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.

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.

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.

A blocking ELISA for the detection of specific antibodies to bovine ephemeral fever virus.

A blocking ELISA (B/ELISA) for detecting antibodies to bovine ephemeral fever virus (BEFV) in cattle is described. In this test, the binding capacity of a monoclonal antibody specific for an epitope on antigenic site G1 of the BEF virus glycoprotein is blocked in the presence of positive serum. The sensitivity of the B/ELISA was compared with the virus neutralisation (VN) test using a total of 380 sera from cattle. Of these, 118 were from an area known to be free of bovine ephemeral fever, 181 from naturally and experimentally BEFV-infected cattle, 33 sequential serum samples from a sentinel steer from which Berrimah virus (BERV) had been isolated, 9 from a sentinel cow from which Kimberley virus (KIMV) was isolated and a panel of 39 sera supplied as a blind trial. The B/ELISA results overall compared favourably with those of the VN tests. The monospecificity of the test was demonstrated using hyperimmune mouse ascitic fluid to other BEF serogroup viruses, namely KIM and BER viruses and the results showed no significant cross-reaction. The greater simplicity and sensitivity of the test when compared with the VN test makes it the preferred test for the diagnosis and monitoring of clinical bovine ephemeral fever.

Improved SPECT using simultaneous emission and transmission tomography.

A method is proposed to simultaneously record single photon emission and transmission tomographic (SPECT) studies to produce a map of attenuation coefficients (mu) for the body. A dual radionuclide SPECT acquisition is performed with a transmission source attached to a rotating gamma camera of lower energy than the emission radionuclide. Scatter from the emission source into the transmission window is removed by subtracting the predicted scatter distribution. The transmission image is then reconstructed to yield the map of attenuation coefficients for anatomic display or attenuation correction purposes. Experimental work has shown that the method can accurately derive mu values to +/- 2.5% in both phantom and patient studies, without increasing acquisition time. Preliminary attenuation correction experiments have demonstrated an accuracy of better than 5% for estimated activity.

RNA polymerase (L) gene and genome terminal sequences of ephemeroviruses bovine ephemeral fever virus and Adelaide River virus indicate a close relationship to vesiculoviruses.

The sequence of the RNA genome of bovine ephemeral fever virus (BEFV) was determined from the start of the L (polymerase) gene to the end of the untranslated 5' trailer sequence, completing the sequence of the 14900 nucleotide (nt) genome. The 6470 nt L gene encodes a single long ORF of 2144 amino acids with a deduced molecular weight of 249766 Da. The 70 nt BEFV 5' trailer region displays partial terminal complementarity with the 3' leader sequence and contains a 26 nt direct repeat of the U-rich domain of the 3' leader region. The 47 nt 5' trailer region of Adelaide River virus (ARV) displays terminal sequence similarity to the BEFV trailer and partial terminal complementarity with the ARV 3' leader sequence, but does not contain the direct repeat sequence. The BEFV L protein contains all characteristic sequence motifs of amino acid blocks I-VI, conserved among RNA polymerase proteins of single-stranded (-) RNA viruses, separated by regions of lower homology. Phylogenetic analysis using the complete BEFV L protein sequence indicated a closer relationship to vesicular stomatitis virus than to rabies virus. Sequence comparison of two conserved central domains encompassing blocks II and III and block VI of the BEFV and ARV L proteins indicated they are closely related. An extended phylogenetic analysis using the block III sequence, confirmed the relationship of these ephemeroviruses to vesiculo- and lyssaviruses and to other single-stranded (-) RNA viruses.

Neurotoxicity in uremia.

The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms which may be impaired in the abnormal chemical environment imposed in renal failure. It is the behaviors we comprehend as indicators of disordered nervous mechanisms. Therefore, it is logical that neurophysiological and neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective endpoint measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results illustrate that: 1) measures of conduction velocity, distal latency and response amplitudes, as employed by us, were relatively insensitive in the patients and circumstances studied; 2) several neurophysiological measures, i.e., the spontaneous EEG, VER latency and, perhaps, photic stimulation, on the other hand, are highly correlated with the severity of renal failure; 3) behavioral measures of sustained attention and alertness (TMT), of short-term memory (ASTM) and of cognitive manipulation of symbols (AR) are also highly correlated with the severity of renal failure; 4) some measured abnormalities improve following dialysis, but not always to normal--three residual impairments may indicate dialysis in adequacy; 5) several of these measures can provide objective evidence for adequacy of dialysis and other clinical and treatment effects in patients with renal failure.

A protein immunoblot test for detection of bovine leukemia virus p24 antibody in cattle and experimentally infected sheep.

A protein immunoblot test for detecting antibody to the bovine leukemia virus p24 antigen is described. The test employs a crude antigen preparation derived from concentrated cell culture fluid, and an optimised biotin-streptavidin-peroxidase amplification system for immunodetection. The test is highly specific and is more sensitive than the gp51 agar gel immunodiffusion (AGID) test for detection of BLV antibody in cattle and experimentally infected sheep. In a selected set of 30 field sera from cattle which had given equivocal results in the gp51-AGID test, 21 were positive, 4 were negative, and 5 gave an uncertain result in the p24-immunoblot test.

An enzyme-linked immunosorbent assay for detection of bovine leukaemia virus p24 antibody in cattle.

