Biomedical subjects

Benjamin H Natelson

Publications and source records attributed to Benjamin H Natelson.

At least 19 recordsLinked to original sources

PubMed2006

Electroencephalogram characteristics of autonomic arousals during sleep in healthy men.

OBJECTIVE: Many sleep disorders involve frequent, brief arousals, not appreciated during conventional sleep stage scoring due to lack of electroencephalogram (EEG) desynchronization. We evaluated the temporal relation between heart rate (HR) changes, an index of autonomic activation, and EEG in seven healthy subjects during sleep. METHODS: We identified bouts of tachycardia-bradycardia and performed spectral analysis of EEG during these. We also identified cortical arousals by the appearance of EEG alpha activity. This allowed us to dichotomize bouts of tachycardia-bradycardia by presence or absence of cortical arousal. RESULTS: During non-rapid eye movement (REM) sleep, bouts with or without cortical arousal occurred with approximately equal frequency. Those with cortical arousals usually preceded onset of EEG changes. Those without cortical arousals were followed by increases in delta but not alpha power. EEG did not change during bouts in REM sleep. CONCLUSIONS: Capturing bouts of tachycardia-bradycardia is relatively easy via computerized algorithm. Bouts occur with cortical arousal or with slow wave synchronization suggestive of subcortical arousal. Thus, changes in HR may be useful index of arousal. SIGNIFICANCE: These brief bursts of tachycardia-bradycardia are consistent with autonomic arousal. Such a measure may be among the first in a continuum of arousal ending with frank awakening.

Adult↗

PubMed2006

Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow.

Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POTS(HC) and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC).

Adolescent↗

PubMed2006

Sub-typing CFS patients on the basis of 'minor' symptoms.

The diagnosis of chronic fatigue syndrome (CFS), an illness characterized by medically unexplained fatigue, depends on a clinical case definition representing one or more pathophysiological mechanisms. To prepare for studies of these mechanisms, this study sought to identify subtypes of CFS. In 161 women meeting 1994 criteria for CFS, principal components analysis of the 10 'minor' symptoms of CFS produced three factors interpreted to indicate musculoskeletal, infectious and neurological subtypes. Extreme scores on one or more of these factors characterized about 2/3 of the sample. Those characterized by the neurological factor were at increased risk of reduced scores on cognitive tests requiring attention, working memory, long-term memory or rapid performance. In addition, the neurological subtype was associated with reduced levels of function. Those characterized by the musculoskeletal factor were at increased risk for the diagnosis of fibromyalgia (chronic widespread pain and mechanical allodynia) and reduced physical function. Those characterized by the infectious factor were less likely to evidence co-occurring fibromyalgia, and showed lesser risk of functional impairment. The prevalence of disability was increased in those with the highest scores on any of the subtypes, as well as in those with high scores on multiple factors. Depression and anxiety, while frequently present, were not more prevalent in any particular subtype, and did not increase with the severity of specific symptom reports. Results suggest that subtypes of CFS may be identified from reports of the minor diagnostic symptoms, and that these subtypes demonstrate construct validity.

Adult↗

PubMed2006

The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome.

OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome (CFS), accounting for comorbid fibromyalgia (FM) and controlling for aerobic fitness. METHODS: Twenty-nine patients with CFS only, 23 patients with CFS plus FM, and 32 controls completed an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual responses were measured. Results were determined for the entire sample and for 18 subjects from each group matched for peak oxygen consumption. RESULTS: In the overall sample, there were no significant differences in cardiorespiratory parameters between the CFS only group and the controls. However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO2, and higher ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS plus FM group rated exercise as more effortful than did controls. Patients with CFS plus FM rated exercise as significantly more painful than did patients with CFS only or controls. In the subgroups matched for aerobic fitness, there were no significant differences among the groups for any measured cardiorespiratory response, but perceptual differences in the CFS plus FM group remained. CONCLUSION: With matching for aerobic fitness, cardiorespiratory responses to exercise in patients with CFS only and CFS plus FM are not different from those in sedentary healthy subjects. While CFS patients with comorbid FM perceive exercise as more effortful and painful than do controls, those with CFS alone do not. These results suggest that aerobic fitness and a concurrent diagnosis of FM are likely explanations for currently conflicting data and challenge ideas implicating metabolic disease in the pathogenesis of CFS.

Adolescent↗

PubMed2006

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow.

Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder. Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.

