Challenges in choosing the appropriate guidelines for use in children and adolescents with hypertension.

BACKGROUND: This study was designed to observe the effect of antihypertensive treatment on blood pressure (BP) and target organ damage in patients followed up according to the American Academy of Pediatrics Hypertension Guidelines (AAPG). The results were also assessed in comparison with the definitions and target organ damage according to the European Society of Hypertension Guidelines 2016 (ESHG). MATERIALS AND METHODS: A total of 44 (34 male) out of 140 patients were enrolled in the study and the mean age was 14±3.19years. The follow-up period was at least 12months. All patients underwent the following assessments: anthropometrical measurements of body mass index (BMI), left ventricular mass index (LVMI), and biochemical parameters according to the relevant guidelines. The pre-treatment and post-treatment datasets collected were compared. RESULTS: The frequency of symptomatic patients decreased from 88% to 30%. After treatment, 29.4% (n=13) of patients still had elevated and stage 1 hypertension (HT) according to the AAPG. These patients were older and had higher BMI z-scores, LVMI z-scores, mean BP indices, and also had longer symptom duration than normotensive patients (P<0.001). When patients were assessed according to the ESHG, 34.1% (n=15) of patients had high-normal stage 1 and stage 2 HT. While 53.3% (n=8) of the patients aged 13-15years were classified as having high-normal stage 1 and stage 2 HT according to the ESHG, 33.3% (n=5) were classified as having elevated BP and stage 1 HT according to the AAPG. Additionally, 36.4% (n=4) of the patients aged≥16years were classified as having high-normal and stage 1 HT according to the ESHG, whereas 45.5% (n=5) were classified as having elevated BP and stage 1 HT according to the AAPG. CONCLUSION: To control HT in children with higher BMI z-scores, higher LVMI z-scores, and higher BP indices, an earlier and more intensive approach is needed. Considering that the duration of exposure to HT may also affect the LVMI, adjusting age and gender or decreasing the current thresholds for LVMI may lead to an earlier diagnosis for more patients. According to the present classifications, the ESHG covers more children aged between 13 and 15years in contrast to the AAPG, which covers more patients aged≥16years. However, further studies are needed to confirm these results.

Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats.

INTRODUCTION: Despite the developments in modern medicine, acute renal injury is still a challenging and common health problem. It is well known that ischaemia and reperfusion takes place in pathological mechanisms. Efforts to clarify the pathophysiology and interventions to improve outcomes are essential. Our study aimed to investigate whether the prophylactic use of paricalcitol is beneficial in renal ischaemia/reperfusion (I/R) injury. METHODS: Twenty-four Wistar albino rats were assigned randomly to four groups. Right nephrectomies were performed at the time of renal arterial clamping. Sham surgery was performed on the rats in group 1. For the rats in group 2, the left renal artery was clamped for 45 minutes. The rats in group 3 received paricalcitol for seven days (0.2µg/kg/day); following this, a right nephrectomy and left renal arterial clamping were not performed. The rats in group 4 received paricalcitol for seven days (0.2µg/kg/day); following this, a right nephrectomy and left renal arterial clamping for 45 minutes were performed. Tissue thiobarbituric acid reactive substances (TBARS), superoxide dismutase, sulfhydryl groups as well as nitric oxide metabolites, serum urea and creatinine levels were measured for all four groups. RESULTS: In group 4, there were some improvements in terms of TBARS, nitrite, nitrate, superoxide dismutase and creatinine levels. In the histopathological evaluation, paricalcitol therapy improved tubular necrosis and medullar congestion but there was no significant difference in terms of tubular cell swelling, cellular vacuolisation or general damage. Immunohistopathological examination revealed lower scores for vascular endothelial growth factor in the group 4 rats than in group 2. CONCLUSIONS: Paricalcitol therapy improved renal I/R injury in terms of serum and histopathological parameters. These potential beneficial effects need to be further investigated.

Arterial tortuosity syndrome: case report.

