Research Posters

Poster presentations of research added alternative and international perspective to the conference. Most were done by teams of researchers, and the name listed here is that of the member who officially presented the poster at the conference. Several studies that have been reported previously in the Chronicle are not included here.

Epidemiology posters
The relationship between CFS, fibromyalgia and multiple chemical sensitivity (MCS) was explored by Albert Donnay. Of 100 patients in Grace Ziem's MCS practice, 88 met the criteria for CFS, with more than half of them also meeting the criteria for fibromyalgia. Only 10 patients had MCS without meeting criteria for CFS or fibromyalgia.

In an effort to identify causative and/or influencing factors that would differentiate patients who met criteria for CFS from those with chronic fatigue who did not meet CFS criteria, Brigitta Evengard of Sweden used a variety of questionnaires with nearly 400 patients. They found no differences between the groups in functional capacity, sense of coherence, depression and symptoms. Those who met the CFS criteria were more likely to be female, had an infectious-type onset and sought specialized care sooner after becoming ill.

A team of medical school researchers in Brazil found that only 35% of doctors and community health workers were familiar with CFS. Those who were believe CFS is a rare disorder and that it is associated with personal and family problems, stress and viral infections. Luis C. Nacul reported that prevalence of CFS in Brazil appears similar to that in developed countries.

An Italian group reported its efforts to classify several hundred CFS patients there into subgroups on the basis of various lab tests, brain scans, neuropsychological tests and symptoms. Delia Racciatti reported that CFS in Italy appears to be a heterogeneous illness with several causes and patterns.

Hypothesizing that patients may not reliably perceive improvement or decline in their condition, researchers in Tulsa, Okla., established a baseline of patients' physical and mental functioning using a Short Form 36 (SF-36) assessment and repeated it one year later. At that one-year point, patients were asked to rate their condition from much better to much worse. There was no correlation between how patients reported their condition and either positive or negative changes in the SF-36 assessment. Stanley N. Schwartz concluded that reliance on patient self-assessment may be one reason certain treatments have appeared to yield different results in different studies.

Lana A. Tiersky and colleagues in New Jersey questioned whether the 1988 and 1994 CFS case definitions identified the same illness. Of 62 subjects analyzed for symptoms and illness course, 45 met both the 1988 and 1994 criteria, while 17 met only the 1994 criteria. Those who met the 1988 criteria were found to suffer from a more severe form of the illness, with a sudden onset following a flu-like infection. The researchers concluded that the two case definitions appear to identify distinct groups. They hypothesized an infectious cause for the illness in those meeting the 1988 definition.

Neil McGregor and colleagues in Australia challenged the current case definition for CFS to determine if it identified a homogeneous or heterogeneous set of patients. The researchers analyzed data from several CFS studies based on patient symptoms, onset events, urinary amino and organic acid and serum lipid profiles. They found many ways to subdivide CFS patients, but the various factors produced inconsistent groupings. The researchers concluded that the current CFS definitions either lack standardization or the exclusion criteria are insufficient to exclude all other fatigue disorders.

In another effort to subdivide CFS patients, Theresa L. Walker of Eli Lilly and Co. interviewed 40 patients at a University of Michigan clinic and found the subjects easily divided into two groups based on a self-rating of symptom severity. However, those two groups were not distinguishable by age, exercise, activity (work vs. disability), sleep habits, medications (allopathic or alternative), weight gain or loss, and their perception of the cause of their illness. That subdivision of patients also did not correlate with improvement in health or disability after a year's treatment.

Clinical posters
Immune activation of coagulation and thickening of blood can be treated with the anticoagulant drug heparin, said David Berg of HEMEX Laboratories in Phoenix, Ariz. His laboratory tested the heparin on a small group of CFS patients whose blood tests showed thickening, and most patients reported improvement of headache, fatigue and pain symptoms.

As an alternative to growth hormone, Paul R. Cheney of North Carolina treated a small number of patients with plant-derived bioactive polypeptides known to increase IGF-1 levels. After 60 days of treatment, more than half the patients reported improvement of symptoms, and IGF-1 levels were normalized in those who responded.

