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[Return to digest index] --------------------------------------------- This is a special digest of Co-Cure Research & Medical posts only Problems? Write to mailto:firstname.lastname@example.org --------------------------------------------- ---------------------------------------------------------------------- Date: Tue, 27 Feb 2007 12:40:28 -0500 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: A Nationwide Study of Connective Tissue Disease and Other Rheumatic Conditions Among Danish Women With Long-Term Cosmetic Breast Implantation A Nationwide Study of Connective Tissue Disease and Other Rheumatic Conditions Among Danish Women With Long-Term Cosmetic Breast Implantation. Ann Epidemiol. 2007 Feb 23; [Epub ahead of print] Fryzek JP, Holmich L, McLaughlin JK, Lipworth L, Tarone RE, Henriksen T, Kjoller K, Friis S. From the International Epidemiology Institute, Rockville, MD, and the Departments of Medicine (J.P.F., J.K.M., R.E.T.) and Preventive Medicine (L.L.), Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN; and Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (L.H., T.H, K.K., S.F.). PMID: 17321754 PURPOSE: Numerous epidemiologic studies have demonstrated that breast implants are not associated with connective tissue diseases (CTDs). However, many CTDs are rare, and continued follow-up of women with breast implants is warranted. METHODS: We extended by 5 years the follow-up of our earlier population-based cohort study of Danish women with cosmetic breast implants (n = 2761) and comparison groups of women with other types of cosmetic surgery (n = 8807). All women were followed from January 1977 through December 2001. Hospitalization and outpatient data for CTD and ill-defined and other rheumatic conditions in the implant and comparison groups were compared with those in the general Danish population. Additionally, CTDs and fibromyalgia were confirmed through medical chart review, and direct comparisons of the breast implant cohort with the comparison cohort were performed. RESULTS: When compared with general population rates, CTDs were not statistically significantly elevated in either the implant or the comparison cohorts. However, unspecified rheumatism was similarly increased in the implant (standardized rate ratio = 1.9; 95% confidence interval = 1.6 to 2.2) and comparison (standardized rate ratio = 1.5; 95% confidence interval = 1.4 to 1.7) cohorts. In analyses of diagnoses validated by chart review, women with cosmetic breast implants compared with those having other types of plastic surgery or consultation for plastic surgery had no statistically significant excess for any specific confirmed CTD or combined CTDs (hazard ratio = 1.3; 95% CI = 0.9 to 1.9). In addition, there was no relation between breast implants and confirmed fibromyalgia (hazard ratio = 1.2; 95% CI = 0.6 to 2.1). CONCLUSIONS: This extension of our earlier cohort study further supports the consensus of epidemiologic research that breast implants are unrelated to the development of CTD. [Return to top] ------------------------------ Date: Tue, 27 Feb 2007 19:25:45 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Suhadolnik receive $1M grant from NIH for HIV amd CFS research Source: Temple University Date: February 27, 2007 Author: Vicky Thomas <email@example.com> URL: http://media.www.temple-news.com/media/storage/paper143/news/2007/02/27/News/Doctors.Receive.1m.Grant.For.Hiv.Prevention.Research-2744077.shtml Doctors receive $1M grant for HIV prevention research ----------------------------------------------------- Through the use of gene therapy, researchers are striving to find ways to stop the spread of HIV. Dr. Robert Suhadolnik, in his laboratory, isolates DNA from a carrier. Suhadolnik and his research team have worked for 20 years toward attaining a treatment alternative for the HIV infection. Researchers in the School of Medicine are making progress in the understanding and treatment of two diseases caused by abnormalities in the human antiviral pathway: HIV and Chronic Fatigue Syndrome. According to the Centers for Disease Control and Prevention, approximately 40,000 people will be infected with HIV this year in the United States alone. The virus' rapid mutation rate allows it to resist many drug therapies, making it impossible for a vaccine to guard the body against the spread of an infection. But the research team, headed by Dr. Robert J. Suhadolnik, a professor of biochemistry in the School of Medicine, is developing a way to immunize against the spread of HIV through the use of gene therapy. After 20 years of researching the intracellular immunization approach to inhibit HIV, Suhadolnik's six-member team was recently awarded a $1 million research grant by the National Institutes of Health to continue its work. "We have shown now that we can protect the cell from HIV infection in vitro, in the laboratory," Suhadolnik said. Gene therapy immunization, as opposed to vaccines, introduces an antiviral pathway into a patient's genes. The gene replicates and becomes incorporated into the patient's system. When the HIV virus is introduced to the body, the gene becomes active and kills the virus. "The HIV virus has developed ways to counteract the natural antiviral pathways," said Suhadolnik, adding that this new therapy could stop the spread of HIV because the delivery of antiviral genes to cells would restore the antiviral defense pathways. "Gene therapy is extremely interesting because we're using the body's own immune system to combat the virus without outside chemicals or agents," said Sean Roberts, a graduate student in the School of Medicine and a member of the research team. "It's important towards finding a cure. Our primary goal is to find a cure." Suhadolnik said the earlier antiviral construct had shortcomings because there was a chance that the modified cell could contain infectious particles. "Now we have a self inactivating vector that we can put the antiviral pathway in by way of gene therapy, and the target cells get activated when the virus comes along," said Suhadolnik. He also explained that, like a vaccination, the particles would be inactive until infection was introduced. "When you get vaccinated, you don't know that those antibodies are present, but when an infectious particle comes in the body, then the antibodies are made and the disease is wiped out," Suhadolnik said. Gene therapy has also been successful in curing other immune deficiency diseases, such as Severe Combined Immunodeficiency or "Bubble Boy" disease, which was once considered a fatal condition. The study of antiviral pathways has been the center of Suhadolnik's research program and is also applied to the team's research on CFS, said Nancy Reichenbach, an associate scientist in the School of Medicine and a member of the research team. According to Suhadolnik, the cause of CFS is unknown and can occur suddenly with flu-like symptoms and debilitating fatigue. The illness, which was once believed to be a psychological disorder connected to depression, is common in women. But Suhadolnik and his research team have found that CFS is not a clinical depression disease, but rather caused by a defect in the antiviral defense pathway. While HIV turns off the human antiviral defense mechanism, CFS is a disorder