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Succinate dehydrogenase (SDH) is a crucial metabolic enzyme complex that is involved in ATP production, playing roles in both the tricarboxylic cycle and the mitochondrial respiratory chain (complex II). Isolated complex II deficiency is one of the rarest oxidative phosphorylation disorders with mutations described in three structural subunits and one of the assembly factors; just one case is attributed to recessively inherited SDHD mutations. We report the pathological, biochemical, histochemical and molecular genetic investigations of a male neonate who had left ventricular hypertrophy detected on antenatal scan and died on day one of life. Subsequent postmortem examination confirmed hypertrophic cardiomyopathy with left ventricular non-compaction. Biochemical analysis of his skeletal muscle biopsy revealed evidence of a severe isolated complex II deficiency and candidate gene sequencing revealed a novel homozygous c.275A>G, p.(Asp92Gly) SDHD mutation which was shown to be recessively inherited through segregation studies. The affected amino acid has been reported as a Dutch founder mutation p.(Asp92Tyr) in families with hereditary head and neck paraganglioma. By introducing both mutations into Saccharomyces cerevisiae, we were able to confirm that the p.(Asp92Gly) mutation causes a more severe oxidative growth phenotype than the p.(Asp92Tyr) mutant, and provides functional evidence to support the pathogenicity of the patient's SDHD mutation. This is only the second case of mitochondrial complex II deficiency due to inherited SDHD mutations and highlights the importance of sequencing all SDH genes in patients with biochemical and histochemical evidence of isolated mitochondrial complex II deficiency.

We report a baby girl with an antenatal diagnosis of biventricular non-compaction and complete heart block detected at 22 weeks' gestation. Postnatal echocardiography confirmed severe biventricular non-compaction hypertrophic cardiomyopathy, multiple muscular ventricular septal defects, and mild-moderate pulmonary valve stenosis. Skeletal muscle biopsy confirmed complex 1 mitochondrial respiratory chain deficiency. An epicardial VVI pacemaker was implanted on day 3 of life and revised at 7 years of age. She remains stable at 8 years of age following pacing and medical treatment with carvedilol, aspirin, co-enzyme Q10, and carnitine. This represents the first report of biventricular non-compaction hypertrophic phenotype in association with congenital complete heart block and complex 1 mitochondrial respiratory chain deficiency in a child.

Objective: The aim of this study is to document the detection of fetal congenital heart defect (CHD) in relation to the following: (1) indication for referral, (2) chromosomal and (3) extracardiac abnormalities., Method: All fetal echocardiograms performed in our institution from 2007 to 2011 were reviewed retrospectively. Indication for referral, cardiac diagnosis based on the World Health Organization International Classification of Diseases tenth revision criteria and the presence of chromosomal and extracardiac defects were recorded., Results: Of 1262 echocardiograms, 287 (22.7%) had CHD. Abnormal anatomy scan in pregnancies originally considered to be at low risk of CHD was the best indicator for detecting CHD (91.2% of positive cardiac diagnoses), compared with other indications of family history (5.6%) or maternal medical disorder (3.1%). Congenital anomalies of the cardiac septa comprised the largest category (n = 89), within which atrioventricular septal defects were the most common anomaly (n = 36). Invasive prenatal testing was performed for 126 of 287 cases, of which 44% (n = 55) had a chromosomal abnormality. Of 232 fetuses without chromosomal abnormalities, 31% had an extracardiac defect (n = 76)., Conclusions: Most CHDs occur in pregnancies regarded to be at low risk, highlighting the importance of a routine midtrimester fetal anatomy scan. Frequent association of fetal CHD and chromosomal and extracardiac pathology emphasises the importance of thorough evaluation of any fetus with CHD., (© 2015 John Wiley & Sons, Ltd.)

Objectives: Prostate cancer staging MR examinations commonly include abdominal sequences to assess for non-regional (common iliac or para-aortic) nodal metastasis. In our experience the diagnostic yield of this is limited, but incidental findings are frequent, often necessitating further investigations. The aim of this study is to assess the diagnostic utility of abdominal sequences in routine prostate cancer MR staging studies., Methods: Findings on abdominal sequences of consecutive MRI prostate studies performed for staging newly diagnosed prostate cancer between September 2011 and September 2013 were reviewed with respect to adenopathy and additional incidental findings. Results were correlated with Gleason grade and serum prostate-specific antigen (PSA) level in each case., Results: 355 MRI prostate examinations were reviewed. 4 (1.1%) showed enlarged non-regional lymph nodes. Incidental findings were found in 82(23.1%) cases, neccessitating further investigation in 45 (12.7%) cases. Enlarged non-regional nodes were associated with higher PSA level and Gleason grade (p=0.007, p=0.005 respectively). With a combined threshold of PSA > 20 ng/mL and/or Gleason grade ≥ 8 the sensitivity, specificity, PPV and NPV were 100, 60, 3 and 100% respectively for predicting the presence of non-regional adenopathy., Conclusions: Routine abdominal sequences are of very low yield in routine prostate cancer MR staging, frequently resulting in incidental findings requiring further work-up and should be reserved for high-risk cases. Our experience supports the use of an abdominal staging sequence in high-risk cases only., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: No data are available for the outcome of children undergoing cardiac transplantation with shared care programs in different countries. We sought to investigate the outcome of a shared care transplant program between 2 countries given the complex immunologic, cardiac, and psychologic needs of these young people., Methods: We investigated the results of a shared care program for children who underwent cardiac transplantation between our center in the Republic of Ireland and 2 centers in the United Kingdom over 2 decades., Results: Between 1990 and 2013, 22 patients underwent 23 cardiac transplants. The median age at transplant was 3.2 years (range, 0.3-13.3 years), median age at listing was 30 months (range, 0.1-13.3 years), and the median waiting list time was 2.8 months (range, 0.3-14 months). The median time to return to the referral center from the time of transplant was 3 weeks (range, 2-8 weeks). The referral center treated 4 of 5 late rejection episodes. Angiography was undertaken in the transplant center at annual or biannual review. Outcomes for rejection, coronary vasculopathy, and survival were comparable between the referral and transplant centers., Conclusions: This report of shared care for pediatric transplant patients between 2 sovereign nations demonstrates good results, with comparable outcomes to the specialist transplant center. These data may encourage liberalization of follow-up in other centers., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We describe a 6-year-old male, diagnosed at birth with double outlet right ventricle (DORV), anterior aorta, multiple ventricular septal defects, pulmonary stenosis, microcephaly and mildly dysmorphic craniofacial findings. Chromosomal analysis showed a normal male karyotype but on subsequent array comparative genomic hybridization (array CGH) analysis a de novo 2.5 Mb loss in chromosome 13q at 13q33.3q34, together with an inherited gain at 4p12, were detected. The propositus underwent placement of a Blalock Taussig shunt and subsequently a Glenn and Fontan operation was performed. In this report we propose that COL4A1 and COL4A2 may be candidate genes for congenital heart disease (CHD) in individuals with a deletion in 13q within the 6Mb critical region for cardiac development proposed by Huang et al., [2012]., (© 2015 Wiley Periodicals, Inc.)

