Improving Prenatal Diagnosis of Coarctation of the Aorta

Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

Influence of mesh materials on collagen deposition in a rat model.

Alterations of the extracellular matrix (ECM) with its major component collagen are increasingly discussed as possible risk factors implicated in the development of abdominal-wall herniation. Because of the widespread use of alloplastic meshes for the surgical repair of hernias, an animal study was performed to analyze the influence of various mesh materials on the quantity and quality of collagen deposition. In 60 male Sprague-Dawley rats an abdominal replacement was performed using three different kinds of mesh materials: polyester (PE), a pure polypropylene (PP), and a composite mesh made of polypropylene and polyglactin (PG). A simple fascia suture repair served as control. The count of fibroblasts, the collagen/protein ratio, the type I/III collagen ratio, and the expression of basic fibroblast growth factor (b-FGF) at the interface were analyzed after 7, 21, and 90 days. The ratio of collagen to overall protein (microg/mg) showed significant differences comparing different mesh materials (sham controls 38.44 +/- 16.33 microg/mg, PE 68.5 +/- 23.8 microg/mg, PP 101.6 +/- 32.3 microg/mg, PG 49.6 +/- 11.6 microg/mg at day 90). The ratio of collagen type I/III increased over time in all groups. However, 90 days after mesh implantation the ratio was always significantly lowered compared to the controls. No significant difference was found comparing different mesh materials. The alteration of the scar composition is closely connected to an increased b-FGF expression. b-FGF and count of fibroblasts highly correlated (r =.95) and showed significant elevated levels compared to simple suture repair. The results of our study strongly support the notion that wound healing is affected by mesh implantation. The quality of the ECM deposition as determined by collagen type I/III ratio is impaired in general, whereas the quantity of ECM deposition is markedly influenced by the kind of mesh material.     

Local hemostasis in subarachnoid hemorrhage

Fibrinopeptide A (FPA), platelet-secreted protein, platelet factor 4 and beta-thromboglobulin were determined in the cerebrospinal fluid of patients who had suffered from subarachnoid hemorrhage and were treated with 6 g tranexamic acid or 4 million KIU aprotinin to prevent rebleeding. Platelet-secreted proteins and FPA were cleared from the cerebrospinal fluid within 3 days after bleeding. Their vasoactive and thrombotic capability is limited to the initiation period of vasospasm that usually comes to clinical observation 3-8 days after bleeding. Increased thrombotic activity of the cerebrospinal fluid, as reflected by high levels of FPA and platelet-secreted protein, seemed to promote the occurrence of neurological deficits.     

Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities

A series of substituted indolyldihydropyridazinones and related compounds 1-18 were synthesized and evaluated for positive inotropic activity. In rats, most of these indole derivatives produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. Compound 13, 4,5-dihydro-5-methyl-6-(2-pyridin-4-yl-1H-indol-5-yl)pyrazin-3(2H) -one (BM 50.0430), was further investigated in cats. The increase in contractility in this animal model was not mediated via stimulation of beta-adrenergic receptors. After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h. However, the cardiotonic effect of 13 was at least 2-fold that of pimobendan after this period of time. The structural requirements necessary for optimal cardiotonic activity within this novel class of indole derivatives are a heterocyclic aromatic ring in position 2, a hydrogen or a methyl group in position 3, and a dihydropyridazinone ring system in position 5 of the indole.     

Early complications of stenting in patients with congenital heart disease: a multicentre study.

AIMS: Stenting has become an established interventional cardiology procedure for congenital heart disease. Although most stent procedures are completed successfully, complications may occur. This multicentre study evaluated early complications after stenting in patients with congenital heart disease, including potential risk factors. METHODS AND RESULTS: In this combined Dutch-Belgian retrospective study, 309 consecutive patients had undergone 366 catheterizations and received 464 stents in 13 different anatomical positions (418 sites). Seventy-two stenting-related complications (19%) occurred, of which 24 (5.7%) were major. Seven procedure-related deaths were documented (2.3%). Stent malpositioning and embolization were most common (7.7%). The use of non-premounted stents tended to be associated with higher complication rates. Centre inexperience with stenting and stenting of native vs. post-surgical stenosis tended to be associated with increased major complication rates. CONCLUSION: After stenting, complications are common for congenital heart disease. The vast diversity of stenotic sites combined with relatively small patient populations makes these procedures sensitive to complications. Combining operator experience may reduce the risks of stenting in congenital heart disease. The availability of premounted stents for greater vessel diameters will likely reduce incidences of stent migration and embolization.     

Biomaterial-dependent MMP-2 expression in fibroblasts from patients with recurrent incisional hernias

With regard to the pathogenesis of recurrent incisional hernia, an impaired connective tissue quality leading to an aberrant scarring process has been proposed. For the matrix metalloproteinase (MMP-2) a pathogenetic involvement in direct inguinal hernia development is reported. With mesh implantation as the gold standard treatment for incisional hernias, the aim of the present study was to investigate the MMP-2 expression in patients with recurrent incisional hernias with and without mesh-materials. In primary fibroblast cultures obtained from skin scars in patients with and without recurrent incisional hernias, MMP-2 synthesis and gene expression were investigated. Furthermore, MMP-2 synthesis and gene expression of fibroblasts were compared after incubation with two different mesh materials: polypropylene and absorbable polyglactin filaments. MMP-2 enzyme activity was determined by semiquantitative zymography and mRNA synthesis by quantitative RT-PCR. Both MMP-2 enzyme activity and mRNA expression were similar in hernia and control fibroblasts in vitro. In control fibroblasts mesh incubation did not significantly affect MMP-2 expression, whereas polypropylene mesh contact of fibroblasts from patients with recurrent incisional hernias led to a major decrease of MMP-2 activity and of mRNA expression. In the absence of biomaterials fibroblasts from recurrent incisional hernia, patients have no alterations of their MMP-2 synthesis compared to control fibroblasts, whereas a specific response was found after biomaterial contact hereby indicating differences in fibroblast phenotype. This work was supported by IZKF-BIOMAT, RWTH-Aachen, project no. TV B66 and by the Deutsche Forschungsgemeinschaft grant KL 1320/2-1     

Are hypodense eosinophils in children activated or immature?

In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils.