Tag: Natelson

Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome

Abstract:

The purpose of this study was to evaluate immune function through the assessment of lymphocyte subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells, NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-10, IL-12, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) from peripheral blood lymphocytes.

Subjects included two groups of patients meeting published case definitions for chronic fatigue syndrome (CFS)-a group of veterans who developed their illness following their return home from participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively.

We found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II+ T cells and a significantly higher percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells, than the respective controls.

In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-gamma, and TNF-alpha than the controls. These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness.

 

Source: Zhang Q, Zhou XD, Denny T, Ottenweller JE, Lange G, LaManca JJ, Lavietes MH, Pollet C, Gause WC, Natelson BH. Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome. Clin Diagn Lab Immunol. 1999 Jan;6(1):6-13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC95652/ (Full article)

 

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

Abstract:

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.

 

Source: Pollet C, Natelson BH, Lange G, Tiersky L, DeLuca J, Policastro T, Desai P, Ottenweller JE, Korn L, Fiedler N, Kipen H. Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity. J Med. 1998;29(3-4):101-13. http://www.ncbi.nlm.nih.gov/pubmed/9865452

 

Physical activity before and after exercise in women with chronic fatigue syndrome

Abstract:

We measured physical activity after strenuous exercise in 20 women with chronic fatigue syndrome (CFS), compared to 20 sedentary healthy volunteers who exercised no more than once per week.

Activity was measured for 2 weeks using a portable waist-worn vertical accelerometer. After the first week of activity monitoring, all participants returned for a maximal treadmill test, followed by continued activity monitoring for the second week. Five activity measures were derived from the data: (i) average activity; (ii) total activity; (iii) duration of waking day; (iv) duration; and (v) number of daily rests. A repeated measures ANCOVA was used to determine post-treadmill group differences accounting for pre-treadmill differences.

There was a significant reduction in overall average activity after the treadmill test, with the greatest decrease on days 12 through 14. This reduction was accompanied by a significant increase in the duration of the waking day and number of daily rests. Thus, marked exertion does produce changes in activity, but later than self-report would suggest, and are apparently not so severe that CFS patients cannot compensate.

 

Source: Sisto SA, Tapp WN, LaManca JJ, Ling W, Korn LR, Nelson AJ, Natelson BH. Physical activity before and after exercise in women with chronic fatigue syndrome. QJM. 1998 Jul;91(7):465-73. http://qjmed.oxfordjournals.org/content/91/7/465.long (Full article)

 

Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine the effect of exhaustive exercise on cognitive performance of patients with chronic fatigue syndrome(CFS) and sedentary healthy controls (CON).

Subjects were 19 women with CFS and 20 CON. A test battery consisting of 4 cognitive tests (CTB) was given pre-, immediately post-, and 24 hours post-treadmill exercise to exhaustion. No differences were seen on the CTB pre-exercise.

CFS patients improved at a slower rate than CON on the Symbol Digit Modalities Test (SDMT), Stroop Word Test (SWT), and Stroop Color Test (SCT). When compared with CON, a lower number of correct responses was seen for the CFS immediately postexercise on the SDMT (61 +/- 3 vs 66 +/- 2), SWT (137 +/- 6 vs 146 +/- 6), and SCT (99 +/- 4 vs 107 +/- 3), and 24 hours postexercise on the SDMT (64 +/- 3 vs 69 +/- 2), SWT (134 +/- 7 vs 148 +/- 5), and SCT (101 +/- 4 vs 106 +/- 3).

We conclude that after physically demanding exercise, CFS subjects demonstrated impaired cognitive processing compared with healthy individuals.

