Melanoma secretion of transforming growth factor-ß2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration.

BACKGROUND: For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis. OBJECTIVES: The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-ß signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity. METHODS: Immunohistochemistry was used to analyse AMBRA1 and TGF-ß2 in a cohort of 109 AJCC all-stage melanomas, and TGF-ß2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-ß2 signalling evaluated in primary keratinocytes. RESULTS: Increased tumoral TGF-ß2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-ß2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05). CONCLUSIONS: Collectively, these data suggest a paracrine mechanism whereby TGF-ß2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.

Effect of nutrient deprivation on the expression and the epigenetic signature of sirtuin genes.

BACKGROUND AND AIM: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutrient availability. In the present study we evaluated the effect of nutrient deprivation on expression, DNA methylation and chromatin status of the sirtuin genes. METHODS AND RESULTS: We performed these studies in mouse hepatoma cells, that were grown in standard medium, or in media containing low glucose concentration, or no glucose, or no amino acids. We applied quantitative real-time PCR to cDNA, methylation-enriched DNA and nuclease-treated DNA in order to evaluate gene expression, DNA methylation, and chromatin condensation, respectively. This study shows that the expression of sirtuin genes varies following nutrient deprivation. Moreover, we observed that changes of DNA methylation and chromatin condensation occur at the transcription start site of sirtuin genes following nutrient deprivation. CONCLUSIONS: Epigenetic mechanisms may have a role in the sirtuin response to nutrient deprivations in cultured hepatoma cells. Replicating these results in vivo to achieve a comprehensive understanding of the epigenetic control of sirtuin expression following nutrient deprivations might open up novel therapeutic possibilities to cure metabolic diseases and promote human health.

Evolution of Ventricular Energetics in the Different Stages of Palliation of Hypoplastic Left Heart Syndrome: A Retrospective Clinical Study.

Hyperplastic left heart syndrome (HLHS) patients are palliated by creating a Fontan-type circulation passing from different surgical stages. The aim of this work is to describe the evolution of ventricular energetics parameters in HLHS patients during the different stages of palliation including the hybrid, the Norwood, the bidirectional Glenn (BDG), and the Fontan procedures. We conducted a retrospective clinical study enrolling all HLHS patients surgically treated with hybrid procedure and/or Norwood and/or BDG and/or Fontan operation from 2011 to 2016 collecting echocardiographic and hemodynamic data. Measured data were used to calculate energetic variables such as ventricular elastances, external and internal work, ventriculo-arterial coupling and cardiac mechanical efficiency. From 2010 to 2016, a total of 29 HLHS patients undergoing cardiac catheterization after hybrid (n = 7) or Norwood (n = 6) or Glenn (n = 8) or Fontan (n = 8) procedure were retrospectively enrolled. Ventricular volumes were significantly higher in the Norwood circulation than in the hybrid circulation (p = 0.03) with a progressive decrement from the first stage to the Fontan completion. Ventricular elastances were lower in the Norwood circulation than in the hybrid circulation and progressively increased passing from the first stage to the Fontan completion. The arterial elastance and Rtot increased in the Fontan circulation. The ventricular work progressively increased. Finally, the ventricular efficiency improves passing from the first to the last stage of palliation. The use of ventricular energetic parameters could lead to a more complete evaluation of such complex patients to better understand their adaptation to different pathophysiological conditions.

Syndromic non-compaction of the left ventricle: associated chromosomal anomalies.

Non-compaction of the left ventricle (NCLV) is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intertrabecular recesses. Associated extracardiac anomalies occur in 14-66% of patients of different series, while chromosomal anomalies were reported in sporadic cases. We investigated the prevalence of chromosomal imbalances in 25 syndromic patients with NCLV, using standard cytogenetic, subtelomeric fluorescent in situ hybridization, and array-comparative genomic hybridization (CGH) analyses. Standard chromosome analysis disclosed an abnormality in three (12%) patients, including a 45,X/46,XX mosaic, a 45,X/46,X,i(Y)(p11) mosaic, and a de novo Robertsonian 13;14 translocation in a child affected by hypomelanosis of Ito. Cryptic chromosome anomalies were found in six (24%) cases, including 1p36 deletion in two patients, 7p14.3p14.1 deletion, 18p subtelomeric deletion, 22q11.2 deletion associated with velo-cardio-facial syndrome, and distal 22q11.2 deletion, each in one case. These results recommend accurate clinical evaluation of patients with NCLV, and suggest that chromosome anomalies occur in about one third of syndromic NCLV individuals, without metabolic/neuromuscular disorder. Array-CGH analysis should be included in the diagnostic protocol of these patients, because different submicroscopic imbalances are causally associated with this disorder and can pinpoint candidate genes for this cardiomyopathy.

