만성피로증후군 새소식

 

미국학회에 보고된 박태홍선생의 감마그로부린

치료결과의 논문 전문

 

Cytokine production and modulation after

low dose IVγ-globulin therapy in patients

with chronic fatigue syndrome (CFS)

El-Mezayen Rabab, MD, Akemi Tomoda, MD, Tomoaki Matsumoto,

MD, Takako Joudoi, MD,　Tae Hong Park, MD,

and Teruhisa Miike, MD

Department of Child Development, School of Medicine

Kumamoto University, Kumamoto, Japan

Correspondence address:

Dr. El-Mezayen Rabab

Department of Child Development

Kumamoto University School of Medicine

      1. Honjo, Kumamoto 860-0811, Japan

E-mail: tomo@kaiju.medic.kumamoto-u.ac.jp

Fax: + 81-96-373-5200 TEL: +81-96-373-5197

ACKNOWLEDGEMENTS

This study was performed through Special Coordination Funds for Promoting Science and Technology from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.

ABSTRACT

Objective: The purpose of this study was to investigate the cytokine production pattern in patients with chronic fatigue syndrome (CFS) and, normal controls. In five CFS patients, we examined cytokine production as well as patients' performance status scores (PS) before and after IV γ-globulin therapy.

Methods: This study examined 23 healthy controls and 15 patients with CFS, all meeting Center for Disease Control (CDC) diagnostic criteria. Their PBMC were cultured with LPS or PHA. Cytokine concentration was measured in culture supernatants by enzymatic immunoassay.

Results: In patients with CFS, there was a significant decrease in TGF-β1 production in LPS-stimulated PBMC culture supernatants; the level of mRNA was decreased as well. Significant improvement of performance status score (PS) was observed in four of five patients who received low dose IV γ-globulin treatment for four months.

Conclusions: Cytokine dysregulation might be one factor involved in CFS pathogenesis. Also, TGF-β1 might be a key factor in inflammatory characteristics of CFS; it may help in evaluation of treatment effectiveness. Low dose IVγ-globulin therapy was inferred to be a successful treatment for CFS.

Key words: Peripheral blood mononuclear cells (PBMC); Chronic fatigue syndrome (CFS); Cytokines; TGF-β1.

1. Introduction

Chronic fatigue syndrome (CFS) is a condition that is characterized by unexplained, disabling fatigue; it is often accompanied by low-grade fever and subtle indication of immune system activation (1). In addition, unrefreshing sleep, impaired concentration and memory, and depressed mood and anxiety are common (2). Although pathogenesis of CFS is still a subject of intensive study, some studies suggest that a persistent viral infection is of etiologic importance (6,7); one recent report of a variety of immunologic abnormalities in a high proportion of patients suggests involvement of an immunoregulatory defect(8,9).

Cytokines have been implicated in pathogenesis and clinical manifestation of CFS via their effects on CNS (10,11). Moreover, one striking feature of CFS is its sudden onset following an acute, presumably viral, illness and persistence or recurrence of flu-like symptoms; such symptoms have been attributed to persistent cytokine production (12,13,14). To date, there is no clearly effective therapy for this disorder (3), although conflicting data from placebo-controlled studies suggest intravenous immuno-globulin may be beneficial (4,5).

The patient group included in this study received low dose intravenous gamma globulin therapy in the form of a 1 gm biweekly dose. This study investigates effectiveness of this treatment and its relation to immunoactivity depending on the evaluation of cytokine production before and after receiving this treatment for four consecutive months.

Here, we describe cytokine production in culture supernatants and in plasma of patients with CFS　before and after IVγ-globulin treatment because cytokine dysregulation might be an important factor involved in pathogenesis of this syndrome; also, such knowledge might facilitate evaluation of effectiveness of this treatment.

2. Methods

2.1. Subjects

This study comprised 15 patients with CFS (8 men, 7 women), aged 20.3±9.47 years and 23 normal controls(14 men, 9 women), aged 23±2.27 years. All patients were referred to our hospital because of CFS symptoms. These patients met Center For Disease Control (CDC) diagnostic criteria for CFS. The period of CFS symptoms was longer than 12 mos. (avg. 1.3 years; range, 1 to 3 years). Their performance status scores (PS) on admission were higher than 7 (avg. 8.3 mos.; range, 8 to 9 mos.).

2.2. Cell culture

For this study, PBMC were isolated by density gradient centrifugation, washed three times, and then adjusted to 1×106 cells/ml with RPMI 1640 medium containing 10% heat -inactivated fetal calf serum(FCS), (FCS-free medium for TGF-β1 study), and 2 mM L-glutamine. Cells were then cultured with 5 μ/ml phytohemaglutinin (PHA) or 50 ng/ml lipopolysaccharide (LPS) and incubated three days at 37℃ under 5% CO2.

