Plasma Low-density Lipoprotein Receptor-related Protein 1 Concentration is not Associated with Human Abdominal Aortic Aneurysm Presence.

OBJECTIVE/BACKGROUND: Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. METHODS: Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. RESULTS: Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 µg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 µg/mL [IQR 3.44-5.84], respectively; p = .48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32]; p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively; p < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. CONCLUSIONS: These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.

Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. METHODS: The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. RESULTS: Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2) = 0 per cent). CONCLUSION: This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA.

Angiogenic response to passive movement and active exercise in individuals with peripheral arterial disease.

Peripheral arterial disease (PAD) is caused by atherosclerosis and is associated with microcirculatory impairments in skeletal muscle. The present study evaluated the angiogenic response to exercise and passive movement in skeletal muscle of PAD patients compared with healthy control subjects. Twenty-one PAD patients and 17 aged control subjects were randomly assigned to either a passive movement or an active exercise study. Interstitial fluid microdialysate and tissue samples were obtained from the thigh skeletal muscle. Muscle dialysate vascular endothelial growth factor (VEGF) levels were modestly increased in response to either passive movement or active exercise in both subject groups. The basal muscle dialysate level of the angiostatic factor thrombospondin-1 protein was markedly higher (P < 0.05) in PAD patients compared with the control subjects, whereas soluble VEGF receptor-1 dialysate levels were similar in the two groups. The basal VEGF protein content in the muscle tissue samples was ∼27% lower (P < 0.05) in the PAD patients compared with the control subjects. Analysis of mRNA expression for a range of angiogenic and angiostatic factors revealed a modest change with active exercise and passive movement in both groups, except for an increase (P < 0.05) in the ratio of angiopoietin-2 to angiopoietin-1 mRNA in the PAD group with both interventions. PAD patients and aged individuals showed a similar limited angiogenic response to active exercise and passive movement. The limited increase in muscle extracellular VEGF combined with an elevated basal level of thrombospondin-1 in muscle extracellular fluid of PAD patients may restrict capillary growth in these patients.

Modelling spatio-temporal patterns of long-distance Culicoides dispersal into northern Australia.

Novel arboviruses, including new serotypes of bluetongue virus, are isolated intermittently from cattle and insects in northern Australia. These viruses are thought to be introduced via windborne dispersal of Culicoides from neighbouring land masses to the north. We used the HYSPLIT particle dispersal model to simulate the spatio-temporal patterns of Culicoides dispersal into northern Australia from nine putative source sites across Indonesia, Timor-Leste and Papua New Guinea. Simulated dispersal was found to be possible from each site, with the islands of Timor and Sumba highlighted as the likely principal sources and February the predominant month of dispersal. The results of this study define the likely spatial extent of the source and arrival regions, the relative frequency of dispersal from the putative sources and the temporal nature of seasonal winds from source sites into arrival regions. Importantly, the methodology and results may be applicable to other insect and pathogen incursions into northern Australia.

Geriatric Syndromes in Older Surgical Patients: A Literature Review.

With the ageing of the population, surgical wards are caring for an increased proportion of older patients. Geriatric syndromes are common in older hospitalised medical and hip fracture patients and are important predictors of poor outcomes in these groups, however the extent of presenting and hospital acquired geriatric syndromes in other older inpatients is less clear. This systematic literature review aimed to identify the proportion of patients aged 60 or older, cared for in usual-care surgical wards, who presented with and/or developed geriatric syndromes. Observational studies in English were identified through searches in CINAHL and Medline databases from 1985-2012. Studies of hip fracture patients and those requiring surgical intensive care (eg cardiac surgery) were excluded. The review included 25 studies. The majority of studies reported on the incidence of post-operative delirium, which ranged from 2% to 51% and varied with the type of surgery. The prevalence of depression at pre-admission screening varied from 9% to 29%. No studies reported on functional decline. Estimates of falls, malnutrition, pressure ulcers and urinary incontinence were limited by the small number of studies. These findings indicate the need for further studies to improve the understanding of geriatric syndromes in older surgical patients in usual-care wards.

