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Second Administration (second + administration)

Distribution by Scientific Domains

Medical Sciences	72%
Life Sciences	18%

Selected Abstracts

Cooperation between toll-like receptor,2 and,4 in the brain of mice challenged with cell wall components derived from gram-negative and gram-positive bacteria

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2003
Nathalie Laflamme
Abstract In this study we investigated whether induction of toll-like receptor,2 (TLR2) amplifies the effect of a cell wall component derived from gram-positive bacteria, namely peptidoglycan (PGN). Mice received a first systemic lipopolysaccharide (LPS) injection to pre-induce TLR2 in various regions of the brain, and 6,h later, a second administration of either LPS or PGN. The data show a robust transcriptional activation of TLR2, TNF-, and monocyte chemotactic protein-1 (MCP-1) in microglial cells of mice challenged twice with LPS, whereas PGN essentially abolished this response. TLR4 plays a critical role in this process, because C3H/HeJ mice no longer responded to LPS but exhibited a normal reaction to PGN. Conversely, a robust signal for genes encoding innate immune proteinswas found in the brain of TLR2-deficient mice challenged with LPS. However, the second LPS bolus failed to trigger TNF-, and IL-12 in TLR2-deficient mice, while the same treatment caused a strong induction of these genes in the cerebral tissue of wild-type littermates. The present data provide evidence that cooperation exists between TLR4 and TLR2. While TLR4 is absolutely necessary to engage the innate immune response in the brain, TLR2 participates in the regulation of genes encoding TNF-, and IL-12 during severe endotoxemia. Such collaboration between TLR4 and TLR2 may be determinant for the transfer from the innate to the adaptive immunity within the CNS of infected animals. [source]

Oral Impacts on Daily Performance in Norwegian adults: validity, reliability and prevalence estimates

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2005
A. N. Åstrøm
The Oral Impacts on Daily Performance (OIDP) instrument was translated into Norwegian and reviewed for cultural and conceptual equivalence by a group of bilingual academics. A sample of employees from the University of Bergen completed the Norwegian OIDP frequency questionnaire twice. A total of 173 and 108 subjects participated in the first and the second administration, respectively, of this questionnaire. A two-stage proportionate random sample, comprising 2,000 residents (age-range 16,79 yr), was drawn from the national population register by the Central Bureau of Statistics. Information became available for 1,309 persons who completed telephone interviews. The Norwegian OIDP preserved the overall concept of the English version. Test,retest reliability, in terms of Cohen's kappa, was 0.65, and Cronbach's alpha was high (, 0.80). In both samples, variations in the OIDP scores were apparent in relation to self-reported oral health and number of remaining teeth, supporting construct and criterion validity of the inventory. Only three of the OIDP interviews were discarded, which supports face validity. A total of 18.3% confirmed that they had at least one oral impact. Age-specific rates were 17.5%, 19.0%, 17.9% and 18.4% among 16,24, 24,44, 45,66 and 67,79-yr-old participants. The satisfactory psychometric properties provide evidence for the cross-cultural use of the OIDP. The presence of a distinct floor effect indicates poor sensitivity of the OIDP to detect improvements of oral health-related quality of life at a population level. Prevalence estimates were low, suggesting that the current oral health status has little impact on the daily performance of the Norwegian adult population. [source]

The pharmacokinetics and safety of porfimer after repeated administration 30,45 days apart to patients undergoing photodynamic therapy

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010
S. P. Pereira
Summary Background, Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. Aim, To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30,45 days apart in patients undergoing photodynamic therapy. Methods, Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3,5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. Results, Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. Conclusion, Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days. [source]

Success with infliximab in treating refractory hemophagocytic lymphohistiocytosis

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2006
Tomoko Henzan
Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterized by fever, pancytopenia, hepatosplenomegaly, liver dysfunction, and hemophagocytosis. A 29-year-old woman, diagnosed with systemic lupus erythematosus in 1996, developed HLH in early June 2002. HLH remained refractory during 1.5 months of treatment including corticosteroid, cyclosporine, plasma exchange, vincristine, and etoposide. Infliximab (5 mg/kg/day) was then administered twice. After the second administration, the patient attained remission. Because HLH itself is not a neoplasm but an uncontrolled immune reaction, blocking cytokines involved in the reaction should have therapeutic potentials. For HLH patients not responding to conventional therapy, anticytokine treatment with infliximab may represent one of promising options. Am. J. Hematol. 81:59,61, 2006. © 2005 Wiley-Liss, Inc. [source]

Neurokinin-1 receptor desensitization to consecutive microdialysis infusions of substance P in human skin

