Measuring Activated Clotting Time during Cardiac Catheterization and PCI: The Effect of the Sampling Site.

RESULTS: In 100 patients (mean age 67.1, 65% male), no significant differences were observed in ACT values obtained from the guiding catheter and arterial sheath (mean difference (MD) -18.3 s; standard deviation (SD) 96 s; P=0.067). Contrarily, ACT values obtained from the intravenous line were significantly lower as compared to values obtained from the guiding catheter (MD 25.7 s; SD 75.5; P=0.003) and arterial sheath (MD 39 s; SD 102.8; P < 0.001). Furthermore, ACT measurements from the arterial sheath showed a statistically significant proportional bias when compared to the other sampling sites (sheath vs. catheter, r = 0.761, P=0.001; sheath vs. IVL, r = 1.013, P < 0.001). CONCLUSIONS: The present study shows statistical significance and possibly clinically relevant variations between ACT measurements from different sample sites. Bias in ACT measurements may be minimized by using uniform protocols for ACT measurement during cardiac catheterization.

Advances in percutaneous coronary intervention for chronic total occlusions: current antegrade dissection and reentry techniques and updated algorithm.

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) is considered relatively complex with low success rates and high complication rates. Treating a CTO with PCI using the hybrid algorithm increases success rates with acceptable complication rates. An essential part of the hybrid algorithm is antegrade dissection and reentry (ADR). In PCI of a non-CTO coronary lesion, the guidewire over which the stent is advanced and placed stays within the true lumen of the coronary artery. ADR techniques make it possible to cross the lesion through the wall of the coronary artery, the subintimal space, thus creating a small bypass within the architecture of the coronary artery and restoring antegrade blood flow. ADR increases success rates, especially in more difficult CTO procedures. In the last decade, new materials and techniques have been introduced in quick succession, which are summarised in this review. Consequently an updated ADR algorithm is presented, which can support the CTO operator during an ADR procedure.

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

Addition of routinely measured blood biomarkers significantly improves GRACE risk stratification in patients with myocardial infarction.

AIM: To investigate whether blood biomarkers measured routinely at hospital admission in myocardial infarction (MI) patients can improve the admission GRACE score for the composite endpoint of all-cause mortality and non-fatal MI at 6 months. METHODS: 2055 patients treated for MI in the Northwest clinics, the Netherlands, between 2013 and 2016 were examined. As part of the prevailing MI treatment protocol, 19 biomarkers were measured and the GRACE score was ascertained. Information on the composite endpoint was derived from municipal registries and electronic medical records. We applied elastic net logistic regression (LR) analysis to select biomarkers that had statistically significant additive prognostic value on top of the GRACE score. We then studied the prognostic performance of the LR model containing the GRACE score and the selected biomarkers. RESULTS: At six months follow-up 143 (6.96%) reached the composite endpoint. Nine variables were included in the final LR model: GRACE score, urea, sodium, potassium, alkaline phosphatase, LDL cholesterol, glucose, hemoglobin and C-reactive protein. This extended GRACE score model showed improved discrimination (C-statistic 0.76 vs 0.70, p = <0.001) and classification (continuous net reclassification index 0.49, p < 0.001) compared with the GRACE score only. CONCLUSION: The ability of the GRACE score for detecting MI patients at high risk for mortality or MI within 6 months, was significantly improved by adding several biomarkers measured routinely at admission.

Differences in plaque composition and distribution in stable coronary artery disease versus acute coronary syndromes; non-invasive evaluation with multi-slice computed tomography.

BACKGROUND: Plaque composition rather than degree of luminal narrowing may be predictive of acute coronary syndromes (ACS). The purpose of the study was to compare plaque composition and distribution with multi-slice computed tomography (MSCT) between patients presenting with either stable coronary artery disease (CAD) or ACS. METHODS: MSCT was performed in 22 and 24 patients presenting with ACS or stable CAD, respectively. Coronary lesions were classified as calcified, non-calcified or mixed while signal intensity (SI) was measured. RESULTS: In patients with stable CAD, the majority of lesions were calcified (89%). In patients with ACS, less calcifications were observed with a greater proportion of non-calcified (18%) or mixed (36%) lesions (P<0.001). Accordingly, mean SI of plaques was significantly less in ACS (320+/-201 HU versus 620+/-256 HU in stable CAD, P<0.001). Dividing lesions in the ACS group according to culprit versus non-culprit vessel location resulted in no significant difference in average SI between these two groups while still lower as compared to stable CAD (P<0.001). CONCLUSIONS: In patients with ACS, significantly less calcifications were present as compared to stable CAD. Moreover, even in non-culprit vessels, multiple non-calcified plaques were detected, indicating diffuse rather than focal atherosclerosis in ACS.

