Isolated myxopapillary ependymoma of the fourth ventricle: case report and review of literature.

We report a case of isolated myxopapillary ependymoma (MPE) of the fourth ventricle. This is the thirteenth reported case of primary intracranial MPE and the fourth reported case of MPE originating from the fourth ventricle. We suggest that exhaustive clinical and radiological investigation of a spinal ependymoma must be undertaken in all cases of intracranial ependymoma.

Copper physiology in ruminants: trafficking of systemic copper, adaptations to variation in nutritional supply and thiomolybdate challenge.

Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants.

Evaluating sub-typing methods for pathogenic Yersinia enterocolitica to support outbreak investigations in New Zealand.

Incidence of human yersiniosis in New Zealand has increased between 2013 and 2017. For surveillance and outbreak investigations it is essential that an appropriate level of discrimination between pathogenic Yersinia enterocolitica isolates is provided, in order to support epidemiological linking of connected cases. Subtyping of 227 Y. enterocolitica isolates was performed using a range of different typing methods, including biotyping, serotyping and seven loci multiple-locus variable-number tandem-repeat analysis (MLVA). In addition, core genome single-nucleotide polymorphism (core SNP) analysis and multi-locus sequence typing were performed on a subset of 69 isolates. Sixty-seven different MLVA types were identified. One MLVA profile was associated with an outbreak in the Bay of Plenty region, supported by epidemiological data. Core SNP analysis showed that all the outbreak-related isolates clustered together. The subtyping and epidemiological evidence suggests that the outbreak of yersiniosis in the Bay of Plenty region between October and December 2016 could be attributed to a point source. However, subtyping results further suggest that the same clone was isolated from several regions between August 2016 and March 2017. Core SNP analysis and MLVA typing failed to differentiate between Y. enterocolitica biotype 2 and biotype 3. For this reason, we propose that these biotypes should be reported as a single type namely: Y. enterocolitica biotype 2/3 and that the serotype should be prioritised as an indicator of prevalence.

Colonial histories, racism and health-The experience of Maori and Indigenous peoples.

The health of Maori, the Indigenous peoples of Aotearoa, New Zealand, like that of almost all Indigenous peoples worldwide, is characterised by systematic inequities in health outcomes, differential exposure to the determinants of health, inequitable access to and through health and social systems, disproportionate marginalisation and inadequate representation in the health workforce. As health providers, we are often taught that 'taking a history' is a critical component of a patient consultation to ensure that the underlying conditions are treated rather than the often superficial presenting symptoms. In the same way, attempts to make sense of the health and well-being of Indigenous peoples is inadequate unless health providers engage critically with the history of their respective nations and any subsequent patterns of privilege or disadvantage. Understanding this history, within the framework of western imperialism and other similar colonial projects, allows us to make sense of international patterns of Indigenous health status. While health commentators acknowledge the unequal health outcomes of Indigenous people, and an increasing number also link these inequities to Indigenous marginalisation resulting from historic events, very few go further and expose the deep relationship between racism and coloniality and how these continue to be the basic determinants of Indigenous health today. This work includes honest examination of the role that science and the health disciplines have played historically in colonisation through the subjugation of Indigenous ways of knowing and knowledge production, as well as being complicit in the creation and maintenance of a fabricated hierarchy of humankind. Despite the 'science' of this racial hierarchy being discredited, it retains a false validity in our societies. As long as oppressive systems that continue to re-inscribe racism and white privilege remain in communities, including our academic communities, coloniality continues its discrimination. Indigenous voices on migration, ethnicity, racisma and health will always demand the elimination of inequities in health but to do so will require a parallel commitment to critically interrogating all of our histories and our disciplines, as well as examining how our practice, including research, disrupts or maintains global systems of racism and coloniality.

Re-evaluation of the regulation of omeprazole in racehorses: An evidence-based approach.

Medication control and doping control have been established in horse racing to ensure the integrity of the sport and the welfare of the horses. This ensures that horses do not compete under the influence of any drugs, including omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome. In this study, pharmacokinetic data were produced in equine plasma and urine following an oral administration of 4 mg/kg of generic buffered formulation of omeprazole to six Thoroughbred horses in five daily doses to determine an appropriate screening limit and detection time in equine plasma and to assess whether the current detection time of 72 hr in equine urine would be applicable when an alternative omeprazole product is administered. Cmax of 436-2,432 ng/ml and AUC0-tau of 1,476-4,371 ng hr ml-1 were obtained for plasma and indicated, in conjunction with other published oral omeprazole studies, that an appropriate plasma screening limit would be 500 pg/ml with a detection time of 48 hr. Urine analysis showed that omeprazole could be detected for up to 25 hr above the previously established urine screening limit of 500 pg/ml and thus indicated that the detection time advice could be potentially reduced from 72 to 48 hr to allow more comprehensive treatment of gastric lesions.