Percutaneous treatment of abdominal coarctation in children using a covered stent.

Coarctation of the abdominal aorta is extremely rare. It generally involves a long segment of the descending aorta and causes uncontrolled and unexplainable hypertension in children. The therapeutic choice is very challenging because acute and chronic complications are reported for both the surgical and the percutaneous approaches. The two reported cases of abdominal coarctation were treated primarily and successfully through the use of covered stents. Three covered stents were implanted in two children. No complication occurred with either procedure. At this writing, an 18-month follow-up assessment has found the patients in good health with no restenosis at the coarctation site. Covered stent implantation in children with abdominal coarctation is a feasible, safe, and effective procedure. It provides adequate relief of symptoms and reduces the risk of aneurysm formation. To avoid covering important side branches with polytetrafluoroethylene, this type of procedure must be preceded by precise study of the aorta and its branches.

Total laparoscopic hysterectomy in early-stage endometrial cancer using an intrauterine manipulator: is it a bias for frozen section analysis? Case-control study.

STUDY OBJECTIVE: To evaluate whether the systematic use of an intrauterine manipulator influences the accuracy of frozen section analysis in early-stage endometrial cancer. DESIGN: Case-control study (Canadian Task Force classification II-1). PATIENTS: Three hundred fourteen consecutive women with early-stage endometrial cancer. INTERVENTIONS: Between January 2004 and December 2009, 314 women with early-stage endometrial cancer underwent staging at laparoscopy (case group) or laparotomy (control group). All women in the case group underwent total laparoscopic hysterectomy using an intrauterine manipulator. MEASUREMENTS AND MAIN RESULTS: The positive predictive value of frozen section analysis for myometrial infiltration, histotype, and grade of differentiation was 97.2%, 100%, and 97.2%, respectively. The correct diagnosis rate was of 85.7%. The accuracy of frozen section analysis, rate of correct diagnosis, and rate of tumor vascular invasion did not seem to be significantly modified by systematic use of an intrauterine manipulator for total laparoscopic hysterectomy compared with total abdominal hysterectomy in early-stage endometrial cancer staging. CONCLUSIONS: Frozen section analysis of early-stage endometrial cancer is highly accurate, and systematic use of an intrauterine manipulator does not represent a bias for correct evaluation of the specimen.

Long-term assessment of clinical outcomes and disease progression in patients with corrected Tetralogy of Fallot.

OBJECTIVE: Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. PATIENTS AND METHODS: Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspid regurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. RESULTS: Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. CONCLUSIONS:  Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.

Major histocompatibility complex-independent recognition of a distinctive pollen antigen, most likely a carbohydrate, by human CD8+ alpha/beta T cells.

