|
Volume 2, Number 1 |
1st March 1999 |
Choppa PC., Vojdani A., Tagle C., Andrin R and Magtoto L. Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome. Molecular and Cellular Probes, 1998, 12, 5, 301-308.
A multiplex polymerase chain reaction (PCR) assay was used to detect mycoplasma infection in DNA samples from 100 people with CFS (CDC criteria '94) and 100 healthy controls. The researchers found an overall Mycoplasma genus infection rate of 52% in CFS patients and 15% in the controls. Mycoplasma fermentans, M. hominis and M. penetrans were detected in 32, 9 and 6% of the CFS patients while they were detected in 8, 3 and 2% of the healthy subjects, respectively.
The role played by mycoplasma remains uncertain. M. fermentans was found in 44.5% of saliva samples from healthy controls, suggesting that it is a benign colonizer of the oral mucosa in the adult population. On the other hand, it was the only infectious agent identified in biopsies and blood samples taken from previously healthy non-AIDS patients with severe chronic fatigue or a flu-like illness. These patients recovered following adequate antimicrobial therapy.
Conti, F., Pittoni, V., Sacerdote, P., Priori, R., Meroni, PL and Valesini, G. Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with chronic fatigue syndrome. Clinical and Experimental Rheumatology, 1998, 16, 6, 729-732.
This study involved 16 patients with CFS (CDC criteria '94, 11 with post-exertional malaise) and 10 healthy controls. Beta-endorphin concentrations were measured in peripheral blood mononuclear cells (PBMC) by radioimmunoassay performed with antibodies specific for the C-terminal portion of human beta-endorphin.
Beta-endorphin concentrations in the PBMC of CFS patients were significantly lower (p<0.001) than in the healthy subjects (mean 8.5 vs. 42.6).
This finding may reflect the condition of chronic immune activation in CFS that has been reported in previous investigations. "Beta-endorphin concentrations in PBMC seem to mirror the central nervous system homeostasis of the opioid. Therefore, we would postulate that the fatigue and weakness typical of CFS could be related to low beta-endorphin concentrations at the central nervous system level."
Ogawa, M., Nishiura, T., Yoshimura, M., Horikawa, Y., Yoshida, H., Okajima, Y., Matsumura, I., Ishikawa, J., Nakao, H., Tomiyama, Y., Kanayama, Y., Kanakura, Y and Matsuzawa, Y. Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome. European Journal of Clinical Investigation, 1998, 28, 11, 937-943.
L-Arginine (L-Arg), one of the essential amino acids, has been reported to have an immunomodulatory effect. The precise mechanism of the L-Arg-induced natural killer (NK) cell activation remains unresolved, and the effect of L-Arg on NK cells in CFS patients has not been estimated. In this study, NK cell function was evaluated in 20 subjects with CFS (CDC criteria '88) and compared with that in 21 healthy individuals.
There were no differences between the groups in terms of baseline NK activity. While treatment with L-Arg significantly increased NK activity in the controls, the same treatment failed to enhance NK activity in the CFS group. Studies then focused on L-Arg metabolism, which involves nitric oxide (NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in PBMC was not significantly different between healthy control subjects and CFS patients. However, as expected, the L-Arg-mediated NK cell activation was abolished by addition of NG-monomethyl-L-arginine, an inhibitor for iNOS. Furthermore, incubation with S-nitroso-N-acetyl-penicillamine, an NO donor, stimulated NK activity in healthy control subjects, as predicted, but not in CFS patients.
"These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients." This is not related to a defect in cytokine production.
Roberts, TK., McGregor, NR., Dunstan, RH., Donohoe, M., Murdoch, RN., Hope, D., Zhang, S., Butt, HL., Watkins, JA and Taylor, WG. Immunological and haematological parameters in patients with chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1998, 4, 4, 51-65.
Red and white blood cell parameter profiles and pokeweed mitogen responses were investigated in 57 patients with CFS (CDC criteria '88) and 34 age-and sex-matched controls.
CFS patients had significantly different red and white blood cell profiles compared with controls. Red cell distribution width (RDW) was the primary regression factor differentiating the groups. RDW was positively associated with mean platelet volume (MPV) in control subjects, but negatively correlated with MPV in CFS patients, indicating a reversal of the functional relationship between these parameters in CFS patients.
Haematological parameters, and not the immunological parameters studied, were more important in differentiating CFS patients from healthy control subjects. Female CFS patients had significant increases in RDW and mean platelet volume, and decreases in the numbers of T-helper cells, T-cells and lymphocytes compared with control females. These alterations were not observed in corresponding male comparisons. There were no differences in the pokeweed mitogen (PWM) response between the CFS and control groups. However, in control subjects, a significant association was observed between pokeweed mitogen responses and Rh(D) antigen status, whereas no similar association was measured in CFS patients. Rh(D)-negative control subjects had a significantly increased mitogen response compared with Rh(D)-positive subjects, whereas in CFS patients, no difference was found.
In summary, substantial alterations in red and white blood cell functions and interactions were found. It was concluded that future blood parameter and lymphocyte mitogen response studies in CFS patients should be controlled for sex and Rh status, respectively.
See, DM., Cimoch, P., Chou, SW., Chang, J and Tilles, J. The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Integrative Physiological and Behavioral Science, 1998, 33, 3, 280-287.
In humans, eight monosaccharides are required for the synthesis of glycoproteins. Dietary supplements that supply these crucial sugars are known as glyconutrients. A glyconutrient compound was added to PBMC isolated from 90 normal controls and 91 patients with CFS (CDC criteria '94). The in-vitro immunomodulatory effects were investigated.
