Tag: 1995

Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients have a urinary metabolite labeled CFSUM1 with increased incidence (P < 0.004) and relative abundance (P < 0.00003). The relative abundances of urinary CFSUM1 and beta-alanine were associated with alterations in metabolite excretion and symptom incidence.

In 20 CFS patients and 45 non-CFS subjects, symptom/metabolite associations were investigated by assessing symptom sensitivity and specificity, and symptom indices of total symptom incidence, CFS core symptoms, cognitive, neurological, musculoskeletal, gastrointestinal, infection-related and genitourinary symptom indices, as well as a visual analogue pain scale of average pain intensity. Thirty-three symptoms had significant (P < 0.005) sensitivity and specificity in the CFS patients compared to that in the non-CFS controls.

Severe fatigue was the only symptom with 100% sensitivity and specificity and CFSUM1 excretion was the primary metabolite for expression of this symptom. All nine symptom indices had elevated responses in the CFS patients (all P < 0.0000001). Multiple regression analyses indicated that all the symptom indices had significant correlations (R) with changes in the urinary excretion of metabolites (P < 0.0001).

CFSUM1 and beta-alanine were the first and second metabolites correlated with the CFS core symptom index and CFSUM1 was primarily associated with infection-related and musculoskeletal indices whereas beta-alanine was primarily associated with gastrointestinal and genitourinary indices. The strong associations of CFSUM1 and beta-alanine with CFS symptom expression provide a molecular basis for developing an objective test for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome. Biochem Mol Med. 1996 Jun;58(1):85-92. http://www.ncbi.nlm.nih.gov/pubmed/8809350

 

Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs

Abstract:

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression.

Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression.

In a series of studies, commencing in patients with Cushing’s disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide.

In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.

 

Source: Gold PW, Licinio J, Wong ML, Chrousos GP. Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. Ann N Y Acad Sci. 1995 Dec 29;771:716-29. http://www.ncbi.nlm.nih.gov/pubmed/8597444

 

Seroepidemiology of chronic fatigue syndrome: a case-control study

Abstract:

We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.

 

Source: Mawle AC, Nisenbaum R, Dobbins JG, Gary HE Jr, Stewart JA, Reyes M, Steele L, Schmid DS, Reeves WC. Seroepidemiology of chronic fatigue syndrome: a case-control study. Clin Infect Dis. 1995 Dec;21(6):1386-9. http://www.ncbi.nlm.nih.gov/pubmed/8749620

 

Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome

Abstract:

The Chronic Fatigue Syndrome (CFS) was formally defined to describe disabling fatigue of multifactorial ethology with depression and immunologic dysfunctions linked to some currently recognized infectious agents. In most cases neurophysiological tests reveal abnormalities.

In this paper the Authors use low (11 pps) and high (51-71 pps) frequency ABR to evaluate the electrophysiological function of auditory brainstem responses. Eighteen patients with suspected CFS, between the ages of 17 and 63, were examined. Eleven subjects had clinically diagnosed “true” CFS (CDC criteria modified by Fukuda). The 11 pps frequency test did not reveal a high number of abnormalities in the patients in question.

However, the high frequency stimulation test (with 51 and 71 pps) which was statistically significant (P = 0.009) revealed numerous aberrations in 7 patients; absence of the first wave in 1 case, in 5 numerous wave gap delays and in 1 patient absence of the first wave and numerous wave gap delays. The high frequency test did not show many abnormalities for the 4 remaining patients. For the 7 “non CFS” subjects, the clinical-audiological comparison showed no statistical significance (P = 0.920).

The Authors hypothesize that the absence of the first wave in the CFS Subject may well indicate a cyto-neural junction disease in the organ of Corti. The combined analysis of clinical and audiological data showed that the described tests are more reliable when employed in dealing with patients with clinically assessed “true” CFS.

 

Source: Bianchedi M, Croce A, Moretti A, Neri G, Barberio A, Iezzi A, Pizzigallo E. Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome. Acta Otorhinolaryngol Ital. 1995 Dec;15(6):403-10. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/8711992

 

New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6

Abstract:

The paper describes events that in the last fifteen years, have led to the identification of the aetiological agents of three widely known diseases: cat scratch disease, erythema infectiosum and exanthem subitum. The particular features of Afipia felis and Rochalimaea, Parvovirus B 19 and Herpesvirus 6 are presented.

