An investigation of a novel behavioural test to assess pain in piglets following castration

2016 ◽  
Vol 96 (3) ◽  
pp. 376-385 ◽  
Author(s):  
Kayla Bilsborrow ◽  
Yolande M. Seddon ◽  
Jennifer Brown ◽  
Cheryl Waldner ◽  
Joseph M. Stookey
Keyword(s):  
Postoperative Pain ◽  
Post Treatment ◽  
Objective Method ◽  
Specific Time ◽  
Time Points ◽  
Behavioural Test ◽  
Standardized Method

A novel behavioural test using a handling chute was evaluated over two trials as an objective method to assess pain in piglets following castration. Piglet (n = 98) navigation time (NT) through a handling chute was measured at specific time points up to 24 h post treatment. In trial 1, comparing the NT of castrates (C) and sham castrates (SC), C piglets had a longer NT than SC at 0 and 15 min post treatment (P < 0.05), with no differences thereafter. In trial 2, the effect of an analgesic to control postoperative pain on NT was examined, with castrated piglets given a half (CH) or full (CF) dose of meloxicam 1 h prior to treatment, compared with piglets castrated and given saline (CS) or sham castrated and given saline (SS). Post treatment, CS piglets had a longer NT than SS at 0 min (P < 0.005), and at 15 min, piglets CS had a longer NT than all groups (P < 0.001). No significant associations were found between piglet behaviour in the home pen and NT during the 60 min following treatment. These data demonstrate potential for the use of a handling chute to measure NT as a quick, standardized, method to assess piglet pain in response to castration.

scholarly journals Cancer antigen 125 is associated with disease status in uterine carcinosarcoma

Rare Tumors ◽  
2019 ◽  
Vol 11 ◽  
pp. 203636131988415
Author(s):  
Malcolm Strachan Ross ◽  
Chelsea Kilpatrick Chandler ◽  
Koji Matsuo ◽  
John Austin Vargo ◽  
Esther Elishaev ◽  
...  
Keyword(s):  
Overall Survival ◽  
Uterine Cancer ◽  
Disease Status ◽  
Post Treatment ◽  
Uterine Carcinosarcoma ◽  
Cancer Antigen 125 ◽  
Cancer Antigen ◽  
Time Points ◽  
Potential Biomarker ◽  
Significant Difference

Uterine carcinosarcoma is a rare and aggressive tumor with poor outcomes. Cancer antigen 125 is routinely used to track the disease course of ovarian cancer and has been suggested as a biomarker in other aggressive forms of uterine cancer. We sought to characterize cancer antigen 125 as a potential biomarker of disease status in uterine carcinosarcoma. Clinical and pathological data were abstracted for patients who had surgical staging for a pathologically confirmed uterine carcinosarcoma at our institution from January 2000 to March 2014. Non-parametric tests were used to compare changes in cancer antigen 125. Elevated cancer antigen 125 (>35 U/mL) as a predictor of survival was assessed via Kaplan–Meier curves. Among the 153 patients identified, 66 patients had at least one paired measure of cancer antigen 125 drawn preoperatively, post-treatment, or at the time of disease recurrence, and 19 patients had cancer antigen–125 levels at all three time points. Analysis of the 51 patients with both preoperative and post-treatment values found a significant drop in cancer antigen 125 ( p < 0.001). Among the 30 patients who had end-of-treatment and recurrence levels, a significant increase was noted ( p = 0.001). There was no significant difference in cancer antigen–125 levels preoperatively compared to at recurrence among the 23 patients with levels at both time-points ( p = 0.99). Elevated preoperative cancer antigen 125 was not associated with overall survival ( p = 0.12); elevated post-treatment cancer antigen 125 was associated with a worse overall survival ( p < 0.001). Based on this dataset, there seems to be utility in trending a cancer antigen–125 level in patients with uterine carcinosarcoma. A cancer antigen–125 level could predict recurrence and provide prognostic information regarding survival.