2.3. Cytokine measurement

(IL-6, TNFα, IL-1β): Concentration of these cytokines in the culture supernatant of LPS-stimulated PBMC was measured by two step (sandwich) enzyme immunoassay from Immunotech (Marseille, France). Samples and standards were incubated in microtitre plate wells, then coated with the first monoclonal antibody. The wells were emptied and washed; then, a second monoclonal antibody linked to acetylcholinestrase was added. After incubation, the wells were emptied and washed; then, bound enzymatic activity was measured by adding a chromogenic substrate. The resultant color intensity is proportional to cytokine concentration. The sensitivity of this ELISA assay is 3 pg/ml for IL-6, 5 pg/ml for TNFα, and 15 pg/ml for IL-1β.

(TGF-β1): concentration in cell culture supernatants of LPS- stimulated PBMC was assayed using the quantitative sandwich enzyme immunoassay technique from R&D Systems, (Minneapolis, MN). The TGFβ1 soluble receptor type II, which binds TGFβ1, was pre-coated onto a microplate. Standards and samples were pipetted into wells; consequently, all TGFβ1 was bound by the immobilized receptor. The minimum detectable dose of TGF-β 1 is less than 7 pg/ml.

(IFN-γ): from PHA-stimulated PBMC culture supernatants, This assay employs ELISA from R&D Systems. Sensitivity of this assay is 8 pg/ml.

(IL-4 and IL-18): IL-4 concentration in the culture supernatant of PHA stimulated PBMCs was measured by ELISA from Biosource International, Inc. (Camarillo, CA). The sensitivity of this assay is < 2.0 pg/ml. The IL-18 concentration in the culture supernatant of LPS-stimulated PBMC was measured by an ELISA kit obtained from Medical and Biological Laboratoriesn (Nagoya, Japan). Minimum sensitivity for this assay is 12.5 pg/ml.

Study of TGF-β1 mRNA expression

For RNA extraction, 5×106 PBMCs were cultured with LPS for three hours; then mRNA was isolated using the Rneasy Mini Kit (QIAGEN). Samples were hybridized with gene-specific biotin-labeled capture oligonucleotide probes and digoxigenin-labeled detection probes on streptavidin-coated microplate (Colorimetric mRNA Quantitation Kit; R&D Systems) according to the manufacturer instructions. The standard curve was linear from 6.25 to 400 attomole/ml(amol/ml) of TGFβ1 mRNA.

2.4. Statistical Analysis　

Reported data were logarithmically transformed before statistical analysis; they were expressed as gm and 1 sd range. The Mann-Whitney U-test was used to compare study groups for significant differences. Probability (P) values of less than 0.05 were considered statistically significant.

3. RESULTS

Before IV γ-globulin treatment

TGF-β1 protein production in the culture supernatant of LPS-stimulated PBMC from CFS subjects (gm 4,642 and 1sd range 3,033-7,102) was significantly decreased when compared to normal controls (6,330 & 4,449-9,006) P=0.018. TGF-beta1 mRNA production in LPS stimulated (PBMC) was significantly decreased in CSF patients (gm 35.8 & 1,9-6,6) when compared to normal controls (gm 92.54 & 6,55-13,1) and P＜0.001. However, no statistical significant differences were detected when IL-10, IL-18, IL-4, TNFα, IFNγ, and IL-6 were measured. Table 1 shows those results.

After IV -γglobulin treatment

In four of five patients with CFS who received treatment, TGF-β1 protein production and mRNA were found to be progressively increased by receiving low dose -γ globulin treatment 1 gm/biweekly for 4 mos. Importantly, the study of patients' performance status scores (PS), demonstrated that three of five patients who received the treatment showed improvement in their performance status score as shown in Figs. 1A and 1B.

4. Discussion

The present study demonstrated: cytokine production pattern in patients with chronic fatigue syndrome (CFS); and comparative evaluation of cytokines production before and after receiving low-dose IV γ-globulin treatment for four months in five patients who completed the protocol. Abnormal regulation of cytokine activity may contribute to pathophysiology and clinical manifestations of CFS (10,11).

The present study suggests that intravenous gamma globulin (low dose IV γ-globulin) therapy is likely to be of clinical benefit in treatment of patients with chronic fatigue syndrome. We infer this from improvement of the status performance score in four of the five CFS patients; they showed improvement in their abilities to participate in daily activities and their degree of involvement in work or school, sports and different social activities, in contrast to their conditions before receiving IV gamma-globulin treatment. These data concur with a previous report of diminished fatigue after intramuscular gamma globulin in patients with chronic mononucleosis syndrome (15).

Silverman et al. presented a pilot study of the effects of IV gamma globulin in systemic juvenile rheumatoid arthritis (JRA). Eight patients with active systemic JRA that was unresponsive to first-line agents, second-line agents, and corticosteroids received this therapy monthly for 6 mos. Outcome measures included changes in articular and extra-articular features, steroid dosage, and laboratory parameters. Following IV gamma globulin therapy, there was significant improvement in arthritis and/ or morning stiffness in five of the eight patients, while extra-articular features significantly improved in seven of the eight patients (25).

