Impact of maternal social vulnerability and timing of prenatal care on outcome of prenatally detected congenital heart disease.

OBJECTIVES: Early prenatal detection of congenital heart disease (CHD) allows mothers to plan for their pregnancy and delivery; however, the effect of certain sociodemographic and fetal factors on prenatal care has not been investigated thoroughly. This study evaluated the impact of maternal and fetal characteristics on the timing of prenatal diagnosis of CHD and fetal and postnatal outcomes. METHODS: This retrospective multicenter cohort study included women with a fetal echocardiographic diagnosis of CHD between 2010 and 2019. Women were grouped into quartiles of social vulnerability (quartiles 1-4; low-high) using the 2014 social vulnerability index (SVI) provided by the Centers for Disease Control and Prevention. A fetal disease severity score (range, 1-7) was calculated based on a combination of CHD severity (mild = 1; moderate = 2; severe, two ventricles = 3; severe, single ventricle = 4 points) and prenatally diagnosed genetic abnormality, non-cardiac abnormality and fetal hydrops (1 point each). Late diagnosis was defined as a fetal echocardiographic diagnosis of CHD after 24 weeks' gestation. Univariate and multivariable regression analyses were used to identify factors associated with late diagnosis, termination of pregnancy (TOP), postnatal death, prenatal-postnatal discordance in CHD diagnosis and severity and, for liveborn infants, to identify which prenatal variables were associated with postnatal death or heart transplant. RESULTS: Among 441 pregnancies included, 94 (21%) had a late diagnosis of CHD. Late diagnosis was more common in the most socially vulnerable quartile, 38% of women in this group having diagnosis > 24 weeks, compared with 14-18% in the other three quartile groups. Late diagnosis was also associated with Catholic or other Christian religion vs non-denominational or other religion and with a lower fetal disease severity score. There were 93 (21%) TOP and 26 (6%) in-utero fetal demises. Factors associated with TOP included early diagnosis and greater fetal disease severity. Compared with the other quartiles, the most socially vulnerable quartile had a higher incidence of in-utero fetal demise and a lower incidence of TOP. Among the 322 liveborn infants, 49 (15%) died or underwent heart transplant during the follow-up period (range, 0-16 months). Factors associated with postnatal death or heart transplant included longer delay between obstetric ultrasound examination at which CHD was first suspected and fetal echocardiogram at which CHD was confirmed and greater fetal disease severity. CONCLUSIONS: High social vulnerability, Catholic or other Christian religion and low fetal disease severity are associated with late prenatal CHD diagnosis. Delays in CHD diagnosis are associated with fewer TOPs and worse postnatal outcome. Therefore, efforts to expedite fetal echocardiography following abnormal obstetric screening, particularly for at-risk women (e.g. those with high SVI), have the potential to impact pregnancy and postnatal outcome among the prenatally diagnosed CHD population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Tension band wiring versus locking plate fixation for simple, two-part Mayo 2A olecranon fractures: a comparison of post-operative outcomes, complications, reoperations and economics.

PURPOSE: Simple displaced transverse olecranon fractures are traditionally managed operatively with a tension band wire device (TBW). We compared clinical outcomes, morbidity and the cost of treatment of TBW versus pre-countered low-profile locking plates for the treatment of Mayo 2A fractures. PATIENT AND METHODS: All olecranon fractures admitted to our unit between 2008 and 2014 were identified (n = 129). Patient notes and radiographs were studied from presentation to final follow-up. Patient outcomes were recorded using the QuickDASH (Disabilities of Arm, Shoulder and Hand) score. Patient demographics and nature of complications were recorded as were the rate and nature of any repeat operation. RESULTS: Eighty-nine patients had Mayo 2A fractures (69%). Sixty-four underwent TBW (n = 48) or locking plate fixation (n = 16). The mean ages of both groups were similar at 57 (15-93) and 60 (22-80), respectively. In the TBW group, the mean post-injury QuickDASH was 12.9, compared with 15.0 for the locking plate group. There was no statistically significant difference between the outcomes for either group. Nineteen of the 48 TBW patients had complications (39.6%). Sixteen of the 48 TBW patients had reoperations (33.3%). In particular, we would highlight that 13 (27.1%) of patients treated with TBW underwent subsequent removal of metalwork for hardware irritation. There were no complications and or reoperations in the 16 patients who received locking plate fixation. Both complication and reoperation rates were statistically significantly different. Despite being initially more expensive, when the cost of reoperation for TBW group was included, locking plates were found to be on average £236.33 less per patient than for TBW. CONCLUSIONS: We suggest that locking plates are superior to TBW concerning post-operative morbidity, reoperation rate and cost for Mayo 2A fractures in contrast to previous articles. LEVEL OF EVIDENCE: Therapeutic study, III.