Survival Analysis

2018 ◽  
pp. 243-256
Author(s):  
Jorge Leite ◽  
Sandra Carvalho ◽  
Munir Boodhwani ◽  
Felipe Fregni
Keyword(s):  
Survival Analysis ◽  
Time Window ◽  
Cumulative Probability ◽  
Specific Time ◽  
Basic Principles ◽  
Hazard Functions ◽  
Time Points ◽  
Clinical Investigator ◽  
Probability Of Survival ◽  
Kaplan Meier

This chapter focuses on basic principles of survival analysis for the clinical investigator. Survival analysis is a specific type of standardized statistical analysis that focuses on assessing the time elapsed since the exposure/intervention to the occurrence of an event. Important concepts such as median survival time, cumulative probability of survival at specific time points by using Kaplan-Meier estimators, and the use of the use of log rank (Mantel–Cox) to compare survival functions are discussed. This chapter also discusses the concept of censoring, which happens when the event occurs outside the pre-specified time window, and how to develop hazard functions when there are several interrelated factors that can contribute to the increase or decrease of survival probability.

scholarly journals Chondroitin Sulfate-Degrading Enzymes as Tools for the Development of New Pharmaceuticals

Catalysts ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 322 ◽  
Author(s):  
Raúl Benito-Arenas ◽  
Sandra Zárate ◽  
Julia Revuelta ◽  
Agatha Bastida
Keyword(s):  
Extracellular Matrix ◽  
Pharmaceutical Industry ◽  
Chondroitin Sulfate ◽  
Biological Tissues ◽  
Sulfated Polysaccharides ◽  
Specific Time ◽  
Time Points ◽  
Therapeutic Applications ◽  
Degrading Enzymes ◽  
Chondroitin Sulfates

Chondroitin sulfates are linear anionic sulfated polysaccharides found in biological tissues, mainly within the extracellular matrix, which are degraded and altered by specific lyases depending on specific time points. These polysaccharides have recently acquired relevance in the pharmaceutical industry due to their interesting therapeutic applications. As a consequence, chondroitin sulfate (CS) lyases have been widely investigated as tools for the development of new pharmaceuticals based on these polysaccharides. This review focuses on the major breakthrough represented by chondroitin sulfate-degrading enzymes and their structures and mechanisms of function in addition to their major applications.

Nomogram to Prognosticate Outcomes in Patients with Chronic Myeloid Leukemia At Any Time-Point During Tyrosine Kinase Inhibitor Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 71-71
Author(s):  
Alfonso Quintás-Cardama ◽  
Xuelin Huang ◽  
Sangbum Choi ◽  
Hagop M Kantarjian ◽  
Jorge E. Cortes
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Specific Time ◽  
Front Line ◽  
Time Points ◽  
Phase Iii Study ◽  
Time Point

Abstract Abstract 71 Background: The NCCN and the European LeukemiaNet guidelines for monitoring patients with chronic myeloid leukemia in chronic phase (CML-CP) provide recommendations for response assessment and treatment at 3, 6, 12, and 18 months based on evidence obtained in clinical trials. A clear limitation of such guidelines is their applicability at time-points different from those pre-specified. To overcome these limitations we have developed a novel statistical approach to CML prognostication. Method: In order to build our prognostic model, we used two cohorts of patients with CML-CP treated in the frontline DASISION phase III study (CA180-056) and the cohort of patients treated after imatinib failure in the dasatinib dose-optimization phase III study (CA180-034). Progression-free survival (PFS) was defined as any of the following: doubling of white cell count to >20×109/L in the absence of complete hematologic response (CHR); loss of CHR; increase in Ph+ BM metaphases to >35%; transformation to AP/BP; or death. A modified Cox proportional hazards model was used to build a prognostic nomogram. Results: A total of 1189 patients were used for this analysis: 519 from DASISION (259 dasatinib and 260 imatinib) and 670 from CA180-034. First, we devised a model to link a BCR-ABL1/ABL1 ratios (according to the International Standard) obtained at specific time points during the course of treatment with patientsÕ outcomes (PFS). For instance, at 18 months after front-line treatment, the future PFS probabilities are shown in Figure 1A. At 6 months after second-line treatment, the future PFS probabilities are shown in Figure 1B. Once the model was validated at specific time points, we next designed a nomogram to calculate patients' outcomes at any time point during the course of therapy by plotting ‘master PFS curves’ derived from the patient cohorts according to time. Figure 2A&B give the 90% quantile of the remaining PFS for patients at any time after front-line and second-line treatment, respectively. These may be used a guideline for considering other treatment options when patients' BCR-ABL1/ABL1 ratios exceed these values. Figure 2 shows that the remaining PFS times for either front- or second-line treated patients depend mostly on the current BCR-ABL/ABL ratio and less on the time at which the ratio is obtained, reflected by the fact that the curves showing future PFS probabilities are characterized by smooth slopes. Figure 2A shows that 10% of front-line treated patients whose BCR-ABL1/ABL1 ratios are 50% or higher will have remaining PFS times of less than 12 months. If BCR-ABL1/ABL1 ratios are 75% or higher, then 10% of them will have remaining PFS times of less than 6 months. Similarly, Figure 2B shows that for second-line treated patients whose BCR-ABL1/ABL1 ratios are 50% or higher, 10% of them will have remaining PFS time shorter than 6 months. Conclusion: We have designed a nomogram that predicts PFS for patients treated in the frontline and second line settings according to their BCR-ABL1/ABL1 ratios, independent from the time at which these ratios are obtained. A similar approach has been taken to predict failure-free and overall survival and will be presented at the meeting. This prognostic tool is readily available for clinical purposes and might greatly facilitate monitoring and prognostication in CML. Disclosures: No relevant conflicts of interest to declare.

