Serum angiotensin-converting enzyme as a marker for the chronic fatigue-immune dysfunction syndrome: a comparison to serum angiotensin-converting enzyme in sarcoidosis

Abstract:

PURPOSE: To study the reliability of a serum angiotensin-converting enzyme (ACE) assay as a marker for the chronic fatigue-immune dysfunction syndrome (CFIDS), and to compare some enzyme characteristics of ACE in CFIDS with that in sarcoidosis.

PATIENTS AND METHODS: Forty-nine patients with CFIDS and 56 endemic control subjects from Lyndonville, New York, and Charlotte, North Carolina; plus 23 untreated patients with active sarcoidosis, 24 with sarcoidosis receiving corticosteroid therapy, and 32 patient controls without sarcoidosis from California. Serum ACE levels were determined with a spectrophotometric method. The effect of freezing and thawing and the effect of storage at 4 degrees C were compared between CFIDS and sarcoidosis samples.

RESULTS: Serum ACE levels were elevated in 80% of patients with CFIDS and 30% of endemic control subjects as compared with 9.4% of nonendemic California control subjects. The ACE activity in CFIDS differed from that in sarcoidosis because of its lability with storage at 4 degrees C in CFIDS and its partial activation with freezing and thawing. Thus, ACE activity was elevated in the majority of CFIDS patients either upon initial assay or upon a subsequent assay after refreezing. ACE activity was elevated in 87% of patients with active sarcoidosis and was not affected by storage or freezing and thawing.

CONCLUSIONS: Serum ACE elevations may be a useful marker for CFIDS, especially if a method can be developed to distinguish ACE in CFIDS from that in sarcoidosis. The sensitivity for CFIDS was 80%, with 68% specificity in an endemic area. The increased prevalence of serum ACE elevations in endemic controls as compared with nonendemic controls suggests that an ACE increase may be an early manifestation of CFIDS and supports the concept that CFIDS is a definite disease state.

 

Source: Lieberman J, Bell DS. Serum angiotensin-converting enzyme as a marker for the chronic fatigue-immune dysfunction syndrome: a comparison to serum angiotensin-converting enzyme in sarcoidosis. Am J Med. 1993 Oct;95(4):407-12. http://www.ncbi.nlm.nih.gov/pubmed/8213873

 

Treatment of the chronic fatigue syndrome. A review and practical guide

Abstract:

The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe a syndrome of severe and disabling fatigue of uncertain aetiology associated with a variable number of somatic and/or psychological symptoms. CFS has been reported in most industrialised countries and is most prevalent in women aged between 20 and 50 years.

Despite occasional claims to the contrary, the aetiology of CFS remains elusive. Although abnormalities in tests of immune function and cerebral imaging have been described in variable numbers of CFS patients, such findings have been inconsistent and cannot be relied upon, either to establish or exclude the diagnosis. Thus, diagnosis rests on fulfillment of the Centers for Disease Control case definition which was revised in 1992. This case definition remains somewhat controversial, largely due to its subjectiveness.

The mainstay of treatment is establishing the diagnosis and educating the patient about the illness. An empathetic clinician can stop further consultations elsewhere (‘doctor shopping’) and subsequent excessive investigations, which frequently occur in such patients.

Most patients should undertake a trial of antidepressant therapy, even if major depression is not present. The choice of antidepressant drug should tailor the tolerability profile to relief of particular CFS symptoms, such as insomnia or hypersomnia. Failure to improve within 12 weeks warrants an alternative antidepressant agent of another class. Many other drugs have been reported anecdotally to be beneficial, but no therapy has been demonstrated to be reproducibly useful in double-blind, placebo-controlled clinical trials with an adequate duration of follow-up.

 

Source: Blondel-Hill E, Shafran SD. Treatment of the chronic fatigue syndrome. A review and practical guide. Drugs. 1993 Oct;46(4):639-51. http://www.ncbi.nlm.nih.gov/pubmed/7506650

 

Functional hypoglycaemia postulated as cause of chronic fatigue syndrome

Comment on: The chronic fatigue syndrome: what do we know? [BMJ. 1993]

 

Editor,-In discussing the various causes of the chronic fatigue syndrome P K Thomas fails to mention one syndrome-namely, functional hypoglycaemia. We do not believe that such a syndrome exists, but in the Netherlands it has become a popular diagnosis among “alternative doctors,” who claim that chronic fatigue is caused by inappropriately increased postprandial insulin concentrations with subsequent hypoglycaemia. This disease is linked to a so called allergy to endogenous glucose.

