Biomedical subjects

B H Natelson

Publications and source records attributed to B H Natelson.

At least 37 records · Page 2Linked to original sources

PubMed1999

Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome.

Presence of MRI brain abnormalities in patients with Chronic Fatigue Syndrome (CFS) was determined and the profile of MRI abnormalities was compared between 39 CFS patients, 18 with (CFS-Psych) and 21 without (CFS-No Psych) a DSM-III-R Axis I psychiatric diagnosis since illness onset, and 19 healthy, sedentary controls (HC). Two neuroradiologists, blind to group membership, separately read the MR films using a detailed protocol for rating and categorizing abnormal signal changes. When findings were incongruent, the two neuroradiologists met to try to reach consensus, otherwise a third neuroradiologist evaluated the MR images and served as a tie-breaker. The CFS-No Psych group showed a significantly larger number of brain abnormalities on T2 weighted images than the CFS-Psych and HC groups. Cerebral changes in the CFS-No Psych group consisted mostly of small, punctate, subcortical white matter hyperintensities, found predominantly in the frontal lobes. No significant difference was found when both CFS groups were combined and compared to the HC group. The use of stratification techniques is an important strategy in understanding the pathophysiology of CFS. This frontal lobe pathology could explain the more severe cognitive impairment previously reported in this subset of CFS patients.

Adult↗

PubMed1999

Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) and Lyme disease often share clinical features, especially fatigue, contributing to concern that Borrelia burgdorferi (Bb), the cause of Lyme disease, may underlie CFS symptoms. We examined 39 CFS patients and 40 healthy controls with a Bb immune complex test. Patients and controls were nonreactive. Centers for Disease Control and Prevention-defined CFS patients lacking antecedent signs of Lyme disease--erythema migrans, Bell's palsy, or large joint arthritis--are not likely to have laboratory evidence of Bb infection.

Adult↗

PubMed1999

A simple biofeedback digital data collection instrument to control ventilation during autonomic investigations.

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.

Biofeedback, Psychology↗

PubMed1999

Mitochondrial oxidative phosphorylation in heart from stressed cardiomyopathic hamsters.

Stress alone is generally not sufficient to produce serious disease, but stress imposed upon pre-existing disease can contribute to disease progression. To explore this phenomenon, cold-immobilization stress was imposed on young 12.5 month, necrotic phase with small vessel coronary spasm) and older (5 month, quiescent phase, between necrosis and heart failure) cardiomyopathic hamsters. Our hypothesis was that changes in mitochondrial energy processes are involved in stress induced pathology. Polarographic and high performance liquid chromatography (HPLC) techniques were used to measure mitochondrial respiration and oxidative phosphorylation and concentrations of phosphocreatine and adenylates, respectively, in hearts from young and old cardiomyopathic hamsters (stressed and unstressed). No significant differences were found between the young (2.5 month) and old (5 month) age groups in unstressed and stressed healthy hamsters and between young (2.5 month) and old (5 month) unstressed cardiomyopathic hamsters with respect to different parameters of mitochondrial oxidative phosphorylation and with respect to concentration of bioenergetic metabolites, except that ADP concentration was higher in older cardiomyopathic hamsters. Application of stress uncovered differences between young and old cardiomyopathic hamsters: respiration control index was lower and State 4 respiration was higher in young compared to old cardiomyopathic hamsters; whereas the total concentration of ATP was decreased to the same level in both cardiomyopathic groups when compared to control. Mitochondrial oxidative phosphorylation in young cardiomyopathic hamsters was more sensitive to Ca2+, as evidenced by partial uncoupling of respiration and oxidative phosphorylation, than in older cardiomyopathic hamsters and controls. In conclusion, young cardiomyopathic hamsters, i.e. in the necrotic phase of disease, were more susceptible to stress induced changes in mitochondrial oxidative phosphorylation than older cardiomyopathic hamsters and controls.

Age Factors↗

PubMed1999

Chronic fatigue syndrome: reviewing the research findings.

