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  • 1
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(7), p.e0131839
    Description: Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM).Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period.Activity counts were increased in cats during treatment with daily meloxicam (p〈0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042).Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: PLoS ONE, 2012, Vol.7(2), p.e31508
    Description: Macrophage inflammatory protein-1α (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR −/− ) mice were transplanted with bone marrow from CCL3 −/− or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3 −/− marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3 −/− recipients after 6 weeks and in male CCL3 −/− recipients after 12 weeks of WD feeding ( P 〈0.05). Surprisingly, male CCL3 −/− recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR −/− recipients of monocyte chemoattractant protein −/− (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR −/− recipients of CCL3 −/− marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR −/− controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3 −/− recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Diabetes And Endocrinology
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(1), p.e0169576
    Description: Accelerometry is used as an objective measure of physical activity in humans and veterinary species. In cats, one important use of accelerometry is in the study of therapeutics designed to treat degenerative joint disease (DJD) associated pain, where it serves as the most widely applied objective outcome measure. These analyses have commonly used summary measures, calculating the mean activity per-minute over days and comparing between treatment periods. While this technique has been effective, information about the pattern of activity in cats is lost. In this study, functional data analysis was applied to activity data from client-owned cats with (n = 83) and without (n = 15) DJD. Functional data analysis retains information about the pattern of activity over the 24-hour day, providing insight into activity over time. We hypothesized that 1) cats without DJD would have higher activity counts and intensity of activity than cats with DJD; 2) that activity counts and intensity of activity in cats with DJD would be inversely correlated with total radiographic DJD burden and total orthopedic pain score; and 3) that activity counts and intensity would have a different pattern on weekends versus weekdays.Results showed marked inter-cat variability in activity. Cats exhibited a bimodal pattern of activity with a sharp peak in the morning and broader peak in the evening. Results further showed that this pattern was different on weekends than weekdays, with the morning peak being shifted to the right (later). Cats with DJD showed different patterns of activity from cats without DJD, though activity and intensity were not always lower; instead both the peaks and troughs of activity were less extreme than those of the cats without DJD. Functional data analysis provides insight into the pattern of activity in cats, and an alternative method for analyzing accelerometry data that incorporates fluctuations in activity across the day.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(4), p.e95624
    Description: To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC).Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome.From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome.An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009).LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 5
    In: PLoS ONE, 2012, Vol.7(6)
    Description: Background Human papillomavirus (HPV) is a causative factor for tonsillar squamous cell carcinoma (TSCC) and patients with HPV positive (HPV + ) TSCC have a better clinical outcome than those with HPV negative (HPV − ) TSCC. However, since not all patients with HPV + TSCC respond to treatment, additional biomarkers are needed together with HPV status to better predict response to therapy and to individualize treatment. For this purpose, we examined whether the number of tumor infiltrating cytotoxic and regulatory T-cells in TSCC correlated to HPV status and to clinical outcome. Methods Formalin fixed paraffin embedded TSCC, previously analysed for HPV DNA, derived from 83 patients, were divided into four groups depending on the HPV status of the tumor and clinical outcome. Tumors were stained by immunohistochemistry and evaluated for the number of infiltrating cytotoxic (CD8 + ) and regulatory (Foxp3 + ) T-cells. Results A high CD8 + T-cell infiltration was significantly positively correlated to a good clinical outcome in both patients with HPV + and HPV - TSCC patients. Similarly, a high CD8 + /Foxp3 + TIL ratio was correlated to a 3-year disease free survival. Furthermore, HPV + TSCC had in comparison to HPV − TSCC, higher numbers of infiltrating CD8 + and Foxp3 + T-cells. Conclusions In conclusion, a positive correlation between a high number of infiltrating CD8 + cells and clinical outcome indicates that CD8 + cells may contribute to a beneficial clinical outcome in TSCC patients, and may potentially serve as a biomarker. Likewise, the CD8 + /Foxp3 + cell ratio can potentially be used for the same purpose.
    Keywords: Research Article ; Biology ; Medicine
    E-ISSN: 1932-6203
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