Reversal of a distractor effect on saccade target selection after superior colliculus inactivation.

The Smith-Kettlewell Eye Research Institute, 2318 Fillmore Street, San Francisco, CA 94115, USA. rmm@ski.org

Recent evidence indicates that inactivation of the primate superior colliculus (SC) results in an increase in saccade target-selection errors. The pattern of errors suggests that a winner-take-all competition selects the saccade goal and that SC inactivation perturbs this process by biasing the competition against stimuli in the inactivated field. To investigate this idea, the difficulty of target selection was manipulated in a color-oddity search task by varying the number of homogeneous distractors in the search array. Previous studies have shown that target selection is easier when a greater number of homogeneous distractors is present, due to perceptual grouping of the distractors. These results were replicated when testing with the SC intact. Surprisingly, during SC inactivation, this normal trend was reversed: target-selection performance declined significantly with more distractors, resulting in a greater proportion of errant saccades to distractors. Examination of the saccade endpoints indicates that after SC inactivation, many errant saccades were directed to distractors adjacent to the target. This pattern of results suggests that the salience signal used by the SC for target selection is relatively broad in spatial scope. As a result, when the area of the SC representing the target location is inactivated, distractors near the target are at a competitive advantage relative to more distant distractors and, consequently, are selected more often as the saccade goal. This contributes to the trend of worse performance with more distractors due to the greater proximity of distractors to the target.

PMID: 18367699 [PubMed - indexed for MEDLINE]

PMCID: PMC2409266

ALT and viral load decline during PEG-IFN alpha-2b treatment for HBeAg-positive chronic hepatitis B.

Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.

BACKGROUND: Alanine aminotransferase (ALT) is one of the main indicators for inflammatory activity in chronic hepatitis B. During interferon-based therapy, approximately 25%-40% of patients exhibit an ALT flare. OBJECTIVES AND STUDY DESIGN: To analyze the relation between ALT and HBV-DNA during pegylated interferon alpha-2b (PEG-IFN) treatment and compare different patterns of on-treatment viral load decline with the occurrence of ALT flares. RESULTS: Of the 123 patients included in this study 31 (25%) exhibited an ALT flare during treatment or follow-up. Six out of 8 (75%) host-induced flares, i.e. ALT flares which were followed by a HBV-DNA decrease associated with a favorable treatment outcome, occurred in patients with a delayed HBV-DNA decline pattern (delayed vs. non-delayed decline, p=.022); 5 of these 8 patients exhibited HBeAg loss and 4 even HBsAg loss at the end of follow-up. The prediction of ALT normalization was possible using on-treatment viral load. Based on the difference from baseline, the evolution of viral load and ALT level were strongly interrelated during treatment and follow-up. With a joint model we estimated a correlation coefficient of 0.38 (p<0.001) during the first 4 weeks of the treatment and of 0.72 (p<0.0001) thereafter. CONCLUSION: There was a strong relation between ALT and viral load in HBeAg-positive chronic hepatitis B patients treated with PEG-IFN alpha-2b, especially after 4 weeks of treatment. Patients with a delayed decline in viral load often exhibited a host-induced flare associated with a favorable outcome.

PMID: 18359663 [PubMed - indexed for MEDLINE]

Constitutive equation for polymer networks with phonon fluctuations.

Center for Fluid Dynamics at DTU, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.

Recent research by Xing [Phys. Rev. Lett. 98, 075502 (2007)] has provided an expression for the Helmholtz free energy related to phonon fluctuations in polymer networks. We extend this result by constructing the corresponding nonlinear constitutive equation, usable for entirely general, volume conserving deformation fields. Constitutive equations for the sliplink model and the tube model are derived and the three models are examined by comparison with each other and with data from Xu and Mark [Rubber Chem. Technol. 63, 276 (1990)] and Wang and Mark [J. Polym. Sci., Part B: Polym. Phys. 30, 801 (1992)]. Elastic moduli are derived for the three models and compared with the moduli determined from the chemical stoichiometry. We conclude that the sliplink model and the phonon fluctuation model are relatively consistent with each other and with the data. The tube model seems consistent neither with the other models nor with the data.

