Evaluation of high-definition and conventional oscillometric blood pressure measurement in anaesthetised dogs using ACVIM guidelines

OBJECTIVES: To evaluate high-definition and conventional oscillometry in comparison with direct blood pressure measurements in anaesthetised dogs. METHODS: Eight simultaneous readings for systolic, diastolic and mean pressure were obtained directly and with each of two devices in nine anaesthetised dogs. Measurement procedure and validation were based on the 2007 ACVIM guidelines. RESULTS: Sixty-three simultaneous readings were evaluated for each device and direct measurements. The mean differences (bias) to direct values were within 10 mmHg for both devices although bias for systolic and diastolic blood pressures was higher for Memodiagnostic. The standard deviations of differences (precision) were within 15 mmHg for Dinamap but exceeded for Memodiagnostic. Correlation coefficients were higher for Dinamap than Memodiagnostic but both failed to reach a correlation of 0.9. Over 50% of values lay within 10 mmHg of direct measures for both devices, but this percentage was greater for Dinamap than Memodiagnostic. Over 80% of values lay within 20 mmHg of direct measures for Dinamap but not for Memodiagnostic. CLINICAL SIGNIFICANCE: Both devices failed to meet ACVIM guideline validation. However, Dinamap only failed with regards to correlation. Memodiagnostic failed on several requirements, and based on poor correlation, accuracy and precision, this device cannot be currently recommended for dogs under anaesthesia.

A high-resolution soil erosion risk map of Switzerland as strategic policy support system

Soil erosion models and soil erosion risk maps are often used as indicators to assess potential soil erosion in order to assist policy decisions. This paper shows the scientific basis of the soil erosion risk map of Switzerland and its application in policy and practice. Linking a USLE/RUSLE-based model approach (AVErosion) founded on multiple flow algorithms and the unit contributing area concept with an extremely precise and high-resolution digital terrain model (2 m × 2 m grid) using GIS allows for a realistic assessment of the potential soil erosion risk, on single plots, i.e. uniform and comprehensive for the agricultural area of Switzerland (862,579 ha in the valley area and the lower mountain regions). The national or small-scale soil erosion prognosis has thus reached a level heretofore possible only in smaller catchment areas or single plots. Validation was carried out using soil loss data from soil erosion damage mappings in the field from long-term monitoring in different test areas. 45% of the evaluated agricultural area of Switzerland was classified as low potential erosion risk, 12% as moderate potential erosion risk, and 43% as high potential erosion risk. However, many of the areas classified as high potential erosion risk are located at the transition from valley to mountain zone, where many areas are used as permanent grassland, which drastically lowers their current erosion risk. The present soil erosion risk map serves on the one hand to identify and prioritise the high-erosion risk areas, and on the other hand to promote awareness amongst farmers and authorities. It was published on the internet and will be made available to the authorities in digital form. It is intended as a tool for simplifying and standardising enforcement of the legal framework for soil erosion prevention in Switzerland. The work therefore provides a successful example of cooperation between science, policy and practice.

Correlates of self-reported nonadherence to antiretroviral therapy in HIV-infected patients: the Swiss HIV Cohort Study

BACKGROUND: Adherence is one of the most crucial issues in the clinical management of HIV-infected patients receiving antiretroviral therapy (ART). METHODS: A 2-item adherence questionnaire was introduced into the Swiss HIV Cohort Study in July 2003. All 3607 eligible patients were on ART for > or =6 months and their current regimen for > or =1 month. Three definitions of nonadherence were considered: missing > or =1 dose, missing > or =2 doses, and taking <95% of doses in the past 4 weeks. RESULTS: Over 30% of patients reported missing > or =1 dose, 14.9% missed > or =2 doses, and 7.1% took <95% of doses in the previous 4 weeks. The rate of drug holidays was 5.8%. Whether using more or less conservative definitions of nonadherence, younger age, living alone, number of previous regimens, and boosted protease inhibitor regimens were independent factors associated with nonadherence. There was a significant association between optimal viral suppression and nonadherence as well as a significant linear trend in optimal viral suppression by missed doses. CONCLUSIONS: Younger age, lack of social support, and complexity of therapy are important factors that are related to nonadherence with ART. Investment in behavioral dimensions of HIV is crucial to improve adherence in ART recipients.

The therapy of pre-school wheeze: appropriate and fair?

