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The contemporary approach to pain measurement in people and animals seeks to measure the affective (emotional) component of the pain experience using structured questionnaires with formal scoring methodology. Chronic pain has wide-ranging impacts which affects the quality of life (QOL) of the individual, whether that is a person or an animal. Accordingly instruments to measure chronic pain are designed to measure its impact on QOL and are called health-related quality of life (HRQL) instruments. In veterinary science instruments to measure pain are based on behavioural observation by the veterinary surgeon/nurse in the case of acute pain and by the owner in the case of chronic pain. The development of HRQL instruments is an expanding field in veterinary science, not just for the measurement of pain, but for other chronic diseases, and it has a wide application in pharmaceutical research and clinical practice to improve patient care. This review highlights the challenges involved in creating such measures for dogs and cats, seeking to provide the reader with an understanding of their development process. It then provides an overview of the current status with regard to acute and chronic pain measurement.

OBJECTIVES To develop a composite measure pain scale tool to assess acute pain in cats and derive an intervention score. METHODS To develop the prototype composite measure pain scale-feline, words describing painful cats were collected, grouped into behavioural categories and ranked. To assess prototype validity two observers independently assigned composite measure pain scale-feline and numerical rating scale scores to 25 hospitalised cats before and after analgesic treatment. Following interim analysis the prototype was revised (revised composite measure pain scale-feline). To determine intervention score, two observers independently assigned revised composite measure pain scale-feline and numerical rating scale scores to 116 cats. A further observer, a veterinarian, stated whether analgesia was necessary. RESULTS Mean ± sd decrease in revised composite measure pain scale-feline and numerical rating scale scores following analgesia were 2 · 4 ± 2 · 87 and 1 · 9 ± 2 · 34, respectively (95% confidence interval for mean change in revised composite measure pain scale-feline between 1 · 21 and 3 · 6). Changes in revised composite measure pain scale-feline and numerical rating scale were significantly correlated (r = 0 · 8) (P < 0001). Intervention level score of ≥4/16 was derived for revised composite measure pain scale-feline (26 · 7% misclassification) and ≥3/10 for numerical rating scale (14 · 5% misclassification). CLINICAL SIGNIFICANCE A valid instrument with a recommended analgesic intervention level has been developed to assess acute clinical pain in cats that should be readily applicable in practice.

Aging is associated with declines in memory and cognitive function. Here, we evaluate the effects of HT-0712 on memory formation and on cAMP response element-binding protein (CREB)-regulated genes in aged mice. HT-0712 enhanced long-term memory formation in normal young mice at brain concentrations similar to those found to increase CRE-mediated gene expression in hippocampal neurons. Aged mice showed significantly poorer contextual and trace conditioning compared with young–adult mice. In aged mice, a single injection of HT-0712 significantly boosted contextual and trace long-term memory. Additional effects of HT-0712 were seen in a spatial memory task. Our parallel biochemical experiments revealed that inductions of the CREB-regulated genes, cFos, Zif268, and Bdnf, after fear conditioning were diminished in aged mice. HT-0712 facilitated expression of these CREB-regulated genes in aged hippocampus, indicating that the drug engages a CREB-regulated mechanism in vivo. These findings corroborate and extend our previous results on the mechanism of action of HT-0712 and its efficacy to enhance memory formation. Our data also indicate that HT-0712 may be effective to treat age-associated memory impairment in humans.

The usefulness of a pain assessment instrument is enhanced in general practice if the score can be linked to an intervention level, which is informative as to whether or not an animal requires analgesic treatment. Previously the authors described the derivation of an intervention level for the Glasgow Composite Measure Pain Scale (CMPS) short form tool for assessing acute pain in dogs (Reid and others 2007). More recently, the authors reported the validation of a behaviour-based tool (the revised composite measure pain scale (rCMPS)-F) for the assessment of acute pain in cats that was developed using psychometric principles (Calvo and others 2014). It takes the form of a structured questionnaire completed by an observer following a standard protocol and includes assessment of spontaneous and evoked behaviours, interactions with the animal and clinical observations. Construction and clinical testing of the tool supported its validity and provided some evidence for responsiveness, but sensitivity was moderate (misclassification, 26.7 per cent). In order to improve the performance of the tool, a simple three-point facial scale, which in preliminary testing had performed very well in classifying cats in pain, was developed (Holden and others 2014) with the intention of embedding it within the behaviour-based cat tool, an approach adopted previously in paediatric medicine (CRIES (Krechel and others 1995); Premature Infant Pain Profile (Stevens and others 1996)). This communication describes a single, multicentre …

