Current evidence for non-pharmaceutical, non-surgical treatments of canine osteoarthritis.

Osteoarthritis is a progressive degenerative disease process that affects a significant proportion of the canine population, impacting these animals' quality of life. Currently, there is no cure and treatment consists of managing the clinical signs of pain and reduced mobility. There are many treatments for canine osteoarthritis and in this review we discuss the evidence base behind non-pharmaceutical, non-surgical treatments of this disease. These treatments include weight management, nutraceuticals, acupuncture, physiotherapies such as therapeutic exercise, hydrotherapy as well as other therapeutic modalities including photobiomodulation therapy, electromagnetic field therapy and others.

Determining predictive metabolomic biomarkers of meniscal injury in dogs with cranial cruciate ligament rupture.

OBJECTIVES: This study used hydrogen nuclear magnetic resonance spectroscopy for the first time to examine differences in the metabolomic profile of stifle joint synovial fluid from dogs with cranial cruciate ligament rupture with and without meniscal injuries, in order to identify biomarkers of meniscal injury. Identifying a biomarker of meniscal injury could then ultimately be used to design a minimally invasive diagnostic test for meniscal injuries in dogs. MATERIALS AND METHODS: Stifle joint synovial fluid was collected from dogs undergoing stifle joint surgery or arthrocentesis for lameness investigations. We used multi-variate statistical analysis using principal component analysis and univariate statistical analysis using one-way analysis of variance and analysis of co-variance to identify differences in the metabolomic profile between dogs with cranial cruciate ligament rupture and meniscal injury, cranial cruciate ligament rupture without meniscal injury, and neither cranial cruciate ligament rupture nor meniscal injury, taking into consideration clinical variables. RESULTS: A total of 154 samples of canine synovial fluid were included in the study. Sixty-four metabolites were annotated to the hydrogen nuclear magnetic resonance spectroscopy spectra. Six spectral regions were found to be significantly altered (false discovery rate adjusted P-value <0.05) between groups with cranial cruciate ligament rupture with and without meniscal injury, including three attributed to nuclear magnetic resonance mobile lipids [mobile lipid -CH3 (P=0.016), mobile lipid -n(CH3 )3 (P=0.017), mobile unsaturated lipid (P=0.031)]. CLINICAL SIGNIFICANCE: We identified an increase in nuclear magnetic resonance mobile lipids in the synovial fluid of dogs with meniscal injury which are of interest as potential biomarkers of meniscal injury.

Advances in the pharmaceutical treatment options for canine osteoarthritis.

Canine osteoarthritis is a significant cause of pain in many dogs and can therefore compromise animal welfare. As the understanding of the biology and pain mechanisms underpinning osteoarthritis grows, so do the number of treatments available to manage it. Over the last decade, there have been a number of advances in the pharmaceutical treatment options available for dogs with osteoarthritis, as well as an increasing number of clinical trials investigating the efficacy of pre-existing treatments. This review aims to examine the current evidence behind pharmaceutical treatment options for canine osteoarthritis, including non-steroidal anti-inflammatory drugs, piprants, monoclonal antibodies, adjunctive analgesics, structure modifying osteoarthritis drugs and regenerative therapies.

Causative alternations of children with specific language impairment.

Alternating verbs to indicate or to relinquish cause requires an understanding of semantic and syntactic knowledge. This study evaluated the ability of children with specific language impairment (SLI) to produce the causative alternation in comparison to age peers and to language peers. The children with SLI were proficient in lexically alternating verbs, yet provided fewer passive and periphrastic constructions and more different verbs and adjectival responses. Overgeneralization error data suggest that the semantic systems of some children with SLI were similar to their age comparisons. Individual differences within the SLI group suggested that some children were adept at providing syntactic responses and overgeneralizations, whereas some of the SLI group provided less mature responses of no alternations and no responses. These findings demonstrate a syntactic deficit in the causative alternation for some children with SLI.

Natural history of isolated bundle branch block.

The purpose of this study was to determine the long-term outcome of patients with bundle branch block (BBB) who have no clinical evidence of cardiovascular disease. Among 110,000 participants in a screening program, 310 subjects with BBB without apparent of suspected heart disease were identified. Their outcome after a mean follow-up of 9.5 years was compared with that of 310 similarly screened age- and sex-matched controls. Among the screened population, isolated right BBB was more prevalent than isolated left BBB (0.18% vs 0.1%, respectively; p<0.001), and the prevalence of each abnormality increased with age (p<0.001). Total actuarial survival was no different for those with left BBB or right BBB and their respective controls. Cardiac mortality, however, was increased in the left BBB group when compared with their controls (p=0.01, log rank test). Left BBB, but not right BBB, was associated with an increased prevalence of cardiovascular disease at the follow-up (21% vs 11%; p=0.04). In the absence of clinically overt cardiac disease, the presence of left BBB or right BB is not associated with increased overall mortality. Isolated left BBB is associated with an increased risk of developing overt cardiovascular disease and increased cardiac mortality.

Lipid levels of expeditioners in Antarctica: response to a reduced-fat, oleic acid and carbohydrate-enriched diet.

