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.     

Handling of biological samples in the determination of the anti-neoplastic drug mitomycin C

A study to ascertain suitable conditions for handling biological samples from patients, treated with the antibiotic mitomycin C (MMC), with the objective of improving the accuracy and reliability of the determination is described. Situations frequently occurring in medical practice are simulated to optimize procedures for reliable and reproducible sampling, sample treatment and determination of MMC. Continuation of drug partitioning in whole blood after sampling can be prevented by immediate cooling in ice before the separation of plasma from cells. The adjustment of the pH of urine samples is shown to be particularly important since a low urinary pH causes decomposition of MMC; moreover, it may decrease extraction recovery. Furthermore, long-term exposure of samples to daylight induces drug decomposition. Frozen storage of plasma and urine samples for periods greater than 3 weeks is to be avoided as this results in a considerable drop in MMC concentration. Repeated cycles of freezing and thawing are shown to have no effect upon the analytical results (6 cycles tested). The analysis of extracts of biological samples may take place up to at least 24 h after their preparation without measurable loss of analyte.     

A denaturated venous homograft as an alternative material for shunts and other reconstructions in congenital cardiac surgery

A human venous homograft "Varivas R", in clinical use for 10 years for vascular access loops and femoropopliteal bypasses, has been used since December 1985 as a material for aortopulmonary shunts and other reconstructive procedures in congenital heart surgery. For this purpose vein segments 5 cm length, varying in diameter from 4 up to 10 mm by steps of 1 mm, were obtained. Our experience with Varivas is limited to 59 patients. Of 47 infants, 18 received a left, and 25 a right sided aortopulmonary shunt, 9 had bilateral aortopulmonary shunts, 2 right ventricle pulmonary conduits, 1 a pulmonary-pulmonary conduit, 3 interrupted aortic arch reconstructions and 4 a central aortopulmonary shunt, 1 with confluence reconstruction, 3 recidives of coarctation a patch repair. Among 11 adults 6 received coronary bypass and 6 others vascular reconstructions. In contrast to other artificial graft materials, the vein material offers easy manipulation similar to the daily routine of handling fresh vein material offers easy manipulation similar to the daily routine of handling fresh vein grafts in coronary surgery. The appropriate diameter sizes match better the infants anatomy, without the risk of kinking and/or anastomosis displacement. Peroperatively it was possible to confirm patency by electromagnetic flow measurement and the postoperative examinations were done by colour Doppler echocardiography. We had to reoperate upon 4 infants because of early thrombosis; on 1 infant for stenosis of the graft and on another 5 for late thrombosis. In an attempt to extend the indications for "inoperable" pulmonary hypoplasia/atresia we were not able to keep the shunt open in 4 infants.     

The vibratory innocent heart murmur in schoolchildren: A case-control Doppler echocardiographic study

Summary In 810 schoolchildren (aged 5–14 years) the prevalence of a grade 1–3/6 vibratory innocent heart murmur (VIHM) is 41%. Restricted to a grade 2 or 3 VIHM, the prevalence is 14%, decreasing from 21% in the age-class 5–6 years to 8% for children 13–14 years of age. The prevalence of a grade 3 VIHM is 1%. Together with a matched control, 84 children with a grade 2 or 3 VIHM underwent further cardiologic examination including electrocardiography, phonocardiography, and Doppler echocardiography. A positive correlation was found between the presence of a VIHM and higher left ventricular voltages on the ECG, but within the normal range; lower heart rate; smaller diameter of the ascending aorta (AAO); and higher blood flow velocity and higher maximal acceleration of the blood flow in the LVOT and the AAO. In 40% of the children with a VIHM, a systolic aortic valve vibration was seen with a frequency 100 Hz and an amplitude 1 mm, whereas this type of vibration was present in only one case control. No significant difference was found concerning the prevalence of false tendons in the left ventricle, systolic and diastolic diameter of the left ventricle, systolic time intervals, and shortening fraction of the left ventricle. The VIHM is strongly associated with a smaller AAO, with higher velocity and acceleration of the blood flow in the LVOT and AAO, and with a vibratory phenomenon of the aortic valve, pointing towards the LVOT-aortic valve region as the site of origin of the VIHM.     