Adult↗

PubMed2006

The war-related illness and injury study centers: a resource for deployment-related health concerns.

Combat veterans often return from deployment having experienced a wide range of exposures, symptoms, and medical conditions. The Department of Veterans Affairs established war-related illness and injury study centers to serve combat veterans with unexplained illnesses. We report the exposures, clinical status, and utilization of 53 combat veterans who participated in the National Referral Program (NRP) from January 2002 until March 2004. Participants were primarily male (81%) and served in the Persian Gulf War (79%). Common diagnoses were chronic fatigue syndrome (n = 23, 43%), neurotic depression (n = 21, 40%), and post-traumatic stress disorder (n = 20, 38%). Self-reported exposures related to weaponry, disease prophylaxis, environmental hazards, stress, and poor hygiene. A small increase in mean SF-36V mental component scores (2.8 points, p = 0.009) and use of rehabilitation therapies (1.6 additional visits, p = 0.018) followed the NRP referral. The small gain in mental function suggests that the NRP may benefit combat veterans with long and complex medical histories.

Adult↗

PubMed2005

Spinal fluid abnormalities in patients with chronic fatigue syndrome.

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.

Adult↗

PubMed2005

Exercise and cognitive performance in chronic fatigue syndrome.

PURPOSE: To determine the effect of submaximal steady-state exercise on cognitive performance in patients with chronic fatigue syndrome (CFS) alone, CFS with comorbid fibromyalgia FM (CFS + FM), and sedentary healthy controls (CON). METHODS: Twenty CFS-only patients, 19 CFS + FM, and 26 CON completed a battery of cognitive tests designed to assess speed of information processing, variability, and efficiency. Tests were performed at baseline, immediately before, and twice following 25 min of either cycle ergometry set at 40% of peak oxygen capacity or quiet rest. RESULTS: There were no group differences in average percentage of peak oxygen consumption during exercise (CFS = 45%; CFS + FM = 47%; Control = 43%: P = 0.2). There were no significant effects of acute exercise on cognitive performance for any group. At baseline, one-way ANOVA indicated that CFS patients displayed deficits in speed of processing, performance variability, and task efficiency during several cognitive tests compared with healthy controls. However, the CFS + FM patients were not different than controls. Repeated measures ANOVA indicated that across all tests (pre- and postexercise) CFS, but not CFS + FM, were significantly less consistent (F2,59 = 3.7, P = 0.03) and less efficient (F2,59 = 4.6, P = 0.01) than controls. CONCLUSION: CFS patients without comorbid FM exhibit subtle cognitive deficits in terms of speed, consistency, and efficiency that are not improved or exacerbated by light exercise. Importantly, our data suggest that CFS + FM patients do not exhibit cognitive deficits either pre- or postexercise. These results highlight the importance of disease heterogeneity in studies determining acute exercise and cognitive function in CFS.

Adolescent↗

PubMed2004

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome.

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs. To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT. While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

Adult↗

PubMed2004

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

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).

Fatigue Syndrome, Chronic↗

PubMed2004

Stress, hormones and disease.

My postdoctoral training under Dr. Gerard Smith began me on a lifetime of investigation on the role of stress, hormones, and disease. The first set of experiments asked what hormone, if any, best reflected the range of aroused behaviors. We found that catecholamines performed substantially better than glucocorticoids did, despite the belief that glucocorticoids were sensitive indices of stress. But we also learned that hormones themselves were nowhere near as good in monitoring stress than motor behaviors were. In a second set of experiments, we tried to understand how stress affected medical disease. We learned that stress can produce disease in a healthy organism but has its most profound effects when disease already exists. Finally, in the early 1990s, I shifted my focus on stress and disease to a broader problem in behavioral medicine, namely, medically unexplained fatigue and pain. Among the studies we have done investigating these disorders, we looked specifically at veterans of the first Gulf War--many of whom developed problems with severe fatigue. A critical question in the literature asked if unexplained fatigue was simply a physical component of concurrent posttraumatic stress disorder (PTSD). In a large epidemiological study, we found that PTSD tracked stressor intensity in a stepwise fashion, while fatiguing illness increased with stressor intensity only on the milder side of the intensity spectrum. This result indicated that the two ailments are both stress sensitive but dissimilar.

Animals↗

PubMed2004

Working memory deficits in chronic fatigue syndrome: differentiating between speed and accuracy of information processing.

