INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 15: 109-116, 2005

The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion

system with dehydroepiandrosterone-cortisol annex MITSUO KODAMA and TOSHIKO KODAMA

Kodama Research Institute of Preventive Medicine, 50-5 Chiyogaoka, Chikusaku, Nagoya, Japan

Received May 6, 2004; Accepted October 4, 2004

Abstract. The year 1995 marked the onset of interstitial pneumonia spread in Nagoya, Japan. For the last 9 years, we have been accumulating clinical experience with the disease control using the combination of prophylactic use of anti­biotics and regular practice of megadose vitamin C infusion with either dehydroepiandrosterone-annex or dehydroepi-androsterone-cortisol annex. The purpose of this study is to assess the usefulness of our new treatment system for the control of interstitial pneumonia alias chronic fatigue syndrome. The results obtained are given as follows: i) The long-term maintenance of the above treatment system was effective not only for decreasing the risk for recurrence of active form pneumonia, but also for prevention of malignancy emergence in aged patients with interstitial pneumonia, ii) Evidence is presented to indicate that interstitial pneumonia was associated with increased risk for depression of which the emergence is a candidate subject causally related to the long-term use of glucocorticoid, iii) A patient with both interstitial pneumonia and depression was found to be less responsive to our treatment system. It is suggested that the use of more dehydroepiandrosterone at the sacrifice of Cortisol in the infusion annex may be a choice for the control of both interstitial pneumonia and depression, iv) The description of chronic fatigue syndrome as regards the endo­crinological, epidemiological and psychiatric charateristics are in good agreement with our experience on patients having interstitial pneumonia, evidence in support of our proposal that there is no convincing raesoning to separate chronic fatigue syndrome from interstitial pneumonia, v) The long-term practice of our treatment system for the control of interstitial pneumonia (an autoimmune disease) was found

Correspondence to: Dr Mitsuo Kodama, Kodama Research Institute of Preventive Medicine, 50-5 Chiyogaoka, Chikusaku, Nagoya 464-0005,Japan

Key words: megadose vitamin C infusion, transition ofintersteroid equilibrium, autoimmune disease, interstitial pneumonia, chronic fatigue syndrome, depression, dehydroepiandrosterone-cortisol balance

to suppress the inflammatory process but not the fibrotic process in the long run. vi) A few innovations were made in our treatment system to reduce the risk of bleeding or thrombosis - vascular complications of pneumonia, vii) The merit of our treatment system is to create a new hormonal environment to improve the state of immunodeficiency by use of a non-steroid substance - vitamin C which encounters little resistance from the feedback mechanism of steroid metabolism in the in vivo system.

Introducation

In January 1995, we experienced a flu epidemic in the infant population of Nagoya, Japan, and another surge of chronic type pneumonia attacked the adult population of the same area with a delay of about two months (1). The former with its zenith in January 1995 followed the way of rapid decline to reach its nadir in December of the same year. In contrast, the latter with its zenith in March 1995 has maintained a level that is much higher than the pre-epidemy level (1).

M. Kodama and T. Kodama, members of the medical staff of the Kodama clinic, were afflicted with the same chronic pneumonia in August to September 1995, and made efforts to investigate the nature of the pneumonia as well as the effects of clinical management with both medical staff and outpatients. Results obtained are summarized as follows: i) the patterns of both symptoms and analytical data find good fitness to both the corresponding patterns of interstitial pneumonia and chronic fatigue syndrome (1,2). So far, we found no evidence to indicate that the above 2 autoimmune disorders should be separated as 2 distinct existences, ii) A patient with active form of interstitial pneumonia (fever, tachycardia and loss of appetite) can better be controlled by combined use of antibiotics (erythromycin and chlor­amphenicol) and megadose vitamin C infusion with dehydroepiandrosterone-cortisol annex than by a single use of any 2 medical manipulations, iii) Long-term observation indicates that prophylactic practice of the above 2 manipulations (continual intake of 2 antibiotics and magedose vitamin C infusion with 2 steroid annexes) rather than the restriction of 2 therapeutic manipulations to an active form of chronic pneumonia was distinctly favorable for either arresting pneumonia progression or preventing outbreak of complications such as blood coagulation-linked

