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Objective Two groups of Gulf War era veterans, one exhibiting blurred vision, balance problems/dizziness, tremors/shaking, and speech difficulty and a second group with post-traumatic stress disorder (PTSD), but not the neurologic syndrome, were assessed for organophosphate-detoxifying enzyme paraoxonase/arylesterase (PON1) and its Q/R isoforms, butyrylcholinesterase (BuChE) and its U/A isoforms and cytokines. Methods Defibrinated peripheral blood was evaluated for enzymes and cytokines. Results Trends toward elevation of Th2 cytokines interleukin-4 (IL-4) and IL-13 were observed in subjects with neurologic syndrome. Neither the activities nor isoforms of the enzyme, the neurologic symptoms, nor PTSD had any relationship to wartime deployment to the theater of combat. Conclusion The negative outcomes described above suggest that exposure to organophosphates or other agents normally detoxified by PON1 and BuChE may not have contributed significantly to neurologic components of Gulf War Illness.

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.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.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.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.

We examined the pattern of cytokine secretion across the 24-hr day for women with widespread pain and tenderness having the diagnosis of fibromyalgia (FM) and matched healthy controls. Subjects were given time to habituate to being in a clinical research laboratory environment and then were sampled for cytokines without their being disturbed for a 24-hr period including an 8-hr sleep period. Cytokine levels were uniformly low but characterized by bursts of secretion. Bursting occurred either in singlets or in doublets with a range from 88 to 131 mins between doublet bursts. There was an element of synchronization of these bursts with most occurring at the beginning of sampling. FM patients showed a shift to increased IL-10 in the nighttime compared to controls. The relation between this anti-inflammatory cytokine to the pro-inflammatory cytokines studied also differed between groups: FM patients showed an increased ratio of IL-10 burst amplitude to that of pro-inflammatory cytokines IL-1β, IL-8, and TNF-α. We interpret this to indicate a skew away from the normal balance favoring pro-inflammatory cytokines in controls toward one favoring an anti-inflammatory response in FM. These changes toward anti-inflammatory predominance in FM may explain their common complaint of disturbed sleep because these cytokines are known to disrupt sleep.

In our present study we tested the health effects among women of controlled exposures to volatile organic compounds (VOCs), with and without ozone (O3), and psychological stress. Each subject was exposed to the following three conditions at 1-week intervals (within-subject factor): VOCs (26 mg/m3), VOCs + O3 (26 mg/m3 + 40 ppb), and ambient air with a 1-min spike of VOCs (2.5 mg/m3). As a between-subjects factor, half the subjects were randomly assigned to perform a stressor. Subjects were 130 healthy women (mean age, 27.2 years; mean education, 15.2 years). Health effects measured before, during, and after each 140-min exposure included symptoms, neurobehavioral performance, salivary cortisol, and lung function. Mixing VOCs with O3 was shown to produce irritating compounds including aldehydes, hydrogen peroxide, organic acids, secondary organic aerosols, and ultrafine particles (particulate matter with aerodynamic diameter < 0.1 microm). Exposure to VOCs with and without O3 did not result in significant subjective or objective health effects. Psychological stress significantly increased salivary cortisol and symptoms of anxiety regardless of exposure condition. Neither lung function nor neurobehavioral performance was compromised by exposure to VOCs or VOCs + O3. Although numerous epidemiologic studies suggest that symptoms are significantly increased among workers in buildings with poor ventilation and mixtures of VOCs, our acute exposure study was not consistent with these epidemiologic findings. Stress appears to be a more significant factor than chemical exposures in affecting some of the health end points measured in our present study.

Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls. Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having comorbid depression than those with normal fluid. In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls. The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.

Vaginocervical stimulation (VS) significantly elevated the concentration of oxytocin (OT) in spinal cord superfusates of 8 intact urethane-anesthetized rats measured 10–15 min after VS (median [interquartile range]: 1.7 [1.00–3.37] pg/ml) compared to that measured 10–15 min before VS (1.1 [1.01–1.40] pg/ml). When VS was administered once (n = 8), it produced a 55% increase over baseline values; when administered a second time 45 min later (n = 6), it produced only a 22% increase over pre-VS values. The effects of estrogen on the VS-induced release of OT were then investigated using ovariectomized rats that were treated either with estradiol benzoate (EB; 10 µg/100 g bw) (n = 6) or with an oil vehicle (n = 6) subcutaneously for 3 days. The EB treatment significantly elevated the basal levels of OT released into spinal cord superfusates above vehicle control levels. Within 5–10 min after the onset of VS, OT concentrations in the superfusates were significantly higher in EB-treated than in vehicle-treated rats. The vehicle-treated rats did not show a significant elevation in OT concentration following VS. To rule out the possibility that the posterior pituitary gland was the source of this OT, the effect of hypophysectomy (HYPOX) was assessed on the VS-induced release of OT into spinal cord superfusates and plasma. The concentration of OT in spinal cord superfusates of both the HYPOX (n = 5) and intact rats (n = 6) increased significantly from 5.8 [4.4–6.5] pg/ml pre-VS to 7.9 [6.7–10.3] pg/ml immediately after VS, and from 4.4 [3.8–5] pg/ml pre-VS to 5.1 [4.6–5.7] pg/ml immediately after VS, respectively. There was no significant difference in baseline levels of OT in cerebrospinal fluid between the two groups. By contrast, plasma OT levels, while significantly elevated in response to VS from 3.42 [2.9–5.34] pg/ml baseline to 7.25 [5.33–15.77] pg/ml in the intact group, failed to respond significantly to VS in the HYPOX group (n = 5). The present findings provide evidence of a direct estrogen-dependent release of OT within the spinal cord in response to VS, presumably via descending oxytocinergic neurons.

