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The in-vitro genotoxicity of nanosized TiO(2) rutile and anatase was assessed in comparison with fine TiO(2) rutile in human bronchial epithelial BEAS 2B cells using the single-cell gel electrophoresis (comet) assay and the cytokinesis-block micronucleus test. BEAS 2B cells were exposed to eight doses (1-100 microg/cm(2)) of titanium(IV) oxide nanosized rutile (>95%, <5% amorphous SiO(2) coating; 10 x 40 nm), nanosized anatase (99.7%; <25 nm), or fine rutile (99.9%; <5 microm) for 24, 48, and 72 h. Fine rutile reduced cell viability at lower doses than nanosized anatase, which was more cytotoxic than nanosized rutile. In the comet assay, nanosized anatase and fine rutile induced DNA damage at several doses with all treatment times. Dose-dependent effects were seen after the 48- and 72-h treatments with nanosized anatase and after the 24-, 48- (in one out of two experiments), and 72-h treatments (one experiment) with fine rutile. The lowest doses inducing DNA damage were 1 microg/cm(2) for fine rutile and 10 microg/cm( 2) for nanosized anatase. Nanosized rutile showed a significant induction in DNA damage only at 80 microg/cm(2) in the 24-h treatment and at 80 and 100 microg/ cm(2) in the 72-h treatment (with a dose-dependent effect). Only nanosized anatase could elevate the frequency of micronucleated BEAS 2B cells, producing a significant increase at 10 and 60 microg/cm( 2) after the 72-h treatment (no dose-dependency). At increasing doses of all the particles, MN analysis became difficult due to the presence of TiO(2) on the microscopic slides. In conclusion, our studies in human bronchial epithelial BEAS 2B cells showed that uncoated nanosized anatase TiO(2) and fine rutile TiO(2) are more efficient than SiO( 2)-coated nanosized rutile TiO(2) in inducing DNA damage, whereas only nanosized anatase is able to slightly induce micronuclei.

In patients operated with atrial switch for transposition of the great arteries (TGA), the left ventricle (LV) supports the pulmonary circulation and is thus pressure unloaded. Evaluation of LV function in this setting is of importance, as LV functional abnormalities have been documented and might contribute to development of symptoms. The ventricular contraction pattern in 14 Senning-operated TGA patients and 14 healthy controls was studied using tissue Doppler and magnetic resonance imaging. In the subpulmonary LV free wall, longitudinal strain was greater than circumferential strain (-23.6 +/- 3.6% vs. -19.1 +/- 3.2%, p = 0.002) as in the normal right ventricle (RV) (-30.7 +/- 3.3% vs. -15.8 +/- 1.3%, p < 0.001), but opposite to findings in the normal LV (-16.5 +/- 1.7% vs. -25.7 +/- 3.1%, p < 0.001). Subpulmonary strain and strain rate values were intermediate between those in the normal LV and RV. Ventricular free-wall torsion was reduced in the subpulmonary LV compared with both the normal LV (5.7 +/- 3.2 degrees vs. 16.7 +/- 5.6 degrees , p < 0.001) and RV (5.7 +/- 3.2 degrees vs. 11.4 +/- 2.6 degrees , p < 0.05). Furthermore, early diastolic filling of the subpulmonary LV differed from that of the normal LV. The subpulmonary LV displayed predominantly longitudinal shortening, as did its functional counterpart, the normal RV. However, the degree and rate of both longitudinal and circumferential shortening were intermediate between those of the normal LV and RV. This could represent a partial adaptation to the reduced pressure load. Decreased ventricular torsion and diastolic abnormalities might indicate subclinical ventricular dysfunction.

This review discusses the evidence for endocrine treatment in postmenopausal patients with metastatic breast cancer. First line treatment with non-steroid aromatase inhibitors (AI) yields response rates of 30% and improves progression free survival, but not overall survival, compared to tamoxifen. With second line treatment using steroid AI, estrogen antagonists or selective estrogen receptor modulators prolonged disease stabilisation is achieved in 40% of patients. With third line treatment using steroid AI and estrogen antagonists disease stabilisation is achieved in up to 30% of patients.

This review discusses the indications and purposes of treatment for metastatic breast cancer with chemotherapy and monoclonal antibody against the erbB-2 receptor(trastuzumab). There is no curative treatment for this condition, but first line chemotherapy with anthracyclines or taxanes improves the overall survival and offers palliation of disease-related symptoms. For patients with HER-2 positive tumour the combination of chemotherapy and trastuzumab can increase the response rates and survival. Palliation of symptoms is also achievable with second line chemotherapy. For patients with symptoms and good performance status, third line treatment should be considered, but there are no standard recommendations.

Adjuvant hormonal therapy results in substantial improvements in disease-free and overall survival for women with operable breast cancer. Many randomised trials of adjuvant tamoxifen have been published, and an updated overview of their results is presented in this paper. The third-generation aromatase inhibitors have recently been compared with tamoxifen. These studies are also reviewed in this paper. The Danish Breast Cancer Cooperative Group recommends adjuvant hormonal therapy consisting of tamoxifen for 2.5 years followed by the aromatase inhibitor for 2.5 years, or 5 years of the aromatase inhibitor for women with contraindications to tamoxifen.