Detection and pharmacokinetics of salmeterol in thoroughbred horses following inhaled administration.

Salmeterol is a man-made beta-2-adrenergic receptor agonist used to relieve bronchospasm associated with inflammatory airway disease in horses. Whilst judicious use is appropriate in horses in training, they cannot race with clinically effective concentrations of medications under the British Horseracing Authority's Rules of Racing. Salmeterol must therefore be withdrawn prior to race day and pharmacokinetic (PK) studies used to establish formal detection time advice. Salmeterol xinafoate (Serevent Evohaler® ) was administered (0.1 mg twice daily for 4.5 days) via inhalation to six horses. Urine and blood samples were taken up to 103 h postadministration. Hydrolysed samples were extracted using solid phase extraction. A sensitive Ultra high performance tandem mass spectrometry (UPLC-MS/MS) method was developed, with a Lower limit of quantification (LLOQ) for salmeterol of 10 pg/mL in both matrices. The majority of salmeterol plasma concentrations, postlast administration, were below the method LLOQ and so unusable for PK analysis. Urine PK analysis suggested a half-life consistent with duration of pharmacological effect. Average estimated urine concentration at steady-state was obtained via PK modelling and used to estimate a urine concentration of 59 ± 34 pg/mL as a marker of effective lung concentration. From this, potential detection times were calculated using a range of safety factors.

Detection and pharmacokinetics of salbutamol in thoroughbred racehorses following inhaled administration.

Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post last administration, lie below the LLOQ of the method and so cannot be used for plasma PK analysis. Urine PK analysis suggests a half-life consistent with the pharmacological effect duration. An estimate of the urine average concentration at steady-state was collected by averaging the concentration measurements in the dosing period from -12 to 0 h relative to the last administered dose. The value was averaged across the six horses and used to estimate an effective urine concentration as a marker of effective lung concentration. The value estimated was 9.6 ng/mL and from this a number of detection times were calculated using a range of safety factors.

Characteristics of AZD9708, a novel, selective ß2-adrenoceptor agonist with rapid onset and long duration of action.

Here we describe the pre-clinical pharmacological profile of AZD9708, a novel long-acting ß(2)-adrenoceptor agonist that has potential as a once-daily therapy for asthma and chronic obstructive pulmonary disease (COPD). AZD9708 is a potent and selective agonist at the human ß(2)-adrenoceptor, with selectivity over human ß(1)- and ß(3)-adrenoceptors of >500 and >24 fold, respectively. AZD9708 relaxes carbachol-induced contraction of human bronchial rings with a time to 90% of maximal relaxation of 13-20 min, similar to that seen with formoterol and quicker than salmeterol. In anesthetized guinea pigs, AZD9708 provides significant protection against histamine-induced airway constriction at 24 h after intratracheal and nebulized doses. This is longer than with intratracheal salmeterol, which is bronchoprotective for approximately 8 h, and formoterol, which is bronchoprotective for 8 and 12 h following nebulized and intratracheal dosing, respectively. AZD9708 also shows the potential for a greater therapeutic margin than widely used ß(2)-adrenoceptor agonists such as formoterol. At a defined efficacy dose that provides 80% bronchoprotection (ED(80)), formoterol leads to a decrease in blood potassium levels in guinea pigs, whilst AZD9708 is not associated with significant reductions in potassium levels at doses up to 7 times the ED(80). [(14)C]AZD9708 is associated with extensive protein binding in both human (mean 1.0% free) and rat (mean 2.6% free) plasma. This pharmacological profile indicates the potential of AZD9708 to become an important addition to the range of bronchodilators available for the treatment of patients with obstructive airways disease.

The evolution and distribution of phage ST160 within Salmonella enterica serotype Typhimurium.

