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On the basis of models of otolith functioning, one would expect that, during sinusoidal linear self-motion in darkness, percepts of body tilt are experienced. However, this is normally not the case, which suggests that the otoliths are not responsive to small deviations from the vertical of the gravito-inertial force vector acting on them. Here we show that this is incorrect. Subjects usually know on what kind of linear motion device they are (going to be) moved, having seen it prior to experimentation. This may result in a cognitive suppression of such otolith responses. In the present study, subjects were kept completely unaware of how they were moved and were asked to report on how they thought they moved. About 50% of the reports included tilt percepts almost immediately. It is concluded that this reveals the presence of otolith responsiveness to even small and short-lived deviations of the gravito-inertial force vector from verticality, a responsiveness which is suppressed when (prior) cognitions exist that the motion path is purely in the horizontal plane.

This study establishes functions that specify self-reported sleep disturbance in relation to the exposure to nighttime transportation noise, by reanalyzing pooled data from previous studies. Results are based on data from 28 original datasets obtained from 24 field studies (4 studies collected data regarding 2 sources) including almost 23,000 participants exposed to nighttime levels ranging from 45 to 65 dB. Functions are presented that give the percentage highly sleep disturbed, sleep disturbed, and (at least) a little sleep disturbed people due to aircraft, road traffic, and railway noise in relation to the average nighttime outdoor exposure level at the facade most exposed to the source concerned. These functions show that at the same average nighttime noise-exposure level, aircraft noise is associated with more self-reported sleep disturbance than road traffic, and road traffic noise is associated with more sleep disturbance than railways. The association of noise-induced sleep disturbance with age has an inverse U-shape, with the strongest reaction found between 50 and 56 years of age.

Context: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. Objective: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. Data Sources/Study Selection: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. Data Extraction: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. Data Synthesis: The studies included 7377 incident invasive breast cancer cases occurring among 351825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend = .08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend = .54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend = .12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. Conclusion: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.

We studied the relationships among different polymorphisms of FVII gene in determining FVII levels, in a sample of 335 male and female Italian volunteers. The hypervariable region 4 (HVR4), the promoter decanucleotide insertion (-323 0/10 bp) and the R353Q polymorphisms of FVII gene were evaluated. The association of HVR4 or -323 0/10 bp polymorphism with plasma FVII levels differed between gender (Interaction term: p = 0.02 and p = 0.03, respectively), showing stronger effect in males than in females. In males, the R353Q and the HVR4 polymorphisms showed an incremental influence on FVII variance (F = 8.9, p < 0.001 and F = 4.4, p = 0.01, respectively). Moreover, the effects of Q and 10 bp alleles on the reduction of FVII activity levels were significantly potentiated by the presence of H7 allele of HVR4 (Interaction term p = 0.03 for R353Q*HVR4 and p = 0.03 for -323 0/10 bp*HVR4). In conclusion, the effect of FVII polymorphisms on FVII levels was gender dependent and derived from a complex interaction among them. HVR4 polymorphism seems to add an independent, albeit small, contribution to the regulation of FVII plasma levels.

Objective. Life expectancy without chronic morbidity, or morbidity-free life expectancy (MFLE), was calculated to measure changes in population health status between 1989 and 2000 on the basis of gender and socioeconomic status. Methods. Sullivan's method was used to calculate morbidity-free life expectancy. Prevalence rates for chronic morbidity were derived from the Netherlands Continuous Health Interview Survey. Four socioeconomic groups were distinguished on the basis of educational level. Results. Between 1989 and 2000, total life expectancy increased for males and females and for all socioeconomic groups. Morbidity-free life expectancy decreased significantly for males (from 54.7 years to 53.9 years) and females (from 55.3 years to 51.0 years). The gap between males and females in MFLE has reversed, from 0.6 years in favor of females in 1989 to 2.9 years in favor of males in 2000. The gap between the upper and lower classes seems to have narrowed (for males from 11 years to 8.5 years and for females from 4.7 years to 4.0 years). Conclusions. The results indicate that morbidity-free life expectancy is falling for males and females and in all socioeconomic groups. Part of this decrease could be attributed to earlier diagnosis of chronic diseases. A widening gap in MFLE was observed between males and females in favor of males. The gap between the upper and lower socioeconomic groups seems to be narrowing. ©2005 Association of Schools of Public Health.