Detection of malignant right coronary artery anomaly by multi-slice CT coronary angiography.

Coronary artery anomalies occur in 0.3-0.8% of the population and infer a high risk for sudden cardiac death in young adults. Diagnosis is usually established during coronary angiography, which is hampered by poor spatial visualization. Magnetic resonance imaging is an alternative, but it is not feasible in the presence of metal objects or claustrophobia. In this report, a 15-year-old boy experienced ventricular fibrillation and was successfully resuscitated. Cardiac catheterization was inconclusive, and pacemaker implantation prohibited the use of MR imaging. Multi-slice CT coronary angiography revealed a malignant anomalous right coronary artery.

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens development and differentiation.

Here we report the isolation of a novel forkhead gene, Foxe3, that plays an important role in lens formation. During development Foxe3 is expressed in all undifferentiated lens tissues, and is turned off upon fiber cell differentiation. Foxe3 maps to a chromosomal region containing the dysgenetic lens (dyl) mutation. Mice homozygous for dyl display several defects in lens development. dyl mice also show altered patterns of crystallin expression suggesting a dysregulation of lens differentiation. We have identified mutations in Foxe3 that cosegregate with the dyl phenotype and are a likely cause of the mutant phenotype. Head ectoderm expression of Foxe3 is absent in Rx-/- and Small eye embryos indicating that Rx and Pax6 activity are necessary for Foxe3 expression.

Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow.

BACKGROUND: The distribution of macrophages and smooth muscle cells (SMCs) within atherosclerotic plaques is highly variable. This is clinically relevant because these cell types have opposite effects on the stability of atherosclerotic plaques. The present study was designed to investigate whether local variations in arterial flow over the plaque surface could relate to differences in the distribution of SMCs and macrophages in plaques. METHODS AND RESULTS: Thirty-three entire carotid plaques were collected at autopsy and marked at their proximal (in relation to the direction of the blood flow) ends, and the cell composition of upstream parts (where high flow and high shear prevail) was compared with that of downstream parts (low flow and low shear stress). Seventy percent of plaques showed more SMCs in their downstream part, and 67% of plaques contained more macrophages in the upstream part. Immunostained macrophage areas were larger in upstream parts (P=0. 011). Immunostained SMC areas were larger in downstream parts (P=0. 031). Rupture sites of 6 of 9 ruptured plaques were in the upstream part. CONCLUSIONS: Significant differences in cell composition between upstream and downstream parts of plaques indicate a role for arterial flow in the distribution of different cell types. The low-flow/low-shear downstream areas of plaques contain significantly more SMCs, which could provide the background for slowly progressive growth at distal ends of plaques. The significantly high number of macrophages in the upstream areas suggests a relationship between high flow/high shear and plaque instability.

The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1.

Genes of the Polycomb group (PcG) of Drosophila encode proteins necessary for the maintenance of transcriptional repression of homeotic genes. PcG proteins are thought to act by binding as multiprotein complexes to DNA through Polycomb group response elements (PREs); however, specific DNA binding has not been demonstrated for any of the PcG proteins. We have identified a sequence-specific DNA binding protein that interacts with a PRE from the Drosophila engrailed gene. This protein (PHO) is a homolog of the ubiquitous mammalian transcription factor Yin Yang-1 and is encoded by pleiohomeotic, a known member of the PcG. We propose that PHO acts to anchor PcG protein complexes to DNA.

Budhead, a fork head/HNF-3 homologue, is expressed during axis formation and head specification in hydra.

Accumulating evidence indicates that a common set of genes and mechanisms regulates the developmental processes of a variety of triploblastic organisms despite large variation in their body plans. To what extent these same genes and mechanisms are also conserved among diploblasts, which arose earlier in metazoan evolution, is unclear. We have characterized a hydra homologue of the fork head/HNF-3 class of winged-helix proteins, termed budhead, whose expression patterns suggest a role(s) similar to that found in vertebrates. The vertebrate HNF-3 beta homologues are expressed early in embryogenesis in regions that have organizer properties, and later they have several roles, among them an important role in rostral head formation. In the adult hydra, where axial patterning processes are continuously active, budhead is expressed in the upper part of the head, which has organizer properties. It is also expressed during the formation of a new axis as part of the development of a bud, hydra's asexual form of reproduction. Expression during later stages of budding, during head regeneration and the formation of ectopic heads, indicates a role in head formation. It is likely that budhead plays a critical role in head as well as axis formation in hydra.

