Impact of a cuff-based device calibration method on the agreement between invasive and noninvasive aortic and brachial pressure.

Introduction: Brachial cuff-based methods are increasingly used to estimate aortic systolic blood pressure (aoSBP). However, there are several unresolved issues.

Aims: to determine to what extent the scheme used to calibrate brachial records (1) can affect noninvasive obtained aoSBP levels, and consequently, the level of agreement with the aoSBP recorded invasively, and (2) how different ways of calibrating ultimately impact the relationship between aoSBP and cardiac properties.

Direct estimation of central aortic pressure from measured or quantified mean and diastolic brachial blood pressure: agreement with invasive records.

Background: Recently it has been proposed a new approach to estimate aortic systolic blood pressure (aoSBP) without the need for specific devices, operator-dependent techniques and/or complex wave propagation models/algorithms. The approach proposes aoSBP can be quantified from brachial diastolic and mean blood pressure (bDBP, bMBP) as: aoSBP = bMBP/bDBP. It remains to be assessed to what extent the method and/or equation used to obtain the bMBP levels considered in aoSBP calculation may affect the estimated aoSBP, and consequently the agreement with aoSBP invasively recorded.

Importance of diffuse atherosclerosis in the functional evaluation of coronary stenosis in the proximal-mid segment of a coronary artery by myocardial fractional flow reserve measurements.

The objective of this study was to evaluate the impact of diffuse coronary atherosclerosis on the functional evaluation of moderate coronary lesions in the proximal-mid segment of a coronary artery and its clinical implications. This was a prospective study including 100 consecutive patients with a moderate lesion (45 ± 9% diameter stenosis) in the proximal-mid coronary segment who were evaluated with fractional flow reserve (FFR) measurement. No patient had any other angiographic stenosis distal to the evaluated coronary stenosis.

Incidence, predictive factors, and prognostic value of myocardial injury following uncomplicated transcatheter aortic valve implantation.

Objectives: This study sought to: 1) determine the incidence, degree, and timing of the rise in serum cardiac markers of myocardial injury associated with uncomplicated transcatheter aortic valve implantation (TAVI); and 2) evaluate the predictive factors and prognostic value of myocardial injury associated with TAVI.

Background: Very few data exist on the occurrence and clinical relevance of myocardial injury during TAVI procedures.

Methods: A total of 101 patients who underwent successful TAVI (transfemoral [TF] approach, n = 38; transapical [TA] approach, n = 63) were included.

Performance-based functional assessment of patients undergoing transcatheter aortic valve implantation.

Background: Very few data exist on the functional evaluation of patients with severe symptomatic aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). The aims of this prospective study were (1) to evaluate the Duke Activity Status Index (DASI) as a measure of functional status pre-TAVI and post-TAVI, (2) to determine the clinical parameters associated with DASI changes after TAVI, and (3) to compare functional status as evaluated by DASI and the New York Heart Association (NYHA) class with exercise capacity as evaluated by the 6-minute walk test (6MWT) in such patients.

Methods: A total of 76 patients (80 ± 8 years old) who underwent successful TAVI were included.

Diastolic dysfunction in diabetic patients assessed with Doppler echocardiography: relationship with coronary atherosclerotic burden and microcirculatory impairment.

Introduction And Objectives: Diabetes mellitus (DM) is associated with the development of both impaired left ventricular diastolic function (LVDF) and pathological changes in the coronary macro- and microcirculation. The aim of this study was to investigate the relationship between these manifestations of diabetic heart disease.

Methods: The severity of atherosclerosis in the left anterior descending coronary artery (LAD) was quantified using intravascular ultrasound (IVUS) in 13 patients with DM and ischemic heart disease.

Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement.

Aims: Very few data exist on the occurrence of acute kidney injury (AKI) associated with transcatheter aortic valve implantation (TAVI). The objectives of the present study were (i) to determine the incidence, predictive factors, and prognostic value of AKI following TAVI, and (ii) to compare the occurrence of AKI in TAVI vs. surgical aortic valve replacement (SAVR) in patients with pre-procedural chronic kidney disease (CKD).

Electrocardiographic changes and clinical outcomes after transapical aortic valve implantation.

Background: Transapical aortic valve implantation (TAVI) for the treatment of severe aortic stenosis requires the insertion of a large catheter through the left ventricular apex. However, the electrocardiographic (ECG) changes associated with the incision and repair of the left ventricular apex and the potential damage to the conduction system caused by implanting a balloon-expandable valve in aortic position are not known. The objective of our study was to determine the incidence, type, and timing of ECG changes associated with TAVI.

Analysis of fetal breathing movements at 30-38 weeks of gestation.

Aims: This study reports the changes in patterns of fetal breathing movements recorded with a photogrammetric method in three successive periods of gestation.

Methods: Respiratory movements were studied in fetuses of 28 healthy women with uncomplicated pregnancies of 30-38 weeks of gestation. Women were divided into three groups according to gestational age of the fetus: 30-32 weeks, 7 fetuses; 33-36 weeks, 9 fetuses; and 37-38 weeks, 12 fetuses.

