Ruhi Özyürek

TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children

The recently described family of toll-like receptors (TLRs) is a key player in host immunity by mediating inflammatory reactions against a wide range of pathogens. Mutations and polymorphisms in TLRs have revealed the importance of TLRs in human defence against diseases. TLR-2 is reported to interact with different bacterial structures, including lipoproteins, peptidoglycan and lipoteichoic acid. To assess the role of TLR-2 gene polymorphism in acute rheumatic fever (ARF) etiopathology, 61 independent Caucasian Turkish patients and 91 child and 116 adult controls were studied. Antistreptolycin O, C-reactive protein, sedimentation and white blood cell counts were studied to evaluate the clinical characteristics of the patients. Genomic DNA was extracted from peripheral blood using a standard column extraction technique. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. The PCR products for the TLR-2 gene were analysed on 1.5% agarose gel pre-stained with ethidium bromide. Compared with healthy adult controls, the Arg753Arg genotype was significantly decreased in the entire group of ARF cases [odds ratio (OR) 0.01, 95% confidence interval (95% CI) 0.0034–0.031, p<0.0001]. Significantly, ARF patients were just 16 times more frequent with Gln allele (OR 15.6, 95% CI 7.87–30.8, p<0.0001). Moreover, evidence for an intensifying effect of the Gln allele was noteworthy when patients with Arg753Gln genotype were compared with healthy controls (OR 97.1, 95% CI 32.5–290, p<0.0001). However, no Arg677Trp polymorphism was detected in either patients or controls. Our data suggest that there is strong evidence for the biological role of TLR-2 in ARF. The common TLR-2 Arg to Gln polymorphism at position 753 significantly contributes to the pathogenesis of ARF. These results will allow the construction of a profile of individuals prone to ARF and may assist in developing new therapies.

Frequency of acquired von Willebrand's disease in children with congenital heart disease.

Objective — Bleeding tendency of paediatric patients with congenital heart disease has been well recognized.The underlying pathologies of this bleeding tendency have been studied extensively and many causes were identified. Among these causes, we aimed to find the frequency of acquired von Willebrand’s disease (AvWD) in children with congenital heart disease. Material and methods — Forty-nine children with different forms of congenital cardiopathies who were assigned for surgery, are included in the study. Serum von Willebrand factor antigen level as well as ristocetin cofactor agglutination ratios were determined preoperatively and at one week and 6 months postoperatively. Results — Six patients (12.2%) were found to have AvWD. However, we found no relation between bleeding tendency and AvWD status. Conclusion — Although frequency of von Willebrand factor deficiency is higher in children with congenital heart disease than in the normal population, this condition does not result in adverse clinical outcomes like increased bleeding tendency during operation.

Inferior vena cava indices determine volume load in minimal lesion nephrotic syndrome.

Abstract The pathogenesis of edema in nephrotic syndrome has not been entirely understood. We investigated the value of the echographic parameters [inferior vena cava index (IVCI), inferior vena cava collapsibility index (IVCCI), and left atrium diameter (LAD)] to determine the volume load in children with minimal lesion nephrotic syndrome (MLNS). Twelve children with MLNS (seven boys, five girls) were included in this study. The patients were classified into three different stages (stage A: edematous; stage B: 50% decrease in weight gain; stage C: edema free) following measurement of their ideal weights. The ideal weight of patients in stage A was increased 13±7%. Serum total protein, albumin and urine sodium levels were found to be low in these patients. Plasma renin activity (PRA) and serum aldosterone levels in stage A were significantly different from those of the control group (P<0.05). PRA and serum aldosterone levels were not different from those of the control group in stage B (P>0.05). However, the increase in PRA was significant in stage C. Although a significant weight decrease was found in stages B and C, it had no effect on IVCI, LAD, and cardiothoracic index. We consider IVCI, IVCCI, and LAD measurements by echocardiography (ECHO) to be easy and reliable clinical methods for assessing the intravascular volume load in patients with MLNS.

Lack of association between TNFα gene polymorphism at position –308 and risk of acute rheumatic fever in Turkish patients

Objective: Acute rheumatic fever (ARF) is a multisystem inflammatory disease process that follows nasopharyngeal infection caused by group A streptococcus (GAS) (Streptococcus pyogenes). Recent studies have demonstrated that allelic variations at the tumour necrosis factor alpha (TNFα) locus are involved in the nature of rheumatic diseases such as juvenile idiopathic arthritis and rheumatic heart disease. Thus, TNFα polymorphisms at –308 in ARF patients might be useful in contributing to identification of the primary factors associated with pathogenesis of ARF. Methods: We performed a case–control association study between the common G/A promoter polymorphism at position –308 in the TNFα gene and ARF in Turkish patients, investigating whether this locus acts as a risk factor or has a modifying effect. Results and Conclusion: Previous studies have reported that TNFα plays a major role in the pathogenesis of a number of autoimmune and inflammatory diseases. Moreover, significantly elevated TNFα levels were reported in patients with ARF. However, in our sample of patients with ARF (n = 66), no such association was found. No interactive effect was found between the TNFα polymorphism at position –308 and no association was detected with disease progression. These findings suggest that the role of TNFα in ARF may be in linkage disequilibrium with some other severity genes not yet genetically determined.