caused when the antiviral pathway is working too hard, making the patient exhausted. "Initially we reported that the antiviral pathway was abnormal in patients diagnosed with Chronic Fatigue Syndrome," Suhadolnik said. "In subsequent studies, we reported the appearance of an abnormal protein in the blood cells of the patients diagnosed with CFS. In essence, what we showed was the appearance of a new protein." In addition to the grant for their HIV research, Suhadolnik and his team were also granted a U.S. patent for their research and discovery of diagnosis for CFS. -------- (c) 2007 Temple University [Return to top] ------------------------------ Date: Thu, 1 Mar 2007 15:06:44 +0100 From: Jan van Roijen <j.van.roijen CHELLO.NL> Subject: act,med: The NICE approach to ME is outrageous ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 1 March 2007 <<<< Editorship : j.van.roijen chello.nl Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ From: DEnlander aol.com Reference: *RiME's Summary of APPG Meeting* Help ME Circle, February 28: http://www.me-net.combidom.com/index.htm The NICE approach to ME is outrageous. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ It would be akin to a physician treating polio in the 1940's with Graded Exercise Therapy. Exercise then was helpful in reducing atrophy but did little to cure polio. A polio victim was naturally depressed because of the debilitating illness, Cognitive behavioral therapy CBT if it was used then, thank the Lord it was not, may have made the patient less depressed but would have done little to cure the underlying disease. Translate polio to ME and we have the ludicrous modern day equivalent with its waste of scarce research funds and futile efforts to promote a self serving psycho babble. Derek Enlander, M.D. M.R.C.S., L.R.C.P. New York [Return to top] ------------------------------ Date: Thu, 1 Mar 2007 13:05:52 -0500 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Stress, depression and fibromyalgia Stress, depression and fibromyalgia. Acta Neurol Belg. 2006 Dec;106(4):149-56. Van Houdenhove B, Luyten P. Dept of Liaison Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium. boudewijn.vanhoudenhove uz.kuleuven.ac.be PMID: 17323832 There is increasing evidence that stress and depression may play a crucial role in the aetiology and pathophysiology of fibromyalgia (FM). We first review recent studies on the possible role of life stress, including childhood trauma, in FM. Subsequently we focus on clinical and aetio-pathogenetic links between stress, depression and pain. We put forward the hypothesis that chronic stress/depression may contribute to a dysregulation of neuro-endocrine, immune and central pain mechanisms in FM. Finally, we discuss some future directions, including the use of new conceptual models, research topics and strategies, as well as potential implications from recent studies in affective disorders for the treatment of FM. [Return to top] ------------------------------ Date: Fri, 2 Mar 2007 11:58:05 -0500 From: "The CFIDS Association of America <firstname.lastname@example.org> via Co-Cure Moderator" Subject: NOT,MED: March 10 Seminar: kNOw MORE! (Robert Wood Johnson Univ. Hospital in New Brunswick, NJ) Until there is no more chronic fatigue syndrome (CFS), itís vitally important for patients, caregivers and clinicians to know more about this illness. Please plan to join us in New Jersey on Saturday, March 10, 2007, from 11:00 a.m. to 5:15 p.m. for a seminar comprised of three topical sessions on CFS. The seminar will be held at Robert Wood Johnson University Hospital at One Robert Wood Johnson Place in New Brunswick, New Jersey. The CFIDS Association is collaborating with the New Jersey Chronic Fatigue Syndrome Association (NJCFSA) on this special joint program combining the CFIDS Associationís kNOw MORE CFS seminar series and the spring conference of the NJCFSA. The conference will start with a session on the national CFS public awareness campaign sponsored by the Centers for Disease Control and Prevention and the CFIDS Association of America. Registrants will have the opportunity to hear a campaign update from CFIDS Association president and CEO Kimberly McCleary and to see campaign components like the TV and radio PSAs, print ads, online banner ads, patient brochure, CFS toolkit for medical professionals, major press coverage and the acclaimed CFS photo exhibit called "The Faces of Chronic Fatigue Syndrome." This compelling exhibit features the portraits and stories of CFS patients, family members and health care professionals. Two of the participants in the photo exhibit, Jacqueline Niederle and Brian Bernard, will also speak at this session about the power of personal advocacy. Nancy Klimas, MD, of the University of Miami School of Medicine, will provide an update on the current CFS research landscape, with particular attention to research presented at the 8th International Association for CFS Conference in Ft. Lauderdale in January. Dr. Klimas, an internationally known expert on CFS, will help seminar participants understand the significance of new research findings. Alan Pocinki, MD, the speaker for the clinical session, practices in Washington, DC, where he treats both CFS and FM patients in his general medical practice. He will discuss how to work with a clinician to develop individualized treatment programs to accommodate the considerable variability in CFS symptom expression, in symptom severity and in the efficacy of specific treatment protocols. He is an Associate Clinical Professor of Medicine at George Washington University. A joint question-and-answer forum will follow the presentations, allowing participants to interact with speakers, ask questions and learn practical information about CFS and FM and how to manage these medical conditions. Tickets for the seminar are $30 if purchased by March 2, $35 if purchased after this deadline or at the door. Seating is limited so preregistration is encouraged. (Our most recent kNOw MORE program sold out with 280 participants!) To receive a brochure with complete details and a registration form, please send an e-mail to cfids cfids.org with the subject line "KNOW MORE", call 704-364-0466 or visit http://capwiz.com/cfids/utr/1/CSSFGUORZU/LZRJGUOUVQ/1082450201=6 to purchase tickets online. Hope to see you there! [Return to top] ------------------------------ Date: Fri, 2 Mar 2007 13:08:38 -0500 From: Jim Roache <jfroache SYMPATICO.CA> Subject: RES: Fibromyalgia - gene scanning - fibromyalgia syndrome - genetics and the CNS Just taking a flyer here....from Ottawa, Canada: I don't know if member of the group or one that we can locate (in the publish or perish brigade) might be interested in an FM Project. With so many among the world population having it, a drug or other therapy to dampen the genes or mute the symptoms (pain, fatigue and brain fog, etc) would make Billions, plus relieve incredible suffering, increasingly resulting in suicide. Researchers are identifying genes related to medical problems every day now. They have isolated those for ME/CFS/CFIDS (Chronic Fatigue Syndrome) - as I said to one doctor, call it XYZ if you like, so long as we both know what we mean by the term. Three big Pharma companies have drugs coming through the system - numbered only (no names), but I'll bet they are neuropathic....as