A novel homeobox gene PV.1 mediates induction of ventral mesoderm in Xenopus embryos.

The formation of ventral mesoderm has been traditionally viewed as a result of a lack of dorsal signaling and therefore assumed to be a default state of mesodermal development. The discovery that bone morphogenetic protein 4 (BMP4) can induce ventral mesoderm led to the suggestion that the induction of the ventral mesoderm requires a different signaling pathway than the induction of the dorsal mesoderm. However, the individual components of this pathway remained largely unknown. Here we report the identification of a novel Xenopus homeobox gene PV.1 (posterior-ventral 1) that is capable of mediating induction of ventral mesoderm. This gene is activated in blastula stage Xenopus embryos, its expression peaks during gastrulation and declines rapidly after neurulation is complete. PV.1 is expressed in the ventral marginal zone of blastulae and later in the posterior ventral area of gastrulae and neurulae. PV.1 is inducible in uncommited ectoderm by the ventralizing growth factor BMP4 and counteracts the dorsalizing effects of the dominant negative BMP4 receptor. Overexpression of PV.1 yields ventralized tadpoles and rescues embryos partially dorsalized by LiCl treatment. In animal caps, PV.1 ventralizes induction by activin and inhibits expression of dorsal specific genes. All of these effects mimic those previously reported for BMP4. These observations suggest that PV.1 is a critical component in the formation of ventral mesoderm and possibly mediates the effects of BMP4.

Initiation of anterior head-specific gene expression in uncommitted ectoderm of Xenopus laevis by ammonium chloride.

The role of homeobox-containing genes in the regional specification of the vertebrate embryo has been an area of intense research over the last decade. Whereas it appears that the homeobox genes of the Hox gene family play an important role in the specification of the trunk, the genes and processes involved in the specification of the head are less well understood. We have isolated a new head-specific homeobox gene, XANF-2, that appears to be involved in the regional specification of the anterior head of Xenopus embryos. This gene is initially expressed in the anterior dorsal region of early embryos and later exclusively in the primordium of the anterior pituitary gland. XANF-2 represents the earliest marker for the anterior pituitary lineage. Ammonium chloride is able to induce the expression of XANF-2 in uncommitted ectoderm. These and other data indicate that ammonium chloride is capable of inducing a large portion of the anterior dorsal region of the embryo which includes, but is not limited to, the anterior pituitary gland and cement gland anlagen. This implies that changes in intracellular ionic conditions play an important role in the formation of the anterior head region. In addition to NH4Cl, injection of follistatin RNA can induce transcription of XANF-2, suggesting that these two unrelated compounds can activate a chain of events leading to the formation of the amphibian head. Furthermore, we demonstrate that planar induction in Keller sandwiches can induce XANF-2 expression as well as the expression of the cement gland-specific gene, XCG 13, indicating that planar signaling can account for induction of even the most anterior regions of the embryo.

Differential expression of fork head genes during early Xenopus and zebrafish development.

Intense efforts have been devoted to the identification of genes that are causatively involved in pattern-forming events of invertebrates and vertebrates. Several gene families involved in this process have been identified. Here we focus on the Xenopus fork head domain gene family. One of its members, XFKH1/Pintallavis/XFD1, has been shown previously to be involved in axial formation, and the expression patterns of the other family members discussed below suggest that they too play a major role in the initial steps of patterning and axial organization. In this report, we describe four Xenopus fork head genes (XFKH3, 4, 5, and 6) and analyze the distribution of their transcripts during early development. XFKH3 is expressed in developing somites but not notochord, XFKH4 in forebrain, anterior retina, and neural crest cells, and XFKH5 in a subset of epidermal cells and the neural floor plate. Finally, transcripts of XFKH6 are seen in neural crest-derived cranial ganglia. In addition, we show that at least some of the zebrafish fork head genes might serve a comparable function. Zebrafish zf-FKH1 has a similar expression pattern as Xenopus XFKH1/Pintallavis/XFD1. It is transcribed in the notochord and neural floor plate. The polster or "pillow" also shows very high levels of zf-FKH1 mRNA.

Unemployment: more than the loss of a job.

1. Involuntarily imposed work cessation is a very stressful event and represents the loss of one of the central roles and functions of life. 2. Involuntary unemployment, or its anticipation, can lead directly or synergistically to psychological and physical health consequences and behavioral maladaptations, which may be manifest overtly or appear insidiously over time. 3. Occupational health services, in collaboration with community resources and social services, can help prevent negative effects on family and community wellness from the stress of an unemployed family member or the collective stress experienced by aggregates of terminated workers in the community.