The important aspect of our study is that TGF-β 1 might be considered to be an indicator for improvement of CFS patients' condition; supportive evidence for this inference is the progressive increase in its production during treatment concomitant with improvement of those patients' performance status score. Therefore, TGF-β1, as a multifunctional anti-inflammatory cytokine, might be involved in immune function; deficiency of this cytokine reported in CFS patients in the present study may contribute to inflammation which characterizes CFS syndrome, such as myalgia and muscular fatigue. This finding supports the anti-inflammatory and immunosuppressive functions of TGFβ1. Our results are supported by a previous published report: a longitudinal study of the first qPCR evaluation of TGFβ1 mRNA every 2 weeks in conjunction with monthly MRI. That study indicated that TGFβ1 mRNA level inversely correlates with MRI disease activity in multiple sclerosis (MS) (26).

TGFβ1 has also been reported to have important roles in unresolved inflammation, immune suppression, fibrosing processes, and angiogenesis; it was also highly expressed in joints in RA and was considered to be a regulator of anti-inflammation in rheumatoid arthritis (24).

Improvement of patients' performance status score together with progressive increase of TGF-β1 productivity reported here might be emblematic of the effectiveness of this trial as a treatment for patients with CFS.

In the current study, we also investigated in vitro production of the anti-inflammatory cytokine IL-10, which has been reported to inhibit IFN-γ and IL-4 production by Th lymphocytes, IL-1β, IL-6 and TNF-α by mononuclearphagocytes (16,17,18,19). In addition, we also examined cytokines IL-4, IFN-γ, IL-1β, TNF-α, and IL-18. However, these cytokines were found to be of comparable values between CFS patients and normal controls. This is consistent with findings by Larry Borish. For CFS patients with allergies, those results linked both increased production of proinflammatory cytokines IL-1 β and TNF-αand decreased concentration of the anti-inflammatory cytokine IL-10 with the presence of allergy. The results also included the inference that prolonged or excessive production of cytokines secondary to allergen exposure or other immune insults were responsible for CFS development (25). Furthermore, while Starus et al. (21) found no difference in IL-1β levels in CFS patients, Visser et al. reported that IL-4 production and cell proliferation are comparable even though CD4T cells from CFS patients produce less IFN-γthan cells from controls. In other studies, no differences were observed in IL-6 production in CFS patients (22,23).

Previous studies and the results presented herein demonstrate the need for further detailed studies about these cytokines to clarify their roles in pathogenesis of CFS.

In conclusion, results of this study suggest that low dose IV γ-globulin is considered as a successful trial for treatment of CFS. Furthermore, it suggests that cytokine dysregulation is not a singular or dominant factor in pathogenesis of CFS; it is possible that immunological, autonomic, and neuroendocrine abnormalities are mutually-dependent and mutually-reinforcing factors.

References

  1. Strober W. Immunological function in chronic fatigue syndrome. In The Chronic Fatigue Syndrome, SE Strauss (ed). New York, Marcel Dekker, 1994, pp 207-237.
  2. Hickie I, Lloyd A, Hadzi-Pavlovic D, et al. Can the chronic fatigue syndrome be defined by distinct clinical features? Psychol Med 1995;25:925-935.
  3. Wilson A, Hickie I, Lloyd A, et al. Science and speculation: the treatment of chronic fatigue syndrome. Am J Med 1994;96:544-550.
  4. Lloyd A, Hickie L, Wakefield D, et al. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Am J Med 1990;561-568.
  5. Peterson PK, Shepard J, Macres M, et al. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med 1990;89:554-560.
  6. Yousef GE, Bell EJ, Mann GF, et al. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1988;1:146-50.
  7. Archard LC, Bowles NE, Benhan PO, et al. Postviral fatigue syndrome: persistence of enterovirus DNA in muscle and elevated cretonne kinase. J R Soc Med 1988;81:326-9.
  8. Tosato G, Straus S, Henle W, et al. Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis). J Immunol 1985;134:3082-8.
  9. Lloyd AR, Wakefield D, Boughton CR, Dwyer JM. Immunological abnormalities in the chronic fatigue syndrome. Med J Aust 1989;151:122-4.

10- Moutschen M, Triffaux JM, Deonthy J, et al. Pathogenic tracks in fatigue syndrome. Acta Clinica Belgica 1994;49:247-289.

11- Levy JA. Viral studies of chronic fatigue syndrome. Clin Infect Dis 1994;18(suppl):s117-s120.

12- Komaroff AK, Buchwald D. Symptoms and signs of chronic fatigue syndrome. Rev Infect Dis 1991;13-S8-11.

13- Komaroff AL. Chronic fatigue syndromes: Relationship to chronic viral infections. J Virol Methods 1988;21:3-10.

14- Chronic fatigue syndrome: A pamphlet for physicians. Bethesda: US Department of Health Human Services, 1990; National Institutes of Health Pub. No.90-484.

15- Dubois RE. Gamma globulin therapy for chronic mononucleosis syndrome. AIDS Res 1986;2:S191-5.

16- Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell.IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989;170:2081-95.

