Results of rhabdomyosarcoma treatment in a developing country.

Fifty-one children (median age: 4.5 years; 4 months-16 years) diagnosed with rhabdomyosarcoma were treated in our center between 1980-1999. The primary sites were head and neck in 31.4%, the genito-urinary system in 21.6%, and extremities in 9.8% of the patients. The histopathologic subtypes were embryonal in 80.4%, alveolar in 9.8%, and undifferentiated in 9.8%. The majority of the patients were considered group III (47%) and group IV (25.5%) according the criteria of the Intergroup Rhabdomyosarcoma Study (IRS). Primary total tumour resection was performed in only 27.5% of the patients. The patients were treated with assigned regimens of IRS II and IRS III protocols. Radiotherapy was applied to 92.1% of the patients. Thirty-four patients (66.7%) were lost to follow up, and of the remaining 17 patients, 7 patients (41.2%) died, relapse occurred in 9 patients (52.9%) and 10 patients (58.8%) are alive. The percentage of cases lost to follow up during the first 10 years and the following 9 years of the study were 77.4% and 50%, respectively. In compliance with cancer treatment remains a major problem in developing countries.</p

Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. Methods: A high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes. Results: Analyses revealed a mutation detection sensitivity of 97.3 %, an average coverage per gene of 98.0 %, and adequate coverage over 98.6 % of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38 %). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals. Conclusions: We have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.Peer reviewe

Pitfalls in the diagnosis of immune thrombocytopenic purpura in children: 4 case reports

Acute idiopathic thrombocytopenic purpura is the most common cause of thrombocytopenia in childhood, and diagnosis of idiopathic thrombocytopenic purpura is made clinically based on the exclusion of other causes of thrombocytopenia. Patients with diverse causes of thrombocytopenia are sometimes erroneously diagnosed as having idiopathic thrombocytopenic purpura. However, for the prevention of misdiagnoses, careful inspection of peripheral blood smear is of utmost importance. This report presents 4 cases presumed as acute idiopathic thrombocytopenic purpura that were finally identified as pseudothrombocytopenia, inherited macrothrombocytopenia (MHY9 disorders) possibly Epstein syndrome, Bernard-Soulier syndrome, and drug-induced thrombocytopenia. They draw attention to the importance of platelet morphology to exclude inherited macrodirombocytopenia and history to exclude drug-induced thrombocytopenia. Better diagnostic approaches would be possible by the awareness of these relatively rare causes of isolated thrombocytopenia

Pediatric Acute Lymphoblastic Leukemia Complicated by Secondary Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) may be familial or secondary to infections, malignancies, metabolic disorders. Infectious causes are mostly viral and EBV is the mostly frequently seen etiologic agent. In this case, we report a child with acute lymphoblastic leukemia (ALL), who had three episodes of secondary HLH, possibly due to two different viral etiologies, namely CMV and RSV together with her malignancy, during her induction-consolidation treatment. Pediatr Blood Cancer 2009;53: 491-492. (C) 2009 Wiley-Liss, Inc

Effect of maternal and infant vitamin D supplementation on vitamin D levels of breastfed infants

The aim of our study was to investigate the effect of maternal vitamin D-3 (400 U/day) supplementation on breastfed infants at 6 months of age. Mothers (n=96) were enrolled within 1 month after birth and assigned to the 400 IU/day regimen or no vitamin D-3 supplementation for 6 months. All infants received 400 IU/day of vitamin D-3 and were exclusively breastfed until 4 months of age. Of all mothers, 22.2% had vitamin D levels above 20 ng/ml initially. At the end of the study, vitamin D levels of mothers and their infants were similar in both groups. Thirteen percent of the infants in the intervention group and 20.5% in the control group had vitamin D levels below 12 ng/ml. Serum 25-hydroxyvitamin D (25(OH) D) concentrations at 6 months had increased significantly in mothers in the intervention group. Lactating mothers and their children need vitamin D supplementation but further studies are required with higher doses

Is There Any Correlation Between The Elevated Plasma Levels and Gene Variations of Factor VIII in Turkish Thrombosis Patients?

We investigated factor VIII (FVIII) gene mutations in 20 thrombosis patients with high level of FVIII and 20 control healthy participants. Blood samples were used for the determination of FVIII levels using static timing analyze (STA) kits. Informed consent forms were collected from all participants. Factor VIII level was 237 +/- 46 IU/dL in patients group; however, it was 122 +/- 38 IU/dL in healthy control participants. Isolated genomic DNAs were screened using 37 pairs of primers covering promoter region and 26 exons of FVIII gene. Single-strand conformation analysis (SSCA) technique was performed for polymorphism/mutation analyses. We observed polymorph patterns in exon 6, exon 13, exon 14F, exon 19, and exon 25 regions. However, we found no evidence of an association between observed single nucleotide polymorphisms and high thrombosis levels. In conclusion, observed exons polymorphisms do not seem to be associated with a venous thromboembolism

Shunt Operations Improved Thrombocytopenia in a Patient with Congenital Cyanotic Heart Disease

Cardiac and vascular intervention in thrombocytopenic congenitally cyanotic patients is more dangerous. Thrombocytopenia in these patients is related to immune thrombocytopenia, polycythemia, hyperviscosity, pseudothrombocytopenia, and drugs. Herein we report on a thrombocytopenic 8-year-old girl with tricuspid valve atresia and pulmonary valve stenosis admitted for catheterization. Thrombocytopenia (21,000/mm(3)) and shunt occlusion was noticed. Thrombocytopenia did not recover after intravenous immunoglobulin (IVIG) and phlebotomy therapies. During preparation for surgery, she suffered cardiopulmonary arrest. A Gore-tex graft was placed in the right pulmonary artery and truncus brachiocephalicus. After surgery, her platelet count spontaneously increased to within the normal range (178,000/mm(3) to 250,000/mm(3)). After resuscitation, she had right-sided hemiplegia sequelae, though there were no hemorrhagic findings on cranial magnetic resonance imaging (MRI) or computed tomography (CT) scans. Two months after surgery, the Blalock-Taussig (BT) shunt blood flow decreased, thrombocyte count dropped, and peripheral cyanosis reappeared. A Fontan operation was performed without hemorrhagic events, and after surgery the thrombocyte count reached 330,000/mm(3). We suggest that if a patient with cyanotic heart disease has thrombocytopenia and there is no apparent cause, hypoxia-related thrombocytopenia must be considered. After reoxygenation by shunt or corrective surgeries, thrombocyte count and functions will recover. (Ann Thorac Cardiovasc Surg 2008; 14: 329-332