The pulmonary mesenchymal tissue layer is defective in an in vitro recombinant model of nitrofen-induced lung hypoplasia.

PubMed

van Loenhout, Rhiannon B; Tseu, Irene; Fox, Emily K; Huang, Zhen; Tibboel, Dick; Post, Martin; Keijzer, Richard

2012-01-01

Despite modern treatments, congenital diaphragmatic hernia (CDH) remains associated with variable survival and significant morbidity. The associated pulmonary hypoplasia is a major determinant of outcome. To develop better treatments, improved comprehension of the pathogenesis of lung hypoplasia is warranted. We developed an in vitro cell recombinant model to mimic pulmonary hypoplasia and specifically to investigate epithelial-mesenchymal interactions and to decipher which tissue layer is primarily defective in nitrofen-induced CDH-associated lung hypoplasia. Epithelial cells (E) and fibroblasts (F) were isolated from E19 control ((C)) and nitrofen-induced hypoplastic rat lungs ((N)). Cells were recombined and cultured as either homotypic [(F(C))(E(C)) and (F(N))(E(N))] or heterotypic [(F(C))(E(N)) and (F(N))(E(C))] recombinants. Recombinants containing F(N) fibroblasts had a thickened fibroblast tissue layer and there were fewer organized alveolar-like epithelial structures compared with those in control (F(C))(E(C)) recombinants. These F(N) recombinants exhibited a decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 positive cells. Cell proliferation was arrested in recombinants containing F(N) fibroblasts, which also exhibited increased p27(Kip1) and p57(Kip2) expression. In conclusion, fibroblasts, and not epithelial cells, appear to be the defective cell type in nitrofen-induced hypoplastic lungs due to a decreased ability to undergo apoptosis and maintain overall proliferation. This may explain the characteristic pulmonary interstitial thickening and hypoplasia observed in both nitrofen-induced hypoplastic lungs as well as human hypoplastic CDH lungs. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Birth Defects Data and Statistics

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... Syndrome Disorders Gastroschisis Heart Defects Coarctation of the Aorta Hypoplastic left heart syndrome Tetralogy of Fallot Other ...

Hypoplastic left heart syndrome (image)

MedlinePlus

Hypoplastic left heart syndrome is a congenital heart condition that occurs during the development of the heart in the ... womb. During the heart's development, parts of the left side of the heart (mitral valve, left ventricle ...

Facts about Hypoplastic Left Heart Syndrome

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... is very small. The ascending portion of the aorta is underdeveloped or is too small. Often, babies ...

Marfan Syndrome in an Iranian Family: A Case Series

PubMed Central

Davari, Mohammad Hossein; Kazemi, Toba

2014-01-01

Marfan syndrome (MFS) is a genetic disorder which is inherited by autosomal dominant traits. In MFS, lens displacement and cardiovascular involvement are important causes of morbidity and mortality in the clinical course of the disease. In this case study, the ocular involvement in a family with severe penetration of MFS is reported. Twelve members of a family (father, two daughters, three sons, and six grandchildren) had MFS. Lens ectopia was the most common ophthalmic involvement among the family (100%). Other ocular involvements were as follows; Hypoplastic iris or ciliary’s muscle hypoplasia (50%), on gated eyeball (42%), flat cornea (30%), glaucoma and cataract (25%), retinal detachment (16%). Three members of the family underwent eye surgery including lens extraction, glaucoma surgery and retinal surgery. PMID:25031493

Management of Tricuspid Regurgitation in Patients With Hypoplastic Left Heart Syndrome.

PubMed

Pigula, Frank A; Mettler, Bret

2017-01-01

Tricuspid valve (TV) performance is critical for palliation of hypoplastic left heart syndrome. We will review current TV repair techniques, outcomes, and novel approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatoblastoma and hypoplastic kidneys: a new association.

PubMed

Chan, Randall; Mascarenhas, Leo; Venkatramani, Rajkumar

2014-08-01

Both hepatoblastoma and hypoplastic kidneys are rare in children. A review of all patients with hepatoblastoma treated at our institution between 1993 and 2011 revealed three cases of hepatoblastoma occurring in children with hypoplastic kidneys and significantly impaired renal function. Two patients were treated with doxorubicin-based therapy without cisplatin. One was treated with carboplatin. The former two are long-term survivors while the third patient died of sepsis following chemotherapy. This association is unlikely due to chance alone and chemotherapy regimens without cisplatin may be effective in treating these children. © 2014 Wiley Periodicals, Inc.

Psychosocial impact on families with an infant with a hypoplastic left heart syndrome during and after the interstage monitoring period - a prospective mixed-method study.

PubMed

Stoffel, Gaby; Spirig, Rebecca; Stiasny, Brian; Bernet, Vera; Dave, Hitendu; Knirsch, Walter

2017-11-01

To investigate parents' experiences, coping ability and quality of life while monitoring their sick child with hypoplastic left heart syndrome at home. Interstage home monitoring for children with hypoplastic left heart syndrome reduces interstage mortality between Norwood stages I and II. Little is known about the psychosocial impact of interstage home monitoring. Prospective mixed-method study. This study assessed the psychosocial impact on parents during interstage home monitoring. This contains for quantitative assessment the Short Form Health Survey questionnaire and the Impact of Family Scale administered one and five weeks following discharge before and after stage II. For qualitative assessment, semi-structured interviews focussing on the postdischarge coping strategies were conducted twice, five weeks after hospital discharge before and after stage II. Ten infants (eight males) with hypoplastic left heart syndrome (n = 7) or other types of univentricular heart malformations (n = 3), and their parents (nine mother/father two-parent households, one single mother) were included. There were no interstage deaths. Mental Health Composite Summary scores were low in both parents (mothers: 40·45 ± 9·07; fathers: 40·58 ± 9·69) and lowest for the item 'vitality' (mothers: 37·0 ± 19·46; fathers: 43·12 ± 25·9) before and after stage II. Impact of Family Scale values showed higher daily and social burdens for mothers. 'Becoming a family' was the most important task as coping strategy to equilibrate the fragile emotional balance. The parents judged interstage home monitoring as a protective intervention. Although psychosocial burden before and after stage II remains high, becoming a family is an essential experience for parents and confirms their parenthood. Healthcare professionals must be aware of parents' needs during this vulnerable interstage period and to provide psychosocial and nursing support. © 2016 John Wiley & Sons Ltd.

Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta.

PubMed

Smith, Claire El; Whitehouse, Laura LE; Poulter, James A; Brookes, Steven J; Day, Peter F; Soldani, Francesca; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

2017-08-01

We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T, p.(P249L)) in ACPT, the gene encoding acid phosphatase, testicular, which segregates with hypoplastic amelogenesis imperfecta in two unrelated families. ACPT is reported to play a role in odontoblast differentiation and mineralisation by supplying phosphate during dentine formation. Analysis by computerised tomography and scanning electron microscopy of a primary molar tooth from an individual homozygous for the c.746C>T variant revealed an enamel layer that was hypoplastic, but mineralised with prismatic architecture. These findings implicate variants in ACPT as a cause of early failure of amelogenesis during the secretory phase.

Interstage Home Monitoring After Newborn First-Stage Palliation for Hypoplastic Left Heart Syndrome: Family Education Strategies.

PubMed

Nieves, Jo Ann; Uzark, Karen; Rudd, Nancy A; Strawn, Jennifer; Schmelzer, Anne; Dobrolet, Nancy

2017-04-01

Children born with hypoplastic left heart syndrome are at high risk for serious morbidity, growth failure, and mortality during the interstage period, which is the time from discharge home after first-stage hypoplastic left heart syndrome palliation until the second-stage surgical intervention. The single-ventricle circulatory physiology is complex, fragile, and potentially unstable. Multicenter initiatives have been successfully implemented to improve outcomes and optimize growth and survival during the interstage period. A crucial focus of care is the comprehensive family training in the use of home surveillance monitoring of oxygen saturation, enteral intake, weight, and the early recognition of "red flag" symptoms indicating potential cardiopulmonary or nutritional decompensation. Beginning with admission to the intensive care unit of the newborn with hypoplastic left heart syndrome, nurses provide critical care and education to prepare the family for interstage home care. This article presents detailed nursing guidelines for educating families on the home care of their medically fragile infant with single-ventricle circulation. ©2017 American Association of Critical-Care Nurses.

Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Hiromizu; Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro; Kutasy, Balazs; Gosemann, Jan-Hendrik; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.

Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

PubMed

Wang, Xin; Zhao, Yuming; Yang, Yuan; Qin, Man

2015-01-01

Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

[The third dimension tomography versus cranial X-ray cephalometry to predict maxilla advance by distraction in hypoplastic maxilla].

PubMed

Rosas-Muñoz, Arturo; Soriano-Padilla, Fernando; Rendón-Macías, Mario Enrique

2010-01-01

the osteogenic distraction is the treatment for the correction of the hypoplastic maxilla secondary to the repair of a cleft lip-palate. Its planning is based on articulated models. Our objective was to describe the accuracy of three-dimensional Cephalometry (CT3D) for projecting jaw displacement. three patients with hypoplastic maxilla. Interventions estimation of the advance required of lateral maxilla through Cephalometry of skull (CLC), CT3D and an articulated model (gold standard). Two months after distraction finalized the advance predicted was compared. the error of the advance projection in each patient was smaller with the CT3D versus CLC (+1, +1 and +1 mm versus -10, -14 and -9mm). Corrections post-distraction were of +25 %, +26 % and +38.4 % on the programmed one. CT3D predicted better the correction (+19 %, +10.8 %, +33.4 % versus CLC: -50 %; -60.8 % and -34.6 %). Chewing alterations were not seen in any patient. the planning of the necessary advance for distraction in patients with hypoplastic maxilla by CT3D can shorten the time of studies and should be consider as next to the projection of articulated model.

Up-regulation of COUP-TFII gene expression in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Sugimoto, Kaoru; Puri, Prem

2009-02-01

Recent studies have suggested that the retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The exact mechanism by which nitrofen acts in the RSP remains unclear. Targeted ablation of COUP-TFII, a gene encoding a transfactor regulated by the RSP, has been shown to cause Bochdalek-type congenital diaphragmatic hernia. It has been shown that COUP-TFII has 2 main roles in the RSP, (i) repressing the RSP by directly sequestering retinoid X receptors, thereby preventing heterodimerization to retinoid acid receptors and inhibiting gene transcription, and (ii) modulating the transcriptional activity of GATA proteins. We designed this study to investigate the gene expression of COUP-TFII in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9 of gestation. Fetuses were harvested and lungs were dissected on day 15 (D15), D18, and D21 and divided into 2 groups: control (n = 9) and nitrofen (n = 9). Real-time reverse transcription-polymerase chain reaction was performed to evaluate the relative mRNA levels of COUP-TFII expression in the hypoplastic lung. The relative mRNA levels of COUP-TFII at D15 was significantly increased in the nitrofen group (0.76 +/- 0.53) compared to controls (0.45 +/- 0.05) (P < .01). The expression levels of COUP-TFII at D18 and D21 were not significantly different between the nitrofen group and controls. Our results provide evidence for the first time that the pulmonary gene expression of COUP-TFII is up-regulated in the early stages of lung development in the nitrofen-induced hypoplastic lung. We speculate that up-regulation of COUP-TFII gene expression during the stage of branching lung morphogenesis may cause pulmonary hypoplasia by repressing RSP.

Effects of milk flow on the physiological and behavioural responses to feeding in an infant with hypoplastic left heart syndrome.

PubMed

Pados, Britt F; Thoyre, Suzanne M; Estrem, Hayley H; Park, Jinhee; Knafl, George J; Nix, Brant

2017-01-01

Infants with hypoplastic left heart syndrome often experience difficulty with oral feeding, which contributes to growth failure, morbidity, and mortality. In response to feeding difficulty, clinicians often change the bottle nipple, and thus milk flow rate. Slow-flow nipples have been found to reduce the stress of feeding in other fragile infants, but no research has evaluated the responses of infants with hypoplastic left heart syndrome to alterations in milk flow. The purpose of this study was to evaluate the physiological and behavioural responses of an infant with hypoplastic left heart syndrome to bottle feeding with either a slow-flow (Dr. Brown's Preemie) or a standard-flow (Dr. Brown's Level 2) nipple. A single infant was studied for three feedings: two slow-flow and one standard-flow. Oral feeding, whether with a slow-flow or a standard-flow nipple, was distressing for this infant. During slow-flow feeding, she experienced more coughing events, whereas during standard-flow she experienced more gagging. Disengagement and compelling disorganisation were most common during feeding 3, that is slow-flow, which occurred 2 days after surgical placement of a gastrostomy tube. Clinically significant changes in heart rate, oxygen saturation, and respiratory rate were seen during all feedings. Heart rate was higher during standard-flow and respiratory rate was higher during slow-flow. Further research is needed to examine the responses of infants with hypoplastic left heart syndrome to oral feeding and to identify strategies that will support these fragile infants as they learn to feed. Future research should evaluate an even slower-flow nipple along with additional supportive feeding strategies.

Computational models of aortic coarctation in hypoplastic left heart syndrome: considerations on validation of a detailed 3D model.

PubMed

Biglino, Giovanni; Corsini, Chiara; Schievano, Silvia; Dubini, Gabriele; Giardini, Alessandro; Hsia, Tain-Yen; Pennati, Giancarlo; Taylor, Andrew M

2014-05-01

Reliability of computational models for cardiovascular investigations strongly depends on their validation against physical data. This study aims to experimentally validate a computational model of complex congenital heart disease (i.e., surgically palliated hypoplastic left heart syndrome with aortic coarctation) thus demonstrating that hemodynamic information can be reliably extrapolated from the model for clinically meaningful investigations. A patient-specific aortic arch model was tested in a mock circulatory system and the same flow conditions were re-created in silico, by setting an appropriate lumped parameter network (LPN) attached to the same three-dimensional (3D) aortic model (i.e., multi-scale approach). The model included a modified Blalock-Taussig shunt and coarctation of the aorta. Different flow regimes were tested as well as the impact of uncertainty in viscosity. Computational flow and pressure results were in good agreement with the experimental signals, both qualitatively, in terms of the shape of the waveforms, and quantitatively (mean aortic pressure 62.3 vs. 65.1 mmHg, 4.8% difference; mean aortic flow 28.0 vs. 28.4% inlet flow, 1.4% difference; coarctation pressure drop 30.0 vs. 33.5 mmHg, 10.4% difference), proving the reliability of the numerical approach. It was observed that substantial changes in fluid viscosity or using a turbulent model in the numerical simulations did not significantly affect flows and pressures of the investigated physiology. Results highlighted how the non-linear fluid dynamic phenomena occurring in vitro must be properly described to ensure satisfactory agreement. This study presents methodological considerations for using experimental data to preliminarily set up a computational model, and then simulate a complex congenital physiology using a multi-scale approach.

Hypoplastic anaemia complicating myxoedema coma.

PubMed

Song, S H; McCallum, C J; Campbell, I W

1998-10-01

The case of a 68 year old women presenting in myxoedema coma is described. She was found to be anaemic with a haemoglobin of 8.2 g/dl. Further investigations showed a pancytopenia and a hypoplastic anaemia confirmed by bone marrow. The patient recovered and became euthyroid following initial treatment with intravenous tri-iodothyronine (T3) and later oral thyroxine (T4) replacement with resolution of pancytopenia and return of bone marrow to normal.

Rapid prototyping compliant arterial phantoms for in-vitro studies and device testing

PubMed Central

2013-01-01

Background Compliant vascular phantoms are desirable for in-vitro patient-specific experiments and device testing. TangoPlus FullCure 930® is a commercially available rubber-like material that can be used for PolyJet rapid prototyping. This work aims to gather preliminary data on the distensibility of this material, in order to assess the feasibility of its use in the context of experimental cardiovascular modelling. Methods The descending aorta anatomy of a volunteer was modelled in 3D from cardiovascular magnetic resonance (CMR) images and rapid prototyped using TangoPlus. The model was printed with a range of increasing wall thicknesses (0.6, 0.7, 0.8, 1.0 and 1.5 mm), keeping the lumen of the vessel constant. Models were also printed in both vertical and horizontal orientations, thus resulting in a total of ten specimens. Compliance tests were performed by monitoring pressure variations while gradually increasing and decreasing internal volume. Knowledge of distensibility was thus derived and then implemented with CMR data to test two applications. Firstly, a patient-specific compliant model of hypoplastic aorta suitable for connection in a mock circulatory loop for in-vitro tests was manufactured. Secondly, the right ventricular outflow tract (RVOT) of a patient necessitating pulmonary valve replacement was printed in order to physically test device insertion and assess patient’s suitability for percutaneous pulmonary valve intervention. Results The distensibility of the material was identified in a range from 6.5 × 10-3 mmHg-1 for the 0.6 mm case, to 3.0 × 10-3 mmHg-1 for the 1.5 mm case. The models printed in the vertical orientation were always more compliant than their horizontal counterpart. Rapid prototyping of a compliant hypoplastic aorta and of a RVOT anatomical model were both feasible. Device insertion in the RVOT model was successful. Conclusion Values of distensibility, compared with literature data, show that TangoPlus is suitable for manufacturing arterial phantoms, with the added benefit of being compatible with PolyJet printing, thus guaranteeing representative anatomical finishing, and quick and inexpensive fabrication. The appealing possibility of printing models of non-uniform wall thickness, resembling more closely certain physiological scenarios, can also be explored. However, this material appears to be too stiff for modelling the more compliant systemic venous system. PMID:23324211

Rapid prototyping compliant arterial phantoms for in-vitro studies and device testing.

PubMed

Biglino, Giovanni; Verschueren, Peter; Zegels, Raf; Taylor, Andrew M; Schievano, Silvia

2013-01-16

Compliant vascular phantoms are desirable for in-vitro patient-specific experiments and device testing. TangoPlus FullCure 930 is a commercially available rubber-like material that can be used for PolyJet rapid prototyping. This work aims to gather preliminary data on the distensibility of this material, in order to assess the feasibility of its use in the context of experimental cardiovascular modelling. The descending aorta anatomy of a volunteer was modelled in 3D from cardiovascular magnetic resonance (CMR) images and rapid prototyped using TangoPlus. The model was printed with a range of increasing wall thicknesses (0.6, 0.7, 0.8, 1.0 and 1.5 mm), keeping the lumen of the vessel constant. Models were also printed in both vertical and horizontal orientations, thus resulting in a total of ten specimens. Compliance tests were performed by monitoring pressure variations while gradually increasing and decreasing internal volume. Knowledge of distensibility was thus derived and then implemented with CMR data to test two applications. Firstly, a patient-specific compliant model of hypoplastic aorta suitable for connection in a mock circulatory loop for in-vitro tests was manufactured. Secondly, the right ventricular outflow tract (RVOT) of a patient necessitating pulmonary valve replacement was printed in order to physically test device insertion and assess patient's suitability for percutaneous pulmonary valve intervention. The distensibility of the material was identified in a range from 6.5 × 10(-3) mmHg(-1) for the 0.6 mm case, to 3.0 × 10(-3) mmHg(-1) for the 1.5 mm case. The models printed in the vertical orientation were always more compliant than their horizontal counterpart. Rapid prototyping of a compliant hypoplastic aorta and of a RVOT anatomical model were both feasible. Device insertion in the RVOT model was successful. Values of distensibility, compared with literature data, show that TangoPlus is suitable for manufacturing arterial phantoms, with the added benefit of being compatible with PolyJet printing, thus guaranteeing representative anatomical finishing, and quick and inexpensive fabrication. The appealing possibility of printing models of non-uniform wall thickness, resembling more closely certain physiological scenarios, can also be explored. However, this material appears to be too stiff for modelling the more compliant systemic venous system.

Impaired cerebral development in fetuses with congenital cardiovascular malformations: Is it the result of inadequate glucose supply?

PubMed

Rudolph, Abraham M

2016-08-01

Cerebral development may be impaired in fetuses with congenital cardiovascular malformations, particularly hypoplastic left heart syndrome (HLHS) and aortopulmonary transposition (APT). The decreased cerebral arterial pusatility index observed in some of these fetuses led to the belief that cerebral vascular resistance was reduced as a result of arterial hypoxemia and cerebral hypoxia is thought to be responsible for impaired cerebral growth. However, other hemodynamic factors could affect pulsatility index. I propose that cerebral blood flow is reduced in fetuses with HLHS and that reduced glucose, rather than oxygen, delivery interferes with cerebral development. This is based on the fact that most of these fetuses do not have lactate accumulation in the brain.In fetuses with APT, umbilical venous blood, containing oxygen and glucose derived across the placenta, is distributed to the lungs and lower body; venous blood, with low oxygen and glucose content, is delivered to the ascending aorta and brain. Oxygen and glucose delivery may further be reduced by decreased cerebral blood flow resulting from run-off of aortic blood through the ductus arteriosus to the pulmonary circulation during diastole. In APT fetuses, lack of lactate in the brain also supports my proposal that glucose deficiency interferes with cerebral development.

Developmental Toxicity Potential of Nitroguanidine in Rats

DTIC Science & Technology

1988-02-01

shape in which the body was short and thick, particularly through the neck. In the 316 mg/kg/day group, one fetus had bilateral anophthalmia , hypoplastic... Anophthalmia 1/1 Hypoplastic pinnae 1/1 Lowr jaw absent 1/1 Variations Hematoma / /i/ Lips scalloped at edge 1/1 A C.ngle fetus may have more than one...as malformations included cleft palate, malformed mandible, extra vertebrae, anasarca, anophthalmia , abnormal heart, marked enlargement of the

New developments in the treatment of hypoplastic left heart syndrome.

PubMed

Alsoufi, Bahaaldin; Bennetts, Jayme; Verma, Subodh; Caldarone, Christopher A

2007-01-01

In the current decade, the prognosis of newborns with hypoplastic left heart syndrome, previously considered a uniformly fatal condition, has dramatically improved through refinement of rapidly evolving treatment strategies. These strategies include various modifications of staged surgical reconstruction, orthotopic heart transplantation, and hybrid palliation using ductal stenting and bilateral pulmonary artery banding. The variety of treatment approaches are based on different surgical philosophies, and each approach has its unique advantages and disadvantages. Nonetheless, multiple experienced centers have reported improved outcomes in each one of those modalities. The purpose of this review is to outline recent developments in the array of currently available management strategies for neonates with hypoplastic left heart syndrome. Because the vast majority of deaths in this patient population occur within the first months of life, the focus of the review will be evaluation of the impact of these management strategies on survival in the neonatal and infant periods.

Breast cancer in Poland syndrome.

PubMed

Havlik, R J; Sian, K U; Wagner, J D; Binford, R; Broadie, T A

1999-07-01

A 33-year-old African-American woman with a severe manifestation of Poland syndrome developed breast cancer in the ipsilateral breast. She had a severely hypoplastic upper extremity, including symbrachydactyly, and a hypoplastic forearm and upper arm. In addition, she lacked the sternal origin of the pectoralis muscle. She had a very small nipple-areola complex and no axillary hair. This is the first case report of breast cancer developing in the ipsilateral breast of a patient with Poland syndrome.

Downregulation of p300 gene expression in airway mesenchyme of nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Hiromizu; Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro; Takahashi, Toshiaki; Puri, Prem

2014-04-01

Congenital diaphragmatic hernia (CDH) is a relatively common developmental abnormality causing life-threatening respiratory distress at birth. The nitrofen model has been widely used to investigate the pathogenesis of hypoplastic lungs associated with CDH. Embryos lacking p300 and CBP genes are significantly smaller in lung formation. We hypothesized that pulmonary gene expression of p300 and CBP is downregulated during late gestation in the nitrofen-induced CDH model. Time-pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D18 and D21 (n = 8 at each time point). Pulmonary gene expression of p300 and CBP was analyzed by quantitative real-time PCR. Immunohistochemistry was performed to investigate expression and localization of pulmonary p300 and CBP proteins. Relative mRNA expression levels of p300 were significantly decreased in nitrofen-induced hypoplastic lungs on D18 compared to controls (3.00 ± 0.20 vs. 3.76 ± 0.14; p = 0.0039), while CBP levels were not altered. p300 immunoreactivity was markedly diminished in surrounding mesenchymal compartments and nuclei of proximal and distal airway cells, while CBP expression was not altered. Downregulation of p300 gene expression during the early canalicular stage may disrupt epithelial-mesenchymal signaling interactions, contributing to the development of hypoplastic lungs in the nitrofen-induced CDH model.

Nasopharyngoscopic Analyses through Anterior Maxillary Distraction Osteogenesis for Adolescent Patients With Cleft Palate.

PubMed

Imai, Yoshimichi; Nakajo, Tetsu; Nishimura, Kazuaki; Kanzaki, Hiroyuki; Daimaruya, Takayoshi; Satoh, Akimitsu; Igarashi, Kaoru; Tachi, Masahiro

2018-03-01

Anterior maxillary distraction osteogenesis (AMDO) is a novel technique for correcting hypoplastic maxilla by sagittal expansion of the maxilla. Recent reports suggest that AMDO does not have an effect on fragile velopharyngeal function in patients with cleft palate. Furthermore, no studies have evaluated the impact of AMDO on velopharyngeal function.We adopted AMDO to correct severe hypoplastic maxilla in adolescent patients with cleft palate and evaluated its impact on velopharyngeal space and function in 8 patients aged 12 to 21 years who underwent AMDO from 2006 to 2014. All the patients had received treatment for cleft palate; however, they still exhibited marginal velopharyngeal insufficiency. The mean activation of the distractor was 10.9 ± 0.9 mm.We determined changes in velopharyngeal closure ratio and closure pattern via nasopharyngoscopy. Additionally, skeletal changes were evaluated using lateral cephalograms.The mean horizontal advancement in the cephalogram obtained 1 year after the distraction was +6.4 mm. Nasopharyngoscopic examination revealed that no deterioration of velopharyngeal gap had occurred after AMDO in all 8 patients. The velopharyngeal closure pattern changed from coronal to circular in 1 patient.Our results indicate that AMDO achieved correction of hypoplastic maxilla without deterioration in velopharyngeal gap and function. Therefore, AMDO is an effective and optimal approach for correcting hypoplastic maxilla especially in patients with fragile velopharyngeal function, such as those with cleft palate.

Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

PubMed

Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

2016-12-01

Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis. © International & American Associations for Dental Research 2016.

Alagille syndrome with deletion 20p12.2-p12.3 and hypoplastic left heart.

PubMed

Robert, Marie Leema P; Lopez, Tony; Crolla, John; Huang, Shuwen; Owen, Carol; Burvill-Holmes, Lisa; Stumper, Oliver; Turnpenny, Peter D

2007-10-01

We report a male patient born at 37-weeks gestation, weighing 1.885 kg (<0.4th centile). Shortly after birth, he was diagnosed with hypoplastic left heart syndrome for which he underwent a Norwood procedure. Subsequently, he developed problems with failure to thrive and developmental delay. At the age of 4 years his delay in growth and development led to further investigations, which revealed a small de-novo interstitial deletion of chromosome 20p12.2. JAGGED1 haploinsufficiency was confirmed by fluorescence in situ hybridization. Array-comparative genomic hybridization analysis confirmed and quantified an approximate 5.4 Mb interstitial deletion involving the chromosomal region 20p12.2-p12.3. This precise interstitial deletion has not been previously reported. Further clinical evaluation revealed posterior embryotoxon and butterfly vertebrae. He has normal liver function tests, facial features consistent with Alagille syndrome, and mild learning difficulties. To our knowledge this is the first report of Alagille syndrome associated with hypoplastic left heart syndrome.

Normal Range of Fetal Nasal Bone Length during the Second Trimester in an Afro-Caribbean Population and Likelihood Ratio for Trisomy 21 of Absent or Hypoplastic Nasal Bone.

PubMed

Gautier, Manuella; Gueneret, Michèle; Plavonil, Corinne; Jolivet, Eugénie; Schaub, Bruno

2017-01-01

To establish the normal reference range of fetal nasal bone length (NBL) during the second trimester in an Afro-Caribbean population and the likelihood ratio (LR) for fetal trisomy 21. Prenatal records of euploid, non-malformed singleton fetuses who underwent second-trimester ultrasonographic scans at 20-24 weeks of gestation were retrospectively analyzed for NBL and gestational age (GA). Only Afro-Caribbean couples were selected. The relationship between fetal NBL and GA was determined. The data of all fetuses with Down syndrome were provided by the French West Indies Register of Congenital Malformations (REMALAN). There was a significant linear association between fetal NBL and GA (R2 = 0. 354). The 50th percentile for NBL increased from 5.0 to 7.0 mm from week 20 to 24 of gestation. The nasal bone (NB) was absent or hypoplastic in 8.6% of the euploid fetuses and in 69.2% of the trisomy 21 fetuses. The LR for trisomy 21 of absent or hypoplastic NB in an Afro-Caribbean population was 8.02, but only 2.32 when this sign was isolated. The reference range for fetal NBL at 20-24 weeks of gestation in an Afro-Caribbean population and the LR for trisomy 21 of absent or hypoplastic NB differed from the other populations. © 2016 S. Karger AG, Basel.

Anomalous origin of circumflex coronary artery from right pulmonary artery in a hypoplastic left heart syndrome child

PubMed Central

Kansy, Andrzej; Łaniewski-Wołłk, Przemysław

2014-01-01

We describe the case of a newborn with hypoplastic left heart syndrome (HLHS) and aberrant origin of the circumflex coronary artery from the right pulmonary artery. The patient underwent a modified Norwood procedure with direct reimplantation of the circumflex coronary artery to the neo-aorta, but died on the 5th postoperative day because of myocardial failure. Detailed assessment of coronary arteries as part of the routine echocardiographic evaluation of HLHS and intraoperative inspection of them is crucial. PMID:26336423

Prenatal retinoic acid upregulates pulmonary gene expression of PI3K and AKT in nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Sugimoto, Kaoru; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2010-10-01

The precise mechanism of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) still remains unclear. Recently, prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs in the nitrofen model of CDH. The serine/threonine protein kinase B (AKT) plays a key role in lung morphogenesis through epithelial-mesenchymal interaction in phosphatidylinositide 3-kinase (PI3K)-dependent manner. It has been reported that the lung morphogenesis in explants in mice is interfered by inhibitors of PI3K-AKT signaling pathway. Furthermore, we have recently shown that nitrofen inhibits PI3K-AKT signaling during mid-to-late lung morphogenesis in the nitrofen-induced hypoplastic lung. We hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PI3K and AKT in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). 5 mg/kg of RA was given on D18, D19 and D20. The fetuses were harvested on D21, and fetal lungs were obtained and divided into four groups: control, control + RA, nitrofen, nitrofen + RA. The mRNA expression levels of PI3K and AKT were analyzed in each lung by real-time RT-PCR and statistically analyzed. Immunohistochemistry was also performed to evaluate protein expression of PI3K and AKT in the fetal lungs at D21. The pulmonary gene expression levels of PI3K and AKT were significantly upregulated in nitrofen + RA group compared to nitrofen group and control + RA group (p < 0.05), whereas there were no significant differences between controls and control + RA group. Immunoreactivity of PI3K and AKT was markedly increased in nitrofen + RA lungs compared to nitrofen-induced hypoplastic lungs. Upregulation of PI3K and AKT genes after prenatal treatment with RA in the nitrofen-induced hypoplastic lung suggests that RA may have a therapeutic potential in modulating lung alveologenesis by stimulating epithelial-mesenchymal interaction via PI3K-AKT signaling.

Catheter interventions in the staged management of hypoplastic left heart syndrome.

PubMed

Reinhardt, Zdenka; De Giovanni, Joseph; Stickley, John; Bhole, Vinay K; Anderson, Benjamin; Murtuza, Bari; Mehta, Chetan; Miller, Paul; Dhillon, Rami; Stumper, Oliver

2014-04-01

To analyse the current practice and contribution of catheter interventions in the staged management of patients with hypoplastic left heart syndrome. This study is a retrospective case note review of 527 patients undergoing staged Norwood/Fontan palliation at a single centre between 1993 and 2010. Indications and type of catheter interventions were reviewed over a median follow-up period of 7.5 years. A staged Norwood/Fontan palliation for hypoplastic left heart syndrome was performed in 527 patients. The 30-day survival rate after individual stages was 76.5% at Stage I, 96.3% at Stage II, and 99.4% at Stage III. A total of 348 interventions were performed in 189 out of 527 patients. Freedom from catheter intervention in survivors was 58.2% before Stage II and 46.7% before Stage III. Kaplan-Meier freedom from intervention post Fontan completion was 55% at 10.8 years of follow-up. Post-stage I interventions were mostly directed to relieve aortic arch obstruction--84 balloon angioplasties--and augment pulmonary blood flow--15 right ventricle-to-pulmonary conduit interventions; post-Stage II interventions centred on augmenting size of the left pulmonary artery--73 procedures and abolishing systemic venous collaterals--32 procedures. After Stage III, the focus was on manipulating the size of the fenestration--42 interventions--and the left pulmonary artery -31 procedures. Interventional cardiac catheterisation constitutes an integral part in the staged palliative management of patients with hypoplastic left heart syndrome. Over one-third (37%) of patients undergoing staged palliation required catheter intervention over the follow-up period.

Parenting under pressure: a grounded theory of parenting young children with life-threatening congenital heart disease.

PubMed

Rempel, Gwen R; Ravindran, Vinitha; Rogers, Laura G; Magill-Evans, Joyce

2013-03-01

To report a grounded theory study to describe the process of parenting young children who have survived hypoplastic left heart syndrome to inform parent-focused interventions. Technological advances in paediatric cardiology worldwide have improved the survival rates for young children with hypoplastic left heart syndrome who undergo staged surgical palliation. These children, however, are at risk for life-threatening complications and parents are charged with the responsibility to monitor their children at home with minimal support and guidance from healthcare professionals once home. A constructivist grounded theory study. The study was conducted in 2006-2008. Participants were 25 parents (15 mothers, 10 fathers) and 28 grandparents (17 grandmothers, 11 grandfathers) of 15 young children (6 months-4·5 years) who had undergone the Sano surgical approach for hypoplastic left heart syndrome. The 53 interviews were digitally recorded, transcribed and analysed using open and focused coding, constant comparative analysis and memoing. A process of Parenting under Pressure emerged that was characterized by four overlapping and re-emerging phases: (1) realizing and adjusting to the inconceivable; (2) growing increasingly attached; (3) watching for and accommodating the unexpected; and (4) encountering new challenges. In-depth understanding of the phases of Parenting under Pressure provides direction for nurses to support parents of children who survive hypoplastic left heart syndrome. Interventions that help carers of children with complex health conditions move through the phases of our Parenting under Pressure process may help them safeguard the survival of their children, and their own survival as parents as they manage multiple demands. © 2012 Blackwell Publishing Ltd.

Agenesis of the gallbladder with hypoplastic cystic duct diagnosed at laparoscopy.

PubMed

Kwon, A-Hon; Yanagimoto, Hiroaki; Matsui, Yoichi; Imamura, Atsushi

2006-08-01

An 86-year-old man was admitted to our department with complaints of intermittent upper abdominal pain. Ultrasonography of the abdomen showed dilated extrahepatic bile ducts containing stones; however, the gallbladder was not clearly identified. Magnetic resonance cholangiopancreatography showed dilated extrahepatic ducts and choledocholithiasis without gallbladder visualization. The stone extraction was performed with endoscopic sphincterotomy. Three-dimensional images using spiral-computed tomography after intravenous-infusion cholangiography clearly demonstrated an obstruction of the cystic duct. The patient was scheduled for laparoscopic cholecystectomy. At laparoscopy, the gallbladder fossa was not identified on the undersurface of the liver. Despite a thorough examination of the intrahepatic (left-sided within the lesser omentum), retroperitoneal, retrohepatic (within the falciform ligament), retroduodenal, and retropancreatic areas using laparoscopic ultrasonography, the gallbladder was not found. After careful dissection of the hepatoduodenal ligament, the dilated extrahepatic bile duct and a 1-cm length of hypoplastic cystic duct were found. Gallbladder agenesis is usually accompanied by the lack of the cystic duct. The present case is the third report of gallbladder agenesis with a patent or hypoplastic cystic duct.

Septum primum atrial septal defect in an infant with hypoplastic left heart syndrome.

PubMed

Loar, Robert W; Burkhart, Harold M; Taggart, Nathaniel W

2014-08-01

Hypoplastic left heart syndrome (HLHS) is a form of congenital heart disease characterized by severe underdevelopment of the left heart, leading to inadequate systemic blood flow. Several different atrial septal morphologies are observed in HLHS, most commonly a secundum atrial septal defect, patent foramen ovale, intact septum, and leftward displacement of the superior attachment of the septum primum. It has been postulated that atrial septal development is associated with the development of the left heart. We present a case of a newborn infant with HLHS and the unusual finding of a primum ASD.

Reconstructing impairment of secretory ameloblast function in porcine teeth by analysis of morphological alterations in dental enamel

PubMed Central

Witzel, Carsten; Kierdorf, Uwe; Dobney, Keith; Ervynck, Anton; Vanpoucke, Sofie; Kierdorf, Horst

2006-01-01

We studied the relationship between the macroscopic appearance of hypoplastic defects in the dental enamel of wild boar and domestic pigs, and microstructural enamel changes, at both the light and the scanning electron microscopic levels. Deviations from normal enamel microstructure were used to reconstruct the functional and related morphological changes of the secretory ameloblasts caused by the action of stress factors during amelogenesis. The deduced reaction pattern of the secretory ameloblasts can be grouped in a sequence of increasingly severe impairments of cell function. The reactions ranged from a slight enhancement of the periodicity of enamel matrix secretion, over a temporary reduction in the amount of secreted enamel matrix, with reduction of the distal portion of the Tomes' process, to either a temporary or a definite cessation of matrix formation. The results demonstrate that analysis of structural changes in dental enamel allows a detailed reconstruction of the reaction of secretory ameloblasts to stress events, enabling an assessment of duration and intensity of these events. Analysing the deviations from normal enamel microstructure provides a deeper insight into the cellular changes underlying the formation of hypoplastic enamel defects than can be achieved by mere inspection of tooth surface characteristics alone. PMID:16822273

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

PubMed

Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

2015-05-01

To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline (r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height (p < 0.05). Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

Del(12)(p11.21p12.2) associated with an asphyxiating thoracic dystrophy or chondroectodermal dysplasia-like syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagai, T.; Kato, R.; Hasegawa, T.

1995-01-02

We describe a 5-year-old Japanese boy who has some radiographic findings characteristic of asphyxiating thoracic dystrophy (ATD)-chondroectodermal dysplasia with a de novo chromosome abnormality. He also has mild mental retardation, short stature, hypoplastic hair and skin, oligodontia, small thoracic cage, hypoplastic pelvis and cone-shaped epiphyses of hands. On cytogenetic studies he was found to have a de novo del(12)(p11.21p12.2). These results suggest that the locus of the gene associated with ATD-chondroectodermal dysplasia may be situated at 12p11.21p12.2. 11 refs., 2 figs.

The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia.

PubMed

Mahood, Thomas H; Johar, Dina R; Iwasiow, Barbara M; Xu, Wayne; Keijzer, Richard

2016-05-01

We currently do not know how the herbicide nitrofen induces lung hypoplasia and congenital diaphragmatic hernia in rats. Our aim was to compare the differentially expressed transcriptome of nitrofen-induced hypoplastic lungs to control lungs in embryonic day 13 rat embryos before the development of embryonic diaphragmatic defects. Using next-generation sequencing technology, we identified the expression profile of microRNA (miRNA) and mRNA genes. Once the dataset was validated by both RT-qPCR and digital-PCR, we conducted gene ontology, miRNA target analysis, and orthologous miRNA sequence matching for the deregulated miRNAs in silico. Our study identified 186 known mRNA and 100 miRNAs which were differentially expressed in nitrofen-induced hypoplastic lungs. Sixty-four rat miRNAs homologous to known human miRNAs were identified. A subset of these genes may promote lung hypoplasia in rat and/or human, and we discuss their associations. Potential miRNA pathways relevant to nitrofen-induced lung hypoplasia include PI3K, TGF-β, and cell cycle kinases. Nitrofen-induced hypoplastic lungs have an abnormal transcriptome that may lead to impaired development.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

PubMed

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

PubMed Central

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

Comprehensive dental management in a Hallermann-Streiff syndrome patient with unusual radiographic appearance of teeth.

PubMed

Gungor, O Erken; Nur, B Guzel; Yalcin, H; Karayilmaz, H; Mihci, E

2015-01-01

Hallermann-Streiff syndrome (HSS) is a genetic disorder characterized by proportionate dwarfism, birdlike facies, hypotrichosis, skin atrophy, dyscephaly, bilateral microphthalmia, congenital cataracts, a narrow, weak, beaked nose, a hypoplastic mandible, and orodental anomalies. Occurrence is sporadic and distinct patterns of inheritance have not been found. This case report describes the dental management of a 3-year-old girl patient with HSS, who had unusual radiographic appearance of teeth. Furthermore, dental treatments and a 30-month follow-up period of the patient with this rare tooth structure malformation have been presented.

Turner's hypoplasia and non-vitality: A case report of sequelae in permanent tooth

PubMed Central

Geetha Priya, P. R.; John, John B.; Elango, Indumathi

2010-01-01

Hypoplasia is the result of disruption in the process of enamel matrix formation, which in turn causes defect in quality and thickness of enamel. Four cases of Turner's hypoplastic teeth with a previous history of trauma/infection in their primary predecessors at the age of 2-3 years have been reported. These hypoplastic teeth had turned non-vital without any carious insult, cavitation or further trauma. This article thereby stresses the importance of early detection of enamel hypoplasia and proper management at the earliest possible stage to enable an efficient prevention from clinically non-evident microbial invasion in the dentinal tubules and concomitant pulp pathosis. PMID:22114432

Unusual manifestations of ectodermal dysplasia-syndactyly syndrome type I in two Yemeni siblings.

PubMed

Mohammad, Alshami

2015-01-15

Ectodermal dysplasias (EDs) are a group of genodermatoses characterized by malformations of tissues derived from the ectoderm, including the skin, its appendages (hair, nails, sweat glands), teeth, and the breasts. Ectodermal dysplasia syndactyly syndrome (EDSS) is a rare, newly described type of ED involving syndactyly. We report 2 Yemeni siblings with typical EDSS manifestations, including bilateral, partial cutaneous syndactyly of the fingers and toes; sparse, coarse, brittle scalp hair, eyebrows, and eyelashes; and conical, widely spaced teeth with enamel notches. In addition, the siblings presented with other features hitherto not described for this syndrome, such as adermatoglyphia, onychogryphosis, hypoplastic widely spaced nipples, hypoplastic thumbs, and red scalp hair.

A novel homozygous Arg222Trp missense mutation in WNT7A in two sisters with severe Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

PubMed

Kantaputra, Piranit N; Mundlos, Stefan; Sripathomsawat, Warissara

2010-11-01

Al-Awadi/Raas-Rothschild/Schinzel phocomelia (AARRS) syndrome, a rare autosomal recessive disorder, comprises malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. Mutations in WNT7A have been reported as cause of the syndrome. We report on two sisters in a Thai family with short and malformed long bones, absent fibulae, flexion contracture of digits, and a/hypoplastic nails. Fusion between severely malformed femora and slender tibiae has never been reported in patients with WNT7A mutations. Lower limbs were more severely malformed than the upper ones and the pelvis was also severely affected. Multiple fusions of long bones and of the femoral heads to the acetabula were evident. A novel homozygous missense mutation in coding exon 4 of the WNT7A was detected in both affected daughters (c.664C > T) leading to an amino acid exchange from arginine to tryptophan (p.Arg222Trp; R222W). The phenotype is likely to result from an abnormality of all three signaling centers in the developing limb resulting in ventralization with a loss of dorsal structures (aplasia/hypoplasia of nails) a loss of anterior-posterior identity (single distal bones in lower limb without polarity) and an outgrowth defect resulting in distal truncations. © 2010 Wiley-Liss, Inc.

Long-term Results After Open Mitral Commissurotomy for a One-Month-Old Infant With Mitral Stenosis.

PubMed

Kitaichi, Takashi; Sugano, Mikio; Arase, Hiroki; Kawatani, Yohei; Kameta, Kanako; Kurobe, Hirotsugu; Fujimoto, Eiki; Ono, Akemi; Hayabuchi, Yasunobu; Fujita, Hiroshi; Sogabe, Hitoshi; Kitagawa, Tetsuya

2017-01-01

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley's approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle. J. Med. Invest. 64: 187-191, February, 2017.

A novel AMELX mutation causes hypoplastic amelogenesis imperfecta.

PubMed

Kim, Young-Jae; Kim, Youn Jung; Kang, Jenny; Shin, Teo Jeon; Hyun, Hong-Keun; Lee, Sang-Hoon; Lee, Zang Hee; Kim, Jung-Wook

2017-04-01

Amelogenesis imperfecta (AI) is a hereditary genetic defect affecting tooth enamel. AI is heterogeneous in clinical phenotype as well as in genetic etiology. To date, more than 10 genes have been associated with the etiology of AI. Amelogenin is the most abundant enamel matrix protein, most of which is encoded by the amelogenin gene in the X-chromosome (AMELX). More than 16 alternative splicing transcripts have been identified in the murine Amelx gene. The purpose of this study was to identify the genetic cause of an AI family. We recruited a family with hypoplastic AI and performed mutational analysis on the candidate gene based on the clinical phenotype. Mutational analysis revealed a missense mutation in exon 6 (NM_182680.1; c.242C > T), which changes a sequence in a highly conserved amino acid (NP_872621.1; p.Pro81Leu). Furthermore, a splicing assay using a minigene displayed that the mutation changed the mRNA splicing repertory. In this study, we identified a novel AMELX missense mutation causing hypoplastic AI, and this mutation also resulted in altered mRNA splicing. These results will not only expand the mutation spectrum causing AI but also broaden our understanding of the biological mechanism of enamel formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aase syndrome

MedlinePlus

Aase-Smith syndrome; Hypoplastic anemia - triphalangeal thumbs, Aase-Smith type ... Jones KL, Jones MC, Del Campo M, eds. Smith's Recognizable Patterns of Human Malformation . 7th ed. Philadelphia, ...

Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome.

PubMed

Sandeep, Nefthi; Punn, Rajesh; Balasubramanian, Sowmya; Smith, Shea N; Reinhartz, Olaf; Zhang, Yulin; Wright, Gail E; Peng, Lynn F; Wise-Faberowski, Lisa; Hanley, Frank L; McElhinney, Doff B

2018-04-01

Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling. This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed. On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn. In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Impact of noncardiac congenital and genetic abnormalities on outcomes in hypoplastic left heart syndrome.

PubMed

Patel, Angira; Hickey, Edward; Mavroudis, Constantine; Jacobs, Jeffrey P; Jacobs, Marshall L; Backer, Carl L; Gevitz, Melanie; Mavroudis, Constantine D

2010-06-01

Hypoplastic left heart syndrome may coexist with noncardiac congenital defects or genetic syndromes. We explored the impact of such lesions on outcomes after staged univentricular palliation. Society of Thoracic Surgeons database 2002 to 2006: Children diagnosed with hypoplastic left heart syndrome who underwent stage 1 Norwood (n = 1,236), stage 2 superior cavopulmonary anastamosis (n = 702) or stage 3 Fontan (n = 553) procedures were studied. In-hospital mortality, postoperative complications, and length of stay were compared at each stage between those with and without noncardiac-genetic defects. Congenital Heart Surgeons' Society database 1994 to 2001: All 703 infants enrolled in the Congenital Heart Surgeons' Society critical left ventricular outflow tract obstruction study who underwent primary stage 1 palliation were reviewed. The impact of noncardiac defects-syndromes on survival was explored using multivariable parametric models with bootstrap bagging. Society of Thoracic Surgeons database: Stage 1 in-hospital mortality (26% vs 20%, p = 0.04) and mean postoperative length of stay (42 versus 31 days, p < 0.0001) were greater, and postoperative complications significantly more prevalent in infants with noncardiac-genetic defects. Congenital Heart Surgeons' Society database: Noncardiac-genetic defects were present in 55 (8%). Early hazard for death after Norwood was significantly worse in infants with noncardiac defects-syndromes (p = 0.008). Chromosomal defects (n = 14) were highly unfavorable: the early risk of death was doubled (10-year survival 25 +/- 9% vs 54 +/- 2%, p = 0.005). Turner syndrome accounted for the majority of chromosomal defects in this population (11 of 14, 79%). Mode of death was rarely attributable to the noncardiac-genetic defect. Survival in hypoplastic left heart syndrome is strongly influenced by the presence of noncardiac abnormalities. Strategies to improve mortality in infants with noncardiac abnormalities should be explored. Presence of chromosomal defects, especially Turner syndrome, should enter decision-management options for parents and physicians. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Neurodevelopmental Outcome in Children after Fetal Cardiac Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome.

PubMed

Laraja, Kristin; Sadhwani, Anjali; Tworetzky, Wayne; Marshall, Audrey C; Gauvreau, Kimberlee; Freud, Lindsay; Hass, Cara; Dunbar-Masterson, Carolyn; Ware, Janice; Lafranchi, Terra; Wilkins-Haug, Louise; Newburger, Jane W

2017-05-01

To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment. Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory. Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms (P < .001) and similar to published reports in patients with hypoplastic left heart syndrome without fetal intervention; scores in the single ventricular versus biventricular group were 97 ± 19 vs 89 ± 14, respectively (P = .10). On multivariable analysis, independent predictors of a lower General Adaptive Composite score were total hospital duration of stay in the first year of life (P = .001) and, when forced into the model, biventricular status (P = .02). For all other neurodevelopmental questionnaires (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar. Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy have the greatest effect on neurodevelopmental outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

"Missing perikymata"--fact or fiction? A study on chimpanzee (Pan troglodytes verus) canines.

PubMed

Kierdorf, Horst; Witzel, Carsten; Kierdorf, Uwe; Skinner, Matthew M; Skinner, Mark F

2015-06-01

Recently, a lower than expected number of perikymata between repetitive furrow-type hypoplastic defects has been reported in chimpanzee canines from the Fongoli site, Senegal (Skinner and Pruetz: Am J Phys Anthropol 149 (2012) 468-482). Based on an observation in a localized enamel fracture surface of a canine of a chimpanzee from the Taï Forest (Ivory Coast), these authors inferred that a nonemergence of striae of Retzius could be the cause for the "missing perikymata" phenomenon in the Fongoli chimpanzees. To check this inference, we analyzed the structure of outer enamel in three chimpanzee canines. The teeth were studied using light-microscopic and scanning-electron microscopic techniques. Our analysis of the specimen upon which Skinner and Pruetz (Am J Phys Anthropol 149 (2012) 468-482) had made their original observation does not support their hypothesis. We demonstrate that the enamel morphology described by them is not caused by a nonemergence of striae of Retzius but can be attributed to structural variations in outer enamel that result in a differential fracture behavior. Although rejecting the presumed existence of nonemergent striae of Retzius, our study provided evidence that, in furrow-type hypoplastic defects, a pronounced tapering of Retzius increments can occur, with the striae of Retzius forming acute angles with the outer enamel surface. We suggest that in such cases the outcrop of some striae of Retzius is essentially unobservable at the enamel surface, causing too low perikymata counts. The pronounced tapering of Retzius increments in outer enamel presumably reflects a mild to moderate disturbance of the function of late secretory ameloblasts. © 2015 Wiley Periodicals, Inc.

Serial changes in anatomy and ventricular function on dual-source cardiac computed tomography after the Norwood procedure for hypoplastic left heart syndrome.

PubMed

Goo, Hyun Woo

2017-12-01

Accurate evaluation of anatomy and ventricular function after the Norwood procedure in hypoplastic left heart syndrome is important for treatment planning and prognostication, but echocardiography and cardiac MRI have limitations. To assess serial changes in anatomy and ventricular function on dual-source cardiac CT after the Norwood procedure for hypoplastic left heart syndrome. In 14 consecutive patients with hypoplastic left heart syndrome, end-systolic and end-diastolic phase cardiac dual-source CT was performed before and early (average: 1 month) after the Norwood procedure, and repeated late (median: 4.5 months) after the Norwood procedure in six patients. Ventricular functional parameters and indexed morphological measurements including pulmonary artery size, right ventricular free wall thickness, and ascending aorta size on cardiac CT were compared between different time points. Moreover, morphological features including ventricular septal defect, endocardial fibroelastosis and coronary ventricular communication were evaluated on cardiac CT. Right ventricular function and volumes remained unchanged (indexed end-systolic and end-diastolic volumes: 38.9±14.0 vs. 41.1±21.5 ml/m 2 , P=0.7 and 99.5±30.5 vs. 105.1±33.0 ml/m 2 , P=0.6; ejection fraction: 60.1±7.3 vs. 63.8±7.0%, P=0.1, and indexed stroke volume: 60.7±18.0 vs. 64.0±15.6 ml/m 2 , P=0.5) early after the Norwood procedure, but function was decreased (ejection fraction: 64.2±2.6 vs. 58.1±7.1%, P=0.01) and volume was increased (indexed end-systolic and end-diastolic volumes: 39.2±14.9 vs. 68.9±20.6 ml/m 2 , P<0.003 and 107.8±36.5 vs. 162.9±36.2 ml/m 2 , P<0.006, and indexed stroke volume: 68.6±21.7 vs. 94.0±21.3 ml/m 2 , P=0.02) later. Branch pulmonary artery size showed a gradual decrease without asymmetry after the Norwood procedure. Right and left pulmonary artery stenoses were identified in 21.4% (3/14) of the patients. Indexed right ventricular free wall thickness showed a significant increase early after the Norwood procedure (25.5±3.5 vs. 34.8±5.1 mm/m 2 , P=0.01) and then a significant decrease late after the Norwood procedure (34.8±5.1 vs. 27.2±4.2 mm/m 2 , P<0.0001). The hypoplastic ascending aorta smaller than 2 mm in diameter was identified in 21.4% (3/14) of the patients. Ventricular septal defect (n=3), endocardial fibroelastosis (n=2) and coronary ventricular communication (n=1) were detected on cardiac CT. Cardiac CT can be used to assess serial changes in anatomy and ventricular function after the Norwood procedure in patients with hypoplastic left heart syndrome.

[Urethroplasty in hypoplastic-dysplastic corpus spongiosum and short urethra].

PubMed

Vitarelli, Antonio; Divenuto, Lucia; Altomare, Mauro; Masiello, Giuseppe; Pagliarulo, Arcangelo

2013-01-01

Congenital penile curvature and chordee are a rare malformative condition most frequently associated with hypospadias, but varying degrees of penile curvature are observed with an orthotopic meatus. Disease becomes evident after puberty, when curvature becomes more apparent with erection. We present a case of a young man (16 years old), with ventral congenital penile curvature without hypospadias and with hypoplastic-dysplastic corpus spongiosum and short urethra, who could not have normal sexual intercourses. The patient underwent first-stage urethroplasty with urethral opening and graft of buccal mucosa and creation of a temporary hypospadic meatus. No post-operative complications were observed. There were no residual penile curvatures. Results are promising and satisfactory after the first surgical stage and provide a solid ground for the final reconstruction.

Hybrid procedures for an infant with hypoplastic left heart syndrome with intact atrial septum.

PubMed

Suzuki, Shoji; Kise, Hiroaki; Kaga, Shigeaki; Hoshiai, Minako; Koizumi, Keiichi; Hasebe, Yohei; Motohashi, Shinya; Matsumoto, Masahiko

2015-08-01

A boy, prenatally diagnosed as hypoplastic left heart syndrome (HLHS) with intact atrial septum (IAS) was successfully treated by hybrid procedures. He underwent emergent catheter atrial septostomy and stent insertion in the atrial septum on Day 1 and then underwent bilateral pulmonary artery banding, ductal stent insertion, modified Norwood operation, bidirectional Glenn's operation and finally Fontan type operation at 2 years of age. Considering the presence of decompression pathway from the left atrium in HLHS with IAS, we should organize a treatment team for collaborative work and plan an appropriate treatment strategy before delivery. Although his clinical course has been uneventful until now, closer medical observation is warranted because he may have coexisting pulmonary disease.

Hypoplastic left heart syndrome - a review of supportive percutaneous treatment.

PubMed

Moszura, Tomasz; Góreczny, Sebastian; Dryżek, Paweł

2014-01-01

Due to the complex anatomical and haemodynamic consequences of hypoplastic left heart syndrome (HLHS), patients with the condition require multistage surgical and supportive interventional treatment. Percutaneous interventions may be required between each stage of surgical palliation, sometimes simultaneously with surgery as hybrid interventions, or after completion of multistage treatment. Recent advances in the field of interventional cardiology, including new devices and techniques, have significantly contributed to improving results of multistage HLHS palliation. Knowledge of the potential interventional options as well as the limitation of percutaneous interventions will enable the creation of safe and effective treatment protocols in this highly challenging group of patients. In this comprehensive review we discuss the types, goals, and potential complications of transcatheter interventions in patients with HLHS.

Dental stigmata and enamel thickness in a probable case of congenital syphilis from XVI century Croatia.

PubMed

Lauc, Tomislav; Fornai, Cinzia; Premužić, Zrinka; Vodanović, Marin; Weber, Gerhard W; Mašić, Boris; Rajić Šikanjić, Petra

2015-10-01

To analyse the dental remains of an individual with signs of congenital syphilis by using macroscopic observation, CBCT and micro-CT images, and the analysis of the enamel thickness. Anthropological analysis of human skeletal remains from the 16th century archaeological site Park Grič in Zagreb, Croatia discovered a female, 17-20 years old at the time of death, with dental signs supportive of congenital syphilis: mulberry molars and canine defects, as well as non-specific hypoplastic changes on incisors. The focus of the analysis was on three aspects: gross morphology, hypoplastic defects of the molars, canines and incisors, as well as enamel thickness of the upper first and second molars. The observed morphology of the first molars corresponds to the typical aspect of mulberry molars, while that of the canines is characterised by hypomineralisation. Hypoplastic grooves were observed on the incisal edges of all incisors. The enamel of the first molars is underdeveloped while in the second molars a thick-enamelled condition is observed. Our observations for the dental and skeletal evidence are supportive to a diagnosis of congenital syphilis for this specimen from XVI century Croatia. The use of CT imaging helped documenting the diagnostic features and quantifying the effect of the dental stigmata on first molars. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.

PubMed

Santos, Marta; Bastos, Pedro; Gonzaga, Silvia; Roriz, José-Mário; Baptista, Maria J; Nogueira-Silva, Cristina; Melo-Rocha, Gustavo; Henriques-Coelho, Tiago; Roncon-Albuquerque, Roberto; Leite-Moreira, Adelino F; De Krijger, Ronald R; Tibboel, Dick; Rottier, Robbert; Correia-Pinto, Jorge

2006-04-01

Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.

Expression of Iroquois genes is up-regulated during early lung development in the nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Lukošiūtė, Aušra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2011-01-01

Iroquois homeobox (Irx) genes have been implicated in the early lung morphogenesis of vertebrates. Irx1-3 and Irx5 gene expression is seen in fetal lung in rodents up to day (D) 18.5 of gestation. Fetal lung in Irx knockdown mice shows loss of mesenchyme and dilated airspaces, whereas nitrofen-induced hypoplastic lung displays thickened mesenchyme and diminished airspaces. We hypothesized that the Irx genes are up-regulated during early lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed either to olive oil or nitrofen on D9. Fetal lungs harvested on D15 were divided into control and nitrofen groups; and the lungs harvested on D18 were divided into control, nitrofen without congenital diaphragmatic hernia (CDH[-]), and nitrofen with CDH (CDH[+]). Irx gene expression levels were analyzed by reverse transcriptase polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of Irx family. Pulmonary Irx1-3 and Irx5 messenger RNA expression levels were significantly up-regulated in nitrofen group compared with controls at D15. On D15, Irx immunoreactivity was increased in nitrofen-induced hypoplastic lung compared with controls. Overexpression of Irx genes in the early lung development may cause pulmonary hypoplasia in the nitrofen CDH model by inducing lung dysmorphogenesis with thickened mesenchyme and diminished airspaces. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of self-expandable and balloon-expanding stents for hybrid ductal stenting in hypoplastic left heart complex.

PubMed

Goreczny, Sebastian; Qureshi, Shakeel A; Rosenthal, Eric; Krasemann, Thomas; Nassar, Mohamed S; Anderson, David R; Morgan, Gareth J

2017-07-01

We aimed to compare the procedural and mid-term performance of a specifically designed self-expanding stent with balloon-expandable stents in patients undergoing hybrid palliation for hypoplastic left heart syndrome and its variants. The lack of specifically designed stents has led to off-label use of coronary, biliary, or peripheral stents in the neonatal ductus arteriosus. Recently, a self-expanding stent, specifically designed for use in hypoplastic left heart syndrome, has become available. We carried out a retrospective cohort comparison of 69 neonates who underwent hybrid ductal stenting with balloon-expandable and self-expanding stents from December, 2005 to July, 2014. In total, 43 balloon-expandable stents were implanted in 41 neonates and more recently 47 self-expanding stents in 28 neonates. In the balloon-expandable stents group, stent-related complications occurred in nine patients (22%), compared with one patient in the self-expanding stent group (4%). During follow-up, percutaneous re-intervention related to the ductal stent was performed in five patients (17%) in the balloon-expandable stent group and seven patients (28%) in self-expanding stents group. Hybrid ductal stenting with self-expanding stents produced favourable results when compared with the results obtained with balloon-expandable stents. Immediate additional interventions and follow-up re-interventions were similar in both groups with complications more common in those with balloon-expandable stents.

Successful Repair of Hypoplastic Left Heart Syndrome With Intact Atrial Septum, Congenital Diaphragm Hernia, and Anomalous Origin of Coronary Artery: Defying the Odds.

PubMed

Sathanandam, Shyam; Kumar, T K Susheel; Feliz, Alexander; Knott-Craig, Christopher J

2016-07-01

We report a case of an infant who was postnatally diagnosed with hypoplastic left heart syndrome and an intact atrial septum who underwent emergent atrial decompression followed by the Norwood operation. She was also found to have a congenital diaphragmatic hernia on the left side and a congenital eventration of the right diaphragm, both requiring surgical repair. She was later found to have an anomalous origin of the left circumflex coronary artery from the right pulmonary artery that was ligated at the time of the bilateral bidirectional Glenn operation. She is currently thriving at home, defying all odds. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Anomalous Origin of Coronary Artery From Main Pulmonary Artery in Hypoplastic Left Heart Syndrome.

PubMed

Turiy, Yuliya; Douglas, William; Balaguru, Duraisamy

2015-12-01

We report a case of anomalous origin of the left anterior descending coronary artery (LAD) from the main pulmonary artery in a child with hypoplastic left heart syndrome (mitral atresia/aortic atresia). Mechanical circulatory support was necessary because of the inability to wean from cardiopulmonary bypass after the Norwood procedure. The patient died at 4 months of age having continued depressed right ventricular function. The diagnosis was made during a catheterization performed 6 weeks after surgery because of concern for stenosis of Blalock-Taussig shunt. We believe his prolonged postoperative recovery and eventual demise can partially be attributed to lack of cardioplegia to the anomalous LAD territory during surgery. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Unexpected infant death due to hypoplastic left heart syndrome: a case report.

PubMed

Hayashizaki, Yoshie; Usui, Kiyotaka; Moriya, Takuya; Hashiyada, Masaki; Usui, Akihito; Hosokai, Yoshiyuki; Kawasumi, Yusuke; Saito, Haruo; Funayama, Masato

2011-11-01

A female infant was found unresponsive at home. The mother alleged that she delivered the baby at home 13 days prior to the death. The mother did not have any prenatal examinations during the pregnancy and the infant was not examined by a doctor until death. The autopsy revealed that the cause of death was hypoplastic left heart syndrome (HLHS) and the infant's chest showed bilateral breast enlargement. Forensic pathologists may encounter very rare pathological findings with unexpected infant deaths. Some, like HLHS, are serious congenital heart defects related to the cause of death, and others are unique phenomena unrelated to the cause of death such as breast swelling and discharge called "witch's milk." In this case, we observed both findings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Facts about Truncus Arteriosis

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... usual two vessels (the main pulmonary artery and aorta ). What is Truncus Arteriosus Click here to view ...

Infant health after heart surgery.

PubMed

2016-11-08

Background The number of infants who survive initial surgery for complex congenital heart disease (CHD), such as hypoplastic left heart syndrome, is increasing, but they are often left with residual complex health needs.

[Efficacy of coarctation resection and aortoplasty with autologous pulmonary artery patch strategy for treating coarctation of the aorta combined with hypoplastic aortic arch in infants].

PubMed

Ma, Z L; Yan, J; Li, S J; Hua, Z D; Yan, F X; Wang, X; Wang, Q

2018-03-24

Objective: To investigate the outcomes of coarctation resection and aortoplasty with autologous pulmonary artery patch for treating coarctation of the aorta combined with hypoplastic aortic arch in infants. Methods: Clinical data of 21 infants with coarctation of the aorta and hypoplastic aortic arch, who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch in Fuwai hospital from January 2009 to June 2016 were retrospectively analyzed. The age of the patients was 4 (2, 5) months,and the body weight of the patients was (5.3±1.6) kg. The patients were followed up to observe the surgery effect. Results: No perioperative death and serious complications occurred. When the patients were discharged,the systolic blood pressure of the right upper limb was lower than the preoperative systolic blood pressure ((85.7±5.9) mmHg(1 mmHg=0.133 kPa) vs. (100.7±16.6) mmHg, P< 0.001),and the systolic blood pressure of the right lower limb was higher than the preoperative systolic blood pressure ((98.7±13.3) mmHg vs. (85.6±20.8) mmHg, P< 0.001). The pressure gradient of aortic coarctation detected by echocardiography was lower than the preoperative pressure gradient ((13.1±3.8) mmHg vs. (46.2±17.1) mmHg, P< 0.001). No restenosis was detected by echocardiography at discharge. Follow-up data were obtained in 19 patients, and the follow-up time was 18 (8, 45) months.The patients grew well, and no death occurred. Restenosis occurred in 3 cases, 1 patient underwent aortic balloon dilatation and the remaining 2 patients were under follow up observation. Computed tomography angiography showed that the morphology of aortic arch was normal without signs of aortic aneurysm. Conclusion: Coarctation resection with autologous pulmonary artery patch aortoplastystrategy is considered as a safe and effective surgical method for management of infant coarctation with hypoplastic aortic arch, and this surgery method is related with satisfactory early and mid-term outcomes in this patient cohort.

