ABSTRACT
AIMS: To evaluate the proportions of canine mammary gland lesions submitted to a New Zealand diagnostic laboratory, that were neoplastic vs. non-neoplastic and, among neoplasms, malignant vs. benign, and to determine whether age, reproductive status or breed of dog, or size of the mammary mass were associated with the histological diagnosis. METHODS: Canine mammary gland biopsies submitted between the start of 2012 and the end of 2016 were selected from the surgical biopsy database of IDEXX Laboratories, NZ. For each case, details on age, breed, and reproductive status of the patient were registered as reported by the submitting veterinarians, along with the size (classified as small, medium or large) of the lesion and the histological diagnosis reported by the pathologists. χ2 tests and independent sample t-tests were performed to evaluate associations. RESULTS: Samples (n = 895) were submitted from 797 dogs, of which 673 had mammary neoplasms while 124 had non-neoplastic lesions. Neoplasms composed of a single nodule were found in 591/673 (87.8%) dogs, while 82/673 (12.2%) dogs had multiple nodules. Of the total 771 neoplasms, 432 (56.0%) were histologically malignant, while 339 (44.0%) were benign. Among malignancies, the most common histological sub-types were simple carcinoma (160/771; 20.8%), complex carcinoma (54/771; 7%), and ductal carcinoma (32/771; 4.2%), while benign mixed mammary tumour (128/771, 16.6%) and complex adenoma (105/771; 13.6%) were the most frequently reported benign mammary neoplasms. There was no evidence of a difference in age (p = 0.09) or reproductive status (p = 0.79) of the dog or the size of the mass (p = 0.21) between neoplastic and non-neoplastic lesions. However, neoplastic mammary gland lesions were more frequent in purebred dogs (612/671; 91.2%) than crossbred dogs (61/126; 48.4%; p < 0.001). There was no evidence of a difference in age (p = 0.15) reproductive status (p = 0.36) or breed (p = 0.45) of dog between malignant and benign neoplasms. There was an association between size and histological benign or malignant status of a neoplasm (φ = 0.65, p < 0.001). CONCLUSIONS: Most canine mammary gland samples submitted for examination were neoplastic with slightly more malignant than benign lesions. Masses submitted from purebred dogs were more likely to be neoplastic, while large neoplasms were more likely to be malignant. CLINICAL RELEVANCE: The present findings provide the first description of the distribution of mammary gland lesions in a relatively large number of dogs in New Zealand, representing a preliminary investigation of canine mammary gland diseases in this country.
Subject(s)
Adenoma , Carcinoma , Dog Diseases , Mammary Neoplasms, Animal , Adenoma/epidemiology , Adenoma/veterinary , Animals , Carcinoma/veterinary , Dog Diseases/epidemiology , Dogs , Female , Mammary Glands, Animal , Mammary Neoplasms, Animal/epidemiology , New Zealand/epidemiologyABSTRACT
BACKGROUND: Peripheral arterial disease (PAD) affects more than 200 million of the global population. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as patients with a history of coronary or cerebrovascular disease. Despite the high prevalence of PAD and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than those who are being treated for coronary artery disease. Atherosclerotic risk factor identification and modification play an important role in reducing the number of adverse outcomes among patients with atherosclerosis. Risk reduction therapy decreases the risk of cardiovascular mortality and morbidity in patients with PAD. In this study, we aim to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors. METHODS: This is a randomised, parallel group, active-control trial to compare the effectiveness of the risk factor modification intervention programme to standard healthcare in a tertiary vascular care centre, in the reduction of modified risk factors in PAD patients. The primary outcome of this study is to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors at 3 and 12 months. The secondary outcomes are to compare the impact of the programme on clinical outcomes in PAD patients at 12 months. Secondary outcomes include amputation-free survival, clinical improvement, haemodynamic improvement, need for revascularisation procedures, outcomes of revascularisation procedures, changes in quality of life and the incidence of adverse events. DISCUSSION: This study will provide clear evidence on the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors, through a high-quality, well-powered clinical trial. TRIAL REGISTRATION: This trial was registered (11/07/2017) on the European Clinical Trials Database (EudraCT number 2017-002964-41) and ClinicalTrials.gov ( NCT03935776 ) which was registered on 02 May 2019.