Plasma assay for the antineoplastic agent VP 16-213 (etoposide) using high-performance liquid chromatography with electrochemical detection

A sensitive high-performance liquid chromatographic (HPLC) assay of the antineoplastic agent VP 16-213 (etoposide) in plasma is described. The system discriminates between the parent compound and possible metabolites, including the aglycone and the cis isomer. After extraction with 1,2-dichloroethane the drugs are chromatographed on a reversed-phase phenyl column with amperometric detection. Quantitative response is linear up to 250 ng/ml for 1 ml human plasma and up to 40.0 mug/ml for 0.1 ml human plasma. The detection limit is ca 2 ng/ml in plasma. Preliminary pharmacokinetic results show that the sensitivity and selectivity of the assay are adequate to establish plasma concentrations over 8-12 half-lives during elimination of the drug.     

The value of the Hospital Anxiety and Depression Scale (HADS) for comparing women with early onset breast cancer with population-based reference women

BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is frequently used in cancer studies, yet its utility for comparing people with cancer with people in the community is uncertain. METHODS: HADS scores were obtained from population-based samples of women with (n = 731) and without (n = 158) early-onset breast cancer. Psychometric properties were examined using differential item functioning (DIF) which is the presence of systematic group differences in certain response items independent of the trait being measured. RESULTS: Women with breast cancer scored lower than reference women on anxiety (mean (SD) 7.5 (4.3) vs. 8.2 (4.0); p = 0.06) and depression (3.3 (3.2) vs. 4.2 (3.0); p = 0.003). Group differences remained following adjustment for demographics. Time since diagnosis was not related to anxiety or depression scores. DIF was present in two anxiety and five depression items. Adjustment for DIF did not substantially change the anxiety or depression group differences. CONCLUSION: Specific sampling or DIF effects do not explain the observation that women with breast cancer have lower levels of anxiety and depression than population controls. The psychometric properties of the HADS appear to be acceptable in these groups.     

Electrophysiological Correlation Patterns of Resting State Networks in Single Subjects: A Combined EEG–fMRI Study

With combined EEG–fMRI a powerful combination of methods was developed in the last decade that seems promising for answering fundamental neuroscientific questions by measuring functional processes of the human brain simultaneously with two complementary modalities. Recently, resting state networks (RSNs), representing brain regions of coherent BOLD fluctuations, raised major interest in the neuroscience community. Since RSNs are reliably found across subjects and reflect task related networks, changes in their characteristics might give insight to neuronal changes or damage, promising a broad range of scientific and clinical applications. The question of how RSNs are linked to electrophysiological signal characteristics becomes relevant in this context. In this combined EEG–fMRI study we investigated the relationship of RSNs and their correlated electrophysiological signals [electrophysiological correlation patterns (ECPs)] using a long (34 min) resting state scan per subject. This allowed us to study ECPs on group as well as on single subject level, and to examine the temporal stability of ECPs within each subject. We found that the correlation patterns obtained on group level show a large inter-subject variability. During the long scan the ECPs within a subject show temporal fluctuations, which we interpret as a result of the complex temporal dynamic of the RSNs.     

Thermal unfolding and refolding of a lytic polysaccharide monooxygenase from Thermoascus aurantiacus

Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes which promote the degradation of recalcitrant polysaccharides like cellulose or chitin. Here, we have investigated the thermostability of an LPMO from Thermoascus aurantiacus (TaLPMO9A). TaLPMO9A was found to retain most of its initial activity after incubating at 100 °C while its apparent melting temperature (T_m) is 69 °C at neutral pH. Interestingly, our studies show that holoTaLPMO9A, apoTaLPMO9A and deglycosylated TaLPMO9A can fold back to their original conformation upon lowering the temperature. In the presence of β-mercaptoethanol the protein does not refold. Activity of TaLPMO9A and refolded TaLPMO9A was studied by an Amplex® Red assay as well as by TaLPMO9A catalysed oxidation of phosphoric acid swollen cellulose (PASC). These studies confirm the functional regain of TaLPMO9A activity upon going through one cycle of unfolding and refolding. The thermal unfolding and refolding of TaLPMO9A was measured spectroscopically. Utilizing the two-state model, detailed thermodynamic parameters were obtained for holoTaLPMO. Furthermore, we have investigated the kinetics of TaLPMO9A unfolding and refolding. Our results have implications in understanding LPMO stability, which is crucial for the efficient application of LPMOs as biocatalysts during biomass degradation.

TaLPMO9A regains its catalytic power after a thermal unfolding and refolding cycle.