In a five-year follow-up of young patients treated with intravenous gammaglobulin, Katherine Rowe of Victoria, Australia, reported that there was no persistent deterioration in function related to CFS in any young person, although a significant number remained disabled. The subjects' immune responses before the trial did not predict functional outcome after five years.

Responding to findings that urinary serine levels were low in most CFS patients, Rosamund Vallings of New Zealand offered patients serine supplementation. Patients reported "considerable" benefit from the treatment.

Immunology posters
Lymphocytes from eight patients and 14 controls were cultured in the presence and absence of different mutagens in a laboratory study led by Kenny De Meirleir in Brussels. The findings suggest abnormalities in intracellular protein metabolism and increased sensitivity to alcohol.

Immune activation as defined by elevated T-cells is associated with measures of psychological distress and attitudes about oneself, according to a study by Lynn Helder of Biodoron Psychology, Hollywood, Fla. Psychological distress may have a stronger relationship with immunologic functioning in those CFS patients who are the most ill, as suggested by T-cell analysis.

Noting that exercise can be a useful tool in stimulating an immune response, John LaManca and colleagues in New Jersey matched CFS patients and non-exercising controls. While the exercise evoked significant immune response as measured by blood testing of lymphocytes, cytokines and NK cells, there were no significant group differences between patients and controls.

Testing a hypothesis about possible allergies to various metals being a part of CFS, Gudrun Lindh and colleagues in Sweden found that nickel sulphate allergy was significantly more common among the CFS patients, and particularly females, than among controls. The researchers suggested that nickel or metals reacting with it might play a role in causing a chronic stimulation of the immune system, or nickel allergy could simply be a symptom of that immune stimulation.

The presence of virus-like structures in peripheral blood lymphocytes may correlate with patients who relate onset of CFS to an acute fever, according to laboratory study by Michael Holmes of New Zealand.

Nancy Klimas of Florida reported that her ongoing study involving lymph node biopsies supports the hypothesis that CFS is a disease of the immune system, based on the concentrations of activated T-cells.

Jeroen Visser of the Netherlands presented laboratory research showing that cytokine production is affected abnormally by glucocorticoids in CFS patients.  

Interdisciplinary posters
Only about half of family doctors in the Netherlands use the diagnosis of CFS, while only 10% felt able to give sufficient information about CFS to their patients, Ellen Bazelmans reported. Doctors said they were less sympathetic to CFS patients' complaints, attributing those complaints mainly to psychosocial factors, while patients mainly attributed their illness to physical causes.

The same Dutch research group studied whether CFS affects more women than men because women are at greater risk for overload by the demands of work, home and family. They also theorized that since women who become sick may not be able to quit the latter roles as easily as men, they would have a worse prognosis for improving their health. They found little evidence for the theory, except that women who had children at home, regardless of whether they worked, experienced a worsening of impairment during the study.

Bazelman's colleague, Gijs Bleijenberg, reported a comparison of fatigue in cancer patients who in remission to fatigue in CFS patients. In contrast to CFS patients, cancer patients in remission had lower scores for depression and perceived few physical, social and emotional health problems, although those who suffered from the most severe fatigue had scores for depression and reported other symptoms at rates comparable to CFS patients.

Bleijenberg also reported on a comparison of bedridden CFS patients to non-bedridden CFS patients. Twenty bedridden patients were recruited by the Dutch M.E. Association and were visited at home. The researchers found the bedridden patients were more fatigued, experienced more impairment in basic activities, were less active, had more current psychiatric disorders., appeared more focused on physical discomfort, and reported more physical complaints.

Christopher Christodoulou in New Jersey reported a study based on the tendency of CFS patients to be dissatisfied with their cognitive functioning, even when neuropsychological studies show that cognitive deficits are more mild than perceived. The study involving just five patients used functional MRI scans to examine the pattern of neural activation associated with that dissatisfaction. The results suggested that those who viewed their cognitive performance as substandard might be delayed in developing a routine brain response and so may perceive greater fatigue. Using the same set of subjects and functional MRI scans, Gudrun Lange implicated changes in specific brain regions for impaired performance on a memory task.

The fatigue experienced by multiple sclerosis (MS) patients is different from the fatigue experienced by CFS patients, according to research presented by Christodoulou. Relative to total fatigue scores, on which CFS patients were higher, CFS patients showed greater mental fatigue while MS patients showed greater physical fatigue. The researchers suggest that clinicians treating CFS through gradual increases in activity may want to include mentally demanding activities, such as balancing a checkbook, in addition to purely motor activities.

