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NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) is a condition where previous exposure to hydrophobic organic solvents or pesticides appears to render people hypersensitive to a wide range of chemicals, including organic solvents. The hypersensitivity is often exquisite, with MCS individuals showing sensitivity that appears to be at least two orders of magnitude greater than that of normal individuals. This paper presents a plausible set of interacting mechanisms to explain such heightened sensitivity. It is based on two earlier theories of MCS: the elevated nitric oxide/peroxynitrite theory and the neural sensitization theory. It is also based on evidence implicating excessive NMDA activity in MCS. Four sensitization mechanisms are proposed to act synergistically, each based on known physiological mechanisms: Nitric oxide-mediated stimulation of neurotransmitter (glutamate) release; peroxynitrite-mediated ATP depletion and consequent hypersensitivity of NMDA receptors; peroxynitrite-mediated increased permeability of the blood-brain barrier, producing increased accessibility of organic chemicals to the central nervous system; and nitric oxide inhibition of cytochrome P450 metabolism. Evidence for each of these mechanisms, which may also be involved in Parkinson's disease, is reviewed. These interacting mechanisms provide explanations for diverse aspects of MCS and a framework for hypothesis-driven MCS research.

Animals↗

Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity.

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.

Adult↗

Environmental issues and work: women with multiple chemical sensitivities.

Multiple chemical sensitivities (MCS) is an acquired condition in which exposure to low levels of chemicals causes symptoms in multiple organ systems. Some 12%-16% of the U.S. population has some level of chemical sensitivity, 80% of whom are women. Attempts to reduce chemical exposures leads to enormous life difficulties at home, school, and workplace. We base our article on an ethnographic study of MCS in the United States and Canada. We describe here themes related to work issues in terms of a general trajectory of becoming sick from work exposures, coping with toxic physical environments and dealing with coworkers and, when unable to continue working, applying for workers' compensation, or disability status, or both.

Activities of Daily Living↗

A critical analysis of multiple chemical sensitivities.

Multiple chemical sensitivities (MCS) is a chronic condition of irritation and inflammation of sensory organs, gastrointestinal distress, fatigue, and compromised neurological function, including learning and memory deficits, unpleasant smells, tingling of nerves, and sensory discomfort. Victims report these symptoms after exposure to unfamiliar chemicals. Some studies have linked MCS to immune system dysregulation. MCS is believed to be a disease that spreads between various target organs, and is caused by sensitization to chemicals with very different structures. MCS is often attributed to free radical production and stress, which indirectly cause spreading because of damage to the immune system.

Free Radicals↗

Model development and research vision for the future of multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) is characterized by heightened self-reported sensitivity to extremely low concentrations of chemicals. It has numerous symptoms in common with the sick building syndrome, the Gulf War syndrome, and chronic fatigue. Despite much research, reproducible objective findings are lacking for MCS, as is a sound model to explain it. This paper proposes a 2-step model combining the needed epidemiologic terminology with that of psychophysiological activation and sensitization. It is suggested that different environmental stressors act as initiators. After initiation, the limbic system and other parts of the brain become sensitized and hyperreactive to environmental triggers. Odor acts as one important trigger. Future research should use more biological assessments in combination with environmental and psychosocial data and involve patient groups with similar symptoms, although diagnosed as suffering from different entities. The similarities and differences of patients with such entities need to be understood before the entities themselves can be understood, diagnosed, treated, and prevented.

Humans↗

[Formaldehyde exposure and multiple chemical sensitivity].

Multiple chemical sensitivity (MCS) is characterized by various somatic symptoms which cannot be explained organically and by sensitivity to extremely low concentrations of chemicals including formaldehyde. In the absence of a widely accepted definition of MCS, contradictory etiological hypotheses and therapeutic suggestions are discussed. Formaldehyde is a flammable, colorless and readily polymerized gas at ambient temperature. It is present in the environment as a result of natural processes and from man-made sources, including motor vehicle exhaust, residues, emissions, or wastes produced during the manufacture of formaldehyde, and cigarette smoke. Formaldehyde exposure is considered to be one of the causes of MCS. This review describes the current knowledge about MCS and preventive measures of the administration.