A human melanoma xenograft in a nude rat responds to isolated limb perfusion with TNF plus melphalan.

Background: Isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) and melphalan for advanced extremity malignancies achieves significant complete response rates. To study molecular mechanisms underlying this response, a nude rat ILP model with a human melanoma xenograft was developed.

Methods: NIH1286 human melanoma was grown subcutaneously in the hind limb of nude rats.

Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis.

The majority of neurones and glia of the enteric nervous system (ENS) are derived from the vagal neural crest. Shortly after emigration from the neural tube, ENS progenitors invade the anterior foregut and, migrating in a rostrocaudal direction, colonise in an orderly fashion the rest of the foregut, the midgut and the hindgut. We provide evidence that activation of the receptor tyrosine kinase RET by glial cell line-derived neurotrophic factor (GDNF) is required for the directional migration of ENS progenitors towards and within the gut wall.

Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice.

The expression of transgene loci in mammals often occurs in a heterocellular fashion resulting in variegated patterns of expression. We have examined the effect of chromosomal integration site, copy number, and transcriptionally activating sequences on the variegation of a keratin 5-lacZ (K5Z) construct in the stratified epithelia of transgenic mice. lacZ expression in these mice is always mosaic, and the beta-gal activity per cell is usually higher in the lines with a higher proportion of expressing cells.

Loss- and gain-of-function mutations show a polycomb group function for Ring1A in mice.

The products of the Polycomb group (PcG) of genes act as transcriptional repressors involved in the maintenance of homeotic gene expression patterns throughout development, from flies to mice. Biochemical and molecular evidence suggests that the mouse Ring1A gene is a member of the PcG of genes. However, genetic evidence is needed to establish PcG function for Ring1A, since contrary to all other murine PcG genes, there is no known Drosophila PcG gene encoding a homolog of the Ring1A protein.

RYBP, a new repressor protein that interacts with components of the mammalian Polycomb complex, and with the transcription factor YY1.

The products of the Polycomb group (PcG) of genes are necessary for the maintenance of transcriptional repression of a number of important developmental genes, including the homeotic genes. A two-hybrid screen was used to search for putative new members of the PcG of genes in mammals. We have identified a new Zn finger protein, RYBP, which interacts directly with both Ring1 proteins (Ring1A and Ring1B) and with M33, two mutually interacting sets of proteins of the mammalian Polycomb complex.

Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system.

RET is a member of the receptor tyrosine kinase (RTK) superfamily, which can transduce signalling by glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) in cultured cells. In order to determine whether in addition to being sufficient, RET is also necessary for signalling by these growth factors, we studied the response to GDNF and NTN of primary neuronal cultures (peripheral sensory and central dopaminergic neurons) derived from wild-type and RET-deficient mice. Our experiments show that absence of a functional RET receptor abrogates the biological responses of neuronal cells to both GDNF and NTN.

Multipotential progenitors of the mammalian enteric nervous system capable of colonising aganglionic bowel in organ culture.

The enteric nervous system of vertebrates is derived from neural crest cells that invade the gut wall and generate a highly organised network of enteric ganglia. Among the genes that play an important role in ENS development is c-Ret, mutations of which result in failure of formation of enteric ganglia (intestinal aganglionosis). To further understand the development of the mammalian ENS in general and the mechanism of action of the RET RTK in particular, we have developed and used an organotypic culture system of mouse fetal gut.

Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain.

In Drosophila, the products of the Polycomb group (Pc-G) of genes act as chromatin-associated multimeric protein complexes that repress expression of homeotic genes. Vertebrate Pc-G homologues have been identified, but the nature of the complexes they form and the mechanisms of their action are largely unknown. The Polycomb homologue M33 is implicated in mesoderm patterning in the mouse and here we show that it acts as a transcriptional repressor in transiently transfected cells.

The zebrafish homologue of the ret receptor and its pattern of expression during embryogenesis.

The c-ret proto-oncogene, a member of the receptor tyrosine kinase gene superfamily, plays a critical role in the development of the excretory system and the enteric and autonomic nervous systems of mammalian embryos. To study the potential function of the c-ret locus in lower vertebrates, we have isolated its zebrafish homologue, ret1 and established its expression pattern during embryogenesis. Ret1 mRNA first appears during early somitogenesis in the presumptive brain, spinal cord and excretory system.

GDNF signalling through the Ret receptor tyrosine kinase.

Mutational analysis in humans and mice has demonstrated that the Ret, the product of the c-ret proto-oncogene, a member of the receptor tyrosine kinase (RTK) superfamily, is essential for development of the enteric nervous system and kidney. Despite the established role of Ret in mammalian embryogenesis, its cognate ligand(s) is currently unknown. Here we demonstrate, by using a Xenopus embryo bioassay, that glial-cell-line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor (TGF)-beta superfamily, signals through the Ret RTK.