New Studies Depression and Insomnia 1. Am J Chin Med. 2009;37(5):837-42. The effect on serotonin and MDA levels in depressed patients with insomnia when far-infrared rays are applied to acupoints. Chang Y, Liu YP, Liu CF. Jenteh Junior College of Medicine and Nursing Management, Miaoli, Taiwan. Abstract Little is known about the effect of far-infrared rays (FIR) on serotonin and malondialdehyde levels in depressed patients with insomnia. The purpose of this study is to assess the effect of far-infrared rays on depressed people with insomnia. A randomized design was used to determine this effect. A total of 70 inpatients were recruited with the clinical diagnosis of depression with sleep disturbance. In the experimental group, FIR was applied to three chosen acupuncture points by a patch-like sticker for a period of 15 minutes twice a week. The three acupuncture points are Nei-Kuan (PC6), Shenmen (HT7) and Sanyinjiao (SP6). The total duration of experiment was four weeks. For both experimental and control groups, serum levels of serotonin (5HT) and malondialdehyde (MDA) were examined before and after the introduction of FIR. The experimental group revealed disparate changes over different dependent variables, in which serotonin increased but MDA decreased after the introduction of FIR. These observations indicate that the serotonin pathway is involved in the pathophysiological mechanism responsible for the damaging effects of MDA on depressed patients with insomnia. 2. Psychosom Med. 2005 Jul-Aug;67(4):643-7. Repeated thermal therapy diminishes appetite loss and subjective complaints in mildly depressed patients. Masuda A, Nakazato M, Kihara T, Minagoe S, Tei C. Psychosomatic Medicine, Respiratory and Stress Care center, Kagoshima University Hospital, Kagoshima City, Japan. Abstract OBJECTIVE: We observed that repeated thermal therapy improved appetite loss and general well-being in patients with chronic heart failure. The purpose of this study is to clarify the effects of repeated thermal therapy in mildly depressed patients with appetite loss and subjective complaints. METHODS: Twenty-eight mildly depressed inpatients with general fatigue, appetite loss, and somatic and mental complaints were randomly assigned to thermal therapy group (n = 14) or nonthermal therapy group (n = 14). Patients in the thermal therapy group were treated with 60 degrees C far-infrared ray dry sauna for 15 minutes and were then kept at bed rest with a blanket for 30 minutes once a day, 5 days a week for a total of 20 sessions in 4 weeks. RESULTS: Four weeks after admission, somatic complaints, hunger, and relaxation scores significantly improved (p < .001, p < .0001, p < .0001, respectively) and mental complaints slightly improved (p = .054) in the thermal therapy group compared with the nonthermal therapy group. Furthermore, the plasma ghrelin concentrations and daily caloric intake in the thermal therapy group significantly increased compared with the nonthermal therapy group (p < .05). CONCLUSIONS: These findings suggest that repeated thermal therapy may be useful for mildly depressed patients with appetite loss and subjective complaints. Diabetes 3. Acta Med Okayama. 2010 Apr;64(2):143-7. The effect of leg hyperthermia using far infrared rays in bedridden subjects with type 2 diabetes mellitus. Kawaura A, Tanida N, Kamitani M, Akiyama J, Mizutani M, Tsugawa N, Okano T, Takeda E. Department of Physical Therapy, School of Health Science, KIBI International University, Takahashi, Okayama 716-8508, Japan. Abstract We examined the effect of leg hyperthermia on oxidative stress in bedridden subjects with type 2 diabetes mellitus using 15-min sessions of far infrared rays over a two-week period. Four subjects (male 1, female 3) incapacitated by a stroke were recruited for this study. All patients were admitted to Takahashi Central Hospital and ate the same hospital meals. Fasting plasma glucose, HbA1c, tumor necrosis factor (TNF)alpha, free fatty acid, leptin, adiponectin and plasma 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) levels as a marker of oxidative stress were measured on admission, just before and 2 weeks after local heating of the leg. Results showed that plasma total 8-epi-PGF2alpha levels were decreased significantly while TNFalpha levels were increased significantly. On the other hand, glucose, HbA1c, free fatty acid, leptin and adiponectin levels were not changed during the study period. These results suggest that repeated leg hyperthermia may protect against oxidative stress. Cardiovascular Disease 4. Can Fam Physician. 2009 Jul;55(7):691-6. Far-infrared saunas for treatment of cardiovascular risk factors: summary of published evidence. Beever R. Abstract OBJECTIVE: To review the literature about the health benefits of far-infrared sauna (FIRS) use. QUALITY OF EVIDENCE: A search of Web of Science, EBSCO, Ovid MEDLINE, Ovid HealthSTAR, and EMBASE using the terms far-infrared and sauna, refined by limiting the search to studies of humans published in English, yielded 9 relevant papers (level I or level II evidence). MAIN MESSAGE: Far-infrared saunas are approved by the Canadian Standards Association and are sold to the public. The manufacturers claim numerous health benefits; however, the published evidence to substantiate these claims is limited. Four papers support the use of FIRS therapy for those with congestive heart failure and 5 papers support its use for those with coronary risk factors. CONCLUSION: There is limited moderate evidence supporting FIRS efficacy in normalizing blood pressure and treating congestive heart failure; fair evidence, from a single study, supporting FIRS therapy in chronic pain; weak evidence, from a single study, supporting FIRS therapy in chronic fatigue syndrome; weak evidence, from a single study, supporting FIRS therapy for obesity; and consistent fair evidence to refute claims regarding the role of FIRSs in cholesterol reduction. 