The implementation of a nationwide anomaly screening programme improves prenatal detection of major cardiac defects: an 11-year national population-based cohort study.

OBJECTIVE: To evaluate whether a nationwide prenatal anomaly screening programme improves detection rates of univentricular heart (UVH) and transposition of great arteries (TGA), and whether maternal risk factors for severe fetal heart disease affect prenatal detection. DESIGN: Population-based cohort study. SETTING: Nationwide data from Finnish registries 2004-14. POPULATION: A total of 642 456 parturients and 3449 terminated pregnancies due to severe fetal anomaly. METHODS: Prenatal detection rates were calculated in three time periods (prescreening, transition and screening phase). The effect of maternal risk factors (obesity, in vitro fertilisation, pregestational diabetes and smoking) was evaluated. MAIN OUTCOME MEASURES: Change in detection rates and impact of maternal risk factors on screening programme efficacy. RESULTS: In total, 483 cases of UVH and 184 of TGA were detected. The prenatal detection rate of UVH increased from 50.4% to 82.8% and of TGA from 12.3% to 41.0% (P < 0.0001). Maternal risk factors did not affect prenatal detection rate, but detection rate differed substantially by region. CONCLUSIONS: A nationwide screening programme improved overall UVH and TGA detection rates, but regional differences were observed. Obesity or other maternal risk factors did not affect the screening programme efficacy. The establishment of structured guidelines and recommendations is essential when implementing the screening programme. In addition, a prospective screening register is highly recommended to ensure high quality of screening. TWEETABLE ABSTRACT: Implementation of a nationwide prenatal anomaly screening improved detection rates of UVH and TGA.

Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18:1), LPC(18:2), LPC(20:3); phosphatidlycholines (PCs) PC(32:2; PC(34:2), PC(36:4), PC(0-34-3) and sphingomyelin (SM) SM(d18:1/24:0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD.

Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis.

Psychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. In this study, we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients. We applied comprehensive metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. While corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline, that is, lipids known to be associated with increased liver fat. Our study suggests that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain.

Direct reconstruction of the pulmonary artery during the arterial switch operation: an interesting surgical option with excellent hemodynamic results.

BACKGROUND: In transposition of the great arteries, reconstruction of the neo-pulmonary artery is a challenging surgical detail during the arterial switch procedure. We present early and midterm clinical and hemodynamic results of a direct reconstruction of the pulmonary artery avoiding prosthetic and autologous material. METHODS: Between 1990 and June 1996, a total of 189 patients underwent the arterial switch procedure because of D-transposition of the great vessels. Of them, 47 underwent direct pulmonary artery reconstruction. Mean age at operation was 5.2+/-4.1 days and mean weight was 3.75+/-0.85 kg. Simple transposition of the great arteries was present in 13, transposition of the great arteries plus ventricular septal defect in 27, and more complex forms of transposition of the great arteries in 7 patients. The great vessels were side-by-side in 4 patients and in the anteroposterior position in 43 patients. The technique of direct pulmonary reconstruction includes extensive mobilization of both pulmonary artery branches into the hilum, posterior incision of the mean pulmonary artery into the bifurcation, and resuspension of the posterior commissure of the neo-pulmonary valve. A large anastomosis without any tension is then performed, using the anterior remnant aortic sinus of Valsalva to fit out the expected size of the neo-pulmonary artery. RESULTS: Early mortality was 8.5% (4/47) in this particular group of patients. Postoperative echocardiography was performed before hospital discharge, 3 to 6 months postoperatively, and after a mean follow-up of 24 months. Of the 43 survivors, 37 patients had a pressure gradient across the pulmonary valve of less than 15 mm Hg. Mild pulmonary stenosis (pressure gradient of 15 to 30 mm Hg) was present in 4 and more severe supravalvar stenosis (pressure gradient > 30 mm Hg) in 2 patients. After a mean follow-up of 36 months, there was one redo operation to enlarge the right ventricular outflow tract. CONCLUSIONS: Direct reconstruction of the neo-pulmonary artery-avoiding autologous pericardium and prosthetic material-may represent an interesting option during the arterial switch operation when the great vessels lie in the anteroposterior position. This technique is simple, and the hemodynamic midterm results are very favorable. The incidence of postoperative supravalvar pulmonary stenosis is low, and there may be considerable potential for unlimited tissue growth.

