Periprosthetic joint infections:Advances in diagnosis, treatment and outcome

Arthroplasty surgery, especially total hip arthroplasty (THA), is considered amongst the most successful surgical procedures of all time. However, complications may occur that are disabling for patients. Of all complications, periprosthetic joint infection (PJI) is one of the worst, requiring additional surgery and prolonged periods of antibiotic treatment, in a best-case scenario. In the last decades, an increasing number of studies on PJI have been performed, but we still have not won the battle against microorganisms: up to 2% of patient develop PJI after arthroplasty surgery. This thesis aims to further the cause of this fight against PJI. Treatment of PJI consists of both administration of antibiotic agents, and surgery; the treatment of choice depends on several different factors. We performed a survey study to show that diagnosis and treatment differed between hospitals and between the Netherlands and Belgium. The alpha-defensin test is subject of the next three chapters, which shows good sensitivity and specificity for all three currently used definitions. A laboratory study was perfomed, in which the novel endolysin XZ.700 showed good results in the static model and performed excellently in the dynamic model, and demonstrated no toxicity on human osteocyte-like cells. A report on the results of using topical gentamicin sponges in DAIR (debridement, antibiotics, irrigation and implant retention) treatment for PJI after THA showed a success rate of 70%, and duration of symptoms for more than four weeks was associated with treatment failure. The success of DAIR treatment was studied in a larger, multicenter cohort, in which a 66% success rate was found, and several factors were identified that contributed to treatment failure: a history of rheumatoid arthritis, late infection (more than two years after initial surgery), erythrocyte sedimentation rate (ESR) of more than 60 mm/hour at presentation, duration of symptoms of more than one week, and coagulase-negative Staphylococcus PJI. Fungal PJI is very uncommon, and a systematic review showed that fungal PJI should be treated, like chronic bacterial PJI, with two-stage revision. The last two chapters describe outcomes after one-stage and two-stage revision, which seem to be comparable to outcomes after hip revision surgery in general. The thesis is concluded with discussing the different chapters, and pointing out the important items in PJI diagnosis, treatment and outcome

Resonant X-Ray Raman Spectra of Cu dd Excitations in Sr2CuO2Cl2

We present resonant x-ray Raman scattering results on Sr2CuO2Cl2, a model compound for high-Tc superconductors. We demonstrate that the dd excitations can be observed and show that the polarization dependence can be used to identify the dd excitations. We find the transition from the dx²-y² ground state to the dxy excited state at 1.35 eV and to the degenerate dxz and dyz excited states at 1.7 eV. From analysis of the polarization dependence we conclude that the d3z²-r² orbital energy is at 1.5 eV and not in the midinfrared (0.5 eV) as recently suggested. We use recent theoretical arguments to show that the d3z22r2 excitation is accompanied by a local spin flip resulting in a shift upwards of 0.2 eV due to the exchange interaction with the neighboring spins

Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus?

Apoptotic cells are thought to play an essential role in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesise that delayed or altered clearance of apoptotic cells after UV irradiation will lead to inflammation in the skin of SLE patients. Fifteen SLE patients and 13 controls were irradiated with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB). Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days, for numbers of apoptotic cells, T cells, macrophages, and deposition of immunoglobulin and complement. Additionally, to compare results with cutaneous lesions of SLE patients, 20 biopsies of lupus erythematosus (LE) skin lesions were analysed morphologically for apoptotic cells and infiltrate. Clearance rate of apoptotic cells after irradiation did not differ between patients and controls. Influx of macrophages in dermal and epidermal layers was significantly increased in patients compared with controls. Five out of 15 patients developed a dermal infiltrate that was associated with increased epidermal influx of T cells and macrophages but not with numbers of apoptotic cells or epidermal deposition of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies. Inflammatory lesions in these patients were localised near accumulations of apoptotic keratinocytes similar as was seen in the majority of LE skin lesions. In vivo clearance rate of apoptotic cells is comparable between SLE patients and controls. However, the presence of inflammatory lesions in the vicinity of apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE patients, suggests that these lesions result from an inflammatory clearance of apoptotic cells

Responses to iron deficiency in Arabidopsis thaliana : The Turbo iron reductase does not depend on the formation of root hairs and transfer cells

Arabidopsis thaliana (L.) Heynh. Columbia wild type and a root hair-less mutant RM57 were grown on iron-containing and iron-deficient nutrient solutions. In both genotypes, ferric chelate reductase (FCR) of intact roots was induced upon iron deficiency and followed a Michaelis-Menten kinetic with a K m of 45 and 54 μM Fe III -EDTA and a V max of 42 and 33 nmol Fe 2+ ·(g FW) −1 ·min −1 for the wild type and the mutant, respectively. The pH optimum for the reaction was around pH 5.5. The approximately four fold stimulation of FCR activity was independent of formation of root hairs and/or transfer cells induced by iron deficiency. Iron-deficiency-induced chlorosis and the development of a rigid root habit disappeared when ferric chelate was applied to the leaves, while FCR activity remained unchanged. The time course of the responses to iron deficiency showed that morphological and physiological responses were controlled separately.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47479/1/425_2004_Article_BF00195707.pd

A gene expression based predictor for high risk myeloma treated with intensive therapy and autologous stem cell rescue

Myeloma is characterized by a highly variable clinical outcome. Despite the effectiveness of high-dose therapy, 15% of patients relapse within 1 year. We show that these cases also have a significantly shorter post-relapse survival compared to the others (median 14.9 months vs. 40 months, p = 8.03 × 10(- 14)). There are no effective approaches to define this potentially distinct biological group such that treatment could be altered. In this work a series of uniformly treated patients with myeloma were used to develop a gene expression profiling (GEP)-based signature to identify this high risk clinical behavior. Gene enrichment analyses applied to the top differentially expressed genes showed a significant enrichment of epigenetic regulators as well as "stem cell" myeloma genes. A derived 17-gene signature effectively identifies patients at high risk of early relapse as well as impaired overall survival. Integrative genomic analyses showed that epigenetic mechanisms may play an important role on transcription of these genes