Potential use of Pain Vision as an objective method to evaluate chemotherapy-induced peripheral neuropathy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20557-e20557 ◽  
Author(s):  
Yuko Tanabe ◽  
Chikako Shimizu ◽  
Akihiro Hirakawa ◽  
Eriko Nara ◽  
Emi Noguchi ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Post Treatment ◽  
Objective Method ◽  
Questionnaire Item ◽  
Evaluation Point ◽  
Treatment Comparisons ◽  
To Receive ◽  
Potential Use ◽  
Reproducible Manner ◽  
Clinical Trial Information

e20557 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event, but no objective method exists to evaluate CIPN in an easy-to-use and reproducible manner. Pain Vision (PS-2100; Nipro Co., Osaka, Japan) (PV) was developed to quantitatively evaluate peripheral neuropathy using minimum threshold electric current (mTEC) by painless stimulus. PV has been reported useful in evaluating diabetic neuropathy and neuropathic pain induced by other causes. We investigated the usefulness of PV as an objective method to evaluate CIPN. Methods: Breast and ovarian cancer patients, who were intended to receive adjuvant chemotherapy including paclitaxel (PTX), were enrolled in a clinical study to explore SNPs related to CIPN (UMIN000005294). CIPN was prospectively evaluated at baseline, mid-treatment after receiving a total PTX dosage of 480mg/m2 and three weeks following treatment completion using NCI-CTC (v4), FACT-Neurotaxane (FACT-Ntx) and mTEC as measured by PV. Correlations between changes of mTEC readings and NCI-CTC or FACT-Ntx were analyzed using generalized estimating equations. Results: Ninety-four women were enrolled in this study between April 2011 and December 2012, 15 patients had not reached the post-treatment evaluation point at time of this analysis. Median age was 50 years (range, 27-78) and the incidence of CIPN was 99%. No patient had CIPN at baseline. Mid-treatment and post-treatment CIPN grades were 0/1/2/3=9/70/15/0 and 3/41/30/5 using NCI-CTC while median mTEC readings at baseline, mid-treatment and post-treatment points were 7.8 (4.9-19.9), 8.6 (5.1-17.8) and 9.7 (5.3-22.4)μA, respectively. In baseline and post-treatment comparisons, median mTEC reading changes were significantly correlated with every NCI-CTC grade (median mTEC changes for grades 1/2/3=0.39/0.36/0.64; p=0.003/0.019/0.004) and FACT-Ntx questionnaire item nine, “I have trouble feeling the shape of small objects when they are in my hand” (median mTEC change of 0.14; p=0.049). Conclusions: PV may be potentially useful as an objective method to evaluate CIPN, in particular sensory dominant CIPN, but further study is necessary. Clinical trial information: 000005294.

scholarly journals Transgenic expression of human gp100 and RANTES at specific time points for suppression of melanoma

Gene Therapy ◽  
2009 ◽  
Vol 16 (11) ◽  
pp. 1329-1339 ◽  
Author(s):  
K Aravindaram ◽  
H-H Yu ◽  
C-W Lan ◽  
P-H Wang ◽  
Y-H Chen ◽  
...  
Keyword(s):  
Specific Time ◽  
Transgenic Expression ◽  
Time Points

scholarly journals In Vitro Cell Death Discrimination and Screening Method by Simple and Cost-Effective Viability Analysis