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.

Elevated basal plasma corticosterone concentrations have been observed for several days after the cessation of severe stress. In the present study, we examined whether or not the acute plasma corticosterone response to stress is necessary to elicit increased basal plasma corticosterone concentrations the following day. Pretreatment with metyrapone (100 mg/kg, intraperitoneal) 1 h before inescapable stress (40 2mA tailshocks delivered over a 1-h period) (IS) blocked the acute plasma corticosterone response to IS. However, elevated basal plasma corticosterone concentrations still emerged the next day. These results suggest that the corticosterone response to stress, and its attendant feedback, are not necessary to produce persistent hypothalamic-pituitary-adrenal axis (HPAA) activation.

Exposure of rats to inescapable stressors (IS) results in persistent elevations in plasma corticosterone (CORT), which are selective to the trough of the circadian rhythm. Although affective disorders (depression, anxiety) in humans are also characterized by persistent hypothalamic-pituitary-adrenal axis (HPAA) activation, the predominant measure of HPAA activation in clinical studies is 24-h urinary cortisol. To facilitate interspecies comparisons regarding the persistent effects of stress on HPAA activity, we compared the effects of IS on plasma and urinary CORT in rats. Male Sprague-Dawley rats were exposed to three 2-h sessions of IS (40, 2.0 mA tailshocks) or remained in their home cages. The 24-h urine samples were collected daily from 2 days prior to stress to 5 days after stressor cessation, then weekly for 3 weeks. In addition, plasma samples were obtained at 08:00 (trough) and 20:00 hours (peak) for the first 3 days after stressor cessation and weekly for 3 weeks thereafter. Consistent with our earlier work, plasma CORT elevations were apparent in the trough, but not the peak samples for 3 days after stressor cessation. The 24-h urinary CORT levels were elevated during stressor exposure, and remained elevated for 3 days after stressor cessation. Persistent stress-induced urinary CORT elevations in rats are reminiscent of the clinical HPAA abnormalities described for major depression and affective disorders.

The detrimental effects of spinal cord injury (SCI) on spermatogenesis in the rat can be attenuated by exogenous testosterone (T) but enhanced by exogenous follicle-stimulating hormone (FSH). These results suggest that T-dependent cellular events may be involved in testicular injury after SCI and that such events may be associated with modification of FSH effects on Sertoli cell function. The current study compared the responses of Sertoli cells to exogenous T and FSH after SCI or sham surgery using steady-state levels of Sertoli cell protein mRNA transcripts as markers of responsiveness. Rats underwent sham surgery or SCI and then were treated for 7 or 14 days with T-filled silastic capsules (2 × 5 cm) and/or daily injections of 0.1 units of porcine FSH. Vehicle-treated control rats received 5-cm empty capsules and daily injections of saline vehicle. Two weeks after sham surgery, levels of mRNA for the androgen receptor (AR), FSH receptor (FSHR), androgen-binding protein (ABP), or sulfated glyco...

Objective The objective of this study was to examine whether inappropriate cardiovascular responses to stressors may underlie symptoms in Gulf War veterans with chronic fatigue. Methods Psychophysiological stress testing was performed on 51 Gulf War veterans with chronic fatigue (using the 1994 case definition of the Centers for Disease Control and Prevention) and 42 healthy veterans. Hemodynamic responses to cold pressor, speech, and arithmetic stressors were evaluated using impedance cardiography. Results Veterans with chronic fatigue had diminished blood pressure responses during cognitive (speech and arithmetic) stress tests due to unusually small increases in total peripheral resistance. The cold pressor test, however, evoked similar blood pressure responses in the chronic fatigue and control groups. Low reactivity to cognitive stressors was associated with greater fatigue ratings among ill veterans, whereas an opposite relation was observed among healthy veterans. Self-reported neurocognitive decline was associated with low reactivity to the arithmetic task. Conclusions These results suggest a physiological basis for some Gulf War veterans' reports of severe chronic fatigue. A greater deficit with responses processed through cerebral centers, as compared with a sensory stimulus (cold pressor), suggests a defect in cortical control of cardiovascular function. More research is needed to determine the specific mechanisms through which the dissociation between behavioral and cardiovascular activities identified in this study may be contributing to symptoms in Gulf War veterans.

Pyridostigmine bromide (PB) is a reversible, peripherally active inhibitor of acetylcholinesterase (AChE) activity, and is recommended by the military as a pretreatment against potential nerve gas exposure. Recent evidence suggests that exposure to inescapable stressors allows PB to cross the blood–brain barrier, and thereby affect central AChE activity in mice. Here, we evaluated the functional impact of a stress/PB treatment interaction on acoustic startle responding and plasma butyrylcholinesterase (BuChE) activity in male Sprague–Dawley rats. To model the treatment protocol used by the military, PB was delivered in the drinking water of rats for 7 consecutive days. The morning after the start of PB treatment, and for the next 6 days, half the rats were exposed to 1 h of supine restraint stress. We therefore employed a 2 × 2 (stress × PB treatment) between-groups design. Exposure to supine stress alone induced a persistent decrease in plasma BuChE activity. Further decreases in BuChE activity were not observed in rats exposed to supine restraint and PB treatment. Exposure to stress also induced an exaggerated startle response, evident on the last day of stress and 24 h after stressor cessation. Treatment with PB alone produced an exaggerated startle response over the same time period, albeit to a lesser degree. Although treatment with PB concurrent with stress did not produce further changes in either BuChE activity or acoustic startle responding, stress-induced alterations in drinking behavior (and thereby the dose of PB ingested) may have affected these results. Persistent stress-induced reductions in BuChE activity may increase the risk of adverse reactions to cholinomimetics.

