On Tautomerism and Amphoterism: An In-Depth Structural and Physicochemical Characterization of Ammeline and Some of Its Salts.

Ammeline is a simple, readily available, molecular compound, which has been known for nearly 200 years. Despite that, no proper structural characterization of ammeline has been conducted so far. For this reason, the prevalent tautomeric form of ammeline in the solid remained unknown to this date. In the course of this study, its crystal structure was finally established by single-crystal X-ray diffraction. In this structure, ammeline is exclusively found as its 4,6­diamino-1,3,5-triazin-2(1H)-one tautomer and adopts layered structure with an exceptionally high hydrogen bond density. Ammeline shows an interesting amphoteric behavior. Therefore, the synthesis and structural characterization of some of its salts were carried out to investigate the influence of the protonation degree on its molecular structure. In particular, the crystal structure of silver ammelinate monohydrate was solved as the first reported structure containing deprotonated ammeline. Moreover, the crystal structures of three different modifications of ammelinium perchlorate were elucidated and the transformation conditions between them were studied. Lastly, the crystal structure of ammelinediium diperchlorate monohydrate, containing unprecedented doubly protonated ammeline, was determined. The products' thermal behavior was studied by differential thermal analysis and thermogravimetric analysis. The perchlorate salts were additionally examined for their potential as insensitive high-energy-density materials.

1- and 2-Tetrazolylacetonitrile as Versatile Ligands for Laser Ignitable Energetic Coordination Compounds.

1- and 2-Tetrazolylacetonitrile (1- and 2-TAN) have been synthesized by the reaction of chloroacetonitrile with 1H-tetrazole under basic conditions. They further were reacted with sodium azide in the presence of zinc(II) chloride to form 5-((1H-tetrazol-1-yl)methyl)-1H-tetrazole (1-HTMT) and 5-((2H-tetrazol-2-yl)methyl)-1H-tetrazole (2-HTMT). The nitrogen-rich compounds have been applied as ligands for Energetic Coordination Compounds (ECCs) and show interesting coordinative behavior due to different bridging modes. The structural variability of the compounds has been proved by low-temperature X-ray analysis. The ECCs were analyzed for their sensitivities to provide information about the safety of handling and their capability to serve as primary explosives in detonator setups to replace the commonly used lead styphnate and azide. All colored ECCs were evaluated for their ignitability by laser initiation in translucent polycarbonate primer caps. In addition, the spin-crossover characteristics of [Fe(1-TAN)6](ClO4)2 were highlighted by the measurement of the temperature-dependent susceptibility curve.

Synthesis of Bridged Tetrazoles with Promising Properties and Potential Applications by a One-Step Finkelstein Reaction.

Numerous nitramine bridged compounds which show promising combinations of properties have already been identified in the area of energetic materials. In this work, four new nitrazapropane bridged tetrazoles, as well as four new trinitrazaheptane tetrazoles and three oxapropane bridged tetrazoles were synthesized and fully characterized. These new compounds can all be synthesized by a simple, one-step synthesis using Finkelstein conditions. All of these new energetic materials were characterized using NMR spectroscopy, single crystal X-ray diffraction, vibrational analysis and elemental analysis. The thermal behaviour of these compounds was studied by differential thermal analysis (DTA) and partly by thermogravimetric analysis (TGA). The BAM standard method was used to determine the sensitivities towards impact (IS) and friction (FS). The enthalpies of formation were calculated at the CBS-4M level, and the energetic performances were calculated using the EXPLO5 (V6.06.01) computer code. The properties of the new compounds were compared to each other as well as to the known energetic material RDX. Moreover, the iron(II) and copper(II) perchlorate complexes with 1,3-bis-1,1-tetrazolylnitrazapropane as ligand were prepared and investigated.

The Adjustability of Physicochemical Properties: Comparison of 1-Vinyl-5H-tetrazole and 1-Allyl-5H-tetrazole as Ligands in 3d Metal Energetic Coordination Compounds.

