Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation.

AIMS: Increased cardiovascular morbidity is manifested a long time after the repair of aortic coarctation (CoA). By way of impaired flow-mediated vasodilation (FMD) and increased intima media thickness (IMT), surrogate parameters of atherosclerosis, cardiovascular risk factors (RFs) can be correlated with early vascular wall changes in children. This study investigated whether changes in arterial wall function and morphology are detectable in children after coarctation repair. METHODS AND RESULTS: We examined 28 children after successful repair of CoA vs. 30 control subjects. All children underwent identical screening, with a broad RF profile and FMD/IMT measurements. CoA-children presented significantly (P < 0.001) impaired FMD (4.87 +/- 2.6 vs. 10.2 +/- 3.1%) and higher IMT values (P < 0.001) than the controls (0.48 +/- 0.08 vs. 0.38 +/- 0.05 mm). The blood pressure during rest and exercise and the left ventricular mass were significantly elevated, but no additional RF could be identified in CoA-children. Only a remaining pressure gradient related significantly to FMD. CONCLUSION: This study documents early vascular wall changes in children after successful coarctation repair. Arterial hypertension and a resting pressure gradient are the major contributing factors to early atherosclerotic development and should be primary targets for therapy. Vascular status should be monitored regularly by FMD and IMT.

Computer-aided design of novel siderophores: pyridinochelin.

Pyridinochelin, a novel tetradentate catecholate-type siderophore, has been designed on the basis of the active analog enterobactin and was then synthesized. Growth promotion tests indicate that this synthetic siderophore feeds various pathogenic bacteria most effectively with iron even though it lacks one catecholate group compared to enterobactin. The superposition of the mentioned siderophore structures suggests that the structure of the skeleton connecting the catecholate groups might be an important factor for the iron transport.

[Lactobacillus paracasei endocarditis in an 18-yeard-old patient with trisomy 21, atrioventricular septal defect and Eisenmenger complex: therapeutic problems]. / Lactobacillus-paracasei-Endokarditis bei einer 18-jährigen Patientin mit Trisomie 21, atrioventrikulärem Septumdefekt und Eisenmengerreaktion--therapeutische Probleme.

Endocarditis caused by lactobacilli is very rare and so far has been rarely published in adults with cardiac valve diseases especially after dental manipulations. Because of diagnostic and therapeutical problems we hereby report on one case of a female adolescent with Down's syndrome who did not undergo surgical correction of atrioventricular septal defect because of early development of Eisenmenger's syndrome. The onset was subacut and the diagnostic procedures were considerably delayed. Risk factors for the development of endocarditis in this case were preceding antibiotic treatments which increased the risk of selective growth of the causative germs as well as the tricuspidal valve incompetence with simultaneous pulmonary hypertension. The antimicrobial treatment was difficult due to resistance to antibiotic drugs generally applied in such cases and the restricted bacteriological diagnostic methods. Finally we had successfully administered chloramphenicol. The course was complicated by cerebral embolic events. FACIT: Lactobacillus species are facultative pathogenic which should be consideration in cases of subacute endocarditis in children and adolescents with ventricular septal defects and valve diseases. The determination of minimal bactericidal concentration of antibiotic agents and time-kill studies of combined antibiotics are recommended. For initial therapy we recommend high dose penicillin combined with an aminoglycoside. In cases of resistance chloramphenicol should be taken into account as second choice antibiotic drug. The duration of antibiotic therapy should at least over six weeks. In cases of risk systemic embolization is suspected therapy with low dose acetylsalicyclic acid or cardiosurgery should be assumed as therapeutic options.

Safety and efficacy of interventional occlusion of patent ductus arteriosus with detachable coils: a multicentre experience.

UNLABELLED: In order to define the safety and efficacy of Cook detachable coils for interventional closure of patent ductus arteriosus, we performed a retrospective analysis of all patients who underwent cardiac catheterization in seven centres for intended interventional occlusion of patent arterial duct. From January 1995 until March 1998, cardiac catheterization for intended interventional occlusion of patent arterial duct was performed in 317 consecutive children. Successful placement of at least one coil was achieved in 282 children (89%). The mean diameter of the ductus in children treated with Cook detachable coils was 1.65 mm, mean fluoroscopy time was 10.7 min. Occlusion rates were 62% 10 min after the procedure, 82% at the time of discharge, 91% at 4 months and 95% at late follow-up (2 years). In children with a ductus diameter of < or = 2.5 mm the rate of successful coil deployment was 94% with a 98% occlusion rate at late follow-up. Complications occurred in 11 procedures (3.5%) including haemolysis (3 patients), embolization of a coil to the pulmonary artery (7 patients, 2.3%) and inability to release a coil (1 patient). CONCLUSION: In our opinion, Cook detachable coils are safe and effective especially in the treatment of persistent ductus arteriosus with a diameter < or = 2.5 mm. Due to the low costs these coils appear to be superior to other devices in this subgroup of patients.

