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Write to mailto:email@example.com --------------------------------------------- ---------------------------------------------------------------------- Date: Tue, 27 Mar 2007 14:44:42 +0200 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Submaximal exercise variables in Women with CFS Source: Archives of Medical Research Preprint/Vol. 38, #3, pp 350-353 Date: April 2007 URL: http://www.sciencedirect.com/science/journal/01884409 [Brief Report] Can Submaximal Exercise Variables Predict Peak Exercise Performance in Women with Chronic Fatigue Syndrome? ---------------------------------------------------------------------- Jo Nijs(a,b), Seppe Demol(a) and Karen Wallman(c) a Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit, Brussels, Belgium b Division of Musculoskeletal Physiotherapy, Department of Health Care Sciences, University College Antwerp, Antwerp, Belgium c Human Movement & Exercise Science, University of Western Australia, Perth, Australia * Address reprint requests to: Jo Nijs, Vrije Universiteit Brussel, MFYS/Sport, KRO-gebouw e1, Laarbeeklaan 101, B-1090 Brussels, Belgium; E-mail: Jo.Nijs@vub.ac.be Received for publication September 1, 2006; accepted October 26, 2006 Abstract This study aimed at examining whether physiological exercise variables at the submaximal level, defined as 75% of the age-predicted target heart rate, are able to predict peak exercise performance in women with chronic fatigue syndrome (CFS) (n=222). Subjects performed a bicycle ergometric test against a graded increase in workload until exhaustion with continuous monitoring of electrocardiographic and ventilatory variables. Oxygen uptake at the submaximal level (VO_2SUBMAX) correlated strongly with peak oxygen uptake (VO_2PEAK) (r=0.70). For the prediction of VO_2PEAK, linear regression analysis determined the line of best fit as: VO_2PEAK = 0.95 x VO_2SUBMAX + 372.3. Using this equation, the mean error in the prediction was 14.6 p/m 11.2% (range 0.1-63.7%). It is concluded that the prediction of VO_2PEAK based on VO_2SUBMAX might be useful for analyzing group differences or treatment effects but not for individual (clinical) purposes. Key Words: Submaximal, Exercise test, Prediction, Chronic fatigue syndrome, Fibromyalgia. Introduction Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by debilitating fatigue, widespread musculoskeletal pain, sleep impairments, headache, and symptoms of poor concentration and memory (1). Maximal or peak exercise performance testing is widely used for the assessment of people with CFS, and it appears to be both reproducible and valid (2). Peak exercise capacity variables correlate with activity limitations and participation restrictions (3), supporting the clinical importance of peak exercise testing in individuals with CFS. However, the role of maximal exercise tests is limited in people whose performance may be limited because of pain or fatigue rather than exertion (4). In CFS, symptoms are typically made worse after a peak exercise stress test (5,6), and a delayed recovery from exercise appears characteristic of the disorder (7). Therefore, a submaximal exercise test appropriate for CFS patients would have a number of advantages over a test performed until exhaustion: submaximal testing is likely to diminish symptom exacerbations following peak exercise testing (8) and consequently, decrease recovery time; it may encourage more severely disabled people with CFS to participate in research studies using exercise testing (8); and it has greater (clinical) applicability (for instance, to physical therapists) (4). The Aerobic Power Index Test has been used as a submaximal test in people with CFS: the test-retest reliability has been established (9), and it was the first submaximal test able to replicate previous findings of decreased exercise performance in CFS cases compared to healthy controls (8). However, there are currently no published data indicating that a submaximal exercise test is able to predict peak exercise performance in CFS patients. Prediction of peak aerobic capacity is one of the primary goals of submaximal exercise testing (4). Therefore, the present study aimed at examining whether physiological exercise data corresponding to a submaximal level, defined as 75% of the age-predicted target heart rate (8), are able to predict peak exercise performance in women with CFS. Materials and Methods Patient Recruitment and Research Design The exercise capacity testing data of all women with CFS attending our university-based Chronic Fatigue Clinic between November 2003 and December 2005 were reanalyzed. The study focused on women to preclude bias originating from pooling of gender data (10). All participants fulfilled the Centers for Disease Control and Prevention criteria for CFS (1). Therefore, all patients underwent an extensive medical evaluation prior to exercise testing (for more details regarding the diagnostic strategies as applied in the present study the reader is referred to Reference 11). To be selected for data analyses, women had to be within the age range of 18e65 years at the time of exercise testing. Accordingly, 222 women with CFS were selected. The mean age was 38.6 p/m 9.8 years (range: 18-61 years) and the mean illness duration was 6.2 p/m 6.4 years (range: 1-31 years). The study protocol was approved by the local ethics committee (Academic Hospital Vrije Universiteit Brussel; O.G. 016). Exercise Testing The participants performed a bicycle ergometric test against a graded increase in workload until exhaustion was reached (12). There was continuous monitoring of electrocardiographic and ventilatory variables. In order to obtain an optimal test duration of 8-12 min (13), subjects started the test at 10 W, with an increase of 10 W/min (12). The age-predicted peak heart rate (HRPEAK) was calculated as 220 minus the subject's age in years (14). For a detailed description of the exercise test as applied in the present study, the reader is referred to Reference 15. Statistical Analysis All data were analyzed using SPSS 14.0 for Windows (SPSS Inc., Chicago, IL). A one-sample Kolmogorov-Smirnov (K-S) goodness-of-fit test was used to examine whether the variables were normally distributed. In case of normality, the associations between the submaximal and peak exercise performance data were analyzed using Pearson product-moment correlation analysis. If a variable was not normally distributed, then a Spearman correlation analysis was applied. If certain submaximal exercise performance variables correlated strongly with their corresponding peak variables, then a linear regression analysis was performed for constructing a regression equation for the prediction of the peak exercise performance. Accuracy of the prediction was determined