MRI characterization of hemodynamic patterns of human fetuses with cyanotic congenital heart disease.

OBJECTIVES: To characterize, using magnetic resonance imaging (MRI), the distribution of blood flow and oxygen transport in human fetuses with subtypes of congenital heart disease (CHD) that present with neonatal cyanosis. METHODS: Blood flow was measured in the major vessels of 152 late-gestation human fetuses with CHD and 40 gestational-age-matched normal fetuses, using cine phase-contrast MRI. Oxygen saturation (SaO2 ) was measured in the major vessels of 57 fetuses with CHD and 40 controls. RESULTS: Compared with controls, we found lower combined ventricular output in fetuses with single-ventricle physiology, with the lowest being observed in fetuses with severe forms of Ebstein's anomaly. Obstructive lesions of the left or right heart were associated with increased flow across the contralateral side. Pulmonary blood flow was reduced in fetuses with Ebstein's anomaly, while those with Ebstein's anomaly and tricuspid atresia had reduced umbilical flow. Flow in the superior vena cava was elevated in fetuses with transposition of the great arteries, normal in fetuses with hypoplastic left heart, tetralogy of Fallot or tricuspid atresia and reduced in fetuses with Ebstein's anomaly. Umbilical vein SaO2 was reduced in fetuses with hypoplastic left heart or tetralogy of Fallot. Ascending aorta and superior vena cava SaO2 were reduced in nearly all CHD subtypes. CONCLUSIONS: Fetuses with cyanotic CHD exhibit profound changes in the distribution of blood flow and oxygen transport, which result in changes in cerebral, pulmonary and placental blood flow and oxygenation. These alterations of fetal circulatory physiology may influence the neonatal course and help account for abnormalities of prenatal growth and development that have been described in newborns with cyanotic CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Treatment of fetal circular shunt with non-steroidal anti-inflammatory drugs.

A circular shunt (CS) is a life-threatening condition involving massive shunting of systemic arterial blood via the ductus arteriosus to the left ventricle without traversing the lungs. In the prenatal setting, it occurs mainly in fetuses with severe forms of Ebstein's anomaly (EA) owing to unrestricted ductal flow and significant pulmonary and tricuspid regurgitation. We aimed to improve the fetal hemodynamics and chances of survival of affected fetuses by inducing ductal constriction using transplacental non-steroidal anti-inflammatory drugs (NSAIDs). Following initiation of treatment between 26 and 34 weeks' gestation, three (75%) of four fetuses with EA/CS responded with sustained ductal constriction and improved hemodynamic function, which allowed continuation of pregnancy for 3-7 weeks and elective delivery. All successfully treated cases underwent neonatal surgery immediately after birth to eliminate the CS and survived. This included two neonates that underwent single-ventricle palliation surgery that required postoperative extracorporeal membrane oxygenation and hemofiltration for transient respiratory and renal failure. The one case that did not respond to treatment with NSAIDs was delivered prematurely for progressive fetal compromise and died shortly after birth. Transplacental treatment with NSAIDs represents a novel approach to controlling fetal CS, avoiding in-utero death and prolonging the pregnancy to a more advanced gestational age, thereby potentially increasing the chances of neonatal survival. This treatment should be considered and initiated at an early stage of systemic steal to prevent brain injury due to hypoperfusion. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Off-label use of the amplatzer ductal occluder II additional size for percutaneous treatment of acute aortic occlusion in a baby.

We describe the case of a 5-month-old baby with a pro-coagulative condition, referred for rapid atrial tachycardia. At echocardiography we found a large free-floating atrial thrombus that spontaneously embolized into the descending aorta and produced acute sub-renal occlusion. Aorta and iliac vessels were cleared using the ADO II additional sizes device. © 2016 Wiley Periodicals, Inc.

Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep.