2017 ◽  
Vol 41 (3) ◽  
pp. 1011-1019 ◽  
Author(s):  
Katharina Helm ◽  
Marlena Beyreis ◽  
Christian Mayr ◽  
Markus Ritter ◽  
Martin Jakab ◽  
...  
Keyword(s):  
Metabolic Activity ◽  
Screening Method ◽  
Cellular Metabolism ◽  
Cost Effective ◽  
Post Treatment ◽  
Time Points ◽  
Viability Analysis ◽  
Starting Point ◽  
Apoptosis And Necrosis

Background/Aims: For in vitro cytotoxicity testing, discrimination of apoptosis and necrosis represents valuable information. Viability analysis performed at two different time points post treatment could serve such a purpose because the dynamics of metabolic activity of apoptotic and necrotic cells is different, i.e. a more rapid decline of cellular metabolism during necrosis whereas cellular metabolism is maintained during the entire execution phase of apoptosis. This study describes a straightforward approach to distinguish apoptosis and necrosis. Methods: A431 human epidermoid carcinoma cells were treated with different concentrations/doses of actinomycin D (Act-D), 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), Ro 31-8220, H2O2 and photodynamic treatment (PDT). The resazurin viability signal was recorded at 2 and 24 hrs post treatment. Apoptosis and necrosis were verified by measuring caspase 3/7 and membrane integrity. Results: Calculation of the difference curve between the 2 and 24 hrs resazurin signals yields the following information: a positive difference signal indicates apoptosis (i.e. high metabolic activity at early time points and low signal at 24 hrs post treatment) while an early reduction of the viability signal indicates necrosis. For all treatments, this dose-dependent sequence of cellular responses could be confirmed by independent assays. Conclusion: Simple and cost-effective viability analysis provides reliable information about the dose ranges of a cytotoxic agent where apoptosis or necrosis occurs. This may serve as a starting point for further in-depth characterisation of cytotoxic treatments.

scholarly journals Clinical use of the parasympathetic tone activity index as a measurement of postoperative analgaesia in dogs undergoing ovariohysterectomy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ismael Hernández-Avalos ◽  
Alex Valverde ◽  
José Antonio Ibancovichi-Camarillo ◽  
Pedro Sánchez-Aparicio ◽  
Sergio Recillas-Morales ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Activity Index ◽  
Pain Scale ◽  
Objective Method ◽  
Clinical Use ◽  
Significant Difference ◽  
Clinical Relationship ◽  
Baseline Values ◽  
Parasympathetic Tone ◽  
The University

Abstract Introduction While the current tools to assess canine postoperative pain using physiological and behavioural parameters are reliable, an objective method such as the parasympathetic tone activity (PTA) index could improve postoperative care. The aim of the study was to determine the utility of the PTA index in assessing postoperative analgaesia. Material and Methods Thirty healthy bitches of different breeds were randomly allocated into three groups for analgaesic treatment: the paracetamol group (GPARAC, n = 10) received 15 mg/kg b.w., the carprofen group (GCARP, n = 10) 4 mg/kg b.w., and the meloxicam group (GMELOX, n = 10) 0.2 mg/kg b.w. for 48 h after surgery. GPARAC was medicated orally every 8 h, while GCARP and GMELOX were medicated intravenously every 24 h. The PTA index was used to measure the analgaesia–nociception balance 1 h before surgery (baseline), and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 36, and 48 h after, at which times evaluation on the University of Melbourne Pain Scale (UMPS) was made. Results The baseline PTA index was 65 ± 8 for GPARAC, 65 ± 7 for GCARP, and 62 ± 5 for GMELOX. Postoperatively, it was 65 ± 9 for GPARAC, 63 ± 8 for GCARP, and 65 ± 8 for GMELOX. No statistically significant difference existed between baseline values or between values directly after treatments (P = 0.99 and P = 0.97, respectively). The PTA index showed a sensitivity of 40%, specificity of 98.46% and a negative predictive value of 99.07%. Conclusion Our findings suggest that the PTA index measures comfort and postoperative analgaesia objectively, since it showed a clinical relationship with the UMPS.