Many researchers have studied acute responses to stress in animals and how they are modified by prior stressor exposure, but relatively few have examined whether responses to stressors might last for prolonged periods of time. We have previously demonstrated that trough plasma corticosterone levels in rats are elevated for three to five days after single or repeated exposures to mild restraint and inescapable tailshock. The current study measured other aspects of the adrenal axis, and activity in other neuroendocrine systems, 24 hours after one or three consecutive exposures to the same stress paradigm. The data indicated persistent activation of the adrenal axis and prolactin levels, whereas the thyroid and reproductive hormone axes were inhibited after either one or three stress sessions. These changes are remarkable in that one would have expected acute responses to even intense stressors to have ended within hours after the end of the stressor. It will be important to understand the interactions among these responding neuroendocrine systems and to know how long such persistent changes last. Finally, it will be critical to understand the relative contributions of neuroendocrine and psychological factors in maintaining these persistent neuroendocrine changes after exposure to intense stressors.

The study assessed peripheral sensory function and its relation to self-reported wartime exposures to potentially neurotoxic substances in Gulf War veterans with chronic fatigue syndrome (CFS). Male Gulf veterans fulfilling the 1994 CDC diagnostic criteria for CFS were compared with matched controls. Quantitative sensory testing was performed to establish thresholds of perception for the sense of light touch and radiant heat. The Devens survey was used to collect data on self-reported exposures to by-products of combustion and organophosphate compounds. Gulf veterans with CFS had elevated tactile but normal thermal thresholds compared with their controls. Sick veterans had greater rates of self-reported exposures and/or noxious side effects for all assessed toxicants. Interestingly, both Gulf veteran groups, including those reporting no symptoms, had impaired perception of light touch when compared with age-matched samples of non-Gulf war veteran men. The results of this study are consistent with a hypothesis that Gulf veterans with CFS have a subtle neurological deficit that might reflect underlying peripheral neuropathy. The association between this deficit and self-report of multiple potentially neurotoxic exposures suggests that war zone pollutants may be possible contributing factors. Copyright © 1999 John Wiley & Sons, Ltd.

Background: Some research immunologists have suggested that major depression amd chronic fatigue syndrome (CFS) are characterized by immune activation. To test this hypothesis, we compared immunological function in patients with major depression and in patients with CFS who developed major depression after the onset of CFS to that of sedentary healthy controls. Methods: Subjects completed the Centers for Epidemiological Study–Depression (CES-D) questionnaire and allowed venisection. We performed flow cytometric analysis on 13 groups of white blood cells and used a reverse transcriptase PCR method to assay m-RNA of eight cytokines. Results: CES-D scores were high in both patient groups and did not differ significantly. We found no evidence for immune activation in either patient group. Instead the data suggested immunological downregulation in depression. Limitations: Not all the subjects in the two patient groups were off antidepressants. Conclusions: The data indicate that immune activation is not necessary in depression—either alone or with CFS.

The study was an examination of the effects of spinal cord injury (SCI) on spermatogenesis and Sertoli cell functions in adult rats with Sertoli cell-enriched (SCE) testes. The effects of SCI on the seminiferous epithelium were characterized by abnormalities in the remaining spermatogenic cells during the first month after SCI. Three days after SCI, serum testosterone levels were 80% lower, while serum FSH and LH levels were 25% and 50% higher, respectively, than those of sham control SCE rats. At this time, the levels of mRNA for androgen receptor (AR), FSH receptor (FSH-R), and androgen-binding protein (ABP) were normal whereas those for transferrin (Trf) had decreased by 40%. Thereafter, serum testosterone levels increased, but they remained lower than those of the sham control rats 28 days after SCI; and serum FSH and LH levels returned to normal. The levels of mRNA for AR, ABP, and Trf exhibited a biphasic increase 7 days after SCI and remained elevated 28 days after SCI. FSH-R mRNA levels were also elevated 90 days after SCI. Unexpectedly, active spermatogenesis, including qualitatively complete spermatogenesis, persisted in > 40% of the tubules 90 days after SCI. These results suggest that the stem cells and/or undifferentiated spermatogonia in SCE testes are less susceptible to the deleterious effects of SCI than the normal testes and that they were able to proliferate and differentiate after SCI. The presence of elevated levels of mRNA for Sertoli cell FSH-R and AR, as well as of that for the Sertoli cell proteins, in the SCE testes during the chronic stage of SCI suggests a modification of Sertoli cell physiology. Such changes in Sertoli cell functions may provide a beneficial environment for the proliferation of the stem cells and differentiation of postmeiotic cells, thus resulting in the persistence of spermatogenesis in these testes.

Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats. Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 25-30%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.

This study was conducted to evaluate the immunological response to an exhaustive treadmill exercise test in 20 female chronic fatigue syndrome patients compared to 14 matched sedentary controls. Venipuncture was performed at baseline and 4 min, 1 hr, and 24 hr postexercise. White blood cells were labeled for monoclonal antibody combinations and were quantified by FACsan. Cytokines were assayed utilizing quantitative RT/PCR. No group difference was seen in VO2peak (28.6 +/- 1.6 vs 30.9 +/- 1.2 ml.kg-1.min-1; P > 0.05). However, 24 hr after exercise the patients' fatigue levels were significantly increased (P 0.05). The immune response of chronic fatigue syndrome patients to exhaustive exercise is not significantly different from that of healthy nonphysically active controls.