Obesity is thought to affect quality of life, but limited objective data exist to support this supposition. The current study aim was to use a questionnaire to determine health-related quality of life (HRQOL) both before and after weight loss, in obese client-owned dogs. Fifty obese dogs were included, and represented a variety of breeds and genders. Prior to weight loss, owners were asked to complete a validated standardised questionnaire to determine HRQOL. Thirty of the dogs successfully completed their weight loss programme and reached target, and owners then completed a follow-up questionnaire. The completed questionnaire responses were transformed to scores corresponding to each of four factors (vitality, emotional disturbance, anxiety and pain), and scored on a scale of 0–6. Changes in the scores were used to explore the sensitivity of the questionnaire, and scores were correlated with responses to direct questions about quality of life and pain, as well as weight loss. Dogs that failed to complete their weight loss programme had lower vitality and higher emotional disturbance scores than those successfully losing weight (P = 0.03 for both). In the 30 dogs that completed, weight loss led to an increased vitality score (P < 0.001), and decreased scores for both emotional disturbance (P < 0.001) and pain (P < 0.001). However, there was no change in anxiety (P = 0.09). The change in vitality score was positively associated with percentage weight loss (rP = 0.43, P = 0.02) and percentage body fat loss (rP = 0.39, P = 0.03). These results indicate demonstrable improvement in HRQOL for obese dogs that successfully lose weight.

The use of corneocytes in suspension as a medium for the study of the effect of antifungal drugs on Trichophyton mentagrophytes arthroconidia was investigated. In the presence of clotrimazole or griseofulvin, arthroconidia germination in a suspension of corneocytes and in Sabouraud glucose liquid medium was significantly reduced compared with germination in drug-free media. Where antifungals were added to arthroconidia after an activation period during which germination occurred, any further germination was inhibited. The data showed that the growth of T. mentagrophytes in the presence of corneocytes offered a simple, rapid, inexpensive and relevant model for the assessment of antifungal activity of compounds for the treatment of dermatophytosis.

Summary: A clinical and mycological evaluation of the effectiveness of bifonazole gel was undertaken in general practice, the preparation being applied once daily for either 2 or 3 weeks with a final assessment at 4 weeks. There were 38 mycologically proven cases of tinea infection, 25 of tinea pedis and 13 of tinea cruris. A further 82 clinical cases were included to assess the acceptability of the gel, but were not included in the analysis of the results. After treatment, all signs and symptoms resolved in 60% of tinea pedis and 46% of tinea cruris infections (p < 0.01). Trichophyton rubrum was the commonest infecting organism (22 cases, 61%), followed by Trichophyton mentagrophytes var. interdigitale and Epidermophyton floccosum (7 cases each, 18% each). T. verrucosum and Microsporum canis were isolated from one case each respectively. Of 32 patients, where repeat examinations were undertaken, 10 (31%) were still positive at day 14, but only 2 (7%) at day 28, representing a mycological cure rate of 91%. There were no side-effects of any importance and, aesthetically, the gel preparation was highly acceptable to the patients. Zusammenfassung: Es wurde eine klinische und mykologische Bewertung der Wirkung von Bifonazol-Gel in der Allgemeinpraxis vorgenommen. Das Praparat wurde einmal taglich uber 2 oder 3 Wochen angewendet; die endgultige Bewertung wurde 4 Wochen nach Behandlungsbeginn vorgenommen. In die Studie gingen 38 Falle nachgewiesener Dermatophytosen-Infektionen ein, 25 davon betrafen Tinea pedis und 13 Tinea cruris. Weitere 82 klinische Falle wurden in die Bewertung der Gel-Akzeptanz, nicht jedoch klinisch und mykologisch bewertet. Nach der Behandlung waren 60% der Tinea pedis- und 46% der Tinea cruris-Infektionen klinisch geheilt (p < 0.01). Trichophyton rubrum war der haufigste Erreger (22 Falle, 61%), gefolgt von Trichophyton mentagrophytes var. interdigitale und Epidermophyton floccosum (je 7 Falle, je 18%). T. verrucosum und Microsporum canis wurden je einmal angezuchtet. Bei 32 Patienten wurden Wiederholungsuntersuchungen unternommen; davon waren 10 (31%) am 14. Tag noch positiv, aber nur 2 (7%) am 28. Tag, was einer Heilungsrate von 91% entspricht. Nebenwirkungen wurden nicht beobachtet. Das Gel wurde gut von den Patienten angenommen.