Passive mode locking of an optically pumped, InP-based, 1550 nm semiconductor disk laser by using a GaInNAs saturable absorber mirror is demonstrated. To reduce material heating and enable high-power operation, a 50 microm thick diamond heat spreader is bonded to the surface of the gain chip. The laser operates at a repetition frequency of 2.97 GHz and emits near-transform-limited 3.2 ps pulses with an average output power of 120 mW.

Objectives: To determine whether the present system of reimbursement, based on diagnosis-related groups and regular financial budgeting, covers the costs incurred during hospitalisation of 7 children undergoing the three stages of the Norwood sequence for surgical treatment of hypoplastic left heart syndrome., Methods: Between January and September 2003, 7 patients underwent initial surgical palliation with the Norwood procedure at the Rikshospitalet University Hospital. A prospective methodology was developed by our group to measure the costs associated with each individual patient. The patients were closely observed, and the relevant data was collected during their stay in hospital. The stay was divided into four different periods of requirements of resources, defined as heavy intensive care, light intensive care, intermediate care, and ordinary care. At each stage, we recorded the number of staff involved and the duration of surgery and other major procedures, as well as the cost of pharmaceuticals and other consumables. Based on these data, we calculated the cost for each patient. These costs were compared with the corresponding revenue received by the hospital for each of the patients., Results: We found the total mean cost for the three stages of the Norwood sequence was 138,934 American dollars, while the corresponding revenue received by the hospital was 43,735 American dollars. During this period, one patient died during the first stage of the Norwood sequence., Conclusions: Our study shows that steps involved in the Norwood sequence are low-volume but high-cost procedures. The reimbursement received by our hospital for the procedures was less than one-third of the recorded costs.

An optically pumped, high-power, single-frequency semiconductor disk laser is demonstrated. A thin (50 microm) diamond bonded to an InGaAsP gain chip provides the combined functions of heat removal and spectral filtering, thus eliminating the need for the additional intracavity etalons that are usually employed for single-frequency operation. In a short cavity (4 mm) configuration we obtained a maximum output power of 470 mW at 0 degrees C and 170 mW at 20 degrees C in a near-diffraction-limited beam (M2 < 1.2). The emission wave-length was 1549 nm and the linewidth was less than 200 MHz.

Aims: To register mortality and causes of death in patients with congenital heart defects (CHDs)., Methods: Prospective population-based observational study., Results: 553 infants with CHD (1.1% of live born) were observed for 1-22 y (median 10 7/12 y). Sixty-four died (11.6%), of whom 32 (50%) died during the first 4 wk, and 51 (79.7%) during the first year of life. Of the total neonatal deaths in the population (3 per 1000), CHDs occurred in 21.5%. Mortality for children with CHDs was not significantly different between the cohorts born in 1982-1991 and 1992-2002, for either neonatal deaths or deaths later on (p>0.05). Out of 170 patients in whom therapeutic procedures (surgery, catheter interventions) were undertaken, 34 (20%) died. Nine cases (1.6%) died with unrecognized CHDs; seven of these on the first day of life with severe extracardiac malformations. In 50 (78.1%) cases, death was judged to be caused directly or indirectly from the CHD, and in 14 (21.9%) from extracardiac malformations or other conditions., Conclusion: CHDs occur in a substantial number of neonatal deaths. Most deaths are caused by cardiac insufficiency. The mortality rate remained unchanged.

Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 microg ml(-1)), methacholine (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a global marker of mucinous secretion and alpha(2)-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level (P<0.01-0.05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of alpha(2)-macroglobulin (P<0.01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways.

The aim of this study was to assess the feasibility and comparability of metabonomic data in clinical studies conducted in different countries without dietary restriction. A (1)H NMR-based metabonomic analysis was performed on urine samples obtained from two separate studies, both including male and female subjects. The first was on a group of healthy British subjects (n = 120), whilst the second was on healthy subjects from two European countries (Britain and Sweden, n = 30). The subjects were asked to provide single, early morning urine samples collected on a single occasion. The (1)H NMR spectra obtained for urine samples were visually inspected and analysed chemometrically using principal components analysis (PCA). These inspections highlighted outliers within the urine samples and displayed interesting differences, revealing characteristic dietary and cultural features between the subjects of both countries, such as high trimethylamine-N-oxide (TMAO)-excretion in the Swedish population and high taurine-excretion, due to the Atkins diet. This study suggests that the endogenous urinary profile is subject to distinct cultural and severe dietary influences and that great care needs to be taken in the interpretation of 'biomarkers of disease and response to drug therapy' for diagnostic purposes.

Transforming growth factor-beta(1) (TGF-beta(1)) induces alpha-smooth muscle actin (alpha-SMA) and collagen synthesis in fibroblast both in vivo and in vitro and plays a significant role in tissue repair and the development of fibrosis. During these processes the fibroblasts differentiate into activated fibroblasts (so called myofibroblasts), characterized by increased alpha-SMA expression. Because TGF-beta(1) is considered the main inducer of the myofibroblast phenotype and cytoskeletal changes accompany this differentiation, the main objective of this investigation was to study how TGF-beta(1) alters protein expression of cytoskeletal-associated proteins. Metabolic labeling of cell cultures by [(35)S]methionine, followed by protein separation on two-dimensional gel electrophoresis, displayed approximately 2500 proteins in the pI interval of 3-10. Treatment of TGF-beta(1) led to specific spot pattern changes that were identified by mass spectrometry and represent specific induction of several members of the contractile apparatus such as calgizzarin, cofilin, and profilin. These proteins have not previously been shown to be regulated by TGF-beta(1), and the functional role of these proteins is to participate in the depolymerization and stabilization of the microfilaments. These results show that TGF-beta(1) induces not only alpha-SMA but a whole set of actin-associated proteins that may contribute to the increased contractile properties of the myofibroblast. These proteins accompany the induced expression of alpha-SMA and may participate in the formation of stress fibers, cell contractility, and cell spreading characterizing the myofibroblasts phenotype.

