Aberrant right subclavian artery as a new cardiac sign in second- and third-trimester fetuses with Down syndrome

OBJECTIVE: The right subclavian artery arises normally as the first vessel from the brachiocephalic artery of the aortic arch. An aberrant right subclavian artery arises as a separate vessel from the aortic isthmus and crosses to the right, behind the trachea. This variant is present in <1% of the normal population; however, in subjects with Down syndrome, an incidence between 19% and 36% was reported. The purpose of this study was to assess the possibility of the detection of an aberrant right subclavian artery in fetuses with Down syndrome. STUDY DESIGN: Fourteen consecutive fetuses with prenatally detected Down syndrome were examined between 18 and 33 weeks of gestation. The presence of an aberrant right subclavian artery was determined by visualization of the transverse 3-vessel trachea view of the upper thorax with color Doppler ultrasonography. RESULTS: The right subclavian artery was visualized in 100% of fetuses (14/14) with Down syndrome. An aberrant right subclavian artery was identified in 35.7% of trisomy 21 fetuses (5/14). In 1 fetus, the aberrant right subclavian artery was the only abnormal ultrasound finding. In 3 fetuses, an aberrant right subclavian artery was associated with an intracardiac echogenic focus plus additional extracardiac markers. In the fourth fetus, an aberrant right subclavian artery was associated with an atrioventricular septal defect. All 9 fetuses with Down syndrome with a normal origin of the right subclavian artery had additional cardiac and/or extracardiac abnormalities. In 12 cases, pregnancy was terminated; 2 fetuses were live born. CONCLUSION: This preliminary study suggests that the in utero identification of an aberrant right subclavian artery may be a new ultrasound marker to be found in fetuses with Down syndrome. Further studies are required to assess the incidence of aberrant right subclavian artery in normal fetuses.     

Flow compensation in balanced SSFP sequences.

In balanced steady-state free precession (b-SSFP) sequences, uncompensated first-order moments of encoding gradients induce a nonconstant phase evolution for moving spins within the excitation train, resulting in signal loss and image artifacts. To restore these flow-related phase perturbations, "pairing" of consecutive phase-encoding (PE) steps is compared with a fully flow-compensated sequence using compensating gradient waveforms along all three encoding directions. In volunteer studies, the quality of images acquired with the "pairing" technique was comparable to that of images obtained with the fully flow-compensated technique, regardless of the selected view-ordering scheme used for data acquisition. Nevertheless, the results of phantom experiments indicate that the pairing technique becomes ineffective at flow velocities exceeding roughly 0.5-1 m/s. Consequently, the additional scan time required to null the first gradient moments in a flow-compensated b-SSFP sequence makes the "pairing" technique preferable for applications in which slow to moderate flow velocities can be expected.     

Giving birth: the voices of Orthodox Jewish women living in Canada

OBJECTIVE: To describe the meaning of the childbirth experience to Orthodox Jewish women living in Canada. DESIGN: In this phenomenologic study, audiotaped interviews were conducted. Tapes were transcribed verbatim and analyzed for emergent themes. Demographic data also were collected. SETTING AND PARTICIPANTS: Thirty Orthodox Jewish women who had given birth to healthy full-term newborns at a university-affiliated Jewish hospital in Montreal, Canada, participated in the study. Data were collected within 2 weeks after childbirth, either in the mother's postpartum hospital room or in her home. RESULTS: The following themes reflecting spiritual/cultural dimensions of the childbirth experience were identified: (a) birth as a significant life event, (b) birth as a bittersweet paradox, (c) the spiritual dimensions of giving birth, (d) the importance of obedience to rabbinical law, and (e) a sense of support and affirmation. CONCLUSION: This study documents cultural, religious, and spiritual dimensions of the childbirth experience of Orthodox Jewish women living in Canada. Knowledge and appreciation of the multiple dimensions of childbirth reflected by this study's findings can contribute to holistic and culturally competent nursing care of women and newborns.     

High-resolution contrast-enhanced magnetic resonance angiography of the carotid arteries using fluoroscopic monitoring of contrast arrival: diagnostic accuracy and interobserver variability