17- Yssel H, de Waal, Malefyt R, et al. IL-10 is produced by subsets of human CD4+Tcell clones and peripheral blood T cells. J Immunol 1992;149:2378-84.

18- Malefyt Rd, Abrams J, Bennett B, et al. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991;174:1209-20.

19- D'Andrea A, Aste-Amezaga M, Vaiante NM, et al. Interleukin 10 (IL-10) inhibits human lymphocyte interferon-g production by suppressing natural killer cell stimulatory factor/Il-12 synthesis in accessory cells. J Exp Med 1993;178:1041-8.

20- Borish L, Schmaling K, Diclementi J, et al. Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables. J Allergy Clin Immunol 1998;102(2):222-30.

21- Strauss SE, et al. Circulating lymphokine levels in the chronic fatigue syndrome. J Infect Dis 1998;160(6):1085-1086.

22- Visser J, et al. Cd4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. J Infect Dis 1998;177(2):451-454.

23- See DM, et al. In vitro effect of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome. Immunopharmacology 1997;35:229-235.

24- Sugiura Y, Niimi T, Sato S, et al. Transforming growth factor beta1 gene polymorphism in rheumatoid arthritis. Ann Rheum Dis 2002;61(9):826-8.

25- Silverman ED, Laxer RM, Greenwald M, et al. Intravenous gamma globulin therapy in systemic juvenile rheumatoid arthritis. Arthritis Rheum 1990;33(7):1015-2.

26- Bertolotto A, Capobianco M, Malucchi S, et al. Transforming growth factor beta1 (TGFbeta1) mRNA level correlates with magnetic resonance imaging disease activity in multiple sclerosis patients. Neurosci Lett 1999;19;263(1):21-4.

Table 1. Cytokine levels in culture supernatants and plasma before IV γ-globulin therapy.

*gm (Geometric means and 1sd range)

Cytokine (pg/ml)

Control

(n= 23)

Patient

(n= 14)

P

TGF-beta1 (in vitro)

6. 330*

(4. 449-9. 006)

4. 642

(3. 033-7. 102)

=0.018

TGF-beta1 mRNA

(amol/ml)

92. 54

(6. 55-13. 1)

35. 8

(1. 9-6.6)

＜0.001

TGF-beta1 (plasma)

5. 2

(0. 96-3. 46)

4. 9

(0. 26-1.1)

IL-6 (in vitro)

11. 7

(3. 9-4. 2)

13. 5

(3. 8-4. 4)

IL-6 (plasma)

1. 3

(0. 12-0. 35)

1. 2

(0. 16-0. 38)

TNF-α(in vitro)

5. 48

(2. 3-3. 2)

8. 11

(2. 6-3. 2)

IL-1-β(in vitro)

4. 16

(2. 3-2. 9)

3. 42

(2. 2-2. 8)

IL-10 (in vitro)

44. 6

(3. 1-3. 8)

29,6

(3. 4-3. 9)

IL-18 (in vitro)

60. 7

(2. 5-2. 6)

58. 5

(1. 6-1. 9)

IFN-γ(in vitro)

21. 3

(1. 6-2. 9)

33. 4

(1. 7-2. 5)

IL-4 (in vitro)

8. 2

(0.43-1.4)

16. 1

(0.45-1.9)

FIGURE LEGENDS

Fig. 1A

TGF-β1 protein production for five patients with CFS: culture supernatants of PBMC were stimulated with LPS for three days before and after IV gamma-globulin treatment. M, month; P.S, performance status score.

Case 1 ●, PS, 7→8 Case 2 ◇, PS, 7→2

Case 3 ■, PS, 8→6 Case 4 ○, PS, 7→5

Case 5 □, PS, 7→4

Fig. 1B

TGF-β1 mRNA production in PBMC stimulated with LPS for three hours before and after IV gamma-globulin treatment.

- 14 -

 

 

미국만성피로학회보고.

이번 미국 WASHINGTON D.C.에서열린

미국만성피로학회에서의 가장 초점은

만성피로증후군와 바이러스의 연관성이다

그중 HHV-6바이러스 발견자인

DR.ABLASHI는 80%이상의 환자에서

HHV-6바이러스가 활성화된다고 말하고 있다.

실제로 본크리닉에서도 감염의 가능성이있는

경우가 많이 보인다.

즉 MOTHER TO DAUGHTER 전염같은

가능성을 볼수가있다

이런 경우 DR.ABLASHI는

TRANSFER FACTOR를 쓰라고 알려주었다.

 

 일본만성피로학회

에서 GUEST SPEAKER로

초청된 DR.TAE HONG PARK.M.D.

 

이번 2월14일에서 15일까지

일본 TOTTORI에서

열리는 일본의 제8차 만성피로연구회에

외국인으로 유일하게 한국의

박태홍만성피로크리닉의 박태홍선생이

일본만성피로학회에 초청연사로 강연을

하게된다.이사실은 이번 일본만성피로학회장인

DR.SIRENGI에 의하여 알려졌다.