A tissue proteomics process is presented where hepatocyte cell isolation in combination with two-dimensional (2-D) gel electrophoresis and mass spectrometric identification were used to annotate the liver proteome. Laser microdissection of 8 microm liver tissue sections was performed and protein expression profiling was compared using a variety of quantities of input cells, and gel separation conditions. The 30 microm diameter laser generated the highest protein yields from the polymer coated caps following microsolubilization. We found that 6000 laser pulses (approximately 7200 hepatocytes) were required in order to generate high-resolution gel maps. Within homogeneous tissue samples, this could be accomplished in a total cycle time of 20 min using an automated dissection procedure. Close to 1000 high-quality gel annotations were generated from the corresponding 2-D gel expression profiles which matched closely the corresponding patterns of analytical-scale liver preparations detected by silver staining.

Respiratory diseases are an important health problem throughout the world. Whether caused by industrial pollutants, infections, smoking, cancer or metabolic diseases, damage to the lungs and airways often lead to morbidity or death. Bronchoalveolar lavage (BAL) obtained by fiber-optic bronchoscopy is a biofluid mirroring the expression of normally secreted pulmonary proteins and the products of activated cells and destructive processes. The characterization of the proteome within this compartment provides an opportunity to establish temporal and prognostic indicators of airway disease. The objective of this study was to develop methods of analysis of BAL samples, which achieved the highest level of annotation of the expression map of this proteome. We have optimized the process of sample preparation after investigating a variety of techniques including dialysis, ultramembrane filtration, precipitation and gel filtration. We have further studied methods to remove albumin from BAL in order to unmask proteins hidden on two-dimensional gels. In a pilot application of the method, BAL protein profiles obtained from healthy nonsmokers and smokers at risk for developing chronic obstructive pulmonary disease showed distinct differences.

In a population based study including 35,218 infants born alive during the 15-year period 1982-1996, 360 (1%) were diagnosed having a congenital heart defect (CHD). At a follow-up 3-18 years later (median 9.5 years) 154 patients (42.8%) were spontaneously cured, of whom 142 (92.2%) had ventricular septal defects (VSD). 42 patients (11.7%) had died, 22 of whom (52.4%) during the neonatal period (0-28 days after birth). A total of 119 patients (33.1%) underwent therapeutic procedures (surgery, catheter interventions), of whom 24 (20.2%) died. Of the 95 children surviving therapeutic procedures 54 (56.8%) had their defects completely repaired, while 41 (43.2%) had residual defects or cardiac sequelae, often of minor importance. Of 69 children (19.2%) with persistent untreated defects, 43 (62.3%) had VSD. A chromosomal disorder, various syndromes or extracardiac malformations occurred in 72 children (20%). The study underlines the fact that CHD presents itself in varying degrees of severity, including a high neonatal mortality rate as well as a high rate of spontaneous cure.

Noradrenaline release, graded by frequency variation of field stimulation (0.1-2 Hz), in atrial myocardial specimens (n=45) from children (n=21) with congenital heart defects, was used to examine the inotropic responses of graded, receptor-selective, endogenous stimulation. Muscle trabeculae subjected to autonomic blockage by timolol, prazosin and atropine showed a slight positive force-frequency relationship (staircase phenomenon). Blockage by atropine/prazosin (i.e. beta-adrenoceptor stimulation) or atropine/timolol (i.e. alpha1-adrenoceptor stimulation) both resulted in positive inotropic effects. A group of specimens opposed by atropine and primarily subjected to frequency variation, secondly was returned to 1 Hz. Stabilization was followed by sequential reversal by beta-blocker (timolol), alpha 1-adrenoceptor stimulation by exogenous noradrenaline, reversal by alpha 1-blocker (prazosin), and finally supramaximal beta-adrenoceptor stimulation (isoprenaline). The maximal levels of inotropic responses mediated by exogenous alpha 1- and beta-adrenoceptor stimulation was estimated. Analysis of the contraction-relaxation cycles revealed that alpha1- and beta-adrenoceptors were recruited differentially. The alpha1-adrenoceptor mediated, endogenous inotropic effect at 1 Hz was close to the level obtained by exogenous noradrenaline stimulation. In contrast, less than 70% of the beta-adrenoceptor mediated, exogenous inotropic effect was expressed by endogenous noradrenaline at the same stimulating frequency, thus indicating that the alpha1-adrenoceptors may be located closer to the adrenergic nerve terminals than the beta-adrenoceptors. There may be a heterogeneous relationship within the same heart as to the relative distance between the nerve terminals and the adrenoceptors. Spatial localization of adrenergic receptors relative to adrenergic nerve terminals adds another aspect to adrenergic regulation. The alpha1-adrenoceptor pathway may play an important role, especially in low-intensity sympathetic inotropic myocardial control, whereas the beta-adrenoceptor pathway adds important effects to the high-intensity sympathetic regulation. Sympathetic activity may thus tonically stimulate the alpha1-adrenoceptor pathway, without necessarily stimulating the beta-adrenoceptor pathway to the same extent.