A randomized prospective study comparing mobile-bearing against fixed-bearing PFC Sigma cruciate-retaining total knee arthroplasties with ten-year minimum follow-up.

AIMS: This study compares the PFC total knee arthroplasty (TKA) system in a prospective randomized control trial (RCT) of the mobile-bearing rotating-platform (RP) TKA against the fixed-bearing (FB) TKA. This is the largest RCT with the longest follow-up where cruciate-retaining PFC total knee arthroplasties are compared in a non-bilateral TKA study. PATIENTS AND METHODS: A total of 167 patients (190 knees with 23 bilateral cases), were recruited prospectively and randomly assigned, with 91 knees receiving the RP and 99 knees receiving FB. The mean age was 65.5 years (48 to 82), the mean body mass index (BMI) was 29.7 kg/m2 (20 to 52) and 73 patients were female. The Knee Society Score (KSS), Knee Society Functional Score (KSFS), Oxford Knee Score (OKS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and 12-Item Short-Form Health Survey Physical and Mental Component Scores (SF-12 PCS, SF-12 MCS) were gathered and recorded preoperatively, at five-years' follow-up, and at ten years' follow-up. Additionally, Knee Injury and Osteoarthritis Outcome Scores (KOOS) were collected at five- and ten-year follow-ups. The prevalence of radiolucent lines (RL) on radiographs and implant survival were recorded at five- and ten-year follow-ups. RESULTS: At the ten-year follow-up, the RP group (n = 39) had a statistically significant superior score in the OKS (p = 0.001), WOMAC (p = 0.023), SF-12 PCS (p = 0.019), KOOS Activities of Daily Living (ADL) (p = 0.010), and KOOS Sport and Recreation (Sport/Rec) (p = 0.006) compared with the FB group (n = 46). The OKS, SF-12 PCS, and KOOS Sport/Rec at ten years had mean scores above the minimal clinically important difference (MCID) threshold. There was no significant difference in prevalence of radiolucency between groups at five-years' follow-up (p = 0.449), nor at ten-years' follow-up (p = 0.08). Implant survival rate at 14 years postoperative was 95.2 (95% CI 90.7 to 99.8) and 94.7 (95% CI 86.8 to 100.0) for the RP and FB TKAs, respectively. CONCLUSION: At ten-year follow-up, the mobile-bearing knee joint arthroplasty had statistically and clinically relevant superior OKS, SF-12 PCS, and KOOS (Sport/Rec) than the fixed-bearing platform. No difference was seen in prevalence of radiolucent lines. There was a greater than 94% implant survival rate for both cohorts at 14 years. Cite this article: Bone Joint J 2018;100-B:1336-44.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

The treatment of olecranon fractures in adults.

Olecranon fractures are common. They are usually managed surgically with open reduction and either tension band wiring or plate fixation. Currently, there are few studies comparing fracture treatments. We aim to review the available literature to guide the orthopaedic surgeon on the management of these fractures. A literature review of peer-reviewed publications in international orthopaedic journals detailing olecranon fracture treatment was conducted. An additional focus was placed on the evidence base for and surgical outcomes of tension band wiring for common two-part fractures. Our novel illustrations aim to educate the reader, and our treatment algorithm provides guidance for management. 10% of all upper limb fractures involve the olecranon, and most are simple two-part injuries. These should be managed with tension band wire constructs. Non-displaced fractures can be treated conservatively. Displaced complex injuries necessitate locking plate fixation. Currently, there exits a lack of studies comparing these treatments. There may be an emerging role for intramedullary nail fixation. Non-operative management in the elderly comorbid patient remains controversial. Prospective, randomised controlled trials of matched patients and fracture patterns comparing operative techniques are needed as there is a lack of level I/II evidence to support the use of one implant over another.