such, they will not be effective in FMS. I have tried some off label - and as expected - nothing. There have been great breakthroughs in FMS research in the last 18 months using gene scanning. It's genetic and effects the CNS (brain and spinal column), in turn unbalancing the neurotransmitters (confirmed by spinal tap if necessary), disrupting blood flow to the pain centres of the brain (fMRIs show it) and causing up to 50+ pseudo symptoms - the body feeling pain and dysfunction that is NOT there (in the normal sense) - except in the CNS (HPS Axis), autonomic nervous system and the DNA. They now have one or two genes targeted - but there are at least five subsets of the condition. And there are more genes to be isolated (more gene scanning). Our family has confirmed cases to the third cousin, multi-generational level and controls (no FMS). My niece, sister, uncles, aunts and third cousins have confirmed cases (severe). Others have none. I think we would be a great collection of lab rats - 5-6 generations (that's the only way third cousins could have it as well as my niece). And there are family "controls"....perfect because like many, they think we are hypochondriacs. We are literally all over North America. Any gene lab wanting to isolate the additional genes would at least get a great paper for peer review publication - and then big pharma might come running if the study were to find a consistent pattern of under and over active genes....as has happened with CFS. The Health Sciences Centre at Memorial University in St. John's, NF now has a Genetics Lab, and they have agreed to at least test my sister and me for genetic abnormalities (mutations) in common, but we are wait listed. I have been active with several national organizations in Canada, and we have an International Consensus Document (as you know) that has become something of a clinical standard, a new paradigm for Dx and Rx (as opposed to the older WHO research standard) which was as helpful to physicians outside the lab or to patients trying to prove they really did have a problem illness. In Canada, as elsewhere, we lobby government and educate the public. I spend a lot of time peer-counselling and trying to figure out what is happening in the HPA axis with so many people - 15% of whom are disabled by a pain amplification syndrome that was until recently a total mystery. My family (not all) will volunteer to participate in genetics studies to isolate the genes - the equivalent of turning your stereo top high and being unable to locate the volume button again, or turning the thermostat top high and breaking the switch. I realize isolating the genes is only the first step, but then I think big pharma will support development of medications to dampen the genes or break that closed loop we have in the CNS - as in the stereo or thermostat i.e. block the signal to the furnace to fun top high or cut the wire to the streeo or its speakers and stop or reduce the the pain. Pain medications to date - NSAIDs, narcotics and neuropathic drugs - act on the wrong pain receptors - the incoming signal or stimulus. What we need to do is find something to act on the outgoing signal from the brain to the HPA axis and the autonomic nervous system - having first targeted the genes that have been triggered (in one of several ways) to cause the CNS to respond in the wrong way - the gas peddle is stuck to the floor with the car in neutral and were have to get the engine off or breal the like - peddle to carburetor to engine before other damage is done. I don't think the study has to be large, given what we have come to know in the last 18 months. If the pattern is consistent in a large family like ours, it will be identical with most if not all others (at least for slow onset FMS). I have not even discussed this with the lab in question, but simply thought I would look for someone interested in doing or funding (grant money - trusts) such a research project. Since we have one interested and willing - in a medical teaching and research facility - if the possibility of funding were there, and a perfect study group (lab rats) is in place (us), I thought I could/should at least ask. This can be done though our national organizations, the University/ies, the Medical School/s, the neurology department/s (specific physician/s) or the genetics lab/s. I have known for a long time that FMS is a CNS syndrome. Genetics has just proven it. Now the next step is a good study - what could be better than one extended family with it's own controls and people of some knowledge of the condition plus genetics. At the end of the day, the pharmacy company producing the medication would make billions -a huge international market awaits the medication. Royalties could go back to the national organizations and to further genetic research. Win-win. Some could even go back to additional related research while the medication is under patent. Am I even close here? Jim Roache, MBA Ottawa, ON Canada [Return to top] ------------------------------ Date: Sat, 3 Mar 2007 13:25:25 -0500 From: Fred Springfield <fredspringfield VERIZON.NET> Subject: RES: Incidence, Prognosis, and Risk Factors for Fatigue and Chronic Fatigue Syndrome in Adolescents: A Prospective Community Study Incidence, Prognosis, and Risk Factors for Fatigue and Chronic Fatigue Syndrome in Adolescents: A Prospective Community Study Journal: PEDIATRICS Vol. 119 No. 3 March 2007, pp. E603-E609 (doi:10.1542/peds.2006-2231) Authors: Katharine A. Rimes, DPhil [a], Robert Goodman, PhD [b], Matthew Hotopf, PhD [a], Simon Wessely, MD [a], Howard Meltzer, PhD [c] and Trudie Chalder, PhD [a] Affiliation: King's College London, Institute of Psychiatry [a] Section of General Hospital Psychiatry [b] Department of Child and Adolescent Psychiatry, London, United Kingdom [c] Academic Department of Psychiatry, Brandon Mental Health Unit, Leicester General Hospital, Leicester, United Kingdom NLM Citation: PMID: 17332180 OBJECTIVE. The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds. METHODS. A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined. RESULTS. The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue. CONCLUSIONS. The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue. Key Words: chronic fatigue . incidence . prognosis . risk factors . prevalence Abbreviations: CFS-chronic fatigue syndrome . CF-chronic fatigue . CDC-Centers for Disease Control and Prevention . GHQ-General Health Questionnaire . CI-confidence interval Accepted Oct 16, 2006. [Return to top] ------------------------------ Date: Sun, 4 Mar 2007 14:44:23 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Alpha-Delta sleep in CFS Source: American Journal of the Medical Sciences Vol. 333, #2, pp 78-84 Date: February 2007 URL: http://www.amjmedsci.com/pt/re/ajms/home.htm http://www.amjmedsci.com/pt/re/ajms/issuelist.htm http://www.amjmedsci.com/pt/re/ajms/toc.00000441-200702000-00000.htm Defining the Occurrence and Influence of Alpha-Delta Sleep in Chronic Fatigue Syndrome ----------------------------------------------------------------------------- Elke Van Hoof, PhD; Pascale De Becker, PhD; Charles Lapp, MD; Raymond Cluydts, PhD; Kenny De Meirleir, PhD >From the Department of Human Physiology (EVH, PDB, KDM) and the Department of Psychology (EVH, RC), Vrije Universiteit, Brussels, Belgium; and