There are about 500 new cases of congenital heart disease per year in Norway. Modern diagnostic skills, surgical techniques and follow-up programs have contributed to higher survival rates among patients. Based on international experience, 85-90 per cent of these children will survive into adulthood. Half will suffer from conditions which should be followed up by cardiologists. This article is based upon recommendations on long-term follow-up of patients with congenital heart disease.

The first heart transplantation in the Nordic countries was performed at Rikshospitalet, Oslo in 1983. In this paper, we present our experience with this treatment up to 1999. 317 heart transplantations have been performed, an average of 23 transplantations per year. 82% of the recipients were males; 50% had heart failure due to coronary heart disease. Mean age of the recipients was 47 years (range 1-64). Our indications and contraindications are similar to most other transplantation centres. Triple immunosuppression with ciclosporin, prednisolone and azathioprine have been used as standard treatment. The survival rate after one and ten years are 85% and 53% respectively, with a significantly higher survival rate among recipients younger than 50 at transplantation, especially if the graft was from a donor younger than 35 years. The most common early postoperative complications were acute cellular rejections and infections. Transplant accelerated coronary heart disease and cancer were the main causes of late death. We believe that close co-operation between Riskshospitalet and local centres will provide the best treatment for patients needing a heart transplant.

Measurement of plasma levels of natriuretic peptides are now in clinical use in adult patients with heart failure. Experiences in adult medicine cannot be extended to paediatric cardiology due to important physiological differences between adults and children. The haemodynamic background of heart failure in children with congenital heart disease is diverse, and there is no relevant functional or echocardiographic grading system. The authors present results from published studies and summarizes the results of a research project concerning the clinical potential of N-terminal proatrial natriuretic peptide (Nt-proANP) in paediatric cardiology. Peptide levels in newborn children with or without disease are not fully clarified. In children above three months of age, an elevated Nt-proANP value strongly indicates haemodynamic imbalance. This may be important in the follow-up of children with congenital heart disease. A normal value does not exclude the presence of heart disease. A case report illustrates the clinical use of Nt-proANP, and peptide levels in different haemodynamic situations are discussed.

We postulated previously that variables related to pulmonary flow are independent predictors of levels of atrial natriuretic peptide in children with congenital heart disease. The aim of this study was to test this hypothesis in relation to other hemodynamic and clinical variables. During catheterization we measured the levels of plasma N-terminal atrial natriuretic peptide prohormone in the plasma of 68 children with congenital heart disease. All had undergone complete clinical, echocardiographic and invasive hemodynamic investigations. The influence on the prohormone was analyzed for 10 different variables in a multiple linear regression model. The variability could be explained in large parts (adjusted R2 =77.2%) by variations in atrial pressures or sizes, together with the degree of excessive pulmonary blood flow and signs of heart failure. A value for atrial natriuretic peptide prohormone above 800 pmol/l predicted hemodynamic imbalance (defined as elevated pressures in left or right atrium or the pulmonary arteries, and/or Qp/Qs > 1.5) with a specificity of 94%, a sensitivity of 73%, a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29. In conclusion, variables related to pulmonary blood flow are influential determinants of the levels of atrial natriureic peptide in children with congenital heart disease. Atrial pressures, and symptoms of heart failure are also of major importance.

To analyse the possible influence of endogenous muscarinic activity on the inotropic effects of endogenously released noradrenaline in field stimulated myocardial preparations from atria of children with congenital heart defects, we studied the maximal effect of the muscarinic antagonist atropine (1.5 micromol L(-1)). Maximal force of contraction increased by 12.8 +/- 2.0% (SEM), while the maximal rate of development of the force increased by 16.7 +/- 2.7% (SEM). Time to half maximal developed force was 57 +/- 5 s (SEM). Time to peak force, time to relax to the 20% level and relaxation time all decreased significantly after atropine. Compared with endogenous adrenoceptor stimulation alone, the combined effects of partial muscarinic and adrenergic receptor stimulation thus were moderate reductions of the maximal force of contraction and maximal rate of development of the force and increased time to peak force, time to relax to the 20% level and relaxation time. The main effect of the endogenous muscarinic activity probably was to attenuate the effect of the beta-adrenoceptor stimulation. The endogenous muscarinic activity in field stimulated atrial preparations from children is significant, and has to be taken into account in experimental set-ups.

Background: The aim of the study was to elucidate the changes in thyroid function during and after cardiopulmonary bypass (CPB) in children., Methods: Triiodothronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined preoperatively, at specific times throughout CPB, and serially up to 48 h postoperatively, in 10 children (median age 35, range 23-68 months) undergoing elective surgery for congenital heart disease., Results: T3 decreased from 2.01 +/- 0.08 preoperatively to 0.94 +/- 0.10 nmol/l 24 h postoperatively (P < 0.05). T4 levels followed a pattern similar to changes in T3. FT4 increased from 17.4 +/- 0.7 preoperatively to 30.0 +/- 0.4 pmol/l after 30 min of CPB (P < 0.05). TSH decreased from 2.44 +/- 0.43 preoperatively to 0.93 +/- 0.21 24 h postoperatively (P < 0.05)., Conclusion: T3, T4 and TSH are significantly depressed after open heart surgery in children.

