John E. Ottenweller

Responses to controlled diesel vapor exposure among chemically sensitive Gulf War veterans

Objective: A significant proportion of Gulf War veterans (GWVs) report chemical sensitivity, fatigue, and unexplained symptoms resulting in ongoing disability. GWVs frequently recall an association between diesel and petrochemical fume exposure and symptoms during service. The purpose of the present study among GWVs was to evaluate the immediate health effects of acute exposure to chemicals (diesel vapors with acetaldehyde) with and without stress. Methods: In a single, controlled exposure to 5 parts per million (ppm) diesel vapors, symptoms, odor ratings, neurobehavioral performance, and psychophysiologic responses of 12 ill GWVs (GWV-I) were compared with 19 age- and gender-matched healthy GWVs (GWV-H). Results: Relative to baseline and to GWV-H, GWV-I reported significantly increased symptoms such as disorientation and dizziness and displayed significantly reduced end-tidal CO2 just after the onset of exposure. As exposure increased over time, GWV-I relative to GWV-H reported significantly increased symptoms of respiratory discomfort and general malaise. GWV-I were also physiologically hyporeactive in response to behavioral tasks administered during but not before exposure. Conclusions: Current symptoms among GWV-I may be exacerbated by ongoing environmental chemical exposures reminiscent of the Gulf War. Both psychologic and physiologic mechanisms contribute to current symptomatic responses of GWV-I.

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.

Stress triggers different pathophysiological mechanisms in younger and older cardiomyopathic hamsters

OBJECTIVES Because cardiomyopathic hamsters (CMHs) in the lesion-forming period of their disease are more susceptible to the lethal effects of stress than older CMHs, we tested the hypothesis that different pathophysiological effects of stress may occur: coronary vasospasm in younger CMHs and congestive heart failure in older ones. METHODS CMHs aged 2.5 and 6.5 months were stressed with 2 h supine cold immobilization for 5 consecutive days. Three, 5 and 7 days after stress, the hearts were excised and perfused using a modified Langendorff system. Maximum +/- dP/dt, developed pressure, ventricular relaxation time (Tau) and coronary vascular resistance (CVR) were recorded and CVR was also measured following coronary infusion of arginine vasopressin (AVP). RESULTS Stress produced ventricular dysfunction (decreased maximum +/- dP/dt, developed pressure, and increased Tau) in older CMHs (P < 0.05) but not in younger CMHs. Baseline CVR in younger CMHs was significantly higher than in older CMHs (P < 0.01) and AVP infusion produced a bigger increase in CVR in younger stressed CMHs than in either younger nonstressed or older stressed CMHs (P < 0.05). CONCLUSION The younger CMH heart exhibits greater resting vascular tone and stress produces coronary vasoconstriction that is consistent with coronary spasm. In contrast, the older CMH experiences a decrease in cardiac function which remains 7 days after stress and indicates an exacerbation of CHF from the mild form existing prior to stress. The lethal effects of stress may occur because of the activation of different pathological processes in younger and older CMHs.

Daily rhythm of plasma corticosterone binding activity in the white-throated sparrow, Zonotrichiaalbicollis

Abstract There is a bimodal daily rhythm of plasma corticosterone binding activity (CBA) in the white-throated sparrow, Zonotrichia albicollis , in the spring migratory condition. Low levels occurred at the beginning (0500) and at the end (2100) of a 16-hour daily photoperiod. Peak CBA occurred at 0900 and 0100, as did peak locomotor activity in this nocturnal migrant. Comparisons of CBA with total plasma corticosteroid concentrations from a previous study of the same group of birds indicate a positive correlation during most of the day but not during the early hours of darkness. The daily rhythm of locomotor activity may account for the rhythm of CBA which, in turn, may be partially responsible for the daily rhythm of plasma corticosteroid concentration.

Persistent Hormonal Effects of Stress Are Not Due to Reduced Food Intake or Exposure to Stressed Rats

Exposure to inescapable stress elicits persistent effects on the physiology and behavior of rats. Elevated basal plasma corticosterone concentrations have been observed for several days after cessation of stress. In this study, we measured hormonal concentrations in multiple axes at multiple levels, 24 h after one or three consecutive exposures to the same stress paradigm. The data indicated persistent activation of plasma corticosterone and prolactin concentrations, whereas plasma triiodothyronine, thyroxine, luteinizing hormone, and growth hormone concentrations were inhibited after either one or three stress sessions. In addition, we isolated the effects of restraint/tail shock per se from the effects of being moved and exposed to other stressed rats, and from the effects of reduced feeding produced by our stress protocol. The data clearly indicated that the stress paradigm, rather than exposure to stressed rats or decreased nutrient intake, is necessary to induce the persistent physiologic changes we observe after stressor exposures.