Women with CFS who participated in group therapy to help them deal with their illness and life situations reported the therapy was helpful, particularly through the exchange of personal experiences. However, their fatigue and formally measured quality of life were not affected, according to a presentation by Brigitta Evengard of Sweden.

Peter Madill conducted a group therapy experiment at his private practice in Sebastopol, Calif. Results suggested that group sharing in the model of the Stanford University cancer therapy group program and qigong exercises enhanced cognitive behavior therapy in the group setting, at significantly reduced cost to individual therapy.

When CFS patients and controls were compared on four cognitive tasks during rested and fatigued states, only small differences were found in cognitive functioning and electrical brain activity, according to research presented by Ronald Gordon of the University of California at Irvine. The most significant differences were on tasks that required neural mechanisms for motor preparation and execution.

CFS and MS groups were comparable in their depressive style in attributing causes for good and bad events and shared a difficulty in describing and differentiating emotions, reported Susan K. Johnson of the University of North Carolina at Charlotte. This likely reflects the demoralizing effects of coping with a chronic, disabling illness. However, CFS patients showed a lack of trust in medical professionals, reflecting the added burden on CFS subjects of an illness that lacks medical legitimacy.

Lana A. Tiersky of New Jersey reported a study that looked at whether individuals with CFS experience more negative and stressful life events than healthy individuals. CFS subjects reported significantly more negative life events than healthy controls. CFS patients with a psychiatric disorder predating CFS experienced even more negative life events following the onset than did others. The researchers concluded that a pre-illness psychiatric history could make individuals particularly vulnerable to the negative experiences associated with chronic illness.

Microbiology posters
Root canal teeth contain significant amounts of xenobiotic toxins (an antibiotic chemical substance not produced by the body), according to analysis of teeth removed from five CFS patients. Paul R. Cheney of North Carolina concluded that a subset of patients may respond significantly to extraction of root canal teeth, but clinical improvement may not result because teeth may not be the only source of toxins.

Three human pathogenic mycoplasma species (fermentans, hominis and penetrans) were detected at rates of about 50% in persons with CFS, fibromyalgia, rheumatoid arthritis and Gulf War syndrome, according to Paul Choppa of Immunosciences Laboratories in Beverly Hills, Calif.

A study that looked for evidence of Borna disease virus in Swedish CFS patients found no evidence for an involvement of Borna disease virus in CFS. However, the response to a control antigen used in the testing of these 169 patients leaves open the hypothesis that an unknown infection may be involved, according to researcher Brigitta Evengard.

However, Susan Levine of New York tested serum samples from 77 CFS patients and 33 controls for Borna disease virus. Thirteen samples from CFS patients and two from controls showed immunoreactivity to Borna disease virus proteins. Both researchers said more study was needed.

Researchers in Scotland spent two years looking for evidence of Borna disease virus and five other infective agents in CFS patients. Kathleen Simpson reported that none of the controls showed evidence of any of the viruses. Four of the CFS patients were infected with hepatitis B, three each with varicella zoster virus and Borna disease virus, and two with brucella. None had enteroviruses or influenza B. None of the infectious agents were present in a statistically significant number of cases and none of the patients had evidence of dual infection. The researchers stated that the data highlights one difficulty of working with CFS patients-that patients may be suffering from undiagnosed, less common infections, and that could make data from CFS research misleading.

Lawrence A. Klapow of Burlingame, Calif., found decayed evidence of a suspected roundworm, cryptostrongylus pulmoni, in sputum samples from 11 of 28 CFS patients he examined. The usual indicators of roundworm infection-high levels of eosinophil blood cells and positive stool tests-were not present.

Physiology posters
Teen-agers with CFS had a distinct response to orthostatic stress (tilt table), with increased tendency to rapid heart rate and decreased cerebral blood flow velocity, and an exaggerated response to isoproterenol, according to Mark E. Alexander of Boston, Mass. Therapy for orthostatic intolerance improved the reported well-being of the CFS group. In another tilt-table study, Antonio Sisto of Italy reported results that support the association between CFS and neurally mediated hypotension.