In this article the importance of mineral suppletion for teeth and jawbone is explained in a step-wise manner. The steps discussed are the pre-eruptive phase of teeth and the growth, adult and ageing phase of the skeleton. Mineral suppletion should be seen as a measure to prevent dental caries (fluoride) and to ensure a maximal resistance against the spontaneous bone loss during ageing. Therefore, it seems not suitable for therapy of osteoporosis. If an enhanced bone loss occurs as a result of decreased production of sex hormones or immobility, mineral suppletion will probably have a minor effect. An optimal mineral intake will ensure a maximal peak bone mass built up during the growth phase of bone, a maintenance of this peak bone mass as much as possible during the phase of neutral bone balance and a minimal bone loss during the ageing period with negative bone balance.

Clotting factor V has a dual function in coagulation: after activation, procoagulant factor V stimulates the formation of thrombin, whereas anticoagulant factor V acts as a cofactor for activated protein C (APC) in the degradation of factor VIII/VIIIa, thereby reducing thrombin formation. In the present study, we evaluated whether plasma factor V levels, either decreased or increased, are associated with venous thrombosis. High procoagulant factor V levels may enhance prothrombinase activity and increase the thrombosis risk. Low anticoagulant factor V levels could reduce APC- cofactor activity in the factor VIII inactivation (APC-resistant phenotype), which might also promote thrombosis. Low factor V levels in combination with factor V Leiden could lead to a more severe APC-resistant phenotype (pseudohomozygous APC resistance). To address these issues, we have measured factor V antigen (factor V:Ag) levels in 474 patients with thrombosis and 474 control subjects that were part of the Leiden Thrombophilia Study (LETS). Factor V:Ag levels increased by 7.6 U/dL for every successive 10 years of age. Mean factor V:Ag levels were 134 (range 41 to 305) U/dL in patients and 132 (range 47 to 302) U/dL in controls. Neither high nor low factor V:Ag levels were associated with venous thrombosis. We found that factor V:Ag and factor VIII antigen levels in plasma were correlated, but factor V did not modify the thrombotic risk of high factor VIII levels. The normalized APC ratio was not influenced by the factor V:Ag level in subjects with or without factor V Leiden. We conclude that neither low nor high factor V:Ag levels are associated with venous thrombosis and that factor V:Ag levels do not mediate the thrombotic risk associated with high factor VIII levels. Chemicals/CAS: factor V Leiden; Factor V, 9001-24-5; Factor VIII, 9001-27-8; Protein C

Fibrinogen is an acute phase reactant, and there, fore its plasma levels increase after severe injury. Polymorphisms in the fibrinogen α and β genes have been found to be associated with plasma levels of fibrinogen, and it has also been suggested that they are associated with the fibrinogen increase in acute phase situations. In forty-five consecutive patients admitted to the Intensive Care Unit after acute cranial or thoracic trauma, we investigated the influence of four polymorphisms at the fibrinogen loci (-455G/A and BclI (β gene), TaqI and T/A312 (α gene)) on the post-trauma increase of the fibrinogen levels. At admission, fibrinogen levels were comparable in the patients with the different genotypes for the four polymorphisms studied. However, patients carrying the -455A allele of the -455G/A polymorphism had a significantly wider variation and higher peak levels of fibrinogen, during their stay at the intensive care unit, than did the -455GA homozygotes (5.1 g/I (SD 1.3) and 5.9 g/1 (SD 1.0), respectively, p<0.05). Such difference was not found for the other studied polymorphisms. The present study suggests that the increase of fibrinogen level in acute phase situations like severe trauma is associated with the β-gene -455G/A polymorphism.

Memory plays a major role in the formation of food expectations. How accessible and how accurate is incidentally acquired and stored product information? In the present experiment the memory for variations in texture (and flavour) was tested with a new and ecologically valid method. Subjects (N = 69:35 women, 34 men, age 19-59 yrs) came to the institute before having had breakfast and received a breakfast of several items (including breakfast drinks, biscuits and pâté). Subsequently, during the day, they answered questions about their hunger feelings every hour and returned for a taste experiment at the end of the day. When unexpectedly confronted with a series of multiple samples of four texture variations of each of the breakfast items mentioned above, they had to indicate which of these variations they had eaten at breakfast. Signal detection measures showed that most subjects recognised the eaten versions well for all three of the food items. Women remembered better than men. Both men and women used an equally conservative criterion. © 2002 Elsevier Science Ltd. All rights reserved.

