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Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of this signalling pathway for disease pathobiology is not clear. The objective of this study was to quantify VEGF-A, VEGFR2, pVEGFR2, the VEGF co-receptor Neuropilin 1 (NRP-1) and the E3 ubiquitin protein ligase c-Cbl in canine scMCT, and to evaluate their association with disease outcome. Immunohistochemical staining for biomarkers was quantified from 14 cases of canine scMCT using manual and computer-assisted methods. Kaplan-Meier curves were generated for disease-free survival (DFS) and compared using Mantel-Cox log-rank analysis. Cases with high levels of neoplastic cell VEGFR2, pVEGFR2 or c-CBL immunoreactivity had significantly reduced DFS. All cases displayed neoplastic cells positive for VEGF-A, which was significantly associated with pVEGFR2 immunoreactivity. There were also significant positive correlations between VEGFR2 and pVEGFR2, and between c-CBL and pVEGFR2 levels. This pilot study demonstrates the potential utility of these markers in a subset of scMCT in dogs.

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BACKGROUND: Available measures of patient-reported outcomes for complementary and alternative medicine (CAM) inadequately capture the range of patient-reported treatment effects. The Self-Assessment of Change questionnaire was developed to measure multi-dimensional shifts in well-being for CAM users. With content derived from patient narratives, items were subsequently focused through interviews on a new cohort of participants. Here we present the development of the final version in which the content and format is refined through cognitive interviews. METHODS: We conducted cognitive interviews across five iterations of questionnaire refinement with a culturally diverse sample of 28 CAM users. In each iteration, participant critiques were used to revise the questionnaire, which was then re-tested in subsequent rounds of cognitive interviews. Following all five iterations, transcripts of cognitive interviews were systematically coded and analyzed to examine participants' understanding of the format and content of the final questionnaire. Based on this data, we established summary descriptions and selected exemplar quotations for each word pair on the final questionnaire. RESULTS: The final version of the Self-Assessment of Change questionnaire (SAC) includes 16 word pairs, nine of which remained unchanged from the original draft. Participants consistently said that these stable word pairs represented opposite ends of the same domain of experience and the meanings of these terms were stable across the participant pool. Five pairs underwent revision and two word pairs were added. Four word pairs were eliminated for redundancy or because participants did not agree on the meaning of the terms. Cognitive interviews indicate that participants understood the format of the questionnaire and considered each word pair to represent opposite poles of a shared domain of experience. CONCLUSIONS: We have placed lay language and direct experience at the center of questionnaire revision and refinement. In so doing, we provide an innovative model for the development of truly patient-centered outcome measures. Although this instrument was designed and tested in a CAM-specific population, it may be useful in assessing multi-dimensional shifts in well-being across a broader patient population.

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OBJECTIVE: The aim of this study was to investigate autonomic activity by means of heart rate variability analysis in a sample of irritable bowel syndrome (IBS) patients, allowing stratification into IBS symptom subgroups. METHODS: Thirty-three female IBS patients (mean age 37 yr) and 21 healthy female controls (mean age 38 yr) participated. Patients were stratified into 16 subjects with only lower bowel symptoms (IBS only) and 17 subjects with both lower bowel and dyspeptic symptoms (IBS+D). The protocol included standard polysomnography to assess stages of sleep with concomitant electrocardiographic measurement of beat-to-beat intervals of the cardiac cycle. Fifteen-min segments were selected from presleep waking, stage 2 of non-rapid eye movement (REM), and REM sleep and analyzed by spectral analysis of heart rate variability to calculate the high-frequency band, a measure of vagal tone, and the low-frequency/high-frequency ratio, an indicator of sympathovagal balance. RESULTS: The high-frequency band power during REM sleep was significantly lower, indicating substantial vagal withdrawal in IBS-only patients compared with IBS+D patients and controls. The low-frequency/high-frequency band ratio was significantly higher during REM sleep for IBS-only patients. CONCLUSIONS: IBS-only patients had greater sympathetic dominance, indicated by elevated low-frequency/high-frequency band ratio, during REM sleep because of vagal withdrawal. Autonomic functioning, unique to REM sleep, differentiates IBS symptom subgroups, suggesting that autonomic functioning during REM sleep may be a useful biological marker to identify IBS patient subgroups.

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OBJECTIVES: The goal of this study was to investigate behavioral (self-reported) and physiological sleep characteristics in irritable bowel syndrome (IBS) patients with and without concurrent dyspeptic symptoms, as compared to control subjects. METHODS: A total of 31 women with IBS were stratified into two groups: 15 with bowel symptoms only (IBS-only) and 16 with both lower and upper dyspeptic symptoms (IBS+D). In addition, 23 healthy women served as controls. For 4 consecutive days, subjective sleep quality, insomnia symptoms, alertness, state anxiety, perceived daytime stress, and daytime and nighttime GI symptoms were assessed. On night 4, subjects underwent polysomnographic (PSG) monitoring for an objective assessment of sleep quality including microarousals and respiratory parameters. Saliva samples were collected for cortisol analyses each morning and evening across the 4 days of the study. Psychological disturbances were assessed with the SCL. RESULTS: Patients reported significantly more dissatisfaction with their sleep quality and increased daytime fatigue as a result of both insomnia-type symptomatology and nonrestful sleep. These complaints were significantly greater in IBS+D compared to IBS-only for some measures. A significant proportion of patients, particularly IBS+D patients, reported nighttime GI symptoms. Patients reported significantly greater average anxiety across the 4 days, which was greatest in IBS+D. Although both patient subgroups showed normal levels and circadian changes in cortisol compared to controls, IBS+D had significantly increased morning salivary cortisol levels compared to IBS-only. PSG data showed no significant differences between the patient groups and controls. Significant correlations were found between psychological distress and retrospective subjective sleep complaints for patients. CONCLUSIONS: This study confirms the importance of sleep complaints and nighttime GI symptoms in women with IBS that are not substantiated by any objective, physiological evidence. Rather, there is a reporting bias regarding sleep disturbances, which appears to be related to symptom severity and psychological disturbances.

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