We have isolated CD8+ alpha/beta T cells from the blood of atopic and healthy individuals which recognize a nonpeptide antigen present in an allergenic extract from Parietaria judaica pollen. This antigen appears to be a carbohydrate because it is resistant to proteinase K and alkaline digestion, is hydrophilic, and is sensitive to trifluoromethane-sulphonic and periodic acids. In addition, on a reverse-phase high performance liquid chromatography column the antigen recognized by CD8(+) T cells separates in a fraction which contains >80% hexoses (glucose and galactose) and undetectable amounts of proteins. Presentation of this putative carbohydrate antigen (PjCHOAg) to CD8+ T cell clones is dependent on live antigen presenting cells (APCs) pulsed for >1 h at 37 degrees C, suggesting that the antigen has to be internalized and possibly processed. Indeed, fixed APCs or APCs pulsed at 15 degrees C were both unable to induce T cell response. Remarkably, PjCHOAg presentation is independent of the expression of classical major histocompatibility complex (MHC) molecules or CD1. CD8+ T cells stimulated by PjCHOAg-pulsed APCs undergo a sustained [Ca2+]i increase and downregulate their T cell antigen receptors (TCRs) in an antigen dose- and time-dependent fashion, similar to T cells stimulated by conventional ligands. Analysis of TCR Vbeta transcripts shows that six independent PjCHOAg-specific T cell clones carry the Vbeta8 segment with a conserved motif in the CDR3 region, indicating a structural requirement for recognition of this antigen. Finally, after activation, the CD8+ clones from the atopic patient express CD40L and produce high levels of interleukins 4 and 5, suggesting that the clones may have undergone a Th2-like polarization in vivo. These results reveal a new class of antigens which triggers T cells in an MHC-independent way, and these antigens appear to be carbohydrates. We suggest that this type of antigen may play a role in the immune response in vivo.

How to perform the Wiltse posterolateral spinal approach: Technical note.

BACKGROUND: The paraspinal, posterolateral, or Wiltse approach is an old technique that observes the principles of an MIS procedure. The aim of this study was to provide a step-by-step description from the literature of the Wiltse paraspinal approach and analyze its main advantages and limitations. METHODS: Here, we provide a step-by-step description of the Wiltse approach. Utilizing PubMed and Lilacs and the Mesh terms "Wiltse approach," "paraspinal approach," "muscle sparing approach," and "lumbar spine," we identified 10 papers. We then put together, based on these publications, a step-by-step analysis of the preparation, patient positioning, skin incision, fascial opening, dissection, bone identification, retractors, deperiostization, decompression, discectomy, instrumentation, arthrodesis, and closure for the Wiltse technique. RESULTS: Most papers underscored the minimally invasive aspects of the typical Wiltse approach. Advantages included minimal intraoperative bleeding, a shorter hospital length of stay, and a low infection rate. CONCLUSION: The classical approach described by Wiltse is essentially minimally invasive, sparing both the muscle planes and soft tissues, allowing for ample far lateral lumbar decompression, including discectomy and fusion, with a low complication rate.

Successful pregnancy in stage IE primary non-Hodgkin's lymphoma of uterine cervix treated with neoadjuvant chemotherapy and conservative surgery.

BACKGROUND: Primary non-Hodgkin's lymphoma involving the uterine cervix is extremely rare with a frequency of 0.008% of all cervical tumors. No standard treatment has been defined for this disease. CASE: A 29-year-old Caucasian woman with primary non-Hodgkin stage IE lymphoma of the uterine cervix was treated with neoadjuvant chemotherapy and conservative surgery. Three years after completion of primary treatment, she became pregnant and successfully delivered a full-term healthy baby. CONCLUSION: This case report supports the data that a conservative strategy consisting of neoadjuvant chemotherapy followed by a uterine-preserving approach represents an adequate option for young highly motivated patients who desire to preserve the childbearing potential.

C/EBPbeta (NF-M) is essential for activation of the p20K lipocalin gene in growth-arrested chicken embryo fibroblasts.

The p20K gene is induced in conditions of reversible growth arrest in chicken embryo fibroblasts (CEF). This expression is dependent on transcriptional activation and on a region of the promoter designated the quiescence-responsive unit (QRU). In this report, we describe the regulatory elements of the QRU responsible for activation in resting cells and characterize the trans-acting proteins interacting with these elements. We show that the QRU consists of functionally distinct domains including quiescence-specific and weak proliferation-responsive elements. The quiescence responsiveness of the QRU was mapped to two C/EBP binding sites, and the activity of the p20K promoter and its QRU was inhibited by the expression of a dominant negative mutant of C/EBPbeta in nondividing cells. The activation of QRU in response to serum starvation and contact inhibition correlated with the presence of a growth arrest-specific complex in electrophoretic mobility shift assays. This complex was supershifted by antibody for C/EBPbeta. C/EBPbeta accumulated in conditions of contact inhibition as a result of transcriptional activation. Therefore, C/EBPbeta was itself regulated as a growth arrest-specific gene in CEF. Finally, we show that the expression of p20K is regulated by linoleic acid, an essential fatty acid binding to p20K. The addition of linoleic acid to contact-inhibited CEF markedly repressed the synthesis of p20K without inducing mitogenesis. The activity of the QRU was inhibited by linoleic acid or the peroxisome proliferator-activated receptor PPARgamma2 in transient expression assays. Therefore, we have identified C/EBPbeta as a key activator of a growth arrest-specific gene in CEF and implicated an essential fatty acid, linoleic acid, in regulation of the QRU and the p20K lipocalin gene.