Air Pollution, Indoor↗

Odor processing in multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) is characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the mechanisms behind the reported hypersensitivity are unknown. Using the advantage of the well-defined trigger (odor), we investigated whether subjects with MCS could have an increased odor-signal response in the odor-processing neuronal circuits. Positron emission tomography (PET) activation studies with several different odorants were carried out in 12 MCS females and 12 female controls. Activation was defined as a significant increase in regional cerebral blood flow (rCBF) during smelling of the respective odorant compared to smelling of odorless air. The study also included online measurements of respiratory frequency and amplitude and heart rate variations by recording of R wave intervals (RR) on the surface electrocardiogram. The MCS subjects activated odor-processing brain regions less than controls, despite the reported, and physiologically indicated (decreased RR interval) distress. In parallel, they showed an odorant-related increase in activation of the anterior cingulate cortex and cuneus-precuneus. Notably, the baseline rCBF was normal. Thus, the abnormal patterns were observed only in response to odor signals. Subjects with MCS process odors differently from controls, however, without signs of neuronal sensitization. One possible explanation for the observed pattern of activation in MCS is a top-down regulation of odor-response via cingulate cortex.

Adult↗

Does the kindling model of epilepsy contribute to our understanding of multiple chemical sensitivity?

Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report an increased sensitivity to low levels of chemicals in the environment. Kindling is a model of synaptic plasticity whereby repeated low-level electrical stimulation to a number of brain sites leads to permanent increases in seizure susceptibility. Stimulation that is initially subthreshold for subclinical seizure provocation comes, over time, to elicit full-blown motor seizures. Kindling can also be induced by chemical stimulation, and repeated exposures to some pesticides have been shown to induce signs of behavioral seizure, facilitate subsequent electrical kindling, and induce subclinical electrographic signs of hyperexcitability in the amygdala. Many of the symptoms of MCS suggest that CNS limbic pathways involved in anxiety are altered in individuals reporting MCS. Limbic structures are among the most susceptible to kindling-induced seizures, and persistent cognitive and emotional sequelae have been associated with temporal lobe epilepsy (TLE) in humans and kindling in animals. Thus, a number of parallels exist between kindling and MCS phenomena, leading to initial speculations that MCS may occur via a kindling-like mechanism. However, kindling requires the activation of electrographic seizure discharge and has thus been primarily examined as a model for TLE. Events leading to the initial evocation of a subclinical electrographic seizure have been much less well studied. It is perhaps these events that may serve as a more appropriate model for the enhanced chemical responsiveness characteristic of MCS. Alternatively, kindling may be useful as a tool to selectively increase sensitivity in subcomponents of the neural fear circuit to address questions relating the role of anxiety in the development and expression of MCS.

Amygdala↗

Clinical features of multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) could be called a phenomenon rather than an illness. No single widely accepted test of physiological function can be shown to correlate with the symptoms presented by the patients. In addition to allergy and asthma, patient history can include various "illnesses", and the "diagnosis" is often made by the patient, usually alone or with the help of clinical ecologists. This paper reports the experiences from a department of occupational medicine. More than 80% of the patients were women and solvent exposure was the most common cause of chemical intolerance reported by the patients. Many patients also reported psychosocial stressors. The patients also showed mood disorders with irritability, anxiety, sleep disturbances and depression, often with thoughts centered around different organ symptoms. The symptomatology of MCS is still nonspecific and in no way diagnostic of a specific illness or a medically acceptable syndrome. It may indicate many other conditions, both organic disease and psychopathology.

Diagnosis, Differential↗

A 4-year-old girl with manifestations of multiple chemical sensitivities.

