Keith Claypoole

Immunologic, psychological, and neuropsychological factors in multiple chemical sensitivity : a controlled study

During the last decade, physicians practicing primary care, occupational medicine, and allergy/immunology have encountered a growing number of patients with symptoms attributed to low-level chemical exposure. These patients typically have a wide array of respiratory, neuropsychological, and systemic symptoms without well-defined physical or laboratory findings. One syndrome, variously labeled environmental illness or multiple chemical sensitivity, has been described as an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposures to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects [1]. Immunologic, neurotoxic, and psychiatric causes have been proposed, but the cause and treatment of chemical sensitivity remain controversial. Some physicians with special interest in chemical sensitivity, particularly clinical ecologists or environmental physicians, emphasize the role of immunologic abnormality in chemical sensitivity [2]. They contend that accumulated everyday exposure to synthetic chemicals causes immunologic overload and an immunologically mediated sensitivity to common chemical exposures. Treatment regimens may include dietary changes, unorthodox desensitization techniques, and strict avoidance of common low-level chemical exposures. These recommendations can cause major life disruption and severe social withdrawal. The limited scientific data available do not clarify the role of immunologic abnormality in multiple chemical sensitivity and similar disorders attributed to low-level chemical exposure. A number of small case series describe elevated immunoglobulin levels [3, 4], antichemical antibodies [5-9], autoantibodies [5], elevated levels of TA1-positive cells [5, 7, 8], and various changes in lymphocyte subsets [5, 7-9]. These reports, however, reveal no consistent pattern of immunologic abnormality. Results from two larger series of patients selected from a referral occupational medicine clinic [10] and from a group of disability applicants [11] showed no abnormality of immunoglobulin and complement levels, B-cell, T-cell, and T-cell subset levels. None of these investigations, however, included systematic selection of patients with chemical sensitivity from a defined population, blinded assessment, or comparison with appropriate controls. Traditional medical organizations express skepticism about the immunologic basis of chemical sensitivity and the practice of clinical ecologists [12-14]. A recent report of the American Medical Associations Council on Scientific Affairs concluded that multiple chemical sensitivity should not be considered a recognizable clinical syndrome [15]. After reviewing medical records of patients claiming compensation for work-related chemical sensitivity symptoms, Terr [16] reported that most patients reported similar symptoms before exposure at the workplace. A double-blind evaluation of the neutralization-provocation techniques used by some clinical ecologists found that patients with multiple food sensitivities were unable to distinguish placebo from low-level food or chemical exposures [17]. Previous psychological studies of patients with multiple chemical sensitivity have all reported elevated levels of anxiety and depression and have implicated psychological distress in the cause of the syndrome [18-22]. Two of these studies, however, considered patients specifically referred for psychiatric evaluation [18, 19], and none systematically sampled a defined population of patients with chemical sensitivity. Three of these reports included no control group [18-20], and the remaining two [21, 22] compared patients with multiple chemical sensitivity to community volunteers or mildly ill controls who might be expected to report less psychological distress. Fiedler and colleagues [10] recently described moderate levels of psychological morbidity in a series of eight patients with chemical sensitivity referred to a occupational health clinic, but no comparison group was included. To address some of these gaps in knowledge, we compared immunologic, psychologic, and neuropsychological factors in a systematically selected sample of patients with multiple chemical sensitivity and a medically ill control group. Methods Study Sample Patients with chemical sensitivity were recruited from the practice of a community allergist with special interest in treating chemical sensitivity. All patients with a recorded diagnosis of chemical sensitivity seen between January 1989 and June 1990 were identified from computerized billing records. We then reviewed standardized history questionnaires included in clinical records for the following eligibility criteria: duration of illness 3 months or more; symptoms reported in at least three organ systems, including the central nervous system; and reported sensitivity to 4 or more substances from a list of 14 