Search

BackgroundAboriginal and Torres Strait Islander children experience a higher prevalence of ear, nose, and throat (ENT) diseases than non-Indigenous children. Many programs exist that aim to prevent and treat these diseases. Culturally appropriate and timely specialist outreach services may help improve access, service use, and outcomes but there has been a lack of rigorous evaluation of ENT outreach programs to date.ObjectiveTo examine the ability of ENT outreach programs to improve health outcomes among Aboriginal and Torres Strait Islander peopleMethodsWe performed a systematic literature search of nine databases (Medline, CINAHLS, PsychINFO, Embase, Cochrane, Scopus, Global health, Informit Rural health database and Indigenous collection) and grey literature sources for primary studies evaluating ENT outreach services for Aboriginal and Torres Strait Islander Australians. Two authors independently evaluated the eligible articles and extracted relevant information.ResultsOf the 506 studies identified, 15 were included in this review. These 15 studies evaluated eight different programs/activities. Studies were heterogeneous in design so a meta-analysis could not be conducted. Seven studies measured health-related outcomes in middle ear or hearing status; six reported overall positive changes one reported no clinically significant improvements. Five programs/activities and their corresponding studies involved Aboriginal and Torres Strait Islander people and organisations in delivery and evaluation, but involvement in program or study design was unclear.ConclusionWhile some studies demonstrated improved outcomes, the overall ability of ENT programs/activities to improve health outcomes for Aboriginal and Torres Strait Islander children is unclear. The impact of ENT outreach may be limited by a lack of evidence quality, a lack of coordination of services, and the provision of potentially unsustainable services. Improvements in the quality of evidence, service coordination and sustainability would likely improve health outcomes.Strengths and limitations of this studyStudies were identification based on a clearly defined and extensive search strategy based on a priori inclusion and exclusion criteriaStudy appraisal was performed using a relevant tool for mixed methods studiesThe involvement of Aboriginal and Torres Strait Islander people in all aspects of programs and their evaluation was examinedPROSPERO registration numberCRD42019134757

ObjectiveTo examine the ability of ear, nose and throat (ENT) outreach programmes to improve health outcomes among Aboriginal and Torres Strait Islander people.MethodsWe conducted a systematic literature search of nine databases (Medline, CINAHLS, PsycINFO, Embase, Cochrane, Scopus, Global health, Informit Rural health database and Indigenous collection) and grey literature sources for primary studies evaluating ENT outreach services for Aboriginal and Torres Strait Islander people. This review included English language studies of all types, published between 2000 and 2018, that supplied ENT outreach services to Aboriginal and Torres Strait Islander Australians and provided data to evaluate their aims. Two authors independently evaluated the eligible articles and extracted relevant information. Risk of bias was assessed using the Mixed Methods Assessment Tool.ResultsOf the 506 studies identified, 15 were included in this review. These 15 studies evaluated eight different programs/activities. Studies were heterogeneous in design so a meta-analysis could not be conducted. Seven studies measured health-related outcomes in middle ear or hearing status; six reported overall positive changes one reported no clinically significant improvements. Five programmes/activities and their corresponding studies involved Aboriginal and Torres Strait Islander people and organisations in delivery and evaluation, but involvement in programme or study design was unclear.ConclusionWhile some studies demonstrated improved outcomes, the overall ability of ENT programmes to improve health outcomes for Aboriginal and Torres Strait Islander children is unclear. The impact of ENT outreach may be limited by a lack of quality evidence, service coordination and sustainability. Community codesign and supporting and resourcing local capacity must be a component of outreach programmes and ongoing evaluation is also recommended. Improvements in these areas would likely improve health outcomes.PROSPERO registration numberCRD42019134757.