Multiple chemical sensitivities (MCS) syndrome, also known as idiopathic environmental intolerance, is a controversial diagnosis that encompasses a wide range of waxing and waning, subjective symptoms referable to more than one body system and provoked by exposure to low levels of chemicals, foods, or other agents in the environment. Although MCS has been studied extensively, a unifying mechanism explaining the illness remains obscure, and clinicians are divided as to whether such a medical entity exists separately from psychosomatic syndromes. MCS is an adult diagnosis; there is little reference to pediatric cases in the scientific literature. In this case from the Pediatric Environmental Health Subspecialty Unit at Boston's Children's Hospital, I present the case of a preschool child who had suffered from milk allergy and poor weight gain as an infant, and then later developed asthma, allergic symptoms, sinusitis, headaches, fatigue, and rashes precipitated by an expanding variety of chemicals, foods, and allergens. I review definitions, mechanisms, diagnostic strategies, and management, and discuss some uniquely pediatric features of MCS as illustrated by this case.

Adaptation, Psychological↗

What can research contribute to regulatory decisions about the health risks of multiple chemical sensitivity?

Multiple Chemical Sensitivity (MCS), which may not be caused by chemicals at all, is a serious medical problem of unknown origin and uncertain etiology that raises many fundamental science and policy questions. Regulators, for example, are confronted with a dilemma: what, if anything, should be done to protect people from the scientifically uncertain health risks of exposures to extremely low levels of environmental chemicals. Regulatory agencies, such as the Environmental Protection Agency, do not have the luxury of waiting until conclusive scientific evidence is available before making a decision; however, our present lack of scientific understanding about MCS is so acute that it is not possible to ascertain whether the cause of MCS-related symptoms is chemical, biological, physical, psychosocial, or some combination thereof. Nevertheless, many MCS sufferers and advocates for the chemically induced hypothesis are clamoring for regulatory action to reduce putative health risks from very-low-level exposures to chemicals in the environment. Unless steps are taken to improve the quantity and quality of the existing scientific data base, we cannot, with any acceptable degree of certainty, evaluate the extent to which regulatory decisions about MCS are either protective of public health or cost-effective. This article examines how research can strengthen the scientific basis for risk-related decisions about MCS, and proposes a framework for establishing research directions and priorities. It is argued that high-priority research on MCS is distinguishable by four attributes: (1) results are valuable for risk-related decisions; (2) findings significantly advance scientific knowledge and understanding; and the hypothesis being tested is both (3) biologically plausible and (4) readily testable.

Decision Making↗

[Questionable procedures in environmental medicine using an example of "multiple chemical sensitivity"].

"Multiple Chemical Sensitivity" (MCS) has to be regarded as a merely subjective concept without etiological and pathological background or objective criteria for diagnosis. Most of the "MCS" patients suffer from various psychiatric disorders; in a small minority somatic diseases can be found. The data recently won in the German multicenter study on MCS underline this point of view. The informal German "MCS network" consisting of patients' self-help groups, "therapists" with or without medical background and law firms specialised in compensation claims nevertheless strictly denies any psychogenic model. They do, however, propose a whole range of diagnostic and therapeutic procedures based on different theoretical concepts. Some of the procedures are derived from scientifically based medicine, others have an unconventional and esoteric background. Most of them are logically incompatible; however, they are applied in a polypragmatic manner. None of these so-called diagnostic or therapeutic procedures or health technologies can be regarded as evidence-based. Some of them, however, are extremely expensive and/or pose significant risks for patients' health. In any case, wrong subjective disease concepts are perpetuated iatrogenically. Additionally, those procedures make effective help for the real underlying medical and/or psychiatric conditions impossible.

Clinical Trials as Topic↗

Increased capsaicin cough sensitivity in patients with multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) is characterized by chemically induced symptoms from multiple organ systems. No consistent physical findings or laboratory abnormalities have been determined for the associated symptoms. Twelve patients with chemically induced airway symptoms, who satisfied Cullen's criteria for MCS, were provoked double-blind, randomized with saline and three increments of inhaled capsaicin. The recordings were compared with those of a control group of healthy individuals. The results found that the patients coughed more than the control subjects at each dose of capsaicin (P < 0.05 for 0.4 mumol/L capsaicin and P < 0.005 for 2 mumol/L and 10 mumol/L). The capsaicin provocation also induced significantly more symptoms in patients with MCS. We conclude that airway sensory reactivity is increased in patients with MCS, a finding which suggests that neurogenic factors may be of importance in this condition.