Altered regulation of breathing after bilateral lung transplantation.

In our previous animal studies on dogs, regulation of breathing was found to be altered after en bloc transplantation of the heart and both lungs. During carbon dioxide (CO2) inhalation the minute volume was increased due to an increase of tidal volume after transplantation whereas before transplantation both respiratory frequency and tidal volume increased. The success of the heart-lung transplantation was based on experiments on baboons as no long-term survivors were obtained in dogs. It was thought that the regulation of breathing is different in dogs and primates. We therefore decided to study the regulation of breathing in humans after bilateral lung transplantation during CO2 stimulation. The regulation of breathing was tested 2 to 4 months after bilateral lung transplantation in six patients. Six healthy subjects with intact lungs were tested as controls. The test persons were allowed to breathe first room air, then 5% CO2 in air for 4 min and then room air again. The frequency of respiration, tidal volume and minute ventilation were recorded using a phneumotachograph. Simultaneously samples of arterial blood were drawn from a cannulated brachial artery for analysis of pressure of arterial oxygen (PaO2), pressure of arterial carbon dioxide (PaCO2), base excess (BE) and pH. During inhalation of CO2 for 4 min the minute volume doubled in both transplant patients and in controls. The tidal volume of the transplant patients increased significantly more than that of the controls (P < 0.005) whereas respiratory frequency increased significantly only in the controls with intact lungs (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

St. Jude versus CarboMedics: follow-up after prosthetic valve replacement.

BACKGROUND: The purpose of the present study was to evaluate the immediate and long-term outcome of patients with two types of mechanical bileaflet heart valves operated on in the same institution by the same group of surgeons. METHODS: A comparative analysis was made in 229 consecutive patients receiving either the St. Jude Medical (SJM) or CarboMedics (CMS) bileaflet mechanical valve in 1990-1991. There were no differences in the preoperative demographics between the two groups. At operations simultaneous coronary bypass operation was performed in 40 patients out of 134 (30%) in the SJM group and 95 (44%) in the CMS group (p=0.026). Sixteen patients in the SJM group underwent replacement of the ascending aorta with a composite graft and none in the CMS group. RESULTS: There was no difference in hospital mortality between the SJM (6.7%) and CMS (6.3%) groups or in other immediate postoperative complications. The patients were followed up to 32 months. There were more patients in the NYHA class I and II in the CMS group (88%) than in the SJM group (69%), p<0.002. Three were 11 thromboembolic events (0.051% per patient year) in the SJM group and one thromboembolic event (0.008% per patient year) in the CMS group. There were no other differences between the groups in long-term survival, rate of bleeding, infective endocarditis or perivalvular leakage. CONCLUSIONS: With the exception of a little more favourable exercise tolerance and fewer thromboembolic events in the CMS group there were no other differences in the outcome of patients with these two types of bileaflet mechanical valves.

Coronary endothelial damage after crystalloid cardioplegia.

There is considerable clinical experience to suggest that damage to the myocardium during ischaemic arrest can be prevented by cardioplegic solutions. However, very little is known about the effects of these cardioplegic solutions on the coronary endothelium. The effects of three different cardioplegic solutions on the coronary endothelium are reported here. Preservation of the myocardium was studied with biochemical assays. Blood cardioplegia did not damage the coronary endothelium. Crystalloid cardioplegia caused disappearance of the endothelial cells and gross deformity of the flow surface. The addition of albumin to the crystalloid solution preserved most of the endothelial lining. Preservation of the myocardial high energy compounds seemed to be dependent only on the cooling effect of the cardioplegia and not on the composition of the solution. There was no correlation between high energy compounds and endothelial changes. The present study favours the use of cold blood cardioplegia which preserves both the coronary endothelium and the myocardial energy sources during ischaemic cardiac arrest.

Effect of addition of magnesium to potassium-containing fluorocarbon cardioplegic preparations. An experimental study.

