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We introduce a novel method for electronic recording of cardiac signals from a single point at the skin in contrast to classical differential electrocardiography (ECG). Ultralownoise transistor devices with an adaptable, auto-stabilizing transimpedance amplifier are able to measure tiny skin potential modulations from a single contact electrode located at an individual’s wrist (single-point cardiography-SPC). Although SPC signals were highly prone to interspersed noise, they contained periodic patterns. In an electromagnetically shielded setting, we could clearly extract breathing and cardiac rhythms from the acquired SPC signals. As the reference, we measured ECG in parallel. Several signal-processing techniques like smoothening, correlation, decomposition and signal extraction showed that SPC signals contain breathing and periodic heart potential variations, which are time-correlated with ECG. In the future, we intent to use this novel technique to measure heart signals from patients in different health conditions.

Background: Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival., Methods: Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence., Results: Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm., Conclusion: In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although the use of the indigenous Southern African plant, Sutherlandia frutescens (SF) for the treatment of HIV/AIDS has previously been described, the risk which it may pose to the safety and efficacy of ARVs and the potential mechanisms which underlie such effects may have clinical significance and relevance. The protease inhibitor (PI), atazanavir (ATV) is a substrate of the efflux transporter, P-gp which modulates absorption in the small intestine, as well as CYP3A4 and CYP3A5enzymes which facilitate metabolism in the small intestine and liver. The objective of this study was to investigate the effect of SF on the pharmacokinetics (PK) of atazanavir (ATV) and to use a population PK analysis to fit and explain plasma concentration vs. time profiles of ATV generated in a previously conducted study in healthy male subjects in order to understand and postulate on the potential mechanism(s) of the drug-drug interaction. The population PK Compartmental Analysis of ATV before and after a two-week regimen of Phyto Nova Sutherlandia SU1 tablets which contain SF plant material indicated that a two compartment model with a dual absorption mechanism best explained the data. The dual absorption mechanism is hypothesized to reflect "passive" (first-order, Ka parameter) and "active" (zero-order, K0 parameter) absorption processes. The model suggested that the mechanism by which SF reduced the overall bioavailability of ATV may be modulated via the inhibition of the "active" absorption process. This study has highlighted the utility of population PK analyses in postulating probable mechanism(s) whereby an ATM or a herbal medicine interacts with an allopathic drug.

The nature of emerging patterns concerning water quality stressors and the evolution of hypoxia within sub-estuaries of the Chesapeake Bay has been an important unresolved question among the Chesapeake Bay community. Elucidation of the nature of hypoxia in the tributaries of the Chesapeake Bay has important ramifications to the successful restoration of the Bay, since much of Bay states population lives within the watersheds of the tributaries. Very little to date, is known about the small sub-estuaries of the Chesapeake Bay due to limited resources and the difficulties in resolving both space and time dimensions on scales that are adequate to resolve this question. We resolve the spatio-temporal domain dilemma by setting up an intense monitoring program of water quality stressors in the Severn and South Rivers, MD. Volume rendered models were constructed to allow for a visual dissection of the water quality times series which illustrates the life cycle of hypoxia and anoxia at the mid to upper portions of the tidal tributaries. The model also shows that unlike their larger Virginian tributary counterparts, there is little to no evidence of severe hypoxic water intrusions from the main-stem of the Chesapeake Bay into these sub-estuaries.

Introduction: The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its individual components., Methods: 64,046 participants aged 18-80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMI<25, normal weight; BMI 25-30, overweight; BMI≥30 kg/m2, obese). MetS was defined according to the revised criteria of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III). Within each BMI class and smoking subgroup (non-smoker, former smoker, <20 and ≥20 g tobacco/day), the cross-sectional association between alcohol and individual MetS components was tested using regression analysis., Results: Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7-71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values<0.001). HDL cholesterol levels were lower when they were also a former or current smoker (<20 and ≥20 g tobacco/day). Consumption of ≤1 drink/day indicated a trend towards lower triglyceride levels (non-significant). Concurrent use alcohol (>1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks., Conclusion: Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS.