Choroidal excavation in choroidal osteoma complicated by choroidal neovascularization.

PurposeTo describe multimodal imaging features of choroidal osteoma (CO) complicated by choroidal neovascularization (CNV) and focal choroidal excavation (FCE).MethodsPatients presenting with CO and CNV between January and October 2016 were considered for this study. Diagnosis of CO was confirmed by ultrasound examination. All patients underwent multimodal imaging including optical coherence tomography (OCT), swept-source OCT angiography (DRI OCT Triton, Topcon, Inc., Tokyo, Japan) and fluorescein angiography (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany).ResultsTwo patients (one with bilateral CO) were included in the study. OCT showed a FCE in two eyes of two patients (one in correspondence of the CNV and the other adjacent to the CNV). OCT-A demonstrated presence of microvascular flow within neovascular network of the CNVs. Decalcification of the tumor was noted in correspondence of one eye with FCE.ConclusionsFCE may be found in eyes with choroidal osteoma and CNV. OCT-A was a valuable tool for detection of CNV complicating choroidal osteoma. Decalcification of choroidal osteoma may represent a common pathogenic pathway for development of FCE and CNV in choroidal osteoma.

A poly(ether-ester) copolymer for the preparation of nanocarriers with improved degradation and drug delivery kinetics.

This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs.

The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPbeta in v-src transformed chicken embryo fibroblasts.

The CEF-4/9E3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus (RSV). This aberrant induction is controlled at the transcriptional and post-transcriptional levels. Transcriptional activation depends on multiple elements of the CEF-4 promoter composing a Src-responsive-Unit or SRU. The SRU includes a TPA responsive element, a PRDII/kappaB domain and a CAAT box. In this report, we identify C/EBPbeta as a component of the trans-acting factor interacting with the CAAT box of the CEF-4 promoter. In addition, we show that C/EBPbeta binds to a second element located in proximity of the TRE. A mutation of this distal CAAT box impaired the activation of the CEF-4 promoter by pp60(v-src) indicating that this element is also part of the SRU. Using the RCASBP retroviral vector, we expressed a dominant negative mutant of C/EBPbeta (designated Delta184-C/EBPbeta) in RSV-transformed CEF. Delta184-C/EBPbeta decreased the accumulation of the CEF-4 mRNA and activation of the CEF-4 promoter by pp60(v-src). The induction of the Cox-2 gene (CEF-147) was also reduced by Delta184-C/EBPbeta. The effect of the dominant negative mutant was observed within 1 h of the activation of a thermolabile pp60(v-src) suggesting that C/EBPbeta is an early target of v-src transformation. The dominant negative mutant did not inhibit the transformation of CEF by RSV and in fact accentuated the transformed cell phenotype. Therefore, the activation of C/EBPbeta is important for the expression of v-src regulated genes but is not required for the in vitro transformation of CEF by pp60(v-src).

Tailoring the hybrid palliation for hypoplastic left heart syndrome: A simulation study using a lumped parameter model.