Chronic Fatigue and Sexual Dysfunction in Female Gulf War Veterans

Chronic fatigue (CF) is one of the most common conditions reported by Gulf War veterans. This study evaluated female sexual dysfunction (FSD) in veterans with or without complaints of CF. Subjects were screened for medical and psychiatric causes of CF. They included 22 healthy subjects and 26 with fatiguing symptoms. FSD was reported by 10% of controls and by 60% of the fatigued ( p < .002) while 19% versus 81% ( p < .001) noted decreased libido. FSD was more prevalent in fatigued veterans than in the controls. This relationship was not mediated by an Axis I diagnosis. This appears to be the first report of sexual dysfunction in CF.

Effect of stress and food restriction on blood pressure and lifespan of Dahl salt-sensitive rats

Objective: To evaluate the long‐term consequences of stress in rats with genetic hypertension. Design: Rapp‐Dahl salt‐sensitive rats, maintained on a low‐salt diet, were stressed periodically over 8 weeks during which time their blood pressures were measured. In experiment 1 both stressed and unstressed control rats were given ad libitum access to food. Because of significant differences in body weights, in experiment 2 the unstressed controls were pair‐fed to maintain their food intake at a level similar to that of the stressed rats. Methods: Rats were subjected to 2‐h sessions of supine immobilization stress 5 days a week every other week for 8 weeks. Blood pressures were measured during non‐stress weeks, at least 4 days after the last exposure to the stressor and at monthly intervals thereafter. Survival curves were also established. Results: In experiment 1 stressed rats developed hypertension at a slower rate than controls and lived significantly longer, but also weighed significantly less than controls, presumably because of diminished food intake. In experiment 2, in which food intake was controlled, body weights were similar in the two groups of rats, and hypertension developed at the same rate in both groups. Survival curves were not significantly different. Food restriction extended life compared with free feeding. Conclusions: Stress need not have long‐term, deleterious health consequences in rats with genetically inherited hypertension, whereas caloric restriction is protective.

Sex Differences in Plasma Prolactin Response to Tryptophan in Chronic Fatigue Syndrome Patients With and Without Comorbid Fibromyalgia

BACKGROUND Some think chronic fatigue syndrome (CFS) and fibromyalgia (FM) are variants of the same illness process. This would imply that CFS patients with and without comorbid FM have similar biological underpinnings. To test this, we compared serotonergic-based responses, plasma prolactin (PRL), and self-reported measures of fatigue to intravenous infusion of tryptophan among patients with CFS alone, CFS + FM, and healthy controls. METHODS Men and women with CFS alone or CFS + FM and healthy subjects, none with current major depressive disorder (MDD), were given 120 mg of L-tryptophan per kg lean body mass intravenously (i.v.). Before and after tryptophan infusion, blood samples were collected, and plasma PRL, tryptophan, and kynurenine concentrations were determined. RESULTS Women with CFS alone, but not CFS + FM, showed upregulated plasma PRL responses compared with controls. There were no differences among groups of men. Plasma tryptophan and kynurenine concentrations did not differ among groups. CONCLUSIONS These results indicate that women with CFS alone have upregulated serotonergic tone that is not seen in those with comorbid FM. The lack of effect in men suggests a mechanism that might explain, in part, the increased prevalence of CFS in women. The data support the interpretation that CFS in women is a different illness from FM.

THE ROLE OF STRESSOR INTENSITY AND UNDERLYING VASCULOPATHY IN ALTERING CORONARY REACTIVITY IN CARDIOMYOPATHIC HAMSTERS

Objective Our previous work showed that stress sensitized the vessels of cardiomyopathic hamsters (CMHs), but only hamsters in the lesion-forming period of their life. We hypothesized that we would find an interaction between stressor intensity and microvascular vulnerability. Method Male CMHs at ages of 1.5, 2.5, and 3.5 months were stressed with supine immobilization for five consecutive days. Stressor intensity was manipulated by immobilizing groups of CMHs at room temperature for 0 minutes, 15 minutes, 30 minutes, 1 hour, or 2 hours. CMHs were anesthetized and sacrificed 5 days after stress, and their hearts were perfused using a modified Langendorff system. Body weight changes and baseline coronary vascular resistance (CVR) were recorded, and CVR was also measured after coronary artery infusion of arginine vasopressin (AVP). Results Stress produced no effect on coronary vasculature in 1.5-month-old CMHs. In 2.5-month-old CMHs, only the two highest-intensity stressors enhanced coronary reactivity to AVP. In 3.5-month-old CMHs, higher-intensity stressors produced a marginal AVP-induced increase in CVR; but this marginal increase was significantly lower than the increases seen with the two highest-stressor intensities in the 2.5-month-old CMHs. Conclusion The stress-induced coronary hyperreactivity to AVP seen in 2.5-month-old CMHs diminished when microvascular vulnerability was lower in 3.5-month-old CMHs. For 1.5-month-old CMHs, the resting CVR was extremely high, so that the addition of stress produced no further increase. Thus, stressor intensity interacted with microvascular vulnerability to alter the consequences of stress.