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre-school children in the community. We sent a postal questionnaire to the parents of a random population-based sample of 4,277 UK children aged 1-5 years; 3,410 participated (children of south Asian decent were deliberately over-represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple-trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre-school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under-treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over-treatment of mild and episodic viral wheeze and chronic cough.

Association between reported exposure to road traffic and respiratory symptoms in children: evidence of bias

BACKGROUND: Many studies showing effects of traffic-related air pollution on health rely on self-reported exposure, which may be inaccurate. We estimated the association between self-reported exposure to road traffic and respiratory symptoms in preschool children, and investigated whether the effect could have been caused by reporting bias. METHODS: In a random sample of 8700 preschool children in Leicestershire, UK, exposure to road traffic and respiratory symptoms were assessed by a postal questionnaire (response rate 80%). The association between traffic exposure and respiratory outcomes was assessed using unconditional logistic regression and conditional regression models (matching by postcode). RESULTS: Prevalence odds ratios (95% confidence intervals) for self-reported road traffic exposure, comparing the categories 'moderate' and 'dense', respectively, with 'little or no' were for current wheezing: 1.26 (1.13-1.42) and 1.30 (1.09-1.55); chronic rhinitis: 1.18 (1.05-1.31) and 1.31 (1.11-1.56); night cough: 1.17 (1.04-1.32) and 1.36 (1.14-1.62); and bronchodilator use: 1.20 (1.04-1.38) and 1.18 (0.95-1.46). Matched analysis only comparing symptomatic and asymptomatic children living at the same postcode (thus exposed to similar road traffic) showed similar ORs, suggesting that parents of children with respiratory symptoms reported more road traffic than parents of asymptomatic children. CONCLUSIONS: Our study suggests that reporting bias could explain some or even all the association between reported exposure to road traffic and disease. Over-reporting of exposure by only 10% of parents of symptomatic children would be sufficient to produce the effect sizes shown in this study. Future research should be based only on objective measurements of traffic exposure.

Integrative analysis of RUNX1 downstream pathways and target genes

BACKGROUND: The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML). The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. RESULTS: Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1) cell lines with RUNX1 mutations from FPD-AML patients, 2) over-expression of RUNX1 and CBFbeta, and 3) Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes) significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFbeta. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. CONCLUSION: This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications.

Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies

OBJECTIVE: To evaluate pharmacokinetics of ketamine and norketamine enantiomers after constant rate infusion (CRI) of a subanesthetic dose of racemic ketamine or S-ketamine in ponies. ANIMALS: Five 6-year-old Shetland pony geldings that weighed between 101 and 152 kg. PROCEDURES: In a crossover study, each pony received a CRI of racemic ketamine (loading dose, 0.6 mg/kg; CRI, 0.02 mg/kg/min) and S-ketamine (loading dose, 0.3 mg/kg; CRI, 0.01 mg/kg/min), with a 1-month interval between treatments. Arterial blood samples were collected before and at 5, 15, 30, 45, and 60 minutes during drug administration and at 5, 10, 30, and 60 minutes after discontinuing the CRI. Plasma ketamine and norketamine enantiomers were quantified by use of capillary electrophoresis. Individual R-ketamine and S-ketamine concentration-versus-time curves were analyzed by use of a monocompartmental model. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating the area under the concentration-versus-time curve (AUC), maximum concentration (Cmax), and time until Cmax. RESULTS: Plasma concentrations of S-ketamine decreased and biodegradation products increased more rapidly after S-ketamine CRI, compared with results after racemic ketamine CRI. The R-norketamine was eliminated faster than was the S-norketamine. Significant differences between treatments were found for the AUC of S-ketamine and within the racemic ketamine CRI for the AUC and Cmax of norketamine isomers. CONCLUSIONS AND CLINICAL RELEVANCE: CRI of S-ketamine may be preferable over CRI of racemic ketamine in standing equids because the S-enantiomer was eliminated faster when infused alone instead of as part of a racemic mixture.

The mean anatomical shape of the tibial plateau at the knee arthroplasty resection level: an investigation using MRI

Clinical assessments after Total Knee Arthroplasty (TKA) show persisting pain after implantation in over 20% of patients. Impingement of soft tissue around the knee, due to imprecise geometry of the tibial implant, can be one reason for persisting ailment. Two hundred and thirty seven MRI scans were evaluated using an active contour detection algorithm (snake) to obtain a high-resolution mean anatomical shape of the tibial plateau. Differences between female and male, older and younger (40) and left and right averaged shapes were determined. The shapes obtained were asymmetric throughout. Absolute differences between the subgroups fell short of inter-individual variations represented by calculated one-sigma confidence intervals. Our results indicate that a differentiation in TKA tibial plateau design by gender, age, or side is of minor relevance.

Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype

Striated muscle exhibits a pronounced structural-functional plasticity in response to chronic alterations in loading. We assessed the implication of focal adhesion kinase (FAK) signalling in mechano-regulated differentiation of slow-oxidative muscle. Load-dependent consequences of FAK signal modulation were identified using a multi-level approach after electrotransfer of rat soleus muscle with FAK-expression plasmid vs. empty plasmid-transfected contralateral controls. Muscle fibre-targeted over-expression of FAK in anti-gravitational muscle for 9 days up-regulated transcript levels of gene ontologies underpinning mitochondrial metabolism and contraction in the transfected belly portion. Concomitantly, mRNA expression of the major fast-type myosin heavy chain (MHC) isoform, MHC2A, was reduced. The promotion of the slow-oxidative expression programme by FAK was abolished after co-expression of the FAK inhibitor FAK-related non-kinase (FRNK). Elevated protein content of MHC1 (+9%) and proteins of mitochondrial respiration (+165-610%) with FAK overexpression demonstrated the translation of transcript differentiation in targeted muscle fibres towards a slow-oxidative muscle phenotype. Coincidentally MHC2A protein was reduced by 50% due to protection of muscle from de-differentiation with electrotransfer. Fibre cross section in FAK-transfected muscle was elevated by 6%. The FAK-modulated muscle transcriptome was load-dependent and regulated in correspondence to tyrosine 397 phosphorylation of FAK. In the context of overload, the FAK-induced gene expression became manifest at the level of contraction by a slow transformation and the re-establishment of normal muscle force from the lowered levels with transfection. These results highlight the analytic power of a systematic somatic transgene approach by mapping a role of FAK in the dominant mechano-regulation of muscular motor performance via control of gene expression.

Trajectory of posttraumatic stress disorder caused by myocardial infarction: a two-year follow-up study

OBJECTIVE: A substantial proportion of patients develop posttraumatic stress disorder (PTSD) following myocardial infarction (MI). Previous research on the trajectory over time of PTSD in post-MI patients is scant and refers to self-rated posttraumatic symptoms. The aim of this study was to investigate the longitudinal course of an interviewer-rated diagnosis of PTSD and PTSD symptom severity following MI. METHODS: Study participants were 40 patients (78% men, mean age 54 +/- 8 years) who were diagnosed with PTSD using the Clinician-administered PTSD Scale (CAPS) after an average of 5 +/- 4 months (range 2-16 months) following an index MI. After a mean follow-up of 26 +/- 6 months (range 12-36 months), 24 patients underwent a second diagnostic interview. RESULTS: Two-thirds of patients (n = 16) still qualified for a diagnosis of PTSD at follow-up. In all 24 patients, total PTSD symptoms (p = 0.001), re-experiencing symptoms (p < 0.001), avoidance symptoms (p = 0.015), and, with borderline significance, hyperarousal symptoms (p < 0.06) had all decreased over time. However, in the subgroup of the 16 patients who had retained PTSD diagnostic status at follow-up, symptoms of avoidance (p = 0.23) and of hyperarousal (p = 0.48) showed no longitudinal decline. Longer duration of follow-up was associated with a greater decrease in avoidance symptoms (p = 0.029) and, with borderline significance, in re-experiencing symptoms (p < 0.07) across all patients. CONCLUSION: Although PTSD symptomatology waned over time and in relation to longer follow-up, two-thirds of patients still qualified for a diagnosis of PTSD 2 years after the initial diagnosis. In post-MI patients, clinical PTSD is a considerably persistent condition.

[Treatment of ascites, hyponatremia and hepatorenal syndrome in liver cirrhosis]

Ascites and hyponatremia are frequent complications of advanced liver cirrhosis. Over 50 % of cirrhotic patients develop ascites and about one third gets hyponatremic. The development of ascites is due to an increased sodium retention in the kidneys, leading to expansion of extracellular volume and accumulation of fluid in the peritoneum. Hyponatremia is related to an impairment in the renal capacity to eliminate solute-free water that causes water retention that is disproportionate to the sodium retention, thus causing a reduction in serum sodium concentration. The exact pathogenesis of sodium retention is not clear, yet. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of vasopressin from the neurohypophysis. There is evidence suggesting that hyponatremia predisposes to hepatic encephalopathy. Impairment in glomerular filtration rate in hepatorenal syndrome is due to renal vasoconstriction. Treatment of ascites consists of potassium sparing diuretics, loop diuretics, and/or paracentesis. The current standard of care of hyponatremia based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by specifically antagonizing the effects of vasopressin on the V2 receptors located in the kidney, is evaluated for their role in the management of hyponatremia. Because data on long-term administration are still incomplete, they cannot be used routinely, yet. Liver transplantation is the treatment of choice for hepatorenal syndrome. As bridge to transplantation long-term administration of intravenous albumin and vasoconstrictors can be used.

