Bristol Rabbit Pain Scale (BRPS): clinical utility, validity and reliability.

BACKGROUND: The Bristol Rabbit Pain Scale (BRPS) was developed using a combination of methods, focus groups and behavioural observation, that led to a composite pain scale of six categories (Demeanour, Locomotion, Posture, Ears, Eyes and Grooming) with four intensities of pain (0, 1, 2, and 3), and a total score of 0-18. The aim of this study was to assess the clinical utility, validity and reliability of the BRPS. MATERIALS AND METHODS: The clinical utility of the BRPS was tested using a questionnaire composed of ten questions each on a five-point Likert scale ranging from one (strongly disagree) to five (strongly agree). The respondents, (veterinary surgeons and veterinary nurses), were asked to assess up to four rabbits in acute pain, using the novel pain. They then completed the questionnaire which asked whether the BRPS was easy and quick to use and whether it provided information that was clinically useful. The questionnaire was tested for internal reliability using the Cronbach's alpha reliability coefficient. The construct validity (how well the tool measures the concept it was designed for) was measured by observers blindly rating 20 rabbits pre- and post-surgery whilst the criterion validity (the degree to which the tool correlates with a gold standard) was assessed by correlating BRPS scores with scores using a numerical rating scale (NRS) with a total score of 0-10. Inter-rater reliability was tested by quantifying the agreement in the pain scores given by nine participants when assessing the same 40 video clips. The intra-rater reliability was measured by testing how consistent the participants were when rating the same clips one month later. RESULTS: The median score of the ten questions of the clinical utility test was 4 (range 2-5). The Cronbach's alpha reliability coefficient of the clinical utility test was good (α = 0.811) demonstrating good internal consistency. The median (range) pain score of the BRPS and the NRS were 3 (0-14) and 0 (0-8) before surgery and 12 (1-18) and 7 (0-10) after surgery respectively. The BRPS demonstrated high construct validity (Z = -11.452; p < 0.001) and there was a strong correlation between the BRPS and the NRS (Rho = 0.851; p < 0.001) indicating high criterion validity. The inter-rater and the intra-rater agreements were α = 0.863 and α = 0.861 respectively, which is considered good. CONCLUSIONS: This study showed that the BRPS is a suitable tool for quantifying pain in rabbits in a clinically useful, valid and reliable way.

Sudden unexpected death from an undiagnosed histiocytic sarcoma in an adolescent female.

A previously well 15-year-old female who was awaiting medical investigations for a proptosed right eye collapsed and died suddenly while walking. Postmortem examination revealed diffuse distortion and infiltration of multiple organs by a suspected neoplastic process. Histology confirmed the invasion of multiple organs by atypical cells and myocardial infiltration was the likely cause of death. An extensive panel of immunohistochemistry established the diagnosis of a histiocytic sarcoma. Sudden unexpected death due to a clinically undiagnosed neoplasia in childhood and adolescence is uncommon. This is the first report of a histiocytic sarcoma causing sudden unexpected death and highlights the importance of considering undiagnosed hematological malignancies when examining a case of sudden death at postmortem.

The odour of an unfamiliar stressed or relaxed person affects dogs' responses to a cognitive bias test.

Dogs can discriminate stressed from non-stressed human odour samples, but the effect on their cognition is unstudied. Using a cognitive bias task, we tested how human odours affect dogs' likelihood of approaching a food bowl placed at three ambiguous locations ("near-positive", "middle" and "near-negative") between trained "positive" (rewarded) and "negative" (unrewarded) locations. Using odour samples collected from three unfamiliar volunteers during stressful and relaxing activities, we tested eighteen dogs under three conditions: no odour, stress odour and relaxed odour, with the order of test odours counterbalanced across dogs. When exposed to stress odour during session three, dogs were significantly less likely to approach a bowl placed at one of the three ambiguous locations (near-negative) compared to no odour, indicating possible risk-reduction behaviours in response to the smell of human stress. Dogs' learning of trained positive and negative locations improved with repeated testing and was significant between sessions two and three only when exposed to stress odour during session three, suggesting odour influenced learning. This is the first study to show that without visual or auditory cues, olfactory cues of human stress may affect dogs' cognition and learning, which, if true, could have important consequences for dog welfare and working performance.

Preferential cell response to anisotropic electro-spun fibrous scaffolds under tension-free conditions.

