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Biomedical subjects

N Fiedler

Publications and source records attributed to N Fiedler.

At least 19 recordsLinked to original sources

Cognitive functioning in Gulf War Illness.

A comprehensive neuropsychological battery was administered to 48 veterans with Gulf War Illness (GWI) characterized by severe fatigue (GV-F) and 39 healthy veterans (GV-H). Subjects were matched on intelligence and did not differ on age, gender, race, and alcohol consumption. Compared to GVs-H, GVs-F were significantly impaired on four tasks: three attention, concentration, information processing tasks and one measure of abstraction and conceptualization. After considering the presence of post-war Axis I psychopathology, GWI remained a significant predictor of cognitive performance on one of the attention, concentration, and information processing tasks and one abstraction and conceptualization measure. Performance on the remaining two attention, concentration, and information processing tasks was only significantly predicted by Axis I psychopathology with post-war onset. The results suggest that Gulf War Illness is associated with some aspects of cognitive dysfunction in Gulf Veterans, over and above the contribution of psychopathology.

Adult↗

Controlled exposures to volatile organic compounds in sensitive groups.

Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low-level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of volatile organic compounds. Sensitive subgroups include subjects who met Cullen's 1987 criteria for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self-reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE-sensitive). All studies include comparison of age- and sex-matched healthy controls. Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose-response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl ethyl alcohol. In blinded, controlled exposures to clean air, gasoline, gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with MTBE-sensitive subjects reporting significantly increased symptoms to gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end-tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals. For example, Gulf War veterans with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while exposure to MTBE did not produce any psychophysiologic changes in MTBE-sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de-adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.

Adult↗

Optimised conditions for the production of hepatitis B virus from cell culture.

In chronically infected patients, hepatitis B virus (HBV) particles reach numbers as large as >10(9) genome equivalents (GE)/ml of serum. However, expression of infectious HBV particles in cell culture only yields 10(5)-10(6) GE/ml, which is insufficient for many studies. HBV transcription and possibly replication is dependent on hepatocyte-specific differentiation. Thus, we tested several cell culture parameters that have been reported to enhance the expression of hepatocyte-specific markers, such as growth on different extracellular matrices, different cell culture media, low concentrations of fetal calf serum (FCS) and the addition of dimethyl sulfoxide (DMSO) to the medium. Lower concentrations of FCS, growth on collagen and inclusion of DMSO in the medium only moderately enhanced HBV production in vitro when applied individually. However, combinations of these parameters optimised cell culture conditions and reproducibly increased the release of HBV particles about 100-fold to titres >10(8) GE/ml of culture medium.

Cell Culture Techniques↗

Medical follow-up of Persian Gulf War Veterans with severe medically unexplained fatigue: a preliminary study.

An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans.

Adult↗

Stressors, personality traits, and coping of Gulf War veterans with chronic fatigue.

OBJECTIVES: preliminary surveys of Persian Gulf veterans revealed a significant prevalence of self-reported symptoms consistent with chronic fatigue syndrome (CFS). The purpose of this study was to compare self-reported life stressors, combat, and chemical exposures, personality and coping between Gulf War veterans with CFS and healthy veterans. METHODS: following a complete physical, psychiatric, and neuropsychological evaluation, 45 healthy veterans, 35 veterans with CFS and co-morbid psychiatric disorder, and 23 veterans with CFS and no co-morbid psychiatric disorder completed questionnaires assessing war and non-war-related life stressors, self-reports of environmental exposure (e.g. oil well fires, pesticides), personality, and coping. RESULTS: measures of personality, self-reported combat and chemical exposures, and negative coping strategies significantly differentiated healthy veterans from those with CFS. CONCLUSION: a biopsychosocial model of veterans' illness was supported by the fact that personality, negative coping strategies, life stress after the war, and environmental exposures during the war were significant predictors of veterans' current physical function.

Adaptation, Psychological↗

A controlled short-term exposure study to investigate the odor differences among three different formulations of gasoline.