Cell surface expression of the glycoproteins CD5, CD8, and CD11a were significantly lower in patients with CFS compared to normal controls. Addition of glyconutrient homogenate to PBMC from patients with CFS stimulated with phytohemagglutinin significantly increased the expression of each glycoprotein. Furthermore, natural killer (NK) cell function was reduced in CFS patients. The glyconutrient preparation significantly enhanced NK cell activity versus human herpes virus 6 (HHV-6)-infected H9 cells in an 8 h 51Cr release assay compared to placebo in blood from patients with CFS (p<.01). Finally, apoptosis was significantly higher in patients with CFS. The percentage of apoptotic cells was significantly decreased in PBMC from patients with CFS that had been incubated for 48 hours with glyconutrients. Thus, glyconutrients improved abnormal immune parameters in vitro in patients with CFS.
Commenting on the immunological findings, the authors note that "it is therefore apparent that CFS is a heterogeneous disorder with multiple subgroups... Some subgroups may benefit from glyconutritional supplementation... Immune dysfunction is present in some patients".
Fischler, B., Flamen, P., Everaert, H., Bossuyt, A and De Meirleir, K. Physiopathological significance of 99mTc HMPAO SPECT scan anomalies in chronic fatigue syndrome: A replication study. Journal of Chronic Fatigue Syndrome, 1998, 4, 4, 15-30.
Regional cerebral blood flow, measured by SPECT imaging, was studied in 22 people with CFS (Oxford and CDC criteria '94) and 15 healthy controls.
Larger right>left asymmetry at the parietotemporal level in CFS as compared to controls was observed. However, there was no hypoperfusion in the brainstem as documented in other studies. Indeed, hyperperfusion was demonstrated in several frontal and temporal regions. No significant correlations were found between frontal tracer uptake and R-L parietotemporal asymmetry, on the one hand, and clinically relevant CFS dimensions, on the other.
[Ed. note: There is no normative data on the degree of disability, type of onset or link to infection in the CFS group.]
Berwaerts, J., Moorkens, G and Abs, R. Secretion of growth hormone in patients with chronic fatigue syndrome. Growth Hormone & IGF Research, 1998, 8, 127-129.
Twenty patients with CFS (CDC criteria '94, 30-60 years) and age-and sex-matched controls were tested for peak GH responses to insulin-induced hypoglycaemia and arginine administration. Nocturnal secretion of GH and serum levels of insulin-like growth factor I (IGF-I), were also measured.
Serum IGF-I was significantly lower in patients with CFS than in controls (p=0.02). Patients with CFS also tended to have reduced nocturnal secretion of GH (NS), but peak GH responses to insulin- induced hypoglycaemia and arginine administration did not differ significantly between the two groups. It is not clear whether the tendency for impaired spontaneous nocturnal GH secretion in patients with CFS is a cause or an effect of the condition.
Hamilos, DL., Nutter, D., Gershtenson, J., Redmond, DP., Di Climenti, JD., Schmaling, KB., Make, BJ and Jones, JF. Core body temperature is normal in chronic fatigue syndrome. Biological Psychiatry, 1998, 43, 293-302.
A study of 7 patients with CFS (CDC criteria '92, two with depression), 7 healthy controls, 7 people with seasonal allergies and 7 individuals with depression, revealed no differences in (24-hour) core body temperature between the groups. There were also no differences in the profile of plasma cortisol.
MacHale, SM., Cavanagh, JTO., Bennie, J., Carroll, S., Goodwin, GM and Lawrie, SM. Diurnal variation of adrenocortical activity in chronic fatigue syndrome. Neuropsychobiology, 1998, 38, 4, 213-217.
Baseline morning and evening serum cortisol and ACTH concentrations, and diurnal changes in hormone levels, were measured in 30 patients with CFS (CDC criteria '94, 10 taking anti-depressants but without concurrent depressive disorder) and a control group of 15 weight-, age- and sex-matched healthy volunteers.
Morning cortisol levels were non-significantly lower in CFS patients, while evening levels were non-significantly higher. ACTH concentrations were non-significantly higher in both the morning and evening. The diurnal change in cortisol levels was significantly less in CFS than in controls (p<0.05). In CFS subjects, evening levels of cortisol correlated modestly but significantly with measures of general health and physical functioning, while diurnal change in cortisol was positively correlated with measures of functional improvement over the past year and current social functioning. Cortisol levels did not correlate with symptoms.
There were no notable differences when patients on antidepressants were not included in the analysis.
"These results suggest that there is a relationship between adrenocortical function and disability in CFS, but do not reveal the causal connection."
Moorkens, G., Wynants, H and Abs, R. Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study. Growth Hormone & IGF Research, 1998, 8, 131-133.
The efficacy of growth hormone (GH) therapy was evaluated in 20 patients with CFS (CDC criteria '94) who had peak serum GH levels below 10 µg/l during stage-controlled sleep. They were randomized to receive placebo or GH therapy, 6.7 µg/kg/day (0.02 IU/kg/day), for 12 weeks. Following this double-blind treatment period, the 17 patients remaining in the study were given GH therapy at the above dose for a period of 9 months.
Mean serum levels of insulin-like growth factor I (IGF-I) increased during GH treatment (p<0.001). Fat-free mass and total body water were significantly increased after 12 months of treatment. Although quality of life, as assessed using two different questionnaires, did not improve significantly during GH treatment, four patients were able to resume work after a long period of sick leave.
