Beneficial effects of conversion from cyclosporine to azathioprine on fibrinolysis in renal transplant recipients

Cyclosporin A (CsA) has been implicated as one of the factors contributing to the high cardiovascular morbidity and mortality after renal transplantation. This may be mediated by either a high prevalence of conventional risk factors for atherosclerosis, such as hypertension, hypercholesterolemia, and diabetes mellitus, or by impairment of the fibrinolytic activity evoked by CsA, possibly through interference with prostanoid metabolism. We therefore assessed the impact of conversion of CsA to azathioprine immunosuppressive treatment on parameters of fibrinolytic activity and plasma concentration of the prostanoids prostaglandin E2 and thromboxane B2 in 18 stable renal transplant recipients. During CsA, mean arterial pressure and serum creatinine were significantly higher than during azathioprine (116+/-15 mm Hg versus 106+/-13 mm Hg, P=0.0003; and 147+/-34 micromol/L versus 127+/-35 micromol/L, P=0.002; mean+/-SD). On conversion, the plasma tissue plasminogen activator activity increased from 1.2 (1.1 to 1.7; median, 95% CI) to 1.8 (1.6 to 2.0) IU/mL (P=0.011), without a significant change of the plasminogen activator antigen concentration. This was associated with a substantial decrease in plasminogen activator inhibitor-1 activity from 10.4 (8.5 to 16.7) to 6.4 (5.6 to 9.2) IU/mL (P=0.009). Furthermore, plasma levels of prostaglandin E2 and thromboxane B2 markedly decreased (from 9.7 [7.4 to 12.9] to 4.6 [4.3 to 8.1] pg/mL, P=0.0006; and from 106.1 [91.7 to 214.2] to 70.2 [50.3 to 85.6] pg/mL, P=0.002, respectively). During CsA, but not azathioprine, plasma tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels correlated significantly with prostaglandin E2 (r=0.53, P=0.02; and r=0.60, P=0.008, respectively), and thromboxane B2 (r=0.75, P=0.0001; and r=0.77, P=0.0001, respectively) levels. In conclusion, CsA induced substantial impairment of fibrinolytic activity, which recovered after conversion to azathioprine. The impaired fibrinolysis observed during CsA treatment may be caused by modulation of eicosanoid production or metabolism in vascular endothelial cells and possibly contributes to the high incidence of cardiovascular disease after kidney transplantation

Effecten van Phytophthora spp.- besmetting op de zaadkieming van groot zeegras (Zostera marina) Implicaties voor zeegrasherstel

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A clinical prediction rule for renal artery stenosis

Background: Renal artery stenosis is a rare cause of hypertension. The gold standard for diagnosing renal artery stenosis, renal angiography, is invasive and costly. Objective: To develop a prediction rule for renal artery stenosis from clinical characteristics that can be used to select patients for renal angiography. Design: Logistic regression analysis of data from a prospective cohort of patients suspected of having renal artery stenosis. A prediction rule was derived from the regression model for use in clinical practice. Setting: 26 hypertension clinics in the Netherlands. Patients: 477 hypertensive patients who underwent renal angiography because they had drug- resistant hypertension or an increase in serum creatinine concentration during therapy with angiotensin-converting enzyme inhibitors. Results: Age, sex, atherosclerotic vascular disease, recent onset of hypertension, smoking history, body mass index, presence of an abdominal bruit, serum creatinine concentration, and serum cholesterol level were selected as predictors. The regression model was reliable (goodness-of-fit test, P > 0.2) and discriminated well between patients with stenosis and those with essential hypertension (area under the receiver-operating characteristic curve, 0.84). The diagnostic accuracy of the regression model was similar to that of renal scintigraphy, which had a sensitivity of 72% and a specificity of 90%. Conclusions: In the diagnostic workup of patients suspected of having renal artery stenosis, the clinical prediction rule can be considered as an alternative to renal scintigraphy. It can help to select patients for renal angiography in an efficient manner by reducing the number of angiographic procedures without the risk for missing many renal artery stenoses

Phytophthora ramorum sp. nov., a new pathogen on Rhododendron and Viburnum

Since 1993, a hitherto unidentified Phytophthora species has been found associated with twig blight disease in Rhododendron and, sporadically, Viburnum. The morphology and growth characteristics of fourteen isolates from Germany and the Netherlands were investigated, together with their breeding system, the internal transcribed spacer (ITS) regions of the ribosomal DNA, amplified fragment length polymorphism (AFLP) fingerprints, and isozyme profiles, which were compared to those of a number of outgroup species. Morphologically the isolates are characterized by abundant production of chlamydospores and elongate, ellipsoid, deciduous sporangia with a short pedicel, in which they resemble P. palmivora. However, sporangia were semi-papillate, chlamydospores were much larger and cardinal temperatures much lower than those of P. palmivora. Oogonia with amphigynous antheridia and plerotic oospores were produced in dual cultures with an A2 mating type strain of P. cryptogea. ITS1 and ITS2 sequences of the unidentified species were closest to those of P. lateralis, but differed in three and eight nucleotides respectively from the latter species AFLP fingerprints and isozyme patterns of malate dehydrogenase (MDH-2) and malic enzyme (MDHP) showed that the isolates formed a homogeneous group, distinct from all examined outgroup species, including P. lateralis. It was concluded that they represent a new Phytophthora species, described here as P. ramorum sp. nov. In pathogenicity tests all isolates of P. ramorum were pathogenic to Rhododendron

Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure

Objectives.We sought to assess the prognostic value of heart rate variability measures, including Poincaré plots, in patients with mild to moderate chronic heart failure.Background.Mortality is high in patients with heart failure, and many of them die suddenly. However, identification of high risk patients, particularly those with an increased risk for sudden death, has remained difficult.Methods.We studied 95 patients with heart failure (mean [±SD] age 60 ± 8 years, left ventricular ejection fraction 0.29 ± 0.09, New York Heart Association functional class II [81%] and III [19%]) during up to 4 years of follow-up. Heart rate variability measures and Poincaré plots were obtained from 24-h Holter recordings.Results.During follow-up, 17 (18%) of the 95 patients died. In 15 patients, death was cardiac related (11 patients experienced sudden death). None of the conventional time and frequency domain measures of heart rate variability were related to survival. In contrast, abnormal Poincaré plots identified a significantly higher risk for all-cause cardiac death (Cox proportional hazards ratio 5.7, 95% confidence interval [CI] 1.6 to 20.6, univariate analysis) and for sudden cardiac death (hazards ratio 6.8, 95% CI 1.5 to 31.4) compared with those with normal Poincaré plots. Patients with abnormal Poincaré plots were shown to have a lower left ventricular ejection fraction (0.26 ± 0.10 vs. 0.31 ± 0.08, p < 0.05) and higher plasma norepinephrine concentrations (506 ± 207 pg/ml vs. 411 ± 175 pg/ml, p < 0.05). In multivariate analysis, abnormal Poincaré plots still had independent prognostic value, both for all-cause cardiac mortality and for sudden cardiac death (hazards ratio 5.3, 95% CI 1.2 to 17.1, hazards ratio 4.5, 95% CI 1.0 to 27.5, respectively.Conclusions.Heart rate variability analysis, as assessed by Poincaré plots, has independent prognostic value in patients with mild to moderate chronic heart failure and identifies an increased risk for all-cause and sudden cardiac death in these patients

Data from: Predator-induced collapse of niche structure and coexistence on islands

Biological invasions represent both a pressing environmental challenge and an opportunity to investigate fundamental ecological processes, such as the role of top predators in regulating species diversity and food-web structure. In whole-ecosystem manipulations of small Caribbean islands where brown anole lizards (Anolis sagrei) were the native top predator, we experimentally staged invasions by competitors (green anoles, A. smaragdinus) and/or novel top predators (curly-tailed lizards, Leiocephalus carinatus). We show that curly-tails destabilized coexistence of competing prey species, contrary to the classic idea of keystone predation. Fear-driven avoidance of predators collapsed the spatial and dietary niche structure that otherwise stabilized coexistence, intensifying interspecific competition within predator-free refuges and contributing to green-anole population extinctions. Moreover, whereas adding either green anoles or curly-tails lengthened food chains, adding both species reversed this effect, in part because apex predators were trophic omnivores. Our results underscore the importance of top-down control in community ecology, but show that its outcomes hinge on prey behavior, spatial structure, and omnivory. Diversity-enhancing effects of top predators cannot be assumed, and non-consumptive effects of predation risk may be a widespread constraint on species coexistence

Predator-induced collapse of niche structure and species coexistence

Biological invasions are both a pressing environmental challenge and an opportunity to investigate fundamental ecological processes, such as the role of top predators in regulating biodiversity and food-web structure. In whole-ecosystem manipulations of small Caribbean islands on which brown anole lizards (Anolis sagrei) were the native top predator, we experimentally staged invasions by competitors (green anoles, Anolis smaragdinus) and/or new top predators (curly-tailed lizards, Leiocephalus carinatus). We show that curly-tailed lizards destabilized the coexistence of competing prey species, contrary to the classic idea of keystone predation. Fear-driven avoidance of predators collapsed the spatial and dietary niche structure that otherwise stabilized coexistence, which intensified interspecific competition within predator-free refuges and contributed to the extinction of green-anole populations on two islands. Moreover, whereas adding either green anoles or curly-tailed lizards lengthened food chains on the islands, adding both species reversed this effect—in part because the apex predators were trophic omnivores. Our results underscore the importance of top-down control in ecological communities, but show that its outcomes depend on prey behaviour, spatial structure, and omnivory. Diversity-enhancing effects of top predators cannot be assumed, and non-consumptive effects of predation risk may be a widespread constraint on species coexistence