Energetic coordination compounds (ECCs) show promising properties to be used as potential substitutes for highly toxic lead-containing primary explosives. The concept is to combine the three building blocks: (i) ligand, (ii) transition metal, and (iii) anion, acting as (i) fuel, (ii) matrix, and (iii) oxidizer (e.g., ClO4-, NO3-, ClO3-) or energetic component (e.g., DN-, N3-, picrate, styphnate, trinitrophloroglucinate). By variation of the ligands, the complexes' properties can be adjusted toward their desired performance and sensitivities. In the present study, 1-vinyl-5H-tetrazole (1-VTZ, 1) and 1-allyl-5H-tetrazole (1-ATZ, 2) were used as nitrogen-rich endothermic ligands to form 3d metal (Mn2+, Fe2+, Cu2+, Zn2+, Co2+, Ni2+)-based ECCs. The influence of the introduction of an unsaturated C-C bond (1-ETZ vs 1-VTZ and 1-PTZ vs 1-ATZ) on the performance and sensitivity of the complexes is discussed, as is the lengthening of the alkenyl chain (1-VTZ vs 1-ATZ). For further insights, the novel complexes were compared to literature-known complexes based on N1-substituted C2- and C3-derived tetrazole ligands, respectively. The ligand 1-VTZ (1) was prepared by elimination of hydrogen chloride from 1-(2-chloroethyl)-5H-tetrazole in methanolic KOH solution. 1-ATZ (2) was obtained by a heterocyclization reaction of allylamine with triethyl orthoformate and sodium azide in an acetic acid medium. All compounds were intensively characterized with analytical methods such as XRD, IR, EA, DTA, TGA, and sensitivity measurements (IS and FS). The energetic performances were visibly evaluated in fast heating experiments. Furthermore, PETN initiation and laser ignition experiments were carried out for promising ECCs.

Diagnostic value of open incisional biopsies in suspected, difficult-to-diagnose periprosthetic hip joint infection prior to revision surgery.

INTRODUCTION: Prior to revision of total hip arthroplasty (THA), low-grade chronic periprosthetic joint infection (PJI) is often difficult to diagnose. We aimed to determine the diagnostic accuracy of open incisional tissue biopsy for the prediction of PJI prior to THA revision in cases with culture-negative or dry tap joint aspirates. MATERIALS AND METHODS: This retrospective single-center study includes 32 consecutive THA revision cases with high clinical suspicion of low-grade chronic PJI of the hip with culture-negative or dry tap joint aspirates and without systemic signs of infection. Open incisional biopsy (OIB) was performed prior to revision surgery. Periprosthetic tissue samples were analyzed by microbiology and histopathology for PJI. During definitive revision arthroplasty, identical diagnostics were repeated. Results from both procedures were compared and sensitivity, specificity, positive and negative predictive values of OIB for the final diagnosis were calculated. RESULTS: Average age at revision was 69.3 ± 13.5 years. The sensitivity of the OIB procedure was 80% (microbiology), 69% (histology) and 82% for combined analyses (microbiology and histology). Specificity of OIB was 80% (microbiology), 94% (histology) and 60% for combined analyses. CONCLUSIONS: Open tissue biopsy performed in cases with culture-negative or inconclusive synovial fluid aspirates prior to revision of THA has limited diagnostic accuracy for the prediction of PJI. The procedure does not reliably close the diagnostic gap in a substantial number of cases. In this difficult patient population, risk of an open procedure may outweigh benefits and alternative less invasive methods should be considered for the preoperative diagnosis of PJI.

1-(Nitratomethyl)-5H-tetrazole: A Highly Sensitive Ligand with Improved Oxygen Balance for Laser-Ignitable Coordination Compounds.

For the first time, the highly sensitive 1-(nitratomethyl)-5H-tetrazole (1-NAMT) was synthesized, representing the shortest possible 1-(nitratoalkyl)-5H-tetrazole with a combined nitrogen and oxygen content of 81.4%. Compared to its related ethyl derivative, 1-(nitratoethyl)-5H-tetrazole, it exhibits improved oxygen balance, resulting in higher detonation parameters. 1-NAMT was thoroughly analyzed by single-crystal diffraction experiments accompanied by elemental analysis, IR spectroscopy, and multinuclear (1H, 13C, and 14N) NMR measurements. The thermal behavior of 1-NAMT was analyzed by differential thermal analysis supported by thermogravimetric analysis. Furthermore, energetic coordination compounds (ECCs) of Cu with different inorganic (e.g., nitrate, chlorate, and perchlorate) and nitroaromatic anions (e.g., picrate and styphnate) were synthesized and thoroughly analyzed. It is shown that the formation of ECCs with nitroaromatic anions (Tdec ∼ 180 °C) is a suitable strategy to improve the rather low thermal stability of 1-NAMT (125 °C).

