Post-infection immunocomplex glomerulonephritis and Legionnaires' disease in a patient with adult Still's disease during treatment with interleukin 1 receptor antagonist anakinra: a case report

<p>Abstract</p> <p>Introduction</p> <p>Legionellosis is a systemic disease that primarily affects the lungs. However, dysfunction in many organ systems, including the kidneys, has also been described. There are only a few reported cases of renal dysfunction in patients with legionellosis.</p> <p>Case presentation</p> <p>A 27-year-old Caucasian woman with known adult Still's disease was admitted to our hospital for community-acquired pneumonia, due to <it>Legionella </it>infection, with acute renal failure. Although her respiratory symptoms responded well to antibiotic treatment, her renal function worsened, with severe proteinuria and edema. A renal biopsy showed extracapillary and endocapillary proliferative glomerulonephritis with accompanying chronic and acute interstitial nephritis. This was consistent with a post-infection immunocomplex glomerulonephritis. After initiation of steroid therapy, her renal function improved. Additionally, therapy with diuretics and an angiotensin-converting enzyme inhibitor was initiated because of persistent proteinuria. Under this treatment regimen, her severe edema and proteinuria disappeared.</p> <p>Conclusion</p> <p>To the best of our knowledge, there is only a handful of reported cases of post-infection glomerulonephritis with a nephrotic syndrome in a patient with legionellosis. Our findings suggest that, in patients with Legionnaires' disease with renal failure, post-infection immunocomplex glomerulonephritis should be considered and steroid therapy may be an effective modality to treat the renal complication.</p

Challenges facing educators’ in the inclusion of Attention Deficit Hyperactivity Disordered (ADHD) learners in the mainstream classroom

Submitted in fulfillment of the requirements for the degree MASTERS IN EDUCATION In the Department of Educational Psychology and Special Education of the Faculty of Education at the University of Zululand, 2010.The aim of this study was to investigate the challenges facing educators’ in the inclusion of ADHD learners in the mainstream classroom. As an introduction to the study the challenges faced by educators’ in the inclusion of ADHD learners in mainstream classes were reviewed by means of a study of available and relevant literature. Educators are people who make learning and teaching possible and their own challenges in what is happening in the classroom are of crucial importance. Research done in South Africa on challenges faced by educators’ in inclusive education indicated that educators in mainstream classrooms generally express negative attitudes to mainstreaming policies and thus finds himself with many challenges. In the new education dispensation educators in mainstream classrooms have to accommodate learners with impairments, such as the ADHD child. Inclusion makes additional demands on educators because of the special educational needs of learners with impairments. The challenges facing educators in inclusion and their efficacy in meeting the special needs of learners with impairments play a determining role in the successful implementation of an inclusive education policy. For the purpose of the empirical investigation a self-structured questionnaire was utilized. An analysis was done of 110 questionnaires completed by primary school educators from the Mafukezela Gandhi district on the North Coast of KwaZulu Natal. The data was processed and interpreted by means of descriptive statistics. Essentially the following were the main findings from the empirical study: Educators lack the necessary knowledge, skills, training and experience of learners with special educational needs. Educators have difficulty in identifying ADHD learners. Educators needed to change their teaching methods to accommodate learners with diverse educational needs. The study concludes with a summary and findings from the literature study and descriptive statistics. Based on these findings the following recommendations were made: The development of curricula, institutions and methods of assessments must include a variety of strategies to accommodate learners with special educational needs, such as ADHD learners. The basic training of educators must include compulsory courses such as orthopedagogics that will enable them to cope with the demands for inclusion of learners with special educational needs

Interspecies evaluation of a physiologically based pharmacokinetic model to predict the biodistribution dynamics of dendritic nanoparticles.

The exposure of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) was determined in mouse, rat and dog, with the aim of investigating interspecies differences facilitating clinical translation. Plasma area under the curves (AUCs) were found to be dose proportional across species, while dose normalized concentration time course profiles in plasma, liver and spleen were superimposable in mouse, rat and dog. A physiologically based pharmacokinetic (PBPK) model, previously developed for mouse, was evaluated as a suitable framework to prospectively capture concentration dynamics in rat and dog. The PBPK model, parameterized either by considering species-specific physiology or using alternate scaling methods such as allometry, was shown to capture exposure profiles across species. A sensitivity analysis highlighted API systemic clearance as a key parameter influencing released API levels. The PBPK model was utilized to simulate human exposure profiles, which overlaid dose-normalized data from mouse, rat and dog. The consistency in measured interspecies exposures as well as the capability of the PBPK model to simulate observed dynamics support its use as a powerful translational tool

Rat biodistribution data and model fits in plasma, liver and spleen.

Total API data is represented by open circles and released API data by stars. Total API simulated profiles are shown in solid lines; released API simulated profiles are shown in dotted lines (in–vitro scaled API CL value = 2.8 L/h/Kg), or dashed line (in–vivo/measured API CL = 2.1 L/h/Kg.</p

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The exposure of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) was determined in mouse, rat and dog, with the aim of investigating interspecies differences facilitating clinical translation. Plasma area under the curves (AUCs) were found to be dose proportional across species, while dose normalized concentration time course profiles in plasma, liver and spleen were superimposable in mouse, rat and dog. A physiologically based pharmacokinetic (PBPK) model, previously developed for mouse, was evaluated as a suitable framework to prospectively capture concentration dynamics in rat and dog. The PBPK model, parameterized either by considering species-specific physiology or using alternate scaling methods such as allometry, was shown to capture exposure profiles across species. A sensitivity analysis highlighted API systemic clearance as a key parameter influencing released API levels. The PBPK model was utilized to simulate human exposure profiles, which overlaid dose-normalized data from mouse, rat and dog. The consistency in measured interspecies exposures as well as the capability of the PBPK model to simulate observed dynamics support its use as a powerful translational tool.</div

Mouse biodistribution data and model fits in plasma, liver and spleen.

Total API data is represented by open circles and released API data by stars. Total API simulated profiles are shown in solid lines; released API simulated profiles are shown in dotted lines (in–vitro scaled API CL value = 2 L/h/Kg), dashed–dotted line (value obtained from previous publication CL = 1 L/h/Kg) or dashed line (in–vivo/measured API CL = 2.3 L/h/Kg).</p

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The exposure of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) was determined in mouse, rat and dog, with the aim of investigating interspecies differences facilitating clinical translation. Plasma area under the curves (AUCs) were found to be dose proportional across species, while dose normalized concentration time course profiles in plasma, liver and spleen were superimposable in mouse, rat and dog. A physiologically based pharmacokinetic (PBPK) model, previously developed for mouse, was evaluated as a suitable framework to prospectively capture concentration dynamics in rat and dog. The PBPK model, parameterized either by considering species-specific physiology or using alternate scaling methods such as allometry, was shown to capture exposure profiles across species. A sensitivity analysis highlighted API systemic clearance as a key parameter influencing released API levels. The PBPK model was utilized to simulate human exposure profiles, which overlaid dose-normalized data from mouse, rat and dog. The consistency in measured interspecies exposures as well as the capability of the PBPK model to simulate observed dynamics support its use as a powerful translational tool.</div