PMID: 18351868 [PubMed]

Muscle activation during selected strength exercises in women with chronic neck muscle pain.

Lersø Parkalle 105, DK 2100 Copenhagen, Denmark. LLA@NRCWE.DK

BACKGROUND AND PURPOSE: Muscle-specific strength training has previously been shown to be effective in the rehabilitation of chronic neck muscle pain in women. The aim of this study was to determine the level of activation of the neck and shoulder muscles using surface electromyography (EMG) during selected strengthening exercises in women undergoing rehabilitation for chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia). SUBJECTS: The subjects were 12 female workers (age=30-60 years) with a clinical diagnosis of trapezius myalgia and a mean baseline pain intensity of 5.6 (range=3-8) on a scale of 0 to 9. METHOD: Electromyographic activity in the trapezius and deltoid muscles was measured during the exercises (lateral raises, upright rows, shrugs, one-arm rows, and reverse flys) and normalized to EMG activity recorded during a maximal voluntary static contraction (MVC). RESULTS: For most exercises, the level of muscle activation was relatively high (>60% of MVC), highlighting the effectiveness and specificity of the respective exercises. For the trapezius muscle, the highest level of muscle activation was found during the shrug (102+/-11% of MVC), lateral raise (97+/-6% of MVC), and upright row (85+/-5% of MVC) exercises, but the latter 2 exercises required smaller training loads (3-10 kg) compared with the shrug exercise (20-30 kg). DISCUSSION AND CONCLUSION: The lateral raise and upright row may be suitable alternatives to shrugs during rehabilitation of chronic neck muscle pain. Several of the strength exercises had high activation of neck and shoulder muscles in women with chronic neck pain. These exercises can be used equally in the attempt to achieve a beneficial treatment effect on chronic neck muscle pain.

PMID: 18339796 [PubMed - indexed for MEDLINE]

Antimicrobial activities of twenty lysine-peptoid hybrids against clinically relevant bacteria and fungi.

Department of Natural Sciences, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.

BACKGROUNd: This paper describes the antimicrobial activities of 20 lysine-peptoid hybrids against a selection of clinically relevant bacteria and fungi. METHODS: Minimal inhibitory concentrations were determined against methicillin-susceptible Staphylococcus aureus (ATCC 29213), methicillin-resistant S. aureus (ATCC 33591), vancomycin-intermediate S. aureus (ATCC 700699 MU50), vancomycin-resistant Enterococcus faecium (ATCC 700221), Pseudomonas aeruginosa (ATCC 27853), Salmonella typhimurium (clinical isolate), Klebsiella pneumoniae (clinical isolate), amphotericin-B-resistant C. albicans (ATCC 200955) and Cryptococcus neoformans (clinical isolate). RESULTS: The lysine-peptoid hybrids proved to be active against all strains tested, except K. pneumoniae. For each susceptible strain, we identified at least 4 lysine-peptoid hybrids showing excellent activity. The most active compounds displayed minimal inhibitory concentrations ranging from < or =1.6 to 6.25 microM. CONCLUSION: This study demonstrates that lysine-peptoid hybrids show activity against drug-resistant pathogens.

PMID: 18332629 [PubMed - indexed for MEDLINE]

The impact of temporal regularization on estimates of the BOLD hemodynamic response function: a comparative analysis.

Department of Radiology, Wake Forest University School of Medicine, Winston Salem, NC, USA. casanova@wfubmc.edu