Nerve Surgery to Treat Intractable Genitofemoral Neuropathic Pain following Laparoscopic Live Kidney Donation.

To date live laparoscopic donor nephrectomies (LLDN) are frequently performed. The most common complications entail bleeding, wound infection, and incisional hernia. Here we discuss a 50-year-old patient with a severe less known complication, namely, postoperative persistent neuropathic pain in the scrotum and left upper leg. Satisfactory pain control could not be obtained in 3 years of postoperative pain treatment which consisted of neuroleptic drugs, blocks of the L1/L2 dorsal roots with local anaesthetics, and pulsed radiofrequency lesioning. Exploratory laparoscopy was performed to assess the aspect of the genitofemoral nerve (GFN). A hemoclip used for the closure of the ureter at the time of nephrectomy was found in close relation to the GFN. The clip was removed and the GFN was subsequently cut proximal to the side of this clip. Soon after surgery the patient was completely pain-free and could return to his normal activities. Surgery should be considered in case of GFN neuropathic pain following LLDN.

Persistent Q fever and ischaemic stroke in elderly patients.

Whether persistent or chronic Q fever may act as a risk factor for stroke is unknown. A case-control study was conducted in the Hospital Universitario de Burgos (Spain) between February 2011 and December 2012. A total of 803 samples from 634 consecutive hospitalized patients ≥65 years old were tested, of whom 111 were cases (patients with prevalent or incident ischaemic stroke and/or transient ischaemic attack) and 523 were controls (patients without ischaemic stroke and/or transient ischaemic attack). Immunoglobulin G (IgG) antibody titres phase I and II against Q fever, and IgG antibodies levels against Chlamydia pneumoniae and cytomegalovirus (CMV), were determined using immunofluorescence assay and ELISA methods, respectively. Phase I IgG titres against Coxiella burnetii ≥1:256 (compatible with chronic or persistent Q fever) were detected in 16 of 110 (14.5%) cases and in 32 of 524 (6.1%) controls; P = .004, odds ratio (OR) 2.6, 95% confidence interval (CI) 1.3 to 4.9. This ratio was maintained after adjusting for age, sex, hypertension, dyslipidaemia, cardioembolic focus, smoking, diabetes, other cardiovascular diseases, C-reactive protein, and leukocyte count (OR 2.6, 95% CI 1.3 to 5.3). High-titre IgG antibodies (top quartile) against CMV (OR 2.1, 95% CI 1.3 to 3.5), but not against C. pneumoniae (OR 0.9, 95% CI 0.5 to 1.6), also were associated with ischaemic stroke after adjustment for risk factors. In conclusion, serology compatible with persistent or chronic Q fever is associated with ischaemic stroke in elderly patients. High levels of IgG antibodies against CMV, but not against C. pneumoniae, also are associated with ischaemic stroke in these patients.

[Thromboprophylaxis and platelet aggregation inhibitors in spinal surgery: perioperative management]. / Thromboseprophylaxe und Aggregationshemmer in der Wirbelsäulenchirurgie: perioperative Management.