5. J Cardiol. 2009 Apr;53(2):214-8. Epub 2009 Jan 18. Waon therapy improves the prognosis of patients with chronic heart failure. Kihara T, Miyata M, Fukudome T, Ikeda Y, Shinsato T, Kubozono T, Fujita S, Kuwahata S, Hamasaki S, Torii H, Lee S, Toda H, Tei C. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Abstract BACKGROUND: We developed a Waon therapy (soothing warm therapy) and have previously reported that repeated Waon therapy improves hemodynamics, peripheral vascular function, arrhythmias, and clinical symptoms in patients with chronic heart failure (CHF). The aim of this study was to investigate the effect of Waon therapy on the prognosis of CHF patients. PATIENTS AND METHODS: We studied 129 patients with CHF in NYHA functional class III or IV who were admitted to our hospital between January 1999 and March 2001. In the Waon therapy group, 64 patients were treated with a far infrared-ray dry sauna at 60 degrees C for 15min and then kept on bed rest with a blanket for 30min. The patients were treated daily for 5 days during admission, and then at least twice a week after discharge. In the control group, 65 patients, matched for age, gender, and NYHA functional class, were treated with traditional CHF therapy. The follow-up time was scheduled for 5 years. RESULTS: Recent, complete follow-up data on each patient were obtained. The overall survival rate was 84.5% (Kaplan-Meier estimate). Twelve patients died in the control group and 8 patients died in the Waon therapy group at 60 months of follow-up. Cardiac events due to heart failure or cardiac death occurred in 68.7% of the control group but only 31.3% of the Waon therapy group (P<0.01) at 60 months of follow-up. CONCLUSION: Waon therapy reduced cardiac events in patients with CHF. This therapy is a promising non-pharmacological treatment for CHF. 6. J Cardiol. 2008 Oct;52(2):79-85. Epub 2008 Aug 27. Beneficial effects of Waon therapy on patients with chronic heart failure: Results of a prospective multicenter study. Miyata M, Kihara T, Kubozono T, Ikeda Y, Shinsato T, Izumi T, Matsuzaki M, Yamaguchi T, Kasanuki H, Daida H, Nagayama M, Nishigami K, Hirata K, Kihara K, Tei C. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduated School of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Abstract BACKGROUND: We conducted a prospective multicenter case-control study to confirm the clinical efficacy and safety of Waon therapy on chronic heart failure (CHF). METHODS: Patients (n=188) with CHF were treated with standard therapy for at least 1 week, and then were randomized to Waon therapy (n=112) or a control group (n=76). All patients continued conventional treatment for an additional 2 weeks. The Waon therapy group was treated daily with a far infrared-ray dry sauna at 60 degrees C for 15min and then kept on bed rest with a blanket for 30min for 2 weeks. Chest radiography, echocardiography, and plasma levels of brain natriuretic peptide (BNP) were measured before and 2 weeks after treatment. RESULTS: NYHA functional class significantly decreased after 2 weeks of treatment in both groups. Chest radiography also showed a significant decrease of the cardiothoracic ratio in both groups (Waon therapy: 57.2+/-8.0% to 55.2+/-8.0%, p<0.0001; control: 57.0+/-7.7% to 56.0+/-7.1%, p<0.05). Echocardiography demonstrated that left ventricular diastolic dimension (LVDd), left atrial dimension (LAD), and ejection fraction (EF) significantly improved in the Waon therapy group (LVDd: 60.6+/-7.6 to 59.1+/-8.4mm, p<0.0001; LAD: 45.4+/-9.3mm to 44.1+/-9.4mm, p<0.05; EF: 31.6+/-10.4% to 34.6+/-10.6%, p<0.0001), but not in the control group (LVDd: 58.4+/-10.3mm to 57.9+/-10.4mm; LAD: 46.3+/-9.7mm to 46.2+/-10.1mm; EF: 36.6+/-14.1% to 37.3+/-14.0%). The plasma concentration of BNP significantly decreased with Waon therapy, but not in the control group (Waon: 542+/-508pg/ml to 394+/-410pg/ml, p<0.001; control: 440+/-377pg/ml to 358+/-382pg/ml). CONCLUSION: Waon therapy is safe, improves clinical symptoms and cardiac function, and decreases cardiac size in CHF patients. Waon therapy is an innovative and promising therapy for patients with CHF. 7. J Cardiol. 2008 Apr;51(2):106-13. Repeated waon therapy improves pulmonary hypertension during exercise in patients with severe chronic obstructive pulmonary disease. Umehara M, Yamaguchi A, Itakura S, Suenaga M, Sakaki Y, Nakashiki K, Miyata M, Tei C. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduated School of Medicine, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima 890-8520, Japan. Abstract OBJECTIVES: Repeated Waon therapy, which uses a far infrared-ray dry sauna system, improved the vascular endothelial function and the cardiac function in patients with chronic heart failure. In patients with chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH) is associated with a poor prognosis. We investigated whether repeated Waon therapy improves PH, cardiac function, exercise tolerance, and the quality of life (QOL) in patients with COPD. METHODS: Consecutive 13 patients with COPD, who met the Global Initiative for Chronic Obstructive Lung Disease criteria and had breathlessness despite receiving conventional treatments, were recruited for this study. They underwent Waon therapy at 60 degrees C in sauna for 15 min following 30 min warmth with blankets outside of the sauna room. This therapy was performed once a day, for 4 weeks. Cardiac function, exercise tolerance, and St. George’s Respiratory Questionnaire (SGRQ) were assessed before and 4 weeks after Waon therapy. RESULTS: Right ventricular positive dP/dt at rest elevated significantly from 397 +/- 266 to 512 +/- 320 mmHg/s (p = 0.024) after the therapy. While the PH at rest did not significantly decrease, the PH during exercise decreased significantly from 64 +/- 18 to 51 +/- 13 mmHg (p = 0.028) after Waon therapy. Furthermore, the therapy prolonged the mean exercise time of the constant load of cycle ergometer exercise test from 360 +/- 107 to 392 +/- 97 s (p = 0.032). The total scores of SGRQ improved from 59.7 +/- 16.9 to 55.3 +/- 17.2 (p = 0.002). In addition, no adverse effects were observed related to Waon therapy. CONCLUSIONS: Repeated Waon therapy improved right ventricular positive dP/dt, PH during exercise, exercise tolerance and the QOL in patients with severe COPD. 8. Photodermatol Photoimmunol Photomed. 