The paternity of new diseases (i.e. bacillary angiomatosis, bacillary peliosis hepatitis, LES-like syndrome, chronic fatigue syndrome, petechial glove and sock syndrome, etc.) has also been attributed to some of these pathogens as has the paternity of some older ones (i.e. aplastic crisis, erythroblastosis fetalis, trench fever, hepatitis, opportunistic infection, etc.).

It has been argued that the same pathogen can cause different diseases depending on the immunogenic state of the subject. To date, persisting difficulties in isolating the pathogen or differentiating between latent or active infection, still in some cases raises doubts concerning the attribution of the disease to a specific agent.

New immunological or molecular techniques, allowing the direct detection of in vivo replication, are still needed in order to establish a sure connection between some of these agents and some of these diseases. Progress here will both give more accurate data about the epidemiology of some diseases and allow us to apply more appropriate treatment and prevention techniques.

 

Source: Zannolli R, Morgese G. New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6. Panminerva Med. 1995 Dec;37(4):238-47. http://www.ncbi.nlm.nih.gov/pubmed/8710408

 

Life-events and the course of chronic fatigue syndrome

Abstract:

Life-events have been implicated in the onset and course of various illnesses. The present study examined their role in chronic fatigue syndrome, in the context of the ongoing illness. Using the PERI list, events experienced during the past year were elicited in interviews with 130 patients. The analyses were restricted to those events implying moderate or major life change, and separate analyses were carried out for positive and negative events.

Positive events were found to be associated with lower scores for fatigue, impairment, anxiety and depression, as assessed at the time of the life-events interview, and these relationships were also significant when prior scores at the beginning of the year were statistically controlled. Negative life-events were associated with higher anxiety, but were unrelated to the other measures.

It was concluded that positive life-events and experiences may contribute to the process of recovery in chronic fatigue syndrome, though their occurrence may also be facilitated by a preceding lifting of symptoms.

 

Source: Ray C, Jefferies S, Weir WR. Life-events and the course of chronic fatigue syndrome. Br J Med Psychol. 1995 Dec;68 ( Pt 4):323-31. http://www.ncbi.nlm.nih.gov/pubmed/8688371

 

Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data

Comment on: Exercise responses and psychiatric disorder in chronic fatigue syndrome. [BMJ. 1995]

 

EDITOR,-In their study of exercise responses and psychiatric disorder in the chronic fatigue syndrome Russell J M Lane and colleagues claim to have detected abnormal lactate responses to subanaerobic threshold exercise in 31 of 96 patients. As no data are offered to support this statement, however, objective assessment of the validity of their findings is difficult.

The authors’ definition of an abnormal response is “lactate concentrations exceeding the upper 99% reference limit for normal control subjects at two or more time points.” However, only three samples were taken (before, immediately after, and 30 minutes after exercise), and a raised lactate concentration in the sample obtained before exercise began cannot be described as an abnormal response to exercise. Neither the method used to measure lactate nor its precision is given; assessment of the importance of the “abnormal” lactate concentrations could not be guessed at without this information, even if the authors had given details of the patients’ concentrations.

You can read the full comment along with the authors’ reply here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551191/pdf/bmj00618-0070a.pdf

 

Source: Hutchison AS. Exercise responses in the chronic fatigue syndrome. Objective assessment of study is difficult without knowledge of data. BMJ. 1995 Nov 11;311(7015):1304. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551191/pdf/bmj00618-0070a.pdf

 

Abnormalities of carnitine metabolism in chronic fatigue syndrome

Abstract:

Carnitine may be involved in the pathogenesis of the chronic fatigue syndrome (CFS). However, no information about the cellular metabolism of carnitine in CFS patients is currently available. Therefore, we aimed to measure the levels of carnitine (total, free and short-chain) in both peripheral blood lymphocytes (PBLs) and sera from patients with CFS.