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in the white population. Mutation of the CF transmembrane conductance regulator gene on chromosome 7 results in production of abnormally viscous mucus and secretions in the lungs of patients with CF. A similar pathologic process occurs in the gastrointestinal tract, pancreas, and hepatobiliary system. Inspissated mucus causes luminal obstruction and resultant clinical and radiologic complications associated with the disease process. Pancreatic involvement can result in exocrine and endocrine insufficiency, pancreatic atrophy, fatty replacement, or lipomatous pseudohypertrophy. Acute and chronic pancreatitis, pancreatic calcification, cysts, and cystosis also occur. Hepatic manifestations include hepatic steatosis, focal biliary and multilobular cirrhosis, and portal hypertension. Biliary complications include cholelithiasis, microgallbladder, and sclerosing cholangitis. The entire digestive tract can be involved. Distal ileal obstruction syndrome, intussusception, appendicitis, chronic constipation, colonic wall thickening, fibrosing colonopathy, pneumatosis intestinalis, gastroesophageal reflux, and peptic ulcer disease have been described. Renal manifestations include nephrolithiasis and secondary amyloidosis. The educational objectives of this review are to reveal the abdominal manifestations of CF to facilitate focused analysis of cross-sectional imaging in adult patients. Life expectancy in patients with CF continues to improve because of a combination of aggressive antibiotic treatment, improved emphasis on nutrition and physiotherapy, and development of promising new CF transmembrane conductance regulator modulators. As lung function and survival improve, extrapulmonary conditions, including hepatic and gastrointestinal malignancy, will be an increasing cause of morbidity and mortality. Awareness of the expected abdominal manifestations of CF may assist radiologists in identifying acute inflammatory or neoplastic conditions. (©)RSNA, 2015.

We report a 23-month old girl who presented with bilateral epiphora who underwent bilateral lacrimal probing and syringing, during which a cocaine adrenaline solution was used. Two hours after the procedure she developed acute pulmonary oedema secondary to myocardial ischaemia. The patient was treated with intravenous glyceryltrinitrate and milrinone infusions; cardiac enzymes and left ventricular function normalised over the subsequent 72 hours. Topical administration of cocaine and adrenaline solution may have dangerous systemic cardiac effects and should always be used judiciously.

A two-year-old boy with a background history of Down syndrome and partial atrioventricular septal defect presented with acute respiratory distress requiring intubation and mechanical ventilation. He continued to deteriorate, despite ventilation; direct laryngoscopy, bronchoscopy, and computed tomography demonstrated severe long segment tracheal stenosis. He was placed on extracorporeal membrane oxygenation to stabilise his condition. A slide tracheoplasty and complete repair of the partial atrioventricular septal defect was successfully undertaken. His post-operative recovery was complicated by myocardial infarction and stroke but he made a full recovery. This represents the first report of slide tracheoplasty and partial atrioventricular septal defect repair in a child following extracorporeal membrane oxygenation support.

We describe a case of an 11-year-old boy who underwent orthotopic heart transplant for dilated cardiomyopathy. He developed a normocytic, normochromic anaemia with a low reticulocyte count 1 month after transplant. A bone marrow biopsy was performed, which showed a mildly hypocellular bone marrow with few red blood cell precursors with giant pro-erythroblasts indicative of a pure red cell aplasia. Parvovirus B19 polymerase chain reaction in the blood was positive 2 months after transplant. Intravenous immunoglobulin administration resulted in a resolution of the anaemia over several months. Unexplained pure red cell aplasia in immunosuppressed patients should alert one to the possibility of parvovirus B19 infection.

We describe a case of a baby girl born with hypoplastic left heart syndrome consisting of mitral atresia, aortic atresia, hypoplastic ascending aorta, and left ventricle. The pulmonary arteries were hypoplastic, measuring 3 mm. Fluorescence in situ hybridisation analysis demonstrated a microduplication of chromosome 22q11.2. Subsequent array comparative genomic hybridisation showed a gain of 2.3 Mb in one copy of chromosome 22q at band 22q11.21. The proband underwent a successful Norwood procedure with Sano shunt and subsequently underwent bi-directional Glenn shunt and Fontan procedure. This report highlights the association between hypoplastic left heart syndrome with hypoplastic pulmonary arteries and chromosome 22q11.21 microduplication.

Objective: To determine the mode of delivery in pregnancies complicated by complex fetal congenital heart disease (CHD)., Study Design: Five-year retrospective cohort study at a tertiary fetal medicine center (2007 to 2011). Cases of complex fetal CHD (n=126) were compared with 45 069 non-anomalous singleton infants ⩾500 g to determine rates of emergency intrapartum cesarean section (CS), preterm delivery and induction of labor., Result: Intrapartum CS is significantly higher in fetal CHD than non-anomalous controls (21% vs 13.5%, odds ratio (OR) 1.7, 95% confidence interval (CI): 1.0 to 2.7; P=0.035), predominantly related to CS for non-reassuring fetal status (OR 2.2, 95% CI: 1.1 to 4.1; P=0.022). Although fetal CHD did not increase emergency CS rates in nulliparous women, CS was significantly increased in multiparous pregnancies (OR 2.4, 95% CI: 1.8 to 4.6; P=0.014). Rates of preterm delivery (OR 3.4, 95% CI: 2.0 to 5.4; P<0.0001) and induction of labor (OR 1.9, 95% CI: 1.3 to 2.9; P=0.001) were higher in the CHD cases., Conclusion: Emergency CS is increased in fetal CHD, attributed to a higher rate of CS for non-reassuring fetal status and seen mostly in multiparous women.

