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Veel te vroeg geboren kinderen lopen een groter risico op neurosensorische handicaps en ontwikkelingsproblemen dan op tijd geboren kinderen. Vroeggeboorte, intra-uteriene groeiachterstand, en de combinatie hiervan, zijn ook mogelijke risicofactoren voor lichamelijke ziekten op de volwassen leeftijd. Omdat hier tot nu toe weinig onderzoek naar is verricht, zijn in de pops-cohort (Project On Preterm and Small for gestational age infants) de eerste tekenen hiervan bekeken. Vroeggeboorte lijkt een risicofactor te zijn voor het ontwikkelen van insulineresistentie. Bij een latere neiging tot vetzucht is dat risico extra groot. Nog groter wordt dat als hieraan een intra-uteriene groeiachterstand voorafging. De systolische bloeddruk is gemiddeld hoger bij ex-prematuren maar is niet gerelateerd aan de mate van intra-uteriene groeiretardatie. De nierfunctie (klaring en eiwituitscheiding) is op de jongvolwassen leeftijd minder gunstig voor die individuen die naast de vroeggeboorte ook zijn blootgesteld aan intra-uteriene groeiretardatie. Te vroeg geboren kinderen hebben als jongvolwassenen meer luchtwegklachten en een minder goede longfunctie. De conclusie is dat neonatale follow-up niet alleen noodzakelijk is voor veel te vroeg geboren kinderen maar ook voor kinderen met een ernstige intra-uteriene groeiachterstand. De kinderarts moet in het contact met zowel ouders en kind als met de huisarts benoemen dat een voorgeschiedenis van vroeggeboorte of groeiachterstand ook een mogelijke risicofactor is voor chronische ziekten op de volwassen leeftijd. Bij te vroeg geboren kinderen met intra-uteriene groeiachterstand is actieve preventie van obesitas vanaf jonge leeftijd geïndiceerd. Vanaf jongvolwassen leeftijd zal de huisarts extra alert moeten zijn op het ontstaan van met name hypertensie en microalbuminurie door dit bijvoorbeeld tweejaarlijks te controleren. Voor het kind zelf kan de voorgeschiedenis een extra reden zijn om overgewicht te vermijden, om aan sport te doen en om niet te beginnen met roken.

Objectives: To obtain an overview of inhalable β(1→3)glucans levels in Dutch industrial bakeries and explore possible associations with reported respiratory health effects in bakery workers. Methods: β(1→3)glucan levels were analysed in 186 personal inhalable dust measurements obtained from a random population of bakery workers. Association between respiratory health effects and exposure to β(1→;3)glucan was explored in a population of industrial bakery workers participating in a Health Surveillance System for flour processing sectors. Based on their job, bakery workers were assigned to low or high exposure categories given the average job exposure estimates obtained from the measurement study. Results: Bread bakers and dough makers had the highest exposures to β(1→3)glucans (GM 1.48 μg/m3 and 1.37 μg/m3 respectively). Strong correlations were found between airborne levels of inhalable dust and β(1→3)glucans, and between β(1→3)glucans and wheat allergens (Pearson correlation coefficients were 0.74 and 0.68 respectively). No significant associations could be identified between β(1→3)glucan exposure and work-related respiratory symptoms. Conclusion: This study has shown that bakery workers are exposed to inhalable β(1→3)glucan levels comparable with exposure levels found in other occupational settings. More refined exposure assessment is necessary to fully understand the role of β(1→3)glucan exposure on respiratory health in bakery workers.

Objective: Many obstetric interventions are performed to improve long-term neonatal outcome. However, long-term neonatal outcome is usually not a primary outcome because it is time-consuming and expensive. The aim of this project was to identify different perinatal risk indicators and to develop prediction models for neurologic morbidity at 2 and 5 years of age. Study design: Data from a Dutch cohort study of preterm and small-for-gestational-age infants was used. Neonates who were born in The Netherlands in 1983 with a gestational age of <34 weeks and without congenital abnormalities were included (n = 753). Infants were divided in 3 groups: no handicap, minor handicap, and major handicap. Results: Common risk indicators for major handicaps at 2 and 5 years of age were male sex (odds ratio, 2.7 and 3.0, respectively), seizures after <2 days of life (odds ratio, 5.8 and 5.8, respectively), and intracranial hemorrhage (odds ratio, 3.8 and 2.6, respectively). Conclusion: In this cohort, male sex, intracranial hemorrhage, and seizures seem to be important risk indicators for long-term neurologic morbidity. © 2011 Mosby, Inc. All rights reserved.