110 KODAMA and KODAMA: INTERSTITIAL PNEUMONIA ALIAS CHRONIC FATIGUE SYNDROME

circulatory disease or manifestation of malignancy, iv) The use of glucocorticoid annex in the treatment of interstitial pneumonia alias chronic fatigue syndrome should be restricted to its minimal effective dose when a patient has an inclination to depression, because the administration of glucocorticoid to a depression-prone patient may aggravate the lung disease by inducing the predisposed sleeplessness of the patient.

Four members of the medical staff of Yonsei University College of Medicine, Seoul, Korea, visited the Kodarna clinic to discuss the usefulness of the dehydroepiandrosterone (DHEA)-annexed vitamin C infusion therapy for autoimmune disease in general. It was noted that our megadose vitamin C infusion system has undergone some theoretical and technical innovations to meet clinical problems derived from a variety of autoimmune diseases including interstitial pneumonia alias chronic fatigue syndrome (CFS). Thus, we were motivated to write a report to supplement the content of our twin reports with the main theses of 'The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS)' (1,2).

Materials and methods

This study is an extension of ref s. 1 and 2, and the description of Materials and methods which had already been presented in the twin reports will be reduced to the minimum ensuring comprehension.

We started a clinical study of interstitial pneumonia alias chronic fatigue syndrome in 1995. The diagnosis of interstitial pneumonia was made on the basis of long-lasting throat pain, fatigue, malaise, dyspnea, unstable sleep, and above all the manifestation of reticulonodular and/or diffuse patterns in the lower lung fields bilaterally, more on the right, as detected by use of both the posteroanterior and lateral chest X-ray (3).

Our pneumonia study covers a time range from 1995 to 2004, and includes outpatients and 2 medical staff of the Kodarna clinic, 2 long-term follow-up cases of interstitial pneumonia. Regular practice of megadose vitamin C infusion with dehydroepi-androserone (DHEA) annex, intermittent intramuscular injection of 25 mg Cortisol acetate/1 g kanamycin set and continual oral intake of erythromycin and chloramphenicol constituted the core of interstitial pneumonia in the Kodarna clinic. The megadose vitamin C infusion set contained 4-8 grams of sodium ascorbate, cardial stimulant (vitacampher or Coffeine sodium bezoate) and DHEA, 500 mg or less/bag, disolved in 500 ml of 5% glucose solusion bag. The frequency of both the megadose vitamin C infusion treatment and the i.m. injection of Cortisol/ kanamycin set varied from once biweekly to twice weekly depending on the clinical feasibility of a pneumonia patient. At later stages of our pneumonia study, we started to add novo-heparin as a new annex to minimize the risks for both thrombosis and bleeding. At later stages, active interstitial pneumonia was often found to increase the risk of inducing fatal bleeding by way of disseminated intravascular coagulation abridged DIC (4). The quantitative ratio between DHEA in the vitamin C infusion set and Cortisol in the i.m.

injection set was also subject to change as will be exemplified later in Results - a dynamic aspect of the steroid therapy of autoimmune disease in general. Dermatomyositis was an autoimmune disease that was known to be very often associated with the presence of interstitial pneumonia in one and the same patient, as indicated in the authentic texbook of Internal Medicine (5). We experienced that the skin lesion (dermatomyositis) of one patient with interstitial pneumonia was dramatically improved by the local application of one skin cream containing DHEA but not by that of another skin cream containing Cortisol. The reasoning for the differential effects of 2 steroid creams will also be given in Discussion of this report.

