Non –Hodgkin lymphoma in Sudanese Children

Background: Non-Hodgkin Lymphoma is a very heterogeneous  lymphoproliferative disease with clinical and histological pattern different from children to adults.Objective: To characterize the clinical and pathological pattern of Non -Hodgkin`s lymphoma among Sudanese children.Materials and Methods: This study was undertaken prospectively on paediatric cases (≤16 years) referred to histopathology department, Radio-Isotope Centre, Khartoum which is the main Centre for cancer  management in Sudan from January 2008 to December 2012. The clinical and demographical data of these patients were recorded. The H&E stained slides of each case were examined initially, then the confirmed cases of non-Hodgkin`s lymphoma were classified according to the 2008 WHO classification of neoplastic diseases of the haematopoietic lymphoid tissue following immunostaining of sections cut from formalin-fixed, paraffin embedded (FFPE) tissue blocks with the following panel of antibodies:-LCA, CD3, CD5, CD10, CD20, CD23, BCL2, CyclinD1, MUM1,CD15,CD30 andKi67.Results: Age range was 9 months to 16years. Fifty percent of the cases occurred between the age 2-5 years and only one case below one year. Male to female ratio was 1.6. Extranodal lymphoma (60%) was higher than nodal type (40%).The most commonly affected site was the  gastrointestinal tract. Most of the gastrointestinal lymphoma presented with abdominal mass. The most common histological type was Burkitt`s  lymphoma. None of the cases were small lymphocytic, follicular or T- cell type. Bone marrow involvement was in 87.5% of the cases at the time of diagnosis.Conclusion: Burkitt`s lymphoma is the predominant paediatric lymphoma in Sudan. The majority of the cases presented late with bone marrow involvement.Key words: Non -Hodgkin`s lymphoma, immunohistochemistry, Paediatric, Sudan

Effect of exacerbations on health status in subjects with chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD). The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations.</p> <p>Methods</p> <p>A total of 156 subjects with COPD (mean age 71.4 ± 6.3 years) were included in the analysis. At baseline and after 6 months, their pulmonary function and health status were evaluated using the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). An acute exacerbation was defined as a worsening of respiratory symptoms requiring the administration of systemic corticosteroids or antibiotics, or both.</p> <p>Results</p> <p>Forty-eight subjects experienced one or more exacerbations during the 6-month study period, and showed a statistically and clinically significant decline in Symptom scores on the SGRQ, whereas subjects without exacerbations did not show a clinically significant decline. Logistic multiple regression analyses confirmed that the exacerbations significantly influenced the Fatigue and Mastery domains of the CRQ, and the Symptoms in the SGRQ. Twelve subjects with frequent exacerbations demonstrated a more apparent decline in health status.</p> <p>Conclusion</p> <p>Although pulmonary function did not significantly decline during the 6-month period, acute exacerbations were responsible for a decline in health status. To minimize deteriorations in health status, one must prevent recurrent acute exacerbations and reduce the exacerbation frequencies in COPD subjects.</p

The Maltase Involved in Starch Metabolism in Barley Endosperm Is Encoded by a Single Gene

During germination and early seedling growth of barley (Hordeum vulgare), maltase is responsible for the conversion of maltose produced by starch degradation in the endosperm to glucose for seedling growth. Despite the potential relevance of this enzyme for malting and the production of alcoholic beverages, neither the nature nor the role of maltase is fully understood. Although only one gene encoding maltase has been identified with certainty, there is evidence for the existence of other genes and for multiple forms of the enzyme. It has been proposed that maltase may be involved directly in starch granule degradation as well as in maltose hydrolysis. The aim of our work was to discover the nature of maltase in barley endosperm. We used ion exchange chromatography to fractionate maltase activity from endosperm of young seedlings, and we partially purified activity for protein identification. We compared maltase activity in wild-type barley and transgenic lines with reduced expression of the previously-characterised maltase gene Agl97, and we used genomic and transcriptomic information to search for further maltase genes. We show that all of the maltase activity in the barley endosperm can be accounted for by a single gene, Agl97. Multiple forms of the enzyme most likely arise from proteolysis and other post-translational modifications

ICE COLD ERIC – International collaborative effort on chronic obstructive lung disease: exacerbation risk index cohorts – Study protocol for an international COPD cohort study

<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is a systemic disease; morbidity and mortality due to COPD are on the increase, and it has great impact on patients' lives. Most COPD patients are managed by general practitioners (GP). Too often, GPs base their initial assessment of patient's disease severity mainly on lung function. However, lung function correlates poorly with COPD-specific health-related quality of life and exacerbation frequency. A validated COPD disease risk index that better represents the clinical manifestations of COPD and is feasible in primary care seems to be useful. The objective of this study is to develop and validate a practical COPD disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2–4.</p> <p>Methods/Design</p> <p>We will conduct 2 linked prospective cohort studies with COPD patients from GPs in Switzerland and the Netherlands. We will perform a baseline assessment including detailed patient history, questionnaires, lung function, history of exacerbations, measurement of exercise capacity and blood sampling. During the follow-up of at least 2 years, we will update the patients' profile by registering exacerbations, health-related quality of life and any changes in the use of medication. The primary outcome will be health-related quality of life. Secondary outcomes will be exacerbation frequency and mortality. Using multivariable regression analysis, we will identify the best combination of variables predicting these outcomes over one and two years and, depending on funding, even more years.</p> <p>Discussion</p> <p>Despite the diversity of clinical manifestations and available treatments, assessment and management today do not reflect the multifaceted character of the disease. This is in contrast to preventive cardiology where, nowadays, the treatment in primary care is based on patient-specific and fairly refined cardiovascular risk profile corresponding to differences in prognosis. After completion of this study, we will have a practical COPD-disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2–4. In a second step we will incorporate evidence-based treatment effects into this model, such that the instrument may guide physicians in selecting treatment based on the individual patients' prognosis.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Archive NCT00706602</p

Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola

<p>Abstract</p> <p>Background</p> <p>Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.</p> <p>Methods</p> <p>Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in <it>Plasmodium falciparum </it>was investigated in the <it>pfmdr1 </it>(N86Y) and <it>pfcrt </it>(K76T) genes, associated with CQ resistance, as well as in <it>pfdhfr </it>(C59R) and <it>pfdhps </it>(K540E), conferring SP resistance.</p> <p>Results</p> <p>The frequencies of <it>pfmdr1 </it>mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of <it>pfcrt </it>mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For <it>pfdhfr </it>the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning <it>pfdhps</it>, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).</p> <p>Conclusion</p> <p>The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.</p

Caenorhabditis elegans HIM-18/SLX-4 Interacts with SLX-1 and XPF-1 and Maintains Genomic Integrity in the Germline by Processing Recombination Intermediates

Homologous recombination (HR) is essential for the repair of blocked or collapsed replication forks and for the production of crossovers between homologs that promote accurate meiotic chromosome segregation. Here, we identify HIM-18, an ortholog of MUS312/Slx4, as a critical player required in vivo for processing late HR intermediates in Caenorhabditis elegans. DNA damage sensitivity and an accumulation of HR intermediates (RAD-51 foci) during premeiotic entry suggest that HIM-18 is required for HR–mediated repair at stalled replication forks. A reduction in crossover recombination frequencies—accompanied by an increase in HR intermediates during meiosis, germ cell apoptosis, unstable bivalent attachments, and subsequent chromosome nondisjunction—support a role for HIM-18 in converting HR intermediates into crossover products. Such a role is suggested by physical interaction of HIM-18 with the nucleases SLX-1 and XPF-1 and by the synthetic lethality of him-18 with him-6, the C. elegans BLM homolog. We propose that HIM-18 facilitates processing of HR intermediates resulting from replication fork collapse and programmed meiotic DSBs in the C. elegans germline

Anthroponotic transmission of Cryptosporidium parvum predominates in countries with poorer sanitation - a systematic review and meta-analysis

Background: Globally cryptosporidiosis is one of the commonest causes of mortality in children under 24 months old and may be associated with important longterm health effects. Whilst most strains of Cryptosporidium parvum are zoonotic, C. parvum IIc is almost certainly anthroponotic. The global distribution of this potentially important emerging infection is not clear. Methods: We conducted a systematic review of papers identifying the subtype distribution of C. parvum infections globally. We searched PubMed and Scopus using the following key terms Cryptospor* AND parvum AND (genotyp* OR subtyp* OR gp60). Studies were eligible for inclusion if they had found C. parvum within their human study population and had subtyped some or all of these samples using standard gp60 subtyping. Pooled analyses of the proportion of strains being of the IIc subtype were determined using StatsDirect. Meta-regression analyses were run to determine any association between the relative prevalence of IIc and Gross Domestic Product, proportion of the population with access to improved drinking water and improved sanitation. Results: From an initial 843 studies, 85 were included in further analysis. Cryptosporidium parvum IIc was found in 43 of these 85 studies. Across all studies the pooled estimate of relative prevalence of IIc was 19.0% (95% CI: 12.9–25.9%), but there was substantial heterogeneity. In a meta-regression analysis, the relative proportion of all C. parvum infections being IIc decreased as the percentage of the population with access to improved sanitation increased and was some 3.4 times higher in those studies focussing on HIV-positive indivduals. Conclusions: The anthroponotic C. parvum IIc predominates primarily in lower-income countries with poor sanitation and in HIV-positive individuals. Given the apparent enhanced post-infectious virulence of the other main anthroponotic species of Cryptosporidium (C. hominis), it is important to learn about the impact of this subtype on human health

Anthroponotic transmission of Cryptosporidium parvum predominates in countries with poorer sanitation - a systematic review and meta-analysis

Background: Globally cryptosporidiosis is one of the commonest causes of mortality in children under 24 months old and may be associated with important longterm health effects. Whilst most strains of Cryptosporidium parvum are zoonotic, C. parvum IIc is almost certainly anthroponotic. The global distribution of this potentially important emerging infection is not clear. Methods: We conducted a systematic review of papers identifying the subtype distribution of C. parvum infections globally. We searched PubMed and Scopus using the following key terms Cryptospor* AND parvum AND (genotyp* OR subtyp* OR gp60). Studies were eligible for inclusion if they had found C. parvum within their human study population and had subtyped some or all of these samples using standard gp60 subtyping. Pooled analyses of the proportion of strains being of the IIc subtype were determined using StatsDirect. Meta-regression analyses were run to determine any association between the relative prevalence of IIc and Gross Domestic Product, proportion of the population with access to improved drinking water and improved sanitation. Results: From an initial 843 studies, 85 were included in further analysis. Cryptosporidium parvum IIc was found in 43 of these 85 studies. Across all studies the pooled estimate of relative prevalence of IIc was 19.0% (95% CI: 12.9–25.9%), but there was substantial heterogeneity. In a meta-regression analysis, the relative proportion of all C. parvum infections being IIc decreased as the percentage of the population with access to improved sanitation increased and was some 3.4 times higher in those studies focussing on HIV-positive indivduals. Conclusions: The anthroponotic C. parvum IIc predominates primarily in lower-income countries with poor sanitation and in HIV-positive individuals. Given the apparent enhanced post-infectious virulence of the other main anthroponotic species of Cryptosporidium (C. hominis), it is important to learn about the impact of this subtype on human health