Wetenschappelijke ontwikkelingen
Het volgende overzicht van enkele wetenschappelijke onderzoeken is samengesteld door mevrouw Osterman.
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Int J Hyg Environ Health. 2004 Feb;207(2):159-63.
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Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity
Kimata H.
Department of Allergy, Ujitakeda Hospital, 24-1, Umonji, Uji, Uji-City, Kyoto Prefecture, 611-0021, Japan. unitikah@m12.alphanet.ne.jp
Plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, but not histamine, were elevated in patients with self-reported multiple chemical sensitivity (sMCS). Exposure to volatile organic compounds (VOC) increased plasma levels of all parameters in these patients, while it had no effect in normal subjects or patients with atopic eczema/dermatitis syndrome (AEDS). Exposure to VOC also enhanced skin wheal responses induced by histamine in patients with sMCS, while it failed to do so in normal or AEDS subjects. These results indicate that exposure to VOC may enhance neurogenic inflammation with concomitant enhancement of histamine-induced responses.
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Environ Health Perspect. 2003 Sep;111(12):1461-4.
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Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity: central role of N-methyl-D-aspartate receptors in the sensitivity mechanism
Pall ML.
School of Molecular Biosciences, 301 Abelson Hall, Washington State University, Pullman, WA 99164, USA. martin_pall@wsu.edu
The elevated nitric oxide/peroxynitrite and the neural sensitization theories of multiple chemical sensitivity (MCS) are extended here to propose a central mechanism for the exquisite sensitivity to organic solvents apparently induced by previous chemical exposure in MCS. This mechanism is centered on the activation of N-methyl-D-aspartate (NMDA) receptors by organic solvents producing elevated nitric oxide and peroxynitrite, leading in turn to increased stimulating of and hypersensitivity of NMDA receptors. In this way, organic solvent exposure may produce progressive sensitivity to organic solvents. Pesticides such as organophosphates and carbamates may act via muscarinic stimulation to produce a similar biochemical and sensitivity response. Accessory mechanisms of sensitivity may involve both increased blood-brain barrier permeability, induced by peroxynitrite, and cytochrome P450 inhibition by nitric oxide. The NMDA hyperactivity/hypersensitivity and excessive nitric oxide/peroxynitrite view of MCS provides answers to many of the most puzzling aspects of MCS while building on previous studies and views of this condition.
Bijna overal aanwezig (o.a. UvA) behalve in Leiden.
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Occup Med (Lond). 2004 Sep;54(6):408-18. Epub 2004 Sep 03.
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Case-control study of multiple chemical sensitivity, comparing haematology, biochemistry, vitamins and serum volatile organic compound measures
Baines CJ, McKeown-Eyssen GE, Riley N, Cole DE, Marshall L, Loescher B, Jazmaji V.
University of Toronto, 12 Queen’s Park Crescent W, Room 401C, Toronto, Ontario, Canada M5S 1A8. cornelia.baines@utoronto.ca
BACKGROUND: Multiple chemical sensitivity (MCS), although poorly understood, is associated with considerable morbidity. AIM: To investigate potential biological mechanisms underlying MCS in a case-control study. METHODS: Two hundred and twenty-three MCS cases and 194 controls (urban females, aged 30-64 years) fulfilled reproducible eligibility criteria with discriminant validity. Routine laboratory results and serum levels of volatile organic compounds (VOCs) were compared. Dose-response relationships, a criterion for causality, were examined linking exposures to likelihood of case status. RESULTS: Routine laboratory investigations revealed clinically unimportant case-control differences in means. Confounder-adjusted odds ratios (OR) showed MCS was negatively associated with lymphocyte count and total plasma homocysteine, positively associated with mean cell haemoglobin concentration, alanine aminotransferase and serum vitamin B6, and not associated with thyroid stimulating hormone, folate or serum vitamin B12. More cases than controls had detectable serum chloroform (P = 0.001) with the OR for detectability 2.78 (95% confidence interval = 1.73-4.48, P < 0.001). Chloroform levels were higher in cases. However, cases had significantly lower means of detectable serum levels of ethylbenzene, m&p-xylene, 3-methylpentane and hexane, and means of all serum levels of 1,3,5- and 1,2,3-trimethylbenzene, 2- and 3-methylpentane, and m&p-xylene. CONCLUSIONS: Our findings are inconsistent with proposals that MCS is associated with vitamin deficiency or thyroid dysfunction, but the association of lower lymphocyte counts with an increased likelihood of MCS is consistent with theories of immune dysfunction in MCS. Whether avoidance of exposures or different metabolic pathways in cases explain the observed lower VOC levels or the higher chloroform levels should be investigated.