The New Concept of Univentricular Heart

PubMed Central

Frescura, Carla; Thiene, Gaetano

2014-01-01

The concept of univentricular heart moved from hearts with only one ventricle connected with atria [double inlet ventricle or absent atrioventricular (AV) connection] to hearts not amenable to biventricular repair, namely hearts with two ventricles unable to sustain separately pulmonary and systemic circulations in sequence. In the latter definition, even hearts with one hypoplastic ventricle are considered “functional” univentricular hearts. They include pulmonary/aortic atresia or severe stenosis with hypoplastic ventricle, and rare conditions like huge intramural cardiac tumors and Ebstein anomaly with extreme atrialization of right ventricular cavity. In this setting, the surgical repair is univentricular with “Fontan” operation, bypassing the ventricular mass. In other words, functionally univentricular heart is a condition in which, after surgery, only one ventricle sustain systemic circulation. Univentricular hearts (double inlet or absent AV connection) almost invariably show two ventricular chambers, one main and one accessory, which lacks an inlet portion. The latter is located posteriorly when morphologically left and anteriorly when morphologically right. As far as double inlet left ventricle, this is usually associated with discordant ventriculo-arterial (VA) connection (transposition of the great arteries) and all the blood flow to the aorta, which takes origin from the hypoplastic anterior right ventricle, is ventricular septal defect (bulbo-ventricular foramen) dependent. If restrictive, an aortic arch obstruction may be present. Double inlet left ventricle may be rarely associated with VA concordance (Holmes heart). As far as double inlet right ventricle with posterior hypoplastic left ventricular cavity, ventriculo-arterial connection is usually of double outlet type; thus the term double inlet–outlet right ventricle may be coined. Absent right or left AV connection may develop in the setting of both d- or l-loop, whatever the situs. In this condition, the contra-lateral patent AV valve may be either mitral or tricuspid in terms of morphology and the underlying ventricle (main chamber) either morphologically left or right. Establishing the loop, whatever right or left (also called right or left ventricular topology), is a fundamental step in the segmental-sequential analysis of congenital heart disease. PMID:25072035

Combined Brown syndrome and superior oblique palsy without a trochlear nerve: case report.

PubMed

Yang, Hee Kyung; Kim, Jae Hyoung; Kim, Ji-Soo; Hwang, Jeong-Min

2017-08-25

Congenital Brown syndrome is characterized by limited elevation particularly during adduction. The pathogenesis of congenital Brown syndrome is still controversial. A 6-year-old boy had been tilting his head to the left since infancy. He showed right hypertropia (RHT) of 2 prism diopters (Δ) in the primary position. He showed RHT 6Δ in right gaze, RHT 2Δ in left gaze, RHT 12Δ in right head tilt, and orthotropia in left head tilt. The right eye showed limitation of elevation and depression on adduction, and the left eye showed overdepression on adduction. MR images showed an absent right trochlear nerve with a hypoplastic ipsilateral superior oblique muscle. Congenital Brown syndrome may be associated with an absent trochlear nerve and hypoplastic superior oblique muscle suggesting an etiologic mechanism of congenital cranial dysinnervation disorder.

Laparoscopic hemi-hysterectomy in treatment of a didelphic uterus with a hypoplastic cervix and obstructed hemi-vagina.

PubMed

Boudhraa, K; Barbarino, A; Gara, Mohamed Faouzi

2008-11-01

Maldevelopment of the Müllerian duct system may result in various urogenital anomalies including didelphic uterus with a hypoplastic cervix and obstructed hemi-vagina. We report a patient with this anomaly who was treated by laparoscopic hemi-hysterectomy and hysteroscopic resection of hemi-vagina. A 16-year-old patient who had complained of vaginal pus-like discharge on and off for 1 year was diagnosed by MRI to have a double uterus with obstructed right hemi-vagina and ipsilateral renal agenesis. After hysteroscopic identification of hypoplasia of the right uterine cervix, laparoscopic resection of the right uterus and right fallopian tube and hysteroscopic assisted resection of the vaginal septa were performed successfully. We think that combined laparoscopy and hysteroscopy may be an effective alternative in the management and diagnosis of Mullerian anomalies.

Hypoplastic left heart syndrome: a review

PubMed Central

Gobergs, Roberts; Salputra, Elza; Lubaua, Ingūna

2016-01-01

Background. Hypoplastic left heart syndrome (HLHS) is an etiologically multifactorial congenital heart disease affecting one in 5,000 newborns. Thirty years ago there were no treatment options for this pathology and the natural course of the disease led to death, usually within the first weeks of life. Recently surgical palliative techniques have been developed allowing for a five-year survival in more than half the cases. Materials and methods. We reviewed literature available on HLHS, specifically its anatomy, embryology and pathophysiology, and treatment. The Pubmed and ClinicalKey databases were searched using the key words hypoplastic left heart syndrome, foetal aortic valvuloplasty, foetal septoplasty, Norwood procedure, bidirectional Glenn procedure, Fontan procedure, hybrid procedure. The relevant literature was reviewed and included in the article. We reported a case from Children’s Clinical University Hospital, Riga, to illustrate treatment tactics in Latvia. Results. There are three possible directions for therapy in newborns with HLHS: orthotopic heart transplantation, staged surgical palliation and palliative non-surgical treatment or comfort care. Another treatment mode – foetal therapy – has arisen. Staged palliation and full Fontan circulation is a temporary solution, however, the only means for survival until heart transplantation. Fifty to 70% of patients who have gone through all three stages of palliation live to the age of five years. Conclusions. The superior mode of treatment is not yet clear and the management must be based on each individual case, the experience of each clinic, as well as the financial aspects and will of the patient’s parents. PMID:28356795

Exploring the relationship between hypoplasia and odontometric asymmetry in Isola Sacra, an imperial Roman necropolis.

PubMed

Hoover, Kara C; Corruccini, Robert S; Bondioli, Luca; Macchiarelli, Roberto

2005-01-01

Anthropological studies reporting odontometric asymmetry values or dental enamel hypoplasia frequencies use these markers as a record of physiological perturbations occurring during dental development. While both markers indirectly suggest the amount of relative stress a population might have experienced, a relationship between the two has been explored only recently in the literature. In this study, we address the possibility of such a relationship in two ways. First, Kendall's tau B correlations test the degree of relationship on the level of the individual between hypoplasia presence/absence (P/A) and severity of hypoplasia appearance (PS) data for the anterior dentition and directional (DA) and fluctuating asymmetry (FA) data for concurrently developing molars pairs. Second, an F-test explores between-group (ranked hypoplastic individuals and non-hypoplastic individuals) variance about the mean, expecting the hypoplastic individuals to be more variable. The sample consists of 72 individuals from the Isola Sacra necropolis, which is associated with Portus, the port city of ancient Rome. Results indicated only a very weak predictive relationship between some variables and few significant differences in variation. However, variance follows trends in published literature. Possible explanations for the lack of interaction on the level of the individual include both etiological and genetic susceptibility factors that are significant in and of themselves as they suggest a more complex reading of the hard tissue evidence for stress in archaeological populations. Copyright 2005 Wiley-Liss, Inc

Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs

PubMed Central

Smith, Lachlan J; Martin, John T; O'Donnell, Patricia; Wang, Ping; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

2012-01-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in various tissues including those of the spine. Associated spine disease can be due to abnormalities in the vertebrae, the intervertebral discs, or other spine tissues. The goal of this study was to determine if neonatal gene therapy could prevent lumbar spine disease in MPS VII dogs. MPS VII dogs were injected intravenously with a retroviral vector (RV) expressing canine GUSB at 2 to 3 days after birth, which resulted in transduction of hepatocytes that secreted GUSB into blood. Expression was stable for up to 11 years, and mean survival was increased from 0.4 years in untreated dogs to 6.1 years in treated dogs. Despite a profound positive clinical effect, 6-month-old RV-treated MPS VII dogs still had hypoplastic ventral epiphyses with reduced calcification in the lumbar spine, which resulted in a reduced stiffness and increased range of motion that was not improved relative to untreated MPS VII dogs. At six to 11 years of age, ventral vertebrae remained hypoplastic in RV-treated MPS VII dogs, and there was desiccation of the nucleus pulposus in some discs. Histochemical staining demonstrated that discs did not have detectable GUSB activity despite high serum GUSB activity, which is likely due to poor diffusion into this relatively avascular structure. Thus, neonatal gene therapy cannot prevent lumbar spine disease in MPS VII dogs, which predicts that enzyme replacement therapy (ERT) will similarly be relatively ineffective even if started at birth. PMID:22510705

The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.

PubMed

Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F

2015-01-01

Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.

The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus

PubMed Central

Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J.; Zykovich, Artem; Coon, Steven L.; Klein, David C.; Rath, Martin F.

2014-01-01

Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9−/− mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9−/− mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9−/− mice at 5–8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9−/−mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus. PMID:24647753

Physiology of Breastfeeding

USDA-ARS?s Scientific Manuscript database

This powerpoint presentation summaries physiology of lactation and the impact of a variety of clinical practices on lactation from delivery through weaning. Factors that inhibit lactogenesis stage II are explained, including retained placenta, excess blood loss during delivery, and hypoplastic brea...

Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects.

PubMed

Mäenpää, Heidi; Häkkinen, Arja; Sarajuuri, Anne

2016-01-01

To compare changes in motor development from 1 to 5 years of age among 18 children with hypoplastic left heart syndrome and 12 with univentricular heart to 42 children without heart defect. Motor development was assessed with the Alberta Infant Motor Scale and Movement Assessment Battery for Children (Movement ABC). Children with hypoplastic left heart syndrome or univentricular heart had significantly lower scores on the Alberta Infant Motor Scale test at the age of 1 and on the Movement ABC test at the age of 5 years compared with controls. Children with clear abnormalities on brain magnetic resonance imaging had lower scores compared with those with normal images or mild changes, and their relative motor scores decreased during follow-up. Some children with univentricular heart defects may benefit from physiotherapeutic interventions to support their motor development.

Congenital aplastic-hypoplastic lumbar pedicle in infants and young children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yousefzadeh, D.K.; El-Khoury, G.Y.; Lupetin, A.R.

1982-01-01

Nine cases of congenital aplastic-hypoplastic lumbar pedicle (mean age 27 months) are described. Their data are compared to those of 18 other reported cases (mean age 24.7 years) and the following conclusions are made: (1) Almost exclusively, the pedicular defect in infants and young children is due to developmental anomaly rather than destruction by malignancy or infectious processes. (2) This anomaly, we think, is more common than it is believed to be. (3) Unlike adults, infants and young children rarely develop hypertrophy and/or sclerosis of the contralateral pedicle. (4) Detection of pedicular anomaly is more than satisfying a radiographic curiositymore » and may lead to discovery of other coexisting anomalies. (5) Ultrasonic screening of the patients with congenital pedicular defects may detect the associated genitourinary anomalies, if present, and justify further studies in a selected group of patients.« less

De morseir syndrome presenting as ambiguous genitalia.

PubMed

Thukral, Anubhav; Chitra, S; Chakraborty, Partho P; Roy, Ajitesh; Goswami, Soumik; Bhattacharjee, Rana; Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukherjee, Satinath; Chowdhury, Subhankar

2012-12-01

A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

[Horseshoe lung with normal pulmonary venous return].

PubMed

Gondra Sangroniz, A; Elorz Lambarri, J; Villar Alvarez, M A; Lecumberri Cortes, I; Ayala Curiel, J

2010-09-01

Horseshoe lung is a rare congenital anomaly characterised by a midline isthmus of pulmonary parenchyma connecting the posterior basal segments of the lungs behind the heart in conjunction with unilateral pulmonary hypoplasia. Of all cases, 80% are associated with scimitar syndrome, consisting of right anomalous pulmonary venous drainage, pulmonary hypoplasia of the right lung and systemic arterial perfusion to some lung areas. A six year old girl who had recurrent lower respiratory infections since birth. Chest Rx, angioCT and MR showed: hypoplasia of the right lung, dextrocardia and pulmonary isthmus bridging both lungs behind the pericardium. The right hypoplastic lung had little systemic supply coming from the abdominal aorta. The right pulmonary artery was hypoplastic. The right pulmonary venous drainage was normal. We present a case of horseshoe lung without abnormal venous drainage. 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Hypoplastic uterus and clitoris enlargement in Swyer syndrome.

PubMed

Hétu, Valérie; Caron, Evelyne; Francoeur, Diane

2010-02-01

Swyer syndrome is associated with absent testicular differentiation in a 46XY phenotypic female. A 17-year-old female presented with primary amenorrhea and 46XY karyotype. Breast and pubic hair development were Tanner 2, and clitoral enlargement was noted. Magnetic resonance imaging revealed a hypoplastic uterus and 2 "normal ovaries." Serum follicle-stimulating hormone and luteinizing hormone were elevated. Testosterone and androstenedione were in the female range. Dehydroepiandrosterone sulfate was slightly elevated. Laparoscopic bilateral gonadectomy was performed. Pathology reports showed bilateral microscopic benign hilar cell tumors. The diagnosis was a real puzzle for the clinicians because of the association of clitoral hypertrophy without hirsutism, female internal genitalia, and a 46XY karyotype. Clitoral enlargement can be explained by transient androgen secretion by the hilar cells found in the resected gonads. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

One and a half ventricular repair as an alternative for hypoplastic right ventricle.

PubMed

Maluf, Miguel Angel; Carvalho, Antonio Carlos; Carvalho, Werther Brunow

2010-01-01

Patients with complex congenital heart disease, characterized by right ventricle hypoplasia, had a palliative surgical option with one and a half ventricular repair. From July 2001 to March 2009, nine patients (mean age 5.2 years, range 3 to 9 years) with hypoplastic right ventricle, underwent correction with one and a half ventricle technique. Preoperative diagnoses included: pulmonary atresia with intact ventricular septum, in six and Ebstein's anomaly, in three cases. Six patients had bidirectional cavo-pulmonary shunt (Glenn operation) previously. The surgical approach was performed with cardiopulmonary bypass to correct intracardiac defects: atrial septal defect closure (nine cases); right ventricle outlet tract reconstruction with porcine pulmonary prosthesis (seven cases); tricuspid valvuloplasty (three cases). There was one (11.1%) hospital death. All the patients left the hospital in good clinical conditions. One patient presented pulmonary stenosis at distal prosthesis anastomosis and needed surgical correction. There was one (12.5%) late deaths after reoperation. At mean follow-up of 39.8 months (range 16 months to 8.4 years) seven patients are alive in functional class I (NYHA). Surgical treatment of congenital cardiac anomalies in the presence of a hypoplastic right ventricle by means of one and a half ventricle repair has the advantages of reducing the surgical risk of biventricular repair compared to the Fontan circulation; it maintains a low right atrium pressure, a pulsatile pulmonary blood flow and improves the systemic oxygen saturation with short and medium-term promising results. Longer follow-up is needed to prove the efficacy of such a repair in the long term.

Alterations of peroxisome proliferator-activated receptor γ and monocyte chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic lung.

PubMed

Gosemann, Jan-Hendrik; Doi, Takashi; Kutasy, Balazs; Friedmacher, Florian; Dingemann, Jens; Puri, Prem

2012-05-01

Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in normal lung development. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) is detectable at 18 days of gestation in fetal rat lungs, and levels peak just before birth. Peroxisome proliferator-activated receptor γ agonists are reported to stimulate lung development, whereas inhibition of PPARγ disrupts postnatal lung maturation. Monocyte chemoattractant protein 1 (MCP-1), which is inhibited by PPARγ, is reported to disrupt late lung morphogenesis. This study was designed to investigate the hypothesis that PPARγ expression is downregulated and that MCP-1 expression is upregulated during the late stages of lung development in nitrofen-induced hypoplastic lungs. Pregnant rats were treated with nitrofen or vehicle on D9. RNA was extracted from fetal lungs (D18 and D21), and relative mRNA expression levels of PPARγ and MCP-1 were determined by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression/distribution of PPARγ and MCP-1. Relative mRNA expression levels of PPARγ were significantly downregulated in the nitrofen group compared with controls on D21, whereas MCP-1 levels were upregulated. Immunohistochemical study showed markedly decreased PPARγ and increased MCP-1 immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls on gestational day 21. Altered pulmonary gene expression of PPARγ and MCP-1 during late gestation may impair lung development and maturation, contributing to pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia model. Copyright © 2012 Elsevier Inc. All rights reserved.

Morphological Variables Associated With Ruptured Middle Cerebral Artery Aneurysms.

PubMed

Zhang, Jian; Can, Anil; Mukundan, Srinivasan; Steigner, Michael; Castro, Victor M; Dligach, Dmitriy; Finan, Sean; Yu, Sheng; Gainer, Vivian; Shadick, Nancy A; Savova, Guergana; Murphy, Shawn; Cai, Tianxi; Wang, Zhong; Weiss, Scott T; Du, Rose

2018-05-30

Geometric factors of intracranial aneurysms and surrounding vasculature could affect the risk of aneurysm rupture. However, large-scale assessments of morphological parameters correlated with intracranial aneurysm rupture in a location-specific manner are scarce. To investigate the morphological characteristics associated with ruptured middle cerebral artery (MCA) aneurysms. Five hundred sixty-one patients with 638 MCA aneurysms diagnosed between 1990 and 2016 who had available computed tomography angiography (CTA) were included in this study. CTAs were evaluated using the Vitrea Advanced Visualization software for 3-dimensional (3D) reconstruction. Morphological parameters examined in each model included aneurysm projection, wall irregularity, presence of a daughter dome, presence of hypoplastic or aplastic A1 arteries and hypoplastic or fetal posterior communicating arteries (PCoA), aneurysm height and width, neck diameter, bottleneck factor, aspect and size ratio, height/width ratio, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine the association of morphological characteristics with rupture of MCA aneurysms. Logistic regression was used to build a predictive MCA score. Greater bottleneck and size ratio, and irregular, multilobed, temporally projecting MCA aneurysms are associated with higher rupture risk, whereas higher M1/M2 ratio, larger width, and the presence of an ipsilateral or bilateral hypoplastic PCoA were inversely associated with rupture. The MCA score had good predictive capacity with area under the receiver operating curve = 0.88. These practical morphological parameters specific to MCA aneurysms are easy to assess when examining 3D reconstructions of unruptured aneurysms and could aid in risk evaluation in these patients.

The Various Applications of 3D Printing in Cardiovascular Diseases.

PubMed

El Sabbagh, Abdallah; Eleid, Mackram F; Al-Hijji, Mohammed; Anavekar, Nandan S; Holmes, David R; Nkomo, Vuyisile T; Oderich, Gustavo S; Cassivi, Stephen D; Said, Sameh M; Rihal, Charanjit S; Matsumoto, Jane M; Foley, Thomas A

2018-05-10

To highlight the various applications of 3D printing in cardiovascular disease and discuss its limitations and future direction. Use of handheld 3D printed models of cardiovascular structures has emerged as a facile modality in procedural and surgical planning as well as education and communication. Three-dimensional (3D) printing is a novel imaging modality which involves creating patient-specific models of cardiovascular structures. As percutaneous and surgical therapies evolve, spatial recognition of complex cardiovascular anatomic relationships by cardiologists and cardiovascular surgeons is imperative. Handheld 3D printed models of cardiovascular structures provide a facile and intuitive road map for procedural and surgical planning, complementing conventional imaging modalities. Moreover, 3D printed models are efficacious educational and communication tools. This review highlights the various applications of 3D printing in cardiovascular diseases and discusses its limitations and future directions.

[Fetal echocardiography efficiency. Clinical experience].

PubMed

San Luis Miranda, Raúl; Arias Monroy, Laura Guadalupe; Gutiérrez González, Gladis Alicia; León Avila, José Luis; Cruz Rodríguez, Armando; Osornio Correa, Porfirio Rafael

2008-12-01

Congenital heart disease diagnostic has a high diagnostic precision with fetal echocardiography. This study has been reported in populations with high risk and with a sensibility of 86 to 99% and specificity of 91 to 100%. To know sensibility and specificity of fetal echocardiography in high-risk pregnancies, and to describe types and frequency of congenital heart disease in utero. 229 files of pregnant women with high-risk factors, more than 15 weeks of gestation, and at birth cardiovascular exam were analyzed. This analysis was made by means of simple frequencies, sensibility, specificity, positive and negative predictive value, and truth index calculation. We found 62 (27%) cases with fetal heart disease. Mean of maternal age was 27 +/- 5.5 years, and of gestational age 31 +/- 5 weeks. Risk factors that require study were: four-chamber abnormality in routine ultrasound, dysmorphy, fetal bradicardia, and poll and oligohydramnios. There were 55 (88.7%) high-risk heart diseases, and most frequent were Ebstein's anomaly, unique ventricle, hypoplastic left ventricle syndrome, and tumors. Sensibility was 98.41%, specificity was 97.59%, positive prognostic value was 97.59%, and negative prognostic value was 99.39%. Fetal echocardiography has a high diagnosis certainty in our hospital unit, thus, it has to be a normal prenatal exam in pregnant women with high-risk factors.

Down-regulation of lung Kruppel-like factor in the nitrofen-induced hypoplastic lung.

PubMed

Lukošiūtė, A; Doi, T; Dingemann, J; Ruttenstock, E M; Puri, P

2011-01-01

Pulmonary hypoplasia is a primary cause of high morbidity and mortality in neonates with Congenital Diaphragmatic Hernia (CDH). However, the precise pathogenesis of PH associated with CDH is still not clearly understood. It has been recently reported that lung Kruppel-like factor (LKLF), a member of the Kruppel-like factor family of transcription factors, is predominantly expressed in lungs and plays an important role in lung morphogenesis and functional maturation. It has been reported that homozygous deletion of LKLF gene in mice results in reduced lung morphogenesis. It is further reported that chimeric mice derived from LKLF (-/-) embryonic stem cells exhibit delayed lung development especially in the later gestational stages. We therefore designed this study to test the hypothesis that the LKLF gene is down-regulated during later stages of lung development in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups:control, nitrofen without CDH(CDH(-)) and nitrofen with CDH(CDH(+)) (n=24 for each group). Real-time RT-PCR analysis was performed to investigate pulmonary gene expression levels of LKLF. Differences between the 3 groups at each time point were tested statistically and significance was accepted at p<0.05. Immunohistochemistry was also performed to evaluate LKLF protein expression and distribution. The relative mRNA expression levels of LKLF on D18 and D21 were significantly decreased (p<0.01) in CDH(-) and CDH(+) groups compared to controls. The gene expression levels of LKLF on D15 did not differ significantly between the nitrofen group and controls. Immunohistochemical study showed strong LKLF immunoreactivity on D18 and D21 in nitrofen-induced hypoplastic lung compared to controls, whereas no difference was seen on D15. Our results provide evidence for the first time that LKLF is down-regulated in the later stages of lung development in nitrofen-induced hypoplastic lungs. These data suggest that the down-regulation of LKLF during this critical period of lung morphogenesis may impair lung development and maturation, resulting in pulmonary hypoplasia in the nitrofen CDH model. © Georg Thieme Verlag KG Stuttgart · New York.

Challenging embryological theories on congenital diaphragmatic hernia: future therapeutic implications for paediatric surgery.

PubMed Central

Jesudason, E. C.

2002-01-01

Lung hypoplasia is central to the poor prognosis of babies with congenital diaphragmatic hernia (CDH). Prolapse of abdominal organs through a diaphragmatic defect has traditionally been thought to impair lung growth by compression. The precise developmental biology of CDH remains unresolved. Refractory to fetal correction, lung hypoplasia in CDH may instead originate during embryogenesis and before visceral herniation. Resolving these conflicting hypotheses may lead to reappraisal of current clinical strategies. Genetic studies in murine models and the fruitfly, Drosophila melanogaster are elucidating the control of normal respiratory organogenesis. Branchless and breathless are Drosophila mutants lacking fibroblast growth factor (FGF) and its cognate receptor (FGFR), respectively. Sugarless and sulphateless mutants lack enzymes essential for heparan sulphate (HS) biosynthesis. Phenotypically, all these mutants share abrogated airway branching. Mammalian organ culture and transgenic models confirm the essential interaction of FGFs and HS during airway ramification. Embryonic airway development (branching morphogenesis) occurs in a defined spatiotemporal sequence. Unlike the surgically-created lamb model, the nitrofen rat model permits investigation of embryonic lung growth in CDH. Microdissecting embryonic lung primordia from the nitrofen CDH model and normal controls, we demonstrated that disruption of stereotyped airway branching correlates with and precedes subsequent CDH formation. To examine disturbed branching morphogenesis longitudinally, we characterised a system that preserves lung hypoplasia in organ culture. We tested FGFs and heparin (an HS analogue) as potential therapies on normal and hypoplastic lungs. Observing striking differences in morphological response to FGFs between normal and hypoplastic lung primordia, we postulated abnormalities of FGF/HS signalling in the embryonic CDH lung. Evaluating this hypothesis further, we examined effects of an HS-independent growth factor (epidermal growth factor, EGF) on hypoplastic lung development. Visible differences in morphological response indicate an intrinsic abnormality of hypoplastic lung primordia that may involve shared targets of FGFs and EGE. These studies indicate that lung hypoplasia precedes diaphragmatic hernia and may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. What does this imply for human CDH? Fetal surgery may be 'too little, too late' to correct an established lung embryopathy. In utero growth factor therapy may permit antenatal lung rescue. Prevention of the birth defect by preconceptual prophylaxis may represent the ultimate solution. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 PMID:12215028

77 FR 41412 - Determination That CHLOROMYCETIN (Chloramphenicol) Capsules, 250 Milligrams, Were Withdrawn From...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... most serious being bone marrow depression (anemia, thrombocytopenia, and granulocytopenia temporally... succinate injection and chloramphenicol capsules states that serious hypoplastic anemia, thrombocytopenia... anemia associated with administration of the drug and aplastic anemia attributed to chloramphenicol that...

Facts about dextro-Transposition of the Great Arteries (d-TGA)

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... the heart – the main pulmonary artery and the aorta – are switched in position, or “transposed.” What is ...

Early abnormalities of cardiovascular structure and function in middle-aged Korean adults with prehypertension: The Korean Genome Epidemiology study.

PubMed

Kim, Seong Hwan; Cho, Goo-Yeong; Baik, Inkyung; Lim, Sang Yup; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Park, Juri; Kim, Jinyoung; Shin, Chol

2011-02-01

Prehypertension is associated with increased cardiovascular morbidity and mortality. However, there are few population-based studies on the changes of cardiovascular structure and function that characterize prehypertension. The aim of this study was to assess whether prehypertension is associated with abnormalities of cardiovascular structure and function in the general Korean population. We analyzed the cross-sectional relationships between prehypertension and cardiovascular structure and function in a sample from the Korean Genome Epidemiology Study. A total of 1,671 individuals (54.5% women; mean age: 53 ± 6 years) without hypertension and diabetes mellitus were enrolled. Cardiovascular structure and function were assessed by conventional echocardiography, tissue Doppler imaging (TDI), carotid ultrasonography, and pulse wave velocity (PWV). The left ventricular (LV) mass index was significantly higher in subjects with prehypertension than in those with normotension (41 ± 8 g/m²·⁷ vs. 38 ± 7 g/m²·⁷, P < 0.001). LV diastolic parameters, such as the E/A ratio, TDI E(a) velocity, and E/E(a) ratio, were also impaired in subjects with prehypertension (all P < 0.001). Compared with normotension, prehypertension was characterized by a significantly higher common carotid artery intima-media thickness and a higher brachial-ankle PWV (all P < 0.001). These abnormalities of cardiovascular structure and function remained significant after adjustment for covariates. In this population-based cohort, we found that subtle alterations in cardiovascular structure and function were already present at the prehypertensive stage. Whether such subtle alterations convey an increased risk of cardiovascular events and whether the changes are reversible with treatment warrant further study.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schimmenti, L.A.; Berry, S.A.; Tuchman, M.

The authors report on a male infant with developmental delay, growth failure, hypotonia, dolichocephaly, hypoplastic midface, epicanthal folds, down-slanting palpebral fissures, foveal hypoplasia, tracheomalacia, pectus excavatum, supraventricular tachycardia, gut malrotation, hypospadias, talipes equinovarus, short third metatarsals, capillary hemangiomata, and a de novo terminal deletion at 9q34.3.

Microanatomical bases for intraoperative division of the posterior communicating artery.

PubMed

Gabrovsky, N

2002-11-01

Micro-anatomical parameters of the hypoplastic posterior communicating artery (PCoA) are assessed and compared with the micro-anatomical parameters of the adult type PCoA. Based on the results obtained, the safest place is proposed for PCoA division during basilar tip aneurysm surgery via the pterional route. In 35 human cadaver brains, red coloured latex was injected and micro-anatomical dissection was performed. Seventy PCoA were found. Adult type PCoA was found in 29 cases (41.43%) with mean length 12.58 mm. Reduction of the PCoA diameter from its anterior to its posterior third by up to 20% was found in 27% and by more than 20% in 10% of the cases. The mean perforating vessel number was 8.17, distributed in each third: 3.48, 2.90 and 1.79, respectively. A hypoplastic PCoA was found in 33 cases (47.14%) with mean length 16.09 mm. The PCoA's diameter reduction by up to 20% was found in 24% and by more in 27% of the cases. In 6% of the cases an extreme reduction by up to 70% was observed. The mean perforating vessel (PV) number was 8.82, distributed in each third: 3.18, 3.36 and 2.27, respectively. Hypoplastic PCoA tends to be longer and with a more distinct diameter reduction from the anterior to the posterior third than the adult type PCoA. The PV anatomical parameters are similar for both groups. The posterior third of the PCoA seems to be the area where the risk of perforating vessel damage is the least when performing intra-operative PCoA division.

Insulin receptor is downregulated in the nitrofen-induced hypoplastic lung.

PubMed

Ruttenstock, Elke; Doi, Takashi; Dingemann, Jens; Puri, Prem

2010-05-01

The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is still poorly understood. During fetal lung development, the insulin receptor (IR) plays an important role by mediating the cellular uptake of glucose, which is a major substrate for the biosynthesis of surfactant phospholipids. In fetal rat lung, IR gene expression has been revealed on type II pneumocytes. Recent studies have demonstrated that downregulation of pulmonary IR in late gestation causes pulmonary hypoplasia by inhibition of surfactant synthesis. We hypothesized that pulmonary gene expression of IR is downregulated during the late stages of lung development in the nitrofen-induced CDH model. Timed pregnant Sprague-Dawley rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Cesarean deliveries were performed on D15, D18, and D21. Fetal lungs were divided into 3 groups: control, nitrofen without CDH (CDH[-]), and nitrofen with CDH (CDH[+]) (n = 8 at each time-point, respectively). Relative messenger RNA (mRNA) levels of IR were determined by using real time reverse transcription polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of IR. Relative expression levels of IR mRNA on D21 were significantly decreased in CDH(-) and CDH(+) group (3.99 +/- 1.50 and 5.14 +/- 0.99, respectively) compared to control (7.45 +/- 3.95; P < .05). Immunohistochemistry showed decreased IR expression in the proximal alveolar epithelium on D21 in hypoplastic lungs compared to control lungs. Downregulation of IR gene and protein expression in hypoplastic lung during late stages of lung development may interfere with normal surfactant synthesis, causing pulmonary hypoplasia in the nitrofen-induced CDH model. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Spatiotemporal alterations in Sprouty-2 expression and tyrosine phosphorylation in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Alvarez, Luis A J; Corcionivoschi, Nicolae; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition of newborns presenting with congenital diaphragmatic hernia (CDH). Sprouty-2 functions as a key regulator of fibroblast growth factor receptor (FGFR) signalling in developing foetal lungs. It has been reported that FGFR-mediated alveolarization is disrupted in nitrofen-induced PH. Sprouty-2 knockouts show severe defects in lung morphogenesis similar to nitrofen-induced PH. Upon FGFR stimulation, Sprouty-2 is tyrosine-phosphorylated, which is essential for its physiological function during foetal lung development. We hypothesized that Sprouty-2 expression and tyrosine phosphorylation are altered in nitrofen-induced PH. Time-pregnant rats received either nitrofen or vehicle on gestation day 9 (D9). Foetal lungs were dissected on D18 and D21. Pulmonary Sprouty-2 gene and protein expression levels were analyzed by qRT-PCR, Western blotting and immunohistochemical staining. Relative mRNA expression of Sprouty-2 was significantly decreased in hypoplastic lungs without CDH (0.1050±0.01 vs. 0.3125±0.01; P<.0001) and with CDH (0.1671±0.01 vs. 0.3125±0.01; P<.0001) compared to controls on D18. Protein levels of Sprouty-2 were markedly decreased in hypoplastic lungs on D18 with decreased tyrosine phosphorylation levels on D18 and D21 detected at the molecular weight of Sprouty-2 consistent with Sprouty-2 tyrosine phosphorylation. Sprouty-2 immunoreactivity was markedly decreased in hypoplastic lungs on D18 and D21. Spatiotemporal alterations in pulmonary Sprouty-2 expression and tyrosine phosphorylation during the late stages of foetal lung development may interfere with FGFR-mediated alveolarization in nitrofen-induced PH. © 2013.

Birth weight and prematurity in infants with single ventricle physiology: pediatric heart network infant single ventricle trial screened population.

PubMed

Williams, Richard V; Ravishankar, Chitra; Zak, Victor; Evans, Frank; Atz, Andrew M; Border, William L; Levine, Jami; Li, Jennifer S; Mahony, Lynn; Mital, Seema; Pearson, Gail D; Prakash, Ashwin; Hsu, Daphne T

2010-01-01

Although congenital heart disease is associated with low birth weight and prematurity, there is little information about these birth outcomes in infants with single ventricle physiology. We describe the birth outcomes (i.e., gestational age and birth weight) in neonates with single ventricle physiology screened for enrollment in the Pediatric Heart Network's Infant Single Ventricle Trial, compare these outcomes with US norms, and examine the association of birth outcomes with anatomic diagnosis and race. All neonates with single ventricle physiology presenting to Infant Single Ventricle Trial centers were screened for enrollment. Demographic data and anatomic diagnoses were obtained from medical records. A total of 1245 neonates with single ventricle physiology were screened at 10 centers (63 to 266 per center). Diagnoses included hypoplastic left heart syndrome in 49%, unbalanced atrioventricular septal defect in 12%, and tricuspid atresia in 9%. Preterm birth occurred in 16% of neonates with single ventricle physiology vs. 12% in normal neonates (P < .001), low birth weight (<2.5 kg) in 18% vs. 8% in normals (P < .001), and small for gestational age (<10th percentile by definition) in 22% vs. 10% in normals (P < .001). A genetic syndrome was reported in 8%. The percentage of preterm birth, low birth weight, and small for gestational age was similar between screened neonates with and without hypoplastic left heart syndrome. In this large, contemporary cohort of neonates with single ventricle physiology, rates of preterm birth, low birth weight, and small for gestational age were higher than in the general population, but similar between screened neonates with and without hypoplastic left heart syndrome.

Regulation of chromatin structure in the cardiovascular system.

PubMed

Rosa-Garrido, Manuel; Karbassi, Elaheh; Monte, Emma; Vondriska, Thomas M

2013-01-01

It has been appreciated for some time that cardiovascular disease involves large-scale transcriptional changes in various cell types. What has become increasingly clear only in the past few years, however, is the role of chromatin remodeling in cardiovascular phenotypes in normal physiology, as well as in development and disease. This review summarizes the state of the chromatin field in terms of distinct mechanisms to regulate chromatin structure in vivo, identifying when these modes of regulation have been demonstrated in cardiovascular tissues. We describe areas in which a better understanding of chromatin structure is leading to new insights into the fundamental biology of cardiovascular disease. 

Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: Postnatal Outcomes of the First 100 Patients

PubMed Central

Freud, Lindsay R.; McElhinney, Doff B.; Marshall, Audrey C.; Marx, Gerald R.; Friedman, Kevin G.; del Nido, Pedro J.; Emani, Sitaram M.; Lafranchi, Terra; Silva, Virginia; Wilkins-Haug, Louise E.; Benson, Carol B.; Lock, James E.; Tworetzky, Wayne

2015-01-01

Background Fetal aortic valvuloplasty (FAV) can be performed for severe mid-gestation aortic stenosis (AS) in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after FAV. The postnatal outcomes and survival of the BV patients, compared to those managed as HLHS, have not been reported. Methods and Results We included 100 patients who underwent FAV for severe mid-gestation AS with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and LV volume, were significantly larger in the BV group at the time of birth (p-values <0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank p=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic and/or mitral valve replacement. On most recent echocardiogram, the median LV end-diastolic volume z-score was +1.7 (range: -1.3, +8.2), and 80% had normal ejection fraction. Conclusions Short- and intermediate-term survival among patients who underwent FAV and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and on-going assessment is warranted. PMID:25052401

Rare copy number variants in a population-based investigation of hypoplastic right heart syndrome.

PubMed

Dimopoulos, Aggeliki; Sicko, Robert J; Kay, Denise M; Rigler, Shannon L; Druschel, Charlotte M; Caggana, Michele; Browne, Marilyn L; Fan, Ruzong; Romitti, Paul A; Brody, Lawrence C; Mills, James L

2017-01-20

Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. We genotyped 32 HRHS cases identified from all New York State live births (1998-2005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were ≥20 Kb, contained ≥10 SNPs and had minimal overlap with CNVs from in-house controls, the Database of Genomic Variants, HapMap3, and Childrens Hospital of Philadelphia database. We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16-2p23 duplication spanning LBH, a limb and heart development transcription factor. Lbh mis-expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed SOS1, a factor associated with pulmonary valve stenosis in Noonan syndrome. Sos1 -/- mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5 Mb deletion associated with Williams-Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24 Kb deletion upstream of the TGFβ ligand ITGB8. Embryos genetically null for Itgb8, and its intracellular interactant Band 4.1B, display lethal cardiac phenotypes. To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. Birth Defects Research 109:16-26, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[A case of pycnodysostosis--observation of the skull by CT scan].

PubMed

Anegawa, S; Bekki, Y; Furukawa, Y; Yokota, S; Torigoe, R

1987-07-01

A 13-year-old boy was presented to the Department of Neurosurgery, Saiseikai Fukuoka General Hospital for further examinations concerning abnormal findings in the skull radiogram taken when he struck his head. His physical features showed some characteristics the same as those of pycnodysostosis as follows--proportionate dwarfism, prominent forehead, short spoon-shaped fingers, bilateral exophthalmos. A skull radiogram revealed widely open cranial sutures with no healing of the fracture and craniotomy which was performed for an acute epidural hematoma 6 years ago. Furthermore, the mandible was hypoplastic with a virtual loss of mandibular angle. CT of the soft tissues showed somewhat dilated cortical sulci and ventricles without any structural abnormalities in the brain. CT of bone algorithm revealed specific characteristics of this disease. The paranasal sinuses were quite hypoplastic. Especially in the maxillary sinuses, frontal sinuses and mastoid air cells, none of developments of sinuses were noted, even though the middle and internal ear seemed to be normal. Moreover, the ethmoid and sphenoid sinuses were noted, although their developments were poor. The appearance of skull base was normal, including the inlets and outlets of cranial nerves or vessels and synchondroses. However, the density of the skull base, especially in the diploe, was higher than normal in Hansfield number. Furthermore, detailed measurements of skull base demonstrated that the skull base itself was also dwarfism. Pycnodysostosis is a generalized skeletal disease whose cardinal features are moderate generalized osteosclerosis and dwarfism. However, the detailed observation on the cranium by CT has not been reported. In our study, the development of sinuses in bones with intramembranous ossification are worse than that with endochondral ossification.(ABSTRACT TRUNCATED AT 250 WORDS)

Rare Copy Number Variants in a Population Based Investigation of Hypoplastic Right Heart Syndrome

PubMed Central

Dimopoulos, Aggeliki; Sicko, Robert J.; Kay, Denise M.; Rigler, Shannon L.; Druschel, Charlotte M.; Caggana, Michele; Browne, Marilyn L.; Fan, Ruzong; Romitti, Paul A.; Brody, Lawrence C.; Mills, James L.

2016-01-01

Background Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. Methods We genotyped 32 HRHS cases identified from all New York State live births (1998–2005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were ≥20Kb, contained ≥10 SNPs and had minimal overlap with CNVs from in-house controls, the Database of Genomic Variants, HapMap3 and CHOP database. Results We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16–2p23 duplication spanning LBH, a limb and heart development transcription factor. Lbh mis-expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed SOS1, a factor associated with pulmonary valve stenosis in Noonan syndrome. Sos1−/− mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5Mb deletion associated with Williams Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24Kb deletion upstream of the TGFβ ligand ITGB8. Embryos genetically null for Itgb8, and its intracellular interactant Band 4.1B, display lethal cardiac phenotypes. Conclusions To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. PMID:28009100

Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs.

PubMed

Smith, Lachlan J; Martin, John T; O'Donnell, Patricia; Wang, Ping; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

2012-09-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in various tissues including those of the spine. Associated spine disease can be due to abnormalities in the vertebrae, the intervertebral disks, or other spine tissues. The goal of this study was to determine if neonatal gene therapy could prevent lumbar spine disease in MPS VII dogs. MPS VII dogs were injected intravenously with a retroviral vector (RV) expressing canine GUSB at 2 to 3 days after birth, which resulted in transduction of hepatocytes that secreted GUSB into blood. Expression was stable for up to 11 years, and mean survival was increased from 0.4 years in untreated dogs to 6.1 years in treated dogs. Despite a profound positive clinical effect, 6-month-old RV-treated MPS VII dogs still had hypoplastic ventral epiphyses with reduced calcification in the lumbar spine, which resulted in a reduced stiffness and increased range of motion that were not improved relative to untreated MPS VII dogs. At six to 11 years of age, ventral vertebrae remained hypoplastic in RV-treated MPS VII dogs, and there was desiccation of the nucleus pulposus in some disks. Histochemical staining demonstrated that disks did not have detectable GUSB activity despite high serum GUSB activity, which is likely due to poor diffusion into this relatively avascular structure. Thus, neonatal gene therapy cannot prevent lumbar spine disease in MPS VII dogs, which predicts that enzyme replacement therapy (ERT) will similarly be relatively ineffective even if started at birth. Copyright © 2012 Elsevier Inc. All rights reserved.

Staged surgical palliation in hypoplastic left heart syndrome and its variants.

PubMed

Delmo Walter, Eva Maria B; Hübler, Michael; Alexi-Meskishvili, Vladimir; Miera, Oliver; Weng, Yuguo; Loforte, Antonio; Berger, Felix; Hetzer, Roland

2009-01-01

Surgical options for infants with hypoplastic left heart syndrome (HLHS) and/or its variants are cardiac transplantation or the heart-preserving staged palliation with Norwood operation,followed by a two-staged Fontan procedure. We describe our 17-year experience with staged palliation of HLHS and/or its variants. Between December 1989 and December 2006, 64 patients with HLHS and/or its variants underwent a Norwood procedure (mean age/weight, 11.8+/-2.5 days/3.4 kg). Forty-four patients had classical HLHS. Twenty-eight percent had associated congenital cardiac, structural, and genetic anomalies. Subsequently, 25 patients underwent a bidirectional Glenn procedure (stage II) and 11 patients a modified Fontan procedure (stage III). Others await stage II and/or stage III. The follow-up was 143.2 patient-years. Including the learning curve, overall early mortality from 1989 to 1999 after the Norwood procedure was 39.06%. This decreased tremendously for the last seven years, and reduced to 12.8% in 2000 to 2003 until 0% in 2004 to 2006 (p < 0.005). The causes of mortality were sepsis, capillary leak,or heart failure. Three patients died between stages II and III. One patient underwent heart transplantation after the second stage because of heart failure. Among 34 Norwood survivors, four are slightly tachypneic from a mild pulmonary hyperperfusion; one presents symptoms of minimal brain disease. This report identified an outcome improvement after staged palliation of HLHS, attributed to an increase in experience and expertise gained over time. Lower operative weight, ascending aortic size, prolonged duration of cardiopulmonary bypass, and hypothermic circulatory arrest were identified to significantly influence early mortality after the Norwood procedure.

Perioperative Management of a Child with Hypoplastic Left Heart Syndrome of the Jehovah's Witness Faith Presenting for Hybrid Comprehensive Stage II Procedure.

PubMed

Karuppiah, Sathappan; Mckee, Christopher; Hodge, Ashley; Galantowicz, Mark; Tobias, Joseph; Naguib, Aymen

2016-09-01

Over the years, there has been a growing recognition of the potential negative sequelae of allogeneic blood products on postoperative outcomes following cardiac surgery. In addition, followers of the Jehovah's Witness (JW) faith have a religious restriction against receiving blood or blood components. Advances in perioperative care, cardiopulmonary bypass (CPB), and surgical technique have minimized the need for allogeneic blood products. Specific blood conservation strategies include maximizing the preoperative hematocrit and coagulation function as well as intraoperative strategies, such as acute normovolemic hemodilution and adjustments of the technique of CPB. We report a 7-month-old patient whose parents were of the JW faith who underwent a comprehensive stage II procedure for hypoplastic left heart syndrome without exposure to blood or blood products during his hospital stay. Perioperative techniques for blood avoidance are discussed with emphasis on their application to infants undergoing surgery for congenital heart disease.

A thermodynamically consistent model for granular-fluid mixtures considering pore pressure evolution and hypoplastic behavior

NASA Astrophysics Data System (ADS)

Hess, Julian; Wang, Yongqi

2016-11-01

A new mixture model for granular-fluid flows, which is thermodynamically consistent with the entropy principle, is presented. The extra pore pressure described by a pressure diffusion equation and the hypoplastic material behavior obeying a transport equation are taken into account. The model is applied to granular-fluid flows, using a closing assumption in conjunction with the dynamic fluid pressure to describe the pressure-like residual unknowns, hereby overcoming previous uncertainties in the modeling process. Besides the thermodynamically consistent modeling, numerical simulations are carried out and demonstrate physically reasonable results, including simple shear flow in order to investigate the vertical distribution of the physical quantities, and a mixture flow down an inclined plane by means of the depth-integrated model. Results presented give insight in the ability of the deduced model to capture the key characteristics of granular-fluid flows. We acknowledge the support of the Deutsche Forschungsgemeinschaft (DFG) for this work within the Project Number WA 2610/3-1.

Aesthetic composite veneers for an adult patient with amelogenesis imperfecta: a case report.

PubMed

Brignall, Ian; Mehta, Shamir B; Banerji, Subir; Millar, Brian J

2011-11-01

This case has been presented as part of the continual assessment requirement for the MSc in Aesthetic Dentistry, King's College Dental Institute. Amelogenesis imperfecta (AI) is a hereditary disorder of enamel formation, affecting both the permanent and deciduous dentitions. It can be classified into hypoplastic, hypomaturation and hypocalcified types and presents with different hereditary patterns. The aim of this article is to provide an overview of amelogenesis imperfecta, including a detailed case report for an aesthetically concerned adult patient presenting in general practice with a Witkop's Type IA defect managed with the placement of direct, layered resin composite veneers. Amelogenesis imperfecta patients are susceptible to the restorative cycle of replacement restorations like any other patient, but start with a distinct disadvantage.This case report demonstrates a minimally invasive, relatively simple and cost-effective option for the aesthetic correction of a case of hypoplastic amelogenesis imperfecta with layered composite veneers. Dent Update 2011; 38:594-603

Perioperative Management of a Child with Hypoplastic Left Heart Syndrome of the Jehovah's Witness Faith Presenting for Hybrid Comprehensive Stage II Procedure

PubMed Central

Karuppiah, Sathappan; Mckee, Christopher; Hodge, Ashley; Galantowicz, Mark; Tobias, Joseph; Naguib, Aymen

2016-01-01

Abstract: Over the years, there has been a growing recognition of the potential negative sequelae of allogeneic blood products on postoperative outcomes following cardiac surgery. In addition, followers of the Jehovah's Witness (JW) faith have a religious restriction against receiving blood or blood components. Advances in perioperative care, cardiopulmonary bypass (CPB), and surgical technique have minimized the need for allogeneic blood products. Specific blood conservation strategies include maximizing the preoperative hematocrit and coagulation function as well as intraoperative strategies, such as acute normovolemic hemodilution and adjustments of the technique of CPB. We report a 7-month-old patient whose parents were of the JW faith who underwent a comprehensive stage II procedure for hypoplastic left heart syndrome without exposure to blood or blood products during his hospital stay. Perioperative techniques for blood avoidance are discussed with emphasis on their application to infants undergoing surgery for congenital heart disease. PMID:27729708

Successful conservative treatment outcomes and clinical characteristics of congenital hypoplasia of the extensor tendon central slip.

PubMed

Hidaka, N; Uemura, T; Nakamura, H

2017-03-01

Congenital hypoplasia of the extensor tendon central slip is a rare entity. This article describes the clinical characteristics in a series of 22 fingers in 16 patients (mean age: 10 months), and the outcomes of conservative treatment. Nine of 22 fingers were classified as slender or hypoplastic. Treatment with bracing was successful in 21 digits, resulting in full active extension of the proximal interphalangeal joint at a mean of 8.5 months after treatment. Bracing was unsuccessful in one digit, in which operative treatment resulted in a successful outcome. Some residual deformity was observed in ten fingers after a mean follow-up period of 2 years and 1 month. Congenital hypoplasia of the central slip can be treated successfully by the conservative hand bracing when worn with full compliance. Treatment time is extended by the infrequent application of the hand brace or in the case of hypoplastic slender fingers. IV.

Prenatally diagnosed partial trisomy 3q case with an omphalocele and less severe phenotype

PubMed Central

Arıkan, Deniz Cemgil; Coşkun, Ayhan; Arıkan, İlker; Kıran, Gürkan; Ceylaner, Gülay

2010-01-01

Trisomy 3q is a very rarely reported chromosomal disorder. Duplication of part of the long arm of human chromosome 3 causes a distinct and severe syndrome that leads to multiple congenital abnormalities. A 27 year-old pregnant woman was admitted to our clinic at 17 weeks of gestation. Prenatal sonography identified a fetus with an omphalocele that contained the liver and bowel, mild ventriculomegaly and polyhydramnios. Amniocentesis revealed the karyotype of 46, XY, der (3) (3qter→3q21: : 3pter→3qter). The pregnancy was subsequently terminated. Postnatally, the proband showed midfacial hypoplasia, micrognathia, hypoplastic 12th ribs, omphalocele and prominent heels. We reported this partial trisomy 3q case because he had less marked malformations compared to other reported cases and also different features such as an omphalocele and hypoplastic 12th rib which have not been described previously in an isolated Trisomy 3q case with this karyotype. PMID:24591944

The oculo-dento-digital syndrome: male-to-male transmission and variable expression in a family.

PubMed

Ioan, D M; Dumitriu, L; Belengeariu, V; Fryns, J P

1997-01-01

We report two siblings--a 5 1/2 year old female and her 4 1/2 year old brother, both presenting the classical clinical findings of oculo-dento-digital dysplasia (ODD). 1. Digital anomalies: bilateral complete cutaneous syndactyly of fingers IV-V (III-IV-V at the left hand of the boy) and camptodactyly IV. 2. Facial and ocular anomalies: microphtalamos-epicanthal folds, small midfacies, thin nose with hypoplastic alae nasi and small nares. 3. Dental anomalies with partial dental agenesis and enamel hypoplasia. Examination of the parents showed a bilateral cutaneous syndactyly IV-V in the father as the sole partial manifestation of ODD. The findings in the present family confirm the autosomal dominant inheritance of ODD with great variability in clinical expression. Moreover, the facial morphology (thin, hypoplastic nose) observed in several ODD patients suggests nosological overlap with the Hallerman-Streiff syndrome and could indicate that both syndromes are variable expressions of a contiguous gene deletion syndrome.

Cleidocranial dysplasia

PubMed Central

Dixit, Ramakant; Dixit, Kalpana; Paramez, A. R.

2010-01-01

Cleidocranial dysplasia is a rare autosomal dominant condition with generalized dysplasia of bone, characterized by delayed closer of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We present a seven-year-old female child presenting with classical features of cleidocranial dysplasia. PMID:20931042

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

PubMed

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Congenital Diaphragmatic Hernia

PubMed Central

2012-01-01

Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted. PMID:22214468

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

Rare case of tibial hemimelia, preaxial polydactyly, and club foot

PubMed Central

Granite, Guinevere; Herzenberg, John E; Wade, Ronald

2016-01-01

A seven-month old female presented with left tibial hemimelia (or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot (congenital talipes equinovarus). Definitive amputation surgery disarticulated the lower limb at the knee. This case report describes the anatomical findings of a systematic post-amputation examination of the lower limb’s superficial dissection, X-rays, and computed tomography (CT) scans. From the X-rays and CT scans, we found curved and overlapping preaxial supernumerary toes, hypoplastic first metatarsal, lack of middle and distal phalanges in one supernumerary toe, three tarsal bones, hypoplastic middle phalanx and no distal phalanx for fourth toe, and no middle or distal phalanges for fifth toe. The fibula articulated with the anteromedial calcaneus and the tibia was completely absent. We identified numerous muscles and nerves in the superficial dissection that are described in the results section of the case report. Due to the rarity of this combination of anatomical findings, descriptions of such cases are very infrequent in the literature. PMID:28035313

Rare case of tibial hemimelia, preaxial polydactyly, and club foot.

PubMed

Granite, Guinevere; Herzenberg, John E; Wade, Ronald

2016-12-16

A seven-month old female presented with left tibial hemimelia (or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot (congenital talipes equinovarus). Definitive amputation surgery disarticulated the lower limb at the knee. This case report describes the anatomical findings of a systematic post-amputation examination of the lower limb's superficial dissection, X-rays, and computed tomography (CT) scans. From the X-rays and CT scans, we found curved and overlapping preaxial supernumerary toes, hypoplastic first metatarsal, lack of middle and distal phalanges in one supernumerary toe, three tarsal bones, hypoplastic middle phalanx and no distal phalanx for fourth toe, and no middle or distal phalanges for fifth toe. The fibula articulated with the anteromedial calcaneus and the tibia was completely absent. We identified numerous muscles and nerves in the superficial dissection that are described in the results section of the case report. Due to the rarity of this combination of anatomical findings, descriptions of such cases are very infrequent in the literature.

Extensive basal ganglia edema caused by a traumatic carotid-cavernous fistula: a rare presentation related to a basal vein of Rosenthal anatomical variation.

PubMed

Ract, Isabelle; Drier, Aurélie; Leclercq, Delphine; Sourour, Nader; Gabrieli, Joseph; Yger, Marion; Nouet, Aurélien; Dormont, Didier; Chiras, Jacques; Clarençon, Frédéric

2014-07-01

The authors report a very rare presentation of traumatic carotid-cavernous fistula (CCF) with extensive edema of the basal ganglia and brainstem because of an anatomical variation of the basal vein of Rosenthal (BVR). A 45-year-old woman was admitted to the authors' institution for left hemiparesis, dysarthria, and a comatose state caused by right orbital trauma from a thin metal rod. Brain MRI showed a right CCF and vasogenic edema of the right side of the brainstem, right temporal lobe, and basal ganglia. Digital subtraction angiography confirmed a high-flow direct CCF and revealed a hypoplastic second segment of the BVR responsible for the hypertension in inferior striate veins and venous congestion. Endovascular treatment was performed on an emergency basis. One month after treatment, the patient's symptoms and MRI signal abnormalities almost totally disappeared. Basal ganglia and brainstem venous congestion may occur in traumatic CCF in cases of a hypoplastic or agenetic second segment of the BVR and may provoke emergency treatment.

Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta.

PubMed

Poulter, James A; El-Sayed, Walid; Shore, Roger C; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

2014-01-01

The conventional approach to identifying the defective gene in a family with an inherited disease is to find the disease locus through family studies. However, the rapid development and decreasing cost of next generation sequencing facilitates a more direct approach. Here, we report the identification of a frameshift mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta (AI). Whole-exome sequencing of three affected family members and subsequent filtering of shared variants, without prior genetic linkage, sufficed to identify the pathogenic variant. Simultaneous analysis of multiple family members confirms segregation, enhancing the power to filter the genetic variation found and leading to rapid identification of the pathogenic variant. LAMB3 encodes a subunit of Laminin-5, one of a family of basement membrane proteins with essential functions in cell growth, movement and adhesion. Homozygous LAMB3 mutations cause junctional epidermolysis bullosa (JEB) and enamel defects are seen in JEB cases. However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB.

Enamel biorhythms of humans and great apes: the Havers-Halberg Oscillation hypothesis reconsidered.

PubMed

Mahoney, Patrick; Miszkiewicz, Justyna J; Pitfield, Rosie; Deter, Chris; Guatelli-Steinberg, Debbie

2017-02-01

The Havers-Halberg Oscillation (HHO) hypothesis links evidence for the timing of a biorhythm retained in permanent tooth enamel (Retzius periodicity) to adult body mass and life history traits across mammals. Potentially, these links provide a way to access life history of fossil species from teeth. Recently we assessed intra-specific predictions of the HHO on human children. We reported Retzius periodicity (RP) corresponded with enamel thickness, and cusp formation time, when calculated from isolated deciduous teeth. We proposed the biorhythm might not remain constant within an individual. Here, we test our findings. RP is compared between deciduous second and permanent first molars within the maxillae of four human children. Following this, we report the first RPs for deciduous teeth from modern great apes (n = 4), and compare these with new data for permanent teeth (n = 18) from these species, as well as with previously published values. We also explore RP in teeth that retain hypoplastic defects. Results show RP changed within the maxilla of each child, from thinner to thicker enameled molars, and from one side of a hypoplastic defect to the other. When considered alongside correlations between RP and cusp formation time, these observations provide further evidence that RP is associated with enamel growth processes and does not always remain constant within an individual. RP of 5 days for great ape deciduous teeth lay below the lowermost range of those from permanent teeth of modern orangutan and gorilla, and within the lowermost range of RPs from chimpanzee permanent teeth. Our data suggest associations between RP and enamel growth processes of humans might extend to great apes. These findings provide a new framework from which to develop the HHO hypothesis, which can incorporate enamel growth along with other physiological systems. Applications of the HHO to fossil teeth should avoid transferring RP between deciduous and permanent enamel, or including hypoplastic teeth. © 2016 Anatomical Society.

Computer-aided patch planning for treatment of complex coarctation of the aorta

NASA Astrophysics Data System (ADS)

Rietdorf, Urte; Riesenkampff, Eugénie; Kuehne, Titus; Huebler, Michael; Meinzer, Hans-Peter; Wolf, Ivo

2009-02-01

Between five and eight percent of all children born with congenitally malformed hearts suffer from coarctations of the aorta. Some severe coarctations can only be treated by surgical repair. Untreated, this defect can cause serious damage to organ development or even lead to death. Patch repair requires open surgery. It can affect patients of any age: newborns with severe coarctation and/or hypoplastic aortic arch as well as older patients with late diagnosis of coarctation of the aorta. Another patient group are patients of varying age with re-coarctation of the aorta or hypoplastic aortic arch after surgical and/or interventional repair. If anatomy is complex and interventional treatment by catheterization, balloon angioplasty or stent placement is not possible, surgery is indicated. The choice of type of surgery depends not only on the given anatomy but also on the experience the surgical team has with each method. One surgical approach is patch repair. A patch of a suitable shape and size is sewed into the aorta to expand the aortic lumen at the site of coarctation. At present, the shape and size of the patch are estimated intra-operatively by the surgeon. We have developed a software application that allows planning of the patch pre-operatively on the basis of magnetic resonance angiographic data. The application determines the diameter of the coarctation and/or hypoplastic segment and constructs a patch proposal by calculating the difference to the normal vessel diameter pre-operatively. Evaluation of MR angiographic datasets from 12 test patients with different kinds of aortic arch stenosis shows a divergence of only (1.5+/-1.2) mm in coarctation diameters between manual segmentations and our approach, with comparable time expenditure. Following this proposal the patch can be prepared and adapted to the patient's anatomy pre-operatively. Ideally, this leads to shorter operation times and a better long-term outcome with a reduced rate of residual stenosis and re-stenosis and aneurysm formation.

IGFBP-4 gene overexpression in the nitrofen-induced hypoplastic lung.

PubMed

Ruttenstock, E M; Doi, T; Dingemann, J; Puri, P

2011-01-01

The precise mechanism of pulmonary hypoplasia (HP) associated with congenital diaphragmatic hernia (CDH) remains unclear. Insulin-like growth factors (IGFs) play an essential role in fetal lung development through IGF receptors (IGFRs) by regulating cellular proliferation, differentiation and survival. It has been reported that the expression of genes involved in IGF-IGFR signaling is altered in the nitrofen-induced hypoplastic lung during the later stages of lung development. IGF-binding proteins (IGFBPs) control bioavailability, activity and disruption of IGFs through the high affinity IGFBP/IGF complexes. IGFBP-4 is a key inhibitor of IGF-IGFR signaling-mediated cell proliferation. It has been revealed that cell proliferation in fetal lung fibroblasts is inhibited by increased IGFBP-4 production. We hypothesized that IGFBP-4 gene expression is increased during the later stages of lung development in the nitrofen-induced CDH lung. Pregnant Sprague-Dawley rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. Fetuses were harvested by cesarean section on D18 and D21. Fetal lungs were divided into 3 groups: control, nitrofen without CDH [CDH(-)] and nitrofen with CDH [CDH(+)] (n=24 at each time point). Relative mRNA levels of IGFBP-4 were determined using real-time RT-PCR. Immunohistochemistry was performed to evaluate the protein expression of IGFBP-4. The relative expression levels of IGFBP-4 mRNA were significantly increased in CDH(-) and CDH(+) groups on D18 and D21 compared to controls. Immunohistochemistry showed increased IGFBP-4 expression in mesenchymal compartments on D18 and D21 in hypoplastic lungs compared to controls. Overexpression of pulmonary IGFBP-4 during the later stages of lung development may contribute to pulmonary hypoplasia in the nitrofen-induced CDH model by inhibiting IGF-mediated cell proliferation. © Georg Thieme Verlag KG Stuttgart · New York.

Expression of T-box transcription factors 2, 4 and 5 is decreased in the branching airway mesenchyme of nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2017-02-01

Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH. We hypothesized that the expression of Tbx2, Tbx4 and Tbx5 is decreased in the branching airway mesenchyme of hypoplastic rat lungs with nitrofen-induced CDH. Time-mated rats received either nitrofen or vehicle on gestational day 9 (D9). Fetuses were killed on D15, D18 and D21, and dissected lungs were divided into control and nitrofen-exposed specimens. Pulmonary gene expression of Tbx2, Tbx4 and Tbx5 was investigated by quantitative real-time polymerase chain reaction. Immunofluorescence double staining for Tbx2, Tbx4 and Tbx5 was combined with the mesenchymal marker Fgf10 to assess protein expression and localization in branching airway tissue. Relative mRNA levels of Tbx2, Tbx4 and Tbx5 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Tbx2, Tbx4 and Tbx5 in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Decreased expression of Tbx2, Tbx4 and Tbx5 in the pulmonary mesenchyme during fetal lung development may lead to a decrease or arrest of airway branching, thus contributing to PH in the nitrofen-induced CDH model.

The impact of the maternal-foetal environment on outcomes of surgery for congenital heart disease in neonates.

PubMed

Gaynor, James William; Parry, Samuel; Moldenhauer, Julie S; Simmons, Rebecca A; Rychik, Jack; Ittenbach, Richard F; Russell, William W; Zullo, Erin; Ward, John Laurenson; Nicolson, Susan C; Spray, Thomas L; Johnson, Mark P

2018-02-13

Pregnancies with congenital heart disease in the foetus have an increased prevalence of pre-eclampsia, small for gestational age and preterm birth, which are evidence of an impaired maternal-foetal environment (MFE). The impact of an impaired MFE, defined as pre-eclampsia, small for gestational age or preterm birth, on outcomes after cardiac surgery was evaluated in neonates (n = 135) enrolled in a study evaluating exposure to environmental toxicants and neuro-developmental outcomes. The most common diagnoses were transposition of the great arteries (n = 47) and hypoplastic left heart syndrome (n = 43). Impaired MFE was present in 28 of 135 (21%) subjects, with small for gestational age present in 17 (61%) patients. The presence of an impaired MFE was similar for all diagnoses, except transposition of the great arteries (P < 0.006). Postoperative length of stay was shorter for subjects without an impaired MFE (14 vs 38 days, P < 0.001). Hospital mortality was not significantly different with or without impaired MFE (11.7% vs 2.8%, P = 0.104). However, for the entire cohort, survival at 36 months was greater for those without an impaired MFE (96% vs 68%, P = 0.001). For patients with hypoplastic left heart syndrome, survival was also greater for those without an impaired MFE (90% vs 43%, P = 0.007). An impaired MFE is common in pregnancies in which the foetus has congenital heart disease. After cardiac surgery in neonates, the presence of an impaired MFE was associated with lower survival at 36 months of age for the entire cohort and for the subgroup with hypoplastic left heart syndrome. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Assessment of Cardiovascular Risk in Collegiate Football Players and Nonathletes

ERIC Educational Resources Information Center

Dobrosielski, Devon A.; Rosenbaum, Daryl; Wooster, Benjamin M.; Merrill, Michael; Swanson, John; Moore, J. Brian; Brubaker, Peter H.