See also, Berwaets et al. Journal of Chronic Fatigue Syndrome, 1998, 4, 4, 81-91, for a review on the research into the role of GH in CFS.
Paul, L., Wood, L., Behan, WMH and Maclaren, WM. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. European Journal of Neurology, 1999, 6, 63-69.
Patients with CFS complain consistently of a delay in recovery of peripheral muscle function after exercise. A fatiguing exercise was therefore carried out on the quadriceps muscle group of 10 patients with CFS (Oxford and CDC criteria '88 and '94 plus others*), and 10 sedentary controls. They had no history of psychiatric illness or other neurological conditions. The test consisted of 18 maximum voluntary contractions (MVCs) and further tests at 5, 10, 15, 20, 35, 50, 65, 80, 110, 140, 170, and 200 minutes post-exercise. A further test (3 MCVs) was conducted after 24 hours.
The initial peak force values were higher in the controls compared to the patients with CFS (p=0.006) but there were no differences between the groups in terms of the pattern of decline over the 18 contractions.
Recovery was prolonged in the people with CFS, as shown by reduced force compared to initial MCV values (73% in the CFS group compared to 91% in the controls, p<.01). Indeed, while the recovery of force in the controls was complete by 200 minutes post-exercise, "an even further decline in force" was observed among the CFS group at 24 hours.
The greater loss in force may reflect reduced aerobic capacity. Given that the controls were sedentary, the delayed recovery is unlikely to be the result of deconditioning. "The findings support the clinical complaint of delayed recovery after exercise in patients with CFS".
*[Ed. note: The use of various criteria in this study suggest the population had an illness consistent with ME.]
Stewart, J., Weldon, A., Arlievsky, N., Li, K. and Monoz, J. Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head up tilt testing in children with chronic fatigue syndrome. Clinical Autonomic Research, 1998, 8, 4, 221-230.
Sixteen patients aged 11-19 with CFS (CDC criteria '94) underwent head-up tilt tests (up to 80') for 40 minutes or until syncope. Data were compared to 26 patients evaluated for syncope and with 13 normal control subjects.
Thirteen CFS patients fainted (CFS+, 5/13 pure vasodepressor syncope) and three patients did not (CFS-). Sixteen syncope patients fainted (all mixed vasodepressor-cardioinhibitory) and 10 did not (S-). Four control patients fainted (Control+, all mixed vasodepressor-cardioinhibitory) and nine did not (Control-). Baseline indices of heart rate variability (HRV) decreased in CFS patients compared to all other groups. With HUT, sympathovagal indices were relatively unchanged in CFS.
"CFS is associated with NMH during HUT in children... Taken together these data may indicate autonomic impairment in patients with CFS."
See also Stewart, et al. Orthostatic tachycardia in adolescents with chronic fatigue syndrome (Meeting Abstract on 26 adolescents) Circulation, 1998, 98 (17 Suppl.) 366.
Stewart, JM., Gewitz, MH., Weldon, A., Arlievsky, N., Li, K and Munoz, J. The nature of neurally mediated hypotension in children with chronic fatigue syndrome. Pediatrics, 1998, 102 (Suppl.), 686.
The researchers measured heart rate and blood pressure in response to head-up tilt (HUT) in 26 adolescents with CFS, a group of adolescents who were being investigated for fainting and 13 healthy controls.
One person with CFS had a normal HUT. The others had severe orthostatic symptoms associated with syncope, or orthostatic tachycardia with or without hypotension. None of the control or simple faint patients experienced comparable acral or tachycardic findings.
The researchers conclude that CFS in adolescence is associated with neurally mediated hypotension. A partial autonomic defect may contribute to the symptomatology.
Teh, J., Scott, L., Dinan, E., Sohaib, A and Reznek, RH Adrenal size in chronic fatigue syndrome. Radiology, 1998, 209P (Suppl.), 411-412.
Abstract reporting a study of 8 patients with CFS (CDC criteria) who had a subnormal response on an ACTH stimulation test. A CT scan revealed that the right and left adrenal glands were reduced by 50% when compared with those of 55 healthy controls.
Watson, WS., McMillan, DC, Chaudhuri, A and Behan, PO. Increased resting energy expenditure in the chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1998, 4, 4, 3-14.
It has been suggested that resting energy expenditure may be raised in CFS due to an upregulation of transmembrane ion transport. The researchers measured resting energy expenditure by indirect calorimetry in 11 women with chronic fatigue (own criteria) and in 11 healthy women. Total body potassium, by whole body counting, and total body water, extracellular water and intracellular water, by a bioelectrical impedance method, were also measured.
When individual resting energy expenditure was predicted on the basis of total body potassium values for the chronic fatigue group, 5 out of 11 of these subjects had resting energy expenditure above the upper limit of normal as defined by the control group data. This is consistent with the hypothesis that there is upregulation of the sodium-potassium pump in CFS.
There was no evidence that the results were due to lack of activity (this would also have affected total body water estimates).
Endicott, NA. Chronic fatigue syndrome in psychiatric patients: Lifetime and premorbid personal history of physical health. Psychosomatic Medicine, 1998, 60, 6, 744-751.
The lifetime prevalence of reported physical disorders was compared among 46 CFS patients, all of whom were referred to the author for psychiatric disorders, 92 relatively physically healthy psychiatric patients (C-I), and 46 psychiatric patients selected without regard to physical health (C-II). All patients were matched on age, sex, and psychiatric diagnosis and were drawn from the same psychiatric practice. The same groups were compared on a 7-point scale of lifetime physical health by three raters independently evaluating physical health narratives of the CFS patients up to the time of onset of CFS and that of the controls up to the corresponding age.