2006 Apr;22(2):78-86. Biological effect of far-infrared therapy on increasing skin microcirculation in rats. Yu SY, Chiu JH, Yang SD, Hsu YC, Lui WY, Wu CW. Institute of Molecular and Cellular Biology, Department of Life Science, National Tsing-Hua University, Hsinchu, and Division of General Surgery, Department of Surgery, Veterans General Hospital, Taipei, Taiwan. Abstract BACKGROUND/PURPOSE: Insufficient microcirculation of skin leads to acute and chronic tissue ischemia in cases of trauma, reconstructive surgery, diabetes mellitus and peripheral arterial occlusive disease. The autonomic nervous system and nitric oxide (NO) play important roles in maintaining blood perfusion of the skin. Far-infrared (FIR) therapy provides low energy of light emitted from an artificial radiator and has been used to treat many vascular-related disorders. Nevertheless, the mechanisms through which FIR works remain unclear. The present study aims to test the hypothesis that the effect of FIR is through increasing skin microcirculation by a mechanism other than its thermal effect. METHODS: Sixty rats were used in the present study. A WS TY301 FIR emitter was placed 20 cm above the rats. Skin temperature and blood flow were continuously measured by a K-type thermocouple. Under laboratory control, the abdominal skin temperature steadily increased from 38-39 degrees C, and was kept at constant temperature. Skin microcirculation was measured with a continuous laser Doppler flowmeter. RESULTS: There was no significant change of skin blood flow during FIR treatment. Skin blood flow increased significantly soon after the removal of the FIR emitter. The stimulating effect on skin blood flow was more significant in the rats treated with FIR for 45 min and could be sustained as long as 60 min. These findings suggested a non-thermic biological effect of FIR on skin microcirculation. The promotive effect of FIR on increasing skin blood flow was not influenced by pretreatment of APP (atropine, propranolol and phentolamine), but was suppressed by pretreatment with NG-nitro-L-arginine methyl ester (an endothelial nitric oxide synthase inhibitor). CONCLUSION: In conclusion, FIR therapy exerts a NO-related biological effect to increase skin microcirculation in rats. This might bring into perspective the clinical application of FIR to treat ischemic disease by augmenting L-arginine/NO pathway. 9. Circ J. 2006 Apr;70(4):463-70. Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia. Akasaki Y, Miyata M, Eto H, Shirasawa T, Hamada N, Ikeda Y, Biro S, Otsuji Y, Tei C. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Sakuragaoka, Japan. Abstract BACKGROUND: Nitric oxide (NO), constitutively produced by endothelial NO synthase (eNOS), plays roles in angiogenesis. Having reported that thermal therapy up-regulated the expression of arterial eNOS in hamsters, we investigated whether this therapy increased angiogenesis in mice with hindlimb ischemia. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient mice, which were divided into control and thermal therapy groups. The latter mice were placed in a far-infrared dry sauna at 41 degrees C for 15 min and then at 34 degrees C for 20 min once daily for 5 weeks. Laser Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls (0.79+/-0.04 vs 0.54+/-0.08, p<0.001). Significantly greater capillary density was seen in thermal therapy group (757+/-123 /mm2 vs 416+/-20 /mm2, p<0.01). Western blotting showed thermal therapy markedly increased hindlimb eNOS expression. To study possible involvement of eNOS in thermally induced angiogenesis, thermal therapy was given to mice with hindlimb ischemia with or without N(G)-nitro-L-arginine methyl ester (L-NAME) administration for 5 weeks. L-NAME treatment eliminated angiogenesis induced using thermal therapy. Thermal therapy did not increase angiogenesis in eNOS-deficient mice. CONCLUSION: Angiogenesis was induced via eNOS using thermal therapy in mice with hindlimb ischemia. 10. Circ J. 2005 Jun;69(6):722-9. Repeated sauna therapy increases arterial endothelial nitric oxide synthase expression and nitric oxide production in cardiomyopathic hamsters. Ikeda Y, Biro S, Kamogawa Y, Yoshifuku S, Eto H, Orihara K, Yu B, Kihara T, Miyata M, Hamasaki S, Otsuji Y, Minagoe S, Tei C. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kogoshima, Japan. Abstract BACKGROUND: Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. METHODS AND RESULTS: Normal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39 degrees C followed by 20 min at 30 degrees C. This procedure raised the rectal temperatures by about 1 degrees C. Arterial endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein expressions were examined, and serum concentrations of nitrate were measured. The expression of eNOS mRNA in the aortas of normal controls did not change, whereas those of the TO-2 hamsters decreased with age. Four weeks of sauna therapy significantly increased eNOS mRNA expression in the aortas of TO-2 hamsters compared with those that did not undergo sauna therapy. Sauna therapy also upregulated aortic eNOS protein expression. Serum nitrate concentrations of the TO-2 hamsters were increased by 4 weeks of sauna therapy compared with those that did not undergo sauna. CONCLUSION: Repeated sauna therapy increases eNOS expression and NO production in cardiomyopathic hamsters with heart failure. 