The main aim of this study was to establish the convergent and discriminant validity of a single-item measure of daily fatigue ("How fatigued do you currently feel?") in a daily diary context. Convergent validity of our measure was examined by relating it to a validated multiple-item measure of fatigue (Profile of Mood States; McNair, Lorr, & Droppelman, 1971) and to other daily (work-home interference, sleep complaints, work-related effort) and global (fatigue, health complaints, work-home interference, job pressure) measures that are conceptually related to fatigue. Discriminant validity was assessed by relating the single-item fatigue measure to daily (work pleasure) and global (job control, social support, motivation to learn) measures that are conceptually distinct from fatigue. Data were collected among 120 academic staff members, who completed a general questionnaire (tapping the global measures under study) and who took part in a 9-d daily diary study (3 measurements daily). Correlation patterns and multilevel analyses revealed strong and significant associations between the single-item fatigue measure and the variables incorporated to assess convergent validity (especially with the POMS: r=0.80), thus supporting the convergent validity of our measure. Relations with variables included to examine discriminant validity were weak or insignificant, supporting the discriminant validity of the single-item fatigue measure. Despite this study's limitations (i.e., exclusive use of self-reporting, specific sample) we conclude that this single-item fatigue measure offers a valid way to assess daily fatigue.

The objectives of the present study were to compare the bioavailability of vitamin A from liver paste and from a vitamin A supplement at three nutritionally relevant levels of intake, and to estimate levels of "safe" intake based on concentrations of retinoic acid and its metabolites in plasma after a single dose of vitamin A from liver paste. Women (n = 35; 19-47 y of age) consumed 3.0, 7.5 or 15 mg vitamin A as liver paste or as a vitamin A supplement with a test meal in a randomized design, with a combined crossover (two sources) and parallel approach (three dosages). Retinyl esters and retinoic acid (RA) metabolites were quantified in blood samples at 2-24 h after dosing. The areas under the time-response curves (AUC) were calculated to evaluate responses in plasma vitamin A after intake of liver paste and the vitamin A supplements. For retinyl esters, the AUC was significantly affected by the dosage, but not by the source. The formation of 13-cis-RA, 13-cis-4-oxo-RA, and to a lesser extent all-trans-RA was significantly higher after consumption of liver paste compared with the supplement, especially at higher dosages. Long-term baseline concentrations of retinol were not affected by a single intake of vitamin A. In conclusion, the bioavailability of vitamin A from single doses of liver paste and a vitamin A supplement does not differ, but the plasma concentrations of RA metabolites are higher after intake of liver paste. Thus, pregnant women should indeed limit the intake of vitamin A from liver products. Chemicals/CAS: Tretinoin, 302-79-4; Vitamin A, 11103-57-4

In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear.

Objectives: Coffee, tea, and fluid consumption have been thought to influence bladder cancer incidence. In a large prospective study, these associations were investigated. Methods: In 1986, cohort members (55-69 years) completed a questionnaire on cancer risk factors. Follow-up was established by linkage to cancer registries until 1992. The multivariable case-cohort analysis was based on 569 bladder cancer cases and 3123 subcohort members. Results: The incidence rate ratios (RR) for men consuming < 2 cups of coffee/day was 0.89 (95% CI 0.51-1.5) using the median consumption category (4-< 5 cups/day) as reference. This RR increased to 1.3 (95% CI 0.94-1.9) for men consuming ≥7 cups/day, although no clear dose-response association was found. The RRs decreased from 1.2 (95% CI 0.56-2.7) for women consuming <2 cups of coffee/day to 0.36 (95% CI 0.18-0.72) for women consuming ≥5 cups/day compared to the median consumption category (3-<4 cups/day). Men and women who abstained from drinking tea had a RR of 1.3 (95% CI 0.97-1.8) compared to those consuming 2-<3 cups of tea per day (median consumption c category). The RR for men and women comparing highest to lowest quintile of total fluid consumption was 0.87 (95% CI 0.63-1.2). Conclusion: The data suggest a possible positive association between coffee consumption and bladder cancer risk in men and a probable inverse association in women. Tea consumption was inversely associated with bladder cancer. Total fluid consumption did not appear to be associated with bladder cancer.