Arterial tortuosity syndrome (ATS; OMIM 208050) is a rare autosomal recessive condition characterized by dysmorphic features, elongation, tortuosity, and aneurysm of the large and middle sized arteries. We report on a 13-year-old boy who presented with a malformed ascending aorta mimicking coarctation of aorta and a cutis laxa-like facial dysmorphia. Based on angiogram, a diagnosis of ATS was made and subsequently confirmed by a homozygous one base-pair deletion at position g.318 of SLCA10. We stress similarities (facial appearance, inguinal herniae, ..) between ATS and autosomal recessive cutis laxa, both being connective tissue disorders disorganizing the elastin network.

Takayasu arteritis and ulcerative colitis; coexistence or misdiagnosis?

Takayasu arteritis is a chronic inflammatory disease that primarily affects large arteries such as the aorta and its proximal branches. The association between Takayasu arteritis and ulcerative colitis is an extremely rare condition. Ulcerative colitis is an inflammatory bowel disease, clinical presentation is not specific and may mimic Crohn's disease, radiation colitis, ischemic colitis, a variety of infectious processes, and colitis related to medications. Herein we report a case of Takayasu arteritis who had been misdiagnosed and treated as ulcera-

Brucella myocarditis in a 3-month-old: probable transplacental transmission.

A 3-month-old girl presented with myocarditis owing to brucellosis. Her mother had been diagnosed with brucellosis at 28 weeks gestation but did not receive treatment until after delivery. The infant had intrauterine retardation and had gained little weight since birth. It is considered likely that the brucellosis was transmitted transplacentally.

Neu-Laxova syndrome: a case report and review of the literature.

Neu-Laxova syndrome (NLS) is a rare autosomal recessive syndrome, characterized by severe intrauterine growth retardation (IUGR), microcephaly, abnormal brain development, oedema and ichthyosis. It was first reported in 1971 by Neu et al. (Pediatrics 47: 610-612) and since then no more than 60 cases have been reported. A newborn girl delivered from a 29-year-old healthy mother was admitted to hospital with a thick membrane covering her body and dismorphic appearance. The diagnosis of NLS was made according to characteristic features. The syndrome is known to have a poor prognosis and the baby lived for 9 weeks. This case is one of the longest living cases of NLS and the fourth case reported from Turkey.

Elimination of *O(2)(-)/H(2)O(2) by alpha-lipoic acid mediates the recovery of basal EDRF/NO availability and the reversal of superoxide dismutase-induced relaxation in diabetic rat aorta.

AIM: The aims of this study were to ascertain the mechanism(s) of relaxant action of exogenous superoxide dismutase (SOD) in aortic rings obtained from 12-week, streptozotocin(STZ)-diabetic and age-matched control rats, and to examine the effects of alpha-lipoic acid (ALA) treatment (for 6 weeks, after 6 weeks of untreated diabetes) on SOD-induced relaxations. MATERIALS AND METHODS: Thoracic aorta rings were suspended to isolated tissue chamber, and the changes in isometric tension were recorded. RESULTS: SOD produced a greater relaxation in untreated-diabetic rings compared with control rings. ALA treatment partially reversed SOD-induced relaxation in diabetic aorta. Pretreatment of rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microm) inhibited SOD-induced relaxation. This effect of L-NAME was markedly observed in control and ALA-treated-diabetic rings compared with untreated-diabetic rings. SOD-induced relaxation was also inhibited by catalase (60 U/ml) in untreated-diabetic rings but not in ALA-treated-diabetic and control rings. Pretreatment with the cyclooxygenase inhibitor, indomethacin, or the catalase inhibitor, aminotriazole, had no effect on SOD-induced relaxation in any ring. CONCLUSION: Findings suggested that: (i) in normal physiological conditions, the relaxant effect of SOD is related to the inhibition of superoxide anion radicals (*O(2)(-))-induced endothelium-derived relaxing factor/nitric oxide (EDRF/NO) destruction in the rat aorta; (ii) in diabetic state, excess *O(2)(-) increasingly inhibits basal EDRF/NO, and the dismutation of excess *O(2)(-) to H(2)O(2) is enhanced by exogenous SOD. H(2)O(2) a vasorelaxant molecule, which probably accounts for the increased responsiveness of diabetic rings to exogenous SOD; and (iii) the reversal effect of in vivo ALA treatment on SOD-induced relaxation in diabetic aorta is probably linked with the elimination of *O(2)(-)/H(2)O(2), which mediates the recovery of basal EDRF/NO availability.