Transformation of local medicinal knowledge in the Andean Highlands: Case studies from Peru and Bolivia

In the Andean highlands, indigenous environmental knowledge is currently undergoing major changes as a result of various external and internal factors. As in other parts of the world, an overall process of erosion of local knowledge can be observed. In response to this trend, some initiatives that adopt a biocultural approach aim at actively strengthening local identities and revalorizing indigenous environmental knowledge and practices, assuming that such practices can contribute to more sustainable management of biodiversity. However, these initiatives usually lack a sound research basis, as few studies have focused on the dynamics of indigenous environmental knowledge in the Andes and on its links with biodiversity management. Against this background, the general objective of this research project was to contribute to the understanding of the dynamics of indigenous environmental knowledge in the Andean highlands of Peru and Bolivia by investigating how local medicinal knowledge is socially differentiated within rural communities, how it is transformed, and which external and internal factors influence these transformation processes. The project adopted an actor-oriented perspective and emphasized the concept of knowledge dialogue by analyzing the integration of traditional and formal medicinal systems within family therapeutic strategies. It also aimed at grasping some of the links between the dynamics of medicinal knowledge and the types of land use systems and biodiversity management. Research was conducted in two case study areas of the Andes, both Quechua-speaking and situated in comparable agro-ecological production belts - Pitumarca District, Department of Cusco (Southern Peruvian Highlands) and the Tunari National Park, Department of Cochabamba (Bolivian inner-Andean valleys). In each case study area, the land use systems and strategies of 18 families from two rural communities, their environmental knowledge related to medicine and to the local therapeutic flora, and an appreciation of the dynamics of this knowledge were assessed. Data were collected through a combination of disciplinary and participatory action-research methods. It was mostly analyzed using qualitative methods, though some quantitative ethnobotanical methods were also used. In both case studies, traditional medicine still constitutes the preferred option for the families interviewed, independently of their age, education level, economic status, religion, or migration status. Surprisingly and contrary to general assertions among local NGOs and researchers, results show that there is a revival of Andean medicine within the younger generation, who have greater knowledge of medicinal plants than the previous one, value this knowledge as an important element of their way of life and relationship with “Mother Earth” (Pachamama), and, at least in the Bolivian case, prefer to consult the traditional healer rather than go to the health post. Migration to the urban centres and the Amazon lowlands, commonly thought to be an important factor of local medicinal knowledge loss, only affects people’s knowledge in the case of families who migrate over half of the year or permanently. Migration does not influence the knowledge of medicinal plants or the therapeutic strategies of families who migrate temporarily for shorter periods of time. Finally, economic status influences neither the status of people’s medicinal knowledge, nor families’ therapeutic strategies, even though the financial factor is often mentioned by practitioners and local people as the main reason for not using the formal health system. The influence of the formal health system on traditional medicinal knowledge varies in each case study area. In the Bolivian case, where it was only introduced in the 1990s and access to it is still very limited, the main impact was to give local communities access to contraceptive methods and to vaccination. In the Peruvian case, the formal system had a much greater impact on families’ health practices, due to local and national policies that, for instance, practically prohibit some traditional practices such as home birth. But in both cases, biomedicine is not considered capable of responding to cultural illnesses such as “fear” (susto), “bad air” (malviento), or “anger” (colerina). As a consequence, Andean farmers integrate the traditional medicinal system and the formal one within their multiple therapeutic strategies, reflecting an inter-ontological dialogue between different conceptions of health and illness. These findings reflect a more general trend in the Andes, where indigenous communities are currently actively revalorizing their knowledge and taking up traditional practices, thus strengthening their indigenous collective identities in a process of cultural resistance.