The CFS patients had a significantly higher reported lifetime prevalence of irritable bowel syndrome (IBS), infectious mononucleosis-like syndromes (IM) and herpes (other than genital or perioral herpes) than one or both control groups. The CFS group also had a higher incidence of allergic rhinitis or asthma compared to the combined controls. On the independent ratings, the CFS patients had significantly more impaired physical health up to the time of onset of the CFS than C-I at a comparable age. Among the CFS patients, 89% had a lifetime diagnosis of major depression.
There were more parents with health problems (across all organ systems) in the CFS group and they had died at an earlier age. Patients who developed CFS after referral to the author (n=16) had a higher rate of physical health problems than those who had CFS on referral.
The results, particularly the differences between the groups, do not support the view that CFS is the result of somatization or attribution, or overreporting of all symptoms. "The findings suggest that a general health factor may be involved in the pathogenesis of some cases of CFS."
Morriss, RK., Wearden, AJ and Mullis, R. Exploring the validity of the Chalder fatigue scale in chronic fatigue syndrome. Journal of Psychosomatic Research, 1998, 45, 5, 411-417.
These researchers examined the constructs of the 14-item Chalder fatigue scale in a sample of 136 patients with CFS (Oxford criteria, 46% with psychiatric disorders) through principal components analysis, followed by correlations with measures of subjective and objective cognitive performance, physiological measures of strength and functional work capacity, depression, anxiety (HAD), and subjective sleep difficulties.
There were four factors of fatigue explaining 67% of the total variance:
The results support the validity of the less widely used 11-item version which does not include the 'loss of interest' item (see factor 4 above). Without that item, it may be argued that the 14-item version also measures the two constructs of mental and physical fatigue. The researchers recommend scoring on a two-point scale (presence/absence), rather than the four-point Likert scoring.
Saltzstein, BJ., Wyshak, G., Hubbuch, JT and Perry, JC. A naturalistic study of the chronic fatigue syndrome among women in primary care. General Hospital Psychiatry, 1998, 20, 5, 307-316.
This study explored subjects' perceptions of the variables that mediated the course of their illness and identified coping strategies in 15 women with CFS (CDC criteria '94) referred from the practice of a primary care physician.
Exploratory semistructured interviews were adapted from Kleinman's Illness Narratives. Measures included the Beck Depression Inventory, the Sickness Impact Profile, a modified Karnofsky scale (Bell), and the Defense Mechanism Rating Scale. Of the 15 women, 60% reported improvement and/or recovery at the time of the interview. Improvement was associated with social support and lower levels of depressive symptoms. Nearly three-quarters were working full or parttime. All had current or previous psychotherapy.
Health status was influenced by how subjects perceived their illness, their future, and the doctor's prognosis; and by early diagnosis, validation of the CFS, and intensive medical follow-up.
No evidence was found to support the view that CFS is an illness behaviour resulting from a need to opt out of work or family obligations (cf. Ware).
Obsessional and healthy neurotic defense levels predominated, which differs from historical comparison groups with dysthymia and panic disorder. Psychological adaptation to CFS is similar to adaptive coping in other chronic illnesses: subjective perceptions of health status can predict functional status." Physician validation is particularly important given the controversial status of CFS. Maintaining relationships with others, doctor, work, family, and group/spiritual activities reflected healthy coping strategies that promoted hope and attitudinal shifts. The finding of a mixture of neurotic and healthy defenses and a low proportion of defenses associated with personality disorders has not been previously reported in the CFS literature and warrants further investigation.
See also editorial by Sharpe, M. Doctors' diagnoses and patients' perceptions - Lessons from chronic fatigue syndrome. Ibid, 335-338.
[Ed. note: In this article, Sharpe focuses on the problems associated with the diagnosis of unexplained fatigue. "Many of us may feel that it is not helpful to give a patient a medical diagnosis of CFS or ME but is a psychiatric diagnosis of 'undifferentiated somatoform disorder' any better, especially if the patient does not accept it?" He does not mention the possibility that the hostility to a psychiatric diagnosis may be because it's inaccurate. In his opinion, it is related to misinformation or faulty (prejudicial) beliefs about psychiatric disorders. He discusses the option of recognising and respecting the patients beliefs and then attempting to change any that are unhelpful (e.g. the view among his and Prof. Wessely's patients that "activity is harmful".)Sharpe implies that there are a large number of sufferers who believe that CFS is "purely medical" and that the illness is "fixed"; a notion which is inconsistent with the evidence. As in other articles, he does not acknowledge that many patients with CFS have quite complex and realistic views of aetiology and that they use sensible coping strategies (see above). As a result, he reinforces the stereotype of the stupid patient and thereby adds to the stigmatisation of CFS.]
Scholey, A., McCue, P and Wesnes, KA. A comparison of the cognitive deficits seen in myalgic encephalomyelitis to Alzheimer's Disease. Proceedings of the British Psychological Society, 1999, January, 12.
Abstract. Twenty people with myalgic encephalomyelitis (ME, London criteria) were compared to age and gender matched controls on a number of cognitive tests. The performance of the ME patients was found to be markedly inferior to the controls and significantly different.
When the results were compared to those from 782 patients with Alzheimer's Disease (AD, from database information), the ME group fell between mild and moderate Alzheimer's patients on most tasks. Only episodic verbal memory was not disrupted to the degree seen in AD. "The extent as well as the range of the impairments... confirms the severe nature of ME."