Objective To assess the frequency of community pharmacists' advice-giving to women and to determine pharmacists' attitudes and perceived knowledge, confidence and embarrassment in providing such advice. Method A postal questionnaire was sent to a random sample of 600 Northern Ireland community pharmacists for self-completion. One reminder was sent. The questionnaire asked pharmacists to rate their knowledge on a list of women's health topics and to rate their confidence in dealing with women's health issues. Pharmacists were asked what actions they took to increase women's comfort in discussing potentially sensitive topics. They were also asked about the availability of women's health services locally. Closed response data were entered into SPSS for analysis while open question responses were collated and analysed separately. Key findings Pharmacy customers were predominantly female and the majority of pharmacists reported providing advice on women's health on a daily basis. Most pharmacists reported being confident and knowledgeable on women's health issues. Pharmacists had strategies to ensure that women felt comfortable discussing personal problems and they were not embarrassed dealing with such problems. Respondents felt more comfortable responding to, rather than initiating, such discussions. Personal views made it difficult for some respondents to provide advice on emergency contraception. Male pharmacists considered themselves to be less confident, less knowledgeable, more embarrassed and to have greater difficulty initiating a conversation on sensitive issues compared with female pharmacists. Conclusion Pharmacists on the whole were confident when dealing with requests for advice. Counselling confidence was related to counselling frequency. Initiation of conversations on women's health issues was difficult for some pharmacists. More active collaboration with the providers of other professional services available to women may enhance pharmacists' overall service provision for women customers.

OBJECTIVES To describe the development of a facial expression tool differentiating pain-free cats from those in acute pain. METHODS Observers shown facial images from painful and pain-free cats were asked to identify if they were in pain or not. From facial images, anatomical landmarks were identified and distances between these were mapped. Selected distances underwent statistical analysis to identify features discriminating pain-free and painful cats. Additionally, thumbnail photographs were reviewed by two experts to identify discriminating facial features between the groups. RESULTS Observers (n = 68) had difficulty in identifying pain-free from painful cats, with only 13% of observers being able to discriminate more than 80% of painful cats. Analysis of 78 facial landmarks and 80 distances identified six significant factors differentiating pain-free and painful faces including ear position and areas around the mouth/muzzle. Standardised mouth and ear distances when combined showed excellent discrimination properties, correctly differentiating pain-free and painful cats in 98% of cases. Expert review supported these findings and a cartoon-type picture scale was developed from thumbnail images. CLINICAL SIGNIFICANCE Initial investigation into facial features of painful and pain-free cats suggests potentially good discrimination properties of facial images. Further testing is required for development of a clinical tool

The purpose of this study was to compare resistance and cross-resistance development in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients to commonly used antipseudomonal antibiotics. Isolates were repeatedly exposed to subinhibitory concentrations of either azlocillin, tobramycin, ceftazidime or ciprofloxacin. On 10 consecutive occasions, samples were removed from the half-MIC well of a microtitre plate and regrown in drug-free medium to provide the next inoculum for MIC determination. The increase in MIC at the end of the treatment period was significant (p

A study was designed to investigate the association between heart rate, respiratory rate and pupil dilation and a subjective pain score allocated using a numerical rating scale (NRS). Four groups of dogs (n = 17 to 20 per group) were included: orthopaedic surgery cases, soft tissue surgery cases, dogs with medical conditions and healthy dogs. Each dog was examined by five veterinary surgeons within a four-hour period. When examining each dog, the observers recorded heart rate, respiratory rate, pupil dilation (present or absent) and a pain score using a NRS (range 0 to 10). For surgical cases, all study assessments were carried out between 21 and 27 hours following the end of surgery. The correlation coefficients between physiological parameters and NRS score were small but, depending on the analysis, were significant for heart rate and NRS score (P < 0·05). However, the size of the coefficient, 0·168, indicated that the relationship was not biologically significant. There was no association between respiratory rate and NRS score. Analysis of the relationship between NRS score and pupil dilation indicated that there was an association between this factor and pain, depending on the analysis. This was significant for the surgical groups (P < 0·05) but not for the other groups. These findings indicate that heart rate and respiratory rate are not useful indicators of pain in hospitalised dogs. It is also unlikely that pupil dilation will be a useful tool in the assessment of pain.

