Research News

Gender may affect drug reaction
Men and women may have dramatically different reactions to medications, yet very few drugs have been studied to determine the proper dose and potential side effects according to sex. Scientists are just beginning to learn how hormones and other gender differences interact with certain drugs and affect their potency. For instance, certain male hormones seem to protect men from the irregular heartbeat side effect of the allergy drug Seldane. Also, women's hormones fluctuate according to their menstrual cycle; women with asthma seem to metabolize theophylline much more slowly during ovulation, thus improving their lung function during that time.
 
To complicate matters, researchers are also discovering dozens of enzymes that help certain drugs get inside the body's cells, and some of those enzymes are more prevalent in one gender than the other. One study found, for instance, that morphine controls pain much better in women than in men, while another study suggested that the over-the-counter painkiller ibuprofen is more effective for men.
 
It wasn't until the early 1990s that the FDA forced drug manufacturers to allow women of childbearing age into drug studies. Last August, the FDA began requiring manufacturers to consider gender as a factor in analyzing responses to experimental drugs. These changes could be significant for persons with illnesses such as CFIDS and fibromyalgia, a majority of whom are women.

FM common in inflammatory bowel disease
A team of researchers at Ben-Gurion University in Israel sought to estimate the prevalence of fibromyalgia in 113 patients with either Crohn's disease or ulcerative colitis. Nearly 20% of patients with ulcerative colitis and 49% of those with Crohn's disease met the American College of Rheumatology's criteria for fibromyalgia. Patients with Crohn's disease had more tenderness and more tender points and they reported more frequent and more severe fibromyalgia symptoms than did those with ulcerative colitis.
 
The researchers suggested that recognizing fibromyalgia in patients with inflammatory bowel disease would help to ensure correct treatment. The paper, titled "Fibromyalgia in inflammatory bowel disease," by D. Buskila, et. al., was published in the May 1999 issue of the Journal of Rheumatology.

Response to hypoglycemia reduced in FM
The hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system are impaired in women with fibromyalgia, resulting in reduced production of adrenocorticotropic hormone (ACTH) and epinephrine in response to hypoglycemia. The study, led by Dr. Gail K. Adler of Harvard Medical School, involved only 15 patients and 13 healthy controls, all of them premenopausal women. While the ACTH and epinephrine responses to hypoglycemia (low blood sugar) was 30% lower in women with fibromyalgia compared with controls, the prolactin, norepinephrine, cortisol and dehydroepiandrosterone (DHEA) responses were similar in the two groups. The study was published in the May 1999 issue of the American Journal of Medicine.

Selective review agitates CFIDS supporters 
A review article (Barsky, A.J., and Borus, J.F., 1999. "Functional somatic syndromes." Annals of Internal Medicine, 130:910-921) suggests that CFIDS is a form of mass hysteria/somatisation disorder, along with sick building syndrome, multiple chemical sensitivity, repetitive stress injury, the side effects of silicone breast implants, Gulf War syndrome, irritable bowel syndrome, candidiasis hypersensitivity, mitral valve prolapse, chronic Lyme disease and fibromyalgia. The authors suggest that the "suffering of these patients is exacerbated by a self-perpetuating, self-validating cycle in which common, endemic, somatic symptoms are incorrectly attributed to serious abnormality, reinforcing the patient's belief that he or she has a serious disease." They argue that the sick role is reinforced and the disability perpetuated by sensationalized media coverage, sympathetic physicians, litigation, disability compensation and hotlines.
 
While the authors state that patients often "dismiss medical authority and epidemiologic evidence that conflicts with their beliefs," the authors themselves seem to have done the same thing. Psychologist Ellen Goudsmit, commenting on this paper for the Capita Selecta Quarterly, wrote that this paper "ignores or distorts research evidence," often refers to articles on fatigue when focusing on chronic fatigue syndrome, and dismisses medical evidence as "premature, though this does not apply to theories relating to phobic avoidance, etc." She notes that the authors' search of published articles "seems to have missed all the studies and reviews suggesting that biological factors play a major role.(and) the various studies challenging the effectiveness of CBT," despite their use of more than 200 references.
 
The authors are psychiatrists at Brigham and Women's Hospital in Boston. Their review research was supported in part by a grant from the National Institute of Mental Health.
 