BACKGROUND: The perioperative use of anticoagulants (AC) and platelet aggregation inhibitors (PAI) in the field of spinal surgery suggests an increased rate of epidural bleeding. However, evidence is lacking and these medications are most often indispensable in the prevention of thromboembolic complications. Comprehensive recommendations for the correct use of AC and PAI are lacking. OBJECTIVE: The aim of this study was an analysis of the current situation with regards to the use of AC and PAI in spinal surgery and development of new recommendations. MATERIAL AND METHODS: Two independent surveys on the perioperative use of AC and PAI were obtained from centers for spinal surgery in Germany. The study obtained information on the perioperative use of AC and PAI, risk assessment of thromboembolic and hemorrhagic events as well as on the type and extent of the substance groups used. RESULTS: Almost the entire patient collective (98%) received perioperative low molecular weight heparin. In 64% the medical prophylaxis was started before surgery and in 36% after surgery. The period of prophylaxis was determined arbitrarily. Approximately 40% of interviewees employed paravertebral infiltration and 19% injected into the epidural space in patients on PAI medication. Open spinal canal surgery was performed in 30% of PAI medicated patients and closed spinal canal surgery was executed in 40%. The risk assessment of PAI differed significantly between aspirin and receptor blocker medication as well as dual administration of PAI. DISCUSSION: The use of AC and PAI in spinal surgery in Germany is very heterogeneous and large deviations from the guidelines frequently occurred. Therefore, there is a strong need for further studies to accurately assess the perioperative use of AC and PAI and to formulate precise recommendations.

High fluoride and low calcium levels in drinking water is associated with low bone mass, reduced bone quality and fragility fractures in sheep.

UNLABELLED: Chronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass. INTRODUCTION: Understanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures. METHODS: Dorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (µCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy. RESULTS: The fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure. CONCLUSIONS: Our data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone mass and (ii) can cause fragility fractures and (iii) that the prevalence of skeletal fluorosis especially due to groundwater exposure should be reviewed in many areas of the world as low bone mass alone does not exclude fluorosis.

Association between serological evidence of past Coxiella burnetii infection and atherosclerotic cardiovascular disease in elderly patients.

Q fever, caused by Coxiella burnetii, may cause vascular complications, but the role that this infection may play in the development of atherosclerotic cardiovascular disease remains unknown. This study examined the association between Q fever serology and cardiovascular disease in a region where Q fever is endemic. A case-control study was conducted in the Hospital Universitario de Burgos (Spain) between February 2011 and June 2012. A total of 513 samples were tested, from 454 hospitalized patients ≥65 years old, of whom 164 were cases (patients with prevalent or incident coronary heart, cerebrovascular or peripheral artery, disease) and 290 controls (patients without cardiovascular disease). Serum IgG antibody phase II titres against Q fever were determined by immunofluorescence assay. Seropositivity (titres ≥1:256) was detected in 84/164 (51.2%) cases and in 109/290 (37.6%) controls (p = 0.005; OR, 1.7; 95% CI, 1.1-2.5). This ratio increases when adjusted for sex, hypertension, dyslipidaemia, smoking, diabetes and atrial fibrillation (OR, 2.6; 95% CI, 1.5-4.7). The geometric mean titre (GMT) for C. burnetii phase II assay was higher in cases than in controls (p = 0.004). We found no significant relationship between cardiovascular disease and C. pneumoniae, and Cytomegalovirus seropositivity (both determined by the IgG ELISA method). In conclusion, serological evidence of past Q fever is associated with atherosclerotic cardiovascular disease in elderly patients in an endemic region.

[Understand the neurodevelopment of language: a necessity to prevent learning disabilities in children]. / Comprendre le neurodéveloppement du langage, une nécessité pour prévenir les troubles des apprentissages de l'enfant ?

Clinical and radiological knowledge of language development in the former premature infant compared to the newborn allows us to argue for exploration of the sensorimotor co-factors required for proper language development. There are early representations of the maternal language in the infant's visual, auditory, and sensorimotor areas, activated or stabilized by orofacial and articulatory movements. The functional architecture of language is different for vulnerable children such as premature infants. We have already mentioned the impact of early dysfunction of the facial praxis fine motor skills in this population presenting comprehension disorders. A recent meta-analysis confirms the increasing difficulty of understanding between 3 and 12 years, questioning the quality of the initial linguistic processes. A precise analysis of language, referenced from 3 years of age, should be completed by sensorimotor tests to assess possible constraints in automating neurolinguistic foundations. The usual assessment at this age can exclude sensory disturbances and communication and offers guidance and socialization. However, a recent study shows the ineffectiveness of "language-reinforced immersion" at 2 and 3 years in a population of vulnerable children. The LAMOPRESCO study of language and motor skills in the premature infant (National PHRC 2010) has assessed language and sensorimotor skills of preterm-born (<33 weeks) 3.5-year-old children without cerebral palsy. Fragile children were randomized into 2 groups, 1 stimulated by a specific individual protocol, the other given guidance. The primary endpoint was phonology, assuming that it is composed of very early good-quality sensorimotor integration stabilized by the child's oral facial motor skills before 5 years of age. This developmental integrative dynamic validates the "motor theory of speech perception." Early and accurate assessment of language and the patient's constraints should differentiate and specify management strategies for all children, whatever their background and pathologies.