Gibbons, R., Pheby, DFH., Richards, C and Bray, FI. Severe CFS/ME of juvenile onset - a report from the CHROME database. Journal of Chronic Fatigue Syndrome, 1998, 4, 4, 67-80.
CHROME has been collecting data in the UK since 1995 on very severely disabled patients with ME, in order to assess aspects of physical and cognitive levels of disability at the onset of the illness and to monitor progress. Results of the first two years data (225 cases, diagnosis consistent with CDC criteria '94) are reported.
The modal age of onset for this severe group of patients was 11-15. Patients tended to deteriorate between onset and recruitment in terms of cognitive and functional ability (including standing, raising arm above head), and sensory and sleep disturbance. There was no obvious change in nausea.
"The findings underline the case for special attention to be given to this particular group of patients, in resource allocation, in planning and providing services to meet their needs, and in the training of health, social care and education professionals involved in their care."
Cleare, AJ., Heap., E., Malhi, GS., Wessely, S., O'Keane, V and Miell, J. Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet, 1999, 353, 455-458.
A short trial assessing the effect of hydrocortisone (5 or 10 mg for one month) versus placebo (for one month). The sample comprised 32 patients with CFS (Oxford and CDC criteria '94, no comorbid psychiatric disorders, 59% infectious onset).
There was a modest but significant reduction in fatigue and disability compared to placebo. Endogenous adrenal function was not suppressed. There were no drop outs and only three patients on the drug noted side-effects. Patients with lower baseline GHQ levels responded better than those with higher scores (indicating psychological distress). There was no difference according to the dose used.
With commentary from Jeffcoate (p. 424-5) noting the limited response and theoretical risk of longterm problems.
[Ed. note: the researchers did not select patients with low cortisol levels.]
Van de Luit, L., van der Meulen, J., Cleophas, TJM and Zwinderman, AH. Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: Improvement by inopamil but not by melatonin. Angiology, 1998, 49, 11, 903-908.
The research studied rhythms of heart rate and systolic and diastolic blood pressure in 17 patients with CFS (CDC '88) compared with 12 age-matched normotensive controls. It also assessed the effects of melatonin and inopamil on such rhythms in 4 patients in an 8-week open-label evaluation.
The data revealed amplitudes in heart rate and systolic and diastolic blood pressure rhythms which were 2.8, 2.8, and 9.0 times the size of the control group's (p<0.001, p<0.001, and p<0.0001, respectively). Moreover, systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks each, inopamil was found to reduce nighttime hypotension (p<0.05), whereas melatonin increased nighttime hypotension (p<0.02).
"Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be".
Calkins, H and Rowe, PC. Relationship between chronic fatigue syndrome and neurally mediated hypotension. Infectious Diseases in Clinical Practice, 1998, 7, 7, 312-321.
Review focusing on the relationship between CFS and neurally mediated hypotension.
Klimas, N. Pathogenesis of chronic fatigue syndrome and fibromyalgia. Growth Hormone & IGF Research, 1998, 8 (suppl.), 123-126.
Short article includes evidence of ongoing pathology in CFS and fibromyalgia. Estimated prevalence of CFS is considered to be 3 per 1000 at most.
Baraniuk, JN., Clauw, DJ., Gaumond, E. Rhinitis symptoms in chronic fatigue syndrome. Annals of Allergy, Asthma & Immunology, 1998, 81, 4, 359-365.
In this study, 51 people with CFS (CDC criteria '94), 34 healthy individuals, 27 people with allergic rhinitis (AR), and 17 patients with other rheumatologic diseases filled out an Airway Symptom Severity self-report questionnaire to determine the frequencies of nasal, sinus, and chest symptoms, and a Systemic Complaints self-report questionnaire to determine the frequencies of complaints referable to neurologic, rheumatologic, gastrointestinal, and other systems. All subjects received a standard set of allergy skin tests, and were subdivided into those with positive and negative results.
Allergy skin tests were positive in 35% of CFS and 44% of healthy subjects (NS). Significant rhinitis complaints were present in 83% of skin test positive CFS, 76% of skin test negative CFS, 74% of AR, and 23% of healthy subjects. Systemic Complaints scores were significantly elevated in skin test positive (94%) and negative (94%) CFS groups compared with AR (35%) and healthy (6%) groups. This score could significantly discriminate between CFS and healthy subjects.
Among symptoms which were significantly more common in the CFS patients compared with the other three groups were fatigue, tension headaches, dizziness and balance problems, cardiac complaints and cystitis symptoms.
"These data indicate that in this CFS population, 24% had no significant rhinitis complaints, 30% had positive skin tests suggesting the potential for allergic rhinitis complaints, and 46% had non-allergic rhinitis. The mechanism of the nonallergic component may offer insights into the pathogenesis of CFS".
Atopy is present at the same rate in CFS patents as in the general population. Moreover, the similarity of airway and systemic symptoms between skin test positive and negative patients suggests that IgE-related mechanisms do not play a major role in the initiation of CFS.
Beecham, L. Better services needed for 'ME'. British Medical Journal, 1998, 317, 966.
Short item on the recommendations of the National Task Force Report on NHS services.
Evengard, B., Nilsson, CG., Lindh, G., Lindquist, L., Eneroth, P., Fredrikson, S., Terenius, L and Henriksson, KG. Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome. Pain, 1998, 78, 2, 153-155.
Levels of substance P were determined in the cerebrospinal fluid (CSF) in 15 patients with CFS (CDC criteria '94?). All values were within the normal range. This is in contrast to fibromyalgia (FM). The majority of patients with FM have increased substance P values in the CSF. The results support the notion that FM and CFS are different disorders in spite of overlapping symptomatology.