using the coefficient of determi- nation (r2), the standard error of the estimate (SEE), and the mean error or 'the mean absolute percentage deviation' counted as predicted peak value measured peak value/predicted peak value. Significance level was set at 0.01 to help protect against potential type I errors. Results Of the 222 study participants, only 156 (71%) achieved the submaximal level (defined as 75% of the age-predicted tar- get heart rate) and were used for further data analysis. The descriptive statistics of the exercise testing variables are presented in Table 1. In addition to the peak ( p=0.045) and submaximal work capacity attained p=0.025), all variables were normally distributed. The outcome of the correlation analysis is presented in Table 2. Oxygen uptake at the submaximal level (VO2_SUBMAX) correlated strongly with peak oxygen uptake (VO2_PEAK) (r=0.70; F=151.2; df=154; p<0.001). For the prediction of VO2PEAK, linear regression analysis determined the line of best fit as: VO_2PEAK=0.95 x VO_2SUBMAX + 372.3 where both VO_2PEAK and VO_2SUBMAX are in mL/min. Using this equation, the mean error in the prediction was 14.6 p/m 11.2% (range 0.1-63.7%; r2=.49; SEE=224.4) when compared with measured VO_2PEAK. Likewise, the body weighted-adjusted VO_2SUBMAX correlated strongly with the body weight-adjusted VO_2PEAK (r=0.69; F=144.7; df=154; p<0.001). For the prediction of body-weight adjusted VO_2PEAK, linear regression analysis determined the line of best fit as: VO_2PEAK=0.98 x VO_2SUBMAX + 5.47 where both VO_2PEAK and VO_2SUBMAX are given in mL/kg per min. Using this equation, the mean error in the prediction was 14.6 p/m 10.9% (range 0.1-66.6%; r2=.48; SEE=3.59) when compared with measured VO_2PEAK. The remaining correlations between variables at the submaximal and peak level were lower and were therefore not entered in a regression analysis. Discussion There is a need for standardized submaximal ergometer tests not only for patients with CFS but for people with various disorders that require close monitoring during exercise (4). Therefore, the present study aimed at examining whether a standardized submaximal ergometer test was able to predict peak exercise performance (including peak aerobic work capacity) in people with CFS. We utilized an exercise protocol (starting at 10 W with an increase of 10 W/min) that has previously been used for the assessment of peak exercise performance in people with CFS (3,11,12,15,16) and defined the submaximal level in accordance with the Aerobic Power Index Test (8,9). The results of the study suggest that exercise variables at the submaximal level are strongly associated with their corresponding variables at the peak (maximal) level. Despite this observation, the associations appeared too weak to predict peak exercise variables with an error margin <10%. Both VO_2PEAK and body weight-adjusted VO_2PEAK can be predicted from their corresponding submaximal variable with an error margin of 14.6%. For analyzing group differences or treatment effects (research purposes), an error margin of 14.6% might be acceptable and can be taken into account in an a priori power calculation. However, for individual (clinical) purposes, the error range (0.1->60%) should be taken into account. It is therefore concluded that, for clinical purposes, the submaximal exercise testing protocol used here is unable to make an accurate prediction of peak exercise performance in women with CFS. The results should be interpreted in light of the study limitations. Only 71% of the subjects studied here attained the submaximal exercise level, defined as 75% of the age- predicted target heart rate. Thus, the results (and the regres- sion equations) are applicable solely to women attending a specialized chronic fatigue clinic and able to achieve 75% of the age-predicted target heart rate during graded exercise tests. This limits the external validity of the results. Further studies are warranted, for instance, by using the exercise protocol of the Aerobic Power Index Test (an increase of 25 W every minute) or by applying other exercise testing protocols previously used for studying peak exercise performance in people with CFS. Fulcher and White used a treadmill walking test at a constant speed of 5 kph and a gradient increase of 2.5% every 2 min (17). Sargent et al. applied cycle ergometry starting at 0 W with incrementing the power output by 25 W every 2 min (10). Bazelmans and colleagues applied an individually tailored bicycle ergometer test: the workload was increased every minute in steps of 10% of estimated maximal workload (5). In summary, the results of the study suggest that exercise variables at the submaximal level are strongly associated with their corresponding variables at the peak level in women with CFS. VO2PEAK and body weight-adjusted VO_2PEAK can be predicted from their corresponding submaximal variable with a mean error margin of 14.6%, which might be acceptable for analyzing group differences or treatment effects. For individual (clinical) purposes, the submaximal exercise testing protocol was found inappropriate for predicting peak exercise performance in women with CFS. Acknowledgments The authors are grateful to Kenny De Meirleir for diagnosing the study participants. Tables Table 1. Descriptive statistics of the exercise capacity variables (n=156) -------------------------------------------------------------------------- Variable Mean p/m SD Range -------------------------------------------------------------------------- Submaximal exercise duration (min) 6.8 p/m 2.4 0.38-5.6 Peak exercise duration (min) 9.5 p/m 2.9 3.4-18.2 Submaximal HR (bpm) 135.9 p/m 9.8 60-155 Peak HR (bpm) 152.2 p/m 24.7 80-210 Submaximal RER 1.04 p/m 0.13 0.73-1.43 Peak RER 1.14 p/m 0.13 0.73-1.57 Submaximal workload (W) 72.8 p/m 24.4 10-160 Peak workload (W) 91.5 p/m 28.9 30-180 Submaximal VO2 (mL/min) 951.3 p/m 233.5 305-1862 Peak VO2 (mL/min) 1196.8 p/m 325.9 489-2273 Submaximal VO2 (mL/min/kg) 15.2 p/m 3.5 4.5-27.4 Peak VO2 (mL/min/kg) 19.1 p/m 5.1 9.1-38.0 -------------------------------------------------------------------------- SD, standard deviation; HR, heart rate; RER, respiratory exchange ratio; VO2, oxygen uptake. Table 2. Correlation analysis between the variables at the submaximal and peak level (n=156) -------------------------------------------------------------------------- Variable Pearson correlation p value coefficient -------------------------------------------------------------------------- Submaximal vs. peak exercise duration 0.58 <0.001 Submaximal vs. peak HR 0.43 <0.001 Submaximal vs. peak RER 0.69 <0.001 Submaximal vs. peak workload 0.63^a <0.001^a Submaximal vs. peak VO2 0.70 <0.001 Submaximal vs. peak body weight 0.69 <0.001 adjusted VO2 -------------------------------------------------------------------------- SD, standard deviation; HR, heart rate; RER, respiratory exchange ratio; VO2, oxygen uptake. ^a Non-parametric Spearman correlation analysis. References 1. Fukuda K, Strauss SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The Chronic Fatigue Syndrome, a comprehensive approach to its def- inition and study. Ann Intern Med 1994;121:953-959. 