In fMRI data analysis it has been shown that for a wide range of situations the hemodynamic response function (HRF) can be reasonably characterized as the impulse response function of a linear and time invariant system. An accurate and robust extraction of the HRF is essential to infer quantitative information about the relative timing of the neuronal events in different brain regions. When no assumptions are made about the HRF shape, it is most commonly estimated using time windowed averaging or a least squares estimated general linear model based on either Fourier or delta basis functions. Recently, regularization methods have been employed to increase the estimation efficiency of the HRF; typically these methods produce more accurate HRF estimates than the least squares approach [Goutte, C., Nielsen, F.A., Hansen, L.K., 2000. Modeling the Haemodynamic Response in fMRI Using Smooth FIR Filters. IEEE Trans. Med. Imag. 19(12), 1188-1201.]. Here, we use simulations to clarify the relative merit of temporal regularization based methods compared to the least squares methods with respect to the accuracy of estimating certain characteristics of the HRF such as time to peak (TTP), height (HR) and width (W) of the response. We implemented a Bayesian approach proposed by Marrelec et al. [Marrelec, G., Benali, H., Ciuciu, P., Pelegrini-Issac, M., Poline, J.-B., 2003. Robust Estimation of the Hemodynamic Response Function in Event-Related BOLD fMRI Using Basic Physiological Information. Hum. Brain Mapp. 19, 1-17., Marrelec, G., Benali, H., Ciuciu, P., Poline, J.B. Bayesian estimation of the hemodynamic of the hemodynamic response function in functional MRI. In: R. F, editor; 2001; Melville. p 229-247.] and its deterministic counterpart based on a combination of Tikhonov regularization [Tikhonov, A.N., Arsenin, V.Y., 1977. Solution of ill-posed problems. Washington DC: W.H. Winston.] and generalized cross-validation (GCV) [Wahba, G., 1990. Spline Models for Observational Data. Philadelphia: SIAM.] for selecting the regularization parameter. The performance of both methods is compared with least square estimates as a function of temporal resolution, color and strength of the noise, and the type of stimulus sequences used. In almost all situations, under the considered assumptions (e.g. linearity, time invariance and smooth HRF), the regularization-based techniques more accurately characterize the HRF compared to the least-squares method. Our results clarify the effects of temporal resolution, noise color, and experimental design on the accuracy of HRF estimation.

PMID: 18329292 [PubMed - indexed for MEDLINE]

PMCID: PMC2432527

The prevalence of ESBL-producing E. coli and Klebsiella strains in the Copenhagen area of Denmark.

Department of Clinical Microbiology, Herlev University Hospital, Herlev, Denmark. alf@ssi.dk

The main purpose of the study was to investigate the frequency of ESBL-producing E. coli and Klebsiella strains in the Greater Copenhagen area. Four collections of strains were investigated: A) 380 consecutive E. coli and Klebsiella isolates primarily from urine, B) 200 gentamicin-resistant E. coli and Klebsiella isolates primarily from urine, C) 210 consecutive E. coli isolates from blood cultures, and D) 68 cefuroxime-resistant E. coli and Klebsiella isolates primarily from urine. Only one strain per patient was included. Strains with a zone diameter for cefpodoxime <or=23 mm were tested by a phenotypic confirmatory test for ESBL production and all screening test-positive strains were examined with PCR and nucleotide sequencing in order to detect the following ESBL genes: ctx-m, shv, tem and oxa. Strains resistant to cefoxitin were further examined with cefotetan+/-boronic acid in order to detect AmpC. An ESBL gene was detected in 3/3 confirmatory test-positive isolates from collection A, in 14/17 from collection B, and in 41/48 from collection D. The distribution of isolates with the ESBL and/or AmpC enzymes was as follows: CTX-M (n=41), SHV (n=14), AmpC (n=9), CTX-M and AmpC (n=2), SHV and AmpC (n=1). In conclusion, the frequency of ESBL-producing E. coli and Klebsiella isolates was low in the Copenhagen area of Denmark (0.8 %). The most common ESBL genes found in our study were ctx-m and shv genes.

PMID: 18321362 [PubMed - indexed for MEDLINE]

Delayed metabolism of postprandial triglyceride-rich lipoproteins in subjects with echolucent carotid plaques.

