Nur Olgun

Nutrition, immunity and infections: T lymphocyte subpopulations in protein-energy malnutrition

Protein energy malnutrition (PEM) is one of the most frequent causes of secondary immune deficiency states. Alterations either in cellular or humoral immune mechanisms increase the susceptibility to infections in the malnourished organism. Infections aggravate the interrelationship of malnutrition to immune deficiency and infections, resulting in future adverse effects of malnutrition on humoral and cellular immune systems, IgG, IgM, IgA, C3, and T lymphocyte subpopulations were identified in 29 patients with PEM and 15 healthy infants serving as the control group, ranging between 3 and 24 months of age. Patients with PEM demonstrated elevated levels of IgG, IgM and IgA when compared to the control group (P < 0.01, P < 0.01, P < 0.01), C3 levels were significantly lower than the values of the control group (P < 0.01).

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity.

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

Assessment of clinical impact and predisposing factors for neonatal thrombocytopenia

Thrombocytopenia is a common hemostatic abnormality in the newborn infant. The early diagnosis of thrombocytopenia and the underlying primary pathology process play an important role in reducing the risk of severe complications and mortality. We performed a 2-year prospective study of 643 neonates admitted to our neonatology unit to determine the frequency, predisposing factors, and clinical impact of thrombocytopenia. Thrombocytopenia developed in 18.2% of the preterm neonates and 0.8% of the term neonates. Prematurity, sepsis, hypoxia, intrauterine growth retardation, and disseminated intravascular coagulation were identified as predisposing factors for thrombocytopenia. The incidence of complications and mortality were higher in thrombocytopenic infants. Especially the prognosis was worse in cases who had mucosal hemorrhage, without a relation with the degree of thrombocytopenia. The thrombocytopenia occurred by day 2 in 43% of the infants, and resolved by day 8 in 61%. The platelet count nadir occurred by day 2. Since thrombocytopenic infants are at greater risk for bleeding, and the thrombocytopenia itself may have contributed to the high mortality, predisposing factors such as prematurity, infections, hypoxia must be eliminated by prividing better care, giving adequate hygiene of both mother and the baby during the prenatal, natal, and neonatal period.

ASSESSMENT OF PERIPHERAL LYMPHADENOPATHIES: Experience at a Pediatric Hematology-Oncology Department in Turkey

Since a large variety of disorders may lead to lymph node enlargement, determining the cause of peripheral lymphadenopathy (LAP) in children can be difficult. This retrospective study evaluated 200 children who were admitted to an Oncology-Hematology department because of lymphadenopathy and aimed to determine the clinical and laboratory findings that were valuable for differential diagnosis. A specific cause for lymphadenopathy was documented in 93 (46.5%) cases. One hundred forty (70%) children were classified as having a benign cause for lymph node enlargements. Fourteen (10%) of these cases underwent an excisional lymph node biopsy, and histopathological examination showed a reactive hyperplasia. Sixty (30%) cases were classified as having a malignant disease-causing lymphadenopathy. In terms of differential diagnosis, some associated systemic symptoms, physical findings, and laboratory investigations showed significant difference between benign and malignant lymphadenopathy groups. The following findings were determined as being important to alert the physician about the probability of a malignant disorder: location of the lymphadenopathy (supraclavicular and posterior auricular), duration of the lymph node enlargement (> 4 weeks), size of the lymph node (> 3cm), abnormal complete blood cell findings, abnormalities in chest X-ray, and abdominal ultrasonography.

Protective effect of acetyl‐l‐carnitine against cisplatin ototoxicity: role of apoptosis‐related genes and pro‐inflammatory cytokines

Cisplatin is an anti‐neoplastic agent treatment with which causes many side effects including ototoxicity. The aim of this study was to investigate whether acetyl‐l‐carnitine would have protective effects on cisplatin‐induced ototoxicity in vitro, and if present, to reveal roles of apoptotic gene expressions and pro‐inflammatory cytokines.

Copy number status and mutation analyses of anaplastic lymphoma kinase (ALK) gene in 90 sporadic neuroblastoma tumors.

Somatic and germline mutations of the anaplastic lymphoma kinase (ALK) gene were recently described in neuroblastoma (NB). In this study, we investigated the association of ALK copy number alterations with copy number status 2p24.1 amplicon harboring DEAD box polypeptide 1 (DDX1), MYCN and neuroblastoma-amplified (NAG) genes in 90 primary tumors of sporadic NB cases by multiplex ligation-dependent probe amplification (MLPA). We also performed mutation analysis of ALK gene by directly sequencing the exons 20-28 which cover the region that encodes juxtamembrane and kinase domains. A total of 39 (43.3%) NB cases revealed copy numbers alterations of ALK gene. There was highly significant association of ALK copy number gains with gains of one or more of the genes at 2p24.1 (DDX1, MYCN or NAG) in MYCN unamplified tumors (P<0.000). In addition, 15 of 17 MYCN amplified cases (88.2%) had aberrant ALK status. Solitary gain of ALK with normal copy number status of all other genes was observed only in one case. DNA sequencing of exons 20-28 of ALK revealed two different nucleotide changes in three cases leading to amino acid substitutions of F1245V and R1275Q in tyrosine kinase domain. In conclusion, the frequency of ALK mutations in NB is low and solitary copy number change of it is rarely observed.

