Prediction of pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography.

AIM: To determine whether the pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) can be predicted using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (F-18 FDG-PET). MATERIALS AND METHODS: Twenty-eight patients with PDAC who underwent only neoadjuvant chemotherapy (NAC) before surgery were enrolled in the study. All patients had F-18 FDG-PET examinations before NAC. The resected specimen was pathologically evaluated according to the Classification of Pancreatic Carcinoma (7th edn). Patients were categorised into a non-response group and a response group based on the pathological findings. The non-response group (Grades 1a and 1b) showed ≤50% necrosis in the specimen, while the specimens of the response group (Grades 2-3) showed >50% necrosis. The maximum standardised uptake values (SUVmax) of the tumours on F-18 FDG-PET were measured. The mean values of SUVmax were compared between the two groups. The diagnostic performance of SUVmax in distinguishing the two groups was also evaluated using receiver operating characteristic analysis. RESULTS: The mean SUVmax of the response group was higher than that of the non-response group (9.00 ± 1.78 versus 4.26 ± 2.35; p<0.001). The optimal cut-off value of SUVmax was 9.28 for distinguishing the two groups. The sensitivity, specificity, and accuracy for the prediction in the response group were 80%, 95.7%, and 92.9%, respectively. CONCLUSIONS: SUVmax on F-18 FDG-PET may be useful as a biomarker to predict the pathological response to NAC in patients with PDAC.

Functional expression of equilibrative and concentrative nucleoside transporters in alveolar epithelial cells.

Equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs) mediate the cellular uptake of nucleosides and nucleobases across the plasma membrane and play important roles in the salvage pathways of nucleotide synthesis. However, information about nucleoside transport systems in the lung alveolar epithelial cells is limited. Therefore, in the present study, we examined the function and expression of nucleoside transporters using primary cultured alveolar type II cells and transdifferentiated type I-like cells. The uptake of uridine, a substrate for ENTs and CNTs, in type II and type I-like cells was time, temperature, and concentration dependent, and was inhibited by other nucleoside transporter substrates such as adenosine. Uridine uptake in both cells was insensitive to nanomolar concentrations of NBMPR, a potent ENT1 inhibitor, while it was inhibited by higher concentrations of NBMPR, suggesting that ENT2, but not ENT1, is involved in uridine uptake in these cells. Additionally, uridine uptake was higher in the presence of Na+ than in the absence of Na + and was partially inhibited by a CNT inhibitor phloridzin in these cells, suggesting that CNT is also involved in uridine uptake. In both cells, the mRNA expression of ENT1, ENT2, CNT2, and CNT3 was observed. Finally, the activity of uridine uptake was considerably higher in type II cells than in type I-like cells. In addition, the mRNA expression of ENT2, CNT2, and CNT3, but not ENT1, was lower in type I-like cells than in type II cells. These findings would help understand the functional roles of equilibrative and concentrative nucleoside transporters in alveolar epithelial cells.

Transport of ribavirin in human myelogenous leukemia cell line K562.

The anticancer effect of ribavirin, a purine nucleoside analogue, has been studied using cultured cancer cells such as the human myelogenous leukemia cell line K562. In order to exert its pharmacological effect, ribavirin has to enter cancer cells. However, there is little information concerning the transport mechanism of ribavirin into K562 cells. In this study, therefore, we examined the uptake mechanism of ribavirin in K562 cells. The uptake of ribavirin in K562 cells was time- and temperature-dependent, and was saturable with a Km value of 1.5 mM. Ribavirin uptake was inhibited by nucleosides such as adenosine and uridine, and by inhibitors of equilibrative nucleoside transporter 1 (ENT1) such as S-(4-nitrobenzyl)-6-thioinosine and dipyridamole in a concentration-dependent manner. In addition, the expression of ENT1 mRNA in K562 cells was confirmed by real-time PCR. On the other hand, Na+-dependence of ribavirin uptake was not observed, suggesting the involvement of ENT1, but not Na+-dependent concentrative nucleoside transporters, in ribavirin uptake in K562 cells. Treatment of K562 cells with sodium butyrate induced erythroid differentiation, but ribavirin uptake activity and sensitivity of the uptake to various inhibitors were not different between native and differentiated K562 cells. These results suggest that ribavirin uptake into K562 cells is mainly mediated by ENT1, which may have a pivotal role in anticancer effect of ribavirin.