Evaluation of long-distance dispersal of Culicoides midges into northern Australia using a migration model.

The introduction of novel bluetongue serotypes and genotypes into northern Australia is considered possible via the long-distance windborne dispersal of Culicoides (Diptera: Ceratopogonidae) vectors from Southeast Asia. Initial findings from simulation modelling of potential dispersal over a 15-year period revealed that the greatest risk for incursion of windborne Culicoides from the island of Timor into northern Australia occurs during December-March. The regions at greatest risk for incursion include the top end of the Northern Territory and the Kimberley region in Western Australia, but there is potential for more widespread dispersal into northern Australia based on Timor as the putative source. The establishment of a more pathogenic strain of the virus, or of a novel Culicoides vector introduced by such inter-continental dispersal events, could dramatically alter Australia's current bluetongue disease status.

Lower limb arterio-venous fistula as a late complication of phlebectomy in a patient with Ehlers-Danlos type IV.

Ehlers-Danlos syndrome type IV (EDS type IV), the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture. The timing, frequency and course of these events are unpredictable. We report a 50-year-old patient with previous complications of EDS type IV who presented with recurrent varicose veins that subsequent imaging identified as an arteriovenous fistula (AVF) at the site of previous phlebectomy. Patients with EDS type IV present vascular surgeons manifold management problems. A pre-existing diagnosis of EDS type IV should alert the clinician to the risk of unusual presentations, both acutely and as complications subsequent to intervention. Once identified, appropriate investigation and follow-up of these patients by a vascular surgeon is mandated.

Isolation and characterization of koi herpesvirus (KHV) from Indonesia: identification of a new genetic lineage.

Koi herpesvirus (KHV) is the aetiological agent of an emerging disease (KHVD) associated with mass mortalities in koi and common carp and reported from at least 30 countries. We report the first isolation of KHV from koi and common carp in Indonesia and initial characterization of the isolates. Clinical signs, histopathology and virion morphology are similar to those of isolates from other countries. Phylogenetic analyses using the thymidine kinase gene amplified from each isolate and from carp tissue samples collected from KHVD outbreaks throughout Indonesia indicated that the Indonesian isolates are more closely related to the Asian than the European KHV lineage. Sequence analysis of two other variable regions between ORF29 and ORF31 (marker I) and near the start of ORF 133 (marker II) indicated that all Indonesian isolates displayed a marker I allele (I(++)) previously identified only in isolates of the Asian lineage. However, in the marker II region, all Indonesian isolates displayed the II(-) allele, which has been reported previously only amongst isolates of the European lineage, and nine of these displayed a mixed genotype (II(+)II(-)). The I(++)II(-) genotype has not been reported previously and appears to represent a new intermediate lineage that may have emerged in Indonesia.

Mycotic carotid pseudoaneurysm: staged endovascular and surgical repair.

Mycotic carotid pseudoaneurysms are rare and challenging to manage. Traditional surgical approaches are technically demanding and can be associated with a high morbidity and mortality. The use of endovascular stents in infected fields remains controversial, and long-term efficacy has not been fully clarified. We describe a case where a combined staged endovascular and open surgical approach was used to successfully manage a mycotic carotid pseudoaneurysm that developed following dental extraction. A covered endovascular stent was used to temporarily exclude the infected pseudoaneurysm, before proceeding to early definitive surgical management. We suggest that staged endovascular therapy followed by early surgical repair should be considered for this difficult surgical problem.

15 year experience of carotid endarterectomy at the Royal Brisbane and Women's Hospital: outcomes and changing trends in management.

