The occurrence of cardiac abnormalities in canine steroid-responsive meningitis arteritis.

OBJECTIVES: To document the prevalence of cardiac abnormalities in dogs with steroid-responsive meningitis arteritis and to assess resolution of these abnormalities following corticosteroid therapy. MATERIALS AND METHODS: Steroid-responsive meningitis arteritis was diagnosed based on signalment, physical examination findings, complete blood count, biochemistry and CSF analysis. Echocardiography, C-reactive protein and cardiac troponin I were measured in all cases before and 10 to 14 days after commencing corticosteroid therapy. Fibrinogen was also measured in a proportion of dogs. RESULTS: Fourteen dogs were prospectively enrolled. Increased cardiac troponin I was identified in five of 14 dogs and echocardiographic abnormalities were detected in 12 of 14 dogs, including spontaneous echo contrast (12 of 14), mild pericardial effusion (five of 14) and mildly decreased fractional shortening (five of 14). All dogs had increased C-reactive protein and fibrinogen was increased in 11 of 12. Corticosteroid treatment was associated with clinical improvement and normalisation of C-reactive protein in all dogs. The cardiac troponin I levels normalised in four of five and fibrinogen had normalised in all five dogs which were retested. Spontaneous echo contrast improved or completely resolved in 12 of 12 and pericardial effusion resolved in five of five dogs. Fractional shortening normalised in two of five dogs. CLINICAL SIGNIFICANCE: Cardiac changes are common in dogs with steroid-responsive meningitis arteritis and most resolve with therapy. Further investigation into the cause and significance of these changes is necessary in determining whether antithrombotic therapy or positive inotropic therapy is indicated.

Associations among meniscal damage, meniscal symptoms and knee pain severity.

OBJECTIVE: Meniscal tears occur frequently in patients with knee osteoarthritis (OA). The aim of our study was to determine whether meniscal damage identified on magnetic resonance imaging (MRI) is associated with the severity of knee pain or the frequency of meniscal symptoms in patients with knee OA. METHODS: We performed a cross-sectional study using data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial. We characterized meniscal damage hierarchically as: root tear; maceration; long and short complex or horizontal tears; and simple tears. Subjects completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scale and a survey of frequency of meniscal symptoms. We used multivariable general linear models to assess the relationships between meniscal damage and 1) pain severity; and 2) meniscal symptoms, after adjusting for demographic and radiographic features. In further analysis root tear was considered as a binary variable. RESULTS: Analysis included 227 knees. Root tears were present in 19%, maceration in 14%, long complex or horizontal tears in 22%, short complex or horizontal tears in 30%, and simple tears in 14%. Root tears were associated with higher WOMAC pain scores. The adjusted mean WOMAC pain score was 45.2 (standard error (SE) 2.7) for those with root tear and 38.7 (SE 1.2) for subjects without root tear (P = 0.03). We did not find statistically significant associations between meniscal morphology and frequency of meniscal symptoms. CONCLUSION: Root tears were associated with greater pain than meniscal tears or maceration. We did not find a relationship between meniscal damage and meniscal symptoms.

Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs.

It is recommended that trilostane therapy of canine hyperadrenocorticism is monitored using an ACTH stimulation test, however this has never been validated. Three cortisol concentrations (pre-trilostane, 3-hour posttrilostane and 1-hour post-ACTH stimulation) were compared to a clinical score obtained from an owner questionnaire. There were 110 sets of 3 cortisol measurements and questionnaires obtained from 67 trilostane treated dogs. Questionnaire results were used to classify each dog as well or unwell. Well dogs were then categorised as having excellent, moderate or poor hyperadrenocorticism control, using thresholds produced by 14 independent veterinarians. Correlation co-efficients were used to compare the three cortisol concentrations to the owner score and the Kruskal Wallis and Mann-Whitney U tests were used to compare the three cortisol concentrations between categories of control. Cortisol cut-off values between significantly different categories were determined using ROC curves. Pre-trilostane and 3-hour post-trilostane cortisol were better correlated to the owner score and had cut-offs to differentiate between categories of control that had superior sensitivity and specificity results, than the post-ACTH cortisol. Iatrogenic hypoadrenocorticism was not detected in any unwell dog. This study shows that the pre-trilostane and 3-hour post-trilostane cortisol are potentially better monitoring methods than the ACTH stimulation test.