We describe two children, each with a univentricular circulation who had evidence of elevated pulmonary arterial pressure at cardiac catheterization. Both children developed extensive coronary arterial fistulae detected at cardiac catherization. Each child was medically treated with a combination of phosphodiesterase-5 inhibitor and endothelin antagonist pulmonary vasodilators. The presence of chronic hypoxaemia, elevated filling pressures, and the use of pulmonary vasodilators may contribute to coronary endothelial dysfunction, which may result in coronary vasculopathy. This may necessitate early referral for orthotopic cardiac transplantation. © 2013 Wiley Periodicals, Inc., (© 2013 Wiley Periodicals, Inc.)

The neonatal presentation of cardiac rhabdomyomas varies in severity from severe outflow tract obstruction to minimal cardiac dysfunction. The natural history for these lesions is spontaneous regression in the majority of cases. We describe a newborn boy with severe left ventricular outflow tract obstruction secondary to a large rhabdomyoma. The tumor infiltrated the paraaortic area and extended around the origin of the right coronary artery, making surgical resection challenging. Oral sirolimus therapy resulted in a rapid regression of the tumor and alleviation of outflow tract obstruction within 1 month of treatment. This is the first report of sirolimus therapy in alleviating critical left ventricular outflow tract obstruction in this condition., (Copyright © 2014 by the American Academy of Pediatrics.)

A newborn baby girl was diagnosed with tricuspid atresia, ventricular septal defect, normally related great vessels, and hypoplastic right ventricle with no pulmonary stenosis. There was extensive left ventricular noncompaction cardiomyopathy. The left ventricular ejection fraction was 58%. She underwent placement of a pulmonary arterial band at 4 weeks of age, a bilateral bidirectional Glenn at 10 months of age, and fenestrated extracardiac total cavopulmonary connection at 3 years of age. The presence of left ventricular noncompaction in a patient with univentricular circulation does not necessarily circumvent successful cavopulmonary palliation, when left ventricular function is relatively preserved, as in this patient., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The increasing utilisation of decompressive craniectomy for traumatic brain injury and stroke has led to an increase in the number of cranioplasties undertaken. Cranioplasty is also undertaken following excision of tumours originating from or invading the skull vault, removal of bone flaps due to post-operative infection, and decompressive craniectomy for the management of rarer causes of brain oedema and/or refractory intracranial hypertension. The existing literature which mainly consists of single-centre, retrospective studies, shows a significant variation in practice patterns and a wide range of morbidity. There also exists a need to measure the outcome as perceived by the patients themselves with patient reported outcome measures (PROMs; functional outcome, quality of life, satisfaction with cosmesis). In the UK, the concept of long-term surveillance of neurosurgical implants is well established with the UK shunt registry. Based on this background, we propose to establish the UK Cranial Reconstruction Registry (UKCRR)., Aim: The overarching aim of the UKCRR is to collect high-quality data about cranioplasties undertaken across the UK and Ireland in order to improve outcomes for patients., Methods: Any patient undergoing reconstruction of the skull vault with autologous bone, titanium, or synthetic material in participating units will be eligible for inclusion. Data will be submitted directly by participating units to the Outcome Registry Intervention and Operation Network secure platform. A Steering Committee will be responsible for overseeing the strategic direction and running of the UKCRR., Outcome Measures: These will include re-operation due to a cranioplasty-related issue, surgical site infection, re-admission due to a cranioplasty-related issue, unplanned post-operative escalation of care, adverse events, length of stay in admitting unit, destination at discharge from admitting unit, mortality at discharge from admitting unit, neurological status and PROMs during routine follow-up., Conclusion: The UKCRR will be an important pillar in the ongoing efforts to optimise the outcomes of patients undergoing cranioplasty.

Aim: To determine the incidence of missed femoral head avascular necrosis (AVN) on pelvic computed tomography (CT) performed for clinical indications other than assessment for AVN., Materials and Methods: The study was a Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study. The picture archiving and communication system (PACS) database was queried for patients with diagnosis of femoral head AVN on magnetic resonance imaging (MRI), who also underwent pelvic multidetector CT after or <30 days before the MRI examination. The MRI and CT images of 144 hips of 72 patients (39 patients with reported AVN on MRI and 33 age-matched controls; mean age = 60 years, 28 male, 44 female), were reviewed in consensus by two readers in a randomized, blinded manner. Using MRI-proven CT-visible AVN as a reference standard, the incidence of missed AVN on initial CT interpretation was determined., Results: Readers confirmed AVN in 33 patients on the MRI images. Nine hips with AVN underwent joint replacement of the affected joint(s) prior to subsequent CT and were excluded. Forty-three MRI-proven AVN cases in 28 patients (15 bilateral, 13 unilateral) were available for analysis. The study readers diagnosed 35/43 (81%) MRI-proven AVN cases in 22/28 (79%) patients. Four of the 35 (11%) cases of MRI-proven, CT-visible AVN were prospectively reported in 3/22 (14%) patients at initial clinical interpretation, with a miss rate of 89% per hip and 86% per patient., Conclusion: Multidetector CT has high accuracy for detection of AVN; however, this is frequently missed as an incidental finding (89% missed in the present study). Assessment for signs of femoral AVN should be part of routine search pattern in interpretation of pelvic CT., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

A newborn baby girl was diagnosed with tetralogy of Fallot and an aortopulmonary window. At 3 weeks of age, the coexistent diagnosis of an anomalous left coronary artery from the pulmonary artery was made. Initial surgical intervention included a Takeuchi baffle of the left coronary artery, closure of the aortopulmonary window, and placement of a right Blalock-Taussig shunt. Complete repair was undertaken at 12 months of age. Close pre-operative assessment of the coronary arterial anomaly is crucial in patients with an aortopulmonary window and tetralogy of Fallot.