Twenty-five women with previous verified thromboembolic complications were treated with delteparin (Fragmin) during pregnancy and puerperium. Women with known hereditary thrombophilia (antithrombin, protein C and protein S deficiencies) or with phospholipid antibodies were excluded. The dose at entry was calculated according to body weight and thereafter monitored by anti-FXa activity aiming at 0.20-0.40 IU/ml plasma 3 h post injection. Dalteparin or dextran was used during delivery. Twenty-two women completed the study and 14 of these could be given the same dose throughout pregnancy. There was an increased dose response postpartum. There were no thromboembolic recurrences or severe bleeding complications. The level of antithrombin activity remained normal. Our thrombosis-prone pregnant women had initially increased levels of thrombin markers but no further increase was observed during the dalteparin thromboprophylaxis. Retrospectively, three heterozygous and three homozygous individuals for the FV Leiden mutation leading to activated protein C resistance were identified. In conclusion, dalteparin could safely be used as thromboprophylaxis during pregnancy in these thrombosis-prone women. Women weighing 50-79 kg at entry could be treated with 5000 IU of dalteparin once daily during pregnancy, without monitoring. Postpartum, many of the women were given a reduced dose.

By February 1997, the number of heart transplantations at the National Hospital had reached 265. In our department, the first bridge to transplantation in using Thoratec artificial heart was performed in 1995. A 44 year-old patient with life-threatening heart failure was placed for one week on cardiopulmonary assist with an intra-aortic balloon pump and a veno-arterial cardiopulmonary bypass. Due to unceasing heart failure a Thoratec left ventricular assist device was implanted as a bridge to transplant. The patient was successfully transplanted two days after implantation of Thoratec. After eight months follow-up he is in New York Heart Association (NYHA) functional class I. Another patient, 17 years of age, and with dilated cardiomyopathy, went into cardiogenic shock while awaiting heart transplantation. For three days he had cardiopulmonary assist with intra-aortic balloon pump and venoarterial bypass with an oxygenator. After seven weeks on the left ventricular assist device he was transplanted. Although one episode of severe rejection occurred, be is in NYHA functional class I after four months follow-up. Our early experience is encouraging. Ventricular assist devices should be considered as a life support for patients scheduled for heart transplantation and expected to die within a very short time.

The release of cytokines during cardiopulmonary bypass (CPB) may contribute to haemodynamic alternations encountered after open heart surgery. Regulatory mechanisms exist and include soluble cytokine receptors. We have measured blood levels of tumour necrosis factor (TNF) and its soluble receptor (TNFsr) during and after open heart surgery in children. Correlation analysis to haemodynamic and clinical variables was performed. Using immunoassays the authors registered a significant increase in plasma levels of TNFsr with peak levels 2 h post-operatively at a level of 1702 +/- 170 pg/ml. The concentration of TNFsr remained significantly elevated until 48 h postoperatively but TNF was not significantly elevated. An inverse correlation existed between peak TNFsr and mean arterial pressure (rho = -0.827, P < 0.05), between TNFsr and cardiac index (rho = -0.8, P < 0.05), between TNFsr and left ventricular stroke work index (rho = -0.983, P < 0.01), between TNFsr and weight (rho = -0.85, P < 0.05) and between TNFsr and body surface area (rho = -0.867, P < 0.05). The authors demonstrate that the smallest children experienced the highest TNFsr concentration post-operatively. Furthermore cardiac performance, expressed as cardiac index and left ventricular stroke work index, correlated inversely to peak TNFsr level post-operatively.

The first cardiac transplantation in Norway was performed in November 1983. At the end of 1995 the number of heart transplantations at our institution had reached 238. Five of these patients (2.1%) were transplanted in the early postoperative period of failed conventional cardiac surgery (respectively 20, 26, 54, 84, and 234 hours post surgery). The primary procedure consisted of mitral valve replacement plus left ventricular aneurysm resection, coronary artery bypass grafting, Konz-Konno procedure, aortic valve replacement, and redo coronary artery bypass grafting in patients aged 47, 54, 49, 52, and 43 years respectively. All except one were high-risk patients. All patients were on circulatory support (IABP, LVAD or ECMO) before transplantation. One patient died 12 hours after the transplant due to multiorgan failure that was not reversed by improved pump function. There was one late death four months postoperatively due to severe acute vascular rejection. Three patients are doing well respectively six years, 20 and four months after transplant. We conclude that cardiac transplantation in the early postoperative period of failed conventional heart surgery is an encouraging option in highly selected patients otherwise considered to die in a very short time.

During the five years 1990 through 1994, 70 neonates and infants had surgery for coarctation of the aorta. 30 patients with complex coarctation of the aorta underwent a first stage correction with supplementary ductus ligation and pulmonary artery banding as needed. The mode of surgical repair of coarctation was end-to-end anastomosis in ten patients and patch graft in 20 patient. Mean follow-up was 766 (range 3-1812) days. Mortality after primary procedure was 16.6% (5/30) and after secondary procedure 11.1% (2/18). Three surviving patient developed recoarctation, but only one patients needed re-operation. In spite of improvement in neonatal cardiac surgery, we conclude that a staged approach is still the current treatment in most cases of complex coarctation of the aorta.