The serum levels of total, free and short-chain were comparable in CFS patients, considered as the whole group, to those in healthy control subjects, even though a trend indicating slightly reduced serum concentrations of free carnitine was observed in male patients with CFS. In contrast, the concentrations of total, free and short-chain carnitine in PBLs from patients with CFS were significantly lower than in cells from healthy controls.

Our study indicates that patients with CFS require exogenous carnitine supplementation. The low carnitine concentrations in PBLs from patients with CFS probably reflect the carnitine deficiency occurring in other tissues, including the skeletal muscles. The low cellular concentrations of carnitines may help to explain both the immunological abnormalities and the impaired energy metabolism in skeletal muscles.

 

Source: Majeed T, de Simone C, Famularo G, Marcellini S, Behan PO. Abnormalities of carnitine metabolism in chronic fatigue syndrome. Eur J Neurol. 1995 Nov;2(5):425-8. doi: 10.1111/j.1468-1331.1995.tb00151.x. http://www.ncbi.nlm.nih.gov/pubmed/24283722

 

Silicone breast implant–associated musculoskeletal manifestations

Abstract:

Three hundred consecutive women with silicone breast implants (SBI), referred to the arthritis clinic with a variety of musculoskeletal complaints, were evaluated for the presence of underlying connective tissue disease. A complete history and physical examination were performed, as well as laboratory testing for C-reactive protein, rheumatoid factor; and autoantibody determination by indirect immunofluorescence and immunodiffusion.

The group mean age was 44.4 years (range 25-69), the mean time from initial implant surgery to appearance of symptoms was 6.8 years (range: 6m-19y) and 83.3% of women studied had clinical manifestations highly suggestive of an underlying connective tissue disorder. Fifty-four percent met criteria for fibromyalgia and/or chronic fatigue syndrome, distinct connective tissue diseases was detected in 11%, undifferentiated connective tissue disease or human adjuvant disease was found in 10.6%, and a variety of disorders such as angioneurotic oedema, frozen shoulder, multiple sclerosis-like syndrome were present.

Several other miscellaneous conditions including recurrent unexplained low grade fever, hair loss, skin rash, sicca symptoms, Raynaud’s phenomenon, carpal tunnel syndrome, memory loss, headaches, chest pain, and shortness of breath were also seen accompanying specific and non-specific conditions. Seventy percent of patients who underwent explanation of the implants reported improvement of their systemic symptomatology.

A significant proportion of SBI patients referred for rheumatic evaluation have clinical manifestations highly suggestive of an underlying connective tissue disease. Furthermore, improvement of their symptomatology follows explanation of the implants in over half of the patients.

 

Source: Cuellar ML, Gluck O, Molina JF, Gutierrez S, Garcia C, Espinoza R. Silicone breast implant–associated musculoskeletal manifestations. Clin Rheumatol. 1995 Nov;14(6):667-72. http://www.ncbi.nlm.nih.gov/pubmed/8608686

 

Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous illness characterized by a high prevalence of psychiatric problems. We reasoned that we could reduce heterogeneity by excluding patients with psychiatric problems preceding CFS.

We compared the functional status, mood, fatigue level, and psychiatric status of this more homogeneous group of CFS patients with the same parameters in patients with mild multiple sclerosis and in patients with major depression or dysthymia.

Patients with CFS and those with multiple sclerosis were similar in terms of level of anger, severity of depression, level of anxiety, and frequency of current psychiatric diagnoses. Patients with CFS resembled depressed patients in having impaired vigor and experiencing substantial fatigue and confusion–problems constituting part of the case definition of CFS.

The group with CFS was not psychologically vulnerable before the development of this condition and maintained adequate networks of social support despite disabling illness.

Stratification to exclude patients with prior psychiatric disease and those with mild CFS allowed us to define a group of patients with CFS who more resembled patients with mild MS than patients with major depression or dysthymia and thus were more likely to have illness with an infectious or immunologic cause. Use of such a stratification strategy should prove important in testing of the viral/immunologic hypothesis of the etiology of CFS.

 

Source: Natelson BH, Johnson SK, DeLuca J, Sisto S, Ellis SP, Hill N, Bergen MT. Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis. Clin Infect Dis. 1995 Nov;21(5):1204-10. http://www.ncbi.nlm.nih.gov/pubmed/8589144