Phenotype-specific therapeutic efficacy of ilofotase alfa in patients with sepsis-associated acute kidney injury.

Background: There is no effective treatment for sepsis-associated acute kidney injury (SA-AKI). Ilofotase alfa (human recombinant alkaline phosphatase) has been shown to exert reno-protective properties, although it remains unclear which patients might be most likely to benefit. We aimed to identify a clinical phenotype associated with ilofotase alfa's therapeutic efficacy.

Performance- and cost-benefit analysis of an influenza point-of-care test compared to laboratory-based multiplex RT-PCR in the emergency department.

Introduction: Influenza poses a heavy burden on emergency departments (ED) and hospital wards. Fast and reliable bedside tests are invaluable in obtaining indications for (cohort) droplet isolation precautions and improving patient flow. We performed a cost-benefit analysis comparing influenza point-of-care testing (POCT) to laboratory-based multiplex ligation-dependent probe amplification.

Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells.

Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells.

Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review.

Background: Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained.

Structure and Thermoelectric Properties of BiSbTe₃ Nanowires Grown in Flexible Nanoporous Polycarbonate Templates.

We report the room-temperature growth of vertically aligned ternary BiSbTe₃ nanowires of diameter ~200 nm and length ~12 µm, within flexible track-etched nanoporous polycarbonate (PC) templates via a one-step electrodeposition process. BiSbTe₃ nanowires with compositions spanning the entire range from pure Bi₂Te₃ ( = 0) to pure Sb₂Te₃ ( = 2) were systematically grown within the nanoporous channels of PC templates from a tartaric-nitric acid based electrolyte, at the end of which highly crystalline nanowires of uniform composition were obtained. Compositional analysis showed that the Sb concentration could be tuned by simply varying the electrolyte composition without any need for further annealing of the samples.

Polymorphisms in the multidrug-resistance 1 gene related to glucocorticoid response in rheumatoid arthritis treatment.

A substantial proportion of rheumatoid arthritis (RA)-patients experience an insufficient response to glucocorticoids, an important therapeutic agent in RA. The multidrug-resistance 1 (MDR1) gene product P-glycoprotein (P-gp) is an efflux pump that actively transports substrates, such as glucocorticoids, out of the cell. We investigated if the variation in response might be explained by single-nucleotide polymorphisms (SNPs) in the MDR1 gene.

Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848.

Background: Many patients with asthma have a T-helper type 2 (Th2) driven inflammation of the lung, whereas toll-like receptor 7 (TLR7) agonists, by inducing type I interferons, inhibit Th2 responses. In man, oral or parenteral TLR7 agonists can induce influenza-like symptoms through systemic induction of type I interferons. Design of a TLR7 agonist that is only active in the lung could reduce the risk of side effects and offer a new means for treating asthma.

Is hydroxyethyl starch necessary for sedimentation of bone marrow?

Hydroxyethyl starch (HES) is used to separate hematopoietic progenitor cells after bone marrow (BM) collection from red blood cells. The aims were to study alternatives for HAES-steril (200 kDa; not available anymore) and to optimize the sedimentation process. Using WBC-enriched product (10 × 10(9) WBC/L), instead of BM, sedimentation at 10% hematocrit using final 0.

Optimization of the freezing process for hematopoietic progenitor cells: effect of precooling, initial dimethyl sulfoxide concentration, freezing program, and storage in vapor-phase or liquid nitrogen on in vitro white blood cell quality.

Background: Adding dimethyl sulfoxide (DMSO) to hematopoietic progenitor cells (HPCs) causes an exothermic reaction, potentially affecting their viability. The freezing method might also influence this. The aim was to investigate the effect of 1) precooling of DMSO and plasma (D/P) and white blood cell (WBC)-enriched product, 2) DMSO concentration of D/P, 3) freezing program, and 4) storage method on WBC quality.

The optimal process of self-sampling in fisheries: lessons learned in the Netherlands.

At-sea sampling of commercial fishery catches by observers is a relatively expensive exercise. The fact that an observer has to stay on-board for the duration of the trip results in clustered samples and effectively small sample sizes, whereas the aim is to make inferences regarding several trips from an entire fleet. From this perspective, sampling by fishermen themselves (self-sampling) is an attractive alternative, because a larger number of trips can be sampled at lower cost.

Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment.

Introduction: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis.

A novel α(0) -thalassemia deletion in a Greek patient with HbH disease and β-thalassemia trait.

Objectives: To determine the molecular basis in a Greek child suspected of having HbH disease and β-thalassemia trait.

Methods:   Standard hematology, Hb electrophoresis, and HPLC. Multiplex ligation-dependent probe amplification (MLPA), direct sequencing, and breakpoint characterization by NimbleGen fine-tiling array analysis.

CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial.

Objective: C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects of a CCR5 antagonist in collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in patients with active RA were explored.

Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions.

