Wednesday, October 31, 2007

Multiple Chemical Sensitivity Syndrome in Sjögren's Syndrome Patients: Casual Association or Related Diseases?

Arch Environ Occup Health. 2006 Nov-Dec;61(6):285-7.Click here to read

Multiple Chemical Sensitivity Syndrome in Sjögren's Syndrome Patients: Casual Association or Related Diseases?

Department of Rheumatology at San Pietro- Fatebenefratelli Hospital and the Centro Ricerche, Association Fatebenefratelli for Research, Rome, Italy.

Multiple chemical sensitivity (MCS) is defined by multiple symptoms, affecting multiple organs, that wax and wane in response to varying chemical exposures at or below previously tolerated levels. Sjögren's syndrome (SS) is a common autoimmune disease affecting 3% of women aged over 55 years. Except for keratoconjunctivitis sicca (which is associated with SS not MCS), systemic features are common between the 2 diseases, leading to considerable morbidity and, occasionally, mortality. The authors report 3 cases of association between SS and MCS. Three women who were diagnosed with SS showed MCS symptoms and also were diagnosed with MCS. Further studies are needed to understand physiopathogenic mechanisms that eventually may be revealed as common to the 2 syndromes.

PMID: 17967752 [PubMed - in process]

Air pollutant effects on fetal and early postnatal development.

Birth Defects Res C Embryo Today. 2007 Oct 26;81(3):144-154 [Epub ahead of print]Click here to read Links

Air pollutant effects on fetal and early postnatal development.

Center for Health and the Environment, University of California, Davis, California.

Numerical research on the health effects of air pollution has been published in the last decade. Epidemiological studies have shown that children's exposure to air pollutants during fetal development and early postnatal life is associated with many types of health problems including abnormal development (low birth weight [LBW], very low birth weight [VLBW], preterm birth [PTB], intrauterine growth restriction [IUGR], congenital defects, and intrauterine and infant mortality), decreased lung growth, increased rates of respiratory tract infections, childhood asthma, behavioral problems, and neurocognitive decrements. This review focuses on the health effects of major outdoor air pollutants including particulates, carbon monoxide (CO), sulfur and nitrogen oxides (SO(2), NOx), ozone, and one common indoor air pollutant, environmental tobacco smoke (ETS). Animal data is presented that demonstrate perinatal windows of susceptibility to sidestream smoke, a surrogate for ETS, resulting in altered airway sensitivity and cell type frequency. A study of neonatal monkeys exposed to sidestream smoke during the perinatal period and/or early postnatal period that resulted in an altered balance of Th1-/Th2-cytokine secretion, skewing the immune response toward the allergy-associated Th2 cytokine phenotype, is also discussed. Birth Defects Research (Part C) 81:144-154, 2007. (c) 2007 Wiley-Liss, Inc.

PMID: 17963272 [PubMed - as supplied by publisher]

Position Statement on Multiple Chemical Sensitivity

Position Statement: Multiple Chemical Sensitivity


If you agree with this position statement, you may sign it at:


Multiple chemical sensitivity (MCS) is an environmental illness (EI) in which negative neurological, pulmonary, cardiac, and rheumatic health effects, among others, are experienced from exposure to common environmental chemicals including fragrances, cleaners, pesticides, and other petrochemicals at concentrations that are below regulatory toxicity thresholds and that are normally deemed as safe.1-2   In 1989, consensus criteria were established for the diagnoses and definition of MCS and later revised in 1999.3  The case criteria, currently under revision, define MCS for diagnostic purposes as meeting six criteria: 3


1. The condition is chronic.

2. Symptoms recur reproducibly with repeated chemical exposure.

3. Symptoms recur in response to lower levels of chemicals than previously tolerated.

4. Symptoms appear in response to multiple chemically unrelated substances.

5. Symptoms improve or resolve when chemical incitants are removed.

6. Multiple organ systems are affected.


This paper will support the position that MCS is a disorder of organic biological origin induced by toxic environmental insults, and requires immediate recognition in the workplace, medical community, school system, and public places across America; and that it is crucial that environmental toxicants are identified and reduced or effectively regulated and enforced through legislation to prevent additional injury to citizens.


Current Evidence of MCS


Nuclear medicine utilizes SPECT (Single Photon Emission Computerized Tomography) technology to perform brain scans which records brain functioning by measuring perfusion (blood flow).4  MCS patients commonly have a lower baseline flow of blood to the brain, and develop further decreases in brain perfusion upon exposure to perfumes and petrochemicals.5-7  Individuals with chronic symptoms show long-term reduced blood flow to the brain and reduced ability of the brain to take up the tracer substance in the early phase of injection, indicating a pattern of neurotoxic metabolic abnormality.7-11  Over 90% of MCS patients exhibit a pattern of neurotoxic metabolic abnormalities in the brain that is consistent with toxic encephalopathy, but that  is not consistent with the changes associated with psychiatric disease.10-11  SPECT brain scans on MCS patients with chronic symptoms following toxic exposure to various petrochemical, perfume, and related compounds have thus provided evidence to support an organic, biological basis to MCS when compared with healthy control subjects.6-11


Numerous studies have documented toxic encephalopathy and other adverse reactions resulting from low level chronic exposure to various chemicals.12-15  Researchers have identified numerous physiological abnormalities in MCS subjects, including cardiac abnormalities16-18, reactive upper airway disease155, vasculitis19, thrombophlebitis20, impaired Phase 1 and Phase II detoxification clearance16, glutathione depletion16,21, tinnitus22, thyroid and adrenal abnormalities23, gastrointestinal disturbances155, T-cell activation/impaired NK cell function/auto-immune disorders16,25-26, vitamin and mineral deficiencies16,27, nuerocognitive decline16,28-29, rhinitis30, sinusitis30, respiratory inflammation17, abnormal methacholine challenge17, somatosensory abnormality31, peripheral neuropathy16, sleep disturbance32, impaired balance16, and elevated levels of xenobiotics25 among others. 