Background Feline herpesvirus 1 (FHV-1) is a common cause of ocular and upper respiratory disease in cats and kittens, and a potential cause of eosinophilic dermatitis. Hypothesis The systemic anti-herpes drug, famciclovir (Famvir; Novartis), would be effective in the clinical management of disease attributable to FHV-1, including conjunctivitis, keratitis, corneal sequestra, rhinosinusitis and FHV-1 associated dermatitis. Clinical outcome Oral famciclovir was used to treat signs considered referable to FHV-1 in 10 cats: four had primary ocular disease, two had rhinosinusitis and four had FHV-1 associated dermatitis. Patients treated in Australia (five cats) and Europe (one cat) were given 62.5 mg of famciclovir once or twice daily. Four cats treated in the USA were given 125 mg three times daily. Famciclovir was uniformly well tolerated and, in all cases, had a positive impact on the patient's condition. The apparent improvement in lesions was superior to what had been achieved previously using other therapeutic strategies. One cat with severe destructive rhinosinusitis was significantly improved by a 4-month course of famciclovir in combination with antibacterials. Corneal sequestra detached in two out of three cats treated; cats with ocular signs were qualitatively more comfortable, with reduced clinical signs and an improved appearance of the eyes. Critically, oral famciclovir therapy was considered more convenient than topical ocular therapy. All four cats with FHV-1 associated dermatitis improved substantially, although relapse occurred subsequently in three patients. A further cat with presumptive FHV-1 associated dermatitis responded to topical aciclovir cream before famciclovir could be sourced. Conclusions Famciclovir appears to be a promising systemic drug for treating diseases associated with FHV-1 infection. More rigorous clinical trials are required to optimise the dosing regimen for safe and effective specific anti-herpes treatment in feline clinical medicine.

That mast cells participate in inflammatory reactions is beyond argument. A major question posed by mast cell biologists is whether specific functions in inflammation are subserved by different subsets of the mast cell population. We have investigated the two major subsets of human mast cells (MC(T) and MC(TC)), in the chronic inflammatory processes associated with rheumatoid arthritis (RA). Whereas normal synovium contains mainly MC(TC) mast cells, the MC(T) subset is selectively expanded in early RA, in numbers that correlate with synoviocyte hyperplasia and T-lymphocyte infiltration. In contrast, in RA of long duration, MC(TC) mast cells predominate in numbers that correlate with clinical indices of rapidity of disease progression. We suggest that MC(T) mast cells participate in active inflammatory events, whereas MC(TC) mast cells may be more relevant in repair or damage to connective tissues.

OBJECTIVES To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity. METHODS Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MC T and MC TC mast cells and correlations were sought between clinical and histological data. RESULTS The overall mean synovial mast cell density was 40.3 cells/mm 2 , with regional densities of 60.6 and 34.2 mast cells/mm 2 in the superficial and deeper synovial layers respectively. The MC T subset predominated, outnumbering MC TC by 3:1. There was a significant correlation between the histological inflammation index and the MC T density, ( r = 0.4, p TC subset. The regional distribution and predominant subset of mast cells varied in individual patient’s synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement. CONCLUSIONS The mast cell response in early RA is characterised by substantial expansion of predominantly MC T mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MC TC cells in synovial damage and disease progression, these results suggest that MC T and MC TC mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.

Objective. Thrombospondin 1 (TSP1) is a potent active site inhibitor of leukocyte elastase and cathepsin G. This effect is markedly dependent on the disulfidebond conformation of TSPI, with one isoform, TSPI0.1, being the most potent. The aims of this study were to examine the expression of different disulfide-bonded isoforms of TSP1 in inflammatory environments in which elastase and cathepsin G are present in variable amounts, and to determine the relationship between these proteinases and their potential inhibitor. Methods. Immunohistochemical staining and histomorphometric analysis were used to examine adjacent sections of synovial tissue from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and meniscal trauma (MT), for expression of TSPl and the TSPl0.1 isoform, elastase, cathepsin G, and chymase. Results. TSPl localized to vessels and cells within the synovium. TSPl expression was highly up-regulated in RA (mean density 98 cells and vessels / mm2, compared with 13 / mm2 in OA and 17 / mm2 in MT). The TSPl0.1 isoform was found virtually exclusively in RA, with 44% of vascular TSPl staining being due to the TSPl0.1 isoform in RA, as compared with 7% in OA (P = 0.0047). Elastase- and cathepsin G-positive cells were abundant in RA, with mean densities of 106 cells / mm2 and 103 cells / mm2, respectively, compared with 2 cells / mm2 and 11 cells / mm2 in OA. There was a wide range of both TSPl and proteinase expression within the RA group, but samples containing large numbers of elastase- and cathepsin G-positive cells also showed high expression of TSPl, especially TSPl0.1,. A strong correlation was found between elastase or cathepsin G densities and TSPl0.1 expression in blood vessels (r = 0.86 and r = 0.76 respectively, P < 0.01). Conclusion. TSPl0.1, with the most potent inhibitory activity in vitro, is specifically up-regulated in RA, and this up-regulation is in proportion to the numbers of surrounding leukocytes containing elastase and cathepsin G. One role of TSPl may be to act as a matrix-based regulator of leukocyte-derived serine proteinases in vivo.