Micro‐ and nanoparticles prepared from the biodegradable and biocompatible polymers poly(lactide‐co‐glycolide) (PLGA) and polymethylmethacrylate (PMMA) have been successfully used as immunopotentiating antigen delivery systems. In our study, this approach was used to improve polyclonal antibody production to clenbuterol (CBL), a model hapten. PLGA and PMMA nanoparticles were loaded with either CBL alone or with a clenbuterol‐transferrin conjugate (CBL—Tfn) and administered subcutaneously to mice. PLGA nanoparticles were administered with or without the saponin adjuvant Quil A. The anti‐CBL titres present in experimental sera were determined by an enzyme immunoassay (ELISA). CBL‐Tfn‐loaded PLGA nanoparticles co‐administered with Quil A had obvious advantages immunologically over the currently used method of raising antibodies to CBL (the positive control). The combined adjuvanticity of Quil A and PLGA nanoparticles resulted in a positive response in all four of the mice tested and in higher antibody titres...

Community pharmacists' awareness of the COMA report on “Weaning and the weaning diet” and their knowledge of its recommendations was assessed in a questionnaire distributed to all (n=81) community pharmacists in the Western Health and Social Services Board in Northern Ireland. Sources of information and adequacy of training on childhood nutritional issues were determined. A knowledge score was computed for each pharmacist depending on their responses to questions based on key issues in the COMA report. Completed questionnaires were returned by 48 pharmacists (59 per cent). The COMA report had been read by 14.5 per cent of respondents while 12.5 per cent knew of its recommendations. Others had heard of it but not read it (52 per cent) or had never heard of it (21 per cent). The mean knowledge score was 66 per cent (±17.5). Scores ranged from 18 per cent to 90 per cent, indicating wide variability in pharmacists' knowledge of key recommendations for weaning. Only 29 per cent of pharmacists felt that they were adequately trained to give advice on weaning; 50 per cent felt that they did not have sufficient knowledge and 21 per cent were unsure. Pharmacists indicated that, on average, parents approached them weekly about a weaning topic, which emphasises the need for them to be well informed about current weaning recommendations.

Objectives To describe the development, preliminary validation and reliability testing of a shortened web-based form of GUVQuest, a structured questionnaire to measure health-related quality of life in dogs. Methods The original 109 items were reduced using expert judgement and factor analysis. Validity was established by factor analysis and in a subsequent field trial using a “known groups” approach and classical test theory. Test–retest reliability was assessed using intraclass correlation coefficients. Results The instrument comprises 46 items each of which is rated by dog owners using a 7-point Likert scale. Factor analysis revealed a sensible structure containing four health-related quality of life domains (vitality, pain, distress and anxiety) accounting for 64·1% of the variability in the data. The field test involving 125 dogs demonstrated very good discriminative properties and intraclass correlation coefficient values of greater than 0·6. Clinical Significance This is the first report of a valid and reliable companion animal health-related quality of life instrument, the contemporary approach to animal welfare measurement, which is presented in a web-based format, with automated production of a health-related quality of life profile. It offers major advantages to dog owners, practitioners and researchers.

Spatial variability is an important feature in many environmental studies, which influences comparison estimates of environmental radioactivity from soil samples and in-situ or airborne γ-ray spectrometry. Comparisons between ground based and airborne gamma ray spectrometry are needed both for interpretation and for calibration purposes. However, under normal environmental conditions such comparisons may be affected by the considerable differences in the spatial response of these measurement techniques. A sampling methodology is presented which enables soil sample derived estimates of environmental radioactivity to be effectively compared with in-situ and aerial survey results. Examples of calibration sites and derived sensitivity estimates for 137 Cs are presented for a range of environmental contexts.

The non-parenteral delivery of vaccines is reviewed with emphasis on particulate systems. The oral route predominates although there is now increasing work on the nasal routes of delivery. Intravaginal and intrarectal delivery makes use of the common mucosal immune system. Published work suggests that single dose mucosal vaccination using a biodegradable controlled-release delivery system is now a viable proposition. Drug regulatory aspects are considered and some of the control procedures necessary highlighted.

