Pharmacokinetics of ofloxacin and levofloxacin for prevention and treatment of multidrug-resistant tuberculosis in children.

Limited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment, serum concentrations following oral doses of levofloxacin (15 mg/kg of body weight) and ofloxacin (20 mg/kg) were lower than those expected from existing pediatric data, possibly due to differences in the formulations (crushed tablets). Drug exposures were lower than those in adults following standard doses and below the proposed pharmacodynamic targets, likely due to more rapid elimination in children. No QT prolongation was observed.

Supraventricular tachycardia in children.

The mechanisms causing different supraventricular tachycardias can be identified with the aid of the 12-lead ECG using Tipple's approach. The main aims of this retrospective study were to use the 12-lead ECG to determine the underlying mechanisms of supraventricular arrhythmias and to evaluate the effectiveness of the treatment modalities used. Forty-one patients were included in the study. The main findings were: nine of the 41 patients had atrial tachycardias while junctional tachycardia occurred in 32/41 of our patients. The underlying mechanisms causing the junctional tachycardias were: AVNRT (n = 21), AVRT (n = 10) and JET (n = 1). Of the 10 patients presenting with AVRT, eight were less than one year old. AVNRT occurred more often in the older age group (>1 year of age). Fifteen of the 41 patients had spontaneous cessation of their supraventricular tachycardia. The drug most commonly used during the acute and long-term phases was digoxin. Amiodarone was used in six patients with an 80% success rate. In the early 80s verapamil was used in five patients with a 100% success rate. It is important to note that verapamil is no longer used in children due to its side effects. Lately, adenosine phosphate is the drug of choice in most supraventricular tachycardias. The management of supraventricular tachycardias in paediatric practice is mainly based on clinical studies and individual experience. Care must therefore be taken to choose medication regimens that are likely to be effective with the minimum risk of potentiating abnormal haemodynamics or conduction.

Mitral valve prolapse: a study of 45 children.

The knowledge pertaining to mitral valve prolapse is mainly based on studies in adults. In this study, the clinical profile as described in adults was compared with that found in children up to the age of 13 years. Forty-five children with echocardiographic-proven mitral valve prolapse and who met the inclusion criteria were included in the study. The male:female ratio in this study was 1:1.37 and was not statistically significantly different from reported ratios. Most of the children were asymptomatic. Twenty-one of the 31 patients referred from outside the hospital had an incidentally found murmur. The symptoms found in this study were not similar to those described in adults. The most commonly found symptoms were shortness of breath and fatigue, in contrast to those of chest pain and palpitations described in adults. Comparing males to females in this study, significantly lower weight (p = 0.005) and body mass index (p = 0.003) were found in girls, and a significantly lower pulse rate (p = 0.002) in boys. Left-sided cardiac enlargement was diagnosed in 11 patients on chest X-ray and in six patients on electrocardiogram. One patient had Marfan syndrome and four others had a Marfanoid appearance. In conclusion, most children with mitral valve prolapse are asymptomatic. Mitral valve prolapse is not an uncommon finding in children younger than 13 years of age. Patients with mitral valve regurgitation were advised to take infective endocarditis prophylaxis prior to invasive procedures.

Factors influencing successful closure with indomethacin of the patent ductus arteriosus in premature infants.

The incidence of persistent patency of the ductus arteriosus (PDA) is inversely related to birth weight. A PDA contributes to pathological conditions in the neonate and timely closure in these low-L birth-L weight infants could potentially prevent these complications. Prostaglandin inhibition with indomethacin is one treatment strategy currently available. This retrospective descriptive study evaluated the parameters that influenced the effectiveness of indomethacin in closure of the PDA in 101 consecutive premature infants and the adverse effects of indomethacin in these infants. Independent variables found to increase the risk of unsuccessful closure with indomethacin significantly were caesarean section, lower haematocrit at delivery and severity of hyaline membrane disease. Non-L closure also resulted in prolonged ventilation. No significant adverse effects were recorded in the infants who received indomethacin but neonatal jaundice was more common in those infants who responded to indomethacin.

Diagnosis of haemodynamically significant patent ductus arteriosus in neonates-- is the ECG of diagnostic help?

The presence of a haemodynamically significant patent ductus arteriosis (PDA) in the premature newborn may contribute to the development of brochopulmonary dysplasia, intraventricular haemorrhage and necrotising enterocolitis. It is therefore essential that the diagnosis of such a PDA be made in time in order to intervene medically or surgically. Echocardiography is at present the prime diagnostic tool, but it is mainly available in tertiary hospitals. Chest roentgenography is of little diagnostic value especially in the presence of respiratory disease, which is often present in premature babies. Very little is known about the diagnostic value of the electrocardiogram (ECG) in premature babies. The aim of this study was to describe the standard 12-lead ECG findings in low-birth-weight babies with haemodynamically significant PDAs. Thirty-two babies with haemodynamically significant PDAs, as established by echocardiography, were included in the study. Standard 12-lead ECGs were done in all these babies. In 15 patients ECG abnormalities were found; only 22% had left atrial and left ventricular enlargement indicative of significant left-to-right shunting, while 78% had no ECG changes indicative of left-to-right shunting. In conclusion, the ECG cannot be used to identify haemodynamically significant PDAs.