Use of neutrophil to lymphocyte ratio for predicting histopathological grade of canine mast cell tumours.

Canine mast cell tumours (MCTs) are variable in their biological behaviour and treatment decisions depend heavily on the histopathological grade. Biomarkers such as neutrophil to lymphocyte ratio (NLR) and albumin to globulin ratio are used to predict the biological behaviour of human neoplasms, but have not been widely studied in dogs. A retrospective analysis identified 62 cases of gross MCT (14 high-grade, 48 low-grade tumours). Median NLR was significantly different between high- and low-grade MCT and tumours at different locations. A multivariable model identified increasing NLR (OR 2.0) and age (OR 1.7) to be associated with an increased risk of high-grade MCT. Receiver operating characteristic curve analysis identified an NLR threshold value of 5.67 (sensitivity 85.7 per cent; specificity 54.2 per cent) for predicting a high-grade MCT. An NLR threshold of 5.67 could be useful alongside existing tools (appearance, location, etc.) to help to predict the grade of MCT. With further validation, this biomarker could be used to guide clinical decisions before obtaining a histopathological diagnosis.

Diagnostic value of neutrophil-lymphocyte and albumin-globulin ratios in canine soft tissue sarcoma.

OBJECTIVE: To investigate the ability of neutrophil-to-lymphocyte ratio and albumin-to-globulin ratio to differentiate soft tissue sarcoma from benign soft tissue tumours. METHODS: A retrospective study of pretreatment haematology and biochemistry in dogs diagnosed with soft tissue sarcoma or benign soft tissue tumours. The neutrophil-to-lymphocyte ratio and albumin-to-globulin ratio were compared between the two groups. In dogs diagnosed with soft tissue sarcoma, the relationship of neutrophil-to-lymphocyte ratio and albumin-to-globulin ratio to histological tumour grade (I to III) was assessed. RESULTS: In the dogs with soft tissue sarcoma (n=22), the neutrophil-to-lymphocyte ratio was significantly increased and the albumin-to-globulin ratio decreased compared to those with benign soft tissue tumours (n=14). The neutrophil-to-lymphocyte ratio and albumin-to globulin ratio were not useful as predictors of tumour grade in dogs diagnosed with soft tissue sarcoma. CLINICAL SIGNIFICANCE: Pretreatment neutrophil-to-lymphocyte ratio and albumin-to globulin ratio may aid with diagnosis and optimal treatment planning. Further investigation into their prognostic implications is warranted.

Clinical experience and psychometric properties of the Children's Dermatology Life Quality Index (CDLQI), 1995-2012.

The Children's Dermatology Life Quality Index (CDLQI) is a widely used questionnaire to measure the quality of life of children aged from 4 to 16 years. The purpose of this review is to summarize all published data regarding the clinical experience of the CDLQI and its psychometric properties as a single reference source for potential users. A literature search was carried out to identify all articles describing the use of the CDLQI from 1995 to November 2012. One hundred and six articles were identified, with four excluded. The CDLQI has been used in 28 countries in 102 clinical studies and is available in 44 languages, including six cultural adaptations; a cartoon version is available in 10 languages. It has been used in 14 skin conditions and used in the assessment of 11 topical drugs, nine systemic drugs, 13 therapeutic interventions and two epidemiological and other studies. There is evidence of high internal consistency, test-retest reliability, responsiveness to change, and significant correlation with other subjective and objective measures. Rasch analysis has not been carried out and more information is needed concerning minimal clinically important difference; these are areas requiring further study.

Seven years' experience of Mohs micrographic surgery in a UK centre, and development of a UK minimum dataset and audit standards.