Chronic fatigue syndrome, which can occur after acute infection and last for years, is characterized by severe and persistent fatigue. Others have reported decreases in mouse running activity following infection and have suggested this may provide an animal model for studying chronic fatigue. Voluntary running is a highly motivated activity in mice, which will often run 5–7 mi/day in our laboratory. Following 2 weeks of acclimation to running wheels with food and water available ad lib, female BALB/c mice received 0.2-mL tail vein injections of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on voluntary running and grooming behavior were determined. Injection of BA caused an immediate large decrease in running and a lack of grooming. Vehicle injections produced no changes in behavior. After the first several days of reduced running behavior, levels of running and grooming slowly returned back to normal over the next 2–4 weeks, with substantial individual differences in the rate of recovery. The pattern of running during recovery was intriguing in that BA mice first ran at normal levels just after the lights went out, but they stopped after only 1–2 h. As recovery proceeded, they gradually increased the duration of the running bout during the night. Because this model uses voluntary exertion and the ability to run for longer periods of time characterizes recovery, the model may be a good one for studying the biologic underpinnings of chronic fatigue.

Cardiomyopathic hamsters (CMH) develop heart disease early in life which leads to congestive heart failure and death as these hamsters age. We have previously shown that living in constant light or other non-24-h light-dark (LD) cycles can increase longevity in these hamsters, and the current experiment examined potential mechanisms for this effect. Thus, CMH were orchidectomized, pinealectomized, or given melatonin treatment and then placed on either 1:23 or 1:23.6 LD cycles. Orchidectomy had no effect on longevity in either LD cycle, but in 1:23.6 it did lead to death with a greater degree of heart failure. On the other hand, pinealectomy of 1:23 CMH led to changes in life span similar to those produced by placing the hamsters in 1:23.6. Moreover, melatonin implant treatment of CMH in 1:23.6 led to changes in life span that were similar to those caused by life in 1:23, at least over the first half of the survival curves. Thus, it appears that the pineal gland and melatonin may be involved in mediating the effects of non-24-h LD cycles, whether these effects are beneficial or detrimental. In addition, the testes and testosterone appear to have no role in mediating these effects. These data suggest that inhibition, rather than stimulation, of pineal function might be beneficial for those with congestive heart failure, but further experiments are necessary to clarify when during the disease process potential treatments might be helpful.

We have shown that constant light (LL) extends life in hamsters with progressive congestive heart failure (CHF). Since stress impairs ventricular function, we hypothesized that life in LL would protect the hamster from the stress induced exacerbation of failure. Cardiomyopathic hamsters (CMHs) at the age of 2 mo were put into LL or Light:Dark 12h: 12h (LD). A second set of CMHs was received 4 mo later and also split into the 2 lighting conditions. When hamsters were either 6 or 10 mo of age, half were stressed with 2 hr supine cold immobilization for 5 consecutive days, and the other half served as nonstressed controls. In vitro evaluation of ventricular mechanics was done 5 days after stress and revealed that stress decreased ventricular systolic and diastolic function in LD groups but not in LL groups; the effect was most robust in the 6 mo hamsters. The cardiac ventricles of hamsters living in LD became heavier when the hamster aged from 6 mo to 10 mo; this is indicative of the progression of CHF. Life...

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.

For 5 days, rats were exposed to shocks that were signalled by a light 0, 33, 66, or 100% of the time. Basal hormone levels and responses to a light-shock pair were measured daily. Greater predictability was associated with higher basal plasma corticosterone and norepinephrine levels indicative of chronic stress. Habituation of the corticosterone response was also less in the groups with greater predictability. However, predictability did not affect plasma prolactin or epinephrine responses. Because the endocrine systems responded differently, it is unlikely that the changes were due to a unitary process. Greater predictability appeared to be more stressful in this paradigm. Both associative and nonassociative factors have major roles in determining the hormonal responses to repeated presentation of stressors.

The present study has combined recording of circadian locomotor rhythms with light microscopic immunocytochemistry for vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus (SCN) of congenitally anophthalmic mice. These mice, which never develop retinae or optic nerves and do not perceive light, are thus in constant darkness. Our data show a circadian rhythm in expression of VIP in the SCN of anophthalmic mice — expression is maximal during late subjective night/early subjective day and minimal in late subjective day/early subjective night. These observations support the hypothesis that expression of VIP is related to regulation of circadian rhythms by the SCN.

Repeated exposures to a stressor in our rat model of a chronic stress state cause elevated plasma corticosterone levels in the morning for several days after the last stressor. However, plasma corticosterone levels are normally characterized by a circadian rhythm with low levels for much of the morning and higher levels near the onset of darkness. The current experiment examined the question of whether the elevated morning levels after stressor exposures were accompanied by other changes in this circadian rhythm. Male rats were given restraint-shock stressor sessions for 0, 1, or 3 days, after which plasma samples were collected for 3 days at 0900 h and at three other times around the circadian peak (1400, 1800, and 2200 h). Plasma corticosterone levels at 0900 h were elevated for the first 2 days after three stressor exposures and for 1 day after a single stressor exposure compared to those in nonstressed controls. However, levels at 1400, 1800, and 2200 h were not different in stressed and control rats on the first 2 days after stressor exposures. In addition, the amplitude of the corticosterone rhythm was suppressed after three stressor exposures, but not after one. This decease in amplitude was mostly due to increased morning levels, inasmuch as the evening levels were similar in stressed rats and controls. Because the hypothalamic-pituitary-adrenal axis is more sensitive to glucocorticoid feedback in the morning, our data suggest that the mechanisms mediating feedback at this time of day may be disrupted by repeated stressor exposures. However, when feedback sensitivity is lower in the evening, repeated stressor exposures had little or no effect on plasma corticosterone levels.