OBJECTIVE: To determine the efficacy and bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) when administered orally to sheep. DESIGN: Randomised experimental design with four treatment groups: three NSAID groups and one control group (n = 10/group). The study animals were 40 18-month-old Merino ewes with an average weight of 31.4 ± 0.5 kg. METHODS: Treatment was given orally at 24 h intervals for 6 days at dose rates expected to achieve therapeutic levels in sheep: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg). Oil of turpentine (0.1 mL) was injected into a forelimb of each sheep to induce inflammation and pain; responses (force plate pressure, skin temperature, limb circumference, haematology and plasma cortisol) were measured at 0, 3, 6, 9, 12, 24, 36, 48, 72 and 96 h post-injection. NSAID concentrations were determined by ultra-high-pressure liquid chromatography. RESULTS: The NSAIDs were detectable in ovine plasma 2 h after oral administration, with average concentrations of 4.5-8.4 µg/mL for ketoprofen, 2.6-4.1 µg/mL for flunixin and 30-80 µg/mL for carprofen. NSAID concentrations dropped 24 h after administration. Pain response to an oil of turpentine injection was assessed using the measures applied but no effect of the NSAIDs was observed. Although this pain model has been previously validated, the responses observed in this study differed from those in the previous study. CONCLUSIONS AND CLINICAL RELEVANCE: The three NSAIDs reached inferred therapeutic concentrations in blood at 2 h after oral administration. The oil of turpentine lameness model may need further validation.

Closure of the patent ductus arteriosus with the new duct occluder II additional sizes device.

OBJECTIVE: The objective of this study was to evaluate the technical feasibility, safety, and efficacy of the new device Amplatzer duct occluder II additional sizes (ADO II AS) for closure of patent ductus arteriosus (PDA). BACKGROUND: Transcatheter device closure is the standard care for PDA. Currently available technology is not designed for closure of small PDA in young children. METHODS: From April to July 2011, seven children (five females, median age 1.5 years, median weight 11.4 kg) underwent PDA closure with the ADO II AS. Six had isolated PDA, one had PDA associated with preductal coarctation. We evaluated early and short-term results. RESULTS: All but one PDA was closed via an antegrade approach. Mean fluoroscopy and procedural times were 8.0 ± 3.9 and 49.8 ± 27.9 min, respectively. No complications occurred. Immediate trivial residual shunt was present in one patient. In all devices, the retention disks laid flat against the walls of the pulmonary artery and aorta, without protrusion into the vessel lumen. The echocardiography performed after 24 hr did not show any residual shunt. At a median follow-up of 2 months, the PDAs were completely occluded without obstruction of the pulmonary arteries or aorta. CONCLUSIONS: The new device ADO II AS was safely deployed with complete resolution of the PDA shunt. The lower profile and symmetry of this device allows for venous or arterial approach and smaller delivery catheter size. The ADO II AS might be a preferable alternative for closure of small-moderate PDAs.

Interventional treatment of congenital heart disease patients.

During the last 10 years the interventional treatment of congenital and structural heart diseases has known enormous changes in techniques, methods and patients management. Lesions previously treated surgically are now approached in the catheterization laboratory. The advent of multidisciplinary approach of congenital heart disease has made possible the development of hybrid techniques, of fetal medicine and of magnetic resonance imaging (MRI)- guided cardiac catheterization. Technological innovation has introduced new concepts in treatment of congenital heart disease patients and has allowed to adapt different techniques to single patients. The knowledge of the evolution of structural heart disease has allowed to chose the best percutaneous and/ or surgical technique and the best materials to optimize long term results. Improvement in non invasive imaging modality has allowed to diminish the radiation exposure and to provide useful information to interventional cardiologists and cardiac surgeons. Absorbable, drug eluting tools will change the treatment and probably the natural history of congenital and structural cardiac and vascular diseases.

[Utilisation of gastric ring systems for pulmonary artery banding: an animal study]. / Utilisation d'un système de cerclage gastrique comme cerclage réglable de l'artère pulmonaire: une étude chez l'animal.