Objectives - To investigate differences in perinatal death rate and associated obstetric risk factors between ethnic groups in the Netherlands. Design - Retrospective cohort study based on the 1990-1993 birth cohorts in the National Obstetric Registry. Subjects - 569,743 births of which 85,527 were for women belonging to ethnic minorities. Main outcome measures - Perinatal death occurring between 16th week of pregnancy and 24 hours after birth. Method - Bivariate and multivariate analysis of perinatal death rate per ethnic group. A total of 42,282 women living in the three main cities of the Netherlands were classified on the basis of postal code districts into four socioeconomic (SES) classes for analysis of the relation between SES, perinatal death, and preterm birth. Results - Black mothers had the highest perinatal death rate compared with indigenous Dutch (odds ratio 2.2, 95%CI 1.9, 2.4) followed by a group 'others', consisting of women of mixed or unknown ethnicity (odds ratio 1.8, 95%CI 1.5, 2.0), Hindustani (odds ratio 1.4, 95%CI 1.2, 1.6), and Mediterraneans (odds ratio 1.3, 95%CI 1.2, 1.4). Asians (excluding West Indian Asians) and non-Dutch Europeans did not have higher rates than Dutch women. The increased rates of black and Hindustani women could be explained fully and that of the group 'others' partially by higher rates of preterm birth. Controlling for age and parity lowered the odds ratio of the Mediterraneans slightly. The risk of ethnicity was independent of SES. Conclusion - Ethnic minorities in the Netherlands except immigrants from Asia and other European countries have higher rates of perinatal death than indigenous Dutch women. With a twofold increase, black women had the highest rate, which was related to an equally large increased rate of preterm birth.

An important challenge in Web-based health promotion is to increase the reach of the target audience by taking the target groups' desires into consideration. Data from 505 members of a Dutch Internet panel (representative for Dutch Internet users) were used to asses the target group's interests and needs. 28% participated in Web-based tailored lifestyle programs, 57% expressed an interest in such programs, and 15% expressed no interest. Interest in Web-based programs was predominantly caused by a general interest in lifestyle and online tests. Participation in Web-based tailored lifestyle programs should not take more than 17 minutes per occasion. 84% were interested in follow-up testing after the initial participation. Responders were particularly interested in physical activity and nutrition. Hardly anyone was willing to pay for participation. The results from this study support the use of Web-based tailored lifestyle programs in behavior change efforts.

The aim of this study was to investigate the association of the Bcl I β-chain fibrinogen polymorphism with the risk of acute myocardial infarction (AMI) and its relationship with fibrinogen levels in the Italian population. We studied 102 AMI patients, selected within the framework of the GISSI-2 trial, who had a familial history of arterial thrombosis (at least one first- degree relative suffering from AMI or stroke before 65 years) and 173 control subjects (with neither AMI nor personal or familial history of arterial thrombosis). All subjects were Italian. Patients showed fibrinogen levels higher than control subjects. There was a highly significant difference in allele frequency in cases versus control subjects, the B2 allele frequencies being respectively 0.28 versus 0.17 (P=.002). In multivariate analysis, adjusted for sex, age, smoking habits, and history of hyperlipidemia, hypertension, or diabetes, the (B1B2+B2B2) genotype was associated with a higher risk of AMI (odds ratio 2.4, 95% confidence interval, 1.2 to 4.6). The Bcl I genotype was also associated with fibrinogen levels, independently of gender and smoking habits the (B1B2+B2B2) subjects showing the highest levels in both cases and control subjects. The difference in fibrinogen levels between cases and control subjects was significantly influenced by the genotype (significant interaction, P=.042). The B2 allele of the Bcl I polymorphism in the β-chain of the fibrinogen gene is a new factor associated with the risk of familial AMI through its association with fibrinogen levels. These data provide evidence for a causal role of fibrinogen in familial AMI.

The aim of this study was to determine whether the morphology of the muscular femoral artery in patients with atherosclerosis and hyperhomocysteinemia differs from that of atherosclerotic vessels from patients with normal homocysteine levels. Whole-vessel biopsies of the superficial femoral artery were taken from patients with symptomatic atherosclerotic disease with and without hyperhomocysteinemia and from patients without atherosclerosis from traumatic amputations. The morphology of these specimens was studied qualitatively by light and electron microscopy and quantitatively by light microscopy in combination with a video overlay system. Atherosclerotic lesions in patients with hyperhomocysteinemia were morphologically similar to those in patients with normal homocysteine levels, except for a significantly decreased smooth muscle cell/extracellular matrix ratio of the media in hyperhomocysteinemic patients (P=0.02 versus normohomocysteinemic atherosclerotic group and P=0.001 versus group without a history of cardiovascular disease). Hyperhomocysteinemia is associated with a significant decrease of the smooth muscle cell/extracellular matrix ratio of the media of muscular femoral arteries without significant changes in medial thickness. Further investigations should concentrate on the cause of this newly discovered phenomenon and its impact on vascular compliance. Chemicals/CAS: Homocysteine, 454-28-4