Subject(s)
Peripheral Arterial Disease , Delivery of Health Care , Humans , Life Style , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/therapy , Quality of Life , Randomized Controlled Trials as Topic , Risk FactorsABSTRACT
Aim: To describe the common species, antimicrobial susceptibility and multidrug resistance (MDR) of bacteria cultured from samples submitted to veterinary diagnostic laboratories from sheep in New Zealand between 2003 and 2016. Methods: Bacterial culture and antimicrobial susceptibility test data from June 2003 to March 2016 for animals identified as sheep were obtained from two commercial veterinary diagnostic laboratories in New Zealand. Submission information included animal signalment, geographic origin, specimen description, the organisms cultured, and where available, antimicrobial susceptibilities of the isolates. MDR was defined as any isolate with resistance to ≥3 antimicrobial classes. Results: There were 1,971 unique laboratory submissions, yielding 2,188 isolates. Of the 1,971 submissions, the most commonly represented breeds were Romney (933; 47.3%), Romney cross (264; 13.4%), and Coopworth (197; 10.0%), and there were more submissions from females (1,006; 51.0%) than males (184; 9.3%). Most submissions were from Canterbury (549; 27.9%), Southland (471; 23.9%), and Manawatu-Wanganui (272; 13.8%) regions. Other signalment data were inconsistently described. Submitted samples most commonly originated from the gastrointestinal tract (852; 43.2%), faeces (378; 12.1%), or liver (146; 7.4%). Of the 2,188 isolates, 1,771 (80.9%) were identified by species and 247 (11.4%) by genus, with the most common isolates being Salmonella spp. (880; 40.2%), Campylobacter spp. (408; 18.6%), Listeria spp. (140; 6.4%) and Yersinia spp. (113; 5.2%). Susceptibility results were available for 117/2,188 (5.3%) isolates from 51/1,971 (2.6%) submissions. No antimicrobial susceptibility data were available for Salmonella spp., Campylobacter spp., Listeria spp. or Yersinia spp. Overall for the isolates tested, susceptibility to the fluoroquinolones and tetracyclines was greatest, and MDR was found in 24/117 (20.5%) isolates. MDR was a more frequent finding for Enterococcus spp., Bacillus spp., and Proteus mirabilis, but was infrequent in isolates of Staphylococcus aureus, alpha-haemolytic streptococci, Escherichia coli or Enterobacter spp. Conclusions and clinical relevance: This is the first report on antimicrobial susceptibility and MDR for isolates from laboratory submissions from sheep in New Zealand. The low numbers of isolates submitted for antimicrobial susceptibility testing during the period studied mean that these findings provide limited insights into antimicrobial resistance in this population, and highlight the need to address significant gaps in our understanding of why veterinarians do not more frequently submit samples from sheep for bacterial culture and susceptibility testing. Abbreviation: AMR: Antimicrobial resistance; MDR: Multidrug resistance.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Sheep Diseases/drug therapy , Sheep Diseases/microbiology , Animals , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/veterinary , Gram-Positive Bacteria/isolation & purification , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/veterinary , Microbial Sensitivity Tests , New Zealand , SheepABSTRACT
Aims: To describe the common species and the antimicrobial susceptibility of bacteria cultured from samples submitted to commercial veterinary diagnostic laboratories from beef and pre-production dairy cattle between 2003-2016, and to describe the proportion of isolates with multidrug resistance (MDR). Methods: Bacterial culture and antimicrobial susceptibility data from July 2003 to March 2016 were obtained from commercial veterinary diagnostic laboratories in New Zealand. Results were included from samples from beef cattle, irrespective of age or sex, dairy-breed females aged <2 years and dairy-breed males of any age. Submission information provided included the specimen description, the organisms cultured, and the antimicrobial susceptibilities of isolates, if tested. Antimicrobial resistance (AMR) was defined as any isolate not showing susceptibility to an antimicrobial compound and MDR as any isolate showing AMR to ≥3 antimicrobial classes. Results: There were 1,858 unique laboratory submissions, yielding 2,739 isolates. Of these submissions, most were from the Canterbury (389; 21.9%), Manawatu (388; 21.9%) Waikato (231; 12.4%) and Hawke's Bay (136; 7.3%) regions. There were 163 unique species identifications for the 2,739 isolates; the most common were Yersinia pseudotuberculosis (452; 16.5%), Campylobacter jejuni (249; 9.1%), Escherichia coli (230; 8.4%) and Salmonella enterica serovar Typhimurium (143; 5.2%). Only 251/2,739 (9.2%) isolates from 122/1,858 (6.6%) submissions had antimicrobial susceptibility results. There were no sensitivity results for Yersinia spp., and only one each for Salmonella spp., and Campylobacter spp. Amongst the isolates tested, susceptibility to ampicillin was lowest (33/56; 58.9%). Overall, 57/251 (20.7%) isolates tested for antimicrobial susceptibility had MDR, and MDR was most common for Enterococcus spp. (12/17; 71%) and E. coli (13/30; 43%). Conclusions and Clinical Relevance: This is the first report on antimicrobial susceptibility and MDR in New Zealand beef and pre-production dairy cattle. Findings highlight the limited use of bacterial culture and sensitivity testing by veterinarians and deficits in the information accompanying submissions. A national antimicrobial resistance surveillance strategy that specifically includes this population is recommended.