It is clear from this description that there is no scientific basis for this syndrome, and this is confirmed in the literature. Unfortunately, doctors and dietitians who recognise this syndrome have burdened their patients with complicated diets, requiring the elimination of all simple carbohydrates. When we asked an alternative doctor why we never see hypoglycaemia in these patients we were told that we do not measure glucose concentrations at the right moment. The diagnosis should be made after a standard oral glucose tolerance test with measurement of glucose concentrations three and five hours after glucose intake. “Overproduction” of insulin is thus shown by reactive hypoglycaemia.

The use of this non-physiological test to diagnose this syndrome has no scientific basis whatsoever. Nevertheless, tens of thousands of patients are treated for this syndrome in the Netherlands.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1678679/pdf/bmj00039-0047a.pdf

 

Source: Heuft L, Bravenboer B, Ziekenhuis C. Functional hypoglycaemia postulated as cause of chronic fatigue syndrome. BMJ. 1993 Sep 18;307(6906):735. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1678679/

 

Chronic Fatigue Syndrome: New hope from psychoneuroimmunology and community psychology

Abstract:

Chronic Fatigue Syndrome is a baffling disease potentially affecting millions of Americans. New insights and developments in the fields of psychoneuroimmunology and community psychology may offer promising new leads in helping people recover from this debilitating illness. The experiences of a CFS-afflicted person in struggling to overcome this disease are used to illustrate the usefulness to recovery of concepts in the fields of psychoneuroimmunology, community psychology, and primary prevention.

 

Source: Jason LA. Chronic Fatigue Syndrome: New hope from psychoneuroimmunology and community psychology. J Prim Prev. 1993 Sep;14(1):51-71. doi: 10.1007/BF01324655. http://www.ncbi.nlm.nih.gov/pubmed/24258626

 

Exercise performance and fatiguability in patients with chronic fatigue syndrome

Abstract:

To examine the role of delay in recovery of peripheral muscle function following exercise in the fatigue experienced by patients with the chronic fatigue syndrome (CFS) and to examine the influence of effort perception in limiting exercise performance in these patients, a study was carried out on a group of twelve patients with chronic fatigue syndrome and 12 sex and age-matched sedentary control subjects.

Symptom limited incremental cycle exercise tests including measurements of perceived exertion were performed followed by examination of the contractile properties of the quadriceps muscle group for up to 48 hours. Muscle function was assessed by percutaneous electrical stimulation and maximum voluntary contractions.

Muscle function at rest and during recovery was normal in CFS patients as assessed by maximum isometric voluntary contraction, 20:50 Hz tetanic force ratio and maximum relaxation rate. Exercise duration and the relationship between heart rate and work rate during exercise were similar in both groups.

CFS patients had higher perceived exertion scores in relation to heart rate during exercise representing a reduced effort sensation threshold of 3.2 units on an unmodified Borg scale in CFS patients. Patients with chronic fatigue syndrome show normal muscle physiology before and after exercise. Raised perceived exertion scores during exercise suggest that central factors are limiting exercise capacity in these patients.

Comment in: Lactate responses to exercise in chronic fatigue syndrome. [J Neurol Neurosurg Psychiatry. 1994]

 

Source: Gibson H, Carroll N, Clague JE, Edwards RH. Exercise performance and fatiguability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1993 Sep;56(9):993-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC489735/ (Full article)

 

Detection of Epstein-Barr virus and cytomegalovirus in patients with chronic fatigue

Abstract:

Patients with chronic fatigue as a major complaint frequently present with recurrent sore throat, and on physical examination they have hyperemia and lymphoid hyperplasia of the pharyngeal area.

Pharyngeal scrapings were obtained from 41 such patients and analyzed for Epstein-Barr virus or cytomegalovirus DNA by colorimetric in situ hybridization. Results were compared with healthy control subjects matched for age and sex. Epstein-Barr virus-DNA was detected more frequently in male patients, 5/9 (55.6%), than controls, 0/6 (0%), but there was no difference in frequency in female patients, 4/32 (12.5%), than control subjects, 1/29 (3.4%).

Cytomegalovirus-DNA was detected infrequently in patients and controls, 13% versus 22% respectively. The presence of EBV-DNA did not correlate with antibody titers nor with the complaint of sore throat. Four of the five males who had positive EBV-DNA in the pharyngeal smears have now recovered.