The effect of magnesium on potassium fluorocarbon cardioplegia was studied in 20 rabbits. Isolated hearts with ascending aortas were perfused with oxygenated and cooled (+4 degrees C) fluorocarbon solutions. In 10 experiments, the solution contained 20 mmol/l of potassium, in 10 further experiments, 20 mmol/l of potassium and 15 mmol/l of magnesium. Ultrastructural preservation of the myocardium was studied using transmission electron microscopy. In addition, the cation contents of the myocardium were studied by flame atomic absorption spectrophotometry (calcium, magnesium) or electrothermal atomic absorption spectrophotometry (copper). After 120 minutes of ischaemia, areas of moderate or severe ultrastructural myocardial cell damage were observed in both groups but severe damage was more extensive and commoner in the group with no access to magnesium. Preservation of the capillary endothelium was also worse in that group. There was a highly significant increase in magnesium content, a decrease in calcium content and an increase in the magnesium/calcium ratio following magnesium-potassium fluorocarbon infusion. The copper content remained unchanged. A protective effect of magnesium was observed. The electrolyte content of cardioplegic solutions also alters the electrolyte content of the myocardium. This may be important in reperfusion.

Effects of synthetic blood combined with contrast medium on coronary endothelium: an experimental study.

The study described was carried out to evaluate endothelial injury following incubation of coronary material in contrast medium and in contrast medium diluted with fluorocarbon solution. Six porcine hearts were excised and isolated. Immediately thereafter, pieces of the main coronary arteries and ascending aortas were incubated in four different solutions: 1) blood, 2) contrast medium, 3) fluorocarbon solution, 4) fluorocarbon--contrast medium (1:1). Flow surfaces and coronary endothelial morphology were evaluated by scanning electron microscopy (SEM). Porcine blood (at room temperature) preserved endothelial structures intact but, in two samples, small patchy areas of denuded surface were found. Four minutes' immersion in contrast medium resulted in easily visible changes in the endothelial lining and individual cells. Denuded flow surface areas were common, the intact surface morphology was flattened. After 7 minutes, destruction was total. The addition of fluorocarbon solution to contrast medium (1:1) diminished the changes, which also occurred later than after incubation in pure contrast medium. After 7 minutes, separate endothelial cells were still identifiable but the microvilli had disappeared. Fluorocarbon solution preserved the endothelial lining well during a 10-minute follow-up period. The experimental protocol described confirmed the deleterious effect of contrast medium on coronary endothelial lining, which could be reduced to some extent by adding fluorocarbon solution to contrast medium.

Metabolome in progression to Alzheimer's disease.

Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.

Reappearance of Hering-Breuer reflex after bilateral autotransplantation of the lungs.

In combined heart-lung transplantation the afferent nerve pathways inevitably are transsected. In previous studies with en bloc heart-lung transplantation in dogs, we found altered regulation of breathing-abolition of Hering-Breuer reflex and response to hypercapnia inhalation stimulus consisting of augmented tidal volume with no change in respiratory rate-shortly after the operation. The long-term effects of pulmonary denervation on breathing regulation were now studied in dogs after staged bilateral pulmonary autotransplantation. Mechanical and electrical activities of the respiratory muscles were recorded during spontaneous breathing and after deflation and inflation with varying volumes of air. Five months postoperatively the duration of the respiratory cycle increased 2.5 times on inflation with 600 ml of air and occlusion of the airways, compared with tenfold prolongation in intact control dogs, indicating a partial return of the Hering-Breuer reflex after the autotransplantation. The duration of the EMG bursts in respiratory muscles increased in intact dogs and in those with bilateral lung autotransplants. In impulse frequency the response to stretching was less evident after autotransplantation. The mechanism mediating reappearance of Hering-Breuer reflex warrants further study.

Mediastinal neurogenic tumours. Early and late results of surgical treatment.

