Diagnosis of fetal non-chromosomal abnormalities on routine ultrasound examination at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities. METHODS: This was a retrospective study of prospectively collected data from 100 997 singleton pregnancies attending for a routine ultrasound examination of fetal anatomy, performed according to a standardized protocol, at 11-13 weeks' gestation. All continuing pregnancies had an additional scan at 18-24 weeks and 71 754 had a scan at either 30-34 or 35-37 weeks. The final diagnosis of fetal abnormality was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal abnormalities was determined. RESULTS: The study population contained 1720 (1.7%) pregnancies with a fetal abnormality, including 474 (27.6%) detected on the first-trimester scan, 926 (53.8%) detected on the second-trimester scan and 320 (18.6%) detected in the third trimester or postnatally. At 11-13 weeks' gestation, we diagnosed all cases of acrania, alobar holoprosencephaly, encephalocele, tricuspid or pulmonary atresia, pentalogy of Cantrell, ectopia cordis, exomphalos, gastroschisis and body-stalk anomaly and > 50% of cases of open spina bifida, hypoplastic left heart syndrome, atrioventricular septal defect, complex heart defect, left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), lower urinary tract obstruction, absence of extremities, fetal akinesia deformation sequence and lethal skeletal dysplasia. Common abnormalities that were detected in < 10% of cases at 11-13 weeks included ventriculomegaly, agenesis of the corpus callosum, isolated cleft lip, congenital pulmonary airway malformation, ventricular septal defect, abdominal cysts, unilateral renal agenesis or multicystic kidney, hydronephrosis, duplex kidney, hypospadias and talipes. CONCLUSIONS: A routine 11-13-week scan, carried out according to a standardized protocol, can identify many severe non-chromosomal fetal abnormalities. A summary statistic of the performance of the first-trimester scan is futile because some abnormalities are always detectable, whereas others are either non-detectable or sometimes detectable. To maximize prenatal detection of abnormalities, additional scans in both the second and third trimesters are necessary. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Diagnóstico de anomalías fetales no cromosómicas en la ecografía de rutina a las 11-13 semanas de gestación OBJETIVO: Examinar el desempeño de la ecografía de rutina a las 11-13 semanas en la detección de anomalías fetales no cromosómicas. MÉTODOS: Esta investigación fue un estudio retrospectivo de datos recogidos prospectivamente de 100 997 embarazos con feto único que acudieron a un examen ecográfico de rutina de la anatomía fetal, realizado de acuerdo con un protocolo estandarizado, a las 11-13 semanas de gestación. Todos los embarazos que continuaron se sometieron a una exploración adicional a las 18-24 semanas y 71754 se sometieron a una exploración a las 30-34 o a las 35-37 semanas. El diagnóstico final de la anomalía fetal se basó en los resultados del examen postnatal en los casos de nacimientos vivos y en los hallazgos del último examen ecográfico en los casos de interrupción del embarazo, aborto o éxitus fetal. Se determinó el rendimiento de la exploración de las 11-13 semanas en la detección de anomalías fetales. RESULTADOS: La población del estudio contenía 1720 (1,7%) embarazos con una anormalidad fetal, entre ellos 474 (27,6%) detectados en la exploración del primer trimestre, 926 (53,8%) detectados en la del segundo trimestre y 320 (18,6%) detectados en el tercer trimestre o postnatalmente. A las 11-13 semanas de gestación, se diagnosticaron todos los casos de acrania, holoprosencefalia alobar, encefalocele, atresia tricúspide o pulmonar, pentalogía de Cantrell, ectopia cordis, onfalocele, gastrosquisis y anomalía del pedículo embrionario y >50% de los casos de espina bífida abierta, síndrome del hemicardio izquierdo hipoplásico, comunicación auriculoventricular, defecto cardíaco complejo, isomerismo de la aurícula izquierda (vena cava inferior interrumpida con anatomía intracardíaca normal), obstrucción del tracto urinario inferior, ausencia de extremidades, secuencia de deformación de la acinesia fetal y displasia esquelética letal. Las anomalías comunes que se detectaron en <10% de los casos a las 11-13 semanas incluyeron ventriculomegalia, agenesia del cuerpo calloso, labio leporino aislado, malformación congénita de las vías respiratorias pulmonares, comunicación interventricular, quistes abdominales, agenesia renal unilateral o riñón multiquístico, hidronefrosis, duplicidad renal, hipospadias y pie zambo. CONCLUSIÓN: Una exploración rutinaria a las 11-13 semanas, realizada de acuerdo con un protocolo estandarizado, puede identificar muchas anomalías fetales no cromosómicas graves. Un resumen estadístico del desempeño de la exploración del primer trimestre es inútil porque algunas anomalías son siempre detectables, mientras que otras no lo son o solo lo son a veces. Para maximizar la detección prenatal de anormalidades, se necesitan exploraciones adicionales tanto en el segundo como en el tercer trimestre.