Pathogenetic implication of fusion genes in acute promyelocytic leukemia and their diagnostic utility.

Acute promyelocytic leukemia (APL) has been recognized as a discrete subset of hematopoietic malignancies constituting approximately 10% of acute myeloid leukemia cases. The hallmark reciprocal chromosomal translocation t(15;17) involving fusion between the retinoic acid receptor (RARα) gene and promyelocytic leukemia (PML) gene is a characteristic feature in APL which consequently results in the emergence of PML-RARα chimeric gene. This gene has been substantiated to be responsible for cellular transformation and is a prime target of all-trans-retinoic acid (ATRA) as well as arsenic-trioxide (ATO) therapy. Since this initial discovery, about 10 diverse translocation partner genes of RARα have been reported that result in variant APL forms strongly suggesting that disruption of RARα underlies its pathogenesis. The nature of the fusion partner has a significant bearing upon disease characteristics including sensitivity to retinoids and ATO and thereby underpins the need for rapid and accurate diagnosis and also demands a highly specific treatment approach. In this article we laid emphasis on the rearrangement of the RARα gene and its different fusion partners resulting in variant forms of APL, their implication in underlying molecular pathogenesis of APL and also the different diagnostic modalities that should be employed for their rapid and accurate diagnosis.

Reliability of the SF-36 in Japanese patients with systemic lupus erythematosus and its associations with disease activity and damage: a two-consecutive year prospective study.

We aimed to validate the reliability of the Medical Outcomes Study Short Form-36 (SF-36) among Japanese patients with systemic lupus erythematosus (SLE). Japanese patients with SLE ( n = 233) completed the SF-36 and other related demographic questionnaires, and physicians simultaneously completed the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Patients were prospectively followed for a repeat assessment the following year. The SF-36 subscales demonstrated acceptable internal consistency (Cronbach's α of 0.85-0.89), and an overall good test-retest reliability (intraclass correlation coefficient >0.70). The average baseline SF-36 subscale/summary scores except for "bodily pain" were significantly lower than those of the Japanese general population ( p < 0.05). The SDI showed an inverse correlation with the SF-36 subscale/summary scores except for "vitality" and "mental component summary" at baseline, whereas the SLEDAI-2K did not. In the second year, "social functioning" and "mental component summary" of the SF-36 deteriorated among patients whose SDI or SLEDAI-2K score increased (effect sizes < -0.20). In conclusion, the SF-36 demonstrated acceptable reliability among Japanese patients with SLE. Health-related quality of life measured by the SF-36 was reduced in Japanese patients with SLE and associated with disease damage, rather than disease activity.

The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis.

BACKGROUND: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg. L-1 is described in adults. AIMS: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules. METHODS: Pooled intravenous ketorolac (0.5 mg. kg-1 ) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person. RESULTS: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L. h-1. 70 kg-1 and intercompartment clearance was 4.43 (CV 95.6%) L. h-1. 70 kg-1 . Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L. 70 kg-1 and V2 5.53 (CV 47.6%) L. 70 kg-1 . CONCLUSION: Clearance, expressed as L. h-1. kg-1 , decreased with age from infancy. A dosing regimen of 0.5 mg. kg-1 every 6 hours maintains a trough concentration larger than 0.37 mg. L-1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.

Discovery of anti-microbial and anti-tubercular molecules from Fusarium solani: an endophyte of Glycyrrhiza glabra.