OBJECTIVE: The aim of this study was to review the results of carotid endarterectomy (CEA) at the Royal Brisbane and Women's Hospital (RBWH) to provide a benchmark for comparison with carotid stenting and to document changes in imaging and procedural techniques over time. METHODS: Analysis of RBWH CEA database from 1992 to 2007. RESULTS: 1313 consecutive patients (average age 69.2 years, 9% 80 years or older, 69% males) underwent carotid endarterectomy at the RBWH between 1992 and May 2007. Indication for surgery was symptomatic disease in 67%. Preoperative investigations included a duplex scan in 97%, an angiogram in 24% and a CT brain in 33%. Angiogram related neurological events occurred in 3.5% of patients (1.6% stroke, 1.9% TIA). There were 7 deaths (0.5%) and 28 strokes (2.1%) for a combined stroke and death rate of 2.4%. The rate of transient ischemic attacks was 1.1%. Gender patch use and trainees operating with the surgeon unscrubbed predicted a higher combined stroke and death rate. Trends over time included: reduction in preoperative angiography from 66% to <5% and increased rate of patching from 39% to approximately 100%. CONCLUSIONS: Performance of CEA at the RBWH is in keeping with published literature standards. There has been an evolution to surgery performed on the basis of duplex ultrasound alone and an almost universal use of patching.

Effect of type 2 diabetes mellitus on exercise intolerance and the physiological responses to exercise in peripheral arterial disease.

AIMS/HYPOTHESIS: There are conflicting data about the effect of type 2 diabetes mellitus on exercise tolerance in peripheral arterial disease. To elucidate this problem, we compared the tolerance and physiological responses to treadmill and cycle exercise in 31 patients with peripheral arterial disease and intermittent claudication. MATERIALS AND METHODS: One group of these patients had type 2 diabetes (n = 12) and its members were matched for sex and age with a group of patients who did not have diabetes (n = 12). Since BMI and body weight were greater in the diabetic group (28.4 +/- 3.7 vs 25.2 +/- 2.4 kg/m(2); 84.0 +/- 14.6 vs 73.8 +/- 8.0 kg), we also studied a third, 'heavy' group of non-diabetic patients with claudication of similar age (n = 7; BMI = 30.9 +/- 5.3 kg/m(2); body weight = 85.2 +/- 8.2 kg). RESULTS: Compared with the 'light' non-diabetic group, maximum treadmill times were shorter for the diabetic and heavy non-diabetic groups (1,448 vs 845 and 915 s; ANOVA p = 0.01); maximum cycle time also tended to be shorter (ANOVA, p = 0.08) in the diabetic and heavy non-diabetic groups (median = 1,231 vs 730 and 797 s). The majority of physiological responses assessed were not different between the groups, although the time constant of oxygen uptake during submaximal treadmill and cycle exercise was significantly larger (ANOVA p < 0.05) for the diabetic group. CONCLUSIONS/INTERPRETATION: These data demonstrate that exercise tolerance is lower in diabetic than non-diabetic patients with claudication, but that this difference is due to obesity rather than diabetes itself.

Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study.

BACKGROUND: Inflammation is a significant component of atherosclerosis lesions. Bacteria, including periodontopathogens, have been demonstrated in atherosclerotic plaques and cross-reactivity of the immune response to bacterial GroEL with human heat shock protein 60 has been suggested as a link between infections and atherosclerosis. METHODS: In this study, the nature of the inflammatory infiltrate and the presence of human heat shock protein 60 and GroEL were examined in 31 carotid endarterectomy specimens. Additionally, monoclonal antibodies were used to detect the presence of six bacteria, including those implicated in periodontal disease. RESULTS: The inflammatory cell infiltrate of the lesions was dominated by CD14(+) macrophages and CD4(+) T cells. Most cells of the infiltrate as well as the endothelium were HLA-DR(+), indicating activation; however, there was an absence of CD25 expression, demonstrating that the activated T cells were not proliferating. Few CD1a(+) and CD83(+) cells were noted. Human heat shock protein 60 expression was evident on endothelial cells and cells with the appearance of smooth muscle cells and lymphocytes. GroEL and bacteria were detected within intimal cells. Chlamydia pneumoniae, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, and Actinobacillus actinomycetemcomitans were found in 21%, 52%, 34%, 34%, 41%, and 17% of arteries, respectively. CONCLUSION: These results give evidence for a specific immune response associated with atherosclerosis. Whether bacteria initiate the observed inflammation in atherosclerotic lesions is not clear; however, the present study shows that maintenance of inflammation may be enhanced by the presence of periodontopathic bacteria.