A baby boy, the first of triplets born at 33 weeks gestation weighing 1.88 kg, presented with neonatal cyanosis and was diagnosed with mitral atresia, hypoplastic left ventricle, ventricular septal defect, d-transposition of the great arteries, severe pulmonary stenosis, and hypoplastic branch pulmonary arteries. He was treated with prostaglandin until seven weeks of age. The patent ductus arteriosus was curly Q and not suitable for stent placement. Cardiac catheterization was undertaken and using an antegrade approach, a Multi-Link Ultra stent was implanted across the left ventricular outflow tract (LVOT) and inflated to 5 mm to improve antegrade pulmonary blood flow. This allowed reasonable pulmonary arterial growth to allow the patient undergo bidirectional Glenn shunt at five months of age. This first report of LVOT stenting in this setting may provide an alternative to placement of a systemic to pulmonary arterial shunt when ductal stenting is not possible., (Copyright © 2013 Wiley Periodicals, Inc.)

A male infant was born at 28 weeks gestation weighing 850 g. He was diagnosed with pulmonary atresia, ventricular septal defect and major aorto-pulmonary collaterals with severely hypoplastic true pulmonary arteries. A 3.5 mm Gore-Tex central shunt was anastomosed from the ascending aorta to the main pulmonary artery at 4 months of age and a weight of 3.5 kg. The left pulmonary artery measured 1-2 mm and the right pulmonary artery measured 1 mm. His saturations increased from 70% to 85% following placement of the central shunt. At 16 months of age, his oxygen saturation decreased to 68%. Cardiac catheterization, using a retrograde approach, and angiography demonstrated a moderate degree of stenosis within the distal shunt and a severe left pulmonary arterial stenosis. A 4 x 18 mm Multi-Link Vision coronary stent was implanted within the stenotic central shunt and angioplasty of the left pulmonary arterial stenosis was performed. The oxygen saturation improved to 84% after the procedure. Although stenting of the Blalock-Taussig shunt has been described previously, this represents one of the first reports of stenting of a central aortopulmonary shunt. This significantly improved the patient's oxygen saturation and allowed the potential for some further central pulmonary arterial growth prior to unifocalization procedure.

We described a 5-week-old boy with dextrocardia, double outlet right ventricle, and severe pulmonary stenosis with pentalogy of Cantrell. There was a defect within the sternum, diaphragm, and a prominent left ventricular diverticulum. Hypercyanotic spells developed with desaturation to 50%. Two Vision coronary stents were implanted in the right ventricular outflow tract with a significant improvement in oxygen saturation to 85%. This represents the first report of transcatheter pulmonary stent implantation as a form of palliation in a child with pentalogy of Cantrell., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The mechanism of development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. Inflammatory processes are implicated in the development of ischemic stroke and may also predispose to the development of DCI following SAH. The objective of this study was to test whether concentrations of circulating inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin 1 receptor antagonist (IL-1Ra)) were predictive for DCI following SAH. Secondary analyses considered white cell count (WCC) and erythrocyte sedimentation rate (ESR)., Methods: This was a single-center case-control study nested within a prospective cohort. Plasma inflammatory markers were measured in patients up to 15 days after SAH (initial, peak, average, final and rate of change to final). Cases were defined as those developing DCI. Inflammatory markers were compared between cases and randomly selected matched controls., Results: Among the 179 participants there were 46 cases of DCI (26%). In primary analyses the rate of change of IL-6 was associated with DCI (OR 2.3 (95% CI 1.1 to 5.0); p=0.03). The final value and rate of change of WCC were associated with DCI (OR 1.2 (95% CI 1.0 to 1.3) and OR 1.3 (95% CI 1.0 to 1.6), respectively). High values of ESR were associated with DCI (OR 2.4 (95% CI 1.3 to 4.6) initial; OR 2.3 (95% CI 1.3 to 4.2) average; OR 2.1 (95% CI 1.1 to 3.9) peak; and OR 2.0 (95% CI 1.2 to 3.3) final value)., Conclusions: Leucocytosis and change in IL-6 prior to DCI reflect impending cerebral ischemia. The time-independent association of ESR with DCI after SAH may identify this as a risk factor. These data suggest that systemic inflammatory mechanisms may increase the susceptibility to the development of DCI after SAH.

A 13-year-old boy presented with severe systemic hypertension. His upper limb blood pressure measured 190/100 mm Hg and lower limb blood pressure measured 98/64 mm Hg. The brachial pulses were bounding and femoral pulses were not palpable. Echocardiography and magnetic resonance angiography confirmed middle aortic syndrome. There was severe diffuse thoraco-abdominal coarctation with continuous Doppler run-off. Cardiac catheterization was undertaken and using a retrograde approach two Advanta V12 stents were implanted in the complex thoraco-abdominal coarctation. The gradient across the coarctation was reduced from 80 to 40 mm Hg gradient with a significant improvement in the luminal diameter of the aorta. His upper limb blood pressure reduced to 142/78 mm Hg six weeks later., (Copyright © 2013 Wiley Periodicals, Inc.)

We present the case of a 6-year-old child who presented with an episode of life threatening hemoptysis. Investigations revealed multiple areas of endobronchial varices and abnormal pleural vessels as well as severe left pulmonary vein stenosis and an atrial septal defect (ASD). After extensive work up and consultation he underwent repair of the left pulmonary vein using a sutureless technique and ASD closure. This resulted in a marked improvement in the appearances of the left lung. The bronchial varices in the right lung remain unchanged. No further hemoptysis has occurred and the child continues to be monitored., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Cytokines and cytokine receptor concentrations increase in plasma and cerebrospinal fluid (CSF) of patients following subarachnoid haemorrhage (SAH). The relationship between plasma and CSF cytokines, and factors affecting this, are not clear., Methods: To help define the relationship, paired plasma and cerebrospinal fluid (CSF) samples were collected from patients subject to ventriculostomy. Concentrations of key inflammatory cytokines, interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor 2, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and TNF receptors (TNF-R) 1 and 2 were determined by immunoassay of CSF and plasma from 21 patients, where samples were available at three or more time points., Results: Plasma concentrations of IL-1ß, IL-1Ra, IL-10, TNF-α and TNF-R1 were similar to those in CSF. Plasma TNF-R2 and IL-1R2 concentrations were higher than in CSF. Concentrations of IL-8 and IL-6 in CSF were approximately10 to 1,000-fold higher than in plasma. There was a weak correlation between CSF and plasma IL-8 concentrations (r = 0.26), but no correlation for IL-6. Differences between the central and peripheral pattern of IL-6 were associated with episodes of ventriculostomy-related infection (VRI). A VRI was associated with CSF IL-6 >10,000 pg/mL (P = 0.0002), although peripheral infection was not significantly associated with plasma IL-6., Conclusions: These data suggest that plasma cytokine concentrations cannot be used to identify relative changes in the CSF, but that measurement of CSF IL-6 could provide a useful marker of VRI.

