The Forgotten Chamber: Right-Ventricular Functions in Juvenile Idiopathic Arthritis

Cardiac involvement, such as pericarditis, myocarditis, and endocarditis, is seen in juvenile idiopathic arthritis. Although there have been some reports about right-ventricular systolic and diastolic functions of adults with rheumatoid arthritis and left-ventricular systolic and diastolic functions of children with JIA, there have been no studies about RV functions of children with JIA. The aim of this study was to determine RV functions in children with JIA. We performed conventional echocardiography and tissue Doppler imaging measurements of the right ventricle of patients with JIA. All patients were in sinus rhythm at the time of examination without overt LV heart failure and with normal LV ejection fraction. Fifty-five children with the diagnosis of JIA and 33 healthy control subjects were included in the study. Peak systolic, early, and late diastolic tricuspid annular velocities were significantly decreased in JIA patients compared with healthy controls (p < 0.05). Isovolumic accelaration (IVA), as a measure of myocardial acceleration during isovolumic contraction of the right ventricle, was also significantly lower in JIA patients than in healthy controls (p < 0.05). RV systolic and diastolic functions, in addition to the previously shown LV functions, are affected in JIA patients. IVA decreases in JIA patients and may be used as an alternative, noninvasive parameter for the assessment of RV systolic function in children with JIA.     

Effect of heat shock protein-90 (HSP90) and vascular endothelial growth factor (VEGF) on survival in acute lymphoblastic leukemia: an immunohistochemical study

Background The significance of vascular endothelial growth factor (VEGF) and heat shock protein-90 (HSP90) has received only limited attention especially in acute lymphoblastic leukemia (ALL). In this study, we assessed expressions of HSP90 and VEGF in bone marrow samples of patients with ALL and effect of these expression quantities on the mean overall survival. Patients and methods Using immunohistochemical methods, we assessed expression of HSP90 and VEGF in 22 cases of ALL. Results Expression of HSP90 was detected in 19/22 (86.4%) and 3/22 (13.6%) of patients with ALL, for strongly positive and moderate-weakly positive, respectively. Negative HSP90 expression was not detected in patients with ALL. Expression of HSP90 in patients with ALL and in control group were statistically significant (P < 0.001), however, did not reflect the mean overall survival (P = 0.910). Mean OS was evaluated 992 ± 181 and 724.8 ± 88.2 days for moderate-weak and high HSP90 expression, respectively. VEGF expressions were not significantly different between ALL and control groups (P < 0.087). We did not find any relationship between HSP90 and VEGF expressions in bone marrow specimens of patients with ALL. Conclusion This study demonstrated that HSP90 expression grades in patients with ALL were significantly higher than that in controls and presence of strong HSP90 expression was associated with worse overall survival. VEGF expression in patients with ALL was not different from that in control samples. Determination HSP90 with immunohistochemical method in bone marrow can provide information about prognosis.     

Proton pump inhibitors omeprazole, lansoprazole and pantoprazole induce relaxation in the rat lower oesophageal sphincter

Objectives We aimed to investigate effects of the proton pump inhibitors (PPIs) omeprazole, lansoprazole and pantoprazole, which are currently used for the treatment of hyperacidity and gastro‐oesophageal reflux, on the reactivity of the isolated rat lower oesophageal sphincter. Methods Omeprazole, lansoprazole and pantoprazole (all 10^–9–10^–3m , cumulatively) were tested on carbachol‐induced (10^–6m ) contraction. In addition, the effects of PPI preincubation (all 10^–3m ) on the contractions induced by cumulative carbachol (10^?9–10^?5m ), angiotensin‐2 (10^?9–10^–5m ) or electrical field stimulation (EFS; 40 V, 32 Hz, 1 ms, 10 s) were assessed. Finally, the effects of PPI on the spontaneous contractile activity of the tissue were also evaluated. Key findings PPI relaxed precontracted lower oesophageal sphincter in a concentration‐dependent manner and suppressed carbachol‐, angiotensin‐ and EFS‐induced contractions. Furthermore, PPI attenuated spontaneous contractile activity of the tissue. Conclusions Omeprazole, lansoprazole and pantoprazole had a suppressor effect on lower oesophageal sphincter contractions.     

Epidemiology,species distribution,clinical characteristics and mortality of candidaemia in a tertiary care university hospital in Turkey, 2007‐2014

Candidaemia still continues to be a serious medical concern and the epidemiology of candidaemia varies according to geographical areas. We aim to determine the incidence, local epidemiology, Candida species distribution and crude mortality rates of candidaemia. We retrospectively evaluated candidaemia episodes in between January 2007 and August 2014. We compared demographic, clinical, microbiological findings and mortality rates of episodes caused by Candida albicans and non‐albicans Candida species. Overall the candidaemia incidences were 1.23 episodes/1000 admissions. A significant negative slope among candidaemia episodes and years was determined. Overall C. albicans (54.6%) was the most common species followed by Candida glabrata, Candida tropicalis and Candida parapsilosis respectively. Preinfection hospital stay and length of hospital stay were statistically longer in patients with non‐albicans Candida candidaemia than in patients with C. albicans candidaemia. The source of candidaemia was unknown in 52.5% of all episodes. Central venous catheters among non‐albicans Candida candidaemia episodes and urinary system among C. albicans candidaemia episodes were common source of candidaemia compared to each other. Previous antifungal therapy preceding candidaemia and concomitant bacteraemia were significantly associated with non‐albicans Candida candidaemia. Continuous local surveillance will preserve its pivotal importance in formulating empirical antifungal therapy and improving management of candidaemia.     

Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin

Activating mutations of c-KIT lead to ligand-independent growth. Internal tandem duplications (ITDs) of exon 11, which encodes the juxtamembrane domain (JMD), are constitutively activating mutations found in 7% of gastrointestinal stromal tumors (GISTs) but have not been described in childhood acute myeloid leukemia (AML). DNA and cDNA from 60 children with AML were screened by polymerase chain reaction (PCR) for mutations of the JMD. A complex ITD (kit cITD) involving exon 11 and exon 12 was identified with a relative frequency of 7% (4/60). The human kit cITDs were inserted into the murine c-Kit backbone and expressed in Ba/F3 cells. KIT cITD induced factorindependent growth and apoptosis resistance, and exhibited constitutive autophosphorylation. KIT cITD constitutively activated the PI3K/AKT pathway and phosphorylated STAT1, STAT3, STAT5, and SHP-2. Imatinib (IM) or rapamycin (Rap) led to complete inhibition of growth, with IC50 values at nanomolar levels. IM and Rap synergistically inhibited growth and surmounted KIT cITD-induced apoptosis resistance. IM but not LY294002 inhibited phosphorylation of STAT3 and STAT5, suggesting aberrant cross talk between PI3K- and STAT-activating pathways. The findings presented may have immediate therapeutic impact for a subgroup of childhood AML-expressing c-KIT mutations.     

Value of parathyroid hormone assay for preoperative sonographically guided parathyroid aspirates for minimally invasive parathyroidectomy

PURPOSE: The key to successful parathyroid surgery is accurate preoperative tumor localization. This study investigates the use of ultrasound (US)-guided parathyroid fine needle aspiration (FNA) as a confirmatory diagnostic method in patients with hyperparathyroidism undergoing minimally invasive parathyroidectomy. METHODS: Patients were selected for minimally invasive parathyroidectomy based on the finding of a single parathyroid adenoma identified with US and/or sestamibi scans and confirmation of the suspected parathyroid lesion via FNA and parathyroid hormone (PTH) assay. The value of aspirate obtained from the thyroid gland intraoperatively served as the negative control. RESULTS: A total of 56 tissue FNAs were performed in 27 patients. US detected masses suggestive of parathyroid lesion in all 27 patients, and 31 US-guided FNAs were performed. No complications related to the procedure were noted. Intraoperatively, FNA was performed in the thyroids of 25 patients undergoing minimally invasive parathyroidectomy. Aspirates from lesions subsequently confirmed as having developed from the parathyroid gland had a mean PTH level of 4,677 +/- 123 pg/ml (range, 3,600-5,000 pg/ml), which was significantly higher than thyroid aspirates, which yielded a mean PTH level of 48 +/- 7 pg/ml (range, 5-57 pg/ml). The sensitivity of US and sestamibi scans in the detection of abnormal parathyroid glands was 88% and 77%, respectively. The sensitivity of US-guided FNA in confirming the parathyroid origin of a lesion was 100%. CONCLUSION: US-guided FNA for PTH assay can be performed safely for the confirmation of lesions identified with preoperative US for the selection of patients eligible for minimally invasive parathyroidectomy.     

A multi-center survey of childhood asthma in Turkey – I: The cost and its determinants

Successful management of childhood asthma requires a thorough idea of the economic impact of asthma and its determinants, as policy makers and physicians inevitably influence the outcome. The aim of this study was to define the cost of childhood asthma in Turkey and its determinants. In April 2006, a multi-center, national study was performed where data regarding cost and control levels were collected. Asthmatic children (6–18 yr) with at least a 1-yr follow-up seen during a 1-month period with scheduled or unscheduled visits were included. The survey included a questionnaire-guided interview and retrospective evaluation of files. Cost and its determinants during the last year were analyzed. A total of 618 children from 12 asthma centers were surveyed. The total annual cost of childhood asthma was US$1597.4 ± 236.2 and there was a significant variation in costs between study centers (p < 0.05). Frequent physician visits [odds ratio (95% confidence intervals)] [2.3 (1.6–3.4)], hospitalization [1.9 (1.1–3.3)], asthma severity [1.6 (1.1–2.8)], and school absenteeism due to asthma [1.5 (1.1–2.1)] were major predictors of total annual costs (p < 0.05 for each). The comparable cost of asthma among Turkish children with that reported in developed countries suggests that interventions to decrease the economic burden of pediatric asthma should focus on the cost-effectiveness of anti-allergic household measures and on improving the control levels of asthma.     

Treatment of infective endocarditis with recombinant tissue plasminogen activator

Infective endocarditis (IE) caused by microbial infection is virtually always fatal if untreated. High-dose and long-term antibiotic treatment is required to eradicate microorganisms. If increased risk of embolic events, persistent infection, and progressive cardiac failure are present, surgery is indicated. However, surgery can carry an increased risk of mortality and morbidity in critically ill children of whom other treatment options such as administering, a thrombolytic agent; recombinant tissue plasminogen activator (r-tPA) could be an alternative choice. Here, we report a 14-year-old male with Down syndrome and acute myeloblastic leukemia, diagnosed with IE characterized by two large vegetations on aortic and mitral valves, who was successfully treated with r-tPA.