Results

Midterm follow-up study of interstitial pneumonia under the control of the megadose vitamin C infusion with dehydro-epiandrosterone/cortisol (D-C) annex. Fig. 1 presents the clinical course of a 34-year old female with interstitial pneumonia who visited our clinic on May 8, 2002. For the past 4 days, she had been in bed from fever (up to 37.3°C), night sweat and loss of appetite (Case 1). Cardial depression and tachycardia were noted by a routine examination (blood pressure 102-75 with pulse rate 102). By chest X-ray test, interstitial pneumonia was found in both the right and left lungs. In Fig. 1, the primary 2 magadose vitamin C infusions without DHEA annex failed to improve pneumonia signs (fever and tachycardia) but the secondary 3 megadose vitamin C infusions with DHEA annex normalized the 2 pneumonia parameters. On July 17, 2002, she finished her 9th vitamin C infusion and ceased to come to our clinic believing that she was free from the disease without any sign of pneumonia. She came back on June 14, 2003 to our clinic with moderate fever (up to 39°C), fatigue, soft stool and loss of appetite of 2 weeks' duration. Roentgenologically, the pulmonary lesions were worse especially at the left lower field. Her cardial function was depressed with a blood pressure of 98-63 and pulse rate of 98. The same combination of antibiotic therapy (erythromycin and chloramphenicol), i.m. injection of Cortisol (25 mg) and kanamycin (1 g), and megadose vitamin C infusion with D-C annex was resumed. This time, unstable sleep was also recorded. An anti-depressive tranquilizer Depas was added to the oral set of medicine. Her leucocyte count rose to 13000 on December 19, 2003 and to 12600 on February 5, 2004. Through the fight against her pneumonia, quantitative elevation of D (dehydroepiandrosterone) in relative weight to C (Cortisol phosphate) and incessant use of anti-depressants (Depas or Dogmatyl) were beneficial for the suppression of her pneumonia. It is indicated that insomnia (sign of depression) should be counteracted by increase of D/P ratio in the vitamin C infusion set and use of powerful anti-depressant pills to treat advanced interstitial pneumonia. By April 6, 2004, her fight against pneumonia was going on with a blood pressure of 99-64 and pulse rate of 69. The magadose vitamin C infusion kit used on that day contained 4 mg DHEA and 50 mg Cortisol phosphate.

On January 5, 2004, a 69-year old male came to the Kodarna clinic with short-lived nausea (angina fit), insomnia,

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 15: 109-116, 2005 111

Figure 1. Chronological changes of pneumonia signs in Case 1 under the control of megadose vitamin C infusion treatment with (M+) and without (M") dehydroepiandrosterone annex.

loss of appetite, fatigue and fever above the line of 38°C of 3-days' duration. In the routine test of the same day, high leucocyte count (21300) and cardial overload (blood pressure 110-80 and pulse rate 106) were noted. In the chest X-ray test, interstitial pneumonia of an advanced stage was manifested in both the right and left lungs. Signs of dermatomyositis were persistent in his body for the last 10 years. Fig. 2 illustrates the clinical course of the above Case 2. Sequential practice of megadose vitamin C infusion with D-C annex alone was not powerful enough to control advanced interstitial pneumonia with insomnia. The intake of an anti-depression agent (sulpiride alias Dogmatyl), as started on the 7th day of pneumonia treatment, normalized both body temperature and pulse rate in Case 2 who started working 15 days after the onset of pneumonia treatment in our clinic. Roentgenologicl improvements were observed on March 31, 2004. By the

date of April 1, 2004, his pneumonia treatment with the antibiotics intake and the megadose vitamin C infusion with D-C annex is still going on together with the daily intake of Dogmatyl, 3 tabs/day. The vitamin C infusion kit used on that day contained 17 mg D and 50 mg Cortisol phosphate. The patient (Case 2) still has exertional shortbreath, sore throat and cough, but not itching skin rash. The leucocyte count dropped to a level of 9200 on March 11 of 2004.