Background: The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified by smoking behavior. Apolipoproteins (apo) associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) may be altered in MetS. This study aimed to examine the association between smoking and the following parameters: MetS and its components, levels of apolipoproteins and estimated lipoprotein particle size, separately for men and women, and in different body mass index (BMI) classes., Methods: We included 24,389 men and 35,078 women aged between 18 and 80 years who participated in the LifeLines Cohort Study between December 2006 and January 2012; 5,685 men and 6,989 women were current smokers. Participants were categorized into three different body mass index (BMI) classes (BMI <25; BMI 25 to 30; BMI ≥30 kg/m²). MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP:ATPIII) criteria. Blood pressure, anthropometric and lipid measurements were rigorously standardized, and the large sample size enabled a powerful estimate of quantitative changes. The association between smoking and the individual MetS components, and apoA1 and apoB, was tested with linear regression. Logistic regression was used to examine the effect of smoking and daily tobacco smoked on risk of having MetS. All models were age adjusted and stratified by sex and BMI class., Results: Prevalence of MetS increased with higher BMI levels. A total of 64% of obese men and 42% of obese women had MetS. Current smoking was associated with a higher risk of MetS in both sexes and all BMI classes (odds ratio 1.7 to 2.4 for men, 1.8 to 2.3 for women, all P values <0.001). Current smokers had lower levels of HDL cholesterol and apoA1, higher levels of triglycerides and apoB, and higher waist circumference than non-smokers (all P <0.001). Smoking had no consistent association with blood pressure or fasting blood glucose. In all BMI classes, we found a dose-dependent association of daily tobacco consumption with MetS prevalence as well as with lower levels of HDL cholesterol, higher triglyceride levels and lower ratios of HDL cholesterol/apoA1 and, only in those with BMI <30, LDL cholesterol/apoB (all P <0.001)., Conclusions: Smoking is associated with an increased prevalence of MetS, independent of sex and BMI class. This increased risk is mainly related to lower HDL cholesterol, and higher triglycerides and waist circumference. In addition, smoking was associated with unfavorable changes in apoA1 and apoB, and in lipoprotein particle size. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/196.

Background: Thyroid disorders are prevalent in Western society, yet many subjects experience limited symptoms at diagnosis, especially in hypothyroidism. We hypothesize that health-related quality of life (HR-QOL) is more severely impaired in subjects with more abnormal thyroid hormone function tests., Methods: This is a cross-sectional study of Dutch adults participating in the LifeLines Cohort Study between December 2009 and August 2010. In 9491 Western European participants (median age 45 years; 3993 men and 5498 women), without current or former use of thyroid medication, we compared HR-QOL using the RAND 36-Item Health Survey between subjects with normal thyrotropin (TSH) values and subjects with disturbed thyroid hormone status (serum TSH, free thyroxine, and free triiodothyronine). The influence of possible confounders (age, smoking, co-morbidity) on HR-QOL was evaluated as well., Results: Suppressed TSH values (TSH < 0.5 mU/L) were found in 114 (1.2%), while 8334 (88.8%) had TSH within the normal range, 973 participants (10.3%) had TSH between 4 and 10 mU/L, and 70 (0.7%) had TSH > 10 mU/L. Men had a higher HR-QOL than women (70-92 vs. 65-89; p < 0.001), except for the domain "general health" (72 vs. 72; p = 0.692). Men with suppressed or elevated TSH values did not score significantly lower than euthyroid men for any of nine domains of the RAND 36-Item Health Survey. Compared with euthyroid women, women with suppressed TSH scored significantly lower in the domains "physical functioning" (84 vs. 89, p = 0.013) and "general health" (67 vs. 72, p = 0.036). Women with markedly elevated TSH (> 10 mU/L) had a score in all HR-QOL domains that was similar to that of women with normal TSH values. There were no differences in the physical component score and the mental component score between any of the TSH groups. Physical component score and mental component score were mainly determined by smoking status, co-morbidity, and body mass index or waist circumference., Conclusions: In this population-based study, HR-QOL scores of subjects with suppressed TSH values or markedly elevated TSH values were generally not significantly lower than those of subjects with normal or mildly elevated TSH values.