Characterization of three diaminopyrimidines as potent and selective antagonists of P2X3 and P2X2/3 receptors with in vivo efficacy in a pain model.

BACKGROUND AND PURPOSE: P2X3 and P2X2/3 receptors are highly localized on the peripheral and central pathways of nociceptive signal transmission. The discovery of A-317491 allowed their validation as chronic inflammatory and neuropathic pain targets, but this molecule has a very limited oral bioavailability and CNS penetration. Recently, potent P2X3 and P2X2/3 blockers with a diaminopyrimidine core group and better bioavailability were synthesized and represent a new opportunity for the validation of P2X3-containing receptors as targets for pain. Here we present a characterization of three representative diaminopyrimidines. EXPERIMENTAL APPROACH: The activity of compounds was evaluated in intracellular calcium flux and electrophysiological recordings from P2X receptors expressed in mammalian cells and in a in vivo model of inflammatory pain (complete Freund's adjuvant (CFA) in rat paws). KEY RESULTS: Compound A potently blocked P2X3 (pIC(50)= 7.39) and P2X2/3 (pIC(50)=6.68) and showed no detectable activity at P2X1, P2X2, P2X4 and P2X7 receptors (pIC(50)< 4.7). Whole-cell voltage clamp electrophysiology confirmed these results. Compounds showed good selectivities when tested against a panel of different classes of target. In the CFA model, compound B showed significant anti-nociceptive effects (57% reversal at 3mg·kg(-1) ). CONCLUSIONS AND IMPLICATIONS: The diaminopyrimidines were potent and selective P2X3 and P2X2/3 receptor antagonists, showing efficacy in vivo and represent useful tools to validate these receptors as targets for inflammatory and neuropathic pain and provide promising progress in the identification of therapeutic tools for the treatment of pain-related disorders.

Ventricular size and function assessed by cardiac MRI predict major adverse clinical outcomes late after tetralogy of Fallot repair.

BACKGROUND: Factors associated with impaired clinical status in a cross-sectional study of patients with repaired tetralogy of Fallot (TOF) have been reported previously. OBJECTIVES: To determine independent predictors of major adverse clinical outcomes late after TOF repair in the same cohort during follow-up evaluated by cardiac magnetic resonance (CMR). METHODS: Clinical status at latest follow-up was ascertained in 88 patients (median time from TOF repair to baseline evaluation 20.7 years; median follow-up from baseline evaluation to most recent follow-up 4.2 years). Major adverse outcomes included (a) death; (b) sustained ventricular tachycardia; and (c) increase in NYHA class to grade III or IV. RESULTS: 22 major adverse outcomes occurred in 18 patients (20.5%): death in 4, sustained ventricular tachycardia in 8, and increase in NYHA class in 10. Multivariate analysis identified right ventricular (RV) end-diastolic volume Z >or=7 (odds ratio (OR) = 4.55, 95% confidence interval (CI) 1.10 to 18.8, p = 0.037) and left ventricular (LV) ejection fraction <55% (OR = 8.05, 95% CI 2.14 to 30.2, p = 0.002) as independent predictors of outcome with an area under the receiver operator characteristic curve of 0.850. LV ejection fraction could be replaced by RV ejection fraction <45% in the multivariate model. QRS duration >or=180 ms also predicted major adverse events but correlated with RV size. CONCLUSIONS: In this cohort, severe RV dilatation and either LV or RV dysfunction assessed by CMR predicted major adverse clinical events. This information may guide risk stratification and therapeutic interventions.

Safety and efficacy of carvedilol therapy for patients with dilated cardiomyopathy secondary to muscular dystrophy.