2. Manu P, Affleck G, Tennen H, Morse PA, Escobar JI. Hypochondriasis influences quality-of-life outcomes in patients with chronic fatigue syndrome. Psychother Psychosom 1996;65:76-81. 3. Nijs J, De Meirleir K, Wolfs S, Duquet W. Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions. Clin Rehabil 2004; 18:139-148. 4. Noonan V, Dean E. Submaximal exercise testing: clinical application and interpretation. Phys Ther 2000;80:782-807. 5. Bazelmans E, Bleijenberg, Voeten MJM, van der Meer JWM, Folgering H. Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome. J Psychosom Res 2005;59: 201-208. 6. Lapp CW. Exercise limits in chronic fatigue syndrome. Am J Med 1997;103:83. 7. Paul L, Wood L, Behan WMH, Maclaren WM. Demonstration of de- layed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol 1999;6:63-69. 8. Wallman KE, Morton AR, Goodman C, Grove R. Physiological responses during a submaximal cycle test in chronic fatigue syndrome. Med Sci Sports Exerc 2004;36:1682-1688. 9. Wallman K, Goodman C, Morton A, Grove R, Dawson B. Test-retest reliability of the Aerobic Power Index Test in patients with chronic fatigue syndrome. J Chronic Fatigue Syndr 2003;11:19-32. 10. Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD. Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc 2002;34:51-56. 11. Nijs J, Meeus M, McGregor NR, Meeusen R, De Schutter G, Van Hoof E, et al. Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sports Exerc 2005;37: 1647-1654. 12. De Becker P, Roeykens J, Reynders M, McGregor N, De Meirleir K. Exercise capacity in chronic fatigue syndrome. Arch Intern Med 2000; 160:3270-3277. 13. Davis JA. Direct determination of aerobic power. In: Maud PJ, Foster C, eds. Physiological Assessment of Human Fitness. Cham- paign, IL: Human Kinetics;1995. pp. 9-17. 14. Astrand PO, Rodahl K. Evaluation of physical performance in the basis of tests. In: Astrand PO, Rodahl K, eds. Textbook of Work Physiology: Physiological Bases of Exercise. 3rd ed. New York: McGraw-Hill;1986. pp. 354-387. 15. Nijs J, Vanherberghen K, Duquet W, De Meirleir K. Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability. Phys Ther 2004;84:696-705. 16. Nijs J, De Meirleir K. Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome. Clin Rehabil 2004;18:785-792. 17. Fulcher KY, White PD. Strength and physiological response to exer- cise in patients with chronic fatigue syndrome. J Neurol Neurosurg Neuropsych 2000;69:302-307. -------- (c) 2007 Elsevier/ScienceDirect B.V. (c) 2007 Instituto Mexicano del Seguro Social (IMSS) [Return to top] ------------------------------ Date: Tue, 27 Mar 2007 13:29:17 -0400 From: Fred Springfield <fredspringfield VERIZON.NET> Subject: RES: On commonness and rarity of thyroid hormone resistance: A discussion based on mechanisms of reduced sensitivity in peripheral tissues On commonness and rarity of thyroid hormone resistance: A discussion based on mechanisms of reduced sensitivity in peripheral tissues. Journal: Med Hypotheses. 2007 Mar 23; [Epub ahead of print] Authors: E. Tjørve [*], K.M.C. Tjørve, J.O. Olsen, R. Senum and H. Oftebro Affiliation: Lillehammer University College, 2626 Lillehammer, Norway. [*] Corresponding author. Tel.: +47 612 88 219; fax: +47 612 88 170. Received 16 December 2006; accepted 10 January 2007. Available online 26 March 2007. NLM Citation: PMID: 17383828 Reduced sensitivity to thyroid hormone (TH) in peripheral tissues can occur as defects in TH transport into the cell, intracellular TH metabolism, cytosolic mechanisms, TH entry into the nucleus, thyroxin receptors (TRs) and receptor binding, transcription and post-transcriptional mechanisms. Current literature reveals an extensive list of mutations, drugs, toxins, metabolites and autoimmune antibodies that may impair TH action in the cell, but such impairment may not be picked up by assays of TH and TSH in blood plasma. Substances may induce tissue specific resistance to thyroid hormone (RTH), e.g. by affecting numbers of different TR isoforms. Recent literature also indicates mechanisms by which different conditions, for example, chronic fatigue syndrome (CFS), chronic renal failure (CRF) and nonthyroidal illness, can be accompanied by acquired RTH caused by inhibition of TH metabolism, cell uptake, TR binding and transcription. This prompts us to reassess commonness and rarity of congenital vs. acquired RTH. We hypothesise that observed clinical symptoms of hypothyroidism in chemically euthyroid patients are typically caused by changes in hormonal systems, autoimmune antibodies, metabolites or other substances in the body, leading to reduced sensitivity to TH in peripheral tissues. These changes may be a by-product of other processes and a reversible biological response in the body, and may also result in chronic acquired RTH. Antibodies may prove to be the most common cause of chronic reduction in TH sensitivity. It is argued that the acquired form of RTH, caused by endogenous and exogenous sources, may indeed be more common than the congenital, as in insulin resistance. If acquired RTH exists, then it may not be picked up by blood assays of TH and TSH. An appropriate test to assess TH action in peripheral tissues is therefore greatly desired. Copyright © 2007 Elsevier Ltd All rights reserved. [Return to top] ------------------------------ Date: Tue, 27 Mar 2007 15:31:56 -0400 From: "Dr Julie Donalek <jdonalek depaul.edu> via Co-Cure Moderator Subject: NOT,RES: DePaul University researcher seeks Chicago area families in which an adult has CFS to participate in a research study I am a DePaul nurse researcher seeking Chicago area families in which an adult has CFS. The study particulars are as follows: Families Affected By Chronic Fatigue Syndrome: A Research Study A caring, experienced, knowledgeable nurse-researcher wants to talk to people with CFS and their families about how CFS has affected the family. If you are an adult who has been diagnosed with CFS, are in a family, and have a teenage or older child or children living in the home, Dr. Julie Donalek would like to talk to you about her research. Julie is a nursing faculty member at DePaul University and has worked with people with CFS and their families as part of the DePaul CFS research team. Participants will receive payment for participation. Please call: Dr. Julie Donalek DePaul University Department of Nursing (773-325-7154 jdonalek depaul.edu [Return to top] ------------------------------ Date: Wed, 28 Mar 