11. Circ J. 2004 Dec;68(12):1146-51. Effects of repeated sauna treatment on ventricular arrhythmias in patients with chronic heart failure. Kihara T, Biro S, Ikeda Y, Fukudome T, Shinsato T, Masuda A, Miyata M, Hamasaki S, Otsuji Y, Minagoe S, Akiba S, Tei C. Department of Cardiovascular, Graduate School of Medicine, Kagoshima University, Sakuragaoka, Kagoshima, Japan. Abstract BACKGROUND: The aim of the present study was to determine whether repeated 60 degrees C sauna treatment improves cardiac arrhythmias in chronic heart failure (CHF) patients, because ventricular arrhythmias are an important therapeutic target in CHF. METHODS AND RESULTS: Thirty patients (59+/-3 years) with New York Heart Association functional class II or III CHF and at least 200 premature ventricular contractions (PVCs)/24 h assessed by 24-h Holter recordings were studied. They were randomized into sauna-treated (n=20) or non-treated (n=10) groups. The sauna-treated group underwent a 2-week program of a daily 60 degrees C far infrared-ray dry sauna for 15 min, followed by 30 min bed rest with blankets, for 5 days per week. Patients in the non-treated group had bed rest in a temperature-controlled room (24 degrees C) for 45 min. The total numbers of PVCs/24 h in the sauna-treated group decreased compared with the non-treated group [848+/-415 vs 3,097+/-1,033/24 h, p<0.01]. Heart rate variability (SDNN, standard deviation of normal-to-normal beat interval) increased [142+/-10 (n=16) vs 112+/-11 ms (n=8), p<0.05] and plasma brain natriuretic peptide concentrations decreased [229+/-54 vs 419+/-110 pg/ml, p<0.05] in the sauna-treated group compared with the non-treated group. CONCLUSION: Repeated sauna treatment improves ventricular arrhythmias in patients with CHF. 12. Jpn Heart J. 2004 Mar;45(2):297-303. Repeated sauna therapy reduces urinary 8-epi-prostaglandin F(2alpha). Masuda A, Miyata M, Kihara T, Minagoe S, Tei C. Department of Cardiology, Respiratory and Metabolic Medicine, Kagoshima University, Kagoshima, Japan. Abstract We have reported that repeated sauna therapy improves impaired vascular endothelial function in a patient with coronary risk factors. We hypothesized that sauna therapy decreases urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) levels as a marker of oxidative stress and conducted a randomized, controlled study. Twenty-eight patients with at least one coronary risk factor were divided into a sauna group (n = 14) and non-sauna group (n = 14). Sauna therapy was performed with a 60 degrees C far infrared-ray dry sauna for 15 minutes and then bed rest with a blanket for 30 minutes once a day for two weeks. Systolic blood pressure and increased urinary 8-epi-PGF(2alpha) levels in the sauna group were significantly lower than those in the non-sauna group at two weeks after admission (110 +/- 15 mmHg vs 122 +/- 13 mmHg, P < 0.05, 230 +/- 67 pg/mg x creatinine vs 380 +/- 101 pg/mg x creatinine, P < 0.0001, respectively). These results suggest that repeated sauna therapy may protect against oxidative stress, which leads to the prevention of atherosclerosis. 13. J Am Coll Cardiol. 2001 Oct;38(4):1083-8. Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors. Imamura M, Biro S, Kihara T, Yoshifuku S, Takasaki K, Otsuji Y, Minagoe S, Toyama Y, Tei C. First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Sakuragaoka, Kagoshima, Japan. Abstract OBJECTIVES: We sought to determine whether sauna therapy, a thermal vasodilation therapy, improves endothelial function in patients with coronary risk factors such as hypercholesterolemia, hypertension, diabetes mellitus and smoking. BACKGROUND: Exposure to heat is widely used as a traditional therapy in many different cultures. We have recently found that repeated sauna therapy improves endothelial and cardiac function in patients with chronic heart failure. METHODS: Twenty-five men with at least one coronary risk factor (risk group: 38 +/- 7 years) and 10 healthy men without coronary risk factors (control group: 35 +/- 8 years) were enrolled. Patients in the risk group were treated with a 60 degrees C far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with blankets for 30 min once a day for two weeks. To assess endothelial function, brachial artery diameter was measured at rest, during reactive hyperemia (flow-mediated endothelium-dependent dilation [%FMD]), again at rest and after sublingual nitroglycerin administration (endothelium-independent vasodilation [%NTG]) using high-resolution ultrasound. RESULTS: The %FMD was significantly impaired in the risk group compared with the control group (4.0 +/- 1.7% vs. 8.2 +/- 2.7%, p < 0.0001), while %NTG was similar (18.7 +/- 4.2% vs. 20.4 +/- 5.1%). Two weeks of sauna therapy significantly improved %FMD in the risk group (4.0 +/- 1.7% to 5.8 +/- 1.3%, p < 0.001). In contrast, %NTG did not change after two weeks of sauna therapy (18.7 +/- 4.2% to 18.1 +/- 4.1%). CONCLUSIONS: Repeated sauna treatment improves impaired vascular endothelial function in the setting of coronary risk factors, suggesting a therapeutic role for sauna treatment in patients with risk factors for atherosclerosis. 