BACKGROUND: By the age of 20 years, almost all patients with Duchenne's or Becker's muscular dystrophy have experienced dilated cardiomyopathy (DCM), a condition that contributes significantly to their morbidity and mortality. Although studies have shown carvedilol to be an effective therapy for patients with other forms of DCM, few data exist concerning its safety and efficacy for patients with muscular dystrophy. This study aimed to evaluate the safety and efficacy of carvedilol for patients with DCM. METHODS: A clinical trial at an outpatient clinic investigated 22 muscular dystrophy patients, ages 14 to 46 years, with DCM and left ventricular ejection fraction (LVEF) less than 50%. Carvedilol up-titrated over 8 weeks then was administered at the maximum or highest tolerated dose for 6 months. Baseline and posttreatment cardiac magnetic resonance imaging (CMR), echocardiography, and Holter monitoring were recorded. RESULTS: Carvedilol therapy was associated with a modest but statistically significant improvement in CMR-derived ejection fraction (41% +/- 8.3% to 43% +/- 8%; p < 0.02). Carvedilol also was associated with significant improvements in both the mean rate of pressure rise (dP/dt) during isovolumetric contraction (804 +/- 216 to 951 +/- 282 mmHg/s; p < 0.05) and the myocardial performance index (0.55 +/- 0.18 to 0.42 +/- 0.15; p < 0.01). A trend toward improved shortening fraction, E/E' ratio, and isovolumetric relaxation time also was observed. Two patients had runs of nonsustained ventricular tachycardia exceeding 140 beats per minute (bpm) before carvedilol administration. Ventricular tachycardia exceeding 140 bpm was not observed after carvedilol therapy. Carvedilol was well tolerated, and no serious adverse events were identified. CONCLUSIONS: Carvedilol therapy appears to be safe for patients with DCM secondary to muscular dystrophy and produces a modest improvement in systolic and diastolic function.

Functional modulation of human brain Nav1.3 sodium channels, expressed in mammalian cells, by auxiliary beta 1, beta 2 and beta 3 subunits.

Voltage-gated sodium channels consist of a pore-forming alpha subunit and two auxiliary beta subunits. Excitable cells express multiple alpha subtypes, designated Na(v)1.1-Na(v)1.9, and three beta subunits, designated beta1, beta2 and beta3. Understanding how the different alpha subtypes, in combination with the various beta subunits, determine sodium channel behavior is important for elucidating the molecular basis of sodium channel functional diversity. In this study, we used whole-cell electrophysiological recording to examine the properties of the human Na(v)1.3 alpha subtype, stably expressed in Chinese hamster ovary cells, and to investigate modulation of Na(v)1.3 function by beta1, beta2 and beta3 subunits. In the absence of beta subunits, human Na(v)1.3 formed channels that inactivated rapidly (tau(inactivation) approximately equals 0.5 ms at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using an intracellular solution with aspartate as the main anion, the midpoint for channel activation was approximately -12 mV. The midpoint for inactivation, determined using 100-ms conditioning pulses, was approximately -47 mV. The time constant for repriming of inactivated channels at -80 mV was approximately 6 ms. Coexpression of beta1 or beta3 did not affect inactivation time course or the voltage dependence of activation, but shifted the inactivation curve approximately 10 mV negative, and slowed the repriming rate ca. three-fold. beta2 did not affect channel properties, either by itself or in combination with beta1 or beta3. Na(v)1.3 expression is increased in damaged nociceptive peripheral afferents. This change in channel expression levels is correlated with the emergence of a rapidly inactivating and rapidly repriming sodium current, which has been proposed to contribute to the pathophysiology of neuropathic pain. The results of this study support the hypothesis that Na(v)1.3 may mediate this fast sodium current.

Asymmetric interactions in the adenosine-binding pockets of the MS2 coat protein dimer.