The appropriateness of empiric therapy, how closely prescribers adhered to hospital guidelines for use of antimicrobial drugs and how relevant these guidelines proved in providing cover for the infecting pathogen were assessed from a retrospective survey of culture and sensitivity reports issued during a one-month period in a district general hospital. Blood, stool, pus, sputum and mid-stream urine specimens were reviewed. Urine specimens from a fundholding general practice unit were also included. Catheter specimens of urine and specimens from other body sites were excluded. Of 290 specimens sent for culture, 99 (34 per cent) were positive. One hundred patients, of whom 54 (19 per cent of the total) were subsequently demonstrated to have a positive culture, had been treated empirically. In 38 per cent of cases the pre-report empiric treatment was considered appropriate for the isolated pathogen, while 46 per cent of patients had negative cultures and 16 per cent had positive cultures but had been given unsuitable antibiotics. In hospitalised patients, 73 per cent of antibiotic treatments were prescribed according to hospital guidelines, although this was the case for only 45 per cent of community-based patients. Hospital guidelines were a relevant and useful aid to rational prescribing in that 75 per cent of organisms isolated were sensitive to guideline antibiotics. The guidelines were least appropriate for urine specimens from hospital. This reflects the range of organisms encountered and the emergence of resistant strains, reinforcing the need for regular updating and amending of prescribing recommendations.

Background: Terbinafine has a broad spectrum of action in vitro and primary fungicidal action against many pahtogenic fungi. Its mode of action against dermatophyte fungi in nail keratin is little understood. Objective: Our purpose was to determine the bioavailability of terbinafine in a nail fragment model. Methods: The effect of terbinafine on adherence and germination of arthroconidia of Trichophyton mentagrophytes on nail fragments was assessed by gross examination and light and electron microscopy. Results: Preexposure of nail fragments to terbinafine concentrations (0.001 to 10 mg/L) inhibited fungal growth and acted as a barrier to dermatophyte invasion. Damaged arthroconidia and distorted hyphae on the surface of nail fragments were observed. Conclusion: This in vitro model provides an alternative system for studying the activity of antifungal agents in nail and demonstrates the morphologic changes in dermatophyte fungi after exposure to terbinafine.

The association (adherence) between human corneocytes and arthroconidia of Trichophyton mentagrophytes strains 121 and 126, and T. interdigitale strain 4 was studied in vitro. Adherence of arthroconidia to corneocytes from either the palm and sole occurred and increased with time up to 6 h, by which time germination of arthroconidia had started. Significant differences were seen between the T. mentagrophytes strains and T. interdigitale in their adherence to corneocytes from the palm. When adherence values for plantar corneocytes were compared, significant differences were found between T. mentagrophytes and T. interdigitale. Not all corneocytes from either site had adherent arthroconidia, although there was a time-dependent increase in the numbers of corneocytes with adherent fungal cells. By scanning and transmission electron microscopy it was seen that there was a loose association between arthroconidia and corneocytes with no apparent damage to the corneocyte membrane. Adherence of germlings of T. interdigitale to corneocytes from the palm appeared to be mediated by germling outer cell wall fibrils. Hyphal branches and secondary germlings were observed to enhance the attachment of the parent hypha to adjacent corneocytes.

The morphological modifications of arthroconidia and germ tubes of Trichophyton interdigitale exposed to terbinafine (6·25–100 mgl-1) incorporated into stratum corneum were studied by scanning and transmission electron microscopy after 16 h and 20 h. Changes in arthroconidial morphology were apparent at 16 h. Pores and erosions were present in the cell wall with layers peeling off. The cell membrane was destroyed. Dilated vacuoles and small electron dense areas were evident in the arthroconidial cytosol. Although germination was not arrested, inhibition of hyphal extension was seen. Germ tubes were susceptible to terbinafine with pores appearing along their length following exposure to the drug. Germ tubes were seen to have collapsed at higher drug concentrations. The study suggests that the outer and inner layers of the arthroconidial cell wall are the initial targets of terbinafine action followed by alterations to the cytosol and intracellular organelles.

The influence of experimental protocol on estimation of adherence of P. aeruginosa to buccal epithelial cells is highlighted. Use of membrane filtration to remove non-adherent bacteria was significantly affected by membrane pore size and rinse volume, but was not affected by inoculum size or test isolate. Even with optimum filtration conditions, over 58% of the non-adherent bacterial population were retained on the filters. Separation of non-adherent bacteria was greatly improved when density centrifugation was employed, with less than 30% of non-adherent bacteria present in the buccal epithelial suspension. Adherence values measured by a radiological and fluorometric method were significantly higher than those determined by microscopic counting. Radiological assays had the lowest variance. Gradient centrifugation was used to prepare a standard suspension of buccal epithelial cells. However, cells collected on different days showed significantly different adherence measurements. Adherence of bacteria to trypsinized buccal epithelial cells and to buccal epithelial cells from cystic fibrosis patients was similar, whereas adherence to normal buccal epithelial cells was significantly lower.