Early and late results of surgery for neurogenic mediastinal tumour were evaluated in 66 cases with a mean follow-up of 12 years. The series comprised 48 neurilemmomas, 8 neurofibromas, 7 ganglioneuromas, and neurinoma, neurofibrosarcoma and ganglioneuroblastoma each in one case. There were two early deaths (3%), one due to peroperative bleeding from the left subclavian artery and the other to acute myocardial infarction. Operative complications arose in 12 cases (18%), the most common being wound infection (3 cases). There were 17 late deaths (26.6%). In the neurilemmoma group, 3 of the 13 late deaths were related to the tumour or its treatment, and both deaths in the neurofibroma group were related to malignant transformation. Recurrence of tumour appeared in 3 of the 48 patients with neurilemmoma and also in the single patient with neurinoma as tumour classification. One neurilemmoma was a dumb-bell tumour, and operation in this case resulted in paraplegia. Malignant transformation appeared in 2 of the 8 neurofibromas 5 and 13 years postoperatively. Because of the risks of malignant degeneration and of recurrence, patients operated on for neurogenic mediastinal tumour should be carefully followed up for many years.

Comparative analysis of tilting disc and ball valve prosthesis in aortic position.

In a retrospective analysis, comparison was made between the Cutter-Smeloff ball valve (n = 63) and the Lillehei-Kaster tilting disc valve (n = 256) in the aortic position. No significant intergroup difference was found as regards rate of thromboembolism (0.6/100 patient years for both valve types), endocarditis (0.2 for Cutter-Smeloff and 0.5 for Lillehei-Kaster/100 patient years) and paraprosthetic leak (0.9 and 0.5, respectively/100 patient years). The actuarial curve of cumulative survival was similar for both valves until 6 years postoperatively. Thereafter the outcome was less favourable for the patients with Cutter-Smeloff valve (actuarial survival 79 +/- 5% than for those with Lillehei-Kaster valve (91.2 +/- 2%). The reason for this, statistically significant, difference may be associated with the difference in valve profiles.

Long-term follow-up of Björk-Shiley mitral valve replacement. 10 years' experience.

Retrospective analysis was made of 176 patients who received a Björk-Shiley mitral valve replacement in the period 1973 through 1982. Actuarial cumulative curves showed the 10-year and 5-year survival rates to be 79 +/- 3.4%. The functional status at follow-up was better than preoperatively in 77.1% of the patients. The hospital mortality was 9.1% and the late mortality was 3.6/100 patient years. Early complications included disc entrapment against the ventricular wall in three cases, wedging of chorda between disc and valve rim in two and posterior perforation of the left ventricle in three patients. There was no structural valve damage. Calculated per 100 patient years, the incidence of thromboembolism was 2.5, endocarditis 1.4 and prosthetic leak 1.8. One thrombosed valve was successfully replaced by a new prosthesis 11 years after the initial implantation. Jamming of the disc by tissue over-growth necessitated a new valve implantation in one case. The incidence of early valve-related complications was high, but the long-term results were comparable with those from other mechanical valves. One early complication--disc entrapment against the ventricular wall--may be avoided by use of a sufficiently small valve if the ventricle is small and thickened.

Coronary endothelium and cardioplegic solutions.

Using surface and transmission electron microscopy in eight isolated sheep hearts it was noted that cold crystalloid cardioplegic solution produced coronary endothelial damage which could be prevented if homologous blood or albumin was added into the preservation fluid. Similar endothelial damage was observed in the endothelium of aorto-coronary saphenous vein bypasses and in the endothelium of the proximal aorta after infusion with cold crystalloid cardioplegic fluid. No endothelial changes were seen after infusion of the grafts with cold blood. There was no correlation between the preservation of the high energy phosphates of the myocardium and the endothelial changes of the coronary arteries.

Effect of lung autotransplantation on breathing regulation. Studies in dogs.

The effect of autotransplantation of the left lung on respiratory regulation was studied in four dogs in pentobarbital anaesthesia. In each dog the electrical and mechanical activity of the inspiratory muscles was studied before and 4-6 weeks, 3, 6 and 12 months after the transplantation. No or very little change was found in comparisons of spontaneous respiration or response to inhalation of carbon dioxide, hypoxia or combined hypercapnia and hypoxia. When the airways were closed after inflation with varying volumes of air, the increase in number and frequency of the electromyographic impulses in the intercostal muscles and the diaphragm (compared with the preceding unobstructed breaths) was greater before than after the lung autotransplantation. The duration of the first respiratory cycle after airway closure increased progressively with the volume of inflation in intact dogs and in dogs with autotransplanted left lung, though the increase was approximately halved following autotransplantation.