from the Hunter-Hopkins Center, Charlotte, North Carolina (CL). Submitted May 11, 2006; accepted in revised form September 11, 2006. Correspondence: Elke Van Hoof, Vakgroep COBI, Faculty of Psychological and Educational Sciences, Pleinlaan 2, 1050 Brussels, Belgium (E-mail: Elke.Van.Hoof vub.ac.be). ABSTRACT Background Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances. Methods Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic descriptive statistical parameters were calculated. Results Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L. Conclusions The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep. KEY INDEXING TERMS Alpha-delta sleep; Median-split; Anxiety; Specificity; CFS. Chronic fatigue syndrome (CFS) is a clinically defined syndrome that is characterized by chronic fatigue and a constellation of other symptoms and physical findings.1-3 In our sample in Brussels, CFS is diagnosed using a clinical case definition established by the Centers for Disease Control and Prevention (CDC) in 19881 that was revised in 1994.4 The major distinguishing symptom is debilitating fatigue of more than 6 months' duration associated with a marked decrease in daily activity that cannot be attributed to any known medical cause. Other nonspecific symptoms including joint pain, night sweats, visual disturbances, exaggerated allergic reactions, memory loss, emotional lability, and sleep problems such as unrefreshing sleep, accompany the fatigue.4 Patients with CFS describe a disordered sleep pattern with difficulty getting to sleep, frequent awakenings, and, less commonly, early morning wakening. Sleep is nonrestorative, with most patients more aware of their symptoms in the mornings and improving slightly as the day progresses.5-7 In the diagnostic process, patients undergo a polysomnographic investigation to exclude a primary sleep disorder. The use of electroencephalographic (EEG) techniques to investigate the sleeping brain reveals a wealth of electrical activity in a seemingly passive body.8 Sleep is divided into rapid eye move- ment (REM) sleep and non-REM sleep. In turn, non-REM sleep is divided into stages 1, 2, 3, and 4, with slow delta waves comprising stages 3 and 4.8,9 In practice, the alpha rhythm normally occurs during quiet wakefulness and is located over the posterior part of the scalp. The onset of sleep is characterized by the disappearance of this rhythm and the appearance of other EEG frequencies such as theta (3-7 Htz), K-complexes, sleep spindles (12-15 Htz), and later, delta or slow waves (0.5-2.5 Htz) or stages 3 and 4 non-REM sleep. Polysomnographic studies in CFS have shown reduced sleep efficiency, a reduction of REM sleep, and a longer sleep initiation.5,7,10-15 CFS patients have a significantly lower percentage of stage 4 sleep and alpha wave intrusion in deep sleep or alpha-delta sleep.10,11,13 Alpha-delta sleep is an abnormal sleep EEG rhythm characterized by alpha activity that is superimposed on delta waves of slow wave sleep stages 3 and 4.16 This activity was first reported by Hauri and Hawkins in 1973 in 9 psychiatric patients with somatic malaise and fatigue.17 Now, alpha sleep has been broadened to include alpha intrusion into all stages of non-REM sleep.18 However, it seems not to be specific for CFS and has been seen in fibromyalgia,19,20 rheumatoid arthritis,21 and other conditions associated with chronic pain.22,23 In sleep architecture, specific reductions in REM sleep have been reported. Due to this reduction, interferences in daily functioning seem inevitable.10,15 Also, CFS patients have a reduced percentage of delta sleep in their non-REM period.14 Chronic fatigue syndrome is associated with several immunologic abnormalities or discrepancies.24 An intracellular immune deregulation is also widely reported in patients with CFS. After the discovery by Suhadolnik and colleagues, the deregulation of the 2-5A synthetase/RNase L antiviral pathway is frequently found in a subset of CFS patients.5 The hyperactivation of RNase L has been reported at length in the scientific literature,5-8 but also the discovery of the abnormal low molecular weight RNase L (37 kDa) in patients with CFS5 was confirmed by several other researchers.7-9 It had been thought that RNase L level gives a clear picture of immune deregulation and that the suggested acquired channelopathy that occurs as a consequence will lead to central fatigue and sleep disturbances.25 Increased RNase L activity creates interaction of ABC transporters with the ankyrin fragment of RNase L upon its release by proteolytic cleavage.26 Subsequently, it is thought that improper ion channel function will develop, leading toward an ac- quired channelopathy of the ABC transporters. This suggested acquired channelopathy with loss of intracellular potassium will lead to metabolic and intracellular abnormalities, including central fatigue and sleep disturbances such as alpha-delta intrusion.25 This article subjects alpha-delta sleep to an indepth study. First of all, the occurrence of alpha-delta sleep in a randomized study group is examined. If alpha-delta sleep is present in this study population, a median split will be used to check whether more alpha-delta sleep is equivalent with more subjective complaints and more immunologic deviances. Correlation analysis may reveal associations between the subjective feeling of unrefreshing sleep, total sleep time, immunologic parameters, and alpha-delta sleep. After the theory presented by Englebienne and De Meirleir, it has been thought that RNase L would be associated with alpha-delta intrusion and other self-reported as well as objective sleep parameters.25,26 If any of the parameters (RNase L, NK-cells, T-cells, total sleep time, or unrefreshing sleep) correlated significantly with alpha-delta sleep, then a regression analysis might reveal the exact associations between the parameters and alpha-delta in CFS patients. Methods Recruitment of CFS Patients Study subjects were recruited from the outpatient fatigue clinic, Vrije Universiteit Brussels between October and February 2003. Generally, patients are referred by their general practitioner to the outpatient fatigue clinic. To fulfill the 1994 CDC criteria for CFS, clinically evaluated, unexplained, persistent, or relapsing chronic fatigue that is of new or definite onset should result in a substantial reduction in previous levels of occupational, educational, social, or personal activities.2 Furthermore, at least 4 of the following symptoms must have persisted or recurred during 6 or more consecutive months and must not have predated the fatigue: impairment in short-term memory or concentration, tender cervical or axillary lymph nodes, muscle pain, multijoint pain, headaches, unrefreshing sleep, and postexertional malaise lasting more than 24 hours.2 Any active medical condition that may explain the presence of chronic fatigue prohibits the diagnosis of CFS. Hence, all subjects underwent an extensive medical evaluation, consisting of a standard physical examination, medical history, exercise capacity test, and routine laboratory tests. The laboratory tests included a complete blood cell count, determination of the erythrocyte sedimentation rate, serum electrolyte panel, measures of renal, hepatic and thyroid function, and rheumatic and viral screens. If