Craniofacial variations in the tricho-dento-osseous syndrome.

Tricho-dento-osseous (TDO) syndrome is an autosomal dominant trait characterized by curly kinky hair at birth, enamel hypoplasia, taurodontism, thickening of cortical bones and variable expression of craniofacial morphology. Genetic studies have identified a 4-bp deletion in the DLX3 gene that is associated with TDO; however, phenotypic characterization and classification of TDO remains unclear in the literature. This study compares the craniofacial variations between 53 TDO-affected subjects and 34 unaffected family members. Standardized cephalograms were obtained and digitized. Cephalometric measurements were analyzed using a general linear model with family as a random effect. Numerous craniofacial measurements from both groups showed marked variability. TDO-affected subjects showed a Class III skeletal pattern (smaller SNA and ANB angles), longer mandibular corpus length (GoGn) and shorter ramus height (p < 0.05).

First report of a Mikrocytos-like parasite in European oysters Ostrea edulis from Canada after transport and quarantine in France.

As part of a disease resistance experiment, 112 apparently healthy European flat oysters Ostrea edulis L. were exported from Canada (Nova Scotia) into France to test their susceptibility to Bonamia ostreae infection. Twelve oysters died in transit and 17 others died within 2 wk of laboratory quarantine acclimation. All oysters were examined histologically, and the 17 that died during quarantine were assayed for microcells (Bonamia sp. and Mikrocytos mackini) using molecular techniques. A microcell parasite was detected in the connective tissue of 5 of the 112 oysters. Morphological appearance, tissue affinity and molecular characterization through PCR, in situ hybridization (ISH), fluorescence in situ hybridization (FISH) and sequencing revealed a protist related to M. mackini. This is the first report of a parasite of the genus Mikrocytos in a species belonging to the genus Ostrea from the Atlantic Ocean.

Melanophore stimulating hormone (MSH) release: inhibition by cytochalasin B and "stimulation" by dimethyl sulfoxide.

Incubation of rat or frog pituitaries in cytochalasin B (10-4 minus 10-8 g/ml) for 2, 4 or 6 hr produces a time-dependent inhibition of MSH release. This inhibition is reversible and, again, time-dependent since longer incubations of pituitaries returned to normal media result in greater hormone secretion. Cytochalasin B inhibits MSH release even at a high concentration (10%) of dimethylsulfoxide (DMSO) which, itself, is "stimulatory" to hormone release. MSH release in high DMSO concentration is also inhibited by ouabain or by the absence of Ca2+ from the medium. In amphibian Ringer enriched with glucose, and in Medium 199, cytochalasin B fails to inhibit the release of MSH from the frog pituitary. Colchicine, vinblastine, and vincristine (10-3 minus 10-6 g/ml) were without effect on MSH release. These data suggest a possible role for microfilaments in the control of MSH release but fail to provide information on the exact nature of the mechanisms involved.

Regulatory light-chain Cys-55 sites on the two heads of myosin can come within 2A of each other.