The Effectiveness of Systemp.desensitizer in the Treatment of Dentine Hypersensitivity

2004 ◽  
Vol os11 (3) ◽  
pp. 71-76 ◽  
Author(s):  
Dominic A Stewardson ◽  
Russell J Crisp ◽  
Siobhan McHugh ◽  
Urs Lendenmann ◽  
FJ Trevor Burke
Keyword(s):  
Repeated Measures ◽  
Post Treatment ◽  
Treatment Area ◽  
Dentine Hypersensitivity ◽  
Time Points ◽  
Dental Practitioners ◽  
Acid Etch ◽  
Practice Based Research ◽  
Dental Practices ◽  
Pro Forma

Purpose This study reports the effectiveness of Systemp.desensitizer (Ivoclar Vivadent, Schaan, Liechtenstein), when used both with and without an acid-etch step, in the treatment of patients with dentine hypersensitivity in UK dental practices. Materials and methods Ten general dental practitioners (GDPs) were selected from two practice-based research groups. The GDPs were each requested to use Systemp.desensitizer in the treatment of at least ten patients who presented with pain due to dentine hypersensitivity. Systemp.desensitizer was applied to the sensitive dentine area in strict accordance with the manufacturer's handling instructions, except that the patients were divided into two groups. For the first, group NE, the procedure was to isolate the tooth, gently blot it dry with cotton wool pellets, rub Systemp.desensitizer into the tooth for 20 seconds, then gently air-dry it. For the second, group E, the procedure was identical except that after isolation, the treatment area was etched for 15 seconds with 35% phosphoric acid. Patients were asked to complete a pro forma using a 10 cm visual analogue scale designed to provide details of the extent of their pain before treatment, 24 hours post-treatment, one week post-treatment, one month post-treatment, and three months post-treatment. The zero end of the scale was marked ‘no pain’ and the 10 cm end was marked ‘extreme pain’. The percentage change in the patients’ perception of their pain, relative to pretreatment, was calculated using repeated measures analysis and suitable follow-up confidence intervals for the mean changes in perceived pain. Comparisons were then made between the treatment groups NE and E. Results Ninety-one patients completed the first pro forma and 77 completed all the pro formas. Overall, there was a significant reduction in pain at each of the time points after treatment but the pattern of pain reduction across the two groups was different. In general, the non-etched group (group NE) saw an ‘immediate’ reduction in pain which was then fairly consistent across the longer term, whilst, in general, the etched group (group E) saw less reduction in pain 24 hours after treatment, and then further reduction in pain at both one week and one month after treatment. Thus the non-etched group experienced an early reduction whilst the etched group took longer to perceive a reduction in pain; however, there were no statistically significant differences between the reductions in pain scores between the two groups at any of the time points after treatment. Conclusion It is concluded that Systemp.desensitizer was effective in reducing pain from dentine hypersensitivity in the patients treated, and this finding was unaffected by whether or not the tooth was acid-etched prior to application of the reagent.

Serum and Urinary Prostate-specific Antigen and Urinary Human Glandular Kallikrein Concentrations Are Significantly Increased after Testosterone Administration in Female-to-Male Transsexuals

2000 ◽  
Vol 46 (6) ◽  
pp. 859-862 ◽  
Author(s):  
Chrisitna V Obiezu ◽  
Erik J Giltay ◽  
Angeliki Magklara ◽  
Andreas Scorilas ◽  
Louis J G Gooren ◽  
...  
Keyword(s):  
Detection Limit ◽  
Prostate Specific Antigen ◽  
Cultured Cells ◽  
Specific Antigen ◽  
Post Treatment ◽  
Mean Values ◽  
Testosterone Treatment ◽  
Time Points ◽  
Glandular Kallikrein ◽  
Testosterone Administration

Abstract Background: The genes that encode prostate-specific antigen (PSA) and human glandular kallikrein (hK2) are up-regulated by androgens and progestins in cultured cells, but no published studies have described the effect of androgen administration in women on serum and urinary PSA or hK2. Methods: We measured serum and urinary PSA and hK2 before, and 4 and 12 months post testosterone treatment by immunofluorometric methods in 32 female-to-male transsexuals. Results: Mean serum PSA increased from 1.1 ng/L to 11.1 ng/L and then to 22 ng/L by 4 and 12 months post treatment, respectively; the corresponding mean values in urine were 17, 1420, and 18 130 ng/L, respectively. Serum hK2, another kallikrein closely related to PSA, remained undetectable at the three time points. However, urinary hK2 concentration rose from below the detection limit (&lt;6 ng/L) before treatment to 18 and 179 ng/L by the 4th and the 12th month of treatment, respectively. All changes were statistically significant (P &lt;0.001) at 4 months. Conclusions: Testosterone administration increases serum and urinary PSA and urinary hK2 in women. These measurements may be useful as indicators of androgenic stimulation in women.

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