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
Brett J. Wong
The neuropeptide substance P is known to be localized in nerve terminals in human skin and substance P-induced vasodilatation is believed to be partially dependent on nitric oxide (NO) and H1 histamine receptor activation. Unlike other neuropeptides investigated in human skin, substance P-induced vasodilatation has been shown to decline during continuous infusion, possibly suggestive of an internalization of neurokinin-1 (NK1) receptors, which are highly specific to substance P. However, questions remain regarding these mechanisms in human skin. Fifteen subjects participated in this series of studies designed to investigate the effect of consecutive infusions and possible mechanisms of substance P-induced vasodilatation in human skin. Two concentrations of substance P (10 ,m and 20 ,m) were tested via intradermal microdialysis in two groups of subjects. Site 1 served as a control and received substance P only. Site 2 received substance P combined with 10 mm l -NAME to inhibit NO synthase. Site 3 received substance P combined with 500 ,m pyrilamine, an H1 receptor antagonist. Site 4 received substance P combined with 10 mm l -NAME plus 500 ,m pyrilamine. Red blood cell (RBC) flux was measured via laser-Doppler flowmetry to provide an index of skin blood flow. Cutaneous vascular conductance was calculated as RBC flux/mean arterial pressure and was normalized to maximal vasodilatation via 28 mm sodium nitroprusside. Substance P was perfused through each microdialysis fibre at a rate of 4 ,l min,1 for 15 min. The subsequent increase in skin blood flow was allowed to return to baseline (,45,60 min) and a stable 5 min plateau was used as a new baseline (post-infusion baseline). A second dose of substance P was then delivered to the skin and skin blood flow was monitored for 45,60 min. Substance P produced a dose-dependent increase in skin blood flow with the concentrations of substance P tested, which was significantly attenuated in the presence of l -NAME and the combination of l -NAME plus pyrilamine. However, substance P-induced vasodilatation was unaffected in the presence of pyrilamine. There was no significant difference between the l -NAME-only sites and the l -NAME plus pyrilamine sites. Importantly, the second dose of substance P did not produce a significant increase in skin blood flow compared to the initial baseline or the post-infusion baseline. These data suggest substance P-induced vasodilatation delivered via microdialysis contains an NO component but does not contain an H1 receptor activation component at the doses tested. Additionally, these data provide evidence for NK1 receptor desensitization as there was no observable increase in skin blood flow following a second administration of substance P. This may provide a useful model for studying the role of substance P in the control of skin blood flow in humans. [source]

Peripheral olfactory sensitivity in rodents after treatment with docetaxel,

THE LARYNGOSCOPE, Issue 4 2010
Frédéric Faure MD
Abstract Objectives/Hypothesis: Clinical studies have documented that cytotoxic chemotherapy is often associated with body weight loss and decreased enjoyment of food. Besides taste, olfaction plays a role in food intake. We assessed whether systemic chemotherapeutic cancer treatment compromises olfactory function in rats and mice treated with docetaxel (Taxotere; Sanofi-Aventis, Paris, France). Study Design: Randomized, controlled trials on mice and rats. Methods: Male mice received a single and male rats either a single, two, or three docetaxel administrations. Olfactory function was tested by means of electroolfactograms (EOGs) from the chemosensory epithelium of the nasal septum and the endoturbinates. We evaluated and compared the magnitude of EOG responses evoked by different odorants recorded at different time points after treatment. Results: In both animal species, docetaxel administration reduced body weight gain, thus evidencing the general toxic effect of the drug. In both animal species, the olfactory mucosa remained responsive to stimulation of odorants during the whole course of experiment, but treatment revealed regional differences of docetaxel susceptibility and induced marked transitory electrophysiological changes. In mice and rats a significant transitory decrease in EOG response magnitude occurred after a single administration. Unexpectedly, in rats we also observed an increase of the olfactory response following the second administration of the drug. Conclusions: Docetaxel exerts a neurotoxic effect on olfactory epithelia of rodents at doses similar to human doses, thus inducing transitory functional alterations. Although moderate, they are consistent with the hypothesis of a dysfunction of olfactory function. Further experiments are needed to elucidate the origin of the electrophysiological effects and their impact on the olfactory perception. Laryngoscope, 2010 [source]

Monitoring stress levels in postgraduate medical training

THE LARYNGOSCOPE, Issue 1 2009
Justin D. Hill MD
Abstract Objectives: The Accreditation Council for Graduate Medical Education (ACGME) mandates that residency Program Directors (PD) monitor resident well-being, including stress. Burnout, as a measure of work-related stress, is defined by a high degree of emotional exhaustion and depersonalization, and a low degree of personal accomplishment using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). The purpose of this study is to describe the use of the MBI-HSS as a method of monitoring stress levels in an academic otolaryngology residency training program and introduce this survey as a tool for wider use in meeting ACGME requirements. Methods: The MBI-HSS was administered to residents in an academic otolaryngology residency training program on three separate occasions: at the beginning, middle, and end of different academic years. In addition, at the time of the third administration, the MBI-HSS was completed by faculty and staff in the same department. Surveys were completed and collected anonymously. Responses were scored against normative data from the MBI-HSS overall sample and the medicine subscale. Low, average, and high levels of burnout were identified for the individual categories of emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA); average levels for each category were calculated. Results: Twenty-two residents completed the first survey, taken near the end of an academic year; 19 completed the second administration in the middle of the following academic year; and 24 completed the third survey at the beginning of the subsequent academic year. Thirteen faculty and 23 staff also completed the third survey. We found that three, one, and one residents reported high levels of burnout on the first, second, and third surveys, respectively. These figures compare to one faculty member and no staff members in the same department reporting high levels of burnout. Conclusions: The MBI-HSS is an established and validated tool for identifying burnout in resident physicians. Residency PDs may find the MBI-HSS useful as an aid in monitoring resident well-being and stress. In our own department, we found levels of burnout comparable to those previously reported for residents and faculty in this specialty. Laryngoscope, 119:75,78, 2009 [source]

