Ali Bay

Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome.

Perforin-mediated cytotoxicity is important for controlling viral infections, but also for limiting immune reactions. Failure of this cytotoxic pathway leads to hemophagocytic lymphohistiocytosis (HLH), a life-threatening disorder of uncontrolled T-cell and macrophage activation. We studied susceptibility to HLH in 2 mouse strains (souris and beige(J)) and a cohort of patients with partial defects in perforin secretion resulting from different mutations in the LYST gene. Although both strains lacked NK-cell cytotoxicity, only souris mice developed all clinical and histopathologic signs of HLH after infection with lymphocytic choriomeningitis virus. The 2 strains showed subtle differences in CTL cytotoxicity in vitro that had a large impact on virus control in vivo. Whereas beige(J) CTLs eliminated lymphocytic choriomeningitis virus infection, souris CTLs failed to control the virus, which was associated with the development of HLH. In LYST-mutant patients with Chediak-Higashi syndrome, CTL cytotoxicity was reduced in patients with early-onset HLH, whereas it was retained in patients who later or never developed HLH. Thus, the risk of HLH development is set by a threshold that is determined by subtle differences in CTL cytotoxicity. Differences in the cytotoxic capacity of CTLs may be predictive for the risk of Chediak-Higashi syndrome patients to develop HLH.

Myelopathy due to intrathecal chemotherapy: report of six cases.

Intrathecal chemotherapy and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system disease in hematologic malignancies. However, intrathecal treatment has some adverse effects, such as arachnoiditis, progressive myelopathy, and leukoencephalopathy. The authors describe six children in whom myelopathy and adhesive arachnoiditis developed after administration of intrathecal chemotherapy including methotrexate, cytosine arabinoside, and prednisolone. Urinary retention and incontinence, the main presenting complaints in all patients, developed within 12 hours after intrathecal therapy and spontaneously resolved within 7 days. Two patients were unable to walk. In these two, weakness in the lower extremities gradually recovered by 1 month but urinary incontinence did not improve. None of the children had sensory loss. On follow-up periodic recurrent urinary tract infection was noted in four patients. MRI findings corresponded to arachnoiditis. No response was recorded on tibial nerve somatosensory evoked potentials in all patients. Intrathecal chemotherapy, especially methotrexate, can cause spinal cord dysfunction in children with acute lymphoblastic leukemia and non-Hodgkins lymphoma. Arachnoiditis should be kept in mind as a causative factor in recurrent urinary tract infection in patients receiving intrathecal chemotherapy.

Surgical Treatment Outcome of Subdural Empyema: A Clinical Study

A retrospective study of 28 patients identified with subdural empyema (SE) at the Department of Neurosurgery between the years 1995 and 2005 was carried out. SE occurred in all patients following bacterial meningitis. The six most frequently encountered clinical features included: (1) fever in 22 (79%) patients; (2) disturbed consciousness in 16 (57%) patients; (3) papilledema in 11 (39%) patients; (4) hemiparesis in 4 (14%) patients; (5) meningismus or meningeal signs in 4 (14%) patients, and (6) seizures in 3 (11%) patients. In the majority of cases, the most frequent causative pathogen of SE was Staphylococcus aureus. Surgery was performed on all patients, which included craniotomy in a group of 20 patients and burr hole drainage in a group of 8 patients. In conclusion, we believe that infants and young children should be carefully monitored following meningitis, in case of SE development, and that surgical intervention in patients presenting with meningitis may facilitate the development of SE. Furthermore, from a surgical point of view, our experience has led us to believe that craniotomy in comparison with burr hole surgery is the best surgical modality for management of SE as the recurrence rate of SE associated with burr hole surgery is high.

Vincristine induced cranial polyneuropathy.

We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.

Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations

The aim of this study was to elucidate the pathologic sequence changes and associated clinical phenotypes in 9 new patients showing homozygosity for perforin gene among a total of 37 (24%) Turkish FHL families studied by linkage analysis. These 9 unrelated patients (5M/4F) were coming from consanguineous families and their presentation ages of systemic symptoms were ranged from birth to 15 years. Direct sequencing of coding exons of the perforin gene led to the identification of five different homozygous alterations. The nonsense W374X mutation was identified in three patients while four different missense mutations namely G149S, V50M, A91V and novel A523D were detected in the rest six patients.