2010-01-01

Collegiate American football players may be at risk for cardiovascular disease. Objective: To compare cardiovascular disease risk factors and cardiovascular structure and function parameters of football players, stratified by position, to a group of sedentary, nonathletes. Participants: Twenty-six collegiate football players and 13 nonathletes…

Editor's Choice - Acute Cardiovascular Care Association Position Paper on Intensive Cardiovascular Care Units: An update on their definition, structure, organisation and function.

PubMed

Bonnefoy-Cudraz, Eric; Bueno, Hector; Casella, Gianni; De Maria, Elia; Fitzsimons, Donna; Halvorsen, Sigrun; Hassager, Christian; Iakobishvili, Zaza; Magdy, Ahmed; Marandi, Toomas; Mimoso, Jorge; Parkhomenko, Alexander; Price, Susana; Rokyta, Richard; Roubille, Francois; Serpytis, Pranas; Shimony, Avi; Stepinska, Janina; Tint, Diana; Trendafilova, Elina; Tubaro, Marco; Vrints, Christiaan; Walker, David; Zahger, Doron; Zima, Endre; Zukermann, Robert; Lettino, Maddalena

2018-02-01

Acute cardiovascular care has progressed considerably since the last position paper was published 10 years ago. It is now a well-defined, complex field with demanding multidisciplinary teamworking. The Acute Cardiovascular Care Association has provided this update of the 2005 position paper on acute cardiovascular care organisation, using a multinational working group. The patient population has changed, and intensive cardiovascular care units now manage a large range of conditions from those simply requiring specialised monitoring, to critical cardiovascular diseases with associated multi-organ failure. To describe better intensive cardiovascular care units case mix, acuity of care has been divided into three levels, and then defining intensive cardiovascular care unit functional organisation. For each level of intensive cardiovascular care unit, this document presents the aims of the units, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region/area. This update emphasises cardiologist training, referring to the recently updated Acute Cardiovascular Care Association core curriculum on acute cardiovascular care. The training of nurses in acute cardiovascular care is additionally addressed. Intensive cardiovascular care unit expertise is not limited to within the unit's geographical boundaries, extending to different specialties and subspecialties of cardiology and other specialties in order to optimally manage the wide scope of acute cardiovascular conditions in frequently highly complex patients. This position paper therefore addresses the need for the inclusion of acute cardiac care and intensive cardiovascular care units within a hospital network, linking university medical centres, large community hospitals, and smaller hospitals with more limited capabilities.

Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Borlaug, Barry A; Roger, Véronique L; Mirzoyev, Sultan A; Rodeheffer, Richard J; Chirinos, Julio A; Redfield, Margaret M

2012-11-01

Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

Pulmonary hypoplasia in Jarcho-Levin syndrome.

PubMed

Rodríguez, Luis M; García-García, Inés; Correa-Rivas, María S; García-Fragoso, Lourdes

2004-03-01

Jarcho-Levin syndrome, also known as spondylothoracic dysplasia and characterized by short trunk dwarfism, "crab-like" rib cage, with ribs and vertebral defects; it is not uncommon in Puerto Ricans. Many patients die in early infancy due to respiratory compromise associated to lung restriction and the reported cases emphasize mostly the skeletal malformations associated to the syndrome. We report the autopsy findings in a newborn with isolated Jarcho-Levin syndrome emphasizing pulmonary pathology. He was a pre-term male who died of respiratory failure at three hours old and, autopsy findings confirmed the clinical diagnosis. Internal examination showed hypoplastic lungs with normal lobation. The histological structure appeared normal and relatively mature; the diaphragm showed eventration and unilateral absence of musculature. This case shows the worst spectum of the Jarcho-Levin syndrome: pulmonary hypoplasia not compatible with extrauterine life. Since thoracic restriction is present during the fetal period, the degree of pulmonary hypoplasia probably defines survival beyond the neonatal period.

Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

PubMed

Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

2011-02-01

Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

Side effects of therapy with prostaglandin E1 in infants with critical congenital heart disease.

PubMed

Lewis, A B; Freed, M D; Heymann, M A; Roehl, S L; Kensey, R C

1981-11-01

The case reports of 492 infants with critical congenital cardiac disease treated with prostaglandin E1 (PGE1) were reviewed to determine the nature and incidence of intercurrent medical events. Forty-three percent of the infants had at least one such event, but only half of these were related to PGE1 and the majority required only minor changes in management. Cardiovascular events were the most common (18% incidence), with cutaneous vasodilation and edema occurring more frequently during intraaortic infusion than during i.v. infusion. Central nervous system events were reported in 16% of the patients. Respiratory depression was reported in 12%, and was particularly common in infants weighing less than 2.0 kg at birth (42%). Hematologic, infectious and renal events appeared for the most part to be unrelated to PGE1. The overall mortality (excluding 19 patients with hypoplastic left-heart syndrome) was 31%; the mortality for the patients with critical coarctation or interruption of the aortic arch was nearly twice that for the cyanotic infants (50% vs 27%). No death was attributed to PGE1 administration. During infusion of PGE1, arterial blood pressure and respiratory activity should be monitored carefully and appropriate supportive steps taken if hypotension or respiratory depression occurs. The development of fever or jitteriness may require reduction of the infusion rate and, in view of the possible increased incidence of infections, the prophylactic use of antibiotics is recommended.

Cardiovascular Impact in Patients Undergoing Maintenance Hemodialysis: Clinical Management Considerations

PubMed Central

Chirakarnjanakorn, Srisakul; Navaneethan, Sankar D.; Francis, Gary S.; Tang, W.H. Wilson

2017-01-01

Patients undergoing maintenance hemodialysis develop both structural and functional cardiovascular abnormalities. Despite improvement of dialysis technology, cardiovascular mortality of this population remains high. The pathophysiological mechanisms of these changes are complex and not well understood. It has been postulated that several non-traditional, uremic-related risk factors, especially the long-term uremic state, which may affect the cardiovascular system. There are many cardiovascular changes that occur in chronic kidney disease including left ventricular hypertrophy, myocardial fibrosis, microvascular disease, accelerated atherosclerosis and arteriosclerosis. These structural and functional changes in patients receiving chronic dialysis make them more susceptible to myocardial ischemia. Hemodialysis itself may adversely affect the cardiovascular system due to non-physiologic fluid removal, leading to hemodynamic instability and initiation of systemic inflammation. In the past decade there has been growing awareness that pathophysiological mechanisms cause cardiovascular dysfunction in patients on chronic dialysis, and there are now pharmacological and non-pharmacological therapies that may improve the poor quality of life and high mortality rate that these patients experience. PMID:28108129

Mining temporal data sets: hypoplastic left heart syndrome case study

NASA Astrophysics Data System (ADS)

Kusiak, Andrew; Caldarone, Christopher A.; Kelleher, Michael D.; Lamb, Fred S.; Persoon, Thomas J.; Gan, Yuan; Burns, Alex

2003-03-01

Hypoplastic left heart syndrome (HLHS) affects infants and is uniformly fatal without surgery. Post-surgery mortality rates are highly variable and dependent on postoperative management. The high mortality after the first stage surgery usually occurs within the first few days after procedure. Typically, the deaths are attributed to the unstable balance between the pulmonary and systemic circulations. An experienced team of physicians, nurses, and therapists is required to successfully manage the infant. However, even the most experienced teams report significant mortality due to the extremely complex relationships among physiologic parameters in a given patient. A data acquisition system was developed for the simultaneous collection of 73 physiologic, laboratory, and nurse-assessed variables. Data records were created at intervals of 30 seconds. An expert-validated wellness score was computed for each data record. A training data set consisting of over 5000 data records from multiple patients was collected. Preliminary results demonstratd that the knowledge discovery approach was over 94.57% accurate in predicting the "wellness score" of an infant. The discovered knowledge can improve care of complex patients by development of an intelligent simulator that can be used to support decisions.

Equine disorders of sexual development in 17 mares including XX, SRY-negative, XY, SRY-negative and XY, SRY-positive genotypes.

PubMed

Villagómez, D A F; Lear, T L; Chenier, T; Lee, S; McGee, R B; Cahill, J; Foster, R A; Reyes, E; St John, E; King, W A

2011-01-01

We described the clinical, cytogenetic and molecular findings of 17 clinical equine cases presented for abnormal sexual development and infertility. Six horses with an enlarged clitoris had an XX, SRY-negative genotype, which displayed male-like behavior (adult individuals). Bilateral ovotestes were noted in 2 of those cases, while another case showed increased levels of circulating testosterone. Six horses with a female phenotype, including normal external genitalia, had an XY, SRY-negative genotype. These individuals had small gonads and an underdeveloped internal reproductive tract. Four horses with normal appearing external genitalia had an XY, SRY-positive genotype, 3 of them had hypoplastic testes and male-like behavior. In addition, one young filly with enlarged clitoris and hypoplastic testes had the same genotype but did not show male-like behavior due to her age. Three of these horses were related with 2 being siblings. These findings demonstrate the diversity of disorders of sexual development seen in the horse. Furthermore, they emphasize the need for further research to identify genes involved in abnormal sex determination and differentiation in the horse. Copyright © 2010 S. Karger AG, Basel.

Acetanilide Oxidation in Phenylbutazone-associated Hypoplastic Anaemia

PubMed Central

Cunningham, J. L.; Leyland, M. J.; Delamore, I. W.; Evans, D. A. Price

1974-01-01

Acetanilide like phenylbutazone is paraoxidized by the liver endoplasmic reticulum as a primary biotransformation step. Both compounds were given at different times to each of 10 healthy volunteer subjects and the plasma disappearances measured. Correlation was shown between plasma clearance values of the two compounds (r = + 0·7067; P < 0·05). Eight patients with hypoplastic anaemia after phenylbutazone therapy were investigated. Plasma clearance values and half lives of acetanilide were measured in this group of patients and compared with those of a group of 30 healthy volunteer controls. There was a significant decrease in clearance (P < 0·01) and lengthening of half lives (P < 0·001 in the patients with phenylbutazone-associated hypoplasia. Five patients with idiopathic aplastic anaemia—that is, without history of antecedent phenylbutazone ingestion—were similarly investigated with acetanilide and there was no significant difference between the results in these patients and those in the control group. It is suggested that relatively poor paraoxidation of phenylbutazone producing high blood concentrations on a given dose may be a factor responsible for the drug-associated hypoplasia even though it does not explain the similar pattern of adverse reactions reported in association with oral administration of the metabolite oxyphenbutazone. PMID:4411815

Acetanilide oxidation in phenylbutazone-associated hypoplastic anaemia.

PubMed

Cunningham, J L; Leyland, M J; Delamore, I W; Evans, D A

1974-08-03

Acetanilide like phenylbutazone is paraoxidized by the liver endoplasmic reticulum as a primary biotransformation step. Both compounds were given at different times to each of 10 healthy volunteer subjects and the plasma disappearances measured. Correlation was shown between plasma clearance values of the two compounds (r = + 0.7067; P < 0.05).Eight patients with hypoplastic anaemia after phenylbutazone therapy were investigated. Plasma clearance values and half lives of acetanilide were measured in this group of patients and compared with those of a group of 30 healthy volunteer controls. There was a significant decrease in clearance (P < 0.01) and lengthening of half lives (P < 0.001 in the patients with phenylbutazone-associated hypoplasia. Five patients with idiopathic aplastic anaemia-that is, without history of antecedent phenylbutazone ingestion-were similarly investigated with acetanilide and there was no significant difference between the results in these patients and those in the control group.It is suggested that relatively poor paraoxidation of phenylbutazone producing high blood concentrations on a given dose may be a factor responsible for the drug-associated hypoplasia even though it does not explain the similar pattern of adverse reactions reported in association with oral administration of the metabolite oxyphenbutazone.

Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

PubMed Central

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

2008-01-01

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

Computational medical imaging and hemodynamics framework for functional analysis and assessment of cardiovascular structures.

PubMed

Wong, Kelvin K L; Wang, Defeng; Ko, Jacky K L; Mazumdar, Jagannath; Le, Thu-Thao; Ghista, Dhanjoo

2017-03-21

Cardiac dysfunction constitutes common cardiovascular health issues in the society, and has been an investigation topic of strong focus by researchers in the medical imaging community. Diagnostic modalities based on echocardiography, magnetic resonance imaging, chest radiography and computed tomography are common techniques that provide cardiovascular structural information to diagnose heart defects. However, functional information of cardiovascular flow, which can in fact be used to support the diagnosis of many cardiovascular diseases with a myriad of hemodynamics performance indicators, remains unexplored to its full potential. Some of these indicators constitute important cardiac functional parameters affecting the cardiovascular abnormalities. With the advancement of computer technology that facilitates high speed computational fluid dynamics, the realization of a support diagnostic platform of hemodynamics quantification and analysis can be achieved. This article reviews the state-of-the-art medical imaging and high fidelity multi-physics computational analyses that together enable reconstruction of cardiovascular structures and hemodynamic flow patterns within them, such as of the left ventricle (LV) and carotid bifurcations. The combined medical imaging and hemodynamic analysis enables us to study the mechanisms of cardiovascular disease-causing dysfunctions, such as how (1) cardiomyopathy causes left ventricular remodeling and loss of contractility leading to heart failure, and (2) modeling of LV construction and simulation of intra-LV hemodynamics can enable us to determine the optimum procedure of surgical ventriculation to restore its contractility and health This combined medical imaging and hemodynamics framework can potentially extend medical knowledge of cardiovascular defects and associated hemodynamic behavior and their surgical restoration, by means of an integrated medical image diagnostics and hemodynamic performance analysis framework.

Utilisation of three-dimensional printed heart models for operative planning of complex congenital heart defects.

PubMed

Olejník, Peter; Nosal, Matej; Havran, Tomas; Furdova, Adriana; Cizmar, Maros; Slabej, Michal; Thurzo, Andrej; Vitovic, Pavol; Klvac, Martin; Acel, Tibor; Masura, Jozef

2017-01-01

To evaluate the accuracy of the three-dimensional (3D) printing of cardiovascular structures. To explore whether utilisation of 3D printed heart replicas can improve surgical and catheter interventional planning in patients with complex congenital heart defects. Between December 2014 and November 2015 we fabricated eight cardiovascular models based on computed tomography data in patients with complex spatial anatomical relationships of cardiovascular structures. A Bland-Altman analysis was used to assess the accuracy of 3D printing by comparing dimension measurements at analogous anatomical locations between the printed models and digital imagery data, as well as between printed models and in vivo surgical findings. The contribution of 3D printed heart models for perioperative planning improvement was evaluated in the four most representative patients. Bland-Altman analysis confirmed the high accuracy of 3D cardiovascular printing. Each printed model offered an improved spatial anatomical orientation of cardiovascular structures. Current 3D printers can produce authentic copies of patients` cardiovascular systems from computed tomography data. The use of 3D printed models can facilitate surgical or catheter interventional procedures in patients with complex congenital heart defects due to better preoperative planning and intraoperative orientation.

Cardiovascular impact in patients undergoing maintenance hemodialysis: Clinical management considerations.

PubMed

Chirakarnjanakorn, Srisakul; Navaneethan, Sankar D; Francis, Gary S; Tang, W H Wilson

2017-04-01

Patients undergoing maintenance hemodialysis develop both structural and functional cardiovascular abnormalities. Despite improvement of dialysis technology, cardiovascular mortality of this population remains high. The pathophysiological mechanisms of these changes are complex and not well understood. It has been postulated that several non-traditional, uremic-related risk factors, especially the long-term uremic state, which may affect the cardiovascular system. There are many cardiovascular changes that occur in chronic kidney disease including left ventricular hypertrophy, myocardial fibrosis, microvascular disease, accelerated atherosclerosis and arteriosclerosis. These structural and functional changes in patients receiving chronic dialysis make them more susceptible to myocardial ischemia. Hemodialysis itself may adversely affect the cardiovascular system due to non-physiologic fluid removal, leading to hemodynamic instability and initiation of systemic inflammation. In the past decade there has been growing awareness that pathophysiological mechanisms cause cardiovascular dysfunction in patients on chronic dialysis, and there are now pharmacological and non-pharmacological therapies that may improve the poor quality of life and high mortality rate that these patients experience. Copyright © 2017 Elsevier B.V. All rights reserved.

Growth retardation, intellectual disability, facial anomalies, cataract, thoracic hypoplasia and skeletal abnormalities: a novel phenotype

PubMed Central

Shah, Hitesh; Bens, Susanne; Caliebe, Almuth; Graham, John M.; Girisha, Katta Mohan

2012-01-01

We report a fourteen year old adolescent girl with growth deficiency, microcephaly, intellectual disability, distinctive dysmorphic features (bulbous nose with wide nasal base, hypotelorism, deeply set eyes, protruding cupped ears and thick lips), cataract, pigmentary retinopathy, hypoplastic thorax, kyphoscoliosis and unusual skeletal changes but without chromosomal imbalances detected by array-CGH who probably represents a novel phenotype. PMID:22987502

Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma.

PubMed

Hegde, Veda; Srikanth, K

2014-01-01

Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

[Clinical and MRI Findings in Patients with Congenital Anosmia].

PubMed

Ogawa, Takao; Kato, Tomohisa; Ono, Mayu; Shimizu, Takeshi

2015-08-01

The clinical characteristics of 16 patients with congenital anosmia were examined retrospectively. MRI (magnetic resonance imaging) was used to assess the morphological changes in the olfactory bulbs and olfactory sulci according to the method of P. Rombaux (2009). Congenital anosmia was divided into two forms: syndromic forms in association with a syndrome, and isolated forms without evidence of other defects. Only three patients (19%) in our series had syndromic forms of congenital anosmia, such as the Kallmann syndrome. Most cases (13 patients, 81%) had isolated congenital anosmia. Psychophysical testing of the olfactory function included T&T olfactometry and the intravenous Alinamin test, which are widely used in Japan. In T&T olfactometry, detection and recognition thresholds for the five odorants are used to assign a diagnostic category representing the level of olfactory function. Most cases (14 patients, 88%) showed off-scale results on T&T olfactometry, and the Alinamin test resulted in no response in all 11 patients who underwent the test. Abnormal MRI findings of the olfactory bulbs and sulci were detected in 15 of 16 patients (94%). Olfactory bulbs were bilaterally absent in nine patients (56%), and two patients (13%) had unilateral olfactory bulbs. Four patients (25%) had bilateral hypoplastic olfactory bulbs, and only one patient had normal olfactory bulbs (6%). The olfactory sulcus was unilaterally absent in one patient (6%), and nine patients (56%) had bilaterally hypoplastic olfactory sulci. Two patients (13%) had a unilateral normal olfactory sulcus and hypoplastic olfactory sulcus. Three patients (19%) had normal olfactory sulci. Quantitative analysis showed that the volume of olfactory bulbs varied from 0 mm3 to 63.5 mm3, with a mean volume of 10.20 ± 18 mm3, and the mean depth of the olfactory sulcus varied from 0 mm to 12.22 mm, with a mean length of 4.85 ± 4.1 mm. Currently, there is no effective treatment for congenital anosmia. However, diagnosis of congenital anosmia is important, as its presence can lead to dangerous situations. Careful examination for hypogonadism is also required in people with anosmia. MRI examinations of the olfactory bulbs and sulci were useful for the diagnosis of congenital anosmia.

Cardiovascular dynamics of Canadian Indigenous peoples.

PubMed

Foulds, Heather J A; Bredin, Shannon S D; Warburton, Darren E R

2018-12-01

Limited understanding of Indigenous adults' cardiovascular structure and function exists despite high rates of cardiovascular disease. This investigation characterised cardiovascular structure and function among young Indigenous adults and compared to age- and sex-matched European descendants. Echocardiographic assessments included apical two- and four-chamber images, parasternal short-axis images and Doppler. Analyses included cardiac volumes, dimensions, velocities and strains. Cardiovascular structure and function were similar between Indigenous (n=10, 25 ± 3 years, 4 women) and European-descendant (n=10, 24 ± 4 years, 4 women,) adults, though European descendants demonstrated greater systemic vascular resistance (18.19 ± 3.94 mmHg∙min -1 ∙L -1 vs. 15.36 ± 2.97 mmHg∙min -1 ∙L -1 , p=0.03). Among Indigenous adults, women demonstrated greater arterial elastance (0.80 ± 0.15 mmHg·mL -1 ·m -2 vs. 0.55 ± 0.17 mmHg·mL -1 ·m -2 , p=0.02) and possibly greater systemic vascular resistance (17.51 ± 2.20 mmHg∙min -1 ∙L -1 vs. 13.93 ± 2.61 mmHg∙min -1 ∙L -1 , p=0.07). Indigenous men had greater cardiac size, dimensions and output, though body size differences accounted for cardiac size differences. Similar cardiac rotation and strains were observed across sexes. Arterial elastance and cardiac size were different between Indigenous men and women while cardiovascular structure and function may be similar between Indigenous and European descendants.

CT findings of the temporal bone in CHARGE syndrome: aspects of importance in cochlear implant surgery.

PubMed

Vesseur, A C; Verbist, B M; Westerlaan, H E; Kloostra, F J J; Admiraal, R J C; van Ravenswaaij-Arts, C M A; Free, R H; Mylanus, E A M

2016-12-01

To provide an overview of anomalies of the temporal bone in CHARGE syndrome relevant to cochlear implantation (CI), anatomical structures of the temporal bone and the respective genotypes were analysed. In this retrospective study, 42 CTs of the temporal bone of 42 patients with CHARGE syndrome were reviewed in consensus by two head-and-neck radiologists and two otological surgeons. Anatomical structures of the temporal bone were evaluated and correlated with genetic data. Abnormalities that might affect CI surgery were seen, such as a vascular structure, a petrosquamosal sinus (13 %), an underdeveloped mastoid (8 %) and an aberrant course of the facial nerve crossing the round window (9 %) and/or the promontory (18 %). The appearance of the inner ear varied widely: in 77 % of patients all semicircular canals were absent and the cochlea varied from normal to hypoplastic. A stenotic cochlear aperture was observed in 37 %. The middle ear was often affected with a stenotic round (14 %) or oval window (71 %). More anomalies were observed in patients with truncating mutations than with non-truncating mutations. Temporal bone findings in CHARGE syndrome vary widely. Vascular variants, aberrant route of the facial nerve, an underdeveloped mastoid, aplasia of the semicircular canals, and stenotic round window may complicate cochlear implantation.

Expression and distribution of hyaluronic acid and CD44 in unphonated human vocal fold mucosa.

PubMed

Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi; Nonaka, Satoshi; Harabuchi, Yasuaki

2009-11-01

The tension caused by phonation (vocal fold vibration) is hypothesized to stimulate vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) to accelerate production of extracellular matrices. The distribution of hyaluronic acid (HA) and expression of CD44 (a cell surface receptor for HA) were examined in human vocal fold mucosae (VFMe) that had remained unphonated since birth. Five specimens of VFMe (3 adults, 2 children) that had remained unphonated since birth were investigated with Alcian blue staining, hyaluronidase digestion, and immunohistochemistry for CD44. The VFMe containing MFe were hypoplastic and rudimentary. The VFMe did not have a vocal ligament, Reinke's space, or a layered structure, and the lamina propria appeared as a uniform structure. In the children, HA was distributed in the VFMe containing MFe. In the adults, HA had decreased in the VFMe containing MFe. In both groups, the VFSCs in the MFe and the fibroblasts in the lamina propria expressed little CD44. This study supports the hypothesis that the tensions caused by vocal fold vibration stimulate the VFSCs in the MFe to accelerate production of extracellular matrices and form the layered structure. Phonation after birth is one of the important factors in the growth and development of the human VFMe.

Histopathologic investigations of the unphonated human child vocal fold mucosa.

PubMed

Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi; Nonaka, Satoshi; Harabuchi, Yasuaki

2012-01-01

Vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) located at both ends of the vocal fold mucosa are inferred to be involved in the metabolism of extracellular matrices. MFe are also considered to be an important structure in the growth and development of the human vocal fold mucosa. Tension caused by phonation (vocal fold vibration) is hypothesized to stimulate VFSCs to accelerate production of extracellular matrices. Human child vocal fold mucosae unphonated since birth were investigated histologically. Histologic analysis of human child vocal fold mucosa. Vocal fold mucosae, which have remained unphonated since birth, of two children (7 and 12 years old) with cerebral palsy were investigated by light and electron microscopy and compared with normal subjects. Vocal fold mucosae and MFe were hypoplastic and rudimentary and did not have a vocal ligament, Reinke's space, or the layered structure. The lamina propria appeared as a uniform structure. Some VFSCs in the MFe showed degeneration and not many vesicles were present at the periphery of the cytoplasm. The VFSCs synthesized fewer extracellular matrices, such as fibrous protein and glycosaminoglycan. The VFSCs appeared to have decreased activity. Vocal fold vibration (phonation) after birth is an important factor in the growth and development of the human vocal fold mucosa. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Structural identifiability analysis of a cardiovascular system model.

PubMed

Pironet, Antoine; Dauby, Pierre C; Chase, J Geoffrey; Docherty, Paul D; Revie, James A; Desaive, Thomas

2016-05-01

The six-chamber cardiovascular system model of Burkhoff and Tyberg has been used in several theoretical and experimental studies. However, this cardiovascular system model (and others derived from it) are not identifiable from any output set. In this work, two such cases of structural non-identifiability are first presented. These cases occur when the model output set only contains a single type of information (pressure or volume). A specific output set is thus chosen, mixing pressure and volume information and containing only a limited number of clinically available measurements. Then, by manipulating the model equations involving these outputs, it is demonstrated that the six-chamber cardiovascular system model is structurally globally identifiable. A further simplification is made, assuming known cardiac valve resistances. Because of the poor practical identifiability of these four parameters, this assumption is usual. Under this hypothesis, the six-chamber cardiovascular system model is structurally identifiable from an even smaller dataset. As a consequence, parameter values computed from limited but well-chosen datasets are theoretically unique. This means that the parameter identification procedure can safely be performed on the model from such a well-chosen dataset. Thus, the model may be considered suitable for use in diagnosis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Prevalence of non-cardiovascular findings on CT angiography in children with congenital heart disease.

PubMed

Malik, Archana; Hellinger, Jeffrey C; Servaes, Sabah; Schwartz, Mathew C; Keller, Marc S; Epelman, Monica

2017-03-01

CT angiography is gaining broader acceptance in the evaluation of children with known or suspected congenital heart disease. These studies include non-cardiovascular structures such as the mediastinum, lung parenchyma and upper abdominal organs. It is important to inspect all these structures for potential abnormalities that might be clinically important and, in some cases, may impact care plans. To determine the prevalence of non-cardiovascular findings in CT angiography of children with congenital heart disease. During 28 months, 300 consecutive children (170 males; mean age: 7.1 years, age range: 6 h-26 years), referred from a tertiary pediatric cardiology center, underwent clinically indicated CT angiography to evaluate known or suspected congenital heart disease. Slightly more than half (n = 169) of the patients were postoperative or post-intervention. Examinations were retrospectively reviewed, and non-cardiovascular findings were recorded and tabulated by organ system, congenital heart disease and operative procedure in conjunction with outcomes from medical charts. Non-cardiovascular findings were identified in 83% (n = 250 / 300) of the studies for a total of 857 findings. In 221 patients (n = 73.7% of 300) a total of 813 non-cardiovascular findings were clinically significant, while in 9.7% (n = 29 / 300) of patients, 5.1% (n = 44 / 857) of the findings were nonsignificant. In 38.3% (n = 115 / 300) of patients with significant non-cardiovascular pathology, the findings were unexpected and directly impacted patient care plans. Commonly involved organs with non-cardiovascular findings were the lungs with 280 non-cardiovascular findings in 176 / 300 (58.7%) of patients, the airway with 139 non-cardiovascular findings in 103 / 300 (34.3%) of patients and the liver with 108 non-cardiovascular findings in 72 / 300 (24.0%) of patients. Syndromic associations were noted in 22% (n = 66 / 300) of the patients. Non-cardiovascular findings are common in children with congenital heart disease who undergo CT angiography. Based upon our study population, if a child with congenital heart disease has a CT angiography, five out of six will have non-cardiovascular findings, while nearly three out of four (73.7%; 221 / 300) will have significant non-cardiovascular findings. Close attention to the non-cardiovascular structures in children with congenital heart disease presenting for a CT angiography is recommended as in nearly 40% of these children, findings were unexpected and directly altered patient care.

Surgical strategy according to the anatomical types of congenital portosystemic shunts in children.

PubMed

Matsuura, Toshiharu; Takahashi, Yoshiaki; Yanagi, Yusuke; Yoshimaru, Koichiro; Yamamura, Kenichiro; Morihana, Eiji; Nagata, Hazumu; Uike, Kiyoshi; Takada, Hidetoshi; Taguchi, Tomoaki

2016-12-01

Congenital portosystemic shunts (CPSS) with intrahepatic portal vein (IHPV) hypoplasia or absence cause encephalopathy or pulmonary hypertension (PH). Acute shunt closure may result in postoperative portal hypertension. The aim of this study was to propose a surgical strategy according to the anatomical types of CPSS and IHPV. Twenty-three CPSS patients were diagnosed from1990 to 2015. All patients were evaluated by computed tomography, angiography, and PV pressure monitoring under a shunt occlusion test. CPSS were categorized into 5 types according to the anatomical shunt location. The median age at diagnosis was 34months. Three of 23 total patients, who had an extrahepatic portosystemic shunt with a hypoplastic IHPV, died before treatment initiation because of severe PH. Fourteen cases received surgical or interventional treatment at the median age of 5years. A total of 6 cases received surgical therapy, including liver transplants for 2 absent IHPV cases. The remaining 8 cases received interventional coiling. All shunt ligations were successfully accomplished in 1-stage ligation without any complications. After the treatment, the hypoplastic IHPV gradually enlarged with an efficient portal inflow. A precise pretreatment anatomical evaluation of CPSS and IHPV types is mandatory for the selection of surgical treatment. Diagnostic study - level II and treatment study - level III. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharyngeal arch deficiencies affect taste bud development in the circumvallate papilla with aberrant glossopharyngeal nerve formation.

PubMed

Okubo, Tadashi; Takada, Shinji

2015-07-01

The pharyngeal arches (PAs) generate cranial organs including the tongue. The taste placodes, formed in particular locations on the embryonic tongue surface, differentiate into taste buds harbored in distinct gustatory papillae. The developing tongue also has a complex supply of cranial nerves through each PA. However, the relationship between the PAs and taste bud development is not fully understood. Ripply3 homozygous mutant mice, which have impaired third/fourth PAs, display a hypoplastic circumvallate papilla and lack taste buds, although the taste placode is normally formed. Formation of the glossopharyngeal ganglia is defective and innervation toward the posterior tongue is completely missing in Ripply3 mutant embryos at E12.5. Moreover, the distribution of neuroblasts derived from the epibranchial placode is severely, but not completely, atenuated, and the neural crest cells are diminished in the third PA region of Ripply3 mutant embryos at E9.5-E10.5. In Tbx1 homozygous mutant embryos, which exhibit another type of deficiency in PA development, the hypoplastic circumvallate papilla is observed along with abnormal formation of the glossopharyngeal ganglia and severely impaired innervation. PA deficiencies affect multiple aspects of taste bud development, including formation of the cranial ganglia and innervation to the posterior tongue. © 2015 Wiley Periodicals, Inc.

Prenatal brain MRI of fetuses with Zika virus infection.

PubMed

Guillemette-Artur, Prisca; Besnard, Marianne; Eyrolle-Guignot, Dominique; Jouannic, Jean-Marie; Garel, Catherine

2016-06-01

An outbreak of Zika virus was observed in French Polynesia in 2013-2014. Maternal Zika virus infection has been associated with fetal microcephaly and severe cerebral damage. To analyze the MRI cerebral findings in fetuses with intrauterine Zika virus infection. We retrospectively analyzed prospectively collected data. Inclusion criteria comprised cases with (1) estimated conception date between June 2013 and May 2014, (2) available US and MRI scans revealing severe fetal brain lesions and (3) positive polymerase chain reaction for Zika virus in the amniotic fluid. We recorded pregnancy history of Zika virus infection and analyzed US and MRI scans. Three out of 12 cases of severe cerebral lesions fulfilled all inclusion criteria. History of maternal Zika virus infection had been documented in two cases. Calcifications and ventriculomegaly were present at US in all cases. MRI showed micrencephaly (n = 3), low cerebellar biometry (n = 2), occipital subependymal pseudocysts (n = 2), polymicrogyria with laminar necrosis and opercular dysplasia (n = 3), absent (n = 1) or hypoplastic (n = 1) corpus callosum and hypoplastic brainstem (n = 1). Severe cerebral damage was observed in our series, with indirect findings suggesting that the germinal matrix is the principal target for Zika virus. The lesions are very similar to severe forms of congenital cytomegalovirus and lymphocytic choriomeningitis virus infections.

Zebrafish as an Alternative Vertebrate Model for Investigating Developmental Toxicity—The Triadimefon Example

PubMed Central

Zoupa, Maria; Machera, Kyriaki

2017-01-01

Triadimefon is a widely used triazole fungicide known to cause severe developmental defects in several model organisms and in humans. The present study evaluated in detail the developmental effects seen in zebrafish embryos exposed to triadimefon, confirmed and expanded upon previous phenotypic findings and compared them to those observed in other traditional animal models. In order to do this, we exposed embryos to 2 and 4 µg/mL triadimefon and evaluated growth until 120 h post-fertilization (hpf) through gross morphology examination. Our analysis revealed significant developmental defects at the highest tested concentration including somite deformities, severe craniofacial defects, a cleft phenotype along the three primary neural divisions, a rigorously hypoplastic or even absent mandible and a hypoplastic morphology of the pharyngeal arches. Interestingly, massive pericardial edemas, abnormal shaped hearts, brachycardia and inhibited or absent blood circulation were also observed. Our results revealed that the presented zebrafish phenotypes are comparable to those seen in other organism models and those derived from human observations as a result of triadimefon exposure. We therefore demonstrated that zebrafish provide an excellent system for study of compounds with toxic significance and can be used as an alternative model for developmental toxicity studies to predict effects in mammals. PMID:28417904

[Perioperative management for open balloon atrial septostomy immediately after caesarean section in a baby with hypoplastic left heart syndrome and intact atrial septum].

PubMed

Yokoi, Nagisa; Toda, Yuichiro; Suzuki, Satoshi; Kanazawa, Tomoyuki; Suemori, Tomohiko; Shimizu, Kazuyoshi; Iwasaki, Tatsuo; Morita, Kiyoshi

2010-10-01

Hypoplastic left heart syndrome (HLHS) with intact atrial septum (IAS) is an extreme type of single ventricle physiology among congenital heart diseases, in which a baby cannot supply oxygenated blood into systemic circulation without alternative pathway. We report the case of the neonate undergoing open balloon atrial septostomy (BAS) and bilateral pulmonary artery banding (PAB) soon after scheduled caesarean sections (C/S). A 35-year-old female was pregnant and fetal echocardiography at 32 weeks revealed one of the twins as HLHS/IAS. Severe hypoxia soon after birth was suspected. Thus, scheduled C/S followed by open BAS was planned. At 36 weeks of gestation, the mother was anesthetized with spinal bupivacaine and the female baby with HLHS/IAS was delivered. After diagnosed definitely by pediatric cardiologists, her trachea was intubated by anesthegiologists and umbilical catheters were placed by neonatologists. Then the baby was transferred to neighboring operating theater for BAS 68 minutes after the birth, while her Sp(O2) was maintained around 75-85% through serial procedures. Open BAS and PAB were performed under general anesthesia without any hemodynamic instability or severe hypoxia. Cooperation among anesthegiologists, neonatologists, pediatric cardiologists, and cardiac surgeons is mandatory in order to successfully complete such a rushed procedure.

Quantitative volumetric analysis of a retinoic acid induced hypoplastic model of chick thymus, using Image-J.

PubMed

Haque, Ayesha; Khan, Muhammad Yunus

2017-09-01

To assess the total volume change in a retinoic acid-induced, hypoplastic model of a chick thymus using Image-J. This experimental study was carried out at the anatomy department of College of Physicians and Surgeons, Islamabad, Pakistan, from February 2009 to February 2010, and comprised fertilised chicken eggs. The eggs were divided into experimental group A and control group C. Group A was injected with 0.3µg of retinoic acid via yolk sac to induce a defective model of a thymus with hypoplasia. The chicks were sacrificed on embryonic day 15 and at hatching. The thymus of each animal was processed, serially sectioned and stained. The total area of each section of thymus was calculated using Image-J. This total area was summed and multiplied with the thickness of each section to obtain volume. Of the 120 eggs, there were 60(50%) in each group. Image analysis revealed a highly significant decrease in the volume of the chick thymus in the experimental group A than its matched control at the time of hatching (p=0.001). Moreover, volumetric depletion progressed with time, being substantially pronounced at hatching compared to the embryonic stage. The volume changes were significant and were effectively quantified using Image-J.

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

PubMed

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R; Matsushita, Mark; Raskind, Wendy H

2008-07-15

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. 2008 Wiley-Liss, Inc.

Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish.

PubMed

Niu, Xubo; Gao, Chuan; Jan Lo, Li; Luo, Yue; Meng, Chunmei; Hong, Jian; Hong, Wanjin; Peng, Jinrong

2012-07-15

The Sec13-Sec31 heterotetramer serves as the outer coat in the COPII complex, which mediates protein trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus. Although it has been studied in depth in yeast and cultured cells, the role of COPII in organogenesis in a multicellular organism has not. We report here that a zebrafish sec13(sq198) mutant, which exhibits a phenotype of hypoplastic digestive organs, has a mutation in the sec13 gene. The mutant gene encodes a carboxyl-terminus-truncated Sec13 that loses its affinity to Sec31a, which leads to disintegration of the ER structure in various differentiated cells in sec13(sq198), including chondrocytes, intestinal epithelial cells and hepatocytes. Disruption of the ER structure activates an unfolded protein response that eventually causes the cells to undergo cell-cycle arrest and cell apoptosis, which arrest the growth of developing digestive organs in the mutant. Our data provide the first direct genetic evidence that COPII function is essential for the organogenesis of the digestive system. Copyright © 2012 Elsevier Inc. All rights reserved.

Function of circle of Willis

PubMed Central

Vrselja, Zvonimir; Brkic, Hrvoje; Mrdenovic, Stefan; Radic, Radivoje; Curic, Goran

2014-01-01

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress. PMID:24473483

Current outcomes and risk factors for the Norwood procedure.

PubMed

Stasik, Chad N; Gelehrter, S; Goldberg, Caren S; Bove, Edward L; Devaney, Eric J; Ohye, Richard G

2006-02-01

Tremendous strides have been made in the outcomes for hypoplastic left heart syndrome and other functional single-ventricle malformations over the past 25 years. This progress relates primarily to improvements in survival for patients undergoing the Norwood procedure. Previous reports on risk factors have been on smaller groups of patients or collected over relatively long periods of time, during which management has evolved. We analyzed our current results for the Norwood procedure with attention to risk factors for poor outcome. A single-institution review of all patients undergoing a Norwood procedure for a single-ventricle malformation from May 1, 2001, through April 30, 2003, was performed. Patient demographics, anatomy, clinical condition, associated anomalies, operative details, and outcomes were recorded. Of the 111 patients, there were 23 (21%) hospital deaths. Univariate analysis revealed noncardiac abnormalities (genetic or significant extracardiac diagnosis, P = .0018), gestational age (P = .03), diagnosis of unbalanced atrioventricular septal defect (P = .017), and weight of less than 2.5 kg (P = .0072) to be related to hospital death. On multivariate analysis, only weight of less than 2.5 kg and noncardiac abnormalities were found to be independent risk factors. Patients with either of these characteristics had a hospital survival of 52% (12/23), whereas those at standard risk had a survival of 86% (76/88). Although improvements in management might have lessened the effect of some of the traditionally reported risk factors related to variations in the cardiovascular anatomy, noncardiac abnormalities and low birth weight remain as a future challenge for the physician caring for the patient with single-ventricle physiology.

Cardiac Structure and Function in Humans: A New Cardiovascular Physiology Laboratory

ERIC Educational Resources Information Center

Song, Su; Burleson, Paul D.; Passo, Stanley; Messina, Edward J.; Levine, Norman; Thompson, Carl I.; Belloni, Francis L.; Recchia, Fabio A.; Ojaimi, Caroline; Kaley, Gabor; Hintze, Thomas H.

2009-01-01

As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another "hands-on" experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle,…

Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography

PubMed Central

Boppart, Stephen A.; Tearney, Gary J.; Bouma, Brett E.; Southern, James F.; Brezinski, Mark E.; Fujimoto, James G.

1997-01-01

Studies investigating normal and abnormal cardiac development are frequently limited by an inability to assess cardiovascular function within the intact organism. In this work, optical coherence tomography (OCT), a new method of micron-scale, noninvasive imaging based on the measurement of backscattered infrared light, was introduced for the high resolution assessment of structure and function in the developing Xenopus laevis cardiovascular system. Microstructural details, such as ventricular size and wall positions, were delineated with OCT at 16-μm resolution and correlated with histology. Three-dimensional representation of the cardiovascular system also was achieved by repeated cross-sectional imaging at intervals of 25 μm. In addition to structural information, OCT provides high speed in vivo axial ranging and imaging, allowing quantitative dynamic activity, such as ventricular ejection fraction, to be assessed. The sensitivity of OCT for dynamic assessment was demonstrated with an inotropic agent that altered cardiac function and dimensions. Optical coherence tomography is an attractive new technology for assessing cardiovascular development because of its high resolution, its ability to image through nontransparent structures, and its inexpensive portable design. In vivo and in vitro imaging are performed at a resolution approaching that of histopathology without the need for animal killing. PMID:9113976

[Magnetic resonance imaging features in two Chinese family with congenital fibrosis of extraocular muscles].

PubMed

Wu, Li; Zhou, Lian-Hong; Liu, Chang-Sheng; Cha, Yun-Fei; Wang, Jiong; Xing, Yi-Qiao

2009-11-01

The aim of this article was to investigate the structural basis of ocular motility and visual abnormalities in humans with congenital fibrosis of the extraocular muscles (CFEOM). 17 volunteers from 2 CFEOM pedigrees Clinical ophthalmic and motility examed and 18 normal control subjects were correlated with thin-sectioned magnetic resonance imaging (MRI) across the orbit and the brain-stem level. Subjects with CFEOM had severe bilateral blepharoptosis, limited supraduction, and variable ophthalmoplegia. In affected subjects, MRI demonstrated atrophy of the levator palpebrae superioris, all EOMs, and the optic nerves, and small or absent orbital motor nerves. The oculomotor nerve was most severely hypoplastic, but the abducens was also affected. Subjects with CFEOM exhibited subclinical but highly significant reduction from normal in mean optic nerve size (P < 0.05). There are also some difference between the two CFEOM pedigrees. These findings suggest that neuronal disease is primary in CFEOM, with myopathy arising secondary to abnormal innervation and the oculomotor nucleus and trochlear nucleus of the abnormalities defects.

Interdisciplinary Full Mouth Rehabilitation of a Patient with Amelogenesis Imperfecta: A Case Report with 8 Years Follow-up

PubMed Central

Sreedevi, S; Sanjeev, R; Ephraim, Rena; Joseph, Mathai

2014-01-01

This case report deals with the interdisciplinary approach of a 28-year-old lady with Amelogenesis imperfecta of the hypoplastic kind. The patient came with a chief illness of worn out teeth, unsatisfactory esthetics and severe sensitivity of teeth. Her family history revealed a related situation in her father’s brother and her sister. On clinical assessment, the crowns of all teeth were worn out. The plan of the treatment was to protect as much tooth structure, restore the vertical dimension, and improve esthetics and masticatory function. The treatment procedures involved prosthodontic, endodontic, and periodontic interventions. After recording the vertical height, endodontic treatment and crown lengthening were performed with respect to the lower anteriors. The lost vertical height was regained in stages by insertion of full coverage crowns for all the teeth. The patient’s esthetic and functional needs were met with systematic and sequential interdisciplinary treatment approach. PMID:25628493

Waardenburg syndrome.

PubMed

Tagra, Sunita; Talwar, Amrita Kaur; Walia, Rattan Lal Singh; Sidhu, Puneet

2006-01-01

Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features of the syndrome, have been depicted in the pedigree.

[Polycystic ovary syndrome: an example of obesity-related cardiovascular complication affecting young women].

PubMed

Orio, Francesco; Cascella, Teresa; Giallauria, Francesco; Palomba, Stefano; De Lorenzo, Anna; Lucci, Rosa; Ambrosino, Elena; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo

2006-03-01

Polycystic ovary syndrome (PCOS) is a good example of obesity-related cardiovascular complication affecting young women. PCOS is not only considered a reproductive problem but rather represents a complex endocrine, multifaceted syndrome with important health implications. Several evidences suggest an increased cardiovascular risk of cardiovascular disease associated with this syndrome, characterized by an impairment of heart structure and function, endothelial dysfunction and lipid abnormalities. All these features, probably linked to insulin-resistance, are often present in obese PCOS patients. Cardiovascular abnormalities represent important long-term sequelae of PCOS that need further investigations.

Fainiting (Syncope)

MedlinePlus

... sudden cardiac arrest and death. Types of Syncope Cardiovascular syncope – The most dangerous but rare type of ... or by structural damage to the heart. Non-cardiovascular syncope – The most common type (also called vasovagal ...

Disturbance of parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Lukosiūte, Ausra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2010-01-01

Despite remarkable progress in resuscitation and intensive care, the morbidity and mortality rates in congenital diaphragmatic hernia (CDH) remain high due to severe pulmonary hypoplasia. The pathogenesis of pulmonary hypoplasia associated with CDH is still not clearly understood. Pulmonary parathyroid hormone-related protein (PTHrP) is expressed in the type II epithelial cells and stimulates surfactant production by a paracrine feedback loop regulated by PTHrP receptor (PTHrP-R), which is expressed in the mesenchyme, during terminal airway differentiation. It has been reported that PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia, disrupting alveolar maturation before birth. We designed this study to test the hypothesis that gene expression of PTHrP and PTHrP-R is downregulated in the late stages of lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, 18, and 21 and divided into three groups: control, nitrofen without CDH [CDH(-)], and nitrofen with CDH [CDH(+)] (n = 8 at each time point for each group, respectively). Total mRNA was extracted from fetal lungs and mRNA expression of PTHrP and PTHrP-R was analyzed by real-time RT-PCR and the significant differences between the groups were accepted at P < 0.05 by statistical analysis. Immunohistochemical studies were also performed to evaluate PTHrP and PTHrP-R protein expression at each time point. Pulmonary mRNA expression of PTHrP-R was significantly decreased in both nitrofen groups [CDH(-) and CDH(+)] compared to controls at D18 and 21. The mRNA level of PTHrP was significantly decreased at D21 in both nitrofen groups compared to controls. Immunoreactivity of PTHrP and PTHrP-R at D18 and 21 was diminished in the distal epithelium and in the mesenchyme, respectively, in the nitrofen-induced hypoplastic lung compared to control lungs. There were no significant differences in both gene/protein expression of PTHrP and PTHrP-R on D15. Downregulation of PTHrP and PTHrP-R gene expression during late lung morphogenesis may cause pulmonary hypoplasia in the nitrofen CDH model, disrupting alveolar maturation and surfactant production by interfering with mesenchymal-epithelial interactions.

Associations of mental health with cardiovascular risk phenotypes and adiposity in adolescence: A cross-sectional community-based study.

PubMed

Lycett, Kate; McNamara, Clare; Mensah, Fiona K; Burgner, David; Kerr, Jessica A; Muller, Josh; Wake, Melissa

2018-06-01

Cardiovascular disease and mental illness commonly co-occur in later life, but it is unknown how early these associations arise. We aimed to determine the extent to which: (i) childhood mental health is associated with functional and structural cardiovascular risk phenotypes and adiposity in late childhood/adolescence, and (ii) associations between mental health and cardiovascular phenotypes may be explained by differential body mass index. This cross-sectional study drew on three longitudinal community-based cohort studies (two enriched for overweight/obesity) in metropolitan Melbourne, Australia, with harmonized follow-up in 2014. Mental health exposures included emotional and behavioural problems (Strength and Difficulties Questionnaire) and psychosocial health and general well-being (Pediatric Quality of Life Inventory (PedsQL)), which were assessed by self- and parent-proxy report. Cardiovascular risk phenotypes and adiposity measures included mean arterial pressure, pulse wave velocity, carotid artery intima-media thickness, retinal arterioleto-venule ratio, waist circumference, % body fat, and BMI z-score. We used multivariable linear regression models, adjusting for age, sex and neighbourhood disadvantage, to examine associations. Of the 364 participants (mean age 14.7, standard deviation 2.0, years), 30% were overweight and 16% obese. All adiposity indicators were positively associated with higher behavioural/emotional problems and poorer psychosocial health and negatively associated with better ratings of positive general well-being, as reported by parents and children (all P ≤ 0.03). However, there was little evidence that cardiovascular functional or structural phenotypes varied by mental health. By late childhood/adolescence, mental health is strongly associated with adiposity but not with cardiovascular structure or function. This suggests that the known relationship between these constructs may not develop until early or mid-adulthood. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

[Effectiveness of a preventive intervention strategy based on structured telephone interviews in a working population with a moderate to high cardiovascular risk].

PubMed

Sierra, Martha Cabrera; Bonacho, Eva Calvo; García, Ángel García; Moraga, Montserrat Ruiz; Gutiérrez, Juan Carlos Sainz; Barrientos, Antonio Chama; Sánchez-Chaparro, Miguel Ángel

2010-10-01

This study assesses the effectiveness of a structured telephone survey on cardiovascular prevention, in modifying lifestyle, on cardiovascular risk parameters, percentage of smoking cessation and overall cardiovascular risk (CVR). Quasi-experimental study of preventive intervention. Ibermutuamur (Spanish Accident and Health Insurance Company). Centres established throughout Spain. A total of 4,792 workers with moderate/high cardiovascular risk who had agreed to be contacted by phone. Subjects with a previous diagnosis of cardiovascular disease and those receiving treatment for hypertension, hypercholesterolemia or diabetes were excluded. A final total of 3,085 workers were contacted and were followed up by telephone surveys on the first, fourth and eighth month after the initial check up (CU) in order to emphasise cardiovascular health advice (Group A); we failed to contact 1,707 workers, who only attended the baseline and one year CUs (Group B). PRINCIPAL OUTCOMES: CUs included medical records and physical examination, with two blood pressure measurements, Body Mass Index (BMI), and biochemical parameters. Cardiovascular risk was stratified following the European cardiovascular SCORE. Individuals with a relative risk higher than 4 were also considered as high-risk. All workers were informed about their cardiovascular risk profile (CVRF) and healthy cardiovascular lifestyle measures. They were also given a letter for their General Practitioner (GP) to inform them on the worker's cardiovascular risk level. A total of 71.5% of the workers were over 45 years, 95.0% males, 76.6% manual workers ("Blue Collar") and 69.7% smokers. Both groups showed improvement in lipid parameters, blood pressure, smoking cessation and overall cardiovascular risk in the second CU. There were significant differences in favour of Group A as regards blood pressure, lipids (except HDL cholesterol), BMI, glycaemia, smoking cessation (A: 23.5%/B: 19.44%, P=0.001) and CVR stratum improvement (A: 46.6%/B: 37.7%, P=0.0001). The large majority (85%) of workers read preventive recommendations; 33% knew their risk level and 73% knew their CVRF. 52.9% gave the letter to the GP, which led them to start therapies on diet (47%), hypertension (19.5%), dyslipidaemia (16.7%), diabetes (4.4%) and smoking (2.9%) and no changes were made in 36.5% of cases. The results of this study suggests that cardiovascular prevention strategy based on structured telephone surveys on high/moderate CVR subjects to promote lifestyle changes could be effective at reducing CVR. A clinical trial is required for confirmation. Sending information on CVRF following routine medial CUs and Primary Care involvement, could contribute to the positive changes observed. Copyright © 2009 Elsevier España, S.L. All rights reserved.

Congenitally absent lumbar pedicle: a reappraisal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortzman, G.; Steinhardt, M.I.

1984-09-01

Three patients who had a diagnosis of congenitally absent lumbar pedicle underwent CT examination. Findings showed that each patient had an aberrant hypoplastic pedicle plus a retroisthmic defect in their ipsilateral lamina rather than an absent pedicle. Axial CT was the diagnostic modality of choice; reformated images were of little value. The differential diagnosis to be considered from the findings of plain film radiography includes pediculate thinning, neoplastic disease, neurofibroma, mesodermal dysplasia associated with neurofibromatosis, and vascular anomalies.

Left isomerism syndrome with total anomalous systemic connection.

PubMed

Vo, Anh Tuan; Cao, Khang Dang; Le, Khoi Minh; Nguyen, Dinh Hoang

2017-01-01

We present a case of left isomerism with total anomalous systemic venous connection where the inferior vena cava was absent and all other systemic veins connected abnormally to the left atrium. The right atrium was hypoplastic with an intact atrial septum. Blood flow to the lungs was through a large ventricular septal defect. The diagnosis was made with echocardiography, angiography, and computed tomography. Complete repair was performed successfully, and the 7-year-old patient had an uneventful recovery.

Upper limb malformations in DiGeorge syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cormier-Daire, V.; Iserin, L.; Sidi, D.

1995-03-13

We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22q11 deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22q11 deletions. 13 refs., 2 figs.

Hypoplastic left heart syndrome and pulmonary veno-occlusive disease in an infant.

PubMed

D'Souza, Marise; Vergales, Jeffrey; Jayakumar, K Anitha

2013-01-01

This report describes an infant with heterotaxy syndrome and severe hypoplasia of the left heart who presented with profound cyanosis at birth despite a large patent ductus arteriosus. Pulmonary venous return was difficult to demonstrate by echocardiography. Angiography showed total anomalous pulmonary venous return via a plexus that drained through the paravertebral veins and bilateral superior vena cavae. Autopsy confirmed these findings, and histopathology demonstrated severe occlusive changes within the pulmonary veins.

[Tapeto-retinal degeneration combined with incomplete general albinism (author's transl)].

PubMed

Ivandić, T

1975-05-01

Report on a family, which presented the rare autosomal dominant transmitted, incomplete general albinism associated with autosomal recessive inherited, diffuse tapeto-retinal degeneration "sine pigmento". hypopigmentation of skin, eyebrows and hair, blue iris and fundus albinoticus with hypoplasia of the macula. In 3 cases additionally appeared: waxy pallor of optic disc, vascular narrowing, reflexless hypoplastic macula, pigmentless periphery, acquired blue-yellow blindness, concentric limitation of the visual field, reduced darkadaptation, abolished electroretinogram and myopic astigmatism.

Population-based analysis of survival for hypoplastic left heart syndrome.

PubMed

Hirsch, Jennifer C; Copeland, Glenn; Donohue, Janet E; Kirby, Russell S; Grigorescu, Violanda; Gurney, James G

2011-07-01

To analyze survival patterns among infants with hypoplastic left heart syndrome (HLHS) in the State of Michigan. Cases of HLHS prevalent at live birth were identified and confirmed within the Michigan Birth Defects Registry from 1992 to 2005 (n=406). Characteristics of infants with HLHS were compared with a 10:1 random control sample. Compared with 4060 control subjects, the 406 cases of HLHS were more frequently male (62.6% vs 51.4%), born prematurely (<37 weeks gestation; 15.3% vs 8.7%), and born at low birth weight (LBW) (<2.5 kg; 16.0% vs 6.6%). HLHS 1-year survival rate improved over the study period (P=.041). Chromosomal abnormalities, LBW, premature birth, and living in a high poverty neighborhood were significantly associated with death. Controlling for neighborhood poverty, term infants versus preterm with HLHS or LBW were 3.2 times (95% CI: 1.9-5.3; P<.001) more likely to survive at least 1 year. Controlling for age and weight, infants from low-poverty versus high-poverty areas were 1.8 times (95% CI: 1.1-2.8; P=.015) more likely to survive at least 1 year. Among infants with HLHS in Michigan, those who were premature, LBW, had chromosomal abnormalities, or lived in a high-poverty area were at increased risk for early death. Copyright © 2011 Mosby, Inc. All rights reserved.

A systematic method for using 3D echocardiography to evaluate tricuspid valve insufficiency in hypoplastic left heart syndrome.

PubMed

Mart, Christopher Robin; Eckhauser, Aaron Wesley; Murri, Michael; Su, Jason Thomas

2014-09-01

With surgical palliation of hypoplastic left heart syndrome (HLHS), the tricuspid valve (TV) becomes the systemic atrioventricular valve and moderate/severe TV insufficiency (TVI), an adverse risk factor for survival to Fontan, has been reported in up to 35% of patients prior to stage I palliation. Precise echocardiographic identification of the mechanism of TVI cannot be determined by two-dimensional echocardiography. Three-dimensional echocardiography (3DE) can provide significant insight into the mechanisms of TVI. It is the intent of this report to propose a systematic method on how to evaluate and display 3DE images of the TV in HLHS which has not been done previously. TV anatomy, function, and the known mechanisms of insufficiency are reviewed. We defined three regions of the TV (anterior, posterior, septal) that can help define valve "leaflets" that incorporates the many variations of TV anatomy. To determine how the surgeon views the TV, a picture of a pathologic specimen of the TV was placed on a computer screen and rotated until it was oriented as it appears during surgery, the "surgeons view." We have proposed a systematic method for evaluating and displaying the TV using 3DE which can provide significant insight into the mechanisms causing TVI in HLHS. This has the potential to improve both the surgical approach to repairing the valve and, ultimately, patient outcomes.

A systematic method for using 3D echocardiography to evaluate tricuspid valve insufficiency in hypoplastic left heart syndrome

PubMed Central

Mart, Christopher Robin; Eckhauser, Aaron Wesley; Murri, Michael; Su, Jason Thomas

2014-01-01

With surgical palliation of hypoplastic left heart syndrome (HLHS), the tricuspid valve (TV) becomes the systemic atrioventricular valve and moderate/severe TV insufficiency (TVI), an adverse risk factor for survival to Fontan, has been reported in up to 35% of patients prior to stage I palliation. Precise echocardiographic identification of the mechanism of TVI cannot be determined by two-dimensional echocardiography. Three-dimensional echocardiography (3DE) can provide significant insight into the mechanisms of TVI. It is the intent of this report to propose a systematic method on how to evaluate and display 3DE images of the TV in HLHS which has not been done previously. TV anatomy, function, and the known mechanisms of insufficiency are reviewed. We defined three regions of the TV (anterior, posterior, septal) that can help define valve “leaflets” that incorporates the many variations of TV anatomy. To determine how the surgeon views the TV, a picture of a pathologic specimen of the TV was placed on a computer screen and rotated until it was oriented as it appears during surgery, the “surgeons view.” We have proposed a systematic method for evaluating and displaying the TV using 3DE which can provide significant insight into the mechanisms causing TVI in HLHS. This has the potential to improve both the surgical approach to repairing the valve and, ultimately, patient outcomes. PMID:25298694

A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study).

PubMed

Kobayashi, Takashi; Nannya, Yasuhito; Ichikawa, Motoshi; Oritani, Kenji; Kanakura, Yuzuru; Tomita, Akihiro; Kiyoi, Hitoshi; Kobune, Masayoshi; Kato, Junji; Kawabata, Hiroshi; Shindo, Motohiro; Torimoto, Yoshihiro; Yonemura, Yuji; Hanaoka, Nobuyoshi; Nakakuma, Hideki; Hasegawa, Daisuke; Manabe, Atsushi; Fujishima, Naohito; Fujii, Nobuharu; Tanimoto, Mitsune; Morita, Yasuyoshi; Matsuda, Akira; Fujieda, Atsushi; Katayama, Naoyuki; Ohashi, Haruhiko; Nagai, Hirokazu; Terada, Yoshiki; Hino, Masayuki; Sato, Ken; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Ohta, Masatsugu; Imataki, Osamu; Uemura, Makiko; Takaku, Tomoiku; Komatsu, Norio; Kitanaka, Akira; Shimoda, Kazuya; Watanabe, Kenichiro; Tohyama, Kaoru; Takaori-Kondo, Akifumi; Harigae, Hideo; Arai, Shunya; Miyazaki, Yasushi; Ozawa, Keiya; Kurokawa, Mineo

2017-12-01

Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences. The overall survival (OS) and AML progression-free survival (AML-PFS) of hMDS were higher than those of non-hMDS, especially in patients at age ≥50 and of lower risk in Revised International Prognostic Scoring System (IPSS-R). In competing risks analysis, hMDS exhibited decreased risk of AML-progression in lower IPSS or IPSS-R risk patients, and higher risk of death from BMF in patients at age ≥50. Poor performance status (PS ≥2) and high karyotype risks in IPSS-R (high and very high) were significant risk factors of death and AML-progression in Cox proportional hazards analysis. © 2017 Wiley Periodicals, Inc.

Dental Caries Experience in Texan Children with Cleft Lip and Palate.

PubMed

Sunderji, Sabrina; Acharya, Bhavini; Flaitz, Catherine; Chiquet, Brett

2017-09-15

The purpose of this study was to assess the caries experience in the primary dentition of children born with cleft lip and palate (CLP). A retrospective chart review was conducted on subjects between two and six years old recruited from a university-based pediatric dentistry residency clinic. The number of dental visits and professional fluoride applications, the plaque index and treatment modality, and the presence/location of caries, white spot lesions, and enamel hypoplastic lesions were compared between CLP patients and healthy age- and gender-matched controls. Descriptive statistics, Student's t test, Mann-Whitney U test, and regression analysis were completed. A total of 183 charts were reviewed. Compared to healthy children, CLP children had increases in number of dental visits (P<0.001), decayed-missing-filled surfaces (dmfs; P<0.001), decayed-missing-filled teeth (dmft; P<0.001), enamel hypoplastic lesions (P=0.003), treatment completed under general anesthesia (P<0.001), plaque score (P<0.001), and caries increment between baseline and most recent oral examination (P=0.003). Regression analysis revealed a positive association between age and dmft scores within the CLP group (P=0.018). The caries experience of unilateral and bilateral CLP cases was the same (P>0.05). Children with cleft lip and palate are at a greater risk of enamel hypoplasia and dental caries. No significant caries experience difference was found between unilateral or bilateral CLP cases.

[Disappearance of residual disease confirmed by RT-PCR following induction chemotherapy in two hypoplastic leukemia patients with t(8;21)].

PubMed

Sawada, M; Tsurumi, H; Yamada, T; Hara, T; Oyama, M; Moriwaki, H

1999-04-01

Reverse transcriptase-polymerase chain reaction (RT-PCR) methods often detect the AML1/MTG8 fusion transcript even in acute myelogenous leukemia (AML) patients with t(8;21) who have been in long-term remission. We encountered 2 hypoplastic leukemia patients with t(8;21) who achieved cytogenetic remission with short-term conventional chemotherapy. Patient 1 was a 42-year-old woman. Chromosomal analysis detected t(8;21) (q22;q22) and PCR analysis (35 cycles PCR amplification; detection limit 1 x 10(-5) cells) detected the AML1/MTG8 fusion transcript. Complete remission was obtained with 1 course of chemotherapy consisting of low-dose cytarabine (20 mg x 14 days) and etoposide (50 mg x 14 days). After 2 courses of consolidation chemotherapy consisting of conventional-dose cytarabine and mitoxantrone, the RT-PCR findings were negative for the AML1/MTG8 fusion transcript. Patient 2 was a 67-year-old man. Cytogenetic analysis detected t(8;21) (q22;q22), and was positive for the AML1/MTG8 fusion transcript. After 2 courses of induction chemotherapy comprising low-dose cytarabine (20 mg x 14 days) and etoposide (50 mg x 14 days), and 3 courses of conventional consolidation chemotherapy, RT-PCR analysis confirmed the disappearance of the AML1/MTG8 fusion transcript.

Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.

PubMed

Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

2016-05-05

Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.

Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression

PubMed Central

Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H.; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

2016-01-01

Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2f/f;Bmp4f/fameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling. PMID:27146352

Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997-2011.

PubMed

Interrante, Julia D; Ailes, Elizabeth C; Lind, Jennifer N; Anderka, Marlene; Feldkamp, Marcia L; Werler, Martha M; Taylor, Lockwood G; Trinidad, James; Gilboa, Suzanne M; Broussard, Cheryl S

2017-10-01

To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8-2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9). Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment. Published by Elsevier Inc.

The Miracle Baby Grows Up: Hypoplastic Left Heart Syndrome in the Adult.

PubMed

Lewis, Matthew; Rosenbaum, Marlon

2017-08-01

Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of the mitral valve, left ventricle, and aorta and is ultimately palliated with a single-ventricle repair. Universally fatal in infancy prior to the advent of modern surgical techniques, the majority of HLHS patients will now reach adulthood. However, despite improvements in early survival, the HLHS population continues to face significant morbidity and early mortality. This review delineates common sources of patient morbidity and highlights areas in need of additional research for this growing segment of the adult congenital heart disease population. It has become increasingly clear that palliated adult single ventricle patients, like those with HLHS, face significant life-long morbidity from elevated systemic venous pressures as a consequence of the Fontan procedure. Downstream organ dysfunction secondary to elevated Fontan pressures has the potential to significantly impact long-term management decisions, including strategies of organ allocation. Because of the presence of a morphologic systemic right ventricle, HLHS patients may be at even higher risk than other adult patients with a Fontan. Because the adult HLHS population continues to grow, recognition of common sources of patient morbidity and mortality is becoming increasingly important. A coordinated effort between patients and providers is necessary to address the many remaining areas of clinical uncertainty to help ensure continued improvement in patient prognosis and quality of life.

Patient-specific biomechanical model of hypoplastic left heart to predict post-operative cardio-circulatory behaviour.