Subject(s)
Cattle Diseases/epidemiology , Cattle Diseases/microbiology , Gram-Negative Bacterial Infections/veterinary , Analysis of Variance , Animal Husbandry , Animals , Anti-Bacterial Agents/pharmacology , Cattle , Cattle Diseases/drug therapy , Dairying , Drug Resistance, Multiple, Bacterial , Female , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Male , Microbial Sensitivity Tests , New Zealand/epidemiology , Red MeatABSTRACT
BACKGROUND: Hypertension is a leading modifiable risk factor for premature cardiovascular disease. Research indicates a growing prevalence of hypertension among adults worldwide, with accompanying low levels of patient knowledge, and sub-optimal clinical management. AIMS: This study aims to explore the impact of a structured hypertension educational intervention on patient knowledge, lifestyle behaviours and blood pressure control. DESIGN: An observational, prospective cohort design was selected. METHODS: Participants were recruited through a public blood pressure screening event in a community-based setting. They were asked to complete a self-report questionnaire followed by an assessment of their blood pressure. Participants with high blood pressure were randomly assigned to either a control group or an intervention group. Those in the intervention group received an educational intervention on hypertension 4 weeks later. Both groups were recalled 4 months later for a repeat of the same initial assessment. RESULTS: Eighty-one participants with a mean age of 64 years were included in this study. There were no significant differences in the baseline measures between the two groups. Significant improvements were found in the intervention group compared with the control group in levels of hypertension knowledge and awareness (p = <0.001), exercise levels (p = 0.002) and weight (p = 0.003). Participants who underwent the intervention showed a greater reduction in both systolic (SBP) and diastolic (DBP) blood pressure (SBP 158.8 to 141.6 mmHg, p < 0.0001 and DBP 84.7 to 77.7 mmHg, p < 0.001). CONCLUSION: Providing a tailored educational intervention can positively impact on hypertension knowledge, self-care management and control within community-based settings.
Subject(s)
Hypertension/epidemiology , Public Health/methods , Aged , Education, Medical , Female , Humans , Hypertension/pathology , Ireland , Male , Middle Aged , Prevalence , Prospective Studies , Treatment OutcomeABSTRACT
The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i-IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor-specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next-generation clinical trials.
Subject(s)
Graft Rejection/diagnosis , High-Throughput Nucleotide Sequencing/methods , Inflammation/diagnosis , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Postoperative Complications , T-Lymphocytes/immunology , Graft Rejection/etiology , Graft Rejection/pathology , Humans , Inflammation/etiology , Inflammation/pathology , Prognosis , Research ReportABSTRACT
The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next-generation clinical trials.
Subject(s)
Arteritis/immunology , Complement C4b/immunology , Graft Rejection/classification , Graft Rejection/pathology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Peptide Fragments/immunology , Graft Rejection/etiology , Humans , Research ReportABSTRACT
De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post-dnDSA graft loss was observed more frequently in recipients with C1q-positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.
