Clinical features, anaesthetic management and perioperative complications seen in three horses with pheochromocytoma

Three horses presenting with colic signs to the Equine Referral Hospital at The Royal Veterinary College underwent general anaesthesia between September 2013 and November 2017 for emergency exploratory laparotomy. No obvious cause for the colic signs was identified in two horses, while a haemoperitoneum was identified in the third. All horses were euthanased within 12 hours of surgery due to deteriorating haemodynamic instability and/or intractable pain. Postmortem examination revealed an adrenal mass in each case, confirmed to be a pheochromocytoma on histopathology. In retrospect, each horse had some hallmark characteristics consistent with a functional pheochromocytoma, including hyperglycaemia and hyperlactataemia. Extremely high packed cell volume (PCV) (>65 per cent) was also identified in two horses, with a high-normal PCV found in the haemoperitoneum case. Perioperative haemodynamic instability was predominantly characterised by episodes of intermittent hypertension and tachycardia

Interaction of Stress, Lead Burden, and Age on Cognition in Older Men: The VA Normative Aging Study

BACKGROUND. Low-level exposure to lead and to chronic stress may independently influence cognition. However, the modifying potential of psychosocial stress on the neurotoxicity of lead and their combined relationship to aging-associated decline have not been fully examined. OBJECTIVES. We examined the cross-sectional interaction between stress and lead exposure on Mini-Mental State Examination (MMSE) scores among 811 participants in the Normative Aging Study, a cohort of older U.S. men. METHODS. We used two self-reported measures of stress appraisal-a self-report of stress related to their most severe problem and the Perceived Stress Scale (PSS). Indices of lead exposure were blood lead and bone (tibia and patella) lead. RESULTS. Participants with higher self-reported stress had lower MMSE scores, which were adjusted for age, education, computer experience, English as a first language, smoking, and alcohol intake. In multivariable-adjusted tests for interaction, those with higher PSS scores had a 0.57-point lower (95% confidence interval, -0.90 to 0.24) MMSE score for a 2-fold increase in blood lead than did those with lower PSS scores. In addition, the combination of high PSS scores and high blood lead categories on one or both was associated with a 0.05-0.08 reduction on the MMSE for each year of age compared with those with low PSS score and blood lead level (p < 0.05). CONCLUSIONS. Psychological stress had an independent inverse association with cognition and also modified the relationship between lead exposure and cognitive performance among older men. Furthermore, high stress and lead together modified the association between age and cognition.National Institutes of Health (R01ES07821, R01HL080674, R01HL080674-02S1, R01ES013744, ES05257-06A1, P20MD000501, P42ES05947, ES03918-02); National Center for Research Resources General Clinical Research Center (M01RR02635); Leaves of Grass Foundation; United States Department of Veterans Affair

The Impact Areas Questionnaire (IAQ): A Music Therapy Service Evaluation Tool

Service evaluation is a professional requirement for music therapy practitioners and organisations. Yet service evaluation findings are rarely published within the professional literature, and there is limited documentation of the processes and methods of such evaluations, including the rationale, dilemmas, and challenges encountered. This is perhaps due to the perceived status, methodological weaknesses, and context-specificity of service evaluation work. Drawing on our engagement with service evaluation in diverse settings, we have become aware of its potential beyond its typical current uses in the field as well as of the need for open discussion and debate about the service evaluation tools that are available. This is where the aim of this paper lies: to introduce a service evaluation tool, the Impact Areas Questionnaire (IAQ), alongside the studies that led to its construction. Developed originally through a review of 27 individually designed service evaluation projects, this questionnaire contains a number of different impact areas. Adopting an ecological perspective, these areas refer to music therapy’s perceived impact not only on service users, but also on families/carers/friends, staff, and the organisational context in its entirety. Following its original development within Nordoff Robbins England and Wales, this questionnaire was tested in the context of Nordoff Robbins Scotland with the aim of exploring its applicability and transferability to other music therapy settings. In addition to presenting the findings of this testing, we discuss the potential use of the IAQ, which is included as an appendix to this article, in other settings and its relevance for knowledge and policy making in the field

Modification by hemochromatosis gene polymorphisms of the association between traffic-related air pollution and cognition in older men: a cohort study

Background: Previous studies found effect modification of associations between traffic-related air pollution and cardiovascular outcomes by polymorphisms in the hemochromatosis gene (HFE). As traffic-related air pollution may impact cognition through effects on cardiovascular health or through mechanisms which may also influence cardiovascular outcomes, we hypothesized that HFE polymorphisms would also modify a previously observed association between traffic-related air pollution exposure and cognition in older men. Methods: We considered data from 628 participants of the VA Normative Aging Study. We estimated long term exposure to black carbon (BC), a marker of traffic related air pollution, using a spatio-temporal land use regression model. We assessed cognition using the Mini-Mental State Examination (MMSE), a test of global function, and performance on a battery of other tests, covering a wide range of domains. We investigated whether variants of HFE C282Y and H63D modified the association between BC and having a low MMSE score using logistic models with generalized estimating equations and multiplicative interaction terms. Similarly, we assessed whether HFE variants modified the association between BC and performance on the cognitive battery using linear mixed models with multiplicative interaction terms. Results: Our results suggest modification of the BC-cognition association by HFE C282Y, although the test of interaction did not achieve statistical significance. In multivariable-adjusted models, participants who lacked a HFE C282Y variant (CC) exhibited an adverse association between BC and total cognition z-score (beta for a doubling in BC concentration: -0.061, 95% CI: -0.115, -0.007), while we did not observe an association in participants with at least one variant genotype (CY or YY) (beta for a doubling in BC concentration: 0.073, 95% CI: -0.081, 0.228; p-value for interaction: 0.11). The pattern of association was similar for analyses considering performance on the Mini-Mental State Examination. There was little evidence to support effect modification of the BC-cognition association by the HFE H63D genotype. Conclusions: Our data suggest that older adults who lack an HFE C282Y variant may be more susceptible to an adverse effect of traffic-related air pollution exposure on cognition. This finding and the proposed biological mechanism require confirmation