There has been no study comparing the efficacy of dobutamine and exercise echocardiography in detecting coronary artery disease (CAD) or their physiologic effects at ischemic threshold in the same group of patients. To accomplish this, 52 patients presenting for coronary angiography underwent supine ergometer exercise and dobutamine echocardiography. Compared with angiography, the overall sensitivity of detecting CAD was 78% for exercise and 86% for dobutamine echocardiography (p = NS). The sensitivities of detecting patients with 1-, 2-, 3- and multivessel CAD with exercise echocardiography were 63, 80, 100 and 90%, respectively, and with dobutamine echocardiography 75, 90, 100 and 95%, respectively (p = NS, exercise vs dobutamine). The specificity of both tests was 87%. At ischemic threshold, heart rate was significantly lower with dobutamine than with exercise echocardiography (91 +/- 3 vs 114 +/- 3 beats/min; p < 0.001), systolic blood pressure was significantly lower with dobutamine testing (155 +/- 5 vs 176 +/- 6 mm Hg; p < 0.01), and rate-pressure product was significantly lower with dobutamine stress (14.1 +/- 0.7 vs 19.8 +/- 0.8 x 10(3) beats/min x mm Hg; p < 0.001). It is concluded that the efficacy of detecting CAD by exercise and dobutamine echocardiography is comparable, and the physiology at ischemic threshold of the 2 methods is significantly different and suggests a different means of inducing myocardial ischemia.

Typically, stress-related elevations in rat plasma cholesterol (CHOL) require preexposure to diets high in fats or cholesterol and lengthy stressor protocols. We report on two studies in which we measured plasma CHOL 22-h postressor in rats fed Purina Laboratory Rodent Chow and exposed to 3 (3-day) or 1 (1-day) daily stressor sessions [40, 2 mA tailshocks]. In the first study, both the 3-day and 1-day groups exhibited moderately elevated morning plasma CHOL 22-h poststressor compared to nonshocked controls. Along with the groups in the first study, a second study included a restricted food control, rats transferred to the stressor environment, and rats simply transferred to an adjacent room. Neither restricted feeding nor the room transfers had an effect on morning plasma CHOL. However, the 3-day and 1-day groups again exhibited moderately elevated CHOL. Previous reports did not find elevated plasma CHOL in rats given a single stressor exposure when sampled at the end of the stressor session. Thus, the persistently elevated morning CHOL exhibited by the 1-day group may develop over time. The relatively slow development of plasma CHOL elevations may be related to the time course of stressor-induced thyroid suppression.

Our previous work has shown that constant light can prolong the life of hamsters with heart disease. Although we have seen this result several times, constant light was not protective in our most recent experiment. We undertook this study because we had changed some conditions. As in previous experiments, we found that life in constant light extended life for cardiomyopathic hamsters as compared with others living in a 12:12-hr light:dark environment. A second factor affecting survival was the number of hamsters in a group. Hamsters housed in groups of five lived longer than those housed in groups of two under the same lighting conditions. Data from one experiment suggested that a short photoperiod (6:18 light:dark) was also protective. Although these experiments indicate that the protective effects of different light:dark schedules are not simple ones, they are important because their use may prove to be a helpful adjunct in the treatment of congestive heart failure.

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.

The chronic stress state has previously been defined as persistent visceral arousal coupled with behavioral abnormalities. To determine the number of stressor exposures necessary to induce a chronic stress state, male rats were given 2 hours of inescapable shock on 10, 7, 4, or 3 consecutive days. The 3-day stress group had the most pervasive changes in the variables measured: persistently elevated basal plasma corticosterone (CORT), continued weight loss in the post-stressor period, and abnormal behavior. More exposures to the stress regimen did not produce higher CORT levels or greater behavioral changes. Acutely stressed rats, exposed to 1 day of inescapable shock, had persistent CORT elevations without the other changes seen in the 3-day stress group. The data suggest that 3 days of our stress regimen are sufficient to produce a state of chronic stress and that some signs of this state begin to appear as early as the first exposure to our inescapable stress regimen.

To assess the value of dobutamine echocardiography for detecting coronary artery disease (CAD), 70 men (mean age 62 +/- 8 years) presenting for coronary angiography were prospectively studied. Dobutamine (2.5 to 40 micrograms/kg/min) was infused in 3-minute stages. Digital echocardiograms were recorded on-line at baseline, during low- and high-dose dobutamine infusion, and at recovery. An echocardiogram positive for CAD was defined as one showing a new wall motion abnormality induced by dobutamine. Compared with coronary angiography, the overall sensitivity of dobutamine echocardiography for detecting CAD was 86%, specificity 95% and accuracy 89%. The sensitivity for detecting 3-vessel CAD was 100%, 89% for 2-vessel and 69% for 1-vessel CAD. The accuracy of predicting multivessel disease by 2 methods was 71% and 84%, respectively. Heart rate at the echocardiographic ischemic threshold was lower in patients with 3- and 2-vessel CAD versus 1-vessel CAD (89 +/- 17, 95 +/- 18 and 118 +/- 18 beats/min, respectively, p less than 0.01); rate-pressure product was also lower in patients with 3- and 2-vessel CAD versus 1-vessel CAD (12.7 +/- 3.6, 13.7 +/- 2.8 and 18.9 +/- 44 x 10(3) beats/min x mm Hg, respectively, p less than 0.01). Heart rate was the most important physiologic determinant of ischemia induced by dobutamine. There were no major complications during the study. Thus, dobutamine digital echocardiography is an excellent test for identifying CAD and should be beneficial in patients unable to exercise.

