Unhomely

As winter’s dusk encroaches on The Rocks, under the shadowy reach of the Sydney Harbour Bridge, anonymous and unnoticed by the lively crowds, the shutters open, and the blank upper windows flash alive in vacant Reynold’s Cottage. Through the unraveling night the cottage innards twist and flutter, spit and ooze with glimpses of disarray, despair and turmoil, the windows spirit-lenses on the turbulent world of mid-twentieth century Sydney

Uloga Ivana Merza u liturgijskoj obnovi

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JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia

JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions). JAK2 translocations were restricted to BCR-ABL1-like cases. Momelotinib and ruxolitinib were cytotoxic in both JAK2 translocated and JAK2 mutated cells, although efficacy in JAK2 mutated cells highly depended on cytokine receptor activation by TSLP. However, our data also suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and microenvironment-induced resistance. Furthermore, inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon release of the inhibitors. This preclinical evidence implies that further optimization and evaluation of JAK inhibitor treatment is necessary prior to its clinical integration in pediatric BCP-ALL

Tuberculosis control in Africa in the face of the HIV epidemic.

Contains fulltext : 19281_tubecoina.pdf (publisher's version ) (Open Access)The thesis describes some studies and reflections on aspects of tuberculosis control in Africa, specifically in Malawi, in the face of the HIV epidemic. The scourge of the dual infection reaches catastrophic proportions. The impact on economy and mortality is devastating. In the research agenda of the National Tuberculosis Control Programme in collaboration with the College of Medicine of the University of Malawi several topics have been identified for operational research to improve control measures in the fight against TB and AIDS in Africa. Some of these topics and the studies that resulted from it, form the basis of thesis. Several chapters describe studies in the diagnostic process such as a) gender distribution in access to sputum laboratory services, b) a simple strategy in the diagnosis of tuberculous lymphadenitis, c) the role of traditional healers and traditional medicine in TB patients before they are diagnosed in the conventional health institutions and in an other study the care seeking behaviour these patients express, d) the viability of mycobacteria within and outside the refrigerator which is important in remote areas with poor infrastructure and regular power interruptions. Furthermore, there are two chapters that contain studies in the treatment phase: First, a major UNAIDS sponsored project investigates the effect on survival and morbidity of prophylaxis with two different dosages of cotrimoxazole in 579 HIV seropositive TB patients. It suggests that a single dose of 480 mg is as effective as a double dose and that there is a beneficial effect compared to a historical control cohort and the national TB programme outcome parameters. The second study addresses the problem of treatment compliance of TB patients. In a group of about 100 patients registered as defaulters 80% were actually wrongly registered. Lastly, two chapters reflect on possible strategies of TB control in the face of the HIV epidemic in sub-Saharan Africa, and a special emphasis is put on the problems that accompanies the introduction, the delivery and the monitoring of antiretroviral treatmentKUN, 16 juni 2003Promotores : Meer, J.W.M. van der, Herwaarden, C.L.A. van Co-promotores : Harries, A.D., Zijlstra, E.E119 p

Global clinical trials for the treatment of TB with thioridazine

Item does not contain fulltextCurrent evidence shows that thioridazine (THZ) is ready for global clinical evaluation, while some of its derivatives and other efflux pump inhibitors reach the end stage of preclinical evaluation. In this paper, a clinical trial plan is described that investigates the antituberculosis potency, the safety profile and the role of THZ and/or its derivatives in the treatment of TB in humans, both in patients infected with drug sensitive strains as in patients infected with multi or extensive drug resistant strains of Mycobacterium tuberculosis and some of the patents related to thioridazine are also discussed

Networking in international health: introducing the Federation of European Societies for Tropical Medicine and International Health (FESTMIH).

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Xanthine oxidase inhibition by allopurinol increases in vitro pyrazinamide-induced hepatotoxicity in HepG2 cells.

Contains fulltext : 87446.pdf (publisher's version ) (Open Access)Despite the important role of pyrazinamide in tuberculosis treatment, little is known about the mechanism of pyrazinamide-induced hepatotoxicity. We inhibited xanthine oxidase in HepG2 cells by using a nontoxic concentration of allopurinol, a well-known xanthine-oxidase inhibitor. This increased in vitro pyrazinamide toxicity in HepG2 cells, which suggests that the hydroxy metabolites of pyrazinamide are probably not fully responsible for pyrazinamide-induced toxicity, and that pyrazinoic acid and pyrazinamide are involved in pyrazinamide toxicity.1 juli 201

Therapy for Tuberculous Meningitis

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