 

Source: Wray BB, Gaughf C, Chandler FW Jr, Berry SS, Latham JE, Wood L, DuRant RH. Detection of Epstein-Barr virus and cytomegalovirus in patients with chronic fatigue. Ann Allergy. 1993 Sep;71(3):223-6. http://www.ncbi.nlm.nih.gov/pubmed/8396863

 

Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention

Abstract:

Patients with chronic fatigue syndrome (also known as post-viral fatigue syndrome or myalgic encephalomyelitis) commonly report cognitive difficulties concerning attention, concentration and memory. In this study, patients were compared with matched controls on two questionnaires which assess subjective difficulties with attention and general cognitive functioning, and on two tasks requiring focused attention.

Patients reported significantly greater difficulty with attention on the Everyday Attention Questionnaire and more cognitive symptoms on the Profile of Fatigue-Related Symptoms. The objective tests did not clearly indicate a deficit in patients’ focused attention; patients tended to perform less well on the Embedded Figures Test and the Stroop Colour-Word Interference Test, but these differences were not significant.

There was, however, evidence of psychomotor retardation, with patients having longer response times for word reading and colour naming in the Stroop test. Difficulties in interpreting findings for both subjective and objective cognitive measures are discussed.

 

Source: Ray C, Phillips L, Weir WR. Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention. Br J Clin Psychol. 1993 Sep;32 ( Pt 3):357-64. http://www.ncbi.nlm.nih.gov/pubmed/8251968

 

A brief mental fatigue questionnaire

Abstract:

A brief mental fatigue questionnaire was administered to normal subjects and muscle-diseased, Chronic Fatigue Syndrome (CFS), recovered CFS and depressed patients. The questionnaire was found to have excellent internal consistency and discriminated effectively between CFS and depressed patients on the one hand and recovered CFS, normal and muscle-diseased patients on the other. However, the scale failed to discriminate between CFS and depressed subjects, who were found to experience qualitatively and quantitatively similar mental fatigue symptoms.

 

Source: Bentall RP, Wood GC, Marrinan T, Deans C, Edwards RH. A brief mental fatigue questionnaire. Br J Clin Psychol. 1993 Sep;32 ( Pt 3):375-9. http://www.ncbi.nlm.nih.gov/pubmed/7902751

 

Behavioural problems associated with the chronic fatigue syndrome

Abstract:

Disturbances of memory, concentration and motor function are often reported by patients with the chronic fatigue syndrome (CFS). The present study objectively evaluated these behavioural problems using a computerized test battery measuring memory, attention and motor skills.

Fifty-seven CFS patients were compared with 19 matched controls and all subjects completed the performance test battery and filled in questionnaires measuring psychopathology and mood. The patients reported significantly higher levels of depression, anxiety, physical symptoms and cognitive failures than the controls. Similarly, they reported more negative affect at the time of testing.

The patients were slower on psychomotor tasks, showed increased visual sensitivity and impaired attention. Digit span and free recall were not impaired but retrieval from semantic memory and logical reasoning were slower. None of the performance differences between patients and controls could be attributed to differences in psychopathology. These results agree with recent findings from other laboratories, and it is now time to consider the nature of the neurological dysfunction underlying these effects.

 

Source: Smith AP, Behan PO, Bell W, Millar K, Bakheit M. Behavioural problems associated with the chronic fatigue syndrome. Br J Psychol. 1993 Aug;84 ( Pt 3):411-23. http://www.ncbi.nlm.nih.gov/pubmed/8401992

 

The “anti-Ki” syndrome: major clinical features

Abstract:

OBJECTIVE: To describe the major clinical features of patients with high titers of anti-Ki antibodies.

METHOD AND RESULTS: Four of 172 patients with connective tissue diseases showed high titers (> 1/256) of anti-Ki antibodies. In these four patients, (1) the common clinical findings were alopecia, disabling chronic fatigue, muscle weakness, tenosynovitis, dry mouth, and abnormal glucose tolerance test; (2) anti-Ki antibodies were positive not only in patients with sicca lupus, but also in those with nonsicca lupus. In this case, anti-insulin receptor antibody was positive and there was a regulatory insufficiency of the pituitary. (3) Symptoms of anti-Ki antibodies share many clinical and laboratory features of chronic fatigue syndrome and fibromyalgia, that is, they may share either a common etiologic agents or a common pathogenetic pathway or both.

CONCLUSION: “Anti-Ki antibody” syndrome may be a subset of sicca lupus.

 

Source: Matsunaga K. The “anti-Ki” syndrome: major clinical features. Rinsho Byori. 1993 Aug;41(8):882-7. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/8371504