그동안 미국학자의 초청강연은 있었으나

일본학회에 초청연사로 한국인

의사가 초청되기는 이번이 처음있는일이다.

관심이 있는분들은 영광스러운 자리에 참석을

하여 박수를 보낼일이다.

이제는 세계적인 만성피로전문의가

우리나라에도 있다는 사실에

겸손한 마음을 가질 때인 것 같다.

 

 

 

 

 금년 세계 만성피로학회소식

 

금년 1월 30일에 미국 워싱턴근교의

chantilly,virginia에서 세계 만성피로학회가

열린다. 이번 학회에는 본인과 일본 구마모도대학의

DR.MIIKE가 합동으로

만성피로증후군의 LOW DOSE GAMMAGLOBULINE

IV THERAPY의 발표가있다.

많은 환자들이 기다리든 기쁜 소식일될 것이다

그이유는 그전의 IV GAMMAGLOBULINE

THERAPY는 대량 2GM/KG을 사용하여

그 비용이 대단히 높기에 실용성이 없었고

그리고 효과 또한 일정하지를 않았다

그러나 이번에 발표되는 일본 구마모도대학과

본인의 공동연구는 저량으로 비용이 적고 모든환자에게

적용이 가능하고 그리고 무었보다도

80%이상의 높은 치유율을 보이고

그리고 그환자의 숫자가 4000명이상이라는

사실이 대단한 반응을 불러오고 있다.

일본에서는 일부의 의사들이 본인에게

치료법을 의뢰해오고 있는 실정이다.

그리고 미국의 제일 내과학회지인

AMERICAN JOURNAL OF MEDICINE에

곧 계제가되여 세계적으로 인정을 받은

것으로 우리나라의 저력을

세상에 알리는 좋은 계기가 된것이다

 

 

만성피로증후군의 산재승소 소식.

Court recognizes Chronic Fatigue Syndrome as job-related illness  
 

A Seoul court ruled yesterday that Chronic Fatigue Syndrome (CFS) should be regarded as a work-related illness.

The Seoul Administrative Court ordered the Korea Labor Welfare Corporation to provide a former taxi driver, identified as a 45-year-old man by the name of Eom, be awarded financial compensation for medical expenses. Eom, who claimed to have developed CFS due to exhaustion and stress, filed a lawsuit after the Korea Labor Welfare Corporation turned down his application for compensation for job-related illness.

In handing out the ruling, the court said it finds that long working hours and constant worries about causing traffic accidents damaged Eom's health.

Eom claimed that he worked for about 12 hours everyday and had only two days off each month.

He was involved in an auto accident in 1999 and had since suffered extreme stress because of the accident.

The court said it accepts CFS as a legitimate illness although its exact causes have not yet been identified.

"It has already been acknowledged in medical circles as a disease that requires treatment," the court added.

CFS is an ailment characterized by six months of severe fatigue that is made worse by physical or mental exertion. It causes debilitating symptoms that can last for years resulting in some sufferers becoming too exhausted to either work or lead normal lives.

Although some attribute it to a virus, it has no clear underlying cause.

Eom began suffering from extreme tiredness and had a nervous breakdown following a minor accident involving a motorcycle in December, 1999. In the same month, he was diagnosed as having CFS at a general hospital in Seoul.

An official of the Korea Labor Welfare Corporation said this is the second time that a court has ordered the organization to grant compensation in relation to CFS.

(mhkim@koreaherald.co.kr)

 
2001.05.23





 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

위의 글은 우리나라에서 잊혀진 만성피로증후군 환자의 산재소송의

승소 판결문이 일본 만성피로학회모임에 보고가 된 것을

운영자가 다시 역으로 한국에 보고를 한다.

우리는 잊어 버린일을 그들은 빠짐없이 주시를 하고 있다는

사실에 그저 놀랄뿐이다.

 

 

일본만성피로학회소식

 

 

일본만성피로학회는 2003년

2월13일부터 14일까지

일본만성피로연구회를 가진다

장소는 요나고시

주최는 tottori university 다.


YONAGO BIG Ship
74 Suehiro-cho Yonago City 683-0043 Tottori Prefecture Japan
TEL:0859-35-8111 FAX:0859-39-0700

TOTTORI University
DEPARTMENT OF BIOSIGNALING FACULTY OF MEDICINE TOTTORI UNIVERSITY
Yonago City TOTTORI Pref. JAPAN


8th JACFS President
Prof.TSUYOSHI Sairenji
DEPARTMENT OF BIOSIGNALING FACULTY OF MEDICINE TOTTORI UNIVERSITY

오스트랄리아 학회소식

 

이번2001년 11월달에 오스트랄리아에서

만성피로증후군 세계학술대회가열린다

연사로 하바드의대의 DR.KOMAROFF,

영국의 UNIVERSITY OF GLASCO의 DR.BEEHAN

등 유명한 만성피로연구진이 모인다

관심이있는분은 본운영자에게

연락을 주시면 자세한 것을 알려드립니다

 

세계만성피로학회참관소식

 

제5차 세계만성피로증후군학회를참관하고왔다

역시한국에서는 본운영자외에는 아무도 참석한자가없었다.

