Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe.

CONTEXT: A new group of novel psychoactive substance, the N-methoxybenzyl (NBOMe) derivatives of substituted phenethylamine, has recently emerged on the drug market, among which 25I-NBOMe and 25B-NBOMe have previously been implicated in clinical intoxications and fatalities. We report two cases of acute intoxication associated with these substances. CASE DETAILS: Two male patients (17 and 31 years of age) had ingested drugs labelled as 'NBOMe' or 'Holland film' and developed confusion, agitation, hypertension, tachycardia, hyperthermia, sweating and dilated pupils. Other features included convulsion, rhabdomyolysis and deranged liver function. The patients required benzodiazepines and other drugs for the control of symptoms. Urine samples from both patients were analysed using liquid-chromatography tandem mass spectrometry (LC-MS/MS) following glucuronidase digestion and solid-phase extraction. Identification was based upon comparison of the retention time and enhanced product ion scan with reference standards. In both urine samples, 25B-NBOMe was detected. Additionally, 25C-NBOMe was identified in one of the urine samples. DISCUSSION: The NBOMe compounds are highly potent 5HT2A receptor agonists and are also agonists at alpha-adrenergic receptors, which likely account for their serotonergic and sympathomimetic symptoms. The clinical testing of NBOMe drugs is not commonly available. Clinicians as well as laboratory staff play an important role in facilitating the detection of this group of potentially dangerous emerging drugs.

Successful treatment of severe fetal chylothorax resistant to repeated pleuroamniotic shunting by OK-432 pleurodesis.

We report the first case of successful fetal pleurodesis with OK-432 for recurrent severe fetal primary chylothorax after failing repeated pleuroamniotic shunting. Shunting and pleurodesis could be complementary to each other in the treatment of fetal chylothorax.

Serotonin syndrome following overdose of a non-prescription slimming product containing sibutramine: a case report.

INTRODUCTION: Non-prescription slimming products are popular and can be easily purchased from the Internet. However, adulteration of these products with undeclared substances including prescription drugs is not uncommon. We report a case of serotonin syndrome after an overdose of a non-prescription product containing sibutramine. CASE REPORT: A 21-year-old woman presented with somnolence, sinus tachycardia, generalised increase in tone, hyper-reflexia and clonus more prominent in the lower limbs after an intentional overdose of a non-prescription slimming product obtained from the Internet. The product was later found to contain sibutramine and other substances such as animal thyroid tissues, caffeine and phenolphthalein. Quantitative analysis of patient's serum on presentation revealed a sibutramine concentration of 112 ng/mL, which far exceeded the reported peak serum concentration after a single oral dose of 15 mg (the maximum daily recommended dose). No other culpable agent was identified. The overall clinical presentation was compatible with serotonin syndrome associated with sibutramine overdose. The patient made a full recovery after supportive management. DISCUSSION AND CONCLUSION: This case highlighted the health threat posed by non-prescription slimming products sold over the Internet. Sibutramine overdose can result in serotonin syndrome, as in overdose of other serotonergic agents. Early recognition and timely supportive treatment are essential to ensure a good clinical outcome.

Birth-weight prediction using three-dimensional sonographic fractional thigh volume at term in a Chinese population.

OBJECTIVES: To develop and validate new birth-weight prediction models in Chinese pregnant women using fractional thigh volume. METHODS: Healthy late third-trimester fetuses within 5 days of delivery were prospectively examined using two- (2D) and three- (3D) dimensional ultrasonography. Measurements were performed using 2D ultrasound for standard fetal biometry and 3D ultrasound for fractional thigh volume (TVol) and middle thigh circumference. The intraclass correlation coefficient (ICC) was used to analyze the inter- and intraobserver reliability of the 3D ultrasound measurements of 40 fetuses. Five birth-weight prediction models were developed using linear regression analysis, and these were compared with previously published models in a validation group. RESULTS: Of the 290 fetuses studied, 100 were used in the development of prediction models and 190 in the validation of prediction models. The inter- and intraobserver variability for TVol and middle thigh circumference measurements was small (all ICCs ≥ 0.95). The prediction model using TVol, femur length (FL), abdominal circumference (AC) and biparietal diameter (BPD) provided the most precise birth-weight estimation, with a random error of 4.68% and R(2) of 0.825. It correctly predicted 69.5 and 95.3% of birth weights to within 5 and 10% of actual birth weight. By comparison, the Hadlock model with standard fetal biometry (BPD, head circumference, AC and FL) gave a random error of 6.41%. The percentage of birth-weight prediction within 5 and 10% of actual birth weight was 46.3 and 82.6%, respectively. CONCLUSION: Consistent with studies on Caucasian populations, a new birth-weight prediction model based on fractional thigh volume, BPD, AC and FL, is reliable during the late third trimester in a Chinese population, and allows better prediction than does the Hadlock model.