AIMS: Glycyrrhiza glabra is a high-value medicinal plant thriving in biodiversity rich Kashmir Himalaya. The present study was designed to explore the fungal endophytes from G. glabra as a source of bioactive molecules. METHODS AND RESULTS: The extracts prepared from the isolated endophytes were evaluated for anti-microbial activities using broth micro-dilution assay. The endophytic strain coded as A2 exhibiting promising anti-bacterial as well as anti-tuberculosis activity was identified as Fusarium solani by ITS-5.8S ribosomal gene sequencing technique. This strain was subjected to large-scale fermentation followed by isolation of its bioactive compounds using column chromatography. From the results of spectral data analysis and comparison with literature, the molecules were identified as 3,6,9-trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]isochromene-5,10-dione (1), fusarubin (2), 3-O-methylfusarubin (3) and javanicin (4). Compound 1 is reported for the first time from this strain. All the four compounds inhibited the growth of various tested bacterial strains with MIC values in the range of <1 to 256 µg ml-1 . Fusarubin showed good activity against Mycobacterium tuberculosis strain H37Rv with MIC value of 8 µg ml-1 , whereas compounds 1, 3 and 4 exhibited moderate activity with MIC values of 256, 64, 32 µg ml-1 , respectively. CONCLUSIONS: To the best of our knowledge, this is the first study that reports significant anti-tuberculosis potential of bioactive molecules from endophytic F. solani evaluated against the virulent strain of M. tuberculosis. This study sets background towards their synthetic intervention for activity enhancement experiments in anti-microbial drug discovery programme. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to the chemoprofile variation of same endophyte with respect to source plant and ecoregions, further studies are required to explore endophytes of medicinal plants of all unusual biodiversity rich ecoregions for important and or novel bioactive molecules.

Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Validation of the Japanese version of the Systemic Lupus Activity Questionnaire that includes physician-based assessments in a large observational cohort.

The Systemic Lupus Activity Questionnaire (SLAQ) is a patient-reported outcome for systemic lupus erythematosus (SLE). We aimed to translate it into Japanese and further investigate its validity and reliability. The English version of the SLAQ was translated into Japanese and administered to Japanese SLE patients at our university clinic. Physicians assessed disease activity using the SLE Disease Activity Index 2000 (SLEDAI-2K). The patients were prospectively followed for repeat assessment a year later. Ultimately, 255 patients participated. The patients' 10-point ratings of disease activity and SLAQ scores were significantly correlated (Spearman's ρ = 0.53). The SLAQ score was weakly correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K)-nolab (omitting laboratory items; ρ = 0.18) but not with the SLEDAI-2K (ρ = 0.02). These results suggested its convergent and discriminant validity. The SLAQ demonstrated acceptable internal consistency (Cronbach's α = 0.80), and good test-retest reliability (intraclass correlation coefficient = 0.85). The effect sizes and the standardized response means of the SLAQ were as follows: clinical worsening, 0.26 and 0.31, and improvement, -0.39 and -0.41, respectively, which indicated a small but significant responsiveness. The Japanese version of the SLAQ demonstrated acceptable reliability and validity; its performance was comparable to that of the original version.

Anterior mediastinal solid tumours in adults: characterisation using dynamic contrast-enhanced MRI, diffusion-weighted MRI, and FDG-PET/CT.

AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults.

Psychological stress has the potential to cause a decline in the epidermal permeability barrier function of the horny layer.