2007 01:55:29 +0200 From: Jan van Roijen <j.van.roijen CHELLO.NL> Subject: not,res: Female volunteers sought for study of ME/CFS ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 28 March 2007 <<<< Editorship : j.van.roijen chello.nl Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ http://www.c-n.com/apps/pbcs.dll/article?AID=/20070327/FRONT01/70327029 Courier News Female volunteers sought for study of chronic fatigue syndrome ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The National Institutes of Health in Bethesda, Md., are supporting an ongoing study by the UMDNJ Pain and Fatigue Study Center to further investigate the clinical nature of chronic fatigue syndrome. The study requires 80 female volunteers in the New York/New Jersey area. The research team, led by Dr. Benjamin Natelson, a professor of neurosciences at New Jersey Medical School, theorizes that the cause of chronic fatigue syndrome may be related to a type of substance in the blood called cytokines, which are related to immune function and which can specifically affect feelings of alertness. Natelson hypothesizes that cytokines may be malfunctioning in people with chronic fatigue syndrome. For example, those cytokines that in healthy people would cause them to become tired at night and awake during the day may make those with chronic fatigue syndrome sleepy during the day and "wired" at night. A successful outcome could lead to therapies that could "rebalance" patients' immune systems. Because about three of every four cases of CFS affect women — and because cytokine levels also are affected by gender —the study is only seeking women volunteers at this time. Researchers would like to study a mix of women diagnosed with chronic fatigue syndrome and women who are healthy, but lead a relatively sedentary lifestyle. (Vigorous exercise also affects cytokine levels.) Finding healthy women to volunteer for this study is critical, so the researchers have a proper basis for comparison. Volunteers will be asked to sleep in a research lab at The University Hospital in Newark on three to four nights, to be completed over a few months. Volunteers will be compensated for their time, depending on the circumstances of their medical history and also will receive a travel allowance. All medical treatment will be free. If you or a family member may be interested in participating in the study, contact FitzGibbons at (973) 972-4800 or at firstname.lastname@example.org. For more information on chronic fatigue syndrome, visit www.umdnj.edu/cfs [Return to top] ------------------------------ Date: Wed, 28 Mar 2007 17:03:22 -0400 From: Co-Cure Moderator <ray CO-CURE.ORG> Subject: NOT,MED: Kent Holtorf, MD, on Treating Chronic Fatigue Syndrome & Fibromyalgia - An Update Dr. Kent Holtorf, MD, is Medical Director of the Holtorf Medical Group Center for Hormone Imbalance, Hypothyroidism and Fatigue in Torrance, California. He specializes in treatment of CFS and FM patients. Question: Dr. Holtorf, in your article on the effective treatment of Chronic Fatigue Syndrome and Fibromyalgia you stated that "individuals with these syndromes have measurable hypothalamic, pituitary, immune and coagulation dysfunction. These abnormalities then result in a cascade of further abnormalities, in which stress plays a role." Could you discuss in detail how you approach testing for and treating these problems in CFS and FM patients? Dr. Holtorf: There is a mixture of underlying causes of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM), and each underlying abnormality can trigger further problems. This results in a cascade of multiple physiologic abnormalities and a perpetuating vicious cycle. Successful treatment requires that this vicious cycle be addressed on multiple levels. This cascade of abnormalities [beginning with the "Genetic Predisposition" and then "Triggering Event of Physiologic Stress"] is graphically depicted below - and a few of the abnormalities are also discussed. Read this Q&A at http://www.immunesupport.com/library/showarticle.cfm?id=7856 [Return to top] ------------------------------ Date: Wed, 28 Mar 2007 14:16:57 -0700 From: "charles stafford <luceat1 yahoo.co.uk> [via Co-Cure Moderator] Subject: MED, ACT: myalgic encephalomyelitis From: charles stafford <email@example.com> For Posting. I was diagnosed 30 years ago, with acute onset myalgic encephalomyelitis by a tenured Harvard M.D. who had personally studied one of the USA outbreaks. This definitely is not the same as Chronic Fatigue Syndrome. I have suffered and still suffer from the confusion that the creation of CFS causes my medical providers, the community as a whole and my friends. Part of the consequence of this is that all the research into CFS has been, as far as the ME patients are concerned, a tragic waste of our time and our money. The data are invalid due to the lack of specificity of the inclusion criteria, and their replication is uncertain. Even where the data are based on a classic epidemic of Myalgic encephalomyelitis such as the Lake Tahoe epidemic, they still are published under CFS. Unfortunately, Myalgic encephalomyelitis affects many people. We can be diagnosed under both the Ramsey definition and the Canadian Consensus definition. We need to be studied as Myalgic encephalomyelitis, WHO ICD 10 G 93.3. We are not a sub-set of CFS, which has a separate WHO ICD 10 code. Yours Sincerely, Luceat [Return to top] ------------------------------ Date: Thu, 29 Mar 2007 11:44:27 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Fibromyalgia, cognitive problems and independence:physical activity may be useful in home health care Fibromyalgia, cognitive problems and independence:physical activity may be useful in home health care. Home Health Care Serv Q. 2007;26(1):19-28. Karper WB. School of Health and Human Performance, PO Box 26170, Greensboro, NC, 27402, wbkarper uncg.edu PMID: 17387049 Home health care providers often deal with older clients who have cognitive deficits. Cognitive problems have a negative impact on independence. Certain chronic pain conditions present with cognitive dysfunction as a co-morbidity. Fibromyalgia syndrome is one such condition. Home health care providers need to know that mild-moderate exercise may positively affect fibromyalgia-related cognitive deficits at very low cost. All of the above is discussed in this paper along with advice concerning the provision of exercise for older, homebound people. [Return to top] ------------------------------ Date: Fri, 30 Mar 2007 13:36:44 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Subgroups of fibromyalgia [Subgroups of fibromyalgia.] [Article in German] Schmerz. 