BACKGROUND: The X-ray structure of the MS2 coat protein-operator RNA complex reveals the existence of quasi-synmetric interactions of adenosines -4 and -10 in pockets formed on different subunits of the coat protein dimer. Both pockets utilize the same five amino acid residues, namely Val29, Thr45, Ser47, Thr59, and Lys61. We call these sites the adenosine-binding pockets. RESULTS: We present here a heterodimer complementation analysis of the contributions of individual A-pocket amino acids to the binding of A-4 and A-10 in different halves of the dimer. Various substitutions of A-pocket residues were introduced into one half of single-chain coat protein heterodimers where they were tested for their abilities to complement Y85H or T91I substitutions (defects in the A-4 and A-10 half-sites, respectively) present in the other dimer half. CONCLUSIONS: These experiments provide functional tests of interactions predicted from structural analyses, demonstrating the importance of certain amino acid-nucleotide contacts observed in the crystal structure, and showing that others make little or no contribution to the stability of the complex. In summary, Val29 and Lys61 form important stabilizing interactions with both A-4 and A-10. Meanwhile, Ser47 and Thr59 interact primarily with A-10. The important interactions with Thr45 are restricted to A-4.

Allelic diversity at the het-c locus in Neurospora tetrasperma confirms outcrossing in nature and reveals an evolutionary dilemma for pseudohomothallic ascomycetes.

Vegetative cells of the filamentous ascomycete Neurospora tetrasperma are typically heterokaryotic, possessing haploid nuclei of both A and a mating types. As a consequence, N. tetrasperma is self-fertile. This life cycle, referred to as pseudohomothallism, clearly derives from true heterothallism of the type exhibited by related species such as N. crassa. Occasional homokaryotic, single-mating-type (heterothallic) isolates occur; in the laboratory, such strains can be outcrossed. The potential for outcrossing in N. tetrasperma raises the question of how this organism avoids heterokaryon incompatibility. Heterokaryon incompatability in vegetatively growing fungi is controlled by multiple loci. Two strains must be identical at each het locus (11 in N. crassa) to form a stable heterokaryon. Prior to the present survey, it seemed plausible that N. tetrasperma avoids heterokaryon incompatibility by maintaining compatible allele combinations through continual selfing. A survey of het-c variation among wild-type isolates in this study demonstrated that N. tetrasperma outcrosses in nature and that such matings can result in incompatible combinations of het-c alleles. Whereas individual wild-type isolates are invariably homoallelic for het-c, closely related strains may possess functionally different het-c alleles, which predate the origin of N. tetrasperma. Therefore, pseudohomothallic ascomycetes such as N. tetrasperma face an apparent evolutionary dilemma: the benefits of outcrossing must be balanced against the fact that matings can produce unstable heterokaryons and disrupt the pseudohomothallic life cycle.

Outcome in infants with pulmonary atresia, intact ventricular septum, and right ventricle-dependent coronary circulation.

Management of all patients with pulmonary atresia, intact ventricular septum, and right ventricle-dependent coronary circulation (n = 12) with staged surgery directed toward a Fontan palliation resulted in an 83% 5-year actuarial survival. Both deaths in the study were presumably related to coronary ischemia and occurred in the first 4 months of life.

Recognition of structurally diverse substrates by type II 3-hydroxyacyl-CoA dehydrogenase (HADH II)/amyloid-beta binding alcohol dehydrogenase (ABAD).