BACKGROUND: Mohs micrographic surgery (MMS) is the gold-standard treatment for high-risk basal cell carcinomas and a variety of other cutaneous tumours, including dermatofibromasarcoma protuberans and microcystic adnexal carcinoma. Previous large-scale case series, audits and reviews have allowed evaluation of MMS outcomes, such as BCC recurrence rates. However, to date there has been no systematic UK MMS audit, and certain important aspects of care, such as postoperative functional outcomes, have not yet been subject to scrutiny. AIMS: To review audit data from our centre, and from this to develop a minimum dataset and audit standards for UK MMS centres, on behalf of the British Society of Dermatological Surgery (BSDS). METHODS: An MMS database was developed locally and modified in response to repeated audit cycles since the introduction of the MMS service. A minimum dataset was developed using this experience. RESULTS: In our department, primary BCC recurrence rates are reassuringly low at 0.3%, at both 2 and 5 years. Histopathological discordance is < 2%, and aesthetic and functional outcomes at 3 months are good. CONCLUSIONS: The collation of audit data has been simplified by use of the minimum dataset, which we propose for all UK MMS centres, on behalf of the BSDS.

Acquisition, evolution and maintenance of the normal gut microbiota.

The gut is sterile at birth, but is rapidly colonised by faecal and vaginal bacteria of maternal origin. Over the succeeding weeks, months and years, a complex microbiota develops that plays a major role in host physiology. While the digestive tract is colonised to varying degrees by micro-organisms throughout its length, due to acid pH and the short retention time of gastric contents, bacterial numbers in the stomach are usually low. The rapid passage of digestive materials through the upper gut does not provide time for significant bacterial growth to occur, but cell numbers increase considerably in the distal ileum. The rate of movement of intestinal contents slows in the colon, which facilitates the development of complex bacterial communities. The large intestine is an intricate ecosystem that contains a complex microbiota composed of several hundred different types of bacteria. The growth and metabolism of microbial communities in the large intestine are determined by many factors, such as diet, environment and host physiological processes, as well as the anatomic structure of the digestive tract, disease, immunity, host genetics, drugs and ageing. Modifications in diet and host immune system activity, as well as physiological changes in the digestive tract affect microbiota composition in older people. The elderly have fewer bifidobacteria and higher numbers of enterobacteria and clostridia than young adults. Increased antibiotic use in older people and simply going into hospital have been shown to change bacterial community structure in the colonic microbiota, although the metabolic significance of this is unclear.

Detection of Dientamoeba fragilis by culture.

Symptoms associated with Dientamoeba fragilis include diarrhoea, abdominal pain, nausea, vomiting, epigastric pain and weight loss. A possible link between D. fragilis and irritable bowel syndrome (IBS)-like symptoms has been reported, and therefore the presence of this parasite should be excluded before making a diagnosis of IBS. Over a six-month period, 976 faecal samples were submitted to NPHS Microbiology Aberystwyth for routine microbiological analysis. All samples were also cultured for parasites using Robinson's xenic medium. Trichrome staining was undertaken whenever practicable, but many stools had insufficient material. D. fragilis was isolated from 25 (2.6%) patients, whereas Cryptosporidium spp. was detected in 16 (1.6%) patients. D. fragilis was only detected in nine (1.3%) out of 685 specimens stained with trichrome, although four of the 25 culture-positive stools had insufficient sample for staining. Parasite culture proved to be less laborious than trichrome staining and dramatically increased D. fragilis detection rate.

Pathological features of breast cancer response following neoadjuvant treatment with either letrozole or tamoxifen.

Morphological characteristics, grading features, proliferation marker MIB1, apoptosis (by Tdt-mediated duTP-biotin nick-end labelling (TUNEL)), Bcl-2 expression, oestrogen receptor (ER) and progesterone receptor (PgR) status were compared in ER-positive breast cancers before and after 3 months of neoadjuvant therapy with either letrozole or tamoxifen. Daily treatment was with letrozole 2.5 mg (12 patients) or 10 mg (12 patients), or with tamoxifen 20 mg(24 patients). Letrozole treatment was associated with a pathological response in 17 of 24 (71%) patients. The predominant change in grading features was a decrease in mitosis, and the expression of MIB1 was reduced in all of the 22 evaluable cases. Whilst only marginal changes were observed in ER expression following letrozole therapy, PgR reactivity was reduced in 20 of 21 evaluable cases which were initially PgR-positive, becoming undetectable in 16 patients. Tamoxifen treatment was associated with pathological response in 15 of 24 (63%) tumours. In contrast to letrozole, the dominant change in grading feature was an increase in tubule formation, ER score was markedly reduced in most cases, and the most common effect on PgR was an increased expression. Following treatment with either tamoxifen or letrozole, variable effects were observed on the apoptotic index and expression of Bcl-2. These results indicate that both letrozole and tamoxifen have marked influences on the pathological features of breast cancer during neoadjuvant therapy. However, the effects of the two agents varied such that the phenotypes of letrozole- and tamoxifen-treated tumours differ markedly. Effects on clinical, pathological and biological endpoints were frequently disconcordant--future studies will therefore require the evaluation of multiple parameters in order to fully assess tumour response.

