391 research outputs found

    A validation of the Oswestry Spinal Risk Index

    Get PDF
    Purpose The purpose of this study was to validate the Oswestry Spinal Risk Index (OSRI) in an external population. The OSRI predicts survival in patients with metastatic spinal cord compression (MSCC). Methods We analysed the data of 100 patients undergoing surgical intervention for MSCC at a tertiary spinal unit and recorded the primary tumour pathology and Karnofsky performance status to calculate the OSRI. Logistic regression models and survival plots were applied to the data in accordance with the original paper. Results Lower OSRI scores predicted longer survival. The OSRI score predicted survival accurately in 74% of cases (p = 0.004). Conclusions Our study has found that the OSRI is a significant predictor of survival at levels similar to those of the original authors and is a useful and simple tool in aiding complex decision making in patients presenting with MSC

    Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring the PfCRT SVMNT type

    Get PDF
    The loss of chloroquine due to selection and spread of drug resistant Plasmodium falciparum parasites has greatly impacted malaria control, especially in highly endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines to treat falciparum malaria suggest combination therapies, preferentially with an artemisinin derivative. One of the recommended partner drugs is amodiaquine, a pro-drug that relies on its active metabolite monodesethylamodiaquine, and is still effective in areas of Africa, but not in regions of South America. Genetic studies on P. falciparum parasites have shown that different pfcrt mutant haplotypes are linked to distinct levels of chloroquine and amodiaquine responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon positions 72-76) is stably present in several areas where amodiaquine was introduced and widely used. Parasites with this haplotype are highly resistant to monodesethylamodiaquine and also resistant to chloroquine. The presence of this haplotype in Africa was found for the first time in 2004 in Tanzania and a role for amodiaquine in the selection of this haplotype was suggested. This commentary discusses the finding of a second site in Africa with high incidence of this haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt haplotypes in every country currently using amodiaquine and to re-evaluate current combination therapies in areas where SVMNT type parasites are prevalent

    Paraneoplastic Hypercalcemia Secondary to Canine Mammary Tumors

    Get PDF
    Background: Paraneoplastic syndromes are complexes symptom that occur at a distinct site from the primary tumor or its metastasis by the production of hormone by the tissue in which the tumor appears. Paraneoplastic hypercalcemia is associated with an abnormal elevation of serum calcium levels and the mainly tumor related to this syndrome in canine is lymphoma, anal sac apocrine gland adenocarcinoma and multiple myeloma. In mammary tumors, the most frequent tumor that affect female dogs, this syndrome was also observed. The aims of this study were to evaluate serum calcium levels in female dogs with malignant mammary tumors and correlate calcium levels with clinicopathological parameters.Materials, Methods & Results: It was evaluated fifty-one female dogs with mammary carcinomas (simple carcinomas and carcinoma in mixed tumors) for serum calcium levels using colorimetric test. Clinical-histopathological data as spray status, pseudopregnancy, tumor size, ulceration, clinical staging, histopathological type and tumor grade were also evaluated in association with serum calcium levels. All dogs were treated with unilateral mastectomy. It was observed that 18 animals (35%) had calcium serum levels increased (>11.5 mg/dL) and 56% (10/18 cases) of these animals had serum calcium levels higher than 12 mg/dL. All dogs with hypercalcemia were asymptomatic, including two female dogs that presented the highest levels (13.43 mg/dL and 14.28 mg/dL). Hypercalcemia of malignancy was related to mammary carcinomas after the exclusion of other causes of hypercalcemia through laboratory tests (complete blood count and serum biochemistry) and abdominal ultrasound. No correlation was verified between the corrected serum calcium values with clinical and histopathological parameters evaluated.Discussion: In this study, it was observed a high incidence of paraneoplastic hypercalcemia associated with canine mammary tumors (35%). In humans, this syndrome is related in up to 10% of all patients with advanced cancer and with worse prognosis. The most frequent clinical signs of hypercalcemia are nonspecific and can be confused with other diseases, such as polyuria, polydipsia, anorexia, constipation, lethargy and weakness. The treatment of this syndrome is based on tumor resection and when necessary other treatments can be performed with fluid containing 0.9% sodium chloride, furosemide, prednisolone and calcitonin. Patients with asymptomatic or mildly symptomatic hypercalcemia (calcium levels <12 mg/ dL) do not require immediate treatment. Clinical signs occur more frequently with serum calcium levels higher than 15 mg/dL. Calcium levels higher than 18 mg/dL are considered a medical emergency and the clinical signs observed are trigger seizures, cardiac arrhythmia, acute renal failure and death. Most animals of this study presented mild hypercalcemia, that could justify the absence of clinical signs related to this syndrome, and the treatment for this syndrome was the tumor removal. The high serum calcium levels did not show correlation with more aggressive tumors and poorer prognosis, conditions evaluated by histological type, tumor grade and clinical stage. The evaluation of serum calcium levels is an important clinical test to be done in female dogs with mammary tumors, besides to be an affordable and technically simple test. The clinical signs related to this syndrome are nonspecific and may be confused with other diseases commonly observed in older dogs. The data suggest that there are no correlation between serum calcium levels with aggressiveness of canine mammary tumors and with other clinical features