Center for Atherothrombotic Research in Tromsø, Institute of Clinical Medicine, University of Tromsø, 9037, Tromsø, Norway. anntrude@fagmed.uit.no

Subjects with echolucent carotid plaques have an increased risk of ischemic cerebrovascular events independent of degree of stenosis. Low plasma lipoprotein lipase (LPL) activity promotes a proatherogenic lipid profile, and delayed chylomicron clearance is a risk factor for atherosclerosis. This study was conducted to determine plasma LPL activity and postprandial metabolism of triglycerides in relation to carotid plaque morphology. Plaque echogenicity was assessed by B-mode ultrasound and analysis of the grey scale median (GSM). Echolucent plaques were defined as GSM < or = 63 (the median) and echogenic plaques as GSM > 63, and 57 subjects with carotid plaques and 38 subjects without carotid plaques were recruited. Blood samples were collected before and at 2-h interval for 8 h after a standard high fat meal. LPL activity and mass was determined before and after heparin administration. Postheparin LPL activity was decreased in subjects with echolucent plaques compared to subjects with echogenic plaques (P = 0.06) and to controls (P = 0.04). Plaque echogenicity increased linearly with increasing levels of postheparin LPL activity (P = 0.02) and mass (P = 0.03). Subjects with echolucent plaques had delayed postprandial clearance of chylomicron triglycerides compared to controls (P = 0.04). Low postheparin LPL activity due to attenuated mobilization of LPL from capillary endothelium may play an important role in the formation of echolucent plaques by modulation of postprandial lipids and subsequent fat accumulation in the arterial wall.

PMID: 18320250 [PubMed - indexed for MEDLINE]

Mycolactone is responsible for the painlessness of Mycobacterium ulcerans infection (buruli ulcer) in a murine study.

Department of Human Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

Buruli ulcer is a chronic skin disease caused by Mycobacterium ulcerans, which produces a toxic lipid mycolactone. Despite the extensive necrosis and tissue damage, the lesions are painless. This absence of pain prevents patients from seeking early treatment and, as a result, many patients experience severe sequelae, including limb amputation. We have reported that mice inoculated with M. ulcerans show loss of pain sensation and nerve degeneration. However, the molecules responsible for the nerve damage have not been identified. In order to clarify whether mycolactone alone can induce nerve damage, mycolactone A/B was injected to footpads of BALB/c mice. A total of 100 microg of mycolactone induced footpad swelling, redness, and erosion. The von Frey sensory test showed hyperesthesia on day 7, recovery on day 21, and hypoesthesia on day 28. Histologically, the footpads showed epidermal erosion, moderate stromal edema, and moderate neutrophilic infiltration up to day 14, which gradually resolved. Nerve bundles showed intraneural hemorrhage, neutrophilic infiltration, and loss of Schwann cell nuclei on days 7 and 14. Ultrastructurally, vacuolar change of myelin started on day 14 and gradually subsided by day 42, but the density of myelinated fibers remained low. This study demonstrated that initial hyperesthesia is followed by sensory recovery and final hypoesthesia. Our present study suggests that mycolactone directly damages nerves and is responsible for the absence of pain characteristic of Buruli ulcer. Furthermore, mice injected with 200 microg of mycolactone showed pulmonary hemorrhage. This is the first study to demonstrate the systemic effects of mycolactone.

PMID: 18316387 [PubMed - indexed for MEDLINE]

PMCID: PMC2346717

Immunomodulatory effects of honey cannot be distinguished from endotoxin.

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. mt@farma.ku.dk

In recent years, the use of honey has re-emerged as a remedy for wound treatment. Effects of honey have been related to the presence of an unidentified component that induces release of inflammatory cytokines from monocytic cells. The present study was intended to further characterize the reported in vitro effects of honey. Our results show that natural honeys induce interleukin-6 release from Mono Mac 6 cells as well as release of reactive oxygen species from all-trans retinoic acid (ATRA) differentiated HL-60 cells. The natural honeys contained substantial amounts of endotoxin, and the responses observed in the cell based assays were similar to the responses induced by endotoxin alone. In addition, we determined that the immunomodulatory component present in the natural honeys was retained in the ultra filtrated fraction with a molecular weight greater than 20 kDa. The component was resistant to boiling and its immunomodulatory activity could be abrogated by the addition of polymyxin B. We speculate that the observed in vitro immunomodulatory effects of honey might solely be explained by the endotoxin content in the natural honeys.