Impact of dialysis adequacy on cardiac function in pediatric CAPD patients.

BACKGROUND: Left ventricular hypertrophy is a major cause of morbidity and mortality among patients with chronic renal failure. Uremia-related risk factors play a fundamental role in its occurrence, thus better prognosis and prolonged survival can be attained by successful dialytic therapies. OBJECTIVE: To investigate whether dialysis adequacy has a beneficial effect on cardiac structure and function in children receiving continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study in the Pediatric Peritoneal Dialysis Unit of a university hospital. PATIENTS: Eighteen children, aged 13.3 +/- 2.8 years, being treated with CAPD, and 20 healthy age- and sex-matched control subjects were enrolled in this study. MAIN OUTCOME MEASURES: Echocardiographic evaluation was performed in all subjects. Dialysis adequacy indices [weekly urea (Kt/V) and creatinine clearance (TCCr)] were calculated in the dialysis group. RESULTS: Interventricular septal thickness, left ventricular (LV) posterior wall thickness, LV mass index (LVMI), and LV end systolic and diastolic dimensions were all found to be significantly higher in the CAPD group compared to the control subjects (p < 0.01). Ejection fraction and fractional shortening of the LV were not significantly different between the two groups. Mean Kt/V was 2.02 +/- 0.71 and mean TCCr was 58 +/- 33 L/wk/1.73 m2. There were significant negative correlations between dialysis adequacy indices and LV end systolic and diastolic dimensions (p < 0.05 and p < 0.001). Ejection fraction and fractional shortening were positively correlated with Kt/V (p < 0.01). Systolic and diastolic blood pressures were positively correlated with LVMI (r= 0.501 and r = 0.523). Significant inverse correlations between mean arterial pressure and both Kt/V and TCCr (r = -0.555 and r = -0.520) were detected. CONCLUSION: These data clearly document that cardiac structure and function are remarkably influenced by the uremic state and dialysis therapy in pediatric CAPD patients. The close relationships between echocardiographic findings and dialysis adequacy indices suggest that adequate dialysis has a beneficial effect on cardiac function via effective removal of toxic substances.

Histidine-rich protein 2 of the malaria parasite, Plasmodium falciparum, is involved in detoxification of the by-products of haemoglobin degradation.

The histidine-rich protein 2 (PfHRP2) of Plasmodium falciparum has been implicated in the detoxification of ferriprotoporphyrin IX (FP) moieties that are produced as by-products of the digestion of haemoglobin. In this work, we have used a spectroscopic analysis to confirm that recombinant PfHRP2 binds FP. A monoclonal antibody that recognises both recombinant and authentic PfHRP2 was used in immunofluorescence microscopy studies. We found that PfHRP2 is mainly located in the erythrocyte cytosol of infected erythrocytes, however, dual labelling studies suggest that the location of a sub-population of the PfHRP2 molecules overlaps with that of the food vacuole-associated protein, P-glycoprotein homologue (Pgh-1). A semi-quantitative analysis of the level of PfHRP2 in infected erythrocytes suggests a concentration of a few micromolar in the food vacuole. Under conditions designed to mimic the parasite food vacuole, we found that 1.2 microM PfHRP2 is sufficient to catalyse the conversion of about 30% of a 100 microM sample of FP to beta-haematin within 24 h. Moreover, PfHRP2 is capable of promoting the H(2)O(2)-induced degradation of FP at pH 5.2. PfHRP2 also efficiently enhances the ability of FP to catalyse the H(2)O(2)-mediated oxidation of the model co-factor, ortho-phenylene diamine (OPD). These data suggest that PfHRP2 may promote the detoxification of FP and reactive oxygen species within the food vacuole. By contrast, PfHRP2 inhibits the destruction of FP by glutathione (GSH) at pH 7.4. This suggests that PfHRP2 is not a catalyst of FP degradation outside the food vacuole.

Inhibition of heme detoxification processes underlies the antimalarial activity of terpene isonitrile compounds from marine sponges.