Simultaneous real-time imaging of four-chamber and left ventricular outflow tract views using xPlane imaging capability of a matrix array probe.

OBJECTIVES: To determine the feasibility and reliability of using xPlane imaging to examine simultaneously the four-chamber and left ventricular outflow tract (LVOT) views in real time, to assess rotation angles from the four-chamber view to the LVOT view, and to investigate factors affecting the angles. METHODS: In 145 fetuses at 11-37 weeks' gestation, we visualized the four-chamber view in one of three cardiac positions: a subcostal view with the apex at the 3 or 9 o'clock position; an apical view with the apex at the 12 or 6 o'clock position; or a view with the fetal heart apex midway between these two positions. We then used the rotation function of xPlane imaging, using the four-chamber view as the reference plane, to visualize the LVOT view simultaneously in real time on the secondary image plane, on the right side of the split screen, by rotating a reference line from 0° with a rotation step of 5°. The rotation angle necessary for the first appearance of LVOT was recorded as the first rotation angle. The reference line was then rotated until the LVOT was just out of view, and this last rotation angle was recorded as the second rotation angle. The difference between these two angles was recorded as the angle span of the LVOT display. Reliability was assessed by intraclass correlation coefficient (ICC). RESULTS: Of the 145 fetuses examined, 29 had cardiac defects. Using xPlane imaging, the LVOT was visualized successfully after 14 weeks in 95.1% of cases. The first and second rotation angles varied significantly with cardiac position (P < 0.001); when the fetal heart was examined using a subcostal approach with the apex at the 3 or 9 o'clock position, the first rotation angle was smaller than that at the apical view for normal hearts (20° vs. 50°, P < 0.001). There was also a significant difference for the second rotation angle and for the angle span, between fetuses with and without normal LVOT (P = 0.038 and 0.006, respectively). Regarding intra- and interobserver reliability for measurement of first and second rotation angles, the ICCs were high (range, 0.847-0.980). CONCLUSION: Using xPlane imaging, it is feasible to examine simultaneously the four-chamber and LVOT views in real time, and measurement of the rotation angles between these two views is reproducible. The rotation angles depend on the position of the fetal heart, and the normality of the LVOT. Proposed algorithms for examination of the fetal heart with three-/four-dimensional ultrasonography may need to be adapted to optimize visualization of the standard planes.

Haemoglobin level, proportion of haemoglobin Bart's and haemoglobin Portland in fetuses affected by homozygous α0-thalassemia from 12 to 40 weeks' gestation.

OBJECTIVES: To determine haematological parameters in fetuses affected by homozygous α(0)-thalassemia. METHODS: This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α(0)-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. RESULTS: There were significant differences in the haematological parameters between homozygous α(0)-thalassemia (n = 183) and control (n = 363) which were either heterozygous α(0)-thalassemia (alpha thalassemia trait) or normal. In homozygous α(0)-thalassemia, the median Hb level, proportion of Hb Bart's (γ(4)) and Hb Portland 1(ζ(2)γ(2)) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. CONCLUSION: Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ(2)γ(2)) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia.

Comparison of inter- and intraobserver agreement and reliability between three different types of placental volume measurement technique (XI VOCAL, VOCAL and multiplanar) and validity in the in-vitro setting.

OBJECTIVES: To compare XI VOCAL (eXtended Imaging Virtual Organ Computer-aided AnaLysis) for three-dimensional (3D) ultrasound volumetry of the placenta and of phantom objects with a rotational method using VOCAL and with the multiplanar method. METHODS: We acquired 3D volume datasets from 32 fetuses at 11-14 weeks' gestation. Placental volume was calculated twice by each of two observers using XI VOCAL (with 5, 10, 15 and 20 slices), multiplanar (1-mm interval) and VOCAL (with 12 degrees, 18 degrees and 30 degrees rotation) methods. In addition, validity was assessed using the in-vitro setting with three phantom objects of known volume. RESULTS: Both inter- and intraobserver reliabilities were very high for all three methods. There was no systematic bias between any two methods except between XI VOCAL (10 slices) and the multiplanar (1-mm interval) method, with a smaller volume using the former method. The limits of agreement were wide between any two of the three methods. In the in-vitro setting, there was a trend towards less valid measurements with the XI VOCAL technique and fewer slices. With the same number of steps, measurements made with VOCAL (12 degrees and 18 degrees) were more valid than were those made with XI VOCAL (15 and 10 slices, respectively). CONCLUSION: XI VOCAL cannot be used interchangeably with VOCAL or multiplanar techniques in measuring placental volume at 11-14 weeks' gestation.