Purpose: To assess the feasibility of combining three-dimensional fast spin echo (3D-FSE) and Iterative-decomposition-of water-and-fat-with-echo asymmetry-and-least-squares-estimation (IDEAL) at 1.5 Tesla (T), generating a high-resolution 3D isotropic proton density-weighted image set with and without "fat-suppression" (FS) in a single acquisition, and to compare with 2D-FSE and 3D-FSE (without IDEAL)., Materials and Methods: Ten asymptomatic volunteers prospectively underwent sagittal 3D-FSE-IDEAL, 3D-FSE, and 2D-FSE sequences at 1.5T (slice thickness [ST]: 0.8 mm, 0.8 mm, and 3.5 mm, respectively). 3D-FSE and 2D-FSE were repeated with frequency-selective FS. Fluid, cartilage, and muscle signal-to-noise ratio (SNR) and fluid-cartilage contrast-to-noise ratio (CNR) were compared among sequences. Three blinded reviewers independently scored quality of menisci/cartilage depiction for all sequences. "Fat-suppression" was qualitatively scored and compared among sequences., Results: 3D-FSE-IDEAL fluid-cartilage CNR was higher than in 2D-FSE (P < 0.05), not different from 3D-FSE (P = 0.31). There was no significant difference in fluid SNR among sequences. 2D-FSE cartilage SNR was higher than in 3D FSE-IDEAL (P < 0.05), not different to 3D-FSE (P = 0.059). 2D-FSE muscle SNR was higher than in 3D-FSE-IDEAL (P < 0.05) and 3D-FSE (P < 0.05). Good or excellent depiction of menisci/cartilage was achieved using 3D-FSE-IDEAL in the acquired sagittal and reformatted planes. Excellent, homogeneous "fat-suppression" was achieved using 3D-FSE-IDEAL, superior to FS-3D-FSE and FS-2D-FSE (P < 0.05)., Conclusion: 3D FSE-IDEAL is a feasible approach to acquire multiplanar images of diagnostic quality, both with and without homogeneous "fat-suppression" from a single acquisition., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: To compare prostate gland volume (PV) estimation of automated computer-generated multifeature active shape models (MFAs) performed with 3-T magnetic resonance (MR) imaging with that of other methods of PV assessment, with pathologic specimens as the reference standard., Materials and Methods: All subjects provided written informed consent for this HIPAA-compliant and institutional review board-approved study. Freshly weighed prostatectomy specimens from 91 patients (mean age, 59 years; range, 42-84 years) served as the reference standard. PVs were manually calculated by two independent readers from MR images by using the standard ellipsoid formula. Planimetry PV was calculated from gland areas generated by two independent investigators by using manually drawn regions of interest. Computer-automated assessment of PV with an MFA was determined by the aggregate computer-calculated prostate area over the range of axial T2-weighted prostate MR images. Linear regression, linear mixed-effects models, concordance correlation coefficients, and Bland-Altman limits of agreement were used to compare volume estimation methods., Results: MFA-derived PVs had the best correlation with pathologic specimen PVs (slope, 0.888). Planimetry derived volumes produced slopes of 0.864 and 0.804 for two independent readers when compared with specimen PVs. Ellipsoid formula-derived PVs had slopes closest to one when compared with planimetry PVs. Manual MR imaging and MFA PV estimates had high concordance correlation coefficients with pathologic specimens., Conclusion: MFAs with axial T2-weighted MR imaging provided an automated and efficient tool with which to assess PV. Both MFAs and MR imaging planimetry require adjustments for optimized PV accuracy when compared with prostatectomy specimens., (© RSNA, 2012.)

Purpose: The primary purpose was to determine the prevalence of renal artery stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema (FPE), without identifiable cause using contrast-enhanced magnetic resonance angiography (CE-MRA) of renal arteries. A secondary goal was to correlate clinical parameters at presentation with the presence or absence of RAS., Materials and Methods: Patients presenting with acute pulmonary oedema without identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was considered significant. Clinical parameters (blood pressure, serum creatinine, history of hypertension/hyperlipidaemia) were compared in patients with and without RAS using an unpaired t-test. Results expressed; mean (+/-SD)., Results: 20 patients (4 male, 16 female, age 78.5+/-11 years) underwent CE-MRA. 9 patients (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP was higher in patients with RAS (192+/-38 mm Hg) than those without (134+/-30 mm Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+/-23 mm Hg) than those without (76+/-17 mm Hg) (p<.01). All patients with RAS and 6/11(55%) patients without RAS had a history of hypertension. No significant difference in creatinine or hyperlipidaemia history was observed., Conclusion: The prevalence of RAS in patients presenting with FPE is 45%. The diagnosis should be considered in patients presenting with unexplained acute pulmonary oedema, particularly if hypertensive at presentation., (Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication., Materials and Methods: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of 'elevated tumour marker' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated., Results: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: 'elevated tumour marker'. They underwent 29 imaging studies (mean [+/-standard deviation (SD)] per patient = 1.2 [+/-0.4]), and had 42 elevated tumour marker serology tests (mean [+/-SD] per patient = 1.7 [+/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker., Conclusion: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of 'elevated tumour marker'. 'Elevated tumour marker', in the absence of a known underlying malignancy, should not be considered an independent indication for imaging.

Magnetic resonance (MR) imaging is an important imaging technique in the evaluation of scrotal masses, providing a useful adjunct to ultrasonography (US). Although US is the modality of choice for initial evaluation of scrotal pathologic conditions because of its wide availability, low cost, and high sensitivity for detection of testicular and paratesticular disease processes, US findings may occasionally be inconclusive. MR imaging may provide additional information in these cases, often affecting patient management. This article reviews and illustrates the MR imaging features of solid extratesticular and intratesticular benign and malignant scrotal tumors, as well as nonneoplastic lesions that can mimic neoplasia. Normal scrotal MR anatomic features and optimal MR imaging technique are also presented.