Background and Aims of the Study: Mechanical valves are the prosthesis of choice in valve replacement in children. However, the problem of somatic growth leading to patient-valve mismatch remains present, and the appropriate anticoagulation regimen remains controversial. We present our experience of valve replacement in a young population over 20 years., Materials and Methods: Between 1972 and 1992, 48 patients (34 males and 14 females), mean age 11.2 years (range 0.4-27.4 years), underwent mechanical valve replacement at our institution. Aortic valve replacement was performed in 28 patients (58.3%), mitral valve replacement in 13 (27.1%), tricuspid valve replacement in six (12.5%) and pulmonary valve replacement in one patient (2.1%). The prostheses used were: St. Jude Medical (n = 2), Björk-Shiley (n = 14), Medtronic Hall (n = 16), Duromedics (n = 2) and CarboMedics (n = 14). Early mortality was 14.3%, 10.7% for aortic valve replacement and 30.8% for mitral valve replacement. Mean follow up for all patients was 8.3 years (range 0-22 years), with a total of 398 patient-years., Results: Seven patients died during the follow up (17.1%). Survival after 10 years, including operative mortality, was 81% for aortic valve replacement, 33% for mitral valve replacement, 83% for tricuspid valve replacement and 100% for pulmonary valve replacement. All patients were anticoagulated with warfarin. In eight patients (16.7%) an antiplatelet drug (aspirin or dipyridamole) was added. Major events included paravalvular leak in six patients (1.5%/pty), valve thrombosis in five (mitral position in two, tricuspid in three) (1.3%/pty) and endocarditis in one patient (0.3%/pty). Minor thromboembolic events occurred in three patients (0.8%/pty) and minor hemorrhagic events in three (0.8%/pty). No patients developed hemolytic anemia and there was no case of structural failure., Conclusions: In our experience, mechanical prostheses in congenital heart disease were associated with significant morbidity and mortality, however long term survival after aortic valve replacement was good (81% at 10 years). Thromboembolic and hemorrhagic events were of minor significance. Atrio-ventricular valve replacement carried the highest risk of valve thrombosis and we now give warfarin and an antiplatelet drug to children undergoing mechanical valve implantation in this position.

Interleukin-6 (IL-6) and the complement activation products C3bc and terminal complement complex (TCC) were measured in three groups of children undergoing open heart surgery. One group was treated with intraoperative extracorporeal ultrafiltration and postoperative autotransfusion of shed mediastinal blood, one group was subjected to autotransfusion only and in one group none of these procedures were performed. No differences between the groups were observed concerning the degree of complement activation. Peak and total accumulated level of IL-6 was significantly higher in the group subjected to ultrafiltration and autotransfusion compared to the group treated conventionally with no interventions. IL-6 may be a sensitive marker of maneuvres increasing the inflammatory load during and after open heart surgery in children.

A case of a 62-year-old woman suffering an acute cardiac arrest during a court dispute is presented. Cardiopulmonary resuscitation was immediately started by bystanders. In hospital there were signs of intrathoracic bleeding. A left thoracotomy revealed a cardiac rupture of the left ventricle and a large pericardial tear. Intraoperative evaluation of the heart as well as postoperative enzyme levels and ECG did not indicate acute myocardial infarction. The rupture may therefore be traumatic. The cardiac rupture was sutured five hours after the initial resuscitation, and the patient discharged from the intensive care unit two days after the rupture without clinical signs of neurological injury. A precordial thump is advised before start of external chest compression. One beneficial effect may be that the ventricles empty and the risk of traumatic rupture during compression is reduced.

Cellular activation with release of cytokines such as interleukin-6 (IL-6) occurs during cardiopulmonary bypass. IL-6 regulates a number of physiologic processes, and a possible role of IL-6 was recently postulated in the pathogenesis of changes in serum thyroid hormone concentrations in patients with nonthyroidal illness. The perioperative concentrations of triiodothyronine (T3) and IL-6 were determined in ten children undergoing open-heart surgery. Significant fall in T3 concentration was found postoperatively, while IL-6 increased significantly, peaking 2 hours postoperatively. The total accumulated IL-6 level 2 hours postoperatively was correlated to postoperative T3 concentration. A significant inverse correlation was found between T3 levels 24 and 48 hours postoperatively and total accumulated IL-6, and also between the percentage decrease in T3 concentrations and total accumulated IL-6. IL-6 release thus correlated inversely to T3 levels after cardiopulmonary bypass.

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.