This study examined the effects of aging and chronic congestive heart failure on plasma corticosterone and cortisol levels in hamsters. It also assessed the effects of aging and heart failure on glucocorticoid responses to acute and chronic stress. Aging in healthy hamsters increased plasma cortisol levels, decreased corticosterone levels, and did not change total glucocorticoid levels. A similar pattern occurred as cardiomyopathic (CM) hamsters aged, until they developed severe heart failure. Plasma cortisol levels fell in CM hamsters with severe heart failure, and corticosterone levels remained low, so total glucocorticoid levels fell. Adrenocortical function similarly declined in very old healthy hamsters near the ends of their lives. Adrenocortical responses to acute and chronic stress were diminished in old healthy hamsters, and heart failure in CM hamsters also reduced the glucocorticoid responses to chronic stress. However, heart failure greatly enhanced the cortisol and total glucocorticoid responses to acute stress, but not that of corticosterone. These data suggest a number of conclusions. First, aging clearly changes the the ratio of corticosterone to cortisol in hamster plasma without changing total glucocorticoid levels and blunts adrenocortical responses to acute and chronic stress. Second, ill health, in the form of severe heart failure in CM hamsters and very old age in health hamsters, decreases adrenocortical function. At the same time, heart failure greatly enhances cortisol responses to acute stress. These results indicate that aging and chronic disease in hamsters have many similar effects on adrenocortical function, but that disease alone sensitizes them to the effects of acute stress.

The causes of poor semen quality following spinal cord injury (SCI) are unknown. One possible mechanism is decreased testicular blood flow. Chronic testicular ischemia in non-SCI animals has been shown to have significant adverse impact on spermatogenesis. This study was designed to evaluate testicular blood flow following SCI in the Sprague Dawley rat. Testicular blood flows were determined in 11 rats with SCI at thoracic level nine (T9) and six sham control rats three days prior and three days and 14 days after SCI. Testicular blood flow velocity was measured with a Doppler flow probe. Blood flows were compared between groups using T-tests. There were no significant changes in blood flow in the sham operated rats three or 14 days after surgery. However, three days after SCI, blood flow had decreased in the SCI rats to 78 +/- 5 percent of the pre-SCI flow (t = -4.65 with 10 df, p < 0.001). At 14 days after SCI, blood flow was still decreased to 77 +/- 8 percent, (t = -3.40 with 3 df, p < 0.05). This study established that following SCI, testicular blood flow decreases in the Sprague Dawley rat.

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.

The current experiment examined the effects of exogenous testosterone (T) on spermatogenesis in rats with spinal cord injury (SCI) and their relationship with the cellular distribution of a cyclic AMP-responsive element modulator (CREM) in testicular cells. Implantation of T-filled Silastic capsules (TCs, 1–20 cm) resulted in dose-dependent, biphasic changes in testicular T levels and spermatogenesis in SCI rats. However, dose responsiveness of spermatogenesis to exogenous T in SCI rats differed from that in sham control rats. Specifically, implantation of 2-cm TCs enhanced the effects of SCI on spermatogenesis, resulting in total regression of the seminiferous epithelium. Although 3-cm TCs maintained complete spermatogenesis in sham control rats, this regimen failed to support complete spermatogenesis in SCI rats. Although complete spermatogenesis was maintained in SCI rats given 5-20-cm TC implants, various abnormalities persisted. Cellular distribution of CREM remained normal in SCI rats but was altered in those SCI rats that received 3- or 5-cm TC implants. Such effects were associated with reduced CREM proteins in testicular tissues. These results were consistent with altered cAMP signaling and its regulation in testicular cells after SCI and provided possible mechanistic explanations for the effects of SCI on spermatogenesis. Conclusion: SCI resulted in changes in the responsiveness of spermatogenesis to exogenous T. These effects were associated with altered cAMP/CREM signaling in testicular cells. Further studies, including a study of the relationship between serum T levels and normalcy of sperm functions and the role of neural-endocrine interactions in mediating the effects of SCI on spermatogenesis and sperm function, are needed so that therapeutic regimens can be designed for clinical use.

Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors. The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress. We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

To develop a spinal cord injury (SCI) animal model for the study of bladder stones and compare this model with a non-SCI animal model.Small pieces of catheters were implanted into the bladders of Sprague-Dawley rats as a nidus for bladder stone formation. Three weeks later, the rats underwent an SCI surgery (SCI transection or sham SCI). Control rats had SCI surgery, but no catheters were implanted into their bladders.Bladder stone number, weight, and composition were determined in two groups of SCI and sham SCI animals: Group A (recent spinal shock: 2 weeks post-SCI/sham SCI surgery) and Group B (out of spinal shock: 3 weeks to 3 months post-SCI/sham SCI surgery). A chi2 test was used to compare the incidence of bladder stones in SCI vs sham SCI animals. A Student t test was used to compare the weight of bladder stones in the 2 groups.Group A (recent spinal shock): Of the 20 SCI rats, 8 (40%) had stones. None of the sham SCI rats with implanted catheters (n = 5) had stones (0%). Group B (out of spinal shock): All 6 of the SCI rats with implanted catheters had stones (100%). Of the 10 sham SCI animals with implanted catheters, 3 (30%) had stones. Stones were more common in the SCI rats than in the sham SCI rats (chi2(1) = 4.9, P0.05). The mean weight of the bladder stones in SCI rats (42.2 +/- 16.3 mg) was greater than that in sham SCI rats (5.4 +/- 1.5 mg) (P0.01). Group C (controls: SCI surgery, but no catheter implanted): At 3 weeks post-SCI, control rats had no stones (n = 7); control rats at 3 months post-SCI also had no stones (n = 9). Stone composition in the 3 sham SCI animals was calcium apatite (90%) and calcium oxylate (10%). In the 14 SCI rats, 10 had struvite stones (100%), 1 had struvite (70%) and carbonate apatite (30%) stones, 1 had brushite (100)% stones, and 2 had carbonate apatite (90%) stones.Bladder stones occurred earlier and more frequently and attained a larger size in SCI rats with catheters compared with sham SCI rats with catheters. There were no stones in SCI rats without catheter implants, even at 3-month follow-up. The bladder stone composition in SCI rats was similar to that in humans with SCI. The Sprague-Dawley rat model appears to be an excellent animal model for the study of bladder stones following SCI.