가장두드러진 변한 것은 만성피로증후군이

아주경한 다발성경화증(multiple sclerosis)

과 그발생기전이나 원인이 같다는 의견이다.

대단히 놀라운 사실을 발표를 하고 있는 것이다

일부에서는 아주경한 다발성경화증이 만성피로증후군

이라는 주장까지(DR.DAVID BELL)나왔다.

놀라운 사실이 아닐수가없다

단지피로하다고 느끼는 많은 사람들이

뇌척추신경의 손상으로 불구가 된다는 말들을

하고 있는 것이다.실제로 운영자가본 많은 환자들은

뇌신경계통의 손상이 아주흔히보인다

이런 현상을 우리가 발견하는 것은 결국은 이들이 말하는

다발성경화증의 경한 경우가 만성피로증후군이라고말을할수가있는 것이다

그리고 본운영자가 치료하는 방법이 세계적으로 인정이되는 가장합리적이고

그리고 그치유율이 타의 추종을 불허하는 치유율을 가지고 있다는

인정을 세계적으로 인정을 받았다는 사실이다.

한국인으로 대단한 영광을 안고온 것이이번 학술대회였다

 

1.학회소식

제 5차 세계만성피로증후군 학회가

미국 시아틀에서 2001.1.26부터 2001.1.30일까지

열립니다.참가를 원하시는 분은

http://www.aacfs.org

으로 직접 예약을 하십시요.우리나라에서 알아온

만성피로 증후군의지식과 세계학술대회에서 듣고 오는 새로운

지식의 차이는 여러분들을 놀라게 해줄 것입니다.

 

2.만성피로증후군과 심장

닥터 마틴러너는 최근카나다 토론토심장학회에 발표한

연설에서 만성피로증후군환자의 95%가 심장에 이상이

온다고 발표,그리고 이것은 CMV,EBV등의바이러스성일

가능성이 높다고 발표.

 

3.만성피로증후군 증상의 악화에

   oxidative stress가 작용한다고-

   오스트랄리아의 닥터 단스탄 구룹은 methemoglobin이

   이환자들에게서 정상인 보다 월등히 많이 혈중에

   있다고 보고--즉 이들은 많은양의 free radical의 생성이

    이병의 병리현상에 기여하고 증상의 심한 정도와도

    관련이 있다고 보고

 

4.만성피로증후군에 성장홀몬의 저하현상

   벨지움 대학병원의 닥터 안트와르 벅사는

   성장홀몬이 만성피로증후군 환자에게서 저하되는

   것을 발견.

   그리고 이들환자에게서 높은 프로락틴 래밸도  동반하는

   것을 발견

 

5.닥터 데비드 밸(유명한 만성피로전문의)

   은 최근에 획기적인 사실을 발표를 하였다

   즉 만성피로증후군 환자에게서 정상인의 70%밖에 안되는

   혈액양을 가지고 있다고 발표, 일부의 환자는 정상인의

    50%밖에 않되는 혈액양으로 --거의 shock이 오는상태--

    살고 있다고 보고를 하고 있다.

    이런 이유로 이환자들의 혈액순환 특히 뇌혈액순환에

    지장을 줄 수 있다고

 

6.하바드의대의 닥터 코마로프는 만성피로증후군환자의

MRI SCAN에 보이는 UBO(흰반점)은 뇌말초혈관의 질환이라고

발표(미국 방사선학회지):이런현상을 뇌의 회백질에온

ARTERIOLAR VASCULOPATHY이라고 말하고있다

(차후에 만성피로증후군 환자의 MRI 사진은 운영자가

이홈페이지에 올릴예정입니다.)

그리고 SPECT.SCAN에 보이는 현상은 뇌세포의 직접적인

염증,싸이토카인에 의한 뇌세포기능장애,그리고 혈관염(VASCULITIS)

에의한 뇌혈류의 감소라고 말하고 있다.

(환우여러분은 http://www.cfids.org을 열어보십시요,

이곳은 미국에서 가장오래된 만성피로증후군환자 support group입니다.이곳에서 충분한 자료를 얻을 수 있습니다)

 

7 미국 켈리포니아대학(센프란시스코)의 닥터 래비(에이즈바이러스

공동발견자)는 영국의 유명한 의학잡지 란셋(lancet)에 만성피로증후군은

만성의 면역이상항진현상(chronic immune activation)이라고

발표.즉 면역억제세포(CD8)의 감소와 면역항진세포(CD38,HLA-DR)

의 증가가 90%의 환자에서 보인다고 말하고 있다.

이런현상은 다량의 싸이토카인을 생산하고 이것은 만성피로증후군

의 많은 증상(근육통,관절통,두통,신경통--)의 원인이 된다

 

8.존스홉킨스 대학의 닥터 피터로우는

만성피로증후군환자의 85%에서 NMH--neurally mediated hypotension--

이있다고 발표.즉 이병환자는 갑자기 누웠다 일어나거나 하면

심한 현기증이 오고 혈압이 떨어지는현상을 이야기한다

이런 현상을 검사로 tilt-table test라는 것을 한다.