Hall, GH; Hamilton, WT; Round, AP. Increased illness experience preceding chronic fatigue syndrome. Journal of the Royal College of Physicians of London, 1998, 32, 4, 389.
Letter responding to comments by Speight (ibid 1998, p. 274).
[Ed. note: The arguments supporting the notion that symptoms reported prior to the diagnosis of CFS may represent abnormal illness behaviour ignores the heterogeneity of CFS].
Heijmans, M and de Ridder, D. Assessing illness representations of chronic illness: explorations of their disease-specific nature. Journal of Behavioral Medicine, 1998, 21, 5, 485-503.
Study of the illness representations of 130 patients with CFS (recruited from the Dutch ME Society) and 110 people with Addison's Disease (AD).
The results conflict with the self-regulation model of Leventhal (1980) since the illness representations differed according to the type of disease. A belief in an external cause was not correlated with cognitive-avoidant coping.
Jumrussirikul, P., Rowe, PC and Calkins, H. Relationship between baseline blood pressure and the pattern of hemodynamic intolerance observed during tilt among patients with the chronic fatigue syndrome. Circulation, 1998, 98 (17 Suppl.), 706.
Abstract reporting study on 334 patients with CFS (not defined) who underwent a three-stage upright tilt test (70').
Fifteen per cent had postural orthostatic tachycardia syndrome (POTS) and 63% had neurally mediated hypotension (NMH). The baseline blood pressure was lower in the CFS patients with POTS compared with those with NMH. Further studies are required to see if these differences have therapeutic implications.
Korszun, A., Papadopoulos, E., Demitrack, M., Engleberg, C and Crofford, L. The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 1998, 86, 4, 416-420.
A study of 34 patients with CFS (CDC '88), 36 with fibromyalgia and 22 with both, found that 42% reported a prior diagnosis of temporomandibular disorder, 46% had a history of irritable bowel syndrome, 42% had had premenstrual syndrome, and 19% had a history of interstitial cystitis.
Of the patients with temporomandibular disorders, the great majority reported an onset of generalized symptoms before the onset of facial pain. Despite this, 75% had been treated exclusively for temporomandibular disorders, usually with bite splints.
"The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals."
Lynch, S and Fraser, J. Fluoxetine and graded exercise in chronic fatigue syndrome. British Journal of Psychiatry, 1998, 173, 353.
Lynch and Fraser respond to the article by Wearden et al (ibid, 172, 491), asking whether the mood symptoms had become refractory to treatment, as a result of which there was only a modest response to fluoxetine.
In his reply, Morriss (p. 353) notes that many CFS patients with depressive disorders improved on the drug and placebo, so there is no evidence that their depression was difficult to treat. The disappointing results were primarily due to the failure of non-depressed patients to respond to the treatment.
Moldofsky, H., Lue, FA., Dickstein, J., Poplonski, L., Jiang, CG and Gorczynski, R. Disordered circadian sleep-wake neuroendocrine and immune functions in chronic fatigue/fibromyalgia syndrome. Arthritis and Rheumatism, 1998, 41 (Suppl.), S255, no. 1337.
Abstract describing a study where blood samples were taken for 24 hours from 11 patients with CFS/fibromyalgia, When the data were compared with symptomatic and non-symptomatic controls, differences were found in terms of low NK cells, diurnal pattern of cortisol and prolactin, higher alpha nonREM ratings and more pre-sleep fatigue, and pain. "These findings are consistent with the theory of chronobiological disturbances in CFS/fibromyalgia".
National Task Force on CFS/ME. NHS services for people with CFS/ME. From Westcare, 155 Whiteladies Road, Clifton, Bristol BS8 2RF. Pb. £14.95.
Consensus report on services which are and should be available to people with CFS in the UK. It estimates that the economic burden of CFS to the UK community is £1 billion per year. The report proposes an initial minimum service catering for 0.1% of the population. Doctors require more written information, more training and more multidisciplinary clinics. It suggests that the strongest evidence favours graded exercise and CBT, but the report itself recommends pacing. The publication includes a list of CFS clinics currently providing a service on the NHS.
[Ed. note: ME is not described. The focus is on CFS as defined in 1994. In some places, there is confusion between pacing and graded activity, and the report fails to mention that all trials in the UK on CBT have been on selected populations, particularly on people with maladaptive beliefs, phobic avoidance and/or psychiatric illness. This makes it difficult to draw firm conclusions. The emphasis in the sections on definition and prevalence reflect the views of the psychiatrists from the CBT school and ignores important data. There is no recent information on subgroups, as a result of which some of the advice on treatment may be inappropriate (e.g. there's no mention that graded exercise, as opposed to pacing, may be helpful where there is no evidence of active disease and the fatigue is perpetuated by depression or phobic avoidance etc).]
Panay, N and Studd, JWW. The psychotherapeutic effects of estrogens. Gynecological Endocrinology, 1998, 12, 5, 353-365.
Review article with section on CFS. The authors studied 28 women with CFS, of whom 79% had PMS and 25% had low oestradial levels. Of these, just over a half had low bone density. About 80% improved on oestradiol patches. Oestrogen may therefore help a subset of women with CFS.
Poteliakhoff, A. Fatigue syndromes and the aetiology of autoimmune disease. Journal of Chronic Fatigue Syndrome, 1998, 4, 4, 31-49.