(Editor's note: The CFIDS Association has asked a number of respected physicians and researchers to respond professionally to the article.)

CBT: Best option for sick veterans?
 Cognitive behavioral therapy (CBT) may help veterans affected by Gulf War syndrome manage their symptoms and lead more productive lives, according to a report in the June 1999 issue of the Journal of Occupational and Environmental Medicine.
 
"Patients must be helped to the recognition (and they must discover it themselves) that there is no specific treatment for neurotoxic disease and that clinical improvement will involve learning to live with what they have, to increase endurance and strength, and to move past this phase of their lives," conclude Drs. Michael J. Hodgson of the University of Connecticut Health Center and Howard M. Kipen of the University of Medicine and Dentistry of New Jersey.
 
Even if some environmental exposure is found to be the cause of the muscle aches, fatigue, headaches, memory problems and other symptoms, an effective treatment probably will not be found, Drs. Hodgson and Kipen write. "With this in mind, we believe it is critical to address the practical question of what to do for those Gulf War veterans and family members who suffer."
 
In the same issue of the journal, Drs. Timothy R. Gerrity and John R. Feussner of the Veterans Health Administration announce the largest, best designed trial to date to study whether a combination of CBT and exercise can help relieve the symptoms of Gulf War syndrome.

Chiari I malformation studied
 An analysis of the Chiari I malformation based on close examination of 364 patients determined that the symptoms, often duplicative of those of CFIDS, seem to be related to disturbances in the cerebrospinal fluid and direct compression of nerve tissue. The study, by Dr. Thomas H. Milhorat of the State University of New York Health Science Center in Brooklyn, was published in the May 1999 issue of Neurosurgery.
 
The Chiari I malformation is a disorder involving the crowding of the back portion of the brain with herniation of brain tissue through the foramen magnum, the opening in the back of the skull where the brain and spinal cord are connected. Symptoms may result from a broader range of abnormalities in the brainstem and upper spinal cord than were previously understood, according to the study. The most common symptoms are pressure headaches at the back of the head and neck, fatigue and muscle weakness, vision disturbances, short-term memory difficulties and dizziness. Since these and many less common symptoms overlap with those of CFIDS, research is currently under way to determine whether this condition may be the cause of illness in some patients with CFIDS and fibromyalgia (see article in the May/June 1999 Chronicle).

From the Journal of Chronic Fatigue Syndrome
The following briefs summarize articles in the Journal of Chronic Fatigue Syndrome, Vol. 5(1), 1999. (Articles are available for a fee from The Haworth Document Delivery Service: 800/342-9678, or by E-mail at getinfor@haworthpressinc.com ).

M. Reyes, et. al., Chronic Fatigue Syndrome Progression and Self-Defined Recovery: Evidence from the CDC Surveillance System. 
155 patients from the CFS surveillance study undertaken from 1989 through 1993 were followed through 1997. The CDC researchers determined that the cumulative probability of recovery was 31% during the first five years of illness and 48% during the first 10 years. Patients reporting recovery and those remaining ill were similar, with no significant differences with respect to age at onset, race, gender, education, presence of children, income or prior hospitalizations. Recovery rates were similar for those with sudden and gradual onset. All patients, including those who reported recovery, continued to have some CFS-defining symptoms. While sudden onset cases reported many more symptoms at onset than gradual onset cases, particularly sore throats and fevers, over time the two groups reported similar symptom profiles. The researchers recommended that a standard definition of recovery in CFS be developed and that studies take into account the variable duration of illness.

N. Endicott, Chronic Fatigue Syndrome in Psychiatric Patients: Evidence of Premorbid Anomalous Patterns of Brain Organization.
This psychiatrist examined 46 patients from his practice who had developed CFS and compared them to his patients who had not. He focused on 20 different anomalous brain conditions, such as speech disorders, fingernail biting, motion sickness, mixed handedness, migraines, seizures and learning disorders. He determined that psychiatric patients who later developed CFS had a higher number of pre-CFS anomalous brain conditions than did patients who did not develop CFS. The findings support the hypothesis that central nervous system dysregulation is an integral aspect of the pathogenesis of CFS.