Subject(s)
Complement C1q/immunology , Graft Rejection/etiology , Graft Survival/immunology , Isoantibodies/immunology , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Tissue Donors , Adult , Allografts , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Isoantibodies/blood , Kidney Function Tests , Male , Prognosis , Risk Factors , Survival Rate , Transplant RecipientsABSTRACT
AIMS: To identify and describe culture and antimicrobial resistance (AMR) patterns in bacteria isolated from canine urinary samples submitted to a New Zealand veterinary diagnostic laboratory. METHODS: Records from a veterinary diagnostic laboratory were examined for bacterial isolates cultured from canine urine samples between January 2005 and December 2012. Culture and susceptibility results were compiled with information on the age, sex and breed of dog. Repeat submissions were removed. Susceptibility was assessed using results of the Kirby-Bauer disk diffusion method, for a standard panel including amoxicillin-clavulanic acid (AMC), cefovecin (from 2010-2012), cephalothin, clindamycin, enrofloxacin and trimethoprim-sulphonamide (TMS). RESULTS: A total of 5,786 urine samples were submitted for analysis, and 3,135 bacterial isolates were cultured from 2,184 samples. Of these 3,135 isolates, 1,104 (35.2%) were Escherichia coli, 442 (14.1%) were Staphylococcus spp., 357 (11.4%) Proteus mirabilis and 276 (8.8%) were Enterococcus spp. The frequency of culture-positive samples increased with increasing age in both female and male dogs (p<0.001). The percentage of E. coli isolates resistant to AMC and cephalothin increased between 2005 and 2012 (p<0.001), as did resistance to enrofloxacin (p=0.022), but there was no change in resistance to TMS (p=0.696). Enrofloxacin was the antimicrobial with the least resistance shown by the four most common bacteria isolated during the course of the study. CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study provide important regional information regarding the prevalence of bacterial uropathogens and their susceptibility patterns. There was an increase in resistance to some commonly used antimicrobials in the treatment of urinary tract infections. Having access to regional antimicrobial susceptibility results is crucial when forming guidelines for the use of antimicrobials for the treatment of urinary tract infections. Given changes in practising habits and antimicrobial usage over time, ongoing monitoring and surveillance of resistance in pathogens is needed.
Subject(s)
Anti-Bacterial Agents/pharmacology , Dog Diseases/microbiology , Drug Resistance, Bacterial , Urinary Tract Infections/veterinary , Animals , Dog Diseases/epidemiology , Dog Diseases/urine , Dogs , Female , Laboratories , Male , New Zealand/epidemiology , Time Factors , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology , Veterinary MedicineABSTRACT
Cystine is widely used in cell culture media. Cysteine, the reduced form of cystine, is widely used to scavenge dissolved Ag in eco-toxicological studies to differentiate dissolved vs. nanoparticle uptake and toxicity. However, little is known about the impact of cysteine and cystine on the aggregation behavior of Ag NPs, in particular as a function of Ag NP concentration. Herein, we investigate how cystine (0-300µM) affects the stability of citrate-, polyvinylpyrrolidone-, and polyethylene glycol-coated silver nanoparticles (cit-Ag NPs, PVP-Ag NPs and PEG-Ag NPs, respectively) with and without Suwannee River fulvic acid (SRFA) as a function of Ag NPs concentration using UV-vis spectroscopy at environmentally and ecotoxicologically relevant Ag NP concentrations (ca. 125-1000µgL(-1)). The results demonstrate, for the first time, the concentration-dependent aggregation of cit-Ag NPs in the presence of cystine with a shift in the critical coagulation concentration (CCC) to lower cystine concentrations at lower cit-Ag NP concentrations. At the highest cit-Ag NP concentration (1000µgL(-1)), reaction limited aggregation was only observed and no CCC was measured. SRFA slowed the aggregation of cit-Ag NPs by cystine and aggregation occurred in reaction limited aggregation (RLA) regime only. No CCC value was measured in the presence of SRFA. Cystine replaces citrate, PVP and PEG coatings, resulting in aggregation of both electrostatically and sterically stabilized Ag NPs. These findings are important in understanding the factors determining the behavior of Ag NPs in cell culture media. Also due to the similarity between cystine and cysteine, these results are important in understanding the uptake and toxicity of Ag NPs vs. Ag ions, and suggest that the reduction of the toxicity of Ag NPs in the presence of cysteine could be due to a combined effect of scavenging Ag(+) ions and Ag NP aggregation in the presence of cysteine.