14. Jpn Circ J. 2001 May;65(5):434-8. Repeated thermal therapy upregulates arterial endothelial nitric oxide synthase expression in Syrian golden hamsters. Ikeda Y, Biro S, Kamogawa Y, Yoshifuku S, Eto H, Orihara K, Kihara T, Tei C. The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan. Abstract It has been previously reported that sauna therapy, a thermal therapy, improves the hemodynamics and clinical symptoms in patients with chronic heart failure and also improves endothelial function, which is impaired in such patients. The present study investigated whether the improvements observed with sauna therapy are through modulation of arterial endothelial nitric oxide synthase (eNOS) expression. Eight male Syrian golden hamsters underwent sauna therapy, using an experimental far infrared-ray dry sauna system, at 39 degrees C for 15 min followed by 30 degrees C for 20 min daily for 4 weeks. Control group hamsters were placed in the sauna system switched off at room temperature of 24 degrees C for 35 min. Immunohistochemistry found greater amounts of the immunoreactive products of eNOS in the endothelial cells of the aorta and carotid, femoral and coronary arteries in the sauna group than in the control group. Western blot analysis also revealed that 4-week sauna therapy significantly increased eNOS expression in aortas by 50% in 4 series of independent experiments with an identical protocol (p<0.01). In reverse transcription polymerase chain reaction assay, the eNOS mRNA in aortas was greater in the sauna group than in controls, with a peak at 1-week of sauna therapy (approximately 40-fold increase). In conclusion, repeated thermal therapy upregulates eNOS expression in arterial endothelium. Hemodialysis (Kidney) 15. Am J Chin Med. 2009;37(2):215-26. Effects of far infrared acupoint stimulation on autonomic activity and quality of life in hemodialysis patients. Su LH, Wu KD, Lee LS, Wang H, Liu CF. Nursing Department, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin County, Taiwan. Comment in: Am J Chin Med. 2009;37(5):1011-2. Abstract Patients receiving regular hemodialysis sessions have been known to suffer from fatigue and depression. This experiment was designed to determine the effects of far infrared ray (FIR) stimulation on acupoints of patients suffering from renal failure who are receiving regular hemodialysis. Patients receiving long-term and regular hemodialysis who volunteered for this procedure were randomly selected to undergo either FIR or heat pad (HP) therapy to determine the impact of FIR treatment on these patients. Both the activities of the autonomic nervous system and changes in quality of life were measured before and after treatment to determine the effectiveness of the FIR treatment. Results from this study show that FIR therapy decreases both stress and fatigue levels of these patients. It also stimulates autonomic nervous system (ANS) activity in patients who are diagnosed with end-stage renal disease (ESRD) and are receiving regular hemodialysis (HD). Therefore, benefits of FIR stimulation on these patients are clearly demonstrated in this preliminary study. 16. J Am Soc Nephrol. 2007 Mar;18(3):985-92. Epub 2007 Jan 31. Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients. Lin CC, Chang CF, Lai MY, Chen TW, Lee PC, Yang WC. Division of Nephrology, Institute of Clinical Medicine and School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. Comment in: Nat Clin Pract Nephrol. 2007 Aug;3(8):422-3. Abstract Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD(02) monitor during HD. The Qa(1)/Qa(2) and Qa(3)/Qa(4) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 +/- 114.7 versus -33.4 +/- 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Delta(Qa(4) – Qa(3)) (36.2 +/- 82.4 versus -12.7 +/- 153.6 ml/min; P = 0.027), Delta(Qa(3) – Qa(1)) (36.3 +/- 166.2 versus -51.7 +/- 283.1 ml/min; P = 0.035), Delta(Qa(4) – Qa(2)) (99.2 +/- 144.4 versus -47.5 +/- 244.5 ml/min; P < 0.001), and Delta(Qa(4) – Qa(2)) – Delta(Qa(3) – Qa(1)) (62.9 +/- 111.6 versus 4.1 +/- 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01). In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects. 17. J Chin Med Assoc. 2009 Mar;72(3):109-16. Prognostic factors influencing the patency of hemodialysis vascular access: literature review and novel therapeutic modality by far infrared therapy. Lin CC, Yang WC. National Yang-Ming University School of Medicine, Taiwan, Republic of China. Abstract In Taiwan, more than 85% of patients with end-stage renal disease undergo maintenance hemodialysis (HD). The native arteriovenous fistula (AVF) accounts for a prevalence of more than 80% of the vascular access in our patients. Some mechanical factors may affect the patency of hemodialysis vascular access, such as surgical skill, puncture technique and shear stress on the vascular endothelium. Several medical factors have also been identified to be associated with vascular access prognosis in HD patients, including stasis, hypercoagulability, endothelial cell injury, medications, red cell mass and genotype polymorphisms of transforming growth factor-beta1 and methylene tetrahydrofolate reductase. According to our previous study, AVF failure was associated with a longer dinucleotide (GT)n repeat (n > or = 30) in the promoter of the heme oxygenase-1 (HO-1) gene. Our recent study also demonstrated that far-infrared therapy, a noninvasive and convenient therapeutic modality, can improve access flow, inflammatory status and survival of the AVF in HD patients through both its thermal and non-thermal (endothelial-improving, anti-inflammatory, antiproliferative, antioxidative) effects by upregulating NF-E2-related factor-2-dependent HO-1 expression, leading to the inhibition of expression of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. 18. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):739-45. Epub 2008 Jan 17. Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1. Lin CC, Liu XM, Peyton K, Wang H, Yang WC, Lin SJ, Durante W. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Abstract OBJECTIVE: Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation. METHODS AND RESULTS: Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-alpha-mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis. CONCLUSIONS: These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients. Fibromyalgia 19. Intern Med. 2008;47(16):1473-6. Epub 2008 Aug 15. Efficacy of Waon therapy for fibromyalgia. Matsushita K, Masuda A, Tei C. The First Department of Internal Medicine, Kagoshima University Hospital. Abstract OBJECTIVE: Fibromyalgia syndrome (FMS) is a chronic syndrome characterized by widespread pain with tenderness in specific areas. We examined the applicability of Waon therapy (soothing warmth therapy) as a new method of pain treatment in patients with FMS. METHODS: Thirteen female FMS patients (mean age, 45.2+/-15.5 years old; range, 25-75) who fulfilled the criteria of the American College of Rheumatology participated in this study. Patients received Waon therapy once per day for 2 or 5 days/week. The patients were placed in the supine or sitting position in a far infrared-ray dry sauna maintained at an even temperature of 60 degrees C for 15 minutes, and then transferred to a room maintained at 26-27 degrees C where they were covered with a blanket from the neck down to keep them warm for 30 minutes. Reductions in subjective pain and symptoms were determined using the pain visual analog scale (VAS) and fibromyalgia impact questionnaire (FIQ). RESULTS: All patients experienced a significant reduction in pain by about half after the first session of Waon therapy (11-70%), and the effect of Waon therapy became stable (20-78%) after 10 treatments. Pain VAS and FIQ symptom scores were significantly (p<0.01) decreased after Waon therapy and remained low throughout the observation period. CONCLUSION: Waon therapy is effective for the treatment of fibromyalgia syndrome. Allergic Rhinitis 20. Conf Proc IEEE Eng Med Biol Soc. 2007;2007:1479-82. Clinical effects of far-infrared therapy in patients with allergic rhinitis. Hu KH, Li WT. Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li, 32023 Taiwan, ROC. Abstract Allergic rhinitis (AR) is the sixth most common chronic illness worldwide, which has a significant impact on patients’ quality of life. The actual cost of AR is staggering, approximately $5.6 billion being spent annually in direct medical costs and other indirect costs. Therefore, it should be taken seriously upon its evaluation and treatment. AR is an IgE-mediated inflammation, which symptoms are likely due to increased vascular permeability. Current therapeutic options such as avoidance of allergen, medication and immunotherapy are unsatisfactory. Far-infrared (FIR) is an invisible electromagnetic wave with a wavelength longer than that of visible light. It has been used to treat vascular diseases as a result of an increase in blood flow. The objective of this study was to evaluate the clinical effects of FIR therapy in patients with AR. Thirty-one patients with AR were enrolled in this study. A WS TY101 FIR emitter was placed to face the patient’s nasal region at a distance of 30 cm. The treatment was performed for 40 min every morning for 7 days. Every day, patients recorded their symptoms in a diary before and during treatment. Each symptom of rhinitis was rated on a 4-point scale (0-3) according to severity. During the period of FIR therapy, the symptoms of eye itching, nasal itching, nasal stuffiness, rhinorrhea and sneezing were all significantly improved. Smell impairment was not improved until after the last treatment. No obvious adverse effect was observed in the patients during treatment and follow-up. We concluded that FIR therapy could improve the symptoms of AR and might serve as a novel treatment modality for AR. Cancer 21. Health Phys. 2006 Dec;91(6):630-45. ICNIRP statement on far infrared radiation exposure. International Commission on Non-Ionizing Radiation Protection. Quote: “The medical use of infrared radiation has a long history. It has been widely used in physical medicine for treatment of sports injuries, muscle aches, pain, and some chronic diseases (Licht 1967; Vaupel and Kruger 1992, 1995). In recent years there has been an interest in the use of IR-A sources for hyperthermic treatment of cancers (von Ardenne 1994, 1997; Vaupel and Kruger 1995; Wehner et al. 2001). Because of the deeper penetration of IR-A, this is used almost exclusively, and water filtering of IR to achieve pure IR-A has been recommended in therapeutics. There are also special IR-A therapeutic apparatuses that have been used for hyperthermic treatment of cancers and Raynaud’s syndrome (i.e., white finger disease). The typical treatment irradiance of several therapeutic IR devices fall in the range of 800 W m_2. A German standard (DIN 5031-10; DIN 2000) limits IR-A to 1,200 W m_2 in therapeutic equipment.” Licht S. Therapeutic electricity and ultraviolet radiation. New Haven: New Haven Press; 1967. von Ardenne M. Principles and concept 1993 of the Systemic Cancer Multistep Therapy (SCMT). Extreme whole-body hyperthermia using the infrared-A technique IRATHERM 200-selective thermosensitisation by hyperglycemia- circulatory back-up by adapted hyperoxemia. Strahlenther Onkol 170:581-589; 1994. von Ardenne M, ed. Systemische Krebs-Mehrschritt-Therapie-Hyperthermie und Hyperglykamie als Therapiebasis. Stuttgart: Hippokrates Verlag; 1997. Vaupel P, Kruger W. Waermetherapie mit wassergefilterter Infrarotstrahlung-Grundlagen und Anwendungsmoglichkeiten. Stuttgart: Hippokrates Verlag; 1995 (in German). Wehner H, von Ardenne A, Kaltofen S. Whole-body hyperthermia with water-filtered infrared radiation: technicalphysical aspects and clinical experiences. Int J Hyperthermia 17:19 -30; 2001. 22. Med Oncol. 