PubMed

Cutrì, Elena; Meoli, Alessio; Dubini, Gabriele; Migliavacca, Francesco; Hsia, Tain-Yen; Pennati, Giancarlo

2017-09-01

Hypoplastic left heart syndrome is a complex congenital heart disease characterised by the underdevelopment of the left ventricle normally treated with a three-stage surgical repair. In this study, a multiscale closed-loop cardio-circulatory model is created to reproduce the pre-operative condition of a patient suffering from such pathology and virtual surgery is performed. Firstly, cardio-circulatory parameters are estimated using a fully closed-loop cardio-circulatory lumped parameter model. Secondly, a 3D standalone FEA model is build up to obtain active and passive ventricular characteristics and unloaded reference state. Lastly, the 3D model of the single ventricle is coupled to the lumped parameter model of the circulation obtaining a multiscale closed-loop pre-operative model. Lacking any information on the fibre orientation, two cases were simulated: (i) fibre distributed as in the physiological right ventricle and (ii) fibre as in the physiological left ventricle. Once the pre-operative condition is satisfactorily simulated for the two cases, virtual surgery is performed. The post-operative results in the two cases highlighted similar hemodynamic behaviour but different local mechanics. This finding suggests that the knowledge of the patient-specific fibre arrangement is important to correctly estimate the single ventricle's working condition and consequently can be valuable to support clinical decision. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Right-ventricular global longitudinal strain may predict neo-aortic arch obstruction after Norwood/Sano procedure in children with hypoplastic left heart syndrome.

PubMed

Raucci, Frank J; Seckeler, Michael D; Saunders, Christine; Gangemi, James J; Peeler, Benjamin B; Jayakumar, K Anitha

2013-01-01

Neo-aortic arch obstruction (NAAO) is a common complication following the Norwood/Sano procedure (NP) for hypoplastic left heart syndrome (HLHS) and is associated with increased morbidity and mortality. However, there is currently no objective method for predicting which patients will develop NAAO. This study was designed to test the hypothesis that hemodynamic changes from development of NAAO after NP in patients with HLHS will lead to changes in myocardial dynamics that could be detected before clinical symptoms develop with strain analysis using velocity vector imaging. Patients with HLHS who had at least one cardiac catheterization after NP were identified retrospectively. Strain analysis was performed on all echocardiograms preceding the first catheterization and any subsequent catheterization performed for intervention on NAAO. Twelve patients developed NAAO and 30 patients never developed NAAO. Right ventricular strain was worse in the group that developed NAAO (-6.2 vs. -8.6 %, p = 0.040) at a median of 59 days prior to diagnosis of NAAO. Those patients that developed NAAO following NP were significantly younger at the time of first catheterization than those that did not develop NAAO (92 ± 50 vs. 140 ± 36 days, p = 0.001). This study demonstrates that right ventricular GLS is abnormal in HLHS patients following NP and worsening right ventricular strain may be predictive of the future development of NAAO.

Cardiovascular problems associated with aviation safety.

DOT National Transportation Integrated Search

1976-01-01

In April 1975, the American College of Cardiology held its Eighth Bethesda Conference Conference on Cardiovascular Problem in Aviation Safety. : Perhaps the most meaningful purpose of this meeting was to make clear, in a structured fashion, the avail...

The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children.

PubMed

Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele

2017-07-07

The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

Preeclampsia, prematurity and cardiovascular health in adult life.

PubMed

Lewandowski, Adam J; Leeson, Paul

2014-11-01

Investigations into how perinatal growth and intrauterine environment may 'programme' risk of later cardiovascular disease have been ongoing for over two decades. One of the more recent outcomes of these studies is the observation that certain pregnancy-related conditions, such as preterm birth, have an unusually large impact on the long-term cardiovascular health of the offspring. In the present paper, we review the current literature of how preterm birth affects the long-term cardiovascular structure and function of the offspring, considering three major areas of investigation: firstly, outlining the long-term cardiovascular phenotypic changes in preterm-born individuals; secondly, investigating factors related to preterm birth that may be modifying cardiovascular phenotype, such as preeclampsia, perinatal interventions, and physiological disturbances; and thirdly, the expected clinical relevance of these cardiovascular changes. This review discusses the importance of continued research focused on the mechanistic understanding of these cardiovascular alterations in order to develop specific primary prevention strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two sisters resembling Gorlin-Chaudhry-Moss syndrome.

PubMed

Aravena, Teresa; Passalacqua, Cristóbal; Pizarro, Oscar; Aracena, Mariana

2011-10-01

The Gorlin-Chaudhry-Moss syndrome (GCMS), was describe initially by Gorlin et al. [Gorlin et al. (1960)] in two sisters with craniosynostosis, hypertrichosis, hypoplastic labia majora, dental defects, eye anomalies, patent ductus arteriosus, and normal intelligence. Two other sporadic instances have been documented. Here, we report on two sisters with a condition with some similarities to GCMS as well as some differences, which could represent either previously unreported variability in GCMS, or it may represent a novel disorder. Copyright © 2011 Wiley-Liss, Inc.

New Lethal Skeletal Dysplasia with Dandy-Walker Malformation, Congenital Heart Defects, Abnormal Thumbs, Hypoplastic Genitalia, and Distinctive Facies

PubMed Central

Stevens, Cathy A.; Lachman, Ralph S.

2011-01-01

We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles, dumbbell femurs, and absence of talus and calcaneus ossification. Other clinical features include Dandy-Walker malformation, congenital heart defects, joint contractures, genital hypoplasia, and distinctive facial features. These sibs appear to have a previously undescribed skeletal dysplasia, which is most likely inherited in an autosomal recessive fashion. PMID:20602491

The 48, XXXX/49,XXXXY/49,XXXX,i(Yq) mosaicism in a 3-year-old boy from a twin pregnancy.

PubMed

Kaluzewski, B; Podkul, D; Zaborowska, I; Moruzgala, T; Jakubowski, L

1977-07-26

A 3-year-old boy from twin pregnancy with the features of marked dystrophia from birth, deficient growth, considerable retardation of physical and mental development, numerous somatic defects, suspected congenital heart disease, and hypoplastic external genitalia, is reported. The 48,XXXX/49,XXXXY/49,XXXX,i(Yq) karyotype was diagnosed. The boy's brother, normally developed, had a 46,XY karyotype. It was found on the basis of serologic findings that the brothers were dizygotic twins.

Mycotic pulmonary artery aneurysm following pulmonary artery banding.

PubMed

Kumar, R V; Roughneen, P T; de Leval, M R

1994-01-01

A neonate with situs inversus, transposition of the great arteries, ventricular septal defect, criss-cross ventricles and hypoplastic right ventricle underwent pulmonary artery banding at the age of 7 days. The course was complicated by septicaemia and subsequently the development of an aneurysm of the pulmonary artery. Serratia marcessans was grown from the band site. The pulmonary artery aneurysm was resected and the pulmonary artery was repaired. The literature is reviewed with the emphasis on diagnosis, natural history and surgical management.

Cancer as a Risk Factor for Cardiovascular Disease.

PubMed

Giza, Dana Elena; Iliescu, Gloria; Hassan, Saamir; Marmagkiolis, Konstantinos; Iliescu, Cezar

2017-06-01

Improvements in early diagnosis and cancer treatments have contributed to high survival rates for many cancer patients. However, these patients often die of cardiovascular disease rather than recurrence of their cancer. Heart disease manifesting after cancer may be due to several mechanisms: shared cardiovascular risks between cancer and cardiovascular disease, inflammatory states associated with malignancies, and/or cardiotoxic effects of cancer therapy. Cancer treatment increases the risk of cardiovascular diseases directly by damaging critical structures of the heart or indirectly by promoting accelerated atherosclerosis. Estimating cardiovascular risk by using advanced imaging and monitoring of the cardiac biomarkers can be used for early detection and treatment of subclinical cardiac injury. Better knowledge of these early and late cardiac effects in cancer patients will enable adoption of both primary and secondary prevention measures of long-term treatment complications in cancer survivors.

Applications of 3D printing in cardiovascular diseases.

PubMed

Giannopoulos, Andreas A; Mitsouras, Dimitris; Yoo, Shi-Joon; Liu, Peter P; Chatzizisis, Yiannis S; Rybicki, Frank J

2016-12-01

3D-printed models fabricated from CT, MRI, or echocardiography data provide the advantage of haptic feedback, direct manipulation, and enhanced understanding of cardiovascular anatomy and underlying pathologies. Reported applications of cardiovascular 3D printing span from diagnostic assistance and optimization of management algorithms in complex cardiovascular diseases, to planning and simulating surgical and interventional procedures. The technology has been used in practically the entire range of structural, valvular, and congenital heart diseases, and the added-value of 3D printing is established. Patient-specific implants and custom-made devices can be designed, produced, and tested, thus opening new horizons in personalized patient care and cardiovascular research. Physicians and trainees can better elucidate anatomical abnormalities with the use of 3D-printed models, and communication with patients is markedly improved. Cardiovascular 3D bioprinting and molecular 3D printing, although currently not translated into clinical practice, hold revolutionary potential. 3D printing is expected to have a broad influence in cardiovascular care, and will prove pivotal for the future generation of cardiovascular imagers and care providers. In this Review, we summarize the cardiovascular 3D printing workflow, from image acquisition to the generation of a hand-held model, and discuss the cardiovascular applications and the current status and future perspectives of cardiovascular 3D printing.

Ideal cardiovascular health in childhood-Longitudinal associations with cardiac structure and function: The Special Turku Coronary Risk Factor Intervention Project (STRIP) and the Cardiovascular Risk in Young Finns Study (YFS).

PubMed

Laitinen, Tomi T; Ruohonen, Saku; Juonala, Markus; Magnussen, Costan G; Mikkilä, Vera; Mikola, Hanna; Hutri-Kähönen, Nina; Laitinen, Tomi; Tossavainen, Päivi; Jokinen, Eero; Niinikoski, Harri; Jula, Antti; Viikari, Jorma S A; Rönnemaa, Tapani; Raitakari, Olli T; Pahkala, Katja

2017-03-01

Ideal cardiovascular health (CVH), defined by the American Heart Association, is associated with incident cardiovascular disease in adults. However, association of the ideal CVH in childhood with current and future cardiac structure and function has not been studied. The sample comprised 827 children participating in the longitudinal Special Turku Coronary Risk Factor Intervention Project (STRIP) and The Cardiovascular Risk in Young Finns Study (YFS). In STRIP, complete data on the seven ideal CVH metrics and left ventricular (LV) mass measured with echocardiography were available at the age of 15 (n=321), 17 (n=309) and 19 (n=283) years. In YFS, the cohort comprised children aged 12-18years (n=506) with complete ideal CVH metrics data from childhood and 25years later in adulthood, and echocardiography performed in adulthood. In STRIP, ideal CVH score was inversely associated with LV mass during childhood (P=0.036). In YFS, childhood ideal CVH score was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume in adulthood (all P<0.01). In addition, improvement of the ideal CVH score between childhood and adulthood was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume (all P≤0.03). Childhood ideal CVH score has a long-lasting effect on cardiac structure and function, and the association is evident already in childhood. Our findings support targeting the ideal CVH metrics as part of primordial prevention of cardiovascular diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dental Aspect of Distal Tubular Renal Acidosis with Genu Valgum Secondary to Rickets: A Case Report

PubMed Central

Bahadure, Rakesh N.; Thosar, Nilima; Kriplani, Ritika; Baliga, Sudhindra; Fulzele, Punit

2012-01-01

Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis). Distal renal tubular acidosis (type I RTA) is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic), pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year. PMID:22567455

Arachnoid membranes in the posterior half of the incisural space: an inverted Liliequist membrane-like arachnoid complex.

PubMed

Zhang, Xi-An; Qi, Song-Tao; Fan, Jun; Huang, Guang-Long; Peng, Jun-Xiang

2014-08-01

The aim of this study was to describe the similarity of configuration between the arachnoid complex in the posterior half of the incisural space and the Liliequist membrane. Microsurgical dissection and anatomical observation were performed in 20 formalin-fixed adult cadaver heads. The origin, distribution, and configuration of the arachnoid membranes and their relationships with the vascular structures in the posterior half of the incisural space were examined. The posterior perimesencephalic membrane and the cerebellar precentral membrane have a common origin at the tentorial edge and form an arachnoid complex strikingly resembling an inverted Liliequist membrane. Asymmetry between sides is not uncommon. If the cerebellar precentral membrane is hypoplastic on one side or both, the well-developed quadrigeminal membrane plays a prominent part in partitioning the subarachnoid space in the posterior half of the incisural space. The arachnoid complex in the posterior half of the incisural space can be regarded as an inverted Liliequist membrane. This concept can help neurosurgeons to gain better understanding of the surgical anatomy at the level of the tentorial incisura.

Anesthetic management during a cesarean section in a patient with cleidocranial dysplasia: a case report.

PubMed

Nishio, Yumiko; Hiraki, Teruyuki; Taniguchi, Hiroko; Ushijima, Kazuo

2018-01-01

Cleidocranial dysplasia is a type of skeletal dysplasia, which is primarily characterized by delayed ossification of skeletal structures. It causes facial and oral abnormalities, resulting in difficult airway management and neuraxial anesthesia. The patient was a 24-year-old primipara (height 138 cm, weight 42 kg) with a hypoplastic right clavicle, patent fontanelles, dental malalignment, and a high palate. She was diagnosed with cleidocranial dysplasia at birth, although gene examination has not been performed. The fetus was confirmed to have short limbs and large fontanelles during an examination performed at 28 weeks gestation, suspected to have cleidocranial dysplasia. The mother was scheduled for a cesarean section at 37 weeks and 1 day due to cephalopelvic disproportion. Preoperative radiography and magnetic resonance imaging revealed no vertebral and spinal abnormalities, which allowed combined spinal-epidural analgesia (CSEA) to be performed. The surgery was safely concluded under CSEA with no intraoperative respiratory or circulatory problems. Patients with cleidocranial dysplasia exhibit facial, oral abnormalities, and often vertebral abnormalities. Imaging assessments before neuraxial anesthesia and careful preparation for airway management are required.

Opinions of community pharmacists on the value of a cardiovascular polypill as a means of improving medication compliance.

PubMed

Burns, Kharis; Turnbull, Fiona; Patel, Anushka; Peiris, David

2012-06-01

Cardiovascular disease is a major public health problem despite established treatment guidelines and significant healthcare expenditure worldwide. Poor medication compliance accounts in part for some of the observed evidence/practice gaps. Trials of fixed-dose combination pills are currently underway, but the attitudes of relevant health professionals to the routine use of a cardiovascular polypill are generally unknown. Pharmacists are a group of providers who play an important role in patient compliance with long-term medications. The objective was to identify the main perceived barriers to compliance and to investigate pharmacists' opinions regarding the routine use of a cardiovascular polypill. The setting was community pharmacies in the metropolitan and greater areas of New South Wales, Australia. Structured questionnaires were administered to a random sample of community pharmacists and peer-to-peer, semi-structured interviews were conducted with a sub-sample. Quantitative data were analysed using SPSS V16.0 and interviews were analysed thematically. Questionnaires were completed by 72 of the 250 pharmacists invited to participate. The major barrier to cardiovascular medication compliance identified by respondents was polypharmacy. Other barriers included patient disinterest, time constraints and costs. Most pharmacists agreed that a cardiovascular polypill could be one potential solution to poor compliance by simplifying the treatment regimen (73.6% agreed) and reducing patient costs (79.2% agreed). Inability to tailor treatment and to ascribe side effects was among some of the identified concerns. The use of a cardiovascular polypill as a means of increasing patient compliance with long-term cardiovascular preventive therapies is seen as potentially valuable by community pharmacists. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

Aromatase Deficiency due to a Homozygous CYP19A1 Mutation in a 46,XX Egyptian Patient with Ambiguous Genitalia.

PubMed

Mazen, Inas; McElreavey, Ken; Elaidy, Aya; Kamel, Alaa K; Abdel-Hamid, Mohamed S

2017-01-01

Aromatase deficiency (AD) is a very rare disorder resulting from mutations in the CYP19A1 gene encoding aromatase, a cytochrome P450 enzyme that plays a pivotal role in androgen conversion to estrogens. AD is inherited in an autosomal recessive trait, and to date only 35 cases have been described in the literature. Herein, we depict a new patient reared as a male, who presented at the age of 21 years with no palpable testis, hypoplastic scrotum, penis-like phallus (3 cm), and penoscrotal hypospadias. The patient was born to consanguineous parents, his karyotype was 46,XX, and SRY was negative. Pelvic sonar showed a small hypoplastic uterus, and no testis could be identified. Serum testosterone was within the reference range of females along with high gonadotropins. Pathology of gonadal biopsy showed ovarian stroma negative for oocytic follicle consistent with streak gonads. All these data were suggestive of AD, which was subsequently confirmed by molecular investigation of the CYP19A1 gene. A homozygous splice site mutation in the donor splice site of exon 9 was identified, c.1263 + 1G>T. This is the first report of such a rare disorder in an Egyptian patient. Our results reinforce the importance of considering AD in patients with 46,XX disorders of sex development after ruling out congenital adrenal hyperplasia. © 2018 S. Karger AG, Basel.

Downregulation of insulin-like growth factor binding protein 3 and 5 in nitrofen-induced pulmonary hypoplasia.

PubMed

Ruttenstock, Elke; Doi, Takashi; Dingemann, Jens; Puri, Prem

2010-01-01

The high mortality in congenital diaphragmatic hernia (CDH) is mainly attributed to pulmonary hypoplasia. Recent studies suggest that retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The insulin-like growth factor (IGF) system plays a crucial role in fetal lung development by interaction of IGFBP-3 and IGFBP-5 with RSP. We hypothesized that pulmonary IGFBP-3 and IGFBP-5 gene expression levels are downregulated in the nitrofen-induced pulmonary hypoplasia. Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9.5 (D9.5) of gestation. Fetal lungs were harvested on D18 and D21 and divided into control and nitrofen groups. IGFBP-3 and IGFBP-5 pulmonary gene and protein expression were determined using real-time RT-PCR and immunohistochemistry. Relative levels of IGFBP-3 mRNA were significantly decreased in the nitrofen group (8.00 +/- 14.44) in D21 compared to controls (14.81 +/- 16.11; p < 0.05). Expression levels of IGFBP-5 mRNA were also significantly decreased in nitrofen group (10.66 +/- 4.83) on D18 compared to controls (17.92 +/- 4.77). Immunohistochemistry showed decreased IGFBP-3 expression on D21 and decreased IGFBP-5 immunoreactivity on D18 in hypoplastic lungs compared to controls. Downregulation of IGFBP-3 and IGFBP-5 gene expression may cause pulmonary hypoplasia in the nitrofen-induced CDH model by interfering with retinoid signaling pathway.

Prevalence of dental anomalies in a population of cleft lip and palate patients.

PubMed

Al Jamal, Ghaida A; Hazza'a, Abdalla M; Rawashdeh, Ma'amon A

2010-07-01

The aim of our study was to investigate radiographically the prevalence of dental anomalies in a group of Jordanian cleft lip and/or palate subjects. This is a retrospective review of panoramic radiographs of 78 subjects with cleft lip and/or palate that were evaluated from their file records and investigated for possible dental anomalies. Dental anomalies were found frequently in cleft lip and/or palate subjects. Missing teeth were found in 66.7% of the patients; the tooth most commonly missing was the maxillary lateral incisor. Supernumerary teeth were found in 16.7% of patients; 37% had microdontia; 70.5% had taurodontism; 30.8% had transposition and/or ectopic teeth; 19.2% had dilacerations; and 30.8% had hypoplastic teeth. There was no statistically significant difference in the above anomalies' prevalence between males and females. However, it was found that subjects with bilateral cleft lip and/or palate had significantly more microdontia (p = .005), dilaceration (p = .002), and hypoplastic teeth (p = .0001) than subjects with unilateral cleft lip and/or palate. The prevalence of dental anomalies in cleft lip and/or palate patients was higher than what had been reported in the normal Jordanian population. This emphasizes the relation of cleft lip and/or palate to all dental anomalies studied. Although our study represents a thorough and complete description of dental anomalies present in a sample of cleft lip and/or palate subjects, larger samples are required to effectively determine the relationship of each dental anomaly with cleft type.

Complications of congenital portosystemic shunts in children: therapeutic options and outcomes.

PubMed

Franchi-Abella, Stéphanie; Branchereau, Sophie; Lambert, Virginie; Fabre, Monique; Steimberg, Clarisa; Losay, Jean; Riou, Jean-Yves; Pariente, Danièle; Gauthier, Frédéric; Jacquemin, Emmanuel; Bernard, Olivier

2010-09-01

Congenital portosystemic shunts are rare vascular malformations that lead to severe complications. Their management is controversial. The aim of this study was to propose a clear definition of the risks and management of congenital portosystemic shunts in children according to our experience and a review of the literature. Twenty-two children with a complicated congenital portosystemic shunt were studied in our institution. When necessary, management included portal pressure measurement and portal vein angiography during an occlusion test and closure of the shunt by surgical and/or endovascular methods. Five neonates with intrahepatic shunts presented with cholestasis that resolved spontaneously, and 17 older children presented with liver tumors (13) and/or hepatopulmonary syndrome (2), pulmonary artery hypertension (3), portosystemic encephalopathy (3), heart failure (1), and glomerulonephritis (1). The portosystemic shunt was extrahepatic (11) or intrahepatic (6). Portosystemic shunts were closed by endovascular methods in 5 children and surgically in 10, 4 of whom had portal pressure during occlusion above 35 mmHg and extremely hypoplastic or undetectable portal veins requiring banding of the fistula before closure. Shunt closure resulted in restoration of intrahepatic portal flow in all, with complete or partial regression of benign liver masses, and regression or stabilization of pulmonary, cardiac, neurological, and renal complications. Congenital portosystemic shunt carries risks of severe complications in children. Closure of a shunt persisting after age 2 years should be considered preventively. Intrahepatic portal flux restoration can be expected, even when intrahepatic portal veins are extremely hypoplastic or undetectable.

Correction of penile ventral curvature in patients with minor or no hypospadias: a single surgeon's experience of 43 cases.

PubMed

Seo, Shogo; Ochi, Takanori; Yazaki, Yuta; Murakami, Hiroshi; Okawada, Manabu; Doi, Takashi; Miyano, Go; Koga, Hiroyuki; Lane, Geoffrey J; Yamataka, Atsuyuki

2016-10-01

To report our experience of correcting penile ventral curvature associated with minor or no hypospadias. We reviewed 43 penile ventral curvature patients treated by a single surgeon from 1997 to 2015. Of these, 23 had minor hypospadias. Curvature was corrected using degloving, chordectomy, dorsal plication (DP), tunica albuginea incision (TAI), or a combination of these. Outcome was confirmed by induced artificial erection and post-operative appearance. Mean age at curvature correction was 3.2 ± 2.6 years. 17/43 had degloving and chordectomy (DC), 16/43 had DP after DC, and 10/43 had TAI after DC, because of ventral shortening and severe curvature caused by a short hypoplastic urethra. Other procedures required were primary meatoplasty (n = 4) and urethroplasty (UP; n = 1) at the time of curvature correction, and UP after correction of curvature (n = 11). Complications included recurrence of curvature after DP (n = 3/16; 18.8 %) and urethral stenosis after UP with tubed peritoneum (n = 1/10; 10 %). There were no recurrences of curvature in TAI cases. Parents reported penile cosmesis as good (n = 38; 88.4 %), acceptable (n = 4; 9.3 %), or poor (n = 1; 2.3 %). We recommend TAI followed by UP for correcting penile ventral curvature with short hypoplastic urethra. Tubed peritoneum is not recommended for UP.

Separation of the PROX1 gene from upstream conserved elements in a complex inversion/translocation patient with hypoplastic left heart

PubMed Central

Gill, Harinder K; Parsons, Sian R; Spalluto, Cosma; Davies, Angela F; Knorz, Victoria J; Burlinson, Clare EG; Ng, Bee Ling; Carter, Nigel P; Ogilvie, Caroline Mackie; Wilson, David I; Roberts, Roland G

2009-01-01

Hypoplastic left heart (HLH) occurs in at least 1 in 10 000 live births but may be more common in utero. Its causes are poorly understood but a number of affected cases are associated with chromosomal abnormalities. We set out to localize the breakpoints in a patient with sporadic HLH and a de novo translocation. Initial studies showed that the apparently simple 1q41;3q27.1 translocation was actually combined with a 4-Mb inversion, also de novo, of material within 1q41. We therefore localized all four breakpoints and found that no known transcription units were disrupted. However we present a case, based on functional considerations, synteny and position of highly conserved non-coding sequence elements, and the heterozygous Prox1+/− mouse phenotype (ventricular hypoplasia), for the involvement of dysregulation of the PROX1 gene in the aetiology of HLH in this case. Accordingly, we show that the spatial expression pattern of PROX1 in the developing human heart is consistent with a role in cardiac development. We suggest that dysregulation of PROX1 gene expression due to separation from its conserved upstream elements is likely to have caused the heart defects observed in this patient, and that PROX1 should be considered as a potential candidate gene for other cases of HLH. The relevance of another breakpoint separating the cardiac gene ESRRG from a conserved downstream element is also discussed. PMID:19471316

Congenital hypoplastic bone marrow failure associated with a de novo partial deletion of the MECOM gene at 3q26.2.

PubMed

Kjeldsen, Eigil; Veigaard, Christopher; Aggerholm, Anni; Hasle, Henrik

2018-05-20

Congenital hypoplastic bone marrow failure is a rare condition in neonates. The genetics and mechanisms behind are largely obscure. Here we characterize a neonate presenting with congenital thrombocytopenia and anemia. During the first 2-4 weeks after birth the neonate developed severe neutropenia while the lymphoid lineages were unaffected. The neonate was without dysmorphic signs. A de novo mono-allelic constitutional microdeletion of 175.1 kb at 3q26.2 affecting exon 2 of MECOM, involving MDS1 but not EVI1, was identified as the only copy number alteration by oligo-based array-CGH analysis. Expression analysis showed profoundly reduced expression of multiple MECOM transcripts in the bone marrow cells. Whole exome sequencing detected no pathogenic mutations in genes known to be associated with inherited bone marrow failure syndromes. The patient was successfully treated with hematopoietic stem cell transplantation at 5 months of age. Interstitial deletions encompassing the 3q26.2 region are very rare. A literature search revealed two previous cases with microdeletions involving this region, and the cases were associated with congenital thrombocytopenia and anemia, but unaffected lymphopoiesis. Together these data indicate that MECOM may be important for normal myeloid hematopoiesis in humans but dispensable for lymphoid differentiation. We suggest that partial deletion in MECOM may be a primary event associated with congenital pancytopenia. Copyright © 2018 Elsevier B.V. All rights reserved.

A defect in early myogenesis causes Otitis media in two mouse models of 22q11.2 Deletion Syndrome

PubMed Central

Fuchs, Jennifer C.; Linden, Jennifer F.; Baldini, Antonio; Tucker, Abigail S.

2015-01-01

Otitis media (OM), the inflammation of the middle ear, is the most common disease and cause for surgery in infants worldwide. Chronic Otitis media with effusion (OME) often leads to conductive hearing loss and is a common feature of a number of craniofacial syndromes, such as 22q11.2 Deletion Syndrome (22q11.2DS). OM is more common in children because the more horizontal position of the Eustachian tube (ET) in infants limits or delays clearance of middle ear effusions. Some mouse models with OM have shown alterations in the morphology and angle of the ET. Here, we present a novel mechanism in which OM is caused not by a defect in the ET itself but in the muscles that control its function. Our results show that in two mouse models of 22q11.2DS (Df1/+ and Tbx1+/−) presenting with bi- or unilateral OME, the fourth pharyngeal arch-derived levator veli palatini muscles were hypoplastic, which was associated with an earlier altered pattern of MyoD expression. Importantly, in mice with unilateral OME, the side with the inflammation was associated with significantly smaller muscles than the contralateral unaffected ear. Functional tests examining ET patency confirmed a reduced clearing ability in the heterozygous mice. Our findings are also of clinical relevance as targeting hypoplastic muscles might present a novel preventative measure for reducing the high rates of OM in 22q11.2DS patients. PMID:25452432

Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

PubMed

Elmaleh-Bergès, M; Baumann, C; Noël-Pétroff, N; Sekkal, A; Couloigner, V; Devriendt, K; Wilson, M; Marlin, S; Sebag, G; Pingault, V

2013-01-01

Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

Deterministic chaos and fractal complexity in the dynamics of cardiovascular behavior: perspectives on a new frontier.

PubMed

Sharma, Vijay

2009-09-10

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts.

Deterministic Chaos and Fractal Complexity in the Dynamics of Cardiovascular Behavior: Perspectives on a New Frontier

PubMed Central

Sharma, Vijay

2009-01-01

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts. PMID:19812706

Protective Effects of Terpenes on the Cardiovascular System: Current Advances and Future Perspectives.

PubMed

Alves-Silva, Jorge M; Zuzarte, Monica; Marques, Carla; Salgueiro, Ligia; Girao, Henrique

2016-01-01

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide that seriously affect patient's life quality and are responsible for huge economic and social burdens. It is widely accepted that a plant-based diet may reduce the risk of CVDs by attenuating several risk factors and/or modulating disease's onset and progression. Plants are rich in secondary metabolites, being terpenes the most abundant and structurally diverse group. These compounds have shown broad therapeutic potential as antimicrobial, antiviral, anti-inflammatory and antitumor agents. Despite their popularity, scientific evidence on terpenes cardiovascular effects remains sparse, limiting their potential use as cardioprotective and/or cardiotherapeutic agents. Bearing in mind the lack of comprehensive and systematic studies, the present review aims to gather the knowledge and some of the most scientific evidence accumulated over the past years on the effect of terpenes in the cardiovascular field with focus on CVDs namely ischemic heart disease, heart failure, arrhythmias and hypertension. Several popular search engines including PubMed, Science Direct, Scopus and Google Scholar were consulted. The bibliographic research focused primarily on English written papers published over the last 15 years. A systematic and comprehensive update on the cardiovascular effects of terpenes is provided. Moreover, whenever known, the possible mechanisms of action underlying the cardiovascular effects are pointed out as well as an attempt to identify the most relevant structure- activity relationships of the different classes of terpenes. Overall, this review enables a better understanding of the cardiovascular effects of terpenes, thus paving the way towards future research in medicinal chemistry and rational drug design.

Echocardiography in the Era of Multimodality Cardiovascular Imaging

PubMed Central

Shah, Benoy Nalin

2013-01-01

Echocardiography remains the most frequently performed cardiac imaging investigation and is an invaluable tool for detailed and accurate evaluation of cardiac structure and function. Echocardiography, nuclear cardiology, cardiac magnetic resonance imaging, and cardiovascular-computed tomography comprise the subspeciality of cardiovascular imaging, and these techniques are often used together for a multimodality, comprehensive assessment of a number of cardiac diseases. This paper provides the general cardiologist and physician with an overview of state-of-the-art modern echocardiography, summarising established indications as well as highlighting advances in stress echocardiography, three-dimensional echocardiography, deformation imaging, and contrast echocardiography. Strengths and limitations of echocardiography are discussed as well as the growing role of real-time three-dimensional echocardiography in the guidance of structural heart interventions in the cardiac catheter laboratory. PMID:23878804

A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems.

PubMed

Xu, Jiaxi; Mukerjee, Snigdha; Silva-Alves, Cristiane R A; Carvalho-Galvão, Alynne; Cruz, Josiane C; Balarini, Camille M; Braga, Valdir A; Lazartigues, Eric; França-Silva, Maria S

2016-01-01

ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation.

A structural model of health behavior modification among patients with cardiovascular disease.

PubMed

Goong, Hwasoo; Ryu, Seungmi; Xu, Lijuan

2016-02-01

The purpose of the study was to test a structural equation model in which social support, health beliefs, and stage of change predict the health behaviors of patients with cardiovascular disease. A cross-sectional correlational design was used. Using convenience sampling, a survey about social support, health belief, stage of change, and health behavior was completed by 314 adults with cardiovascular disease from outpatient clinics in 2 university hospitals in Korea. Data were analyzed using a structural equation model with the Analysis of Moment program. The participants were aged 53.44±13.19 years (mean±SD), and about 64% of them were male. The proposed model fit the data from the study well, explaining 19% and 60% of the variances in the stage of change and health behavior, respectively. The findings indicate that the performance of health behavior modification among the patients with cardiovascular disease can be explained by social support, health belief, and stage of change based on a health-belief and stage-of-change model. Further studies are warranted to confirm the efficacy of health-promoting strategies in initiating and maintaining the performance of health behaviors by providing social support from family and medical staff and enhancing health belief. Copyright © 2015 Elsevier Inc. All rights reserved.

Cranioplasty Using a Modified Split Calvarial Graft Technique in Cleidocranial Dysplasia

PubMed Central

Jung, Young Taek; Cho, Jae Ik

2015-01-01

Cleidocranial dysplasia is a well-documented rare autosomal dominant skeletal dysplasia characterized by hypoplastic/aplastic clavicles, brachycephalic skull, patent sutures and fontanelles, midface hypoplasia, and abnormalities of dentition. Patients with cleidocranial dysplasia often complain about undesirable esthetic appearance of their forehead and skull. Notwithstanding many studies of molecular, genetics and skeletal abnormalities of this congenial disorder, there have been very few written reports of cranioplasty involving cleidocranial dysplasia. Thus, we report a rare case of successful cranioplasty using a modified split calvarial graft technique in patient with cleidocranial dysplasia. PMID:26279819

Seckel syndrome: a report of a case.

PubMed

Ramalingam, K; Kaliyamurthy, S D; Govindarajan, M; Swathi, S

2012-01-01

Seckel syndrome, first defined by Seckel in 1960, is a rare (incidence 1:10,000), genetically heterogeneous autosomal recessive disorder presenting at birth. This syndrome is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly with a "bird-headed" like appearance (beaked nose, receding forehead, prominent eyes, and micrognathia), and mental retardation. The significance of dental alterations in this syndrome resides in the defect, hypoplastic enamel, being limited to the primary dentition; in most instances the second primary molar tooth is not affected. A case of the Seckel syndrome is presented.

Mosaic Trisomy 9p in a Patient with Mild Dysmorphic Features and Normal Intelligence.

PubMed

Brar, Randeep; Basel, Donald G; Bick, David P; Weik, LuAnn; vanTuinen, Peter; Peterson, Jess F

2017-01-01

To the Editor: Partial and whole duplications of the short arm of chromosome 9 have been commonly reported in the literature with characteristic phenotypic features and intellectual disabilities. The clinical features of 9p duplications are broad and can include growth retardation, developmental delay, intellectual disability, microbrachycephaly, deep set eyes, hypertelorism, downslanting palpebral fissures, prominent nasal root, bulbous nasal tip, low-set ears, short fingers and toes with hypoplastic nails, and delayed bone age (Bonaglia et al., 2002; Zou et al., 2009; Guilherme et al., 2014).

Anterior spinal and bulbar artery supply to the posterior inferior cerebellar artery revealed by a ruptured aneurysm: case report.

PubMed

Gabrieli, Joseph; Sourour, Nader-Antoine; Chauvet, Dorian; Di Maria, Federico; Chiras, Jacques; Clarençon, Frédéric

2017-02-01

The posterior inferior cerebellar artery (PICA) is a vessel located between the intra- and extracranial circulation. The artery is characterized by a complex embryological development and numerous anatomical variants. The authors present a case of the PICA supplied by both a hypertrophic anterior spinal artery and a hypoplastic bulbar artery. This unusual arrangement somehow completes the list of previously published variants, and the spontaneous rupture of a related aneurysm confirmed the fragility of this network. The authors discuss anatomical and treatment considerations.

Total cavo-pulmonary connection without foreign material for asplenic heart associated with partial anomalous pulmonary venous connection.

PubMed

Agematsu, Kouta; Naito, Yuji; Aoki, Mitsuru; Fujiwara, Tadashi

2008-04-01

The presented case was a 3-year-old boy diagnosed with asplenia (SLL), double outlet right ventricle, pulmonary stenosis, atrioventricular septal defect, hypoplastic left ventricle and partial anomalous pulmonary venous connection to the superior vena cava. Partial anomalous pulmonary venous connection was repaired by translocation of pulmonary artery to avoid pulmonary venous obstruction when Glenn anastomosis was performed. Total cavo-pulmonary connection was established by re-routing the inferior vena cava to pulmonary artery using the atrial septal remnant and the left atrium free wall flap.

Dorsal dimelia in patau syndrome: a case report.

PubMed

Fattah, A; Pickford, M A

2007-10-01

We present a case of a child with Patau syndrome that exhibits features consistent with congenital palmar nail syndrome. The literature is reviewed and evidence presented to demonstrate that this is a defect in the dorso-ventral patterning of the limb and thus a form of dorsal dimelia. In order to differentiate this from other instances of ectopic nail tissue we suggest congenital palmar nail syndrome should be more specifically defined as duplicated nails, absent flexion creases, non-glabrous skin on the palmar surface, reduced movement at the interphalangeal joints and hypoplastic terminal phalanges.

Idiopathic aplastic anemia: diagnosis and classification.

PubMed

Dolberg, Osnat Jarchowsky; Levy, Yair

2014-01-01

Aplastic anemia (AA) is a disease characterized by pancytopenia and hypoplastic bone marrow caused by the decrease of hematopoietic stem cells. The pathogenesis of AA is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies and immunity disorders. Survival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. Herein, we will update the main issues concern AA according to our literature review. Copyright © 2014 Elsevier B.V. All rights reserved.

Lateral idiopathic subluxation of the radial head. Case report.

PubMed

Lancaster, S; Horowitz, M

1987-01-01

Idiopathic subluxation of the radial head (ISRH) is a rare entity that is separate from congenital dislocations of the radial head, both symptomatically and radiographically. ISRH causes pain and restriction of rotation. A dome-shaped radial head, a hypertrophied ulna, and a hypoplastic capitellum are not present in ISRH, as they are in a congenital dislocation of the radial head (CDRH). A true lateral ISRH is used as an example to demonstrate these differences. Remodeling of the radial head may preserve motion in the joint surface deformed by growth along abnormal planes of motion.

Congenital Anomalies of the Hand--Principles of Management.

PubMed

Little, Kevin J; Cornwall, Roger

2016-01-01

Physicians who specialize in pediatric orthopedics and hand surgery frequently encounter congenital hand abnormalities, despite their relative rarity. The treating physician should be aware of the associated syndromes and malformations that may, in some cases, be fatal if not recognized and treated appropriately. Although these congenital disorders have a wide variability, their treatment principles are similar in that the physician should promote functional use and cosmesis for the hand. This article discusses syndactyly, preaxial polydactyly and post-axial polydactyly, and the hypoplastic thumb. Copyright © 2016 Elsevier Inc. All rights reserved.

ACCF/AHA methodology for the development of quality measures for cardiovascular technology: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures.

PubMed

Bonow, Robert O; Douglas, Pamela S; Buxton, Alfred E; Cohen, David J; Curtis, Jeptha P; Delong, Elizabeth; Drozda, Joseph P; Ferguson, T Bruce; Heidenreich, Paul A; Hendel, Robert C; Masoudi, Frederick A; Peterson, Eric D; Taylor, Allen J

2011-09-27

Consistent with the growing national focus on healthcare quality, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have taken a leadership role over the past decade in developing measures of the quality of cardiovascular care by convening a joint ACCF/AHA Task Force on Performance Measures. The Task Force is charged with identifying the clinical topics appropriate for the development of performance measures and with assembling writing committees composed of clinical and methodological experts in collaboration with appropriate subspecialty societies. The Task Force has also created methodology documents that offer guidance in the development of process, outcome, composite, and efficiency measures. Cardiovascular performance measures using existing ACCF/AHA methodology are based on Class I or Class III guidelines recommendations, usually with Level A evidence. These performance measures, based on evidence-based ACCF/AHA guidelines, remain the most rigorous quality measures for both internal quality improvement and public reporting. However, many of the tools for diagnosis and treatment of cardiovascular disease involve advanced technologies, such as cardiac imaging, for which there are often no underlying guideline documents. Because these technologies affect the quality of cardiovascular care and also have the potential to contribute to cardiovascular health expenditures, there is a need for more critical assessment of the use of technology, including the development of quality and performance measures in areas in which guideline recommendations are absent. The evaluation of quality in the use of cardiovascular technologies requires consideration of multiple parameters that differ from other healthcare processes. The present document describes methodology for development of 2 new classes of quality measures in these situations, appropriate use measures and structure/safety measures. Appropriate use measures are based on specific indications, processes, or parameters of care for which high level of evidence data and Class I or Class III guideline recommendations may be lacking but are addressed in ACCF appropriate use criteria documents. Structure/safety measures represent measures developed to address structural aspects of the use of healthcare technology (e.g., laboratory accreditation, personnel training, and credentialing) or quality issues related to patient safety when there are neither guidelines recommendations nor appropriate use criteria. Although the strength of evidence for appropriate use measures and structure/safety measures may not be as strong as that for formal performance measures, they are quality measures that are otherwise rigorously developed, reviewed, tested, and approved in the same manner as ACCF/AHA performance measures. The ultimate goal of the present document is to provide direction in defining and measuring the appropriate use-avoiding not only underuse but also overuse and misuse-and proper application of cardiovascular technology and to describe how such appropriate use measures and structure/safety measures might be developed for the purposes of quality improvement and public reporting. It is anticipated that this effort will help focus the national dialogue on the use of cardiovascular technology and away from the current concerns about volume and cost alone to a more holistic emphasis on value.

[Aging and blood pressure].

PubMed

Mendes, Romeu; Themudo Barata, J L

2008-01-01

High blood pressure is a major risk factor of cardiovascular diseases and has a high prevalence in the older individuals becoming in a risk factor associated with high cardiovascular mortality and morbidity among these population. This study has the objective to analyze the changes in the cardiovascular system inherent to the aging process, that provoke the increase of blood pressure levels with the advance of age and that can origin hypertension. With the aging process, changes in the anatomy and cardiovascular physiology occur, even in the absence of illness. High blood pressure is characterized as a systemic condition that involves the presence of structural changes of the arteries and the myocardium, associated to an endotelial and baroreceptors dysfunction.

Implementing a Graduate Certificate Program in Cardiovascular Epidemiology: The Jackson Heart Study

PubMed Central

Campbell Jenkins, Brenda W.; Addison, Clifton; Wilson, Gregory; Young, Lavon; Fields, Regina; Woodberry, Clevette; Payton, Marinelle

2015-01-01

The Jackson Heart Study (JHS) is committed to providing opportunities for expanding the understanding of the epidemiology, diagnosis, prevention, and treatment of cardiovascular diseases. The JHS Graduate Training and Education Center (GTEC) has initiated the Daniel Hale Williams Scholar (DHWS) program where students are afforded the opportunity to interact with epidemiologists and other biomedical scientists to learn to identify, predict, and prevent cardiovascular disease using the Jackson Heart Study data. This study describes the structured programs developed by JHS GTEC seeking to alleviate the shortage of trained professionals in cardiovascular epidemiology by training graduate students while they complete their academic degrees. The DHWS program provides: (1) an enrichment curriculum; (2) a learning community; (3) quarterly seminars; and (4) a Summer Institute. Students attend enrichment activities comprising: (1) Applied Biostatistics; (2) Cardiovascular Disease Epidemiology; (3) Social Epidemiology; (4) Emerging Topics; and (5) Research Writing. Training focuses on developing proficiency in cardiovascular health knowledge. The DHWS program is a unique strategy for incorporating rigorous academic and career-focused training to graduate students and has enabled the acquisition of competencies needed to impact cardiovascular disease management programs. PMID:26703701

Interaction Studies of Withania Somnifera's Key Metabolite Withaferin A with Different Receptors Assoociated with Cardiovascular Disease.

PubMed

Ravindran, Rekha; Sharma, Nitika; Roy, Sujata; Thakur, Ashoke R; Ganesh, Subhadra; Kumar, Sriram; Devi, Jamuna; Rajkumar, Johanna

2015-01-01

Withania somnifera commonly known as Ashwagandha in India is used in many herbal formulations to treat various cardiovascular diseases. The key metabolite of this plant, Withaferin A was analyzed for its molecular mechanism through docking studies on different targets of cardiovascular disease. Six receptor proteins associated with cardiovascular disease were selected and interaction studies were performed with Withaferin A using AutoDock Vina. CORINA was used to model the small molecules and HBAT to compute the hydrogen bonding. Among the six targets, β1- adrenergic receptors, HMG-CoA and Angiotensinogen-converting enzyme showed significant interaction with Withaferin A. Pharmacophore modeling was done using PharmaGist to understand the pharmacophoric potential of Withaferin A. Clustering of Withaferin A with different existing drug molecules for cardiovascular disease was performed with ChemMine based on structural similarity and physicochemical properties. The ability of natural active component, Withaferin A to interact with different receptors associated with cardiovascular disease was elucidated with various modeling techniques. These studies conclusively revealed Withaferin A as a potent lead compound against multiple targets associated with cardiovascular disease.

Effects of primary care team social networks on quality of care and costs for patients with cardiovascular disease.

PubMed

Mundt, Marlon P; Gilchrist, Valerie J; Fleming, Michael F; Zakletskaia, Larissa I; Tuan, Wen-Jan; Beasley, John W

2015-03-01

Cardiovascular disease is the leading cause of mortality and morbidity in the United States. Primary care teams can be best suited to improve quality of care and lower costs for patients with cardiovascular disease. This study evaluates the associations between primary care team communication, interaction, and coordination (ie, social networks); quality of care; and costs for patients with cardiovascular disease. Using a sociometric survey, 155 health professionals from 31 teams at 6 primary care clinics identified with whom they interact daily about patient care. Social network analysis calculated variables of density and centralization representing team interaction structures. Three-level hierarchical modeling evaluated the link between team network density, centralization, and number of patients with a diagnosis of cardiovascular disease for controlled blood pressure and cholesterol, counts of urgent care visits, emergency department visits, hospital days, and medical care costs in the previous 12 months. Teams with dense interactions among all team members were associated with fewer hospital days (rate ratio [RR] = 0.62; 95% CI, 0.50-0.77) and lower medical care costs (-$556; 95% CI, -$781 to -$331) for patients with cardiovascular disease. Conversely, teams with interactions revolving around a few central individuals were associated with increased hospital days (RR = 1.45; 95% CI, 1.09-1.94) and greater costs ($506; 95% CI, $202-$810). Team-shared vision about goals and expectations mediated the relationship between social network structures and patient quality of care outcomes. Primary care teams that are more interconnected and less centralized and that have a shared team vision are better positioned to deliver high-quality cardiovascular disease care at a lower cost. © 2015 Annals of Family Medicine, Inc.

Effects of Primary Care Team Social Networks on Quality of Care and Costs for Patients With Cardiovascular Disease

PubMed Central

Mundt, Marlon P.; Gilchrist, Valerie J.; Fleming, Michael F.; Zakletskaia, Larissa I.; Tuan, Wen-Jan; Beasley, John W.

2015-01-01

PURPOSE Cardiovascular disease is the leading cause of mortality and morbidity in the United States. Primary care teams can be best suited to improve quality of care and lower costs for patients with cardiovascular disease. This study evaluates the associations between primary care team communication, interaction, and coordination (ie, social networks); quality of care; and costs for patients with cardiovascular disease. METHODS Using a sociometric survey, 155 health professionals from 31 teams at 6 primary care clinics identified with whom they interact daily about patient care. Social network analysis calculated variables of density and centralization representing team interaction structures. Three-level hierarchical modeling evaluated the link between team network density, centralization, and number of patients with a diagnosis of cardiovascular disease for controlled blood pressure and cholesterol, counts of urgent care visits, emergency department visits, hospital days, and medical care costs in the previous 12 months. RESULTS Teams with dense interactions among all team members were associated with fewer hospital days (rate ratio [RR] = 0.62; 95% CI, 0.50–0.77) and lower medical care costs (−$556; 95% CI, −$781 to −$331) for patients with cardiovascular disease. Conversely, teams with interactions revolving around a few central individuals were associated with increased hospital days (RR = 1.45; 95% CI, 1.09–1.94) and greater costs ($506; 95% CI, $202–$810). Team-shared vision about goals and expectations mediated the relationship between social network structures and patient quality of care outcomes. CONCLUSIONS Primary care teams that are more interconnected and less centralized and that have a shared team vision are better positioned to deliver high-quality cardiovascular disease care at a lower cost. PMID:25755035

A Path Analysis of a Randomized "Promotora de Salud" Cardiovascular Disease-Prevention Trial among At-Risk Hispanic Adults

ERIC Educational Resources Information Center

de Heer, Hendrik Dirk; Balcazar, Hector G.; Castro, Felipe; Schulz, Leslie

2012-01-01

This study assessed effectiveness of an educational community intervention taught by "promotoras de salud" in reducing cardiovascular disease (CVD) risk among Hispanics using a structural equation modeling (SEM) approach. Model development was guided by a social ecological framework proposing CVD risk reduction through improvement of…

Hyperthyroidism and the Heart.

PubMed

Osuna, Patricia Mejia; Udovcic, Maja; Sharma, Morali D

2017-01-01

Thyroid hormones have a significant impact on cardiac function and structure. Excess thyroid hormone affects cardiovascular hemodynamics, leading to high-output heart failure and, in late stages, dilated cardiomyopathy. In this review, we discuss how hyperthyroidism affects cardiovascular pathophysiology and molecular mechanisms and examine the complications caused by excess thyroid hormone, such as heart failure and atrial fibrillation.

Left Ventricular Structure and Function in Children with and without Developmental Coordination Disorder

ERIC Educational Resources Information Center

Chirico, Daniele; O'Leary, Deborah; Cairney, John; Klentrou, Panagiota; Haluka, Karen; Hay, John; Faught, Brent

2011-01-01

Children with developmental coordination disorder (DCD) are more likely to develop cardiovascular disease risk factors such as obesity and reduced cardio-respiratory fitness. However, there is limited data using laboratory measures for assessing the risk of cardiovascular disease associated with DCD. The purpose of this study was to examine…

Cardiovascular disease in childhood: the role of obesity.

PubMed

Herouvi, Despina; Karanasios, Evangelos; Karayianni, Christina; Karavanaki, Kyriaki

2013-06-01

In recent years, childhood obesity is becoming an epidemic health problem. It is now evident from many studies that childhood obesity is correlated with adult excess weight status and the development of risk factors for cardiovascular diseases in adulthood, including hypertension, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The exposure to obesity and to the above risk factors during childhood subsequently lead to atherosclerotic development, such as altered vascular structure and function, although the mechanisms are still unclear. Several non-invasive, and thus easy-to-obtain measures of arterial structure and function, have been shown to be clinically useful in providing information about vasculature early in the course of atherosclerosis, including measurement of endothelial function, carotid intima media thickness, and arterial stiffness. The early detection of cardiovascular abnormalities is essential because the control of the atherogenic process is more effective during its early stages. The present review focuses on the cardiovascular consequences of obesity, on the mechanisms and the methods of measurement of endothelial dysfunction in obese children and adolescents, and on the ways of intervention for the improvement of vascular health.

Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations.

PubMed

Simonet, Jacqueline C; Sunnen, C Nicole; Wu, Jue; Golden, Jeffrey A; Marsh, Eric D

2015-09-01

Mutations in the Aristaless-Related Homeobox (ARX) gene cause structural anomalies of the brain, epilepsy, and neurocognitive deficits in children. During forebrain development, Arx is expressed in both pallial and subpallial progenitor cells. We previously demonstrated that elimination of Arx from subpallial-derived cortical interneurons generates an epilepsy phenotype with features overlapping those seen in patients with ARX mutations. In this report, we have selectively removed Arx from pallial progenitor cells that give rise to the cerebral cortical projection neurons. While no discernable seizure activity was recorded, these mice exhibited a peculiar constellation of behaviors. They are less anxious, less social, and more active when compared with their wild-type littermates. The overall cortical thickness was reduced, and the corpus callosum and anterior commissure were hypoplastic, consistent with a perturbation in cortical connectivity. Taken together, these data suggest that some of the structural and behavioral anomalies, common in patients with ARX mutations, are specifically due to alterations in pallial progenitor function. Furthermore, our data demonstrate that some of the neurobehavioral features found in patients with ARX mutations may not be due to on-going seizures, as is often postulated, given that epilepsy was eliminated as a confounding variable in these behavior analyses. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The impact of congenital cardiovascular malformations on the assessment and surgical management of infants with cleft lip and/or palate.

PubMed

Harry, Brian L; TeBockhorst, Seth; Deleyiannis, Frederic W-B

2013-05-01

The purpose of this study was to assess the cardiac evaluation of cleft lip and/or palate patients, characterize their cardiovascular malformations, and determine the impact of cardiovascular malformations on surgical management. A single-institution retrospective study of 329 consecutive cleft patients was performed. Cardiovascular malformations were categorized according to involvement of cardiac septa, vasculature, and valves. Their impact on the need for cardiac surgery, timing of cleft repair, need for subacute bacterial endocarditis (SBE) prophylaxis, and the perioperative experience was evaluated. Ten percent (33/329) of cleft patients had a cardiovascular malformation, and 3% underwent cardiac surgery prior to cleft repair. Malformations of the septa, vasculature, and valves were present in 9%, 6%, and 2% of cleft infants, respectively. Murmur as a sign of structural cardiovascular disease was 79% sensitive and 97% specific. Cleft palate repair was delayed by 2 months in patients with a cardiovascular malformation (P = .001). Subacute bacterial endocarditis prophylaxis was recommended, not recommended, or not specified by cardiology in 18%, 33%, and 48% of cleft patients with a cardiovascular malformation, respectively. Postoperative stay and surgical complications were not associated with cardiovascular malformation. Even in the absence of a murmur, echocardiographic screening should be considered in infants with nonspecific signs of cardiovascular disease. Greater awareness of the guidelines for SBE prophylaxis is needed. Most cleft patients with a cardiovascular malformation do not require cardiac surgery and do not experience an increased rate of complications associated with cleft surgery.

Genetic Predictors for Cardiovascular Disease in Hispanics

PubMed Central

Qi, Lu; Campos, Hannia

2012-01-01

A less favorable cardiovascular risk factor profile, but paradoxically lower cardiovascular morbidity and mortality have been observed in Hispanics, a pattern often referred to as the Hispanic Paradox. It was proposed the specific genetic susceptibility of this admixed population and gene-environment interactions may partly explain the paradox. The past few years have seen great advances in discovering genetic risk factors using genome-wide association studies (GWAS) for cardiovascular disease especially in Caucasians. However, there is no GWAS of cardiovascular disease that have been reported in Hispanics. In the Costa Rican Heart Study we reported both the consistency and disparity of genetic effects on risk of coronary heart disease (CHD) between Hispanics and other ethnic groups. We demonstrated the improvement in the identified genetic markers on discrimination of CHD in Hispanics was modest. Future genetic research in Hispanics would consider the diversities in genetic structure, lifestyle and socioeconomics among various sub-populations, and comprehensively evaluate potential gene-environment interactions in relation to cardiovascular risk. PMID:22498015

Effects of High-Intensity Interval Training versus Continuous Training on Physical Fitness, Cardiovascular Function and Quality of Life in Heart Failure Patients.

PubMed

Benda, Nathalie M M; Seeger, Joost P H; Stevens, Guus G C F; Hijmans-Kersten, Bregina T P; van Dijk, Arie P J; Bellersen, Louise; Lamfers, Evert J P; Hopman, Maria T E; Thijssen, Dick H J

2015-01-01

Physical fitness is an important prognostic factor in heart failure (HF). To improve fitness, different types of exercise have been explored, with recent focus on high-intensity interval training (HIT). We comprehensively compared effects of HIT versus continuous training (CT) in HF patients NYHA II-III on physical fitness, cardiovascular function and structure, and quality of life, and hypothesize that HIT leads to superior improvements compared to CT. Twenty HF patients (male:female 19:1, 64±8 yrs, ejection fraction 38±6%) were allocated to 12-weeks of HIT (10*1-minute at 90% maximal workload-alternated by 2.5 minutes at 30% maximal workload) or CT (30 minutes at 60-75% of maximal workload). Before and after intervention, we examined physical fitness (incremental cycling test), cardiac function and structure (echocardiography), vascular function and structure (ultrasound) and quality of life (SF-36, Minnesota living with HF questionnaire (MLHFQ)). Training improved maximal workload, peak oxygen uptake (VO2peak) related to the predicted VO2peak, oxygen uptake at the anaerobic threshold, and maximal oxygen pulse (all P<0.05), whilst no differences were present between HIT and CT (N.S.). We found no major changes in resting cardiovascular function and structure. SF-36 physical function score improved after training (P<0.05), whilst SF-36 total score and MLHFQ did not change after training (N.S.). Training induced significant improvements in parameters of physical fitness, although no evidence for superiority of HIT over CT was demonstrated. No major effect of training was found on cardiovascular structure and function or quality of life in HF patients NYHA II-III. Nederlands Trial Register NTR3671.

Technological Innovations in Magnetic Resonance for Early Detection of Cardiovascular Diseases.

PubMed

Santarelli, Maria F; Positano, Vincenzo; Martini, Nicola; Valvano, Giuseppe; Landini, Luigi

2016-01-01

Most recent technical innovations in cardiovascular MR imaging (CMRI) are presented in this review. They include hardware and software developments, and novelties in parametric mapping. All these recent improvements lead to high spatial and temporal resolution and quantitative information on the heart structure and function. They make it achievable ambitious goals in the field of magnetic resonance, such as the early detection of cardiovascular pathologies. In this review article, we present recent innovations in CMRI, emphasizing the progresses performed and the solutions proposed to some yet opened technical problems.

Benefits of Balloon-Dilatable Bilateral Pulmonary Artery Banding in Patients With Hypoplastic Left Heart Syndrome and Other Complex Cardiac Anomalies.

PubMed

Kise, Hiroaki; Suzuki, Shoji; Hoshiai, Minako; Toda, Takako; Koizumi, Keiichi; Hasebe, Yohei; Kono, Yosuke; Honda, Yoshihiro; Kaga, Shigeaki; Sugita, Kanji

2015-12-01

The purpose of this study was to evaluate the potential of balloon-dilatable bilateral pulmonary artery banding (b-PAB) and its impact on the configuration of the pulmonary artery (PA). We have previously used balloon-dilatable b-PAB as first-stage palliation for patients with hypoplastic left heart syndrome (HLHS) and other complex cardiac anomalies. Two pliable tapes were placed around each branch of the PA and tightened with 7-0 polypropylene sutures in a manner that allowed for the subsequent adjustment of PA diameters. We retrospectively examined the adjustability of PA diameters by balloon dilation and the need for surgical PA angioplasty at later stages. From January 2010 to October 2013, we performed b-PAB in 8 patients, including 3 borderline cases between biventricular repair (BVR) and univentricular repair (UVR). The b-PAB procedures were performed at a median age of 6.5 days (range, 2-10 days). Balloon dilations were performed in 10 lesions in 4 patients. All of the procedures were performed safely. Two patients reached definite BVR. The remaining 6 patients underwent open palliative procedures with univentricular physiologies that resulted in 2 deaths unrelated to the initial b-PAB. In all but 1 of the patients, the PA configuration was properly maintained and did not require surgical pulmonary angioplasty. Balloon-dilatable b-PAB can be performed safely and prevents PA distortion at later stages. This technique should be considered for patients with complex cardiac anomalies if uncertainty exists regarding the optimal surgical strategy (BVR or UVR) in early infancy. © 2015, Wiley Periodicals, Inc.

External versus Internal Distraction Devices in Treatment of Obstructive Sleep Apnea in Craniofacial Anomalies.

PubMed

Rachmiel, Adi; Nseir, Saleh; Emodi, Omri; Aizenbud, Dror

2014-07-01

Obstructive sleep apnea is often associated with congenital craniofacial malformations due to hypoplastic mandible and decreased pharyngeal airway. In this study, we will compare external and internal distraction devices for mandibular lengthening in terms of effectiveness, results, patient comfort, and complications. Thirty-seven patients were treated by bilateral mandibular distraction osteogenesis for obstructive sleep apnea: 20 with external and 17 with internal distraction devices. Lengthening of the mandible and increase of the pharyngeal airway were obtained in all patients. Using the external devices, the average mandibular elongation was 30 mm versus 22 mm with the internal devices; however, after 1 year, the results were more stable with internal devices. External devices carried greater risk for pin tract infection than the internal devices (27.5% vs 5.88%). In addition, pin loosening in 22.5% required pin replacement or led to reduced retention period. Internal devices had a precise and predictable vector of lengthening and left less visible scars at the submandibular area but carried the disadvantage of requiring a second operation for device removal. In very young children with severe micrognathia, it was impossible to place internal devices, and external devices were used. Internal devices should be the first choice because they are more comfortable to the patients, more predictable vector of lengthening, are less vulnerable to dislodgement, and leave reduced scarring, with the great disadvantage of second operation for removal. However, external devices still should be considered mainly in severely hypoplastic cases, and the surgeon should be prepared for both options.

Deletion of OTX2 in neural ectoderm delays anterior pituitary development

PubMed Central

Mortensen, Amanda H.; Schade, Vanessa; Lamonerie, Thomas; Camper, Sally A.

2015-01-01

OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. PMID:25315894

Management Options and Outcomes for Neonatal Hypoplastic Left Heart Syndrome in the Early Twenty-First Century.

PubMed

Kane, Jason M; Canar, Jeff; Kalinowski, Valerie; Johnson, Tricia J; Hoehn, K Sarah

2016-02-01

Without surgical treatment, neonatal hypoplastic left heart syndrome (HLHS) mortality in the first year of life exceeds 90 % and, in spite of improved surgical outcomes, many families still opt for non-surgical management. The purpose of this study was to investigate trends in neonatal HLHS management and to identify characteristics of patients who did not undergo surgical palliation. Neonates with HLHS were identified from a serial cross-sectional analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 2000 to 2012. The primary analysis compared children undergoing surgical palliation to those discharged alive without surgery using a binary logistic regression model. Multivariate logistic regression was conducted to determine factors associated with treatment choice. A total of 1750 patients underwent analysis. Overall hospital mortality decreased from 35.3 % in 2000 to 22.9 % in 2012. The percentage of patients undergoing comfort care discharge without surgery also decreased from 21.2 to 14.8 %. After controlling for demographics and comorbidities, older patients at presentation were less likely to undergo surgery (OR 0.93, 0.91-0.96), and patients in 2012 were more likely to undergo surgery compared to those in prior years (OR 1.5, 1.1-2.1). Discharge without surgical intervention is decreasing with a 30 % reduction between 2000 and 2012. Given the improvement in surgical outcomes, further dialogue about ethical justification of non-operative comfort or palliative care is warranted. In the meantime, clinicians should present families with surgical outcome data and recommend intervention, while supporting their option to refuse.

[Comparative results of Fontan surgery in patients with and without hypoplastic left heart syndrome].

PubMed

Becker Rencoret, Pedro; Besa Bandeira, Santiago; Riveros González, Sergio; Frangini Sanhueza, Patricia; Springmüller Pinto, Daniel; González Foretic, Rodrigo; Urcelay Montecinos, Gonzalo

During the last few years, numerous patients with univentricular heart disease have been treated surgically with total cavopulmonary anastomosis according to a staged surgery protocol in our institution. To evaluate the perioperative outcomes and survival of patients with hypoplastic left heart syndrome (HLHS) after the Fontan procedure and compare them with other types of univentricular heart disease. A total of 102 patients underwent a Fontan procedure between April 1996 and March 2014, 25 with HLHS (group I), and 77 patients with other types of univentricular heart disease (group II). Groups survival, demographics, hemodinamic studies, morbimortality, mechanical ventilation, surgical drains, post-operative stay, isotopes score, pacemaker use, and requiriment of Fontan takedown were analyzed. Intraoperative mortality was 4% (n=1) for group I, and 7.8% (n=6) for group II (P=.451). A difference was only found in hospital length of stay (LOS), being 17 days (6-47) for group I and 12 days (5-103) for group II (P=.017). Mean follow-up was 4.24±2.08 years for group I, and 8.7±4.67 for group II. Survival rate at 8 years for both groups was 88%, and 81% at 10 years for group II. The Fontan procedure had similar mortality, but longer LOS, in patients with HLHS compared to those with another types of single ventricle anatomy. Long term survival was comparable between both groups. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Urban-rural differences in Roman Dorset, England: A bioarchaeological perspective on Roman settlements.

PubMed

Redfern, Rebecca C; DeWitte, Sharon N; Pearce, John; Hamlin, Christine; Dinwiddy, Kirsten Egging

2015-05-01

In the Roman period, urban and rural ways of living were differentiated philosophically and legally, and this is the first regional study of these contrasting life-ways. Focusing on frailty and mortality risk, we investigated how these differed by age, sex, and status, using coffin type as a proxy for social status. We employed skeletal data from 344 individuals: 150 rural and 194 urban (1st-5th centuries A.D.) from Dorset, England. Frailty and mortality risk were examined using indicators of stress (cribra orbitalia, porotic hyperostosis, nonspecific periostitis, and enamel hypoplastic defects), specific metabolic and infectious diseases (rickets, scurvy, and tuberculosis), and dental health (carious lesions and calculus). These variables were studied using Chi-square, Siler model of mortality, Kaplan-Meier analysis, and the Gompertz model of adult mortality. Our study found that overall, mortality risk and survivorship did not differ between cemetery types but when the data were examined by age, mortality risk was only significantly higher for urban subadults. Demographic differences were found, with urban cemeteries having more 0-10 and >35 year olds, and for health, urban cemeteries had significantly higher frequencies of enamel hypoplastic defects, carious lesions, and rickets. Interestingly, no significant difference in status was observed between rural and urban cemeteries. The most significant finding was the influence of the skeletal and funerary data from the Poundbury sites, which had different demographic profiles, significantly higher frequencies of the indicators of stress and dental health variables. In conclusion, there are significant health, demographic, and mortality differences between rural and urban populations in Roman Britain. © 2015 Wiley Periodicals, Inc.

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome.

PubMed

Rachmiel, Adi; Turgeman, Shahar; Emodi, Omri; Aizenbud, Dror; Shilo, Dekel

2018-02-01

Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation.

