Zülal Ülger

A randomized controlled 1-year study of daily deferiprone plus twice weekly desferrioxamine compared with daily deferiprone monotherapy in patients with thalassemia major.

Background and Objectives The aim of this prospective, randomized, 1-year study was to compare the efficacy and safety of oral deferiprone (DFP) with those of combinations of parenteral desferrioxamine (DFO) with oral DFP. Design and Methods A total of 24 patients with thalassemia major were randomized to receive one of the following two treatments; DFP given at a daily dose of 75 mg/kg in combination with DFO (40–50 mg/kg twice weekly) (n=12) or as single agent (n=12). In addition, 12 patients treated with 40–50 mg/kg DFO 5 days weekly were included as a reference group without randomization. Changes in liver iron concentration (LIC) and serum ferritin (SF) were assessed; total iron excretion (TIE), urinary iron excretion (UIE) and iron balance were calculated. Cardiac function and toxicity were also examined. Design and Methods SF and LIC were significantly reduced after 1 year of combination therapy (p=0.01 and 0.07, respectively). A decrease of LIC was observed in all but one patient (87.5%) following the combination therapy but in only 42% of patients treated with DFP monotherapy. In the DFO reference group, a statistically significant decrease in LIC (p=0.01) associated with a substantial decrease in SF (p=0.08) was observed after 1 year. The combination regimen resulted in greater TIE compared to DFP monotherapy (p=0.08) and was the regimen associated with the highest iron balance compared to DFP monotherapy (p=0.04) or standard DFO treatment (p=0.006). Interpretations and Conclusions The addition of subcutaneous DFO twice weekly to oral DFP 75 mg/kg is a highly efficacious and safe chelation therapy providing superior chelation activity to that of DFP and likely has an efficacy profile comparable to that of standard DFO.

Follow-up of cardiac abnormalities in female adolescents with anorexia nervosa after refeeding.

Objectives — Anorexia nervosa is a life-threatening eating disorder, with significant risk for sudden death due to severe cardiac complications. The aim of this prospective study was to evaluate the cardiac abnormalities in female adolescents with anorexia nervosa and to examine the long-term results and reversibility of the detected cardiac abnormalities. Methods — We prospectively studied eleven female adolescents (13.5-17 years old) with anorexia nervosa diagnosed according to DSM IV criteria. On admission they were all on a weight-losing course with a mean body mass index of 13.71 ± 1.54 (11.38-17.05) kg/m2. The mean follow-up duration was 2.45 ± 1.17 (1-4.5) years. All patients reached normal weight after treatment. The control group was composed of 12 healthy, age-matched, adolescent girls of normal weight. The patients with anorexia nervosa and the control group underwent a complete clinical examination, electrocardiographic and echocardiographic evaluations.These evaluations were repeated one year after refeeding. Results — Patients with anorexia nervosa had a lower heart rate and blood pressure than the control group and they increased to normal levels as found in the control group after refeeding. QT and QTc were significantly longer and R wave amplitudes in V6 were significantly lower in the patients with anorexia nervosa than in the control group. QT and QTc dispersions were significantly greater in anorexia nervosa patients compared to the control group. Left ventricular mass and left ventricular mass index were significantly lower in the anorexia nervosa group. One year after refeeding, there was a significant decrease in QT, QTc, QTd and QTcd. Although in anorexia nervosa patients, R wave amplitudes in V6 increased after refeeding; they did not reach the levels found in the control group. Control echocardiograms of anorexia nervosa patients after refeeding showed an increase in LV diameters and cardiac mass.There was a strong correlation between QT dispersion and left ventricular mass index. Conclusions — The adolescent girls with anorexia nervosa had significant structural and functional cardiac abnormalities in comparison to the control group. All these abnormalities were reversible except low R wave amplitude in V6.

Eponym. Scimitar syndrome.

Scimitar syndrome is a rare congenital anomaly, characterized by partial or complete anomalous pulmonary venous drainage of the right or left lung into the inferior vena cava. The syndrome is commonly associated with hypoplasia of the right lung, pulmonary sequestration, persisting left superior vena cava, and dextroposition of the heart. The pathogenesis of the syndrome is unclear, but it seems to originate from a basic developmental disorder of the entire lung bud early in embryogenesis. Two main forms of scimitar syndrome have been described. Signs and symptoms can start during infancy (infantile form) or beyond (childhood/adult form). The infantile form generally presents within the first 2 months of life with tachypnea, recurrent pneumonia, failure to thrive, and signs of heart failure. The diagnosis of scimitar syndrome is usually made based on the characteristic chest X-ray films and can be confirmed by angiography; however, it is now done mostly by transthoracic or transesophageal echocardiography, noninvasive computed tomography, or magnetic resonance angiography. Fetal echocardiography using three-dimensional power Doppler imaging permits prenatal diagnosis. Most frequently, patients are asymptomatic in the absence of associated abnormalities and can be followed conservatively. For patients with congestive heart failure, repeated pneumonia, or pulmonary-to-systemic blood flow ratios greater than 1.5 and pulmonary hypertension, it is important to reroute the anomalous right pulmonary veins and repair the associated cardiac defects in order to avoid progression to right ventricular failure. The triad of respiratory distress, right lung hypoplasia, and dextroposition of the heart should alert the clinician to think of scimitar syndrome.

The relation of arterial stiffness with intrauterine growth retardation.