Permanent junctional re-entry tachycardia. A multicentre long-term follow-up study in infants, children and young adults.

AIMS: Permanent junctional re-entry tachycardia is a relatively uncommon form of re-entry tachycardia with antegrade conduction occurring through the atrioventricular node and retrograde conduction over an accessory pathway usually located in the postero-septal region. It was the aim of the study to investigate the course of permanent junctional re-entry tachycardia with particular regard to the effectiveness of pharmacological treatment and ablation procedures; evaluation was performed with respect to the patient's symptoms, tachycardia rate, frequency of the tachycardia and left ventricular function. METHODS AND RESULTS: The long-term follow-up of 32 patients with permanent junctional re-entry tachycardia was evaluated. The first presentation with supraventricular tachycardia occurred between the 27th week of gestation and 27 years. The tachycardia rate ranged from 100 to 250 beats.min-1. During Holter-ECG, permanent junctional re-entry tachycardia was documented as present for over 50% of the time in 24 h in 22 patients (69%). Left ventricular performance was impaired in nine patients (28%) due to a tachycardia-related cardiomyopathy. Symptoms or signs of heart failure were mild to moderate in eight and severe in four patients; 20 patients showed no clinical impairment. Follow-up time was 1 to 31 (mean 10) years; current age of the patients ranged from 1.5 months to 35 (mean = 15 x 3) years. Four patients needed no therapy because of the infrequency of permanent junctional re-entry tachycardia episodes. Twenty-five patients initially received antiarrhythmic drugs, which were effective or partially effective in 14 (56%). Eight of them are still on medical therapy; in five treatment was discontinued because of absence of symptoms. Eleven patients had ablation of the accessory pathway during follow-up, three underwent ablation as a primary procedure. CONCLUSION: Permanent junctional re-entry tachycardia in our experience is an arrhythmia with a large variety of clinical symptoms. Patients with a slow tachycardia rate and infrequent episodes of tachycardia may never develop symptoms and therefore do not need any therapy. Patients with frequent permanent junctional re-entry tachycardia, a fast tachycardia rate and impaired left ventricular function need effective therapy. In infancy and early childhood medical therapy is recommended as a first option, whereas in older and symptomatic patients catheter ablation is an effective and safe procedure.

Solution structure of the cytoplasmic domain of the human CD4 glycoprotein by CD and 1H NMR spectroscopy: implications for biological functions.

The human T cell receptor CD4 is a type I integral membrane glycoprotein that is involved in T cell activation and also acts as the primary coreceptor for human immunodeficiency viruses (HIV). Here the structure of a synthetic 38 amino acid peptide corresponding to the complete cytoplasmic domain of CD4 (CD4CYTO) has been investigated under a variety of solution conditions using a combination of circular dichroism and homonuclear two-dimensional 1H nuclear magnetic resonance spectroscopy. In the presence of the membrane mimetic 2,2,2-trifluoroethanol (TFE), a conformational change of CD4CYTO from a random coil to an alpha-helical structure was observed. In keeping with this, CD4CYTO has the potential to associate with membranes as demonstrated by binding studies of in vitro phosphorylated CD4CYTO with microsomal membranes. Both chemical shift and nuclear Overhauser enhancement data in 50% 2,2, 2-trifluoroethanol solution provide direct experimental evidence for the predominance of a short amphiphatic alpha-helix that is approximately 4 turns in length and extends from positions Arg-402 to Lys-417. The present data provide, for the first time, compelling experimental evidence that only a fraction of CD4CYTO has a propensity for adopting secondary structure under conditions that are assumed to exist at or near to the membrane surface and that this alpha-helical structure is located in the membrane-proximal region of CD4CYTO. The N-terminal residues, that link the alpha-helix to the transmembrane anchor of CD4, and a substantial C-terminal portion (14-18 residues) of CD4CYTO are unstructured under the solution conditions investigated. Correlation of our structural data with recent studies on the biological activity of CD4CYTO indicates that the alpha-helix is of crucial importance for the interaction of CD4 with Nef and Vpu in the process of HIV-mediated CD4 down-regulation.

[Experiences in therapy of bradycardic cardiac arrhythmias in childhood with ipratropium bromide]. / Erfahrungen zur Therapie bradykarder Herzrhythmusstörungen im Kindesalter mit Ipratropiumbromid.