2007 Mar 29; [Epub ahead of print] Muller W, Schneider M, Joos T, Hsu HY, Stratz T. Rheumatologische Forschungsabteilung, Park-Klinik Bad Sackingen, Weihermatten 1 , 79713, Bad Sackingen, Deutschland. PMID: 17393187 As has been shown by a number of working groups, primary fibromyalgia syndrome does not represent a single clinical entity. It is possible to distinguish between a subgroup with high pain sensitivity and no associated psychiatric condition, a second subgroup characterized by depression and concomitant pain symptoms associated with fibromyalgia syndrome, and a third group with somatoform pain disorder of the fibromyalgia type. Bland inflammatory processes must be considered as the cause in the first group, while depression is the underlying reason for the development of pain in the second group. In the third group, serious previous or still existing psychological problems or also insufficient coping with illness symptoms must be regarded as the reason for pain chronification. Group 1 benefits from a blocking of the 5-HT3 receptors by means of tropisetron, for example. This not only affects pain chronification but also the inflammatory process itself. Group 2 needs antidepressant treatment, whereas the focus should be on psychotherapy is group 3. Groups 1 and 2 will also profit from multimodal physical treatment programs; to a certain extent this applies to group 3 as well. So-called mixed types require a combination of therapeutic measures. [Return to top] ------------------------------ Date: Fri, 30 Mar 2007 13:40:54 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Gabapentin in the treatment of fibromyalgia: A randomized, double-blind, placebo-controlled, multicenter trial Gabapentin in the treatment of fibromyalgia: A randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum. 2007 Mar 28;56(4):1336-1344 [Epub ahead of print] Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE Jr, Welge JA, Bishop F, Stanford KE, Hess EV, Hudson JI. University of Cincinnati College of Medicine, Cincinnati, Ohio. PMID: 17393438 OBJECTIVE: To assess the efficacy and safety of gabapentin in patients with fibromyalgia. METHODS: A 12-week, randomized, double-blind study was designed to compare gabapentin (1,200-2,400 mg/day) (n = 75 patients) with placebo (n = 75 patients) for efficacy and safety in treating pain associated with fibromyalgia. The primary outcome measure was the Brief Pain Inventory (BPI) average pain severity score (range 0-10, where 0 = no pain and 10 = pain as bad as you can imagine). Response to treatment was defined as a reduction of >/=30% in this score. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect. RESULTS: Gabapentin-treated patients displayed a significantly greater improvement in the BPI average pain severity score (P = 0.015; estimated difference between groups at week 12 = -0.92 [95% confidence interval -1.75, -0.71]). A significantly greater proportion of gabapentin-treated patients compared with placebo-treated patients achieved response at end point (51% versus 31%; P = 0.014). Gabapentin compared with placebo also significantly improved the BPI average pain interference score, the Fibromyalgia Impact Questionnaire total score, the Clinical Global Impression of Severity, the Patient Global Impression of Improvement, the Medical Outcomes Study (MOS) Sleep Problems Index, and the MOS Short Form 36 vitality score, but not the mean tender point pain threshold or the Montgomery Asberg Depression Rating Scale. Gabapentin was generally well tolerated. CONCLUSION: Gabapentin (1,200-2,400 mg/day) is safe and efficacious for the treatment of pain and other symptoms associated with fibromyalgia. [Return to top] ------------------------------ Date: Sat, 31 Mar 2007 11:13:39 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Social functioning and peer relationships of adolescents with juvenile fibromyalgia syndrome Social functioning and peer relationships of adolescents with juvenile fibromyalgia syndrome. Arthritis Rheum. 2007 Mar 29;57(3):474-480 [Epub ahead of print] Kashikar-Zuck S, Lynch AM, Graham TB, Swain NF, Mullen SM, Noll RB. Cincinnati Children's Hospital Medical Center, and the University of Cincinnati College of Medicine, Cincinnati, Ohio. PMID: 17394218 OBJECTIVE: To assess peer relationships of adolescents with juvenile primary fibromyalgia syndrome (JPFS) compared with matched classroom comparison peers (MCCPs) without a chronic illness. JPFS is characterized by chronic musculoskeletal pain, sleep disturbance, fatigue, and difficulty with daily functioning. Adolescents with JPFS often report problems with school and participating in peer activities, placing them at risk for social isolation from their peers and psychosocial adjustment problems. METHODS: Participants were 55 adolescents with JPFS (ages 12-18 years) from a pediatric outpatient rheumatology clinic and 55 MCCPs. Data on peer reputation and peer acceptance were collected from teachers, peers, and self report in a classroom setting with no focus on JPFS. RESULTS: Adolescents with JPFS were perceived (by peer and self reports) as being more isolated and withdrawn and less popular. Adolescents with JPFS were less well liked, were selected less often as a best friend, and had fewer reciprocated friendships. CONCLUSION: Our findings suggest that adolescents with JPFS are experiencing problems with peer relationships. Given the central role that peer relationships play in psychological development of children, and because peer rejection and isolation have been associated with subsequent adjustment problems, these findings are concerning. Longitudinal studies of adolescents with JPFS are needed to ascertain whether these patients are at long-term risk and will provide a foundation for the need for early interventions. Results are discussed within the context of earlier findings for other adolescents with chronic illness and rheumatic conditions, such as juvenile idiopathic arthritis, who demonstrated no social problems. [Return to top] ------------------------------ Date: Sat, 31 Mar 2007 11:23:28 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Fibromyalgia, Facial Expression and Emotional Experience Fibromyalgia, Facial Expression and Emotional Experience. Psychopathology. 