Objectives: The critical health effects of formaldehyde exposure include sensory irritation and the potential to induce tumours in the upper respiratory tract. In literature, a concentration as low as 0.24 ppm has been reported to be irritating to the respiratory tract in humans. Nasal tumour-inducing levels in experimental animals seem to be 1-2 orders of magnitude larger. In this paper, the subjectively measured sensory irritation threshold levels in humans are discussed in line with findings obtained in animal experiments. In addition, a Benchmark dose (BMD) analysis of sensory irritation was used to estimate response incidences at different formaldehyde concentrations. Methods: Data on respiratory irritation and carcinogenicity of formaldehyde were retrieved from public literature and discussed. BMD analysis was carried out on human volunteer studies using the US-EPA BMD software. Results: Subjective measures of irritation were the major data found in humans to examine sensory (eye and nasal) irritation; only one study reported objectively measured eye irritation. On a normalized scale, mild/slight eye irritation was observed at levels ≥1 ppm, and mild/slight respiratory tract irritation at levels ≥2 ppm. With the BMD software, it was estimated that at a level of 1 ppm, only 9.5% of healthy volunteers experience 'moderate' (i.e., annoying) eye irritation (95% upper confidence limit). An important factor modulating the reported levels of irritation and health symptoms most probably includes the perception of odour intensity. In several studies, the 0-ppm control condition was missing. From the results of the long-term inhalation toxicity studies in experimental animals, a level of 1 ppm formaldehyde has been considered a NOAEL for nasal injury. Conclusions: Sensory irritation is first observed at levels of 1 ppm and higher. From both human and animal studies, it was concluded that at airborne levels for which the prevalence of sensory irritation is minimal both in incidence and degree (i.e., <1 ppm), risks of respiratory tract cancer are considered to be negligibly low. © 2005 Elsevier Inc. All rights reserved.

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire Results: The prevalence of doctor-diagnosed asthma was significantly higher in the ex-preterms than in the general population, whereas eczema and hay fever were significant lower. Women reported more symptoms than men. Preterm women vs controls: asthma 13% vs 5% (p<0.001); hay fever 8% vs 20% (p<0.001); eczema 10% vs 42% (p<0.001). Preterm men vs controls: asthma 9% vs 4% (p=0.007); hay fever 8% vs 17% (p=0.005); eczema 9% vs 31% (p<0.001) Preterm women reported more wheeze and shortness of breath during exercise (sob) than controls: wheeze 30% vs 22% (p=0.009); sob 27% vs 16% (p<0.001); 19-year-old women with BPD reported a higher prevalence of doctor diagnosed asthma compared to controls (24% vs 5% p <0.001) and shortness of breath during exercise (43% vs 16% p=0.008). The prevalence of reported symptoms by men with BPD were comparable with the controls. Conclusions: Our large follow-up study shows a higher prevalence of asthma, wheeze and shortness of breath in the prematurely born young adults. 19-year-old women reported more respiratory symptoms than men. Compared to the general population atopic diseases as hay fever and eczema were reported less often. © 2005 Vrijlandt et al., licensee BioMed Central Ltd.

Objectives: To obtain a Spanish version of the TNO-AZL Preschool Children Quality of Life Questionnaire (TAPQOL) that would be both semantically and culturally equivalent to the original. Material and methods: The TAPQOL questionnaire was designed to measure health-related quality of life in children aged 3 months to 5 years and contains 43 questions distributed in 12 subdimensions. The Spanish version was obtained by using the forward/back-translation method with expert, bilingual translators. Cognitive debriefing interviews were carried out with the parents of healthy children and with those of children with respiratory disease. Results: During the adaptation phase, four items were modified after input from the authors of the original version to retain the meaning of the original. At the end of the adaptation process, 37 of the 43 items were classified as A, i.e. without difficulty in the adaptation. Four mothers and two fathers participated in the cognitive debriefing interviews. Four had secondary level education, and two had university level education. Their children were aged between 16 and 60 months. The average time taken to complete the questionnaire was 13.5 minutes. No comprehension problems regarding the questionnaire's content were found, and no items were modified after this phase of the study. The mothers of children with respiratory disease considered the questions related to their children's symptoms to be appropriate. Conclusions: The Spanish version of the TAPQOL has proven to be acceptable and culturally equivalent to the original version. Future studies should investigate the psychometric properties of this questionnaire and compare them with those of the original version.