PMID: 18313938 [PubMed - indexed for MEDLINE]

Integral assessment of estrogenic potentials of sediment-associated samples. Part 1: The influence of salinity on the in vitro tests ELRA, E-Screen and YES.

German Federal Institute of Hydrology, Am Mainzer Tor 1, 56068 Koblenz, Germany.

GOAL, SCOPE AND BACKGROUND: Exogenic endocrine-active substances are also called 'Endocrine Disrupting Chemicals' (EDC). They imitate or hinder the function of natural endogenic hormones or disturb the synthesis or the metabolism of hormones or of hormone receptors. The Enzyme-Linked Receptor Assay (ELRA) can detect estrogenic and anti-estrogenic effects at the level of receptor binding and is a useful tool for the integrative detection of contaminant effects. Although the test system has been used repeatedly in sediment assessments, the questions have remained concerning how it responds to variations in the physico-chemical matrix. For some bioassays, the salinity of the sample is a critical factor. This is especially relevant when testing wastewater samples or when sediment-associated samples in the tidal reaches of rivers are tested. Sediments in the tidal reaches of rivers change their salinity several times a day. Against this background, it would be beneficial to have a test procedure of known salinity tolerance. On account of this, the salinity tolerance of the ELRA was tested, assessed with reference substances at several salinity levels, and compared with the E-Screen method and a Yeast Estrogen Screen (YES), which are also frequently applied in environmental testing. The aim of this paper was to explore when the salinity limits within these test procedures are applicable. The trials should reveal the working range to be expected, characterize the salinity-dependent variations in sensitivity of the test, and provide options for methodological adjustments to improve the stability against increased salinity. METHODS: The ELRA was carried out with the human Estrogen Receptor alpha. (ER) using the same principle like a competitive immunoassay based on ligand-protein interaction. However, an essential difference is the use of a physiologically relevant receptor instead of an antibody as a linking protein. The ELRA measures the competition of sample estrogens and anti-estrogens against estradiol supplied as a BSA-coating conjugate for the binding site of dissolved ER. Estradiol or xeno-estrogen binding is quantified by a biotynilated anti-ER antibody and the subsequent measurement of peroxidase activity by a streptavidin-POD-biotin complex. The E-Screen was performed with the human breast cancer cell line MCF-7, which expresses the estrogen receptor constitutively. Cell proliferation depends on binding of estrogens or xeno-estrogens with the receptor. After incubation, estrogen-dependent cell growth was measured by sulforhodamin B staining. The YES was performed with a recombinant yeast strain, transfected with a receptor and a reporter plasmid bearing the estrogen receptor and a vitellogenin gene fused with the reporter gene lacZ. Estrogen or xeno-estrogen-dependent gene induction was measured indirectly by LacZ activity. The salinity levels were simulated in varying concentrations with NaCl from 0 to 40 per thousand or Artificial Sea Water (ASW) from 0 to 32 per thousand. RESULTS: The study characterized the factor 'salinity' for the prospective application fields of the ELRA. With reference substances such as 17-beta-estradiol, the ELRA showed classical sigmoidal concentration-effect relations in a range from 0.05 to 100 microg/l under physiological conditions. After a methodological adjustment to compensate decreasing receptor-binding affinity of estrogens and xeno-estrogens at higher salinity levels, the ELRA became applicable under salinity conditions up to concentrations of 20.5 per thousand. In tests, the ELRA reached under the influence of salinity a mean limit of detection of 0.062 microg/l 17-beta-estradiol. The mean relative inter-test error was around 11%. Above concentrations of 20.5 per thousand there is a risk of false negative assessment. Compared with the E-Screen method using the MCF7 cell line and the yeast estrogen test system (YES), the ELRA shows a lower sensitivity to 17-beta-estradiol. In the E-Screen, the cell proliferation was strongly reduced by sodium chloride induced cytotoxicity. In comparison with the E-Screen, the salinity tolerance of the YES and YAS methods is significantly higher. DISCUSSION: Despite adaption, total salinity tolerance could not be achieved with the ELRA. Freshwater samples were generally appraisable. Higher salinity levels above 20.5 per thousand would tend towards false negative results. The low inter-test error of 11% makes the ELRA suitable for the detection of estrogenic and anti-estrogenic potentials of single substances, substance mixtures, and of environmental samples. CONCLUSIONS: The ELRA is very fast and reproducible, it can be used for high-throughput screening in a microplate format at low cost, it is robust to microbial contamination, and is less susceptible to cytotoxic interferences than cell culture methods. RECOMMENDATIONS AND PERSPECTIVES: In their established form, the YES and the E-Screen methods are not applicable for liquid phase testing at higher salinity conditions. The salinity-adapted test version of the ELRA described here shows a broader working range for samples. Native water samples of more or less brackish origin or high-salinity effluent samples are testable. Results of tests with sediment associated samples of different salinity will be subject of a forthcoming publication.