Long-term follow-up study of interstitial pneumonia under the control of megadose vitamin C Infusion with D-C annex. The two members of the medical staff of the Kodarna clinic, (Case 3) and (Case 4) were afflicted with interstitial pneumonia alias chronic fatigue syndrome in the summer of 1995. The clinical course of Case 3 in 1995 and early 1996 was presented in ref. 2 which placed much emphasis on the comparison of therapeutic effects of megadose vitamin C infusions with and without dehydroepiandrosterone annex. Initially, 1000 ml of infusion liquid containing a total of 16 g vitamin C (8 g of vitamin C for each 500 ml bag) was given to Case 3 on Monday and Thursday every week. The DHEA annex (100 mg in weight) was used only once a week. A continual intake of 2 antibiotics and intermittent practice of an i.m. injection of cortisol/kanamycin (CK) was practiced whenever hoarseness manifested itself as the side-effect of DHEA.

In parallel with the progress of time, the frequency of hoarseness (and also the frequency of CK injection) increased as shown in the upper line of Table I. To meet the changing situation of pneumonia control, a reduced dose (4 mg) of DHEA annex was used for every megadose vitamin C infusion so that a total of 8 mg DHEA was consumed every week for the pneumonia control of Case 3. In spite of the above reduction of DHEA in the vitamin C infusion, the number of CK injection kept on increasing till the year 2002 (Table I, progression of masculinization of the vocal chord). In addition, there were signs indicating that the blood circulation system

Figure 2. Clinical course of Case 2 with inclination to insomnia under the control of megadose vitamin C infusion treatment with dehydroepiandrosterone annex (+).

112 KODAMA and KODAMA: INTERSTITIAL PNEUMONIA ALIAS CHRONIC FATIGUE SYNDROME

Table I. Relationship between clinical nuisances and therapeutic innovations of pneumonia control in Case 3.

Abbreviations: "Cortisol acetate + kanamycin. ba-trans-7t oxocamphor or Coffeine sodium benzoate.

was entering into a stage of crisis: electrocardio-graphically, Case 3 in 1995 was associated with 2 disorders - inverted T and inferior infarction (suspected). On November 27, 2002, the patient felt distinct pain at the heart region. He received i.v. injection of an anticoagulant kit (heparin), and heart pain vanished instantaneously. In the time range of November of 2002 to January of 2003, the outbreak of arhythmia such as atrial fibrilation or atrial flatter was clearly increasing in incidence - a warning that heralds the risk increase of fatal thrombosis. A number of innovations were introduced into both the vitamin C infusion kit and the intake of a drug set: the new megadose vitamin C infusion set contained novo-heparin 500 U, Cortisol phosphate 50 mg, cardial stimulater 1 ampoule (vitacampher or Coffeine sodium benzoate), DHEA 50 mg and vitamin C 16 g in one liter infusion liquid, and a new cardial stimulator (aminophylin powder, 0.3 g/day) was added to the old oral drug set to fortify cardial function, as shown in Table I. Surprisingly, the electorocardiogram analysis, as conducted on February 4, 2004, revealed one minor abnormal change - prolongation of P-R time (Table I, bottom line). Thanks to the enlistment of Cortisol phosphate as the new member of the vitamin C infusion kit, the frequency of CK injection (upper line of Table I) dramatically decreased in 2003 and 2004. It was indicated that the use of the new vitamin C infusion kit succeeded in eliminating the deteriolating changes of the arterial wall including the heart in Case 3. The purpose of new enlistment of kanamycin (an antibiotic) in the oral medicine set is to test the possibility of whether or not the bacterial colony in the

lung of Case 3 is now becoming resistant to chloramphenicol action. This problem is still under investigation.