OBJECTIVE: Psychological stress is known to have a negative effect on a large number of skin diseases. However, there is little research on the relationship between psychological stress and the epidermal permeability barrier function (EPBF) of healthy individuals. We hypothesize that psychological stress deteriorates EPBF and aimed to investigate this relationship. METHODS: Psychological stress was assessed using salivary alpha-amylase (sAmy; KIU L(-1) ), and chromogranin A level corrected with total protein (CgAP; pmol mg(-1) protein) as psychological stress biomarkers. Measurements were obtained from 16 healthy female students during two periods of presumed higher stress (final examinations and returning from a long vacation), and a period considered as a control. The EPBF level was evaluated by measuring transepidermal water loss (TEWL; g m(-2)  h(-1) ). The TEWL was measured three times: just before (TEWL [Intact]), immediately after (TEWL [Str]) and 4 h after (TEWL [4 h]) barrier disruption by tape stripping. The rate of barrier disruption was evaluated by comparing the difference between the TEWL [Intact] and the TEWL [Str] (delta-BD: g m(-2)  h(-1) ). The recovery was assessed by comparing the difference between the TEWL [Intact] and TEWL [4 h] (delta-RE: g m(-2)  h(-1) ). RESULTS: The subjects demonstrated a significant increase in the sAmy value after the long vacation compared with the control. There was no change in the CgAP value between the groups. Meanwhile, the EPBF level showed significant deterioration during both higher stress periods. There was a significant increase in delta-BD and delta-RE after the long vacation. CONCLUSIONS: The results indicate the possibility that psychological stress causes a decline in EPBF and deterioration in barrier disruption and recovery. Furthermore, it implies a relationship between psychological stress and the exacerbation or protracted healing of skin disease.

Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal polyps in western countries) and non-eosinophilic chronic rhinosinusitis (characterized by Th1-dominant inflammation). OBJECTIVE: To investigate local IgE production and class switch recombination to IgE in these two subtypes of chronic rhinosinusitis with nasal polyps. METHODS: The identity of IgE-positive cells was determined using double-immunofluorescent staining for IgE and cell-type-specific molecular markers. To investigate the local class switch recombination to IgE and IgE synthesis in the mucosa, we performed real-time polymerase chain reaction to examine the mRNA expression of Th2 cytokines and class-switch-related molecules, including IL-4, IL-5, IL-13, ε germline gene transcripts, IgE mature transcript, IgG mature transcript, RAG1, RAG2 and activation-induced cytidine deaminase in eosinophilic polyps, non-eosinophilic polyps and controls. RESULTS: The concentrations of total IgE and number of IgE-positive cells were significantly higher in the eosinophilic polyps compared with control and non-eosinophilic polyps. IgE-positive cells were predominantly mast cells in eosinophilic polyps and significantly correlated with the number of FcεR1-positive cells in the subepithelial layer. IL-5 and IL-13 mRNA and ε germline gene transcripts expression levels were significantly higher in eosinophilic polyps compared with control and non-eosinophilic polyps. In contrast, the number of plasma cells and the expression of IgG mature transcripts were increased in non-eosinophilic polyps compared with eosinophilic polyps. RAG2 mRNA was significantly increased in both eosinophilic and non-eosinophilic polyps compared with control mucosa. CONCLUSION AND CLINICAL RELEVANCE: The current study suggests local class switching to IgE, production of IgE and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in the Japanese population. The difference in the IgE-related profiles between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Tumour necrosis factor inhibitor-associated sinusitis.

AIM: To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors. METHODOLOGY: A retrospective review of the medical records between 2003 and 2011 revealed that five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment. RESULTS: The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor. CONCLUSION: Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.

Technical Note: Novel imaging method to obtain gray matter-attenuated inversion recovery image using low-field magnetic resonance imaging systems.

INTRODUCTION: The double inversion recovery (DIR) technique suppresses two types of tissue signals with different T1 values by applying two inversion recovery (IR) pulses with different inversion times (TI). In contrast, the double tissue suppression with multi-echo acquisition and single TI combining HIRE (DOMUST-HIRE) method, is a technique enabling the white-matter-attenuated inversion recovery (WAIR) images by setting one inversion time (TI) in a sequence based on the multi-echo method and subtracting the second echo image from the first echo image. Here, we propose a new sequence that can provide the gray-matter-attenuated inversion recovery image based on the DOMUST-HIRE method. METHODS: In this small clinical study, we performed determination of optimal TI and physical evaluation by imaging a subject's head with T1WI and our proposed method for GAIR images. RESULTS: Our proposed method could increase the contrast ratio and the contrast-to-noise ratio between white matter (WM) and gray matter (GM), whereas the signal-to-noise ratio WM and GM decreased than with T1WI method. CONCLUSIONS: Our proposed method can be used to suppress GM and CSF signals. IMPLICATIONS FOR PRACTICE: The use of our proposed method in low-field MRI systems could provide GAIR image.