Differential expression of a Distal-less homeobox gene Xdll-2 in ectodermal cell lineages.

Neural induction in Xenopus requires the activation of new sets of genes that are necessary for cellular and regional specification of the neural tube. It has been reported earlier that members of the Distal-less homeobox gene family are specifically activated in distinct regions of the central nervous system (CNS) of Xenopus embryos (Dirksen et al., 1993; Papalopulu and Kintner, 1993). In this paper we describe in detail a Xenopus homeobox containing gene Xdll-2, which belongs to the Distal-less gene family. In contrast to other previously described Xenopus family members, Xdll-2 is expressed in the embryonic ectoderm and is specifically repressed in the CNS. This repression can be mimicked in isolated animal caps by treatment with activin. Expression of Xdll-2 persists in the epidermis and some neural crest cells. Because of its spatial and temporal expression pattern this gene is a good candidate to have a regulatory function in the initial formation of the epidermis. Its high level of expression in adult skin indicates that its function is continuously required in this tissue.

Expression of a Xenopus Distal-less homeobox gene involved in forebrain and cranio-facial development.

Homeobox-containing genes are thought to perform essential functions in the process of pattern formation in vertebrates and invertebrates. They provide cells with positional information critical for normal embryonic development. Since most of the identified homeobox genes in Xenopus seem to provide positional information for the development of the trunk, we have concentrated on genes that may be specifically involved in the formation of the head region. Using a polymerase chain reaction strategy we have searched for Xenopus homeobox-containing genes that might provide positional cues for correct development of the brain. In this paper we report the identification and cloning of a novel gene that by homology appears to be a member of the Distal-less homeobox gene family. We show that its temporal expression patterns in the cement gland, neural crest derived visceral arches, retina and forebrain, while quite diverse, does suggest shared developmental features which may be required for correct craniofacial development and the regionalization of the Xenopus brain. Furthermore, expression of this gene at later stages is primarily restricted to the tadpole forebrain suggesting that the Distal-less gene product continues to play a role after the initial brain patterning is complete.

A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain.

The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-specific cDNA libraries for genes containing the fork head box sequence that encodes a DNA-binding domain similar to that of the Drosophila homeotic gene fork head and rat hepatocyte nuclear factor HFN3 beta. These genes were subsequently tested for expression in the organizer region of blastula/gastrula-stage embryos as well as inducibility by activin. Our effort resulted in the isolation of a gene, XFKH1, that is primarily expressed in the dorsal blastopore lip of early gastrulae and is inducible by activin. At later stages it is expressed in the notochord and neural floor plate. Because of its spatial and temporal expression pattern, as well as its inducibility by activin, this gene is a good candidate to have a regulatory function in the initial processes of axis formation in Xenopus laevis embryos.

Rufloxacin once daily in acute exacerbations of chronic bronchitis.

In this open study the efficacy and tolerability of rufloxacin in a single dose of 400 mg the first day and 200 mg the nine consecutive days was studied in 26 patients with an acute exacerbation of chronic bronchitis. Twenty-two patients were evaluable for efficacy. Four patients stopped treatment prematurely after five days because of clinical cure. At the enrollment visit a pathogen was isolated in the sputum sample in 19 of 22 evaluable patients. The predominant pathogens were Streptococcus pneumoniae and Moraxella catarrhalis. In 17 of these 19 bacteriologically evaluable patients the initial infecting organism was eradicated from specimens obtained within 48 hours after the end of therapy. There was one case of persistent infection caused by S. pneumoniae (MIC 4 mg/l), one patient had a superinfection with Serratia marcescens (MIC 1 mg/l) susceptible to rufloxacin and therapy was stopped after five days due to clinical failure. One week after the end of therapy, 15 patients remained free from infection whilst one patient experienced reinfection with Klebsiella pneumoniae (MIC 0.5 mg/l). Clinical cure or improvement was observed in 21 of 22 patients. Mild adverse events were reported by two of 26 enrolled patients. In one patient, complaining of headache and dizziness, the adverse events were considered possibly study drug related. No abnormal laboratory findings were reported. Nadir plasma levels of rufloxacin were measured and no accumulation in plasma was observed during treatment. A ten day course of an oral single dose of rufloxacin proved efficacious and was well tolerated in patients with an acute exacerbation of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)