이것은 환자를 70도로 비스듬이 45분동안세워두면 양성반응이있는

환자는 혈압의 저하와 현기증을 느낀다.

이런현상은 환자치료에 대단히 중요한 사실로 실제로

대부분의 만성피로증후군환자들(우리나라)은 이런 현기증을 이르키는

저혈압을 가지고 있다. 이런 의미에서 다량의 수분과 염분의 섭취는

과학적인 근거에서 비롯된 것이고 실제로 대부분의 환자들은

혈압의 조절이 정상으로 돌아오면 만성피로증후군 증상들이

대단히 호전되는 것을 볼수가있다.(jounal of american medical

association으로부터).

 

 

9.American Journal of Pediatric로부터-

미국 뉴욕대학의 소아과 연구팀들은

어린이 만성피로증후군 환자의 서있는 자세에서 혈압과 맥박을

측정하고 tilt-table test를 시행하였다.

90명의 어린이 만성피로증후군 환자중 92%가 6분 이내에

혈압이떨어지고 맥박이 빨라졌으며 이중 8%는 기절을하였다고보고

즉 이런현상은 뇌기능의 장애로 혈압을 올려주는 말초혈관의

수축이 않일어나고 오히려 피가 다리나 복부로 몰리고

상대적으로 뇌혈류는 감소하는 것을 발견하였다.

즉이들은 뇌에 전달되어야할 산소량이 급격히 저하됨으로

심한 인지능력의 저하와 감정조절의 이상을

가지고온다고 설명을 하고있다

 

 10.미국 아리조나대학의 닥터 아이리스벨은

만성피로증후군 잡지(jounrnal of chronoc fatigue syndrome)에

발표한 글에서 유기용매에 노출된 사람의 60%에서 만성피로증후군과같은

증상을 가지고 있다고발표 특히 이들은 인지능력--집중력,기억력,건망증--

등이 심하게 저하되여있다고발표.

실제로 한연구에서는 농약으로쓰는 살충제 농도가 만성피로증후군

환자에게서는 다량으로검출되는 것도 보고하고 있다.

이렇게 우리가 먹는음식 마시는 공기 일하는 작업장에서의

화학물질은 만성피로증후군의 원인이라는 사실은 이런연구결과

를 보면 대단히 명확해지고 실제로 이런 사실을 명심하면

우리는 이병의 예방법을 손쉽게 알수도있다.

또한 치료에도 이런 독성물질에 노출되지 않는 것과 농약섭취를

않하는 것이 얼마나 중요하다는 사실을 알게해주는 것이다.

 

 

11.최근 발표된 연구논문들을 원문으로 계제합니다

이렇게 많은 만성피로증후군에대한 논문들이 나오고있읍니다

 

Ferrari R.  The biopsychosocial model-a tool for rheumatologists.
Baillieres Best Pract Res Clin Rheumatol. 2000 Dec;14(4):787-795.
PMID: 11092802

De Becker P, Roeykens J, Reynders M, McGregor N, De Meirleir K.
Exercise Capacity in Chronic Fatigue Syndrome.  Arch Intern Med. 2000
Nov 27;160(21):3270-3277.  PMID: 11088089

Altemus M, Dale JK, Michelson D, Demitrack MA, Gold PW, Straus SE.
Abnormalities in response to vasopressin infusion in chronic fatigue
syndrome.  Psychoneuroendocrinology.  2001 Feb 1;26(2):175-188.
PMID: 11087963

Hannan KL, Berg DE, Baumzweiger W, Harrison HH, Berg LH, Ramirez R,
Nichols D.  Activation of the coagulation system in Gulf War Illness:
a potential pathophysiologic link with chronic fatigue syndrome. A
laboratory approach to diagnosis.  Blood Coagul Fibrinolysis. 2000
Oct;11(7):673-8.  PMID: 11085289; UI: 20535739

Neeck G, Crofford LJ.  Neuroendocrine perturbations in fibromyalgia
and chronic fatigue syndrome. Rheum Dis Clin North Am.  2000
Nov;26(4):989-1002.  PMID: 11084955; UI: 20537125

Naschitz JE, Rosner I, Rozenbaum M, Gaitini L, Bistritzki I,
Zuckerman E, Sabo E, Yeshurun D.  The capnography head-up tilt test
for evaluation of chronic fatigue syndrome.  Semin Arthritis Rheum.
2000 Oct;30(2):79-86.  PMID: 11071579; UI: 20521258

Starr A, Scalise A, Gordon R, Michalewski HJ, Caramia MD.
Motor cortex excitability in chronic fatigue syndrome.
Clin Neurophysiol.  2000 Nov 1;111(11):2025-2031.  PMID: 11068238

