Avian influenza and poultry workers, Peru, 2006

Background Currently numerous countries in Asia, Africa and Europe are encountering highly pathogenic avian influenza (AI) infections in poultry and humans. In the Americas, home of the world’s largest poultry exporters, contingency plans are being developed and evaluated in preparation for the arrival of these viral strains. Objectives With this cross‐sectional study, to our knowledge the first in its kind in Central or South America, we sought to learn whether Peruvian poultry workers had evidence of previous AI infection and if so, to determine the risk factors for infection. Methods We performed a cross‐sectional seroprevalence study among 149 workers on a Peruvian poultry farm (132 exposed to poultry and 17 non‐exposed controls), serum samples were tested for human influenza virus exposure using a hemagglutination inhibition (HI) assay. Microneutralization assays were performed on all serum samples to detect antibodies against prototypic AI strains H4 through H12. Results Using multivariate proportional odds modeling we found that the prevalence of elevated titers against AI viruses was low in both groups, exposed and non‐exposed controls. Conclusions No evidence of previous AI infection among Peruvian poultry workers was found in this first cross‐sectional study performed in South America. This first occupational study of AI in Latin America was encouraging, but it likely reflects the sector of poultry production with higher biosecurity.     

Plasma TNF-α and IL-10 Level-Based Prognostic Model Predicts Outcome of Patients with Diffuse Large B-Cell Lymphoma in Different Risk Groups Defined by the International Prognostic Index

Tumor necrosis factor (TNF)-α and interleukin (IL)-10 are key cytokines involved in lymphoma development. Their pretreatment plasma levels were reported to influence the clinical course of non-Hodgkin’s lymphoma. In this study the impact of combined elevation of TNF-α and IL-10 on disease features and outcome of patients with diffuse large B-cell lymphoma (DLBCL) were investigated. Plasma TNF-α and IL-10 levels were determined at the time of diagnosis in a group of 106 DLBCL patients uniformly treated with anthracycline-based regimens. Three risk groups depending on the pretreatment levels of the cytokines were identified: low-, intermediate-, and high-risk groups. In univariate analysis, the cytokine intermediate- and high-risk groups were associated with lower probability of achieving a complete remission (odds ratio [OR] = 0.2, 95% confidence interval [CI] 0.06–0.6, p = 0.006 and OR = 0.05, 95% CI 0.01–0.2, p < 0.0001, respectively) and shorter progression-free survival (PFS) (OR = 4.4, 95% CI 1.9–10.2, p < 0.001 and OR = 9.7, 95% CI 4.1–23.0, p < 0.0001, respectively) and overall survival (OS) (OR = 4.2, 95% CI 1.7–10.1, p = 0.002 and OR = 11.2, 95% CI 4.4–28.4, p < 0.0001, respectively) in comparison with the cytokine low-risk group. In multivariate analysis, the cytokine intermediate- and high-risk groups also correlated with shorter PFS (relative risk [RR] = 4.5, 95% CI 1.9–10.9, p = 0.001 and RR = 5.8, 95% CI 2.2–15.3, p < 0.0001, respectively) and OS (RR = 4.6, 95% CI 1.8–12.0, p = 0.001 and RR = 7.5, 95% CI 2.7–20.9, p < 0.0001, respectively) regardless of the International Prognostic Index (IPI) scoring system. The TNF-α and IL-10 level-based index may work as an additional model to the IPI for predicting the survival of DLBCL patients. This model may help to identify patients in a given IPI risk group for whom more accurate and risk-adapted treatment could be advised.     