The results of Hybrid procedure (HP) for the hypoplastic left heart syndrome (HLHS) depend on several variables: pulmonary artery banding tightness (PAB), atrial septal defect size (ASD) and patent ductus arteriosus stent size (PDA). A HP complication could be the aortic coarctaction (CoAo). The reverse Blalock-Taussig shunt (RevBT) placement was proposed to avoid CoAo effects. This work aims at developing a lumped parameter model (LPM) to investigate the effects of the different variables on HP haemodynamics. A preliminary verification was performed collecting measurements on a newborn HLHS patient to calculate LPM input parameters to reproduce patient's baseline. Results suggest that haemodynamics is affected by ASD (ASD: 0.15-0.55 cm, pulmonary to systemic flow ratio Qp/Qs: 0.73-1, cardiac output (CO): 1-1.5 l/min and ventricular stroke work SW: 336-577 ml mmHg) and by the PAB diameter (PAB: 0.07-0.2 cm, Qp/Qs: 0.46-2.1, CO: 1.3-1.6 l/min and SW: 591-535 ml mmHg). Haemodynamics was neither affected by RevBT diameter nor by PDA diameter higher than 0.2 cm. RevBT implantation does not change the HP haemodynamics, but it can make the CoAo effect negligible. LPM could be useful to support clinical decision in complex physiopathology and to calibrate and personalise the parameters that play a role on flow distribution.

Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

INTRODUCTION AND RESULTS: Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. CONCLUSIONS: In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients.

Hypertrophic cardiomyopathy and mtDNA depletion. Successful treatment with heart transplantation.

Cardiomyopathy associated with a mitochondrial DNA depletion syndrome is a rare condition. We report on a child with a hypertrophic cardiomyopathy and a mitochondrial depletion syndrome who was successfully treated by heart transplantation, given the tissue-specific nature of her mitochondrial disorder.

Morphological, phenotypic and karyotypic characterization of a novel natural-killer-cell target - evidence of involvement of MHC class-I molecules in NK cell recognition.

A new cell line from a neoplastic ascites was established. This strain, designated PAT-206, was characterized by plastic adherence and a high proliferative potential without any specific growth factor requirement. Karyotype analysis showed that the line was of human chromosomal constitution and aneuploid. Surface marker analysis showed that CD45, CD33 and CD15 were positive. In addition, the presence of human cytokeratins was detected by cytoplasmic immunofluorescence. Interestingly, the cell line did not express major hystocompatibility complex (MHC) class I and II, and was more sensitive than the 'classic' K562 cell line, to killing mediated by fresh uncultured peripheral blood lymphocytes. Following differentiation with interferon-gamma, the cell line expressed MHC class I antigens and resulted resistant to natural killing mediated lysis. This novel NK cell target seems to be suitable for further studies on NK cell specificities.

Cardiac catheterization through the internal jugular vein in pediatric patients. An alternative to the usual femoral vein access.

The percutaneous femoral vein approach is used routinely for cardiac catheterization in the pediatric age but in some children, it may be impossible as in the case of iliac vein or inferior vena cava thrombosis due to previous cardiac catheterization, or inconvenient as for right ventricular endomyocardial biopsies. In the period between 1982 and 1990, 160 cardiac catheterizations or right ventricular endomyocardial biopsies were performed in 102 children. Patients ranged in age between 2 months and 17 years (mean, 3.8 years) and in weight from 3.2 to 57.3 kg (mean, 14.4 kg). Indications for the internal jugular vein approach were as follows: (1) thrombosis of the inferior vena cava due to previous cardiac catheterization in 42 patients (41 percent); (2) right ventricular endomyocardial biopsy after cardiac transplant in 19 patients (19 percent); (3) control catheterization of the pulmonary arteries following classic or bidirectional cavopulmonary anastomosis in 16 patients (16 percent); (4) superior vena cava obstruction following Mustard's procedure in 14 patients (14 percent); (5) failed percutaneous femoral venous approach in six patients (6 percent); and (6) absence of the hepatic segment of the inferior vena cava in four patients (4 percent). The right or left internal jugular vein could be entered in all but three procedures (98 percent). Seventeen patients had more than one procedure through the same internal jugular vein and the vein was found patent in all. A complete right heart cardiac catheterization was performed using this route. Right ventricular endomyocardial biopsy and interventional procedure were performed through this route. Two major complications occurred. A patient developed a central transient ischemic attack and another patient developed a persistent Horner syndrome. Accidental carotid puncture occurred in five patients without consequences. Our data indicate that cardiac catheterization in infants and children can be performed safely through the internal jugular vein, with a high success rate and a low incidence of major complications.