Ayse Palanduz

Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma

Whole-exome sequencing reveals a homozygous splice-site mutation in the gene encoding STIM1 in a child with classic Kaposi sarcoma.

Brucellosis in a mother and her young infant: probable transmission by breast milk.

Brucellosis, although primarily a zoonotic infection, is also a threat for human health. Infection can be transmitted to humans through direct contact with infected animals, products of conception, or animal discharges, and through consumption of potentially infected milk, milk products, or meat. Human-to-human transmission is rare. There have been case reports of transmission via blood transfusion and bone marrow transplantation from infected donors. Sexual intercourse is a possible means of transmission. Neonatal infection can be acquired transplacentally or during delivery. This report describes a mother with brucellosis who probably transmitted the infection to her 3-month-old baby by breast milk.

Sonographic assessment of ceftriaxone-associated biliary pseudolithiasis in children

Ceftriaxone is a widely used third‐generation cephalosporin. In this prospective study, we used sonography to investigate the incidence and outcome of biliary complications in children receiving ceftriaxone therapy.

Effects of lipopolysaccharide on the radiation-induced changes in the blood-brain barrier and the astrocytes.

The use of radiation to improve the efficacy of chemotherapy on malignant brain tumors is also known to cause side effects on vascular endothelial cells and astrocytes in normal parts of the brain. We investigated the effects of lipopolysaccharide (LPS) on the functional and structural properties of blood-brain barrier (BBB) and the activity of astrocytes during whole-brain irradiation in rats. The permeability of the BBB to Evans blue (EB) dye significantly increased in the cerebral cortex, diencephalon and cerebellum regions of rats exposed to irradiation (P<0.01). In contrast, the BBB permeability in irradiated rats was significantly reduced by LPS (P<0.05). Tumor necrosis factor-alpha (TNF-alpha) levels were increased following LPS, irradiation and irradiation plus LPS (P<0.05, P<0.01). Irradiated brain vessels showed a considerable loss of staining intensity of tight junction proteins Zonula occludens-1 (ZO-1) and occludin. Staining for Zonula occludens-1 and occludin was intensive in animals treated with LPS and irradiation plus LPS. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in very few astrocytes of irradiated brains. However, this staining showed an increased positive intensity in the brain sections of LPS-treated as well as of irradiation plus LPS-treated animals. These results indicate that LPS reduces the passage of exogenous vascular tracer EB-binding albumin into the brain, at least partly, by increasing the expression of tight junction proteins and GFAP, following the irradiation. We suggest that irradiation may affect paracellular permeability through disruption of tight junction proteins, Zonula occludens-1 and occludin, and LPS could provide beneficial effects on the BBB integrity and the astrocytes against irradiation damage.

Classic Kaposi Sarcoma in 3 Unrelated Turkish Children Born to Consanguineous Kindreds

Infection by human herpesvirus 8 (HHV-8) in childhood is common in the Mediterranean basin; however, classic Kaposi sarcoma (KS) is exceedingly rare in children not infected with HIV and not receiving immunosuppression, with only 30 cases having been reported since 1960. We recently reported 2 children with autosomal and X-linked recessive primary immunodeficiencies underlying KS in a context of multiple clinical manifestations. These reports suggested that classic KS in otherwise healthy children might also result from inborn errors of immunity more specific to HHV-8. In this article, we describe 3 unrelated Turkish children with classic KS born to first-cousin parents. The first patient, a girl, developed KS at 2 years of age with disseminated cutaneous and mucosal lesions. The clinical course progressed rapidly, and the patient died within 3 months despite treatment with vincristine. The other 2 children developed a milder form of KS at the age of 9 years, with multiple cutaneous lesions. A boy treated with interferon α therapy for 12 months is now in full remission at the age of 14, 2 years after treatment. The second girl is currently stabilized with etoposide, which was begun 4 months ago. None of the 3 children had any relevant familial history or other clinical features. The occurrence of classic KS in 3 unrelated Turkish children, each born to consanguineous parents, strongly suggests that autosomal recessive predisposition may drive the rare occurrence of HHV-8–associated classic KS in children.

Accounting for genetic heterogeneity in homozygosity mapping: application to Mendelian susceptibility to mycobacterial disease

Introduction Genome-wide homozygosity mapping is a powerful method for locating rare recessive Mendelian mutations. However, statistical power decreases dramatically in the presence of genetic heterogeneity. Methods The authors applied an empirical approach to test for linkage accounting for genetic heterogeneity by calculating the sum of positive per-family multipoint LOD scores (S) across all positions, and obtaining corresponding empirical p values (EmpP) through permutations. Results The statistical power of the approach was found to be consistently higher than the classical heterogeneity LOD by simulations. Among 21 first-cousin matings with a single affected child, for five families linked to a locus of interest and 16 families to other loci, S/EmpP achieved a power of 40% versus 28% for heterogeneity LOD at an α level of 0.001. The mean size of peak linkage regions was markedly higher for true loci than false positive regions. The S/EmpP approach was applied to a sample of 17 consanguineous families with Mendelian susceptibility to mycobacterial disease, leading to the identification of two mutations in IL12RB1 and TYK2 from the largest of six linkage regions at p<10−3. Conclusions The S/EmpP approach is a flexible and powerful approach that can be applied to linkage analysis of families with suspected Mendelian disorders.