Purpose: To evaluate the diagnostic accuracy of high-resolution contrast-enhanced magnetic resonance angiography (CE-MRA) of the supra-aortic arteries using the CareBolus technique. Digital subtraction angiography was the standard of reference. Material and Methods: Fifty consecutive patients with suspected internal carotid artery stenosis underwent CE-MRA and digital subtraction angiography. CE-MRA was performed on a 1.5-T superconducting scanner with the CareBolus technique. CareBolus combines a nearly real-time 2D-FLASH (fast low angle shot) sequence for fluoroscopic triggering and a high-resolution 3D-FLASH with elliptical centric view order for the angiographic pulse sequence (6.0/2.16 ms [TR/TE], 30° flip angle, 30.98 s acquisition time, 0.88 mm effective (interpolated) partition thickness and a 160×512 matrix). Intra-arterial digital subtraction angiography and CE-MRA studies were evaluated independently by four blinded readers. Internal carotid artery stenoses were graded according to the NASCET criteria. Results: CE-MRA had an accuracy of 92.53%, a sensitivity of 95.64%, and a specificity of 90.39% for the identification of carotid artery stenoses ≥70% (grade 3). Image quality for suppression of stationary tissue and venous contrast was good, but was reduced in five cases due to patient motion. Conclusion: The CareBolus technique is a useful non-invasive method for high-resolution imaging of the supra-aortic vessels because of its easy application and high sensitivity and specificity. Limitations can occur in non-compliant patients due to motion artifacts during the measurement time.     

Noquist: reduced field-of-view imaging by direct Fourier inversion.

A novel technique called "Noquist" is introduced for the acceleration of dynamic cardiac magnetic resonance imaging (CMRI). With the use of this technique, a more sparsely sampled dynamic image sequence is reconstructed correctly, without Nyquist foldover artifact. Unlike most other reduced field-of-view (rFOV) methods, Noquist does not rely on data substitution or temporal interpolation to reconstruct the dynamic image sequence. The proposed method reduces acquisition time in dynamic MRI scans by eliminating the data redundancy associated with static regions in the dynamic scene. A reduction of imaging time is achieved by a fraction asymptotically equal to the static fraction of the FOV, by omitting acquisition of an appropriate subset of phase-encoding views from a conventional equidistant Cartesian acquisition grid. The theory behind this method is presented along with sample reconstructions from real and simulated data. Noquist is compared with conventional cine imaging by retrospective selection of a reduced data set from a full-grid conventional image sequence. In addition, a comparison is presented, using real and simulated data, of our technique with an existing rFOV technique that uses temporal interpolation. The experimental results confirm the theory, and demonstrate that Noquist reduces scan time for cine MRI while fully preserving both spatial and temporal resolution, but at the cost of a reduced signal-to-noise ratio (SNR).     

Diagnosis of patent foramen ovale with multiplane transesophageal echocardiography in adult cardiac surgical patients

OBJECTIVE: To evaluate multiplane transesophageal echocardiography (TEE) for detection of patent foramen ovale (PFO) and to compare multiplane TEE with visual inspection (VI) for PFO detection. DESIGN: A prospective observational study. SETTING: University hospital (single institution). PARTICIPANTS: Patients presenting for cardiac surgery requiring TEE. INTERVENTIONS: Multiplane TEE including 2 atrial views with color-flow Doppler (CFD) and contrast echocardiography (CE) with a provocative respiratory maneuver (PRM) and comparison of multiplane TEE and VI with respect to PFO detection. MEASUREMENTS AND MAIN RESULTS: The cohort size was 187. PFO prevalence was 27.3%. CFD with serial decrease of the Nyquist limit detected 51% of all PFO: 41.2% in the bicaval view alone, 27.5% in the 4-chamber view alone, and 9.8% in both views. CE detected 78.4% of all PFO: 72.5% with PRM, 45.1% with no PRM, and 27.4% with/without PRM. PFO detection by multiplane TEE and visual inspection were correlated in 41 subjects. TEE diagnosed 11 PFO (26.8% prevalence, 3 missed by VI). VI diagnosed 12 PFO (29.3% prevalence, 4 missed by TEE). CONCLUSIONS: Multiplane TEE is a gold standard for detection of PFO. Despite advances in TEE technology, 2-dimensional imaging does not detect all PFO. To maximize PFO detection, multiple TEE modalities are required in multiple views, despite a low Nyquist limit for CFD or a PRM for CE. Even though multiplane TEE is equivalent to VI for PFO detection, the discrepancy rate may be an important consideration in the individual case.     

Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters

Several of the ATP-binding cassette (ABC) transporters confer resistance to anticancer agents and/or antiviral agents when overexpressed in drug-sensitive cells. Recently a MRP1 (ABCC1) tricyclic isoxazole inhibitor, LY475776 was shown to be a glutathione-dependent photoaffinity label of human MRP1 and showed poor labeling of murine mrp1, an ortholog that does not confer anthracycline resistance. In the present study, the specificity of LY475776 was examined for its ability to modulate or photolabel orthologs of MRP1 and several other drug efflux transporters of the ABC transporter family. LY475776 modulated MRP1 and Pgp-mediated resistance (MDR, ABCB1) in, respectively, HeLa-T5 and CEM/VLB(100) cells to both vincristine and doxorubicin. LY475776 photolabeled 170kDa Pgp and was inhibited by the potent Pgp inhibitor LY335979 (Zosuquidar.3HCl). The labeling of the 190kDa MRP1 protein in membranes of HeLa-T5 cells was inhibited by substrates of MRP1 such as leukotriene C(4), vincrisine, and doxorubicin and by the inhibitor, MK571. LY475776 did not photolabel human MRP2 (ABCC2), MRP3 (ABCC3), MRP5 (ABCC5) or breast cancer resistance protein (ABCG2). Because LY475776 photolabels murine mrp1 less well than human MRP1 and binds to a region believed important for anthracycline binding, studies were conducted with monkey and canine MRP1 which also show a reduced ability to confer resistance to anthracyclines. Unlike murine mrp1, both orthologs were photolabeled well by LY475776. These studies indicate that the specificity of LY475776 is fairly limited to Pgp and MRP1 and further studies will help to define the binding regions.     

