Long-term effects of endovascular angioplasty on orthostatic vasocutaneous autoregulation in patients with peripheral atherosclerosis

OBJECTIVE: To test the hypothesis that endovascular revascularization of femoropopliteal lesions improves the impaired venoarteriolar response (VAR) in patients with atherosclerosis. METHODS: We prospectively compared VARs in 15 healthy controls (18 legs) and 14 patients (17 legs) with mild to moderate peripheral arterial disease before and after successful peripheral endovascular angioplasty of femoropopliteal lesions. In all subjects, foot skin blood flow was assessed by laser Doppler flowmetry in the horizontal (HBF) and sitting (SBF) positions. VAR was calculated as (HBF - SBF)/HBF x 100. RESULTS: In patients with peripheral arterial disease, mean HBF (in arbitrary units [AU]; mean +/- SD) was similar before (25.6 +/- 15.3 AU) and after (27.0 +/- 16.4 AU) angioplasty (P = .67), whereas SBF was significantly lower after than before the endovascular procedure (11.6 +/- 7.7 AU to 18.4 +/- 14.1 AU; P < .05). Intragroup differences between SBF and HBF were significant before and after angioplasty (P < .001). VAR was higher after angioplasty (55.1% +/- 21.2%) compared with VAR before intervention (33.4% +/- 20.2%; P = .015). Although VAR increased after the intervention, VAR was still lower than in healthy controls (68.4% +/- 20.5%; P = .025). During the 6 months of follow-up, the ankle-brachial index and VAR remained unchanged (P > .05). CONCLUSIONS: Patients with mild to moderate peripheral arterial disease have an impaired orthostatic autoregulation that improves after successful endovascular revascularization of femoropopliteal obstructive lesions. The effect on VAR is sustained in the absence of restenosis.

Feasibility of future epidemiological studies on possible health effects of mobile phone base stations

The increasing deployment of mobile communication base stations led to an increasing demand for epidemiological studies on possible health effects of radio frequency emissions. The methodological challenges of such studies have been critically evaluated by a panel of scientists in the fields of radiofrequency engineering/dosimetry and epidemiology. Strengths and weaknesses of previous studies have been identified. Dosimetric concepts and crucial aspects in exposure assessment were evaluated in terms of epidemiological studies on different types of outcomes. We conclude that in principle base station epidemiological studies are feasible. However, the exposure contributions from all relevant radio frequency sources have to be taken into account. The applied exposure assessment method should be piloted and validated. Short to medium term effects on physiology or health related quality of life are best investigated by cohort studies. For long term effects, groups with a potential for high exposure need to first be identified; for immediate effect, human laboratory studies are the preferred approach.

Beneficial cardiovascular effects of endothelin ET(A) receptor blockade in established long-term heart failure after myocardial infarction

Although experimental prevention studies have suggested therapeutic potential of endothelin (ET) antagonists for the treatment of heart failure, the results of clinical trials using ET antagonists on top of standard heart failure medications have been largely disappointing. This experimental study investigated the effects of chronic ET(A) receptor blockade in long-term survivors of myocardial infarction who had developed stable chronic heart failure in the absence of other treatments. Systolic blood pressure, heart rate, organ weights of the right atrium and ventricle, and the lungs were determined, and tissue ET-1 peptide levels were measured in cardiac tissue, lung, and aorta. The results show that chronic blockade of ET(A) receptors stabilizes systolic blood pressure and reverses the heart failure-induced weight increases of right heart chambers and lung. The changes observed occurred independently of tissue ET-1 concentrations and heart rate, suggesting mechanisms independent of local cardiac or pulmonary ET-1 synthesis, which are yet to be identified.

Long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication

Supervised exercise training has been shown to improve walking capacity in several studies of patients with intermittent claudication. However, data on long-term outcome are quite limited. The aim of this prospective study was to evaluate long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication. Patients and methods: Sixty-seven consecutive patients with intermittent claudication who completed a supervised 12-week exercise training program were asked for follow up evaluation 39 +/- 20 months after program completion. Pain-free walking distance (PWD) and maximum walking distances (MWD) were assessed by treadmill test and several questionnaires. Results: Forty (60%) patients agreed to participate, 22 (33%) refused participation, and 5 (7%) died during follow-up. PWD and MWD significantly improved at completion of 12-weeks supervised exercise training as compared to baseline (PWD 114 +/- 100 vs. 235 +/- 248, p = 0.002; MWD 297 +/- 273 vs. 474 +/- 359, p = 0.001). Improvement of PWD and MWD could be maintained at follow up (197 +/- 254, p = 0.014; 390 +/- 324, p = 0.035, respectively) with non-smokers showing significantly better sustained PWD and MWD improvement as compared to baseline. Overall, walking capacity correlated with functional status of quality of life. Conclusions: Major findings of this investigation were that improvement in walking capacity is sustained after completion of supervised exercise training program with best results in patients who quitted or never smoked. Improved walking capacity is associated with increased functional status of quality of life.

Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption

BACKGROUND: Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. MATERIALS AND METHODS: The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. RESULTS: Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. CONCLUSIONS: The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits.

Long-term quality of life after hepatic resection: health is not simply the absence of disease

BACKGROUND: Due to advances in operative methods and perioperative care, mortality and morbidity following major hepatic resection have decreased substantially, making long-term quality of life (QoL) an increasingly prominent issue. We evaluated whether postoperative diagnosis was associated with long-term QoL and health in patients requiring hepatic surgery for benign or malignant disease. METHODS: QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver-specific QLQ-LMC21 module. RESULTS: Between 2002 and 2006, 249 patients underwent hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred thirty-five patients were available for QoL analysis after a mean of 26.5 months. There was no statistical difference in global QoL scores between patients with malignant and benign diseases (p = 0.367). Neither the extent of the resection (> or =2 segments vs. <2 segments; p = 0.975; OR = 0.988; 95% CI = 0.461-2.119) nor patient age had a significant influence on overall QoL (p = 0.092). CONCLUSIONS: These results indicate that long-term QoL for patients who underwent liver resection for malignant disease is quite good and that a poor clinical prognosis does not seem to correlate with a poor QoL.

A Gift is not always a Gift: Heterogeneity and Long Term Effects in a Gift Exchange Experiment

We study gift exchange in a field experiment where a random subsample of participants in the Swiss Labour Force Survey received vouchers to be used in adult training. Actual voucher redemption can be traced, giving us the unique opportunity to study whether gift exchange in the form of participation in future rounds of the survey depends on the perceived usefulness of the gift. The group of voucher recipients as a whole has significantly higher response rates. There is considerable heterogeneity, however. Our results point to a long-lasting gift exchange relationship only for the subgroup that redeemed their vouchers.

Effects of neonatal high-dose short-term glucocorticoid treatment on the lung: a morphologic and morphometric study in the rat

Glucocorticoids are often applied in neonatology and perinatology to fight the problems of respiratory distress and chronic lung disease. There are, however, many controversies regarding the adverse side effects and long-term clinical benefits of this therapeutic approach. In rats, glucocorticoids are known to seriously impair the formation of alveoli when applied during the first two postnatal weeks even at very low dosage. The current study investigates short-term and long-term glucocorticoid effects on the rat lung by means of morphologic and morphometric observations at light and electron microscopic levels. Application of a high-dosage protocol for only few days resulted in a marked acceleration of lung development with a precocious microvascular maturation resulting in single capillary network septa in the first 4 postnatal days. By postnatal d 10, the lung morphologic phenotype showed a step back in the maturational state, with an increased number of septa with double capillary layer, followed by an exceptional second round of the alveolarization process. As a result of this process, there was an almost complete recovery in the parenchymal lung structure by postnatal d 36, and by d 60, there were virtually no qualitative or quantitative differences between experimental and control rats. These findings indicate that both dosage and duration of glucocorticoid therapy in the early postnatal period are very critical with respect to lung development and maturation and that a careful therapeutic strategy can minimize late sequelae of treatment.

Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study

OBJECTIVES Non-steroidal anti-inflammatory drugs (NSAIDs) may cause kidney damage. This study assessed the impact of prolonged NSAID exposure on renal function in a large rheumatoid arthritis (RA) patient cohort. METHODS Renal function was prospectively followed between 1996 and 2007 in 4101 RA patients with multilevel mixed models for longitudinal data over a mean period of 3.2 years. Among the 2739 'NSAID users' were 1290 patients treated with cyclooxygenase type 2 selective NSAIDs, while 1362 subjects were 'NSAID naive'. Primary outcome was the estimated glomerular filtration rate according to the Cockroft-Gault formula (eGFRCG), and secondary the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formula equations and serum creatinine concentrations. In sensitivity analyses, NSAID dosing effects were compared for patients with NSAID registration in ≤/>50%, ≤/>80% or ≤/>90% of assessments. FINDINGS In patients with baseline eGFRCG >30 mL/min, eGFRCG evolved without significant differences over time between 'NSAID users' (mean change in eGFRCG -0.87 mL/min/year, 95% CI -1.15 to -0.59) and 'NSAID naive' (-0.67 mL/min/year, 95% CI -1.26 to -0.09, p=0.63). In a multivariate Cox regression analysis adjusted for significant confounders age, sex, body mass index, arterial hypertension, heart disease and for other insignificant factors, NSAIDs were an independent predictor for accelerated renal function decline only in patients with advanced baseline renal impairment (eGFRCG <30 mL/min). Analyses with secondary outcomes and sensitivity analyses confirmed these results. CONCLUSIONS NSAIDs had no negative impact on renal function estimates but in patients with advanced renal impairment.