Fig. 3 compares the clinical course of Case 3 in January for each of 9 years in terms of 2 pneumonia parameters -pulse rate and leucocyte count. As judged from the second parameter (leucocyte count), the efficacy of pneumonia countrol for January could be ranked as 'excellent' in the years 1996, 1997 and 2001. Intermittent outbreak of acute pneumonia, as expressed in terms of leucocytosis surge, took place in the years 1998, 1999, 2000, 2003 and 2004. It is noteworthy that, except for a few sets, a rise of leucocyte count does not accompany another consonant rise of pulse rate in all of the 9 scatter diagrams - a finding to indicate that a rise of leucocyte count is a marker of which the diagnostic significance for assessing the emergence of acute pneumonia is to be limited. In spite of the above statement, the changes of both leucocyte count and pulse rate for the years 2003 and 2004 are distinctly less stable than those for the year 2001. In addition, the putative regression lines of pulse rate data is increasing in height in parallel with the chronological order from AD 2000 to AD 2004. It is concluded that the functional change of pulmonary gas exchange is following a way of declination. By inspection, the profile of leucocyte count is gradually taking the form of Fourier series from AD 2000 to AD 2004. The physiological significance of the above transition remains unknown.

Case 4, a 75-year female, had undergone surgical therapy of fibroadenoma of her breast at her young age. In 1993, the X-ray test of the chest revealed the presence of pathological

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1) Heparin 500 U 2) Cortisol phosphate 50 mg 3) Cardial stimulator11 1A

Oral intake of new drugs 1) Kanamycin 2) Aminophyllin

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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 15: 109-116,2005 113

Figure 3. Clinical course of Case 3 from 1996 to 2004, as controlled by megadose vitamin C infusion treatment with dehydroepiandrosterone/ Cortisol annex.

years to reach that size. The causal relationship between the genesis of an autoimmune disease and the genesis of malignancy in an aged population has been known with lung cancer (interstitial pneumonia) and multiple neoplasis including myelogenic leukemia (dermatomyositis) (see refs. 5 and 6). Two years post-operation, she was found to have local tumor recurrence, and the necessity of anti-pneumonia therapy became all the more urgent, because the anti-tumor agent now in use (cyclophosphamide) is known to accelerate the progression of interstitial pneumonia. Before closing the present section, we feel that the name and frequency of malignant growth found in our clinic since 1996 will be worth mentioning: colon cancer (1); lung cancer (2); pancreas cancer (1); cardia (stomach) cancer (1); ovarian cancer (1); breast cancer (Case 4). It is our impression that insufficient practice of either megadose vitamin C infusion therapy or oral intake of antibiotics is associated with manifestation of malignancy. A subject with cardia cancer had refused to start any medical treatment after hearing our diagnosis - interstitial pneumonia. Three years later, he was found to have cardia cancer, and underwent radical operation. Soon after leaving the hospital, he had to come back to the hospital to start the treatment of active form of pneumonia. He is sill alive with distinct cough seisure and without a sign of tumor recurrence. Two subjects with cancers of the lung and the pancreas were associated with a year-long blanc period after leaving our clinical office. The lung cancer patient passed away from rapid tumor progression, and the pancreas cancer patient is still alive for over one year under megadose vitamin C infusion therapy in spite of lack of radical operation (technically impossible).

changes of her lower lobes of both sides. In the absence of pneumonia-like complaints, she failed to start prophylactic intake of antibiotics until the turn of the year from 1995 to 1996. On January 2 of 1996, she felt sick, and her chest X-ray of that day revealed that she was afflicted with an active form of interstitial pneumonia. From that day on, she started to undergo regular practice of megadose vitamin C infusion (8 g vitamin C with dehydroepiandrosterone annex twice every week and also continual intake of 2 anti-biotics. In early October of 1996, while abroad, she felt pulse acceleration (sign of acute pneumonia) in the absence of antibiotics intake. After that experience, she has been observing the regular practice of megadose vitamin C infusion therapy (8 g of ascorbic acid and 50 mg DHEA in 500 ml of glucose solution) twice a week. She is also taking 2 antibiotics regularly. In spite of the above prophylactic cautions she again felt pneumonia-like signs on December 21, 1996, and the chest X-ray taken on that day indicated that she was again associated with acute form of interstitial pneumonia, which was later settled by intensifying anti-pneumonia maneuvers including rest therapy. In mid-June of 2000, she was found to have breast cancer at the r-front chest, and underwent radical surgery on June 26, 2000. Is there any causal relationship between the persistence of interstitial pneumonia and later (an intermission of 4 years) emergence of breast malignancy? Dr S. Miura, a surgeon in charge of her radical operation in the Aichi Cancer Center Hospital, stated that the new growth, based on his life-long experience, could have taken over 3