Background: Previous studies using conventional cTnI assays reported conflicting results on the evolution of cTnI levels during hemodialysis. The determinants and prognostic significance of changes in cTnI during hemodialysis are presently unknown. The aim of this prospective study was to characterize the determinants and prognostic significance of intra-dialysis changes in cTnI using a sensitive assay., Methods: cTnI was measured before and after hemodialysis with a sensitive assay in 90 chronic patients without acute cardiac symptoms. Multivariable regression analyses were used to identify factors that were associated with intra-dialysis rise in cTnI. The prognostic effect of an intra-dialysis rise in cTnI during a 52-month follow-up was evaluated using Cox regression models. The primary and secondary endpoint was the incidence of major adverse cardiovascular events and all-cause mortality, respectively., Results: Pre-dialysis cTnI was elevated in 31 patients (34 %). cTnI increased significantly during dialysis and this had a trend to be associated with longer dialysis vintage. A greater intra-dialysis rise in cTnI was associated with a significantly higher incidence of cardiovascular events, also after correction for age, gender, dialysis vintage, residual diuresis, previous cardiovascular events, and pre-dialysis cTnI levels (HR per 10 ng/L rise in cTnI: 1.21; CI 1.06-1.38; p 0.005)., Conclusion: TnI levels rise significantly during hemodialysis and a greater intra-dialysis rise in cTnI is associated with an increased incidence of cardiovascular events. These findings suggest that hemodialysis has an acute deleterious effect on the heart. An intra-dialysis rise in cTnI may help identify patients who are susceptible to the hemodynamic stress of hemodialysis.

Background: Vitamin B(12) deficiency occurs frequently, especially among the elderly. However, screening for vitamin B(12) deficiency is hampered by poor sensitivity of the existing total vitamin B(12) assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B(12) deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B(12) deficiency in a mixed patient population., Methods: Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B(12) and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS)., Results: Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B(12) in detecting vitamin B(12) deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 μmol/L. The combination of vitamin B(12) and holoTC did not improve diagnostic accuracy at this cut-off level., Conclusions: HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45μmol/L) in a mixed patient population.

Background: Determination of the aldosterone-to-renin ratio (ARR) in blood is the preferred screening test for primary aldosteronism. Renin can be measured as the plasma renin activity (PRA) or the plasma renin concentration (PRC). Consequently, the ARR can be measured either based on the PRA (ARR(pra)) or based on the PRC (ARR(prc)). In contrast with the ARR(pra), the data on reference values for the ARR(prc) are limited. Moreover, whether the ARR(pra) or ARR(prc) is affected by variations in salt intake is unknown., Methods: We measured the PRA, the PRC, and serum aldosterone in 100 normotensive individuals between 20 and 70 years of age before and after a 3-day oral sodium-loading test (SLT). Participants were stratified according to age and sex. Data are presented as the median and interquartile range (IQR)., Results: Urinary sodium excretion after the SLT was ≥200 mmol/24 h in all participants. Serum aldosterone, PRA, and PRC values were significantly reduced after the SLT. PRC and PRA results were highly correlated [Spearman rank correlation r(s) = 0.80 and 0.74 before and after SLT, respectively; P < 0.001 for both]. The central 95% reference intervals for ARR(pra) before and after SLT were 0.07-1.45 h(-1) and 0.06-1.84 h(-1), respectively. The corresponding reference intervals for ARR(prc) were 4.1-81.3 pmol/ng and 3.9-74.8 pmol/ng. The median ARR(prc) decreased after the SLT from 19.5 pmol/ng (IQR, 13.0-29.4 pmol/ng) to 18.6 pmol/ng (IQR, 9.4-27.1 pmol/ng) (P = 0.005), whereas the median ARR(pra) did not change (P = 0.12). Both the ARR(prc) and ARR(pra) at baseline were higher in women than in men, whereas no sex difference was observed after sodium loading., Conclusions: We present reference values for the ARR(prc) for healthy individuals. The ARR is affected to a variable degree by sex and sodium intake.

Context: Abdominal fat contributes to anovulation., Objective: We compared body fat distribution measurements and their contribution to anovulation in obese ovulatory and anovulatory infertile women., Design: Seventeen ovulatory and 40 anovulatory women (age, 30 +/- 4 yr; body mass index, 37.7 +/- 6.1 kg/m(2)) participated. Body fat distribution was measured by anthropometrics, dual-energy x-ray absorptiometry, and single-sliced abdominal computed tomography scan. Multiple logistic regression analysis was applied to determine which fat compartments significantly contributed to anovulation., Results: Anovulatory women had a higher waist circumference (113 +/- 11 vs. 104 +/- 9 cm; P < 0.01) and significantly more trunk fat (23.0 +/- 5.3 vs. 19.1 +/- 4.2 kg; P < 0.01) and abdominal fat (4.4 +/- 1.3 kg vs. 3.5 +/- 0.9 kg; P < 0.05) on dual-energy x-ray absorptiometry scan than ovulatory women despite similar body mass index. The volume of intraabdominal fat on single-sliced abdominal computed tomography scan was not significantly different between the two groups (203 +/- 56 vs. 195 +/- 71 cm(3); P = 0.65), but anovulatory women had significantly more sc abdominal fat (SAF) (992 +/- 198 vs. 864 +/- 146 cm(3); P < 0.05). After multiple logistic regression analysis, only trunk fat, abdominal fat, and SAF were associated with anovulation., Conclusions: Abdominal fat is increased in anovulatory women due to a significant increase in SAF and not in intraabdominal fat. SAF and especially abdominal and trunk fat accumulation are associated with anovulation.