Stress as a Potential Modifier of the Impact of Lead Levels on Blood Pressure: The Normative Aging Study

Background: Lead exposure and psychological stress have been independently associated with hypertension in various populations, and animal studies suggest that when they co-occur, their effects may be exacerbated. Objectives: We examined whether psychological stress modifies the impact of cumulative lead exposure (measured as bone lead levels) on hypertension and blood pressure in Boston-area community–exposed men participating in the Normative Aging Study. Methods: We evaluated the modifying effect of stress on lead exposure on baseline hypertension status (513 participants) and on blood pressure in those without hypertension (237 participants), cross-sectionally. In baseline nonhypertensives, we examined the same risk factors in relation to prospective risk of developing hypertension. Results: Cross-sectional analysis revealed a positive interaction between stress and tibia lead on systolic blood pressure, after adjusting for age, body mass index, family history of high blood pressure, education, smoking, alcohol consumption, physical activity, and nutritional factors. In prospective multivariate analyses, high stress also modified the effect of tibia lead and patella lead on the risk of developing hypertension. Those reporting high stress had 2.66 [95% confidence interval (CI), 1.43–4.95] times the risk of developing hypertension per standard deviation increase in tibia lead and had 2.64 (95% CI, 1.42–4.92) times the risk per standard deviation increase in patella lead. Conclusion: To our knowledge, these are the first analyses to look at interactive effects of stress and lead on hypertension in humans. These results suggest that the effect of lead on hypertension is most pronounced among highly stressed individuals, independent of demographic and behavioral risk factors

The heterogeneity of systemic inflammation in bronchiectasis

BACKGROUND: Systemic inflammation in bronchiectasis is poorly studied in relation to aetiology and severity. We hypothesized that molecular patterns of inflammation may define particular aetiology and severity groups in bronchiectasis. METHOD: We assayed blood concentrations of 31 proteins from 90 bronchiectasis patients (derivation cohort) and conducted PCA to examine relationships between these markers, disease aetiology and severity. Key results were validated in two separate cohorts of 97 and 79 patients from other centres. RESULTS: There was significant heterogeneity in protein concentrations across the derivation population. Increasing severity of bronchiectasis (BSI) was associated with increasing fibrinogen (rho = 0.34, p = 0.001 -validated in a second cohort), and higher fibrinogen was associated with worse lung function, Pseudomonas colonisation and impaired health-status. There were generally similar patterns of inflammation in patients with idiopathic and post-infectious disease. However, patients with primary immunodeficiency had exaggerated IL-17 responses, validated in a second cohort (n = 79, immunodeficient 12.82 pg/ml versus idiopathic/post-infectious 4.95 pg/ml, p = 0.001), and thus IL-17 discriminated primary immunodeficiency from other aetiologies (AUC 0.769 (95%CI 0.661-0.877)). CONCLUSION: Bronchiectasis is associated with heterogeneity of systemic inflammatory proteins not adequately explained by differences in disease aetiology or severity. More severe disease is associated with enhanced acute-phase responses. Plasma fibrinogen was associated with bronchiectasis severity in two cohorts, Pseudomonas colonisation and health status, and offers potential as a useful biomarker

Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Observational Limits on Machos in the Galactic Halo

We present final results from the first phase of the EROS search for gravitational microlensing of stars in the Magellanic Clouds by unseen deflectors (machos: MAssive Compact Halo Objects). The search is sensitive to events with time scales between 15 minutes and 200 days corresponding to deflector masses in the range 1.e-7 to a few solar masses. Two events were observed that are compatible with microlensing by objects of mass of about 0.1 Mo. By comparing the results with the expected number of events for various models of the Galaxy, we conclude that machos in the mass range [1.e-7, 0.02] Mo make up less than 20% (95% C.L.) of the Halo dark matter.Comment: 4 pages, 3 Postscript figures, to be published in Astronomy & Astrophysic

The effect of metallicity on the Cepheid distance scale and its implications for the Hubble constant (H0H_0) determination

Recent HST determinations of the expansion's rate of the Universe (the Hubble constant, H_0) assumed that the Cepheid Period-Luminosity relation at V and I are independent of metallicity (Freedman, et al., 1996, Saha et al., 1996, Tanvir et al., 1995). The three groups obtain different vales for H_0. We note that most of this discrepancy stems from the asumption (by both groups) that the Period-Luminosity relation is independent of metallicity. We come to this conclusion as a result of our study of the Period-Luminosity relation of 481 Cepheids with 3 millions two colour measurements in the Large Magellanic Cloud and the Small Magellanic Cloud obtained as a by-product of the EROS microlensing survey. We find that the derived interstellar absorption corrections are particularly sensitive to the metallicity and when our result is applied to recent estimates based on HST Cepheids observations it makes the low-H_0 values higher and the high-H_0 value lower, bringing those discrepant estimates into agrement around $H_0 \approx 70 km/s Mpc^{-1}$.Comment: 4 pages, Latex, with 2 .ps accepted for publication astronomy and astrophysics Letter