Phylogenetic relationships among rhabdoviruses inferred using the L polymerase gene.

RNA viruses of the family Rhabdoviridae include arthropod-borne agents that infect plants, fish and mammals, and also include a variety of non-vector-borne mammalian viruses. Herein is presented a molecular phylogenetic analysis, the largest undertaken to date, of 56 rhabdoviruses, including 20 viruses which are currently unassigned or assigned as tentative species within the Rhabdoviridae. Degenerate primers targeting a region of block III of the L polymerase gene were defined and used for RT-PCR amplification and sequencing. A maximum-likelihood phylogenetic analysis of a 158-residue L polymerase amino acid sequence produced an evolutionary tree containing the six recognized genera of the Rhabdoviridae and also enabled us to identify four more monophyletic groups of currently unclassified rhabdoviruses that we refer to as the 'Hart Park', 'Almpiwar', 'Le Dantec' and 'Tibrogargan' groups. The broad phylogenetic relationships among these groups and genera also indicate that the evolutionary history of rhabdoviruses was strongly influenced by mode of transmission, host species (plant, fish or mammal) and vector (orthopteran, homopteran or dipteran).

Cross-reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis.

BACKGROUND/AIMS: Chronic infections such as those caused by Chlamydia pneumoniae and periodontopathic bacteria such as Porphyromonas gingivalis have been associated with atherosclerosis, possibly due to cross-reactivity of the immune response to bacterial GroEL with human heat shock protein (hHSP) 60. METHODS: We examined the cross-reactivity of anti-GroEL and anti-P. gingivalis antibodies with hHSP60 in atherosclerosis patients and quantified a panel of six pathogens in atheromas. RESULTS: After absorption of plasma samples with hHSP60, there were variable reductions in the levels of anti-GroEL and anti-P. gingivalis antibodies, suggesting that these antibodies cross-reacted with hHSP60. All of the artery specimens were positive for P. gingivalis. Fusobacterium nucleatum, Tannerella forsythia, C. pneumoniae, Helicobacter pylori, and Haemophilus influenzae were found in 84%, 48%, 28%, 4%, and 4% of arteries, respectively. The prevalence of the three periodontopathic microorganisms, P. gingivalis, F. nucleatum and T. forsythia, was significantly higher than that of the remaining three microorganisms. CONCLUSIONS: These results support the hypothesis that in some patients, cross-reactivity of the immune response to bacterial HSPs including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may be a possible mechanism for the association between atherosclerosis and periodontal infection.

Bovine ephemeral fever in Australia and the world.

Bovine ephemeral fever (BEF) is a disabling viral disease of cattle and water buffaloes. It can cause significant economic impact through reduced milk production in dairy herds, loss of condition in beef cattle and loss of draught animals at the time of harvest. Available evidence indicates clinical signs of BEF, which include bi-phasic fever, anorexia, muscle stiffness, ocular and nasal discharge, ruminal stasis and recumbency, are due primarily to a vascular inflammatory response. In Australia, between 1936 and 1976, BEF occurred in sweeping epizootics that commenced in the tropical far north and spread over vast cattle grazing areas of the continent. In the late 1970s, following several epizootics in rapid succession, the disease became enzootic in most of northern and eastern Australia. In Africa, the Middle East and Asia, BEF occurs as also epizootics which originate in enzootic tropical areas and sweep north or south to sub-tropical and temperate zones. The causative virus is transmitted by haematophagous insects that appear to be borne on the wind, allowing rapid spread of the disease. Bovine ephemeral fever virus (BEFV) has been classified as the type species of the genus Ephemerovirus in the Rhabdoviridae. It has a complex genome organization which includes two glycoprotein genes that appear to have arisen by gene duplication. The virion surface glycoprotein (G protein) contains four major antigenic sites that are targets for neutralizing antibody. An analysis of a large number of BEFV isolates collected in Australia between 1956 and 1992 has indicated remarkable stability in most neutralization sites. However, epitope shifts have occurred in the major conformational site G3 and these have been traced to specific mutations in the amino acid sequence. BEFV isolates from mainland China and Taiwan are closely related to Australian isolates, but some variations have been detected. Natural BEFV infection induces a strong neutralizing antibody response and infection usually induces durable immunity. Several forms of live-attenuated, inactivated and recombinant vaccines have been reported but with variable efficacy and durability of protection. The BEFV G protein is a highly effective vaccine antigen, either as a purified subunit or expressed from recombinant viral vectors.