Mast cell activation and disorders of porphyrin metabolism have also been linked to MCS.16,33  Those with mastocytosis can be exquisitely sensitive to even small amounts of chemicals.33  A group of MCS patients tested for mast cell disease showed some patients actually had mastocytosis and others were found to have a mast cell disorder.33   Porphyrin enzyme abnormalities have also been shown to manifest in blood enzyme deficiencies and chemical sensitivity in 86% of subjects.34


Research suggests substantial individual differences in chemical sensitivity, often spanning orders of magnitude.35  Genetic differences relating to detoxification processes were present more often in those with MCS than those without.67  Five genetic polymorphisms have a statistically significant role in determining MCS prevalence.67  People with a ''high'' expression of two specific genes (CYP2D6 and NAT2) were shown to be 18 times more likely to have MCS.67   Each of these genes encodes proteins that metabolize chemicals previously implicated in MCS, notably some organophosphorus pesticides (PON1 and PON2 genes) and the organic solvents (CYP2D, NAT1 and NAT2 genes). 67   Chemicals shown to initiate MCS must be in a specific chemical form to be active; therefore, individuals who metabolize them at different rates vary in their susceptibility to MCS.67   Genetic predisposition for MCS may involve altered biotransformation of environmental chemicals.66   Haley found similar, confirmatory results with the PON1 gene in studies of the Gulf War syndrome veterans65, findings that have been confirmed by Furlong, Hulla, and Thier.156-158   


Another study analyzed genetic variants of four genes: NAT2, GSTM1, GSTT1, and GSTP1.  The GST- genes code for enzymes in the glutathione system, the body's frontline defense against xenobiotics.37  Individuals who are NAT2 slow acetylators and those with homozygously deleted GSTM1 and GSTT1 genes are significantly more likely to develop chemical sensitivity.37  Glutathione S-transferases act to inactivate chemicals; people without these GSTM1 and GSTT1 genes are less able to metabolize environmental chemicals.37   Glutathione S-transferases play a crucial role in the process of detoxification of chemicals.37  The deletion of another gene, the GSTP1 gene, leaves individuals more susceptible to developing MCS, as lack of these genes means a loss of protection from oxidative stress.37 


MCS may also be caused by low molecular weight chemicals that bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators.38   Brain inflammation is correlated with symptoms of MCS.39   An accumulating body of evidence implicates elevated nitric oxide (NO) and peroxynitrite (ONOO-) as the etiology of MCS and other multi-system illnesses, including fibromyalgia (FM), chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD), and Gulf War syndrome.39  Peroxynitrite (ONOO-) is oxidized from nitric oxide.39-40  Excess peroxynitrite, implicated in MCS and related illnesses, depletes energy stores, which in turn causes extreme fatigue.39-40  Peroxynitrite also increases the permeability of the blood brain barrier; excess levels allow chemicals greater chemical access to the brain.40   The key effect of nitric oxide (NO) in the body is inhibition of cytochrome P-450 activity and slowing degradation of hydrophobic organic chemicals.39-40  Excess nitric oxide levels, as found in MCS patients, slows down the body's natural detoxification processes leaving chemical toxicants in the body for a longer period of time.39-40  A reduced blood-brain barrier and increased time to naturally detoxify the body may render MCS patients subject to permanent and long-term brain and nervous system damage and toxic encephalopathy.  At least thirteen stressors are implicated as initiators that begin the NO/ONOO cycle of biochemistry in these multi-system illnesses through chronic low-level exposure or a sudden acute exposure to an inciting agent, including carbon monoxide exposure, organophosphate poisoning , and ionizing radiation exposures.39,41


Prior Paradigms


There have been various claims that MCS is caused by some ill-defined and unsupported psychogenic mechanisms.42-44,50  One such theory suggests that MCS may be a Pavlovian learned fear response.44  There is no supporting evidence for the claim of a Pavlovian learned response, as Pavlovian conditioning requires the formation of an association between a conditioned stimulus (CS) and an unconditioned stimulus (US) through repetition in order for learning to occur.45   The subject would have to know, understand, and connect the dangers of chemical ingredients of the same nature as incitants, despite these ingredients being generally regarded as safe and, in the case of fragrances and many cleaning chemicals, unlabeled on the product under HHS § 720.9 of the Food and Drug Administration.46  It is quite conceivable that MCS patients learn of the chemical content of common products used in the environment after they develop MCS, when they are thus forced to educate themselves in order to practice avoidance to improve and ultimately remain well.  Subjects reliably react to fragrances in provocation tests in which their nose was clamped, showing symptoms were not transmitted via the olfactory nerve, since the subjects could not smell the perfume.47-48,60-61  Much like those unaware of chemical exposure to virtually odorless products, such as carbonless copy paper or sick buildings, patients with MCS also react to chemicals which are odorless, giving no hint of impending exposure and invalidating the theory of MCS being a fear induced olfactory response or learned behavior.24,47-48,60


Psychological proponents have also purported that co-occurring depression and/or anxiety in a portion of subjects causes MCS.50-51  If this were true, then 100%, or at least a statistically significant proportion, of the subjects would have co-occurring mental illnesses, and that illness would likely have been present prior to MCS onset.  Since that is not the case and the rate of co-occurring mental illness in MCS patients is similar to that of other physiologically based chronically ill populaces, then depression and/or anxiety may be ruled out as an etiologic mechanism and instead considered reactionary.52-57    Further evidence against this theory is provided by statistics that show psychotherapy and psychoactive drugs intended to cure MCS have been shown to be more likely to harm patients than help them.58    A study shows 80% of MCS patients report no benefit from psychotherapy to cure MCS and 15% have reported further harm.58   Though 65% find psychotherapy helpful to cope with the dramatic life changes MCS bestows upon them, psychotherapy is obviously not a cure, as MCS is not a psychologically mediated disease.58  Further, psychiatric drugs such as Zoloft, Prozac, Elavil, and other antidepressants were reported to harm an average of 60% of those who tried them and had no effect on an additional 25%.58  Drugs such as Valium and Xanax proved to harm 45% and had no effect on an additional 30%.58   There is not a single empirical study that shows any significant remission rate in the symptoms of a cohort of environmental illness patients from counseling or psychiatric drug therapy. 