Human type II hydroxyacyl-CoA dehydrogenase/amyloid-beta binding alcohol dehydrogenase (HADH II/ABAD) is an oxidoreductase whose salient features include broad substrate specificity, encompassing 3-hydroxyacyl-CoA derivatives, hydroxysteroids, alcohols and beta-hydroxybutyrate, and the capacity to bind amyloid-beta peptide, leading to propagation of amyloid-induced cell stress. In this study, we examine the structure and enzymatic activity of the homologous rat HADH II/ABAD enzyme. We report the crystal structure of rat HADH II/ABAD as a binary complex with its NADH cofactor to 2.0 A resolution, as a ternary complex with NAD(+) and 3-ketobutyrate (acetoacetate) to 1.4 A resolution, and as a ternary complex with NADH and 17 beta-estradiol to 1.7 A resolution. This first crystal structure of an HADH II confirms these enzymes are closely related to the short-chain hydroxysteroid dehydrogenases and differ substantially from the classic, type I 3-hydroxyacyl-CoA dehydrogenases. Binding of the ketobutyrate substrate is accompanied by closure of the active site specificity loop, whereas the steroid substrate does not appear to require closure for binding. Despite the different chemical nature of the two bound substrates, the presentation of chemical groups within the active site of each complex is remarkably similar, allowing a general mechanism for catalytic activity to be proposed. There is a characteristic extension to the active site that is likely to accommodate the CoA moiety of 3-hydroxyacyl-CoA substrates. Rat HADH II/ABAD also binds amyloid-beta (1-40) peptide with a K(D) of 21 nM, which is similar to the interaction exhibited between this peptide and human HADH II/ABAD. These studies provide the first structural insights into HADH II/ABAD interaction with its substrates, and indicate the relevance of the rodent enzyme and associated rodent models for analysis of HADH II/ABAD's physiologic and pathophysiologic properties.

Coronary echocardiography in tetralogy of fallot: diagnostic accuracy, resource utilization and surgical implications over 13 years.

OBJECTIVES: This study sought to determine the diagnostic accuracy and impact of the systematic use of coronary echocardiography in a large group of preoperative patients with tetralogy of Fallot (TOF). BACKGROUND: Accurate preoperative identification of an anomalous coronary artery crossing the right ventricular outflow tract (RVOT) in patients with TOF is important to prevent coronary injury during surgical repair. METHODS: A retrospective review identified 598 patients with TOF between 1983 to 1995 who underwent an echocardiogram at <2 years old before complete surgical repair. Associated diagnoses included pulmonary stenosis (n = 433), pulmonary atresia (n = 121), common atrioventricular canal (n = 17), absent pulmonary valve syndrome (n = 24) and aortopulmonary window (n = 3). RESULTS: Based on intraoperative findings, 32 patients (5.4%) were found to have a major coronary artery crossing the RVOT. The use and diagnostic performance of coronary echocardiography increased over time, while the number of patients undergoing preoperative cardiac catheterization declined. During the most recent study period (1991 to 1995, n = 274), 97% of patients underwent coronary echocardiography yielding a sensitivity of 82%, specificity of 99% and accuracy of 98.5%. Of the 18 patients with TOF and pulmonary stenosis who had abnormal coronary arteries during this period, only 6 (33%) required an extracardiac conduit as part of their complete repair. CONCLUSIONS: Coronary echocardiography is an accurate noninvasive tool to delineate coronary anatomy in infants with TOF before complete repair. Routine preoperative cardiac catheterization solely for diagnosis of coronary anatomy is not necessary. The use of an extracardiac conduit can be avoided in the majority of patients with TOF and pulmonary stenosis who have a major coronary artery crossing the RVOT.

3D-shaded surface rendering of gadolinium-enhanced MR angiography in congenital heart disease.

BACKGROUND: Gadolinium-enhanced three-dimensional (3D) MR angiography is a useful imaging technique for patients with congenital heart disease. OBJECTIVE: This study sought to determine the added value of creating 3D shaded surface displays compared to standard maximal intensity projection (MIP) and multiplanar reformatting (MPR) techniques when analyzing 3D MR angiography data. MATERIALS AND METHODS: Seventeen patients (range, 3 months to 51 years old) with a variety of congenital cardiovascular defects underwent gadolinium-enhanced 3D MR angiography of the thorax. Color-coded 3D shaded surface models were rendered from the image data using manual segmentation and computer-based algorithms. Models could be rotated, translocated, or zoomed interactively by the viewer. Information available from the 3D models was compared to analysis based on viewing standard MIP/ MPR displays. RESULTS: Median postprocessing time for the 3D models was 6 h (range, 3-25 h) compared to approximately 20 min for MIP/MPR viewing. No additional diagnostic information was gained from 3D model analysis. All major findings with MIP/MPR postprocessing were also apparent on the 3D models. Qualitatively, the 3D models were more easily interpreted and enabled adjacent vessels to be distinguished more readily. CONCLUSION: Routine use of 3D shaded surface reconstructions for visualization of contrast enhanced MR angiography in congenital heart disease cannot be recommended. 3D surface rendering may be more useful for presenting complex anatomy to an audience unfamiliar with congenital heart disease and as an educational tool.