Objectives: Chemosensory effects of stimulation by a chemical can either be irritating (trigeminal stimulation) or odorous (olfactory stimulation) or both. For odorous irritants, a clear-cut distinction between odour and irritation is difficult to make. The differences in the lowest concentration found to be irritating to the respiratory tract in humans when compared to experimental animals has brought much debate in the process of setting occupational exposure limits (OELs) for such chemicals. In this paper it will be discussed as to how far subjectively measured sensory irritation threshold levels can be used to establish OELs. Methods: Data on respiratory irritation of four odorous irritants were retrieved from public literature and discussed, viz. acetone, formaldehyde, furfural and sulphur dioxide. Results: Objective measures of irritation yielded results that differed from subjective evaluations. Important factors modulating the reported levels of irritation and health symptoms include the perception of odour intensity, exposure history and the individual's bias to report irritation on the basis of his/her prejudice or knowledge of the compound. Conclusions: Subjective measures alone are less appropriate for establishing sensory irritation thresholds of odorous irritants and are, therefore, less suitable to establish OELs without supporting evidence. Objectively measured irritation in humans, the Alarie assay (an experimental animal test assessing the concentration that results in a 50% reduction of the breathing frequency) and repeated exposure studies in animals may be of help to study objective irritation. If subjective measurements are used to study sensory irritation, the study design should at least include: Measurement of both incidence and severity determined at several concentrations, an appropriate (0 ppm) control condition, preferably a non-irritant odorant control exposure, validated questionnaires and correct concentration measurements. © Springer-Verlag 2005.

Objectives: The aim of this study was to assess the magnitude of the silicosis and cancer risk among construction workers. Methods: In 1998, 1335 of 4173 invited construction workers with expected high cumulative exposure to quartz were studied for early signs of silicosis. In 2002 the study was repeated for 96 persons. Exposure measurements were performed among 34 construction workers. Silicosis risk was assessed by converting study results to the whole group of construction workers and by risk analysis based on exposure data combined with documented exposure response relations. Excess risk for cancer was also calculated from available exposure measures. Results: The initial study among construction workers revealed a prevalence of 0.8% of workers with rounded opacities on chest X-rays. The follow-up showed a much higher percentage (12%) of persons with rounded opacities on X-rays. The results were confirmed by high-resolution computed tomography. It was estimated that roughly 9% of the population initially studied (N=1335) would have been observed with rounded opacities at follow-up. On the basis of the exposure data, a lifetime risk of silicosis above 5% is expected for workers exposed to levels above the occupational exposure limits. An excess lifetime risk for lung cancer is expected when workers are exposed to quartz levels above the occupational exposure limit. Due to the scarcity of exposure data, an estimation of the size of the group at risk is not yet possible. Conclusions: All available data indicate that construction workers exposed to quartz levels above occupational exposure limits are clearly at elevated risk of silicosis and other respiratory diseases. This work is licensed under a Creative Commons Attribution 4.0 International License.