Ipratropiumbromid is used in adults for a variety of bradyarrhythmias. In contrast this therapy has not yet been established in childhood, where symptomatic bradyeardias are less frequent. Since Ipratropiumbromid has less side effects (especially concerning the central nervous system) and a longer half time than atropin, we investigated the efficacy of Ipratropiumbromid in 12 children (mean age 7.2 yrs.) in the course of 2 1/2 years. We found a significant increase of the minimal and mean heart rate in Holter-Eeg-recordings. Only in 7 of 12 patients we obtained a sufficient therapeutic effect. In one patient we had to terminate the therapy because of side effects. In two patients with atrioventricular block and two children with higher degree sinus node dysfunction could be removed only by implantation of a pacemaker. In another case we observed the proarrhythmical effect of Ipratropiumbromid. Summarizing we think, that the therapy with Ipratropiumbromid may be useful in symptomatical supranodal bradyarrhythmias in childhood in regard of side effects.

Arrhythmias in infants and children with primary cardiac tumours.

Twenty-one patients, aged from 1 day to 16 years (median 8 months), with primary cardiac tumours, were studied with regard to the occurrence of arrhythmias. Standard electrocardiogram (ECG) was available in 20 cases and 24 h ambulatory ECG in 19; nine patients had prospective follow-up investigations (mean follow-up time 3.0 years). Standard ECG revealed preexcitation in two and arrhythmias in six patients. Ambulatory ECG disclosed seven patients with significant rhythm disturbances and in four of these, the arrhythmia was the symptom leading to the diagnosis of a cardiac tumour. Three patients were symptomatic from arrhythmia and two of them were successfully treated with antiarrhythmic agents. The remaining patient with recurrent life-threatening ventricular tachycardia underwent partial resection of a large left ventricular fibroma; no further episodes of ventricular tachycardia were observed postoperatively. Only one of the 15 patients with cardiac rhabdomyomas required antiarrhythmic therapy. None of the nine patients prospectively followed developed arrhythmias requiring therapy. The present data underline the fact that infants and children with cardiac tumours rarely need surgery because of arrhythmia resistant to medical treatment. As far as possible, conservative management is indicated in infants with suspected rhabdomyomas.

Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase.

The effect of ten naturally occurring and two synthetic inhibitors of NADH:ubiquinone oxidoreductase (complex I) of bovine heart, Neurospora crassa and Escherichia coli and glucose:ubiquinone oxidoreductase (glucose dehydrogenase) of Gluconobacter oxidans was investigated. These inhibitors could be divided into two classes with regard to their specificity and mode of action. Class I inhibitors, including the naturally occurring piericidin A, annonin VI, phenalamid A2, aurachins A and B, thiangazole and the synthetic fenpyroximate, inhibit complex I from all three species in a partially competitive manner and glucose dehydrogenase in a competitive manner, both with regard to ubiquinone. Class II inhibitors including the naturally occurring rotenone, phenoxan, aureothin and the synthetic benzimidazole inhibit complex I from all species in an non-competitive manner, but have no effect on the glucose dehydrogenase. Myxalamid PI could not be classified as above because it inhibits only the mitochondrial complex I and in a competitive manner. All inhibitors affect the electron-transfer step from the high-potential iron-sulphur cluster to ubiquinone. Class I inhibitors appear to act directly at the ubiquinone-catalytic site which is related in complex I and glucose dehydrogenase.

[Coronary artery fistula--surgical or percutaneous embolization treatment?]. / Koronararterienfistel--chirurgische oder perkutane Embolisationsbehandlung?

Three children aged 4 months, 2.7 and 7 years with the unusual fistula of the left coronary artery to the right atrium were observed over a 2-year period. The two younger children underwent emergency surgery although they showed no clinical symptoms. The reasons for surgical intervention were an aneurysm in the right atrium with obstruction of the vena cava superior and a considerably enlarged fistula, respectively. In the older child, we percutaneously embolized a terminate fistula of the ramus circumflexus with two platinum microcoils without complications. Two-dimensional-echocardiography and color flow mapping were used to confirm the diagnosis. After such diagnosis we recommend a coronary angiography in every case. The transcatheter-coil-embolization is an alternative method to surgical closure in selected cases. We recommend an early onset intervention in case of congenital coronary artery fistula.

Atrial automatic tachycardia in infancy and childhood.