common exposures including fresh paint, newspapers, perfume, hair spray, and solvent fumes. All potential participants were sent a letter requesting their participation. Of the 76 patients with chemical sensitivity identified from records, 32 did not respond to letters and 3 were judged to be ineligible (2 reported complete resolution of chemical sensitivity and 1 described respiratory symptoms only). The remaining 41 patients (56% of those potentially eligible) were enrolled. Controls were selected from two university-based clinics for patients with musculoskeletal injuries: an occupational musculoskeletal clinic and a back injury specialty clinic. We reviewed clinic charts to identify all patients seen between January 1989 and June 1990 whose ages were within the range of the chemical sensitivity cases and who resided within 25 miles of the study clinics. Patients with any systemic illness (such as rheumatoid arthritis) likely to affect the results of immunologic testing were excluded, and potential controls were frequency matched to cases by sex and 5-year age strata. This procedure identified 85 potential controls (34 from the occupational clinic and 51 from the back clinic) who were sent a letter requesting participation in the comparison group for a study of chemical-related health problems. Forty-nine did not respond (17 from the occupational clinic and 32 from the back clinic) and 2 patients (both from the back clinic) were judged ineligible because of reported symptoms of chemical sensitivity. The remaining 34 patients (41% of those potentially eligible) were enrolled. The primary diagnosis was low-back pain for all 17 control patients from the back clinic and for 4 from the musculoskeletal clinic. Of the remaining control patients, 8 had repetitive-motion syndromes and 5 had other chronic symptoms following work-related musculoskeletal injuries. Laboratory Methods All immunologic studies were performed by a commercial laboratory with special interest in the evaluation of chemical sensitivity. Laboratory personnel assisted in design of the immunologic battery but remained blinded to case/control status during testing. Total leukocyte count, red cell count, hemoglobin, and hematocrit concentration were measured on a Coulter T140 Cytometer (Coulter Electronics, Hialeah, Florida). For cell-surface marker studies, mononuclear cells were isolated using a Ficoll-induced density gradient followed by 50% dilution in saline and triple washing in Hanks balanced salt solution to remove serum protein. Phenotypic marking of lymphocytes was performed using monoclonal antibodies against CD5 (total T cells), CD4 (T-helper cells), CD8 (T-suppressor cells), CD19 (total B cells), and CD25 (interleukin-2 receptor-positive cells) (all from Becton Dickinson; Los Angeles, California), then counterstained with mouse antihuman IgG coupled to fluorescein. The monoclonal antibody against CD26 (TA1-positive cells) (Coulter) was directly coupled to rhodamine. The percentage of labeled cells was determined using fluorescence microscopic examination. Autoantibodies against parietal cells, mitochondria, smooth muscle, brush border, and nuclear components (Medica; Carlsbad, California) were screened at a dilution of 1:20 in phosphate-buffered saline, pH 7.0, by incubation with species substrate in a room temperature humidifier. Counterstaining was with Evans blue, and fluorescence was classified as present or absent. Each assay run included positive and negative controls. For assay of interleukin-1 generation, peripheral blood monocytes were isolated from sodium heparinized blood by differential centrifugation, washed, and isolated by adherence to tissue culture plates. Monocytes were incubated overnight at 37 C in the presence of lipopolysaccharide (1500 g/mL) and phorbol (1 mg/mL) in 10% fetal calf serum. The supernatant was collected and frozen for later assay. Generated interleukin-1 was measured with an enzyme-linked immunoassay technique using microtiter plates coated with a monoclonal capturing antibody and polyclonal second antibody (Cistron; Pine Brook, New Jersey) linked to peroxidase. Each run included standard and control specimens. Psychological and Neuropsychological Evaluation Patients in both groups completed a questionnaire assessing demographic data, work and chemical exposure history, as well as type, frequency, and duration of chemical sensitivity symptoms. Psychological evaluation included the Hopkins Symptom Checklist-90 (SCL-90), a self-report measure of psychiatric symptoms [23], and the Diagnostic Interview Schedule [24], a highly structured psychiatric diagnostic interview based on the criteria of the American Psychiatric Associations DSM-IIIR [25]. Diagnoses assessed by the structured interview included panic disorder, generalized anxiety, depression, and somatization (a tendency to seek care for physical symptoms that have no apparent medical explanation). The standard Diagnostic Interview Sc