Subject(s)
Cystine/chemistry , Metal Nanoparticles/chemistry , Models, Chemical , Silver/chemistry , Benzopyrans/chemistry , Citric Acid/chemistry , PovidoneABSTRACT
BACKGROUND: Selecting outcome measures in cardiovascular prevention trials should be informed by their importance to selected populations. Major vascular event outcomes are usually prioritized in these trials with considerably less attention paid to cognitive and functional outcomes. AIM: To examine views on importance of outcome measures used in clinical trials. DESIGN: Cross-sectional survey. METHODS: Of 367 individuals approached, 280 (76%) participated: outpatients attending cardiovascular prevention clinics (n = 97), active retirement groups members (n = 75), medical students (n = 108). Participants were asked to rank, in order of importance, outcome measures, which may be included in cardiovascular prevention trials. Results were compared between two groups: <65s (n = 157) and ≥65s (n = 104). RESULTS: When asked what outcomes were most important to measure in cardiovascular prevention trials, respondents reported: death (31.6%) stroke (28.5%), dementia (26.9%), myocardial infarction (MI) (7.9%) and requiring nursing home (NH) care (5.1%). When asked the most relevant outcomes regarding successful ageing respondents reported; maintaining independence (32.4%), avoiding major illness (24.3%), good family life (23.6%), living as long as possible (15.8%), avoiding NH care (3.1%) and contributing to society (0.8%) as most important. When asked what outcome concerned them most about the future, respondents reported: dementia (32.6%), dependence (30.4%), death (12.8%), stroke (12.5%), cancer (6.2%) requiring NH care (4.8%) and MI (0.7%). Maintaining independence was considered most important in younger and older cohorts. CONCLUSION: Cognitive and functional outcomes are important patient-relevant outcomes, sometimes more important than major vascular events. Incorporating these outcomes into trials may encourage patient participation and adherence to preventative regimens.
Subject(s)
Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/psychology , Patients/psychology , Adult , Age Distribution , Aged , Attitude of Health Personnel , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Outcome Assessment, Health Care , Patient Participation , Randomized Controlled Trials as Topic , Social Class , Young AdultABSTRACT
CASE HISTORY AND CLINICAL FINDINGS: On 9 January 2014 (Day 0) a mare from a stud farm in the Waikato region presented with urinary incontinence without pyrexia. Over the following 33 days 15 mares were clinically affected with neurological signs. All but one mare had a foal at foot. The most commonly observed clinical signs were hind limb paresis and ataxia. In some cases recumbency occurred very early in the course of disease and seven mares were subject to euthanasia for humane reasons. LABORATORY FINDINGS: Equid herpesvirus (EHV) type 1 was detected using PCR in various tissues collected post mortem from two mares with neurological signs. DNA sequencing data from the DNA polymerase gene of the virus showed a nucleotide transition at position 2254, a mutation encoding amino acid D752 that is highly associated with the neuropathogenic genotype of EHV-1. In total 12/15 mares were confirmed positive for EHV-1 on PCR. Results from a virus neutralisation test and ELISA on paired serum samples, and PCR on whole blood and nasal swabs, indicated that of four paddocks in a high-risk area where a cluster of cases had occurred, 20/21 (95%) horses were likely to have been exposed or were confirmed infected with EHV-1. Subsequent to the outbreak two mares aborted, one at 9 months and one at 10 months of gestation. The cause of abortion was confirmed as EHV-1 with the same genotype as that involved in the outbreak. DIAGNOSIS: Equine herpesvirus myeloencephalopathy. CLINICAL RELEVANCE: The outbreak described shows the considerable impact that can occur in outbreaks of equine herpesvirus myeloencephalopathy in New Zealand. Early biosecurity controls not only reduced the effect on the farm but mitigated the potential for the virus to spread to other horse enterprises.
Subject(s)
Disease Outbreaks/veterinary , Encephalomyelitis/veterinary , Herpesviridae Infections/veterinary , Herpesvirus 1, Equid , Horse Diseases/virology , Animals , Encephalomyelitis/epidemiology , Encephalomyelitis/virology , Female , Horse Diseases/epidemiology , HorsesSubject(s)
Horse Diseases/microbiology , Nocardia Infections/veterinary , Nocardia/isolation & purification , Placenta Diseases/veterinary , Pregnancy Complications, Infectious/veterinary , Animals , Female , Horse Diseases/epidemiology , Horses , New Zealand/epidemiology , Nocardia/classification , Nocardia Infections/epidemiology , Nocardia Infections/pathology , Placenta Diseases/epidemiology , Placenta Diseases/microbiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/microbiologyABSTRACT
Previous studies suggest that quantifying donor-reactive memory T cells prior to kidney transplantation by interferon gamma enzyme-linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation-01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6- or 12-month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell-depleting, rabbit anti-thymocyte globulin (ATG). Within the no-ATG subset, IFNγELISPOT(neg) subjects had higher 6- and 12-month eGFRs than IFNγELISPOT(pos) subjects, independent of biopsy-proven AR, peak PRA, human leukocyte antigen mismatches, African-American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor-reactive memory T cells.