Analysis of preoperative condition and interstage mortality in Norwood and hybrid procedures for hypoplastic left heart syndrome using the Aristotle scoring system.

PubMed

Lloyd, David F A; Cutler, Lindsay; Tibby, Shane M; Vimalesvaran, Sunitha; Qureshi, Shakeel Ahmed; Rosenthal, Eric; Anderson, David; Austin, Conal; Bellsham-Revell, Hannah; Krasemann, Thomas

2014-05-01

The 'hybrid procedure', consisting of surgical banding of the pulmonary arteries with intraoperative stenting of the arterial duct, was developed as primary palliation in hypoplastic left heart syndrome (HLHS), avoiding the risks of cardiopulmonary bypass. In many centres, it is reserved for low birth weight, premature or unstable neonates; however, its role in such high risk cases of HLHS has yet to be defined. The preoperative condition of all patients with HLHS who underwent either the hybrid or the Norwood procedure for HLHS between 2005-2011 was analysed retrospectively, using a modified comprehensive Aristotle score. We then compared operative, interstage and 1 year mortalities between the groups after Aristotle adjustment via Cox proportional hazards analyses. Of 138 patients with HLHS, 27 had hybrid and 111 Norwood procedures. The hybrid group had significantly higher Aristotle scores (mean 4.1 vs 1.8; p<0.001); however, there was no significant difference in mortality at any stage. At 1 year, the overall unadjusted survival among Norwood and hybrid patients was 58.6% and 51.9%, respectively, yielding an Aristotle adjusted hazard ratio for mortality among hybrid patients of 1.09 (95% CI 0.56 to 2.11, p=0.80). Applying a hybrid approach to high risk patients with HLHS produces a comparable early and interstage mortality risk to lower risk patients undergoing the Norwood procedure. Prospective studies are needed to establish whether the hybrid procedure is a viable alternative to the Norwood procedure in all HLHS patients in terms of both mortality and long term morbidity.

[Pulsatile total cavopulmonary shunt for hypoplastic right heart syndrome with abnormal systemic venous return--a case report].

PubMed

Oiwa, H; Kawauchi, M; Chikada, M; Yagyu, K; Kotsuka, Y; Furuse, A

1995-01-01

A pulsatile total cavopulmonary shunt was successfully performed on a 5-year-old girl with hypoplastic right heart syndrome associated with abnormal systemic venous return; at the same time, modified mitral valve replacement was performed for mitral regurgitation. The right atrium, tricuspid valve and right ventricle were all extremely dimunitive. The diameter of the tricuspid valve was 50% of normal and the volume of the right ventricle was 8.6% of normal. In addition, there were severe subpumonary stenosis, a restrictive ventricular septal defect (VSD) and an atrial septal defect (ASD). The bilateral superior venae cavae (SVCs) and the hepatic vein drained to the left atrium, and the inferior vena cava was infrahepatically interrupted with a hemiazygos connection to the left superior vena cava. At the operation, each SVC was anastomosed end-to-side to each branch of the pulmonary artery (PA). The restrictive ventricular septal defect and stenotic subpulmonary lesion were left. The diameter of the ASD was reduced from 12 mm to 7 mm. The main PA was neither divided nor banded. The pulsatile blood flow from the left heart to the PA was regurated by a native restrictive VSD and stenotic subpulmonary lesion, and that from the right heart via the ASD was limited by reducing the size of the ASD. These described anatomic arrangements produced adequate antegrade pulsatile flow in the PA, which might prevent the development of pulmonary arteriovenous fistulae and, besides permit transfer of drainage of the hepatic vein from the left to the right atrium via the ASD in future.

Is "treat your child normally" helpful advice for parents of survivors of treatment of hypoplastic left heart syndrome?

PubMed

Rempel, Gwen R; Harrison, Margaret J; Williamson, Deanna L

2009-04-01

Developing technology affords children with complex congenitally malformed hearts a chance for survival. Parents gratefully pursue life-saving options on behalf of their children, despite the risks to the life of their child, and uncertainty about outcomes. Little is known about how mothers and fathers experience parenting a child whose new state as a survivor may include less than optimal developmental sequels. Our study involved multiple interactive interviews with 9 mothers and 7 fathers of infants and preschool children with hypoplastic left heart syndrome who had survived the Norwood surgical approach. Qualitative methodology included grounded theory methods of simultaneous collection and analysis of data, and we used open and selective coding of transcribed interviews. Parents used normalization in the context of uncertainty regarding the ongoing survival of their child. Parents described their underweight children as being on their own growth curve, and viewed their developmental progress, however delayed, as reason for celebration, as they had been prepared for their child to die. There is growing evidence that children with congenitally malformed hearts who require surgical intervention during the first year of life may experience developmental delay. The use of normalization by their parents may be effective in decreasing their worry regarding the uncertain future faced by their child, but may negatively affect the developmental progress of the child if they do not seek resources to assist development. Advice from paediatric specialists for parents to view their children as normal needs to be balanced with assistance for parents to access services to support optimal growth and development of their child.

An Animal Model of Chronic Aplastic Bone Marrow Failure Following Pesticide Exposure in Mice

PubMed Central

Chatterjee, Sumanta; Chaklader, Malay; Basak, Pratima; Das, Prosun; Das, Madhurima; Pereira, Jacintha Archana; Dutta, Ranjan Kumar; Chaudhuri, Samaresh; Law, Sujata

2010-01-01

The wide use of pesticides for agriculture, domestic and industrial purposes and evaluation of their subsequent effect is of major concern for public health. Human exposure to these contaminants especially bone marrow with its rapidly renewing cell population is one of the most sensitive tissues to these toxic agents represents a risk for the immune system leading to the onset of different pathologies. In this experimental protocol we have developed a mouse model of pesticide(s) induced hypoplastic/aplastic marrow failure to study quantitative changes in the bone marrow hematopoietic stem cell (BMHSC) population through flowcytometric analysis, defects in the stromal microenvironment through short term adherent cell colony (STACC) forming assay and immune functional capacity of the bone marrow derived cells through cell mediated immune (CMI) parameter study. A time course dependent analysis for consecutive 90 days were performed to monitor the associated changes in the marrow’s physiology after 30th, 60th and 90th days of chronic pesticide exposure. The peripheral blood showed maximum lowering of the blood cell count after 90 days which actually reflected the bone marrow scenario. Severe depression of BMHSC population, immune profile of the bone marrow derived cells and reduction of adherent cell colonies pointed towards an essentially empty and hypoplastic marrow condition that resembled the disease aplastic anemia. The changes were accompanied by splenomegaly and splenic erythroid hyperplasia. In conclusion, this animal model allowed us a better understanding of clinico-biological findings of the disease aplastic anemia following toxic exposure to the pesticide(s) used for agricultural and industrial purposes. PMID:24855541

Prominent gelatinous bone marrow transformation presenting prior to myelodysplastic syndrome: a case report with review of the literature.

PubMed

Nakanishi, Ryota; Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Takashi; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

2013-01-01

Gelatinous bone marrow transformation (GMT) is a rare disorder characterized by the presence of fat cell atrophy, loss of hematopoietic cells, and deposition of extracellular gelatinous materials. GMT is not a specific disease, but is strongly associated with malnutrition and drugs. Albeit extremely rare, GMT has been reported in patients with myeloproliferative disorders. Herein, we report the second documented case of hypoplastic myelodysplastic syndrome (MDS) accompanying GMT. A 73-year-old Japanese male with excellent nutrition status and no history of alcohol or drug intake was detected with pancytopenia. The initial bone marrow aspirate specimen reveled hypocellular marrow without dysplastic signs in the myeloid cells. Bone marrow biopsy demonstrated hypocellular bone marrow with prominent GMT. He received blood transfusions, however, pancytopenia continued to progress. The second bone marrow aspirate specimen showed dysplastic changes, such as pseudo-Pelger-Huët cells, hypogranular or agranular granulocytes, and megakaryocytes with multiple small nuclei. Cytogenetic study demonstrated deletion of chromosome 7. Therefore, an ultimate diagnosis of hypoplastic MDS accompanying GMT was made. Only a limited number of cases of myeloproliferative disorders with GMT have been reported. Our analysis of these cases revealed that chromosome 7 abnormality is frequently observed in this condition. Moreover, findings from the current case suggested that myeloproliferative disorders including MDS must be included in the differential diagnostic considerations of GMT patients, who have no history of malnutrition or drugs, and careful examination of the bone marrow smear specimen and cytogenetic analysis are necessary for early detection of underlying myeloproliferative disorders.

Surgical correction of brachycephalic syndrome in dogs: 62 cases (1991-2004).

PubMed

Riecks, Todd W; Birchard, Stephen J; Stephens, Julie A

2007-05-01

To assess results of surgical correction of brachycephalic syndrome (including stenotic nares, elongated soft palate, and everted laryngeal saccules) in dogs and determine whether dogs with hypoplastic trachea have a less favorable long-term outcome. Retrospective case series. 62 dogs with brachycephalic syndrome. Medical records from 1991 to 2004 were reviewed for information regarding signalment, clinical signs, diagnosis, surgery, and long-term outcome. Surgical outcome was rated by owners as excellent, good, fair, or poor. Common abnormalities, treatments, and long-term outcomes among the 62 dogs were assessed. Predominantly affected breeds included English Bulldog, Pug, and Boston Terrier. Elongated soft palate was the most common abnormality (54/62 [87.1%] dogs); the most common combination of abnormalities was elongated soft palate, stenotic nares, and everted saccules (16/62 [25.8%] dogs). The English Bulldog was the most common breed for all abnormalities, including elongated soft palate (27/54 [50%] dogs), stenotic nares (14/36 [38.9%] dogs), everted saccules (20/36 [55.6%] dogs), hypoplastic trachea (7/13 [53.9%] dogs), and laryngeal collapse (2/5 [40%]). No dogs had everted saccules alone. Outcome did not differ between dogs under-going staphylectomy by use of laser or scissor resection. Follow-up information was obtained for 34 dogs; 16 (47.1%) had an excellent outcome, and 16 (47.1%) had a good outcome. Overall treatment success rate was 94.2%, and overall mortality rate was 3.2%. Surgical treatment of brachycephalic syndrome in dogs appeared to be associated with a favorable long-term outcome, regardless of age, breed, specific diagnoses, or number and combinations of diagnoses.

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome

PubMed Central

Rachmiel, Adi; Emodi, Omri; Aizenbud, Dror; Shilo, Dekel

2018-01-01

Background: Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Methods: Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Results: Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. Conclusions: We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation. PMID:29616174

Norwood with right ventricle-to-pulmonary artery conduit is more effective than Norwood with Blalock-Taussig shunt for hypoplastic left heart syndrome: mathematic modeling of hemodynamics.

PubMed

Mroczek, Tomasz; Małota, Zbigniew; Wójcik, Elżbieta; Nawrat, Zbigniew; Skalski, Janusz

2011-12-01

The introduction of right ventricle to pulmonary artery (RV-PA) conduit in the Norwood procedure for hypoplastic left heart syndrome resulted in a higher survival rate in many centers. A higher diastolic aortic pressure and a higher mean coronary perfusion pressure were suggested as the hemodynamic advantage of this source of pulmonary blood flow. The main objective of this study was the comparison of two models of Norwood physiology with different types of pulmonary blood flow sources and their hemodynamics. Based on anatomic details obtained from echocardiographic assessment and angiographic studies, two three-dimensional computer models of post-Norwood physiology were developed. The finite-element method was applied for computational hemodynamic simulations. Norwood physiology with RV-PA 5-mm conduit and Blalock-Taussig shunt (BTS) 3.5-mm shunt were compared. Right ventricle work, wall stress, flow velocity, shear rate stress, energy loss and turbulence eddy dissipation were analyzed in both models. The total work of the right ventricle after Norwood procedure with the 5-mm RV-PA conduit was lower in comparison to the 3.5-mm BTS while establishing an identical systemic blood flow. The Qp/Qs ratio was higher in the BTS group. Hemodynamic performance after Norwood with the RV-PA conduit is more effective than after Norwood with BTS. Computer simulations of complicated hemodynamics after the Norwood procedure could be helpful in establishing optimal post-Norwood physiology. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome.

PubMed

Jean-St-Michel, Emilie; Chetan, Devin; Schwartz, Steven M; Van Arsdell, Glen S; Floh, Alejandro A; Honjo, Osami; Conway, Jennifer

2016-02-01

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.

Coarctation of the aorta and ventricular septal defect: should we perform a single-stage repair?

PubMed

Isomatsu, Y; Imai, Y; Shin'oka, T; Aoki, M; Sato, K

2001-09-01

Optimal management for coarctation of the aorta and ventricular septal defect remains controversial. The current study was undertaken to determine outcome, including recoarctation after 2-stage repair, at our institution. Between 1984 and 1998, 79 patients younger than 3 months with coarctation and ventricular septal defect underwent 2-stage repair at our institution. The first-stage operation consisted of subclavian flap angioplasty and pulmonary banding. The median age at the time of first operation was 28 days (range, 4-90 days), and median weight was 3.2 kg (range, 1.2-5.1 kg). Hypoplastic aortic arch was present in 27 patients, and coexisting anomalies were present in 13 patients. After a mean interval of 10.4 +/- 9.6 months, they underwent a second-stage repair, with closure of the ventricular septal defect and pulmonary debanding. There were 2 hospital deaths and 4 late deaths. Mean follow-up was 9.2 +/- 4.9 years (range, 2.0-18.3 years), and actuarial survival was 92.3% at 10 years (95% confidence interval, 86.6%-98.3%). Age at first operation, body weight, hypoplastic arch, and coexisting anomalies had no significant influence on overall mortality. Freedom from recoarctation rate was 90.4% at 10 years (95% confidence interval, 83.7%-97.2%). To diminish mortality and the recoarctation rate and also to decrease the possibility of complications related to circulatory arrest and allogeneic blood transfusion, 2-stage repair is still an effective technique for coarctation of the aorta associated with ventricular septal defect.

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

Hyperthyroidism and the Heart

PubMed Central

Osuna, Patricia Mejia; Udovcic, Maja; Sharma, Morali D.

2017-01-01

Thyroid hormones have a significant impact on cardiac function and structure. Excess thyroid hormone affects cardiovascular hemodynamics, leading to high-output heart failure and, in late stages, dilated cardiomyopathy. In this review, we discuss how hyperthyroidism affects cardiovascular pathophysiology and molecular mechanisms and examine the complications caused by excess thyroid hormone, such as heart failure and atrial fibrillation. PMID:28740583

ACCF/AHA methodology for the development of quality measures for cardiovascular technology: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures.

PubMed

Bonow, Robert O; Douglas, Pamela S; Buxton, Alfred E; Cohen, David J; Curtis, Jeptha P; Delong, Elizabeth; Drozda, Joseph P; Ferguson, T Bruce; Heidenreich, Paul A; Hendel, Robert C; Masoudi, Frederick A; Peterson, Eric D; Taylor, Allen J

2011-09-27

Consistent with the growing national focus on healthcare quality, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have taken a leadership role over the past decade in developing measures of the quality of cardiovascular care by convening a joint ACCF/AHA Task Force on Performance Measures. The Task Force is charged with identifying the clinical topics appropriate for the development of performance measures and with assembling writing committees composed of clinical and methodological experts in collaboration with appropriate subspecialty societies. The Task Force has also created methodology documents that offer guidance in the development of process, outcome, composite, and efficiency measures. Cardiovascular performance measures using existing ACCF/AHA methodology are based on Class I or Class III guidelines recommendations, usually with Level A evidence. These performance measures, based on evidence-based ACCF/AHA guidelines, remain the most rigorous quality measures for both internal quality improvement and public reporting. However, many of the tools for diagnosis and treatment of cardiovascular disease involve advanced technologies, such as cardiac imaging, for which there are often no underlying guideline documents. Because these technologies affect the quality of cardiovascular care and also have the potential to contribute to cardiovascular health expenditures, there is a need for more critical assessment of the use of technology, including the development of quality and performance measures in areas in which guideline recommendations are absent. The evaluation of quality in the use of cardiovascular technologies requires consideration of multiple parameters that differ from other healthcare processes. The present document describes methodology for development of 2 new classes of quality measures in these situations, appropriate use measures and structure/safety measures. Appropriate use measures are based on specific indications, processes, or parameters of care for which high level of evidence data and Class I or Class III guideline recommendations may be lacking but are addressed in ACCF appropriate use criteria documents. Structure/safety measures represent measures developed to address structural aspects of the use of healthcare technology (e.g., laboratory accreditation, personnel training, and credentialing) or quality issues related to patient safety when there are neither guidelines recommendations nor appropriate use criteria. Although the strength of evidence for appropriate use measures and structure/safety measures may not be as strong as that for formal performance measures, they are quality measures that are otherwise rigorously developed, reviewed, tested, and approved in the same manner as ACCF/AHA performance measures. The ultimate goal of the present document is to provide direction in defining and measuring the appropriate use-avoiding not only underuse but also overuse and misuse-and proper application of cardiovascular technology and to describe how such appropriate use measures and structure/safety measures might be developed for the purposes of quality improvement and public reporting. It is anticipated that this effort will help focus the national dialogue on the use of cardiovascular technology and away from the current concerns about volume and cost alone to a more holistic emphasis on value. Copyright © 2011 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PubMed

Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem; Dehmer, Greg J; Doherty, John U; Schoenhagen, Paul; Amin, Zahid; Bashore, Thomas M; Boyle, Andrew; Calnon, Dennis A; Carabello, Blase; Cerqueira, Manuel D; Conte, John; Desai, Milind; Edmundowicz, Daniel; Ferrari, Victor A; Ghoshhajra, Brian; Mehrotra, Praveen; Nazarian, Saman; Reece, T Brett; Tamarappoo, Balaji; Tzou, Wendy S; Wong, John B; Doherty, John U; Dehmer, Gregory J; Bailey, Steven R; Bhave, Nicole M; Brown, Alan S; Daugherty, Stacie L; Dean, Larry S; Desai, Milind Y; Duvernoy, Claire S; Gillam, Linda D; Hendel, Robert C; Kramer, Christopher M; Lindsay, Bruce D; Manning, Warren J; Mehrotra, Praveen; Patel, Manesh R; Sachdeva, Ritu; Wann, L Samuel; Winchester, David E; Wolk, Michael J; Allen, Joseph M

2018-04-01

This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities. Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines. A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario. The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined. Copyright © 2017. Published by Elsevier Inc.

ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease : A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PubMed

Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem

2017-12-01

This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities.Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines.A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario.The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined.

Therapeutic potential of chalcones as cardiovascular agents.

PubMed

Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

2016-03-01

Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

PubMed Central

Marzetti, Emanuele; Csiszar, Anna; Dutta, Debapriya; Balagopal, Gauthami; Calvani, Riccardo

2013-01-01

Advanced age is associated with a disproportionate prevalence of cardiovascular disease (CVD). Intrinsic alterations in the heart and the vasculature occurring over the life course render the cardiovascular system more vulnerable to various stressors in late life, ultimately favoring the development of CVD. Several lines of evidence indicate mitochondrial dysfunction as a major contributor to cardiovascular senescence. Besides being less bioenergetically efficient, damaged mitochondria also produce increased amounts of reactive oxygen species, with detrimental structural and functional consequences for the cardiovascular system. The age-related accumulation of dysfunctional mitochondrial likely results from the combination of impaired clearance of damaged organelles by autophagy and inadequate replenishment of the cellular mitochondrial pool by mitochondriogenesis. In this review, we summarize the current knowledge about relevant mechanisms and consequences of age-related mitochondrial decay and alterations in mitochondrial quality control in the cardiovascular system. The involvement of mitochondrial dysfunction in the pathogenesis of cardiovascular conditions especially prevalent in late life and the emerging connections with neurodegeneration are also illustrated. Special emphasis is placed on recent discoveries on the role played by alterations in mitochondrial dynamics (fusion and fission), mitophagy, and their interconnections in the context of age-related CVD and endothelial dysfunction. Finally, we discuss pharmacological interventions targeting mitochondrial dysfunction to delay cardiovascular aging and manage CVD. PMID:23748424

Uniform data collection in routine clinical practice in cardiovascular patients for optimal care, quality control and research: The Utrecht Cardiovascular Cohort.

PubMed

Asselbergs, Folkert W; Visseren, Frank Lj; Bots, Michiel L; de Borst, Gert J; Buijsrogge, Marc P; Dieleman, Jan M; van Dinther, Baukje Gf; Doevendans, Pieter A; Hoefer, Imo E; Hollander, Monika; de Jong, Pim A; Koenen, Steven V; Pasterkamp, Gerard; Ruigrok, Ynte M; van der Schouw, Yvonne T; Verhaar, Marianne C; Grobbee, Diederick E

2017-05-01

Background Cardiovascular disease remains the major contributor to morbidity and mortality. In routine care for patients with an elevated cardiovascular risk or with symptomatic cardiovascular disease information is mostly collected in an unstructured manner, making the data of limited use for structural feedback, quality control, learning and scientific research. Objective The Utrecht Cardiovascular Cohort (UCC) initiative aims to create an infrastructure for uniform registration of cardiovascular information in routine clinical practice for patients referred for cardiovascular care at the University Medical Center Utrecht, the Netherlands. This infrastructure will promote optimal care according to guidelines, continuous quality control in a learning healthcare system and creation of a research database. Methods The UCC comprises three parts. UCC-1 comprises enrolment of all eligible cardiovascular patients in whom the same information will be collected, based on the Dutch cardiovascular management guideline. A sample of UCC-1 will be invited for UCC-2. UCC-2 involves an enrichment through extensive clinical measurements with emphasis on heart failure, cerebral ischaemia, arterial aneurysms, diabetes mellitus and elevated blood pressure. UCC-3 comprises on-top studies, with in-depth measurements in smaller groups of participants typically based on dedicated project grants. All participants are followed up for morbidity and mortality through linkage with national registries. Conclusion In a multidisciplinary effort with physicians, patients and researchers the UCC sets a benchmark for a learning cardiovascular healthcare system. UCC offers an invaluable resource for future high quality care as well as for first-class research for investigators.

Current progress in 3D printing for cardiovascular tissue engineering.

PubMed

Mosadegh, Bobak; Xiong, Guanglei; Dunham, Simon; Min, James K

2015-03-16

3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

Mokken scaling analysis of the Hospital Anxiety and Depression Scale in individuals with cardiovascular disease.

PubMed

Cosco, Theodore D; Doyle, Frank; Watson, Roger; Ward, Mark; McGee, Hannah

2012-01-01

The Hospital Anxiety and Depression Scale (HADS) is a prolifically used scale of anxiety and depression. The original bidimensional anxiety-depression latent structure of the HADS has come under significant scrutiny, with previous studies revealing one-, two-, three- and four-dimensional structures. The current study examines the latent structure of the HADS using a non-parametric item response theory method. Using data conglomerated from four independent studies of cardiovascular disease employing the HADS (n=893), Mokken scaling procedure was conducted to assess the latent structure of the HADS. A single scale consisting of 12 of 14 HADS items was revealed, indicating a unidimensional latent HADS structure. The HADS was initially intended to measure mutually exclusive levels of anxiety and depression; however, the current study indicates that a single dimension of general psychological distress is captured. Copyright © 2012 Elsevier Inc. All rights reserved.

Congenital brainstem disconnection associated with a syrinx of the brainstem.

PubMed

Barth, P G; de Vries, L S; Nikkels, P G J; Troost, D

2008-02-01

We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon, medulla oblongata and bridging tissue fragments. A fragile tube walled by mature brainstem tissue could be reconstructed. It enveloped a cylinder of fluid within the ventral pons extending to the mesencephalon and the lower brainstem. The aqueduct was patent and outside the lesion. The basilar artery was represented by a tiny median vessel. The ventral and lateral parts of the posterior brainstem were surrounded by heterotopic glial tissue. The olivary nucleus was absent and the cerebellar dentate nucleus was dysplastic. Considering the maturity of the remaining parts of the pons, the onset of structural decline is likely to be close to the time of birth. Probable causes are progressively insufficient perfusion through an hypoplastic basilar artery, and obstructed venous drainage through an abnormal glial barrier surrounding the posterior brainstem. The morphological findings can be characterized as a syrinx, known from disorders in which brainstem or spinal cord are damaged by a combination of mechanical and circulatory factors.

Tricho-Dento-Osseous Syndrome: Diagnosis and Dental Management

PubMed Central

Al-Batayneh, Ola B.

2012-01-01

Tricho-dento-osseous (TDO) syndrome is a rare, autosomal dominant disorder principally characterised by curly hair at infancy, severe enamel hypomineralization and hypoplasia and taurodontism of teeth, sclerotic bone, and other defects. Diagnostic criteria are based on the generalized enamel defects, severe taurodontism especially of the mandibular first permanent molars, an autosomal dominant mode of inheritance, and at least one of the other features (i.e., nail defects, bone sclerosis, and curly, kinky or wavy hair present at a young age that may straighten out later). Confusion with amelogenesis imperfecta is common; however, taurodontism is not a constant feature of any of the types of amelogenesis imperfecta. Management of TDO requires a team approach, proper documentation, and a long-term treatment and follow-up plan. The aim of treatment is to prevent problems such as sensitivity, caries, dental abscesses, and loss of occlusal vertical dimension through attrition of hypoplastic tooth structure. Another aim is to restore function of the dentition and enhance the esthetics and self-esteem of the patient. This paper proposes treatment approaches that include preventive, restorative, endodontic, prosthetic, and surgical options to management. In addition, it sheds light on the difficulties faced during dental treatment of such cases. PMID:22969805

A rare association--amelogenesis imperfecta, platispondyly and bicytopenia: a case report.

PubMed

Laouina, Samir; El Alaoui, Siham Chafai; Amezian, Rachida; Al Bouzidi, Abderrahmane; Sefiani, Abdelaziz; El Alloussi, Mustapha

2015-10-28

Amelogenesis imperfecta is an inherited disease characterized by generalized structural abnormalities of the enamel on all teeth, including both primary and permanent dentition. To the best of our knowledge, this is the first case report of a rare association of amelogenesis imperfecta, platyspondyly, and bicytopenia. A 5-year-old Moroccan boy was examined in the Centre for Dental Consultation and Treatment, Faculty of Dentistry, Rabat. He was a child of consanguineous parents (first degree). The child failed to thrive (-4 standard deviation score) and displayed delayed overall development. A dental examination revealed a hypoplastic amelogenesis imperfecta with a bacterial biofilm deposit on tooth surfaces. A complete blood count revealed bicytopenia (normocytic-normochromic anemia with thrombocytopenia). A radiographic examination of the spinal column showed a deviation of the spine in the frontal plane in the form of thoracolumbar scoliosis. The interpedicular distance was not expanded; but a mild platyspondyly exists, especially pronounced in T11 and T12. No other family members presented amelogenesis imperfecta, bicytopenia, or platyspondyly. The consanguineous marriage suggested an autosomal recessive mode of inheritance. Further studies are necessary to clarify the genetic defect producing this syndrome, and the symptomatic associations of amelogenesis imperfecta, platyspondyly and bicytopenia.

EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Congenital left-sided heart obstruction

PubMed Central

Carr, Michelle; Curtis, Stephanie; Marek, Jan

2018-01-01

Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of the left ventricular outflow tract obstruction (LVOTO) and the variable degree of left ventricular hypoplasia as well as the associated lesions such as arch hypoplasia and coarctation. PMID:29681546

Congenital anomalies of the breast.

PubMed

Caouette-Laberge, Louise; Borsuk, Daniel

2013-02-01

Poland syndrome is a combination of chest wall deformity and absent or hypoplastic pectoralis muscle and breast associated with shortening and brachysyndactyly of the upper limb. Clinical presentation varies widely; therefore, reconstructive procedures have to be adapted to the deformity, ranging from chest wall stabilization or augmentation, dynamic muscle transfer, nipple and areola repositioning, and breast augmentation using prosthesis or autologous tissue transfer. Other congenital breast anomalies include supernumerary nipple and areola (polythelia) and breast (polymastia), which can generally be found on the embryonic mammary ridge. Absence of the nipple, areola (athelia), or the breast tissue (amastia) is less frequent.

Congenital Anomalies of the Breast

PubMed Central

Caouette-Laberge, Louise; Borsuk, Daniel

2013-01-01

Poland syndrome is a combination of chest wall deformity and absent or hypoplastic pectoralis muscle and breast associated with shortening and brachysyndactyly of the upper limb. Clinical presentation varies widely; therefore, reconstructive procedures have to be adapted to the deformity, ranging from chest wall stabilization or augmentation, dynamic muscle transfer, nipple and areola repositioning, and breast augmentation using prosthesis or autologous tissue transfer. Other congenital breast anomalies include supernumerary nipple and areola (polythelia) and breast (polymastia), which can generally be found on the embryonic mammary ridge. Absence of the nipple, areola (athelia), or the breast tissue (amastia) is less frequent. PMID:24872738

Phocomelia: Case report and differential diagnosis.

PubMed

Osadsky, Captain Rasto

2011-01-01

While rarely seen in the present-day Western world, phocomelia is not uncommon in underdeveloped countries. Phocomelia is an abnormality in which the limbs are not fully formed. It may be inherited as an autosomal recessive or dominant disorder. This case concerns a 12-year-old Afghan boy with multiple skeletal anomalies, most prominently of his right arm, including aplasia of the entire proximal humerus, hypoplasia of the clavicle and scapula, and absence of the radial ray and thumb. A hypoplastic left thumb was also present. Other anomalies included thoracic scoliosis, upper thoracic hemivertebrae, and mild cardiomegaly. The differential diagnosis and likely diagnosis are discussed.

Hepatopathy in an adult, secondary to congenital untreated panhypopituitarism and ectopic posterior pituitary gland.

PubMed

Valle-Murillo, Miguel A; Perez-Diaz, Ivan

2012-09-01

We report a rare case of an adult with advanced liver failure in the setting of an untreated congenital panhypopituitarism. A 32-years-old man presented with a newly onset seizure episode secondary to hypoglycemia. In the initial exploration, we found eunuchoid habitus, absence of secondary sexual characteristics, ascites, and hepatic encephalopathy. Hormonal evaluation confirmed the absence of anterior hypophyseal hormones and the liver function tests showed derangement of liver function. Magnetic Resonance Imaging (MRI) showed hypoplastic adenohypophysis and ectopic posterior pituitary gland. In the approach to liver disease, no cause was identified, besides the untreated panhypopituitarism.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

Anomalies of vertebrae and ribs: Jarcho Levin syndrome. Description of a case and literature review.

PubMed

Vázquez-López, María E; López-Conde, María I; Somoza-Rubio, Carlos; Pérez-Pacín, Roberto; Morales-Redondo, Ramón; González-Gay, Miguel A

2005-05-01

Jarcho Levin syndrome is a congenital disorder characterized by the presence of rib and vertebral defects at birth. This syndrome is usually diagnosed in newborns with short neck and trunk and short stature. They present multiple vertebral anomalies at different levels of the spine, including "butterfly vertebrae", hemivertebrae and fused hypoplastic vertebrae. The small size of the thorax in newborns frequently leads to respiratory compromise and death in infancy. We report a new case with short trunk and neck and vertebral and costal anomalies without respiratory problems. A literature review was conducted.

Radiation-induced cerebrovascular disease in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, T.L.; Bresnan, M.J.

1976-06-01

Radiation-induced internal carotid artery occlusion has not been well recognized previously as a cause of childhood cerebrovascular disease. A child who had received radiation as a neonate for a hemangioma involving the left orbit at the age of 6 years experienced a recurrent right-sided paresis, vascular headaches, and speech difficulties. Angiography showed a hypoplastic left carotid artery with occlusion of both the anterior and middle cerebral arteries. Collateral vessels bypassed the occluded-stenotic segments. Review of the literature showed two additional cases of large vessel occlusion in childhood associated with anastomatic telangiectatic vessel development following early radiation therapy of facial hemangioma.

A newborn with unilateral limb enlargement.

PubMed

Sharma, Shanel; Maino, Anna P F; Husain, Shad M; Adams, Gill G W

2012-03-01

On routine neonatal examination, a newborn term male was noted to have unilateral enlargement of the right lower limb, loose thickened red skin over the palm and widening of all the fingers on the right hand. His body was pinker and warmer on the right side compared with the left and he had a right undescended testicle and hypoplastic scrotum. Radiological examination of the lower limbs demonstrated the enlargement of the soft tissue of the right lower limb compared to the left (Fig. 1). Therefore, the diagnosis was unclear from this constellation of findings and an ophthalmic assessment was requested.

Spectacle fitting with ear, nose and face deformities or abnormalities.

PubMed

Eng, Helen; Chiu, Roger Sin Fai

2002-11-01

Spectacle frame selection and dispensing remain significant components of optometry. Occasionally, we encounter patients who are unable to wear conventional spectacles due to abnormalities or deformities following injury and/or surgery to their nose, ears or head. In these cases, spectacle frame fitting may be more complex and customized frame adjustments may be required to account for the anatomical variations. A patient with a microtia (hypoplastic pinna) was fitted with a tailored spectacle frame. The details are presented together with a summary of different frames and modifications available for ears, nose and face abnormalities.

Pearson disease in an infant presenting with severe hypoplastic anemia, normal pancreatic function, and progressive liver failure.

PubMed

Shapira, Adi; Konopnicki, Muriel; Hammad-Saied, Mohammed; Shabad, Evelyn

2014-07-01

Pearson disease is a rare, usually fatal, mitochondrial disorder affecting primarily the bone marrow and the exocrine pancreas. We report a previously healthy 10-week-old girl who presented with profound macrocytic anemia followed by pancytopenia, synthetic liver dysfunction with liver steatosis, and metabolic acidosis with high lactate levels. She had no pancreatic involvement. Multiple cytoplasmic vacuoles in myelocytes and monocytes were seen upon microscopic evaluation of the bone marrow. Genetic analysis of the mitochondrial genome revealed a 5 kbp deletion, thus establishing the diagnosis of Pearson disease.

Three-year-old child with middle aortic syndrome treated by endovascular stent implantation.

PubMed

Moszura, Tomasz; Goreczny, Sebastian; Dryzek, Pawel; Niwald, Marek

2013-04-01

Middle aortic syndrome (MAS) is an extremely rare anomaly and represents both a diagnostic and therapeutic challenge, particularly in young children. A case of a 3.5 year-old child with MAS and arterial hypertension is reported, where owing to the patient's young age and the length of the hypoplastic aortic segment, surgical correction with end-to-end anastomosis was not feasible. Instead of palliative bypass grafting between the thoracic and abdominal aorta, successful percutaneous balloon angioplasty and stenting of the lesion was performed with the assistance of three-dimensional rotational angiography.

Downregulation of Midkine gene expression and its response to retinoic acid treatment in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Shintaku, Mika; Dingemann, Jens; Ruttenstock, Elke; Puri, Prem

2011-02-01

Nitrofen-induced congenital diaphragmatic hernia (CDH) model has been widely used to investigate the pathogenesis of pulmonary hypoplasia (PH) in CDH. Recent studies have suggested that retinoids may be involved in the molecular mechanisms of PH in CDH. Prenatal treatment with retinoic acid (RA) has been reported to improve the growth of hypoplastic lung in the nitrofen CDH model. Midkine (MK), a RA-responsive growth factor, plays key roles in various organogenesis including lung development. In fetal lung, MK mRNA expression has its peak at E13.5-E16.5 and is markedly decreased during mid-to-late gestation, indicating its important role in early lung morphogenesis. We designed this study to investigate the hypothesis that the pulmonary MK gene expression is downregulated in the early lung morphogenesis in the nitrofen-induced PH, and to evaluate the effect of prenatal RA treatment on pulmonary MK gene expression in the nitrofen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into control, nitrofen with or without CDH [CDH(+) or CDH(-)]. In addition, RA was given on days D18, D19, and D20 and fetal lungs were harvested on D21, and then divided into control + RA and nitrofen + RA. The pulmonary gene expression levels of MK were evaluated by real-time RT-PCR and statistically analyzed. Immunohistochemistry was also performed to examine protein expression/distribution of MK in fetal lung. The relative mRNA expression levels of MK were significantly downregulated in nitrofen group compared to controls at D15 ((§)p < 0.01), whereas there were no significant differences at D18 and D21. MK gene expression levels were significantly upregulated in nitrofen + RA (0.71 ± 0.17) compared to the control (0.35 ± 0.16), CDH(-) (0.24 ± 0.15), CDH(+) (0.39 ± 0.19) and control + RA (0.47 ± 0.13) (*p < 0.05). Immunoreactivity of MK was also markedly decreased in nitrofen lungs compared to controls on D15, and increased in nitrofen + RA lungs compared to the other lungs on D21. Downregulation of MK gene on D15 may contribute to primary PH in the nitrofen CDH model by disrupting early lung morphogenesis. Upregulation of MK gene after RA treatment in the nitrofen-induced hypoplastic lung suggests that RA may have a therapeutic potential to rescue PH in CDH through RA-responsive growth factor signaling.

Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study.

PubMed

Gaudino, Rossella; Garel, Catherine; Czernichow, Paul; Léger, Juliane

2005-04-01

To determine the proportion of the various types of thyroid disorders among newborns detected by the neonatal TSH screening programme, with a normally located thyroid gland. Patients and methods Of the 882 575 infants screened in our centre between 1981 and 2002, 85 infants with a normally located gland had persistent elevation of serum TSH values (an incidence of 1/10 383). Six of these 85 patients were lost to follow-up and were therefore excluded from the study. During follow-up, patients were classified as having permanent or transient hypothyroidism. Among the 79 patients included in the study, transient (n = 30, 38% of cases) and permanent (n = 49, 62% of cases) congenital hypothyroidism (CH) was demonstrated during the follow-up at the age of 0.7 +/- 0.6 years and 2.6 +/- 1.8 years (P < 0.0001), respectively. The proportion of premature births was significantly higher in the group with transient CH (57%) than in the group with permanent CH (2%) (P < 0.0001). A history of iatrogenic iodine overload was identified during the neonatal period in 69% of transient cases. Among permanent CH cases (n = 49), patients were classified as having a goitre (n = 27, 55% of cases), a normal sized and shaped thyroid gland (n = 14, 29% of cases) or a hypoplastic gland (n = 8, 16% of cases). The latter patients demonstrated global thyroid hypoplasia (n = 3), a right hemithyroid (n = 2), hypoplasia of the left lobe (n = 2), or asymmetry in the location of the two lobes (n = 1). Patients with a normal sized and shaped thyroid gland showed a significantly less severe form of hypothyroidism than those with a goitre or a hypoplastic thyroid gland (P < 0.0002). Among permanent CH cases, those with a goitre (n = 27) had an iodine organification defect (n = 10), Pendred syndrome (n = 1), a defect of thyroglobulin synthesis (n = 8), or a defect of sodium iodine symporter (n = 1), and in seven patients no aetiology could be determined. Among permanent cases with a normal sized and shaped thyroid gland (n = 14), a specific aetiology was found in only one patient (pseudohypoparathyroidism) and two patients had Down's syndrome. Among those with a globally hypoplastic gland, a TSH receptor gene mutation was found in two patients. A precise description of the phenotype can enhance our understanding of various forms of neonatal hypothyroidism as well as their prevalence and management. It also helps to identify cases of congenital hypothyroidism of unknown aetiology, which will need to be investigated in collaboration with molecular biologists.

Predisposing factors for atrial fibrillation in the elderly

PubMed Central

Wasmer, Kristina; Eckardt, Lars; Breithardt, Günter

2017-01-01

Atrial fibrillation (AF) in the elderly occurs as a consequence of cardiovascular aging and an age related increase of comorbidity. Several predisposing factors for AF have been identified for the overall AF population. Most of them, cardiovascular disease in particular, play a role in younger and older patients. The longer time period during which these risk factors can cause structural changes that ultimately lead to AF may, at least in part, explain the association between age and AF. In addition, less well defined age-related changes in cellular electrophysiologic properties and structure predispose to AF in the elderly. PMID:28592961

Application of stem cells for cardiovascular grafts tissue engineering.

PubMed

Wu, Kaihong; Liu, Ying Long; Cui, Bin; Han, Zhongchao

2006-06-01

Congenital and acquired heart diseases are leading causes of morbidity and mortality world-wide. Currently, the synthetic materials or bioprosthetic replacement devices for cardiovascular surgery are imperfect and subject patients to one or more ongoing risks including thrombosis, limited durability and need for reoperations due to lack of growth in children and young adults. Suitable replacement grafts should have appropriate characteristics, including resistance to infection, low immunogenicity, good biocompatability and thromboresistance, with appropriate mechanical and physiological properties. Tissue engineering is a new scientific field aiming at fabrication of living, autologous grafts having structure or function properties that can be used to restore, maintain or improve tissue function. The use of autologous stem cells in cardiovascular tissue engineering is quite promising due to their capacity of self-renewal, high proliferation, and differentiation into specialized progeny. Progress has been made in engineering the various components of the cardiovascular system, including myocardial constructs, heart valves, and vascular patches or conduits with autologous stem cells. This paper will review the current achievements in stem cell-based cardiovascular grafts tissue engineering, with an emphasis on its clinical or possible clinical use in cardiovascular surgery.

Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives.

PubMed

Cussons, Andrea J; Stuckey, Bronwyn G A; Watts, Gerald F

2006-04-01

The new millennium has brought intense focus of interest on the risk of cardiovascular disease in women. The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women characterised by hyperandrogenism and oligomenorrhoea. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Echocardiography, imaging of coronary and carotid arteries, and assessments of both endothelial function and arterial stiffness have recently been employed to address this question. These studies have collectively demonstrated both structural and functional abnormalities of the cardiovascular system in PCOS. These alterations, however, appear to be related to the presence of individual cardiovascular risk factors, particularly insulin resistance, rather than to the presence of PCOS and hyperandrogenaemia per se. However, given the inferential nature of the evidence to date, more rigorous cohort studies of long-term cardiovascular outcomes and clinical trials of risk factor modification are required in women with PCOS.

Thinking on building the network cardiovasology of Chinese medicine.

PubMed

Yu, Gui; Wang, Jie

2012-11-01

With advances in complex network theory, the thinking and methods regarding complex systems have changed revolutionarily. Network biology and network pharmacology were built by applying network-based approaches in biomedical research. The cardiovascular system may be regarded as a complex network, and cardiovascular diseases may be taken as the damage of structure and function of the cardiovascular network. Although Chinese medicine (CM) is effective in treating cardiovascular diseases, its mechanisms are still unclear. With the guidance of complex network theory, network biology and network pharmacology, network-based approaches could be used in the study of CM in preventing and treating cardiovascular diseases. A new discipline-network cardiovasology of CM was, therefore, developed. In this paper, complex network theory, network biology and network pharmacology were introduced and the connotation of "disease-syndrome-formula-herb" was illustrated from the network angle. Network biology could be used to analyze cardiovascular diseases and syndromes and network pharmacology could be used to analyze CM formulas and herbs. The "network-network"-based approaches could provide a new view for elucidating the mechanisms of CM treatment.

Organogenesis of heart-vascular system derived from mouse 2 cell stage embryos and from early embryonic stem cells in vitro.

PubMed

Ishiwata, Isamu; Tamagawa, Tomoharu; Tokieda, Yuko; Iguchi, Megumi; Sato, Kahei; Ishikawa, Hiroshi

2003-03-01

Regenerative medical treatment with embryonic stem cells (an ES cell) is a goal for organ transplantation. Structures that are tubular in nature (i.e. blood capillaries) were induced from early embryonic stem (EES) cells in vitro using embryotrophic factor (ETFs). In addition, cardiac muscle cells could be identified as well. However, differentiation of EES cells into a complete cardiovascular system was difficult because 3 germ layer primordial organs are directed embryologically in various ways and it is not possible to guide only cardiovascular organs. Thus, we introduced ETFs after the formation of an embryoid body and were successful in cloning cell clusters that beat, thus deriving only cardiovascular organs. The application of this to the treatment of various cardiovascular diseases is promising.

Integrative analysis of transcriptomic and metabolomic data via sparse canonical correlation analysis with incorporation of biological information.

PubMed

Safo, Sandra E; Li, Shuzhao; Long, Qi

2018-03-01

Integrative analysis of high dimensional omics data is becoming increasingly popular. At the same time, incorporating known functional relationships among variables in analysis of omics data has been shown to help elucidate underlying mechanisms for complex diseases. In this article, our goal is to assess association between transcriptomic and metabolomic data from a Predictive Health Institute (PHI) study that includes healthy adults at a high risk of developing cardiovascular diseases. Adopting a strategy that is both data-driven and knowledge-based, we develop statistical methods for sparse canonical correlation analysis (CCA) with incorporation of known biological information. Our proposed methods use prior network structural information among genes and among metabolites to guide selection of relevant genes and metabolites in sparse CCA, providing insight on the molecular underpinning of cardiovascular disease. Our simulations demonstrate that the structured sparse CCA methods outperform several existing sparse CCA methods in selecting relevant genes and metabolites when structural information is informative and are robust to mis-specified structural information. Our analysis of the PHI study reveals that a number of gene and metabolic pathways including some known to be associated with cardiovascular diseases are enriched in the set of genes and metabolites selected by our proposed approach. © 2017, The International Biometric Society.

Heart rate complexity in sinoaortic-denervated mice.

PubMed

Silva, Luiz Eduardo V; Rodrigues, Fernanda Luciano; de Oliveira, Mauro; Salgado, Hélio Cesar; Fazan, Rubens

2015-02-01

What is the central question of this study? New measurements for cardiovascular complexity, such as detrended fluctuation analysis (DFA) and multiscale entropy (MSE), have been shown to predict cardiovascular outcomes. Given that cardiovascular diseases are accompanied by autonomic imbalance and decreased baroreflex sensitivity, the central question is: do baroreceptors contribute to cardiovascular complexity? What is the main finding and its importance? Sinoaortic denervation altered both DFA scaling exponents and MSE, indicating that both short- and long-term mechanisms of complexity are altered in sinoaortic denervated mice, resulting in a loss of physiological complexity. These results suggest that the baroreflex is a key element in the complex structures involved in heart rate variability regulation. Recently, heart rate (HR) oscillations have been recognized as complex behaviours derived from non-linear processes. Physiological complexity theory is based on the idea that healthy systems present high complexity, i.e. non-linear, fractal variability at multiple scales, with long-range correlations. The loss of complexity in heart rate variability (HRV) has been shown to predict adverse cardiovascular outcomes. Based on the idea that most cardiovascular diseases are accompanied by autonomic imbalance and a decrease in baroreflex sensitivity, we hypothesize that the baroreflex plays an important role in complex cardiovascular behaviour. Mice that had been subjected to sinoaortic denervation (SAD) were implanted with catheters in the femoral artery and jugular vein 5 days prior to the experiment. After recording the baseline arterial pressure (AP), pulse interval time series were generated from the intervals between consecutive values of diastolic pressure. The complexity of the HRV was determined using detrended fluctuation analysis and multiscale entropy. The detrended fluctuation analysis α1 scaling exponent (a short-term index) was remarkably decreased in the SAD mice (0.79 ± 0.06 versus 1.13 ± 0.04 for the control mice), whereas SAD slightly increased the α2 scaling exponent (a long-term index; 1.12 ± 0.03 versus 1.04 ± 0.02 for control mice). In the SAD mice, the total multiscale entropy was decreased (13.2 ± 1.3) compared with the control mice (18.9 ± 1.4). In conclusion, fractal and regularity structures of HRV are altered in SAD mice, affecting both short- and long-term mechanisms of complexity, suggesting that the baroreceptors play a considerable role in the complex structure of HRV. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Sex and the Cardiovascular System: The Intriguing Tale of How Women and Men Regulate Cardiovascular Function Differently

ERIC Educational Resources Information Center

Huxley, Virginia H.

2007-01-01

The ability to recognize and appreciate from a reproductive standpoint that males and females possess different attributes has been long standing. Only more recently have we begun to look more deeply into both the similarities and differences between men and women, as well as between boys and girls, with respect to the structure and function of…

Family-Based Approaches to Cardiovascular Health Promotion.

PubMed

Vedanthan, Rajesh; Bansilal, Sameer; Soto, Ana Victoria; Kovacic, Jason C; Latina, Jacqueline; Jaslow, Risa; Santana, Maribel; Gorga, Elio; Kasarskis, Andrew; Hajjar, Roger; Schadt, Eric E; Björkegren, Johan L; Fayad, Zahi A; Fuster, Valentin

2016-04-12

Cardiovascular disease is the leading cause of mortality in the world, and the increasing burden is largely a consequence of modifiable behavioral risk factors that interact with genomics and the environment. Continuous cardiovascular health promotion and disease prevention throughout the lifespan is critical, and the family is a central entity in this process. In this review, we describe the potential rationale and mechanisms that contribute to the importance of family for cardiovascular health promotion, focusing on: 1) mutual interdependence of the family system; 2) shared environment; 3) parenting style; 4) caregiver perceptions; and 5) genomics. We conclude that family-based approaches that target both caregivers and children, encourage communication among the family unit, and address the structural and environmental conditions in which families live and operate are likely to be the most effective approach to promote cardiovascular health. We describe lessons learned, future implications, and applications to ongoing and planned studies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification

NASA Astrophysics Data System (ADS)

Bertazzo, Sergio; Gentleman, Eileen; Cloyd, Kristy L.; Chester, Adrian H.; Yacoub, Magdi H.; Stevens, Molly M.

2013-06-01

The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

PubMed Central

de Munnik, Sonja A; Bicknell, Louise S; Aftimos, Salim; Al-Aama, Jumana Y; van Bever, Yolande; Bober, Michael B; Clayton-Smith, Jill; Edrees, Alaa Y; Feingold, Murray; Fryer, Alan; van Hagen, Johanna M; Hennekam, Raoul C; Jansweijer, Maaike C E; Johnson, Diana; Kant, Sarina G; Opitz, John M; Ramadevi, A Radha; Reardon, Willie; Ross, Alison; Sarda, Pierre; Schrander-Stumpel, Constance T R M; Schoots, Jeroen; Temple, I Karen; Terhal, Paulien A; Toutain, Annick; Wise, Carol A; Wright, Michael; Skidmore, David L; Samuels, Mark E; Hoefsloot, Lies H; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

2012-01-01

Meier–Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identified in individuals with MGS. Here, we report on genotype–phenotype studies in 45 individuals with MGS (27 females, 18 males; age 3 months–47 years). Thirty-five individuals had biallelic mutations in one of the five causative pre-replication genes. No homozygous or compound heterozygous null mutations were detected. In 10 individuals, no definitive molecular diagnosis was made. The triad of microtia, absent/hypoplastic patellae, and short stature was observed in 82% of individuals with MGS. Additional frequent clinical features were mammary hypoplasia (100%) and abnormal genitalia (42% predominantly cryptorchidism and hypoplastic labia minora/majora). One individual with ORC1 mutations only had short stature, emphasizing the highly variable clinical spectrum of MGS. Individuals with ORC1 mutations had significantly shorter stature and smaller head circumferences than individuals from other gene categories. Furthermore, compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4 and more frequently pulmonary emphysema in CDT1. A lethal phenotype was seen in four individuals with compound heterozygous ORC1 and CDT1 mutations. No other clear genotype–phenotype association was observed. Growth hormone and estrogen treatment may be of some benefit, respectively, to growth retardation and breast hypoplasia, though further studies in this patient group are needed. PMID:22333897

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial.

PubMed

Tarui, Suguru; Ishigami, Shuta; Ousaka, Daiki; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2015-11-01

Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS). In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up. No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion. Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Follistatin-like 1 expression is decreased in the alveolar epithelium of hypoplastic rat lungs with nitrofen-induced congenital diaphragmatic hernia.

PubMed

Takahashi, Toshiaki; Zimmer, Julia; Friedmacher, Florian; Puri, Prem

2017-05-01

Pulmonary hypoplasia (PH), characterized by incomplete alveolar development, remains a major therapeutic challenge associated with congenital diaphragmatic hernia (CDH). Follistatin-like 1 (Fstl1) is a crucial regulator of alveolar formation and maturation, which is strongly expressed in distal airway epithelium. Fstl1-deficient mice exhibit reduced airspaces, impaired alveolar epithelial cell differentiation, and insufficient production of surfactant proteins similar to PH in human CDH. We hypothesized that pulmonary Fstl1 expression is decreased during alveolarization in the nitrofen-induced CDH model. Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D18 and D21 and divided into control-/nitrofen-exposed specimens. Alveolarization was assessed using morphometric analysis techniques. Pulmonary gene expression of Fstl1 was determined by qRT-PCR. Immunofluorescence-double-staining for Fstl1 and alveolar epithelial marker surfactant protein C (SP-C) was performed to evaluate protein expression/localization. Radial alveolar count was significantly reduced in hypoplastic lungs of nitrofen-exposed fetuses with significant down regulation of Fstl1 mRNA expression on D18 and D21 compared to controls. Confocal-laser-scanning-microscopy revealed strikingly diminished Fstl1 immunofluorescence and SP-C expression in distal alveolar epithelium of nitrofen-exposed fetuses with CDH-associated PH on D18 and D21 compared to controls. Decreased expression of Fstl1 in alveolar epithelium may disrupt alveolarization and pulmonary surfactant production, thus contributing to the development of PH in the nitrofen-induced CDH model. 2b (Centre for Evidence-Based Medicine, Oxford). Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal treatment with retinoic acid activates parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Sugimoto, Kaoru; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2011-01-01

Prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs (HL) in the nitrofen model of congenital diaphragmatic hernia (CDH). Parathyroid hormone-related protein (PTHrP) promotes alveolar maturation by stimulating surfactant production, regulated by PTHrP receptor (PTHrP-R). PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia. We have recently reported that nitrofen inhibits PTHrP signaling in the nitrofen-induced HL. Because both PTHrP and PTHrP-R genes have RA-inducible element, we hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PTHrP and PTHrP-R in the nitrofen-induced HL. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). RA was given on days D18, D19 and D20. Fetal lungs were obtained on D21 and divided into four groups: control, control + RA, nitrofen, nitrofen + RA. RT-PCR and Immunohistochemistry were performed to investigate the pulmonary PTHrP and PTHrP-R gene and protein expression in each group, respectively. The pulmonary gene expression levels of PTHrP and PTHrP-R were significantly increased in nitrofen + RA group compared to nitrofen group (p < 0.05). Immunoreactivity of PTHrP and PTHrP-R was also remarkably increased in nitrofen + RA group compared to nitrofen group. Upregulation of PTHrP and PTHrP-R genes after prenatal treatment with RA in the nitrofen-induced HL suggests that RA may have a therapeutic potential in reverting lung hypoplasia in CDH, by stimulating surfactant production and alveolar maturation.

Mortality-related resource utilization in the inpatient care of hypoplastic left heart syndrome.

PubMed

Danford, David A; Karels, Quentin; Kulkarni, Aparna; Hussain, Aysha; Xiao, Yunbin; Kutty, Shelby

2015-10-22

Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF). A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children's hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of stay (LOS) were recorded. In all, 11,122 HLHS admissions were identified which account for total LOS of 277,027 inpatient-days and $3,928,794,660 in BC. There were 1145 inpatient deaths (10.3%). LOS was greater among inpatient deaths than among patients discharged alive (median 17 vs. 12, p < 0.0001). BC were greater among inpatient deaths than among patients discharged alive (median 4.09 × 10(5) vs. 1.63 × 10(5), p < 0.0001). 16% of all LOS and 21% of all BC were accrued by patients who did not survive their hospitalization. These proportions showed no significant change year-by-year. The highest volume institutions had lower mortality rates, but there was no relation between institutional volume and the MRRUF. These data should alert providers and consumers that current practices often result in major resource expenditure for inpatient care of HLHS that does not result in survival to hospital dismissal. They highlight the need for data-driven critical review of standard practices to identify patterns of care associated with success, and to modify approaches objectively.

Initial shunt type at the Norwood operation impacts myocardial function in hypoplastic left heart syndrome.

PubMed

Ruotsalainen, Hanna K; Pihkala, Jaana; Salminen, Jukka; Hornberger, Lisa K; Sairanen, Heikki; Ojala, Tiina

2017-08-01

We investigated the impact of initial shunt type, a Blalock-Taussig (BT) shunt versus a right ventricle to pulmonary artery conduit (RV-PA) on myocardial function at different stages of surgical palliation in patients with hypoplastic left heart syndrome (HLHS). A population-based cohort of 63 Finnish children with HLHS (BT n  = 23, RV-PA n  = 40) born between 2003 and 2010 were studied retrospectively by echocardiography prior to Stages 1, 2 and 3 palliation and 0.5-3 years after Stage 3. For comparison of systolic myocardial function, we evaluated the RV fractional area change (FAC), strain, strain rate and mechanical synchrony from the apical 4-chamber view by velocity vector imaging. There were no intergroup differences in demographics during the study period. At baseline, no intergroup differences were detected in RV systolic myocardial function. Before Stage 2, RV FAC was higher ( P  = 0.03) in the RV-PA conduit group. At Stage 3, an increase in all systolic myocardial functional parameters was observed in the BT shunt group. After Stage 3, the BT shunt group had better RV systolic function. In multiple regression analysis, the shunt type and the stage of palliation had an impact on myocardial function. Although patients with HLHS initially palliated with a BT shunt demonstrate lower RV FAC after Stage I, RV FAC improves after Stage 2 with better systolic performance after Stage 3 compared with those initially palliated with an RV-PA conduit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Staged surgical management of hypoplastic left heart syndrome: a single institution 12 year experience

PubMed Central

McGuirk, S P; Griselli, M; Stumper, O F; Rumball, E M; Miller, P; Dhillon, R; de Giovanni, J V; Wright, J G; Barron, D J; Brawn, W J

2006-01-01

Objective To describe a 12 year experience with staged surgical management of the hypoplastic left heart syndrome (HLHS) and to identify the factors that influenced outcome. Methods Between December 1992 and June 2004, 333 patients with HLHS underwent a Norwood procedure (median age 4 days, range 0–217 days). Subsequently 203 patients underwent a bidirectional Glenn procedure (stage II) and 81 patients underwent a modified Fontan procedure (stage III). Follow up was complete (median interval 3.7 years, range 32 days to 11.3 years). Results Early mortality after the Norwood procedure was 29% (n  =  95); this decreased from 46% (first year) to 16% (last year; p < 0.05). Between stages, 49 patients died, 27 before stage II and 22 between stages II and III. There were one early and three late deaths after stage III. Actuarial survival (SEM) was 58% (3%) at one year and 50% (3%) at five and 10 years. On multivariable analysis, five factors influenced early mortality after the Norwood procedure (p < 0.05). Pulmonary blood flow supplied by a right ventricle to pulmonary artery (RV‐PA) conduit, arch reconstruction with pulmonary homograft patch, and increased operative weight improved early mortality. Increased periods of cardiopulmonary bypass and deep hypothermic circulatory arrest increased early mortality. Similar factors also influenced actuarial survival after the Norwood procedure. Conclusion This study identified an improvement in outcome after staged surgical management of HLHS, which was primarily attributable to changes in surgical technique. The RV‐PA conduit, in particular, was associated with a notable and independent improvement in early and actuarial survival. PMID:15939721

[Hypoplastic left heart syndrome: 10 year experience with staged surgical management].

PubMed

Urcelay, Gonzalo; Arancibia, Francisca; Retamal, Javiera; Springmuller, Daniel; Clavería, Cristián; Garay, Francisco; Frangini, Patricia; González, Rodrigo; Heusser, Felipe; Arretz, Claudio; Zelada, Pamela; Becker, Pedro

2016-01-01

Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease in 95% of non-treated patients. Surgical staging is the main form of treatment, consisting of a 3-stage approach, beginning with the Norwood operation. Long term survival of treated patients is unknown in our country. 1) To review our experience in the management of all patients seen with HLHS between January 2000 and June 2012. 2) Identify risk factors for mortality. Retrospective analysis of a single institution experience with a cohort of patients with HLHS. Clinical, surgical, and follow-up records were reviewed. Of the 76 patients with HLHS, 9 had a restrictive atrial septal defect (ASD), and 8 had an ascending aorta ≤2mm. Of the 65 out of 76 patients that were treated, 77% had a Norwood operation with pulmonary blood flow supplied by a right ventricle to pulmonary artery conduit, 17% had a Norwood with a Blalock-Taussig shunt, and 6% other surgical procedure. Surgical mortality at the first stage was 23%, and for Norwood operation 21.3%. For the period between 2000-2005, surgical mortality at the first stage was 36%, and between 2005-2010, 15% (P=.05). Actuarial survival was 64% at one year, and 57% at 5years. Using a multivariate analysis, a restrictive ASD and a diminutive aorta were high risk factors for mortality. Our immediate and long term outcome for staged surgical management of HLHS is similar to that reported by large centres. There is an improvement in surgical mortality in the second half of our experience. Risk factors for mortality are also identified. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Time-to-Surgery and Pre-operative Cerebral Hemodynamics Predict Post-operative White Matter Injury in Neonates with Hypoplastic Left Heart Syndrome

PubMed Central

Lynch, Jennifer M.; Buckley, Erin M.; Schwab, Peter J.; McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Xiao, Rui; Goff, Donna A.; Nicolson, Susan C.; Montenegro, Lisa M.; Fuller, Stephanie; Gaynor, J. William; Spray, Thomas L.; Yodh, Arjun G.; Naim, Maryam Y.; Licht, Daniel J.

2014-01-01

Objective Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately half of the HLHS survivors exhibit neurobehavioral symptoms believed to be associated with this injury, though the exact timing of the injury is not known. Methods Neonates with HLHS were recruited for pre- and post-operative monitoring of cerebral oxygen saturation (ScO2), cerebral oxygen extraction fraction (OEF), and cerebral blood flow (CBF) using two non-invasive optical-based techniques, namely diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomical magnetic resonance imaging (MRI) scans were performed prior to and approximately one week after surgery in order to quantify the extent and timing of the acquired white matter injury. Risk factors for developing new or worsened white matter injury were assessed using uni- and multi-variate logistic regression. Results Thirty-seven neonates with HLHS were studied. In a univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time-to-surgery (p=0.0003). In a multivariate model, longer time between birth and surgery (i.e., time-to-surgery), delayed sternal closure, and higher pre-operative CBF were predictors of post-operative white matter injury. Additionally, longer time-to-surgery and higher pre-operative CBF on morning of surgery were correlated with lower ScO2 (p=0.03 and p=0.05) and higher OEF (p=0.05 and p=0.05). Conclusions Longer time-to-surgery is associated with new post-operative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation may decrease the likelihood of acquiring postoperative white matter injury. PMID:25109755

Repair for Congenital Mitral Valve Stenosis.

PubMed

Delmo Walter, Eva Maria; Hetzer, Roland

2018-03-01

We report the techniques and long-term outcome of mitral valve (MV) repair to correct congenital mitral stenosis in children. Between 1986 and 2014, 137 children (mean age 4.1 ± 5.0, range 1 month-16.8 years) underwent repair of congenital mitral stenosis (CMS). In 48 patients, CMS is involved in Shone's anomaly. The typical congenital MS (type I) was seen in 56 patients. Hypoplastic MV (type II, n = 15) was associated with severe left ventricular outflow tract abnormalities and hypoplastic left ventricular cavity and muscle mass. Supravalvar ring (type III, n = 48) ranged from a thin membrane to a thick discrete fibrous ridge. Parachute MV (type IV, n = 10) have 2 leaflets and barely distinguishable commissures, but all chordae merged either into 1 major papillary muscle or asymmetric papillary muscles-1 dominant and the other minuscule. Hammock valve (type IV, n = 8) appeared dysplastic with shortened chordae directly inserted into the posterior left ventricular muscle mass. MV repair was performed using commissurotomy, chordal division, papillary muscle splitting and fenestration, and mitral ring resection, each applied according to the presenting morphology. During the 28-year follow-up period, 23 patients underwent repeat MV repair and 3 underwent MV replacement after failed attempts at repeat repair. At 1 and 15 years postoperatively, freedom from reoperation was 89.3 ± 5.1% and 52.8 ± 11.8%, and cumulative survival rates were 92.3 ± 4.3% and 70.3 ± 8.9, respectively. Mortality unrelated to repair accounted for 9 (20%) deaths. Long-term functional outcome of MV repair in children with CMS is satisfactory. Repeat repair or replacement may be deemed necessary during the course of follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

Catheter interventional treatment of congenital portosystemic venous shunts in childhood.

PubMed

Knirsch, Walter; Benz, Dominik C; Bühr, Patrick; Quandt, Daniel; Weber, Roland; Kellenberger, Christian; Braegger, Christian P; Kretschmar, Oliver

2016-06-01

The study aimed on the catheter interventional treatment of congenital portosystemic venous shunt (CPSVS) in childhood and the impact on vascular growth of hypoplastic portal veins. Clinical course and follow up of partial or complete closure of CPSVS are described. CPSVS is a very rare vascular malformation of the portal venous drainage resulting in potentially life threatening abdominal, pulmonary, cerebral, and cardiac complications. The anatomic type, clinical course, and diagnosis must be determined for optimal management. Single centre case series. Eight (6 female) children with extrahepatic (n = 5) and intrahepatic (n = 3) CPSVS were diagnosed invasively by catheterization, including test balloon occlusion of the shunt and simultaneous retrograde angiography, and treated by catheter interventions (n = 5) with partial (n = 2) and complete (n = 3) occlusion of CPSVS at a median age of 3.9 years (range 0.7-21). Congenital heart disease (CHD) was the most frequent associated organ manifestation (n = 5) followed by mild to severe pulmonary arterial hypertension (n = 4), hepatopulmonary syndrome (n = 2), and portosystemic encephalopathy (n = 1). CHD was simple (n = 3) or complex type (n = 2). Three patients were untreated so far, because they were in excellent clinical condition at an age <1 year, refused treatment, or planned for later treatment. Accurate invasive diagnosis of CPSVS with test balloon occlusion of the shunt is mandatory to depict the anatomic situation. Catheter interventional treatment of CPSVS offers a feasible and safe approach with complete or partial closure of the vascular malformation inducing potentially significant vascular growth of a former hypoplastic portal venous system. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

In-hospital mortality for children with hypoplastic left heart syndrome after stage I surgical palliation: teaching versus nonteaching hospitals.