W.M.H. Behen, et. al., In Vitro Study of Muscle Aerobic Metabolism in Chronic Fatigue Syndrome.
This study in Scotland examined muscle tissue from 16 CFS patients and 10 controls to determine if there were defects in the way that the muscle fibers in a CFS patient use oxygen. The researchers found evidence of mild aerobic defects in some cases of CFS, although the defects were not consistent. They concluded the results support their hypothesis that some cases of CFS might be due to mitochondrial disorders.

Jiaxu, C., and Weiyi, Y., Treatment of Chronic Fatigue Syndrome with Chinese Medicine.
These authors argue that Chinese herbs, some that have been used for 4,000 years, may be effective in treating severe fatigue. They believe that fatigue results from a disturbance in the flow of qi or energy force, rather than the more traditional theory of a deficiency in one of the qi pathways called the spleen meridian. With the support of the National Natural Science Foundation Committee of China, they plan a study to test the effects of specific Chinese herbs on stress-induced fatigue in rats and to attempt to understand how the herbs work.

Layander, J.A., A Nutrient/Toxin Interaction Theory of the Etiology and Pathogenesis of Chronic Pain-Fatigue Syndromes: Part I and II.
This paper by a graduate student at the University of New Mexico proposed the theory that CFS, fibromyalgia and Gulf War syndrome share a common underlying etiology at the subcellular level: a deficiency of magnesium and an excess of fluoride. The author argues that these syndromes present a growing worldwide public health problem due to decreasing magnesium intake in diet and increasing exposure to fluoride compounds in industry, agriculture, medicine and personal hygiene products. Hormones make women more vulnerable to the condition, he argues, and stress and various other minerals also affect the interaction of magnesium and fluoride. The author argues that, if the theory is correct, effective treatment would include increasing intake of magnesium, eliminating exposure to fluoride (including fluoridated water, certain types of seafood, gelatin, and many toothpastes and mouthwashes), adding other specific vitamins and dietary supplements, eliminating alcohol, managing pain and lifestyle aggressively to reduce stress, and maintaining a regular exercise program.

The following briefs summarize articles in the Journal of Chronic Fatigue Syndrome, Vol. 5(2), 1999.

Bell, I.R., et. al., Differing Patterns of Cognitive Dysfunction and Heart Rate Reactivity in Chemically Intolerant Individuals With and Without Lifestyle Changes.
These researchers looked at people with the symptom of intolerance to low levels of environmental chemicals (a common symptom in CFS). They attempted to differentiate between those who had made lifestyle changes as a result of the symptoms and those who had not. While the study group was quite small, just 18 persons, the group that was forced to make lifestyle changes showed a higher rate of family history of alcohol problems, abuse and attention deficit disorder. The ultimate conclusion, however, was that persons with chemical intolerance "comprise a heterogeneous population."

Ax, S., Coping Differences Between Chronic Fatigue Syndrome Sufferers and Their Careers.
This study in England considered coping strategies used by CFS patients and caregivers. Strategies include "planful problem solving, positive reappraisal, self-controlling, escape/avoidance, accepting responsibility and distancing." The results indicated no differences in strategies between patients who were supported by a caregiver and those who were not. There were few differences by gender. Male caregivers were the least active in seeking social support, and husband carers reported the lowest use of coping strategies of any group. The author did not attempt to determine whether the coping strategies reported by sufferers and carers were perceived as helpful. 

Green, J., Romei, J., and Natelson, B., Stigma and Chronic Fatigue Syndrome.
The results of this study in New Jersey supported the hypothesis that persons seeking relief from symptoms of CFS would feel stigmatized, and that the stigma was made worse when doctors attributed the symptoms to psychological causes. More than three-quarters of the subjects had been labeled a psychological case by at least one physician. The same percentage coped by using an educating strategy, while 39% saw a need to be secretive about their symptoms in some circumstances. The researchers concluded that ignorance or skepticism of CFS by physicians might influence attempts by patients to legitimize their symptoms, especially by educating others, and to seek out another doctor.

New service alerts scientists to funding 
The CFIDS Association of America has started an E-mail announcement list for scientists who are interested in receiving news about possible funding sources for their CFIDS research. For more information, visit the web site www.onelist.com/subscribe.cgi/cfsgrant-info or contact Vicki Walker at vwalker@cfids.org.