Salmonellosis is an internationally important disease of mammals and birds. Unique epidemics in New Zealand in the recent past include two Salmonella serovars: Salmonella enterica subsp. enterica serovar Typhimurium definitive type (DT) 160 (S. Typhimurium DT160) and S. Brandenburg. Although not a major threat internationally, in New Zealand S. Typhimurium DT160 has been the most common serovar isolated from humans, and continues to cause significant losses in wildlife. We have identified DNA differences between the first New Zealand isolate of S. Typhimurium DT160 and the genome-sequenced strain, S. Typhimurium LT2. All the differences could be accounted for in one cryptic phage ST64B, and one novel P22-like phage, ST160. The majority of the ST160 genome is almost identical to phage SE1 but has two regions not found in SE1 which are identical to the P22-like phage ST64T, suggesting that ST160 evolved from SE1 via two recombination events with ST64T. All of the New Zealand isolates of DT160 were identical indicating the clonal spread of this particular Salmonella. Some overseas isolates of S. Typhimurium DT160 differed from the New Zealand strain and contained SE1 phage rather than ST160. ST160 was also identified in New Zealand isolates of S. Typhimurium DT74 and S. Typhimurium RDNC-April06 and in S. Typhimurium DT160 isolates from the USA. The emergence of S. Typhimurium DT160 as a significant pathogen in New Zealand is postulated to have occurred due to the sensitivity of the Salmonella strains to the ST160 phage when S. Typhimurium DT160 first arrived.

Accumulation of Brain Hypointense Foci on Susceptibility-Weighted Imaging in Childhood Ataxia Telangiectasia.

BACKGROUND AND PURPOSE: SWI hypointense cerebral lesions have been reported in adults with the inherited cerebellar neurodegenerative disorder ataxia telangiectasia. This study aims to establish the prevalence, age-dependency, and spatial distribution of these lesions in children and young people with ataxia telangiectasia. MATERIALS AND METHODS: Participants with classic ataxia telangiectasia and matched controls underwent SWI acquisition at 3T at 1 or 2 time points. SWI hypointense lesions were manually labeled according to the Microbleed Anatomical Rating Scale. Differences in prevalence of lesion number between groups with ataxia telangiectasia and without ataxia telangiectasia were tested with the Fisher exact test, and differences in age between participants with ataxia telangiectasia with and without lesions were tested using independent samples Mann-Whitney U test. The relationship between age and lesion number was modeled as an exponential function. RESULTS: Analyzable SWI datasets from 17 participants with ataxia telangiectasia (with median age at first scan of 12.4 years; range, 4.6-20.2 years; 8 [47%] were female) and 22 matched healthy controls showed prevalence of SWI hypointense lesions in 41% of participants with ataxia telangiectasia and 0% in controls (P = .001, Fisher exact test). Lesions were exclusively supratentorial and predominantly lobar. Participants with ataxia telangiectasia with SWI hypointense lesions were older than those without (median age 5.2 years versus 9.3 years, U = 10.5, P = .014). An exponential curve described the relationship between age and lesion number (R 2 = 0.67). CONCLUSIONS: SWI hypointense lesions are common in children and young people with ataxia telangiectasia, accumulating from 12 years of age onward. In contrast to cerebellar-dominant neurodegeneration in ataxia telangiectasia, SWI hypointense lesions were exclusively supratentorial. Further investigation is needed to establish the clinical relevance of these imaging-detected lesions.

Review: the ubiquitin-proteasome system: contributions to cell death or survival in neurodegeneration.

The significance of the accumulation of ubiquitin-positive intraneuronal inclusions in the brains of those affected with different neurodegenerative diseases is currently unclear. While one interpretation is that the disease mechanism(s) involves dysfunction of an ubiquitin-mediated process, such as the ubiquitin-proteasome system, the inclusions are also found in surviving neurones, suggesting a possible neuroprotective role. Here we review recent evidence in support of these seemingly opposing notions gleaned from cell and animal models as well as investigations of patient samples, with particular emphasis on studies relevant to Parkinson's disease.

Transmissibility of 2009 pandemic influenza A(H1N1) in New Zealand: effective reproduction number and influence of age, ethnicity and importations.

The first wave of pandemic influenza A(H1N1) has subsided in New Zealand as in other southern hemisphere countries. This study aimed to estimate the effective reproduction number (R) of 2009 pandemic influenza A(H1N1) taking into account imported cases. It also aimed to show the temporal variation of R throughout the New Zealand epidemic, changes in age- and ethnicity-specific cumulative incidence, and the effect of school holidays. Using a new modelling method to account for imported cases, we have calculated the peak R during the containment phase of the pandemic as 1.55 (95% confidence interval: 1.16 to 1.86). This value is less than previously estimated in the country early in the pandemic but in line with more recent estimates in other parts of the world. Results also indicated an increase in the proportion of notifications among school-age children after the school holiday (3-19 July 2009). This finding provides support for the potential effectiveness of timely school closures, although such disruptive interventions need to be balanced against the severity of the pandemic.