PubMed

Berry, Jay G; Cowley, Collin G; Hoff, Charles J; Srivastava, Rajendu

2006-04-01

Teaching hospitals are perceived to provide a higher quality of care for the treatment of rare disease and complex patients. A substantial proportion of stage I palliation for hypoplastic left heart syndrome (HLHS) may be performed in nonteaching hospitals. This study compares the in-hospital mortality of stage I palliation between teaching and nonteaching hospitals. The authors conducted a retrospective cohort study using the Kids' Inpatient Database 1997 and 2000. Patients with HLHS undergoing stage I palliation were identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedural codes. Seven hundred fifty-four and 880 discharges of children with HLHS undergoing stage I palliation in 1997 and 2000, respectively, were identified. The in-hospital mortality for the study population was 28% in 1997 and 24% in 2000. Twenty percent of stage I palliation operations were performed in nonteaching hospitals in 1997. Two percent of operations were performed in nonteaching hospitals in 2000. In 1997 only, in-hospital mortality remained higher in nonteaching hospitals after controlling for stage I palliation hospital volume and condition-severity diagnoses. Low-volume hospitals performing stage I palliation were associated with increased in-hospital mortality in 1997 and 2000. Patients with HLHS undergoing stage I palliation in nonteaching hospitals experienced increased in-hospital mortality in 1997. A significant reduction in the number of stage I palliation procedures performed in nonteaching hospitals occurred between 1997 and 2000. This centralization of stage I palliation into teaching hospitals, along with advances in postoperative medical and surgical care for these children, was associated with a decrease in mortality. Patients in low-volume hospitals performing stage I palliation continued to experience increased mortality in 2000.

Developmental and Post-Eruptive Defects in Molar Enamel of Free-Ranging Eastern Grey Kangaroos (Macropus giganteus) Exposed to High Environmental Levels of Fluoride

PubMed Central

Kierdorf, Uwe; Death, Clare; Hufschmid, Jasmin; Witzel, Carsten; Kierdorf, Horst

2016-01-01

Dental fluorosis has recently been diagnosed in wild marsupials inhabiting a high-fluoride area in Victoria, Australia. Information on the histopathology of fluorotic marsupial enamel has thus far not been available. This study analyzed the developmental and post-eruptive defects in fluorotic molar enamel of eastern grey kangaroos (Macropus giganteus) from the same high-fluoride area using light microscopy and backscattered electron imaging in the scanning electron microscope. The fluorotic enamel exhibited a brownish to blackish discolouration due to post-eruptive infiltration of stains from the oral cavity and was less resistant to wear than normally mineralized enamel of kangaroos from low-fluoride areas. Developmental defects of enamel included enamel hypoplasia and a pronounced hypomineralization of the outer (sub-surface) enamel underneath a thin rim of well-mineralized surface enamel. While the hypoplastic defects denote a disturbance of ameloblast function during the secretory stage of amelogenesis, the hypomineralization is attributed to an impairment of enamel maturation. In addition to hypoplastic defects, the fluorotic molars also exhibited numerous post-eruptive enamel defects due to the flaking-off of portions of the outer, hypomineralized enamel layer during mastication. The macroscopic and histopathological lesions in fluorotic enamel of M. giganteus match those previously described for placental mammals. It is therefore concluded that there exist no principal differences in the pathogenic mechanisms of dental fluorosis between marsupial and placental mammals. The regular occurrence of hypomineralized, opaque outer enamel in the teeth of M. giganteus and other macropodids must be considered in the differential diagnosis of dental fluorosis in these species. PMID:26895178

[Symbrachydactyly--a roentgenographic and clinical study of 126 cases].

PubMed

Senrui, H

1984-07-01

One hundred and twenty-six cases of symbrachydactyly were analyzed roentgenographically and clinically. This curious anomaly of the hand is sporadic and of unknown etiology. It is predominantly one-sided, either isolated or combined with ipsilateral pectoral muscle defect (fifty-one cases). On X-ray pictures, the skeletal abnormalities of the hands ranged from mild involvement featured with hypoplastic or aplastic middle phalanges to the most severe involvement in which all the phalanges were missing, providing a continuous spectrum. Even in the mildly affected hands hypoplasia involves all the phalanges and metacarpals, most severely in the middle phanges followed by distal, proximal phalanges and metacarpals in turn. The forearms and arms are less affected than the hands. The tendency is observed in the severely affected hands. In the most severely affected hand all the digits are missing, but there exist several finger-buds which carry often nail rudiments. Synostosis is seen in the remaining hypoplastic metacarpals often and in carpals infrequently. Although remarkable shortening and curving forearm bones are observed often, the humeral involvement remains mild. Abnormalities of muscles and tendons are frequently observed in the hand and forearm. The anomaly is classified roentgenographically into three types: Type I (brachydactyly type) which is featured with fingers having three or two phalanges (fifty-four hands), Type II (partial ectrodactyly type) in which one to four digits have only one phalanx or none(thirty-nine hands), and Type III(total ectrodactyly type) in which all the digits have only one phalanx or none (thirty-five hands). The symbrachydactyly seems to be caused by a extensive defect in an undifferentiated mesenchyme of the arm bud at about developmental stage 16, which may later cause a failure of separation of skeletal and muscular tissues of the hand and forearm or an arrest in their development.

Long-term donor site morbidity after free nonvascularized toe phalangeal transfer.

PubMed

Garagnani, Lorenzo; Gibson, Marc; Smith, Paul J; Smith, Gillian D

2012-04-01

Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. This study assessed long-term morbidity in the feet using this technique. We reviewed 40 children treated between 1991 and 2007 by free nonvascularized toe phalangeal transfer. The diagnosis was digital hypoplasia resulting from symbrachydactyly in 33 cases, constriction ring syndrome in 3 cases, thumb hypoplasia in 3 cases, and perinatal subclavian venous thrombosis in 1 case. The patients were followed up after surgery for a mean of 10 years (range, 3-19 y). The Oxford Ankle Foot Questionnaire was administered to patients and families to assess patient symptoms and patient and parental satisfaction. We assessed toe length ratio, the presence of visible deformity, and distal hypoplasia of the donor toes clinically and radiographically. Emotional problems related to foot appearance were common. We also found functional problems with footwear in some patients. All patients had floppy unstable toes with visible deformity. Increasing foot deformity was seen with growth, which led to deterioration in foot aesthetics, particularly where multiple donor toes had been harvested. We identified distal and middle phalangeal and metatarsal hypoplasia in the donor toes. Donor site morbidity for free toe phalangeal transfer is greater than previously documented. This should be considered during surgical decision making for reconstruction of hypoplastic digits. Preoperative counseling should include discussion regarding possible consequences of phalangeal harvest on donor toes and options for donor site reconstruction. Long-term follow-up of the donor site is essential to accurately assess results. Therapeutic III. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Parents' perceptions during the transition to home for their child with a congenital heart defect: How can we support families of children with hypoplastic left heart syndrome?

PubMed

March, Sarita

2017-07-01

The aim of the study was to explore the literature related to transitions in healthcare between the hospital and home that caregivers experience with a child who has a congenital heart defect (CHD), specifically related to hypoplastic left heart syndrome (HLHS). A systematic literature review was conducted searching OVID Medline, CINAHL, and PubMed to discover the caregivers' perceptions on their transitions between hospital care and home care of their child with a CHD. Articles included those with focus on the transitions of caregivers between hospital and home care for children with CHD. Excluded articles were studies focused on adolescents, transition to adult healthcare, mortality results, other diseases associated with CHDs, comparison of CHD treatments, feasibility studies, differences in care between hospitals, home monitoring, and comparison of videoconference and telephone home communication. Ten articles were selected. Many parents voiced their concerns with feeding their child, learning medical skills and knowledge, reported a disrupted relationship between parents and their child, and identified stress and anxiety associated with taking care of a child with a CHD. There were limited studies on caregivers' transitions with a child with HLHS, but there also was limited focus on the caregivers' experiences with transitions between hospital and home care for their child with any CHD. Research on the transition experience between hospital care and home care for caregivers of children born with a CHD, and a specific focus on HLHS from the caregivers' viewpoint, would provide insight into the perspective of caregivers during the numerous transitions. © 2017 Wiley Periodicals, Inc.

Use of mathematic modeling to compare and predict hemodynamic effects of the modified Blalock-Taussig and right ventricle-pulmonary artery shunts for hypoplastic left heart syndrome.

PubMed

Bove, Edward L; Migliavacca, Francesco; de Leval, Marc R; Balossino, Rossella; Pennati, Giancarlo; Lloyd, Thomas R; Khambadkone, Sachin; Hsia, Tain-Yen; Dubini, Gabriele

2008-08-01

Stage one reconstruction (Norwood operation) for hypoplastic left heart syndrome can be performed with either a modified Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. Both methods have certain inherent characteristics. It is postulated that mathematic modeling could help elucidate these differences. Three-dimensional computer models of the Blalock-Taussig shunt and right ventricle-pulmonary artery shunt modifications of the Norwood operation were developed by using the finite volume method. Conduits of 3, 3.5, and 4 mm were used in the Blalock-Taussig shunt model, whereas conduits of 4, 5, and 6 mm were used in the right ventricle-pulmonary artery shunt model. The hydraulic nets (lumped resistances, compliances, inertances, and elastances) were identical in the 2 models. A multiscale approach was adopted to couple the 3-dimensional models with the circulation net. Computer simulations were compared with postoperative catheterization data. Good correlation was found between predicted and observed data. For the right ventricle-pulmonary artery shunt modification, there was higher aortic diastolic pressure, decreased pulmonary artery pressure, lower Qp/Qs ratio, and higher coronary perfusion pressure. Mathematic modeling predicted minimal regurgitant flow in the right ventricle-pulmonary artery shunt model, which correlated with postoperative Doppler measurements. The right ventricle-pulmonary artery shunt demonstrated lower stroke work and a higher mechanical efficiency (stroke work/total mechanical energy). The close correlation between predicted and observed data supports the use of mathematic modeling in the design and assessment of surgical procedures. The potentially damaging effects of a systemic ventriculotomy in the right ventricle-pulmonary artery shunt modification of the Norwood operation have not been analyzed.

Improved Lung Perfusion After Left Pulmonary Artery Patch Enlargement During the Norwood Operation.

PubMed

Salehi Ravesh, Mona; Scheewe, Jens; Attmann, Tim; Al Bulushi, Abdullah; Jussli-Melchers, Marka-Jill; Jerosch-Herold, Michael; Gabbert, Dominik D; Wegner, Philip; Kramer, Hans-Heiner; Rickers, Carsten

2018-05-01

Optimal pulmonary perfusion is crucial for a well-functioning Fontan circulation in patients with hypoplastic left heart syndrome (HLHS). To obtain an adequate size of the left pulmonary artery (LPA), patch enlargement is a routine part of the hemi-Fontan procedure in our center. However, LPA patch enlargement at the time of the modified Norwood procedure may have surgical advantages. Therefore, the aim of this study was to evaluate whether anatomic and functional effects of the new approach are superior. A total of 51 consecutive HLHS patients underwent a cardiovascular magnetic resonance imaging study including assessment of LPA anatomy and lung perfusion. The LPA of 20 patients was enlarged during the modified Norwood procedure (group N) and of 31 patients during the hemi-Fontan procedure (group HF). The median indexed cross-sectional area of the LPA in group N was significantly higher than in group HF (49.5 versus 27.9 mm 2 /m 2 , p < 0.0001). The regional pulmonary perfusion as measured by first-pass, contrast-enhanced signal intensity upslope was significantly improved in group N (left side 0.67 s -1 versus 0.40 s -1 , p = 0.002; right side 0.84 s -1 versus 0.52 s -1 , p = 0.01). The total hemi-Fontan bypass and procedure times were significantly shorter in group N (both p < 0.001). These first magnetic resonance imaging data show that HLHS patients after LPA patch enlargement during the modified Norwood procedure have significantly higher LPA cross-sectional areas and show improved lung perfusion and shorter overall procedure time as compared with LPA patching during second stage (hemi-Fontan). Therefore, this promising surgical technique may improve blood flow dynamics of the Fontan circulation in the long run. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

External stenting: A reliable technique to relieve airway obstruction in small children.

PubMed

Ando, Makoto; Nagase, Yuzo; Hasegawa, Hisaya; Takahashi, Yukihiro

2017-05-01

Airway obstruction in children may be caused by conditions such as vascular compression and congenital tracheobronchomalacia. Obstructive pulmonary vascular disease may be a detrimental sequel for patients with congenital heart disease. We evaluate our own original external stenting technique as a treatment option for these patients. Ninety-eight patients underwent external stenting (1997-2015). Cardiovascular anomalies were noted in 82 (83.7%). Nine patients had hypoplastic left heart syndrome and 6 had other types of single-ventricular hearts. The median age at the first operation was 7.2 months (range, 1.0-77.1 months). The mechanisms were tracheobronchomalacia with (n = 46) or without (n = 52) vascular compression. Patients underwent 127 external stentings for 139 obstruction sites (62 trachea, 55 left bronchus, and 22 right bronchus). The stent sizes varied from 12 to 16 mm. There were 14 (8 in the hospital and 6 after discharge) mortality cases. Nine required reoperation for restenosis and 3 required stent removal for infection. The actuarial freedom from mortality and any kind of reoperation was 74.7% ± 4.6% after 2.8 years. The negative pressure threshold to induce airway collapse for congenital malacia (n = 58) improved from -15.9 to -116.0 cmH 2 O. A follow-up computed tomography scan (>2.0 years interval from the operation; n = 23) showed the mean diameter of the stented segment at 88.5% ± 13.7% (bronchus) and 94.5% ± 8.2% (trachea) of the reference. External stenting is a reliable method to relieve airway compression for small children, allowing an age-proportional growth of the airway. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Inner ear dysplasia is common in children with Down syndrome (trisomy 21).

PubMed

Blaser, Susan; Propst, Evan J; Martin, Daniel; Feigenbaum, Annette; James, Adrian L; Shannon, Patrick; Papsin, Blake C

2006-12-01

Middle and external ear anomalies are well recognized in Down syndrome (DS, trisomy 21). Inner ear anomalies are much less frequently described. This study reviews inner ear morphology on imaging to determine the prevalence of cochlear and vestibular anomalies in children with DS. The authors conducted a retrospective review of imaging features of (DS) inner ear structures. Fifty-nine sequential patients with DS with imaging of the inner ear were identified by a radiology report text search program. Quantitative biometric assessment of the inner ear was performed on patients with high-resolution computed tomography or magnetic resonance images of the petrous bone. Petrous imaging was performed for evaluation of inflammatory disease or hearing loss. Spinal imaging, which included petrous views, was performed in most cases to exclude C1 to 2 dislocation, a potential complication of DS. Measurements were compared with normative data. Inner ear dysplasia is much more common in DS than previously reported. Inner ear structures are universally hypoplastic. Vestibular malformations are particularly common and a small bony island of the lateral semicircular canal (<3 mm in diameter) appears highly typical. Additional findings in some patients were persistent lateral semicircular anlage with fusion of the lateral semicircular canal and vestibule into a single cavity, vestibular aqueduct and endolymphatic sac fossa enlargement, cochlear nerve canal hypoplasia, and stenosis or duplication of the internal auditory canal. Stenosis of the external meatus, poor mastoid pneumatization, middle ear and mastoid opacification, and cholesteatoma were common, as expected.

Morbidity of Cushing's Syndrome and Impact of Treatment.

PubMed

Webb, Susan M; Valassi, Elena

2018-06-01

Cortisol excess in Cushing's syndrome is associated with metabolic, cardiovascular, and cognitive alterations, only partially reversible after resolution of hypercortisolism. Elevated cardiovascular risk may persist after eucortisolism has been achieved. Fractures and low bone mineral density are also described in Cushing's syndrome in remission. Hypercortisolism may induce irreversible structural and functional changes in the brain, leading to neuropsychiatric disorders in the active phase of the disease, which persist. Sustained deterioration of the cardiovascular system, bone remodeling, and cognitive function along with neuropsychological impairment are associated with high morbidity and poor quality of life before and after remission. Copyright © 2018 Elsevier Inc. All rights reserved.

Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

PubMed Central

Molina, Víctor M.; Carrasco, Rodrigo A.; Figueroa, Elías; Letelier, Pablo; Castillo, Rodrigo L.

2017-01-01

Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs. PMID:28862654

Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress.

PubMed

Farías, Jorge G; Molina, Víctor M; Carrasco, Rodrigo A; Zepeda, Andrea B; Figueroa, Elías; Letelier, Pablo; Castillo, Rodrigo L

2017-09-01

Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia-reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs.

Structural, biochemical and non-traditional cardiovascular risk markers in PCOS.

PubMed

Christakou, Charikleia; Diamanti-Kandarakis, Evanthia

2013-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes.

SAP: structure, function, and its roles in immune-related diseases.

PubMed

Xi, Dan; Luo, TianTian; Xiong, Haowei; Liu, Jichen; Lu, Hao; Li, Menghao; Hou, Yuqing; Guo, Zhigang

2015-01-01

Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

What happens to the heart in chronic kidney disease?

PubMed

Rutherford, E; Mark, P B

2017-03-01

Cardiovascular disease is common in patients with chronic kidney disease. The increased risk of cardiovascular disease seen in this population is attributable to both traditional and novel vascular risk factors. Risk of sudden cardiac or arrhythmogenic death is greatly exaggerated in chronic kidney disease, particularly in patients with end stage renal disease where the risk is roughly 20 times that of the general population. The reasons for this increased risk are not entirely understood and while atherosclerosis is accelerated in the presence of chronic kidney disease, premature myocardial infarction does not solely account for the excess risk. Recent work demonstrates that the structure and function of the heart starts to alter early in chronic kidney disease, independent of other risk factors. The implications of cardiac remodelling and hypertrophy may predispose chronic kidney disease patients to heart failure, arrhythmia and myocardial ischaemia. Further research is needed to minimise cardiovascular risk associated with structural and functional heart disease associated with chronic kidney disease.

Consequences of Circadian and Sleep Disturbances for the Cardiovascular System.

PubMed

Alibhai, Faisal J; Tsimakouridze, Elena V; Reitz, Cristine J; Pyle, W Glen; Martino, Tami A

2015-07-01

Circadian rhythms play a crucial role in our cardiovascular system. Importantly, there has been a recent flurry of clinical and experimental studies revealing the profound adverse consequences of disturbing these rhythms on the cardiovascular system. For example, circadian disturbance worsens outcome after myocardial infarction with implications for patients in acute care settings. Moreover, disturbing rhythms exacerbates cardiac remodelling in heart disease models. Also, circadian dyssynchrony is a causal factor in the pathogenesis of heart disease. These discoveries have profound implications for the cardiovascular health of shift workers, individuals with circadian and sleep disorders, or anyone subjected to the 24/7 demands of society. Moreover, these studies give rise to 2 new frontiers for translational research: (1) circadian rhythms and the cardiac sarcomere, which sheds new light on our understanding of myofilament structure, signalling, and electrophysiology; and (2) knowledge translation, which includes biomarker discovery (chronobiomarkers), timing of therapies (chronotherapy), and other new promising approaches to improve the management and treatment of cardiovascular disease. Reconsidering circadian rhythms in the clinical setting benefits repair mechanisms, and offers new promise for patients. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Reductions in Cardiovascular Risk After Bariatric Surgery

PubMed Central

Benraoune, Fethi; Litwin, Sheldon E.

2012-01-01

Purpose of review Obesity is commonly associated with multiple conditions imparting adverse cardiovascular risk including, hypertension, dyslipidemia and insulin resistance or diabetes. In addition, sleep disordered breathing, inflammation, left ventricular hypertrophy, left atrial enlargement and subclinical left ventricular systolic and diastolic dysfunction may collectively contribute to increased cardiovascular morbidity and mortality. This review will describe improvements in cardiovascular risk factors after bariatric surgery. Recent findings All of the cardiovascular risk factors listed above are improved or even resolved after bariatric surgery. Cardiac structure and function also have shown consistent improvement after surgically-induced weight loss. The amount of improvement in cardiac risk factors is generally proportional to the amount of weight lost. The degree of weight loss varies with different bariatric procedures. Based on the improvement in risk profiles, it has been predicted that progression of atherosclerosis could be slowed and the 10 year risk of cardiac events would decline by ~ 50% in patients undergoing weight loss surgery. In keeping with these predictions, 2 studies have demonstrated reductions in 10-year total and cardiovascular mortality of approximately 50% in patients who had bariatric surgery. Summary These encouraging data support the continued, and perhaps expanded use of surgical procedures to induce weight loss in severely obese patients. PMID:21934498

Endurance exercise in a rat model of metabolic syndrome.

PubMed

Cameron, Isabelle; Alam, Mohammad Ashraful; Wang, Jianxiong; Brown, Lindsay

2012-11-01

We have measured the responses to endurance exercise training on body composition and glucose regulation, as well as cardiovascular and liver structure and function in rats fed a high carbohydrate and high fat (HCHF) diet as a model of human metabolic syndrome. Male Wistar rats (9-10 weeks old) were randomly allocated into corn starch (CS) or HCHF diet groups for 16 weeks; half of each group were exercised on a treadmill for 20, 25, and then 30 min/day, 5 days/week, during the last 8 weeks of the protocol. Metabolic, cardiovascular, and liver parameters were monitored. The HCHF diet induced symptoms of metabolic syndrome, including obesity, dyslipidemia, impaired glucose tolerance, and increased systolic blood pressure associated with the development of cardiovascular remodeling and nonalcoholic steatohepatitis. Exercise in HCHF rats decreased body mass, abdominal fat pads and circumference, blood glucose concentrations, plasma lipid profiles, systolic blood pressure, left ventricular diastolic stiffness, collagen deposition and inflammatory cell infiltration in the left ventricle, improved aortic contractile and relaxation responses, and decreased liver mass and hepatic fat accumulation. This study demonstrates that endurance exercise is effective in this rat model of diet-induced metabolic syndrome in improving body composition and glucose regulation, as well as cardiovascular and liver structure and function.

Twin-to-Twin Heart Transplantation: A Unique Event With a 25-Year Follow-Up.

PubMed

Blitzer, David; Yedlicka, Grace; Manghelli, Joshua; Dentel, John; Caldwell, Randall; Brown, John W

2017-04-01

Solid organ transplantation in pediatric patients has been a reality since 1954, when the first kidney transplantation was successfully performed between identical twins. We report the long-term outcomes, with more than 25 years of follow-up, in a patient born with hypoplastic left heart syndrome (HLHS) who received a heart transplant from a dizygotic twin. While we would not wish for this situation to reoccur, we hope that in reporting it, we can add to the discussion surrounding pediatric heart transplantation and the management of HLHS. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Clinical, biochemical and molecular investigations of three Taiwanese children with Laron syndrome.

PubMed

Yang, Chen; Chen, Julia Yi-Ru; Lai, Chien-Cherng; Lin, Hsiu-Chen; Yeh, Geng-Chang; Hsu, Hsun-Hui

2004-02-01

Three children of two Taiwanese families were diagnosed with Laron syndrome, two sisters and one boy. Both sets of parents were consanguineous. Clinically, all three presented with the typical craniofacies of Laron syndrome, consisting of prominent forehead and hypoplastic nasal bridge, high-pitched voice, short stature, and central obesity. Biochemically, their levels of serum IGF-I were less than 5 microg/ml before and after an IGF-I generation test, and levels of IGFBP-3 were reduced in all three patients. Sequence analysis of the growth hormone receptor gene revealed that all three carried a homozygous missense D152G mutation in exon 6.

Antenatal diagnosis of anophthalmia by three-dimensional ultrasound: a novel application of the reverse face view.

PubMed

Wong, H S; Parker, S; Tait, J; Pringle, K C

2008-07-01

The prenatal diagnosis of anophthalmia can be made on the demonstration of absent eye globe and lens on the affected side(s) on two-dimensional ultrasound examination, but when the fetal head position is unfavorable three-dimensional (3D) ultrasound may reveal additional diagnostic sonographic features, including sunken eyelids and small or hypoplastic orbit on the affected side(s). We present two cases of isolated anophthalmia diagnosed on prenatal ultrasound examination in which 3D ultrasound provided additional diagnostic information. The reverse face view provides valuable information about the orbits and the eyeballs for prenatal diagnosis and assessment of anophthalmia.

Amelogenesis Imperfecta, Facial Esthetics and Snap-On Smile.

PubMed

Wilson, Lee; Bradshaw, Jonathan P; Marks, Murray K

2015-01-01

Amelogenesis imperfecta is a hereditary enamel protein disorder affecting deciduous and secondary crown formation. The prevalence ranges from 1:700 to 1:14,000 depending on the population. These teeth may be hypoplastic, hypomineralized, or hypermineralized and are often discolored, sensitive and caries vulnerable. Patients often present with psychosocial issues due to appearance. Primary teeth are often treated with stainless steel crowns while secondary teeth are treated with full coverage esthetic crowns. The presenting preteen male here was fitted with Snap-On Smile? (www.snaponsmile.com). This treatment option provided cosmetic enhancement of the patient's appearance besides stabilization without altering the primary and secondary dentition during adolescent development.

The fenestrated Kawashima operation for single ventricle with interrupted inferior vena cava.

PubMed

Hannan, Robert L; Rossi, Anthony F; Nykanen, David G; Lopez, Leo; Alonso, Francisco; White, Jeffrey A; Burke, Redmond P

2003-01-01

An 8-month-old boy with double outlet right ventricle with hypoplastic left ventricle, heterotaxy, left atrial isomerism, bilateral superior vena cavae without bridging vein, and interruption of the inferior vena cava with azygous continuation to the left superior cava underwent a bilateral bidirectional cavopulmonary anastomosis. A calibrated 3-mm connection between the right pulmonary artery and the common atrium was constructed with the proximal right superior vena cava to allow right to left shunting, analogous to a fenestration in a Fontan operation. We hypothesize that in small young patients undergoing the Kawashima operation a fenestration may improve postoperative hemodynamics.

Congenital costo-vertebral fibrous band and congenital kyphoscoliosis: a previously unreported combination.

PubMed

Eid, Tony; Ghostine, Bachir; Kreichaty, Gaby; Daher, Paul; Ghanem, Ismat

2013-05-01

Congenital kyphoscoliosis (CKS) results from abnormal vertebral chondrification. Congenital fibrous bands occur in several locations with variable impact on vertebral development. We report a previously unreported case of a female infant with CKS presenting with an L2 hypoplastic vertebra and a costo-vertebral fibrous band extending to the skin in the form of a dimple. We also describe the therapeutic approach, consisting of surgical excision of the fibrous band and postoperative fulltime bracing, with a 7-year follow-up. We recommend a high index of suspicion in any unusual presentation of CKS and insist on case by case management in such cases.

The importance of sphingolipids and reactive oxygen species in cardiovascular development.

PubMed

de Faria Poloni, Joice; Chapola, Henrique; Feltes, Bruno César; Bonatto, Diego

2014-06-01

The heart is the first organ in the embryo to form. Its structural and functional complexity is the result of a thorough developmental program, where sphingolipids play an important role in cardiogenesis, heart maturation, angiogenesis, the regulation of vascular tone and vessel permeability. Sphingolipids are necessary for signal transduction and membrane microdomain formation. In addition, recent evidence suggests that sphingolipid metabolism is directly interconnected to the modulation of oxidative stress. However, cardiovascular development is highly sensitive to excessive reactive species production, and disturbances in sphingolipid metabolism can lead to abnormal development and cardiac disease. Therefore, in this review, we address the molecular link between sphingolipids and oxidative stress, connecting these pathways to cardiovascular development and cardiovascular disease. © 2014 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy.

PubMed

Cohen, Emily; Wong, Flora Y; Horne, Rosemary S C; Yiallourou, Stephanie R

2016-06-01

Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease.

The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels.

PubMed

Paneni, Francesco; Diaz Cañestro, Candela; Libby, Peter; Lüscher, Thomas F; Camici, Giovanni G

2017-04-18

Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients. Next, the authors summarize the current understanding of the mechanisms implicated in cardiovascular aging, and the potential for targeting novel pathways implicated in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling, and genomic instability. Lastly, the authors consider critical aspects of vascular repair, including autologous transplantation of bone marrow-derived stem cells in elderly patients. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The impact of nitric oxide in cardiovascular medicine: untapped potential utility.

PubMed

Pepine, Carl J

2009-05-01

The structural integrity and functional activity of the endothelium play an important role in atherogenesis and related adverse outcomes. Cardiovascular disease risk conditions contribute to oxidative stress, which causes a disruption in the balance between nitric oxide (NO) and reactive oxygen species, with a resulting relative decrease in bioavailable NO and/or the NO-soluble guanylate cyclase cascade in blood vessels. This leads to endothelial and vascular smooth muscle cell dysfunction, resulting in increased tone and alterations in cell growth and gene expression that create a prothrombotic, proinflammatory environment. This leads to formation, progression, and destabilization of atherosclerotic plaques which may result in myocardial infarction, stroke, and cardiovascular death. NO clearly has a critical role in the maintenance and repair of the vasculature, and a decrease in bioavailable NO is linked to adverse outcomes. This background provides the rationale for exploring the potential therapeutic role for NO-donating agents in the prevention of adverse cardiovascular outcomes.

Cardiovascular Magnetic Resonance in Cardiology Practice: A Concise Guide to Image Acquisition and Clinical Interpretation.

PubMed

Valbuena-López, Silvia; Hinojar, Rocío; Puntmann, Valentina O

2016-02-01

Cardiovascular magnetic resonance plays an increasingly important role in routine cardiology clinical practice. It is a versatile imaging modality that allows highly accurate, broad and in-depth assessment of cardiac function and structure and provides information on pertinent clinical questions in diseases such as ischemic heart disease, nonischemic cardiomyopathies, and heart failure, as well as allowing unique indications, such as the assessment and quantification of myocardial iron overload or infiltration. Increasing evidence for the role of cardiovascular magnetic resonance, together with the spread of knowledge and skill outside expert centers, has afforded greater access for patients and wider clinical experience. This review provides a snapshot of cardiovascular magnetic resonance in modern clinical practice by linking image acquisition and postprocessing with effective delivery of the clinical meaning. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Adults with genetic syndromes and cardiovascular abnormalities: Clinical history and management

PubMed Central

Lin, Angela E.; Basson, Craig T.; Goldmuntz, Elizabeth; Magoulas, Pilar L.; McDermott, Deborah A.; McDonald-McGinn, Donna M.; McPherson, Elspeth; Morris, Colleen A.; Noonan, Jacqueline; Nowak, Catherine; Pierpont, Mary Ella; Pyeritz, Reed E.; Rope, Alan F.; Zackai, Elaine; Pober, Barbara R.

2009-01-01

Cardiovascular abnormalities, especially structural congenital heart defects (CHDs), commonly occur in malformation syndromes and genetic disorders. Individuals with syndromes comprise a significant proportion of those affected with selected CHDs such as complete atrioventricular canal, interrupted arch type B, supravalvar aortic stenosis and pulmonary stenosis. As these individuals age, they contribute to the growing population of adults with special health care needs. Although most will require longterm cardiology followup, primary care providers, geneticists and other specialists should be aware of (1) the type and frequency of cardiovascular abnormalities, (2) the range of clinical outcomes, and (3) guidelines for prospective management and treatment of potential complications. This article reviews fundamental genetic, cardiac, medical and reproductive issues associated with common genetic syndromes which are frequently associated with a cardiovascular abnormality. New data are also provided about the cardiac status of adults with a 22q11.2 deletion and with Down syndrome. PMID:18580689

Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample.

PubMed

Lorbeer, Roberto; Baumeister, Sebastian E; Dörr, Marcus; Felix, Stephan B; Nauck, Matthias; Grotevendt, Anne; Markus, Marcello R P; von Sarnowski, Bettina; Völzke, Henry; Vasan, Ramachandran S; Wallaschofski, Henri; Lieb, Wolfgang

2015-02-01

Higher circulating Angiopoietin-2 (Ang-2) levels predict cardiovascular events and mortality in clinical samples and in the general population. To better understand the underlying mechanisms, we investigated the association of circulating Ang-2 and sTie-2 (the soluble form of the Ang-2 receptor) levels with various measures of subclinical cardiovascular disease. Cross-sectional data of 3204 participants (1654 women) aged 25-88 years from the population-based Study of Health in Pomerania were analysed. LV mass (LVM) and fractional shortening were determined echocardiographically as indices of cardiac structure and function, respectively. Intima media thickness (IMT) of the common carotid artery, the number of carotid plaques and flow-mediated dilation (FMD) were used to characterise large and medium-sized arterial structure and function. Multivariable-adjusted linear and negative binomial regression models revealed an inverse association of circulating Ang-2 levels (independent variable) with fractional shortening (ß=-0.51 per 1 SD increment; 95% CI -0.86 to -0.16, p=0.005) and a positive association with number of carotid plaques (rate ratio=1.04 95% CI 1.01 to 1.07, p=0.019). No associations of Ang-2 or sTie-2 with LVM, IMT and FMD were found. Circulating Ang-2 levels were associated with select subclinical cardiovascular disease traits, consistent with the notion that the Ang-2-pathway plays a role in mediating cardiovascular morbidity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mechanisms and Clinical Application of Tetramethylpyrazine (an Interesting Natural Compound Isolated from Ligusticum Wallichii): Current Status and Perspective.

PubMed

Zhao, Yingke; Liu, Yue; Chen, Keji

Tetramethylpyrazine, a natural compound from Ligusticum wallichii ( Chuan Xiong ), has been extensively used in China for cardiovascular and cerebrovascular diseases for about 40 years. Because of its effectiveness in multisystems, especially in cardiovascular, its pharmacological action, clinical application, and the structural modification have attracted broad attention. In this paper its mechanisms of action, the clinical status, and synthetic derivatives will be reviewed briefly.

Alterations in left ventricular, left atrial, and right ventricular structure and function to cardiovascular risk factors in adolescents with type 2 diabetes participating in the TODAY clinical trial

USDA-ARS?s Scientific Manuscript database

Data on cardiovascular disease (CVD) risk in adolescents with type 2 diabetes (T2D) are limited. Echocardiography was performed in the last year of the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial (median 4.5 yr from diagnosis of T2D, average age 18 yr), incl...

Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

PubMed Central

Wei, C M; Kim, C H; Miller, V M; Burnett, J C

1993-01-01

This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. Images PMID:8408658

Recent Advances in the Discovery and Development of Marine Natural Products with Cardiovascular Pharmacological Effects.

PubMed

Zhou, Jie-Bin; Luo, Rong; Zheng, Ying-Lin; Pang, Ji-Yan

2018-01-01

Numerous studies have indicated that marine natural products are one of the most important sources of the lead compounds in drug discovery for their unique structures, various bioactivities and less side effects. In this review, the marine natural products with cardiovascular pharmacological effects reported after 2000 will be presented. Their structural types, relevant biological activities, origin of isolation and information of strain species will be discussed in detail. Finally, by describing our studies as an example, we also discuss the chances and challenges for translating marine-derived compounds into preclinical or clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optimizing Cardiovascular Benefits of Exercise: A Review of Rodent Models

PubMed Central

Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

2013-01-01

Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health. PMID:24436579

Reduction of atlantoaxial dislocation prevented by pathological position of the transverse ligament in fixed, irreducible os odontoideum: operative illustrations and radiographic correlates in 41 patients.

PubMed

Dlouhy, Brian J; Policeni, Bruno A; Menezes, Arnold H

2017-07-01

OBJECTIVE Os odontoideum (OO) is a craniovertebral junction (CVJ) abnormality in which an ossicle (small bone) is cranial to a hypoplastic dens by a variable gap. This abnormality can result in instability, which may be reducible or irreducible. What leads to irreducibility in OO is unclear. Therefore, the authors sought to better understand the causes of irreducibility in OO. METHODS A retrospective review was conducted, which identified more than 200 patients who had undergone surgical treatment for OO between 1978 and 2015 at the University of Iowa Hospitals and Clinics. Only the 41 patients who had irreducible OO were included in this study. All inpatient and outpatient records were retrospectively reviewed, and patient demographics, clinical presentation, radiographic findings, surgical treatment, and operative findings were recorded and analyzed. RESULTS The cohort of 41 patients who were found to have irreducible OO included both children and adults. A majority of patients were adults (61% were 18 years or older). Clinical presentation included neck pain and headache in the majority of patients (93%). Weakness, sensory disturbances, and myelopathy were invariably present in all 41 patients (100%). Down syndrome was much more common in the pediatric cohort than in the adult cohort; of the 16 pediatric patients, 6 had Down syndrome (38%), and none of the adults did. Of the 16 pediatric patients, 5 had segmentation failure (31%) in the subaxial spine, and none of the adults did. A form of atlantoaxial dislocation was seen in all cases. On CT imaging, atlantoaxial facets were dislocated in all 41 cases but did not have osseous changes that would have prevented reduction. On MRI, the transverse ligament was identified anterior and inferior to the ossicle and superior to the hypoplastic odontoid process in all cases in which these studies were available (i.e., post-MRI era; 36 of 36 cases). The ligament was hypointense on T2-weighted images but also had an associated hyperintense signal on T2 images. Intraoperatively, the transverse ligament was identified anterior and inferior to the ossicle and superior to the hypoplastic odontoid process in all 41 cases. CONCLUSIONS In the largest series to date of irreducible OO and the only study to examine variable factors that lead to irreducibility in OO, the authors found that the position of the transverse ligament anterior and inferior to the ossicle is the most common factor in the irreducibility of OO. The presence of granulation tissue and of the dystopic variant of OO is also associated with irreducibility. The presence of Down syndrome and segmentation failure probably leads to faster progression of ligamentous incompetence and therefore earlier presentation of instability and irreducibility. This is the first study in which intraoperative findings regarding the transverse ligament have been correlated with MRI.

Short-term effects of fine particulate air pollution on cardiovascular hospital emergency room visits: a time-series study in Beijing, China.

PubMed

Su, Chang; Breitner, Susanne; Schneider, Alexandra; Liu, Liqun; Franck, Ulrich; Peters, Annette; Pan, Xiaochuan

2016-05-01

The link between particulate matter (PM) and cardiovascular morbidity has been investigated in numerous studies. Less evidence exists, however, about how age, gender and season may modify this relationship. The aim of this study was to evaluate the association between ambient PM2.5 (PM ≤ 2.5 µm) and daily hospital emergency room visits (ERV) for cardiovascular diseases in Beijing, China. Moreover, potential effect modification by age, gender, season, air mass origin and the specific period with 2008 Beijing Olympic were investigated. Finally, the temporal lag structure of PM2.5 has also been explored. Daily counts of cardiovascular ERV were obtained from the Peking University Third Hospital from January 2007 to December 2008. Concurrently, data on PM2.5, PM10 (PM ≤ 10 µm), nitrogen dioxide and sulfur dioxide concentrations were obtained from monitoring networks and a fixed monitoring station. Poisson regression models adjusting for confounders were used to estimate immediate, delayed and cumulative air pollution effects. The temporal lag structure was also estimated using polynomial distributed lag (PDL) models. We calculated the relative risk (RR) for overall cardiovascular disease ERV as well as for specific causes of disease; and also investigated the potential modifying effect of age, gender, season, air mass origin and the period with 2008 Beijing Olympics. We observed adverse effects of PM2.5 on cardiovascular ERV--an IQR increase (68 μg/m(3)) in PM2.5 was associated with an overall RR of 1.022 (95% CI 0.990-1.057) obtained from PDL model. Strongest effects of PM2.5 on cardiovascular ERV were found for a lag of 7 days; the respective estimate was 1.012 (95% CI 1.002-1.022). The effects were more pronounced in females and in spring. Arrhythmia and cerebrovascular diseases showed a stronger association with PM2.5. We also found stronger PM-effects for stagnant and southern air masses and the period of Olympics modified the air pollution effects. We observed a rather delayed effect of PM2.5 on cardiovascular ERV, which was modified by gender and season. Our findings provide new evidence about effect modifications and may have implications to improve policy making for particulate air pollution standards in Beijing, China.

A Critical Review on Metallic Glasses as Structural Materials for Cardiovascular Stent Applications.

PubMed

Jafary-Zadeh, Mehdi; Praveen Kumar, Gideon; Branicio, Paulo Sergio; Seifi, Mohsen; Lewandowski, John J; Cui, Fangsen

2018-02-27

Functional and mechanical properties of novel biomaterials must be carefully evaluated to guarantee long-term biocompatibility and structural integrity of implantable medical devices. Owing to the combination of metallic bonding and amorphous structure, metallic glasses (MGs) exhibit extraordinary properties superior to conventional crystalline metallic alloys, placing them at the frontier of biomaterials research. MGs have potential to improve corrosion resistance, biocompatibility, strength, and longevity of biomedical implants, and hence are promising materials for cardiovascular stent applications. Nevertheless, while functional properties and biocompatibility of MGs have been widely investigated and validated, a solid understanding of their mechanical performance during different stages in stent applications is still scarce. In this review, we provide a brief, yet comprehensive account on the general aspects of MGs regarding their formation, processing, structure, mechanical, and chemical properties. More specifically, we focus on the additive manufacturing (AM) of MGs, their outstanding high strength and resilience, and their fatigue properties. The interconnection between processing, structure and mechanical behaviour of MGs is highlighted. We further review the main categories of cardiovascular stents, the required mechanical properties of each category, and the conventional materials have been using to address these requirements. Then, we bridge between the mechanical requirements of stents, structural properties of MGs, and the corresponding stent design caveats. In particular, we discuss our recent findings on the feasibility of using MGs in self-expandable stents where our results show that a metallic glass based aortic stent can be crimped without mechanical failure. We further justify the safe deployment of this stent in human descending aorta. It is our intent with this review to inspire biodevice developers toward the realization of MG-based stents.

Structural social support and cardiovascular disease risk factors in Hispanic/Latino adults with diabetes: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

PubMed

Hernandez, Rosalba; Carnethon, Mercedes; Giachello, Aida L; Penedo, Frank J; Wu, Donghong; Birnbaum-Weitzman, Orit; Giacinto, Rebeca Espinoza; Gallo, Linda C; Isasi, Carmen R; Schneiderman, Neil; Teng, Yanping; Zeng, Donglin; Daviglus, Martha L

2017-02-23

Cross-sectional and longitudinal studies have yielded inconsistent findings on the associations of social support networks with cardiovascular health in Hispanic/Latino adults with diabetes. We examined the cross-sectional associations of structural social support and traditional cardiovascular disease (CVD) risk factors in a diverse sample of Hispanic/Latino adults with diabetes. This analysis included 2994 adult participants ages 18-74 with diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL - 2008-2011). Select items from the Social Network Inventory (SNI) were used to assess indices of structural social support, i.e. network size (number of children, parents, and in-laws) and frequency of familial contact. Standardized methods were used to measure abdominal obesity, BMI, hypertension, hypercholesterolemia, and smoking status. Multivariate regression was used to examine associations of structural support with individual CVD risk factors with demographics, acculturation, physical health, and psychological ill-being (depressive symptoms and anxiety) included as covariates. There were no significant cross-sectional associations of structural support indices with abdominal obesity, hypertension, hypercholesterolemia, or smoking status. There was a marginally significant (OR: 1.05; 95%CI 0.99-1.11) trend toward higher odds of obesity in participants reporting a larger family unit (including children, parents, and in-laws) and those with closer ties with extended family relatives (OR: 1.04; 95%CI 0.99-1.09). Structural social support was marginally associated with higher odds of obesity in Hispanic/Latino adults with diabetes. Alternate forms of social support (e.g. healthcare professionals, friends, peers) should be further explored as potential markers of cardiac risk in Hispanics/Latinos with diabetes.

A Critical Review on Metallic Glasses as Structural Materials for Cardiovascular Stent Applications

PubMed Central

Jafary-Zadeh, Mehdi; Praveen Kumar, Gideon

2018-01-01

Functional and mechanical properties of novel biomaterials must be carefully evaluated to guarantee long-term biocompatibility and structural integrity of implantable medical devices. Owing to the combination of metallic bonding and amorphous structure, metallic glasses (MGs) exhibit extraordinary properties superior to conventional crystalline metallic alloys, placing them at the frontier of biomaterials research. MGs have potential to improve corrosion resistance, biocompatibility, strength, and longevity of biomedical implants, and hence are promising materials for cardiovascular stent applications. Nevertheless, while functional properties and biocompatibility of MGs have been widely investigated and validated, a solid understanding of their mechanical performance during different stages in stent applications is still scarce. In this review, we provide a brief, yet comprehensive account on the general aspects of MGs regarding their formation, processing, structure, mechanical, and chemical properties. More specifically, we focus on the additive manufacturing (AM) of MGs, their outstanding high strength and resilience, and their fatigue properties. The interconnection between processing, structure and mechanical behaviour of MGs is highlighted. We further review the main categories of cardiovascular stents, the required mechanical properties of each category, and the conventional materials have been using to address these requirements. Then, we bridge between the mechanical requirements of stents, structural properties of MGs, and the corresponding stent design caveats. In particular, we discuss our recent findings on the feasibility of using MGs in self-expandable stents where our results show that a metallic glass based aortic stent can be crimped without mechanical failure. We further justify the safe deployment of this stent in human descending aorta. It is our intent with this review to inspire biodevice developers toward the realization of MG-based stents. PMID:29495521

The Polish National Registry for Fetal Cardiac Pathology: organization, diagnoses, management, educational aspects and telemedicine endeavors.

PubMed

Slodki, Maciej; Szymkiewicz-Dangel, Joanna; Tobota, Zdzislaw; Seligman, Neil S; Weiner, Stuart; Respondek-Liberska, Maria

2012-05-01

We describe the National Registry for Fetal Cardiac Pathology, a program under the Polish Ministry of Health aimed at improving the prenatal diagnosis, care, and management of congenital heart disease (CHD). An online database was created to prospectively record diagnosis, prenatal care, delivery, follow-up, and still images and video for fetuses with CHD. A certification program in fetal cardiac ultrasound was also implemented. Optimal screening and referral centers were identified by number of fetuses entered in the Registry yearly by each center. From 2004 to 2009, 2910 fetuses with CHD were registered (2473 structural, 437 functional anomalies). The most common reasons for referral for fetal echocardiography were abnormal four-chamber view (56.0%) and extra-cardiac anomalies (8.2% ), while the most common diagnoses were atrioventricular septal defects (10.2%) and hypoplastic left heart syndrome (9.7%). Prenatal diagnosis increased yearly, from 10.0% of neonatal diagnoses in 2003 to 38.0% in 2008. From inception of the registry up to 2009 there has been a fourfold increase in the number of neonates referred for cardiac surgery in whom the condition was prenatally diagnosed. Equally important achievements include the establishment of a certification program for fetal echocardiography and the organization of prenatal and neonatal management. © 2012 John Wiley & Sons, Ltd.

De novo partial duplication 7(q11.2{r_arrow}q21.2) in a dysmorphic, developmentally retarded boy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ross, M.; Pinsky, L.; Teebi, A.

Chromosomal abnormalities involving chromosome 7q are rare; we report a case of partial duplication 7q. The propositus was born at 34 weeks by cesarian section, decided because of oligohydramnios, severe intrauterine growth retardation and fetal immobility. At birth, the baby was under the 5th percentile for height, weight and head circumference and had dysmorphic features, including slight asymmetry of the face, bilateral epicanthus, hypoplastic nasal bridge, short globular nose, asymmetrical dysplastic ears, fifth finger clinodactyly, short second and fifth toe. Ultrasound examination showed atrial and ventricular septal defects. At 18 months, the child had a fracture of the femur, secondarymore » to a minor trauma; skeletal X-rays showed generalized osteoporosis and normal healing. The karyotype with GTG-banding showed a de novo partial duplication of the long arm of chromosome 7 (46,XX,dup(7)(q11.23{r_arrow}q21.2)). Fluorescence in situ hybridization with a painting probe specific for chromosome 7 confirmed the intra-chromosomal rearrangement. The patient`s phenotype and his chromosomal abnormality do not match the previously reported cases of partial trisomy 7q. This case confirms the importance of FISH for the delineation of the chromosomal inbalance in structural chromosomal aberrations.« less

Cerebrovascular profile assessment in Parkinson's disease patients.

PubMed

Perju-Dumbravă, Laura; Muntean, Maria-Lucia; Muresanu, Dafin Fior

2014-01-01

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and PD patients can present a variety of comorbidities that increase with age. Among them, cardiovascular and cerebrovascular diseases are the most prominent. To assess the cardiovascular and cerebrovascular profiles of PD patients. The cardiovascular risk factors of 126 PD patients were assessed according to laboratory tests (fasting blood sugar, serum cholesterol, triglycerides, and total lipids), Doppler ultrasound examinations and personal histories of cerebrovascular disease (ischemic/hemorrhagic), cardiovascular disease (myocardial infarct or angina confirmed by electrocardiogram), hypertension and diabetes. All patients underwent cerebral structural imaging procedures: computed tomography or magnetic resonance imaging. 58.73% of the patients presented with hypertension, with a slight predominance of female patients (65.38% vs 47.92%, P = 0.05). Carotid or vertebral atheromatosis was present in 39 (30.95%) and 28 (22.22%) of patients, respectively, and was statistically correlated with the presence of ischemic lesions on cerebral imaging. Regarding the computed tomography findings, 33 patients (28.21%) presented with cortical atrophy that was not correlated with any of the investigated cardiovascular factors. Our findings indicate that risk factors for cardiovascular and cerebrovascular diseases are common in PD patients, possibly due to their older age. The presence of atherosclerosis and its complications can be detected in cerebral imaging studies.

Education for nurses working in cardiovascular care: a European survey.

PubMed

2014-12-01

Nurses represent the largest sector of the workforce caring for people with cardiovascular disease in Europe. Little is known about the post-registration education provided to nurses working within this specialty. The aim of this descriptive cross sectional survey was to describe the structure, content, teaching, learning, assessment and evaluation methods used in post-registration cardiovascular nurse education programmes in Europe. A 24-item researcher generated electronic questionnaire was sent to nurse representatives from 23 European countries. Items included questions about cardiovascular registered nurse education programmes. Forty-nine respondents from 17 European countries completed questionnaires. Respondents were typically female (74%) and educated at Masters (50%) or doctoral (39%) level. Fifty-one percent of the cardiovascular nursing education programmes were offered by universities either at bachelor or masters level. The most frequently reported programme content included cardiac arrhythmias (93%), heart failure (85%) and ischaemic heart disease (83%). The most common teaching mode was face-to-face lectures (85%) and/or seminars (77%). A variety of assessment methods were used with an exam or knowledge test being the most frequent. Programme evaluation was typically conducted through student feedback (95%). There is variability in the content, teaching, learning and evaluation methods in post-registration cardiovascular nurse education programmes in Europe. Cardiovascular nurse education would be strengthened with a stronger focus upon content that reflects current health challenges faced in Europe. A broader view of cardiovascular disease to include stroke and peripheral vascular disease is recommended with greater emphasis on prevention, rehabilitation and the impact of health inequalities. © The European Society of Cardiology 2013.

Estrogenic Compounds, Estrogen Receptors and Vascular Cell Signaling in the Aging Blood Vessels

PubMed Central

Smiley, Dia A.; Khalil, Raouf A.

2010-01-01

The cardiovascular benefits of menopausal hormone therapy (MHT) remain controversial. The earlier clinical observations that cardiovascular disease (CVD) was less common in MHT users compared to non-users suggested cardiovascular benefits of MHT. Also, experimental studies have identified estrogen receptors ERα, ERβ and GPR30, which mediate genomic or non-genomic effects in vascular endothelium, smooth muscle, and extracellular matrix (ECM). However, data from randomized clinical trials (RCTs), most notably the Women's Health Initiative (WHI) study, have challenged the cardiovascular benefits and highlighted adverse cardiovascular events with MHT. The discrepancies have been attributed to the design of RCTs, the subjects' advanced age and preexisting CVD, and the form of estrogen used. The discrepancies may also stem from age-related changes in vascular ER amount, distribution, integrity, and post-receptor signaling pathways as well as structural changes in the vasculature. Age-related changes in other sex hormones such as testosterone may also alter the hormonal environment and influence the cardiovascular effects of estrogen. Investigating the chemical properties, structure-activity relationship and pharmacology of natural and synthetic estrogens should improve the effectiveness of conventional MHT. Further characterization of phytoestrogens, selective estrogen-receptor modulators (SERMs), and specific ER agonists may provide substitutes to conventional MHT. Conditions with excess or low estrogen levels such as polycystic ovary syndrome (PCOS) and Turner syndrome may provide insight into the development and regulation of ER and the mechanisms of aberrant estrogen-ER interactions. The lessons learned from previous RCTs have led to more directed studies such as the Kronos Early Estrogen Prevention Study (KEEPS). Careful design of experimental models and RCTs, coupled with the development of specific ER modulators, hold the promise of improving the actions of estrogen in the aging blood vessels and thereby enhancing the efficacy and safety of MHT in postmenopausal CVD. PMID:19442151

Three-Dimensional Reconstruction of Thoracic Structures: Based on Chinese Visible Human

PubMed Central

Luo, Na; Tan, Liwen; Fang, Binji; Li, Ying; Xie, Bing; Liu, Kaijun; Chu, Chun; Li, Min

2013-01-01

We managed to establish three-dimensional digitized visible model of human thoracic structures and to provide morphological data for imaging diagnosis and thoracic and cardiovascular surgery. With Photoshop software, the contour line of lungs and mediastinal structures including heart, aorta and its ramus, azygos vein, superior vena cava, inferior vena cava, thymus, esophagus, diaphragm, phrenic nerve, vagus nerve, sympathetic trunk, thoracic vertebrae, sternum, thoracic duct, and so forth were segmented from the Chinese Visible Human (CVH)-1 data set. The contour data set of segmented thoracic structures was imported to Amira software and 3D thorax models were reconstructed via surface rendering and volume rendering. With Amira software, surface rendering reconstructed model of thoracic organs and its volume rendering reconstructed model were 3D reconstructed and can be displayed together clearly and accurately. It provides a learning tool of interpreting human thoracic anatomy and virtual thoracic and cardiovascular surgery for medical students and junior surgeons. PMID:24369489

Imaging of cardiovascular structures using near-infrared femtosecond multiphoton laser scanning microscopy.

PubMed

Schenke-Layland, Katja; Riemann, Iris; Stock, Ulrich A; König, Karsten

2005-01-01

Multiphoton imaging represents a novel and very promising medical diagnostic technology for the high-resolution analysis of living biological tissues. We performed multiphoton imaging to analyzed structural features of extracellular matrix (ECM) components, e.g., collagen and elastin, of vital pulmonary and aortic heart valves. High-resolution autofluorescence images of collagenous and elastic fibers were demonstrated using multifluorophore, multiphoton excitation at two different wavelengths and optical sectioning, without the requirement of embedding, fixation, or staining. Collagenous structures were selectively imaged by detection of second harmonic generation (SHG). Additionally, routine histology and electron microscopy were integrated to verify the observed results. In comparison with pulmonary tissues, aortic heart valve specimens show very similar matrix formations. The quality of the resulting three-dimensional (3-D) images enabled the differentiation between collagenous and elastic fibers. These experimental results indicate that multiphoton imaging with near-infrared (NIR) femtosecond laser pulses may prove to be a useful tool for the nondestructive monitoring and characterization of cardiovascular structures. Copyright 2005 Society of Photo-Optical Instrumentation Engineers.

Cardiovascular cast model fabrication and casting effectiveness evaluation in fetus with severe congenital heart disease or normal heart.

PubMed

Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng

2016-04-01

To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.

Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension

PubMed Central

Chen, Selena; Tang, Chaoshu

2016-01-01

Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases. PMID:27721913

Early, structured disease modifying anti-rheumatic drug (DMARD) therapy reduces cardiovascular risk in rheumatoid arthritis--a single centre study using non-biologic drugs.

PubMed

Chatterjee, Sumit; Sarkate, Pankaj; Ghosh, Sudip; Biswas, Monodeep; Ghosh, Alakendu

2013-08-01

Rheumatoid arthritis, being a chronic disease requires long-term management of patients with drugs. The increasing cost of biologics in this era of disease management led us to devise a treatment regime, optimal for use in a developing country like India, which was economical as well as effective in controlling disease activity. To investigate if combination therapy with DMARDs can reduce cardiovascular risk in early Rheumatoid Arthritis, besides controlling disease activity. A small cohort of early Rheumatoid subjects with disease duration less than 1 year were treated with a structured DMARD regime and were followed up over a year. Disease activity score, C-reactive protein (CRP) and cardiac risk markers like lipid panel and carotid intima-medial thickness were monitored at 6 months and 1 year. A significant reduction (p < 0.001) of disease activity as well as cardiac risk parameters were observed. Our study showed that treatment of early rheumatoid arthritis with a combination regime of traditional DMARDs is highly effective in controlling disease activity as well as cardiovascular risk.

Cardiac 3D Printing and its Future Directions.

PubMed

Vukicevic, Marija; Mosadegh, Bobak; Min, James K; Little, Stephen H

2017-02-01

Three-dimensional (3D) printing is at the crossroads of printer and materials engineering, noninvasive diagnostic imaging, computer-aided design, and structural heart intervention. Cardiovascular applications of this technology development include the use of patient-specific 3D models for medical teaching, exploration of valve and vessel function, surgical and catheter-based procedural planning, and early work in designing and refining the latest innovations in percutaneous structural devices. In this review, we discuss the methods and materials being used for 3D printing today. We discuss the basic principles of clinical image segmentation, including coregistration of multiple imaging datasets to create an anatomic model of interest. With applications in congenital heart disease, coronary artery disease, and surgical and catheter-based structural disease, 3D printing is a new tool that is challenging how we image, plan, and carry out cardiovascular interventions. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The second phase in creating the cardiac center for the next generation: beyond structure to process improvement.

PubMed

Woods, J

2001-01-01

The third generation cardiac institute will build on the successes of the past in structuring the service line, re-organizing to assimilate specialist interests, and re-positioning to expand cardiac services into cardiovascular services. To meet the challenges of an increasingly competitive marketplace and complex delivery system, the focus for this new model will shift away from improved structures, and toward improved processes. This shift will require a sound methodology for statistically measuring and sustaining process changes related to the optimization of cardiovascular care. In recent years, GE Medical Systems has successfully applied Six Sigma methodologies to enable cardiac centers to control key clinical and market development processes through its DMADV, DMAIC and Change Acceleration processes. Data indicates Six Sigma is having a positive impact within organizations across the United States, and when appropriately implemented, this approach can serve as a solid foundation for building the next generation cardiac institute.

Cardiac 3D Printing and Its Future Directions

PubMed Central

Vukicevic, Marija; Mosadegh, Bobak; Min, James K.; Little, Stephen H.

2017-01-01

3D printing is at the crossroads of printer and materials engineering; non-invasive diagnostic imaging; computer aided design (CAD); and structural heart intervention. Cardiovascular applications of this technology development include the use of patient-specific 3D models for medical teaching, exploration of valve and vessel function, surgical and catheter-based procedural planning, and early work in designing and refining the latest innovations in percutaneous structural devices. In this review we discuss the methods and materials being used for 3D printing today. We discuss the basic principles of clinical image segmentation including co-registration of multiple imaging datasets to create an anatomic model of interest. With applications in congenital heart disease, coronary artery disease, and in surgical and catheter-based structural disease – 3D printing is a new tool that is challenging how we image, plan, and carry out cardiovascular interventions. PMID:28183437

NO Signaling in the Cardiovascular System and Exercise.

PubMed

Fernandes, Tiago; Gomes-Gatto, Camila V; Pereira, Noemy P; Alayafi, Yahya R; das Neves, Vander J; Oliveira, Edilamar M

2017-01-01

Nitric oxide (NO) is a small molecule implicated in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. The identification of NO synthase (NOS) isoforms and the subsequent characterization of the mechanisms of cell activation of the enzymes permitted the partial understanding of both the physiological and pathological processes. NO bioavailability plays an important role in the pathophysiology of cardiovascular disease and its reduction in endothelial cells is strictly associated to endothelial dysfunction which, in turn, correlates with cardiovascular mortality. Indeed, endothelial NO synthase (eNOS) has a key role in limiting cardiac dysfunction and remodeling in heart diseases, in part by decreasing myocyte hypertrophy. Conversely, exercise training is recommended to prevent and treat cardiovascular diseases-associated disorders at least by enhanced NO synthase activity and expression, and increased production of antioxidants, which prevents premature breakdown of NO. Exercise training may cause an improvement in endothelial function for both experimental animals and humans; Studies in both healthy subjects and patients with impaired NO-related vasorelaxation remarked exercise training ability to improve vascular structure and function and endothelial homeostasis. This chapter will briefly consider the importance of NO signaling in the maintenance of cardiovascular physiology, and discuss recent insights into the effect of exercise training on the signaling pathways that modulate NO synthesis and degradation in health and cardiovascular disease. In addition, we will highlight the molecular mechanisms via which microRNAs (miRs) target NO signaling in the cardiovascular system, and NO as a candidate molecule for development of new therapies.

Targeted delivery of miRNA therapeutics for cardiovascular diseases: opportunities and challenges.

PubMed

Kwekkeboom, Rick F J; Lei, Zhiyong; Doevendans, Pieter A; Musters, René J P; Sluijter, Joost P G

2014-09-01

Dysregulation of miRNA expression has been associated with many cardiovascular diseases in animal models, as well as in patients. In the present review, we summarize recent findings on the role of miRNAs in cardiovascular diseases and discuss the opportunities, possibilities and challenges of using miRNAs as future therapeutic targets. Furthermore, we focus on the different approaches that can be used to deliver these newly developed miRNA therapeutics to their sites of action. Since siRNAs are structurally homologous with the miRNA therapeutics, important lessons learned from siRNA delivery strategies are discussed that might be applicable to targeted delivery of miRNA therapeutics, thereby reducing costs and potential side effects, and improving efficacy.

Review: nanoparticles in delivery of cardiovascular drugs.

PubMed

Arayne, M Saeed; Sultana, Najma; Qureshi, Faiza

2007-10-01

Everything in nature is built upward from the atomic level to define limits and structures to everything. Nanomedicines marked the field of medicine from nanobiotechnology, biological micro-electromechanical systems, microfluidics, biosensors, drug delivery, microarrays to tissue microengineering. Since then nanoparticles has overcome many challenges from blood brain barrier to targeting tumors. Where solid biodegradable nanoparticles were a step up liposome, targeting nanoparticles opened a whole new field for drug delivery. In this article, we attempt to discuss how the pioneered technique is serving in the drug delivery to cardiovascular system and how with the manipulation of their properties, nanoparticles can be made to fulfill desired function. Also how nanocarriers are improving molecular imaging to help improve diagnosis and treatment of cardiovascular disease is focused in this article.

Recent findings in cardiovascular physiology with space travel.

PubMed

Hughson, Richard L

2009-10-01

The cardiovascular system undergoes major changes in stress with space flight primarily related to the elimination of the head-to-foot gravitational force. A major observation has been that the central venous pressure is not elevated early in space flight yet stroke volume is increased at least early in flight. Recent observations demonstrate that heart rate remains lower during the normal daily activities of space flight compared to Earth-based conditions. Structural and functional adaptations occur in the vascular system that could result in impaired response with demands of physical exertion and return to Earth. Cardiac muscle mass is reduced after flight and contractile function may be altered. Regular and specific countermeasures are essential to maintain cardiovascular health during long-duration space flight.

Electron probe microananlysis of fluorotic bovine teeth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shearer, T.R.; Kolstad, D.L.; Suttie, J.W.

1978-09-01

Incisor teeth were obtained from adult cattle which since 4 months of age to 5 or 6 years were maintained on rations containing a yearly average of 40 ppM F in the forage. Microchemical analyses were performed on the fluorotic bovine incisors. The microdistribution of fluoride varied markedly at different sites within the same tooth. Fluoride concentrations varied with depth from the tooth surface and were influenced by the concentrations of fluoride present in the forage during amelogenesis, and the presence of hypoplastic pits and hyperplastic coronal cementum in enamel. The cementum in these lesions contained remarkably high concentrations ofmore » fluoride, and it was less calcified and more porous than adjacent enamel. 5 figures.« less

Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.

PubMed

Meinecke, P; Passarge, E

1991-11-01

The clinical and radiological findings in a pair of sibs with microcephalic osteodysplastic primordial dwarfism (MOPD) are described, a boy who survived for 5 1/2 years and his more severely affected younger sister, who died at the age of 6 months. Neuropathological studies in this girl showed marked micrencephaly with severely hypoplastic, poorly gyrated frontal lobes and absent corpus callosum. Our observation supports the hypothesis that types I and III MOPD probably constitute a spectrum of one and the same entity and published data together with this report are consistent with autosomal recessive inheritance. The pathogenesis of this condition is as yet unknown, but its characteristics indicate a basic defect affecting cell proliferation and tissue differentiation.

Trigeminal neuralgia due to Dandy-Walker syndrome.

PubMed

Zhang, Wenhao; Chen, Minjie; Zhang, Weijie

2013-07-01

Trigeminal neuralgia (TN) is a common pain in the orofacial region. Dandy-Walker syndrome (DWS) is a congenital malformation of the cerebellar and the fourth ventricle foramina atresia. Dandy-Walker syndrome is rarely found in patients with TN. This article presents a 36-year-old man with the symptoms of typical TN. His physical examination was entirely normal. An enhanced magnetic resonance imaging was taken. Magnetic resonance imaging revealed the bilateral lateral ventricle, the fourth and third ventricle significantly enlarged with severe obstructive hydrocephalus, a huge posterior fossa cyst connected with the fourth ventricle, and hypoplastic vermis. The pain was controlled by Tegretol. The reported case suggests that DWS is an unusual cause of TN.

Doubtful descent, dilemma and diagnosis: a case of Kallmann syndrome.