A bicycle exercise test was used by Pascale De Becker of Brussels in an effort to find an objective measure of "50% reduced activity." CFS and fibromyalgia patients had a working capacity that was at least 40% lower than the controls, which the research team said objectively proved their physical disability. They speculated that severe muscle weakness, not deconditioning, was the reason most patients did not reach 85% of their target heart rate. De Becker also examined the prevalence of respiratory symptoms in CFS patients and considered the value of pulmonary function testing. Compared to a control group, CFS patients had similar total lung capacity, but there were significant differences in vital capacity (the amount of air that can be expelled) and residual volume. This may explain, at least partially, the respiratory symptoms observed in most CFS patients.

Following reports of elevated substance P (which contributes to pain signals in the nervous system) in fibromyalgia patients, a study in Sweden attempted to find the same condition in CFS patients. The levels of substance P were normal in patients who met the criteria for CFS but not for fibromyalgia. Brigitta Evengard reported this supports the notion that fibromyalgia and CFS are different disorders.

John Gow of Scotland reported that the passage of calcium ions across cell membranes might be a factor in CFS, as excessive calcium influx into muscle cells leads to depletion of energy reserves. Analysis of muscle biopsies from 16 patients indicated an upregulation of the muscle genes involved in handling the calcium ions.

Case histories of two female athletes who were overtraining before onset of CFS suggest that overtraining may have suppressed their immune function and increased their susceptibility to develop CFS, according to J. Mantalvan of Fitness/Works LLC in Bethesda, Md.

CFS patients and controls have similar balance before exercise, but after exercise, CFS patients had poorer balance, but only with eyes closed, according to Lorna Paul of Scotland. Because between 30% and 70% of CFS patients suffer from dysequilibrium, the researchers are pursuing further studies with more sensitive measurements in more dynamic conditions.

Hirohiko Kuratsune of Japan reported a study that found a possible correlation between blood flow in the brain and concentrations of acylcarnatine, suggesting that metabolism of acylcarnatine may be related to the pathogenesis of CFS. Similarly, research in Italy reported by Delia Racciatti confirmed brain perfusion impairment in CFS, providing objective evidence of central nervous system dysfunction.

Studies expand knowledge of RNase L in CFS
Several presentations were made about the RNase L research in Dr. Robert Suhadolnik’s lab at Temple University. Dr. Suhadolnik hypothesizes that the 2-5A synthetase/RNase L pathway is not functioning normally in people with CFS. This pathway is a natural defense against viruses and regulates cell growth and differentiation. RNase L, the key enzyme in the pathway, degrades RNA, especially viral RNA.

Previous studies (funded by The CFIDS Association of America) have shown this pathway to be overactive (or upregulated) in CFS. In 1997, Dr. Suhadolnik’s research group published the first evidence for a new, smaller form of RNase L in some people with CFS. It was named low molecular weight (LMW) RNase L because it is smaller (37 kDa) than the usual form (80 kDa).

On the basis of these results, an expanded study was designed in collaboration with Drs. Dan Peterson and Paul Cheney. The 53 CFS patients in this study fit the 1988 and 1994 definitions for CFS, had a Karnofsky score of 60 or less, and expressed fatigue, neurocognitive complaints and pain as their main symptoms. Consistent with earlier samples, the CFS group had higher concentrations of bioactive 2-5A compared to 37 healthy controls, a higher activity of RNase L and more of the LMW RNase L.

In addition, as the amount of the normal RNase L increased, the amount of the LMW RNase L decreased. This may mean that the LMW RNase L is formed from the larger 80 kDa RNase L. All measurements of the pathway activity increased as the Karnofsky score decreasd. In other words, the patients who felt the sickest had the highest level of dysfunction in the 2-5A synthetase pathway.

Dr. Suhadolnik also learned that the smaller LMW RNase L is more active and harder to control compared to the normal 80 kDa RNase L.

Continuing studies (supported by the National Institutes of Health) aim to determine whether the LMW RNase L is unique to CFS and could eventually be used as a diagnostic test for CFS, and to test the hypothesis that the LMW RNase L originates from the 80 kDa RNase L.

--Nancy Lee Reichenbach