Sacral insufficiency fractures are not uncommon in elderly patients. We have diagnosed 20 cases in a five-year period, and have reviewed the clinical records, radiographs, CT and bone scans. We also assessed the degree of osteoporosis by measuring bone density using dual-energy X-ray absorptiometry and bone histomorphometry, and monitored the patients' functional outcome. Bone scans were positive in all 20 patients, CT showed a fracture or sclerosis in 7 of 12 patients and was useful in excluding malignancy. Plain radiographs were the least helpful, showing sclerosis in only 4 of the 20 patients. Involutional osteoporosis with a reduced bone formation rate was the most common underlying cause. Seventeen patients had complete resolution of pain within nine months, and no patient lost independence in daily activities. Increased awareness of these fractures may help to avoid unnecessary investigation and treatment. Bedrest and analgesia followed by rehabilitation provide good relief of symptoms.

Vasculitis of the ovary is a rare condition that can occur as an isolated finding or in association with systemic vasculitis. We describe a case of a 36-year-old female with vasculitis involving the left ovary on a background of severe active systemic lupus erythematosus (SLE). Despite a florid histopathological picture of ovarian vasculitis, the clinical and imaging findings were nonspecific. We have compared the current case to the literature on ovarian vasculitis, including relating to SLE. Ovarian vasculitis in SLE may be an underestimated entity as it may not be looked for routinely in the context of vasculitic involvement of other organs.

A 14-year-old immunocompetent adolescent presented systemically unwell with left knee septic arthritis. Within several days, disseminated bone and soft tissue collections became evident, associated with deep venous thrombosis and pulmonary involvement. Methicillin-sensitive Staphylococcus aureus was isolated, harbouring Panton-Valentine leucocidin genes. Aggressive antibiotic and surgical therapies eventually lead to recovery. Intrafamilial spread of the pathogenic isolate was shown by household screening. This presentation is consistent with 'PVL Syndrome' and is typical of severe S. aureus infection emerging in young populations globally.

Rheumatoid synovitis is characterized by a mast cell response in which tryptase containing mast cells (MCT) associate with T lymphocyte infiltration, and tryptase and chymase containing mast cells (MCTC) correlate more closely with tissue damage or repair events. We investigated expression of the alphaEbeta7 integrin and its ligand E-cadherin in rheumatoid and normal synovium and compared this expression to synovial mast cell responses.Immunohistochemical analysis was used to determine the expression of alphaEbeta7 and E-cadherin in rheumatoid (n = 17) and normal (n = 6) synovium. The density of MCT and MCTC mast cell subsets was compared to the density of alphaEbeta7 positive mast cells.The mean density of alphaEbeta7 positive cells in rheumatoid synovia was 25.2 cells/mm2 (range 0.3-102.9), of which 26.7% (range 0-68.6%) were mast cells. A mean of 11.9% (range 0-30.4%) of rheumatoid synovial mast cells expressed alphaEbeta7 compared to 0% in normal synovium (p0.0001). There was a strong correlation between the density of alphaEbeta7 positive cells and the total mast cell density in rheumatoid synovium (r2= 0.74). alphaEbeta7 positive mast cell density correlated significantly with the MCT subset density (r2 = 0.5, p = 0.014), but not with the MCTC subset density. E-cadherin expression was increased in rheumatoid compared with normal synovium, but did not colocalize or correlate with alphaEbeta7 expression.These results indicate a role for alphaEbeta7 in the mast cell response that occurs in rheumatoid synovitis, in particular the MCT mast cell subset expansion associated with inflammatory events and interactions with infiltrating lymphocytes.