Earlier studies demonstrated that the effects of spinal cord injury (SCI) on spermatogenesis were associated with altered Sertoli cell responses to treatment with follicle-stimulating hormone (FSH) and/or testosterone (T). Because of the importance of the cyclic adenosine 3',5'-monophosphate (cAMP) signal pathway in hormonal actions on Sertoli cells and spermatogenesis, the purpose of this study was to determine whether cAMP signaling in testicular cells is altered after SCI.Rats with SCI were treated with FSH, T, or FSH + T for 7 or 14 days. Northern blot cDNA hybridization was used to measure testicular levels of Sertoli and germ cell-specific transcripts encoded by genes that contain cAMP responsive element (CRE) and/or steroid hormone responsive element (HRE). Cellular distribution of CRE modulator (CREM) was determined by immunohistochemistry.Treatment of sham control rats with FSH or T + FSH for 2 weeks resulted in decreases in mRNAs for CREM and CRE binding protein (CREB). Concomitantly, levels of mRNA for Sertoli cell inhibin alpha and germ cell-specific protamine 1 (Pm-1), transition protein 2 (TP-2), and lactate dehydrogenase C (LDHC) were all reduced. In contrast, identical FSH and/or T treatments resulted in increases in levels of CREM and CREB mRNAs in the testes of SCI rats; these effects were associated with similar changes in mRNAs for inhibin alpha, Pm-1, TP-2, and LDHC. The effects of SCI on CREM expression were corroborated by similar changes in its distribution in testicular cells.SCI is associated with changes in FSH and/or T regulation of cAMP/CRE and HRE signaling in testicular cells. These effects may mediate the effects of SCI on spermatogenesis.

Pyridostigmine bromide (PB), a peripheral cholinesterase inhibitor, has been shown to have central cholinesterase inhibition properties under certain conditions (such as when ingested with other chemical compounds or following a high level of stress). Here we tested if stressing rats, using an intermittent 1 hr tailshock protocol, affected the degree of brain acetylcholinesterase (AChE) inhibition caused by a subsequent single injection of PB (2.0 mg/kg) or neostigmine bromide (NB, 0.32 mg/kg), another peripheral carbamate cholinesterase inhibitor. Stressed rats treated with PB had lower levels of AChE activity in the basal forebrain/striatum, but not in other brain areas. Stressed rats treated with NB did not show basal forebrain/striatum AChE activity changes but did show minor reductions of AChE activity in the cortex and cerebellum. These results confirm that prior stress can change the characteristic actions of certain peripherally acting drugs, thus possibly leading to unexpected central nervous system effects. Possible causes for these effects are discussed.

Chronic fatigue syndrome (CFS) is a debilitating disease characterized by severe, unexplained fatigue and postexertional exacerbation of symptoms. We examined basal endocrine function in a group of CFS patients and a carefully matched group of sedentary controls. The subjects then completed a graded, maximal exercise test on a treadmill, and additional blood samples were drawn 4 min and a day after the end of exercise. There were no differences in basal hormone levels before exercise. Plasma adrenocorticotropin, epinephrine, prolactin and thyrotropin responses 4 min after exercise were lower in the CFS group, but the growth hormone response may have been exaggerated, and the plasma norepinephrine response was similar to that in controls. The next day, there were no differences in hormone levels between the groups, which suggests that long-term changes in endocrine function are unlikely to be a cause of the prolonged fatigue that occurs in CFS patients after a bout of exertion.

In the rat, regression of spermatogenesis during the chronic stages of spinal cord injury (SCI) occurs in the presence of normal function of the pituitary-testis hormone axis, thus suggesting that nonendocrine mechanisms might be involved. The current study examined whether disruption of neural input to the testis contributes to the cascade that leads to the regression of spermatogenesis. Four weeks after denervation of the superior spermatic nerve (SSN), testis weight was 25% lower (p < 0.01) than that of the contralateral sham-operated testis. Defects in spermatogenesis including phagocytosis of mature spermatids, vacuolization of spermatid nuclei, delayed spermiation and incomplete cellular associations were observed in >60% of the tubules. In the remaining 30–40% of tubules, the seminiferous epithelium was severely regressed. While cutting the inferior spermatic nerve (ISN) alone did not affect spermatogenesis significantly, it enhanced the effect of SSN denervation on both spermatogenesis and testis weight (p < 0.01). Spermatogenesis was totally regressed in the SSN/ISN-denervated testes. At this time, quantitatively normal spermatogonial proliferation was maintained in SSN- or ISN-denervated testes. Twelve weeks after surgery, regression of the seminiferous epithelium characterized by absence of proliferating spermatogonia, while undifferentiating spermatogonia were present, was observed in all SSN-denervated testes. At this time, regression of the seminiferous epithelia also occurred in >30% of the tubules in ISN-denervated testes. At both times, serum follicle-stimulating hormone, luteinizing hormone and testosterone levels were normal and >60% of normal testicular testosterone concentrations were maintained in the denervated testes. These results indicate that disruption of neural input to the testis is not a cause for the decrease in spermatogonial proliferation during the acute phase of SCI, but may contribute to the chronic effects of SCI on spermatogenesis.