PubMed

Chakraborty, P P; Chowdhury, S R; Mandal, S K; Bandyopadhyay, D

2007-03-01

A 16-year-old boy with a diagnosis of bilateral cryptorchidism was referred for preoperative evaluation. He had diminished hearing and difficulty in vision since birth, with inattentiveness, poor school performance and delayed milestones. He was previously operated on for cleft lip. General survey revealed bilateral short fourth metacarpals and an operative scar mark over the left nostril and upper lip. He had a micropenis, small soft testes with anosmia, and sensory-motor deafness. The hormonal assay was consistent with hypogonadotrophic hypogonadism. Magnetic resonance imaging of the brain and computed tomography cisternography revealed almost hypoplastic olfactory bulb with an ill-defined olfactory tract and sulci, supporting the clinical diagnosis of Kallmann syndrome.

[Experiences with the extracardial conduit in the reconstruction of the right ventricular outflow tract].

PubMed

Egloff, L; Schönbeck, M; Arbenz, U; Turina, M; Senning, A

1982-12-18

Operative correction of certain congenital cardiac malformations with discontinuity between the right ventricle and pulmonary artery is technically possible today with satisfactory late results. The atretic or hypoplastic outflow tract can be bridged by an external tubular graft containing a valvular prosthesis. Of 22 patients operated upon from 1978-1981, 16 survived the operation and perioperative period. There was one late death. Routine cardiac catheterization was performed in 6 non-selected patients between 7 and 22 months after surgery. No hemodynamically important gradients were found. The extracardiac conduit between the right ventricle and pulmonary artery has become an important tool in correcting certain forms of congenital heart disease.

Congenital Anomaly of Single Dominant Right Coronary Artery with Hypoplastic Left Coronary Artery.

PubMed

Chuang, Cheng-Yen; Chen, Yen-Chou; Cheng, Ho-Shun; Hsieh, Ming-Hsiung

2015-11-01

With the popularization of new imaging technology, more people are deciding to undergo non-invasive studies such as multidetector computerized tomography (MDCT) before receiving coronary angiography. For this reason, coronary anomalies of coronary artery are being encountered more frequently. We here report a 68-year-old male presenting with typical angina. The MDCT images suggested chronic total occlusion of the left anterior descending (LAD) artery with collateral circulation from the right coronary artery (RCA). The patient's coronary angiography showed a congenital coronary anomaly with a single dominant RCA supplying the entire coronary circulation of the heart with both LAD and left circumflex artery hypoplasia. Angiography; Anomaly; Computerized tomography; Coronary artery.

A new case of partial trisomy 19q (q13.2-->qter) owing to an unusual maternal translocation.

PubMed Central

Valerio, D; Lavorgna, F; Scalona, M; Conte, A

1993-01-01

A new case of trisomy 19q13.2-->qter is described in a male child which was caused by a maternal balanced translocation (13;19)(p13;q13.2). The major clinical features detected in the patient included the following: facial dysmorphism, bilateral coloboma, narrow and hypoplastic nails, cardiac malformations (Fallot's tetralogy), genitourinary and gastrointestinal anomalies, and agenesis of the corpus callosum. A comparison with other reported cases of partial trisomy 19q is presented. A hypothesis is proposed to account for the involvement of p13 regions of different acrocentrics in some cases of familial translocations involving a chromosome 19. Images PMID:8411060

Enamelin Is Critical for Ameloblast Integrity and Enamel Ultrastructure Formation

PubMed Central

Hu, Jan C.-C.; Hu, Yuanyuan; Lu, Yuhe; Smith, Charles E.; Lertlam, Rangsiyakorn; Wright, John Timothy; Suggs, Cynthia; McKee, Marc D.; Beniash, Elia; Kabir, M. Enamul; Simmer, James P.

2014-01-01

Mutations in the human enamelin gene cause autosomal dominant hypoplastic amelogenesis imperfecta in which the affected enamel is thin or absent. Study of enamelin knockout NLS-lacZ knockin mice revealed that mineralization along the distal membrane of ameloblast is deficient, resulting in no true enamel formation. To determine the function of enamelin during enamel formation, we characterized the developing teeth of the Enam−/− mice, generated amelogenin-driven enamelin transgenic mouse models, and then introduced enamelin transgenes into the Enam−/− mice to rescue enamel defects. Mice at specific stages of development were subjected to morphologic and structural analysis using β-galactosidase staining, immunohistochemistry, and transmission and scanning electron microscopy. Enamelin expression was ameloblast-specific. In the absence of enamelin, ameloblasts pathology became evident at the onset of the secretory stage. Although the aggregated ameloblasts generated matrix-containing amelogenin, they were not able to create a well-defined enamel space or produce normal enamel crystals. When enamelin is present at half of the normal quantity, enamel was thinner with enamel rods not as tightly arranged as in wild type suggesting that a specific quantity of enamelin is critical for normal enamel formation. Enamelin dosage effect was further demonstrated in transgenic mouse lines over expressing enamelin. Introducing enamelin transgene at various expression levels into the Enam−/− background did not fully recover enamel formation while a medium expresser in the Enam+/− background did. Too much or too little enamelin abolishes the production of enamel crystals and prism structure. Enamelin is essential for ameloblast integrity and enamel formation. PMID:24603688

Diagnosis of secondary pulmonary lymphangiectasia in congenital heart disease: a novel role for chest ultrasound and prognostic implications.

PubMed

Lam, Christopher Z; Bhamare, Tanmay Anant; Gazzaz, Tamadhir; Manson, David; Humpl, Tilman; Seed, Mike

2017-10-01

Secondary pulmonary lymphangiectasia is a complication of congenital heart disease that results from chronic pulmonary venous obstruction. We aimed to evaluate the performance of chest ultrasound (US) in diagnosing secondary pulmonary lymphangiectasia and to review the clinical course of children with secondary pulmonary lymphangiectasia. Chest US was performed on 26 children with hypoplastic left heart syndrome, total anomalous pulmonary venous connection or cor triatriatum in a prospective observational study. Thirteen children had pulmonary venous obstruction (62% male; median age: 17 days old, range: 1-430 days old) and 13 children did not have obstruction (62% male; median age: 72 days old, range: 4-333 days old). US features of secondary pulmonary lymphangiectasia were documented and diagnostic performance was determined. Clinical course of patients with secondary pulmonary lymphangiectasia was reviewed. Eleven of 13 (84.6%) patients in the obstructed group had a clinical and/or biopsy diagnosis of secondary pulmonary lymphangiectasia. Statistically significant chest US criteria for diagnosis were presence of irregular lung surface (likelihood ratio [LR] 6.8, 95% confidence interval [CI] 1.9-25.1), subpleural cystic appearing structures (LR 3.6, 95% CI 1.2-10.7), and combination of subpleural cystic appearing structures and surface irregularity together (LR 10.9, 95% CI 1.6-75.0). Seven of 11 (63.6%) patients with secondary pulmonary lymphangiectasia died during follow-up, the majority due to cardiopulmonary failure or complications. Chest US is an accurate and reproducible bedside method for diagnosing secondary pulmonary lymphangiectasia in patients with pulmonary venous obstruction. These patients may have worse prognoses.

Assessing the consequences of gestational diabetes mellitus on offspring's cardiovascular health: MySweetHeart Cohort study protocol, Switzerland.

PubMed

Di Bernardo, Stefano; Mivelaz, Yvan; Epure, Adina Mihaela; Vial, Yvan; Simeoni, Umberto; Bovet, Pascal; Estoppey Younes, Sandrine; Chiolero, Arnaud; Sekarski, Nicole

2017-11-14

Gestational diabetes mellitus (GDM) is a state of glucose intolerance with onset during pregnancy. GDM carries prenatal and perinatal risks as well as long-term risks for the mother and her child. GDM may be involved in the foetal programming of long-term cardiovascular health. However, evidence is sparse and the effect of GDM on cardiovascular health is unknown. To address these issues, we will conduct MySweetHeart Cohort study. The objectives are to assess the effect of GDM on offspring's cardiovascular health early in life by using surrogate markers of cardiovascular disease and atherosclerosis. This is a cohort study of 100 offspring of women with GDM and 100 offspring of women without GDM. At inclusion, a baseline assessment of the mothers will be conducted through means of self-report questionnaires, a researcher-administrated interview, blood pressure and anthropometric measurements, and a maternal blood sampling. Between the 30th and 34th weeks of gestation, a foetal echography will be performed to assess the foetal cardiac structure and function, the fetomaternal circulation and the hepatic volume. At birth, maternal and neonatal characteristics will be assessed. An echocardiography will be performed to assess cardiac structure and function 2-7 days after birth; carotid intima-media thickness will be also measured to assess vascular structure. MySweetHeart Cohort is linked to MySweetHeart Trial (clinicaltrials.gov/ct2/show/NCT02890693), a randomised controlled trial assessing the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve the cardiometabolic and mental health of women with GDM and their offspring. A long-term follow-up of children is planned. Ethical approval has been obtained through the state Human Research Ethics Committee of the Canton de Vaud (study number 2016-00745). We aim to disseminate the findings through regional, national and international conferences and through peer-reviewed journals. ClinicalTrials.gov (clinicaltrials.gov/ct2/show/NCT02872974). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development

PubMed Central

Paige, Sharon L.; Thomas, Sean; Stoick-Cooper, Cristi L.; Wang, Hao; Maves, Lisa; Sandstrom, Richard; Pabon, Lil; Reinecke, Hans; Pratt, Gabriel; Keller, Gordon; Moon, Randall T.; Stamatoyannopoulos, John; Murry, Charles E.

2012-01-01

Summary Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Though it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells, the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development, including the homeobox gene MEIS2. We demonstrate using the zebrafish model that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions. PMID:22981225

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

PubMed Central

Borovjagin, Anton V.; Ogle, Brenda; Berry, Joel; Zhang, Jianyi

2016-01-01

Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional two-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and pre-clinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents. PMID:28057791

Diverse physiological effects of long-chain saturated fatty acids: implications for cardiovascular disease.

PubMed

Flock, Michael R; Kris-Etherton, Penny M

2013-03-01

The purpose of this review is to discuss the metabolism of long-chain saturated fatty acids and the ensuing effects on an array of metabolic events. Individual long-chain saturated fatty acids exhibit unique biological properties. Dietary saturated fat absorption varies depending on chain-length and the associated food matrix. The in-vivo metabolism of saturated fatty acids varies depending on the individual fatty acid and the nutritional state of the individual. A variety of fatty acid metabolites are formed, each with their own unique structure and properties that warrant further research. Replacing saturated fatty acids with unsaturated fatty acids improves the blood lipid profile and reduces cardiovascular disease risk, although the benefits depend on the specific saturated fatty acid(s) being replaced. Acknowledging the complexity of saturated fatty acid metabolism and associated metabolic events is important when assessing their effects on cardiovascular disease risk. Investigating the biological effects of saturated fatty acids will advance our understanding of how they affect cardiovascular disease risk.

Commonly Used Antioxidant Botanicals: Active Constituents and their Potential Role in Cardiovascular Illness

PubMed Central

Wang, Chong-Zhi; Mehendale, Sangeeta R.; Yuan, Chun-Su

2009-01-01

Cardiovascular disease continues to be the leading cause of death in the US. Recent studies found that reactive oxygen species (ROS) have been incriminated in the pathogenesis of both acute and chronic heart disease. Many botanicals possess antioxidant properties, and these herbal antioxidants may protect against cardiovascular diseases by contributing to the total antioxidant defense system of the human body. In this article, we reviewed the antioxidant components and properties of four putative antioxidant botanicals (i.e., grape seeds, green tea, Scutellaria baicalensis, and American ginseng), and their potential role in treating cardiovascular illness. The antioxidant activities of the herbal active constituents, and the relationship between their chemical structures and biological functions were also discussed. Further investigations are needed on the mechanisms of action of these botanicals as they affect salient cellular and molecular pathways involved in major diseases. Data obtained from future studies will have the potential for translation into practical benefits for human health. PMID:17708622

Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development

PubMed Central

Ribas, João; Sadeghi, Hossein; Manbachi, Amir; Leijten, Jeroen; Brinegar, Katelyn; Zhang, Yu Shrike; Ferreira, Lino

2016-01-01

Abstract Cardiovascular diseases are prevalent worldwide and are the most frequent causes of death in the United States. Although spending in drug discovery/development has increased, the amount of drug approvals has seen a progressive decline. Particularly, adverse side effects to the heart and general vasculature have become common causes for preclinical project closures, and preclinical models do not fully recapitulate human in vivo dynamics. Recently, organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system—in particular, heart and general vasculature. These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation. Heart- and vasculature-on-a-chip platforms have been successfully generated to study a variety of physiological phenomena, model diseases, and probe the effects of drugs. Here, we review and discuss recent breakthroughs in the development of cardiovascular organs-on-a-chip platforms, and their current and future applications in the area of drug discovery and development. PMID:28971113

The role of oxidative stress in the metabolic syndrome.

PubMed

Whaley-Connell, Adam; McCullough, Peter A; Sowers, James R

2011-01-01

Loss of reduction-oxidation (redox) homeostasis and generation of excess free oxygen radicals play an important role in the pathogenesis of diabetes, hypertension, and consequent cardiovascular disease. Reactive oxygen species are integral in routine in physiologic mechanisms. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways that promote impairments in insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. Redox control of metabolic function is a dynamic process with reversible pro- and anti-free radical processes. Labile iron is necessary for the catalysis of superoxide anion, hydrogen peroxide, and the generation of the damaging hydroxyl radical. Acute hypoxia and cellular damage in cardiovascular tissue liberate larger amounts of cytosolic and extracellular iron that is poorly liganded; thus, large increases in the generation of oxygen free radicals are possible, causing tissue damage. The understanding of iron and the imbalance of redox homeostasis within the vasculature is integral in hypertension and progression of metabolic dysregulation that contributes to insulin resistance, endothelial dysfunction, and cardiovascular and kidney disease.

Potential Impact and Study Considerations of Metabolomics in Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association.

PubMed

Cheng, Susan; Shah, Svati H; Corwin, Elizabeth J; Fiehn, Oliver; Fitzgerald, Robert L; Gerszten, Robert E; Illig, Thomas; Rhee, Eugene P; Srinivas, Pothur R; Wang, Thomas J; Jain, Mohit

2017-04-01

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine- N -oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine. © 2017 American Heart Association, Inc.

The role of vitamin supplementation in the prevention of cardiovascular disease events.

PubMed

Desai, Chirag K; Huang, Jennifer; Lokhandwala, Adil; Fernandez, Aaron; Riaz, Irbaz Bin; Alpert, Joseph S

2014-09-01

The production, sale, and consumption of multiple vitamins is a multibillion-dollar industry. Most Americans take some form of supplement ostensibly for prevention of cardiovascular disease. It has been claimed that vitamin A retards atherogenesis. Vitamin C is an antioxidant and is thought to possibly decrease free radical-induced endothelial injury, which can lead to atherosclerotic plaque formation. Vitamin E has been extensively studied for its possible effects on platelet function as well as inhibition of foam-cell formation. Low levels of vitamin D have been thought to negatively impact myocardial structure and increase the risk for cardiovascular events. Increased intake of vitamin B6, B12, and folate has been associated with reduction of homocysteine levels; elevated homocysteine blood levels have been associated with the occurrence of stroke, heart attack, and cardiovascular death. The purpose of this study was to review the currently available literature for vitamin supplementation with respect to prevention of cardiovascular disease. Unfortunately, the current evidence suggests no benefit exists with vitamin supplementation in the general US population. Further research is needed to evaluate whether there are specific populations that might benefit from vitamin supplementation. © 2014 Wiley Periodicals, Inc.

Not only cardiovascular, but also coordinative exercise increases hippocampal volume in older adults

PubMed Central

Niemann, Claudia; Godde, Ben; Voelcker-Rehage, Claudia

2014-01-01

Cardiovascular activity has been shown to be positively associated with gray and white matter volume of, amongst others, frontal and temporal brain regions in older adults. This is particularly true for the hippocampus, a brain structure that plays an important role in learning and memory, and whose decline has been related to the development of Alzheimer’s disease. In the current study, we were interested in whether not only cardiovascular activity but also other types of physical activity, i.e., coordination training, were also positively associated with the volume of the hippocampus in older adults. For this purpose we first collected cross-sectional data on “metabolic fitness” (cardiovascular fitness and muscular strength) and “motor fitness” (e.g., balance, movement speed, fine coordination). Second, we performed a 12-month randomized controlled trial. Results revealed that motor fitness but not metabolic fitness was associated with hippocampal volume. After the 12-month intervention period, both, cardiovascular and coordination training led to increases in hippocampal volume. Our findings suggest that a high motor fitness level as well as different types of physical activity were beneficial to diminish age-related hippocampal volume shrinkage or even increase hippocampal volume. PMID:25165446

[Socioeconomic status and inflammatory biomarkers of cardiovascular diseases: How do education, occupation and income operate?].

PubMed

Rosenbach, F; Richter, M; Pförtner, T-K

2015-05-01

In light of the consistent SES gradient in cardiovascular diseases, current research is focusing on possible pathways through which the socioeconomic status (SES) may impact health. Inflammatory processes play a critical role in the development of cardiovascular diseases and are associated with stress. Therefore, they might be one psychobiological pathway explaining how the SES gets under the skin. Considering the different meanings of education, occupation and income, this article gives an overview of the association between inflammatory biomarkers and socioeconomic status. There is high evidence for associations between indicators of SES - education, occupation and income - and inflammatory biomarkers. Possible pathways are health status, health behavior and psychobiological processes as a result of increased exposure to psychosocial stress. The SES gradient in cardiovascular diseases reflects behavioral as well as physiological pathways and systemic inflammation seems to be involved. Low SES is associated with an increased exposure to adverse circumstances of life, which can trigger biological responses and result in an increased risk of cardiovascular diseases. Medical history taking in cardiology should focus on socio-structural exposures and thereby reflect the different meanings of education, occupation and income.

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

PubMed

Miranda, Joana O; Ramalho, Carla; Henriques-Coelho, Tiago; Areias, José Carlos

2017-11-01

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

A review of health utilities using the EQ-5D in studies of cardiovascular disease

PubMed Central

2010-01-01

Background The EQ-5D has been extensively used to assess patient utility in trials of new treatments within the cardiovascular field. The aims of this study were to review evidence of the validity and reliability of the EQ-5D, and to summarise utility scores based on the use of the EQ-5D in clinical trials and in studies of patients with cardiovascular disease. Methods A structured literature search was conducted using keywords related to cardiovascular disease and EQ-5D. Original research studies of patients with cardiovascular disease that reported EQ-5D results and its measurement properties were included. Results Of 147 identified papers, 66 met the selection criteria, with 10 studies reporting evidence on validity or reliability and 60 reporting EQ-5D responses (VAS or self-classification). Mean EQ-5D index-based scores ranged from 0.24 (SD 0.39) to 0.90 (SD 0.16), while VAS scores ranged from 37 (SD 21) to 89 (no SD reported). Stratification of EQ-5D index scores by disease severity revealed that scores decreased from a mean of 0.78 (SD 0.18) to 0.51 (SD 0.21) for mild to severe disease in heart failure patients and from 0.80 (SD 0.05) to 0.45 (SD 0.22) for mild to severe disease in angina patients. Conclusions The published evidence generally supports the validity and reliability of the EQ-5D as an outcome measure within the cardiovascular area. This review provides utility estimates across a range of cardiovascular subgroups and treatments that may be useful for future modelling of utilities and QALYs in economic evaluations within the cardiovascular area. PMID:20109189

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease.

PubMed

Houston, Mark

2018-03-01

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined 'normal' levels of the five risk factors listed above. This is often referred to as the 'CHD gap'. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing.

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease

PubMed Central

Houston, Mark

2018-01-01

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined ‘normal’ levels of the five risk factors listed above. This is often referred to as the ‘CHD gap’. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing. PMID:29316855

Non-Invasive Visualization and Quantitation of Cardiovascular Structure and Function.

ERIC Educational Resources Information Center

Ritman, E. L.; And Others

1979-01-01

Described is a new approach to investigative physiology based on computerized transaxial tomography, in which visualization and measurement of the internal structure of the cardiopulmonary system is possible without postmortem, biopsy, or vivisection procedures. Examples are given for application of the Dynamic Spatial Reconstructor (DSR). (CS)

Cardiovascular responses in type A and type B men to a series of stressors.

PubMed

Ward, M M; Chesney, M A; Swan, G E; Black, G W; Parker, S D; Rosenman, R H

1986-02-01

Fifty-six healthy adult males were administered the Type A Structured Interview and assessed as exhibiting either Type A (N = 42) or Type B (N = 14) behavior pattern. They were monitored for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) responses during a series of six challenging tasks: Mental Arithmetic, Hypothesis Testing, Reaction Time, Video Game, Handgrip, and Cold Pressor. The results indicated that Type A subjects exhibited greater cardiovascular responses than did Type B subjects during some (Hypothesis Testing, Reaction Time, Video Game and Mental Arithmetic) but not all (Handgrip and Cold Pressor) of the tasks. These results are discussed in terms of previously reported findings on conditions that do and do not produce differences in Type A/B cardiovascular stress responses.

Big biomedical data and cardiovascular disease research: opportunities and challenges.

PubMed

Denaxas, Spiros C; Morley, Katherine I

2015-07-01

Electronic health records (EHRs), data generated and collected during normal clinical care, are increasingly being linked and used for translational cardiovascular disease research. Electronic health record data can be structured (e.g. coded diagnoses) or unstructured (e.g. clinical notes) and increasingly encapsulate medical imaging, genomic and patient-generated information. Large-scale EHR linkages enable researchers to conduct high-resolution observational and interventional clinical research at an unprecedented scale. A significant amount of preparatory work and research, however, is required to identify, obtain, and transform raw EHR data into research-ready variables that can be statistically analysed. This study critically reviews the opportunities and challenges that EHR data present in the field of cardiovascular disease clinical research and provides a series of recommendations for advancing and facilitating EHR research.

Creating a Transdisciplinary Research Center to Reduce Cardiovascular Health Disparities in Baltimore, Maryland: Lessons Learned

PubMed Central

Boulware, L. Ebony; Miller, Edgar R.; Golden, Sherita Hill; Carson, Kathryn A.; Noronha, Gary; Huizinga, Mary Margaret; Roter, Debra L.; Yeh, Hsin-Chieh; Bone, Lee R.; Levine, David M.; Hill-Briggs, Felicia; Charleston, Jeanne; Kim, Miyong; Wang, Nae-Yuh; Aboumatar, Hanan; Halbert, Jennifer P.; Ephraim, Patti L.; Brancati, Frederick L.

2013-01-01

Cardiovascular disease (CVD) disparities continue to have a negative impact on African Americans in the United States, largely because of uncontrolled hypertension. Despite the availability of evidence-based interventions, their use has not been translated into clinical and public health practice. The Johns Hopkins Center to Eliminate Cardiovascular Health Disparities is a new transdisciplinary research program with a stated goal to lower the impact of CVD disparities on vulnerable populations in Baltimore, Maryland. By targeting multiple levels of influence on the core problem of disparities in Baltimore, the center leverages academic, community, and national partnerships and a novel structure to support 3 research studies and to train the next generation of CVD researchers. We also share the early lessons learned in the center’s design. PMID:24028238

Psoriasis-associated vascular disease: the role of HDL.

PubMed

Paiva-Lopes, Maria Joao; Delgado Alves, José

2017-09-14

Psoriasis is a chronic inflammatory systemic disease with a prevalence of 2-3%. Overwhelming evidence show an epidemiological association between psoriasis, cardiovascular disease and atherosclerosis. Cardiovascular disease is the most frequent cause of death in patients with severe psoriasis. Several cardiovascular disease classical risk factors are also increased in psoriasis but the psoriasis-associated risk persists after adjusting for other risk factors.Investigation has focused on finding explanations for these epidemiological data. Several studies have demonstrated significant lipid metabolism and HDL composition and function alterations in psoriatic patients. Altered HDL function is clearly one of the mechanisms involved, as these particles are of the utmost importance in atherosclerosis defense. Recent data indicate that biologic therapy can reverse both structural and functional HDL alterations in psoriasis, reinforcing their therapeutic potential.

Cardiovascular complications of anorexia nervosa: A systematic review.

PubMed

Sachs, Katherine V; Harnke, Ben; Mehler, Philip S; Krantz, Mori J

2016-03-01

Anorexia nervosa portends the highest mortality among psychiatric diseases, despite primarily being a disease of adolescents and younger adults. Although some of this mortality risk is attributable to suicide, many deaths are likely cardiovascular in etiology. Recent studies suggest that adverse myocardial structural changes occur in this condition, which could underlie the increased mortality. Given limited prevalence of severe anorexia there is a paucity of clinical and autopsy data to discern an exact cause of death. Given this background we conducted a systematic review of the medical literature to provide a contemporary summary of the pathobiologic sequelae of severe anorexia nervosa on the cardiovascular system. We sought to elucidate the impact of anorexia nervosa in four cardiovascular domains: structural, repolarization/conduction, hemodynamic, and peripheral vascular. A number of cardiac abnormalities associated with anorexia nervosa have been described in the literature, including pericardial and valvular pathology, changes in left ventricular mass and function, conduction abnormalities, bradycardia, hypotension, and dysregulation in peripheral vascular contractility. Despite the prevalent theory that malignant arrhythmias are implicated as a cause of sudden death in this disorder, data to support this causal relationship are lacking. It is reasonable to obtain routine electrocardiography and measurements of orthostatic vital signs in patients presenting with anorexia nervosa. Echocardiography is generally not indicated unless prompted by clinical signs of disease. Admission to an inpatient unit with telemetry monitoring is recommended for patients with severe sinus bradycardia or junction rhythm, marked prolongation of the corrected QT interval, or syncope. © 2015 Wiley Periodicals, Inc.

Non-invasively measured structural and functional arterial characteristics and coronary heart disease risk in middle aged and elderly men.

PubMed

van Trijp, Marijke J C A; Bos, Willem J W; van der Schouw, Yvonne T; Muller, Majon; Grobbee, Diederick E; Bots, Michiel L

2006-07-01

In cardiovascular (CV) epidemiology, interest increases in studying etiologic and prognostic implications of early structural or functional changes of the large arteries. Examples of such measurements are pulse wave velocity (PWV), carotid intima-media thickness (CIMT) and augmentation index (AIx). PWV and CIMT are established markers of CV risk whereas the role of AIx as indicator of risk has not fully been established. Therefore, our aim was to relate AIx to CV risk and to compare the magnitude of relations of PWV, CIMT and AIx to CV risk. Two hundred and ninty-nine men free from cardiovascular disease (mean age 59.2 years), participated in this cross-sectional study. Cardiovascular risk profile was determined and 10-year coronary heart disease risk was estimated using the Framingham risk score (FRS). PWV, CIMT and AIx were measured and data were analyzed using linear regression models. PWV and CIMT were strongest related to FRS whereas AIx showed the weakest relation. Ten-year coronary heart disease risk increased 6.24%, 95% confidence interval (CI) [5.11;7.37] per standard deviation (S.D.) increase in PWV, 6.39% [5.24;7.54] per S.D. increase in CIMT and 2.50% [1.19;3.80] per S.D. increase in AIx. In middle aged and elderly men AIx is related to CV risk. However, compared with AIx, PWV and CIMT seem better markers of cardiovascular risk.

Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Gosemann, Jan-Hendrik; Puri, Prem

2014-10-01

Pulmonary hypoplasia (PH) is a serious condition in newborns with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis. In rodents, LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 days of gestation. Adipocyte differentiation-related protein (ADRP), a functional lipogenic molecular marker characterizing LIFs, is highly expressed in fetal lungs during this critical time period. We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model, which is accompanied by reduced alveolar ADRP expression and lipid content. On embryonic day 9.5 (E9.5), time-mated rats received either nitrofen or vehicle. Fetuses were sacrificed on selected time points E18.5 and E21.5, and dissected lungs were divided into controls and CDH-associated PH. Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction. ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content. Immunofluorescence double staining for alpha smooth muscle actin, which is known to be absent in LIFs, and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts. Relative mRNA expression of ADRP was significantly reduced in lungs of CDH-associated PH on E18.5 and E21.5 compared to controls. ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH-associated PH on E18.5 and E21.5 compared to controls. Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH-associated PH on E18.5 and E21.5 compared to controls. Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen-induced CDH model, which may cause disruption in fetal alveolarization and lipid homeostasis, and thus contribute to the development of PH.

Treatment of right ventricle to pulmonary artery conduit stenosis in infants with hypoplastic left heart syndrome.

PubMed

Münsterer, Andrea; Kasnar-Samprec, Jelena; Hörer, Jürgen; Cleuziou, Julie; Eicken, Andreas; Malcic, Ivan; Lange, Rüdiger; Schreiber, Christian

2013-09-01

To determine the incidence of right ventricle-to-pulmonary artery (RV-PA) conduit stenosis after the Norwood I operation in patients with hypoplastic left heart syndrome (HLHS), and to determine whether the treatment strategy of RV-PA conduit stenosis has an influence on interstage and overall survival. Ninety-six patients had a Norwood operation with RV-PA conduit between 2002 and 2011. Details of reoperations/interventions due to conduit obstruction prior to bidirectional superior cavopulmonary anastomosis (BSCPA) were collected. Overall pre-BSCPA mortality was 17%, early mortality after Norwood, 6%. Early angiography was performed in 34 patients due to desaturation at a median of 8 days after the Norwood operation. Fifteen patients (16%) were diagnosed with RV-PA conduit stenosis that required treatment. The location of the conduit stenosis was significantly different in the patients with non-ringed (proximal) and the patients with ring-enforced conduit (distal), P = 0.004. In 6 patients, a surgical revision of the conduit was performed; 3 of them died prior to BSCPA. Another 6 patients had a stent implantation and 3 were treated with balloon dilatation followed by a BSCPA in the subsequent 2 weeks. All patients who were treated interventionally for RV-PA conduit obstruction had a successful BSCPA. Patients who received a surgical RV-PA conduit revision had a significantly higher interstage (P = 0.044) and overall mortality (P = 0.011) than those who received a stent or balloon dilatation of the stenosis followed by an early BSCPA. RV-PA conduit obstruction after Norwood I procedure in patients with HLHS can be safely and effectively treated by stent implantation, balloon dilatation and early BSCPA. Surgical revision of the RV-PA conduit can be reserved for patients in whom an interventional approach fails, and an early BSCPA is not an option.

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.

PubMed

Johnson-Tesch, Benjamin A; Gawande, Rakhee S; Zhang, Lei; MacMillan, Margaret L; Nascene, David R

2017-06-01

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

Up-regulation of Wnt5a gene expression in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Puri, Prem

2009-12-01

The pathogenesis of pulmonary hypoplasia in nitrofen-induced congenital diaphragmatic hernia (CDH) still remains unclear. Wnt signaling pathways play a critical role in lung development. Whereas canonical Wnt signaling regulates branching morphogenesis during early lung development, the noncanonical Wnt5a controls late lung morphogenesis, including patterning of distal airway and vascular tubulogenesis (alveolarization). Overexpression of Wnt5a in transgenic mice and in the chick has been reported to result in severe pulmonary hypoplasia. We designed this study to test the hypothesis that the pulmonary Wnt5a gene expression is up-regulated in late stages of lung morphogenesis in CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups: control; nitrofen without CDH, CDH(-); and nitrofen with CDH, CDH(+) (n = 8 at each time-point, respectively). Wnt5a pulmonary gene expression was analyzed by real-time reverse transcription polymerase chain reaction. Immunohistochemistry was performed to evaluate Wnt5a protein expression at each time-point. Pulmonary relative mRNA expression levels of Wnt5a were significantly increased in CDH(-) and CDH(+) at D18 (1.61 +/- 0.92 and 1.81 +/- 1.20, respectively) and D21 (2.40 +/- 0.74* and 2.65 +/- 0.35*, respectively) compared to controls at D18 and D21 (0.90 +/- 0.17* and 1.69 +/- 0.53**, respectively) (*P < .05, **P < .001 vs control ). Strong Wnt5a immunoreactivity was seen in the distal epithelium at D18 and D21 in nitrofen-induced hypoplastic lung compared to controls. Up-regulation of pulmonary Wnt5a gene expression in the late lung morphogenesis may interfere with patterning of alveolarization, causing pulmonary hypoplasia in the nitrofen-induced CDH.

Decreased Expression of Integrin Subunits α3, α6, and α8 in the Branching Airway Mesenchyme of Nitrofen-Induced Hypoplastic Lungs.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2018-02-01

 Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major cause of neonatal mortality in newborns with congenital diaphragmatic hernia (CDH). Integrin-mediated cell-matrix interactions play an essential role in the fetal lung mesenchyme by stimulating branching morphogenesis. Mice lacking integrin subunits α3 (Itga3) and α6 (Itga6) exhibit severe PH. Furthermore, Itga8-knockout mice show defective airway branching, suggesting that Itga3, Itga6, and Itga8 are crucial for fetal lung development. We hypothesized that expression of Itga3, Itga6, and Itga8 is decreased in the branching airway mesenchyme of hypoplastic rat lungs in the nitrofen-induced CDH model.  Time-mated rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D15, D18, and D21, and dissected lungs were divided into control and nitrofen-exposed specimens ( n  = 12 per time-point and group, respectively). Pulmonary gene expression of Itga3, Itga6, and Itga8 was analyzed by quantitative real-time polymerase chain reaction. Immunofluorescence double-staining for Itga3, Itga6, and Itga8 was combined with the mesenchymal marker Fgf10 to evaluate protein expression and localization in branching airway tissue.  Relative mRNA expression of Itga3, Itga6, and Itga8 was significantly decreased in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Itga3, Itga6, and Itga8 mainly in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls.  Decreased expression of Itga3, Itga6, and Itga8 in the pulmonary mesenchyme may lead to disruptions in airway branching morphogenesis, thus contributing to PH in the nitrofen-induced CDH model. Georg Thieme Verlag KG Stuttgart · New York.

Health-related quality of life in children with thoracic insufficiency syndrome.

PubMed

Vitale, Michael G; Matsumoto, Hiroko; Roye, David P; Gomez, Jaime A; Betz, Randal R; Emans, John B; Skaggs, David L; Smith, John T; Song, Kit M; Campbell, Robert M

2008-03-01

The traditional techniques to treat thoracic insufficiency syndrome (TIS) are not able to stabilize or improve chest wall size or pulmonary function while allowing spine growth. To this end, vertical expandable prosthetic titanium rib (VEPTR) was specifically designed to treat TIS by allowing growth of the thoracic cavity and control/correction of spine deformity. The purpose of this study was to determine quality of life (QOL) of children with TIS and its impact on their parents before and after implantation of the VEPTR and also compare these results to those of healthy children. As part of the original multicenter evaluation of the VEPTR, a Child Health Questionnaire (CHQ) was collected preoperatively on 45 patients who were subsequently treated with expansion thoracoplasty using the VEPTR. The average age was 8.2 +/- 2.6 years, and the parent form of the CHQ was filled out by the primary caretaker. Patients were divided into 3 diagnostic categories: rib fusion (n = 15), hypoplastic thorax syndromes (n = 17), and progressive spinal deformity (n = 13). There were significant differences between the study patients and healthy children in physical domains. Compared with parents of healthy children, parents of children with TIS experienced more limitations on their time and emotional lives due to their children's health problems. There were no significant differences in CHQ before and after the surgery except for a significant decrease in the self-esteem among a subgroup of patients with hypoplastic thorax syndromes. There were no significant differences in postoperative QOL between patients who had VEPTR-related complications and patients who did not have the complications. The children with TIS had lower physical scores and higher caregiver burden scores than healthy children. However, the scores in psychosocial domains were similar to those in healthy children. Our study demonstrated that QOL of children and burden of care in their parents remained the same after VEPTR instrumentation. Children's QOL seemed to be not affected by whether they had VEPTR-related complications or not.

Abducens Nerve in Patients with Type 3 Duane’s Retraction Syndrome

PubMed Central

Hwang, Jeong-Min

2016-01-01

Background We have previously reported that the presence of the abducens nerve was variable in patients with type 3 Duane’s retraction syndrome (DRS), being present in 2 of 5 eyes (40%) and absent in 3 (60%) on magnetic resonance imaging (MRI). The previous study included only 5 eyes with unilateral DRS type 3. Objectives To supplement existing scarce pathologic information by evaluating the presence of the abducens nerve using high resolution thin-section MRI system in a larger number of patients with DRS type 3, thus to provide further insight into the pathogenesis of DRS. Data Extraction A retrospective review of medical records on ophthalmologic examination and high resolution thin-section MRI at the brainstem level and orbit was performed. A total of 31 patients who showed the typical signs of DRS type 3, including abduction and adduction deficit, globe retraction, narrowing of fissure on adduction and upshoot and/or downshoot, were included. The abducens nerve and any other extraocular muscle abnormalities discovered by MRI were noted. Results DRS was unilateral in 26 patients (84%) and bilateral in 5 patients (16%). Two out of 5 bilateral patients had DRS type 3 in the right eye and DRS type 1 in the left eye. Of the 34 affected orbits with DRS type 3 in 31 patients, the abducens nerve was absent or hypoplastic in 31 eyes (91%) and present in 3 eyes (9%). Patients with a present abducens nerve showed more limitation in adduction compared to patients with an absent abducens nerve (P = 0.030). Conclusions The abducens nerve is absent or hypoplastic in 91% of DRS type 3. Patients with a present abducens nerve showed more prominent limitation of adduction. As DRS type 3 partly share the same pathophysiology with type 1 and 2 DRS, the classification of DRS may have to be revised according to MRI findings. PMID:27352171

Regional cerebral perfusion for surgical correction of neonatal aortic arch obstruction.

PubMed

Zhang, Hui; Cheng, Pei; Hou, Jia; Li, Lei; Liu, Hu; Liu, Ruifang; Ji, Bingyang; Luo, Yi

2009-05-01

One-stage repair of aortic arch obstruction and associated cardiac anomalies is a surgical challenge in infants.The purpose of the present study is to review the current outcome using regional cerebral perfusion (RCP) during a procedure correcting interrupted aortic arch (IAA) and also isolated aortic coarctation (CoA) and CoA combined with hypoplastic aortic arch (CoA-HyAA) in our center. Between January 2007 and July 2008, 24 infant patients with interrupted aortic arch (IAA) (n=3), isolated aortic coarctation (iCoA) (n=9) and aortic coarctation with hypoplastic aortic arch (CoA-HyAA) (n=12) underwent one-stage surgical correction in our hospital. End-to-end anastomosis was employed in 12 infants (IAA n=3 and iCoA n=9); for the other 12 patients with CoA-HyAA, an end-to-end extended anastomosis was used in 8 cases, end-to-side anastomosis in 2 cases, and composite heterologous pericardial patch in 2 cases. RCP with 40 mL/kg/min through the innominate artery during aortic arch reconstruction was employed for all pediatric patients. One single-dose histidine-ketoglutarate-tryptophan (HTK) solution was used for myocardial protection during CPB. Cardiopulmonary bypass time and aortic cross-clamp time were 165.6+/-32.4 min and 81.7+/-30.0 min, respectively. The mean regional cerebral perfusion time was 31.0+/-10.6 min; lowest nasopharyngeal temperature was 19.1+/-1.1 degrees C. Operative mortality rate in both groups was 8.3%. Mean follow-up was 10.5+/-4.8 months. There was no late mortality or postoperative neurologic, renal or hepatic complications. All patients are asymptomatic and are developing normally. One-stage total arch repair using the RCP technique is an excellent method that may minimize neurologic and renal complications. Our surgical strategy for arch anomaly has a low rate of residual and recurrent coarctation when performed in these infants.

Clinical findings in right ventricular noncompaction in hypoplastic left heart syndrome.

PubMed

Gardner, Monique M; Cohen, Meryl S

2017-12-01

Noncompaction is a poorly understood form of cardiomyopathy that typically affects the left ventricle and may be associated with congenital heart disease. Right ventricular noncompaction (RVNC) may occur when the left ventricle is affected but is rarely seen in isolation. RVNC may have clinical significance affecting surgical and long-term outcomes. We describe the diagnosis and clinical course in three patients at our institution. We performed a retrospective review of patients diagnosed with RVNC over a 12-month period at our institution and reviewed their imaging and clinical course. Three patients were identified. All had diagnosis of RVNC by echocardiography (echo) made on postnatal imaging which reviewed degree of trabeculation, and noncompaction-to-compaction ratio of the myocardium. Patient A was a neonate with hypoplastic left heart syndrome (HLHS) who underwent a Norwood operation with Sano modification. Her postoperative course was notable for low-normal RV function. She returned with a pericardial effusion warranting immediate pericardiocentesis. She continued to have effusions, which were medically managed. She was subsequently found to have an RV apical pseudoaneurysm, which required surgical resection. Patient B was a neonate with HLHS who had a Norwood operation with Sano modification. She had low-normal RV function on echo. She required medical management for pericardial effusion. Patient C was a neonate with HLHS who also underwent a Norwood operation with Sano modification. His postoperative course was notable for elevated serum brain natriuretic peptide, which was treated with digoxin. RVNC is a rare diagnosis with limited known clinical impact. One of these patients had a very rare complication after pericardiocentesis (pseudoaneurysm) that may have been related to the RVNC. Our understanding of this disease process is limited and requires additional investigation, but emphasizes the importance of appropriate diagnosis to allow for timely follow-up and counseling for this unique population. © 2017 Wiley Periodicals, Inc.

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

PubMed Central

Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-ha; Wigler, Michael; Levy, Dan

2013-01-01

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable pheno-types and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo. PMID:23979609

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease.

PubMed

Warburton, Dorothy; Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-Yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-Ha; Wigler, Michael; Levy, Dan

2014-01-01

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable phenotypes and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo.

Center Variation and Outcomes Associated with Delayed Sternal Closure Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome

PubMed Central

Johnson, Jason N.; Jaggers, James; Li, Shuang; O’Brien, Sean M.; Li, Jennifer S.; Jacobs, Jeffrey P.; Jacobs, Marshall L.; Welke, Karl F.; Peterson, Eric D.; Pasquali, Sara K.

2009-01-01

Objectives There is debate whether primary or delayed sternal closure (DSC) is the best strategy following Stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS). We describe center variation in DSC following S1P and associated outcomes. Methods Society of Thoracic Surgeons Congenital Database participants performing S1P for HLHS from 2000–2007 were included. We examined center variation in DSC, and compared in-hospital mortality, prolonged length of stay (LOS >6wks), and postoperative infection in centers with low (≤25% of cases), middle (26%–74% of cases), and high (≥75% of cases) DSC utilization, adjusting for patient and center factors. Results There were 1283 patients (45 centers) included. Median age and weight at surgery were 6d (IQR4-9d) and 3.2 kg (IQR2.8–3.5kg); 59% were male. DSC was used in 74% (range 3–100% of cases/center). In centers with high (n=23) and middle (n=17) vs. low (n=5) DSC utilization, there was a greater proportion of patients with prolonged LOS and infection, and a trend toward increased in-hospital mortality in unadjusted analysis. In multivariable analysis, there was no difference in mortality. Centers with high and middle DSC utilization had prolonged LOS [OR (95%CI): 2.83(1.46–5.47) p=0.002 and 2.23(1.17–4.26) p=0.02] and more infection [2.34(1.20–4.57) p=0.01 and 2.37(1.36–4.16) p=0.003]. Conclusions Utilization of DSC following S1P varies widely. These observational data suggest more frequent use of DSC is associated with longer LOS and higher postoperative infection rates. Further evaluation of the risks and benefits of DSC in the management of these complex infants is necessary. PMID:20167337

Prognostic value of troponin in infants with hypoplastic left heart syndrome between Stage I and II of palliation.

PubMed

Christmann, Martin; Valsangiacomo Büchel, Emanuela R; Dave, Hitendu; Klauwer, Dietrich; Cavigelli-Brunner, Anna

2018-01-01

The period between stage I and II procedure for treatment of hypoplastic left heart syndrome (HLHS) bears high mortality and morbidity. We sought to analyze the prognostic value of Troponin T/I (Trop), a well-recognized marker for myocardial damage and heart failure, for predicting outcome in a retrospective analysis of 70 infants with HLHS at our institution between March 2001 and October 2014. Stage I procedure consisted of Norwood I operation in 35 (50%) and Hybrid-approach in 22 (31%) patients. Palliative care was chosen for 13 (19%) patients. Trop values were collected from clinical charts and were analyzed in relation to the overall outcome. Trop was significantly higher after Norwood I operation in comparison to Hybrid-approach (median 7.1 μg/l (0.7-20.9), vs 1.2 μg/l (0.3-17.9), P < 0.001). Overall mortality of treated patients was 39% (22 patients). Survival was 54% (19 patients) after Norwood and 73% (16 patients) after Hybrid-approach. Independently from the procedure used, maximal Trop and initial lactate values were significantly higher in non-survivors than in survivors, with median Trop of 9 μg/l (0.6-18.8) vs. 3.4 μg/l (0.4-20.9), P 0.007, and median lactate of 3.7 mmol/L (1.6-25) vs. 2.9 mmol/L (0.3-14.6), p 0.03. Reinterventions were required in 17 (30%) patients, 4 (11%) after Norwood and 13 (59%) after Hybrid procedure. No correlation was found between the need for reintervention and Trop levels in the interstage period. Patients with HLHS have significantly higher Trop levels after Norwood procedure than after Hybrid-approach. Maximal Trop values were related to mortality, but did not correlate with the need for reinterventions.

Molecular cytogenetic characterization of Xp22.32→pter deletion and Xq26.3→qter duplication in a male fetus associated with 46,Y,rec(X)dup(Xq) inv(X)(p22.3q26.3), a hypoplastic left heart, short stature, and maternal X chromosome pericentric inversion.

PubMed

Chen, Chih-Ping; Chen, Chen-Yu; Chern, Schu-Rern; Wu, Peih-Shan; Chen, Yen-Ni; Chen, Shin-Wen; Lee, Chen-Chi; Town, Dai-Dyi; Lee, Meng-Shan; Yang, Chien-Wen; Wang, Wayseen

2016-10-01

We present molecular cytogenetic characterization of an Xp22.32→pter deletion and an Xq26.3→qter duplication in a male fetus with congenital malformations and maternal X chromosome pericentric inversion. A 22-year-old woman underwent amniocentesis at 17 weeks of gestation because of an abnormal maternal serum screening result. Prenatal ultrasound revealed a hypoplastic left heart and short limbs. Amniocentesis revealed a karyotype of 46,Y,der(X) t(X;?)(p22.31;?). The pregnancy was subsequently terminated, and a malformed fetus was delivered with short stature and facial dysmorphism. Repeat amniocentesis was performed before termination of the pregnancy. Array comparative genomic hybridization was performed on uncultured amniocytes and maternal blood. Conventional cytogenetic analysis was performed on cultured amniocytes, cord blood, and blood from both parents. Fluorescence in situ hybridization was performed on cultured amniocytes. The maternal karyotype was 46,X,inv(X)(p22.3q26.3). The fetal karyotype was 46,Y, rec(X)dup(Xq)inv(X)(p22.3q26.3) or 46,Y, rec(X)(qter→q26.3::p22.3→qter). Array comparative genomic hybridization on uncultured amniocytes revealed a 4.56-Mb deletion of Xp22.33-p22.32 encompassing SHOX, CSF2RA, and ARSE, and a 19.22-Mb duplication of Xq26.3-q28 encompassing SOX3, FMR1, MECP2, RAB39B, and CLIC2 in the fetus. The mother did not have X chromosome imbalance. Detection of X chromosome aberration in a male fetus should give suspicion of a recombinant X chromosome derived from maternal X chromosome pericentric inversion. Copyright © 2016. Published by Elsevier B.V.

Treatment-related Cardiovascular Late-effects and Exercise Training Countermeasures in Testicular Germ Cell Cancer Survivorship

PubMed Central

Christensen, Jesper F; Bandak, Mikkel; Campbell, Anna; Jones, Lee W.; Højman, Pernille

2016-01-01

Background Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies. Results Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders the ‘multiple-hit hypothesis’). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. Conclusion Since exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise-oncology research in this setting, in order to provide exercise-recommendations for optimal germ cell cancer survivorship. PMID:25751759

Emerging role of neurotensin in regulation of the cardiovascular system.

PubMed

Osadchii, Oleg E

2015-09-05

There is increasing evidence in support of an important role played by neurotensin (NT), a tridecapeptide originally found in bovine hypothalamus, in regulation of cardiovascular system. Elevated systemic levels of NT may contribute to pathogenesis of acute circulatory disoders, and predict the risk for cardiovascular morbidity and mortality in population-based studies. Within cardiovascular system, NT-containing neural fibers are found in close contact with atrial and ventricular cardiac myocytes, cardiac conduction system, intracardiac ganglia, as well as coronary vessels in humans and various animal species. The density of NT-immunoreactive innervation is reduced in cardiac disease. NT produces a variety of cardiovascular actions including effects on heart rate, myocardial contractility, systemic blood pressure, coronary vascular tone, venous smooth muscle tone, and regional blood flow in gastrointestinal tract, cutaneous and adipose tissue. NT could trigger cardiovascular reflexes by stimulating primary visceral afferents synaptically connected with preganglionic sympathetic neurons at the spinal cord. Structural determinants of biological activity of NT reside primarily in the C-terminal portion of its molecule which is responsible for receptor activation. NT effects are mediated via activation of NT receptors, or produced indirectly via stimulation of release of various endogenous neuromodulators/neurotransmitters such as histamine, catecholamines and prostaglandins. Three subtypes of NT receptor (NTS1, NTS2 and NTS3) have been shown to be expressed in the myocardium. NTS1, a high-affinity NT binding site coupled to phospholipase C-inositoltrisphosphate transduction pathway, is thought to mediate NT-induced cardiovascular responses. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship.

PubMed

Christensen, Jesper F; Bandak, Mikkel; Campbell, Anna; Jones, Lee W; Højman, Pernille

2015-05-01

Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer-specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies. Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. As exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise oncology research in this setting, in order to provide exercise recommendations for optimal germ cell cancer survivorship.

A Community-based Cross-sectional Study of Cardiovascular Risk in a Rural Community of Puducherry.

PubMed

Shrivastava, Saurabh R; Ghorpade, Arun G; Shrivastava, Prateek S

2015-01-01

The World Health Organization (WHO) / International Society of Hypertension (ISH) risk prediction chart can predict the risk of cardiovascular events in any population. To assess the prevalence of cardiovascular risk factors and to estimate the cardiovascular risk using the WHO/ISH risk charts. A cross-sectional study was done from November 2011 to January 2012 in a rural area of Puducherry. Method of sampling was a single stage cluster random sampling, and subjects were enrolled depending on their suitability with the inclusion and exclusion criteria. The data collection tool was a piloted and semi-structured questionnaire, while WHO/ISH cardiovascular risk prediction charts for the South-East Asian region was used to predict the cardiovascular risk. Institutional Ethics committee permission was obtained before the start of the study. Statistical analysis was done using SPSS version 16 and appropriate statistical tests were applied. The mean age in years was 54.2 (±11.1) years with 46.7% of the participants being male. On application of the WHO/ISH risk prediction charts, almost 17% of the study subjects had moderate or high risk for a cardiovascular event. Additionally, high salt diet, alcohol use and low HDL levels, were identified as the major CVD risk factors. To conclude, stratification of people on the basis of risk prediction chart is a major step to have a clear idea about the magnitude of the problem. The findings of the current study revealed that there is a high burden of CVD risk in the rural Puducherry.

A systematic review of 3-D printing in cardiovascular and cerebrovascular diseases

PubMed Central

Sun, Zhonghua; Lee, Shen-Yuan

2017-01-01

Objective: The application of 3-D printing has been increasingly used in medicine, with research showing many applications in cardiovascular disease. This systematic review analyzes those studies published about the applications of 3-D printed, patient-specific models in cardiovascular and cerebrovascular diseases. Methods: A search of PubMed/Medline and Scopus databases was performed to identify studies investigating the 3-D printing in cardiovascular and cerebrovascular diseases. Only studies based on patient’s medical images were eligible for review, while reports on in vitro phantom or review articles were excluded. Results: A total of 48 studies met selection criteria for inclusion in the review. A range of patient-specific 3-D printed models of different cardiovascular and cerebrovascular diseases were generated in these studies with most of them being developed using cardiac CT and MRI data, less commonly with 3-D invasive angiographic or echocardiographic images. The review of these studies showed high accuracy of 3-D printed, patient-specific models to represent complex anatomy of the cardiovascular and cerebrovascular system and depict various abnormalities, especially congenital heart diseases and valvular pathologies. Further, 3-D printing can serve as a useful education tool for both parents and clinicians, and a valuable tool for pre-surgical planning and simulation. Conclusion: This systematic review shows that 3-D printed models based on medical imaging modalities can accurately replicate complex anatomical structures and pathologies of the cardiovascular and cerebrovascular system. 3-D printing is a useful tool for both education and surgical planning in these diseases. PMID:28430115

Perceived determinants of cardiovascular risk management in primary care: disconnections between patient behaviours, practice organisation and healthcare system.

PubMed

Huntink, E; Wensing, M; Klomp, M A; van Lieshout, J

2015-12-15

Although conditions for high quality cardiovascular risk management in primary care in the Netherlands are favourable, there still remains a gap between practice guideline recommendations and practice. The aim of the current study was to identify determinants of cardiovascular primary care in the Netherlands. We performed a qualitative study, using semi-structured interviews with healthcare professionals and patients with established cardiovascular diseases or at high cardiovascular risk. A framework analysis was used to cluster the determinants into seven domains: 1) guideline factors, 2) individual healthcare professional factors, 3) patient factors, 4) professional interaction, 5) incentives and recourses, 6) mandate, authority and accountability, and 7) social, political and legal factors. Twelve healthcare professionals and 16 patients were interviewed. Healthcare professionals and patients mentioned a variety of factors concerning all seven domains. Determinants of practice according to the health care professionals were related to communication between healthcare professionals, patients' lack of knowledge and self-management, time management, market mechanisms in the Dutch healthcare system and motivational interviewing skills of healthcare professionals. Patients mentioned determinants related to their knowledge of risk factors for cardiovascular diseases, medication adherence and self-management as key determinants. A key finding is the mismatch between healthcare professionals' and patients' views on patient's knowledge and self-management. Perceived determinants of cardiovascular risk management were mainly related to patient behaviors and (but only for health professionals) to the healthcare system. Though health care professionals and patients agree upon the importance of patients' knowledge and self-management, their judgment of the current state of knowledge and self-management is entirely different.

The ICV Study: Integrated Cardiovascular

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Bungo, Michael W.

2009-01-01

This viewgraph presentation describes the effects of long duration manned spaceflight on heart structure and function. Clinical consequences for orthostatic tolerance, cardiac arrhythmias, and countermeasures to prevent clinical problems are also discussed.

Cardiovascular Event Prediction by Machine Learning: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Ambale-Venkatesh, Bharath; Yang, Xiaoying; Wu, Colin O; Liu, Kiang; Hundley, W Gregory; McClelland, Robyn; Gomes, Antoinette S; Folsom, Aaron R; Shea, Steven; Guallar, Eliseo; Bluemke, David A; Lima, João A C

2017-10-13

Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487. © 2017 American Heart Association, Inc.

CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola.

PubMed

Pedro, João M; Rosário, Edite; Brito, Miguel; Barros, Henrique

2016-03-01

Cardiovascular diseases and other non-communicable diseases are major causes of morbidity and mortality, responsible for 38 million deaths in 2012, 75 % occurring in low- and middle-income countries. Most of these countries are facing a period of epidemiological transition, being confronted with an increased burden of non-communicable diseases, which challenge health systems mainly designed to deal with infectious diseases. With the adoption of the World Health Organization "Global Action Plan for the Prevention and Control of non-communicable diseases, 2013-2020", the national dimension of risk factors for non-communicable diseases must be reported on a regular basis. Angola has no national surveillance system for non-communicable diseases, and periodic population-based studies can help to overcome this lack of information. CardioBengo will collect information on risk factors, awareness rates and prevalence of symptoms relevant to cardiovascular diseases, to assist decision makers in the implementation of prevention and treatment policies and programs. CardioBengo is designed as a research structure that comprises a cross-sectional component, providing baseline information and the assembling of a cohort to follow-up the dynamics of cardiovascular diseases risk factors in the catchment area of the Dande Health and Demographic Surveillance System of the Health Research Centre of Angola, in Bengo Province, Angola. The World Health Organization STEPwise approach to surveillance questionnaires and procedures will be used to collect information on a representative sex-age stratified sample, aged between 15 and 64 years old. CardioBengo will recruit the first population cohort in Angola designed to evaluate cardiovascular diseases risk factors. Using the structures in place of the Dande Health and Demographic Surveillance System and a reliable methodology that generates comparable results with other regions and countries, this study will constitute a useful tool for the surveillance of cardiovascular diseases. Like all longitudinal studies, a strong concern exists regarding dropouts, but strategies like regular visits to selected participants and a strong community involvement are in place to minimize these occurrences.

Pentraxin 3 as a Novel Marker in Cardiovascular Diseases?

PubMed Central

Grzesk, Grzegorz; Grzesk, Elzbieta

2011-01-01

Pentraxin 3 (also known as TNFAIP5, TSG-14) belongs to the superfamily of proteins characterized by cyclic multimeric structure. Pentraxin 3 (PTX3) is synthesized locally at the inflammatory sites by endothelial and smooth muscle cells upon exposure to inflammatory signals such as IL-1β, TNF-α or ox-LDL, but not IL-6. Furthermore, PTX3 is highly expressed in vascular cells and myocardial cells in patients with cardiomyopathy. These data suggest that pentraxin 3 may be a useful biomarker for local vascular inflammation and cardiovascular system disorders. PMID:27683398

Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.

PubMed

Iyer, Abishek; Kauter, Kathleen; Alam, Md Ashraful; Hwang, Sung Hee; Morisseau, Christophe; Hammock, Bruce D; Brown, Lindsay

2012-01-01

The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

Assessing the Associations Between Types of Green Space, Physical Activity, and Health Indicators Using GIS and Participatory Survey

NASA Astrophysics Data System (ADS)

Akpinar, A.

2017-11-01

This study explores whether specific types of green spaces (i.e. urban green spaces, forests, agricultural lands, rangelands, and wetlands) are associated with physical activity, quality of life, and cardiovascular disease prevalence. A sample of 8,976 respondents from the Behavioral Risk Factor Surveillance System, conducted in 2006 in Washington State across 291 zip-codes, was analyzed. Measures included physical activity status, quality of life, and cardiovascular disease prevalence (i.e. heart attack, angina, and stroke). Percentage of green spaces was derived from the National Land Cover Dataset and measured with Geographical Information System. Multilevel regression analyses were conducted to analyze the data while controlling for age, sex, race, weight, marital status, occupation, income, education level, and zip-code population and socio-economic situation. Regression results reveal that no green space types were associated with physical activity, quality of life, and cardiovascular disease prevalence. On the other hand, the analysis shows that physical activity was associated with general health, quality of life, and cardiovascular disease prevalence. The findings suggest that other factors such as size, structure and distribution (sprawled or concentrated, large or small), quality, and characteristics of green space might be important in general health, quality of life, and cardiovascular disease prevalence rather than green space types. Therefore, further investigations are needed.

Erich Lexer's mammaplasty.

PubMed

Hinderer, U T; del Rio, J L

1992-01-01

A summary of Hans May's biography of Erich Lexer is reproduced, followed by a translation of Lexer's first publication, in Spain in 1921, on the correction of pendular breasts. Lexer's fundamental contributions to mammaplasty are analyzed. This author was the first in the history of mammaplasty to perform breast reduction with an "open" nipple-areola complex transposition, with preservation of the continuity of the skin to the remaining gland. This feature was far ahead of its time, as the techniques based on this concept did not become popular until after 1955. Lexer also was the first to propose subcutaneous mastectomy for treatment of fibrocystic disease, to perform breast augmentation in the ptotic hypoplastic breast with fat flaps, and to use free fat grafts taken from the abdomen or hips for augmentation mammaplasty.

The internal mammary artery as a shunt in a noncyanotic infant with hemitruncus: surgical and anesthetic management.

PubMed

Mahan, Vicki L; Stevens, Randy M; Mesia, Cesar I; Schwartz, Roy E; Moulick, Achintya N

2016-08-01

The internal mammary artery (IMA) has been used as a systemic-to-pulmonary artery shunt in selected patients with congenital heart disease. Growth and development of hypoplastic pulmonary arteries have been described. We discuss the surgical and anesthetic management of an infant with an atretic-thrombosed right pulmonary artery originating from the ascending aorta in whom the IMA was used to create a systemic-to-pulmonary artery shunt after failure of a previous shunt and later successful pulmonary artery reconstruction. The IMA should be considered as an alternative conduit in patients requiring a systemic-to-pulmonary artery shunt for growth of pulmonary arteries. Copyright © 2016 Elsevier Inc. All rights reserved.

Cancer Management in Kabuki Syndrome: The First Case of Wilms Tumor and a Literature Review.

PubMed

Teranishi, Hideto; Koga, Yuhki; Nakashima, Kentaro; Morihana, Eiji; Ishii, Kanako; Sakai, Yasunari; Taguchi, Tomoaki; Oda, Yoshinao; Miyake, Noriko; Matsumoto, Naomichi; Ohga, Shouichi

2018-02-27

A 3-year-old Japanese girl treated for hypoplastic left heart syndrome and Dandy-Walker syndrome was diagnosed with Kabuki syndrome (KS) with a mutation of KMT2D; c.13285C>T:p.Q4429*. Concurrently, macrohematuria portended the diagnosis of Wilms tumor. Postoperative chemotherapy has achieved complete remission despite a prolonged and reduced regimen due to liver dysfunction and convulsions. Cancer predisposition has been suggested for KS due to oncogenic mutations in KMT2D or KDM6A. The first case of nephroblastoma exemplified the treatability of malignancies in KS patients, as shown in the 9 cases reviewed. Active screening and intervention are recommended for the cure of malignancy in KS children.

A Novel Mitochondrial DNA Deletion in Patient with Pearson Syndrome.

PubMed

Khasawneh, Rame; Alsokhni, Hala; Alzghoul, Bayan; Momani, Asim; Abualsheikh, Nazih; Kamal, Nazmi; Qatawneh, Mousa

2018-04-01

Arteriovenous Pearson syndrome is a very rare multisystemic mitochondrial disease characterized by sideroblastic anemia and exocrine pancreatic insufficiency. It is usually fatal in infancy. We reported a four-month-old infant presented with fever and pancytopenia. Bone marrow examination showed hypoplastic changes and sideroblastic features. Molecular Study showed a novel hetroplasmic mitochondrial deletions (m. 10760 -m. 15889+) in multiple genes (ND4,ND5,ND6, CYTB). In our patient the pathogenic mutation was 5.1 kb heteroplasmic deletions in multiple genes that are important and crucial for intact oxidative phosphorylation pathway and ATP production in the mitochondrial DNA. This mutation was not reported in literature including the mitomap.org website (which was last edited on Nov 30, 2017 and accessed on Jan 13, 2018).

Partial anomalous left pulmonary artery: report of two cases and review of literature.

PubMed

Sen, Supratim; Winlaw, David S; Sholler, Gary F

2015-06-01

We describe two cases of anomalous origin of the left lower-lobe pulmonary artery from the right pulmonary artery. The primary diagnosis was mitral atresia, hypoplastic left ventricle, aortic arch hypoplasia in the first child, and tetralogy of Fallot in the second. In both cases, the pulmonary trunk gave rise to a left pulmonary artery in the normal position. In addition, a second branch of the left pulmonary artery arose from the right pulmonary artery, and passed posterior and inferior to the left main or upper-lobe bronchus to supply the left lower lobe. In this review, we compare our findings with previously reported examples of this extremely rare cardiac malformation, and discuss possible embryological explanations for the lesion.

Regional odontodysplasia involving three quadrants of the jaws: a case report.

PubMed

Quinderé, Lêda Bezerra; Cavalcante, Roberta Barroso; Nonaka, Cassiano Francisco Weege; Miguel, Márcia Cristina da Costa; de Souza, Lélia Batista

2010-01-01

Regional odontodysplasia is a rare developmental anomaly of the teeth that affects enamel and dentin. Its etiology is unknown, but the most accepted theory refers to circulatory disorders associated with vascular nevi. An uncommon case of regional odontodysplasia involving three quadrants of the jaws is reported. An 8-year-old boy was referred to the authors' institution with lack of teeth as a major symptom. There was no hereditary anomaly in the family. Extraoral examination revealed a brown discoloration on the skin on the right side of the face, neck, and chest. Detailed intraoral examination showed hypoplastic and carious teeth. Fistulae and gingival overgrowth were also observed. Radiographically, the affected teeth presented the pathognomonic image of "ghost teeth." Conservative treatment was instituted.

Rathke's cyst with ectopic neurohypophysis presenting as severe short stature with delayed puberty.

PubMed

Dutta, Deep; Roy, Ajitesh; Ghosh, Sujoy; Mukhopadhyay, Pradip; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

Ectopic neurohypophysis (EN) is found in nearly half of children with growth hormone deficiency (GHD). Rathke's cyst (RC) is uncommon in children and when present, hypopituitarism is found in nearly half of them. We present a fourteen and half-year-old girl with severe short stature and delayed puberty who on evaluation was found to have GHD, secondary hypocortisolism, and hypogonadism. Imaging revealed hypoplastic anterior pituitary, stalk agenesis, EN at tuber cinereum and intrapituitary RC. This is perhaps the first report of simultaneous occurrence of EN and RC, which was seen in a girl with multiple pituitary hormone deficiency. A primary defect in pituitary development may explain this simultaneous occurrence of EN and RC and hence this severe anterior pituitary function deficit.

Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.