Evaluation of the Effect of Acetyl L-Carnitine on Experimental Cisplatin Ototoxicity and Neurotoxicity

Introduction: Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent for pediatric tumors, and ototoxicity is one of the dose-limiting side effects. Objective: It was the aim of our study to investigate the effect of acetyl L-carnitine (ALCAR) on experimental CDDP ototoxicity by audiologic tests, histomorphologic, immunohistochemical and ultrastructural examinations and to investigate the apoptotic pathways. Materials and Methods: Wistar albino rats (n = 28) were studied. Baseline audiological tests were performed in 4 groups: group 1, control; group 2, ALCAR; group 3, CDDP; group 4, CDDP + ALCAR-administered rats. Control audiological tests were performed on the 3rd day, and then the rats were sacrificed. Ear and brain specimens were examined by transmission electron microscopy, and caspase 3, 8 and 9 activities were investigated. Results: The CDDP-administered rats showed significant auditory brainstem response threshold shifts using all stimuli (clicks, 6-kHz and 8-kHz tone burst) compared with the control groups. The CDDP + ALCAR-administered rats showed significant auditory brainstem response threshold shifts by only click stimuli compared with the control groups. In the brain, spiral ganglion and organ of Corti, ultrastructural damage was prominent in group 3; the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells and caspase 3, 8 and 9 immunostaining cells was significantly high in group 3. Conclusion: ALCAR improves CDDP-induced auditory impairment, and also antioxidative and antiapoptotic properties of ALCAR on CDDP ototoxicity were supported by the findings.

Platelet activation in congenital heart diseases

The research presented here investigated platelet activation in cyanotic and acyanotic congenital heart diseases (CHD). Children with cyanotic CHD are prone to both thrombosis and hemorrhage. However, patients with acyanotic CHD may also have a mild bleeding disorder. The platelet activation in CHD was investigated in support of a hypothesis that platelet activation may play a role in the hemostatic abnormalities reported in these patients. Platelet activation was determined by using flow cytometry with anti‐CD62 monoclonal antibody (mAb), which has been shown to be a specific marker of platelet activation. Thirteen children with cyanotic CHD, 33 children with acyanotic CHD and 17 healthy children serving as controls were studied. Platelet activation was significantly higher in the cyanotic group and also in the acyanotic group compared with the healthy children (P = 0.0000 and P = 0.019, respectively). In the cyanotic group, platelet activation showed a direct correlation with arterial O2 saturation (SaO2) (P = 0.014). There was no correlation between platelet activation and erythrocyte related parameters in either group. Platelet activation occurs in CHD, particularly in patients with cyanotic CHD (even in patients with no evidence of clinical thrombosis) and it may play a role in the pathogenesis of thrombotic disorders seen in these patients.

The time to diagnosis in childhood lymphomas and other solid tumors.

There are few reports from developing countries on the factors that influence the time to diagnosis (TD) in childhood cancer. The purpose of this study was to investigate the determinants of the TD in Turkish cancer patients.

Paravertebral malignant tumors of childhood: analysis of 28 pediatric patients

PurposeTo evaluate the clinical features and treatment results of the primary paravertebral malignant tumors (PMTs) in our department.MethodsMedical records of 28 children with primary PMTs treated between 1988–2007 were analyzed retrospectively.ResultsPrimary PMTs constituted 4.8% of the cancer cases in our department. Tumor diagnoses were mostly neuroblastoma (46.4%) and soft tissue sarcomas (35.7%). These cases presented with pain (64.3%), motor dysfunction (42.8%), sphincter dysfunction (35.7%), palpable mass (32.1%), and sensory deficits (7.1%). All tumors were extradural. Physical examination revealed motor deficits (53.6%), deep tendon reflex alterations (53.6%), sphincter dysfunction (35.7%), pathologic reflexes (25%), abnormal cutaneous reflexes (25%), and sensory deficits (17.8%). Sixteen had cord compression (CC; 13 clinical, three radiological CC). Eleven of them presented with advanced disease. Seven were managed by surgical departments by primary surgery (three unresponsive). Others were managed by pediatric oncology: five with corticosteroids ± chemotherapy (one unresponsive), one with radiotherapy (RT), and two with surgery for the clinical CC. Surgery was tumor excision in nine, laminectomy in nine, laminotomy in one, and delayed surgery after chemotherapy in two cases. In chemotherapy and surgery groups, there were neurologic sequela associated with the advanced disease at diagnosis in 38% and 37%, respectively. At 3-year median follow-up, nine patients died, 17 are alive (four with neurologic sequela), and two are lost of follow-up.ConclusionMajority of cases presented with advanced disease. Late referral is the major cause of morbidity and mortality. The CC caused by PMTs should be initially managed with corticosteroids ± chemotherapy to avoid the adverse late effects of RT and surgery.