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: effects on feed intake, milk production, and metabolism.

Elevation of ketone bodies in dairy cows frequently occurs in early lactation, usually concomitantly with a lack of energy and glucose. The objective of this study was to induce an elevated plasma β-hydroxybutyrate (BHBA) concentration over 48 h in mid-lactating dairy cows (i.e., during a period of positive energy balance and normal glucose plasma concentrations). Effects of BHBA infusion on feed intake, metabolism, and performance were investigated. Thirteen cows were randomly assigned to 1 of 2 infusion groups, including an intravenous infusion with Na-dl-β-OH-butyrate (1.7 mol/L) to achieve a plasma concentration of 1.5 to 2.0 mmol/L of BHBA (HyperB; n=5), or an infusion of 0.9% saline solution (control; n=8). Blood was sampled before and hourly during the 48 h of infusion. In the liver, mRNA transcripts related to gluconeogenesis (pyruvate carboxylase, glucose 6-phosphatase, mitochondrial phosphoenolpyruvate carboxykinase), phosphofructokinase, pyruvate dehydrogenase complex, and fatty acid synthesis (acetyl-coenzyme A carboxylase, fatty acid synthase) were measured by real-time PCR. Glyceraldehyde-3-phosphate dehydrogenase and ubiquitin were used as housekeeping genes. Changes (difference between before and after 48-h infusion) during the infusion period were evaluated by ANOVA with treatment as fixed effect, and area under the curve of variables was calculated on the second day of experiment. The plasma BHBA concentration in HyperB cows was 1.74 ± 0.02 mmol/L (mean ± SE) compared with 0.59 ± 0.02 mmol/L for control cows. The change in feed intake, milk yield, and energy corrected milk did not differ between the 2 experimental groups. Infusion of BHBA reduced the plasma glucose concentration (3.47 ± 0.11 mmol/L) in HyperB compared with control cows (4.11 ± 0.08 mmol/L). Plasma glucagon concentration in HyperB was lower than the control group. All other variables measured in plasma were not affected by treatment. In the liver, changes in mRNA abundance for the selected genes were similar between 2 groups. Results demonstrate that intravenous infusion of BHBA decreased plasma glucose concentration in dairy cows, but this decrease could not be explained by alterations in insulin concentrations or key enzymes related to gluconeogenesis. Declined glucose concentration is likely functionally related to decreased plasma glucagon concentration.

Copper, ceruloplasmin, and long-term cardiovascular and total mortality (the Ludwigshafen Risk and Cardiovascular Health Study)

BACKGROUND Copper and its main transport protein ceruloplasmin have been suggested to promote the development of atherosclerosis. Most of the data come from experimental and animal model studies. Copper and mortality have not been simultaneously evaluated in patients undergoing coronary angiography. METHODS AND RESULTS We examined whether serum copper and ceruloplasmin concentrations are associated with angiographic coronary artery disease (CAD) and mortality from all causes and cardiovascular causes in 3253 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Age and sex-adjusted hazard ratios (HR) for death from any cause were 2.23 (95% CI, 1.85-2.68) for copper and 2.63 (95% CI, 2.17-3.20) for ceruloplasmin when we compared the highest with the lowest quartiles. Corresponding hazard ratios (HR) for death from cardiovascular causes were 2.58 (95% CI, 2.05-3.25) and 3.02 (95% CI, 2.36-3.86), respectively. Further adjustments for various risk factors and clinical variables considerably attenuated these associations, which, however, were still statistically significant and the results remained consistent across subgroups. CONCLUSIONS The elevated concentrations of both copper and ceruloplasmin are independently associated with increased risk of mortality from all causes and from cardiovascular causes.