Control subjects (CON) and self-reported methyl tertiary butyl ether (MTBE)-sensitive subjects (SRS) were evaluated to distinguish between the following gasoline blends: gasoline versus gasoline + MTBE (15% MTBE v/v); and gasoline versus gasoline + MTBE + reodorant. The study also investigated the ability of a reodorant to conceal the odor of MTBE in a gasoline mixture. In each of two separate sessions, seven men (four CON, three SRS) and seven women (four CON, three SRS) were asked, in a forced-choice format, to sniff 28 randomized bottle pairs to determine if the odors in each pair were the same or different. Chi-square analyses revealed that, with the exception of one male CON, subjects were unable to distinguish between gasoline and gasoline with MTBE or gasoline with MTBE and the reodorant. Thus, a reodorant is of limited value as an additive which alters the ability of an individual to detect MTBE in a blended gasoline. The results suggest that at the level used in the experiment, no mask would be required to blind a participant from the odor of MTBE if that level is used in a controlled human health effects study of the additive.

Adult↗

Odor perception: multiple chemical sensitivities, chronic fatigue, and asthma.

Patients with multiple chemical sensitivities (MCS) often report heightened sensitivity to odors. Odor detection thresholds to phenyl ethyl alcohol (PEA) and pyridine (PYR) were evaluated as a measure of odor sensitivity for 33 MCS subjects, 13 chronic fatigue syndrome subjects, 16 asthmatic subjects, and 27 healthy controls. Odor identification ability (based on University of Pennsylvania Smell Identification Test results) and ratings in response to four suprathreshold levels of PEA and PYR were also assessed. Odor detection thresholds for PEA and PYR and odor identification ability were equivalent for all groups; however, when exposed to suprathreshold concentrations of PEA, MCS subjects reported significantly more trigeminal symptoms and lower esthetic ratings of PEA. No group differences were found in response to suprathreshold concentrations of PYR. In summary, MCS subjects did not demonstrate lower olfactory threshold sensitivity or enhanced ability to identify odors accurately. Furthermore, they were differentiated from the other groups in their symptomatic and esthetic ratings of PEA, but not PYR.

Adult↗

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↗

Controlled human exposure to methyl tertiary butyl ether in gasoline: symptoms, psychophysiologic and neurobehavioral responses of self-reported sensitive persons.

The 1990 Clean Air Act mandated oxygenation of gasoline in regions where carbon monoxide standards were not met. To achieve this standard, methyl tertiary butyl ether (MTBE) was increased to 15% by volume during winter months in many locations. Subsequent to the increase of MTBE in gasoline, commuters reported increases in symptoms such as headache, nausea, and eye, nose, and throat irritation. The present study compared 12 individuals selected based on self-report of symptoms (self-reported sensitives; SRSs) associated with MTBE to 19 controls without self-reported sensitivities. In a double-blind, repeated measures, controlled exposure, subjects were exposed for 15 min to clean air, gasoline, gasoline with 11% MTBE, and gasoline with 15% MTBE. Symptoms, odor ratings, neurobehavioral performance on a task of driving simulation, and psychophysiologic responses (heart and respiration rate, end-tidal CO(2), finger pulse volume, electromyograph, finger temperature) were measured before, during, and immediately after exposure. Relative to controls, SRSs reported significantly more total symptoms when exposed to gasoline with 15% MTBE than when exposed to gasoline with 11% MTBE or to clean air. However, these differences in symptoms were not accompanied by significant differences in neurobehavioral performance or psychophysiologic responses. No significant differences in symptoms or neurobehavioral or psychophysiologic responses were observed when exposure to gasoline with 11% MTBE was compared to clean air or to gasoline. Thus, the present study, although showing increased total symptoms among SRSs when exposed to gasoline with 15% MTBE, did not support a dose-response relationship for MTBE exposure nor the symptom specificity associated with MTBE in epidemiologic studies.