Williams syndrome and subaortic stenosis

To the Editor: Williams syndrome was first diagnosed from its typical facial appearance, mental retardation and supravalvular aortic stenosis. One hundred and fifty cases have so far been reported (Morris et al. 1990). The genetic basis of Williams syndrome is still unclear (Ensing et al. 1989) and the chromosomal location is controversial (McKusick 1992). Supravalvular aortic stenosis is common in Williams syndrome (Morris et al. 1990, Ensing et al. 1989, McKusick 1992). However, our patient had subvalvular aortic stenosis, and we have been unable to find any similar patient in the literature. We would like to report the main characteristics of this case. An 8-year-old boy with chest pain was examined in the Pediatrics Department of Ege University. He had a typical elfin face. There was a systolic ejection murmur and hepatomegaly of 2 cm. Mental retardation was obvious. Scoliosis and markedly delayed bone development were detected. ECG and chest X-ray showed left ventricular hypertrophy, and subvalvular aortic stenosis with a pressure gradient of 35 mmHg was detected by cardiac catheterization. The echocardiographic study also demonstrated subvalvular aortic stenosis. Received 3 February, revised version received I 19 April, accepted for publication 11 May 1993

PLASMA NATRIURETIC PEPTIDES LEVELS AND ECHOCARDIOGRAPHIC FINDINGS IN LATE SUBCLINICAL ANTHRACYCLINE TOXICITY

The purpose of this study was to evaluate late cardiac toxicity by comprehensive echocardiographic study, and to determine whether plasma atrial natriuretic peptide and brain natriuretic peptide levels might be indicators of neurohumoral activation. The study included 49 long-term survivors and 21 controls. A wide variety of echocardiographic parameters were measured or calculated. Plasma peptide levels were determined. Patients had significant changes in different echocardiographic parameters that are suggestive of LV systolic and diastolic dysfunction. Plasma peptide levels were not increased. The authors have found significant subclinic cardiotoxicity by echocardiography. Survivors seem to have normal plasma natriuretic peptide levels in long-term period.

Yenidoğan döneminde kalpteki kitleler nedeniyle tanı alan tüberoskleroz olguları

Sum mary The aim of the study is to evaluate the tuberosclerosis cases diagnosed during the neonatal period presenting with cardiac masses. The clinical and laboratory findings of 4 cases and of tuberosclerosis diagnosed in Ege University Medical Faculty Newborn Clinic were evaluated retrospectively. The first case was admitted to the Newborn Clinic with the diagnosis of cardiac mass detected at the 28th gestational week. Cranial magnetic resonance imaging revealed subependimal hamartomas. Echocardiography showed large masses within the intraventricular cavity and cardiac apex. The second case was admitted to the Newborn Clinic with the diagnosis of cardiac mass detected at the 29th gestational week. Cranial magnetic resonance imaging revealed subependimal hamartomas and cortical tubers. Echocardiography showed multiple masses located at right ventricular outflow, right atrium and left ventricule. In the third case multiple cardiac masses in both ventricules were detected during the neonatal period. Cranial magnetic resonance imaging showed multiple tubers. The fourth case was admitted to the Newborn Clinic with the diagnosis of cardiac mass detected at the 32th gestational week. Three hipopigmented skin lesions were found. Echocardiography showed multiple masses within the right ventricle, left ventricle and interatrial septum. Cranial magnetic resonance imaging revealed subependimal nodules. Cardiac mass should suggest Tubeous Sclerosis, cranial imaging must be performed. (Turk Arch Ped 2013; 48: 57-61)

Konjenital Kalp Hastalığı Olan Hastalarda Anormal Koagülasyon Test Sonuçlarının Oranı

Introduction: Coagluation abnormalities are expected in patients with congenital heart disease. We searched the rate of abnormal coagulation test in children with both cyanotic and non-cyanotic heart disease and investigated the clinical relevance of these abnormal tests. Material and Method: 49 children who have congenital heart disease and needed surgical intervention were prospectively enrolled to this study. Demographic data, primary diagnosis, bleeding complication during and after the intervention and prognosis of the patients were recorded. Platelet counts, prothrombin time, activated partial thromboplastine time and blood fibrinogen levels were measured prior to intervention. Results: 16 patients had prolonged PT, 13 patients had low fibrinogen level, 10 patients had prolonged aPTT and 5 patients had low platelet count. Conclusion: There was no increased complication risk in patients with abnormal test results, but caution must be taken during operation of these patients.Key words:

Influence of feeding regimens on non-invasive inferior vena cava and hepatic vein velocity measurements in infants

The aim of this study was to investigate the effects of feeding type and osmotic load on intravascular volume status. Ninety term, healthy infants 2 mo of age were included in the study. The breastfed and formula‐fed groups each consisted of 45 infants. Echocardiographic examination was performed before and after feeding. The collapse index of the inferior vena cava (IVCIC) and right atrial pressure (RAP) were calculated. No statistically significant differences were found between before‐ and after‐feeding values of IVCIC, RAP and hepatic vein velocities in breastfed infants. In the formula‐fed group, after‐feeding values of IVCIC were significantly lower and RAP, hepatic vein systolic and diastolic velocities were significantly higher compared to the before‐feeding values. Most of the mothers (78%) were unsuccessful at preparing the formula at appropriate concentrations. No statistically significant differences were found between the before‐and after‐feeding values of IVCIC, RAP and hepatic vein velocities in infants being fed appropriately prepared formula. The after‐feeding values of hepatic vein velocities were higher than those of before‐feeding values; after‐feeding values of IVCIC were lower than before‐feeding values in infants being fed highly concentrated formula.