The objectives of this study were to examine the respiratory irritancy of boron trifluoride (BF3) and fluorosulfonic acid (FSA) following acute inhalation exposure. Testing was conducted using groups of 10 male and 10 female rats (BF3) or groups of 6 male rats (FSA). Rats were exposed for a single 4-h period (BF3) or a single 1-h period (FSA) and necropsied 1 or 14 days after exposure (BF3) or 14 days after exposure (FSA). Measurements consisted of clinical signs, body weight, kidney and lung weight, histopathology (BF3), and breathing parameters (FSA) and were used to evaluate the possible irritating effects of these compounds. The results indicated treatment-related findings in the larynx and trachea in the rats exposed to 74.4 mg/m3 BF3, consisting of ventral cartilage necrosis, hemorrhage, and an increase in ventral epithelial hyperplasia and ventral inflammatory cell inflammation 24 h postexposure. In the animals sacrificed 14 days postexposure, the only notable observation was ventral cartilage necrosis, present in 2 animals. The next lower level tested, 24.6 mg/m3 BF, was considered a no-observed-adverse-effects level (NOAEL). A concentration of 4125 mg/m3 FSA resulted in a clearly decreased breathing rate during and shortly after exposure with 67% (4/6) mortality on days 5-9 after exposure. A concentration of 845 mg/m3 FSA resulted in only minor signs of irritation, consisting of slight changes in breathing pattern shorlty after exposure. The results of the present 4-h inhalation study with BF3 indicated that respiratory irritation was present at a level of 74.4 mg/m3 whereas 24.6 mg/m3 was a NOAEL. A single 1-h exposure to 845 mg/m3 FSA resulted in only minor signs of respiratory irritation, indicating that on a mass basis FSA is no more toxic or irritating than hydrogen fluoride (HF) or sulfuric acid. Copyright © Informa Healthcare USA, Inc.

Alpha-cyclodextrin glucosyltransferase (α-CGTase, EC 2.4.1.19) is an amylolytic enzyme used for the production of α-cyclodextrin (α-CD), a novel, soluble dietary fiber, from food-grade starch. The safety of an α-CGTase preparation obtained by batch fermentation from a recombinant strain of Escherichia coli K12 harboring the α-CGTase gene from Klebsiella oxytoca strain M5a1 was examined. In a 13-week subchronic toxicity study in rats, the administration by gavage of the α-CGTase preparation at levels of up to 20ml/kg bw/day, corresponding to a total organic solids dosage of 260mg/kg bw/day, did not cause any systemic toxic effect. Some signs of irritation were observed in the respiratory tract which occurred, however, in one sex only and/or were not dose-related. Accordingly, these changes were considered to be an unspecific consequence of the reflux and aspiration of the dosing solution. There was no evidence of a genotoxic activity in Ames tests and a chromosome aberration test in cultured human lymphocytes. It is concluded that the examined α-CGTase preparation is safe when used for the production of α-CD. © 2004 Elsevier Inc. All rights reserved. Chemicals / CAS: amylase, 9000-90-2, 9000-92-4, 9001-19-8; cyclomaltodextrin glucanotransferase, EC 2.4.1.19; Food Additives; Glucosyltransferases, EC 2.4.1.-

Background: Several studies have found an effect on mortality of between-city contrasts in long-term exposure to air pollution. The effect of within-city contrasts is still poorly understood. Objectives: We studied the association between long-term exposure to traffic-related air pollution and mortality in a Dutch cohort. Methods: We used data from an ongoing cohort study on diet and cancer with 120,852 subjects who were followed from 1987 to 1996. Exposure to black smoke (BS), nitrogen dioxide, sulfur dioxide, and particulate matter ≤ 2.5 μm (PM2.5), as well as various exposure variables related to traffic, were estimated at the home address. We conducted Cox analyses in the full cohort adjusting for age, sex, smoking, and area-level socioeconomic status. Results: Traffic intensity on the nearest road was independently associated with mortality. Relative risks (95% confidence intervals) for a 10-μg/m3 increase in BS concentrations (difference between 5th and 95th percentile) were 1.05 (1.00-1.11) for natural cause, 1.04 (0.95-1.13) for cardiovascular, 1.22 (0.99-1.50) for respiratory, 1.03 (0.88-1.20) for lung cancer, and 1.04 (0.97-1.12) for mortality other than cardiovascular, respiratory, or lung cancer. Results were similar for NO2 and PM2.5, but no associations were found for SO2. Conclusions: Traffic-related air pollution and several traffic exposure variables were associated with mortality in the full cohort. Relative risks were generally small. Associations between natural-cause and respiratory mortality were statistically significant for NO2 and BS. These results add to the evidence that long-term exposure to ambient air pollution is associated with increased mortality.