PMID: 18306891 [PubMed - indexed for MEDLINE]

Comment on:

JAMA. 2007 Jul 18;298(3):299-308.

Review of an article: nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease and death in men and women. Nordestgaard B, Benn M, Schnohr P, Tybjaerg-Hansen A. JAMA 2007;298:299-308.

Deaconess College of Nursing, Manchester, MO 63021, USA.

PMID: 18295165 [PubMed]

Public health nurses' views on their position within a changing health system.

Primary Health Care, MidCentral District Health Board, Palmerston North.

To date nursing research exploring the relevance of the practice environment has focused substantially on the experiences of hospital-based nurses. More recently greater attention has been paid to the community nursing environment and nurses involved in primary health care. This study considers the context of public health nursing in New Zealand, firstly by exploring the creation and development of the public health nursing role and secondly by presenting the results of a survey of nurses' views of their practice environments and of their professional positioning at the time of the introduction of Primary Health Organisations (PHOs). One hundred and sixty seven public health nurses across New Zealand firstly provided quantitative ratings of aspects of their practice environment (utlising the Nursing Work Index Revised (NWR-I)), and secondly gave written responses to: (a) the aspects of a work environment that make it a good place to practice as a public health nurse; (b) preferences for employment within Public Health Units, in PHOs or with Maori health providers; and (c) advantages and disadvantages of all three settings. This paper focuses on the qualitative questions only as the NWI-R findings will be reported elsewhere. Findings suggested the importance of good leadership, education/orientation, support, recognition and resources within a public health nursing environment. The main preference of the participants was for working within a District Health Board Public Health Unit, although disadvantages were acknowledged.

PMID: 18293654 [PubMed - indexed for MEDLINE]

Antigenic profiling of a Chlamydia trachomatis gene-expression library.

Chlamydia Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.

The obligate intracellular bacterium Chlamydia trachomatis is the causative agent of sexually transmitted chlamydia infections. A panel of 116 recombinant C. trachomatis proteins was evaluated comparatively to characterize both cell-mediated and humoral immune responses in patients with confirmed C. trachomatis genital infection. The antigens identified were categorized as being recognized exclusively by T cells (CT004, CT043, CT184, CT509, and CT611), B cells (CT082, CT089, CT322, CT396, and CT681), or both T cells and B cells (CT110 and CT443). This grouping of C. trachomatis antigens was correlated to their predicted cellular localization. The comparative evaluation presented here indicates that T cell antigens are located in all bacterial compartments, whereas antibody targets are mainly localized to the outer membrane (P = .0013). Overall, we have identified 5 T cell antigens, 5 B cell antigens, and 2 T/B cell antigens that are potential components for a future chlamydia vaccine.

PMID: 18288899 [PubMed - indexed for MEDLINE]

IL-21 induces in vivo immune activation of NK cells and CD8(+) T cells in patients with metastatic melanoma and renal cell carcinoma.

Novo Nordisk A/S, Novo Nordisk Park, Maalov, Denmark.