Proponents of a psychological etiology claim that MCS defies classification as a disease because it supposedly lacks evidence, and has no consistent characteristics or objective measurable features; however, all these proponents have shown is their own failure to read and cite the numerous studies in the peer-reviewed literature that report the physiological, biochemical, and genetic findings of MCS.17,30,38,58-62,76  Further, they have failed to provide any explanation for the factors distinguishing the chemicals involved in MCS from those that have no role; they have not shown how a psychological mechanism could stand behind an odorless chemical producing symptoms or a benign odiferous chemical failing to produce symptoms.63  They have also ignored the prospects for objective biomarker tests for MCS that have been published by Kimata, Millqvist, Bell and Fox and their respective colleagues, each of which is based on measurable physiological changes in response to low level chemical exposures in MCS patients.17,58-62  They have disregarded SPECT imaging results showing brain changes which are inconsistent with psychiatric disease and indicate a biological origin for MCS in neurotoxicity.7-11  More importantly, they have overlooked the genetic data of Schnakenberg, McKeown-Eyssen and her colleagues, and the earlier work of Haley and his colleagues showing that the chemicals initiating MCS act as toxicants, not as odors generating some strictly olfactory response.37,65.67 Genetic studies, coupled with known biochemical functions of the genes involved, are the recognized approach to determining the biological mechanism of MCS.66-67 These specific studies provide significant confirmation of the toxicogenic roles of chemicals previously implicated in MCS.66-67 


In the past, MCS patients have been labeled as being psychogenic, largely due to the outward symptoms of physiological neurotoxicity.28,58  Patients with MCS may develop hyperactivity in deep structures of the brain during chemical exposure, explaining the emotional liability some experience, on a physiological rather than psychological basis.68   Petrochemicals and organic solvents are known etiologic mechanisms with an organic basis that induce depression, anxiety, panic attacks, and other apparent mental disorders via known organic etiologic mechanisms; but these manifestations resolve when incitants are removed, thus distinguishing them from true psychiatric illnesses.69-71  The evidence is now abundant that MCS is a true organic, biological illness.17,61-63   Patients may be helped with detoxification protocols, biochemical stabilizing therapy, and/or exposure education, and should not be sent for useless, and often harmful, psychiatric treatment and medications to cure MCS.17,61-63  Patients with MCS desire qualified medical care and the opportunity to return to a full life and career.27,73-73  Many report that they had successful, professional careers prior to becoming ill and reported that they would happily resume their old lives if they found relief from their MCS.28,72-73  This relief includes the recognition and acceptance of MCS, access to proper medical treatment, and accommodations in the school system, workplace, and public community.28,72-73  


Prevalence of MCS


General Populace Reporting Symptoms of MCS

Bell, IR, Schwartz, GE, Peterson, JM and Amend, D. Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures.  Arch Environ Health.  1993;48:6-13.


Bell, IR, Schwartz, GE, Peterson, JM, Amend, D and Stini, WA. Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population. Arch Environ Health.  1993;48:315-27.


Meggs WJ, Dunn KA, Bloch RM, Goodman PE, & Davidoff AL. Prevalence and nature of allergy and chemical sensitivity in a general population. Arch Environ Health.  1996 Jul-Aug;51(4):275-82.


Voorhees, RE.  Memo from Deputy State Epidemiologist Voorhees to Joe Thompson, Special Counsel, Office of the Governor. New Mexico Department of Health; 1998.


Bell, IR, Warg-Damiani, L, Baldwin, CM, Walsh, ME and Schwartz, GE. Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings.  Mil Med. 1998;163:725-32.


(Gulf War Veterans)

Kreutzer R, Neutra RR, & Lashuay N. Prevalence of people reporting sensitivities to chemicals in a population-based survey. Am J Epidemiol.  1999 Jul 1;150(1):1-12.

15.9%          6.3% doctor diagnosed

Caress SM, & Steinemann AC. Prevalence of multiple chemical sensitivities: a population-based study in the southeastern United States. Am J Public Health.  2004 May;94(5):746-7.


Caress SM, & Steinemann AC. A national population study of the prevalence of multiple chemical sensitivity. Arch Environ Health.  2004 Jun;59(6):300-5.


Caress SM, & Steinemann AC. National prevalence of asthma and chemical hypersensitivity: an examination of potential overlap.  J Occup Environ Med. 2005 May;47(5):518-22

11.2%           7.4% doctor diagnosed

All studies report most common in women and not specific to any particular socioeconomic status.




A surprising number of people report sensitivity to ordinary everyday chemicals.74-81  The figures range from an average of eleven to seventeen percent, with spikes as high as thirty percent of subjects who report reactions to multiple chemical incitants.74-81  The figures reveal that at least two percent, and as many as six percent, have been so bothered by chemical exposures that they sought medical care and received a doctor-diagnosis of multiple chemical sensitivity (MCS).79,81   Applying the case definition criteria3 to the average reported chemical sensitivity, it appears that 1.5 out of 10 people suffer from MCS.74-81


Health care utilization costs directly related to MCS have been estimated at approximately $1,581 annually per patient.82   The United States Population is estimated to be 302.8 million.83   Prevalence studies predict that approximately 15% of the United States population, now estimated at 302.8 million, suffers from MCS; therefore, direct health care utilization costs amount to a staggering $71.8 billion dollars per year.74-82  Estimated costs for MCS and other disorders linked to neurotoxicity amount to an additional $81.5 to $167 billion annually in lost productivity.84   Cumulative social and economic costs identified in four case studies of illnesses that are candidates for environmental causation totaled between $568 billion and $793 billion dollars per year.85