the patients' medical history did not exclude a psychiatric problem at the time of disease onset, a structured psychiatric interview, based on the Diagnostic Statistical Manual for Psychiatric Disorders (DSM), was performed. In a number of cases, further neurologic, gynecologic, endocrine, cardiac, and gastrointestinal evaluations were performed. The medical records were also reviewed to determine whether patients suffered from organic or psychiatric illness that could explain their symptoms. If any of the laboratory or additional analyses revealed any active medical or psychiatric condition that could explain the presence of the patient's symptoms, then CFS could not be diagnosed and those patients were excluded from the study. During a 2-night polysomnographic investigation, blood samples were taken. Only CFS patients who completed a 2-night polysomnographic investigation and had a diagnosis of CFS according to the CDC criteria4 were included in the study. Polysomnography Patients spent 2 nights in the sleep unit, with the first night being considered as a habituation night and followed by an all-night polysomnography examination on the second night. Subjects were prepared for the polysomnographic recordings between 10:00 and 11:00 PM and were allowed to retire when they wished (good night time). They were awakened around 7:30 AM if they did not arise spontaneously (good morning time). Polysomnography involved an electroencephalogram, which was recorded from C4-A1, C3-A2, Fpz2-A1, Fpz1-A2, O2-A1, O1-A2 sites, as well as an electrooculogram, a submental electromyogram, and an anterior tibialis electromyogram. Nasal and oral airflow, respiratory effort (thoracic and abdominal belt), and arterial oxygen saturation were recorded during the second night. The sleep recordings were recorded on Nicolet Ultrasom and visualized on screen and scored by trained sleep technicians in 30-second epochs according to standard criteria. The technicians scored during their routine clinical activities, without knowledge of the aims of the study. The studied sleep variables were: slow-wave sleep (min) (SWS), REM sleep (min) (STGE-REM), time awake (min) (awake) from good night time to good morning time, sleep latency (LAPSTGE2), sleep quality index (SE%), micro-awakenings (MAI) (n/h), total sleep time (TST) (min), REM latency (REMLATN) (min), number of shifts between stages (STSHIFTS), percentage time awake in bed (A%TIB), percentage slow-wave sleep (SWS%TIB), percentage of non-REM sleep (Nrem%TIB), percentage total sleep time (TST%TIB), and alpha-intrusion in slowwave sleep (SWS%AI). Patients were excluded if the TST of 1 night was less than 120 minutes. Immunological Data (Immunophenotyping) Anticoagulated blood (EDTA) was collected between 9:00 and 11:00 AM and used for white blood cell enumeration, differential counts (Celldyn 4000, Abbott Laboratories, Abbott Park, IL) and flow cytometric studies. Lymphocyte populations were analysed with dual color direct immunofluorescence on a EPICS xl flow cytometer (Coulter, Miami, FL), with aid of the System I computer software. A collection of 100 muL of whole blood was incubated with the appropriate combination of monoclonal antibodies for 25 minutes at 4&C. Red blood cells were then lysed using lysis buffer (Becton Dickinson) for 7 minutes, centrifuged, and washed once with 2 mL phosphate buffered saline. Resuspension was immediately followed by cell analysis. Commercially available (Becton-Dickinson) phycoerythrin or fluorescein isothiocyanate labeled monoclonal antibodies were used (Table 1). Estimates of absolute numbers of lymphocyte subsets were determined by multiplying peripheral lymphocyte counts by the percentage of each surface marker. Assessment of peripheral blood mononuclear cells, cell extracts, and serum and quantification of 37-kDa 2-5A-BP in peripheral blood mononuclear cell extracts were performed in a similar fashion as the method described by Demettre et al.26 Subjective Complaints A complaint checklist was presented to the patients. They were asked to complete the checklist and rate their complaints on a Likert scale from 0 (absent) to 3 (commonly present). Fatigue, postexertional fatigue, depressive feelings, anxiety, self-perceived personality changes, emotional lability, muscle aches, joint aches, sleep problems, and nonrefreshing sleep were completed. No psychometric parameters are known. Statistical Analyses Basic descriptive statistical parameters are reported. A onetailed Kolmogorov-Smirnov test was performed to check normal distribution. For the reporting of the location and spread of the distribution of the various variables in this study, the median is more appropriate, as most of the data are either ordinal or continous, but skewed. The mean, standard deviation, and range are also reported as additional information, to make a comparison with other studies possible. The relationship between the different variables was quantified using the nonparametric Spearman rank correlation coefficient for the same distributional reasons as given previously. Kendall's tau was also computed but was not reported in the paper because the results were very much in line with the Spearman coefficient. To assess the significance of the correlations, the P-value for the correlation coefficients was determined. Because of the many correlations, a Bonferoni correction was applied to keep the type I error under control. Therefore correlations are considered to be significant when the P-value is less than 0.002 instead of 0.05. The above statistical computations were performed using the SPSS statistical package [SPSS 2000, SPSS Syntax reference 12.0 SPSS Inc. Chicago, Il] Results Subjects Forty-eight patients were included in this study, of which 19 were male (40%) and 29 were female (60%). The mean age of the patients was 45 years (p/m 10.46 years). The mean number of years the pa- tients experienced symptoms was 8.98 (p/m 7.71 years). The mean scores on the immune parameters are presented in Table 2. None of the immune variables fell outside their reference score. Rnase L The mean RNase L was 4.47 (p/m 0.71) with a median of 2.80. The deregulation of the RNase L pathway can be quantified by dividing the amount of 37 kDa RNase L by 83 kDa RNase L, and multiplying this quotient by 10. The outcome of this formula, frequently referred to as RNase L ratio, is considered normal when it remains below 0.5. In any other case, the RNase L ratio is considered increased, suggestive of deregulation of the 2.5A synthetase RNase L pathway.27 Thirty-nine patients (86.67%) presented an increased RNase L ratio. Subjective Complaints Sixty percent of the patients reported significant fatigue. The mean score of fatigue on a scale from 0 to 3 was 2.56 (p/m 0.58). Almost 75% of patients suffered from post-exertional fatigue, with a mean score of 2.66 (p/m 0.70). Almost 75% reported signifi- cant sleep problems with a mean score of 2.09 (p/m 1.04) and significant nonrefreshing sleep with a mean score of 1.94 (p/m 1.17). The other symptoms are summarized in Table 1. Sleep Continuity Table 3 describes the group variables for the sleep parameters. The sleep latency or the time from lights-off until stage 2 was 61.40 minutes (p/m 7.35 minutes). Table 4 shows the results from Fischler et al,13 who also used a Belgian population. Sleep