A series of terpene isonitriles, isolated from marine sponges, have previously been shown to exhibit antimalarial activities. Molecular modeling studies employing 3D-QSAR with receptor modeling methodologies performed with these isonitriles showed that the modeled molecules could be used to generate a pharmacophore hypothesis consistent with the experimentally derived biological activities. It was also shown that one of the modeled compounds, diisocyanoadociane (4), as well as axisonitrile-3 (2), both of which have potent antimalarial activity, interacts with heme (FP) by forming a coordination complex with the FP iron. Furthermore, these compounds were shown to inhibit sequestration of FP into beta-hematin and to prevent both the peroxidative and glutathione-mediated destruction of FP under conditions designed to mimic the environment within the malaria parasite. By contrast, two of the modeled diterpene isonitriles, 7-isocyanoamphilecta-11(20),15-diene (12) and 7-isocyano-15-isothiocyanatoamphilecta-11(20)-ene (13), that displayed little antimalarial activity also showed little inhibitory activity in these FP detoxification assays. These studies suggest that the active isonitrile compounds, like the quinoline antimalarials, exert their antiplasmodial activity by preventing FP detoxification. Molecular dynamics simulations performed with diisocyanoadociane (4) and axisonitrile-3 (2) allowed their different binding to FP to be distinguished.

Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients.

Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever (ARF), have been classified as having poststreptococcal reactive arthritis (PSRA). We reviewed the clinical characteristics, laboratory findings and outcome of 15 patients with PSRA. None of these patients had clinical evidence of carditis. The pattern of joint involvement was variable and included arthritis in five patients and arthralgia in the remaining ten patients. Nine patients were treated with salicylates for one to 16 weeks; the others recovered spontaneously. Usually, the patients with arthralgia responded promptly to salicylates, while the response was poor in patients with arthritis. One patient with monoarthritis developed carditis nine months after his first arthritis attack. Another patient presenting with monoarthritis later had two additional episodes of poststreptococcal reactive arthralgia. It seems there is a wide spectrum of poststreptococcal rheumatic diseases, and patients with PSRA are also at risk for cardiac disease; therefore, prophylactic antibiotic therapy should be considered in these patients.

Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes.

The present study investigated the effects of alpha-lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, oxidative stress and antioxidant status were assessed in non-diabetic controls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined by electron microscopy technique. Alpha-lipoic acid treatment effectively reversed body weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha-lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untreated diabetic rats. Alpha-lipoic acid treatment improved catalase activity in diabetic aorta. The contractile effect of phenylephrine markedly increased in diabetic rings, which was completely reversed by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre-contracted aortic rings exposed to cumulatively increased concentrations of acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium nitroprusside-induced endothelium-independent relaxations were similar in all experimental groups. Various alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha-lipoic acid treatment. The potency of alpha-lipoic acid on the reversal of hypertension by affecting vascular reactivity and morphology as well as general metabolism of diabetic rats confirms the importance of hyperglycemia-induced oxidative stress in the development of diabetes-induced vascular complications and suggests a potential therapeutic approach.

QT/corrected QT (QTc) intervals and QT/QTc dispersions in children with chronic renal failure.

UNLABELLED: We aimed to examine QT/corrected QT (QTc) intervals, QT/QTc dispersions (QTD/QTcD) and also the effect of different clinical and laboratory variables on these parameters in children with chronic renal failure. Serum biochemistry, 12-lead electrocardiogram, telecardiogram, and echocardiography were performed in 50 children with chronic renal failure (23 female and 27 male; aged 12.3+/-3.6 years, range 5 to 20 years). None of them had symptoms related to arrhythmias. When compared with a control group (372 children, aged 7 to 18 years, mean 12.4+/-2.6) patients with chronic renal failure had greater QT/QTc intervals and QT/QTc dispersion values (Patient: QT = 360.9+/-53.3; QTc = 438.5+/-33.2; QTD = 42.4+/-20.8; QTcD = 57.5+/-23.8; CONTROL: QT = 325.9+/-24.1; QTc = 398.7+/-19.7; QTD = 29.9+/-10.2; QTcD = 47.3+/-16.6; P<0.01). QT, QTc, and QTcD values were significantly greater in patients who had renal failure duration longer than 2 years. Patients who had impaired left ventricular systolic function on echocardiogram had greater QTc, QTD, and QTcD values. It was found that sex, cardiomegaly on chest X-ray, and left ventricular hypertrophy on echocardiogram were not related to these parameters. It is concluded that, impaired cardiac systolic function and longer renal failure duration are related to an increase in QT, QTc, QTD, and QTcD values and hence these variables may be risk factors for ventricular arrhythmias in uremic patients.