Combined clopidogrel and aspirin treatment up to surgery increases the risk of postoperative myocardial infarction, blood loss and reoperation for bleeding in patients undergoing coronary artery bypass grafting.

OBJECTIVES: Recent guidelines suggest that patients undergoing coronary artery bypass grafting (CABG) should discontinue clopidogrel and aspirin (ASA) 5 and 2-10 days, respectively, before surgery to reduce postoperative bleeding and its complications. The aim of our study was to evaluate the relationship between the timing of discontinuing clopidogrel + ASA and early clinical outcomes in patients undergoing CABG. METHODS: Four thousand three hundred and thirty consecutive patients underwent isolated CABG from April 2004 to February 2009. Of these, 926 patients received double antiplatelet therapy in the 14 days prior to surgery. Patients were stratified into three groups: clopidogrel + ASA within 5 and 2 days, respectively, before surgery (Group A, n = 287); clopidogrel within 5 days + ASA stopped 2-10 days before surgery or clopidogrel stopped 5 days + ASA within 2 days of surgery (Group B, n = 308) and clopidogrel + ASA discontinued >5 and 10 days, respectively, before surgery (control group, n = 331). RESULTS: Overall mortality was 0.8%. The incidence of postoperative myocardial infarction (MI) was 5.2, 1 and 1.8% in Groups A, B and control, respectively (P = 0.004). Reoperation for bleeding occurred in 4.5, 2.9 and 1.2% (P = 0.04) and total chest drainage was 761 ± 473, 720 ± 421 and 687 ± 302 ml in Groups A, B and control, respectively (P = 0.06). Multivariable analysis revealed that Group A was an independent predictor of postoperative MI (P = 0.02), reoperation for bleeding (P = 0.02), blood transfusions (P = 0.003) and blood losses (P = 0.015). CONCLUSIONS: Clopidogrel in combination with ASA up to the time of surgery is associated with an increased risk of postoperative MI, blood loss and reoperation for bleeding in patients undergoing CABG.

The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an emerging condition in patients undergoing long-term administration of bisphosphonates (BP) for the treatment of osteoporosis and hypercalcaemia associated with malignancy, multiple myeloma, and metastatic breast and prostate cancers. This is a follow-up study, its purpose was to examine the effects in-vitro of intravenous zoledronic acid (ZOL) and pamidronate (PAM) and oral alendronate (FOS) on the human oral cavity using gingival fibroblasts and osteoblasts cells and, in addition, osteogenic sarcoma cells (SaOS-2-cells). MATERIALS AND METHODS: Human gingival fibroblasts, osteoblasts and SaOS-2-cells were seeded on multiple 6-well plates at a density of 5 × 10(5)cells in a 4-week cell culture. Four different concentrations (1, 5, 10, 20 µM) of each BP (ZOL, PAM, FOS) and pyrophosphate were used in this study. RESULTS: All BP decreased collagen production and lowered cell proliferation in-vitro. ZOL was the component with most inhibitory effect. CONCLUSION: The findings in this study suggest that ZOL, PAM and FOS generally diminish cell proliferation and collagen production of human gingival fibroblasts, osteoblasts and SaOS-2-cells. The present follow-up study shows that not only ZOL and PAM but also FOS have a strong inhibitory effect on collagen production and cell survival in-vitro.

Mild renal dysfunction in patients undergoing cardiac surgery as a new risk factor for EuroSCORE.