latency time was lower than in our population. The sleep efficiency index shows 72.35% (p/m 2.15), which is lower than the results presented by Fischler et al13 (Table 4). Our population presented 9.53 (p/m 1.10) micro-awakenings per hour. Again the results in the study performed by Fischler et al13 were relatively lower (Table 4). Sleep Architecture The patients spent 71.49% (p/m 2.19) of the time in sleep. The patients had 70.19 minutes (p/m 5.02) of slow wave sleep or delta-sleep. On average the REM sleep time was 261.96 minutes (p/m .31). The total sleep time was 326.21 minutes (p/m 10.46), which is approximately 5.5 hours of sleep. The test showed a mean number of shifts between stage of 67.29 times (p/m 4.55). The percentage slow wave sleep was 22.49% (p/m 1.71) with a mean non-REM sleep percentage of 80.90% (p/m 1.31). The percentage of alpha waves in slow wave sleep appeared to be 4.32% (p/m 0.80) (Table 3). Alpha-Delta Intrusion A median split was performed on the percentage of alpha waves in slow wave sleep (SWS%AI). A median split was performed to examine whether a high percentage of alpha-delta intrusion results in more subjective complaints or alteration in immune parameters. This method could shed more light on the potential importance of the influence of the alpha-delta intrusion. The median was 2. The meanage of the group with few alpha-delta intrusion was 44.73 years of age (p/m 2.18) and a mean onset of symptoms with a mean of 8.73 years (p/m 1.56). The group with the most alpha-delta intrusion had a mean age of 45.32 years of age (p/m 2.11) with a mean onset of 9.27 years (p/m 1.62). There was no significant difference between the ages of the two groups (chi^X2=2.8; P=0.196). No significant difference could be identified for the onset of both groups (U=268.00, Z=0.374, P=0.708). Table 5 shows the significant differences in subjective complaints and immunologic parameters. Only "subjectively perceived anxiety" differed significantly between the group with high alpha-delta intrusion and low alpha-delta intrusion. The high alpha-delta intrusion group reported the most self-reported anxiety (Table 4). Correlations Alpha-delta intrusion correlated with anxiety, although this was just a statistical trend (R=0.317; P=0.03). No other correlations revealed significant information (data not shown). Because no significant correlations could be found, no regression analyses were performed to reveal exact associations. Discussion Sleep architecture variables demonstrated significantly different sleep onset latency and sleep disturbances in CFS patients (Table 4). Because of the resemblance between the CFS patients used by Fischler et al13 and Fossey et al15 and our CFS population, their results may apply to our sample, although no healthy control group was used. Similar results were already reported by several other authors, such as Whelton et al10 and Stough and Withers.14 CFS patients present less sleep continuity. Patients experience problems falling asleep, represented by the large sleep latency. The low sleep efficiency index and the high number of micro-awakenings objectify the subjectively presented complaints of a distorted sleep pattern and a nonrestorative sleep.5-7 The patients slept about 5.5 hours. They spent almost 30% of the time awake in bed. Interestingly, a lot of shifts between stages are apparent. Again, the results of the sleep architecture underscore the distorted sleep pattern and an unrefreshing sleep. Alpha-delta intrusion is present although a wide range of the percentage of this intrusion indicates its nonspecific nature. This sleep anomaly is thought to be accompanied by indications of vigilance during sleep and the subjective experience of unrefreshing sleep. The latter seems not solely associated with alpha-delta intrusion because no differences in feelings of fatigue and unrefreshing sleep could be found between CFS patients with low or high alpha-delta intrusion. Our results emphasize the nonspecific nature of alpha-delta sleep in CFS patients, a suggestion made by several authors.19-23 For instance, Manu and associates found no correlation between alpha-delta sleep and CFS, fibromyalgia, major depression, primary sleep disorders, or Lyme disease but did find that alpha-delta sleep was more common among chronic fatigue patients without major depressive disorders.23 Although the sample showed high RNase L, no differences were apparent between patients with low and high alpha-delta intrusion. Furthermore, no correlations appeared between alpha-delta sleep and immunologic parameters, including RNase L. So far, it has been thought that a potential acquired channelopathy, a consequence of immune deregulation through RNase L, leads to sleep disturbances including alpha-delta sleep.25,26 Our results suggests that RNase L and the subsequent channelopathy are not associated with alpha-delta intrusion. Moreover, none of the self-reported sleep problems, nor the objective sleep parameters, are associated with RNase L. This result questions at least a part of the suggested hypothesis proposed by Englebienne and De Meirleir.25 The suggested acquired channelopathy with loss of intracellular potassium should lead to metabolic and intracellular abnormalities, including central fatigue and sleep disturbances such as alpha-delta intrusion. Our results do not support the inclusion of sleep disturbances including alpha-delta intrusion in the list of potential consequences of the suggested channelopathy. The results the deregulation of the 2-5A synthetase/RNase L pathway are similar to those of previous studies.27,28 It is still unclear, however, whether the 37 kDa RNase L ratio is representative of the CFS population in general, and whether the 37 kDa RNase L ratio is characteristic of a particular stage in the course of the illness or if it fluctuates over time (as is the case with symptom severity in the majority of CFS patients). Recent research suggest the ratio could be associated with (the severity) of the experienced complaints and its associated clinical causes.25 For instance, the deregulation of the 2-5A synthetase/RNase L pathway appears to accompany different aspects of immune dysfunction in CFS patients. A reduced number and activity (cytotoxicity) of NK-cells have been reported in patients with CFS.29-31 In addition, a negative correlation between the RNase L ratio and both the number and percentage of NK-cells was observed in CFS patients. In our study, no deviant NK-cells percentages were found. Moreover, no correlations were found between the RNase L ratio and the NK-cells. To be a biological gradient, a correlation between the biological parameter of interest (i.e., impairment of the RNase L pathway) and the clinical severity of the disorder of interest (i.e., CFS) is required. No significant correlations regarding self-reported complaints, objective sleep parameters, and immune parameters were found in this study. For interpreting a correlation analysis, however, one should focus on the correlation coefficient rather than interpreting the P-value. Correlation coefficients as low as 0.2, regardless of the P-value, suggest no association is present. Although no significant associations were found, some correlation coefficients suggested possible relationships. The Bonferroni-corrections and the small