Adult↗

Psychiatric diagnoses in Gulf War veterans with fatiguing illness.

The purpose of this study was to determine whether Gulf War Illness (GWI) can be explained by the presence of psychiatric disorders as assessed by DSM-III-R. To reduce the heterogeneity amongst Persian Gulf War veterans with GWI (PGV-F), only those were studied who presented with severe fatigue as a major complaint and also fulfilled clinical case definitions for Chronic Fatigue Syndrome, Idiopathic Chronic Fatigue, and/or Multiple Chemical Sensitivity. A total of 95 Registry PGVs were examined; 53 presented with GWI and 42 did not report any post-war health problems (PGV-H). All subjects were assessed for the presence of DSM-III-R Axis I psychiatric disorders. Compared to PGV-Hs, 49% of PGV-Fs had similar post-war psychiatric profiles: either no, or only one, psychiatric disorder was diagnosed. Psychiatric profiles of the remaining 51% of PGV-Fs were significantly different from PGV-Hs in that most of these veterans suffered from multiple post-war psychiatric diagnoses. The presence of psychiatric disorders as assessed by DSM-III-R criteria cannot explain symptoms of Gulf War Illness among all Persian Gulf veterans with severe fatiguing illness.

Adult↗

Neuropsychological and stress evaluation of a residential mercury exposure.

Residents of a former factory building converted to apartments were exposed to mercury over a 2-year period. The neurobehavioral and emotional health effects of this exposure and subsequent evacuation are presented. Urine mercury levels were measured before (urine1) and 3-10 weeks after evacuation (urine2) of the building, when neurobehavioral and psychological measures were also completed. Performance on neurobehavioral and psychologic measures were compared between subjects above and below the median for urine1 (>=19 microg/g creatinine) and were correlated with urine1 mercury levels. The high urine mercury group made more errors on a test of fine motor function and 84% of the residents reported clinically significant elevations in somatic and psychologic symptoms. Although subclinical tremor from mercury exposure may have affected subtle hand-eye coordination, other tests of motor function were not affected. Therefore, the observation of reduced hand-eye coordination may be due to chance. Significant levels of psychosocial stress were more closely associated with the evacuation necessitated by mercury exposure rather than a direct effect of mercury exposure.

Adult↗

Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity.

The purpose of this study was to determine if Gulf War veterans with complaints of severe fatigue and/or chemical sensitivity (n = 72) fulfill case definitions for chronic fatigue syndrome (CFS) and/or multiple chemical sensitivity (MCS) and to compare the characteristics of those veterans who received a diagnosis of CFS (n = 24) to a group of non-veterans diagnosed with CFS (n = 95). Thirty-three veterans received a diagnosis of CFS with 14 having MCS concurrently; an additional six had MCS but did not fulfill a case definition for CFS. The group of fatigued veterans receiving a diagnosis of CFS was comprised of significantly fewer women and fewer Caucasians than the civilian group, and significantly fewer veterans reported a sudden onset to their illness. Veterans with CFS had a milder form of the illness than their civilian counterparts based on medical examiner assessment of the severity of the symptoms, reported days of reduced activity, and ability to work. Since CFS in veterans seems less severe than that seen in civilians, the prognosis for recovery of veterans with this disorder may be better.

Environmental Exposure↗

Long-term use of organophosphates and neuropsychological performance.

This study evaluated neuropsychological effects due to chronic organophosphate use among farmers with no history of acute poisoning. Fifty-seven male tree fruit farmers (exposed) were compared with 42 age-matched male cranberry/blueberry growers and hardware store owners (unexposed). Univariate analyses of covariance (reading test as covariate) comparing exposed and unexposed subjects revealed significantly slower reaction time. No other significant differences were noted on tests of concentration, visuomotor skills, memory, expressive language, or mood. Based on an exposure metric derived from detailed exposure histories, farmers were divided into high exposure (n = 40) and low exposure (n = 59) groups, and their neuropsychological performance was compared. Analysis of covariance with age and reading test score as covariates revealed that the high exposure group had significantly slower reaction time, dominant hand. Long-term use of organophosphates without evidence of an acute poisoning episode appears to produce, at most, subtle changes in neuropsychological performance.