The study examined the effects of a reduced-fat, oleic acid and carbohydrate-enriched diet on serum lipid profiles and body weight in the setting of an isolated Australian Antarctic station. A 12-week dietary intervention period was provided for 30 healthy, free-living expeditioners against a background diet typical of the Australian population. The diet tested a "modified U.S. Dietary Goals" regimen which increased oleic acid preferentially (29% energy from fat and 46% from carbohydrate, polyunsaturated: monounsaturated: saturated fatty acid ratio [P:M:S] of 0.6:1.3:1.0, 30 g fibre/day, less than 300 mg cholesterol/day). During the intervention period, mean serum HDL-cholesterol (HDL-C) levels remained relatively stable while mean serum total cholesterol (TC) fell significantly (a fall of 0.95 mmol/l, p < 0.05). The mean serum triglyceride (TG) level rose initially (1.44 to 1.64 mmol/l, p < 0.05) but the level returned to baseline (1.41 mmol/l) by the end of the intervention period. The change in TG level was associated with increased dietary carbohydrate but not with changes in body weight, alcohol intake or season. The study demonstrates that a reduced-fat, oleic acid and carbohydrate-enriched diet can result in significant improvements in serum lipid profiles. The diet was acceptable to the subjects and was easily provided in Antarctica with unobtrusive changes to the typical Australian diet.

Familial site-specific ovarian cancer is linked to BRCA1 on 17q12-21.

In a study of nine families with "site-specific" ovarian cancer (criterion: three or more cases of epithelial ovarian cancer and no cases of breast cancer diagnosed at age < 50 years) we have obtained evidence of linkage to the breast-ovarian cancer susceptibility gene, BRCA1 on 17q12-21. If the risk of cancer in these families is assumed to be restricted to the ovary, the best estimate of the proportion of families linked to BRCA1 is .78 (95% confidence interval .32-1.0). If predisposition to both breast and ovarian cancer is assumed, the proportion linked is 1.0 (95% confidence interval .46-1.0). The linkage of familial site-specific ovarian cancer to BRCA1 indicates the possibility of predictive testing in such families; however, this is only appropriate in families where the evidence for linkage to BRCA1 is conclusive.

Energy intake, anthropometry and blood pressure of expeditioners in the Antarctic.

The energy intakes, anthropometry and blood pressure of 62 expeditioners at one Australian sub-Antarctic (Macquarie Island) and two Antarctic stations (Davis and Casey) were examined over a 12 month period. High mean energy intakes were found at all stations (approximately 16,000 kJ/subject/day). Mean subject body weight tended to rise during the winter months (midway during the study) and fall during the spring, although there were no significant changes (p < 0.05) seen at any of the stations over the year. Subjects were generally leaner at the end of 12 months as evidenced by significant falls (p < 0.01) in mean sum of skinfold thickness at two stations over the year. At all stations, blood pressure trended downwards during the year, with significant rises (p < 0.01) seen at one station during the spring. Two 12-week dietary intervention periods were introduced during the year at one of the Antarctic stations to investigate the effects of low-cholesterol (< 300 mg/day), low-fat (< 30% of energy) and high-fibre (> 30 g/day) diets. The average energy intake/day during these two periods (14,973 kJ and 14,515 kJ) was slightly less than during the baseline diet (average of 16,228 kJ). This was reflected in the anthropometric measurements with the mean body weight, sum of skinfold thickness and waist/hip ratios trending down during the diet periods. The study confirms earlier reports of high mean energy intake in Antarctica and suggests that the techniques of measuring intake may have been more accurate than those used in large population studies where intake may have been under-estimated. The results indicate seasonal fluctuations in blood pressure and anthropometric parameters and demonstrate that these anthropometric parameters were affected by the balance of energy intake and activity.

Genetic heterogeneity and localization of a familial breast-ovarian cancer gene on chromosome 17q12-q21.

In a study of 31 breast cancer families and 12 breast-ovarian cancer families, we have obtained clear evidence of linkage to markers on chromosome 17q in the families with ovarian cancer (maximum lod score 3.34 at theta = .04) but only weak evidence in those without ovarian cancer. Recombinant events indicate that the gene lies between D17S588 and D17S250.

Contextual factors in neophobia and its habituation: the role of absolute and relative novelty.

In four experiments we investigated the role of contextual cues in the habituation of neophobia in rats. Experiment 1 showed that the consumption of a novel flavour increased across a series of presentations in one context (A) but fell when the flavour was subsequently presented in a second, novel, context (B). In Experiments 2 and 3, subjects again received exposure to a flavour in context A, but also were familiarized with the test context, B. These subjects consumed the flavour with equal readiness, whether it was presented in Context A or in Context B at test. Experiment 4 replicated the results of Experiment 1 and also showed that the consumption of a novel flavour was not influenced by whether it was presented in a novel or a familiar context. Several mechanisms by which the novelty or familiarity of the context might interact with the novelty or familiarity of the flavour were discussed.