sample size could prevent any significant results. Further research is necessary to clarify possible associations. Using our present results, no significant findings appeared, casting into question the biological gradient of the RNase L ratio regarding the NK-cells and sleep disturbances. Anxiety differed between low and high alpha-delta sleep. People suffering from high alpha-delta intrusion experience more anxiety. Anxiety could be the result of the higher vigilance in slow wave sleep. The major clinical importance of this study is that because of alpha wave intrusion in phase 3 and 4 of the non-REM sleep, full benefit is not taken from the recuperative function of slow wave sleep. This study had several limitations. First, the study was done retrospectively and therefore strong causal relations were difficult to make. Second, a limited number of CFS patients were enrolled and there was no healthy control group, although the results were similar to those of Fischler et al13 and Fossey et al,15 who did include a healthy control group. Therefore, more research is needed, not only with a increased number of CFS patients that would give more accurate results, but also with the same polysomnographic protocol and adequate control subjects, including patients with non-CFS-induced fatigue. The relatively small number of CFS patients in this study was due to recent changes in polysomnographic protocols; only 41 CFS patients were found to have completed a similar 2-night polysomnographic protocol. Moreover, 1-night polysomnographic protocols should be avoided due to the first-night effect.32 In summary, one obvious limitation of the present study is the lack of power due to a small sample size. However, the well-documented expense related to laboratory sleep research,33 as well as the difficulties regularly encountered with subject attrition in such extensive, demanding, and lengthy investigations make small sample size an unfortunate but common consequence. Nevertheless, the comprehensive data collected make an important contribution to CFS research and should form the basis for future investigations. Summarizing, the main findings of this study are as follows: 1) The existence of sleep latency problems and other sleep disturbances are validated, as already suggested by several authors. 2) Alpha-delta-intrusion seems associated with anxiety. 3) An elevated RNase L-ratio did not correlate with alpha-delta sleep. 4) The results from the correlation analysis questions RNase L as a biological gradient. To our knowledge, this is the first study in which immune parameters were correlated to polysomnographic variables in CFS patients. More research is undoubtedly necessary to state causal relationships, although some interesting suggestions have been made. Acknowledgments Our Department would like to thank Kim Borremans in collecting the appropriate data and Nancy Reichenbach for her help in academic writing. Tables Table 1. Subjective Symptoms Reported by the Patients -------------------------------------------------------------------------------- Variable 0-Absent 1 2 3-Present X (SD) all the time -------------------------------------------------------------------------------- Depressive feelings 23% 25% 33% 19% 1.48 (1.05) Anxiety 44% 10% 31% 15% 1.17 (1.16) Self-perceived 46% 17% 27% 10% 1.02 (1.08) personality changes Emotional lability 19% 19% 33% 29% 1.73 (1.09) Muscle aches 23% 6% 27% 42% 1.89 (1.20) Joint aches 31% 10% 29% 27% 1.53 (1.21) -------------------------------------------------------------------------------- Table 2. Group Variables of Immune Parameters -------------------------------------------------------------------------------- Item Reference, % Patients, n Mean SD Median Range -------------------------------------------------------------------------------- RNAse L -- 45 4.47 0.71 2.80 21 CFS marker CD3HLADR 2-9 44 4.55 0.43 4.00 12 CD8 23-41 44 26.73 1.08 26.00 32 CD19 CD5+ 1-4 44 2.15 0.25 2.00 8 CD3-CD16CD56+ 4-22 44 7.07 0.85 5.50 32 CD4/CD8 0.9-2.6 44 2.22 0.13 2.13 4 -------------------------------------------------------------------------------- Table 3. Group Variables for the Sleep Parameters -------------------------------------------------------------------------------- Item Description Mean SD Median Range -------------------------------------------------------------------------------- SWS Slow wave sleepDelta sleep (min) 70.19 5.02 67.50 134 STGE-REM REM-sleep (min) 261.96 7.31 265.50 221 LAPSTGE2 Sleep latency (from lights-off 61.40 7.35 47.00 269 until stage 2) (min) SE% Sleep quality index (%) 72.35 2.15 75.65 56.2 MAI#/u Micro-awakenings (n/u) 9.53 1.10 8.35 28.6 TST Total sleep time (min) 326.21 10.46 334.50 387 STSHIFTS Number of shifts between stages 67.29 4.55 67.50 120 A%TST % Awake time in bed 46.28 5.54 32.25 160.8 SWS%TST % Slow wave sleep 22.49 1.71 20.95 52.7 NREM%TST % Non-REM sleep 80.90 1.31 81.05 42 TST%TIB % Total sleep time 71.49 2.19 75.05 56.2 SWS%AI % Alpha-waves in slow wave sleep 4.32 0.80 2.00 21 -------------------------------------------------------------------------------- Table 4. Comparison with Data of Fischler et al., 1997 (means) -------------------------------------------------------------------------------- Item Fischler's Fischler's CFS Our Controls Patients Population -------------------------------------------------------------------------------- Sleep latency 21.5^a 39^a 61.40 Micro-awakenings 2.8 3.2 9.53 Total sleep time 382a 339a 326.21 REM latency 89.5 96.0 -- Sleep efficiency, % 87.8^a 76.5^a 72.35 Number of shifts 21.9^a 28.7^a 67.29 Stage 1 sleep, % 9.0 13.9 -- Stage 2 sleep, % 45.5^a 38.2^a -- Stage 3 sleep, % 9.0 11.0 -- Stage 4 sleep, % 14.6 8.8 -- SWS% 23.6 19.8 -- REM sleep, % 14.1 12.0 -- -------------------------------------------------------------------------------- ^a Statistically significant at 0.001 Table 5. Differences in Subjective Complaints and Immunologic Parameters Using a Median Split in Alpha-Delta Intrusion -------------------------------------------------------------------------------- Variable Alpha-delta Alpha-delta P-Value^a < Median (SD) > Median(SD) -------------------------------------------------------------------------------- Immunological parameters RNase L 3.62 (0.71) 5.44 (1.28) 0.645 CD4/CD8 2.15 (0.17) 2.29 (0.21) 0.892 CD3-CD16CD56 5.91 (0.70) 8.33 (1.59) 0.371 CD3 HLADR 4.48 (0.60) 4.62 (62) 0.777 CD19 CD5 1.89 (0.35) 2.43 (0.36) 0.169 Subjective complaints Fatigue 2.46 (0.11) 2.68 (0.12) 0.174 Postexertional fatigue 2.60 (0.16) 2.73 (0.12) 0.807 Depressive feelings 1.35 (0.21) 1.64 (0.22) 0.366 Anxiety 0.77 (0.22) 1.64 (0.22) 0.009 Self-perceived personality 0.88 (0.20) 1.18 (0.24) 0.380 changes Emotional lability 1.65 (0.21) 1.82 (0.23) 0.597 Muscle aches 1.80 (0.26) 2.00 (0.24) 0.769 Joint aches 1.56 (0.27) 1.50 (0.24) 0.762 Sleep problems 2.08 (0.20) 2.09 (0.24) 0.809 Nonrefreshing sleep 2.12 (0.22) 1.73 (0.27) 0.297 -------------------------------------------------------------------------------- ^a Statistical significance (Bonferroni-correction): 0.002 References 1. Holmes GP, Kaplan JA, Gantz NM, et al. Chronic fatigue syndrome, a working case definition. Ann Intern Med 1988; 108:387-9. 2. Komaroff AK, Buchwald D. Symptoms and signs of chronic fatigue syndrome. Rev Infect Dis 1991;13:S8-11. 