The clinical course of interstitial pneumonia with history of depression. A 41-year old female came to our clinic on November 15, 2003 with the complaints of 2 weeks long subfebris, throat pain, neck toughness, cough and sputum. She had the history of pneumonia and depression that had taken place 4 years earlier. The routine examination including chest X-ray photography indicated that she was associated with interstitial pneumonia with cardial depression (blood pressure 120-98, with pulse rate 96 and leucocyte count 8300). Tachycardia (up to 113 beats/min), intermittent hypothermia and subfebris and angina pectoris (chest pain) persisted till February 7, 2004. Roentgenological^, chronic type infiltration shadow was present at the lower field of both right and left lungs (antero-posterior photo) and at the apex to upper vertebral region and the heart region (the lateral photo) also on the day of first visit. Distinct improvement was observed at the apex to vertebral region of the lateral X-ray of December 20, 2003, but no change was observed with the antero-posterior photo of the same day. In ECG analysis slight S-T depression was observed on December 27. From January 24 on, her pneumonia with cardial depression became worse with dyspnea, insomnia and loss of appetite. Roentgenological analysis was also in support of the findings of the routine test (aggravation of both the apex region and the heart region in the lateral X-photo and reduction of the dark tint of the anteroposterior photo taken on January 31, 2004). The grade of S-T depression became more distinct as compared with the ECG of December 27, 2003, and blood

114 KODAMA and KODAMA: INTERSTITIAL PNEUMONIA ALIAS CHRONIC FATIGUE SYNDROME

Table II. Chronological transition of the medical concept as well as clinical control of chronic pneumonia, as based on the descriptions of textbooks from 1951 to 2001.

pressure of 113-77 with pulse rate 105 and leucocyte 9400 all pointed to a recurrence of an active pneumonia. The minimal intake of Depas (a light anti-depressant) has been maintained except for the first week of her medical care, Sulpiride being intolerable because of its side-effect - finger tremor. In search of optimal doses of Cortisol and DHEA in the infusion/injection therpy, we reached the conclusion that a combination of minimal dose of Cortisol and maximum tolerable dose of DHEA could lead to the control of both pneumonia and depression. The shift of steroid ratio of Cortisol versus DHEA is now in progress with this patient having dual burdens of interstitial pneumonia and depression. For reference, we started her dual steroid therapy on November 29, 2Q03, with a combination of Cortisol phosphate 100 mg, DHEA 2 mg, vitamin C 6 g in the infusion kit and i.m. injection of kanamycin 1 g and Cortisol acetate 25 mg once weekly, and depression sign (insomnia, dyspnea and loss of appetite) became manifest on January 17 of 2004, a date which was followed by the day of distinct aggravation. Retrospectively, the patient could have been highly vulnerable to the psychogenic action of Cortisol (7).