PubMed Central

Meinecke, P; Passarge, E

1991-01-01

The clinical and radiological findings in a pair of sibs with microcephalic osteodysplastic primordial dwarfism (MOPD) are described, a boy who survived for 5 1/2 years and his more severely affected younger sister, who died at the age of 6 months. Neuropathological studies in this girl showed marked micrencephaly with severely hypoplastic, poorly gyrated frontal lobes and absent corpus callosum. Our observation supports the hypothesis that types I and III MOPD probably constitute a spectrum of one and the same entity and published data together with this report are consistent with autosomal recessive inheritance. The pathogenesis of this condition is as yet unknown, but its characteristics indicate a basic defect affecting cell proliferation and tissue differentiation. Images PMID:1770539

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

PubMed Central

Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

PubMed

Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

Short-term effects of air pollution on daily hospital admissions for cardiovascular diseases in western China.

PubMed

Ma, Yuxia; Zhang, Haipeng; Zhao, Yuxin; Zhou, Jianding; Yang, Sixu; Zheng, Xiaodong; Wang, Shigong

2017-06-01

Controlling the confounding factors on cardiovascular diseases, such as long-time trend, calendar effect, and meteorological factors, a generalized additive model (GAM) was used to investigate the short-term effects of air pollutants (PM 10 , SO 2 , and NO 2 ) on daily cardiovascular admissions from March 1st to May 31st during 2007 to 2011 in Lanzhou, a heavily polluted city in western China. The influences of air pollutants were examined with different lag structures, and the potential effect modification by dust storm in spring was also investigated. Significant associations were found between air pollutants and hospital admissions for cardiovascular diseases both on dust event days and non-dust event days in spring. Air pollutants had lag effects on different age and gender groups. Relative risks (RRs) and their 95% confidence intervals (CIs) associated with a 10 μg/m 3 increase were 1.14 (1.04~1.26) on lag1 for PM 10 , 1.31 (1.21~1.51) on lag01 for SO 2 , and 1.96 (1.49~2.57) on lag02 for NO 2 on dust days. Stronger effects of air pollutants were observed for females and the elderly (≥60 years). Our analysis concluded that the effects of air pollutants on cardiovascular admissions on dust days were significantly stronger than non-dust days. The current study strengthens the evidence of effects of air pollution on health and dust-exacerbated cardiovascular admissions in Lanzhou.

Purtscher-like retinopathy associated with cerebro- or cardiovascular surgery.

PubMed

Oshida, Eiki; Machida, Shigeki; Nishimura, Tomoharu; Sakamoto, Masaki

2017-12-01

To report the findings in five patients of Purtscher-like retinopathy that developed after cerebro- or cardiovascular surgeries. Three women and two men with a mean age of 56.6 years were studied. They had had cerebro- or cardiovascular disease that was treated by major vascular surgery. Postoperatively, all of the patients developed multiple patches of retinal whitening in the area corresponding to the radial peripapillary capillaries in the posterior pole of the eye uni- or bilaterally. In two patients, the optic nerve head was involved which affected their vision severely. Hematological examinations showed hypercoagulable state after the surgeries. The retinal pathologies abated with time. These results indicate that major cardio- or cerebrovascular surgeries can cause Purtscher-like retinopathy. The hypercoagulable state and specific structures of the radial peripapillary capillaries may play a role in pathogenesis of this disease.

Implementation of a cardiovascular disease prevention program among school-aged children: a pilot study.

PubMed

Addison, Clifton C; Jenkins, Brenda W; White, Monique S; Young, Lavon

2006-09-01

The objective of this study was to test students' knowledge of cardiovascular disease information and to determine if a carefully structured training program administered to high school students would increase their knowledge about cardiovascular disease and risk factors that are preventable. A pilot study was conducted during which fifty high school students from nine counties in the State of Mississippi were measured for their knowledge of hypertension both at baseline and after the completion of an intervention training activity. There were significant gains in knowledge between the pre-test and the post-test that the students completed. The gains in knowledge indicate that elimination of risk factors is possible if all health care and school-based prevention programs are implemented to positively impact changes in eating and physical activity behaviors. Students' involvement in such activities could translate into significant changes in risk factors at these ages and throughout their lifetime. It is widely accepted that these behavioral changes, if sustained into adulthood, could have the potential to influence cardiovascular risk reduction.

Implementation of a Cardiovascular Disease Prevention Program among School-Aged Children: A Pilot Study

PubMed Central

Addison, Clifton C.; Jenkins, Brenda W.; White, Monique S.; Young, Lavon

2006-01-01

The objective of this study was to test students’ knowledge of cardiovascular disease information and to determine if a carefully structured training program administered to high school students would increase their knowledge about cardiovascular disease and risk factors that are preventable. A pilot study was conducted during which fifty high school students from nine counties in the State of Mississippi were measured for their knowledge of hypertension both at baseline and after the completion of an intervention training activity. There were significant gains in knowledge between the pre-test and the post-test that the students completed. The gains in knowledge indicate that elimination of risk factors is possible if all health care and school-based prevention programs are implemented to positively impact changes in eating and physical activity behaviors. Students’ involvement in such activities could translate into significant changes in risk factors at these ages and throughout their lifetime. It is widely accepted that these behavioral changes, if sustained into adulthood, could have the potential to influence cardiovascular risk reduction. PMID:16968974

Cell Systems to Investigate the Impact of Polyphenols on Cardiovascular Health

PubMed Central

Grootaert, Charlotte; Kamiloglu, Senem; Capanoglu, Esra; Van Camp, John

2015-01-01

Polyphenols are a diverse group of micronutrients from plant origin that may serve as antioxidants and that contribute to human health in general. More specifically, many research groups have investigated their protective effect against cardiovascular diseases in several animal studies and human trials. Yet, because of the excessive processing of the polyphenol structure by human cells and the residing intestinal microbial community, which results in a large variability between the test subjects, the exact mechanisms of their protective effects are still under investigation. To this end, simplified cell culture systems have been used to decrease the inter-individual variability in mechanistic studies. In this review, we will discuss the different cell culture models that have been used so far for polyphenol research in the context of cardiovascular diseases. We will also review the current trends in cell culture research, including co-culture methodologies. Finally, we will discuss the potential of these advanced models to screen for cardiovascular effects of the large pool of bioactive polyphenols present in foods and their metabolites. PMID:26569293

Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion.

PubMed

Breccia, Massimo; Pregno, Patrizia; Spallarossa, Paolo; Arboscello, Eleonora; Ciceri, Fabio; Giorgi, Mauro; Grossi, Alberto; Mallardo, Mario; Nodari, Savina; Ottolini, Stefano; Sala, Carla; Tortorella, Giovanni; Rosti, Gianantonio; Pane, Fabrizio; Minotti, Giorgio; Baccarani, Michele

2017-04-01

Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia.

A coupling method for a cardiovascular simulation model which includes the Kalman filter.

PubMed

Hasegawa, Yuki; Shimayoshi, Takao; Amano, Akira; Matsuda, Tetsuya

2012-01-01

Multi-scale models of the cardiovascular system provide new insight that was unavailable with in vivo and in vitro experiments. For the cardiovascular system, multi-scale simulations provide a valuable perspective in analyzing the interaction of three phenomenons occurring at different spatial scales: circulatory hemodynamics, ventricular structural dynamics, and myocardial excitation-contraction. In order to simulate these interactions, multiscale cardiovascular simulation systems couple models that simulate different phenomena. However, coupling methods require a significant amount of calculation, since a system of non-linear equations must be solved for each timestep. Therefore, we proposed a coupling method which decreases the amount of calculation by using the Kalman filter. In our method, the Kalman filter calculates approximations for the solution to the system of non-linear equations at each timestep. The approximations are then used as initial values for solving the system of non-linear equations. The proposed method decreases the number of iterations required by 94.0% compared to the conventional strong coupling method. When compared with a smoothing spline predictor, the proposed method required 49.4% fewer iterations.

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues.

PubMed

Borovjagin, Anton V; Ogle, Brenda M; Berry, Joel L; Zhang, Jianyi

2017-01-06

Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional 2-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and preclinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents. © 2017 American Heart Association, Inc.

Role of substance P in the cardiovascular system.

PubMed

Mistrova, Eliska; Kruzliak, Peter; Chottova Dvorakova, Magdalena

2016-08-01

This article provides an overview of the structure and function of substance P signalling system and its involvement in the cardiovascular regulation. Substance P is an undecapeptide originating from TAC1 gen and belonging to the tachykinin family. The biological actions of substance P are mainly mediated through neurokinin receptor 1 since substance P is the ligand with the highest affinity to neurokinin receptor 1. Substance P is widely distributed within the central and peripheral nervous systems as well as in the cardiovascular system. Substance P is involved in the regulation of heart frequency, blood pressure and in the stretching of vessels. Substance P plays an important role in ischemia and reperfusion and cardiovascular response to stress. Additionally, it has been also implicated in angiogenesis, pain transmission and inflammation. The substance P/neurokinin receptor 1 receptor system is involved in the molecular bases of many human pathological processes. Antagonists of neurokinin receptor 1 receptor could provide clinical solutions for a variety of diseases. Neurokinin receptor 1 antagonists are already used in the prevention of chemotherapy induced nausea and vomiting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wall shear stress fixed points in cardiovascular fluid mechanics.

PubMed

Arzani, Amirhossein; Shadden, Shawn C

2018-05-17

Complex blood flow in large arteries creates rich wall shear stress (WSS) vectorial features. WSS acts as a link between blood flow dynamics and the biology of various cardiovascular diseases. WSS has been of great interest in a wide range of studies and has been the most popular measure to correlate blood flow to cardiovascular disease. Recent studies have emphasized different vectorial features of WSS. However, fixed points in the WSS vector field have not received much attention. A WSS fixed point is a point on the vessel wall where the WSS vector vanishes. In this article, WSS fixed points are classified and the aspects by which they could influence cardiovascular disease are reviewed. First, the connection between WSS fixed points and the flow topology away from the vessel wall is discussed. Second, the potential role of time-averaged WSS fixed points in biochemical mass transport is demonstrated using the recent concept of Lagrangian WSS structures. Finally, simple measures are proposed to quantify the exposure of the endothelial cells to WSS fixed points. Examples from various arterial flow applications are demonstrated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Update on apelin peptides as putative targets for cardiovascular drug discovery.

PubMed

Charles, Christopher J

2011-06-01

The physiological importance of GPCR/ligand pathways is highlighted by the fact that numerous pathologies are attributed to their signaling dysfunction. Over 50% of the pharmaceutical drugs currently used to treat human disease are based on compounds that interact with GPCRs. Apelin/APJ constitutes a novel endogenous peptide/GPCR system proposed to be involved in a wide range of physiological functions. Early evidence suggests that apelin/APJ may hold promise as a target for development of novel therapeutic agents which may counteract a number of pathologies including cardiovascular disease. Despite advances in treatment of cardiovascular disease, incidence, prevalence, morbidity and economic costs remain high necessitating the development of new treatment paradigms. This review summarizes apelin/APJ structure, distribution and regulation; presents evidence for a role of apelin in pressure/volume homeostasis and in the pathophysiology of cardiovascular disease; summarizes data on beneficial effects of apelin in preclinical, animal models of cardiovascular disease and measurement of plasma levels of apelin across the full spectrum of cardiovascular disease in humans; and notes the first studies describing bioactivity of apelin peptides in human healthy volunteers and patients with heart failure. More clarity is needed on the precise physiological/pathophysiological role of the apelin/APJ system in human health and disease. Nonetheless, preclinical studies and initial studies in humans show that APJ antagonism may represent a novel therapeutic target for patients with cardiovascular disease. Development of appropriately validated assays for apelin will clarify circulating levels of the peptide in health and disease. Development of suitable agonists/antagonists will pave the way for much needed future studies essential for advancing this promising field of drug discovery.

A new Web-based medical tool for assessment and prevention of comprehensive cardiovascular risk

PubMed Central

Franchi, Daniele; Cini, Davide; Iervasi, Giorgio

2011-01-01

Background: Multifactor cardiovascular disease is the leading cause of death; besides well-known cardiovascular risk factors, several emerging factors such as mental stress, diet type, and physical inactivity, have been associated to cardiovascular disease. To date, preventive strategies are based on the concept of absolute risk calculated by different algorithms and scoring systems. However, in general practice the patient’s data collection represents a critical issue. Design: A new multipurpose computer-based program has been developed in order to:1) easily calculate and compare the absolute cardiovascular risk by the Framingham, Procam, and Progetto Cuore algorithms; 2) to design a web-based computerized tool for prospective collection of structured data; 3) to support the doctor in the decision-making process for patients at risk according to recent international guidelines. Methods: During a medical consultation the doctor utilizes a common computer connected by Internet to a medical server where all the patient’s data and software reside. The program evaluates absolute and relative cardiovascular risk factors, personalized patient’s goals, and multiparametric trends, monitors critical parameter values, and generates an automated medical report. Results: In a pilot study on 294 patients (47% males; mean age 60 ± 12 years [±SD]) the global time to collect data at first consultation was 13 ± 11 minutes which declined to 8 ± 7 minutes at the subsequent consultation. In 48.2% of cases the program revealed 2 or more primary risk factor parameters outside guideline indications and gave specific clinical suggestions to return altered parameters to target values. Conclusion: The web-based system proposed here may represent a feasible and flexible tool for clinical management of patients at risk of cardiovascular disease and for epidemiological research. PMID:21445280

[Quality management in cardiovascular echography].

PubMed

Gullace, Giuseppe

2002-12-01

The quality management of an organization can be defined as the ability to identify, plan and implement programs of measure, analysis, verification and control that allow to monitor management, resources, activities, processes and output/outcome of the same organization, including the satisfaction of the customers. Whatever the model used, it is demonstrated that the management-quality system, either for professional quality or for organization, turns out to be effective even in the health organizations within and to any level of organizational-structural complexity. The present paper concerns the experience of the Italian Society of Cardiovascular Echography (SIEC) on quality certification, both as a scientific society compared to other health organizations and to cardiovascular echo laboratories, and the definition of minimum requirements for the accreditation of the same laboratories. The model most frequently used for quality management is represented by the ISO 9000: Vision 2000, that is a management model with specific reference to the organization and the customer satisfaction. The model applied to the health structure needs a rapid change in mentality that addresses the operators to define, share and achieve objectives to be brought on by means of an active collaboration, group activity and deep sense of belonging necessary to the attainment of expected objectives. When the model is applied by a scientific society, it is necessary to take into account the different structural and functional organization, the constitution and the operators differing on the point of view of origin, experiences, mentality, and roles. The ISO 9000: Vision 2000 model can be applied also to the cardiovascular echo laboratory which may be compared to a simple organization; for its corrected functioning, SIEC has defined minimal requirements for the accreditation, realization and modalities to carry out and manage quality. The quality system represents a new way of operating of an organization that enhances capability and performance of the operators, stimulates their creativity and facilitates the activities of all, to guarantee both the quality of the product and the satisfaction of operators and customers at the same time.

Characterization of X-linked Hypohidrotic Ectodermal Dysplasia (XL-HED) Hair and Sweat Gland Phenotypes Using Phototrichogram Analysis and Live Confocal Imaging

PubMed Central

Jones, Kyle B.; Goodwin, Alice F.; Landan, Maya; Seidel, Kerstin; Tran, Dong-Kha; Hogue, Jacob; Chavez, Miquella; Fete, Mary; Yu, Wenli; Hussein, Tarek; Johnson, Ramsey; Huttner, Kenneth; Jheon, Andrew H.; Klein, Ophir D.

2015-01-01

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia (ED), which encompasses a large group of syndromes that share several phenotypic features such as missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. X-linked hypohidrotic ectodermal dysplasia (XL-HED) is associated with mutations in ectodysplasin (EDA1). Hypohidrosis due to hypoplastic sweat glands and thin, sparse hair are phenotypic features that significantly affect the daily lives of XL-HED individuals and therefore require systematic analysis. We sought to determine the quality of life of individuals with XL-HED and to quantify sweat duct and hair phenotypes using confocal imaging, pilocarpine iontophoresis, and phototrichogram analysis. Using these highly sensitive and non-invasive techniques, we demonstrated that 11/12 XL-HED individuals presented with a complete absence of sweat ducts and that none produced sweat. We determined that the thin hair phenotype observed in XL-HED was due to multiple factors, such as fewer terminal hairs with decreased thickness and slower growth rate, as well as fewer follicular units and fewer hairs per unit. The precise characterization of XL-HED phenotypes using sensitive and non-invasive techniques presented in our study will improve upon larger genotype-phenotype studies and in the assessment of future therapies in XL-HED. PMID:23687000

Neuroimaging of Dandy-Walker malformation: new concepts.

PubMed

Correa, Gustavo Gumz; Amaral, Lázaro Faria; Vedolin, Leonardo Modesti

2011-12-01

Dandy-Walker malformation (DWM) is the most common human cerebellar malformation, characterized by hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and an enlarged posterior fossa with upward displacement of the lateral sinuses, tentorium, and torcular. Although its pathogenesis is not completely understood, there are several genetic loci related to DWM as well as syndromic malformations and congenital infections. Dandy-Walker malformation is associated with other central nervous system abnormalities, including dysgenesis of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube defects. Hydrocephalus plays an important role in the development of symptoms and neurological outcome in patients with DWM, and the aim of surgical treatment is usually the control of hydrocephalus and the posterior fossa cyst. Imaging modalities, especially magnetic resonance imaging, are crucial for the diagnosis of DWM and distinguishing this disorder from other cystic posterior fossa lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection with cerebrospinal fluid signal intensity and a median line communication with the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna presents as an extraaxial fluid collection posteroinferior to an intact cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar hemispheres and the fourth ventricle. Patients with DWM show an enlarged posterior fossa filled with a cystic structure that communicates freely with the fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is of utmost importance for understanding the cerebellar malformations, including DWM, and other related entities.

Oral Rehabilitation of Young Adult with Amelogenesis Imperfecta.

PubMed

Leung, Vincent Ws; Low, Bernard; Yang, Yanqi; Botelho, Michael G

2018-05-01

Amelogenesis imperfecta is a heterogeneous group of hereditary disorders that affect the enamel formation of the primary and permanent dentitions while the remaining tooth structure is normal. Appropriate patient care is necessary to prevent adverse effects on dental oral health, dental disfigurement, and psychological well-being. This clinical report presents a 27-year-old Chinese male with amelogenesis imperfecta (AI) and his restorative management. This clinical report presents a 27-year-old Chinese male with AI and his restorative management. Extraoral examination showed a skeletal class III profile and increased lower facial proportion. Intraorally, all the permanent dentition was hypoplastic with noticeable tooth surface loss and a yellow-brown appearance. This was complicated with a mild maloc-clusion and food packing on his posterior teeth. The patient wanted to improve his appearance and masticatory efficiency. Orthodontic treatment was performed to treat the mild malocclu-sion and create physiological interproximal spacing to minimize tooth preparation and facilitate oral hygiene. This report demonstrates how a multidisciplinary approach for the management of AI can achieve a predictable, functional, and esthetic outcome. Orthodontic treatment facilitated a conservative prosthodontic treatment outcome by selectively increasing interproximal space, minimizing tooth preparation, correcting posterior bilateral cross-bite, as well as an anterior reverse overjet and derotation of the canines. This case report demonstrates the effective restoration of AI using a multidisciplinary approach to overcome crowding using a relatively conservative approach.

Amelogenesis imperfecta

PubMed Central

Crawford, Peter JM; Aldred, Michael; Bloch-Zupan, Agnes

2007-01-01

Amelogenesis imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations. PMID:17408482

A Recessive Mutation Resulting in a Disabling Amino Acid Substitution (T194R) in the LHX3 Homeodomain Causes Combined Pituitary Hormone Deficiency

PubMed Central

Bechtold-Dalla Pozza, Susanne; Hiedl, Stefan; Roeb, Julia; Lohse, Peter; Malik, Raleigh E.; Park, Soyoung; Durán-Prado, Mario; Rhodes, Simon J.

2012-01-01

Background/Aims Recessive mutations in the LHX3 ho-meodomain transcription factor gene are associated with developmental disorders affecting the pituitary and nervous system. We describe pediatric patients with combined pituitary hormone deficiency (CPHD) who harbor a novel mutation in LHX3. Methods Two female siblings from related parents were examined. Both patients had neonatal complications. The index patient had CPHD featuring deficiencies of GH, LH, FSH, PRL, and TSH, with later onset of ACTH deficiency. She also had a hypoplastic anterior pituitary, respiratory distress, hearing impairment, and limited neck rotation. The LHX3 gene was sequenced and the biochemical properties of the predicted altered proteins were characterized. Results A novel homozygous mutation predicted to change amino acid 194 from threonine to arginine (T194R) was detected in both patients. This amino acid is conserved in the DNA-binding homeodomain. Computer modeling predicted that the T194R change would alter the homeodomain structure. The T194R protein did not bind tested LHX3 DNA recognition sites and did not activate the α-glycoprotein and PRL target genes. Conclusion The T194R mutation affects a critical residue in the LHX3 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in the LHX3 gene. PMID:22286346

Functionally univentricular heart and the fontan operation: lessons learned about patterns of practice and outcomes from the congenital heart surgery databases of the European association for cardio-thoracic surgery and the society of thoracic surgeons.

PubMed

Jacobs, Jeffrey Phillip; Maruszewski, Bohdan

2013-10-01

"The term "functionally univentricular heart" describes a spectrum of congenital cardiovascular malformations in which the ventricular mass may not readily lend itself to partitioning that commits one ventricular pump to the systemic circulation and another to the pulmonary circulation." The purpose of this article is to review patterns of practice and outcomes in the Congenital Heart Surgery Databases (CHSDBs) of the European Association for Cardio-Thoracic Surgery (EACTS) and the Society of Thoracic Surgeons (STS) in patients with functionally univentricular hearts undergoing the Fontan operation. We examined all index operations performed on patients with functionally univentricular hearts in the EACTS and STS-CHSDBs over 4 years from 2007 to 2010, inclusive. The most common diagnostic categories are hypoplastic left heart syndrome, tricuspid atresia, and double inlet left ventricle. The Fontan operation makes up 3.2% of all cardiac operations in the EACTS and STS-CHSDBs over 4 years from 2007 to 2010, inclusive. Of all the patients undergoing a Fontan procedure, 65.1% had an extracardiac Fontan, 21.5% had a lateral tunnel, and 5.8% had a Fontan revision or conversion (Re-do Fontan). In operations where fenestration status is known, 68.5% of the Fontan operations were fenestrated. During the four years of this analysis, only 5 patients had ventricular septation. Exclusive of Fontan revision or conversion (Re-do Fontan), all remaining Fontan operations had a discharge mortality of 2.3%. Fontan revision or conversion (Re-do Fontan) had a discharge mortality of 12.8%. The STS database is largest CHSDB in North America. The EACTS database is largest CHSDB in Europe. This review of data from EACTS and STS allows for unique documentation of practice patterns and outcomes. From this analysis, it is clear that patients with functionally univentricular hearts present a challenging problem; however, exclusive of Fontan revision or conversion (Re-do Fontan), the Fontan operation has a discharge mortality of 2.3%.

Towards Robot-Assisted Echocardiographic Monitoring in Catheterization Laboratories : Usability-Centered Manipulator for Transesophageal Echocardiography.

PubMed

Pahl, Christina; Ebelt, Henning; Sayahkarajy, Mostafa; Supriyanto, Eko; Soesanto, Amiliana

2017-08-15

This paper proposes a robotic Transesophageal Echocardiography (TOE) system concept for Catheterization Laboratories. Cardiovascular disease causes one third of all global mortality. TOE is utilized to assess cardiovascular structures and monitor cardiac function during diagnostic procedures and catheter-based structural interventions. However, the operation of TOE underlies various conditions that may cause a negative impact on performance, the health of the cardiac sonographer and patient safety. These factors have been conflated and evince the potential of robot-assisted TOE. Hence, a careful integration of clinical experience and Systems Engineering methods was used to develop a concept and physical model for TOE manipulation. The motion of different actuators of the fabricated motorized system has been tested. It is concluded that the developed medical system, counteracting conflated disadvantages, represents a progressive approach for cardiac healthcare.

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

PubMed

Danias, Peter G; Tritos, Nicholas A; Stuber, Matthias; Kissinger, Kraig V; Salton, Carol J; Manning, Warren J

2003-07-01

Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

A preliminary investigation of the growth of an aneurysm with a multiscale monolithic Fluid-Structure interaction solver

NASA Astrophysics Data System (ADS)

Cerroni, D.; Manservisi, S.; Pozzetti, G.

2015-11-01

In this work we investigate the potentialities of multi-scale engineering techniques to approach complex problems related to biomedical and biological fields. In particular we study the interaction between blood and blood vessel focusing on the presence of an aneurysm. The study of each component of the cardiovascular system is very difficult due to the fact that the movement of the fluid and solid is determined by the rest of system through dynamical boundary conditions. The use of multi-scale techniques allows us to investigate the effect of the whole loop on the aneurysm dynamic. A three-dimensional fluid-structure interaction model for the aneurysm is developed and coupled to a mono-dimensional one for the remaining part of the cardiovascular system, where a point zero-dimensional model for the heart is provided. In this manner it is possible to achieve rigorous and quantitative investigations of the cardiovascular disease without loosing the system dynamic. In order to study this biomedical problem we use a monolithic fluid-structure interaction (FSI) model where the fluid and solid equations are solved together. The use of a monolithic solver allows us to handle the convergence issues caused by large deformations. By using this monolithic approach different solid and fluid regions are treated as a single continuum and the interface conditions are automatically taken into account. In this way the iterative process characteristic of the commonly used segregated approach, it is not needed any more.

Cardiac rehabilitation and the therapeutic environment: the importance of physical, social, and symbolic safety for programme participation among women.

PubMed

Sutton, Erica J; Rolfe, Danielle E; Landry, Mireille; Sternberg, Leonard; Price, Jennifer A D

2012-08-01

To report an exploration of the multidimensionality of safety in cardiac rehabilitation programmes as perceived by women who were enrolled in the Women's Cardiovascular Health Initiative in Toronto, Canada. Cardiovascular disease is the leading cause of death among women. Although cardiac rehabilitation is clinically effective, significantly fewer women than men participate in available programmes. The literature identifies factors affecting women's cardiac rehabilitation participation, and provides possible explanations for this gender disparity. Although safety is mentioned among the barriers to women's cardiac rehabilitation participation, the extent to which safety contributes to programme participation, completion, and maintenance remains under-explored in the cardiac rehabilitation literature. We conducted an exploratory qualitative study to examine the role safety and place play for women engaged in cardiac prevention and rehabilitation at the Women's Cardiovascular Health Initiative. Methods.  From 2005-2006, 14 participants engaged in semi-structured, qualitative interviews lasting 30-90 minutes. Discussions addressed women's experiences at the Women's Cardiovascular Health Initiative. Interview transcripts were analysed using thematic analysis. Three themes were developed: 'Safety', which was sub-categorized according to physical, social, and symbolic interpretations of safety, 'searching for a sense of place', and 'confidence and empowerment'. Feeling physically, socially, and symbolically safe in one's cardiac rehabilitation environment may contribute to programme adherence and exercise maintenance for women. Focusing on comprehensive notions of safety in future cardiac rehabilitation research could offer insight into why many women do not maintain an exercise regimen in currently structured cardiac rehabilitation and community programmes. © 2012 Blackwell Publishing Ltd.

Oral health and cardiovascular care: Perceptions of people with cardiovascular disease

PubMed Central

Salamonson, Yenna; Ajwani, Shilpi; Bhole, Sameer; Bishop, Joshua; Lintern, Karen; Nolan, Samantha; Rajaratnam, Rohan; Redfern, Julie; Sheehan, Maria; Skarligos, Fiona; Spencer, Lissa; Srinivas, Ravi

2017-01-01

Main objective The aim of this study was to explore the perception of patients with cardiovascular disease towards oral health and the potential for cardiac care clinicians to promote oral health. Method A needs assessment was undertaken with twelve patients with cardiovascular disease attending cardiac rehabilitation between 2015 and 2016, in three metropolitan hospitals in Sydney, Australia. These patients participated in face-to-face semi-structured interviews. Data was analysed using thematic analysis. Results Results suggested that while oral health was considered relevant there was high prevalence of poor oral health among participants, especially those from socioeconomic disadvantaged background. Awareness regarding the importance of oral health care its impact on cardiovascular outcomes was poor among participants. Oral health issues were rarely discussed in the cardiac setting. Main barriers deterring participants from seeking oral health care included lack of awareness, high cost of dental care and difficulties in accessing the public dental service. Findings also revealed that participants were interested in receiving further information about oral health and suggested various mediums for information delivery. The concept of cardiac care clinicians, especially nurses providing education, assessment and referrals to ongoing dental care was well received by participants who felt the post-acute period was the most appropriate time to receive oral health care advice. The issues of oral health training for non-dental clinicians and how to address existing barriers were highlighted by participants. Relevance to clinical practice The lack of oral health education being provided to patients with cardiovascular disease offers an opportunity to improve care and potentially, outcomes. In view of the evidence linking poor oral health with cardiovascular disease, cardiac care clinicians, especially nurses, should be appropriately trained to promote oral health in their practice. Affordable and accessible dental care services for people with cardiovascular disease should be considered and offered by health services in Australia. PMID:28727751

Predictive Performance of Echocardiographic Parameters for Cardiovascular Events Among Elderly Treated Hypertensive Patients.

PubMed

Chowdhury, Enayet K; Jennings, Garry L R; Dewar, Elizabeth; Wing, Lindon M H; Reid, Christopher M

2016-07-01

Hypertension leads to cardiac structural and functional changes, commonly assessed by echocardiography. In this study, we assessed the predictive performance of different echocardiographic parameters including left ventricular hypertrophy (LVH) on future cardiovascular outcomes in elderly hypertensive patients without heart failure. Data from LVH substudy of the Second Australian National Blood Pressure trial were used. Echocardiograms were performed at entry into the study. Cardiovascular outcomes were identified over short term (median 4.2 years) and long term (median 10.9 years). LVH was defined using threshold values of LV mass (LVM) indexed to either body surface area (BSA) or height(2.7): >115/95g/m(2) (LVH-BSA(115/95)) or ≥49/45g/m(2.7) (LVH-ht(49/45)) in males/females, respectively, and ≥125g/m(2) (LVH-BSA(125)) or ≥51g/m(2.7) (LVH-ht(51)) for both sexes. In the 666 participants aged ≥65 years in this analysis, LVH prevalence at baseline was 33%-70% depending on definition; and after adjusting for potential risk factors, only LVH-BSA(115/95) predicted both short- and long-term cardiovascular outcomes. Participants having LVH-BSA(115/95) (69%) at baseline had twice the risk of having any first cardiovascular event over the short term (hazard ratio, 95% confidence interval: 2.00, 1.12-3.57, P = 0.02) and any fatal cardiovascular events (2.11, 1.21-3.68, P = 0.01) over the longer term. Among other echocardiographic parameters, LVM and LVM indexed to either BSA or height(2.7) predicted cardiovascular events over both short and longer term. In elderly treated hypertensive patients without heart failure, determining LVH by echocardiography is highly dependent on the methodology adopted. LVH-BSA(115/95) is a reliable predictor of future cardiovascular outcomes in the elderly. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association of A Dilated Coronary Sinus in the Fetus with Actual and Apparent Coarctation of the Aorta and Diminutive Left Heart Structures.

PubMed

Ramaswamy, Prema; Rafii, Daniela; Osmolovsky, Marina; Agarwal, Arpit; Amirtharaj, Cynthia

2016-12-01

Evidence suggests an association between left heart obstructive lesions and dilated coronary sinus (DCS), but this has not been studied in fetuses. A retrospective review of fetal echocardiograms (FE) over an 8-year period was conducted, and patients with DCS were identified and confirmed postnatally. There were 5840 FE performed on 4920 women during this period. Of 49 patients with DCS, 22 had normal intracardiac anatomy and 27 patients had congenital heart disease (CHD) yielding an incidence of 4.6 % in the presence of CHD (27/584). Of 27 patients with DCS and CHD, approximately a third had either hypoplastic left ventricles and/or coarctations (10/27, 37 %). The incidence of left heart obstructive lesions was much higher in the presence of a DCS (37 % vs 45/557, 8 %, p < 0.0001). The odds ratio of left heart hypoplasia in fetuses with CHD and a DCS was 6.6 (95 % CI 2.8-15.3). Comparison of patients with postnatally confirmed coarctation with those with normal intracardiac anatomy with DCS, revealed that in the former, the right ventricle (p = 0.005), pulmonic valve annulus (p = 0.0001) and the tricuspid inflow were larger (p = 0.001) compared to corresponding left-sided structures. The size of the DCS was not significantly different between the two groups, but in the former, the DCS was more closely related to the posterior leaflet of the mitral valve and caused a significant diminution of the mitral inflow. Our study suggests a strong association, possibly causal, between left heart obstructive lesions and DCS in utero.

Inheritance Analysis of Congenital Left Ventricular Outflow Tract Obstruction Malformations: Segregation, Multiplex Relative Risk, and Heritability

PubMed Central

McBride, Kim L.; Pignatelli, Ricardo; Lewin, Mark; Ho, Trang; Fernbach, Susan; Menesses, Andres; Lam, Wilbur; Leal, Suzanne M.; Kaplan, Norman; Schliekelman, Paul; Towbin, Jeffrey A.; Belmont, John W.

2006-01-01

The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71–0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1–6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. PMID:15690347

Histogenesis of retinal dysplasia in trisomy 13

PubMed Central

Chan, Ada; Lakshminrusimha, Satyan; Heffner, Reid; Gonzalez-Fernandez, Federico

2007-01-01

Background Although often associated with holoprosencephaly, little detail of the histopathology of cyclopia is available. Here, we describe the ocular findings in a case of trisomy 13 to better understand the histogenesis of the rosettes, or tubules, characteristic of the retinal dysplasia associated with this condition. Methods A full pediatric autopsy was performed of a near term infant who died shortly after birth from multiple congenital anomalies including fused facial-midline structures. A detailed histopathological study of the ocular structures was performed. The expression of interphotoreceptor retinoid-binding protein (IRBP), cellular retinal-binding protein (CRALBP), rod opsin, and Sonic Hedgehog (Shh) were studied by immunohistochemistry. Results Holoprosencephaly, and a spectrum of anatomical findings characteristic of Patau's syndrome, were found. Cytogenetic studies demonstrated trisomy 13 [47, XY, +13]. The eyes were fused but contained two developed separate lenses. In contrast, the cornea, and angle structures were hypoplastic, and the anterior chamber had failed to form. The retina showed areas of normally laminated neural retina, whereas in other areas it was replaced by numerous neuronal rosettes. Histological and immunohistochemical studies revealed that the rosettes were composed of differentiated retinal neurons and Müller cell glia. In normally laminated retina, Shh expression was restricted to retinal-ganglion cells, and to a population of neurons in the inner zone of the outer nuclear layer. In contrast, Shh could not be detected in the dysplastic rosettes. Conclusion The histopathology of cyclopia appears to be more complex than what may have been previously appreciated. In fact, the terms "cyclopia" and "synophthalmia" are misnomers as the underlying mechanism is a failure of the eyes to form separately during development. The rosettes found in the dysplastic retina are fundamentally different than those of retinoblastoma, being composed of a variety of differentiated cell types. The dysplastic rosettes are essentially laminated retina failing to establish a polarized orientation, resulting in the formation of tubules. Finally, our findings suggest that defective ganglion cell Shh expression may contribute to the ocular pathology of cyclopia. PMID:18088410

Podiatric Medical Education: A Review.

ERIC Educational Resources Information Center

Pollock, George P.

1980-01-01

The basic curricular structure and courses deemed necessary to podiatric medical education are outlined and their rationale explained. Specialties appropriate to podiatric practice, such as electrophysiology and cardiovascular physiology, are noted, and the sequence of coursework suggested. (MSE)

Generative Retrieval Improves Learning and Retention of Cardiac Anatomy Using Transesophageal Echocardiography.

PubMed

Kleiman, Amanda M; Forkin, Katherine T; Bechtel, Allison J; Collins, Stephen R; Ma, Jennie Z; Nemergut, Edward C; Huffmyer, Julie L

2017-05-01

Transesophageal echocardiography (TEE) is a valuable monitor for patients undergoing cardiac and noncardiac surgery as it allows for evaluation of cardiovascular compromise in the perioperative period. It is challenging for anesthesiology residents and medical students to learn to use and interpret TEE in the clinical environment. A critical component of learning to use and interpret TEE is a strong grasp of normal cardiovascular ultrasound anatomy. Fifteen fourth-year medical students and 15 post-graduate year (PGY) 1 and 2 anesthesiology residents without prior training in cardiac anesthesia or TEE viewed normal cardiovascular anatomy TEE video clips; participants were randomized to learning cardiac anatomy in generative retrieval (GR) and standard practice (SP) groups. GR participants were required to verbally identify each unlabeled cardiac anatomical structure within 10 seconds of the TEE video appearing on the screen. Then a correctly labeled TEE video clip was shown to the GR participant for 5 more seconds. SP participants viewed the same TEE video clips as GR but there was no requirement for SP participants to generate an answer; for the SP group, each TEE video image was labeled with the correctly identified anatomical structure for the 15 second period. All participants were tested for intermediate (1 week) and late (1 month) retention of normal TEE cardiovascular anatomy. Improvement of intermediate and late retention of TEE cardiovascular anatomy was evaluated using a linear mixed effects model with random intercepts and random slopes. There was no statistically significant difference in baseline score between GR (49% ± 11) and SP (50% ± 12), with mean difference (95% CI) -1.1% (-9.5, 7.3%). At 1 week following the educational intervention, GR (90% ± 5) performed significantly better than SP (82% ± 11), with mean difference (95% CI) 8.1% (1.9, 14.2%); P = .012. This significant increase in scores persisted in the late posttest session at one month (GR: 83% ± 12; SP: 72% ± 12), with mean difference (95% CI) 10.2% (1.3 to 19.1%); P = .026. Mixed effects analysis showed significant improvements in TEE cardiovascular anatomy over time, at 5.9% and 3.5% per week for GR and SP groups respectively (P = .0003), and GR improved marginally faster than SP (P = .065). Medical students and anesthesiology residents inexperienced in the use of TEE showed both improved learning and retention of basic cardiovascular ultrasound anatomy with the incorporation of GR into the educational experience.

Major depressive disorder with anger attacks and cardiovascular risk factors.

PubMed

Fraguas, Renerio; Iosifescu, Dan V; Bankier, Bettina; Perlis, Roy; Clementi-Craven, Nicoletta; Alpert, Jonathan; Fava, Maurizio

2007-01-01

Depression and anger have been separately associated with cardiovascular risk factors. We investigated if major depressive disorder (MDD) with concomitant anger attacks was associated with cardiovascular risk factors. We measured total serum cholesterol, glycemia, resting blood pressure, and smoking parameters in 333 (52.9% women) MDD nonpsychotic outpatients, mean age of 39.4 years. MDD was diagnosed with the Structured Clinical Interview (SCID) in accordance with the Diagnostic and Statistic Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). The presence of anger attacks was established with the Massachusetts General Hospital Anger Attacks Questionnaire. In a logistic regression analysis, anger attacks were independently associated with cholesterol levels > or = 200 mg/dL (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.18-3.94) and years of smoking > 11 (OR, 2.59; 95% CI, 1.32-5.04). MDD with anger attacks was significantly associated with increased cholesterol levels and years of smoking.

Obesity and Atrial Fibrillation Prevalence, Pathogenesis, and Prognosis: Effects of Weight Loss and Exercise.

PubMed

Lavie, Carl J; Pandey, Ambarish; Lau, Dennis H; Alpert, Martin A; Sanders, Prashanthan

2017-10-17

Both obesity and atrial fibrillation (AF) are increasing in epidemic proportions, and both increase the prevalence of cardiovascular disease events. Obesity has adverse effects on cardiovascular hemodynamics and cardiac structure and function, and increases the prevalence of AF, partly related to electroanatomic remodeling in obese patients. However, numerous studies, including in AF, have demonstrated an obesity paradox, where overweight and obese patients with these disorders have a better prognosis than do leaner patients with the same degree of severity of cardiovascular disease/AF. In this paper, the authors discuss special issues regarding AF in obesity, as well as the evidence that despite the presence of an obesity paradox, there are benefits of weight loss, physical activity/exercise training, and increases in cardiorespiratory fitness on the prognosis of obese patients with AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Exploring the impact of gender inequities on the promotion of cardiovascular health of women in Pakistan.

PubMed

Barolia, Rubina; Clark, Alexander M; Higginbottom, Gina

2017-01-01

Cardiovascular disease exerts an enormous burden on women's health. The intake of a healthy diet may reduce this burden. However, social norms and economic constraints are often factors that restrain women from paying attention to their diet. Underpinned by critical realism, this study explores how gender/sex influences decision-making regarding food consumption among women of low socioeconomic status (SES). The study was carried out at two cardiac facilities in Karachi, Pakistan, on 24 participants (male and female from different ethnic backgrounds), who had received health education. Using an interpretive descriptive approach, the study identified major barriers to a healthy diet: proscribed gender roles and lack of women's autonomy, power, male domination, and abusive behaviours. Cardiovascular risk and disease outcomes for the Pakistani women of low SES are likely to further escalate if individual and structural barriers are not reduced using multifactorial approaches. © 2016 John Wiley & Sons Ltd.

The rhesus (Macaca mulatta) and crab-eating (Macaca fascicularis) monkeys in cardiovascular and aerospace research

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Ritzman, J. R.

1977-01-01

Two nonhuman primate species were used to investigate the effects of gravitoinertial forces on pilot incapacitation and performance impairment, to define human physiologic tolerance and safe exposure limits to these environments, and to obtain data which can be used to evolve new methods to improve man's G tolerance to match the structural capability of new generation aircraft. The macaca fascicularis was used to study the effects of environmental stress and atheroscelerosis on cerebral blood flow and function agents on myocardial and cardiovascular function were studied in the macaca mulatta.

Electrocardiogram and Imaging: An Integrated Approach to Arrhythmogenic Cardiomyopathies.

PubMed

Savino, Ketty; Bagliani, Giuseppe; Crusco, Federico; Padeletti, Margherita; Lombardi, Massimo

2018-06-01

Cardiovascular imaging has radically changed the management of patients with arrhythmogenic cardiomyopathies. This article focuses on the role of echocardiography and MRI in the diagnosis of these structural diseases. Cardiomyopathies with hypertrophic pattern (hypertrophic cardiomyopathy, restrictive cardiomyopathies, amyloidosis, Anderson-Fabry disease, and sarcoidosis), cardiomyopathies with dilated pattern, inflammatory cardiac diseases, and right ventricular arrhythmogenic cardiomyopathy are analyzed. Finally, anatomic predictors of arrhythmias and sudden cardiac death are discussed. Each paragraph is attended by clinical cases that are discussed on the electrocardiogram, after integrated with the anatomic, functional, and hemodynamic modifications of cardiovascular imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Computational design analysis for deployment of cardiovascular stents

NASA Astrophysics Data System (ADS)

Tammareddi, Sriram; Sun, Guangyong; Li, Qing

2010-06-01

Cardiovascular disease has become a major global healthcare problem. As one of the relatively new medical devices, stents offer a minimally-invasive surgical strategy to improve the quality of life for numerous cardiovascular disease patients. One of the key associative issues has been to understand the effect of stent structures on its deployment behaviour. This paper aims to develop a computational model for exploring the biomechanical responses to the change in stent geometrical parameters, namely the strut thickness and cross-link width of the Palmaz-Schatz stent. Explicit 3D dynamic finite element analysis was carried out to explore the sensitivity of these geometrical parameters on deployment performance, such as dog-boning, fore-shortening, and stent deformation over the load cycle. It has been found that an increase in stent thickness causes a sizeable rise in the load required to deform the stent to its target diameter, whilst reducing maximum dog-boning in the stent. An increase in the cross-link width showed that no change in the load is required to deform the stent to its target diameter, and there is no apparent correlation with dog-boning but an increased fore-shortening with increasing cross-link width. The computational modelling and analysis presented herein proves an effective way to refine or optimise the design of stent structures.

Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors

PubMed Central

Bauer, Ashley J.; Martin, Kathleen A.

2017-01-01

Cardiovascular disease is a leading cause of death with increasing economic burden. The pathogenesis of cardiovascular diseases is complex, but can arise from genetic and/or environmental risk factors. This can lead to dysregulated gene expression in numerous cell types including cardiomyocytes, endothelial cells, vascular smooth muscle cells, and inflammatory cells. While initial studies addressed transcriptional control of gene expression, epigenetics has been increasingly appreciated to also play an important role in this process through alterations in chromatin structure and gene accessibility. Chromatin-modifying proteins including enzymes that modulate DNA methylation, histone methylation, and histone acetylation can influence gene expression in numerous ways. These chromatin modifiers and their marks can promote or prevent transcription factor recruitment to regulatory regions of genes through modifications to DNA, histones, or the transcription factors themselves. This review will focus on the emerging question of how epigenetic modifiers and transcription factors interact to coordinately regulate gene expression in cardiovascular disease. While most studies have addressed the roles of either epigenetic or transcriptional control, our understanding of the integration of these processes is only just beginning. Interrogating these interactions is challenging, and improved technical approaches will be needed to fully dissect the temporal and spatial relationships between transcription factors, chromatin modifiers, and gene expression in cardiovascular disease. We summarize the current state of the field and provide perspectives on limitations and future directions. Through studies of epigenetic and transcriptional interactions, we can advance our understanding of the basic mechanisms of cardiovascular disease pathogenesis to develop novel therapeutics. PMID:28428957

Social Support and Networks: Cardiovascular Responses Following Recall on Immigration Stress Among Chinese Americans

PubMed Central

Suchday, Sonia; Wylie-Rosett, Judith

2014-01-01

Social support has been shown to act as a buffer for cardiovascular responses to stress. However, little is known about how social support and networks are related to cardiovascular responses to immigration stress recall. The current study evaluated the impact of structural and functional support on cardiovascular reaction following immigrant stress recall provocation as well as the moderation effect of interdependent self-construal among first-generation Chinese immigrants. One hundred fifty Chinese immigrants were recruited in the New York Chinatown area. Participants completed questionnaires assessing their levels of social support and networks, and interdependent self-construal. Following adaptation, participants recalled a recent post-immigration stress-provoking situation. Cardiovascular measures were taken during adaptation, stressor task, and recovery period. Hierarchical multiple regression analysis was performed. Social network size and type, as well as perceived emotional support were positively predictive of systolic blood pressure (SBP) reactivity changes. Instrumental support seeking was a positive predictor of SBP and diastolic blood pressure (DBP) reactivity. The moderation effect between instrumental support seeking and interdependent self-construal were significantly predictive of DBP reactivity and recovery, suggesting that perceptions about themselves in relation to others is a crucial factor for determining whether support seeking is beneficial or not. Social support was not a direct buffer on cardiovascular responses to stress among Chinese immigrants. Chinese values of interdependence and collectivism may partly explain the disconfirming results. Still, when interdependent self-construal was taken into account, Chinese immigrants who had less interdependent self-construal, but solicited more instrumental support, had faster adaptation to stress over the long term. PMID:24288021

Simulation, identification and statistical variation in cardiovascular analysis (SISCA) - A software framework for multi-compartment lumped modeling.

PubMed

Huttary, Rudolf; Goubergrits, Leonid; Schütte, Christof; Bernhard, Stefan

2017-08-01

It has not yet been possible to obtain modeling approaches suitable for covering a wide range of real world scenarios in cardiovascular physiology because many of the system parameters are uncertain or even unknown. Natural variability and statistical variation of cardiovascular system parameters in healthy and diseased conditions are characteristic features for understanding cardiovascular diseases in more detail. This paper presents SISCA, a novel software framework for cardiovascular system modeling and its MATLAB implementation. The framework defines a multi-model statistical ensemble approach for dimension reduced, multi-compartment models and focuses on statistical variation, system identification and patient-specific simulation based on clinical data. We also discuss a data-driven modeling scenario as a use case example. The regarded dataset originated from routine clinical examinations and comprised typical pre and post surgery clinical data from a patient diagnosed with coarctation of aorta. We conducted patient and disease specific pre/post surgery modeling by adapting a validated nominal multi-compartment model with respect to structure and parametrization using metadata and MRI geometry. In both models, the simulation reproduced measured pressures and flows fairly well with respect to stenosis and stent treatment and by pre-treatment cross stenosis phase shift of the pulse wave. However, with post-treatment data showing unrealistic phase shifts and other more obvious inconsistencies within the dataset, the methods and results we present suggest that conditioning and uncertainty management of routine clinical data sets needs significantly more attention to obtain reasonable results in patient-specific cardiovascular modeling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early physiological markers of cardiovascular risk in community based adolescents with a depressive disorder.

PubMed

Waloszek, Joanna M; Byrne, Michelle L; Woods, Michael J; Nicholas, Christian L; Bei, Bei; Murray, Greg; Raniti, Monika; Allen, Nicholas B; Trinder, John

2015-04-01

Depression is recognised as an independent cardiovascular risk factor in adults. Identifying this relationship early on in life is potentially important for the prevention of cardiovascular disease (CVD). This study investigated whether clinical depression is associated with multiple physiological markers of CVD risk in adolescents from the general community. Participants aged 12-18 years were recruited from the general community and screened for depressive symptoms. Individuals with high and low depressive symptoms were administered a diagnostic interview. Fifty participants, 25 with a current depressive episode and 25 matched healthy controls, subsequently completed cardiovascular assessments. Variables assessed were automatic brachial and continuous beat-to-beat finger arterial blood pressure, heart rate, vascular functioning by pulse amplitude tonometry following reactive hyperaemia and pulse transit time (PTT) at rest. Blood samples were collected to measure cholesterol, glucose and glycohaemoglobin levels and an index of cumulative risk of traditional cardiovascular risk factors was calculated. Depressed adolescents had a significantly lower reactive hyperaemia index and shorter PTT, suggesting deterioration in vascular integrity and structure. Higher fasting glucose and triglyceride levels were also observed in the depressed group, who also had higher cumulative risk scores indicative of increased engagement in unhealthy behaviours and higher probability of advanced atherosclerotic lesions. The sample size and number of males who completed all cardiovascular measures was small. Clinically depressed adolescents had poorer vascular functioning and increased CVD risk compared to controls, highlighting the need for early identification and intervention for the prevention of CVD in depressed youth. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural Evaluation of Radially Expandable Cardiovascular Stents Encased in a Polyurethane Film

NASA Technical Reports Server (NTRS)

Trigwell, Steve; De, Samiran; Sharma, Rajesh; Mazumder, Malay K.; Mehta, Jawahar L.

2004-01-01

A method of encasing cardiovascular stents with an expandable polyurethane coating has been developed to provide a smooth homogeneous inner wall allowing for a confluent growth of endothelial cells. In this design, the metal wire stent structure is completely covered by the polyurethane film minimizing biocorrosion of the metal (stainless steel or nitinol), and providing a homogeneous surface for surface treatment and incorporation of various eluting drugs to prevent platelet aggregation while supporting endothelialization. The polyurethane surface was treated with a helium plasma for sterilization and promotes growth of cells. The paper details the performance of the coated film to expand with the metal stent up to 225 % during deployment. We present stress/strain behavior of polyurethane films, and subsequent plasma treatment of the surface and the adhesion of the coating to the stent structure upon expansion. A film of less than 25 tm was found to be sufficient for corrosion resistance and flexibility without producing any excess stress on the stent structure. Straining the film to 225 % and plasma modification did not affect the mechanical and surface properties while allowing for improved biocompatibility as determined by the critical surface tension, surface chemistry, and roughness.

A Re-Engineered Software Interface and Workflow for the Open-Source SimVascular Cardiovascular Modeling Package.

PubMed

Lan, Hongzhi; Updegrove, Adam; Wilson, Nathan M; Maher, Gabriel D; Shadden, Shawn C; Marsden, Alison L

2018-02-01

Patient-specific simulation plays an important role in cardiovascular disease research, diagnosis, surgical planning and medical device design, as well as education in cardiovascular biomechanics. simvascular is an open-source software package encompassing an entire cardiovascular modeling and simulation pipeline from image segmentation, three-dimensional (3D) solid modeling, and mesh generation, to patient-specific simulation and analysis. SimVascular is widely used for cardiovascular basic science and clinical research as well as education, following increased adoption by users and development of a GATEWAY web portal to facilitate educational access. Initial efforts of the project focused on replacing commercial packages with open-source alternatives and adding increased functionality for multiscale modeling, fluid-structure interaction (FSI), and solid modeling operations. In this paper, we introduce a major SimVascular (SV) release that includes a new graphical user interface (GUI) designed to improve user experience. Additional improvements include enhanced data/project management, interactive tools to facilitate user interaction, new boundary condition (BC) functionality, plug-in mechanism to increase modularity, a new 3D segmentation tool, and new computer-aided design (CAD)-based solid modeling capabilities. Here, we focus on major changes to the software platform and outline features added in this new release. We also briefly describe our recent experiences using SimVascular in the classroom for bioengineering education.

Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease

PubMed Central

Strait, James

2015-01-01

Important changes occur in the cardiovascular system with advancing age, even in apparently healthy individuals. Thickening and stiffening of the large arteries develop due to collagen and calcium deposition and loss of elastic fibers in the medial layer. These arterial changes cause systolic blood pressure to rise with age, while diastolic blood pressure generally declines after the sixth decade. In the left ventricle, modest concentric wall thickening occurs due to cellular hypertrophy, but cavity size does not change. Although left ventricular systolic function is preserved across the age span, early diastolic filling rate declines 30–50% between the third and ninth decades. Conversely, an age-associated increase in late diastolic filling due to atrial contraction preserves end-diastolic volume. Aerobic exercise capacity declines approximately 10% per decade in cross-sectional studies; in longitudinal studies, however, this decline is accelerated in the elderly. Reductions in peak heart rate and peripheral oxygen utilization but not stroke volume appear to mediate the age-associated decline in aerobic capacity. Deficits in both cardiac b-adrenergic receptor density and in the efficiency of postsynaptic b-adrenergic signaling contribute significantly to the reduced cardiovascular performance during exercise in older adults. Although these cardiovascular aging changes are considered “normative”, they lower the threshold for the development of cardiovascular disease, which affects the majority of older adults. PMID:21809160

Apolipoprotein B, the villain in the drama?

PubMed

Yu, Qi; Zhang, Yaping; Xu, Cang-Bao

2015-02-05

Low-density lipoprotein (LDL) is the major atherogenic lipoprotein and the primary target of lipid-lowering therapy for treating ischemic cardiovascular disease. Apolipoprotein B (apoB), an important structural component of LDL, plays a key role in cholesterol transport and removal in vascular wall. On the other hand, under pathological process, apoB interacts with the arterial wall to initiate the cascade of events that leads to atherosclerosis. However, interactions between apoB and vascular wall remain to be determined. Here, we address a pathological role of apoB per se and whole LDL particle in dysfunction of vascular endothelium and smooth muscle cells i.e. decreased endothelium-dependent vasodilation and increased receptor-mediated vasoconstriction. We intend to discuss: i) how apoB is responsible for the deleterious effects of LDL in the development of ischemic cardiovascular disease; ii) why vaccine based on peptides derived from apoB-100 is a promising therapy for treating ischemic cardiovascular disease, and iii) direct inhibition of apoB production should be a better therapeutic option than simple LDL-cholesterol lowering therapy in the patients with severe hypercholesterolemia at high cardiovascular risk with statin intolerance. In conclusion, apoB, but not cholesterol, plays a major role in LDL-induced dysfunction of endothelium, suggesting that direct apoB-targeting agents might be a promising therapy for the treatment of ischemic cardiovascular disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants

PubMed Central

Daskaya-Dikmen, Ceren; Yucetepe, Aysun; Karbancioglu-Guler, Funda; Daskaya, Hayrettin; Ozcelik, Beraat

2017-01-01

Hypertension is an important factor in cardiovascular diseases. Angiotensin-I-converting enzyme (ACE) inhibitors like synthetic drugs are widely used to control hypertension. ACE-inhibitory peptides from food origins could be a good alternative to synthetic drugs. A number of plant-based peptides have been investigated for their potential ACE inhibitor activities by using in vitro and in vivo assays. These plant-based peptides can be obtained by solvent extraction, enzymatic hydrolysis with or without novel food processing methods, and fermentation. ACE-inhibitory activities of peptides can be affected by their structural characteristics such as chain length, composition and sequence. ACE-inhibitory peptides should have gastrointestinal stability and reach the cardiovascular system to show their bioactivity. This paper reviews the current literature on plant-derived ACE-inhibitory peptides including their sources, production and structure, as well as their activity by in vitro and in vivo studies and their bioavailability. PMID:28333109

A comparison of cardiovascular risk indices in patients with polycystic ovary syndrome with and without coexisting nonalcoholic fatty liver disease.

PubMed

Dawson, Alison J; Sathyapalan, Thozhukat; Smithson, Jacqueline A J; Vince, Rebecca V; Coady, Anne-Marie; Ajjan, Ramzi; Kilpatrick, Eric S; Atkin, Stephen L

2014-06-01

Women with polycystic ovary syndrome (PCOS) have an adverse cardiovascular risk profile and an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which is also associated with an adverse cardiovascular risk profile. To compare the cardiovascular risk profile of women with PCOS alone and women with PCOS and NAFLD. Twenty-five oligoanovulatory women with PCOS were screened for NAFLD (including liver biopsy if appropriate) and had their cardiovascular risk factors measured which included the inflammatory marker C-reactive protein (CRP), endothelial function {measured using endoPAT 2000 and serum markers [intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin]}, clot structure and function [maximum absorbance (MA) and lysis potential (LT)]. Twelve patients had confirmed PCOS without evidence of NAFLD, and 13 patients had confirmed PCOS with evidence of NAFLD. The PCOS and NAFLD group were heavier (BMI 43·9 ± 2·2 kg/m(2) ) compared with the PCOS alone group (BMI 37·6 ± 1·4 kg/m(2) P = 0·03). There was no difference in CRP (7·57 ± 0·95 vs 6·59 ± 1·87 mm P = 0·62) or endothelial function (RH-PAT 1·96 ± 0·1 vs 1·74 ± 0·16 P = 0·25), ICAM-1 (221 ± 48 vs 250 ± 60 ng/ml P = 0·19), VCAM-1 (2124 ± 78 vs 2314 ± 91 ng/ml P = 0·13), E-selectin (33·9 ± 3·3 vs 39·5 ± 15·5 ng/ml P = 0·31) and P-selectin (101·0 ± 6·6 vs 95·9 ± 10·2 ng/ml P = 0·69). There was no difference in clot formation or lysis. The patients with PCOS and NAFLD were heavier compared with patients with PCOS alone. Despite this, we were unable to demonstrate differences in inflammatory markers, endothelial function or clot structure and function, suggesting that severity of steatosis is not the most important determinant of cardiovascular risk in PCOS. © 2013 John Wiley & Sons Ltd.

Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.

PubMed

Holopainen, Elina; Vakkilainen, Svetlana; Mäkitie, Outi

2018-08-01

Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Motor development of infants with univentricular heart at the ages of 16 and 52 weeks.

PubMed

Rajantie, Irmeli; Laurila, Maarit; Pollari, Kirsi; Lönnqvist, Tuula; Sarajuuri, Anne; Jokinen, Eero; Mälkiä, Esko

2013-01-01

To compare the motor development of patients with hypoplastic left heart syndrome (HLHS) and other types of univentricular heart (UVH) with peers who are healthy at the ages of 16 and 52 weeks. Motor development was assessed with the Alberta Infant Motor Scale (AIMS). Both the 23 patients with HLHS and the 13 patients with UVH had lower total AIMS scores in both observations than the controls. At the age of 52 weeks, patients with HLHS had significantly lower scores in all 4 AIMS subscales, whereas patients with UVH had lower scores only in the prone and standing subscales. Motor development of patients with HLHS or UVH is delayed during the first year of life, especially in the prone and standing subscales.

The Role of Prokineticins in the Pathogenesis of Hypogonadotropic Hypogonadism

PubMed Central

Abreu, Ana Paula; Kaiser, Ursula B.; Latronico, Ana Claudia

2010-01-01

The prokineticin system comprises two multifunctional secreted proteins, prokineticin-1 (PROK1) and prokineticin-2 (PROK2), and their cognate G protein-coupled receptors. The prokineticins were originally identified as endogenous regulators of gastrointestinal motility. Currently, these bioactive peptides are involved in a wide spectrum of biological functions, including angiogenesis, neurogenesis, circadian rhythms, nociception, hematopoiesis and immune response. Mice homozygous for null mutations in Prokr2 or Prok2 recapitulate the human phenotype of Kallmann syndrome, exhibiting severe atrophy of the reproductive system and hypoplastic olfactory bulbs. Indeed, the evidence from several naturally inactivating mutations in the PROK2 and PROKR2 genes in patients with Kallmann syndrome and normosmic hypogonadotropic hypogonadism also indicate the essential role of PROK2 in olfactory bulb morphogenesis and GnRH secretion in humans. PMID:20502053

Adams-Oliver Syndrome with Unusual Central Nervous System Findings and an Extrahepatic Portosystemic Shunt

PubMed Central

Pérez-García, Carlos; Martín, Yolanda Ruíz; del Hoyo, Alejandra Aguado; Rodríguez, Carlos Marín; Domínguez, Minia Campos

2017-01-01

We report a case of a premature neonate girl with scalp and skull defects and brachydactyly of the feet consistent with an Adams-Oliver syndrome (AOS). The patient had central nervous system abnormalities, such as periventricular calcifications, hypoplastic corpus callosum, and bilateral hemispheric corticosubcortical hemorrhagic lesions. A muscular ventricular septal defect and a portosystemic shunt were diagnosed. To our knowledge, this is the first report of congenital supratentorial grey-white matter junction lesions without dural sinus thrombosis in association with AOS. Some of these lesions may be secondary to birth trauma (given the skull defect) whilst others have a watershed location, perhaps as further evidence of vascular disruption and decreased perfusion during critical periods of fetal brain development as the previously proposed pathogenesis of this syndrome. PMID:28706620

Genoa Syndrome and Central Diabetes Insipidus: A Case Report

PubMed Central

Şıklar, Zeynep; Erdeve, Şenay Savaş; Berberoğlu, Merih; Deda, Gülhiz; Tıraş, Serap Teber; Fitöz, Suat; Öçal, Gönül

2010-01-01

Genoa syndrome was first described by Camera et al in 1993 in two patients with semilobar holoprosencephaly (HPE), craniosynostosis and abnormal small hands with cone−shaped epiphyses and hypoplastic terminal phalanges of fingers (OMIM: 601370). In 2001, Lapunzina et al reported a case of craniosynostosis and HPE associated with several other malformations and suggested that these findings could be attributed to a severe form of Genoa syndrome or to a newly recognized syndrome. Endocrinopathies in association with HPE are frequently reported in the literature. Diabetes insipidus, hypothyroidism, hypocortisolism, and growth hormone deficiency are frequently associated with HPE. We here report a case of semilobar HPE, craniosynostosis and cleft lip/palate, possibly a case of Genoa syndrome, associated with central diabetes insipidus. Conflict of interest:None declared. PMID:21274346

Morphological manifestations of the Dandy-Walker syndrom in female members of a family.

PubMed

Titlić, Marina; Alfirević, Stanko; Kolić, Krešimir; Soldo, Anamarija; Tripalol, Ana Batoš

2015-03-01

The Dandy-Walker syndrome (DWS) is a hereditary disorder, appearing somewhat more frequently in women. The most important characteristics of the DWS are the lack of the cerebellar vermis, varying from a partial lack to a complete agenesis, and enlargement of the cerebrospinal spaces, especially in the fourth ventricle. The above mentioned morphological changes clinically manifest in ataxia, increased intracranial pressure and hydrocephalus. Here is presented a family with DWS, where the disease is contracted only by female members, in two generations, whereas no signs of DWS have been noticed in male family members. DWS is clinically manifested from early childhood to middle age, with the morphological changes varying from hypoplastic cerebellar vermis to widening of the brain ventricles and hydrocephalus and arachnoid cyst in the occipital part.

On-top plasty using a free metacarpal head graft for lengthening of proximal phalanx in symbrachydactyly--a case report.

PubMed

Iba, Kousuke; Wada, Takuro; Yamashita, Toshihiko

2013-01-01

A three-year old patient with symbrachydactyly (didactyly type) presented with a little finger that was too short to allow pinching and consisting of a floppy soft-tissue envelope with hypoplastic phalanges, although the thumb was functional. As the proximal phalanx was too small to permit distraction lengthening or conventional bone grafting, on-top plasty using a 4th metacarpal graft with a cartilage head was undertaken for lengthening the proximal phalanx of the little finger for pinch reconstruction. At ten weeks after surgery, the patient achieved satisfactory pinch function due to the lengthened and bone-stabilised postoperative digit and reconstruction of functional proximal interphalangeal joint. In addition, the grafted metacarpal demonstrated satisfactory bone growth throughout the six-year follow-up period.

Recurrent protein-losing enteropathy and tricuspid valve insufficiency in a transplanted heart: a causal relationship?

PubMed

Aggarwal, Sanjeev; Delius, Ralph E; Walters, Henry L; L'Ecuyer, Thomas J

2012-01-01

This case report describes a toddler who developed a protein-losing enteropathy (PLE) 4 years after orthotopic heart transplantation (OHT). He was born with a hypoplastic left heart syndrome for which he underwent a successful Norwood procedure, a Hemi-Fontan palliation, and a Fontan palliation at 18 months of age. Fifteen months following the Fontan operation, he developed a PLE and Fontan failure requiring OHT. Four years after OHT, he developed a severe tricuspid regurgitation and a PLE. His PLE improved after tricuspid valve replacement. It is now 2 years since his tricuspid valve replacement and he remains clinically free of ascites and peripheral edema with a normal serum albumin level. His prosthetic tricuspid valve is functioning normally. © 2011 Wiley Periodicals, Inc.