Tag: Natelson

Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans

Abstract:

Genes associated with muscle metabolism and physical endurance were evaluated for variants that may contribute to the etiology of medically unexplained severe and chronic fatigue. Subjects included 49 Gulf War veterans and 61 nonveterans with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) and 30 veterans and 45 nonveterans who served as healthy controls. Increased risk for CFS/ICF was associated with alterations of the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene within the Gulf War veteran sample only. The I allele frequency was decreased in affected versus unaffected veterans (0.15 versus 0.48; odds ratio [OR], 5.08; 95% confidence interval [CI], 1.97-13.35; P < 0.0001). Correspondingly, the II genotype was decreased fourfold in affected veterans (0.08 versus 0.35; OR = 5.87; 95% CI: 1.21-28.36; P = 0.02), and the DD genotype was increased twofold (0.78 versus 0.39; OR, 5.4; 95% CI, 1.6-18.4; P = 0.007). Veterans with the DD genotype were eight times more likely to develop CFS/ICF than were those with the II genotype (OR, 8.30; 95% CI, 1.50-56.09; P = 0.009).

 

Source: Vladutiu GD, Natelson BH. Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans. Muscle Nerve. 2004 Jul;30(1):38-43. http://www.ncbi.nlm.nih.gov/pubmed/15221876

 

Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome

Abstract:

OBJECTIVES: Our objectives were to study the temporal correlation of physical activity time series in patients with chronic fatigue syndrome (CFS) during normal daily life and to examine if it could identify the altered physical activity in these patients.

METHODS: Fractal scaling exponents of diurnal and nocturnal physical activity time series in 10 CFS patients and 6 healthy control subjects (CON) were calculated by the detrended fluctuation analysis (DFA) and the wavelet transform modulus maxima (WTMM) method. We hypothesized that, due to their illness- and/or fatigue-induced resting episodes, altered physical activity patterns in CFS patients might be observed at the interruption of activity bursts. Thus, we further developed a new method, the wavelet transform negative modulus maxima (WTNMM) method, which could evaluate the temporal correlation at the interruption of activities. We compared the fractal scaling exponents for CFS and CON by each method.

RESULTS: Both for CFS and CON, we found the fractal time structures in their diurnal physical activity records for at least up to 35 minutes. No group difference was found in nocturnal activities. The WTNMM method revealed that, in diurnal activities, CFS patients had significantly (p < 0.01) smaller fractal scaling exponent (0.87 +/- 0.03) compared to controls (1.01 +/- 0.03). Such a difference was identified neither by the DFA nor WTMM method.

CONCLUSIONS: CFS patients had more abrupt interruptions of voluntary physical activity during diurnal periods in normal daily life, probed by the decreased correlation in the negative modulus maxima of the wavelet-transformed activity data, possibly due to their exaggerated fatigue.

 

Source: Ohashi K, Bleijenberg G, van der Werf S, Prins J, Amaral LA, Natelson BH, Yamamoto Y. Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome. Methods Inf Med. 2004;43(1):26-9. http://www.ncbi.nlm.nih.gov/pubmed/15026831

 

Neuropsychological deficits in patients with chronic fatigue syndrome

Abstract:

The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome(CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning.

On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains.

 

Source: Busichio K, Tiersky LA, Deluca J, Natelson BH. Neuropsychological deficits in patients with chronic fatigue syndrome. J Int Neuropsychol Soc. 2004 Mar;10(2):278-85. http://www.ncbi.nlm.nih.gov/pubmed/15012848

 

Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness

Abstract:

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.

 

Source: Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness. Auton Neurosci. 2003 Oct 31;108(1-2):63-72. http://www.ncbi.nlm.nih.gov/pubmed/14614966

 

Muscle metabolism with blood flow restriction in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) is associated with reduced blood flow and muscle oxidative metabolism. Patients with CFS according to Centers for Disease Control criteria (n = 19) were compared with normal sedentary subjects (n = 11).

Muscle blood flow was measured in the femoral artery with Doppler ultrasound after exercise. Muscle metabolism was measured in the medial gastrocnemius muscle with (31)P-magnetic resonance spectroscopy. Muscle oxygen saturation and blood volume were measured using near-infrared spectroscopy. CFS and controls were not different in hyperemic blood flow or phosphocreatine recovery rate. Cuff pressures of 50, 60, 70, 80, and 90 mmHg were used to partially restrict blood flow during recovery. All pressures reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by 46% and oxidative metabolism by 30.7% in CFS patients.

Hyperemic blood flow during partial cuff occlusion was significantly reduced in CFS patients (P < 0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences were seen in the amount of reduction in metabolism with partially reduced blood flow.

In conclusion, CFS patients showed evidence of reduced hyperemic flow and reduced oxygen delivery but no evidence that this impaired muscle metabolism. Thus CFS patients might have altered control of blood flow, but this is unlikely to influence muscle metabolism. Furthermore, abnormalities in muscle metabolism do not appear to be responsible for the CFS symptoms.

 

Source: McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Muscle metabolism with blood flow restriction in chronic fatigue syndrome. J Appl Physiol (1985). 2004 Mar;96(3):871-8. Epub 2003 Oct 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680353/ (Full article)

 

Aerobic capacity of Gulf War veterans with chronic fatigue syndrome

Abstract:

A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs.

Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 +/- 6.7 mL/kg/min for CFS vs. 30.8 +/- 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 +/- 16.1 bpm for CFS vs. 163.3 +/- 14.9 bpm for controls; p = 0.17), exercise time (9.6 +/- 1.5 minutes for CFS vs. 10.2 +/- 1.4 minutes for controls; p = 0.26), or workload achieved (208 +/- 36.7 W for CFS vs. 224 +/- 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05).

Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

 

Source: Nagelkirk PR, Cook DB, Peckerman A, Kesil W, Sakowski T, Natelson BH, LaManca JJ. Aerobic capacity of Gulf War veterans with chronic fatigue syndrome. Mil Med. 2003 Sep;168(9):750-5. http://www.ncbi.nlm.nih.gov/pubmed/14529252

 

Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome

Abstract:

OBJECTIVE: Altered cardiovascular responses to mental and postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning.

METHODS: Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N = 21) or less severe (N = 22) illness, and in 29 matched control subjects.

RESULTS: Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task.

CONCLUSIONS: These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.

 

Source: Peckerman A, LaManca JJ, Qureishi B, Dahl KA, Golfetti R, Yamamoto Y, Natelson BH. Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome. Psychosom Med. 2003 Sep-Oct;65(5):889-95. http://www.ncbi.nlm.nih.gov/pubmed/14508037

 

Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome

Abstract:

BACKGROUND: Findings indicative of a problem with circulation have been reported in patients with chronic fatigue syndrome (CFS). We examined this possibility by measuring the patient’s cardiac output and assessing its relation to presenting symptoms.

METHODS: Impedance cardiography and symptom data were collected from 38 patients with CFS grouped into cases with severe (n = 18) and less severe (n = 20) illness and compared with those from 27 matched, sedentary control subjects.

RESULTS: The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls and less ill patients. Postexertional fatigue and flu-like symptoms of infection differentiated the patients with severe CFS from those with less severe CFS (88.5% concordance) and were predictive (R2 = 0.46, P < 0.0002) of lower cardiac output. In contrast, neuropsychiatric symptoms showed no specific association with cardiac output.

CONCLUSIONS: These results provide a preliminary indication of reduced circulation in patients with severe CFS. Further research is needed to confirm this finding and to define its clinical implications and pathogenetic mechanisms.

 

Source: Peckerman A, LaManca JJ, Dahl KA, Chemitiganti R, Qureishi B, Natelson BH. Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome. Am J Med Sci. 2003 Aug;326(2):55-60. http://www.ncbi.nlm.nih.gov/pubmed/12920435

 

Functional status, neuropsychological functioning, and mood in chronic fatigue syndrome (CFS): relationship to psychiatric disorder

Abstract:

Individuals with chronic fatigue syndrome (CFS) face chronic physical debilitation, reduced neuropsychological functioning, and changes in emotional well-being that significantly detract from quality of life. The role of psychiatric disturbance in reducing quality of life in CFS remains unclear. In the current investigation, the role of psychiatric status in reducing health-related quality of life in CFS was examined.

Four subject groups were compared on measures of functional well-being, mood, and neuropsychological status: individuals with CFS and no history of psychiatric illness, individuals who had current symptoms of psychiatric illness that began after their CFS diagnosis, individuals who had current symptoms of psychiatric illness that began before their CFS diagnosis, and a healthy sedentary control group.

Overall, it was found that individuals with CFS suffer from profound physical impairment. Concurrent psychiatric illness, however, did not adversely affect physical functional capacity. Physical functional capacity was not worse in individuals with a concurrent psychiatric illness. As expected, concurrent psychiatric illness was found to reduce emotional well-being. Moreover, individuals with a psychiatric illness that predated the onset of CFS suffered the greatest emotional distress. Thus, an individual’s psychiatric history should be considered when attempting to understand the factors maintaining disability in CFS.

 

Source: Tiersky LA, Matheis RJ, Deluca J, Lange G, Natelson BH. Functional status, neuropsychological functioning, and mood in chronic fatigue syndrome (CFS): relationship to psychiatric disorder. J Nerv Ment Dis. 2003 May;191(5):324-31. http://www.ncbi.nlm.nih.gov/pubmed/12819552

 

Psychiatric morbidity in the chronic fatigue syndrome: are patients with personality disorder more physically impaired?

Abstract:

OBJECTIVE: The long-term consequences of chronic fatigue syndrome (CFS) include substantial impairment in physical functioning and high levels of work disability. In the absence of a medical explanation for this impairment, some have speculated that it may be due to comorbid psychiatric illness or personality disorder. We addressed this possibility by comparing the functional status of three CFS groups: no psychiatric diagnosis, psychiatric illness only, psychiatric illness and personality disorder. A second aim of the study was to determine whether a continuous measure of psychological distress could provide a better account of impairment than psychiatric diagnosis.

METHOD: The study sample consisted of 84 consecutive female referrals with CFS. All participants satisfied the case definition and completed an assessment protocol consisting of: physical examination, psychiatric interview and self-report questionnaires.

RESULTS: Psychiatric illness, either alone or in combination with a comorbid personality disorder, was not associated with physical impairment or disability in female participants. A regression model of physical functioning found that psychological distress accounted for 6% and symptom severity for 41% of the variance (P=.06 and <.01, respectively). In the case of disability, the corresponding percentages were 2% and 18% (NS and P<.01, respectively). The modest effects of psychological distress could not be attributed to symptom severity.

CONCLUSIONS: Although psychiatric illness and personality disorder was prevalent, neither could explain the effects of CFS on physical functioning and disability. As yet, there is no psychological or medical explanation for the behavioral consequences of CFS.

 

Source: Ciccone DS, Busichio K, Vickroy M, Natelson BH. Psychiatric morbidity in the chronic fatigue syndrome: are patients with personality disorder more physically impaired? J Psychosom Res. 2003 May;54(5):445-52. http://www.ncbi.nlm.nih.gov/pubmed/12726901