Holographic interferometry forIn Vitro investigation of bioprosthetic valves

Dysfunction of heart valve prostheses—mechanical as well as biological—is a common problem in cardiac surgery. The reasons for the valve failures are still not well understood. Biological valves especially have an unsatisfactory durability; degeneration and calcification very often lead to the failure of the valves. In our opinion, hidden defects present in the valve material prior to implantation of the valves is a plausible explanation for the dysfunction. Hitherto there has been no technique to detect these defects without destructing the specimen. Holographic interferometry proved to be applicable forin vitro evaluation of mechanical heart valve prostheses. In the present paper we describe application of this method to biological valves. Nine porcine bioprostheses and four fresh porcine aortic valves were investigated by means of holographic interferometry. In eight of nine bioprostheses, the results showed irregularities of the leaflet structure which depend on anomalies of the connective tissue of the leaflets of the valves. To make sure that these findings are not due to normal variations of the morphology, the investigations were carried out with fresh and unfixated porcine aortic valves. In the latter, no such anomalies of the structure were detected. The results obtained confirm the above hypothesis on the origin of the later valve dysfunction. Thus, holographic interferometry tests of bioprostheses prior to their implantation prevent the use of potentially dysfunctional valves.Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993     

Lines of Murine Oligodendroglial Precursor Cells Immortalized by an Activated neu Tyrosine Kinase Show Distinct Degrees of Interaction with Axons In Vitro and In Vivo

Replication-defective retroviruses expressing the t- neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr-neu ), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t- neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t- neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.     

Increased CSF neopterin levels in subarachnoid hemorrhage

Neopterin concentrations, reflecting T-cell macrophage activation, were analyzed in serum and cerebrospinal fluid (CSF) obtained from 14 patients with subarachnoid hemorrhage (SAH). Neopterin concentrations were elevated in both the serum and CSF. The increase in neopterin concentrations was most marked in the CSF, rising from Days 1 to 3 through Days 6 to 9; levels were highest in patient suffering from delayed cerebral ischemia. The present data were interpreted as signs of an ongoing T cell activation both systemically and in the CSF compartment following SAH.     

Malignant peripheral neuroectodermal tumors in urology

Summary During the past few years, a new tumor type has emerged in the pediatric and adolescent group of cancer patients, which has been designated malignant peripheral neuroectodermal tumor (MPNT). This tumor has some clinical and pathological signs in common with either soft-tissue sarcomas or classic Ewing's sarcoma, but is defined as a distinct entity because of its immunohistological characteristics. The tumor expresses neuronal markers, but the pattern varies: chromogranin, neuron-specific enolase, synaptophysin, protein S-100 and others. MPNT can occur in the urogenital region. The differential diagnosis on clinical grounds must include Ewing's and soft tissue sarcomas, and also Wilms' tumor and its variants. MPNT are often wide spread in the urogenital region when first diagnosed. Response to radiotherapy and combination chemotherapy is limited. Radical surgery is not always possible. The prognosis therefore remains rather poor at this time. A selection of MPNT patients is presented to demonstrate the various problems associated with this diagnosis. MRI and CT of all patients showed large tumors with direct infiltration of the surrounding structures. MRI is the best imaging modality for diagnosis and therapy monitoring in these tumors, because of its high soft-tissue contrast.     

Comparison of three immunoassays for diagnosing sensitization to latex in children with spina bifida

As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1—3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4—9), healthcare professionals (10—12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.     

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

Summary. In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-¹⁴C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l^-1. The subjects' ages were 64±2.7 and 66±1.1 (mean±SEM) years in the COPD and control groups, respectively. TOR was 0.73±0.06 and 0.52±0.02 mmol min^-1 (P<0.05) in the basal state, 0.33±0.04 and 0.30±0.02 at an insulin level of 50 mU I^-1 and 0.32±0.08 and 0.24±0.02 at an insulin level of 100 mU I^-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98±0.08 and 0.75±0.06 mmol 1^-1 (P<0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.     

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.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.