Incidence of Blastocystis hominis in faecal samples submitted for routine microbiological analysis.

Over a one-year period, 1390 faecal samples were submitted to Aberystwyth Public Health Laboratory for routine microbiological examination. All were stained using a commercial trichrome method. Blastocystis hominis was detected in 96 (6.9%), making it the most common parasite found in the study. Of the B. hominis-positive specimens, 73% were missed on direct microscopy. Molecular typing of B. hominis has revealed extensive genetic diversity in morphologically identical strains and thus detection by microscopy alone may not be sufficient to confirm the role of this organism in human disease.

Maximizing thoracic organ transplant opportunities: the importance of efficient coordination.

BACKGROUND: In Australia, despite large distances and one of the world's lowest multiorgan donor rates (11.4/million population/year), the thoracic organ transplant (TOTx) rate of 9.6/million population/year is one of the world's highest. METHODS: As an example of the Australian approach, a system of transplant coordination and organ allocation has evolved at the Alfred Hospital. Donor organs are assigned locally, or between the 4 major TOTx units on rotation. The recipient team then selects appropriate recipients, matching by blood group, size, cytomegalovirus (CMV) status, prospective cross matching and clinical status. An experienced recipient coordinator takes responsibility for organization of the retrieval and transplant process, including all operating room staff, all medical personnel, and transport for the donor team and the potential TOTx recipients. RESULTS: Between February 1989 and February 1999, 307 hearts, 48 heart/ lung, 124 single and 116 bilateral lung transplants were performed from 452 donor offers (52% beyond 500 miles). This represents 1.74 organs transplanted/thoracic donor and compares favourably to American United Network for Organ Sharing (1.43) and European (1.3) figures. CONCLUSIONS: The Australia TOTx model has enabled high transplant rates by efficiently using the available donor organs. This has been achieved through an enlarged, experience TOTx team, the optimizing of donor acceptance criteria and improving coordination logistics to allow multiple thoracic procedures simultaneously.

Maximizing the utilization of donor organs offered for lung transplantation.

The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors and therapeutic manipulation where appropriate. This study aims to assess the impact of utilization of marginal donors and aggressive donor management. A comparison between published donor criteria and local practice is made, allowing assessment of the effect of using marginal donors on outcome. Donor management included antibiotic therapy, strict fluid management, physiotherapy, bronchoscopy and bronchial toilet, and alteration of ventilatory settings including initiation of pressure support. Blood gases were repeated to assess the results of interventions. Between January 1, 1995 and May 31, 1998, we performed 140 transplants from 112 of 219 (51%) lung donor offers. Of these donors, 48 (43%) satisfied all published criteria for suitable donor organs (Group 1 = ideal donors) and 64 (57%) did not (Group 2 = marginal donors). Criteria breached by the marginal donors were: an initial ratio of arterial oxygen pressure to fraction of inspired oxygen (PaO2/FIO2) < 300 mm Hg (n = 20), abnormal radiology (n = 39), pulmonary infection (n = 24), 20 pack-years smoking (n = 5) and age > 55 yr (n = 4). Therapeutic manipulation resulted in improvement in the PaO2/FIO2 ratio in 20 donors (Group 3) who would not otherwise have been used. Immediate and 24 h postoperative gas exchange and length of intensive care unit (ICU) stay was not different for recipients from donors from all three groups. Overall survival was 94% at 30 d, 83% at 1 yr, 70% at 2 yr, and 62% at 3 yr and was not significantly different from the three groups. We conclude that organ utilization can be maximized by therapeutic manipulation and utilization of marginal donors without compromising results from transplantation.