Discussion

The nature of interstitial pneumonia as an autoimmune disease of the lung was not well recognized before the 1970s, though the clinical importance of this disease as the top killer disease of the lung was known in the 1950s. Table II summarizes the chronological changes in the disease concept as well as the medical treatment of interstitial pneumonia, as extracted

from 6 authentic textbooks of internal medicine from 1951 to 2001 (5,8-12). The differences of opinion between the authentic textbook and our suggestions based on the experience in the Kodama clinic are given as follows: i) The former states that the use of antibiotics should be restricted to the flare-up of active pneumonia. Our experience indicated that the risk of pneumonia flare-up could be minimized by continual use of antibiotics in such a way as to delay (if not arrest) the progression of interstitial pneumonia towards fatal mismatch of function between the lung (complete fibrosis) and the heart. Erythromycin and chloramphenicol will be the choice of the antibiotics treatment. Our experience also suggests that an aged subject with interstitial pneumonia tends to catch malignancy during the blank period (no active control of pneumonia), as described in Results. The author of the latest textbook of internal medicine stated that the 5-year survival rate of this disease ranged from 30 to 50% (12). We can accept the above figure with the patient population in whom the use of antibiotics is restricted to the control of active form pneumonia, ii) The former failed to mention the increased risk of depression in the long-term use of glucocorticoid for the control of interstitial pneumonia. It is interesting to note that a patient with chronic fatigue syndrome has an increased risk of depression (13). Furthermore, the epidemiological study of chronic fatigue syndrome cluster confirmed predominance of female over male and restriction to adult age (13), 2 characteristics that were noted in our cluster population of interstitial pneumonia in 1995, in Nagoya, Japan (1). iii) The same author of 'chronic fatigue syndrome' (13) directed his attention to the

Editor/author of textbook (publication year)11

Cecil/Loeb(1951)

Heilmeyer (1957)

Harrison (1962)

Cecil/Loeb(1971)

Harrison (1987)

Harrison (2001)

Alleged nature of disease

Chronic bronchitis

Unclear

Unclear

Collagen disease

Autoimmune disease

Autoimmune disease

"Refer to the References section for details of the textbooks.

Recommended therapy

Symptomatic therapies

Use of both antibiotics and cortisone/ACTH

Use of antibiotics for active infection but not for prophylaxis

Use of adrenal steroids

Use of antibiotics for active infection only, and another use of oral corticosteroids for the control of inflammation processes. Supplementary use of the same steroids via the i.V. route

Parallel use of glucocorticoids and cytotoxic agents

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 15: 109-116,2005 115

fact that a pat ient with chronic fatigue syndrome was associated with a depression of plasma Cortisol combined with an increase of plasma ACTH. It might not be a mere coincidence that glusocorticoid is accepted as a benediction for the control of interstitial pneumonia, whereas the same steroid exerts an aggravat ing effect on depression. We anticipate that an imbalance between Cortisol and dehydro-epiandrosterone is somehow implicated in the etiologies of 2 entities of disease - interstitial pneumonia alias chronic fatigue syndrome and depression.

What was the meaning of megadose vitamin C in the control of interstitial pneumonia? Ref. 2 cited a series of our reports to prove that vitamin C somehow increases the production of Cortisol via the pituitary ACTH route (14-16). Ref. 2 itself presented evidence to indicate that 17-OHCS (a family of urinary steroid metabolites derived from plasma Cortisol) significantly increased in response to the practice of megadose vitamin C infusion. In clinical medicine, good responsiveness to the therapeutic action of glucocorticoid is a common proper ty that is shared in common by all autoimmune diseases - a finding to suggest that Cortisol may play a cardinal role in the genesis and further development of an autoimmune disease.