The di-thiol reagent, 5,5'-dithiobis (2-nitrobenzoic acid) is shown to induce disulfide bond formation between Mercenaria regulatory light-chain Cys-55 sites on either head of scallop hybrid myosin. This indicates that these two sites on opposite heads of myosin can come within 2A of each other and this confirms a prediction based on earlier data [Chantler, Tao and Stafford (1991) Biophys. J. 59, 1242-1250]. Results demonstrate that myosin heads in solution show a considerable mutual freedom of movement which can be monitored by probes in the vicinity of regulatory light-chain residue 55. Implications for light-chain movement on the myosin head are discussed.

Acquired and innate resistance to the haemoflagellate cryptobia salmositica in sockeye salmon (Oncorhynchus nerka).

Juvenile sockeye salmon (Oncorhynchus nerka, Fulton River stock) were protected from otherwise lethal challenges with the haemoflagellate Cryptobia salmositica by acclimation to elevated water temperatures (20 degrees C). Fish treated in this manner displayed increased immunity to C. salmositica and yielded plasma showing enhanced lytic activity against the parasite. The acquired lytic activity was antibody- and complement-mediated. In contrast, a stock of naive O. nerka from Weaver Creek, previously identified as having a high innate resistance to the lethal effects of C. salmositica, also had plasma factors that destroyed the parasite in vitro. This anti-Cryptobia activity also involved complement because 1) it resulted in lysis of the parasite, 2) it was heat-labile (40 degrees C for 20 min), and 3) it was largely removed from the plasma by substances capable of activating (binding) complement by the classical pathway (an antigen:antibody complex of Renibacterium salmoninarum and its specific antibody) and the alternate pathway (Escherichia coli lipopolyssacharide). The complement-mediated lysis associated with innate resistance was apparently the result of activation by the alternate pathway because it occurred in fish lacking antibodies against the parasite. The reaction was unusual in that a long incubation period (about 2 days) was required for maximum lysis of the parasite. At least one component of the innate lytic system depended on disulphide bonds because lytic activity was destroyed by 2-mercaptoethanol.

Improved prediction of preeclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging.

OBJECTIVE: To assess the value of the early diastolic notch and color Doppler imaging of the uterine arteries at 24 weeks' gestation in a two-stage Doppler screening test for preeclampsia. METHODS: Two thousand fifty-eight unselected women had an initial screening study with continuous-wave Doppler at 18-22 weeks' gestation. Color Doppler imaging was used at 24 weeks' gestation to examine both uterine arteries in 273 women with initial abnormal results (high resistance index or diastolic notch). RESULTS: Three hundred twenty-nine women (16%) had abnormal flow velocity waveforms at the first stage and 104 (5.1%) at the second stage of Doppler screening. The presence of an early diastolic notch in the flow velocity waveform was significantly better than a high resistance index at predicting preeclampsia at both 20 and 24 weeks; the relative risk of developing significant preeclampsia for a woman with a persistent notch at 24 weeks was increased 68-fold. All women delivered before 34 weeks because of severe preeclampsia had abnormal waveforms at both stages of screening. CONCLUSION: An early diastolic notch in the flow velocity waveform is a better predictor of preeclampsia than are conventional impedance indices. Preeclampsia can be predicted effectively by two-stage Doppler screening.

Ablation of acardiac twin by alcohol injection into the intra-abdominal umbilical artery.

BACKGROUND: Twin reversed arterial perfusion sequence is a rare complication of monochorionic twinning, in which the normal pump twin perfuses the abnormal acardiac twin in a reversed fashion via an artery-to-artery placental anastomosis. Mortality in the normal twin exceeds 50% as a result of preterm labor, polyhydramnios, and congestive heart failure. CASE: A twin pregnancy complicated by the twin reversed arterial perfusion sequence developed early hemodynamic decompensation in the pump twin with increasing size of the acardiac twin. Ablation of the acardiac twin at 23 weeks' gestation was achieved successfully by injecting 1 mL of absolute alcohol into the intra-abdominal portion of the single umbilical artery. CONCLUSION: Direct ultrasound-guided intravascular injection of absolute alcohol is an easy and straightforward technique to occlude circulation to the acardiac twin. This vessel can be identified easily by color Doppler ultrasonography away from the main venous trunk. Selection of this target, rather than occlusion at the level of the umbilical cord, could reduce the risks of cord accidents and inadvertent intravenous injection of the ablative material.