The ARX mutations: a frequent cause of X-linked mental retardation

The ARX gene mutations have been demonstrated to cause different forms of mental retardation (MR). Beside FMR1, in families with X-linked mental retardation (XLMR), the ARX dysfunction was demonstrated to be among the most frequent causes of this heterogeneous group of disorders. Nevertheless, in sporadic cases of MR, ARX mutations are extremely rare. In order to evaluate the frequency of ARX mutation in XLMR, we performed mutational analysis of ARX in 165 mentally retarded probands negative for FRAXA and belonging to families in which the condition segregates as an X-linked condition. The same recurrent mutation, an in frame 24 bp insertion (c.428-451 dup (24 bp)), was identified in five patients. In one family, the mother of two affected boys was found not to carry the mutation detected in her sons. These data suggest the presence of germline mosaicism for the mutation in the mother. Our results confirm the significant contribution of ARX mutations in the etiology of MR, especially in this group of patients selected for XLMR (3%). These data, together with those reported in the literature, imply that screening for c.428-451 dup (24 bp) mutation should be recommended in all patients with suspected XLMR.     

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.     

Species density obtained for fish sampled with three seine nets hauled individually towards a stop net or a bank

Researchers continuously search for adequate and inexpensive fish sampling methods and, as such, it is worth remembering the quantitative seine method with three identical nets hauled individually towards a stop net or a bank. A sample obtained by three nets is the absolute minimum for any accurate estimate employing a removal technique, and this procedure provides an estimate of density with a known error, because it allows for calculations of the variance value. Density (the number of individuals calculated from the model, as per defined area or volume), a popular term in the previous century when a secondary production and bioenergetics budget studies were considered to be modern investigations, but now when it is used with different meanings, an attempt has to be undertaken to sort out this terminology.     

Older and new purine nucleoside analogs for patients with acute leukemias

Purine nucleoside analogs (PNAs) compose a class of cytotoxic drugs that have played an important role in the treatment of hematological neoplasms, especially lymphoid and myeloid malignancies. All PNA drugs have a chemical structure similar to adenosine or guanosine, and they have similar mechanisms of action. They have many intracellular targets: they act as antimetabolites, competing with natural nucleosides during DNA or RNA synthesis, and as inhibitors of key cell enzymes. In contrast to other antineoplastic drugs, PNAs act cytotoxically, both in the mitotic and quiescent cell cycle phases. In the last few years, three PNAs have been approved for the treatment of lymphoid malignancies and other hematological disorders: 2-chlorodeoxyadenosine (2-CdA), fludarabine and pentostatin. 2-CdA and fludarabine are also active in the treatment of acute myeloid leukemia (AML). These drugs, in combination with cytarabine and other agents, are commonly used as salvage regimens in relapsed or refractory AML. Moreover, the addition of 2-CdA to the standard induction regimen is associated with an increased rate of complete remission and improved survival of adult patients with AML. More recently three novel PNAs have been synthesized and introduced into clinical trials: clofarabine, nelarabine and forodesine. Clofarabine is the most promising PNA in current clinical trials in pediatric and adult patients with acute leukemias. Nelarabine is more cytotoxic in T-lineage than in B-lineage leukemias. Clofarabine and nelarabine have been approved for the treatment of refractory patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. Clofarabine is also an active drug in AML treatment when administered either alone or in combination regimens as front-line treatment and in relapsed or refractory patients. Unlike other PNA, forodesine is not incorporated into DNA but displays a highly selective purine nucleoside phosphorylase inhibitory action. Forodesine is undergoing clinical trials for the treatment of T-cell malignancies, including T-cell ALL. This article summarizes recent achievements in the mechanism of action, pharmacological properties and clinical activity and toxicity of PNAs, as well as their emerging role in lymphoid and myeloid acute leukemias.     

Extragonadal teratoma in a domestic turkey (Meleagris gallopavo domestica)

This is the first report of a primary, spontaneous and, most probably, congenital teratoma in a domestic turkey, localized in front of the left eyeball. The unique localization allowed surgical excision of the tumour. The histopathological examination revealed that the tumour included structures derived from all three germ cell layers: ectoderm, mesoderm and endoderm (e.g. cartilaginous, osseous, haematopoietic, fibrous, nervous, glandular, squamous epithelial and smooth muscle tissues). The presence of epithelial cells as well as smooth muscle cells was confirmed using anti-cytokeratin and anti-desmin antibodies, respectively. The proliferative activity of the tumour cells was confirmed using proliferating cell nuclear antigen immunostaining. The other cases of teratoma in wild and domestic birds are reviewed briefly.