In Case 3, combination of megadose vitamin C infusion with DHEA or DHEA-cortisol annex and continual intake of erythromycin-chloramphenicol set has been maintained since the establishment of the treatment system in mid-April of 1996, as described in ref. 2. Roentogenologically, the antero­posterior X-ray of the disease onset was associated with bronchopneumonia-like changes at the right lower area, and the corresponding lateral X-ray photo was associated with a sarcoidosis-like mass at the hilus area, and with massive soft shadows at the front-below area, the apex area and the back lower area (2). Recently the same pair of X-ray photos were taken for compar ison on February 3, 2004. The latest anteroposterior photo was associated with lean shadows that looked harder and more streaky as compared with the photo of d isease onset . In the init ial an te ropos te r io r photo , pathological changes were seen only at the right lower area. In the latest one, they extended to the right upper area as well as the left lower area, and assumed the form of fine fibrosis. The latest anteroposterior photo looked less dark in its background tint as compared with initial antroposterior photo - a finding to suggest that fibrotic change has spread to the upper right lung lobe in spite of 9 years ' treatment. In contrast, the latest lateral photo in its tint looked much darker than the initial one. The cloud-like shadows of the initial stage photo was replaced by streaky shadows as a whole, and by some small cloudy patches at the hilus and lower-back areas. Taken together, exdudactive shadow of the initial stage of interstitial pneumonia was almost extinguished thanks to the persistence of the (antibiotics/megadose vitamin C infusion) control system, but the progression of lung fibrosis was not completely arrested in spite of constant inflow of 2 steroids (Cortisol and DHEA).

It will be pertinent for us to recall here the fact that all subjects who developed malignancy in later ages of life represent specified interstitial pneumonia patients who had failed to accept our treatment system as such sometime before the breakout of malignancy, as mentioned in Results.

One should also keep in mind that the traditional Cortisol adminis t ra t ion therapy sooner or later causes adrenal atrophy which in turn leads to a reduction of therapeutic effect of exogenous Cortisol and ultimately to either endless increase of corticol dosage or catastrophic abst inence syndrome. The long-term use of megadose vi tamin C infusion is expected to protect the host adrenal from a suppressing action of exogenous Cortisol. That is the reason why Case 3 has tolerated the use of exogenous Cortisol for 9 years without side-effect of Cortisol (Fig. 3). It seemed that the feed-back mechanism of the host could have undertaken a new balance shift between exogenous Cortisol and endogenous Cortisol through the insertion of an excess amount of vi tamin C into the in vivo sys tem. More specifically, the above creation of a new balance system, as induced by use of a non-hormone substance (vitamin C), will become a good example for remolding the framework of feedback mechanism.

The problem of whether or not the genesis and further development of depression are implicated in some disorder of steroid metabolism is to be answered in future studies.

References

1. Kodarna M, Kodarna T and 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 10: 585-596, 1996.

2. Kodarna M, Kodarna T and 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 10: 575-584, 1996.

3. Hirschmann JV and Muray JF: Pneumonia and lung abscess. In: Harrison's Principles of Internal Medicine. 11th edition. Braunwald E, Isserbacher KJ, Petersdorf RG, Wilson JD, Martin J B and Fauci AS (eds). McGraw-Hill Book Company, New York, pi077, 1987.

4. Handin RI: Disorders of coagulation and thrombosis. In: Harrison's Principles of Internal Medicine. 15th edition. Braunwald E, Fauci AS, Kasper DL. Hauser SL, Longo DL and Jameson JL (eds). MacGraw-Hill, Medical Publishing Division, New York, p754, 2001.

5. Crystal RG: Interstitial lung disorders. In: Principles of Internal Medicine. 11th edition. Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB and Fauci AS (eds). McGraw-Hill Book Company, New York, ppl095-1102, 1987.

6. Bradley WG: Dermatomyositis and polymyositis. In: Harrison's Principles of Internal Medicine. 1 1th edition. Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB and Fauci AS (eds). McGraw-Hill Book Company, New York, p2070, 1987.

7. Thomas JA and Mawhinney: Pharmacology of the adreno­cortical steroids. In: Synopsis of Endocrine Pharmacology. University Park Press, Baltimore, pp76-179, 1973.

8. Richards DW: Chronic bronchitis. In: A Textbook of Medicine. 8th edition. Cecil RL and Loeb RF (eds). W.B. Saunders Co., Philadelphia, pp824-827, 1951.

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