To examine the relative influence of speed of information processing versus working memory ability, CFS participants with psychiatric comorbidity (CFS-Psych) and CFS without a psychiatric history (CFS-noPsych) were examined on tests of visual and auditory processing speed and visual and auditory working memory. Compared to healthy controls (HC) and a group of participants with rheumatoid arthritis (RA), the CFS-noPsych group displayed significantly reduced performance on tests of information processing speed, but not on tests of working memory. No significant differences were observed between the CFS-Psych group and any other group in the study. The implications of group heterogeneity on the understanding of cognitive impairment in CFS are discussed.

Adult↗

PubMed2004

Neuropsychological deficits in patients with chronic fatigue syndrome.

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.

Adult↗

PubMed2004

Functional imaging of pain in patients with primary fibromyalgia.

OBJECTIVE: To examine the function of the nociceptive system in patients with fibromyalgia (FM) using functional magnetic resonance imaging (fMRI). METHODS: Two groups of women, 9 with FM and 9 pain-free, volunteered to participate. In Experiment 1, we assessed psychophysical responses to painful stimuli and prepared participants for fMRI testing. For Experiment 2, subjects underwent fMRI scanning while receiving painful and nonpainful heat stimuli. Conventional and functional MR images were acquired using a 1.5 T MR scanner. Scanning occurred over 5 conditions. Condition 1 served as a practice session (no stimuli). Conditions 2 and 5 consisted of nonpainful warm stimuli. Conditions 3 and 4 consisted of an absolute thermal pain stimulus (47 degrees C) and a perceptually equivalent pain stimulus delivered in counterbalanced order. RESULTS: Experiment 1 indicated that subjects with FM were significantly more sensitive to experimental heat pain than controls (p < 0.001). In Experiment 2, fMRI data indicated that the FM group exhibited greater activity than controls over multiple brain regions in response to both nonpainful and painful stimuli (p < 0.01). Specifically, in response to nonpainful warm stimuli, FM subjects had significantly greater activity than controls in prefrontal, supplemental motor, insular, and anterior cingulate cortices (p < 0.01). In response to painful stimuli, FM subjects had greater activity in the contralateral insular cortex (p < 0.01). Data from the practice session indicated brain activity in pain-relevant areas for the FM group but not for controls. CONCLUSION: Our results provide further evidence for a physiological explanation for FM pain.

Adult↗

PubMed2003

Asymmetrical singularities in real-world signals.

We generalize the wavelet transform modulus maxima approach in order to analyze positive and negative changes separately and show different singularity spectra depending on the direction of changes in (i) human heartbeat interval data during sympathetic blockade, (ii) time series of daytime human physical activity of healthy individuals (but not of patients with debilitating fatigue), and (iii) daily stock price records of the Nikkei 225 in the period 1990-2002--but not of the S&P 500. We conclude that the analysis of asymmetrical singularities provides deeper insights into the underlying complexity of real-world signals that can greatly enhance our understanding of the mechanisms determining the systems' dynamics.

Adrenergic beta-Antagonists↗

PubMed2003

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

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.

Adult↗

PubMed2003

Muscle metabolism with blood flow restriction in chronic fatigue syndrome.

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.

Adult↗

PubMed2003

Post-traumatic stress disorder and chronic fatigue syndrome-like illness among Gulf War veterans: a population-based survey of 30,000 veterans.

The authors estimated the prevalence of post-traumatic stress disorder (PTSD) and illness resembling chronic fatigue syndrome (CFS) in the entire population of Gulf War and non-Gulf-War veterans. They also evaluated the relation between the extent of deployment-related stress and the risk of either PTSD or CFS. In 1995-1997, the authors conducted a health survey in which these two symptom-based medical diagnoses in a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared with those of 15,000 non-Gulf veteran controls. Gulf War veterans, compared with non-Gulf veteran controls, reported significantly higher rates of PTSD (adjusted odds ratio = 3.1, 95% confidence interval: 2.7, 3.4) and CFS (adjusted odds ratio = 4.8, 95% confidence interval: 3.9, 5.9). The prevalence of PTSD increased monotonically across six levels of deployment-related stress intensity (test for trend: p < 0.01), while the prevalence of CFS rose only at the low end of the stress spectrum. While deployment-related stress could account for the higher risks of both PTSD and CFS, additional factor(s) unique to the Gulf environment may have contributed to the risk of CFS among Gulf War veterans.

Adult↗