which ARSA was detected only at the second scan. CONCLUSIONS: Assessment of the position of the right subclavian artery is feasible at the 11 + 0 to 13 + 6-week scan and ARSA is more common in chromosomally abnormal than normal fetuses. However, ARSA in the first trimester is unlikely to be a useful marker of trisomy 21.

Frontomaxillary and mandibulomaxillary facial angles at 11 + 0 to 13 + 6 weeks in fetuses with trisomy 18.

OBJECTIVE: To define the relative position of the maxilla and mandible in fetuses with trisomy 18 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before karyotyping at 11 + 0 to 13 + 6 weeks of gestation in 36 fetuses subsequently found to have trisomy 18, and 200 chromosomally normal fetuses. The frontomaxillary facial (FMF) angle and the mandibulomaxillary facial (MMF) angle were measured in a mid-sagittal view of the fetal face. RESULTS: In the chromosomally normal group both the FMF and MMF angles decreased significantly with crown-rump length (CRL). In the trisomy 18 fetuses the FMF angle was significantly greater and the angle was above the 95(th) centile of the normal range in 21 (58.3%) cases. In contrast, in trisomy 18 fetuses the MMF angle was significantly smaller than that in normal fetuses and the angle was below the 5(th) centile of the normal range in 12 (33.3%) cases. CONCLUSIONS: Trisomy 18 at 11 + 0 to 13 + 6 weeks of gestation is associated with both mid-facial hypoplasia and micrognathia or retrognathia that can be documented by measurement of the FMF angle and MMF angle, respectively.

Frontomaxillary facial angle in chromosomally normal fetuses at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To establish the normal range of the frontomaxillary facial (FMF) angle at 11 + 0 to 13 + 6 weeks of gestation. METHODS: In this prospective study, three-dimensional (3D) volumes of the fetal head were obtained from 500 pregnancies before fetal karyotyping by chorionic villus sampling (CVS), after screening by fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks. Only cases with a normal karyotype were included in this study. The FMF angle was measured off-line. In a subgroup of 150 cases the FMF angle was measured using 2D ultrasound before obtaining a 3D volume. In 50 cases the 3D volumes were used to measure the FMF angle by the same examiner twice and by another examiner once. RESULTS: The mean FMF angle decreased with crown-rump length (CRL) from 84.3 degrees at CRL 45 mm to 76.5 degrees at CRL 84 mm. There was no significant association between the FMF angle and fetal NT or serum PAPP-A or beta-hCG. In the volumes with paired measurements, the difference between two measurements by the same or two sonographers was < 5% in 95% of the cases. In the cases with paired 3D and 2D ultrasound measurements, the difference in FMF angles was < 8% in 95% of the cases. CONCLUSIONS: At 11 + 0 to 13 + 6 weeks the FMF angle decreases with fetal CRL but is not related to fetal NT or serum biochemistry. The measurement is reproducible and the results obtained by 3D and 2D ultrasound are similar.

Frontomaxillary facial angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To investigate the frontomaxillary facial (FMF) angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before karyotyping at 11 + 0 to 13 + 6 weeks of gestation in 23 fetuses with trisomy 13. The FMF angle, defined as the angle between the upper surface of the maxilla and the frontal bone in a midsagittal view of the fetal face, was measured and compared to the angle in 500 chromosomally normal fetuses. RESULTS: In 10 of 12 (83.3%) fetuses with trisomy 13 and holoprosencephaly, the FMF angle was above the 95(th) centile of the normal range. In the 11 fetuses with no holoprosencephaly, the FMF angle was not significantly different from normal. There was no significant difference in the FMF angle between the trisomy 13 fetuses with and without facial cleft. CONCLUSIONS: In fetuses with trisomy 13, the FMF angle at 11 + 0 to 13 + 6 weeks of gestation is increased only in cases with associated holoprosencephaly.

Assessment of the corpus callosum at 20-24 weeks' gestation by three-dimensional ultrasound examination.