Evidence of the Toxicity of Everyday Chemicals


Various studies of product safety generating EPA safe limits have failed to consider the impact of combined exposures in day-to-day living, which add to the body burden of chemicals in humans and must be utilized, expelled, or stored.2,86-116  Many of the chemicals that act as MCS incitants, including fragrances, cleaning products, air fresheners, fabric softeners, disposable diapers, and pesticides, have been scientifically shown to elicit symptoms of toxicity in "normals" at levels of common, and often unavoidable, exposure in the environment. 117-128,130.134,136  At the time the Toxic Substances Control Act (TSCA) of 1976 was passed, the chemical industry effectively grandfathered substances already on the market and exempted them from testing.160  Europe has taken a more pro-actively protective stance than the United States through REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances) legislation.159  The aim of REACH is to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances.159  Products used by United States consumers on a daily basis are continually and routinely recalled for toxic effects, as recent recalls of lead tainted toys, popcorn flavoring, and FEMA trailers, to name a few, demonstrate.138-140 


After inhalation, chemicals enter the limbic system, affecting the hypothalamus and pituitary; and through pituitary control, elicit some symptoms though affecting adrenal, thyroid and reproductive function.130-132    Tests have shown verifiable and chronic changes in brain function after petrochemical exposure and determined that exposure to chemicals through inhalation may aggravate the allergic lung inflammation.64,128,129,132, 135  Developing organisms are generally recognized as differentially sensitive to chemical exposure because of toxicokinetic and/or toxicodynamic factors.141   


Fragrances have been shown to cause sensory irritation, pulmonary irritation, decreases in expiratory airflow velocity, and alterations of the functional observational battery in mice, indicative of neurotoxicity after an hour of normal level exposure to common cologne.  The severity of the symptoms increased after mice were repeatedly exposed to the fragranced product.117  Subsequent analysis of the test atmosphere revealed the presence of chemicals with known irritant and neurotoxic properties, providing a toxicological basis to explain human complaints of adverse reactions to fragrances.117


The use of consumer cleaning agents and air freshener may yield high levels of volatile organic compounds (VOC's).133-134   Consumer cleaning products were shown to contain glycol ethers, which are regulated toxic air contaminants, as well as terpenes, which can react with ozone to form a variety of secondary pollutants such as formaldehyde and ultrafine particles.133  Known chemical toxicants are emitted during air-freshener use, including d-limonene, dihydromyrcenol, linalool, linalyl acetate, beta-citronellol, alpha-pinene, beta-pinene, 3-carene, camphene, benzyl propionate, benzyl alcohol, bornyl acetate, isobornyl acetate, and benzaldehyde.118,133-134  Maternal depression has been significantly associated with air freshener use in the home136  and one name brand air freshener, which contains short chain aliphatic hydrocarbons, was shown to induce fatal ventricular fibrillation.119  Air fresheners, at concentrations to which individuals are actually exposed, have been linked to increases in sensory and pulmonary irritation, decreases in airflow velocity, and abnormalities of behavior as measured by the functional observational battery score, providing a toxicological explanation for human complaints of adverse reactions to air fresheners.120


Laundry products, particularly fabric softener emissions, have been shown to induce sensory irritation, pulmonary irritation, mild inflammation of the lungs, and airflow limitation in mice.121   Dry laundry and linen, like that which consumers wear and sleep on, was shown to emit sufficient chemical residue to cause sensory irritation.121   Analysis of the emissions of a dryer sheet revealed concentrations of the respiratory irritants isopropylbenzene, styrene, trimethylbenzene, phenol, and thymol, and induced respiratory affects when left in a room overnight with mice.121   The results of this study provide a toxicological basis for human complaints of adverse reactions to fabric softener emissions.121


Pesticides are known endocrine disruptors and have been shown to delay sexual maturity and interfere with sex hormone synthesis, and have been linked to increased malaise, chronic illness, asthma, mortality, cancer, leukemia, lupus, Parkinson disease, diabetes, and decreased neuropsychologic functioning scores, neurobehavioral performance, cognitive function, psychomotor function, sensory/motor function, and nerve conduction.123-127,137


Disposable diapers have been demonstrated to emit mixtures of chemicals with documented respiratory toxicity, inducing sensory irritation, reduced mid-expiratory airflow velocity, increased respiratory rates, and increased tidal volume.122   


Advanced stages of multiple chemical sensitivity can lead to organ failure.144-145   Many observable and empirical, scientific facts accompany MCS including SPECT scan changes, vitamin deficiencies, mineral deficiencies, excess amino acid deficiency, and disturbed lipid and carbohydrate metabolism.2,7,9,146   While the germ theory of illness was the main threat to health, the zeal to kill germs with chemical toxicants has now created a health paradigm shift in which chemicals have become the main threats to health, as many diseases are now being linked to chemical and toxic origin.


Worldwide Recognition


The Centers for Disease Control (CDC) recently recognized chemical sensitivity as a symptom of Chronic Fatigue Syndrome (CFS).147    Studies have shown that removal of incitants and proper environmental control is the most efficacious treatment known to date.58,148-151  Ninety-five percent of patients report improvement upon practicing avoidance and 94% report improvement upon moving to a chemical free living space.58  Clearly educating patients to avoid chemical irritants and toxicants is most helpful.58,148-151 


MCS is already formally recognized by the national health care system in Germany.152   The Danish Environmental Protection Agency has already concluded that there is ample evidence that MCS is due to environmental contaminants and has taken initiative to minimize off-gassing materials in the indoor environment in efforts to prevent the development of new cases of MCS.152   The government of Sweden recognizes electrical sensitivity as a disability.152   Canada has also recognized MCS and has taken preventive measures by limiting the use of pesticides, fragrances, and other toxicants.152   Diagnostic criteria for MCS have been accepted internationally and are currently under review to consider new findings; the recognition of MCS at all levels of government is steadily increasing.152   We are now seeing public policy and regulations advance towards protecting people from tobacco smoke, pesticides, fragrances, vehicle exhaust, and other chemicals in public places.152   More than one half of the states in the US have already provided a proclamation deeming at least one day or month dedicated for MCS and/or Toxic Injury Awareness.153