3. Bates DW, Schmitt W, Buchwald D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med 1993;153:2759-65. 4. Fukuda K, Strauss SE, Hickie I, et al. and the interna- tional chronic fatigue syndrome study group: The Chronic Fatigue Syndrome, A comprehensive approach to its defini- tion and Study. Ann Intern Med 1994;121:953-9. 5. Morriss R, Sharpe M, Sharpley AL, et al. Abnormalities of sleep in patients with the chronic fatigue syndrome. BMJ 1993;306:1161-4. 6. Jason LA, Fennell PA, Klein S, et al. An investigation of the different phases of the CFS illness. J Chronic Fatigue Syndr 1999;5:35-45. 7. Sharpley A, Clements A, Hawton K, et al. Do patients with "pure" chronic fatigue syndrome (neurasthenia) have abnormal sleep? Psychosom Med 1997;59:592-6. 8. Culebras A. Biology of sleep. Clinical Handbook of Sleep Disorders. Boston: Butterworth-Heinemann; 1996: 13-51. 9. Rechtschaffen A, Kales A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Los Angeles: Brain Information Service; 1968. 10. Whelton CL, Salit I, Moldofsky H. Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome. J Rheumatol 1992;19:939-43. 11. Krupp LB, Jandorf L, Coyle PK, et al. Sleep disturbance in chronic fatigue syndrome. J Psychosom Res 1993;37: 325-31. 12. Buchwald D, Pascualy R, Bombardier C, et al. Sleep disorders in patients with chronic fatigue. Clin Infect Dis 1994;12:S68-72. 13. Fischler B, Le Bon O, Hoffmann G, et al. Sleep anomalies in the chronic fatigue syndrome: a comorbidity study. Neuro- psychobiology 1997;35:115-22. 14. Stough C, Withers G. Sleep disturbance in patients with chronic fatigue syndrome and chronic fatigue. J Chronic Fatigue Syndr 2000;6:37-43. 15. Fossey M, Libman E, Bailes S, et al. Sleep quality and psychological adjustment in chronic fatigue syndrome. J Be- hav Med 2004;27:581-605. 16. McNamara ME. Alpha sleep: a mini-review and update. Clin Electroencephalogr 1993;24:192-3. 17. Hauri P, Hawkins D. Alpha-delta sleep. Electroencephalogr Clin Neurophysiol 1973;34:233-7. 18. Scheuler W, Stinshoff D, Kubicki S. The alpha sleep pattern : different from other sleep patterns and effects of hypnotics. Neuropsychobiol 1983;10:183-9. 19. Goldenberg DL. Management of fibromyalgia syndrome. Rheumatic Dis Clin North Am 1989;15:499-513. 20. Harding SM. Sleep in fibromyalgia patients: subjective and objective findings. Am J Med Sci 1998;315:367-76. 21. Moldofsky H, Lue FA, Smythe HA. Alpha EEG sleep and morning symptoms in rheumatoid arthritis. J Rheumatol 1983;10:373-9. 22. Watson R, Liebmann KO, Jenson J. Alpha-delta sleep: EEG characteristics, incidence, treatment, psychological cor- relates and personality. Sleep Res 1985;14:226. 23. Greenberg HE, Ney G, Scharf SM, et al. Sleep quality in Lyme disease, Sleep 1995;18:912-6. 24. Maher KJ, Klimas NG, Fletcher MA, et al. Immunology. In: Jason LA, Fennell PA, Taylor RR, editors. Handbook of chronic fatigue syndrome. Hoboken, NJ: Wiley, 2003; p. 124- 151, 2003. 25. De Meirleir K, De Becker P, Nijs J, et al. CFS etiology, the immune system, and infection. In: Englebienne P, De Meirleir K, editors: Chronic Fatigue Syndrome, a Biological Approach, New York, CRC Press, 2002; p. 201-28. 26. Demettre E, Bastide L, D'Hase A, et al. Ribonuclease L proteolysis in pheripheral blood mononulear cells of chronic fatigue syndrome patients, J Biol Chem 2002;277: 35746-51. 27. De Meirleir K, Bisbal C, Camoine I, et al. A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome, Am J Med 2000;108:99-105. 28. Snell CR, VanNess M, Strayer DR, et al. Physical perfor- mance and prediction of 2-5A synthetase RNase L antiviral pathway activity in patients with chronic fatigue syndrome. In Vivo 2002;16:107-10. 29. Tirelli U, Marotta G, Improta S, et al. Immunological abnormalities in patients with chronic fatigue syndrome, Scand J Immunol 1994;40:601-8. 30. Whiteside TL, Friberg D. Natural killer cells and natural killer cell activity in chronic fatigue syndrome, Am J Med 1998;105:27S-34S. 31. Klimas NG, Salvato FR, Morgan R, et al. Immunologic abnormalities in chronic fatigue syndrome. I Clin Microbiol 1990;28:1403-10. 32. Le Bon O, Staner L, Hoffmann G, et al. The first-night effect may last more than one night, J Psychiatric Res 2001; 37:165-72. 33. Komaroff AL, Fagioli L. Medical assessment of fatigue and chronic fatigue syndrome. In Demitrack MA, Abbey SE, edi- tors. Chronic fatigue syndrome - An Integrative Approach to Evaluate and Treatment. New York, Guilford, 1996. -------- (c) 2007 Southern Society for Clinical Investigation (c) 2007 Lippincott Williams & Wilkins [Return to top] ------------------------------ Date: Mon, 5 Mar 2007 15:40:37 -0500 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Rehabilitation of chronic myofascial pain disorders [Rehabilitation of chronic myofascial pain disorders.] [Article in Norwegian] Tidsskr Nor Laegeforen. 2007 Mar 1;127(5):604-8. Wigers SH, Finset A. Opptreningssenteret Jeloy Kurbad Bratengaten 94 1515 Moss. sigrid.wigers c2i.net PMID: 17332816 BACKGROUND: Chronic musculoskeletal pain of diffuse origin affects many, and at a significant cost. Evidence-based guidelines for therapeutic interventions are presented and exemplified. MATERIAL AND METHODS: 200 patients with chronic myofascial pain and/or fibromyalgia who participated in a 4-week multidimensional rehabilitation programme, were included in the study. The programme included education and pain management in a cognitive setting, various forms of aerobic exercises, myofascial pain treatment, relaxation and medication as needed. The patients filled in questionnaires on arrival, at follow-up after six and 12-months and at discharge. They completed visual analogue scales (pain, fatigue, sleep problems, depression), the Nottingham Health Profile, the Fibromyalgia Impact Questionnaire, global subjective improvement, and during the follow-up period also the physical activity level, changes in quality of life and occupational workload. Work capacity, a tender point count and whether patients met the diagnostic criteria for fibromyalgia were assessed at baseline and at discharge. RESULTS: Significant improvements were seen in all variables throughout the follow-up period. 30 % of the fibromyalgia patients no longer met the diagnostic criteria at discharge. There was a significant increase in quality of life over time. After one year, more patients had returned to work and fewer were off sick, but there was also an increased number on disability pensions. The majority did exercise training on a regular basis. INTERPRETATION: Our findings confirm the existing evidence-based guidelines by showing that multidimensional rehabilitation is an effective intervention for patients with widespread chronic pain. It is a challenge for health politicians to change today's common practice towards that described in evidence-based guidelines. [Return to top] ------------------------------ Date: Mon, 5 Mar 2007 20:58:34 -0500 From: "From CF Alliance <cf_alliance yahoo.com> via Co-Cure Moderators" Subject: NOT,MED: Doctors Urged To Change The Way They Prescribe Pain Relievers For Chronic Pain Source: American Heart Association Date: March 4, 2007 Doctors Urged To Change The Way They Prescribe Pain Relievers For Chronic Pain http://www.sciencedaily.com/releases/2007/02/070227105559.htm [Return to top] ------------------------------
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