OBJECTIVES: To determine the range of positions of the fetal head in which a three-dimensional (3D) volume is acquired for subsequent successful imaging of the corpus callosum. METHODS: We used 3D volumes of the fetal head obtained from singleton pregnancies at 20 to 23 + 6 weeks' gestation. The volumes, which had been acquired with the head in different positions, were then reconstructed with the objective of obtaining a mid-sagittal section of the brain to demonstrate the presence of the corpus callosum. RESULTS: In the reconstructed mid-sagittal sections it was possible to demonstrate the corpus callosum in at least 90% of cases when the 3D volume acquisition plane was (1) mid-sagittal with the angle between the transducer and the direction of the fetal nose ranging from 0 degrees to 179 degrees and from 330 degrees to 359 degrees , (2) oblique around the crown-rump axis with an angle from the mid-sagittal plane of less than 30 degrees , (3) oblique around the anteroposterior axis from the axial plane at the level of the biparietal diameter to the mid-sagittal plane or (4) axial at the level of the biparietal diameter with an angle between the transducer and the midline echo of the brain of 60-119 degrees . In the mid-sagittal sections either the translucent corpus callosum or a comma-shaped echogenic structure was seen depending on whether the plane of volume acquisition was sagittal or axial. CONCLUSIONS: In 3D ultrasound examination the extent to which the corpus callosum can be demonstrated to be present is entirely dependent on the plane of volume acquisition.

Biotransformation of letrozole in rat liver microsomes: effects of gender and tamoxifen.

The in vitro metabolic kinetics of letrozole were investigated by incubating letrozole (10-500 microM) in female or male rat liver microsomes to assess the effect of gender and to predict the in vivo biotransformation characteristics of letrozole in rats. The effects of tamoxifen (TAM) on the metabolic kinetics of letrozole were also examined by incubating letrozole in female rat liver microsomes in the presence or absence of TAM. The effects of chronic pretreatment of female rats with TAM (0.5, 1.0, 5.0 mg/kg/day, i.p. for 7 consecutive days) on liver microsomal protein content and metabolic activity were also examined. The formation rate of the carbinol metabolite of letrozole, CGP44 645, was significantly higher (p<0.05) in male rat liver microsomes in comparison to female. The V(max)/K(m) ratio for letrozole metabolism in female rat liver microsomes did not change significantly (p>0.05) in the presence of TAM. After chronic pretreatment of female rats with TAM (up to a dose of 1.0mg/kg/day), the hepatic microsomal protein content was significantly increased but the formation rate of CGP44 645, when normalized for protein content, did not change significantly. These results suggest that there is a marked gender difference in letrozole metabolism in rats. It also appears that acute treatment of female rat liver microsomes with TAM produces negligible inhibitory effect on the CYP mediated metabolic clearance of letrozole. However, chronic pretreatment of female rats with TAM appear to induce CYPs, but does not significantly impact the metabolic activities of the enzymes associated with the formation of the carbinol metabolite of letrozole.

Frontomaxillary facial angle at 11+0 to 13+6 weeks' gestation-reproducibility of measurements.

OBJECTIVE: To assess the intra- and interobserver reproducibility in the measurement of the frontomaxillary facial (FMF) angle at 11+0 to 13+6 weeks' gestation and to investigate the effect of deviations from the exact mid-sagittal view on these measurements. METHODS: Three-dimensional (3D) volumes of the fetal face were used by two operators to measure the FMF angle in 50 chromosomally normal and 50 trisomy 21 fetuses. The measurements were taken in the exact mid-sagittal view and repeated after lateral rotation of the head by 5 degrees, 10 degrees and 15 degrees away from the vertical position of the occipitofrontal diameter axis. Mean difference and 95% limits of agreement between paired measurements of FMF angle by the same and by two different sonographers were determined. RESULTS: In the mid-sagittal plane the maxillary bone was rectangular shaped. Rotation away from this plane became easily recognizable because at a mean of 7 degrees (range, 4-10 degrees) the shape of the maxilla changed with the appearance of the zygomatic process of the maxilla and at a mean of 8 degrees (range, 4-12 degrees) the tip of the nose became invisible. In both the normal and trisomy 21 fetuses the FMF angle measured at 5-15 degrees was not significantly different from the one measured in the mid-sagittal plane. In 95% of the cases, the difference between paired measurements of the FMF angle by the same sonographer at the mid-sagittal plane was between -2.3 degrees and 3.0 degrees and at 15 degrees it was -1.0 degrees to 6.8 degrees. At the mid-sagittal plane, the difference in measurements between two sonographers was -3.1 to 3.0 degrees. CONCLUSION: The landmarks that define the mid-sagittal plane of the fetal face are the tip of the nose and the rectangular shaped maxilla. Measurement of the FMF angle is highly reproducible.