Therefore, it is essential that MCS be immediately and fully recognized in America as an organic physiological disorder induced by toxic environmental insults.  Environmental toxicants and irritants from perfumes, smoke, pesticides, industry, and building materials must be reduced or effectively regulated through legislation and enforcement to prevent injury to all citizens.  Immediate accommodation with a safe environment for school, work, and housing should be granted to MCS victims who are still capable of working, while those permanently injured should receive disability benefits.  The Americans with Disabilities Act must be enforced, to provide the same rights to MCS patients as other disabilities, with protection from abuse, harassment, and discrimination.  As new information is published regarding MCS, it is crucial that it be communicated to the medical and public communities.  Accurate, objective information which is free from conflicts of interests, ties to the chemical industry, and connections to the pharmaceutical industry must be rigorously researched and widely disseminated.  Funding is immediately and direly needed for additional investigation into the etiology, treatment, and prevention of this costly, devastating, and disabling disorder.


The future of America is in our collective hands.  It is crucial that industrial financial gain must not be permitted to compromise the health and well being of all citizens.  There are alternatives to the toxic products and pollution man has created.  A shift to these safer alternatives will be market-driven as accurate information on risks becomes readily available; meanwhile informed and enlightened regulation is highly encouraged in order to prevent MCS in the future and allow current patients to engage fully in society as productive members without threat of further injury.  We must never forget that many MCS patients can and do function normally in exposure free conditions.  It is time to move past the view that science does not a grasp of MCS.154   Sufficient clear and present evidence is currently available to show that MCS is real and disabling, and to justify, indeed to demand, immediate action. 


On Behalf of MCS America,



Lourdes Salvador, President


If you agree with this position statement, you may sign it at:

Multiple Chemical Sensitivities America


Copyrighted © 2007  Lourdes Salvador & MCS America 



Human mast cells release oncostatin M on contact with activated T cells: Possible biologic relevance

Journal of Allergy and Clinical Immunology
Article in Press, Corrected Proof - Note to users

doi:10.1016/j.jaci.2007.08.054    How to Cite or Link Using DOI (Opens New Window)  
Copyright © 2007 American Academy of Allergy, Asthma & Immunology Published by Mosby, Inc.

Original article

Human mast cells release oncostatin M on contact with activated T cells: Possible biologic relevance

Pazit Salamon MSca, *, Nitza G. Shoham PhDa, *, Ilaria Puxeddu PhDb, Yosef Paitan PhDc, Francesca Levi-Schaffer PhDb and Yoseph A. Mekori MDa, Corresponding Author Contact Information, E-mail The Corresponding Author
aFrom the Allergy and Clinical Immunology Laboratory
bDepartment of Pharmacology, Faculty of Medicine, the Hebrew University, Jerusalem
cMicrobiology Laboratory, Meir General Hospital, Kfar Saba, and the Sackler School of Medicine, Tel Aviv University
Received 7 December 2006;  revised 22 August 2007;  accepted 30 August 2007.  Kfar Saba, Tel Aviv, and Jerusalem, Israel.  Available online 29 October 2007.


We have recently demonstrated that mast cells can be activated by heterotypic adhesion to activated T cells.


We sought to perform gene expression profiling on human mast cells activated by either IgE cross-linking or by T cells and to characterize one of the cytokines, oncostatin M (OSM).


Gene expression profiling was done by means of microarray analysis, OSM expression was validated by means of RT-PCR, and the product was measured by means of ELISA in both the LAD 2 human mast cell line and in cord blood–derived human mast cells. Immunocytochemistry was used to localize OSM in human mast cells, and its biologic activity was verified by its effect on the proliferation of human lung fibroblasts.


OSM was expressed and released specifically on T cell–induced mast cell activation but not on IgE cross-linking. OSM was localized to the cytoplasm, and its expression was inhibited by dexamethasone and mitogen-activated protein kinase inhibitors. OSM was also found to be biologically active in inducing lung fibroblast proliferation that was partially but significantly inhibited by anti-OSM mAb. In vivo mast cells were found to express OSM in both biopsy specimens and bronchoalveolar lavage fluid from patients with sarcoidosis.


The production of OSM by human mast cells might represent one link between T cell–induced mast cell activation and the development of a spectrum of structural changes in T cell–mediated inflammatory processes in which mast cells have been found to be involved.

Clinical implications

Mast cells might serve as a target for treating T cell–mediated fibrotic processes.

Key words: Oncostatin M; mast cells; T cells

Abbreviations: BAL, Bronchoalveolar lavage; CBMC, Cord blood mast cell; ERK, Extracellular signal-regulated kinase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; JNK, Jun N-terminal kinase; MAPK, Mitogen-activated protein kinase; OSM, Oncostatin M; PMA, Phorbol 12-myristate 13-acetate; QR-PCR, Quantitative real-time PCR; SCF, Stem cell factor; Tc-m, Nonactivated Jurkat T-cell membrane; Tc*-m, Activated Jurkat T-cell membrane

Supported in part by a research grant from the Israel Science Foundation, founded by the Israel Academy of Sciences and Humanities, and by the Frederick Reiss chair in dermatology, Tel Aviv University.Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
Corresponding Author Contact InformationReprint requests: Yoseph A. Mekori, MD, Department of Medicine B, Meir General Hospital, Kfar Saba 44281, Israel.
* These two authors contributed equally to this work.

Tuesday, October 30, 2007

Accumulation of bisphenol A in hemodialysis patients/Risiko für Dialysepatienten

Accumulation of bisphenol A in hemodialysis patients

Murakami K, Ohashi A, Hori H, Hibiya M, Shoji Y, Kunisaki M, Akita M, Yagi A, Sugiyama K, Shimozato S, Ito K, Takahashi H, Takahashi K, Yamamoto K, Kasugai M, Kawamura N, Nakai S, Hasegawa M, Tomita M, Nabeshima K, Hiki Y, Sugiyama S.

Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan.

Blood Purif. 2007;25(3):290-4. Epub 2007 Jul 2.

Bisphenol A [BPA, 2,2-bis(4-hydoxyphenyl)propane], an industrial chemical used in the production of polycarbonate, epoxide resin, and polyarylate, is considered to be an endocrine-disrupting chemical. BPA may be present in some hollow-fiber dialyzers used in hemodialysis. In this study, we tested the amounts of BPA eluted from various hollow fibers. Furthermore, we measured the BPA concentration in the sera of 22 renal disease predialysis patients, as well as 15 patients who were receiving hemodialysis, to see if there is BPA accumulation in these patients. The elution test of BPA showed that a much larger amount of BPA was eluted from polysulfone (PS), and polyester-polymeralloy hollow fibers. Among renal disease patients who had not undergone hemodialysis, the serum BPA concentration increased as the renal function deteriorated, showing a significant negative association. In a crossover test between PS and cellulose (Ce) dialyzers, the predialysis serum BPA concentration of PS dialyzer users decreased after changing to a Ce dialyzer, and the serum BPA increased again after switching back to PS dialyzers. In patients who were using PS dialyzers, the BPA level significantly increased after a dialysis session. However, in the Ce dialyzer
users, the BPA level decreased. Since accumulation of BPA could affect the endocrine or metabolic system of the human body, it is important to perform further investigations on dialysis patients.
Copyright 2007 S. Karger AG, Basel.

PMID: 17622711 [PubMed - indexed for MEDLINE]

Sunday, October 28, 2007

Feeling Bad in More Ways than One: Comorbidity Patterns of Medically Unexplained and Psychiatric Conditions.

Schur, EA, Afari, N, Furbert, H, Olarte, M, Goldberg, J, Sullivan, PF, & Buchwald, D. 

Feeling Bad in More Ways than One: Comorbidity Patterns of Medically Unexplained and Psychiatric Conditions. 

Journal of General Internal Medicine.  Volume 22, Number 6 / June, 2007.


Background  Considerable overlap in symptoms and disease comorbidity has been noted among medically unexplained and psychiatric conditions seen in the primary care setting, such as chronic fatigue syndrome, low back pain, irritable bowel syndrome, chronic tension headache, fibromyalgia, temporomandibular joint disorder, major depression, panic attacks, and posttraumatic stress disorder.
Objective  To examine interrelationships among these 9 conditions.
Design  Using data from a cross-sectional survey, we described associations and used latent class analysis to investigate complex interrelationships.
Participants  3,982 twins from the University of Washington Twin Registry.
Measurements  Twins self-reported a doctor's diagnosis of the conditions.
Results  Comorbidity among these 9 conditions far exceeded chance expectations; 31 of 36 associations were significant. Latent class analysis yielded a 4-class solution. Class I (2% prevalence) had high frequencies of each of the 9 conditions. Class II (8% prevalence) had high proportions of multiple psychiatric diagnoses. Class III (17% prevalence) participants reported high proportions of depression, low back pain, and headache. Participants in class IV (73% prevalence) were generally healthy. Class I participants had the poorest markers of health status.
Conclusions  These results support theories suggesting that medically unexplained conditions share a common etiology. Understanding patterns of comorbidity can help clinicians care for challenging patients.

KEY WORDS  primary care - fibromyalgia - chronic fatigue syndrome - back pain - depression


Clinicians have long observed that some patients are burdened with a large number of medical complaints, and the challenge of caring for these patients has been acknowledged.1 A subset of these patients has "medically unexplained" or "functional" conditions like chronic fatigue syndrome, irritable bowel syndrome, and fibromyalgia. Common psychiatric disorders such as major depression and anxiety are also frequently comorbid with these unexplained conditions but do not appear to fully explain them.2 It has been proposed that the spectrum of unexplained conditions may reflect one underlying syndrome.3

We therefore examined the associations among 9 conditions usually considered medically unexplained or psychiatric—chronic fatigue syndrome, low back pain, irritable bowel syndrome, chronic tension headache, fibromyalgia, temporomandibular joint disorder, major depression, panic attacks, and posttraumatic stress disorder—using a community-based twin registry. The goals of this study were to (a) describe the associations among these conditions, (b) use latent class analysis (LCA) to investigate complex interrelationships between these conditions, and (c) describe the demographic and clinical characteristics of individuals falling within each class identified by LCA.


All twins were participants in the University of Washington Twin Registry (UWTR), a community-based registry of twin pairs derived from applications for drivers' licenses in Washington State. The University of Washington receives lists of applicants who are twins, and each member of the pair is invited to join the UWTR and complete a health survey. Based on age and sex data for nonrespondents, registry participants are slightly younger and more likely to be female than the pool of potential twins. All UWTR procedures and the data collection involved in this study were approved by the University of Washington Institutional Review Board. Informed consent was obtained from all twins.

Primary Measures

Nine conditions usually considered medically unexplained or psychiatric were chosen a priori for analyses. The presence of each condition was coded by the response to the question "Has your doctor ever told you that you have (specific condition)?" We chose this self-report method because diagnostic criteria for the conditions were not agreed upon or validated measures were unavailable or too lengthy for survey administration.

Demographics and Zygosity Assignment

Demographic characteristics were self-reported. We dichotomized race, marital status, education, and general health status and calculated body mass index (BMI; weight/height2). Twins were asked about childhood similarity. Such questions classify zygosity with an accuracy of approximately 95% of that achieved with biological indicators.4

Statistical Analyses

Initial analyses were conducted with SAS v9.1 (SAS Institute Inc., 2004). Odds ratios (OR) and 95% confidence intervals were calculated as measures of association among all of the conditions. For all analyses, data from each individual twin were considered separately. We used generalized estimating equations to account for the nonindependence of twins and clustering of twins within a pair. For these initial analyses, age and sex were chosen as a priori covariates in the adjusted model. Pairwise comparisons were performed only on adjusted ORs.