2008;25(2):229-37. Epub 2007 Oct 30. The effects inhibiting the proliferation of cancer cells by far-infrared radiation (FIR) are controlled by the basal expression level of heat shock protein (HSP) 70A. Ishibashi J, Yamashita K, Ishikawa T, Hosokawa H, Sumida K, Nagayama M, Kitamura S. Department of Oral and Maxillofacial Anatomy, Medical Science for Oral and Maxillofacial Regeneration, Graduate School of Health Biosciences, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. Abstract We developed a tissue culture incubator that can continuously irradiate cells with far-infrared radiation (FIR) of wavelengths between 4 and 20 microm with a peak of 7-12 microm, and found that FIR caused different inhibiting effects to five human cancer cell lines, namely A431 (vulva), HSC3 (tongue), Sa3 (gingiva), A549 (lung), and MCF7 (breast). Then, in order to make clear the control system for the effect of FIR, the gene expression concerned to the inhibition effect by FIR were analyzed. In consequence, basal expression level of HSP70A mRNA was higher in A431 and MCF7 cells than in the FIR-sensitive HSC3, Sa3, and A549 cells. Also, the over expression of HSP70 inhibited FIR-induced growth arrest in HSC3 cells, and an HSP70 siRNA inhibited the proliferation of A431 cells by irradiation with FIR. These results indicate that the effect of a body temperature range of FIR suppressing the proliferation of some cancer cells is controlled by the basal expression level of heat shock protein (HSP) 70A. This finding suggested that FIR should be very effective medical treatment for some cancer cells which have a low level of HSP70. Still more, if the level of HSP70 in any cancer of a patient was measured, the effect of medical treatment by FIR can be foreseen for the cancer. 23. Cancer Chemother Pharmacol. 2009 Nov;64(6):1079-83. Epub 2009 Mar 11. Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium. Yamada Y, Itoh Y, Aoki S, Nakamura K, Taki T, Naruse K, Tobiume M, Zennami K, Katsuda R, Kato Y, Watanabe M, Nishikawa G, Minami M, Nakahira M, Ukai S,Sawada M, Kitamura A, Honda N. Department of Urology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. Abstract OBJECTIVE: We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. SUBJECTS AND METHODS: The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients’ oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. RESULTS: The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). CONCLUSIONS: The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium. 24. Int J Hyperthermia. 2007 Nov;23(7):591-8. Antitumor effect of whole body hyperthermia with alpha-galactosylceramide in a subcutaneous tumor model of colon cancer. Hattori T, Kokura S, Okuda T, Okayama T, Takagi T, Handa O, Naito Y, Yoshida N, Yoshikawa T. Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Abstract AIM: Whole body hyperthermia (WBH) has been used clinically as an adjunct to radio- and chemotherapy in patients with various cancers. Recently, it has been reported that an activation of the immune system has recently been reported as a possible contributor to the therapeutic effects of WBH. Conversely, the glycolipid alpha-galactosylceramide (alpha-GalCer) is recognized by natural killer (NK) T cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. This study investigated the antitumor effects of WBH combined with alpha-GalCer in a mouse subcutaneous tumor model of colon cancer. METHODS: Colon26 cells were inoculated subcutaneously into male BALB/c mice to establish subcutaneous tumor. Colon26-bearing mice were treated with WBH using far infrared rays three times/week. Rectal temperature was maintained for 60 min at 41 degrees C. In some experimental groups, alpha-GalCer was intraperitoneally injected before WBH. We investigated the therapeutic effects of WBH, alpha-GalCer and combined therapy. RESULTS: (1) Compared with controls, WBH alone resulted in significant inhibition of tumor growth. (2) No inhibitory effect on tumor growth was seen with alpha-GalCer. (3) The combination of WBH and alpha-GalCer showed significant inhibition of tumor growth and prolongation of survival. (4) Serum IFN-gamma increased after 3 h and returned to basal levels by 24 h after alpha-GalCer administration. (5) CTL activity was enhanced following combination therapy with WBH and alpha-GalCer. CONCLUSION: WBH showed antitumor effects in a mouse subcutaneous tumor model of colon cancer. Addition of alpha-GalCer increased the efficacy of WBH, probably via enhancement of immune response. 25. Anticancer Res. 1999 Sep-Oct;19(5B):4125-30. Inhibition by whole-body hyperthermia with far-infrared rays of the growth of spontaneous mammary tumours in mice. Udagawa Y, Nagasawa H, Kiyokawa S. Experimental Animal Research Laboratory, Meiji University, Kawasaki, Japan. Abstract To evaluate possible therapeutic benefits of irradiation with far-infrared rays (FIR) on breast cancer, we examined combined effects of the chronic exposure to FIR at ambient temperature (26.5-27.5 degrees C) and the whole-body hyperthermia induced by FIR (WBH) (35-41 degrees C) on the growth of spontaneous mammary tumours of mice. A high mammary tumour strain of SHN virgin mice born on the normal rack or FIR rack were maintained on the respective racks until mammary tumour appearance. When the mammary tumour size reached approximately 7 mm, some mice in each group received no further treatment (Control and FIR groups, respectively) and the remaining mice received 3 hours of WBH each of 5 consecutive days (C + WBH and FIR + WBH groups, respectively). There was little difference between the control and FIR groups in the tumour growth over 10 days of examination. On the other hand, the tumour growth was inhibited significantly in both C + WBH and FIR + WBH groups and the degree of inhibition was similar. The data confirmed that the chronic exposure to FIR at ambient temperature has little effect on the growth of spontaneous mammary tumours in mice. WBH with FIR, however, strongly inhibited the tumour growth without deleterious side-effects, while chronic FIR irradiation itself again had little effect in this process. This WBH regimen may serve as a useful animal model for long-term studies of a noninvasive treatment of breast cancer. 