In the last decade or so, an impairment of hypothalamic-pituitary-adrenal (HPA) axis activity has been observed in fatigue syndromes. Elevated levels of glucocorticoids help to prevent the immune system from overreacting and generating a damaging autoimmune process. The corollary should be that reduced activity of the HPA axis and diminished levels of plasma cortisol could be associated with autoimmune (Al) disease. Experimental work in mice and rats supports this view. Furthermore, plasma levels of cortisol have been found to be low in the early stages of rheumatoid arthritis. There is some clinical evidence that connective tissue disorders (many of which are regarded as autoimmune diseases) occur approximately one year after the onset of prolonged or chronic fatigue, with the implication that fatigue is not merely a symptom of these disorders but that it precedes them. Changes have been found in the immune system of subjects suffering from CFS (mainly immune activa-tion) which could be conducive to the development of AI disease. It has recently been shown that there is, in CFS, some deficiency of another adrenal steroid, namely that of dehydroepiandrosterone (DHEA). This steroid exerts a regulatory activity on the immune system and a deficiency may well be an additional factor in the genesis of Al disease.
It is hypothesized that mild cortisol insufficiency may allow the immune system to become overactive. If an association can be established between fatigue syndromes and autoimmune disease then these syndromes will need to be addressed in a more concerned manner and prophylactic measures undertaken to forestall AI disease.
See, DM, Tilles, JG., Hirschmann, J and Bertacchini, C. Immunomodulatory effects of a homeopathic agent. American Journal of Natural Medicine, 1998, 6, 10-14.
This article describes two studies. In the first, PBMC from 20 patients with CFS (CDC criteria '88), AIDS and healthy controls were incubated for 24 hours with a homeopathic preparation or placebo. The homeopathic preparation significantly increased natural killer cell activity compared to placebo in samples from all three groups.
In the second study, a homeopathic preparation mixture or placebo was administered to mice for 28 days. The only finding was that splenic NK function was significantly greater in mice treated with the homeopathic agent compared to placebo. In mice pretreated for 0, 7, 14 or 21 days with a homeopathic mixture before inoculation with Coxsackie virus B4, titres of virus were significantly reduced in the pancreas after 21 days pretreatment, compared with mice treated with placebo. The homeopathic mixture did not exhibit any anti-viral effect in vitro.
The homeopathic medication contained dilutions (1:106) of Abies nigra, Arnica, Lachesis, Cactus gradiflorus, Aloe socotrina and Licopoduium as well as calcium carbonate.
Vercoulen, JHMM., Swanink, CMA., Galama, JMD., Fennis, JFM., Jongen, PJH., Hommes, OR., van der Meer, JWM and Bleijenberg, G. The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model. Journal of Psychosomatic Research, 1998, 45, 6, 507-517.
This study involved in 51 patients with CFS (Oxford criteria) and 50 patients with multiple sclerosis (MS) matched for age, gender, and education. Measures assessed fatigue, functional impairment and a limited number of psychological variables.
Attributing complaints to a somatic cause produced low levels of physical activity, which in turn had a causal effect on fatigue severity. Depression had to be deleted from the model. Sense of control over symptoms and focusing on bodily symptoms each had a direct causal effect on fatigue. The proposed model showed an excellent fit for CFS patients, but was rejected for MS patients.
Wright, JB and Beverley, DW. Chronic fatigue syndrome. Archives of Disease in Childhood, 1998, 79, 4, 368-374.
Short account of CFS in children, with the emphasis on the alleged links with inactivity and somatisation.
Bradbury, J. UK working party on organophosphate sheep-dip reports. British Medical Journal, 1998, 352, 1608.
News item noting that the Royal Colleges of Physicians and Psychiatrists' report on organophosphates has recommended that patients seeking advice for symptoms associated with sheep-dip exposure should be treated sympathetically. They have also called for more facilities to treat patients and for more research.
Iriarte, J. Correlation between symptom fatigue and muscular fatigue in multiple sclerosis. European Journal of Neurology, 1998, 5, 6, 579-585.
The aim of this study was to ascertain the existence of muscular fatigue in multiple sclerosis (MS) patients, and to find out if there is a correlation between the subjective symptom of fatigue and muscular fatigue.
Fifty MS patients and 50 age and sex matched volunteers were studied using isometric and isotonic tests involving the dominant hand. Strength was studied in the baseline condition and also after recovery of either an isotonic (experiment A) or isometric effort (experiment B). Maximum strength, strength in relationship to weight, slope of fatiguability in 11 consecutive contractions, and strength and duration of a maximum effort were calculated. Fatigue as a symptom was measured using the Fatigue Severity Scale (FSS) and the Fatigue Descriptive Scale (FDS).
Patients with MS had less isometric and isotonic strength, but the recovery was the same as recovery in the control group. There was a negative linear correlation between the symptom of fatigue and the baseline strength.
In conclusion, this study supports the existence of signs of muscular fatigue in MS patients. However, the recovery after exercise is normal. The correlation between the baseline scores in strength and the symptom of fatigue suggest that the same cause (probably pyramidal deficits) may be involved in both of them.
Penttila, IA., Harris, RJ., Storm, P., Haynes, D., Worswick, DA and Marmion, BP. Cytokine dysregulation in the post-Q-fever fatigue syndrome. Quarterly Journal of Medicine, 1998, 91, 8, 549-560.
The post-Q-fever fatigue syndrome (QFS) involving inappropriate fatigue, myalgia and arthralgia, night sweats, changes in mood and sleep patterns, follows about 20% of laboratory-proven, acute primary Q-fever cases. Cytokine dysregulation resulting from chronic immune stimulation and modulation by persistence of Coxiella burnetii cells or their antigens is hypothesized.