Background: False-positive screening results in newborn screening for cystic fibrosis may lead to parental stress, family relationship problems and a changed perception of the child's health. Aim of the study: To evaluate whether parental anxiety induced by a false positive screening result disappears after six months and to assess whether a special program to inform parents prior and during the screening procedure prevents or diminishes parental anxiety. Methods: Prospective controlled study assessing the long term effects of false-positive test results of newborn screening for cystic fibrosis (NBSCF) on parental anxiety and stress by means of questionnaires sent to parents of 106 infants with a false positive newborn screening test and 318 randomly selected infants with a true negative screening test. Additionally we interviewed 25 parents of the false-positive group. Results: Parents showed negative feelings after being informed about the positive screening test result. After confirmation that their child was healthy and not suffering from CF, most parents felt reassured. After six months no difference in anxiety levels between both groups of parents was found. Well-informed parents in the false positive group experienced less stress. Conclusions: A positive screening test result induces parental anxiety but false positive test results in NBSCF do not seem to cause long-term anxiety. Well-informed parents show lower stress and anxiety levels.

Rationale: Associations between oligomeric isocyanate exposure, sensitization, and respiratory disease have received little attention, despite the extensive use of isocyanate oligomers. Objectives: To investigate exposure-response relationships of respiratory symptoms and sensitization in a large population occupationally exposed to isocyanate oligomers during spray painting. Methods: The prevalence of respiratory symptoms and sensitization was assessed in 581 workers in the spray-painting industry. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and time activity information. Specific IgE and IgG to hexamethylene diisocyanate (HDI) were assessed in serum by ImmunoCAP assay and enzyme immunoassays using vapor and liquid phase HDI-human serum albumin (HDI-HSA) and HSA conjugates prepared with oligomeric HDI. Measurements and Main Results: Respiratory symptoms were more prevalent in exposed workers than among comparison office workers. Log-linear exposure-response associations were found for asthmalike symptoms, chronic obstructive pulmonary disease-like symptoms, and work-related chest tightness (prevalence ratios for an interquartile range increase in exposure of 1.2, 1.3 and 2.0, respectively; P ≤ 0.05). The prevalence of specific IgE sensitization was low (up to 4.2% in spray painters). Nevertheless, IgE to N100 (oligomeric HDI)-HSA was associated with exposure and work-related chest tightness. The prevalence of specific IgG was higher (2-50.4%) and strongly associated with exposure. Conclusions: The results provide evidence of exposure-response relationships for both work-related and non-work-related respiratory symptoms and specific sensitization in a population exposed to oligomers of HDI. Specific IgE was found in only a minority of symptomatic individuals. Specific IgG seems to be merely an indicator of exposure.

Objectives: To describe associations among swimming, respiratory health, allergen sensitisation and Clara cell protein 16 (CC16) levels in Dutch schoolchildren. Trichloramine levels in swimming pool air were determined to assess potential exposure levels. Methods: Respiratory health and pool attendance information was collected from 2359 children, aged 6-13 years. Serum from 419 children was tested for allergen sensitisation and CC16 levels. Trichloramine levels were assessed in nine swimming facilities. Results: Trichloramine levels ranged from 0.03 to 0.78 mg/m 3 (average 0.21 mg/m 3). Reported swimming pool attendance and trichloramine exposure were both not associated with asthma, wheezing, rhinitis or CC16 levels. Birch and house dust mite sensitisation were associated with recent indoor swimming (OR>1.86), but not after considering recent swimming frequency multiplied by trichloramine levels. Sensitisation to house dust mites was associated with frequent baby swimming (ORs=1.75; 95% CI 1.09 to 2.79). Furthermore, sensitisation was associated with lower serum CC16 levels. CC16 levels were associated with average trichloramine concentrations in pools; however, not after considering swimming frequency multiplied by trichloramine levels. Conclusions: Measured trichloramine levels were comparable with other studies but lower than in an earlier Dutch study. Swimming pool attendance was not associated with respiratory symptoms. The association between sensitisation and swimming during the first 2 years of life suggests that early-life exposures might be important, although this needs further study. The interpretation of transient and chronic changes of CC16 and other inflammatory markers in relation to the pool environment and health impacts warrants further investigation. Detailed comparisons with other studies are limited as few studies have measured trichloramine levels.