    Genomic Expansion of Magnetotactic Bacteria Reveals an Early Common Origin of Magnetotaxis with Lineage-specific Evolution

    Get PDF
    The origin and evolution of magnetoreception, which in diverse prokaryotes and protozoa is known as magnetotaxis and enables these microorganisms to detect Earth’s magnetic field for orientation and navigation, is not well understood in evolutionary biology. The only known prokaryotes capable of sensing the geomagnetic field are magnetotactic bacteria (MTB), motile microorganisms that biomineralize intracellular, membrane-bounded magnetic single-domain crystals of either magnetite (Fe3O4) or greigite (Fe3S4) called magnetosomes. Magnetosomes are responsible for magnetotaxis in MTB. Here we report the first large-scale metagenomic survey of MTB from both northern and southern hemispheres combined with 28 genomes from uncultivated MTB. These genomes expand greatly the coverage of MTB in the Proteobacteria, Nitrospirae, and Omnitrophica phyla, and provide the first genomic evidence of MTB belonging to the Zetaproteobacteria and “Candidatus Lambdaproteobacteria” classes. The gene content and organization of magnetosome gene clusters, which are physically grouped genes that encode proteins for magnetosome biosynthesis and organization, are more conserved within phylogenetically similar groups than between different taxonomic lineages. Moreover, the phylogenies of core magnetosome proteins form monophyletic clades. Together, these results suggest a common ancient origin of iron-based (Fe3O4 and Fe3S4) magnetotaxis in the domain Bacteria that underwent lineage-specific evolution, shedding new light on the origin and evolution of biomineralization and magnetotaxis, and expanding significantly the phylogenomic representation of MTB

    Negative Smad Expression and Regulation in the Developing Chick Limb

    Get PDF
    The inhibitory or negative Smads, Smad6 and Smad7, block TGFβ superfamily signals of both the BMP and TGFβ classes by antagonizing the intracellular signal transduction machinery. We report the cloning of one Smad6 and two Smad7 (Smad7a and Smad7b) chick homologs and their expression and regulation in the developing limb. Smad6 and Smad7a are expressed in dynamic patterns reflecting the domains of BMP gene expression in the limb. Activation and inhibition of the BMP signaling pathway in limb mesenchyme indicates that negative Smad gene expression is regulated, at least in part, by BMP family signals

    A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania. In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant <it>pfcrt </it>allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003.</p> <p>Methods</p> <p>The prevalence of the wild type <it>pfcrt </it>allele was assessed in 144 isolates from the years 2005 - 07 by PCR fragment restriction digest and direct sequencing. For haplotype analysis of the chromosomal regions flanking the <it>pfcrt </it>locus, microsatellite analysis was done on a total of 145 isolates obtained in 1995/96 (43 isolates), 2002 (47 isolates) and 2005 - 07 (55 isolates).</p> <p>Results</p> <p>The prevalence of the mutant <it>pfcrt </it>allele decreased from 100% in the years 1995/96 and 2002 to 97% in 2005 - 07. Haplotype analysis showed that in 1995/96 79% of the isolates carried the same microsatellite alleles in a chromosomal fragment spanning 39 kb surrounding the <it>pfcrt </it>locus. In 2002 and 2005 - 07 the prevalence of this haplotype was 62% and 58%, respectively. <it>Pfcrt </it>haplotype analysis showed that all wild type alleles were CVMNK.</p> <p>Conclusion</p> <p>Four years after the withdrawal of CQ from national treatment guidelines the prevalence of the mutant <it>pfcrt </it>allele remains at 97%. The data suggest that the combination of artesunate plus AQ may result in continued selection for the mutant <it>pfcrt </it>haplotype even after discontinuance of CQ usage.</p
    corecore