The spread of pelvic tumors to lymph nodes is an important means of tumor dissemination. Nodal metastases have important management and prognostic impact. Pelvic tumors usually metastasize first to regional lymph nodes, which are specific groups of nodes for each tumor, and are classified according to the TNM system as N-stage disease. If a pelvic tumor spreads to a lymph node outside of the defined regional nodes, this is considered M-stage disease, which usually results in upstaging of the disease to overall stage IV cancer and may potentially affect the patient's treatment options. Knowledge of the regional nodal spread of each tumor is essential in formulating effective search strategies for cross-sectional imaging studies performed for staging. Also important is correct description of the nomenclature of nodal metastases to facilitate proper staging. In this review, the patterns of regional nodal spread and N-stage classification are presented for carcinomas of the anus, bladder, cervix, endometrium, ovary, penis, prostate, rectum, testis, vagina, and vulva. Pelvic lymph node anatomy and nomenclature are reviewed with schematic illustrations and clinical examples from patients with pelvic tumors.

Anomalous pancreaticobiliary junction is an unusual variant of pancreaticobiliary anatomy of clinical importance because it is associated with increased risk of pancreatitis and, also, for the development of cholangiocarcinoma. We report an unusual variant of anomalous pancreaticobiliary junction, occurring in a patient with pancreas divisum, with an anomalous communication between the dorsal pancreatic and the common bile duct. The patient presented with a distal biliary stricture. This variant anatomy was occult on magnetic resonance cholangiopancreatography but was diagnosed on magnetic resonance cholangiopancreatography that was performed with intravenous secretin administration and further delineated by endoscopic retrograde cholangiopancreatography. The features that allowed the diagnosis to be made and the implications of this diagnosis are described in this report.

Although single individual reports have documented outcomes in children with pentalogy of are few data available for postoperative outcome of this cohort of patients after cardiac surgery. The aim of this study was to retrospectively review the clinical details of patients with pentalogy of Cantrell managed at two centers. Two cardiac surgical institutions retrospectively studied all patients with pentalogy of Cantrell and significant congenital heart disease who underwent surgical intervention, excluding PDA ligation, between 1992 and 2004. Seven children with pentalogy of Cantrell underwent surgical intervention at a median age of 60 days (range, 1-11 months). Three patients had tetralogy of Fallot, two double outlet right ventricle, one patient had tricuspid atresia, and one patient a perimembranous ventricular septal defect. The mean duration of postoperative ventilation was 112.8 days (range, 4-335 days) but three patients required ventilation for more than 100 days. Patients who had a preoperative diaphragmatic plication required a longer duration of ventilation (mean = 186.5 days [range, 100-273 days] compared with mean = 132 days [range, 4-335 days]). Four patients survived, with three patients weaned from ventilation. Three patients had withdrawal of care following failure to wean from ventilation, following multisystem organ failure, and at the request of their parents. In conclusion, the postoperative care of children with pentalogy of Cantrell after cardiac surgery is often complicated by prolonged need for ventilatory support and multiple postoperative complications. Earlier surgical intervention does not necessarily reduce morbidity and mortality. These data may help in the counseling of parents prior to surgical intervention.

Prostate cancer is a common tumor among men, with increasing diagnosis at an earlier stage and a lower volume of disease because of screening with prostate-specific antigen (PSA). The need for imaging of the prostate stems from a desire to optimize treatment strategy on a patient and tumor-specific level. The major goals of prostate imaging are (1) staging of known cancer, (2) determination of tumor aggressiveness, (3) diagnosis of cancer in patients who have elevated PSA but a negative biopsy, (4) treatment planning, and (5) the evaluation of therapy response. This article concentrates on the role of dynamic contrast-enhanced MR imaging in the evaluation of patients who have prostate cancer and how it might be used to help achieve the above goals. Various dynamic contrast enhancement approaches (quantitative/semiquantitative/qualitative, high temporal versus high spatial resolution) are summarized with reference to the relevant strengths and compromises of each approach.

We describe a newborn boy diagnosed with Berry syndrome consisting of a distal aortopulmonary septal defect, aortic origin of the right pulmonary artery, and interruption of the aorta. The child was noted to have reduplication of the right thumb. The child's mother had a claw malformation of her left hand but a normal cardiovascular status. Genetic analysis for TBX5 and SALL4 mutations were negative in both the patient and his mother. This case describes the first ever report of Berry syndrome in an infant with reduplication of the right thumb and familial limb malformation.

A comprehensive overview of the current status of magnetic resonance imaging (MRI) in the locoregional assessment and management of rectal adenocarcinoma is presented. Staging systems for rectal cancer and treatment strategies in its management are discussed to give the reader the context that shapes MRI acquisition techniques and interpretation. Findings on MRI are detailed and their accuracy reviewed based on currently available evidence. Optimization of MRI acquisition and relevant pelvic anatomy are reviewed. A detailed description of our approach in interpreting MRI for locoregional staging of rectal cancer is given and future directions are also introduced.