2007 Mar 29;40(4):203-208 [Epub ahead of print] Kirsch A, Bernardy K. Department of Clinical Psychology and Psychotherapy, Saarland University, Saarbrucken, Germany. PMID: 17396046 Background: The present study aims at analyzing the nonverbal affective behavior of female fibromyalgia (FM) inpatients in comparison to healthy women. Methods: Videotaped psychodynamic interviews of each of 15 female FM inpatients and healthy women were analyzed. Afterwards the analyses of facial expression were related to gazing behavior and emotional experience. Results: FM patients exhibited neither a reduction in total activity of facial expression nor in absolute frequency of primary affects in comparison to healthy women, who, however, (also in eye contact) also exhibited a significantly higher proportion of 'genuine joy' and a lower one of 'contempt'. No congruence between the patient's emotional experience and affective expression was found. Conclusions: The absence of reduced total activity of facial expression is in contrast to the elaborate descriptions of complaints provided by the patients. Nevertheless, our detailed analysis shows a lack of elements that stabilize the relationship and the presence of dissociating elements in the interactions. Copyright (c) 2007 S. Karger AG, Basel. [Return to top] ------------------------------ Date: Sun, 1 Apr 2007 10:22:53 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Primer: establishing a clinical trial unit-regulations and infrastructure Primer: establishing a clinical trial unit - regulations and infrastructure. Nat Clin Pract Rheumatol. 2007 Apr;3(4):234-9. Fleischmann R. R Fleischmann is a Clinical Professor of Medicine at the University of Texas Southwestern Medical Center at Dallas, and Co-Medical Director of Metroplex Clinical Research Center, Dallas, TX, USA. PMID: 17396109 The performance of clinical trials can be very rewarding for the practicing or academic clinical rheumatologist. There are at least 50 new compounds-small molecules and biologics-in development for rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, scleroderma, gout and fibromyalgia. Clinical trials are important to try to determine the appropriate use of these compounds, as well as to answer questions about their safety. To carry out clinical trials effectively, the physician-investigator must be aware of, and adhere to, the regulatory requirements. The purpose of this article is to review these requirements in depth, as well as to discuss the infrastructure required to establish a successful clinical trial unit. [Return to top] ------------------------------ Date: Mon, 2 Apr 2007 17:47:45 +0200 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Ampligen Update Source: Philadelphia Business Journal Date: March 30, 2007 Author: John George <jgeorge bizjournals.com> URL: http://eastbay.bizjournals.com/eastbay/othercities/philadelphia/stories/2007/04/02/story8.html?b=1175486400^1439140 Hemispherx finalizing fatigue drug filing ----------------------------------------- Hemispherx BioPharma Inc. is finalizing its new drug application for Ampligen, an experimental treatment for chronic fatigue syndrome that has spent more than 30 years in clinical studies. Dr. William Carter, the Center City biotechnology company's chairman and CEO, said he expects the application will be completed in early April. Carter said he is "cautiously optimistic" the company will be able to secure an accelerated review from the Food and Drug Administration, given the absence of any approved treatments for chronic fatigue syndrome. The Centers for Disease Control and Prevention estimates the disorder afflicts 1 million people in the United States. Accelerated reviews are typically conducted in six months, as opposed to the one-year review for most new drug applications. If the company gets such status for its Ampligen filing, and the FDA approves the application without raising any issues, Hemispherx would be in a position to launch the product by the end of this year or early 2008, Carter said. Carter expressed a sense of vindication that his company has reached this point. "It's been a long and arduous journey... There were a lot of skeptics," he said. The skepticism remains evident in the company's stock price. Hemispherx's stock was trading recently at $1.69 a share, near its 52-week low of $1.65. According to documents filed earlier this month with the Securities and Exchange Commission, Hemispherx has recorded an accumulated deficit of about $167 million since its inception. Hemispherx posted a net loss of $19.4 million last year, up from a deficit of $12.4 million in 2005. The increase was due primarily to higher research and development costs associated with Ampligen and Alferon N, which the company acquired in 2003, is a treatment for genital warts and Hemispherx's only FDA-approved product in the market. The company is testing both Ampligen and Alferon N as potential treatments for viral infections such as avian flu. Carter co-invented Ampligen in the early 1970s when he was a researcher at Johns Hopkins University. Ampligen is a synthetic, specifically configured double-stranded RNA compound designed to work by stimulating and enhancing the ability of a patient's immune system to fight disease. Initially, the drug was tested as a potential treatment for cancer and later for AIDS then for chronic fatigue syndrome. Carter even tinkered with the idea of using the compound to treat tobacco and create a "healthy" cigarette. Hemispherx has spent the past 15 years testing the drug as a treatment for patients with chronic fatigue syndrome. The company estimates the global market for an effective treatment for the disorder to be in excess of $1 billion. "We're not the first company to go into this disease category," Carter said. In a presentation with stock analysts last month, the company noted drugs developed by a half-dozen major pharmaceutical and biotechnology companies - including GlaxoSmithKline, Shire and Cephalon - have been considered as potential treatments for chronic fatigue syndrome, but said none proved to be effective. Jenifer Antonacci, a Cephalon spokeswoman, said the company's flagship drug Provigil, approved as a treatment for narcolepsy and other sleep-related disorders, was tested in patients with chronic fatigue syndrome about two years ago. She said the study was conducted by researchers from outside of the company, with Cephalon support. The clinical trial, which involved 14 patients, did not produce sufficient results for Frazer-based Cephalon to consider seeking approval to expand Provigil's label to include the disorder. Matt Cabrey, a Shire spokesman, said that while company executives have discussed the potential of testing its products for chronic fatigue syndrome, Shire never launched any formal product development program and has no current plans to do so. Based in England, Shire's U.S. headquarters are in Wayne. Up Close -------- COMPANY: Hemispherx BioPharma Inc. LOCATION: Philadelphia CHAIRMAN AND CEO: Dr. William Carter TYPE OF COMPANY: Biopharmaceutical 2006 NET LOSS: $19.4 million 2006 REVENUE: $933,000 52-WEEK HIGH/LOW: $3.85, $1.65 RECENT PRICE: $1.69 MARKET CAPITALIZATION: $122.6 million EMPLOYEES: 52 full time, 19 part time BIG DEVELOPMENT: Finalizing new drug application for Ampligen, an experimental treatment for chronic fatigue syndrome. Source: SEC, company, Yahoo! Finance -------- (c) 2007 Philadelphia Business Journal [Return to top] ------------------------------ Date: Mon, 2 Apr 