Background:  Much epidemiological evidence has linked low birthweight with late cardiovascular risk. Intrauterine growth retardation (IUGR) is associated with the increased risk of cardiovascular disease in adult life; it is unclear whether the relationship is present at younger ages. We evaluated whether abdominal aortic stiffness was altered in patients with IUGR (born at term with birthweight small for gestational age) in younger ages.

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.

Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis

Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene −2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the −2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the −2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the −2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.

Time domain heart rate variability analysis in patients with thalassaemia major

Objective — Cardiac complication is one of the major causes of death in patients with thalassaemia major. Heart rate variability is a non-invasive index of neuronal modulation of heart rate. In this study, autonomic functions of the heart in a preclinical stage of heart disease were evaluated in 48 thalassaemic patients with time domain heart rate variability analysis; the control group consisted of 45 healthy subjects. Methods and results — Mean RR time in the study and control group was 0.73 ± 0.1, and 0.82 ± 0.1 ms respectively (p < 0.001). In the study group; SDNN, SDNN-i, SDANN-i, RMSSD, and PNN50 were found to be 167.4 ± 86.2 ms, 153.9 ± 108.1 ms, 111.4 ± 60.4 ms, 108.9 ± 86.7 ms, and 14.5 ± 13.4%, respectively.Time domain parameters were significantly lower in the study group than the control group (p < 0.001).There was a significant positive correlation between the mean RR time and SDNN, SDNN-i, SDANN-i, RMSSD, and PNN50 (for the RMSSD p < 0.05, r = 0.31; for the others p = 0.000, and r values were 0.65, 0.65, 0.38, 0.37 for the SDNN, SDNN-i, SDANN-i, and PNN50, respectively). Conclusion — The analysis of heart rate variability might be helpful to detect cardiac complications in the preclinical stage of the cardiac involvement.

Psychiatric evaluation of children and adolescents with left ventricular assist devices.

Objectives To evaluate the psychiatric symptoms of children equipped with a ventricular assist device (VAD) and follow them up for 6 months. With the shortage of donor hearts available for the treatment of end-stage heart failure, VADs have been used to provide temporary treatment until a heart becomes available. VADs provide external sources of power for mechanical circulatory support and are capable of sustaining life over weeks and months. This study provides preliminary details about the psychiatric symptoms and disorders of the first eight children equipped with a VAD in Turkey. Methods Eight pediatric patients who recently underwent VAD implantation, aged 1 to 16 years, were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia, Child Behavior Checklist, Children’s Depression Inventory, Beck Depression Inventory, and State-Trait Anxiety Inventory for Children and followed up for 6 months. Results In the first evaluation, five participants had a psychiatric disorder diagnosis. Two patients had adjustment disorder with depressive and anxiety symptoms; one had anxiety disorder, not otherwise specified; and two had major depressive disorder. The anxiety and depressive symptom levels in questionnaires were consistent with psychiatric diagnoses. Two patients had heart transplantation during the follow-up period. Conclusions To determine and treat psychiatric symptoms and disorders at an earlier stage, it is important for children and adolescents with a VAD and those who have undergone heart transplantation to be evaluated by a multidisciplinary consultation liaison team including psychiatrists, psychologists, consultant nurses, and counselors. Abbreviations VAD = ventricular assist device K-SADS = Kiddie Schedule for Affective Disorders and Schizophrenia CBCL = Child Behavior Checklist BDI = Beck Depression Inventory CDI = Children’s Depression Inventory STAI-C = State-Trait Anxiety Inventory for Children MDD = major depressive disorder AD = adjustment disorder PE.I = initial psychiatric evaluation PE.II = second psychiatric evaluation

Acute Guttate Psoriasis Associated With Streptococcal Perianal Dermatitis

not affected. There was a superficial, erythematous, well-marginated, nonconfluent, perianal rash that was moist and tender to touch without any signs of cellulitis. Nails were normal. The rest of the physical examination did not reveal any abnormalities. On complete blood count, leukocyte count was 8900/mm3, hemoglobin 11.6 gr/dL, and platelet count was 364,000/mm3; acute phase reactants were negative (erythrocyte sedimentation rate 10 mm/h, C-reactive protein 0.5 mg/dL). Blood ions, liver, and kidney function tests were normal. Immunoglobulin (Ig) E level was 80 mg/dL and specific IgE, antinuclear antibody were negative. Antistreptolysin O titer was high (695 IU/mL). A perianal swab culture was done, which revealed a pure and heavy growth of group A beta-hemolytic streptococci, but the blood culture was sterile. Perianal swab culture for fungi was negative. Histological examination of the biopsy specimen taken from the lesion on the left leg revealed hyperkeratosis, focal epidermal hyperplasia, slightly elongated rete ridges, and an infiltrate composed of mononuclear cells in the upper dermis. The child was successfully treated with topical corticosteroids for the lesions on the body and oral penicillin-V in a dose of 50 mg/kg/day for a total duration of 2 weeks for perianal streptococcal dermatitis. We did not observe any relapse during the 6 months of follow-up.

Scimitar syndrome associated with partial anomalous pulmonary venous draining into superior vena cava.

Scimitar syndrome is a rare congenital cardiopulmonary malformation characterized by hypoplasia of the right lung and drainage of the right pulmonary veins into the vena cava inferior. It may also be associated with cardiac dextroversion and anomalies of the tracheobronchial system, cardiovascular system, and diaphragm. Some cases are asymptomatic with others diagnosed in early-childhood period with pulmonary hypoplasia and other associated malformations. We present here a patient whose venous return of the middle and lower lobes of the right lung is into the superior vena cava, which is a very unusual finding for this disorder.