Biochemical typing of pathological prion protein in aging cattle with BSE

BACKGROUND: The broad enforcement of active surveillance for bovine spongiform encephalopathy (BSE) in 2000 led to the discovery of previously unnoticed, atypical BSE phenotypes in aged cattle that differed from classical BSE (C-type) in biochemical properties of the pathological prion protein. Depending on the molecular mass and the degree of glycosylation of its proteinase K resistant core fragment (PrPres), mainly determined in samples derived from the medulla oblongata, these atypical cases are currently classified into low (L)-type or high (H)-type BSE. In the present study we address the question to what extent such atypical BSE cases are part of the BSE epidemic in Switzerland. RESULTS: To this end we analyzed the biochemical PrPres type by Western blot in a total of 33 BSE cases in cattle with a minimum age of eight years, targeting up to ten different brain regions. Our work confirmed H-type BSE in a zebu but classified all other cases as C-type BSE; indicating a very low incidence of H- and L-type BSE in Switzerland. It was documented for the first time that the biochemical PrPres type was consistent across different brain regions of aging animals with C-type and H-type BSE, i.e. independent of the neuroanatomical structure investigated. CONCLUSION: Taken together this study provides further characteristics of the BSE epidemic in Switzerland and generates new baseline data for the definition of C- and H-type BSE phenotypes, thereby underpinning the notion that they indeed represent distinct prion disease entities.

Development of two real-time PCR assays for the detection of Mycoplasma hyopneumoniae in clinical samples

In order to improve the diagnosis of enzootic pneumonia (EP) in pigs two real-time polymerase chain reaction (rtPCR) assays for the detection of Mycoplasma hyopneumoniae in bronchial swabs from lung necropsies were established and validated in parallel. As a gold standard, the current "mosaic diagnosis" was taken, including epidemiological tracing, clinical signs, macro- and histopathological lesions of the lungs and immunofluorescence. One rtPCR is targeting a repeated DNA element of the M. hyopneumoniae genome (REP assay), the other a putative ABC transporter gene (ABC assay). Both assays were shown to be specific for M. hyopneumoniae and did not cross react with other bacteria and mollicutes from pig. With material from pigs of defined EP-negative farms the two assays showed to be 100% specific. When testing lungs from pig farms with EP, the REP assay detected 50% and the ABC assay 90% of the farms as positive. Both tests together detected all positive farms. Within a positive herd the two assays tested similarly with on average over 90% of the lung samples analysed from a single farm showing positive scores. A series of samples with suspicion of EP and samples from pigs with diseases other than respiratory taken from current routine diagnostic was assayed. None of the assays showed false positive results. The sensitivities in this sample group were 50% for the REP and 70% for the ABC assays and for both assays together 85%. The two assays run in parallel are therefore a valuable tool for the improvement of the current diagnosis of EP.

Influence of enamel matrix derivative on cells at different maturation stages of differentiation

Enamel matrix derivative (EMD), a porcine extract harvested from developing porcine teeth, has been shown to promote formation of new cementum, periodontal ligament and alveolar bone. Despite its widespread use, an incredibly large variability among in vitro studies has been observed. The aim of the present study was to determine the influence of EMD on cells at different maturation stages of osteoblast differentiation by testing 6 cell types to determine if cell phenotype plays a role in cell behaviour following treatment with EMD. Six cell types including MC3T3-E1 pre-osteoblasts, rat calvarial osteoblasts, human periodontal ligament (PDL) cells, ROS cells, MG63 cells and human alveolar osteoblasts were cultured in the presence or absence of EMD and proliferation rates were quantified by an MTS assay. Gene expression of collagen1(COL1), alkaline phosphate(ALP) and osteocalcin(OC) were investigated by real-time PCR. While EMD significantly increased cell proliferation of all cell types, its effect on osteoblast differentiation was more variable. EMD significantly up-regulated gene expression of COL1, ALP and OC in cells early in their differentiation process when compared to osteoblasts at later stages of maturation. Furthermore, the effect of cell passaging of primary human PDL cells (passage 2 to 15) was tested in response to treatment with EMD. EMD significantly increased cell proliferation and differentiation of cells at passages 2-5 however had completely lost their ability to respond to EMD by passages 10+. The results from the present study suggest that cell stimulation with EMD has a more pronounced effect on cells earlier in their differentiation process and may partially explain why treatment with EMD primarily favors regeneration of periodontal defects (where the periodontal ligament contains a higher number of undifferentiated progenitor cells) over regeneration of pure alveolar bone defects containing no periodontal ligament and a more limited number of osteoprogenitor cells.