 

Source: LaManca JJ, Sisto SA, DeLuca J, Johnson SK, Lange G, Pareja J, Cook S, Natelson BH. Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):59S-65S. http://www.ncbi.nlm.nih.gov/pubmed/9790484

 

Neuroimaging in chronic fatigue syndrome

Abstract:

The diagnosis of chronic fatigue syndrome (CFS) is made difficult by the absence of specific biomedical markers, and depends primarily on determining whether subjective information provided by the patient meets the clinical case definition of this syndrome. Reported cognitive difficulties and/or complaints of headache may instigate referral for brain imaging.

This article will discuss the value of neuroimaging in evaluating CFS, specifically reviewing studies that (1) used static magnetic resonance imaging (MRI) to assess structural abnormalities; and (2) assessed regional cerebral blood flow (rCBF) via detection of Tc-99m hexamethylpropyl-eneamine oxime distribution by single-photon emission computed tomography (SPECT). Future research design considerations are explored including (1) the utilization of positron emission tomography (PET) and other emerging neuroimaging technologies; and (2) methodological concerns, i.e., the influence of psychopathology (such as depression) and neurologic disease (such as multiple sclerosis) as possible confounding factors.

 

Source: Lange G, Wang S, DeLuca J, Natelson BH. Neuroimaging in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):50S-53S. http://www.ncbi.nlm.nih.gov/pubmed/9790482

 

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis

Abstract:

The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses–major depression and multiple sclerosis (MS)–and with data from healthy sedentary controls.

The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables–circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers–the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b-, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3-/CD16+ and CD56+.

Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values-contrary to expectation.

When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS.

These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.

 

Source: Natelson BH, LaManca JJ, Denny TN, Vladutiu A, Oleske J, Hill N, Bergen MT, Korn L, Hay J. Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis. Am J Med. 1998 Sep 28;105(3A):43S-49S. http://www.ncbi.nlm.nih.gov/pubmed/9790481

 

Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue

Abstract:

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.

 

Source: Ottenweller JE, Natelson BH, Gause WC, Carroll KK, Beldowicz D, Zhou XD, LaManca JJ. Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue. Physiol Behav. 1998 Mar;63(5):795-801. http://www.ncbi.nlm.nih.gov/pubmed/9618001

 

Impaired associative learning in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report cognitive difficulties (impaired attention, memory and reasoning). Neuropsychological tests have failed to consistently find cognitive impairments to the degree reported by CFS patients.

We tested patients with CFS and sedentary controls in protocols designed to measure sensory reactivity and acquisition of the classically conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and responsivity to acoustic stimuli.

However, CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. Sensitivity and responsivity to the airpuff stimulus were normal.

In the absence of sensory/motor abnormalities, impaired acquisition of the classically conditioned eyeblink response indicates an associative deficit. These data suggest organic brain dysfunction within a defined neural substrate in CFS patients.

 

Source: Servatius RJ, Tapp WN, Bergen MT, Pollet CA, Drastal SD, Tiersky LA, Desai P, Natelson BH. Impaired associative learning in chronic fatigue syndrome. Neuroreport. 1998 Apr 20;9(6):1153-7. http://www.ncbi.nlm.nih.gov/pubmed/9601685

 

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome

Abstract:

AIM: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect.

METHODS: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial.

FINDINGS: Significant improvement in 3 variables-tension/anxiety, vigor and sexual relations-was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found.

CONCLUSIONS: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

 

Source: Natelson BH, Cheu J, Hill N, Bergen M, Korn L, Denny T, Dahl K. Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology. 1998;37(3):150-4. http://www.ncbi.nlm.nih.gov/pubmed/9597672

 

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors.

METHODS: The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was > or =2 SD below the mean of the healthy controls after controlling for demographic factors.

RESULTS: Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores.

CONCLUSION: A relation was found between cognitive impairment and functional disability which could not be explained entirely on the basis of psychiatric factors.

Comment in: The importance of mental fatigue. [J Neurol Neurosurg Psychiatry. 1998]

 

Source: Christodoulou C, DeLuca J, Lange G, Johnson SK, Sisto SA, Korn L, Natelson BH. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):431-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170049/