Jason LA, Taylor RR, Kennedy CL, Jordan K, Song S, Johnson DE, Torres
SR.  Chronic fatigue syndrome: sociodemographic subtypes in a
community-based sample.  Eval Health Prof. 2000 Sep;23(3):243-63.
PMID: 11067190; UI: 20419399

Gelman IH, Unger ER, Mawle AC, Nisenbaum R, Reeves WC.
Chronic fatigue syndrome is not associated with expression of
endogenous retroviral p15E.  Mol Diagn. 2000 Jun;5(2):155-6. No
abstract available.  PMID: 11066017; UI: 20520168

Brace MJ, Scott Smith M, McCauley E, Sherry DD.  Family reinforcement
of illness behavior: a comparison of adolescents with chronic fatigue
syndrome, juvenile arthritis, and healthy controls.  J Dev Behav
Pediatr. 2000 Oct;21(5):332-9.  PMID: 11064960; UI: 20516773

Knook L, Kavelaars A, Sinnema G, Kuis W, Heijnen CJ.
High nocturnal melatonin in adolescents with chronic fatigue
syndrome.  J Clin Endocrinol Metab. 2000 Oct;85(10):3690-2.
PMID: 11061525; UI: 20513703

Goudsmit E.  Chronic fatigue syndrome and depression.
Br J Psychiatry.  2000 Nov;177:470.  PMID: 11060009; UI: 20514118

Greenlee JE, Rose JW.  Controversies in neurological infectious
diseases.  Semin Neurol. 2000;20(3):375-86.  PMID: 11051301; UI:
20503597

Couper J.  Chronic fatigue syndrome and Australian psychiatry:
lessons from the UK experience.  Aust N Z J Psychiatry. 2000
Oct;34(5):762-9.  PMID: 11037362; UI: 20488833

Taylor RR, Jason LA, Torres A.  Fatigue rating scales: an empirical
comparison.  Psychol Med. 2000 Jul;30(4):849-56.  PMID: 11037093; UI:
20488564

Afari N, Schmaling KB, Herrell R, Hartman S, Goldberg J, Buchwald DS.
Coping strategies in twins with chronic fatigue and chronic fatigue
syndrome.  J Psychosom Res. 2000 Jun;48(6):547-54.  PMID: 11033373;
UI: 20491041

Fiedler N, Lange G, Tiersky L, DeLuca J, Policastro T, Kelly-McNeil
K, McWilliams R, Korn L, Natelson B.  Stressors, personality traits,
and coping of gulf war veterans with chronic fatigue.  J Psychosom
Res. 2000 Jun;48(6):525-35.  PMID: 11033371; UI: 20491039

White C, Schweitzer R.  The role of personality in the development
and perpetuation of chronic fatigue syndrome.  J Psychosom Res.  2000
Jun;48(6):515-24.  PMID: 11033370; UI: 20491038

Hickie IB, Wilson AJ, Wright JM, Bennett BK, Wakefield D, Lloyd AR.
A randomized, double-blind placebo-controlled trial of moclobemide in
patients with chronic fatigue syndrome.  J Clin Psychiatry.  2000
Sep;61(9):643-8.  PMID: 11030484; UI: 20483401

Dalby JT.  Chronic fatigue syndrome and memory complaints.  Scand J
Rheumatol. 2000;29(4):271-2.  PMID: 11028853; UI: 20479824

Spath M, Welzel D, Farber L.  Treatment of chronic fatigue syndrome
with 5-HT3 receptor antagonists--preliminary results.  Scand J
Rheumatol Suppl. 2000;113:72-7.  PMID: 11028837; UI: 20479808

Van Houdenhove B, Vanthuyne S, Neerinckx E.  Chronic fatigue
syndrome.  Am J Med. 2000 Aug 15;109(3):257-9.  PMID: 11023437; UI:
20459997

Jason LA, Taylor RR, Kennedy CL.  Chronic fatigue syndrome,
fibromyalgia, and multiple chemical sensitivities in a
community-based sample of persons with chronic fatigue syndrome-like
symptoms.  Psychosom Med. 2000 Sep-Oct;62(5):655-63.  PMID: 11020095;
UI: 20470774

Nisenbaum R, Jones A, Jones J, Reeves W.  Longitudinal analysis of
symptoms reported by patients with chronic fatigue syndrome.  Ann
Epidemiol. 2000 Oct 1;10(7):458.  PMID: 11018368

Axe E, Satz P.  Psychiatric correlates in chronic fatigue syndrome.
Ann Epidemiol.  2000 Oct 1;10(7):458.  PMID: 11018367

Jason LA, Taylor RR, Kennedy CL, Song S, Johnson D, Torres S.
Chronic fatigue syndrome: occupation, medical utilization, and
subtypes in a community-based sample.  J Nerv Ment Dis. 2000
Sep;188(9):568-76.  PMID: 11009329; UI: 20462853


 이런 과학적인 근거를 바탕으로 치료는 시작 되는 것입니다.

만성피로증후군은 신경성질환도 정신질환도 아닌 면역성질환이라는

증거가 여기에 있읍니다

 

 

 

 

 

 

 

 

.