IgA response of BALB/c mice to orally administered Salmonella typhimurium flagellin-displaying T2 bacteriophages

BIOTECHNOLOGY PROGRESS, Issue 2 2009
Aidan Synnott
Abstract Salmonella typhimurium antigens were displayed on the capsid of a T2 bacteriophage to explore the potential of phage display for an oral vaccine. Segments of the flagellin proteins FliC (H1 antigen) and FljB (H2) were fused to the N-terminal of T2 phage SOC to give two recombinant phages, T2FliCm and T2FljBm. Over 14 days, 19 BALB/c mice were orally administered twice, either with purified recombinant FliCm and FljBm protein, or T2FliCm and T2FljBm with or without host Escherichia coli. Feces were sampled over 10 weeks and examined for phage by plaque assay and for the presence of mucosal IgA by ELISA. Relatively few phages were detected relative to the amount administered (up to 8.21 × 103 PFU/g faeces) and none were detected five days after initial administration. The administration of a large number of phages appeared to cause no clinical symptoms. IgA concentration in feces peaked around four weeks after the second administration and subsided after eight weeks. The highest relative titers were observed in the protein group (0.37% for anti-FliCm and 0.22% for anti-FljBm) and the mouse group which received no E. coli (0.33% and 0.35%) despite the theoretical amount of protein contained in a phage dose being at least 80,465 times lower than the protein dose administered. The possibility that the immuno-stimulatory properties of the phage create an adjuvant effect to enhance the immunogenic properties of the displayed proteins is discussed. We conclude that phage may be valuable as a vector for oral vaccines. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]

One-year stability of the Measure of Processes of Care

CHILD: CARE, HEALTH AND DEVELOPMENT, Issue 5 2007
R. C. Siebes
Abstract Background, The Measure of Processes of Care (MPOC) is a 56-item self-administered measure designed to examine what parents of a child with a chronic health problem think of the services they and their child receive, and to measure the extent to which these services are family-centred. Reliability and validity of the MPOC were established in prior studies. The aim of the present study was to assess the 1-year stability of the MPOC to justify its use as an evaluative tool. Methods, Nine paediatric rehabilitation centres in the Netherlands participated in this short longitudinal survey study. Subjects were 205 parents (response rate 74.8%) of children aged 1,18 years who received care in one of the participating paediatric rehabilitation centres. All subjects filled out two MPOCs with a 1-year interval. Results, All correlations between the scale scores of the MPOC at the first and second administration were relatively high and significant (range: 0.443,0.609, all P < 0.001), demonstrating high inter-individual stability. However, all mean scale scores, except for Providing General Information, significantly reduced after 1 year. Conclusions, The MPOC has a moderate 1-year stability. However, because of its tendency to score lower when repeated after 1 year, its use as an evaluative follow-up instrument to assess the effectiveness of a programme intervention is restricted. [source]

Applicability of an abbreviated version of the oral impacts on daily performances (OIDP) scale for use among Tanzanian students

COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, Issue 1 2003
J. R. Masalu
Abstract , Objectives: The objective was to examine the applicability of an abbreviated version of the oral impact of daily performances (OIDP) inventory to Tanzanian adults attending the University of Dar es Salaam. Method: A total of 1123 students (mean age 26.4 years, response rate 58%) completed a survey instrument designed to measure subjective oral health indicators including the eight-item OIDP frequency scores. After a period of 4 weeks, 228 students (mean age 24.6 years, response rate 65%) were examined clinically for the presence or absence of oral disorders. Results: A total of 51% of the participants reported that an oral problem had affected them on at least one daily performance in the 6 months preceding the survey. Cronbach's alpha for the OIDP frequency items was 0.83 and 0.87 on the first and second administration of the questionnaire. A reliability coefficient (Spearman's rho) of 0.87 was obtained for the OIDP frequency scores. For five of the eight OIDP frequency items, the kappa values ranged from 0.60 to 1.0, whereas one scale item had the less satisfactory value of 0.22. Construct validity was demonstrated in that the OIDP frequency scores were statistically significantly associated in the expected direction with clinically observed oral problems and a global self-report indicator of oral health status, respectively. Conclusion: The OIDP frequency scale seems to have acceptable psychometric properties in the context of a descriptive questionnaire survey among Tanzanian university students. [source]