Subject(s)
Biomarkers/analysis , Enzyme-Linked Immunosorbent Assay/methods , Graft Rejection/diagnosis , Interferon-gamma/analysis , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Postoperative Complications , Adult , Animals , Antilymphocyte Serum/immunology , Child , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Rejection/pathology , Graft Survival , Humans , Kidney Function Tests , Male , Middle Aged , Prognosis , Prospective Studies , Rabbits , Risk Factors , Tissue DonorsABSTRACT
Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.65 mL/min/1.73 m(2) /year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (-2.89 vs. -0.65 mL/min/1.73 m(2) /year, p < 0.0001) and accelerated post-dnDSA (-3.63 vs. -2.89 mL/min/1.73 m(2) /year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell-mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.
Subject(s)
Delayed Graft Function/immunology , Graft Rejection/immunology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , T-Lymphocytes, Regulatory/immunology , Acute Disease , Adult , Age Factors , Allografts/immunology , Child , Child, Preschool , Chronic Disease , Cohort Studies , Disease Progression , Follow-Up Studies , Graft Rejection/pathology , Humans , Isoantibodies/analysis , Kaplan-Meier Estimate , Kidney Transplantation/methods , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Sex Factors , Statistics, Nonparametric , Time Factors , Transplant Recipients , Treatment OutcomeABSTRACT
This paper presents a discretised musculoskeletal multi-body spine model using the LifeMOD Biomechanics Modeller. This was obtained by refining spine segments in cervical, thoracic and lumbar regions into individual vertebra segments, using rotational joints representing the intervertebral discs, building various ligaments between vertebrae and implementing necessary lumbar muscles. To validate the model, two comparison studies were made with in vivo intradiscal pressure measurements of the L4-L5 disc as well as extension moments, axial force and shear force around L5-S1 obtained from spine models available in the literature. The results indicated that the present model is in good correlation with both cases and matches well with experimental data which found that the axial forces are in the range of 3929-4688 N and shear forces up to 650 N. This study provides a preliminary overview of our ongoing work towards building bio-fidelity discretised multi-body spine models for investigating various medical applications. These models can be useful for incorporation into design tools for wheelchairs or other seating systems which may require attention to ergonomics as well as assessing biomechanical behaviour between natural spines and spinal arthroplasty or spinal arthrodesis. Furthermore, these models can be combined with haptic-integrated graphic environments to help surgeons to examine kinematic behaviours of scoliotic spines and to propose possible surgical plans before spine correction operations.
Subject(s)
Computer Simulation , Models, Biological , Software , Spine/physiology , Biomechanical Phenomena , Humans , Ligaments/physiology , Reproducibility of Results , Spinal Fusion/methods , User-Computer Interface , WheelchairsABSTRACT
The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell-mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827-0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781-0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (-0.47 ± 0.33) mid-way between TCMR (-0.20 ± 0.34) and No TCMR (-0.80 ± 0.32) (p < 0.001 for all comparisons). Discriminant scoring for combined borderline/TCMR versus No TCMR (AUC = 0.900; 95% CI 0.859-0.940) applied to a validation cohort robustly distinguished between samples with (-0.08 ± 0.52) and without (-0.65 ± 0.54, p < 0.001) borderline/TCMR (p < 0.001). The TCMR discriminant score was driven by histological t-score, ct-score, donor-specific antibody and biopsy indication, and was unaffected by renal function, interstitial or microcirculatory inflammation, interstitial fibrosis or pyuria. These preliminary findings suggest that urinary metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes.