Atrial tissue removed from the cannulation site prior to cardioplegia (n = 15), and ventricular tissue therapeutically excised from the outflow tract of the right ventricle, (RVOT) (n = 2) were examined with respect to adrenoceptor mediated inotropic effect in children with congenital heart defects (CHD). We used sequential reversal by adrenoceptor antagonists of the tyramine enhanced response to endogenous norepinephrine to quantify the role of the beta- and the alpha 1-adrenoceptors, respectively, in the intropic response. Atrial myocardium had an alpha 1-adrenoceptor mediated component of 14% (median) (range 0-44%) and a beta-adrenoceptor mediated component of 86% (median) (range 56-100%). The patients with the highest alpha 1-adrenoceptor mediated inotropic components, had right ventricular pressure loads in the systemic range. In one specimen from RVOT, the ventricular alpha 1-adrenoceptor component was estimated to be 22% of the total inotropic response, compared to 26% in the corresponding right atrium. In a ventricular specimen from another patient, we could not demonstrate any alpha 1-adrenoceptor mediated inotropic component in contrast to 13% in the right atrium. This patient, however, had infusion of the alpha-adrenoceptor antagonist phentolamine after the excision of atrial tissue, but before the excision of muscular tissue from RVOT. In myocardium of children with CHD we found evidence that endogenous norepinephrine stimulated alpha 1-adrenoceptors in addition to beta-adrenoceptors. The relative contributions from the two adrenoceptors to the inotropic response varied considerably, and may be related to the pressure load of the right ventricle. These observations may be relevant with respect both to pathophysiology and to choice of drug therapy.

From January 1989 to December 1993, 25 patients underwent endarterectomy on the left coronary artery system. Eight of the patients had concurrent endarterectomy of the right coronary artery. The operative mortality consisted of one high-risk patient who died from an intraoperative myocardial infarction. Two patients developed non-fatal perioperative infarction. The follow-up period averaged 27 months (range 4-58 months). At follow-up one patient was lost for evaluation owing to unexpected sudden death, no patients had experienced myocardial infarction, 17 patients (74%) were free of angina, two patients were in NYHA class I and four in NYHA class II. All patients showed an improvement in relation to their preoperative condition. Two asymptomatic patients refused recatheterization, while 21 patients had a control angiographic study. 25 of 34 grafts to endarterectomized vessels were open (patency 74%) compared with 41 of 45 grafts to non-endarterectomized arteries (patency 91%). We find the angiographic and functional results acceptable and they should be acknowledged with reference to patients with diffuse distal coronary artery disease, many of whom would otherwise be considered inoperable.

Small pieces of atrial tissue removed from the cannulation site before cardioplegia were used to develop a method for studying adrenergic regulation of the myocardial contractile force in children operated on for congenital heart defects (CHD). We measured the development of the isometric force of contraction dT/dtmax (T'max). Reduction in basal contractility induced by the beta-adrenoceptor antagonist timolol indicated that the myocardium was about half-maximally stimulated by endogenous norepinephrine (NE), probably released from nerve endings by the electrical stimulation. The inotropic effect of endogenous NE could be further increased by tyramine (EC50 approximately 5 microM). A maximal concentration of tyramine increased T'max by a median of 62.5% above the basal level. Sequential blockade of the beta- and alpha 1-adrenoceptors after tyramine stimulation by timolol and prazosin, respectively, indicated that a near-maximal response to combined adrenoceptor stimulation by endogenous NE was mediated by both beta-adrenoceptors (median 77%) and alpha 1-adrenoceptors (median 23%). The basal level of endogenous NE may conceal inotropic effects by exogenous alpha-agonists added to this type of preparation. This preparation is suitable for studying adrenergic regulation by reversing the effects of endogenous NE.

Surgical repair of tetralogy of Fallot may be a first stage palliation with secondary physiologic correction or repair as a primary procedure. The aim of palliation is to increase the pulmonary blood flow. Since 1981 we have used an interposition shunt between the subclavian and the pulmonary artery for this purpose. Repair comprises closure of the ventricular septal defect and relief of the pulmonary stenosis. A primary repair may be performed if the pulmonary arteries have reached a certain size. The size and function of the left ventricle must also be able to cope with the increased work load. During the last 20 years, 333 operative procedures have been performed in patients with tetralogy of Fallot. This material comprises 107 shunts and 226 repairs. The total mortality while in hospital was 6%. During the last period from 1990 until January 1993 the mortality in hospital was 3% after operative repair. There have been no mortality following palliative procedures during the same period.

The prevalence of radiographic signs of gonarthrosis and its relation to knee injuries were studied in 286 former soccer players--215 nonelite and 71 elite players--and were compared with 572 age-matched controls with a mean age of 55 years. The prevalence of gonarthrosis among the nonelite players was 4.2%, among the elite players 15.5%, and among the controls 1.6%. Seven of the soccer players had known anterior cruciate ligament injuries, and 40 had had meniscectomies. Of the 32 nonelite players with knee injuries, 4 (13%) had gonarthrosis, and of the 183 without known knee injuries 5 (3%) had gonarthrosis. Among the elite players, the prevalence of gonarthrosis in knees without diagnosed injuries was 11%. We conclude that soccer, especially at an advanced level, is associated with an increased risk for gonarthrosis. After excluding subjects with known knee injuries, there was no difference between nonelite players and controls, but we found a higher rate of gonarthrosis among the elite players.

The authors report experiences from Norwood's staged palliation for hypoplastic left heart syndrome performed in Philadelphia on Norwegian children. Although there is no universal agreement that these children should be operated at all, the Norwegian health authorities have decided that all expenses for transport, examination and treatment shall be covered by the National Health Insurance Scheme. Since 1987 a total of 21 children have been transported to USA for operation. Eight of these children have completed all the planned stages of the operative treatment. Two are waiting for stage 3. 11 children have died. The authors discuss how to proceed with regard to treatment of this complicated patient group in future.