Background: Elevation of the tumor marker S-100B in melanoma patients is a highly specific indicator of recurrence., Materials and Methods: The role of S-100B in disease-free survival (DFS) was evaluated in stage III melanoma patients (staged with fluorodeoxyglucose positron emission tomography [FDG-PET] and computed tomography [CT]) with palpable lymph node metastases who underwent therapeutic lymph node dissection. S-100B and LDH were measured on the day before surgery (d = -1) and on days 1, 2, and 7 postoperatively. Multivariate logistic regression was used to study factors associated with preoperative elevation of S-100B. Univariate (log-rank test) and multivariate (Cox regression) survival analyses were performed to identify factors associated with DFS., Results: Between 2004 and 2008, 56 patients (median age 57, range 24-93) years, 27 males (48%) and 29 females (52%) entered the study. Preoperative S-100B elevation was found in 27 patients (48%) and elevated LDH in 20 patients (36%). No association was found between these two markers at any time. Multivariate analysis showed that elevated S-100B preoperatively (hazard ratio [HR] 2.7, P = .03) was associated with DFS. S-100B elevation was associated with increased tumor size (odds ratio [OR] 3.40; P = .03)., Conclusion: Elevated S-100B preoperatively in patients with optimally staged clinical stage III melanoma is associated with decreased disease-free survival. S100-B could be used as a prognostic marker in the stratification of new adjuvant trials to select stage III melanoma patients for adjuvant systematic treatment.

Objective: The effect of thyroid function on cardiovascular risk may extend to the euthyroid range. In euthyroid subjects, we determined whether carotid artery intima media thickness (IMT), a measure of subclinical atherosclerosis, is related to thyroid function., Design and Subjects: Cross-sectional study in a cohort of 78 nonsmoking, predominantly middle-aged, euthyroid subjects (44 men and 34 women, mean age 56 years, TSH between 0.5 mU/l and 4.0 mU/l and FT4 between 11.0 pmol/l and 19.5 pmol/l)., Measurements: IMT (mean of three segments in both carotid arteries by ultrasonography), clinical factors, insulin resistance (HOMA(ir)), plasma lipids, C-reactive protein (CRP), serum FT4, TSH and thyroid autoantibodies., Results: In several multiple linear regression models, age- and sex-adjusted IMT was found to be independently related to either pulse pressure and body mass index (BMI), to high density lipoprotein (HDL) cholesterol or to FT4, but not to TSH, thyroid autoantibodies, HOMA(ir), CRP, non-HDL cholesterol and triglycerides. In a subsequent model which included age, sex, pulse pressure, body mass index (BMI), HDL cholesterol and FT4, IMT was independently and positively related to age (beta = 0.43, P < 0.001), male sex (beta = 0.34, P = 0.014), pulse pressure (beta = 0.29, P = 0.002), BMI (beta = 0.24, P = 0.007) and inversely related to FT4 (beta = -0.19, P = 0.046). IMT was also inversely related to FT4 in a model which included HDL cholesterol, non-HDL cholesterol and triglycerides., Conclusions: In euthyroid subjects, IMT is associated with FT(4), after controlling for clinical factors, lipid levels and thyroid autoantibodies. These findings raise the possibility that, even within the euthyroid range, low normal thyroid function may adversely affect cardiovascular risk.

Objective: To evaluate the outcomes of pregnancies with sonographically detected nuchal cords remote from delivery during the second and third trimesters of gestation., Methods: A retrospective study of patients with and without nuchal cords detected by sonography during the second and third trimesters of gestation (17-36 weeks) was conducted. Variables included maternal age, parity, gestational age at sonography and at delivery, method of delivery, intrapartum fetal heart abnormalities, meconium-stained amniotic fluid, birth weight, 5-minute Apgar score, and neonatal intensive care unit admissions., Results: A total of 233 patients were included in this study, of which 118 had sonographically detected nuchal cords identified in our department during the study period. There were no statistically significant differences between patients with sonographically detected nuchal cords and control patients with respect to maternal age, estimated gestational age at sonography, method of delivery, meconium-stained fluid, birth weight, intrapartum fetal heart abnormalities, 5-minute Apgar scores of less than 7, and neonatal intensive care unit admissions. Patients with nuchal cords detected by sonography were more likely to give birth before 37 weeks' gestation than control patients (21% versus 11%; P = .040)., Conclusions: A sonographically detected nuchal cord is not associated with important perinatal complications.