2007 18:06:15 +0200 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Doctors, friends, and relatives dismiss FM Source: The Ledger Date: April 2, 2007 Author: Gary White <gary.white theledger.com>, phone 863-802-7518. URL: http://www.theledger.com/apps/pbcs.dll/article?AID=/20070402/NEWS/704020367/1004 Some Doctors, Friends, Relatives Dismiss Sickness ------------------------------------------------- As a teenager, Lakeland resident Jiwa Farrell was diagnosed with lupus, an autoimmune disease that affects mostly women and often mimics fibromyalgia and chronic fatigue syndrome. It's easy to make personality judgments about people with fibromyalgia and other chronic pain disorders. The patient's current lethargy and inactivity can yield assumptions of lifelong laziness and aversion to work. Those diagnosed with the ailments say it's a common and frustrating misconception. "I don't think I have ever met a person with fibromyalgia who is lazy," said Lynne Matallana, president of the National Fibromyalgia Association. "Quite the opposite." Matallana said a high percentage of fibromyalgia patients are "Type A" personalities who were high-achieving professionals before the illness struck. Matallana, 51, worked as a partner in a prominent advertising firm and was athletic before she became ill in the early 1990s, eventually spending two years in bed after being wrongly diagnosed with lupus. Local patients have similar backgrounds. Martha Grierson of Winter Haven worked long hours as a sales manager for a large corporation before fibromyalgia prematurely ended her career. Lynn Anderson of Polk City used to show horses in competitions, though fibromyalgia now prevents her from even mounting a horse. Lakeland's Laura Bodner, another fibromyalgia patient, formerly worked as a firefighting trainer and exercised five days a week. Davenport resident Millie Haddad was a nurse with a side business until being diagnosed with chronic fatigue syndrome, and Teresa Kucera, a Lakeland resident with the same disorder, worked as a medical assistant and said she "used to be like a tornado." Government medical agencies have recognized fibromyalgia and CFS as legitimate disorders in the past decade or so, but patients say skepticism remains commonplace, especially among general practitioners. Every fibromyalgia patient seems to have at least one story of rude or dismissive treatment from a doctor. Grierson and other local patients said doctors have suggested their problems are psychological rather than physical. "I've actually had a doctor tell me I need mental health help, that it was all somatic, which is a kind way of saying it's all in your head," Grierson said. Bodner, 45, described the hostility she received from a local doctor after seeking a refill of Darvocet, a prescription pain medicine. "My daughter got real upset because she sees how much pain I'm in, and she goes, 'Can't you just give her something that's going to help her instead of Darvocet?'" Bodner said. "And (the doctor) said, 'I don't even like giving her Darvocet because I think she's overreacting. Somebody who's got fibromyalgia shouldn't be in this pain.' My daughter just went off on the doctor. She was saying, 'You know, I wish you could just have it for one week so you could see what my mother goes through.'" Matallana said the lack of compassion and understanding from doctors compounds the physical and emotional distress of the illness itself. "I know in my case I just had the idea if you got sick you went to a doctor and they treated you," Matallana said. "I never, ever imagined someone would question my pain and my inability to function. That was to me almost as bad as enduring the physical symptoms." Confusion, skepticism The transformation of dynamic people into suffering wrecks, without any apparent cause, prompts confusion and questioning. Fibromyalgia patients say even friends, relatives and spouses find it hard to accept the reality of what has been called an invisible illness. "Even my family was skeptical at first," said Randy Jones, a Dade City resident who receives treatment for her fibromyalgia at Salazar Family Clinic in Mulberry. "Even my husband, it was like, 'Maybe you just don't want to get out of bed.' " Jones, 60, admitted she had doubts about fibromyalgia before the illness struck her in 2000, leaving her incapacitated for long periods. "Nobody walks in your body but you, and how can one person say what another person is feeling?" she said. "Why would I want to do this to myself?" Grierson likewise has had friends and relatives question her condition. "Some I thought would understand have accused me of being drug-seeking, of being lazy, of doing this for attention," she said. "It's just awful the things people will say because they don't understand and it's not a common thing and you don't carry scars on the outside of your body. It makes coping with what's wrong with you that much worse because if you hear it enough you begin to think maybe you are a little crazy. That's the insidious thing of it." If the medical world has been slow to accept fibromyalgia and other chronic pain disorders, it's perhaps no surprise patients describe having difficulties with medical coverage and government disability programs. Grierson said she faced constant battles with her insurance company over payments for treatments, and at one point when she lived in Pennsylvania a doctor sued her over the plan's failure to pay medical bills. She had equal trouble getting approved for Social Security Disability Income, going through two years of denials before she hired a lawyer who helped her prevail in a court hearing. Bodner said she has twice been turned down for SSDI since applying last year. She has enlisted a lawyer to help her push for the government supplement. Anderson has Medicare coverage, but she said the plan doesn't cover massage therapy, the only treatment that offers her significant relief because the effect is temporary. Her sister, Terry Anderson, became a massage therapist after observing Lynn's ordeal, and she sometimes travels from Pinellas County to offer her services. Haddad, who required a court hearing before being approved for SSDI, said, "It took a long time before I was able to collect disability because they didn't believe this till a lot of doctors started getting the disease themselves." 