Discordant blood flow velocity waveforms in left and right brachial arteries in growth-retarded fetuses.

OBJECTIVE: To determine if the increase in cerebral blood flow ("brain-sparing" effect) with fetal hypoxemia is associated with discordant hemodynamics in the upper extremities. METHODS: We studied 12 fetuses with severe growth retardation, absent or reverse end-diastolic blood flow in the umbilical artery, and low pulsatility index (PI) in the middle cerebral artery, and 12 appropriately grown control fetuses with normal fetoplacental Doppler studies. The right and left brachial arteries were identified by high-resolution color Doppler ultrasonography, and the PI was measured in each brachial artery. RESULTS: All growth-retarded fetuses had lower impedance indices in the right than in the left brachial artery (mean delta PI 1.0, 95% confidence interval [CI] 0.7-1.3, P < .001). No differences in the brachial artery impedance indices were found in control fetuses matched for gestational age (mean delta PI 0.0, 95% CI -0.2 to 0.2). CONCLUSIONS: Left and right brachial artery blood flow velocity waveforms are discordant in fetuses with growth retardation and cerebral vasodilation. Because the right arm receives its blood supply from the same source as the brain (brachiocephalic artery) and given the proximity of the left subclavian artery to the ductus arteriosus, we speculate that this might be the result of increased blood flow into the brachiocephalic circulation and/or functional differences in the distribution of left and right ventricular output within the aortic arch in response to fetal hypoxemia.

Fetal hyperechogenic bowel following intra-amniotic bleeding.

OBJECTIVE: To test the hypothesis that increased echogenicity of the fetal bowel at second-trimester scans results from intra-amniotic bleeding. METHODS: We studied 726 patients undergoing second-trimester amniocentesis for advanced maternal age. Three groups were identified according to the color of the amniotic fluid (AF) obtained: clear fluid, blood-stained fluid, and dark brown fluid. Two to 4 weeks after the amniocentesis, all patients had a targeted ultrasound examination for the detection of fetal structural anomalies and markers of chromosomal abnormalities, which included a survey of the fetal bowel. The incidence of hyperechogenic bowel in each group was compared by Fisher exact test. P < .05 was considered significant. RESULTS: In 694 cases, the AF was clear (95%), in 20 blood-stained (3%), and in 12 dark brown (2%). Hyperechogenic bowel was detected in 14 fetuses with clear fluid (2%), in two with blood-stained fluid (10%), and in three with dark brown fluid (25%). Fetuses with proven intra-amniotic bleeding (ie, dark brown or blood-stained AF at amniocentesis) had a significantly higher incidence of hyperechogenic bowel compared to those with clear AF (five of 32 [15.6%] and 14 of 694 [2.0%], respectively; P < .001, 95% confidence interval for the difference in proportions 6.3-17.6%). CONCLUSIONS: Our study demonstrates that intra-amniotic bleeding is associated with an increased incidence of fetal hyperechogenic bowel at second-trimester ultrasound scans. This sonographic phenomenon may be due to the presence of blood in the fetal bowel caused by fetal swallowing of bloody AF.

Recovery and relapse in adolescents with bipolar affective illness: a five-year naturalistic, prospective follow-up.

OBJECTIVE: This study was a 5-year naturalistic prospective follow-up of 54 consecutive admissions of adolescents to a university inpatient service with a diagnosis of bipolar I affective illness. METHOD: Subjects received structured clinical evaluations every 6 months after entry to establish time to recovery and subsequent relapse. Regression models were used to identify predictors of differential course. RESULTS: Rate of recovery varied by polarity of episode at time of entry, with quick recovery observed in subjects with pure mania or mixed states, and a protracted index episode in subjects with pure depression. Multiple relapses were most often seen in subjects with mixed or cycling episodes at intake. CONCLUSIONS: Polarity of illness may have utility in identifying bipolar adolescents with a more recurrent illness. Comparison with adult data suggests that recurrence risks may vary as a function of age at onset or stage of the disease process.

Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval.