Administration, Inhalation↗

A 37-year-old mechanic with multiple chemical sensitivities.

A 37-year-old heating, ventilation, and air-conditioning mechanic developed respiratory, musculoskeletal, and central nervous system symptoms associated with a variety of odorous environmental chemicals. Organic disease was not evident, but the patient was distressed by these symptoms and was at risk for becoming disabled by them. His symptoms fit broadly into the condition recognized as multiple chemical sensitivity. Multiple chemical sensitivity is a diagnostic term for a group of symptoms without demonstrated organic basis. The symptoms are characteristic of dysfunction in multiple organ systems, they increase and decrease according to exposure to low levels of chemical agents in the patient's environment, and they sometimes occur after a distinct environmental change or insult such as an industrial accident or remodeling. Although traditional medical organizations have not agreed on a definition for this syndrome, it is being increasingly recognized and makes up an increasing percentage of the caseload at occupational and environmental medicine clinics. Although there is often dispute about whether the symptoms have a functional or organic basis, an informed approach to evaluation, diagnosis, and management and a careful assessment of impairment, disability, and work relatedness are necessary. Careful exclusion of organic causes is critical, and this should be followed by a judicious approach to coping with symptoms.

Adaptation, Psychological↗

Laboratory testing of the patient with multiple chemical sensitivity.

Multiple diagnostic laboratory tests are frequently used in the clinical evaluation of persons with multiple chemical sensitivity without a clear a priori hypothesis. In addition, many of these tests are performed despite a lack of understanding of the test technical performance characteristics or the clinical significance (test sensitivity and specificity). The result is a plethora of laboratory data that have little clinical relevance and that can be both misleading and misused.

Clinical Laboratory Techniques↗

["Multiple chemical sensitivity syndrome"].

Multiple chemical sensitivity (MCS) has been described as an acquired multiple organ disease typically characterized by central nervous irritative and/or gastrointestinal symptoms. Advocates of this suspected syndrome attribute these disorders to overstressing of the organism caused by exposure to external noxae. Opponents of the theory of MCS attribute all the symptoms to classical conditioning or other psychopathological processes. In so far as controlled data exist, there is no indication of a toxic or immunological cause for this syndrome.

Conditioning, Classical↗

Multiple chemical sensitivity syndrome.

Multiple chemical sensitivity (MCS) is a syndrome in which multiple symptoms reportedly occur with low-level chemical exposure. Several theories have been advanced to explain the cause of MCS, including allergy, toxic effects and neurobiologic sensitization. There is insufficient scientific evidence to confirm a relationship between any of these possible causes and symptoms. Patients with MCS have high rates of depression, anxiety and somatoform disorders, but it is unclear if a causal relationship or merely an association exists between MCS and psychiatric problems. Physicians should compassionately evaluate and care for patients who have this distressing condition, while avoiding the use of unproven, expensive or potentially harmful tests and treatments. The first goal of management is to establish an effective physician-patient relationship. The patient's efforts to return to work and to a normal social life should be encouraged and supported.

Diagnosis, Differential↗

Multiple-chemical sensitivity.

Multiple-chemical sensitivity (MCS) is a condition in which individuals have an acute hypersensitivity to low levels of chemicals found in everyday substances, such as household cleaning agents, pesticides, fresh paint, new carpeting, synthetic building materials, newsprint, perfume, and numerous other petrochemical products. This condition continues to remain somewhat of a mystery to the medical community, and its true prevalence rate is unknown because many cases are not identified and reported as MCS. This article will inform the reader about the condition of MCS.

Female↗