PURPOSE: Human interleukin-21 (IL-21) is a class I cytokine previously reported in clinical studies on immune responsive cancers. Here we report the effects of systemic IL-21 therapy on the immune system in two phase 1 trials with this novel cytokine. EXPERIMENTAL DESIGN: Recombinant IL-21 was administered by intravenous bolus injection at dose levels from 1 to 100 microg/kg using two planned treatment regimens: thrice weekly for 6 weeks (3/week); or once daily for five consecutive days followed by nine dose-free days (5 + 9). The following biomarkers were studied in peripheral blood mononuclear cells (PBMC) during treatment: phosphorylation of STAT3, alterations in the composition of leukocyte subsets, ex vivo cytotoxicity, expression of effector molecules in enriched CD8(+) T cells and CD56(+) NK cells by quantitative RT-PCR, and gene array profiling of CD8(+) T cells. RESULTS: Effects of IL-21 were observed at all dose levels. In the 5 + 9 regimen IL-21 induced a dose dependent decrease in circulating NK cells and T cells followed by a return to baseline in resting periods. In both CD8(+) T cells and CD56(+) NK cells we found up-regulation of perforin and granzyme B mRNA. In addition, full transcriptome analysis of CD8(+) T cells displayed changes in several transcripts associated with increased cell cycle progression, cellular motility, and immune activation. Finally, cytotoxicity assays showed that IL-21 enhanced the ability of NK cells to kill sensitive targets ex vivo. CONCLUSIONS: IL-21 was biologically active at all dose levels administered with evidence of in vivo NK cell and CD8(+) T cell activation.

PMID: 18286285 [PubMed - indexed for MEDLINE]

PMCID: PMC2491425

Pharmacokinetics of hydromorphone hydrochloride in healthy dogs.

PharmCATS and the Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA.

OBJECTIVE: To assess the pharmacokinetics of hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. STUDY DESIGN: Randomized experimental trial. ANIMALS: Seven healthy male neutered Beagles aged 12.13 +/- 1.2 months and weighing 11.72 +/- 1.10 kg. METHODS: The study was a randomized Latin square block design. Dogs were randomly assigned to receive hydromorphone hydrochloride 0.1 mg kg(-1) or 0.5 mg kg(-1) IV (n = 4 dogs) or 0.1 mg kg(-1) (n = 6) or 0.5 mg kg(-1) (n = 5) SC on separate occasions with a minimum 14-day washout between experiments. Blood was sampled via a vascular access port at serial intervals after drug administration. Serum was analyzed by mass spectrometry. Pharmacokinetic parameters were determined with computer software. RESULTS: Serum concentrations of hydromorphone decreased quickly after both routes of administration of either dose. The serum half-life, clearance, and volume of distribution after IV hydromorphone at 0.1 mg kg(-1) were 0.57 hours (geometric mean), 106.28 mL minute(-1) kg(-1), and 5.35 L kg(-1), and at 0.5 mg kg(-1) were 1.00 hour, 60.30 mL minute(-1) kg(-1), and 5.23 L kg(-1), respectively. The serum half-life after SC hydromorphone at 0.1 mg kg(-1) and 0.5 mg kg(-1) was 0.66 hours and 1.11 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone has a short half-life, suggesting that frequent dosing intervals are needed. Based on pharmacokinetic parameters calculated in this study, 0.1 mg kg(-1) IV or SC q 2 hours or a constant rate infusion of hydromorphone at 0.03 mg kg(-1) hour(-1) are suggested for future studies to assess the analgesic effect of hydromorphone.

PMID: 18282253 [PubMed - indexed for MEDLINE]

Porosity of neat and composite bone cement mantles.

Department of Surgery, Section of Orthopaedics, University of Kansas School of Medicine-Wichita, Wichita, Kansas, USA.

The effect of fiber additions to bone cement on femoral cement mantle porosity was determined. Eighteen porcine femurs were implanted with a cemented prosthesis. Three cement types were used: as-received cement, cement with untreated polyethylene terephthalate fibers, and cement with treated polyethylene terephthalate fibers. Radiographs revealed all cement mantles as grade B, with slight radiolucency at the cement-bone interface. The cement mantles were sectioned at 7 levels, and porosity was measured at each level. All specimens had similar porosities, with an overall mean percentage of porosity of 3.3%+/-2.2% and a mean pore count of 208+/-160 per section. The high pore count and porosity were not visible on the standard clinical radiographs.