An explanation of the unusual electrocardiographic findings in a patient with pulmonary agenesis and dextrocardia.

Interpretation of the electrocardiagram (ECG) is extremely helpful in distinguishing between the different forms of dextrocardia. The patient in this report had agenesis of the right lung and dextroposition; the ECG mimicked mirror-image dextrocardia, with elements of dextroversion also present.

Secundum atrial septal defects - a review of 75 patients.

Secundum atrial septal defect (ASD) is the most common type of ASD within the spectrum of congenital cardiac abnormalities in children. In this retrospective study the data on 75 patients with a pure secundum ASD were analysed. The male/female ratio was 1:1,3. This is less than the reported male / female ratio, of 1:2. The symptoms most often found were shortness of breath, cough and susceptibility to fatigue. An ejection systolic heart murmur was found in the majority of the patients. A fixed split second heart sound was only found in 49% of patients. This could have been the result of incomplete documentation, inexperienced clinicians, a fast heart rate or the fact that a split second heart sound is not always present in patients with ASDs. On the chest radiograph the majority of patients presented with right ventricular enlargement, right atrial enlargement and increased pulmonary blood flow. A relatively unexpected finding on echocardiography was left atrial enlargement. This is usually caused by volume overload in the presence of large ASDs. Another unexpected finding was the high number of left QRS-axis deviations (10%) and indeterminate QRS-axis deviations, left rotation (7%) present on the electrocardiogram. This finding is much higher than the reported 3.8% of left QRS-axis deviation present in patients with secundum ASDs. The only explanation for this phenomenon is that during the embryological development of the atrial septum, not only does a secundum ASD develop, but the endocardial cushion becomes involved, giving rise to abnormal conductive pathways.

Second-degree atrioventricular heart block after doxapram administration.

Doxapram, a respiratory stimulant, is used to treat idiopathic apnea of prematurity. The side effects reported are minimal. We present three cases of second-degree atrioventricular block caused by QT interval prolongation associated with doxapram administration. All three infants returned to normal sinus rhythm after doxapram administration was stopped.

Myosin-reactive autoantibodies in rheumatic carditis and normal fetus.

EBV-transformed B cells from a 20-week human fetal spleen and from blood of patients with poststreptococcal rheumatic carditis were studied. Most antibodies from nine fetal and six patient myosin-reactive B cell clones were multireactive (reacting with cardiac myosin, Streptococcus pyogenes, and rat cardiac myocytes) which supports a role for molecular mimicry in stimulation of these autoantibodies. Sequence analysis revealed that fetal and patient anti-myosin repertoires were composed of unrelated clones with diverse V gene usages. Fetal and patient antibodies had reduced VH CDR3 length on average and reduced light chain N region addition with a low rate of somatic mutation in the variable region genes, characteristics generally associated with fetal B cells but also with some adult B cells. Five of six myosin-reactive patient clones used VH3, whereas only two of nine fetal clones used VH3, suggesting skewing from the average 50-60% VH3 gene usage found in randomly selected adult and fetal antibodies.

Cardiac tamponade following umbilical vein catheterisation in a neonate.

Umbilical vein catheterisation (UVC) should not routinely be used in the neonatal intensive care unit, and when it is used special precautions should be taken and guidelines followed. We present an unusual complication which occurred following use of an umbilical vein catheter in a term neonate. This case highlights another potentially lethal complication of UVC, and emphasises the risks associated with the procedure. In order for the benefits of UVC to outweigh the risks, certain guidelines are reviewed. The importance of confirming the position of the catheter tip with both anteroposterior and lateral radiographs is emphasised.

Sydenham's chorea--analysis of 27 patients and a review of the literature.

The first documented epidemic of Sydenham's chorea was in 1418. In 1686 Thomas Sydenham was the first to describe the condition, but it was Richard Bright who in 1831 first made the association between chorea and rheumatic fever. Chorea is one of the major diagnostic criteria for rheumatic fever. Chorea is often considered a benign self-limiting condition. Little is known about the pathophysiological process. A link between the group A beta-haemolytic streptococcus through an antibody-mediated immune response targeting the basal ganglia has been described. Special investigations have been done to ascertain the pathophysiology, but none is of diagnostic value. The aims of this study were to analyse the clinical findings, the role of special investigations in the management and course of Sydenham's chorea and to review the literature. Data on 27 patients were analysed. Special investigations in these patients can be divided into those necessary to assist in diagnosing acute rheumatic fever and those to exclude other causes that mimic chorea. None of these tests was helpful in diagnosing chorea due to other causes; neither did they influence the management of these patients. In conclusion, Sydenham's chorea remains a clinical diagnosis and extensive and expensive special investigations are seldom warranted.

Isolation of the left subclavian artery in tetralogy of Fallot and bronchial anomalies.