Anisotropic alignment of collagen fibres in musculoskeletal tissues is responsible for the resistance to mechanical loading, whilst in cornea is responsible for transparency. Herein, we evaluated the response of tenocytes, osteoblasts and corneal fibroblasts to the topographies created through electro-spinning and solvent casting. We also evaluated the influence of topography on mechanical properties. At day 14, human osteoblasts seeded on aligned orientated electro-spun mats exhibited the lowest metabolic activity (P < 0.001). At day 5 and at day 7, no significant difference was observed in metabolic activity of human corneal fibroblasts and bovine tenocytes respectively seeded on different scaffold conformations (P > 0.05). Osteoblasts and corneal fibroblasts aligned parallel to the direction of the aligned orientated electro-spun mats, whilst tenocytes aligned perpendicular to the aligned orientated electro-spun mats. Mechanical evaluation demonstrated that aligned orientated electro-spun fibres exhibited significant higher stress at break values than their random aligned counterparts (P < 0.006) and random orientated electro-spun fibres exhibited significant higher strain at break values than the aligned orientated scaffolds (P < 0.006). While maintaining fibre structure, we also developed a co-deposition method of spraying and electro-spinning, which enables the incorporation of microspheres within the three-dimensional structure of the scaffold.

Examination of the physical and psychosocial determinants of health behaviour in 4-5-year-old children with congenital cardiac disease.

OBJECTIVES: To assess the general health and activity levels of 4- and 5-year-old children after intervention for congenital cardiac disease. METHODS: Health behaviour outcomes were assessed in 91 children who had surgery or catheter intervention for congenital cardiac disease. The children were classified into four groups according to severity. The main parameters of classification were the presence of residual symptoms, frequency of visits to general practitioner or the Accident and Emergency Department, and ability to participate in physical activity according to a calculated "activity score". RESULTS: Children had very few residual symptoms after "corrective surgery". Those with complex congenital cardiac disease post-Fontan-type repair still had symptoms on average 18.2 days per month. Surprisingly, the complex group had fewer days "sick" from non-cardiac causes and had fewer visits to general practitioner or Accident and Emergency Departments. Regression analysis indicates that three variables had significant relevance to the general practitioner or Accident and Emergency visits: complex congenital cardiac disease, fewer visits; Townsend score - more deprivation - more visits; and maternal worry - higher maternal worry score - more visits. Regression analysis indicates that lower activity score is significantly related to complex cardiac disease and higher maternal worry score. CONCLUSIONS: The majority of this group of 4- and 5-year-old children had few residual symptoms and had good exercise tolerance. Maternal worry is a significant factor in influencing both activity levels and frequency of unscheduled health service demands - general practitioner or Accident and Emergency visits.

A controlled trial of early interventions to promote maternal adjustment and development in infants born with severe congenital heart disease.

Abstract Background Congenital heart disease can have a negative impact on both infant development and maternal adjustment. This study considered the impact of a new programme of early psychosocial interventions on such outcomes, following the birth of a child with severe congenital heart disease. Methods Seventy infants and their mothers were assigned to an intervention or control group based on order of presentation to the unit. Interventions aimed at bolstering mother-infant transactions, through psychoeducation, parent skills training and narrative therapy techniques were implemented. Results Clinically and statistically significant gains were observed at 6-month follow-up on the mental (but not the psychomotor) scale of the Bayleys-II. Positive gains were also manifested on feeding practices, maternal anxiety, worry and appraisal of their situation. Conclusions A programme of generalizable psychosocial interventions is shown to have a positive impact on the infant with severe congenital heart disease and the mother.

Pain and analgesia in pet rabbits: a survey of the attitude of veterinary nurses.

OBJECTIVES: To gain insight into veterinary nurse knowledge of pain recognition and control in rabbits. MATERIALS AND METHODS: We used a survey to establish current attitudes amongst veterinary nurses towards pain management in pet rabbits and factors that might shape those attitudes. The survey was advertised at national and international veterinary conferences, in veterinary publications and on social media. RESULTS: A total of 284 questionnaires (95% from the UK) were completed and analysed. The majority of respondents (78%) nursed 1-10 rabbits per month and 5.6% of the respondents reported regularly running a rabbit clinic. The respondents were regularly involved in nursing during common procedures such as castration and ovariohysterectomy. Responsibility for post-operative pain assessment was reported to be by "nurses only" (50%), "nurses and vets" (42%) and occasionally by "vets only" (3%). The majority of respondents reported that they did not use a pain scale but often relied on behavioural indicators, while 20% used the Rabbit Grimace Scale. The majority of the respondents reported being "fairly confident" at recognising pain in rabbits. CLINICAL SIGNIFICANCE: Veterinary nurses are involved in many aspects of rabbit care, and they are generally confident at nursing this species. This survey also suggests the need for more data on the use of pain assessment tools in rabbits and the importance of teamwork between nurses and veterinarians.