Latent Class Analysis (LCA)   Like cluster analyses, LCA5 attempts to find groupings of individuals defined by responses to a number of items. We used LCA because it has yielded convergent results in prior studies of complex human traits6 and is readily compatible with discrete data. We included all 9 conditions along with sex in the LCA.
To perform the LCA, we used FORTRAN with an efficient estimation-maximization algorithm7 for maximum likelihood estimation. To determine the number of latent classes that gave rise to the observed data, we fit up to 10 latent class models to the data (50 separate runs with randomized starting values run for each to avoid the known problem of local minima). Number of classes was ascertained by using the Schwarz Bayesian criterion,8 an index of parsimony that penalizes the goodness-of-fit statistic by the number of model parameters times the natural logarithm of the sample size. The Schwarz Bayesian criterion helps to determine the number of classes with a balance of goodness-of-fit and model complexity.
Demographic and Clinical Characteristics of Classes   We analyzed variables not entered into the LCA including age; marital status; education; medical, psychiatric, or alternative practitioner visits; total number of visits to a health professional; general health status; BMI; and exercise levels. We used Chi-square tests and linear regression to assess group differences among classes.


The sample included 1,042 monozygotic pairs, 828 dizygotic pairs, and 121 pairs of undetermined zygosity for a total of 3,982 individual twins. Of these, 3,937 had nonmissing data for all conditions and were included in the LCA. The mean age was 32.4 years (SD = 14.7); 86% were white and 61% were female.

Associations Among the 9 Conditions
Table 1 presents unadjusted and adjusted ORs for all possible combinations of the 9 conditions. Strikingly, 31 of 36 comparisons performed were significant. At an alpha level of 0.05, we would expect approximately 2 associations to be significant by chance. Only irritable bowel syndrome had consistently low ORs.
Table 1 Unadjusted and Adjusted Odds Ratios and 95% Confidence Intervals for 9 Conditions Evaluated Among Twins in the University of Washington Twin Registry


Chronic fatigue syndrome

Low back pain

Irritable bowel syndrome

Chronic tension headache


TMJ syndrome

Major depression

Panic attacks

Posttraumatic stress disorder

Chronic fatigue syndrome

4.8 (4.4–5.5)

4.2 (2.1–8.2)

11.5 (8.1–16.6)

38.6 (36.1–41.2)

4.8 (4.0–5.8)

10.6 (6.4–17.7)

6.0 (4.7–7.5)

9.4 (9.3–9.5)

Low back pain

4.2 (4.1–4.3)

3.0 (2.5–3.5)

2.8 (2.0–4.0)

7.5 (6.8–8.2)

2.4 (2.2–2.7)

3.3 (3.1–3.5)

2.8 (2.6–3.0)

3.4 (3.0–3.9)

Irritable bowel syndrome

3.2 (1.6–6.1)

2.1 (1.6–2.8)

2.6 (1.6–4.3)

2.6 (1.1–5.8)

1.5 (0.8–2.8)

1.7 (1.1–2.6)

1.6 (0.6–4.2)

2.3 (1.3–4.3)

Chronic tension headache

10.7 (8.0–14.1)

2.7 (2.0–3.6)

2.6 (1.7–3.9)

6.6 (6.6–6.7)

3.8 (3.4–4.2)

5.1 (4.5–5.8)

4.4 (3.8–5.0)

5.3 (4.6–6.1)


29.1 (26.9–31.5)

5.2 (4.4–5.9)

1.7 (0.8–3.9)

5.0 (4.3–5.7)

10.4 (5.4–20.1)

6.1 (5.3–6.9)

4.2 (3.5–5.0)

9.0 (7.6–10.8)

TMJ syndrome

3.8 (3.4–4.2)

2.1 (1.8–2.3)

1.2 (0.6–2.3)

3.1 (2.6–3.7)

7.0 (3.7–13.4)

4.1 (4.1–4.2)

3.4 (2.4–4.8)

6.6 (6.2–7.1)

Major depression

9.4 (5.2–16.8)

3.2 (2.9–3.5)

1.6 (1.0–2.4)

4.5 (4.2–4.9)

4.6 (3.8–5.7)

3.4 (3.2–3.5)

14.0 (13.1–14.9)

20.3 (19.1–21.5)

Panic attacks

5.1 (4.2–6.2)

2.5 (2.4–2.6)

1.4 (0.5–4.2)

3.9 (3.6–4.1)

3.1 (2.7–3.6)

2.7 (1.8–4.2)

12.7 (11.2–14.4)

16.6 (12.2–22.6)

Posttraumatic stress disorder

7.2 (6.9–8.0)

2.8 (2.4–3.3)

1.6 (0.7–3.5)

4.7 (4.5–4.9)

6.5 (5.6–7.6)

5.4 (4.8–5.9)

18.8 (17.0–20.8)

14.9 (10.8–20.5)

Unadjusted odds ratios are above the diagonal; odds ratios adjusted for age and sex are shown below the diagonal. Pairwise comparisons were performed only on adjusted odds ratios. Strong to very strong associations (odds ratio of 5 or greater) are indicated in bold.
TMJ = temporomandibular joint
Latent Class Analysis
The Schwarz Bayesian criterion declined for 1 to 4 class solutions, had minimal change for 5 classes, and then increased thereafter. Review of the solutions suggested that a 4-class solution best fit the data (see Table 2) and was more interpretable than the 5-class solution, as there was a clear minimum of the Schwarz Bayesian criterion.
Table 2 Latent Class Analysis Results for Sex and 9 Clinical Conditions with Demographic and Clinical Characteristics by Class


Overall sample (N = 3,937)