The emergence of germ tubes from arthroconidia of Trichophyton mentagrophytes on stripped sheets of stratum corneum from different body areas was measured. Arthroconidia increased in size and started germination by 4 h at 37 degrees C. Germ tubes originated from a point on the arthroconidium surface mid-way between the points of attachment to adjacent conidia. With further incubation arthroconidial germination increased and germ tubes extended across the stratum corneum. Histological staining of transverse sections of infected stratum corneum showed hyphae penetrating longitudinally and perpendicularly through the thickness of the stratum corneum. By 7 days' incubation hyphae started to form arthroconidia thereby completing the vegetative growth cycle of the fungus. Scanning electron microscopy revealed penetration of corneocytes by germ tubes resulting in damage to the corneocyte surface.

The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M-SAA3 in mammary tissues was determined using immunocytochemistry. Increases of M-SAA3 and Hp in milk occurred within 12 h of Staphylococcus aureus infusion, with peak concentrations occurring 3 d after infusion of the bacteria. The increase of acute phase proteins in milk (15 h) preceded the increase in serum concentrations of both proteins (24 h). Expression of mRNA for M-SAA3 and Hp increased in both mammary and hepatic tissues 48 h after infusion of the mammary glands. In mammary tissue, the increase of M-SAA3 mRNA was greater than the increase in Hp mRNA expression, whereas in hepatic tissue, the increase in M-SAA3 mRNA was less than that for Hp mRNA. Immunocytochemistry demonstrated that M-SAA3 protein was present within secretory epithelial cells at significantly higher levels in infected mammary glands than in control tissues. These proteins, which have host defense and antibacterial activities, may play a significant role in the early response to invasion of mammary tissues by pathogenic bacteria.

An in vitro method of determining the activity of antibiotics in combination which is simple and convenient to perform and which could be used routinely in clinical microbiology laboratories is desirable. We investigated the activity, against Pseudomonas aeruginosa and Burkholderia cepacia complex clinical isolates, of ceftazidime and tobramycin in combination using a broth macrodilution sensitivity method based on breakpoint minimum inhibitory concentrations and compared the results obtained using this method with those obtained using the microtitre checkerboard method. There was good agreement in interpretation of results between the two methods for both P. aeruginosa (90%) and B. cepacia complex isolates (70%) with tobramycin and for P. aeruginosa isolates (70%) with ceftazidime. As the breakpoint combination sensitivity testing method employs only four tubes and does not require initial determination of individual antibiotic minimum inhibitory concentrations, it is simpler and more convenient for determining the activity of antibiotics in combination than the microtitre checkerboard method. The use of this method in routine microbiology laboratories to determine the activity of antibiotic combinations against clinical isolates should optimise treatment of infection by ensuring that appropriate antibiotic combinations are prescribed.

Background/aims Tail docking neonatal piglets remains a controversial animal welfare issue. Although banned in the UK, it is widely practiced in many countries as a safeguard against tail biting among pigs reared in intensive systems. Concerns exist whether tail docking can induce chronic pain in later life. This preliminary study examined the effects of partial tail amputation on activating transcription factor 3 (ATF3), a marker of peripheral nerve injury and regeneration and NMDA-glutamate receptor NR2B subunit which participates in the mediation of chronic pain. Methods Procedures were performed according to the ethical guidelines for the study of experimental pain in animals. Six piglets (2–3 days old) were tail-docked (a portion of the tail amputated with sterile surgical cutters), six piglets (2–3 days old) were sham-docked. Three animals from each treatment were euthanised 7 and 56 days post-amputation. Coccygeal dorsal root ganglia (DRG) and spinal cord were collected post-mortem for immunohistochemistry. Results ATF3 immunoreactivity (IR) was significantly increased (p p < 0.05) in dorsal horn neurons in tail-docked piglets compared with intact piglets 7 days after docking. There was no difference in NR2B-IR in neurons 56 days post amputation, compared with intact piglets. Conclusions Increased ATF3 and NR2B-IR 7 days after tail-docking suggests that injury to the peripheral nerves in the tail was sufficient to trigger neuronal regeneration and altered dorsal horn signaling respectively, however the effects of tail-docking on neuronal regeneration and nociceptive signaling were relatively short lasting. Tail-docking neonatal piglets does not cause sustained changes in ATF3, which might suggest ongoing nerve fibre damage and NR2B which might be implicated in chronic pain.