Abdominal hydatid disease: Long-term results of percutaneous treatment

Purpose: To evaluate the effectiveness of percutaneous treatment under sonographic guidance in abdominal hydatid cysts. Material and Methods: Fifty‐two hydatid cysts in 33 patients were treated using a percutaneous approach under sonographic guidance. Forty‐five cysts were located in the liver, 6 in the spleen, and 1 in the pancreas. Forty‐nine cysts were type I, and 3 were type II. Thirty‐one cysts in 15 patients were treated with puncture and aspiration of the contents, injection of hypertonic saline solution, and respiration (PAIR); 15 cysts in 14 patients were treated with puncture, aspiration of cyst contents, injection of hypertonic saline solution, drainage, and injection of sclerosing agent (PAIDS); and 6 cysts in 4 patients were treated with puncture, aspiration of cyst contents, injection of sclerosing agent, and re‐aspiration (mPAIDS). Hypertonic saline or alcohol was used as a scolicidal agent. The follow‐up period was between 17 and 53 months. Results: A decrease in the dimensions of the cysts, solidification of the contents, and irregularity in the walls of cysts, all of which were considered signs of cure, were found in all patients. Recurrence was observed in one case and anaphylaxis in one. Conclusion: Percutaneous treatment of abdominal hydatid cysts is a safe, easily applicable, well‐tolerated, and effective method.

Thiamine-responsive megaloblastic anemia syndrome

Thiamine-responsive megaloblastic anemia (TRMA) syndrome usually associated with diabetes mellitus, anemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. The onset of disease is usually seen during infancy or at early childhood and most of the TRMA patients are originated from consanguineous families. In this case, we report a 5-month-old boy who had diagnosis of TRMA during evaluations for his anemia and thrombocytopenia. The diagnosis of TRMA should be kept in mind in differential diagnosis of megaloblastic anemia especially in the populations where the consanguinity is frequent.

The Role of Prohepcidin in Anemia Due to Helicobacter pylori Infection

Background: Hepcidin, a key regulator of iron homeostasis, increases when inflammation and some infections occur. It plays a critical role in macrophage iron retention, which underlies inflammation/infection caused anemia. It is known that Helicobacter pylori (HP) may lead to iron deficiency (ID) due to occult blood loss or reduced iron absorption. This study investigates the role of prohepcidin, hepcidins precursor, in ID and ID anemia (IDA) with a concurrent HP infection. Methods: In this prospectively designed study, 15 patients with IDA and a concurrent HP infection (group 1), 11 patients with an ID and a concurrent HP infection (group 2), and 18 patients with HP infection (group 3) were observed. All groups received only HP eradication therapy. Twenty-five age- and sex-matched children without ID/IDA and HP infection were included in the study as the control group. In all groups and control group, measurements were taken for pre- and posttreatment hemoglobin, serum prohepcidin, serum ferritin, serum iron (SI), transferrin saturation, erythrocyte sedimentation rate, fibrinogen, and C-reactive protein levels. Results: The pretreatment prohepcidin levels were significantly higher only in group 1 compared to the control group (P < .05). In group 1, a significant increase in hemoglobin and SI levels and a significant reduction in prohepcidin levels were additionally observed following HP eradication treatment (P < .05). However, in groups 2 and 3, significant differences in hemoglobin, iron, and prohepcidin levels between pre- and posttreatment were not observed. Conclusion: Elevated serum prohepcidin might indicate the role of inflammation in the etiology of anemia concurrent with HP.

Plasma microRNA profiling of pediatric patients with immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.

Topical Ankaferd hemostat application for the management of oral cavity bleedings in children with hemorrhagic diathesis.

Ankaferd blood stopper (ABS) is a hemostatic agent used topically for controlling bleedings of skin or mucosal surfaces in Turkey. It is currently topically used in bleedings of body injuries, traumas, and minor or major surgical interventions. Here we have evaluated 12 pediatric patients with hemorrhagic diathesis on whom Ankaferd was used for oral bleedings. Topical Ankaferd was administered for hemorrhages of oral cavity during 15 bleeding attacks. ABS administrations successfully stopped the bleedings, except for one patient with oral hemorrhage who did not respond to ABS application. Ankaferd is effective for oral bleedings of children with bleeding diathesis especially when other measures have failed.