Class I (2%) multiplex

Class II (8%) depression and anxiety

Class III (17%) depression

Class IV (73%) unaffected

P value*

Variables in latent class analysis

  Female sex %






  Low back pain %






  Major depression %






  Panic attacks %






  Chronic tension headache %






  Irritable bowel syndrome %






  TMJ syndrome %






  Posttraumatic stress disorder %






  Chronic fatigue syndrome %






  Fibromyalgia %






Demographic and clinical characteristics

  Married or living with partner %







  College education or more %







  Health fair or poor %







  Age in years, mean (SD)

32.3 (14.7)

35.7 (14.9)

42.4 (12.8)

34.9 (14.6)

31.1 (14.6)


  Psychiatric visits in past 3 months, mean (SD) and median

0.30 (1.9)

0.81 (2.1)

1.4 (3.8)

0.51 (2.2)

0.11 (1.4)








  Medical visits in past 3 months, mean (SD) and median

1.3 (3.0)

2.9 (4.9)

2.6 (6.9)

1.7 (2.6)

1.0 (2.2)








  Alternative practitioner visits in past 3 months, mean (SD) and median

0.68 (3.7)

2.3 (5.5)

1.6 (7.6)

0.81 (2.7)

0.5 (3.1)








  Total health visits in past 3 months, mean (SD) and median

2.4 (5.5)

6.0 (8.2)

5.6 (11.2)

3.1 (4.6)

1.6 (4.5)








  Body mass index, mean kg/m2 (SD)

24.7 (5.1)

27.5 (6.9)

25.6 (6.4)

25.4 (5.7)

24.4 (4.7)


  Episodes of vigorous exercise per week, mean (SD)

1.4 (2.7)

0.77 (1.6)

1.1 (2.0)

1.0 (2.0)

1.6 (2.9)


  Episodes of moderate exercise per week, mean (SD)

2.6 (4.1)

2.2 (3.8)

2.9 (7.1)

2.2 (2.6)

2.7 (3.9)


To aid the reader, arrows indicate probabilities that deviate by ≥15% from the overall prevalence
*P values are for differences across all 4 classes
TMJ = temporomandibular joint

Class I (2% of sample) had markedly high proportions of individuals who reported all of the 9 syndromes. Class II (8% of sample) participants had high proportions of multiple mental health conditions including major depression, panic attacks, and posttraumatic stress disorder, and low back pain. Class III (17% of sample) participants reported high proportions of depression, low back pain, and headache. Class IV (73% of sample) had the lowest proportion of females and low probabilities for all 9 conditions. There was poor agreement between class assignments for twin pairs (Cohen's kappa = 0.1).

Demographic and Clinical Characteristics of Classes

Demographic and clinical characteristics of each class are presented in Table 2. The results suggest differences across groups, most notably between class I and class IV. Class I individuals most often reported fair or poor general health status and had the highest mean BMI, the highest total number of health care visits, and the lowest exercise frequencies.


We found consistent patterns of comorbidity between medically unexplained conditions in a community sample of twins. Two percent of our sample had high prevalences of all 9 conditions. Although depression and anxiety also commonly co-occurred with medically unexplained conditions, twins with predominantly mental health conditions appeared to be in distinct classes. Twins with a high burden of physical and mental illness were distinguished from healthy participants by their increased health care use, worse self-reported health status, higher BMI, and lower levels of physical exertion.

Our findings support proposals that a common pathway9 or a single disease process3 may underlie these clinically defined syndromes. The recent identification of candidate genes associated with chronic fatigue syndrome10 could eventually reveal not only the physiological underpinnings of chronic fatigue, but common pathways for multiple currently unexplained syndromes.

Frequencies of medically unexplained syndromes were not markedly increased in the twins with the greatest psychiatric comorbidity and utilization of psychiatric care (class II). In contrast, the primary physical complaint was localized: low back pain. Again, localized symptoms of low back pain and headache predominated over medically unexplained syndromes in sufferers of depression alone (class III). These results concur with literature on both psychiatric comorbidity11 and the association of mental health diagnoses with back pain12 and chronic tension headache.13 The comorbidity of mental illness and localized symptoms may reflect a limited ability to cope with common symptoms like headache or back pain in individuals with depression and anxiety. In sum, we found that twins with predominantly mental illness were distinct from those with the highest burden of medically unexplained syndromes, echoing prior findings.14 For clinicians, these data reiterate the importance of screening for psychiatric conditions when painful or medically unexplained conditions are present.

This study was cross-sectional, thus limiting any conclusions about causality for the observed associations. In addition, the clinical conditions were assessed by single-item self-report of a doctor's diagnosis, which can be subject to response bias. However, our overall prevalences are comparable to available published general population rates for chronic fatigue syndrome,15 low back pain,16 fibromyalgia,17 major depression,11 panic, 18 and posttraumatic stress disorder.19 Our use of self-report data may explain the lower-than-expected overall prevalence of irritable bowel syndrome, as research suggests that a large undiagnosed symptomatic population may exist.20

In summary, this study is unique in its use of a community-based sample of twins and diverse statistical approaches to examine patterns of comorbidity for 9 conditions seen in primary care. We defined a group with multiple medically unexplained syndromes who appeared to be distinct from individuals with primarily mental health diagnoses. Clinicians may find our results helpful for several reasons. First, they suggest individuals should be screened for comorbid disorders such as posttraumatic stress disorder when depression and anxiety are present and for major depression when low back pain and chronic headache are reported. Second, our findings also help clinicians understand that distressed patients are not merely accumulating diagnoses or somatic complaints, but have a constellation of conditions that frequently coexist, analogous to metabolic syndrome. Multiple medications for symptom management alone can be minimized, focusing instead on proven behavioral strategies such as graduated exercise or cognitive behavioral therapy. Finally, research seeking unified etiologies and treatment strategies is needed. Such ground-breaking work may eventually allow clinicians to feel confidence instead of consternation when treating patients with multiple unexplained, comorbid conditions.

Acknowledgements  This research was supported by National Institutes of Health awards 5 U19 AI038429 (Buchwald) and R55AR051524 (Afari). Dr. Schur is funded by a National Institutes of Health Career Development Award K23 DK070826.
Conflict of Interest   None disclosed.


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