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Int J Epidemiol. 2004 Jul 15 [Epub ahead of print]
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Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR
McKeown-Eyssen G, Baines C, Cole DE, Riley N, Tyndale RF, Marshall L, Jazmaji V.
Department of Public Health Sciences, University of Toronto, Toronto; Department of Nutritional Sciences, University of Toronto, Toronto.
BACKGROUND: Impaired metabolism of toxic chemicals is a postulated mechanism underlying multiple chemical sensitivity (MCS). Because genetic variation alters the rate of chemical metabolism, this study was designed to determine if MCS cases differed from controls for genetic polymorphisms in drug-metabolizing enzymes. METHODS: Female Caucasian participants (203 cases and 162 controls) were drawn from a larger case-control study based on a reproducible and validated case definition. Common polymorphisms for CYP2D6, NAT1, NAT2, PON1, and PON2 were genotyped. RESULTS: Comparing cases and controls, significant differences were found in genotype distributions for CYP2D6 (P = 0.02) and NAT2 (P = 0.03). Compared with the referent homozygous inactive (CYP2D6) or slow (NAT2) metabolizers, the odds for being CYP2D6 homozygous active (OR = 3.36, P = 0.01) and NAT2 rapid (OR = 4.14, P = 0.01) were significantly higher in cases than controls. The odds for being heterozygous for PON1-55 (OR = 2.05, P = 0.04) and PON1-192 (OR = 1.57, P = 0.04) were also significantly higher in cases. CONCLUSIONS: A genetic predisposition for MCS may involve altered biotransformation of environmental chemicals. The CYP2D6 enzyme activates and inactivates toxins; the NAT2 enzyme bioactivates arylamines to protein-binding metabolites. A gene-gene interaction between CYP2D6 and NAT2 suggested that rapid metabolism for both enzymes may confer substantially elevated risk (OR = 18.7, P = 0.002). Our finding parallels others’ observation of a link between PON1 heterozygosity and neurological symptoms in Gulf War syndrome. This first demonstration of genetic variation in drug-metabolizing enzymes in association with MCS requires replication. However, it suggests new research directions on genetically variable toxin pathways that might be important in MCS.
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Otolaryngol Clin North Am. 2003 Oct;36(5):917-40.
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Approaches to testing for food and chemical sensitivities
Gordon BR. Aanwezig in bibl. LUMC
Department of Otology and Laryngology, Harvard University, Cambridge, MA, USA.
Testing for food and chemical sensitivities usually becomes necessary as part of the evaluation of otolaryngology patients who have chronic illness. The more complex the patient, and the more recalcitrant the problem is to treatment, the more likely it is that allergies, and especially food or chemical sensitivities, are involved in the pathogenesis of the illness. Failure to consider all major allergen contacts, including foods and chemicals, can lead to inadequate therapy. Similarly, failure to understand total allergic and oxidant load and the effects of chemical toxicity can lead to inappropriate or ineffective treatment. Clinically, food allergies occur in two different types: immediate, anaphylactic, fixed reactions and delayed, chronic, cyclic reactions. Different test methods have been developed for the two types. Fixed food allergies can be safely and efficiently detected by in vitro specific IgE or histamine release tests. Cyclic food allergies are best detected by either oral food challenges or by the IPDFT test. Choosing the best test for a particular patient requires a clear understanding of the two food allergy types and how their clinical presentations differ. Other tests for food allergies are compared and contrasted with these primary tests. Chemical sensitivity also occurs in two different clinical types: allergic, and toxic. True allergy to chemical haptens, either type I, IgE-mediated, or type IV, delayed hypersensitivity, occurs with significant frequency but is often unsuspected. Chemical toxicity can be caused by the aftereffects of an acute exposure or as a result of chronic, low-level exposure, but is even more frequently unsuspected and will not be diagnosed without a high index of suspicion. Both types of chemical sensitivity need to be addressed in any patients who have either a high allergen or chemical exposure load [105]. Either in vitro or in vivo tests can be used for chemical allergy detection; the advantages of each are outlined. Chemical toxicity screening tests are available and useful but do not detect all possible toxicants. Definitive toxic chemical tests usually require specialized laboratory facilities and expert consultation, for which possible sources are specified. The most important point in testing for food or chemical sensitivity is to be aware that food or chemical sensitivity can be contributing to a specific patient’s clinical problems. Only then can appropriate investigations be undertaken to understand and then, perhaps, to intervene successfully in that illness.