Brachycephaly and frontal lobe hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To investigate the incidence of brachycephaly and frontal lobe hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median, 12 + 5) weeks of gestation in 100 fetuses that were subsequently found to have trisomy 21 and in 300 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal head and to demonstrate the biparietal and suboccipitobregmatic views. We measured the biparietal diameter (BPD), the occipitofrontal diameter (OFD) and the frontothalamic distance (FTD) between the inner table of the frontal bone and the posterior thalami. RESULTS: In the chromosomally normal group the BPD, OFD and FTD increased linearly with crown-rump length (CRL) from 16.7 mm, 19.0 mm and 12.1 mm at a CRL of 45 mm to 26.7 mm, 31.7 mm and 18.7 mm, respectively, at a CRL of 84 mm. In the trisomy 21 fetuses, compared to normal fetuses, there was shorter BPD (mean difference = -0.63 mm; 95% CI, -0.97 to -0.30 mm, P < 0.0001), OFD (mean difference = -1.41 mm; 95% CI, -1.75 to -1.07 mm, P < 0.0001) and FTD (mean difference = -0.77 mm; 95% CI, -1.02 to -0.54 mm; P < 0.0001) and higher BPD to OFD ratio (mean difference = 0.022; 95% CI, 0.012 to 0.032, P < 0.0001) but no significant difference in the FTD to OFD ratio (mean difference = 0.004; 95% CI, -0.006 to 0.013, P = 0.448). CONCLUSIONS: In fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation there is evidence of brachycephaIy but not of frontal lobe hypoplasia.

Three-dimensional evaluation of mid-facial hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the mid-facial hypoplasia of fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation, by three-dimensional (3D) evaluation of the maxilla and the nasal bones. METHODS: A 3D volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median 12) weeks of gestation in 80 fetuses that were subsequently found to have trisomy 21 and in 862 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal face and to demonstrate the maxilla, the adjacent rami of the mandible and the nasal bones. The maxillary depth, defined as the distance between the alveolus of the maxilla in the midline anteriorly and the midpoint of the line joining the rami posteriorly, was measured. Ossification of the nasal bones was considered to be normal if both bones were more echogenic than the overlying skin. RESULTS: In the chromosomally normal group the maxillary depth increased linearly with crown-rump length (CRL) from 3.1 mm at a CRL of 45 mm to 4.8 mm at a CRL of 84 mm, and in the trisomy 21 fetuses the depth was significantly smaller than normal (mean difference = - 0.3 mm, P < 0.001). There was no significant association between the delta maxillary depth and delta nuchal translucency thickness in either the trisomy 21 or the chromosomally normal fetuses. Impaired ossification of the nasal bones was observed in 3.1% of the chromosomally normal fetuses and in 60.0% of those with trisomy 21. The mean maxillary depth was significantly smaller in fetuses demonstrating impaired ossification than in those with normal ossification of the nasal bones (mean difference = -0.2 mm; 95% CI, -0.3 to -0.1, P = 0.001). CONCLUSIONS: In a high proportion of fetuses with trisomy 21 there is sonographic evidence of mid-facial hypoplasia at 11 + 0 to 13 + 6 weeks of gestation.