This article reviews the current state of research in chronic fatigue syndrome (CFS). The evolving definition, prevalence, and prognosis of this controversial illness are presented. We review studies examining psychiatric, personality, and psychosocial etiology for CFS. The evidence for pathophysiology in CFS is also presented, and studies investigating viral, immune, neuroimaging, neuroendocrine, and central and autonomic nervous system abnormalities in CFS are assessed. Current evidence indicates that CFS is multi-determined and heterogeneous and that subgrouping patients according to factors such as psychiatric state and symptom onset may be fruitful. The current state of treatment for CFS is reviewed, and the challenges for research aimed at resolving this prototypical mind/body problem are discussed.

Brain↗

PubMed1999

Natural history of severe chronic fatigue syndrome.

OBJECTIVE: To evaluate the natural history of chronic fatigue syndrome (CFS) in a severely ill group of patients at three points in time. DESIGN: Patients were enrolled from April 1992 to February 1994 and were evaluated three times. Time 1 (at enrollment): history, physical evaluation, and psychiatric evaluation; Time 2 (median = 1.6yrs after initial evaluation): postal questionnaire to assess current condition; Time 3 (median = 1.8 yrs after Time 2): medical and psychiatric evaluations. SETTING: The New Jersey CFS Cooperative Research Center, an ambulatory setting. PATIENTS: Twenty-three patients fulfilled the 1988 case definition for CFS and had symptom complaints that were substantial or worse in severity. All patients were ill less than 4.5 years; and none had a DSM-III-R psychiatric disorder in the 5 years before illness onset; none had substance abuse in the 10 years before enrollment. MAIN OUTCOME MEASURES: Severity of CFS symptoms was assessed by self-report questionnaires, laboratory tests, and medical examination. Psychological status was assessed using the Q-D15 and the Centers for Epidemiological Study-Depression Scale. At each time of evaluation, patients were categorized as severe, slightly improved, improved, and recovered. RESULTS: Over the 4 years of the study, 13 patients remained severely ill, 9 improved but still fulfilled the 1994 case definition for CFS, and 1 recovered. Illness duration, mode of onset, psychiatric status or depressed mood at intake, or chemical sensitivity did not predict illness outcome. One patient was diagnosed with an alternate illness, but it probably did not explain her CFS symptoms. Mood improved for those patients whose illness lessened. CONCLUSIONS: The prognosis for recovery was extremely poor for the severely ill subset of CFS patients. The majority showed no symptom improvement and only 4% of the patients recovered. Illness severity between Times 2 and 3 remained stable.

Adult↗

PubMed1999

Examination of Cloninger's basic dimensions of personality in fatiguing illness: chronic fatigue syndrome and multiple sclerosis.

Relatively few studies have examined the personality characteristics of patients with chronic fatigue syndrome (CFS). The personality profiles of 38 CFS subjects were compared with 40 healthy controls and 40 subjects with multiple sclerosis (MS), a chronic illness that shares many symptoms with CFS (e.g., fatigue), but has a known neurological substrate. Subjects were examined within Cloninger's biosocial theory of personality, which delineates basic dimensions of temperament. Both illness groups displayed similarly elevated levels of Harm Avoidance, and lower levels of Reward Dependence as compared with healthy controls. The MS group showed a lower level of Persistence than controls and CFS subjects. Implications for the relationship between chronic illness and personality are discussed.

Adult↗

PubMed1999

Is depression associated with immune activation?

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.

Adult↗

PubMed1999

Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion.

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 counts of WBC, CD3+ CD8+ cells, CD3+ CD4+ cells, T cells, B cells, natural killer cells, and IFN-gamma changed across time (P's < 0.01). No group differences were seen for any of the immune variables at baseline or after exercise (P's > 0.05). The immune response of chronic fatigue syndrome patients to exhaustive exercise is not significantly different from that of healthy nonphysically active controls.

Adult↗

PubMed1999

Cardiovascular response during head-up tilt in chronic fatigue syndrome.