Fetal biometry by an inexperienced operator using two- and three-dimensional ultrasound.

OBJECTIVE: To compare the reproducibility, accuracy and time required for fetal biometric measurements using two-dimensional (2D) and three-dimensional (3D) ultrasonography by an inexperienced operator. METHODS: Fifty consecutive fetuses were evaluated at a gestational age of 17-34 weeks. For every fetus measurements-including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL)-were made by an inexperienced operator using 2D ultrasound and then saved 3D volumes. As a control, measurements were also made by an experienced operator using 2D ultrasonography alone. Each fetal biometric parameter was measured twice by each operator. All images were assessed by two experienced reviewers, blinded to the operator's identity, using a scoring system based on objective evaluation criteria. RESULTS: The interobserver, intraobserver and inter- method variability for 2D ultrasonography by the experienced operator (2D-exp), and 2D and 3D ultrasonography by the inexperienced operator (2D-inexp and 3D-inexp) was small (all intraclass correlation coefficients > or = 0.991). A non-significantly higher proportion of fetal biometric measurements by 3D-inexp than 2D-inexp were within 1 mm of the measurements by 2D-exp. There were no differences in the mean image quality scores of fetal biometry between 2D-exp and 2D-inexp, 2D-exp and 3D-inexp. However, the quality score of AC images obtained by 3D-inexp was greater than that obtained by 2D-inexp (5.5 vs. 5.3, P = 0.018). The mean time required to measure BPD, HC, AC and FL was less for 3D-inexp than for 2D-inexp (67.2 vs. 97.0 s, 64.6 vs. 97.0 s, 60.1 vs. 81.5 s and 65.5 vs. 95.1 s, respectively; all P < 0.001), but was significantly greater than for 2D-exp, with corresponding figures of 24.3, 24.3, 27.9 and 27.2 s. CONCLUSION: Fetal biometric measurements obtained by an inexperienced operator using both 2D and 3D ultrasound were reproducible and showed good agreement with those obtained by an experienced operator. The use of 3D ultrasound by an inexperienced operator allows faster measurements to be made than by 2D ultrasound and also seems to facilitate the acquisition of higher-quality images for measurement of AC.

Monozygotic dichorionic twins heterokaryotypic for duplication chromosome 2q13-q23.3.

We present an evaluation of the diagnosis, management and outcome of a pair of heterokaryotypic monozygotic dichorionic twins. The heterokaryotype was an incidental finding from an amniocentesis performed for prenatal diagnosis of beta-thalassaemia major in a pair of dichorionic twins. Monozygocity was revealed by QF-PCR showing identical short tandem repeat markers on chromosomes 21, 18, 13, X and Y. The twins were heterokaryotypic for duplication chromosome 2q13-q23.3, as shown by array comparative genomic hybridization. Selective foeticide was performed. This case demonstrates that heterokaryotypic monozygotic dichorionic twins are a genetic possibility that does occur.

Comparison of inter- and intraobserver agreement between three types of fetal volume measurement technique (XI VOCAL, VOCAL and multiplanar).

OBJECTIVES: To compare the new XI VOCAL (eXtended Imaging Virtual Organ Computer-aided Analysis) for three-dimensional (3D) ultrasound measurement of fetal volume with the conventional multiplanar technique and a rotational method using VOCAL. METHODS: We acquired 3D volume datasets from 30 fetuses at 11-14 weeks of gestation using a commercially available ultrasound system. Fetal volume was calculated using XI VOCAL (with 5, 10, 15 and 20 slices), multiplanar (1-mm interval) and VOCAL (with 12 degrees, 18 degrees and 30 degrees rotation) techniques. The level of agreement for interobserver and intraobserver variability was determined and evaluated for all methods and reliability was assessed. RESULTS: Fetal volume measurements obtained using XI VOCAL (10 slices) showed good correlation with those obtained using VOCAL (18 degrees) (r = 0.940, P = 0.076; intraclass correlation coefficient (ICC), 0.962 (95% CI, 0.920-0.982), P = 0.182), and XI VOCAL (15 slices) showed good correlation with VOCAL (12 degrees ) (r = 0.961, P = 0.092; ICC, 0.979 (95% CI, 0.957-0.990), P = 0.190). The mean difference between paired measurements by the XI VOCAL (10 slices) and VOCAL (18 degrees ) methods was 1.00 mL, while that by the XI VOCAL (15 slices) and VOCAL (12 degrees) methods was 0.90 mL. 95% limits of agreement were - 2.80 to 4.80 between XI VOCAL (10 slices) and VOCAL (18 degrees) and - 1.90 to 3.70 between XI VOCAL (15 slices) and VOCAL (12 degrees). There was a small difference in the time required to complete the fetal volume measurement between XI VOCAL and VOCAL when a similar number of slices or rotational steps was used (P < 0.05), XI VOCAL taking less time. CONCLUSION: XI VOCAL (with 10, 15 and 20 slices) can be used interchangeably with the multiplanar technique (1-mm interval) for the measurement of fetal volume. XI VOCAL (10 slices) and VOCAL (18 degrees) can be used interchangeably, as can XI VOCAL (15 slices) and VOCAL (12 degrees), for the measurement of fetal volume.