OBJECTIVES: Pulmonary artery banding is often required as a first palliative procedure in infants with congenital heart disease and high pulmonary blood flow or to retrain the left ventricle. The purpose of the study was to demonstrate the safety of a gastric banding system as an adjustable pulmonary artery banding in chronic implantation. METHODS: Five ewes underwent implantation of the banding system around the main pulmonary artery through a left thoracotomy. All had functional evaluation with progressive occlusion and opening of the device every two weeks for a total period of three months. Invasive pressure measurements in the right ventricle and aorta were carried out each time. RESULTS: Devices could be implanted easily. Progressive occlusion and re-opening were possible in all animals during each time point. All animals survived throughout the protocol. Retrieval of the device was achieved in all animals. In one, it was challenging because of the presence of a fibrotic reaction around the device. It died because of pulmonary artery perforation before the sacrifice. At autopsy, microscopic examination showed no signs of myocardial fibrosis. CONCLUSIONS: In animals, gastric banding system is a safe and effective implantable device to adjust pulmonary artery diameter over a prolonged period of time. This new device may be a valuable alternative to the repeated conventional pulmonary artery banding needed for ventricular retraining in humans.

[Anomalous left main coronary artery with an inter-aorto-pulmonary trajectory: diagnostic value of 64-slice CT scan with cardiac synchronisation]. / Anomalie de naissance du tronc coronaire gauche avec un trajet interaortopulmonaire: apport du scanner 64 coupes avec synchronisation cardiaque.

Anomalous left coronary artery arising from the right sinus with an inter-aorto-pulmonary trajectory is a classical cause of sudden death and myocardial ischaemia in young adults. The mechanism is compression of the coronary during physiological dilatation of the great arteries on exercise. The authors report the case of a 12 year old child who had syncope on effort preceded by angina due to this malformation. The CT scan with 3-D reconstruction confirmed the diagnosis and the interarterial trajectory of the left coronary artery and the anatomical relationships with the vessels at the base of the heart. Cardiac CT scan is the investigation of choice for diagnosis and preoperative work-up of congenital coronary anomalies. In the authors' experience, the investigation is performed systematically when an anomalous coronary artery is suspected, in addition to echocardiography and instead of conventional coronary angiography.

Closure of extracardiac Fontan fenestration by using the covered Cheatham Platinum stent.

OBJECTIVE: The purpose of this study was to describe our experience concerning the use of covered Cheatham Platinum (CP) stent in patients with fenestrated total cavopulmonary connection (TCPC). BACKGROUND: Closure of TCPC fenestrations has been achieved by utilizing different devices designed to close intra-cardiac or aorto-pulmonary communications. METHODS: We used the covered CP stent in 6 patients with fenestrated TCPC. Median age and weight were 11 years and 38 Kg, respectively. Femoral approach was used in all but 1 patient having bilateral thrombosis of femoral veins. The CP stent was crimped on a BiB balloon in 5 patients and on a simple balloon in 1 patient. The balloon's diameter was the same size or 1-2 mm larger than the TCPT conduit, according to angiographic diameter. RESULTS: Mean procedural and fluoroscopy time were 41 +/- 8 and 8 +/- 2 min, respectively. Immediate full occlusion of fenestration was obtained in all patients. Mean central venous pressure was not significantly increased from 10.8 +/- 2.5 to 11.8 +/- 2.8 mm Hg and oxygen saturation significantly increased from (91.5 +/- 4.4)% to (98.5 +/- 1.9)% (P = 0.003). No procedural or intra-hospital complications occurred. In particular, no arrhythmias, systemic embolism, or acute venous thrombosis were observed. At a median follow-up of 2.8 months all patients have normal oxygen saturation and are symptom-free. CONCLUSIONS: The covered CP stent can be easily and effectively used for closure of TCPC fenestrations. This method has the advantage to avoid protrusion of prosthetic material into the left atrium and to prevent early or late embolism.

[Use of covered stents to occlude extracardiac Fontan fenestration]. / Utilisation de stents couverts pour la fermeture des fenestrations extracardiaques des dérivations cavopulmonaires totales.