PMID: 18280425 [PubMed - indexed for MEDLINE]

Hepatitis C infection and risk of malignant lymphoma.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. cko@ssi.dk

The association between hepatitis C virus (HCV) infection and risk of malignant lymphoma remains controversial, perhaps due to small-sized studies and low prevalence of HCV in the general population. On the basis of a large Danish-Swedish population-based case-control study, 2,819 lymphoma patients and 1,856 controls of second-generation Danish-Swedish origin were screened for HCV infection using an enzyme-linked immunosorbent assay and a confirming recombinant immunoblot assay (RIBA) test. Positive samples were tested with real-time PCR for the presence of HCV RNA. The association between HCV infection and risk of malignant lymphoma was assessed by logistic regression. When intermediate RIBA test results were interpreted as positive, anti-HCV antibody positivity was associated with a nonsignificant increased risk of non-Hodgkin lymphoma (NHL) overall (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.9-5.3; n = 20 cases), of B-cell lymphomas combined (OR = 2.4 [1.0-5.8]; n = 20) and of lymphoplasmacytic lymphoma (OR = 5.2 [1.0-26.4]; n = 2). No patients with T-cell or Hodgkin lymphoma were HCV-positive. A more conservative definition of HCV positivity (disregarding intermediate RIBA results) resulted in an OR = 1.6 (0.3-8.5; n = 5) for NHL overall. When the definition was further restricted to require HCV RNA positivity, OR was 1.7 (0.2-16.2; n = 3) for NHL overall. Our findings from a population with a low prevalence of HCV suggest a positive association between HCV and risk of NHL, in particular of B-cell origin.

PMID: 18271005 [PubMed - indexed for MEDLINE]

Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis.

US Geological Survey, National Wildlife Health Center, 6006 Schroeder Road, Madison, WI 53711, USA. Tonie_Rocke@usgs.gov

Previous studies have established that vaccination of black-footed ferrets (Mustela nigripes) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis. This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis-infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis-infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period.

PMID: 18263816 [PubMed - indexed for MEDLINE]

Health-related quality of life for veterans with spinal cord injury.

Department of Veterans Affairs (VA) Spinal Cord Injury Quality Enhancement Research Initiative, Center for Management of Complex Chronic Care, Edward Hines Jr VA Hospital, Hines, IL 60141, USA. Bridget.Smith@va.gov

STUDY DESIGN: Cross-sectional. OBJECTIVES: The objective of this study was to examine the association between the characteristics of individuals with spinal cord injury (SCI) and self-reported health-related quality of life (HRQoL). SETTING: The United States. METHODS: Questions from the Behavioral Risk Factor Surveillance System (BRFSS) survey were sent to veterans with SCI. The analyses included 2302 respondents. Logistic regression analysis was used to examine the association between subject characteristics and the following four measures of HRQoL: frequent physical distress (FPD), frequent mental distress (FMD), frequent depressive symptoms (FDS) and poor or fair self-reported health. RESULTS: Approximately 19% of the respondents reported FMD, 27% reported FPD, 17% reported FDS and 29% reported poor or fair health. Veterans who self-reported chronic illnesses, had higher odds of reporting FPD, FMD, FDS and poor or fair health than veterans who did not report chronic illnesses. Smoking was significantly associated with decreased HRQoL. Older veterans had higher odds of reporting poor or fair health and FPD than younger veterans. Higher levels of education were associated with lower odds of FMD, FDS and poor or fair health. CONCLUSIONS: Chronic illnesses and smoking have a substantial effect on HRQoL for persons with SCI, suggesting the importance of continued efforts to improve smoking cessation methods and to treat and prevent chronic conditions.

PMID: 18256674 [PubMed - indexed for MEDLINE]