Relationships between Neuropsychological and Oculomotor Measures in Schizophrenia Patients and Normal Controls

Establishing the relationship between oculomotor and neuropsychological impairments might facilitate a more coherent description of schizophrenia-associated neurocognitive deficits. Therefore, we assessed several aspects of neuropsychological and oculomotor function in 25 medicated schizophrenia patients and 24 age-matched controls. Neuropsychological tasks included the Wisconsin Cart Sort Test (WCST), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test, and finger tapping speed. Oculomotor functions assessed included smooth pursuit, initiation of smooth pursuit, predictive pursuit, fixation, visually guided saccades, remembered saccades, and antisaccades. Among the schizophrenia patients, predictive pursuit performance correlated significantly with finger tapping (dominant hand), TMT (both parts), and one WCST measure (categories completed). The only other significant correlation among the schizophrenia patients was between antisaccade performance and part A of the TMT. Perseverative errors during the WCST and antisaccade performance were the only measures significantly correlated among the normals. Closely related neurocognitive deficits may be responsible for impairments in TMT, WCST, predictive pursuit, and antisaccade performance in schizophrenia.

Transcranial magnetic stimulation reduces pain in patients with major depression: a sham-controlled study.

This study evaluated the change in reported pain in patients with medication-resistant major depression receiving transcranial magnetic stimulation (TMS) compared with sham stimulation. In this study, 68 subjects with major depression were randomized to either TMS or sham stimulation. Repetitive TMS was delivered to the left dorsolateral prefrontal cortex at a frequency of 10 Hz in 5-second trains at 110% of the estimated prefrontal cortex threshold. The level of pain was assessed before, during, and after treatment using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) item for pain in the muscles, bones, and joints. Compared with sham, TMS was associated with a significant (p < 0.05) reduction in the SAFTEE pain item during the study. The reduction in pain could not be explained by the antidepressant effects.

Neuropsychological function in retired workers with previous long-term occupational exposure to solvents

OBJECTIVES: It is plausible that neurodegenerative processes of aging might have a contributing role in the development of chronic effects of exposure to organic solvents. This study evaluated the risk for neuropsychological deficits among retired workers, relative to their histories of exposure to occupational solvents. METHODS: This cross sectional study evaluated retired male workers, 62-74 years of age, including 89 people with previous long-term occupational exposure to solvents (67 retired painters and 22 retired aerospace manufacturing workers), and 126 retired carpenters with relatively minimal previous exposure to solvents. Subjects completed a standardised neuropsychological evaluation and psychiatric interview, structured interviews for histories of occupational exposure and alcohol consumption, and questionnaires assessing neurological and depressive symptoms. RESULTS: By comparison with the carpenters, the painters on average reported greater cumulative alcohol consumption and had lower scores on the WAIS-R vocabulary subtest, usually presumed to reflect premorbid intellectual functioning. These findings, however, were not sufficient to account for the other study findings. Controlling for age, education, vocabulary score, and alcohol use, the painters had lower mean scores on test measures of motor, memory, and reasoning ability; and a subgroup of aerospace workers with moderate to high cumulative exposure to solvents (n = 8) had lower mean scores on measures of visuomotor speed, and motor, attention, memory, and reasoning ability. Subjects were more likely to have an increased number of relatively abnormal test scores (three or more outlier scores on 17 test measures) among both the painter group (odds ratio (OR), 3.1; 95% confidence interval (95% CI) 1.5 to 6.2) and the subgroup of aerospace workers with higher cumulative exposure (OR 5.6; 95% CI 1.0 to 38). The painters, but not the aerospace workers, reported significantly more neurological and depressive symptoms. CONCLUSIONS: The findings are consistent with residual central nervous system dysfunction from long-term exposure to organic solvents, persisting years after the end of exposure.

Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?

This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function. Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2 max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise. The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

Cognitive Risk Factors and Neuropsychological Performance in HIV Infection

Almost all investigations examining the effects of early HIV infection on neuropsychological functioning in homosexual males have excluded subjects with cognitive risk factors such as recreational drug use and head injury. While insuring that results reflect the influence of the virus on cognition, this selection bias limits the ability to generalize findings. Comprehensive neuropsychological evaluations were compared between two groups of homosexual males with a variety of cognitive risk factors. Subjects were 132 HIV seropositive males (108 CDC class II & III and 24 CDC class IVA & IVC2) and 65 HIV seronegative controls. Recreational drug use in the six months prior to exam was found to interact with HIV infection and was associated with selective areas of cognitive decline and a significantly worse overall neuropsychological performance. Although significantly lower functioning in the domains of Verbal Memory and Attention and Speed of Information processing was noted for subjects with CDC class IVA and IVC2 compared to seropositives with CDC class II & III, overall neuropsychological performance was similar in these two groups. At this early stage of HIV infection, we did not find indication of association between neuropsychological performance and decreased immunological status. A history of head injury and recent recreational drug use emerged as primary cognitive risk factors associated with decreased neuropsychological performance. As 50% of our HIV seropositive subjects reported active recreational drug use, this cognitive risk factor in particular may contribute to the appearance of HIV-related cognitive deficits during early stages of HIV infection.

The association between trauma and chronic medical conditions in individuals with severe mental illness.

Abstract Based on the concept of allostatic load, this study proposed and evaluated a model for the relationship between childhood trauma, chronic medical conditions, and intervening variables affecting this relationship in individuals with severe mental illness. Childhood trauma, adult trauma, major depressive disorder symptoms, posttraumatic stress disorder symptoms, health risk factors, and chronic medical conditions were retrospectively assessed using a cross-sectional survey design in a sample of 117 individuals with severe mental illness receiving public mental health services. Path analyses produced a good-fitting model, with significant pathways from childhood to adult trauma and from adult trauma to chronic medical conditions. Multisample path analyses revealed the equivalence of the model across sex. The results support a model for the relationship between childhood and adult trauma and chronic medical conditions, which highlights the pathophysiological toll of cumulative trauma experienced across the life span and the pressing need to prevent retraumatization in this population.