Changes in snuff and smoking habits in Swedish pregnant women and risk for small for gestational age births.

OBJECTIVE: To examine associations between antenatal exposure to Swedish oral moist snuff (which includes essentially only nicotine) and to smoking and risks of small-for-gestational-age (SGA) births and to compare risks among women who stopped or continued using snuff or smoking during pregnancy. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All live singleton births in Sweden 1999-2010. METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis. MAIN OUTCOME MEASURES: SGA birth, also stratified into preterm (≤36 weeks of gestation) and term (≥37 weeks of gestation) SGA births. RESULTS: Compared with non-tobacco users in early pregnancy, snuff users and above all smokers in early pregnancy had increased risks of SGA births: adjusted ORs (95% CI) were 1.26 (1.09-1.46) and 2.55 (2.43-2.67), respectively). Snuff use had, if anything, a stronger association with preterm SGA than term SGA, whereas the opposite was true for smoking. Compared with non-tobacco users, women who stopped using snuff before their first visit to antenatal care had no increased risks of preterm or term SGA, and women who stopped using snuff later during pregnancy had no increased risk of term SGA. Smoking cessation early in pregnancy was associated with a larger reduction in risk than smoking cessation later in pregnancy. CONCLUSIONS: As both smoking and snuff use influence risk of SGA, both nicotine but above all tobacco combustion products are involved in the mechanisms by which maternal smoking increases the risk of SGA.

Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies.

BACKGROUND: Ketorolac, a potent nonsteroidal anti-inflammatory drug used for pain control in children, exists as a racemate of inactive R (+) and active S (-) enantiomers. AIM: To develop a microsampling assay for the enantioselective analysis of ketorolac in children. METHODS: Ketorolac enantiomers were extracted from 50 µl of plasma by liquid­liquid extraction and separated on a ChiralPak AD-RH. Detection was by a TSQ quantum triple quadrupole mass spectrometer with an electrospray ionisation source operating in a positive ion mode. Five children (age 13.8 (1.6) years, weight 52.7 (7.2) kg), were administered intravenous ketorolac 0.5mg/kg (maximum 10mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h post administration. CL, VD and t1/2 were calculated based on non-compartmental methods. RESULTS: The standard curves for R (+) and S (-) ketorolac were linear in the range 0­2000 ng/ml. The LLOQs of the method were 0.15 ng on column and 0.31 ng on column for R (+) and S (-) ketorolac, respectively. The median (range) VD and CL of R (+) and S (-) ketorolac were 0.12 l/kg (0.07­0.17), 0.017 l/h/kg (0.12­0.29) and 0.17 (0.09­0.31) l/kg, 0.049 (0.02­0.1) l/h/kg, p = 0.043), respectively. The median (range) elimination half-life (t1/2) of the R (+) and S (-) ketorolac was 5.0 h (2.5­5.8) and 3.1 h (1.8­4.4), p = 0.043), respectively. CONCLUSION: The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported.

Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases. METHODS: Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ≥4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis. RESULTS: In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ≥4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (≥5.0 × 10(3); OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (≥1.0 × 10(5)) in the SLN was the only independent predictor of ≥4 LN metastases (P=0.014). CONCLUSION: Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ≥4 LN metastases.

Feasibility of salt pads to improve fat suppression in low-field MRI systems.

