Angiotensin administration stimulates renal 11β-hydroxysteroid dehydrogenase activity in healthy men

Angiotensin administration stimulates renal 11β-hydroxysteroid dehydrogenase activity in healthy men.BackgroundWe examined whether acute administration of angiotensin modulates the activity of 11β-hydroxysteroid dehydrogenase (11βHSD), the intracellular enzyme catalyzing the interconversion between the hormonally active cortisol and inactive cortisone.MethodsTwenty-one male healthy subjects were examined after 1week of a low- and high-salt diet (50 and 200mmol/day, respectively). Separate infusions of angiotensin I (Ang I) and II (Ang II) were administered, both at rates of 4 and 8ng/kg/min. The ratios of tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone (THF + allo-THF/THE) and of free cortisol/free cortisone (UFF/UFE) in urine were measured as indices of overall 11βHSD set point and activity of renal 11βHSD type 2, respectively. Glomerular filtration rate (GFR) was measured by constant infusion of 125I-iothalamate.ResultsAng I and Ang II infusion dose-dependently increased mean arterial blood pressure (MAP) and plasma aldosterone, and decreased plasma renin activity (PRA) and GFR at both diets. Ang I and Ang II infusion resulted in a dose-dependent decrease in the excretion of UFF, UFE, and of the UFF/UFE ratio at both diets, without changing the urinary (THF + allo-THF)/THE ratio. Salt restriction did not affect these 11βHSD variables, but was accompanied by a decrease in UFF and UFE excretion.ConclusionThis study suggests that acute angiotensin administration stimulates the activity of 11βHSD type 2 in human kidney. Angiotensin might therefore exert a dual effect on the mineralocorticoid receptor (i.e., an indirect agonistic effect by increasing aldosterone availability and a direct or indirect antagonistic effect by stimulation of renal 11βHSD type 2 activity)

Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients

INTRODUCTION: Dialysis patients are often prescribed a large number of medications to improve metabolic control and manage coexisting comorbidities. However, some studies suggest that a large number of medications could also detrimentally affect patients' health-related quality of life (HRQoL). Therefore, this study aims to provide insight in the association between the number of types of medications and HRQoL in dialysis patients. METHODS: A multicentre cohort study was conducted among dialysis patients from Dutch dialysis centres 3 months after initiation of dialysis as part of the ongoing prospective DOMESTICO study. The number of types of medications, defined as the number of concomitantly prescribed types of drugs, was obtained from electronic patient records. Primary outcome was HRQoL measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS) score (range 0–100) of the Short Form 12. Secondary outcomes were number of symptoms (range 0–30) measured with the Dialysis Symptoms Index and self-rated health (range 0–100) measured with the EuroQol-5D-5L. Data were analysed using linear regression and adjusted for possible confounders, including comorbidity. Analyses for MCS and number of symptoms were performed after categorizing patients in tertiles according to their number of medications because assumptions of linearity were violated for these outcomes. RESULTS: A total of 162 patients were included. Mean age of patients was 58 ± 17 years, 35% were female, and 80% underwent haemodialysis. The mean number of medications was 12.2 ± 4.5. Mean PCS and MCS were 36.6 ± 10.2 and 46.8 ± 10.0, respectively. The mean number of symptoms was 12.3 ± 6.9 and the mean self-rated health 60.1 ± 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional medication (95% confidence interval [95% CI]: −0.9 to −0.2; p = 0.002). MCS was 4.9 point lower (95% CI: −8.8 to −1.0; p = 0.01) and 1.0 point lower (95% CI: −5.1–3.1; p = 0.63) for the highest and middle tertiles of medications, respectively, than for the lowest tertile. Patients in the highest tertile of medications reported 4.1 more symptoms than in the lowest tertile (95% CI: 1.5–6.6; p = 0.002), but no significant difference in the number of symptoms was observed between the middle and lowest tertiles. Self-rated health was 1.5 point lower for each medication (95% CI: −2.2 to −0.7; p < 0.001). DISCUSSION/CONCLUSION: After adjustment for comorbidity and other confounders, a higher number of medications were associated with a lower PCS, MCS, and self-rated health in dialysis patients and with more symptoms

Benefits and problems of electronic information exchange as perceived by health care professionals: an interview study

