A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis

<p>Abstract</p> <p>Background</p> <p>Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements.</p> <p>Methods</p> <p>The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG.</p> <p>Results</p> <p>Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019).</p> <p>Conclusions</p> <p>This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems.</p> <p>Trial registration</p> <p>SANCTR:DOH-27-0411-2436</p

Processes in Pathogenic Biocolloidal Contaminants Transport in Saturated and Unsaturated Porous Media: A Review

There are several classes of subsurface colloids, abiotic and biotic. Basically, small particles of inorganic, organic and pathogenic biocolloids variety exist in natural subsurface system. Transport of these pathogenic biocolloidal contaminants (Viruses, bacteria and protozoa) pose a great risk in water resources and have caused large outbreaks of waterborne diseases. Biocolloid transport processes through saturated and unsaturated porous media is of significant interest, from the perspective of protection of groundwater supplies from contamination, assessment of risk from pathogens in groundwater and for the design of better water treatment systems to remove biocolloids from drinking water supplies This paper has reviewed the large volume of work that has already been done and the progress that has been made towards understanding the various basic multi-processes to predicting the biocolloid transport in saturated and unsaturated porous media. There are several basic processes such as physical, chemical and biological processes which are important in biocolloid transport. The physical processes such as advection, dispersion, diffusion, straining and physical filtration, adsorption and biological processes such as growth/decay processes and include active adhesion/detachment, survival and chemotaxis are strongly affected on biocolloid transport in saturated and unsaturated porous media.The unsaturated zone may play an important role in protecting aquifers from biocolloidal contamination by retaining them in the solid phase during their transport through the zone. Finally, author here highlighted the future research direction based on his critical review on biocolloid transport in saturated and unsaturated porous media

The Family Streptomycetaceae

The family Streptomycetaceae comprises the genera Streptomyces, Kitasatospora, and Streptacidiphilus that are very difficult to differentiate both with genotypic and phenotypic characteristics. A separate generic status for Kitasatospora and Streptacidiphilus is questionable. Members of the family can be characterized as non-acid-alcohol-fast actinomycetes that generate most often an extensively branched substrate mycelium that rarely fragments. At maturity, the aerial mycelium forms chains of few to many spores. A large variety of pigments is produced, responsible for the color of the substrate and aerial mycelium. The organisms are chemoorganotrophic with an oxidative type of metabolism and grow within different pH ranges. Streptomyces are notable for their complex developmental cycle and production of bioactive secondary metabolites, producing more than a third of commercially available antibiotics. Antibacterial, antifungal, antiparasitic, and immunosuppressant compounds have been identified as products of Streptomyces secondary metabolism. Streptomyces can be distinguished from other filamentous actinomycetes on the basis of morphological characteristics, in particular by vegetative mycelium, aerial mycelium, and arthrospores. The genus comprises at the time of writing more than 600 species with validated names. 16S rRNA gene sequence-based analysis for species delineation within the Streptomycetaceae is of limited value. The variations within the 16S rRNA genes—even in the variable regions—are too small to resolve problems of species differentiation and to establish a taxonomic structure within the genus. Comprehensive comparative studies including protein-coding gene sequences with higher phylogenetic resolution and genome-based studies are needed to clarify the species delineation within the Streptomycetaceae