Twenty-one cases (13 male, eight female) of atrial automatic tachycardia (AAT) assessed by standard and Holter-ECG in otherwise healthy infants and children have been documented. AAT was incessant in 12 patients, repetitive in seven, and of undetermined type in the remaining two. The frontal P wave axis suggested an ectopic focus in the high right atrium or right atrial appendage in 13 patients, in the low right atrium in one patient, and in the left atrium in seven patients. Thirteen out of 14 patients with the incessant or undetermined type of AAT were symptomatic, in contrast to only two of seven patients with the repetitive type. All patients were treated with between one and eight (median three) antiarrhythmic drugs. The most effective drug was amiodarone, followed by the class I C antiarrhythmic drugs, propafenone and flecainide. At present, all patients are alive 4 months to 21 years (median 2.5 years) after diagnosis of AAT. Twelve patients are in sinus rhythm, five of them without any medication. Nine patients still have AAT, which, however, is repetitive or intermittent in all but one. In conclusion, AAT is an unusual, and in its incessant form often severely symptomatic arrhythmia, which is resistant to conventional antiarrhythmic medication. However, amiodarone and class I C antiarrhythmic drugs are frequently effective. Since medical treatment with these drugs is often successful, and AAT may resolve completely, a conservative approach is indicated in many cases.

Nannochelins A, B and C, new iron-chelating compounds from Nannocystis exedens (myxobacteria). Production, isolation, physico-chemical and biological properties.

Novel citrate-hydroxamate siderophores, named nannochelins A, B and C, were isolated from the culture broth of the myxobacterium Nannocystis exedens strain Na e485. The new substances showed weak growth-inhibitory activity against some bacteria and fungi.

[Current treatment protocol in cardiovascular diseases in childhood. 1: Heart failure, diseases in the neonatal period, congenital heart defects. 2: Arrhythmias, carditis, cardiomyopathies, shock, hypertension]. / Aktuelle Behandlungsstrategien bei Herzkreislauferkrankungen im Kindesalter. Teil 1: Herzinsuffizienz, Erkrankungen in der Neugeborenenperiode, angeborene Herzfehler. Teil 2: Herzrhythmusstörungen, Karditis, Kardiomyopathien, Schock, Hypertonie.

It is given an overview about actual strategies of the treatment of children suffering from heart diseases. Partly proven drugs are given in an optimized doses e.g. digoxin and digitoxin where as other new drugs and therapeutic principles are introduced e. g. catecholamines and vasodilator agents, antiarrhythmic drugs or electrotherapy and antiarrhythmic surgery. Various functional disturbances of the cardiovascular system can occur in the newborn period. New diagnostic principles especially echocardiography with doppler sonography, holter monitoring and exercise testing have lead to better therapeutic regimens. Heart catheterizations have new therapeutic tools like the balloon valvuloplasty of a stenotic pulmonic valve. At least the advances of cardiac surgery have lead to a shift of the time of correction to early childhood. Two step interventions are more and more removed and the related children and their families will have a better outcome and a better life quality.

[Children after an electric injury. A retrospective 10 year study]. / Kinder nach Stromunfall. Eine retrospektive 10-Jahres-Studie.

We analysed the clinical and laboratory findings of 31 patients who had undergone electrical injuries and who were treated in our hospital from 1979 to 1988. Only in two out of 30 injuries in the low voltage range we found arrhythmias of the heart caused by the accident. The paraclinical findings did not show any unambiguous pathological values. In accordance with the bibliography we are of opinion that children who underwent low voltage electrical shock may be considered as not endangered, of the case history is known and if clinical status and electrocardiogram are normal, so that they should not stay in hospital. Seldom complications and exeptions are mentioned. Because of the higher incidence in the early childhood and the special risk by nonprotected sockets measures should be propagated to increase the safety in the domestic environment of the children.

[Delayed fontanelle closure in infants with cyanotic cardiomyopathies]. / Verzögerter Fontanellenschluss bei Säuglingen mit zyanotischen Kardiopathien.

In comparison with infants not suffering from cyanotic heart failures a different size (width and length) as well as a delayed time of closure of the anterior fontanelle in infants with congenital cyanotic heart failures were detected. In these patients typical phenomenons by ultrasound examinations are described also.

Myxothiazol: a reversible blocker of the cell cycle.

Myxothiazol, a potent inhibitor of the cytochrome bc1 oxidoreductase, was shown by the use of flow cytometry to block reversibly the late G1/S phase of the cell cycle of human lymphoblastic T-cell line Jurkat (clone 886) at concentrations of 0.5 microgram/ml. These observations are compared to those of other drugs, such as antimycin, which effect the respiratory chain, and with O2-deficiency.

Saframycin Mx1, a new natural saframycin isolated from a myxobacterium.

A new natural saframycin was discovered in the culture broth of the myxobacterium, Myxococcus xanthus strain Mx x48. The fermentation and isolation of the antibiotic are described. The name, saframycin Mx1, is proposed. The compound appears to interact with cellular DNA.