Effect of Duroc content, sex and ageing period on meat and eating quality attributes of pork loin.

This study was conducted to determine the effect of percentage Duroc content of entire male and female pigs and ageing period on meat and eating quality attributes of pork loin (M. longissimus thoracis et lumborum). A total of 84 pigs [entire males (n=42) and female (n=42)] of 0% Duroc (100% Large White), 50% Duroc (Duroc×Large White) or 100% Duroc (n=14 pigs per sex×genotype combination) were slaughtered at a liveweight of ∼100 kg. Steaks from the M. longissimus lumborum of female pigs were aged for either 2 or 7 days post-slaughter and evaluated using a consumer taste panel. Eating quality attributes of tenderness, flavour and overall liking of pork loin steaks from female pigs were not (P>0.05) influenced by Duroc content. Pork from 100% Duroc pigs was juicier (P=0.05) and had a higher (1.84%, P=0.05) intramuscular fat content than pork from 0 and 50% Duroc pigs (1.40 and 1.25%, respectively). Pork from entire male pigs had a lower (P<0.001) intramuscular fat content, was darker (P<0.01) in colour and recorded higher (P<0.01) Warner Bratzler shear force values compared with pork from female carcasses. Ageing pork loin steaks in vacuum bags for 7 days improved tenderness (P<0.01), flavour (P<0.05) and overall liking (P<0.05) compared with steaks aged for 2 days post-slaughter. Ageing of pork steaks for 7 days post-slaughter improved eating quality attributes far more effectively than increasing percentage Duroc content of pigs, which only influenced consumer scores for juiciness.

The value of screening in siblings of patients with abdominal aortic aneurysm.

OBJECTIVES: This study aimed to determine the incidence of abdominal aortic aneurysm (AAA) in a large group of siblings of Australian AAA patients to determine if screening in this group is justified. METHODS: 1254 siblings of 400 index AAA patients were identified and offered aortic ultrasound screening. An age and sex matched control group was recruited from patients having abdominal CT scans for non-vascular indications. AAA was defined by an infrarenal aortic diameter of > or =3 cm or a ratio of the infrarenal to suprarenal aortic diameter of > or =2.0. A ratio of 1.0-1.5 was considered normal, and a ratio of >1.5 to <2.0 was considered ectatic. Aortic enlargement was defined as ectasia or aneurysm. RESULTS: 276 (22%) siblings could be contacted and agreed to screening or had previously been diagnosed with AAA. All 118 controls had normal diameter aortas. 55/276 siblings had previously been diagnosed with AAA. The remaining 221 siblings underwent ultrasound screening. Overall, 30% (84/276) had enlarged aortas (5% ectasia, 25% aneurysmal); 43% of male siblings (64/150) and 16% of females siblings (20/126). The incidence was 45% in brothers of female index patients, 42% in brothers of male patients, 23% in sisters of female patients, and 14% in sisters of male index patients. CONCLUSIONS: The overall incidence of aortic enlargement of 30% found in this study warrants a targeted screening approach with ultrasound for all siblings of patients with AAA. A similar targeted approach for screening of the children of AAA patients would also seem advisable.