<p>Abstract</p> <p>Background</p> <p>Various countries are currently implementing a national electronic patient record (n-EPR). Despite the assumed positive effects of n-EPRs, their overall adoption remains low and meets resistance from health care providers. This study aims to increase our understanding of health care providers' attitude towards the n-EPR, by investigating their perceptions of the benefits and problems of electronic information exchange in health care and the n-EPR in particular.</p> <p>Methods</p> <p>The study was conducted in three Dutch health care settings: acute care, diabetes care, and ambulatory mental health care. Two health care organisations were included per setting. Between January and June 2010, interviews were conducted with 17 stakeholders working in these organisations. Relevant themes were deduced by means of thematic qualitative analysis.</p> <p>Results</p> <p>Health care providers perceived electronic information exchange to promote the efficiency and quality of care. The problems they perceived in electronic information exchange mainly concerned the confidentiality and safety of information exchange and the reliability and quality of patient data. Many problems perceived by health care providers did not specifically apply to the n-EPR, but to electronic information exchange in general.</p> <p>Conclusions</p> <p>The implementation of the Dutch n-EPR has mainly followed a top-down approach, thereby neglecting the fact that the perceptions and preferences of its users (health care providers) need to be addressed in order to achieve successful implementation. The results of this study provide valuable suggestions about how to promote health care providers' willingness to adopt electronic information exchange, which can be useful for other countries currently implementing an n-EPR. Apart from providing information about the benefits and usefulness of electronic information exchange, efforts should be focused on minimising the problems as perceived by health care providers. The safety and confidentiality of electronic information exchange can be improved by developing tools to evaluate the legitimacy of access to electronic records, by increasing health care providers' awareness of the need to be careful when using patient data, and by measures to limit access to sensitive patient data. Improving health care providers' recording behaviour is important to improve the reliability and quality of electronically exchanged patient data.</p

Excretion patterns of coccidian oocysts and nematode eggs during the reproductive season in Northern Bald Ibis (Geronticus eremita)

Individual reproductive success largely depends on the ability to optimize behaviour, immune function and the physiological stress response. We have investigated correlations between behaviour, faecal steroid metabolites, immune parameters, parasite excretion patterns and reproductive output in a critically endangered avian species, the Northern Bald Ibis (Geronticus eremita). In particular, we related haematocrit, heterophil/lymphocyte ratio, excreted immune-reactive corticosterone metabolites and social behaviour with parasite excretion and two individual fitness parameters, namely, number of eggs laid and number of fledglings. We found that the frequency of excretion of parasites’ oocysts and eggs tended to increase with ambient temperature. Paired individuals excreted significantly more samples containing nematode eggs than unpaired ones. The excretion of nematode eggs was also significantly more frequent in females than in males. Individuals with a high proportion of droppings containing coccidian oocysts were more often preened by their partners than individuals with lower excretion rates. We observed that the more eggs an individual incubated and the fewer offspring fledged, the higher the rates of excreted samples containing coccidian oocysts. Our results confirm that social behaviour, physiology and parasite burden are linked in a complex and context-dependent manner. They also contribute background information supporting future conservation programmes dealing with this critically endangered species

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group

Renal response to angiotensin II is blunted in sodium-sensitive normotensive men

BACKGROUND In hypertension, sodium sensitivity (SS) of blood pressure is associated with renal hemodynamic abnormalities related to increased activity of the renal renin-angiotensin aldosterone system (RAAS). The renal mechanisms of SS in normotensives are unknown. Therefore, we studied whether SS is related to renal hemodynamics and renal responsiveness to angiotensin II (Angll) in young healthy adults. METHODS Blood pressure (mean arterial pressure (MAP)) and renal function were measured in 34 healthy men after 1-week low-sodium diet (LS; 50 mmol Na+/24 h), 1-week high-sodium diet (HS; 200 mmol Na+/24h), and 1-week HS-ACEi (enalapril 20 mg/day).The responses of effective renal plasma flow (ERPF; I-131-Hippuran clearance) to graded infusion of Angll were assessed during each condition. RESULTS The sodium-induced change in MAP ranged from -7to+14mmHg. SS (a sodium-induced increase in MAP > 3 mm Hg) was present in 13 subjects. ERPF was lower in SS subjects during LS and during HS-ACEi. The Angll-induced decrease in ERPF was blunted in SS on LS (-25 +/- 6 vs. -29 +/- 7% in sodium-resistant (SR) subjects, P <0.05) and on HS (-30 +/- 5 vs. -35 +/- 6%, P <0.05).The blunting was corrected by angiotensin-converting enzyme inhibitors (ACE) (-36 +/- 6 vs. -37 +/- 7%). CONCLUSION SS normotensive subjects have a blunted renal response to exogenous Angll. This is ameliorated by ACE, supporting a role for inappropriately high intrarenal RAAS activity. As these findings cannot be attributed to subclinical renal hypertensive damage, high intrarenal RAAS activity and altered renal hemodynamics may be primary phenomena underlying SS

Reduced cyclooxygenase involvement in vascular endothelial function in rat renal transplantation