INTRODUCTION: A fenestration is usually surgically created to improve the post-operative course of patients undergoing total cavopulmonary connection. It, however, has a potentially deleterious effect on the long-term period. Closure of these fenestrations is usually performed by interventional catheterization. No device has been specially designed and closure of extracardiac fenestration, in particular, can be challenging. We report our experience in occlusion of such fenestrations using covered stents (Numed Inc). METHODS: From July 2005 to October 2005, we attempted to occlude extracardiac Fontan fenestration using CP covered stents in 4 consecutive patients. RESULTS: All patients had a successful occlusion of the fenestration. The procedure was performed from femoral or jugular vein respectively in three and one patient. Mean central venous pressure did not increase significantly (from 11.25 to 12.75 mmHg) whereas mean oxygen saturation increased significantly from 92% to 99% (p=0.0047). Abolition of shunt was obtained immediately after insertion of the covered stent in all patients. No early complications were observed. All patients were ambulatory the day after the procedure. CONCLUSION: The insertion of a covered stent inside the extracardiac Fontan conduit allowed the exclusion of the fenestration in all patients without the need of crossing the fenestration and with no early mortality or morbidity. Long-term follow-up are needed before considering the use of such device as the device of choice in that application.

Three homozygous PTC mutations in the collagen type VII gene of patients affected by recessive dystrophic epidermolysis bullosa: analysis of transcript levels in dermal fibroblasts.

The Hallopeau-Siemens variant of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe inherited skin disease characterized by the absence of collagen type VII (COLVII) and anchoring fibrils (AF), caused by mutations in collagen type VII gene (COL7A1). Mutations leading to the formation of premature termination codons (PTCs) of translation are the characteristic genetic lesions in HS-RDEB patients; many PTC mutations have been found to be associated with a marked reduction or complete absence of COLVII mRNA. In this article, we report homozygosity for three different mutations in the COL7A1 of HS-RDEB patients. One mutation, the R2685X, falling in exon 109, is a novel mutation, whereas the other two, the 425A-->G falling in exon 3 and the 497insA in exon 4, have been previously identified in compound heterozygosity with different mutations in other unrelated RDEB patients. Haplotype analysis in three Italian families carrying the 497insA mutation suggested a common origin of this mutation and indicated that this is an ancestral Italian mutation. All these mutations generate PTCs and are associated with the absence of COLVII expression, as detected by immunofluorescence analysis of the patient's skin. Evaluation of the levels of the mutated COLVII mRNAs in cultured skin fibroblasts of the patients and of their parents showed that all the mutated transcripts were expressed at consistent levels. Therefore, our results indicate that a marked mRNA reduction is not a constant feature associated with PTC mutations in COL7A1.

Delineation of conformational and structural features of the amikacin-Cu(II) complex in water solution by 13C-NMR spectroscopy.

The copper (II) complex of amikacin in water solution at pH 5.5 was investigated by 13C-NMR. The temperature dependence of spin-lattice relaxation rates was measured and fast exchange conditions were shown to apply. The motional correlation time of the complex was approximated by the pseudo-isotropic rotational correlation time of free amikacin in water solution (tau c = 0.17 ns at 300 K). Formation of a pseudo-tetrahedral 1:1 complex was demonstrated by relaxation rates analysis and also by UV-Vis spectrophotometry. Two amino nitrogens of amikacin, together with the amide nitrogen and the hydroxyl in the hydroxyl-aminopropyl carbonyl side chain, were assigned as the copper-binding sites and a model of the complex was built by using copper-carbon distances obtained by NMR analysis as input parameters.

Identification of two splicing mutations in the collagen type VII gene (COL7A1) of a patient affected by the localisata variant of recessive dystrophic epidermolysis bullosa.