Aims: Hypertrophic cardiomyopathy (HCM) is a disease with a heterogeneous clinical and morphological presentation. It can be secondary to mutations in genes encoding for sarcomeric and non-sarcomeric proteins. The pattern of ventricular hypertrophy can vary from isolated basal septal to concentric hypertrophy. We investigated if there are differences in regional myocardial function in different forms of HCM., Methods and Results: We performed echocardiograms on children with (i) isolated asymmetric septal HCM, (ii) isolated concentric HCM, (iii) Friedreich's ataxia associated with concentric HCM, and (iv) healthy controls. Wall thickness, left ventricular dimensions, ejection fraction, and mitral inflow were measured. Peak early diastolic myocardial velocities, peak systolic myocardial velocities, peak systolic strain rate (SR), peak systolic strain (epsilon), post-systolic shortening and time to maximal epsilon were measured in the basal and mid-septum and basal lateral wall to evaluate longitudinal myocardial function. Similar data were acquired and analysed in the anterior septum and infero-lateral wall to evaluate the radial myocardial function. All three groups with HCM had had increased wall thickness, reduced left ventricular dimensions, and evidence of impaired diastolic filling compared to controls. All forms of HCM had reduced early diastolic and systolic myocardial velocities and peak systolic SR and peak systolic epsilon compared with controls in all myocardial segments investigated. Children with asymmetric septal HCM had reduced systolic deformation, increased post-systolic shortening, and prolonged time to maximal epsilon in the basal septum compared with the other two groups with HCM. There were no differences in any echocardiographic variable between patients with isolated concentric HCM and Friedreich's ataxia and resulting HCM., Conclusion: Myocardial deformation is abnormal in all forms of paediatric HCM. Myocardial deformation is more reduced and associated with post-systolic shortening in the more hypertrophied basal septum in patients with asymmetric septal HCM. In contrast, this reduction is uniformly distributed in all myocardial segments in patients with concentric HCM irrespective of whether HCM results from isolated or secondary HCM. Our findings suggest the pattern of hypertrophy influences myocardial deformation more than the underlying cause of HCM.

This report describes the case of a child with Kabuki syndrome, hypoplastic left heart syndrome, and right-sided partial anomalous pulmonary venous drainage to the inferior vena cava. The child underwent successful Norwood and Glenn palliative procedures. At the age of 9 months, the genetic condition was recognized. This represents the first report describing this combination of findings for Kabuki syndrome.

Unlabelled: What is already known about this subject? The naturally occurring interlukin-1 receptor antagonist (IL-1RA) markedly protects rodents against ischaemic, excitotoxic and traumatic brain injury, suggesting it may be of therapeutic value. When administered intravenously to patients soon after stroke, IL-1RA is safe and reduces the peripheral inflammatory response. However, IL-1RA is a large protein (17 kDa), which may limit brain penetration, thereby limiting its potential utility in brain injury. What this study adds. The purpose of these experiments was to determine the pharmacokinetics of IL-1RA in cerebrospinal fluid (CSF) of patients, to allow modelling that would aid development of therapeutic regimens. Peripherally administered IL-1RA crosses slowly into and out of the CSF of patients with subarachnoid haemorrhage and, at steady state, CSF IL-1RA concentration (range 115-886 ng ml(-1)) was similar to that found to be neuroprotective in rats (range 91-232 ng ml(-1)), although there was considerable variability among patients. However, there is a large concentration gradient of IL-1RA between plasma and CSF. These CSF:plasma data are consistent with very low permeation of IL-1RA into the CSF and elimination kinetics from it controlled by the volumetric turnover of CSF., Aim: The naturally occurring interlukin-1 receptor antagonist (IL-1RA) markedly protects rodents against ischaemic, excitotoxic and traumatic brain injury, suggesting it may be of therapeutic value. The aim was to determine the pharmacokinetics of IL-1RA in cerebrospinal fluid (CSF) of patients, to allow modelling that would aid development of therapeutic regimens., Methods: When administered intravenously to patients soon after stroke, IL-1RA is safe and reduces the peripheral inflammatory response. However, IL-1RA is a large protein (17 kDa), which may limit brain penetration, thereby limiting its potential utility in brain injury. In seven patients with subarchnoid haemorrhage (SAH), IL-1RA was administered by intravenous bolus, then infusion for 24 h, and both blood and CSF, via external ventricular drains, were sampled during and after stopping the infusion., Results: Plasma steady-state concentrations were rapidly attained and maintained throughout the infusion, whereas CSF concentrations rose slowly towards a plateau during the 24-h infusion, reaching at best only 4% of that in plasma. Plasma kinetic parameters were within the literature range. Modelling of the combined data yielded rate constants entering and leaving the CSF of 0.0019 h(-1)[relative standard error (RSE) = 19%] and 0.1 h(-1) (RSE = 19%), respectively., Conclusions: Peripherally administered IL-1RA crosses slowly into and out of the CSF of patients with SAH. However, there is a large concentration gradient of IL-1RA between plasma and CSF. These CSF:plasma data are consistent with very low permeation of IL-1RA into the CSF and elimination kinetics from it controlled by the volumetric turnover of CSF.

The proinflammatory cytokine interleukin (IL)-1 mediates several forms of experimentally induced acute brain injury and has been implicated in chronic neurodegenerative disorders. The IL-1 receptor antagonist, IL-1RA, protects rodents against ischaemic brain injury, but its molecular mass (17 kDa) potentially limits the brain penetration of peripherally administered IL-1RA. We therefore sought to identify whether therapeutically effective concentrations of IL-1RA in the rat were also achieved in brain of patients with subarachnoid haemorrhage (SAH), using a peripheral administration regime that had proved to be safe and reduce peripheral inflammation in patients after stroke. An intravenous bolus of IL-1RA, followed by infusion, was administered to rats after induction of focal cerebral ischaemia. The effects of IL-1RA on brain ischaemia and the concentrations achieved in cerebrospinal fluid (CSF), were determined. Interleukin-1 receptor antagonist was similarly administered to patients with SAH, and CSF was sampled via external ventricular drains. In rats, IL-1RA significantly reduced brain injury induced by focal cerebral ischaemia. The plasma IL-1RA concentrations reached 12+/-2 microg/mL by 30 mins, and CSF concentrations were maintained between 91 and 232 ng/mL between 1 and 24 h of infusion. In patients with SAH, IL-1RA reached a steady-state plasma concentration of 22+/-4 microg/mL by 15 mins, and CSF concentrations were maintained at 78 to 558 ng/mL between 1 and 24 h. Intravenous delivery of IL-1RA leads to CSF concentrations in patients comparable to those that are neuroprotective in rats, and might therefore be of therapeutic benefit.

The presence of a residual systemic-to-pulmonary shunt following a bidirectional Glenn operation may be necessary in patients with an elevated pulmonary vascular resistance. It is often possible to perform percutaneous occlusion of these shunts once the resistance has fallen. We report on the use of an Amplatzer Ductal Occluder Device to occlude a residual Sano shunt in an infant with a variant of hypoplastic left heart syndrome.

