The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment

Abstract:

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons:

i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment;

ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS.

We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows:

a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes.

b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies.

c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS.

d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment.

e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS.

f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS.

g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

 

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment. In Vivo. 1996 Nov-Dec;10(6):585-96. http://www.ncbi.nlm.nih.gov/pubmed/8986468

 

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient

Abstract:

A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment.

We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids.

We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows:

a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS.

b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995).

c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment.

d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc).

e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS.

f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS.

In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.

 

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient. In Vivo. 1996 Nov-Dec;10(6):575-84. http://www.ncbi.nlm.nih.gov/pubmed/8986467

 

Prevalence of irritable bowel syndrome in chronic fatigue

Abstract:

The aetiologies of irritable bowel syndrome and chronic fatigue are unknown. Psychological as well as physical factors have been implicated in both. Fatigue is common in irritable bowel syndrome patients. The purpose of the study was to determine the prevalence of irritable bowel syndrome in chronic fatigue sufferers.

A bowel symptom questionnaire was sent to all 4,000 members of a self-help group for fatigue sufferers. Of the 1,797 who responded, 1,129 (63%) fulfilled a diagnosis of irritable bowel syndrome (recurrent abdominal pain and at least three Manning criteria). This greatly exceeds estimates of irritable bowel syndrome prevalence of up to 22% in the general population.

Furthermore, irritable bowel syndrome sufferers within this chronic fatigue population reported more Manning criteria (14% had all six Manning criteria) than irritable bowel syndrome sufferers in the general population. This study demonstrates an overlap of symptoms in chronic fatigue and irritable bowel syndrome. In chronic fatigue, irritable bowel symptoms may be one aspect of a more generalised disorder.

 

Source: Gomborone JE, Gorard DA, Dewsnap PA, Libby GW, Farthing MJ. Prevalence of irritable bowel syndrome in chronic fatigue. J R Coll Physicians Lond. 1996 Nov-Dec;30(6):512-3. http://www.ncbi.nlm.nih.gov/pubmed/8961203

 

Chronic fatigue syndrome. Summary of a report of a joint committee of the Royal Colleges of Physicians, Psychiatrists and General Practitioners

Abstract:

Chronic Fatigue Syndrome (CFS) is not a single diagnostic entity. It is a symptom complex which can be reached by many different routes. The conceptual model of CFS needs to be changed from one determined by a single cause/agent to one in which dysfunction is the end stage of a multifactorial process. Although it is important to recognise the role of factors that precipitate the condition, greater understanding is required of factors that predispose individuals to develop the illness, and those that perpetuate disability.

 

Source: Wessely S. Chronic fatigue syndrome. Summary of a report of a joint committee of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. J R Coll Physicians Lond. 1996 Nov-Dec;30(6):497-504. http://www.ncbi.nlm.nih.gov/pubmed/8961200

 

Immunoglobulin subclass levels in chronic fatigue syndrome

Abstract:

The levels of immunoglobulin subclasses were determined for 46 patients meeting the original Centers for Disease Control case definition of chronic fatigue syndrome and were compared to values obtained for 50 age- and gender-matched healthy volunteer blood donor controls. The levels of immunoglobulin subclasses in these groups were further compared to a third group of additional chronic fatigue syndrome cases from whom samples had been obtained and frozen prospectively over a period of 7 years. These data do not demonstrate significant immunoglobulin subclass deficiencies in patients with chronic fatigue syndrome.

 

Source: Bennett AL, Fagioli LR, Schur PH, Schacterle RS, Komaroff AL. Immunoglobulin subclass levels in chronic fatigue syndrome. J Clin Immunol. 1996 Nov;16(6):315-20. http://www.ncbi.nlm.nih.gov/pubmed/8946275

 

N of 1 trials. Managing patients with chronic fatigue syndrome: two case reports

Abstract:

Chronic fatigue syndrome is a heterogeneous condition with as proves effective treatment. I present two case reports in which N of 1 trials helped me make management decisions. High-dose vitamin B12 injections were ineffective in one case; nimodipine was very effective in the other case.

 

Source: Wiebe E. N of 1 trials. Managing patients with chronic fatigue syndrome: two case reports. Can Fam Physician. 1996 Nov;42:2214-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2146911/ (Full article)

 

Psychosocial risk factors for chronic fatigue and chronic fatigue syndrome following presumed viral illness: a case-control study

Abstract:

This study investigated psychosocial morbidity, coping styles and health locus of control in 64 cases with and without chronic fatigue identified from a cohort of primary care patients recruited 6 months previously with a presumed, clinically diagnosed viral illness. A significant association between chronic fatigue and psychosocial morbidity, somatic symptoms and escape-avoidance coping styles was shown.

Chronic fatigue cases were significantly more likely to have a past psychiatric history and a current psychiatric diagnosis based on a standardized clinical interview. Twenty-three of the cases fulfilled criteria for chronic fatigue syndrome (CFS). Such cases were significantly more fatigued than those not fulfilling criteria, but had little excess psychiatric disorder.