Introduction: Recent studies have shown that even low exposure levels to flour dust and related allergens can cause severe respiratory symptoms. In The Netherlands the Dutch government and responsible branch organizations [from bakeries (traditional & industrial), flour mills and bakery ingredient producers] signed a covenant to reduce exposure to flour dust and decrease the prevalence of work-related occupational airway disease. This paper describes a sector wide survey to measure exposure to flour dust, wheat allergens and fungal α-amylase. The results are being used to underpin various elements of the covenant. Methods: A dataset containing 910 personal measurements was compiled from four field studies containing information on exposure and potential determinants. The dataset represents a baseline estimate of exposure for four major flour processing sectors in The Netherlands. Exposure models for all sectors and agents were generated, based on job, tasks and company size, taking into account worker and company as random effect components. Use of control measures and, where possible, their effect were evaluated. Results: Flour dust and enzyme exposures vary strongly between sectors. The job performed and specific tasks were identified as important determinants of exposure. The number of identified control measures during walk-through surveys, and their effectiveness in reduction of dust exposure was generally limited. The exposure models explained significant exposure variability between companies and workers but performed poorly in explaining day to day differences in exposure. Discussion: The dataset serves as a baseline estimate and will be compared with a post intervention survey in the near future. The information obtained on control measures can be used to optimize the intervention scenarios that will be implemented in the different sectors by external occupational hygienists. The predictive exposure models will provide a relevant measure of average personal exposure that will be used in the sector wide health surveillance system. © The Author 2007. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. Chemicals / CAS: amylase, 9000-90-2, 9000-92-4, 9001-19-8; Allergens; Dust; alpha-Amylase, 3.2.1.1

HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer. The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 h, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent mariner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females; in the HFC 227 study, these were statistically significantly (P < 0.05) higher in males for each HFC 227 and CFC 12 exposure level. In the HFC 134a study, the gender difference in C(max) was only statistically significant (P < 0.05) for CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t( 1/2 )α (α elimination half-life) was short for both CFC 12 and HFC 134a (<11 min). The t( 1/2 )β (β elimination half-life) across all exposure concentrations was a mean of 36 and 42 min for CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean of 42 and 44 min for CFC 12 and HFC 134a, respectively. In the HFC 227 study, t( 1/2 )α for both CFC 12 and HFC 227, at each exposure level, was short (<9 min) and tended to be lower in males than females. For CFC 12 mean t( 1/2 )β ranged from 23 to 43 min and for HFC 227 the mean range was 19-92 min. The values tended to be lower for females than males for HFC 227. For bath CFC 12 and HFC 227, MRT was statistically significantly lower (P < 0.05) in males than females and independent of exposure concentration. For CFC 12, MRT was a mean of 37 and 45 min for males and females, respectively, and for HFC 227 MRT was a mean of 36 and 42 min, respectively. Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC 134a, 8000 ppm HFC 227, and 4000 ppm CFC 12 did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function. (C) 2000 Academic Press. Chemicals/CAS: Aerosol Propellants; Chlorofluorocarbons, Methane; dichlorodifluoromethane, 75-71-8; HFA 134a, 431-89-0; Hydrocarbons, Fluorinated; norflurane, 811-97-2

In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic compounds have been used in human clinical trials with disappointing outcomes. Little is known concerning potential adverse effects on vessel wall integrity and (re)healing, atherosclerotic lesion formation, progression, and plaque stability of these DES. Although efficacy and safety need to be determined clinically, preclinical testing of candidate drugs in well-defined animal models is extremely helpful to gain insight into the basic biological responses to candidate compounds. Here, we discuss and report an animal model which enables rapid screening of candidate drugs for DES on an atherosclerotic background. The results from drug testing using this novel model could help to quickly and cost-effectively establish the dose range of candidate drugs with reasonable potential for DES. © 2006 Elsevier Inc. All rights reserved. Chemicals / CAS: dactinomycin, 1402-38-6, 1402-58-0, 50-76-0; dexamethasone, 50-02-2; everolimus, 159351-69-6; paclitaxel, 33069-62-4; rapamycin, 53123-88-9; tacrolimus, 104987-11-3; thalidomide, 50-35-1; Paclitaxel, 33069-62-4; Sirolimus, 53123-88-9