Effect of sleep deprivation and driving duration on the useful visual field in younger and older subjects during simulator driving

Nine older subjects (40-51 years) and 10 younger subjects (18-30 years) took part in two one-hour driving sessions. They performed a very monotonous task during which they had to follow a vehicle either after a complete night of sleep or after one night of sleep deprivation. While driving their useful visual field was assessed by introducing signals that would appear on the whole road scene.The analysis of the data indicates that the ability to process peripheral signals deteriorates with age, driving duration and sleep deprivation. However, the effects of these three variables on the peripheral visual ability are not similar in a dual task. The driver's useful visual field changes with age and prolongation of the monotonous driving activity according to a tunnel vision phenomenon. On the other hand, a sleep debt deteriorates the useful visual field according to a general interference phenomenon. These results are discussed in terms of decrease in the level of arousal and increase of fatigue.     

Preventive effect of silymarin against taurolithocholate-induced cholestasis in the rat

Increased amounts of monohydroxylated bile salts (BS) have been found in neonatal cholestasis, parenteral nutrition-induced cholestasis and Byler's disease, among others. We analyzed whether the hepatoprotector silymarin (SIL), administered i.p. at the dose of 100mg/kg/day for 5 days, prevents the cholestatic effect induced by a single injection of the model monohydroxylated BS taurolithocholate (TLC, 30 micromol/kg, i.v.) in male Wistar rats. TLC, administered alone, reduced bile flow, total BS output, and biliary output of glutathione and HCO(3)(-) during the peak of cholestasis (-75, -67, -81, and -80%, respectively, P<0.05). SIL prevented partially these alterations, so that the drops of these parameters induced by TLC were of only -41, -25, -60, and -64%, respectively (P<0.05 vs. TLC alone); these differences between control and SIL-treated animals were maintained throughout the whole (120 min) experimental period. Pharmacokinetic studies showed that TLC decreased the intrinsic fractional constant rate for the canalicular transport of both sulfobromophthalein and the radioactive BS [14C]taurocholate by 60 and 68%, respectively (P<0.05), and these decreases were fully and partially prevented by SIL, respectively. SIL increased the hepatic capability to clear out exogenously administered TLC by improving its own biliary excretion (+104%, P<0.01), and by accelerating the formation of its non-cholestatic metabolite, tauromurideoxycholate (+70%, P<0.05). We conclude that SIL counteracts TLC-induced cholestasis by preventing the impairment in both the BS-dependent and -independent fractions of the bile flow. The possible mechanism/s involved in this beneficial effect will be discussed.     

Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity

Thirteen structural analogs of the potent nonpolyglutamatable dihydrofolate reductase inhibitor N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, the para-aminobenzoyl moiety, or the 9,10-bridge were evaluated for the ability to inhibit human recombinant dihydrofolate reductase (DHFR), to utilize the reduced folate carrier (RFC) for influx, and to inhibit the growth of CCRF-CEM human leukemia cells in culture. In spectrophotometric assays of the kinetics of the reduction of dihydrofolate by DHFR in the presence of NADPH, these compounds had K(i) values ranging from 0.2 to 1.3pM, and thus were not greatly different in potency from the parent drug PT523. By comparison, the K(i) values of aminopterin (AMT), methotrexate (MTX), and 10-ethyl-10-deazaaminopterin (EDX) were 3.7, 4.8, and 11pM. In assays of competitive inhibition of [3H]MTX influx into CCRF-CEM cells, the K(i) values ranged from 0.21 to 7.3 micro M, as compared with 0.71, 5.4, and 1.1 micro M for PT523, AMT, and EDX. The K(t) for MTX was also re-analyzed and found to be 4.7 micro M, in better agreement with the literature than our previously reported value of 7.1 micro M. The IC(50) values of these compounds as inhibitors of the growth of CCRF-CEM cells after 72hr of drug exposure ranged from 0.53 to 55nM, and were qualitatively consistent with the other results.