Recurrent pericardial effusion due to gunshot wound of the heart in a hemodynamically stable child--a case report.

A 12-year-old girl presented with recurrent pericardial effusion due to firearm pellet injury to the left ventricle. The pellet was localized by two-dimensional echocardiography within the left ventricular apical wall. Since the patient was asymptomatic, left ventriculotomy was avoided to extract the pellet and only pericardial tube drainage was carried out. A slightly elevated blood lead level of the patient was alarming for potential subsequent lead poisoning due to retained pellets.

Congenital complete atrioventricular block in an infant with long QT syndrome.

A three months old patient with congenital complete atrioventricular block and prolonged QT interval syndrome is presented. Before admission she had had two syncopal attacks. During hospitalization she had an episode of torsade de pointes which was followed by ventricular fibrillation. After a successful cardiopulmonary resuscitation, a permanent epicardial ventricular pacemaker was implanted and she was discharged on propranolol therapy. She is now free of symptoms and doing well, 16 months after discharge.

Role of adenosine in the diagnosis and treatment of tachyarrhythmias in pediatric patients.

Tachyarrhythmias are common rhythm disturbances in infants and children. Despite the availability of diagnostic criteria arrhythmias are sometimes commonly misdiagnosed. Recent reports suggest that an endogenous purine nucleoside, adenosine, has a diagnostic effect in narrow QRS complex tachycardias, in addition to terminating supraventricular tachycardia involving the atrioventricular node. This report reviews the authors' experience with the use of adenosine for diagnosis of narrow and wide complex tachyarrhythmias in children. Adenosine was administered to 43 patients with several types of tachyarrhythmias (mean age, 8.3 +/- 5.24 years). Nineteen patients had structural or acquired heart disease. Of the 43 patients there were 28 (65%) several different types of narrow QRS complex tachycardia and 14 (33%) ventricular arrhythmias. One patient (2%) had long QT. Adenosine terminated supraventricular tachycardia, in 11 of 12 patients (92%), ventricular tachycardia in five of eight patients (63%), and transiently terminated premature ventricular contractions in two of six patients (33%). The diagnostic ability of adenosine was perfect in eight supraventricular tachycardia. In these eight cases the tachycardia mechanism was unclear before the administration of adenosine, which demonstrated three cases of sinus tachycardia, three of atrial flutter, one of atrial fibrillation and one of atrial fibrilloflutter. Confirmation of the primary diagnosis by adenosine was perfect in five tachyarrhythmias including three cases of atrial flutter, one of atrial fibrillation and one of ectopic atrial tachycardia. The average effective dose of adenosine was 212 micrograms/kg (range, 100-400 micrograms/kg). There were no serious side-effects except transient dyspnea, chest pain and flushing. These findings demonstrate adenosine to be helpful and safe in the diagnosis of tachyarrhythmias.

Short- and intermediate-term efficacy of amiodarone in infants and children with cardiac arrhythmia.

The antiarrhythmic effect of amiodarone was examined in this retrospective study in a group of 20 patients with a mean age of 8.5 +/- 6.7 years (range 42 days to 20 years, median 9 years). Five patients with atrial flutter, one patient with atrial fibrillation, two patients with an intermediate rhythm between atrial flutter and atrial fibrillation, four patients with chaotic atrial tachycardia, three patients with atrioventricular reentry tachycardia, two patients with junctional ectopic tachycardia, and three patients with ventricular arrhythmias were treated with amiodarone. The mean duration of therapy was 9.1 +/- 12.3 months (range 1 month to 4 years). Before amiodarone treatment, 18 patients had been unresponsive to various antiarrhythmic drugs (range 1-8, median 2). Two patients received amiodarone as an initial therapy. It was administered orally at a dose of 10 mg/kg once per day for 10 days and then decreased to 5 mg/kg once per day. Amiodarone was effective in 16 patients (80%). Side effects occurred in three patients, including thyroid dysfunction, elevation of liver enzymes, and keratopathy. All side effects disappeared upon cessation of the therapy. We recommend amiodarone for the treatment of childhood arrhythmias, especially for the refractory types.