In the normal left-sided aorta, the vertebral arteries arise from the respective subclavian arteries. Isolation of the left subclavian artery takes place when the distal subclavian artery arises as an extension of a patent ductus arteriosus. This report describes a patient with tetralogy of Fallot and a right-sided aortic arch with isolation of the left subclavian artery. In addition, the patient also has congenital tracheal and bronchial stenosis, with a horseshoe lung.

Congenitally absent pulmonary veins--diagnostic pitfalls. Two case reports.

Two patients with partial absence of the right and left pulmonary veins respectively are described. Congenitally absent pulmonary veins are a rare phenomenon and the diagnosis is often missed or delayed. When children present with haemoptysis and/or recurrent respiratory infections with no obvious underlying cause, absence of the pulmonary veins must be part of the differential diagnosis. Special investigations to be done in these patients are chest roentgenograph to compare the lung volumes, radio-isotope scan, echocardiography and cardiac catheterisation. Magnetic resonance imaging may be helpful in defining the cause and site of obstruction of the pulmonary veins. Depending on the cause, surgery might be considered.

Risk of pulmonary tuberculosis in children with congenital heart disease.

Children with low-flow congenital heart lesions are reported to have an increased incidence of pulmonary tuberculosis. The aim of this study was to investigate if children with congenital heart disease have an increased incidence of pulmonary tuberculosis and to determine if patients with certain heart conditions are more susceptible to pulmonary tuberculosis than others. This retrospective study over a 6-year period showed that pulmonary tuberculosis was 2.5-fold more common in children with congenital heart disease than in normal children from the same community. Children with congenital pulmonary stenosis had a prevalence equal to those with acyanotic (ventricular and atrial septal defects) and cyanotic (transposition of the great arteries) high-flow heart lesions, whereas there were no cases of tuberculosis in children with low-flow cyanotic heart lesions such as tetralogy of Fallot. Cardiac surgery had to be postponed as a result of pulmonary tuberculosis in 7.2% of all patients in whom it was required. Over the 6-year period of the study, cardiac surgery had to be delayed in 60% of cases with pulmonary tuberculosis and congenital heart lesions so antituberculosis therapy could be completed. Physicians treating children with congenital heart lesions should maintain a high index of suspicion for the development of pulmonary tuberculosis, especially in those with acyanotic and cyanotic high-flow lesions and pulmonary stenosis.

Gene for progressive familial heart block type I maps to chromosome 19q13.

BACKGROUND: Progressive familial heart block type I (PF-HBI) is a dominantly inherited cardiac bundle-branch conduction disorder that has been traced through nine generations of a large South African kindred. Similar conduction disorders have been reported elsewhere; however, the cause of these diseases is unknown. The aim of the present study was to determine by linkage analysis the approximate chromosomal position of the gene causing PFHBI, thereby allowing family-based diagnosis and the development of positional cloning strategies to identify the causative gene. METHODS AND RESULTS: Eighty-six members of three pedigrees, 39 members of which were affected with PFHBI, were genotyped at four linked polymorphic marker loci mapped to chromosome 19, bands q13.2-q13.3 (chromosome 19q13.2-13.3). Maximum two-point logarithm of the odds scores (which represent the logarithm of the odds ratio of detecting linkage versus nonlinkage) generated were 6.49 (theta = 0) for the kallikrein locus, 5.72 (theta = 0.01) for the myotonic dystrophy locus, 3.44 (theta = 0) for the creatine kinase muscle-type locus and 4.51 (theta = 0.10) for the apolipoprotein C2 locus. The maximum multipoint logarithm of the odds score was 11.6, with the 90% support interval positioning the PFHBI locus within a 10 cM distance centering on the kallikrein 1 locus. CONCLUSIONS: The gene for PFHBI maps to an area of approximately 10 cM on chromosome 19q13.2-13.3. There are several candidate genes in this interval; although a recombination event ruled out the myotonic dystrophy locus from direct involvement with PFHBI, the proximity of these two loci may be relevant to the observed cardiac abnormalities of myotonic dystrophy. The results provide a means of DNA-based diagnosis in the families studied and a foundation for cloning studies to identify the causative gene.

Repair of aortico-left ventricular tunnel associated with subpulmonary obstruction.

Aortico-left ventricular tunnel is a rare congenital cardiac defect. Because the tunnel traverses the upper portion of the interventricular septum, the potential exists for an aneurysmal tunnel to obstruct the outflow of the right ventricle. We report our clinical experience with such a patient, and emphasize the importance of a two-patch technique to avoid its occurrence.

Progressive familial heart block type I. Clinical and pathological observations.

Progressive familial heart block type I (PFHB-I) is an autosomal inherited disease. It was previously postulated that the disease is limited to the cardiac conduction tissue. The presentation of a patient with dilated cardiomyopathy focused on the possibility that this might be part of PFHB-I. This observation led to routine echocardiographic examination of patients with complete heart block, who belonged to PFHB-I families, and another 5 cases with signs of dilated cardiomyopathy were identified. This is the first time, to our knowledge, that the histological picture of PFHB-I has been described. From these case reports it is clear that in the presence of a dilated cardiomyopathy the prognosis in PFHB-I tends to be poor.