Low level of compliance with tuberculosis treatment in children: monitoring by urine tests.

Abstract Patient compliance should be ensured in an effective tuberculosis control programme. We measured patient compliance by detecting antituberculous drugs in the urine of 237 outpatients receiving one to three antituberculous drugs. Positive controls were 20 hospitalised patients, supervised to receive isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA), and negative controls were not on any drugs. Among the 237 study patients, only 67% were found to be taking the appropriate treatment and 8% had taken none. We conclude that a remarkable number of patients (33%) were non-compliant with treatment. The detection of antituberculous drugs in the urine is a quick, simple and inexpensive means of measuring adherence to treatment. Unless directly observed therapy (DOT) is adopted, we recommend routine urine testing for antituberculous drugs to identify defaulting patients.

Description of pediatric tuberculosis evaluated in a referral center in istanbul Turkey.

Purpose Diagnosis of tuberculosis (TB) in children is more challenging than in adults. This study aimed to describe demographical, clinical and laboratory findings of children diagnosed with tuberculosis in Turkey, including the issues of contact tracing, culture positivity and forms of the disease. Materials and Methods Clinical and laboratory data of 51 children with a mean age of 8.0±4.6 years who were diagnosed with TB were retrospectively reviewed. Main diagnostic tools included tuberculin skin test, chest X-ray, sputum/gastric aspirate culture with sensitivity testing, and direct microscopy for acid-fast bacilli on available samples. Clinical characteristics and outcomes of the patients were examined. Results Thirty-six (70.6%) children were diagnosed with intra-thoracic and 15 (29.4%) with extra-thoracic tuberculosis. Twenty-eight of the patients had a positive Bacillus Calmette-Guérin vaccine scar (28/51, 54.9%) and 23/51 (45.1%) had a positive tuberculin skin test. An adult TB contact was identified in 27 (52.9%) of the cases. On direct microscopy, acid-fast bacilli were found in nine (17.6%) patients and positive culture for Mycobacterium tuberculosis was found in 19 (37.3%). Drug resistance to isoniazid was detected in four (7.8%). One patient with nephrotic syndrome and miliary tuberculosis died during follow-up. All other patients responded well to the treatment. Conclusion Focusing on active contact tracing among all household contacts of tuberculous cases may be helpful in early identification and controlling childhood disease, even in regions with low disease prevalence. Adopting a suspicious and proactive approach in this particular age group is warranted.

Antiplatelet Antibodies and Their Correlation with Clinical Findings in Childhood Immune Thrombocytopenic Purpura

The demonstration of antiplatelet antibodies (PAIgG, PAIgM) and decreased detection of platelet surface antigens (CD41, CD61, CD42b) in children with immune thrombocytopenic purpura (ITP) have a diagnostic role. This study was conducted to determine whether these parameters differed in acute and chronic ITP. Chronic ITP was defined as thrombocytopenia persisting for more than 6 months from the onset of illness. A total of 80 subjects were divided into three groups: group 1 included 39 patients with acute ITP; group 2 included 31 patients with chronic ITP, and group 3 included 10 healthy children. At diagnosis, blood samples were obtained for platelet count, mean platelet volume, plateletcrit and platelet distribution width along with platelet surface antigens and antiplatelet immunoglobulins. We found that platelet surface antigens were significantly decreased in both acute and chronic ITP when compared to the control group (p = 0.001). In contrast, PAIgG was increased in acute and chronic ITP patients compared to the control group. PAIgM was significantly higher in acute ITP. We conclude that decreased platelet surface antigens and increased antiplatelet antibodies are observed in both acute and chronic ITP. In patients with chronic progress, a relatively lower level of PAIgM can be identified.

Effect of antipyretics on polymorphonuclear leukocyte functions in children

The aim of this study was to investigate whether fever and antipyretic drugs had an adverse effect on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity). Twenty febrile children with an axillary temperature of 39-40 degrees C and 20 healthy children without fever were included. Polymorphonuclear leukocytes were isolated. The effects of in vitro addition of antipyretic drugs (acetaminophen, metamizole sodium, nimesulid and ibuprofen) on PMN functions were tested. Phagocytic activity was assayed by the ingestion of yeast cells by PMNs and intracellular killing activity by the ingestion of yeast cells (stained blue) killed by PMNs. PMNs derived from febrile children exhibited better phagocytic activity when ibuprofen was added. In contrast, phagocytic activity was enhanced when acetaminophen, metamizole sodium or nimesulid was added in children without fever. Intracellular killing activity was enhanced when ibuprofen or metamizole sodium was added in children without fever. We conclude the antipyretic drugs at safely achievable concentrations do not suppress PMN function in vitro.