The main aim of this study was to assess the effects of a fitness assessment and exercise consultation on physical activity over 1 year in non-regularly active participants drawn from a socially and economically deprived community. Of 3000 people invited to volunteer for either intervention, 225 fitness assessment volunteers were randomly assigned to an experimental or control group; 145 exercise consultation volunteers were similarly assigned. Physical activity was measured at baseline, 4 weeks, 3 months (plus an intervention re-test), 6 months and 1 year. Analysis of variance and follow-up Bonferroni analysis showed that, for those not regularly active at baseline, physical activity increased significantly to 4 weeks, was maintained to 6 months but had fallen by 1 year. Only those receiving an exercise consultation significantly increased their physical activity after 1 year. Compared with fitness assessments, chi-square analysis showed that significantly more non-regularly active participants volunteered for an exercise consultation and those receiving an exercise consultation had significantly better long-term study adherence than those receiving a fitness assessment. The study also showed that, contrary to popular opinion, those in a socially and economically deprived community are not 'hard to reach' and respond well to physical activity interventions.

An innovative approach using a multiple-study research programme that incorporated five individual projects, each of which can be interpreted independently or as an integral part of the whole

OBJECTIVE: To determine the quality of life of elderly patients with osteoarthritis (OA) compared with that of their peers with no chronic illnesses and to investigate the associations between analgesic use and quality of life. SUBJECTS: Patients >65 years of age with OA taking analgesics with (n = 33) and without (n = 26) comorbidities, and control patients with no chronic illness and not taking analgesics (n = 37). METHODS: Quality of life was assessed by the SF-36 and level of pain was measured by a visual analog scale. Multiple regression analysis was used to determine the medication characteristics and additional patient factors significantly associated with SF-36 scores. RESULTS: OA patients had significantly (p < 0.05) lower scores than control patients in all quality-of-life domains. OA patient scores were lowest for the domains of role-physical, bodily pain, and physical functioning. OA patients with comorbidities also had poorer general and mental health. Pain- and analgesic-related factors were significantly (p < 0.05) associated with physical health status, reduced vitality, general health, and social functioning. A better quality of life was associated with noncompliance, fewer visits to the physician, and taking oral nonsteroidal antiinflammatory agents. Presence of adverse drug reactions and sleep disturbance did not influence SF-36 scores significantly. CONCLUSIONS: Quality of life of elderly OA patients with and without additional comorbidities was significantly poorer than that of their healthy peers, particularly in the domains associated with physical status, but also affecting vitality, social functioning, and general health. Level of pain suffered and perceived effectiveness of analgesic medication in pain control were important factors associated with quality of life.

A new in vitro model for the study of nail invasion by dermatophyte fungi was developed. The dermatophyte Trichophyton mentagrophytes, and fragments of finger-nails and toe-nails were used. Arthroconidia were inoculated on the ventral surface of the nails. After 6 h, adherence and germination of arthroconidia was observed. By 16 h, small germ tubes with side branches were evident. At about 24 h, micro-colonies had become established. At 48 h, a mycelium had formed, and at about 72 h most of the nail fragment was covered with fungal growth. Nail penetration occurred from the ventral surface through the intercellular spaces, and with longer incubation all three layers were invaded by arthroconidia growing through channels. Nail invasion occurred in the absence of added nutrients. Dermatophyte fungi appeared to invade the nail by a combination of mechanical and chemical factors. The model provides a substrate to study the pharmacokinetics and bioavailability of new antifungal agents in situ.

Time-survival studies were conducted to estimate the effects of azlocillin and tobramycin on Pseudomonas aeruginosa NCIMB 8295 (in the exponential phase of growth) at concentrations ranging from one-quarter to twice the MIC. The effects of the individual agents and their combinations were determined by measuring the viable counts (CFU per milliliter) over a 24-h period. The typical pattern observed from the plot of the logarithm of the CFU per milliliter against time was an initial rapid killing; this was followed by a period of stasis and regrowth. Initial rates of killing by tobramycin were concentration dependent, whereas this was not the case with azlocillin. From the time-survivor plots, the area under the curve for viable bacteria was also calculated. It offered a useful method of interpreting the results of time-kill studies, taking the overall pattern of killing and regrowth into consideration. The area under the curve for viable bacteria was concentration dependent for both antibiotics. A 2(2) factorial experimental design was used to analyze the joint effects of azlocillin and tobramycin. In such a factorial experiment, an interaction between two factors, in this case, azlocillin and tobramycin concentrations, is shown by a change in the slope of the plot when the concentration of the interactant is changed. Analysis of variance showed that the combination was synergistic at low concentrations, but this was not significant when the concentration of either interactant was increased.