An ELISA for detecting antibody to the bovine leukaemia virus (BLV) core protein p24 is described. The test uses p24 antigen purified from concentrated cell culture supernate by lectin-affinity chromatography and gel filtration. The sensitivity and specificity of the p24-ELISA for diagnosing BLV infection relative to the gp51 agar gel immunodiffusion test, were 98.1 and 96.7%, respectively. In the event of widespread use of gp51 based vaccines, the p24-ELISA should differentiate effectively between naturally infected and vaccinated animals.

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease.

BACKGROUND: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. METHODS: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g x d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. RESULTS: Although there was not a significant increase in maximal walking time ( approximately 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. CONCLUSIONS: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-L-carnitine.

Infectivity of bovine leukaemia virus infected cattle: an ELISA for detecting antigens expressed in in vitro cultured lymphocytes.

A simple ELISA is described for quantifying expression of bovine leukaemia virus (BLV) antigens in short-term cultures of peripheral blood lymphocytes (PBL) isolated from infected cattle. The PBL-ELISA demonstrated that antigen expression levels in infected cattle could vary by more than 50-fold. Inoculation of sheep with dilutions of lymphocytes from two BLV-infected cattle, differentiated in the PBL-ELISA by 50 to 100-fold, suggested that antigen expression levels were correlated with infectivity. Haematological data indicated that increased antigen expression in PBL cultures was associated with an increased number of circulating B-lymphocytes, irrespective of whether or not an animal had lymphocytosis. This supported the hypothesis that BLV-infected cattle that are PBL-ELISA positive are more infectious and may present a greater risk of transmitting the disease. The applicability of the PBL-ELISA to a field situation was assessed with 98 BLV-infected cattle from three commercial dairy herds with infection prevalences of 11%, 23% and 47%. Similar percentages (49%, 50% and 52%) of PBL-ELISA positive cattle were identified among those infected cattle available for testing in the three herds. An additional 22 infected cattle from an experimental herd were tested to assess the stability of antigen expression levels over an 8 month period. Fewer (27%) of these cattle were identified as PBL-ELISA positive and antigen expression levels were generally lower than those observed in the commercial herds. Antigen expression levels in the experimental herd remained stable over the period of the study. The potential of the PBL-ELISA to assist in BLV eradication programs by identifying those seropositive cattle with the greatest potential to transmit infection is discussed.

External septorhinoplasty in children: Outcome and effect on growth of septal excision and reimplantation.

Outcome and effect on nasal growth of external septorhinoplasty was evaluated in 32 children. All had septal disease anterior to the nasal spine. In all cases, the cartilaginous septum was totally excised, refashioned, and then reinserted. Sixteen children with follow-up for more than 2 years were identified. Nine children had preoperative and postoperative nasal airflow studies and demonstrated a reduction in total nasal airway resistance, from a mean untreated value of 6.1 cm of water per centimeter per second preoperatively to a mean of 2.5 cm of water per centimeter per second postoperatively. IN 10 of these 16 children, six postoperative anthropometric measures and one index were determined, and these measurements were within the range of age- and sex-specific normative data from the Craniofacial Measurements Laboratory at the Hospital for Sick Children, Toronto, Ontario.

Total parathyroidectomy and autotransplantation.

Total parathyroidectomy and autotransplantation of tissue to the forearm was practiced in 50 chronic renal failure patients as treatment for secondary hyperparathyroidism. Four hyperplastic glands were removed in all cases. Followup observation ranged from 3 to 42 months. Serum parathyroid hormone, alkaline phosphatase, calcium and phosphorus levels decreased significantly following the procedure (P less than 0.005) and remained stable during the period of observation. Significant bone pain present in 26 patients improved or ceased in 19; pruritus, present in 39 patients, universally improved. Strong radiographic suggestion of secondary hyperparathyroidism, present in 38 patients, improved or disappeared in 17. Three patients remained functionally hyperparathyroid, requiring further tissue removal. Autograft function 3 to 7 days after transplantation was demonstrated in 3 cases by differential parathyroid hormone concentration determinations. Essentially all patients experienced symptomatic improvement after surgery and most showed objective evidence of improved calcium-phosphorus metabolism and bone healing.

A preliminary evaluation of a prototype western blot confirmatory test kit for syphilis.

A prototype Western blot kit was evaluated as a confirmatory test for syphilis using 131 sera characterized by other serological tests for syphilis. There were 114 treponemal sera (including 94 cases of early syphilis, 83 of which were untreated) and 17 non-treponemal problem sera (11 gave false positive reactions on screening with the TmpA recombinant antigen enzyme immunoassay (EIA), 3 gave false positive fluorescent treponemal antibody absorbed (FTA-abs) tests, and 3 false positive Captia Syphilis G EIA results). Based on the manufacturer's criteria of reactivity in multiple bands for designating a positive result the Western blot test gave a sensitivity of 99.1% (113/114) and a specificity of 88.2% (15/17) when indeterminate reactions were scored positive and 98.2% (112/114) and 100% (17/17) when indeterminate reactions were scored negative. Sensitivity was high in both treated and untreated infection. Corresponding sensitivities for the TPHA and FTA-abs when equivocal reactions were scored negative were 97.5% (111/114) and 99.1% (113/114). The high sensitivity of the FTA-abs in this study is probably due to the large number of untreated primary infections. Our results with the Western blot, confirm earlier studies using 'in-house' test systems and, support a role for a commercial Western blot test in the confirmatory diagnosis of syphilis. Further studies are required to confirm the high specificity and sensitivity of the kit in a larger series including a wider variety of non-treponemal cases as well as patients with untreated and treated infection.