Intraoperative knee anthropometrics: correlation with cartilage wear.

Accurate knee morphology is of value in determining the correct sizing of prosthetic implants. Intraoperative measurement of key linear dimensional variables was carried out on 196 Caucasian knees (osteoarthritic patients: 68 male and 128 female). Of the 196 knees measured, 70 had extensive cartilage degeneration. Statistical analysis was carried out on this large sample size of data. Summary statistics and correlation coefficients between variables were determined and compared between subgroups. Male knees were on average larger than female knees. Higher correlation was found between variables for males than between variables for females. Overall, the patellar dimensions were seen to correlate least well with other anatomical variables. High correlation between femoral variables supports current femoral sizing procedure, although routine patellar resection practices are called into question. Average values for the 70 knees with extensive cartilage degeneration were significantly smaller (P < 0.01) than their counterparts for the other 126 knees. For a measurement not containing cartilage, such as femoral epicondylar width, this difference cannot be accounted for by the loss of cartilage owing to wear. This suggests that, for similar height and weight, a naturally narrower femoral epicondylar width may be associated with severe osteoarthritis.

Laboratory clues to immunodeficiency; missed chances for early diagnosis?

Primary immunodeficiency is seen in an estimated one in 1200 people, and secondary immunodeficiency is increasingly common, particularly with the use of immunosuppresion, cancer therapies and the newer biological therapies such as rituximab. Delays in the diagnosis of immunodeficiency predictably lead to preventable organ damage. Examples of abnormal pathology tests that suggest immunodeficiency from all laboratory specialities are given, where vigilant interpretation of abnormal results may prompt earlier diagnosis. If immunodeficiency is suspected, suggested directed testing could include measuring immunoglobulins, a lymphocyte count and T-cell and B-cell subsets.

An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.

Air weapon fatalities.

AIMS: To describe characteristics of a series of people accidentally and deliberately killed by air powered weapons. METHODS: Five cases of fatal airgun injury were identified by forensic pathologists and histopathologists. The circumstances surrounding the case, radiological examination, and pathological findings are described. The weapon characteristics are also reported. RESULTS: Three of the victims were adult men, one was a 16 year old boy, and one an eight year old child. Four of the airguns were .22 air rifles, the other a .177 air rifle. Two committed suicide, one person shooting himself in the head, the other in the chest. In both cases the guns were fired at contact range. Three of the cases were classified as accidents: in two the pellet penetrated into the head and in one the chest. CONCLUSIONS: One person each year dies from an air powered weapon injury in the United Kingdom. In addition there is considerable morbidity from airgun injuries. Fatalities and injuries are most commonly accidents, but deliberately inflicted injuries occur. Airguns are dangerous weapons when inappropriately handled and should not be considered as toys. Children should not play with airguns unsupervised.

Epidermal growth factor receptor determination on tumour imprints.

Epidermal growth factor receptor (EGFR) is a sensitive prognostic indicator in women with breast cancer. A new technique for the detection of EGFR on breast cancer imprints is described and evaluated in relation to immunohistochemistry on frozen sections. The standard streptavidin-biotin method using the R1 antibody on frozen sections was modified for use on tumour imprints. In the first group (group 1 imprints) 43 tumours were assessed by frozen section and imprint staining. The group 1 imprint method had a sensitivity of 50% and a specificity of 89% compared with the frozen sections. Further modifications were made for the following 32 tumours (group 2) and this method had a much improved sensitivity of 94% while specificity was preserved. This method is simple and could be performed in any hospital histopathology department.

Oral mucosal non-Hodgkin's lymphoma--a dangerous mimic.

Reports of T-cell lymphomas in the oral cavity are rare. Most have presented as a persisting ulcerated swelling. This paper reports two men, one of whom presented with a short history of increasing facial swelling and pain apparently related to a lower premolar tooth, and the other who had recurrent oral ulceration in several sites over a period of years. These types of cases are likely to present initially to general dental practitioners.

Effect of interleukin-2 on CD95 (Fas/APO-1) expression in fresh chronic lymphocytic leukaemia and mantle cell lymphoma cells: relationship to ex vivo chemoresponse.