BACKGROUND: It has recently been suggested that mild renal dysfunction is associated with increased mortality in cardiac surgery; however, this risk factor is not accounted for in the European System for Cardiac Operative Risk Evaluation (EuroSCORE). The aim of the present study was to assess the effect of mild renal dysfunction as a predictor of operative mortality and develop and validate a modified logistic EuroSCORE model. METHODS: This was a retrospective, observational, cohort study of prospectively collected data on 16 086 consecutive patients undergoing cardiac surgery at the Bristol Heart Institute between April 1996 and February 2009. To develop a modified logistic EuroSCORE, data were dived into developmental and validation datasets (11 596 and 4490 patients respectively). The relationship between risk factors and mortality was assessed using univariate and logistic regression analysis. Calibration and discrimination were assessed by Hosmer Lemeshow χ(2) test and receiving operative characteristic (ROC) curve. RESULTS: Overall hospital mortality was 2.6%. At multivariate analysis, 13 out of 18 variables of the EuroSCORE influenced operative mortality; moreover, preoperative mild renal dysfunction, defined as serum creatinine 130-199 µmol/l, was identified as a new risk factor for mortality (OR 1.819, 95% CI 1.353 to 2.447, p<0.0001). EuroSCORE was able to predict mortality; however, modified logistic EuroSCORE had a better discriminatory power (area under ROC: 0.844 vs 0.784, p=0.002). CONCLUSIONS: Preoperative mild renal dysfunction is an independent risk factor for mortality in patients undergoing cardiac surgery. These findings now need to be validated with data from other centres.

A clinical score to predict the need for intraaortic balloon pump in patients undergoing coronary artery bypass grafting.

BACKGROUND: There is no accepted consensus on the definition of high-risk patients who may benefit from the use of intraaortic balloon pump (IABP) in coronary artery bypass grafting (CABG). The aim of this study was to develop a risk model to identify high-risk patients and predict the need for IABP insertion during CABG. METHODS: From April 1996 to December 2006, 8,872 consecutive patients underwent isolated CABG; of these 182 patients (2.1%) received intraoperative or postoperative IABP. The scoring risk model was developed in 4,575 patients (derivation dataset) and validated on the remaining patients (validation dataset). Predictive accuracy was evaluated by the area under the receiver operating characteristic curve. RESULTS: Mortality was 1% in the entire cohort and 18.7% (22 patients) in the group which received IABP. Multivariable analysis showed that age greater than 70 years, moderate and poor left ventricular dysfunction, previous cardiac surgery, emergency operation, left main disease, Canadian Cardiovascular Society 3-4 class, and recent myocardial infarction were independent risk factors for the need of IABP insertion. Three risk groups were identified. The observed probability of receiving IABP and mortality in the validation dataset was 36.4% and 10% in the high-risk group (score >14), 10.9% and 2.8% in the medium-risk group (score 7 to 13), and 1.7% and 0.7% in the low-risk group (score 0 to 6). CONCLUSIONS: This simple clinical risk model based on preoperative clinical data can be used to identify high-risk patients who may benefit from elective insertion of IABP during CABG.

Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia.

PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the expression levels of MRP1 to MRP6 and study their effect on prognosis. EXPERIMENTAL DESIGN: The mRNA expression levels of MRP1 to MRP6 were analyzed by quantitative real-time PCR in leukemic blasts of 105 de novo ALL patients (adults, n=49; children, n=56) including 70% B-lineage and 30% T-lineage ALL patients. RESULTS: Adults showed a higher expressions of MRP1 (P=0.008), MRP2 (P=0.026), and MRP3 (P=0.039) than children. Interestingly, this difference disappeared when patients were categorized based on clinical outcome. Relapsed patients showed a higher expression of all MRP genes, except MRP4. For the total group of ALL patients, the expressions of MRP1, MRP2, MRP3, MRP5, and MRP6 predicted relapse. Moreover, high expression of all MRP genes, except MRP4, was associated with a reduced relapse-free survival in children and adults (MRP1, P=0.005; MRP2, P=0.008; MRP3, P=0.001; MRP5, P=0.016; MRP6, P=0.037). CONCLUSIONS: The present study shows that a subset of ALL patients with high MRP expression has an unfavorable prognosis independently of age.