We compared the occurrence of coxarthrosis in 286 male former soccer players in Malmö with a mean age of 55 years with an age-matched control group. During the last decades about one fifth in both groups had been referred to hip radiography. Coxarthrosis occurred in 5.6 percent of the former soccer players and in 2.8 percent of the control group (P 0.04). Among the 71 élite soccer players the prevalence of coxarthrosis was 14 percent compared with 4.2 percent in age-matched controls and non-élite players. Elite soccer players apparently run an increased risk of developing coxarthrosis.

Percutaneous transluminal coronary angioplasty (PTCA) was performed on 725 occasions at the National Hospital of Norway in 1981-1990. Acute surgical intervention was necessary within 24 hours after PTCA in 15 cases, on indications that included coronary artery dissection (8 cases) and acute thrombotic occlusion (5). Electrocardiographic signs of ischemia were present in 11 patients with anginal pain, while two had severe angina but normal electrocardiogram. Two patients had a non-ischemic indication for surgery. Despite surgery, ten of the 15 patients had acute myocardial infarction. One of the ten died. At follow-up nine of 12 patients were free from angina and three had recurrent symptoms.

Seven single lung transplants are reported. The patients were severely disabled and oxygen dependent below sixty years of age with a poor prognosis. Diagnosis were alfa 1-antitrypsin deficiency (3), sarcoidosis (3) and idiopathic emphysema (1). Multiorgan-harvesting including six hearts, was performed in local or distant hospitals (3). Partial cardiopulmonary bypass simplified transplantation. The surgical procedure was modified with a direct transpericardial approach. Soft tissue wrapping by a vascularized pedicle secured the bronchial anastomosis. The four drug immunosuppressive regimen included cyclosporin A, azathioprine, steroids and antithymocyte globulin. Primary graft function was excellent. Six patients survived the postoperative period and are alive 5-19 months post transplant. Transbronchial biopsies and lung function studies have been helpful in detecting pulmonary rejections. Patient rehabilitation is satisfactory in most patients with improvement in physiologic parameters.

Data from the first 103 human heart transplantations performed on 100 recipients (aged 14-62 years) at a single center from November 1983 to January 1990 were analyzed in order to detect morbidity-causing risk factors. Cumulative one- and five-year graft survival was 82% and 68%. Multivariate analysis revealed three independent risk factors for early rejection, viz. HLA-DR and HLA-B mismatches and no prior cardiac surgery. Graft ischemic time exceeding 71 min was an independent risk factor for rejection, especially for moderate or severe events, and for infection. HLA-DR mismatch was an independent risk factor for moderate and severe rejection events and for infections. Finally, patients operated on because of end-stage ischemic heart disease were at significantly higher risk of rejection than those with other cardiac disorders. The study has several implications: Prospective tissue typing for cardiac transplantation and selection of donors may have an impact on graft function: Damage to the graft by prolonged ischemia may be reduced by improved organ preservation.

A hemodynamic study of men undergoing elective coronary artery bypass surgery was undertaken to elucidate the side effects of protamine given into the ascending aorta (group A, n = 16) or into the central venous line (group V, n = 16). After termination of extracorporeal circulation, protamine was infused over 120 seconds, and the hemodynamic profile was continuously recorded. During the first minute, the systemic arterial pressure fell to about 60% of the preprotamine level in both groups, but the hemodynamic changes occurred more rapidly (p < 0.05) in group V than in group A, with maximal pressure drop at 61.7 +/- 2.7 vs 74.4 +/- 4.9 seconds. Following spontaneous restoration of the systemic blood pressure, the pulmonary artery pressure rose considerably in both groups, as did the pulmonary capillary wedge and central venous pressures, reaching higher levels in the intravenous group. The cardiovascular responses were again more rapid in group V than in group A (p = 0.004). The degree of systemic hypotension thus did not benefit from use of the intraaortic rather than the intravenous route for administering protamine. The more pronounced and more rapid pulmonary circulatory changes in the intravenous group suggest that the hemodynamic effects of protamine are initiated in the lungs.

In 28 patients with the left internal mammary artery (IMA) used as a sequential coronary artery graft, clinical and angiographic evaluation was made 19-47 months postoperatively. Patency was 96% in the proximal anastomoses and 93% in all the anastomoses. Angiography, however, showed optimal function in only 75% of the distal graft ends. These observations indicate that routine use of left IMA as a sequential graft should be restricted to experienced surgeons. Clinical and angiographic findings did not always correlate, emphasizing that evaluation of IMA-graft patency should include angiography.

In a prospective randomised study, performed over a 6-year period, 102 patients with severe lower limb ischaemia or claudication resistant to exercise training were randomised either to percutaneous transluminal angioplasty (PTA) or vascular surgery. Only patients who could be treated by both methods were included, constituting only 5% of the total number of patients treated during this period. The two groups were similar regarding age, severity of symptoms and diabetes. The immediate and 1-year results showed similar success and complication rates. There was, however, a significantly shorter hospital stay for patients treated with PTA. Due to early complications and initial failures PTA should, however, only be used in institutions where vascular surgical facilities are available since PTA demands access to such treatment.