Cells from B-cell chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL) rarely express the CD95 (Fas/APO-1) antigen. Our aims were to determine whether CD95 levels (assessed by flow cytometry) in fresh neoplastic CD19+/CD5+ B-lymphocytes from CLL and MCL could be upregulated using clinically relevant doses of interleukin-2 (IL-2), and to compare this with their ex vivo cytotoxic drug sensitivity (assessed by DiSC assay). CD95-expression was absent/negligible in 13/14 CLL and 7/7 MCL specimens. Following culture (without IL-2) CD95 was expressed on dying CD5+ B-lymphocytes but only on live cells in 2/15 cases. In live cells from 2 CLL specimens, IL-2 caused up-regulation of CD95 and was associated with ex vivo drug resistance. Clinically relevant doses of IL-2 had pleiotropic effects on CD95-levels in fresh CLL cells, but did not induce CD95 in MCL cells. The link between CD95-induction and ex vivo drug resistance may point to a clinically resistant subset of CLL patients.

Atypical mucinous metaplasia and intraepithelial neoplasia of the female genital tract--a case report and review of the literature.

Müllerian metaplasia of the female genital tract is usually of limited extent and subtype. We describe the replacement of the lining of the entire genital tract and much of the overlying pelvic serosa by metaplastic müllerian epithelium, in a nulliparous 65-year-old woman with cervical agenesis. She did not have Peutz-Jeghers syndrome and had not had any form of prior hormonal treatment. The metaplastic epithelium extended from the vagina to the serosal surface of the pelvic organs. Mucinous epithelium predominated. In addition, there was multifocal dysplasia of the metaplastic epithelium; this was most prominent in the fallopian tubes where there was marked papillation with cytoarchitectural features reminiscent of a borderline mucinous ovarian tumor. Although müllerian metaplasia is well recognized at different sites within the female genital tract, this highly unusual finding of multiple metaplastic epithelial subtypes and dysplasia involving the mucinous metaplastic epithelium along the entire genital tract and pelvic serosal surface has not, to the best of our knowledge, been reported previously in the absence of Peutz-Jeghers syndrome.

Determinants of neuropsychological and behavioural outcomes in early childhood survivors of congenital heart disease.

AIMS: To evaluate the relative effect of cyanosis, surgical interventions and family processes on neuropsychological and behavioural outcomes in 4-year-old survivors of serious congenital heart disease (CHD). METHODS: 90 children with a range of cyanotic and acyanotic conditions, who underwent either corrective or palliative surgery, completed a neuropsychological and behavioural evaluation. Families of participants were also profiled by evaluation of maternal mental health, worry, social support, parenting style and family functioning. RESULTS: Compromised neuropsychological outcomes were associated with a combination of cyanotic conditions and open-heart surgery, but this was not exacerbated by having a complex, palliative, status. Both cyanotic and acyanotic conditions were associated with specific sensorimotor delays, regardless of method of the correction. Only children with complex conditions and palliative interventions seemed at risk of poor behavioural outcomes; indeed, children with cyanosis with complete repair showed favourable behavioural outcomes compared with controls. Multivariate analyses highlighted the sometimes greater relevance of family processes (eg parenting style, maternal mental health and worry), rather than disease or surgical factors, in predicting especially behavioural outcomes. CONCLUSIONS: The findings (1) suggest a more complex relationship between cyanosis, surgical methods of correction, neuropsychological and behavioural outcomes than previously charted, (2) highlight that family processes may be aetiologically more important than disease and surgical factors, and (3) indicate specific targets for secondary prevention programmes for this at-risk population.

Topology-based signal separation.

Traditional noise-filtering techniques are known to significantly alter features of chaotic data. In this paper, we present a noncausal topology-based filtering method for continuous-time dynamical systems that is effective in removing additive, uncorrelated noise from time-series data. Signal-to-noise ratios and Lyapunov exponent estimates are dramatically improved following the removal of the identified noisy points.

Lymphomas of the head and neck. 1: Nasofacial T-cell lymphoma.

Nasofacial T-cell lymphoma includes diseases otherwise called "lethal midline granuloma" and "necrosis with atypical cells". It is characterised by relentless destruction of nose and palate in particular but the lymphoma remains localised to the head and neck. The age of onset ranges from 10 to 87 and the survival ranges from a few months to several years. The histological appearances are of a polymorphic infiltrate but including atypical T cells in a background of macrophages. There is a strong association with Epstein-Barr virus infection.

Haemolytic uraemic syndrome and pseudomembranous colitis.

Two cases of haemolytic uraemic syndrome (HUS) associated with pseudomembranous colitis (PMC) are described. The toxin of Clostridium difficile was detected post mortem in the stool of one patient and the other patient showed a good therapeutic response to oral vancomycin, an antibiotic with established efficacy in the management of PMC. When associated with HUS, PMC is probably an independent specific disease that, in common with many other infections, may activate HUS.