Objective. To determine the distribution of mast cell subsets and their density in synovium from normal subjects and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. A sequential double-immunohistochemical staining technique was used to distinguish mast cells as positive for tryptase only (MC T ) or for tryptase plus chymase (MC TC ). Synovial tissue was obtained from RA patients (n = 16), OA patients (n = 18), and normal subjects (n = 15). Sections were analyzed to a depth of 1 mm from the synoviocyte lining layer by quantitative histomorphometry. Immunohistochemical data were correlated with histologic findings and clinical indices of disease activity. Results. In normal synovium, the majority of mast cells belonged to the MC TC subset, outnumbering MC T cells by 5:1. The mean density of mast cells was significantly increased in RA synovia (60.9 cells/mm 2 ) compared with OA (21.7 cells/mm 2 ) and with normal (9.4 cells/mm 2 ) synovia. Selective expansion of the MC T subset accounted for the increased mast cell density in OA. In RA, both subsets expanded and were associated with infiltrating inflammatory cells or with regions of highly cellular fibrous tissue (mainly MC TC ). An association was noted between clinical parameters of activity or progression of rheumatoid disease and the density of MC TC cells, especially the density in the superficial layer of synovium. In RA synovia, we found no evidence of the chymase only, or MC C , immunophenotype. Conclusion. MC TC mast cells expand in RA but not OA, associate with regions of active fibrosis, and correlate with parameters of disease activity or progression of RA. These findings implicate the MC TC subset of mast cells in the pathologic mechanisms that mediate tissue damage in RA.

Thrombospondin 1 (TSP1) is a multidomain glycoprotein from platelets and cells which functions in cell-cell and cell-matrix interactions. The structure of TSPI is regulated by sulfhydryl-disulfide interchange in the carboxy-terminal Ca2+-binding loops and globular domain which markedly influence its interaction with cell surface integrins and its inhibition of neutrophil enzymes. We have identified murine monoclonal antibodies that recognized different disulfide-bonded forms of TSP1, made by preparing TSPI in buffers containing either 0.1 mM or 2 mM Ca2+. Antibody HB8432 recognizes TSPI prepared in buffers containing either 0.1 or 2 mM Ca2+, while antibodies D4.6 and A65M recognized only TSP1 prepared in buffers containing 0.1 mM Ca2+. The antibodies recognize these different TSP1 preparations either adsorbed to plastic or extracellular matrix. Immunohistochemistry of human rheumatoid synovial tissue using HB8432 resulted in staining of numerous blood vessel walls and matrix cells, while D4.6 and A65M stained a subset of the HB8432 positive blood vessels and only occasionally stained matrix cells. These results suggested that different disulfide-bonded forms of TSP1 were being expressed in different areas of inflamed tissue.

A 31 yr old female under treatment for systemic lupus erythematosus complained of episodes of atypical chest pain radiating to the back. Subsequently she suddenly collapsed and died. Post mortem revealed a well-defined, localized area of non-giant cell aortitis extending from the supra-aortic ridge of the aortic valve to the ligamentum arteriosum. Active arteritis with fibrinoid necrosis and obliterative endarteritis of vasa vasorum had resulted in multiple infarcts of differing ages with associated inflammation and disruption of the aortic wall, culminating in aortic dissection and cardiac tamponade.

Sacral insufficiency fractures are not uncommon in elderly patients. We have diagnosed 20 cases in a five-year period, and have reviewed the clinical records, radiographs, CT and bone scans. We also assessed the degree of osteoporosis by measuring bone density using dual-energy X-ray absorptiometry and bone histomorphometry, and monitored the patients' functional outcome. Bone scans were positive in all 20 patients, CT showed a fracture or sclerosis in 7 of 12 patients and was useful in excluding malignancy. Plain radiographs were the least helpful, showing sclerosis in only 4 of the 20 patients. Involutional osteoporosis with a reduced bone formation rate was the most common underlying cause. Seventeen patients had complete resolution of pain within nine months, and no patient lost independence in daily activities. Increased awareness of these fractures may help to avoid unnecessary investigation and treatment. Bedrest and analgesia followed by rehabilitation provide good relief of symptoms.