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Environ Health Perspect. 2003 Sep;111(12):1490-7.
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A review of a two-phase population study of multiple chemical sensitivities
Caress SM, Steinemann AC.
State University of West Georgia, Pafford Building Room 121, 1601 Maple Street, Carrollton, GA 30118, USA. scaress@westga.edu
In this review we summarize the findings of a two-phase study of the prevalence, symptomatology, and etiology of multiple chemical sensitivities (MCS). We also explore possible triggers, the potential linkage between MCS and other disorders, and the lifestyle alterations produced by MCS. The first phase of the study consisted of a random sampling of 1,582 individuals from the
Atlanta, Georgia, metropolitan area to determine the reported prevalence of a hypersensitivity to common chemicals. In this phase, 12.6% of the sample reported a hypersensitivity. Further questioning of individuals with a hypersensitivity indicated that 13.5% (1.8% of the entire sample) reported losing their jobs because of their hypersensitivity. The second phase was a follow-up questioning of the respondents who initially reported hypersensitivity. In this phase, we found that individuals with hypersensitivity experience a variety of symptoms and triggers. A significant percentage (27.5%) reported that their hypersensitivity was initiated by an exposure to pesticides, whereas an equal percentage (27.5%) attributed it to solvents. Only 1.4% had a history of prior emotional problems, but 37.7% developed these problems after the physical symptoms emerged. This suggests that MCS has a physiologic and not a psychologic etiology.
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Environ Health Perspect. 2003 Sep;111(12):1498-504.
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Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity
Gibson PR, Elms AN, Ruding LA.
School of Psychology, James Madison University, MSC 7401, Harrisonburg, VA 22807, USA. gibsonpr@jmu.edu
Multiple chemical sensitivity (MCS) is a condition in which persons experience negative health effects in multiple organ systems from exposure to low levels of common chemicals. Although symptoms experienced from particular chemicals vary across persons, they are generally stable within persons. The sensitivities often spread over time, first to related chemicals and then to other classes of chemicals. This study examined self-reported perceived treatment efficacy of 101 treatments used by 917 persons with self-reported MCS. Treatments examined included environmental medicine techniques, holistic therapies, individual nutritional supplements, detoxification techniques, body therapies, Eastern-origin techniques, newer therapies, prescription items, and others. The three most highly rated treatments were creating a chemical-free living space, chemical avoidance, and prayer. Both creating a chemical-free living space and chemical avoidance were rated by 95% of respondents as helpful. Results for most therapies were mixed. Participants had consulted a mean of 12 health care providers and spent over one-third of their annual income on health care costs. We discuss this drain on personal resources and describe respondents’ attitudes toward the possibility of healing from MCS.
PMID: 12948890 [PubMed - indexed for MEDLINE]
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Arch Environ Health. 2003 Jul;58(7):442-6.
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Health symptoms caused by molds in a courthouse
Lee TG.
Faculty of Environmental Design, The University of Calgary, Calgary, Alberta, Canada. lee@ucalgary.ca
A majority of occupants of a newly renovated historic courthouse in Calgary, Alberta, Canada, reported multiple (3 or more) health-related symptoms, and several reported more than 10 persistent symptoms. Most required at least 1 day outside of the building to recover from their symptoms. Molds that produce mycotoxins, such as Stachybotrys chartarum and Emericella nidulans, were identified in the building, along with fungal organisms of the genera Aspergillus, Penicillium, Streptomyces, Cladosporium, Chaetomium, Rhizopus/Mucor, Alternaria, Ulocladium, and Basidiomycetes. Renovations to this historic had building failed to provide adequate thermal and vapor barriers, thus allowing moist indoor air to migrate into the building enclosure, causing condensation to develop. Mold grew on the condensation and was dispersed throughout the courthouse, including on furniture and files. The courthouse was closed and a new facility was modified with low-offgassing materials, better ventilation and air filtration, and strict building maintenance to accommodate those occupants of the older building who had developed multiple chemical sensitivities.
PMID: 15143857 [PubMed - indexed for MEDLINE]