Pharmacokinetics of carprofen and firocoxib for medication control in racing greyhounds.

Animals used in sport should be treated as required to ensure animal welfare but any such use of medication should also be controlled to ensure integrity. Pharmacokinetic studies on groups of six greyhounds were performed to measure plasma and urine levels of carprofen and firocoxib to inform medication control advice. Using the standard methodology for medication control the Irrelevant Plasma Concentration was determined as 20 and 2 ng/mL for carprofen and firocoxib, respectively. The Irrelevant Urine Concentration was also determined as 0.3 and 2 ng/mL for carprofen and firocoxib, respectively. These Irrelevant Plasma and Urine Concentrations will allow laboratory Screening Limits, Detection Times and Withdrawal Time advice to be determined and publicised by regulators of greyhound racing. The Screening Limits will also inform Recommended Limits of Detection if meat-containing residues of these medications are fed to greyhounds.

Pandemic influenza A(H1N1)v in New Zealand: the experience from April to August 2009.

Following the detection of imported cases of pandemic influenza A(H1N1)v on 25 April 2009, New Zealand implemented containment measures that appeared to slow establishment of the pandemic during May. The pandemic accelerated markedly in June, reaching a peak within four to six weeks, and has been declining since mid-July. By 23 August there had been 3,179 recorded cases (97.8% reported as confirmed), including 972 hospitalisations, 114 intensive care admissions, and 16 deaths. Influenza-like illness (ILI) surveillance in general practice suggests that 7.5% (95% CI: 3.4-11.2) of the population of New Zealand had symptomatic infection, giving a case fatality ratio of 0.005%. Hospitalisations were markedly higher for Maori (age standardised relative risk (RR)=3.0, 95% CI: 2.9-3.2) and Pacific peoples (RR=6.7, 95% CI: 6.2-7.1) compared with Europeans and others. The apparent decline of the pandemic (shown by all surveillance systems) cannot be fully explained. New Zealand remains in the middle of its traditional influenza season, the influenza A(H1N1)v virus appears relatively infectious, and we estimate that only about 11% of the population have been infected by this novel agent.

Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation.

BACKGROUND: While cobalt is an essential micronutrient for vitamin B12 synthesis in the horse, at supraphysiological concentrations, it has been shown to enhance performance in human subjects and rats, and there is evidence that its administration in high doses to horses poses a welfare threat. Animal sport regulators currently control cobalt abuse via international race day thresholds, but this work was initiated to explore means of potentially adding to application of those thresholds since cobalt may be present in physiological concentrations. OBJECTIVES: To devise a scientific basis for differentiation between presence of cobalt from bona fide supplementation and cobalt doping through the use of ratios. STUDY DESIGN: Six Thoroughbred horses were given 10 mL vitamin B12 /cobalt supplement (Hemo-15® ; Vetoquinol, Buckingham, Buckinghamshire, UK., 1.5 mg B12 , 7 mg cobalt gluconate = 983 µg total Co) as an i.v. bolus then an i.v. infusion (15 min) of 100 mg cobalt chloride (45.39 mg Co) 6 weeks later. Pre-and post-administration plasma and urine samples were analysed for cobalt and vitamin B12 . METHODS: Urine and plasma samples were analysed for vitamin B12 using an immunoassay and cobalt concentrations were measured via ICP-MS. Baseline concentrations of cobalt in urine and plasma for each horse were subtracted from their cobalt concentrations post-administration for the PK analysis. Compartmental analysis was used for the determination of plasma PK parameters for cobalt using commercially available software. RESULTS: On administration of a vitamin B12 /cobalt supplement, the ratio of cobalt to vitamin B12 in plasma rapidly increased to approximately 3 and then rapidly declined below a ratio of 1 and then back to near baseline over the next week. On administration of 100 mg cobalt chloride, the ratio initially exceeded 10 in plasma and then declined with the lower 95% confidence interval remaining above a ratio of 1 for 7 days. For two horses with extended sampling, the plasma ratio remained above one for approximately 28 days after cobalt chloride administration. The effect of the administration of the vitamin B12 /cobalt supplement on the urine ratio was transient and reached a peak value of 10 which then rapidly declined. However, a urine ratio of 10 was exceeded, with the lower 95% confidence interval remaining above a ratio of 10 for 7 days after cobalt chloride administration. For the two horses with extended sampling, the urine ratio remained above 10 for about 18 days (442 h) after cobalt chloride administration even though the absolute cobalt urine concentration had dropped below the international threshold of 100 ng/mL after 96 h. MAIN LIMITATIONS: Only one vitamin B12 /cobalt product was evaluated, a limited number of horses were included, the horses were not in full race training and the results may be specific to this population of horses. CONCLUSIONS: The results provide the basis for a potential strategy for allowing supplementation with vitamin B12 products, while controlling the misuse of high doses of cobalt, through a combination of international thresholds and ratios of cobalt to vitamin B12 , in plasma and urine.

