Characterisation of puroindoline genes in wild tetraploid and hexaploid wheats (Triticum araraticum; T. timopheevii and T. zhukovskyi)

Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatin-induced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested

The role of pharmacogenetics in osteosarcoma

Contains fulltext : 139140.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 17 maart 2015Promotores : Hoogerbrugge, P.M., Guchelaar (LUMC), H.J. Co-promotores : Loo, D.M.W.M. te, Coenen, M.J.H

Survival trends and long-term toxicity in pediatric patients with osteosarcoma

Contains fulltext : 109651.pdf (publisher's version ) (Open Access)Background. This study was conducted to investigate the clinical characteristics and treatment results of osteosarcoma in pediatric patients during the past 30 years. Trends in survival rates and long-term toxicity were analyzed. Procedure. 130 pediatric patients under the age of 20 years with primary localized or metastatic high-grade osteosarcoma were analyzed regarding demographic, treatment-related variables, long-term toxicity, and survival data. Results. Comparison of the different time periods of treatment showed that the 5-year OS improved from 58.6% for children diagnosed during 1979-1983 to 78.6% for those diagnosed during 2003-2008 (P = 0.13). Interestingly, the basic treatment agents including cisplatin, doxorubicin, and methotrexate remained the same. Treatment reduction due to acute toxicity was less frequent in patients treated in the last era (7.1% versus 24.1% in patients treated in 1979-1983; P = 0.04). Furthermore, late cardiac effects and secondary malignancies can become evident many years after treatment. Conclusion. We elucidate the prevalence of toxicity to therapy of patients with osteosarcoma over the past 30 years. The overall improvement in survival may in part be attributed to improved supportive care allowing regimens to be administered to best advantage with higher tolerance of chemotherapy and therefore less chemotherapy-related toxicity

Is there a role for the MTHFR 677C>T and 1298A>C polymorphisms in methotrexate-induced liver toxicity?

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[Throat and abdominal symptoms in malignant lymphoma; recognize the alarm signals in children]

In children, a malignant lymphoma can present with life-threatening complications arising from progressive tumour growth, warranting swift diagnosis and treatment. Early recognition can be challenging if a child with paediatric lymphoma presents with abdominal and throat symptoms because of the frequency, and frequently benign nature, of these symptoms in the general paediatric population. In these cases, it is essential for the physician to recognize the alarm signals for suspicion of malignant lymphoma, to allow timely diagnosis and treatment. We present two cases (children age 8 and 16 years) demonstrating the symptoms of malignant lymphoma that should raise alarm in children presenting with unilateral tonsil enlargement or intussusception, and illustrating the importance of timely recognition of these alarm signals, to prevent life-threatening complications due to tumour progression. In patients presenting with unilateral tonsil enlargement, malignant lymphoma should be considered if atypical macroscopic tonsil morphology, cervical lymphadenopathy, dysphagia, snoring, fever or weight loss is present. The presence of a lead point as the cause of intussusception should be considered in children aged > 2 years of age, in a child with an ileo-iliac intussusception and in patients with longstanding abdominal symptoms. In patients presenting with simultaneous symptoms and alarm signals for malignant lymphoma, the relationship between the presenting symptoms should be recognized. Interdisciplinary and intradisciplinary consultation with colleagues can help in the search for an overarching diagnosis, and it is crucial that this should happen without delay to prevent acute life-threatening situations

[Throat and abdominal symptoms in malignant lymphoma; recognize the alarm signals in children]

Contains fulltext : 220389.pdf (Publisher’s version ) (Closed access)In children, a malignant lymphoma can present with life-threatening complications arising from progressive tumour growth, warranting swift diagnosis and treatment. Early recognition can be challenging if a child with paediatric lymphoma presents with abdominal and throat symptoms because of the frequency, and frequently benign nature, of these symptoms in the general paediatric population. In these cases, it is essential for the physician to recognize the alarm signals for suspicion of malignant lymphoma, to allow timely diagnosis and treatment. We present two cases (children age 8 and 16 years) demonstrating the symptoms of malignant lymphoma that should raise alarm in children presenting with unilateral tonsil enlargement or intussusception, and illustrating the importance of timely recognition of these alarm signals, to prevent life-threatening complications due to tumour progression. In patients presenting with unilateral tonsil enlargement, malignant lymphoma should be considered if atypical macroscopic tonsil morphology, cervical lymphadenopathy, dysphagia, snoring, fever or weight loss is present. The presence of a lead point as the cause of intussusception should be considered in children aged > 2 years of age, in a child with an ileo-iliac intussusception and in patients with longstanding abdominal symptoms. In patients presenting with simultaneous symptoms and alarm signals for malignant lymphoma, the relationship between the presenting symptoms should be recognized. Interdisciplinary and intradisciplinary consultation with colleagues can help in the search for an overarching diagnosis, and it is crucial that this should happen without delay to prevent acute life-threatening situations

Association of the genetic variants in the nucleotide excision repair genes XPA and XPC with cisplatin-induced hearing loss in patients with osteosarcoma

Experimentele farmacotherapi

Foreign adopted children are a source of methicillin-resistant Staphylococcus aureus transmission to countries with low prevalence

Item does not contain fulltextWe report a 13.0% prevalence rate of methicillin-resistant Staphylococcus aureus (MRSA) carriers in foreign adopted children, who are frequently hospitalized within the first year after arrival. Hospitalization in the country of origin and special need status are no significant risk factors for MRSA colonization. Healthcare workers are overrepresented among their adoptive parents. These children represent a potential source of MRSA transmission into the healthcare system

Hematopoietic stem cell transplantation corrects the immunologic abnormalities associated with immunodeficiency-centromeric instability-facial dysmorphism syndrome.

Immunodeficiency-centromeric instability-facial dysmorphism syndrome, characterized by variable immunodeficiency, centromeric instability, and facial anomalies caused by epigenetic dysregulation resulting in hypomethylation, is caused in many patients by mutations in DNMT3B, a DNA methyltransferase gene; associated infections are a major cause of serious sequelae and death. Hematopoietic stem cell transplantation may improve the clinical course in immunodeficiency-centromeric instability-facial dysmorphism syndrome. We report 3 unrelated patients with persistent infections and intestinal complications who successfully underwent hematopoietic stem cell transplantation after nonmyeloablative or myeloablative conditioning regimens using HLA-matched donors. In all cases, donor chimerism led to resolution of intestinal complications and infections, growth improvement, and correction of the immunodeficiency

Age as prognostic factor in patients with osteosarcoma

Contains fulltext : 97616.pdf (publisher's version ) (Closed access)Age at diagnosis is a well known prognostic factor in many different malignancies; its significance for patients with osteosarcoma is however controversial. To gain more insight in the prognostic role of age, we performed a retrospective study at our institute. We included 102 patients with de-novo osteosarcoma and formed three age groups to evaluate age specific survival rates: </= 14years, 15-19years and 20-40years. Differences in outcome between patients aged 15-19years treated at either the pediatric department or the adult department of oncology were evaluated. The 5-year overall survival rate (OSR) of the whole population was 53.5%+/-1.5%. OSR of 70.6%+/-0.8% was seen in patients</=14years old, 52.5%+/-1.1% in patients 15-19years old and 33.3%+/-0.9% in the patients aged 20-40years (p=0.01). Significant differences were observed with regard to stage at presentation (higher in older age groups), size of the tumor (larger in younger age groups) and histological response (more good responders in younger age groups). No significant difference was seen between outcomes of patients aged 15-19years treated at the pediatric or adult oncology department. In conclusion, younger patients have a significantly better outcome than older patients