D. GILLILAND, A. LI WAN PO AND E. SCOTT. 1992. The antimicrobial effects of methyl and propyl parabens are investigated, with Escherichia coli as test organism, with a view to determining whether the parabens act synergistically. At appropriate concentrations, the parabens killed E. coli cells according to first order kinetics and the bactericidal effects were quantified by the first order kill rate constants. Combinations of methyl or propyl parabens, at concentrations which slow down or inhibit bacterial growth when used singly, produced definite kill. In this sense, the parabens are therefore synergistic since in combination they produce an effect which is not observed when they are used singly. This effect is not true synergism as shown by the results of our experiments with a factorial design. Analysis of variance indicated no significant interaction between the two parabens.

Five serial exposures of mucoid Pseudomonas aeruginosa from patients with cystic fibrosis to subinhibitory concentrations of ciprofloxacin resulted in stepwise increases in the MIC, with a mean proportional increase of 10. MICs were significantly lower in an iron-limited chemically defined medium than in Iso-Sensitest broth. The mucoid phenotype was maintained in chemically defined medium. Acquired resistance was retained either partially or completely in 85% of the isolates following 10 transfers in drug-free media. In cases in which susceptibility was regained, an increase in the MIC was observed on one further exposure to ciprofloxacin.

Focal points □ A self-selected set of pharmacists participated in a formal women's health care advice programme □ The tools (continuing education needs assessment grid and job competency wheels) proved useful in identifying training needs and assisted the implementation of identified training solutions □ Regular meetings of the set were an essential component of the process □ Motivation and encouragement by peers should not be underestimated □ Action learning in association with an organised programme is a successful and appropriate means of facilitating CPD

Focal points □ The pilot study evaluated the outcome of a pharmacy-based initiative for women starting or having recently started HRT □ At the end of the study over twice as many women in the control group had stopped taking HRT than in the intervention group □ Kupperman menopausal index scores used to indicate control of menopausal symptoms had improved significantly more in the intervention group compared with the control group □ Intervention group patients were more knowledgeable of the benefits of HRT, and of osteoporosis risk factors and preventive measures □ The control group expressed significantly more concerns about HRT at the end of the study compared with the intervention group

An investigation of a possible relationship between Diphyllobothrium (fish tapeworm) infection and microcytic anaemia among Eskimos was carried out during 1957–1958 at the village of Hooper Bay in western Alaska. Such infections did not contribute to anaemia in residents of this region, a finding in agreement with those of Totterman 1947 in Finland. Species of diphyllobothriid cestodes recorded from the lower Kuskokwim River region are listed, and other helminths recorded from man in this area are briefly discussed. Schistocephalus solidus (Mueller 1776) is reported from man, apparently for the first time.

Increased bactericidal activity was observed on addition of inorganic cations to both acid and alkaline glutaraldehyde solutions. Mg2+ ion in particular potentiated activity and this was attributed to cell surface effects due to osmotic forces resulting in greater uptake of disinfectant, reduction in cell volume and interference with enzyme activity associated with the cell wall.

Fungistatic data were obtained from measurements of mycelial growth of several fungal species in the presence of acid or alkaline glutaraldehyde. Alkaline glutaraldehyde in concentrations > 0·1% (w/v) prevented growth of all species examined while 0·5% (w/v) acid glutaraldehyde was necessary to achieve this effect. Further fungistatic data were obtained using a Coulter Counter method to measure spore swelling. Fungicidal determinations resulted in a 99·99% reduction in viable count after 90 min contact with 0·5% (w/v) alkaline glutaraldehyde. A considerable drop in spore production was also observed after treatment with alkaline glutaraldehyde.

Ringworm formed almost 70 per cent of all superficial mycoses diagnosed. The feet and nails were most frequently affected and a single species, Trichophyton rubrum was responsible for the majority of infections that required specialist attention. Scalp ringworm which, until the middle of this century, was the most common form of the disease now constitutes only 5 per cent of infections and the majority of these are caused by the zoophilic fungus Microsporum canis. The anthropophilic dermatophytes which were once so prevalent as the cause of scalp infections are now rarely encountered. Yeasts, especially Candida albicans were most frequently encountered as a cause of mucosal infections but were not unimportant as a cause of disease of skin and nail.