Pressure-volume (p-V) relationships of a segment of the forearm circulation have been measured in nine male healthy subjects. Forearm volume was measured using electrical impedance plethysmography, arterial transmural pressure by subtracting mean arterial pressure measured contralaterally in a finger from the pressure in a cuff placed over the sensing electrodes of the plethysmograph. A special two-phase measurement waveform was designed with which cuff pressure was first increased step wise to a suprasystolic level and held at that level for 120 s, then ramped down to zero pressure in another 300 s. The step phase inflation allowed us to estimate the parameters of the interstitial liquids and total blood compartments. The total blood compartment amounted to 6.2 ml per 100 ml of tissue. The ramp phase deflation allowed us to discriminate between a first phase in which only the arteries refilled and a second phase in which the veins also distended. An arctangent function was fitted to the first phase arterial p-V relationship, describing it in model form. Total arterial volume per 100 ml of tissue amounted to 3.8 ml at physiological pressures, total arterial compliance of the forearm per centimetre length to 19.5 microliter kPa-1 cm-1 (2.6 microliter mmHg-1 cm-1) at physiological pressures, and to 340 microliter kPa-1 cm-1 (45 microliter mmHg-1 cm-1) maximum compliance at the lower, inflection point pressures. These values are in general agreement with the literature. Pulse wave velocity cannot be computed reliably from these data.

In most Westernized societies cardiovascular diseases are the leading cause of death over the age of 45 years and one-quarter of these deaths occur in men below the age of 65 years. The haemostasis system has been identified as an important system in cardiovascular disease (CVD). The European Concerted Action on Prevention from Thrombosis by URokinase Enhancement (ECAPTURE) has focused on the contribution of the urokinase system to CVD. In 2298 patients with angina pectoris the relationship between plasma levels of single-chain urokinase (scu-PA), urokinase antigen (u-PA) and u-PA-inhibitor complex and the risk of cardiovascular events (n = 84) during a 2 year follow-up period was studied. Plasma levels of total u-PA and u-PA-inhibitor complex predicted the risk of cardiovascular events, the adjusted relative risks of the highest quintile versus the lowest were 2.71 [95% confidence interval (CI), 1.34-5.48] and 2.34 (95% CI, 1.08-5.11), respectively. These results suggest that the urokinase system plays a role in cardiovascular disease. © 2001 Lippincott Williams & Wilkins. Chemicals/CAS: Urinary Plasminogen Activator, EC 3.4.21.73

The aim of this study was to characterize soluble fibrin(ogen) species in human, arterial, in-vivo-formed thrombi, using the immunoblotting technique. Specimens were collected via intra-arterial catheters in six patients scheduled for catheter-directed thrombolysis. Unreduced and reduced samples of the supernatants from the arterial thrombi-derived specimens were electrophoresed on polyacrylamide gels and immunoblotted, using specific mono- and polyclonal anti-fibrin(ogen) antibodies. The reduced samples disclosed substantial amounts of high molecular weight material, consistent with α-chain polymers and γγ-dimers, as well as lower molecular weight material, such as α-, β- and γ-chains. No fibrinogen with intact fibrinopeptide A was detectable, and des-AABB fibrin represented a major fibrin derivative in the soluble part of the arterial thrombi. The α-chains were C-terminally degraded, most of them distal to position 259. In conclusion, we have demonstrated the presence of cross-linked fibrin derivatives in soluble, arterial thrombus-related material, without signs of fibrinogen-fibrin hybrids. The fibrin derivatives were C-terminally degraded, thus representing X-oligomeric material, most probably originating from plasmin degradation of insoluble thrombus fibrin. The present study supports the hypothesis of a dynamic equilibrium between clotting and lysis in thrombi. (C) 2000 Lippincott Williams and Wilkins. Chemicals/CAS: Antibodies, Monoclonal; Fibrin, 9001-31-4; Fibrinogen, 9001-32-5; Fibrinopeptide A, 25422-31-5