Adult↗

Chemical sensitivity: the scientific literature.

This article provides an overview of the scientific literature in which chemically sensitive patients have been directly evaluated. For that purpose, consideration of various case definitions is offered along with summaries of subjects' demographic profiles, exposure characteristics, and symptom profiles across studies. Controlled investigations of chemically sensitive subjects without other organic illnesses are reviewed. To date, psychiatric, personality, cognitive/neurologic, immunologic, and olfactory studies have been conducted comparing subjects with primary chemical sensitivity to various control groups. Thus far, the most consistent finding is that chemically sensitive patients have a higher rate of psychiatric disorders across studies and relative to diverse comparison groups. However, since these studies are cross-sectional, causality cannot be implied. Demonstrating the role of low-level chemical exposure in a controlled environment has yet to be undertaken with this patient group and is crucial to the understanding of this phenomenon.

Environmental Health↗

Chemical sensitivities and the Gulf War: Department of Veterans Affairs Research Center in basic and clinical science studies of environmental hazards.

The purpose of the New Jersey Center for Environmental Hazards Research is to define the illness referred to as Persian Gulf Syndrome (PGS). Our preliminary data indicated that more than half of the Persian Gulf Registry (PGR) veterans reported illness characterized by severe fatigue and symptoms consistent with chemical sensitivities. Therefore, our research approach focuses on investigations of veterans with chronic fatigue syndrome (CFS) and multiple chemical sensitivities (MCS). Project 1 is an epidemiological study of 2800 PGR veterans. Symptoms, indices of Chronic Fatigue (CF) and Chemical Sensitivity (CS), and risk factors will be surveyed with mailed questionnaires. Risk factors include demographics, past medical history, psychosocial variables, Gulf War experiences such as prophylactic medication use, occupational and environmental exposures, and pesticide exposures. Symptoms will be clustered to define Gulf War Syndromes. Significant associations between risk factors and these symptom clusters will also be investigated Subjects identified as CF, CS, or both will be recruited into Projects 2 and 3. In Project 2, healthy veterans will be compared to veterans with CF, CS, and CF concurrent with CS. Veterans will undergo four studies: (1) viral-immunological, (2) psychiatric, psychological, behavioral, and neuropsychological, (3) autonomic dysregulation, and (4) marker of P4501A2 induction resulting from exposure to combusting material. The purpose of Project 3 is to test the autonomic, immunologic, neuropsychologic, and psychologic responses of veterans with CS or CF to two stressors: controlled chemical exposure and exercise. CS subjects will undergo chemical exposures in our Controlled Environment Facility (CEF) to assess their biologic and psychologic response to low-level exposure. CF subjects will undergo a maximal treadmill exercise test. Circadian patterns of catecholamines and axillary temperature, viral burden, and cardiovascular and endocrine reactivity will be measured in response to this physical stressor. Project 4 is an animal study evaluating the interaction between stress and pathology/physiology when rats are predisposed to disease by exposure to Soman or to Dioxin. Two strains of rats that differ in stress reactivity will be used to determine the interaction of hereditary factors and chemical exposure.

Comorbidity↗

The assessment of neurobehavioral toxicity: SGOMSEC joint report.

Exposure to neurobehavioral toxicants is a problem of international scope. Although many different procedures are available for the assessment of human behavioral function, performance tests are displacing traditional diagnostic tests for ascertaining the consequences of exposure to neurotoxic chemicals. Performance testing includes variables such as attention and concentration, sensory function, motor control, spatial relations, visuomotor coordination, memory, and affect. Special tests have also been devised for evaluating child development. One of the salient needs in these efforts is the construction of databases allowing access to normative data.

Adult↗