Background: Inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) synthesis are increased in epithelial cells and in tissue macrophages of the inflamed mucosa from patients with inflammatory bowel disease (IBD). Since tissue macrophages are derived from circulating monocytes, we studied iNOS expression in circulating monocytes and related this expression to disease activity. In view of the possible role of NO in monocyte function, we also studied iNOS expression in relation to markers of monocyte activation., Methods: The expression of iNOS in circulating monocytes from 15 patients with active IBD, 6 patients who went into remission and 18 healthy controls was quantified by flow cytometry and correlated with surface markers (CD63, CD11b, HLA-DR) for monocyte activation. In addition, iNOS expression in circulating monocytes was assessed by Western blotting, immunocytochemistry and measurement of the NO metabolites nitrite and nitrate in plasma., Results: The expression of iNOS in circulating monocytes and the percentage of iNOS-positive monocytes were increased in patients with active IBD compared to healthy controls (fluorescence index: 1.3 (0.1-6.3) versus 0.8 (0.0-1.8); P < 0.05: percentage of iNOS positive monocytes: 37.3 (1.0-77.0)% versus 5.3 (0.0-43.3)%; P<0.01). The six patients who went into remission all had a marked reduction of iNOS expression. iNOS expression was confirmed by Western blotting and immunocytochemistry. Plasma nitrite and nitrate levels were elevated in three patients with active 1BD. The surface markers for monocyte activation, CD63 and CD11b, were not elevated. HLA-DR expression was decreased on circulating monocytes from patients with active ulcerative colitis., Conclusions: iNOS is increased in circulating monocytes from patients with active IBD and this increased expression correlates with disease activity. Considering the decreased HLA-DR expression and absence of monocyte activation markers, NO produced by iNOS may have a function in suppressing systemic monocyte activation.

Objective: We studied the activity of a single oral dose of RWJ-67657, a synthetic p38 mitogen-activated protein kinase inhibitor, in preventing dual leukocyte/endothelial activation after endotoxin infusion in healthy volunteers., Design: Prospective placebo-controlled study., Setting: Intensive care unit at a university medical center., Subjects: Twenty-one healthy male volunteers., Interventions: Endotoxin (4 ng/kg) as a 1-min infusion. According to randomization, the volunteers received placebo (n = 6) or 1400 mg (n = 4), 700 mg (n = 6), or 350 mg (n = 5) of RWJ-67657., Measurements and Main Results: Neutrophil activation was investigated by analyzing the extent of membrane expression of adhesion markers by calibrated flow cytometry. Circulating intercellular adhesion molecule-1 and E-selectin were measured by enzyme-linked immunosorbent assays. The endotoxin-induced shedding of L-selectin was diminished in a dose-dependent manner (p <.0001). High-dose RWJ-67657 prevented up-regulation of the integrins CD11b (p <.01) and CD 66b (p <.01) on neutrophils. The endotoxin-induced increase in circulating intercellular adhesion molecule-1 and circulation E-selectin was almost completely prevented by high-dose RWJ-67657., Conclusion: A single oral dose of RWJ-67657 prevented neutrophil and endothelial activation after endotoxin infusion.

Unlabelled: Autoimmunity is suggested to play a pathogenetic role in premature atherosclerosis. Since atherosclerosis and vasculitis seem pathogenetically related, we hypothesized that ANCA, an important antibody in vasculitis, plays a role in atherosclerosis as well. We therefore investigated the prevalence of ANCA in patients with premature atherosclerosis and related the presence of these antibodies to levels of AECA and markers of inflammation., Methods & Results: In a cohort of 286 patients with premature atherosclerosis the prevalence of ANCA was 5.6% (16/286). All had perinuclear ANCA. More females were ANCA-positive (8M/8F vs. 200M/70F, p = 0.03). In a nested case-control study, comparing the 16 ANCA-positive patients with 32 controls, levels of AECA were higher in the first (7.32 +/- 0.91U vs. 5.52 +/- 0.41U, p < 0.05)., Conclusion: ANCA does not seem to play a major role in premature atherosclerosis. Whether elevated levels of AECA in ANCA-positive patients with premature atherosclerosis reflect more extended vascular disease remains to be determined.