Human macrophage-mediated cytotoxicity of Schistosoma mansoni. Functional and structural features of the effector cells.

Human monocytes were purified from peripheral blood and cultured in vitro on hydrophobic membranes. Such cells developed into mature tissue-type macrophages after approximately 1 week in culture. During this maturation period the macrophages developed a potent cytotoxic mechanism whereby they could kill the schistosomula of Schistosoma mansoni in standard in vitro cytotoxicity assays. Cytological and ultrastructural studies of the cells grown in vitro indicated that macrophages developed many of the classical histological and ultrastructural features of 'activated' cells with ruffled plasma membranes and significant increases in rough endoplasmic reticulum and Golgi vesicles. Effective cytotoxicity depended upon contact of the effector cells and their parasite target. Further, experiments using metabolic inhibitors indicated that cytotoxicity was dependent upon protein synthesis. Initial results point to the macrophage factor being distinct from some of the better-characterised macrophage secretory products such as tumour necrosis factor, proteases and products of oxygen metabolism.

Cytotoxic effects in vitro of human monocytes and macrophages on schistosomula of Schistosoma mansoni.

Human peripheral blood monocytes from normal donors were isolated by differential centrifugation and cultured in vitro in hydrophobic Teflon-coated tissue culture bags. Cells were harvested between 0 and 10 days and tested for their ability to kill schistosomula of Schistosoma mansoni in an in-vitro cytotoxicity assay. Freshly isolated, unstimulated monocytes demonstrated minimal cytotoxic capability. However, this was increased if the cells were pretreated with human recombinant gamma interferon (IFN-gamma), or with specific anti-S. mansoni antiserum. As the monocytes matured in vitro there were marked increases in the levels of antibody-independent killing of schistosomula. Monocytes grown in vitro with IFN-gamma (10(4) u/ml) took 2-3 days to develop almost maximal cytotoxicity (mean 94% kill of schistosomula). In contrast, unstimulated monocytes (no IFN-gamma) took between 5 and 7 days to achieve comparable cytotoxicity (mean 99% kill). Killing of the schistosomula was dependent upon a high effector to target ratio, and was a relatively slow phenomenon in vitro, parasite attrition occurring between 17 and 36 h. Supernatants from cytotoxic macrophages were ineffective in mediating cytotoxicity of the parasite.

Automating the analysis of child phonology.

Ingram (1981, in press) introduced a set of procedures for phonological analysis of fundamental importance to research on phonological development and the clinical assessment of phonological disorders. Recent studies employing these procedures demonstrate their utility in research on the course of normal development in English (Ingram, 1981), phonological disorders (Ingram, 1986; Pye, Wilcox and Siren, in press) and cross-linguistic comparisons of phonological development (Ingram, 1981/2, 1983; Pye, Ingram and List, 1987) Despite such theoretical and practical successes, the procedures remain relatively unutilized in clinical practice. This is primarily due to the exhaustive analysis of language samples that the procedures demand. Most of the procedures can be automated, however, which should provide a greater incentive for their use in clinical settings. This report provides an overview of the analytic procedures and demonstrates how the procedures are performed in the PAL implementation. It also addresses the programming decisions which are an integral part of the implementation and which give the programme its flexibility and power.

Clonal analysis of the T-cell response of mice to herpes simplex virus: correlation between lymphokine production in vitro and the induction of delayed-type hypersensitivity and antiviral activity in vivo.

The properties of two morphologically distinct L3T4+, Lyt2- "helper" T-cell clones specific for herpes simplex virus were investigated. Both of the clones produced IL-3 and interferon, but neither produced IL-2. Clone D6.6 produced macrophage agglutinating factor, a fibronectin-like lymphokine, and also a delayed hypersensitivity (DH) response when injected locally into syngeneic mice. Despite the presence of a DH producing clone and a non-DH producing clone, both were able to reduce the local virus titre to an equivalent degree. It is suggested that this protective activity is associated with the production of interferon-gamma. The significance of these results to mechanisms of protection against herpes simplex virus in vivo is discussed.

Mechanically adaptive bone remodelling.

Removal of the ulna in mature sheep causes a slight increase in peak principal walking strains in the radius which can be recorded by rosette strain gauges. The overstrain on the cranial surface of the radius (20%) was more than twice that on the caudal surface (8%) yet over the 50 weeks following ulnar osteotomy new bone was deposited predominantly on the bone's caudal periosteal surface. The total amount of new bone deposited on the radius replaced the area of bone in the removed ulna, thus equilibrating strains due to compression between osteotomised and non-osteomised limbs. Strains due to bending, and consequently total strains, were reduced to below normal suggesting that mechanically adaptive bone remodelling may not be related to absolute strain levels but to the relative distribution of strain. New bone formation can therefore be stimulated as the result of a mechanical reorganization in which total strains are lower than those which normally occur. The new bone deposited on the caudal cortex of the radius became intensively remodelled with secondary osteons while that on the cranial surface remained in its primary form. This suggests that osteonal remodelling may not always be a simple reparative process but may be one influenced by the strain situation possibly to improve the structure and physical properties of the tissue.