Open-label sildenafil treatment of partial and non-responders to double-blind treatment in men with antidepressant-associated sexual dysfunction.

Fifty partial and non-responders (Clinical Global Impression-Sexual Function (CGI-SF) score>2), out of 76 men who completed a 6-week, double-blind, placebo-controlled trial of sildenafil treatment for serotonergic antidepressant-associated sexual dysfunction, were eligible for an additional 6-week trial of open-label sildenafil (50 mg adjustable to 100 mg) under the same protocol, with blind maintained to initial assignment. Participation (double-blind and open-label) required major depressive disorder in remission (MDD-R) and continuing antidepressant medication. Forty-three entered open-label study: 16/17 initially randomized to sildenafil (sildenafil/sildenafil) and 27/33 initially randomized to placebo (placebo/sildenafil). Thirty-five of 43 (81%) achieved full response (CGI-SF

Significance of percutaneous needle biopsy in patients with multiple pulmonary nodules and a single known primary malignancy.

OBJECTIVE: To determine the necessity of percutaneous lung biopsy in patients with a single known primary malignancy and multiple pulmonary nodules. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. RESULTS: We reviewed all percutaneous lung biopsy specimens over a 6-year period. One hundred forty-six patients with a single known primary malignancy and multiple pulmonary nodules had biopsies performed up to 19 years following diagnosis of the primary neoplasm. One hundred thirty-seven biopsy specimens (93.8%) were positive for metastases. Eight patients (5.5%) had a nondiagnostic biopsy specimen; however, subsequent imaging studies and the clinical course strongly suggested diffuse metastatic disease. One patient (< 1%) with breast carcinoma developed nodules 3 years after initial diagnosis and had resolution without a definitive diagnosis or therapy. CONCLUSION: Patients with a single known primary malignancy and multiple pulmonary nodules who present for percutaneous needle biopsy will have pulmonary metastases in the vast majority of cases. Biopsy in these patients rarely changes the clinical course as other diagnoses are rarely established.

Interpretation variability of 18FDG-positron emission tomography studies in dementia.

RATIONALE AND OBJECTIVES: Functional imaging studies such as 18F-fluoro-18-labeled-deoxyglucose-positron emission tomography (18FDG-PET) are being used increasingly in the evaluation of patients with dementia. The authors evaluate inter- and intraobserver interpretation agreement in a diverse group of patients with clinically diagnosed dementia and subjective memory complaints, as well as two healthy control subjects. METHODS: Ninety-six patients with clinical diagnoses of probable Alzheimer's disease (n = 18), possible Alzheimer's disease (n = 33), dementia (n = 26), and mild memory impairment (n = 17), as well as two healthy control subjects were studied using 18FDG-PET. Three observers graded all studies for regional 18FDG uptake in the temporal, parietal, and frontal regions bilaterally. The studies also were interpreted for the presence of bilateral temporoparietal hypometabolism, which typically is present in Alzheimer's disease. The kappa statistic was used to determine intra- and interobserver agreement for regional 18FDG uptake and bilateral temporoparietal hypometabolism. RESULTS: There was excellent intraobserver (kappa = .56, P < 0.0005) and interobserver (kappa = .51, P < 0.0005) interpretation agreement for bilateral temporoparietal hypometabolism. There also was excellent intraobserver (kappa = .61, P < 0.000) and interobserver (kappa = .55, P < 0.000) interpretation agreement of regional 18FDG uptake. Interobserver agreement was extremely high in those patients who were considered clinically to have possible (kappa = .42, P < 0.001) or probable (kappa = .42, P < 0.01) Alzheimer's disease. CONCLUSIONS: Results confirm that bilateral temporoparietal hypometabolism is the metabolic abnormality associated with the diagnosis of probable Alzheimer's disease. Furthermore, intra- and interobserver agreement of visual interpretation of 18FDG-PET images indicates that 18FDG-PET is acceptable as an imaging technique in the clinical evaluation of the dementia patient.