A principal components analysis provided some evidence for chronic fatigue being separable from general psychosocial morbidity but not from the tendency to have other somatic complaints. Past psychiatric history and psychological distress at the time of the viral illness were risk factors for psychiatric ‘caseness’ 6 months later, while presence of fatigue, psychologising attributional style and sick certification were significant risk factors for CFS. These findings extend a previous questionnaire study of predictors of chronic ‘post-viral’ fatigue.

 

Source: Cope H, Mann A, Pelosi A, David A. Psychosocial risk factors for chronic fatigue and chronic fatigue syndrome following presumed viral illness: a case-control study. Psychol Med. 1996 Nov;26(6):1197-209. http://www.ncbi.nlm.nih.gov/pubmed/8931166

 

Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice

Abstract:

Proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha have been proposed to play a role in the pathogenesis of fatigue. In the present study we compared the susceptibility of two mouse strains to immunologically induced fatigue.

Daily running of two strains of mice, Balb/c and C57BL/ 6, was assessed after a single injection of Corynebacterium parvum antigen (2 mg/mouse). Spontaneous running activity of each animal was compared to mean running distance prior to injection. To evaluate the involvement of cytokines in fatigue development, C57BL/6 mice were treated with antibodies to specific cytokines at the time of challenge with C. parvum antigen. Also, cytokine mRNA expression was analyzed in the brains of mice at different time periods after immunologic challenge.

A significant difference in running activity between the two mice strains was observed after C. parvum antigen inoculation: C57BL/6 mice showing a greater (P < 0.05) reduction in running activity (relative to preinjection levels) and slower recovery to baseline than Balb/c mice. Injection of antibodies specific to either IL-1beta or TNF-alpha did not alter immunologically induced fatigue, suggesting a lack of involvement of these cytokines produced outside of the central nervous system (CNS).

However, increased TNF-alpha and IL-1beta mRNA expression was found in the brains of C57BL/6 compared to that seen in Balb/c mice at 6, 10, and 15 days after C. parvum antigen injection. The elevated CNS cytokine mRNA expression corresponded to development of fatigue. These findings are consistent with the hypothesis that expression of proinflammatory cytokines within the CNS plays a role in the pathogenesis of immunologically mediated fatigue.

 

Source: Sheng WS, Hu S, Lamkin A, Peterson PK, Chao CC. Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice. Clin Immunol Immunopathol. 1996 Nov;81(2):161-7. http://www.ncbi.nlm.nih.gov/pubmed/8906747

 

Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome

Abstract:

We have identified and partially characterized the autoantibodies in sera of 60 patients with chronic fatigue syndrome. Approximately 52% of the sera were found to react with nuclear envelope antigens.

The combination of nuclear rim staining observed in immunofluorescence microscopy and immunoblot analysis of highly purified nuclear envelope proteins provided initial characterization of these autoantibodies. Further characterization showed that some sera immunoprecipitated the in vitro transcription and translation product of a human cDNA clone encoding the nuclear envelope protein lamin B1. The autoantibodies were of the IgG isotype.

The occurrence of autoantibodies to a conserved intracellular protein like lamin B1 provides new laboratory evidence for an autoimmune component in chronic fatigue syndrome.

 

Source: Konstantinov K, von Mikecz A, Buchwald D, Jones J, Gerace L, Tan EM. Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome. J Clin Invest. 1996 Oct 15;98(8):1888-96. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/ (Full article)

 

Neuroimmune mechanisms in health and disease: 2. Disease

Abstract:

In the second part of their article on the emerging field of neuroimmunology, the authors present an overview of the role of neuroimmune mechanisms in defence against infectious diseases and in immune disorders. During acute febrile illness, immune-derived cytokines initiate an acute phase response, which is characterized by fever, inactivity, fatigue, anorexia and catabolism.

Profound neuroendocrine and metabolic changes take place: acute phase proteins are produced in the liver, bone marrow function and the metabolic activity of leukocytes are greatly increased, and specific immune reactivity is suppressed.

Defects in regulatory processes, which are fundamental to immune disorders and inflammatory diseases, may lie in the immune system, the neuro endocrine system or both. Defects in the hypothalamus-pituitary-adrenal axis have been observed in autoimmune and rheumatic diseases, chronic inflammatory disease, chronic fatigue syndrome and fibromyalgia.

Prolactin levels are often elevated in patients with systemic lupus erythematosus and other autoimmune diseases, whereas the bioactivity of prolactin is decreased in patients with rheumatoid arthritis. Levels of sex hormones and thyroid hormone are decreased during severe inflammatory disease. Defective neural regulation of inflammation likely plays a pathogenic role in allergy and asthma, in the symmetrical form of rheumatoid arthritis and in gastrointestinal inflammatory disease.

A better understanding of neuroimmunoregulation holds the promise of new approaches to the treatment of immune and inflammatory diseases with the use of hormones, neurotransmitters, neuropeptides and drugs that modulate these newly recognized immune regulators.

 

Source: Anisman H, Baines MG, Berczi I, Bernstein CN, Blennerhassett MG, Gorczynski RM, Greenberg AH, Kisil FT, Mathison RD, Nagy E, Nance DM, Perdue MH, Pomerantz DK, Sabbadini ER, Stanisz A, Warrington RJ. Neuroimmune mechanisms in health and disease: 2. Disease. CMAJ. 1996 Oct 15;155(8):1075-82. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1335357/ (Full article)