Distribution of voltage-gated sodium channel alpha-subunit and beta-subunit mRNAs in human hippocampal formation, cortex, and cerebellum.

The distribution of mRNAs encoding voltage-gated sodium channel alpha subunits (I, II, III, and VI) and beta subunits (beta1 and beta2) was studied in selected regions of the human brain by Northern blot and in situ hybridisation experiments. Northern blot analysis showed that all regions studied exhibited heterogenous expression of sodium channel transcripts. In situ hybridisation experiments confirmed these findings and revealed a predominantly neuronal distribution. In the parahippocampal gyrus, subtypes II and VI and the beta-subunit mRNAs exhibited robust expression in the granule cells of the dentate gyrus and pyramidal cell layer of the hippocampus. Subtypes I and III showed moderate expression in granule cells and low expression in the pyramidal cell layer. Distinct expression patterns were also observed in the cortical layers of the middle frontal gyrus and in the entorhinal cortex. In particular, all subtypes exhibited higher levels of expression in cortical layers III, V, and VI compared with layers I and II. All subtypes were expressed in the granular layer of the cerebellum, whereas specific expression of subtypes I, VI, beta1, and beta2 mRNAs was observed in Purkinje cells. Subtypes I, VI, and beta1 mRNAs were expressed, at varying levels, in the pyramidal cells of the deep cerebellar nuclei. These data indicate that, as in rat, human brain sodium channel mRNAs have a distinct regional distribution, with individual cell types expressing different compliments of sodium channels. The differential distribution of sodium channel subtypes suggest that they have distinct roles that are likely to be of paramount importance in maintaining the functional heterogeneity of central nervous system neurons.

Phase-velocity cine magnetic resonance imaging measurement of pulsatile blood flow in children and young adults: in vitro and in vivo validation.

Quantification of blood flow in vessels provides valuable information that aids management decisions in a variety of cardiac conditions. Current flow measurement techniques are often limited by accuracy, time resolution, convenience, or anatomic localization. This study examined the accuracy of a commercially available phase-velocity cine magnetic resonance imaging (PVC MRI) technique to quantify flow rate in a pulsatile flow phantom. In addition, the equivalence of PVC MRI measurements of pulmonary and systemic flow was evaluated in children and adults without any pathologic shunt. Using a pulsatile flow phantom, volume flow rates measured by PVC MRI were compared to those by a transit-time ultrasound flowmeter over a range of flow rates (1.25-3.5 L/min, 13 trials). Close agreement was found between these techniques (y = 1.02x - 0.02, r = 0.99, Bland-Altman bias = -0.045 L/min, 95% limits of agreement = -0. 19-0.10 L/min). Twenty subjects (median age 12.8 years, range 0.7-49 years) with no pathologic shunt underwent PVC MRI measurement of blood flow in the main pulmonary artery (Q(p)) and the ascending aorta (Q(s)). Data processing time for each location was 20 minutes. The Q(p)/Q(s) ratio closely approximated unity (mean = 0.99, SD = 0. 10, range 0.85-1.19). Interobserver agreement was excellent (Bland-Altman bias = 0.09 L/min, 95% limits of agreement = 0.15-0.33 L/min). PVC MRI is an accurate technique to quantify pulsatile blood flow at a specific location. It can be used to noninvasively calculate Q(p) and Q(s) under normal flow conditions.

Blood flow measurement by magnetic resonance imaging in congenital heart disease.

Investigation of blood flow in the heart and vessels may provide insight into the function of the cardiovascular system and aid patient management decisions. Phase velocity cine magnetic resonance imaging (PVC MRI) is a powerful and accurate noninvasive technique to quantitate and analyze blood flow. This article describes the principles, performance, and potential limitations of PVC MRI measurements. Clinical applications of PVC MRI are then reviewed with an emphasis on the assessment of congenital heart disease.