OBJECTIVE: To investigate the time course of changes in follicular fluid (FF) concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal oocyte collection. STUDY DESIGN: Forty-five patients with tubal infertility were randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for sedation during ultrasound-guided transvaginal oocyte collection. Paracervical block with lignocaine was given for analgesia. Simultaneous blood and FF samples were drawn at 5-minute intervals after the bolus dose for analysis of drug levels. RESULTS: Data were obtained on 15 women receiving midazolam and fentanyl and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak and then fell in an exponential fashion as was expected. The FF levels of the agents continued to rise significantly to 25 minutes after the bolus dose, although the absolute level was low when compared with the blood level. There were no significant differences in fertilization or pregnancy rates in the three groups, but patient numbers were small. CONCLUSION: We conclude that midazolam, fentanyl, and alfentanil are found in FF after a single IV dose, but further investigation needs to be undertaken to investigate any potential influence on fertilization and implantation rates.

Fungal meningitis and intracerebral hemorrhage complicating prosthetic valve endocarditis.

A 50 yr old man presented with meningitis 163 days following aortic valve replacement for congenital bicuspid aortic stenosis. One week later he died of intracerebral hemorrhage and autopsy revealed fungal prosthetic valve endocarditis. Colonies of branching septate hyphae were adherent to the oculomotor nerves and left posterior communicating artery. This pattern of fungal basal meningeal involvement complicating prosthetic valve endocarditis has not been previously described.

Cerebral and renal artery blood flow velocity before and after birth.

OBJECTIVE: To document perinatal changes in cerebral and renal artery haemodynamics in premature growth-retarded and normal term infants. DESIGN: Longitudinal study of individual infants. Doppler ultrasound measurements of blood flow velocity (BFV) in the middle cerebral and renal arteries were obtained before delivery, soon after delivery and during the first week of postnatal life. SETTING: Teaching hospital obstetric and neonatal units. SUBJECTS: 13 severely growth retarded infants born at 28-36 weeks gestation, and eight normally grown infants born at term. RESULTS: In both groups, BFV in the cerebral artery was significantly lower in the first few hours after birth than in fetal life, but subsequently increased to reach pre-delivery values by the end of the first week. In contrast, BFV in the renal artery during the first postnatal day was not significantly different from fetal values, but it also increased during the subsequent week. In six of the preterm growth-retarded infants, fetal blood gases were measured in samples obtained by cordocentesis, and in these cases an increase in blood oxygen content at birth was documented. CONCLUSIONS: Cerebral artery BFV falls at birth and is relatively low during the time that premature infants are at the greatest risk of developing periventricular haemorrhage.

Neuralgia after inguinal hernia repair.

Severe chronic pain after groin hernia repair is uncommon but potentially debilitating. Fifteen patients with this condition were retrospectively reviewed. All patients had severe pain, which prevented their working or normal activity and was refractory to nonoperative treatment. Essentials of therapy included 1) a preoperative attempt to identify the involved nerve and 2) high ligation and division of the involved nerve identified at exploration. Twelve patients obtained excellent results and were able to return to normal activity with no requirement for analgesia. Understanding of the typical nerve anatomy, as well as the individual variation in nerve anatomy, can help prevent this complication and is essential for correction if the complication does develop.

Plasma protein binding of fentanyl: the effect of hyperlipoproteinaemia and chronic renal failure.

Hyperlipoproteinaemic patients with raised pre beta-, or pre beta- and beta-lipoprotein fractions showed a significant (P less than 0.001) increase in binding of fentanyl to whole plasma, compared with normal subjects. The presence of chylomicra had no significant effect on binding. In patients with chronic renal failure, a correlation of probability P less than 0.07 was found between percent binding and concentrations of pre beta-lipoprotein (P = 0.001), serum albumin (P = 0.0101), total protein minus albumin (P = 0.0576) and beta-lipoprotein (P = 0.0625). There was no significant correlation of binding with elevation of alpha- or gamma-globulins, with urea or creatinine concentrations, or with age or sex (P greater than 0.223). The magnitude of changes in the free fraction found in these patients should not produce a clinical effect as the total distribution volume of fentanyl exceeds 200 litres.