In psoriasis, leukocytes that infiltrate skin lesions have been shown to be involved in the pathogenesis of this disease. Previous investigations reporting the presence of CXCR3(+) T lymphocytes in psoriatic lesional skin have suggested a role of this receptor in the recruitment of T cells into the lesion. The purpose of this study was to quantify the mRNA levels of CXCR3 and to perform a systematic analysis of the cell populations that express CXCR3 in human lesional and non-lesional psoriatic biopsies.

Involvement of breast cancer resistance protein expression on rheumatoid arthritis synovial tissue macrophages in resistance to methotrexate and leflunomide.

Objective: To determine whether multidrug-resistance efflux transporters are expressed on immune effector cells in synovial tissue from patients with rheumatoid arthritis (RA) and compromise the efficacy of methotrexate (MTX) and leflunomide (LEF).

Methods: Synovial tissue biopsy samples obtained from RA patients before treatment and 4 months after starting treatment with MTX (n = 17) or LEF (n = 13) were examined by immunohistochemical staining and digital image analysis for the expression of the drug efflux transporters P-glycoprotein, multidrug resistance-associated protein 1 (MRP-1) through MRP-5, MRP-8, MRP-9, and breast cancer resistance protein (BCRP), and the relationship to clinical efficacy of MTX and LEF was assessed.

Results: BCRP expression was observed in all RA synovial biopsy samples, both pretreatment and posttreatment, but not in control noninflammatory synovial tissue samples from orthopedic patients.

Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients.

Objective: To determine the expression of folate receptor beta (FRbeta) in synovial biopsy tissues and peripheral blood lymphocytes from rheumatoid arthritis (RA) patients and to identify novel folate antagonists that are more selective in the targeting and internalization of FRbeta than methotrexate (MTX).

Methods: Immunohistochemistry and computer-assisted digital imaging analyses were used for the detection of FRbeta protein expression on immunocompetent cells in synovial biopsy samples from RA patients with active disease and in noninflammatory control synovial tissues. FRbeta messenger RNA (mRNA) levels were determined by reverse transcription-polymerase chain reaction analysis.

[Finnish questionnaire reasonably good predictor of the incidence of diabetes in The Netherlands].

Objective: To establish whether the Finnish diabetes risk score for predicting the incidence of diabetes (FINDRISK) is also valid in the Netherlands, and to choose cut-off points suitable for the Dutch situation.

Design: . Descriptive.

Clinical identification and treatment of a rapidly progressing disease state in patients with rheumatoid arthritis.

Inflammation is the major factor driving the progression of structural damage in rheumatoid arthritis (RA); therefore, it is critical to achieve rapid suppression of inflammation to maximize disease control. The severity of inflammation and progression of joint damage varies from patient to patient. Some patients have the propensity to change slowly over time and then progress in a more rapid and dynamic fashion.

The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium.

Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha expression in the synovium before initiation of treatment.

Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28).

Quantitative image analysis of synovial tissue.

Quantitative image analysis is a form of imaging that includes microscopic histological quantification, video microscopy, image analysis, and image processing. Hallmarks are the generation of reliable, reproducible, and efficient measurements via strict calibration and step-by-step control of the acquisition, storage and evaluation of images with dedicated hardware and software. Major advantages of quantitative image analysis over traditional techniques include sophisticated calibration systems, interaction, speed, and control of inter- and intraobserver variation.

Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with alpha2 macroglobulin in serum of rheumatoid arthritis patients.

Objective: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in alpha2 macroglobulin/MMP (alpha2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients.

Methods: A total of 102 RA patients from a prospective, double-blind, randomised clinical trial comparing leflunomide and methotrexate were selected; clinical data and blood samples were collected at baseline, at 4 months and at 1 year. Serum MMP activity levels in alpha2M were quantified using low molecular weight fluorogenic substrates, indicating the proportion of activated MMPs that were not inhibited by specific tissue inhibitors of MMP (TIMP).

Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor.

Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin.

Microscopic measurement of inflammation in synovial tissue: inter-observer agreement for manual quantitative, semiquantitative and computerised digital image analysis.

Objectives: To evaluate inter-observer agreement for microscopic measurement of inflammation in synovial tissue using manual quantitative, semiquantitative and computerised digital image analysis.

Methods: Paired serial sections of synovial tissue, obtained at arthroscopic biopsy of the knee from patients with rheumatoid arthritis (RA), were stained immunohistochemically for T lymphocyte (CD3) and macrophage (CD68) markers. Manual quantitative and semiquantitative scores for sub-lining layer CD3+ and CD68+ cell infiltration were independently derived in 6 international centres.

Evidence-based review of biologic markers as indicators of disease progression and remission in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease characterised by inflammation resulting in structural joint damage and functional disability. Tumour necrosis factor-alpha (TNFalpha) is a pivotal mediator and driver of inflammation in RA. Inflammation is closely related to the production of C-reactive protein (CRP), and a close correlation exists between serum CRP and TNFalpha levels.