OBJECTIVE: To develop a risk adjustment method for HbA1c, based solely on administrative data and to determine the extent to which risk-adjusted HbA1c changes the identification of high- or low-performing medical facilities. RESEARCH DESIGN AND METHODS: Through use of pharmacy records, 204,472 diabetic patients were identified for federal fiscal year 1996 (FY96). Complete information (HbA1c levels, demographic data, inpatient records, outpatient pharmacy utilization records) was available on 38,173 predominantly male patients from 48 Veterans Health Administration (VHA) medical facilities. Hierarchical mixed-effects models were used to estimate risk-adjusted unique facility-level HbA1c. RESULTS: Predicted HbA1c demonstrated expected patterns for major factors known to influence glycemic control. Poorer glycemic control was seen in minorities and patients with greater disease severity, longer duration of disease (using treatment type or presence of amputation as surrogates), and more extensive comorbidity (measured by an adapted Charlson index). Better glycemic control was seen in Caucasians, older diabetic patients, and patients with higher outpatient utilization. The number of performance outliers was reduced as a result of risk adjustment. For mean HbA1c levels, 7 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. For high-risk HbA1c (>9.5%) rates, 12 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. CONCLUSIONS: Risk adjustment using only administrative data resulted in substantial changes in identification of high or low performers compared with non-risk-adjusted HbA1c. Although our findings are exploratory, risk adjustment using administrative data may be a necessary and achievable step in quality assessment of diabetes care measured by rates of high-risk HbA1c (>9.5%).

Causes of poor semen quality following spinal cord injury (SCI) are not known. One possible reason, based upon studies that reported improved semen quality in SCI men after several induced ejaculations, is delayed epididymal sperm transport. Our study was designed to establish baseline epididymal sperm transport values in the Sprague Dawley rat and evaluate effects of SCI on this process. Spermatozoa protamine was labeled with tritiated arginine, and the rats were sacrificed various times after injection. Each epididymis was divided into six equal sections from proximal to distal. Sperm tails were dissolved with 8 molar (M) urea in the presence of 2 mM dithiothreitol (DTT); sperm heads were collected by centrifugation (3,000 rpms, 10 min.). The radioactivity in sperm heads from each section was counted and expressed as counts per million sperm heads. To account for different rates of labeled arginine incorporation, the percentage of counts per million sperm heads in each section was calculated relative to the total number of counts in all six sections. Our results showed there was an orderly progression of sperm through the epididymis. It took 8 days for labeled sperm to enter the epididymis and 28 days to peak in the caudal (tail) section in non-SCI rats. Stasis was present 10 days after T-9 SCI in rats compared with transport in sham controls. This was evidenced by a significant increase in the percentage of labeled sperm in proximal sections of the epididymis (sections 1, 2, and 4) in T-9 transected animals (p < 0.01). If similar stasis occurs in SCI men, it could obviously contribute to poor semen quality. However, it remains to be determined how long this stasis persists after SCI in rats.

The fact that many patients with chronic fatigue syndrome (CFS) have an infectiouslike sudden onset to their illness has led to the hypothesis that CFS is a medical illness. If CFS were, on the other hand, a psychiatric disorder related to symptom amplification, one would expect illness onset to occur randomly over the calendar year. This study tested that hypothesis with 69 CFS patients whose illness was on the more severe side of the illness spectrum; all patients reported sudden illness onset with the full syndrome of sore throat, fatigue/malaise, and diffuse achiness developing over no longer than a 2-day period. Date of illness onset was distinctly nonrandom. It peaked from November through January and was at its lowest from April through May. These data support the hypothesis that an infectious illness can trigger the onset of CFS. (Chronobiology International, 17(1), 95–99, 2000).Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by fatigue, pain, and cognitive complain...

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.

Autonomic evaluation using the heart rate spectrum is sensitive to changes in breathing parameters, but few studies using this technique have controlled both the rate and depth of breathing. Fewer still have also measured or controlled inspiration and expiration times, or end-tidal carbon dioxide. This study describes the development of a digital instrument that can be used to alter tidal volume, ventilation rate and the time of inspiration and expiration with paced breathing visual templates displayed on a computer monitor. The digital instrument runs during data acquisition and displays the ventilatory signal from the subject superimposed on the paced breathing templates. Thus, adjustment of ventilatory parameters is achieved by matching the actual breathing signal to the target template. By regulating the ventilation rate and the tidal volume, end-tidal carbon dioxide could be increased or decreased in small increments. This instrument provided ventilatory control to investigate the effects on the heart rate spectrum of breathing depth, ventilation rate, end-tidal carbon dioxide and the time of expiration.

Although it is more common to study the effects of light on circadian systems, nonphotic stimuli can also influence and entrain circadian clocks. Because anophthalmic mice (ZRDCT-AN) have a genetic mutation that prevents the development of the eyes, they do not respond to light or entrain to light–dark cycles. Thus, entrainment of anophthalmic mice requires a nonphotic zeitgeber (entraining stimulus). In the current study we attempted to entrain sighted and anophthalmic mice of the same strain, using restricted access to an unlocked running wheel as the zeitgeber. First, free-running rhythms were established. The running wheels were then locked, and unlocked only from 0930–1130 h each day. Finally, a postentrainment free run was measured. In one group of animals, body temperature and general activity were measured using a Minimitter telemetry system. In another, general activity was measured by a sensitive force plate beneath the cage. Running-wheel activity was recorded in both groups. The force plate proved satisfactory for observing the behavior of the circadian system during wheel locking, and preferable to the temperature transmitters for long-term studies because the battery life of the mouse temperature transmitters was limited. Both sighted and anophthalmic mice were able to entrain to restricted wheel access, although not all animals responded. Mice that did not entrain showed either no effect of wheel locking or exhibited masking.