'The F-Word' Dr. Patrick Wood, an assistant professor of medicine at Louisiana State University, decided to specialize in fibromyalgia in part because it was a verboten term during his training. As Wood points out, many diseases now universally accepted - including malaria, asthma and Parkinson's - were previously dismissed or relegated to non-medical categories. "When I was in medical school, it was the F-word," Wood said. "You didn't even say it around other physicians. I was very intrigued to think there was a medical entity you could choose not to believe in, like a ghost or a fairy... I've always kind of stuck up for the underdog, and fibromyalgia patients are kind of the underdogs of the medical world." Despite recent progress, Wood said, "I've been at the same institution for 10 years, and there's still tremendous hostility toward the disorder (fibromyalgia) and toward the diagnosis from people who certainly should know better." Chronic pain patients and their advocates cite several factors behind the lingering skepticism among many doctors. One is the lack of verifiable causes. The ailments arise gradually in some patients, while others point to a specific traumatic event as the trigger. The trauma can be physical - in Anderson's case, being kicked in the face by a horse - or emotional, such as a divorce or the death of a spouse. Advocates say the varying intensity of symptoms also fosters doubts. "The illness can wax and wane, and when people feel better oftentimes they push themselves so others see them up doing what normal people would do, and the next week they're back in bad," Matallana said. "That doesn't make sense; we think of illness as being continuous." Wood, noting that doctors dislike uncertainty, said many general practitioners are loath to admit they don't have an explanation for a patient's complaints and react by questioning the patient's description. "I don't think it makes me popular with my colleagues, but we're trained to be little gods and anything that challenges our god-like capacity we dismiss," Wood said. "(A doctor) could say, 'There's nothing to objectively demonstrate you're really sick. How do I know you're sick?' You have to trust the patient's report, which we're often not willing to do when it comes to pain." Patients say it often becomes clear they know much more about their conditions than the doctors charged with treating them. Haddad of Davenport has attended countless seminars on chronic fatigue syndrome since being diagnosed with it, and she said most doctors dispense merely obvious advice - eat right, sleep right, lose weight. "A lot of health-care providers feel uncomfortable because of the limits of their expertise," said Dr. Roland Staud, a professor of medicine at the University of Florida specializing in fibromyalgia. "Many physicians wanted these patients to be seen by psychologists and psychiatrists and did not feel equipped to deal with this." A gender issue Matallana and others say the gender factor also affects perceptions of fibromyalgia. The preponderance of patients are women, and advocates cite a long history of medical authorities dismissing female- oriented illnesses as forms of hysteria. "You have to look back on the medical community - it has basically been male-dominated," Matallana said. "I don't think it's something they have done intentionally, but I know when you have experienced something yourself it's much easier to understand what it really is." Lakeland's Jiwa Farrell was diagnosed at age 16 with lupus, an autoimmune disorder that often mimics fibromyalgia and chronic fatigue syndrome and disproportionately affects women. "I'm not trying to make this a feminist movement or anything," she said, "but... it amazes me how many drugs they have out for ED (erectile dysfunction) all of a sudden, and we haven't had a new drug for lupus since the '60s." Fibromyalgia and other chronic pain disorders sometimes occur in family clusters. For example, Bodner said her two daughters, both in their 20s, have been told they have fibromyalgia since she received her own diagnosis, and several other local patients also said relatives share their ailments. The phenomenon might suggest a genetic component to the disorders, but to a skeptical mind it can also raise the prospect of suggestibility. Confusing matters further, fibromyalgia and related disorders seem intertwined with psychological components. Many patients exhibit signs of depression, leading to a chicken-and-egg question about the relation between psychological distress and physical pain. "The question that was raised in the past was in what category of medical illness these symptoms would fall," said Staud, the UF professor. "Many physicians believed they would fall in the psychological-psychiatric area, where some physicians believed it was in the purely physical area, and of course the truth is halfway in between, because for 200 years we know there is no mind-body dichotomy. Every illness has these components. To say someone has a purely psychological illness - this is not an up-to-date approach." Patient profiling Dr. Edward Lubin of Winter Haven's Gessler Clinic said some general practitioners engage in "patient profiling" when they encounter the typical fibromyalgia patient - a middle-aged woman complaining of vague pains. Lubin, a pain-management specialist, also cited the financial pressures that limit the time doctors spend with each patient, discouraging a thorough exploration of the patient's medical history and fostering cynical reactions. "Some physicians have a sketch in their minds," Lubin said, "so when a patient comes to their office with complaints that can be treated with either antidepressants or narcotics, they immediately have a picture in their mind of a patient, and they either don't explore the nature of it or essentially they punt the patient to a pain management doctor." Lubin said some doctors dismiss patients with vague complaints of pain as hypochondriacs or malingerers, lazy people looking for an excuse not to work. Lubin said it doesn't help matters that he and other doctors regularly encounter true malingerers, about whom they must make judgments to determine government disability payments. "Every doctor is faced with being a useful idiot, being a tool for somebody who wants to get out of work," said Lubin, who trained at Yale and Harvard. "I'd rather you fooled me once and then I could say, 'Shame on you,' rather than try to prevent my ego from ever being bruised by assuming everyone whoever asked me for a pill for their pain is a drug-seeker. We can't lose our humanity just because we're afraid of being hoodwinked." -------- (c) 2007 The Ledger [Return to top] ------------------------------ Date: Mon, 2 Apr 2007 18:35:51 -0400 From: "Dr Charles Shepherd <charles.c.shepherd btinternet.com> [via Co-Cure Moderator] Subject: NOT,MED: Northern Ireland ME Association Medical Meeting on Saturday April 14th 2007 MAY BE REPOSTED The programme for this full day meeting for doctors, organised by the Northern Ireland ME Association, can be found in the news section of the MEA website at: www.meassociation.org.uk Charles Shepherd Hon Medical Adviser, MEA [Return to top] ------------------------------
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