Analysis of residual solvents in pharmaceuticals with purge-and-membrane mass spectrometry.

A method using purge-and-membrane mass spectrometry (PAM-MS) was developed for the analysis of residual solvents in pharmaceutical products. The method combines dynamic headspace and membrane inlet mass spectrometry. The limits of detection for the compounds studied, benzene, toluene, chloroform, 2-pentene and 2-methyl- and 3-methylpentane, were 0.05-0.1 mg/kg. In quantitative analysis the method showed good linearity (r(2) > 0.998) and acceptable within-day (RSD = 7.9-18%) and between-day (RSD = 6.8-10%) repeatability. The PAM-MS method combined with the custom-made Solver program was compared with a method using purge-and-trap gas chromatography/mass spectrometry (P&T-GC/MS) for identification of residual solvents from authentic samples. The results showed that PAM-MS/Solver provides reliable identification of the main volatile organic compounds (VOCs) in the pharmaceuticals, but VOCs with low concentrations (below 0.5 mg/kg) were better identified by P&T-GC/MS. Other advantages of the PAM-MS method were short analysis times and non-requirement for pre-treatment of samples.

Cardiac tamponade and different modes of artificial ventilation.

Cardiac tamponade after open-heart surgery often occurs in a situation when the patient is still mechanically ventilated and needs circulatory support with catecholamines. To evaluate the effects of different modes of artificial ventilation and dopamine on cardiac tamponade, an experimental study was carried out in seven mongrel dogs. In pentobarbital - N2O anaesthesia, a cardiac tamponade of 20 mmHg was produced by injecting 120-200 ml of normothermic saline into the pericardium. Intermittent positive pressure ventilation (IPPV) and positive end-expiratory pressure (PEEP) ventilation with frequencies of 12 and 20 were tested before and after producing the tamponade. Cardiac tamponade produced a significant fall in arterial pressure and cardiac output, a significant rise in central venous pressure and only a slight increase in pulmonary arterial pressure. PEEP with the slower ventilation frequency of 12 produced additional, significant falls in cardiac output and systemic arterial pressure, which were not noted with the ventilation frequency of 20 and PEEP. Dopamine infusion increased the cardiac output by increasing the heart rate during tamponade. It is concluded that PEEP ventilation with a slow frequency should not be used if cardiac tamponade is suspected after open-heart surgery, and that dopamine has a favourable effect on haemodynamics even in the presence of a severe cardiac tamponade.

The effects of a centrifugal pump as a left-ventricular-assist device in myocardial infarction.

Cardiogenic shock after acute myocardial infarction and open heart surgery having cardiopulmonary bypass may present a difficult clinical problem with high mortality. The present study was carried out to evaluate a newly developed laminar flow centrifugal pump as a left-ventricular-assist device to support the circulation and prevent myocardial damage in such situations. Experimentally induced acute myocardial infarction in dogs was used as the model. Cardiogenic shock was effected by ligating enough branches of the left coronary artery. In addition to recording the haemodynamic parameters, samples of myocardium were taken with a biopsy needle from the infarcted area, transitional zone and intact myocardium for determination of adenosine triphosphate, creatine phosphate and lactate. In the first phase of the work the effects of acute myocardial infarction on haemodynamics and high-energy compounds were defined, to form a basis for the evaluation of the pump as left-ventricular-assist device. Ligation of the branches of the left coronary artery produced a rapid fall in aortic pressure, cardiac output and cardiac performance, elevation of ST-segment in the ECG and fall in high-energy compounds. However, there was a marked spontaneous recovery in the transitional zone within 120 min, despite the haemodynamic deterioration. The laminar flow pump produced a significant improvement in the haemodynamic and metabolic parameters which exceeded the spontaneous changes noted previously.