Invasive aspergillosis in pediatric oncology patients: a rare event with poor prognosis--case analysis to plan better targeted prophylactic or therapeutic measurement

Despite the implementation of new antifungal drugs, invasive aspergillosis (IA) still remains a considerable challenge in pediatric oncology with a severe mortality. Prophylactic and therapeutic measurement have to be evaluated in these rare but poor prognostic patients. Therefore the entire group of patients at risk of developing IA has to be defined before cooperative prospective trials. In a retrospective analysis including all our patients with malignancies we looked for patients with proven/probable IA. Cases of the period from 2003 to 2008 were analyzed in detail.In the period between 2003 to 2008 24 of 755 patients were affected by proven/ probable IA. Compared to former studies incidence increased from 1.3%in 1980 to 3.4% in 2008. AML patients with or without allogeneic/haploidentical stem cell transplantation were at highest risk (24% and 25% respectively, in comparison to 1% in ALL-patients). Survival after 2 years was 50% for patients with AML and IA. In patients with high risk to develop IA the effect of intensified, intravenous antimycotic prophylaxis has to be proven prospectively in a cooperative and randomized setting.     

Haplotype analysis of two X-chromosome STR clusters in the Pakistani population

Haplotype analysis of closely associated markers has proven to be a powerful tool in kinship analysis especially when X-chromosome short tandem repeats fail to resolve uncertainty in relationship analysis. Microsatellites located on the X chromosome show stronger linkage disequilibrium compared with autosomal microsatellites; hence, it is necessary to estimate the haplotype frequencies directly from population studies as linkage disequilibrium is population-specific. Here, we describe five markers residing in two clusters; cluster I harboring three STR markers DXS6801–DXS6809–DXS6789 and cluster II harboring two STR markers DXS7424–DXS101. A total of 302 male DNA samples of Pakistani descent were analyzed. Theoretically, 847 and 160 different combinations of haplotypes are possible in clusters I and II, but genotyping identified only 129 and 75 haplotypes, respectively. No evidence of linkage disequilibrium was detected, except for the pair (DXS6801–DXS6789), consistent with results obtained with the cluster I in a German population. Our results demonstrate that 83% haplotypes of cluster I and 65% haplotypes of cluster II show <1% frequency in the Pakistani population. This strongly suggests that haplotypes of these two clusters provide a powerful tool for kinship testing and relationship investigations. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was supported in part by Higher Education Commission and Ministry of Science and Technology Islamabad, Pakistan.     

Neuron source energy on resonance absorption

Four different methods are used to study the neutron slowing down and to evaluate the neutron resonance escape probability in an infinite homogeneous medium containing a heavy resonant nuclide [U238] and a light moderator nuclide [H]. Two statistical methods use the Monte Carlo simulation and two deterministic methods are based on the numerical solutions of the neutron slowing down equation and a corresponding adjoint equation with an appropriate adjoint source.This study has been done for several dilutions and for two neutron source energies (E_s = 676.45 eV and E_s = 2 MeV). The cut-off energy is placed at 2.77 eV.We have found that the direct numerical solution of the neutron slowing down equation does not agree with the other three methods. In order to eliminate this disagreement, we have taken account of some corrections concerning the hydrogen cross-section in the thermal region.     

Frequencies of Beta Thalassemia Mutations Show Different Pattern in Bannu Region than Other Parts of Pashtun Population in Khyber Pakhtunkhwa Province Pakistan

Purpose: β-Thalassemia arises as result of mutations in HBB gene, influencing the globin production which results in hypochromic and microcytic anaemia. The present study was aimed to investigate the occurrence of six common β-thal mutations, its inheritance pattern, frequency, and consanguinity in parents of Bannu region Khyber Pakhtunkhwa (KP) province, Pakistan. Conducting such studies may impart important information about thalassemia prevention like prenatal diagnosis (PND), carrier screening and genetic counselling which may be helpful in controlling the suspected births. Methods: During the study, 250 blood samples were retrieved from different families comprising of one transfusion dependent child and sporadic patients from different areas of Bannu region. The collected blood samples were investigated to see if there is any common mutations which may trigger β-Thalassemia employing amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) approach. Results: Amongst the studied mutation in District Bannu, frame shift codons (FSC) 8/9 (+ G) (HBB: c.27_28insG) was observed to be the most common mutation followed by Codons 41/42 (− TTCT), IVS-I-5(G > C) and FSC 5 (− CT) having frequencies of 42, 26, 19 and 13 respectively. The results obtained by the present study were found different from previous studies demonstrated from other Pashtun regions of KP, showing heterogeneity in frequencies of known mutations. Conclusion: These observations may help in implementing parental meetings about disease recurrence in future, large scale mutation screening, and prenatal diagnosis in the whole Pashtun ethnicity including District Bannu.     

DPP-IV inhibitors: Beyond glycaemic control?

Dipeptidyl-peptidase-IV (DPP-IV) inhibitors are a new class of oral hypoglycaemic agents recently approved for the management of type 2 diabetes mellitus. Early data suggested that they had a positive impact on the cardiovascular system: treatment appeared to result in improvements in cardiac performance, blood pressure and lipid levels. However, recent clinical findings bring this into question. Our understanding of the physiological actions of these agents is complicated by the fact that DPP-IV has a wide range of substrates in addition to glucagon-like peptide 1. Indeed, DPP-IV inhibition alters concentrations of a wide variety of cytokines and neuropeptides. A deeper understanding of the physiological effects of these drugs as well as their true impact on cardiovascular risk is needed before consideration can be given to extending their use beyond the treatment of diabetes.