INTRODUCTION: Fat-suppressed images are essential in clinical practice but are often affected by magnetic field inhomogeneity, resulting in poor image quality. We hypothesized that salt (99% sodium chloride [NaCl]) could be used as a magnetic field uniformity assist pad and verified whether salt pads improve magnetic field uniformity and the fat suppression effect in low-field magnetic resonance imaging (MRI) systems. METHODS: We conducted a small clinical study where coronal 2D fast spin-echo T2-weighted MRI with fat suppression was performed. The subjects were 10 healthy volunteers (six men and four women) with no surgical history, with a mean age of 20.5 years (range, 20-30 years). In the clinical study, we performed physical and visual evaluation by imaging a subject's knee with and without salt pads. RESULTS: The results of the clinical study indicated that the use of salt pads improved the magnetic field uniformity, thus increasing the fat suppression effect. CONCLUSIONS: Salt pads improved the homogeneity of the magnetic field and the fat suppression effect in low-field MRI systems. IMPLICATIONS FOR PRACTICE: The use of salt pads in low-field MRI systems could provide more accurate fat suppression images.

Paracetamol prescribing in primary care: too little and too much?

AIMS: To assess the level of paracetamol off label prescribing in the community and the potential for paracetamol under or overdosing. METHODS: The Scottish Practice Team Information (PTI) database containing prescribing data for approximately 35,839 children aged (0-12 years) was analysed for paracetamol prescriptions for the year 2006. Off label prescribing was defined as prescribing outside the BNFc age and dose recommendations. RESULTS: Two thousand seven hundred and sixty-one children aged 0-12 years were issued with 4423 prescriptions for paracetamol. (1446 males). Children 1-5 years (1329, 42.2%) accounted for 48.9% (2164) of all paracetamol prescriptions. Eighteen per cent (793) of individual prescriptions were off label and after accounting for repeat prescriptions 625 (22.75%) individuals were exposed to off label prescriptions. A further 15% (668) of prescriptions contained insufficient dosage data to determine their status, 13.3% (368) being underdosed and 4.4% (121) overdosed at least once during the study year. In total 11.3% (502) of all prescriptions were classified as underdose, 2.9% (127) as overdose and 15% (667) had no dosage instructions. Age was significantly related to non recommended dosage (χ(2) test, P < 0.001). Children 1-3 months old were at highest risk of being overdosed; 27% of prescriptions recommended actual or potential overdosage and 25% (354) of children aged 6-12 years were prescribed an actual or potential underdose. Overall 57.2% of all prescriptions failed to comply with current BNFc recommendations. CONCLUSION: Paracetamol off label prescribing is common in primary care, with relatively high levels of potential overdosing in the youngest children and potential underdosing in the oldest children.

Raised high-sensitivity C-reactive protein and cognitive impairment among African stroke survivors within the first three months following stroke.

Stroke remains a major factor causing death and disabilities such as cognitive impairment. There is conflicting evidence on the role and dynamics of high sensitivity C-reactive protein (hsCRP), an acute phase pro-inflammatory protein, in post-stroke cognitive impairment. This study evaluated cognitive impairment and examined its relationship with serum hsCRP in the first three months following stroke. Cognition was assessed using Montreal Cognitive Assessment test, while serum hsCRP concentrations were assessed using enzyme link immunosorbent assay kit. Data were processed using SPSS Statistics version 20.0. Sixty subjects, comprising of 30 stroke patients and 30 healthy subjects, matched for age, sex and level of education were studied. Cognitive impairment was observed among the stroke patients, while the healthy subjects showed normal cognitive function; and the difference in the cognitive scores of the two groups was highly significant (P = 0.001). There was higher prevalence of cognitive impairment among the stroke survivors compared to the non-stroke subjects. Serum hsCRP was significantly higher among the stroke survivors compared to the healthy subjects (P = 0.001). The high hsCRP level correlates well with duration of stroke and working memory domain of cognition. The data revealed a high prevalence of cognitive impairment and concurrent high serum hsCRP levels among stroke survivors in the first three months following stroke, in contrast with normal subjects. The high hsCRP level correlates with duration of stroke and working memory domain of cognition. The data suggest a role for serum hsCRP and inflammation in the development of post-stroke cognitive impairment.