The researchers studied cytokine release patterns of PBMC stimulated with various ligands in culture from 18 patients with active QFS and 27 controls: six with resolving QFS, five who had had acute primary Q-fever without subsequent QFS, eight healthy people vaccinated against Q-fever and eight healthy subjects without Q-fever antibody. Conditioned media (CM) from PBMC stimulated in short-term culture with Q-fever antigens, PHA or measles antigen (as an unrelated antigen) were assayed for certain cytokines.
Aberrant cytokine release patterns were observed with PBMC from QFS patients when stimulated with Q-fever antigens: an accentuated release of IL-6 which was significantly in excess of that found in the controls. There was no increase following the test with measles virus antigens. With IL-2, the number of responders in the active QFS group was decreased relative to control groups whereas the number of IFN-g responders was increased. Significant correlations were observed between concentrations of IL-6 in CM, total symptom scores, and scores for other key symptoms.
Unwin, C., Blatchley, N., Coker, W., Ferry, S., Hotopf, M., Hull, L., Ismael, K., Palmer, I., David, A and Wessely, S. Health of UK servicemen who served in Persian Gulf War. Lancet, 1999, 353, 169-178.
Study comparing the health of 3284 Gulf War veterans, 1815 servicemen deployed in Bosnia and 2408 servicemen who served in the Gulf but were not deployed there.
Service in the Gulf was associated with various health problems over and above those associated with deployment to an unfamiliar hostile environment. There was a notable relationship between vaccinations (including those against biological warfare agents) and later ill-health. There were unexpected results relating to self-reported chemical and nerve gas exposure in the Bosnian cohort (which may have obscured a relationship in the Gulf War veterans. Ed.). There was evidence of post traumatic stress disorder and psychological distress but these could not explain the findings as a whole. Among respondents from the Gulf, 3.3% reported having CFS or ME compared to only 0.8% in the Bosnian cohort. There was no evidence that Gulf War Syndrome is a single entity.
See also Ismail et al, ibid, p. 179-182.
See also Jamal, GA and Aziz, MA. Gulf War Syndrome - is it a disease of complex interaction of several factors. CME Bulletin Medical Microbiology, 1998, 2, 3, 62-64. Short review with authors arguing that the Gulf War Syndrome has a complex aetiology.
White, PD., Thomas, JM., Amess, J., Crawford, DH., Grover, SA., Kangro, HO and Clare, AW. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. British Journal of Psychiatry, 1998, 173, 475-481.
A prospective cohort study of 250 primary care patients presenting with glandular fever and upper respiratory tract infections (URTI) were assessed using virological tests, a psychiatric interview (SADS), a fatigue questionnaire and the Hospital Anxiety and Depression Scale (HAD). Of the patients, 101 were confirmed as having glandular fever due to Epstein-Barr virus (EBV) and 83 as having non-EBV glandular fever. There were 54 people with URTIs. There were no differences between the three groups in terms of personality, stressful life events in the previous 6 months or their premorbid psychiatric history.
At 6 months, physical fatigue was reported by 40% in the EBV group, 29% in the non-EBV group compared with 15% in the URTI group. Excessive sleep was reported by 22% of those with EBV, 14% with non-EBV glandular fever and 2% with URTI. Of the 73 people with fatigue at 6 months, 38 (52%) met the Oxford criteria for CFS (although 5 also had CFS before onset), and EBV infection was found to be the greatest risk factor. Of the people with CFS, 42% had a psychiatric disorder, particularly depression. However, episodes tended to be of short duration. Of the 17 (23%) people who met the CDC '94 criteria for CFS, only 29% had a psychiatric disorder. There were no groups differences on the HAD at any time.
The incidence of CFS (Oxford criteria) was estimated to be 19% after EBV, 15% after non-EBV glandular fever and 2% after URTI. Using the CDC '94 criteria, the incidence was 9% in the post-infection groups and 0% after URTI.
The researchers conclude that glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection, if they last more than a month.
Shepherd, C. Living With ME. Pb 496pp. London: Vermilion, 1999.
This is a new edition of arguably the most comprehensive self-help guide on ME. Clearly-written and taking a cautious, orthodox medical approach, it contains updated information on the definition, research, management and benefits available. In my view, it's not only an excellent resource for patients, but it's also hard to beat as a guide on the illness for students and doctors. Like previous incarnations, the book is conservative when it comes to complementary medicine, but it's not unfair. In a nutshell, it's sympathetic, balanced and reliable. It informs but does not irritate. Quite simply, essential reading for anyone wishing to know the facts and understand the latest research. Outstanding!
EMG*
This issue was compiled by Dr. E. Goudsmit, Dr. A. Macintyre and Mrs S. Howes. We gratefully acknowledge the help from Georgia Stebbins from the Haworth Press and Mr. D. Axford.
*The opinions expressed do not necessarily represent the views of the editorial team. The book reviewer has no financial links with author, and there are no other conflicts of interest.
The ME and CFS Capita Selecta Quarterly is funded by donations.
Cheques should be made payable to the ME and CFS Medical Update.
Backcopies and other information on ME
and CFS can also be found on-line: http://freespace.virgin.net/david.axford/me/me.htm
or contact david.axford@virgin.net
Copyright EM. Goudsmit 1998.
©
Psychologist/Archivist, London.
All rights reserved. This article may not be reproduced without
permission from the author. See the full
copyright
notice.
Be sure to see the many other valuable articles at our Main M.E. Home Page
|
The MECSQ is funded entirely by donations |
|
Donations
gratefully received and made payable to: |