Subject(s)
Graft Rejection/immunology , Kidney Transplantation , Metabolomics , T-Lymphocytes/immunology , Urine , Adolescent , Child , Female , Humans , Male , Mass SpectrometryABSTRACT
The 12th Banff Conference on Allograft Pathology was held in Comandatuba, Brazil, from August 19-23, 2013, and was preceded by a 2-day Latin American Symposium on Transplant Immunobiology and Immunopathology. The meeting was highlighted by the presentation of the findings of several working groups formed at the 2009 and 2011 Banff meetings to: (1) establish consensus criteria for diagnosing antibody-mediated rejection (ABMR) in the presence and absence of detectable C4d deposition; (2) develop consensus definitions and thresholds for glomerulitis (g score) and chronic glomerulopathy (cg score), associated with improved inter-observer agreement and correlation with clinical, molecular and serological data; (3) determine whether isolated lesions of intimal arteritis ("isolated v") represent acute rejection similar to intimal arteritis in the presence of tubulointerstitial inflammation; (4) compare different methodologies for evaluating interstitial fibrosis and for performing/evaluating implantation biopsies of renal allografts with regard to reproducibility and prediction of subsequent graft function; and (5) define clinically and prognostically significant morphologic criteria for subclassifying polyoma virus nephropathy. The key outcome of the 2013 conference is defining criteria for diagnosis of C4d-negative ABMR and respective modification of the Banff classification. In addition, three new Banff Working Groups were initiated.
Subject(s)
Arteritis/etiology , Complement C4b/metabolism , Graft Rejection/etiology , Isoantibodies/immunology , Organ Transplantation/adverse effects , Peptide Fragments/metabolism , Arteritis/metabolism , Graft Rejection/metabolism , Humans , Research ReportABSTRACT
Follicular dendritic cell secreted protein (FDC-SP) is a secreted peptide predominantly expressed in mucosal tissues. We previously reported that FDC-SP transgenic mice have altered B-cell responses to systemic immunization; however, the role of FDC-SP in mucosal immunity is unknown. Here, we report that FDC-SP functions in regulating immunoglobulin A production. FDC-SP transgenic mice show decreased IgA levels in serum, saliva, and bronchoalveolar lavage fluid. Reciprocally, FDC-SP-deficient mice show significantly increased IgA levels in serum and intestinal lavage, associated with accumulation of IgA+ cells in blood, bone marrow, Peyer's patches, and lymph nodes. FDC-SP-deficient mice generated higher titers of antigen-specific IgA but normal IgG1 responses upon immunization. Purified FDC-SP transgenic B cells generated decreased IgA responses to transforming growth factor ß (TGFß)+interleukin 5 (IL5) stimulation. Consistent with a direct effect of FDC-SP on B cells, recombinant FDC-SP suppressed B-cell IgA production in vitro. Six- to 14-month-old FDC-SP-deficient mice show IgA deposition in kidney glomeruli, which was associated with proteinuria and pathology consistent with mild IgA nephropathy (IgAN). Our results demonstrate a novel biological activity of FDC-SP in controlling B-cell IgA production and identify FDC-SP-deficient mice as a novel mouse model of IgAN.
Subject(s)
Antibody Formation/genetics , Antibody Formation/immunology , Immunoglobulin A/biosynthesis , Immunoglobulin A/immunology , Proteins/genetics , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Disease Models, Animal , Immunoglobulin Isotypes/biosynthesis , Immunoglobulin Isotypes/immunology , Immunomodulation/genetics , Kidney Diseases/genetics , Kidney Diseases/immunology , Male , Mice, Knockout , Mice, Transgenic , Proteins/metabolismABSTRACT
In the present study, polycaprolactone-tricalcium phosphate (PCL/TCP) scaffolds with two different fibre laydown patterns, which were coated with hydroxyapatite and gelatine, were used as an approach for optimizing bone regeneration in a critical-sized calvarial defect. After 12 weeks, bone regeneration was quantified using microcomputed tomography (micro-CT) analysis, biomechanical testing, and histological evaluation. Notably, the experimental groups with coated scaffolds showed lower bone formation and lower biomechanical properties within the defect compared to the uncoated scaffolds. Surprisingly, the different laydown pattern of the fibres resulted in different bone formation and biomechanical properties: the 0°/60°/120° scaffolds revealed lower bone formation and biomechanical properties compared to the 0°/90° scaffolds in all the experimental groups. Therefore, future bone regeneration strategies utilizing scaffolds should consider scaffold architecture as an important factor during the scaffold optimization stages in order to move closer to a clinical application.