A prospective study on the effect of rapid aneuploidy testing (amnio-PCR) on anxiety levels and quality of life measures in women and their partners with positive Down screening result.

OBJECTIVES: To examine the effect of rapid aneuploidy testing by amnio-PCR on anxiety levels and quality of life measures in women and their partners with positive Down screening result. METHODS: In the original design, screen-positive women were to be randomized to have amnio-PCR or not. Of the first 60 women approached to join the study between April 2004 and April 2005, 4 declined amniocentesis, 14 agreed to be randomized, while the other 42 (75%) chose to pay for the amnio-PCR themselves (3 excluded: 2 because of Down syndrome and 1 dropout). The study was thus performed as a prospective observational study on the remaining 39 women of the last group. The longitudinal profile of the state-anxiety and quality of life domain scores for this cohort were studied using the Spielberger State-Trait Anxiety Inventory and WHO Quality of Life Measure--abbreviated version (Hong Kong) Questionnaire at 5 time points: (1) before amniocentesis, (2) 2 days after amniocentesis when amnio-PCR report was disclosed, (3) 3 weeks after amniocentesis when karyotyping report was disclosed, (4) 30-32 weeks' gestation, (5) 6 weeks after delivery. RESULTS: In the final cohort of 39 women and 27 partners, a significant reduction in their state-anxiety scores was found when they received the normal amnio-PCR report. On the other hand, there was no significant change in their quality of life domain scores. CONCLUSIONS: There is a demand from women and their partners who had a positive Down screening result for rapid aneuploidy testing (amnio-PCR) which can effectively alleviate their anxiety. A rapid aneuploidy test should be made available to women in a Down screening programme.

Alpha-thalassaemia.

Alpha-thalassaemia is one of the most common human genetic disorders. Couples in which both partners carry alpha(0)-thalassaemia traits have a 25% risk of having a fetus affected by homozygous alpha-thalassaemia or haemoglobin Bart's disease, with severe fetal anaemia in utero, hydrops fetalis, stillbirth or early neonatal death, as well as causing various maternal morbidities. This disorder is common in southeast Asia and southern China, and the expanding populations of southeast Asian immigrants in the US, Canada, UK and Europe mean that this disorder is no longer rare in these countries.

Comparison of nuchal and detailed morphology ultrasound examinations in early pregnancy for fetal structural abnormality screening: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of a nuchal scan at 10 to 14 + 6 weeks and a detailed morphology scan at 12 to 14 + 6 weeks in screening for fetal structural abnormalities. METHODS: From March 2001 to November 2004, 8811 pregnant women were randomized into either the control group (10 to 14 + 6-week nuchal scan followed by routine 16-23-week scan) or the study group (10 to 14 + 6-week nuchal scan and 12 to 14 + 6-week detailed scan followed by routine 16-23-week scan). RESULTS: We analyzed 7642 cases of singleton pregnancies with viable fetuses at first-trimester ultrasound examination and with known pregnancy outcome. In the control group, the detection rate of structural abnormalities in the first trimester was 32.8% (21/64; 95% CI, 21.6-45.7%) and the overall detection rate was 64.1% (41/64; 95% CI, 51.1-75.7%). In the study group, the detection rate in the first trimester was 47.6% (30/63; 95% CI, 34.9-60.6) and the overall detection rate was 66.7% (42/63; 95% CI, 53.7-78.0%). The overall detection rate in the control group did not differ significantly from that in the study group (P > 0.05). CONCLUSIONS: When the nuchal scan is offered, a basic anatomical survey can be done in conjunction with nuchal translucency thickness measurement. A detailed ultrasound examination at this early gestational age may not be superior to the nuchal scan in screening for fetal abnormalities in the low-risk population. Though a wide range of abnormalities can be detected at 10 to 14 + 6 weeks, the routine 16-23-week scan cannot be abandoned.