This study examined the cardiovascular response to orthostatic challenge, and incidence and mechanisms of neurally mediated hypotension in chronic fatigue syndrome (CFS) during a head-up tilt test. Stoke volume was obtained by a thoracic impedance cardiograph, and continuous heart rate and blood pressure were recorded during a 45-min 70 degrees head-up tilt test. Thirty-nine CFS patients and 31 healthy physically inactive control subjects were studied. A positive tilt, i.e. a drop in systolic blood pressure of > 25 mmHg, no concurrent increase in heart rate and/or development of presyncopal symptoms, was seen in 11 CFS patients and 12 control subjects (P > 0.05). During baseline and the first 5 min of head-up tilt, CFS patients had higher heart rate and smaller pulsatile-systolic area than control subjects (P < 0.05). Among subjects who completed the test, those with CFS had higher heart rate and smaller stroke volume (P < 0.05) than corresponding control subjects. When comparing those who had a positive test outcome in each group, CFS patients had higher heart rates and lower pulse pressure and pulsatile-systolic areas during the last 4 min before being returned to supine (P < 0.05). These data show that there are baseline differences in the cardiovascular profiles of CFS patients when compared with control subjects and that this profile is maintained during head-up tilt. However, the frequency of positive tilts and the haemodynamic adjustments made to this orthostatic challenge are not different between groups.

Adult↗

PubMed1999

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

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.

Adult↗

PubMed1999

Impaired oxygen delivery to muscle in chronic fatigue syndrome.

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced oxygen delivery to muscles. Patients with CFS according to CDC (Center for Disease Control) criteria (n=20) were compared with normal sedentary subjects (n=12). Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemia oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous-wavelength near-IR spectroscopy. Phosphocreatine resynthesis was measured simultaneously using (31)P magnetic resonance spectroscopy. The time constant of oxygen delivery was significantly reduced in CFS patients after exercise (46.5+/-16 s; mean+/-S.D.) compared with that in controls (29.4+/-6.9 s). The time constant of oxygen delivery was also reduced (20.0+/-12 s) compared with controls (12.0+/-2.8 s) after cuff ischaemia. Oxidative metabolism was also reduced by 20% in CFS patients, and a significant correlation was found between oxidative metabolism and recovery of oxygen delivery. In conclusion, oxygen delivery was reduced in CFS patients compared with that in sedentary controls. This result is consistent with previous studies showing abnormal autonomic control of blood flow. Reduced oxidative delivery in CFS patients could be specifically related to CFS, or could be a non-specific effect of reduced activity levels in these patients. While these results suggest that reduced oxygen delivery could result in reduced oxidative metabolism and muscle fatigue, further studies will be needed to address this issue.

Adult↗

PubMed1998

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

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.

Adult↗

PubMed1998

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

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.

Adult↗

PubMed1998

Neuroimaging in chronic fatigue syndrome.

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.

Fatigue Syndrome, Chronic↗

PubMed1998

Impaired associative learning in chronic fatigue syndrome.

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.

Acoustic Stimulation↗

PubMed1998

Patients with epilepsy who die suddenly have cardiac disease.

BACKGROUND: Approximately 1 in 1000 patients with epilepsy dies suddenly and unexpectedly with no obvious medical cause. The purpose of this study was to determine if the hearts of such individuals harbor occult cardiac pathology. DESIGN: Following a comprehensive protocol, we performed careful pathologic evaluations of the hearts of 7 patients with epilepsy who died suddenly and 13 previously healthy people who died by hanging or a drug overdose. Hearts were studied only when there was no history or gross anatomical evidence of heart disease or the use of adrenergic drugs. METHODS: Multiple sections of each heart were evaluated independently by 2 cardiac pathologists who were blinded to patient group. RESULTS: Pathologic conditions were found in 5 hearts in the group with epilepsy and in none of the hearts in the comparison group. Four of the 7 hearts in the group with epilepsy had evidence of irreversible pathology in the form of perivascular and interstitial fibrosis. These 4 hearts plus a fifth had evidence of reversible pathology in the form of myocyte vacuolization. Lesions occurred predominantly in the subendocardium. CONCLUSION: Our results support the hypothesis that patients with epilepsy who die suddenly and unexpectedly have cardiac pathologic conditions that may be responsible for their deaths.

Adolescent↗

PubMed1998

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

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.

Animals↗