Introduction: The relative roles of magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) in the investigation of common bile duct (CD) calculi were evaluated using "evidence-based practice" (EBP) methods., Methods: A focused clinical question was constructed. A structured search of primary and secondary evidence was performed. Retrieved studies were appraised for validity, strength and level of evidence (Oxford/CEBM scale: 1-5). Retrieved literature was divided into group A; MRCP slice thickness >or=5 mm, group B; MRCP slice thickness = 3 mm or 3D-MRCP sequences., Results: Six studies were eligible for inclusion (3 = level 1b, 3 = level 3b). Group A: sensitivity and specificity of MRCP and EUS were (40%, 96%) and (80%, 95%), respectively. Group B: sensitivity and specificity of MRCP and EUS were (87%, 95%) and (90%, 99%), respectively., Conclusion: MRCP should be the first-line investigation for CD calculi and EUS should be performed when MRCP is negative in patients with moderate or high pre-test probability.

Background: The relative roles of magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) in the investigation of malignant common bile duct (CD) strictures were evaluated using "evidence-based practice" (EBP) methodology., Methods: A focused clinical question was constructed. A structured search of primary and secondary evidence was performed. Retrieved studies were appraised for validity, strength and level of evidence (Oxford/CEBM scale: 1-5)., Results: Three studies were eligible for inclusion; there were 2 level 3b and 1 level 4 papers. One paper included a patient group appropriate to the question and contained sufficient data to allow analysis. Sensitivity and specificity of MRCP and EUS were (90%, 65%) and (80%, 80%), respectively., Conclusion: In the diagnosis of malignant CD strictures, EUS is more specific than MRCP and may allow cytology to be obtained via a trans-duodenal approach. A multi modality imaging approach is recommended.

Aims: Hypertrophic cardiomyopathy (HCM) is a disease with marked regional differences in wall thickness. However, the relation between myocardial function and wall thickness has not been well studied. Ultrasonic strain rate (SR) imaging makes it possible to study the regional myocardial deformation. We investigated whether regional systolic deformation is reduced in paediatric patients with HCM and evaluated its relation with wall thickness, electrocardiographic pattern, and exercise capacity., Methods and Results: We studied 41 children with asymmetric HCM (mean age 12.3 years) and 29 controls. Electrocardiograms, exercise testing (when feasible), and echocardiograms with tissue Doppler imaging were performed. Peak systolic SR, strain, post-systolic shortening, and time to maximal strain were calculated in the longitudinal direction from the basal septum, mid-septum, and basal lateral myocardial segments and in the radial direction from the basal antero-septal and infero-lateral myocardial segments. Children with HCM had a significant reduction in deformation in all myocardial segments when compared with controls. In the HCM group, peak systolic SR and strain were significantly lower in the basal septum when compared with the mid-septal and basal lateral myocardial segments. In the basal septum, post-systolic shortening was significantly higher and time to maximal strain significantly longer than in mid-septal and lateral myocardial segments. A strong inverse curvilinear relation between peak systolic strain and wall thickness was found (r = -0.86, P < 0.001), with no further decrease in the regional myocardial function demonstrated once maximal wall thickness exceeded a Z-score of 3.5. Peak systolic strain in the basal part of the septum correlated inversely with exercise capacity (r = 0.68, P < 0.01)., Conclusion: Systolic deformation is significantly and inhomogeneously reduced in children with HCM. This reduction in myocardial function is related to maximal wall thickness and decreased exercise capacity.

Objectives: This study aimed to identify independent predictors of reoperation after successful resection of discrete subaortic stenosis (DSS)., Background: Recurrence of DSS has been reported to range from 0% to 55% of patients. Factors associated with recurrence have not been adequately defined., Methods: Patients were included if they had a diagnosis of DSS, normal segmental cardiac anatomy, previous resection of DSS, and at least 36 months' follow-up. Demographic, surgical, and echocardiographic data were analyzed. Primary outcome was repeat resection of DSS in patients after successful primary resection., Results: Of 111 subjects who had successful surgical resection of DSS, 16 patients (14%) required reoperation. Median follow-up time was 8.2 years. Form of DSS and gender did not differ significantly between those with reoperation and those without. In multivariate analysis, independent predictors of reoperation that would be available before first surgery were <6 mm distance between the aortic valve (AoV) and the obstruction (hazard ratio [HR] 5.1; p = 0.013) and peak gradient by Doppler > or =60 mm Hg (HR 4.2; p = 0.016). If intraoperative variables are also considered, peeling of the membrane from the AoV or mitral valve at first surgery, <6 mm distance between the DSS and AoV, and peak gradient by Doppler > or =60 mm Hg were independent predictors of reoperation., Conclusions: Proximity of the obstructive lesion to the AoV and severe obstruction determined by preoperative echocardiography, as well as involvement of valve leaflets requiring surgical peeling, predict recurrent DSS requiring reoperation.

Background: We hypothesized that recombinant B-type natriuretic peptide (BNP) (nesiritide) could improve urine output and neurohormonal markers of heart failure without worsening renal function in pediatric patients., Methods and Results: We analyzed our experience involving 140 nesiritide infusions in 63 consecutive children. Serum levels of BNP and electrolytes were measured before and after therapy. Dosing was begun at 0.01 mcg.kg.min without a bolus and titrated to a maximum of 0.03 mcg.kg.min, in 0.005-mcg.kg.min increments. Blood pressure, heart rate, and heart rhythm were monitored. In a substudy, 20 patients with decompensated cardiomyopathy-related heart failure received 72 hours of nesiritide with prospective assessment of aldosterone, norepinephrine, plasma renin, and endothelin-1 levels before and after therapy. The heart rate decreased significantly (P = .001). Urine output increased significantly on Days 1 and 3 (P < or = .001 and .004, respectively). The mean serum creatinine level decreased from 1.135 to 1.007 mg/dL (P < or = .001). In the substudy, aldosterone levels decreased from 37.5 +/- 57.1 to 20.5 +/- 41.9 ng/dL (P = .005). Plasma renin, norepinephrine, and endothelin-1 levels decreased nonsignificantly. Two infusions were discontinued because of hypotension., Conclusions: Nesiritide safely treated decompensated heart failure in children. Increased urine output reflected improving renal function. Improved neurohormonal markers were seen after 72 hours of therapy, and complications were uncommon.