Collagen type VII gene (COL7A1) has been demonstrated to be altered in several variants of dystrophic epidermolysis bullosa (DEB), with either recessive or dominant mode of inheritance. We have identified two mutations in a patient affected by a localisata variant of recessive DEB (L-RDEB), which is characterized by the less severe phenotype of the syndrome. These mutations are the first splicing mutations so far described for COL7A1 in DEB. One mutation is a paternally inherited A-->G transition at position -2 of the donor splicing site of intron 3, which results in three aberrant mRNAs, depending on the skipping of exon 3, the usage of a cryptic donor site inside exon 3, or the maintenance of intron 3. The second mutation is a maternally inherited G-->A transition at position -1 of the donor splicing site of intron 95, which induces the activation of a cryptic donor site 7 nt upstream the normal site and gives rise to a deleted mRNA, in addition to the normal one. All aberrant mRNAs show a shift of the reading frame, thus generating premature termination codons of translation. Allele-specific analysis of the transcripts has shown that the maternal mutation does not completely abolish the correct splicing of COLVII pre-mRNA, thus allowing, in the patient, the synthesis of a certain level of a functional protein. This result is compatible with the mild clinical L-RDEB phenotype observed in our patient.

Acute myocardial infarction in a patient with chronic myelogenous leukemia.

A case of acute myocardial infarction in association with chronic myelogenous leukemia is presented. The clinical management and possible reasons for the presentation are discussed.

Cryoglobulinemic peripheral neuropathy: neurophysiologic evaluation in twenty-two patients.

The aim of this study was to evaluate the frequency and degree of peripheral neuropathy in 22 consecutive patients with mixed cryoglobulinemia, whether symptom-free or with subjective neurological symptoms. Electrophysiological investigations were carried out and a biopsy of the sural nerve was performed in six patients. Peripheral neuropathy of the lower limbs was demonstrated, which was mostly sensory and light or moderate in 86% of cases (19 patients). F-Wave and H-reflex recordings were found to be the most reliable methods; in 77% of cases, they were abnormal (17 patients). Using somatosensory evoked potentials, we were able to exclude simultaneous central nervous system involvement in 10 patients.

Determination of fosinopril in pharmaceutical formulations containing hydrochlorothiazide by multiwavelength UV spectrophotometry.

A sensitive, simple, rapid and precise method for the simultaneous determination of fosinopril (FOS) and hydrochlorothiazide (HCT) in pharmaceutical formulations is presented. These active ingredients are extracted in aqueous solution and measured by multiwavelength UV spectrophotometry using the program QUEST. HCT acts as an internal standard to verify the accuracy of the analysis. Some aspects of the chemical, spectroscopic and thermoanalytical behaviour of FOS are also reported.

Ploidy pattern and cell cycle in breast cancer as detected by image analysis and flow cytometry.

Both image analysis (IA) and flow cytometry (FCM) may be applied to detect ploidy pattern and cell cycle fractions. However, they have different performance characteristics and may yield different results. The two approaches are applied in this study to 66 breast cancers: IA on imprints and FCM on fresh tissue. The percent coefficient of variation (CV) ranged from 2.0 to 7.0 (mean 5.5; SD 1.1) in IA and from 2.0 to 7.0 (mean 4.4; SD 1.1) in FCM. The values were well correlated. With regard to ploidy pattern, the agreement between the two methods was 92.4%; disagreements were due to four cases being aneuploid by IA but not detected by FCM and one case being aneuploid by IA but tetraploid by FCM. This suggests that IA is capable of detecting aneuploidy with more sensitivity than FCM. In diploid cases, the percent values of cells in G0/G1, S-phase (SPF), and G2M phase were concordant and well correlated. In aneuploid cases, IA was more sensitive than FCM in detecting aneuploid fraction as well as G2M phase, whereas FCM was more sensitive than IA in detecting SPF. A good correlation was found between the DNA indexes (DIs) obtained with the two methods.

Incorporating biologically based models into assessments of risk from chemical contaminants.

The general approach to assessment of risk from chemical contaminants in drinking water involves three steps: hazard identification, exposure assessment, and dose-response assessment. Traditionally, the risks to humans associated with different levels of a chemical have been derived from the toxic responses observed in animals. It is becoming increasingly clear, however, that further information is needed if risks to humans are to be assessed accurately. Biologically based models help clarify the dose-response relationship and reduce uncertainty.