Background: Cardiovascular disease is a major cause of death following renal transplantation. Mechanisms leading to vascular dysfunction outside the transplanted organ involve common risk factors such as hypertension, hypercholesterolemia, proteinuria, but immune-mediated factors may also be involved. We hypothesized that transplantation-associated risk factors are involved in the development of vascular dysfunction following renal transplantation. Methods: Vascular function was studied in Fisher to Lewis allografts. Lewis to Lewis syngrafted rats served as controls. All rats received cyclo-sporin A for 10 days. Allografts were treated with ACE inhibition or AT1 receptor blockade or left untreated. After 34 weeks, aorta rings were studied for contractile and dilator responses in the presence or absence of L-NMMA and/or indomethacin. Tissue sections were immunostained for COX-1 and COX-2. Results: In contrast to syngrafts and treated allografts, untreated allografts developed proteinuria and hypercholesterolemia. In aortic rings, NOS inhibition similarly increased contractile responses and decreased dilator responses in syngrafts and allografts, indicating comparable NO pathways. In contrast, indomethacin affected contractile and dilator responses in syngrafts, but not in treated and untreated allografts, indicating absence of COX-derived prostanoids in control over vascular tone in allografts. This was in line with immunohistologic analysis demonstrating reduced aortic COX-2 expression in allografts. COX-1 expression was unaltered. Interestingly, RAS blockade quantitatively increased endothelium-dependent dilation without qualitatively altering COX function and expression. Conclusion: Involvement of COX-derived prostaglandins in vascular endothelial function outside the transplanted organ is strongly diminished after allogeneic renal transplantation. RAS blockade improves common cardiovascular risk factors and endothelium-dependent dilation, but fails to restore prostaglandin function. Copyright © 2005 S. Karger AG

Funduscopy: Yes or no? Hypertensive emergencies and retinopathy in the emergency care setting; a retrospective cohort study

Abstract According to international guidelines, patients with a suspected hypertensive emergency (HE) admitted to the emergency department (ED) should undergo comprehensive evaluation including funduscopic examination. However, funduscopy is not always readily available and little is known about the prevalence of retinopathy among these patients in the ED setting. In order to characterize patients who should undergo funduscopy, we studied the prevalence, characteristics and clinical outcome in patients with a suspected HE and retinopathy grade III/IV. We conducted a retrospective cohort study of consecutive patients with severe elevation of blood pressure (BP) admitted to the ED between 2012 and 2015. Patients with a systolic blood pressure (SBP) ≥180 mm Hg or diastolic blood pressure (DBP) ≥120 mm Hg at time of presentation were included. A total of 271 patients were included, of whom 18 (6.6%; 95%CI 3.9‐10.5) had a HE. In 121 patients (44.6%; 95%CI 37.1‐53.3), funduscopy was performed, of whom 17 (14.0%; 95%CI 8.2‐22.5) had retinopathy grade III/IV. Mean SBP and DBP were significantly higher in patients with retinopathy (P < .001). However, retinopathy was also seen in patients with lower BP (SBP < 200 mm Hg and DBP < 120 mm Hg). No differences in other clinical characteristics, including visual disturbances, were found. One patient with retinopathy suffered an ischemic stroke after taking oral medication. The prevalence of retinopathy is high among examined patients. Except for higher BP, no clinical signs or symptoms are associated with the presence of retinopathy grade III/IV. We therefore conclude that funduscopic examination should be performed in every patient with a suspected HE

Supplementary Material for: Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients

Introduction: Dialysis patients are often prescribed a large number of medications to improve metabolic control and manage coexisting comorbidities. However, some studies suggest that a large number of medications could also detrimentally affect patients’ health-related quality of life (HRQoL). Therefore, this study aims to provide insight in the association between the number of types of medications and HRQoL in dialysis patients. Methods: A multicentre cohort study was conducted among dialysis patients from Dutch dialysis centres 3 months after initiation of dialysis as part of the ongoing prospective DOMESTICO study. The number of types of medications, defined as the number of concomitantly prescribed types of drugs, was obtained from electronic patient records. Primary outcome was HRQoL measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS) score (range 0–100) of the Short Form 12. Secondary outcomes were number of symptoms (range 0–30) measured with the Dialysis Symptoms Index and self-rated health (range 0–100) measured with the EuroQol-5D-5L. Data were analysed using linear regression and adjusted for possible confounders, including comorbidity. Analyses for MCS and number of symptoms were performed after categorizing patients in tertiles according to their number of medications because assumptions of linearity were violated for these outcomes. Results: A total of 162 patients were included. Mean age of patients was 58 ± 17 years, 35% were female, and 80% underwent haemodialysis. The mean number of medications was 12.2 ± 4.5. Mean PCS and MCS were 36.6 ± 10.2 and 46.8 ± 10.0, respectively. The mean number of symptoms was 12.3 ± 6.9 and the mean self-rated health 60.1 ± 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional medication (95% confidence interval [95% CI]: −0.9 to –0.2; p = 0.002). MCS was 4.9 point lower (95% CI: −8.8 to –1.0; p = 0.01) and 1.0 point lower (95% CI: −5.1–3.1; p = 0.63) for the highest and middle tertiles of medications, respectively, than for the lowest tertile. Patients in the highest tertile of medications reported 4.1 more symptoms than in the lowest tertile (95% CI: 1.5–6.6; p = 0.002), but no significant difference in the number of symptoms was observed between the middle and lowest tertiles. Self-rated health was 1.5 point lower for each medication (95% CI: −2.2 to –0.7; p &lt; 0.001). Discussion/Conclusion: After adjustment for comorbidity and other confounders, a higher number of medications were associated with a lower PCS, MCS, and self-rated health in dialysis patients and with more symptoms