26. Crit Rev Oncol Hematol. 2002 Jul;43(1):33-56. The cellular and molecular basis of hyperthermia. Hildebrandt B, Wust P, Ahlers O, Dieing A, Sreenivasa G, Kerner T, Felix R, Riess H. Medical Clinic, Department of Hematology and Oncology, Charite Medical School, Humboldt-University, Campus Virchow Clinic, D-13344 Berlin, Germany. Abstract In oncology, the term ‘hyperthermia’ refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40-43 degrees C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial hyperthermia, hyperthermic chemoperfusion, and whole-body hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by hyperthermia. 27. Expert Rev Med Devices. 2010 May;7(3):407-23. Current devices for high-performance whole-body hyperthermia therapy. Jia D, Liu J. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, PR China. Abstract For late-stage cancer, whole-body hyperthermia (WBH) is highly regarded by physicians as a promising alternative to conventional therapies. Although WBH is still under scrutiny due to potential toxicity, its benefits are incomparable, as diversified devices and very promising treatment protocols in this area are advanced into Phase II and III clinical trials. Following the introduction of the WBH principle, this paper comprehensively reviews the state-of-art high-performance WBH devices based on the heat induction mechanisms – radiation, convection and conduction. Through analyzing each category’s physical principle and heat-induction property, the advantages and disadvantages of the devices are evaluated. Technical strategies and critical scientific issues are summarized. For future developments, research directions worth pursuing are presented in this article. 28. Ann Oncol. 2002 Aug;13(8):1173-84. Heating the patient: a promising approach? van der Zee J. Erasmus Medical Center-Daniel den Hoed Cancer Center, Department of Radiation Oncology, Hyperthermia Unit, Rotterdam, The Netherlands. Abstract There is a clear rationale for using hyperthermia in cancer treatment. Treatment at temperatures between 40 and 44 degrees C is cytotoxic for cells in an environment with a low pO(2) and low pH, conditions that are found specifically within tumour tissue, due to insufficient blood perfusion. Under such conditions radiotherapy is less effective, and systemically applied cytotoxic agents will reach such areas in lower concentrations than in well perfused areas. Therefore, the addition of hyperthermia to radiotherapy or chemotherapy will result in at least an additive effect. Furthermore, the effects of both radiotherapy and many drugs are enhanced at an increased temperature. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, regional hyperthermia by perfusion of organs or limbs, or by irrigation of body cavities, and whole body hyperthermia. The use of hyperthermia alone has resulted in complete overall response rates of 13%. The clinical value of hyperthermia in addition to other treatment modalities has been shown in randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, vulva and vagina, and also for melanoma. Additional hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects and/or better overall survival rates. Generally, when combined with radiotherapy, no increase in radiation toxicity could be demonstrated. Whether toxicity from chemotherapy is enhanced depends on sequence of the two modalities, and on which tissues are heated. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. Recent developments include improvements in heating techniques and thermometry, development of hyperthermia treatment planning models, studies on heat shock proteins and an effect on anti-cancer immune responses, drug targeting to tumours, bone marrow purging, combination with drugs targeting tumour vasculature, and the role of hyperthermia in gene therapy. The clinical results achieved to date have confirmed the expectations raised by results from experimental studies. These findings justify using hyperthermia as part of standard treatment in tumour sites for which its efficacy has been proven and, furthermore, to initiate new studies with other tumours. Hyperthermia is certainly a promising approach and deserves more attention than it has received until now. 29. Int J Hyperthermia. 2001 Jan-Feb;17(1):1-18. Hyperthermia in oncology. Falk MH, Issels RD. Medizinische Klinik III, Klinikum Grosshadern, Munich, Germany. Abstract The purpose of this article is to provide an overview on the current clinical application of hyperthermia combined with conventional treatment modalities (e.g. ionizing radiation, chemotherapy) in the treatment of malignant disease. The clinical application of hyperthermia with increase of tissue temperatures (range 40-44 degrees C) has been integrated in multimodal anti-cancer strategies. This review describes selected phase I or II (n = 17) and phase III trials (n = 16) investigating the effect of hyperthermia combined with radiotherapy (n = 10 trials), chemotherapy (n = 15 trials), or both (n = 8 trials) in a total of more than 2200 patients. The trials were performed in a variety of solid tumours (e.g. melanoma, head and neck cancer, breast cancer, cancer of the gastrointestinal or urogenital tract, glioblastoma, sarcoma) in paediatric or adult patients. Profound research has produced a scientific basis for the simultaneous application of hyperthermia in combination with ionizing radiation and/or systemic chemotherapy. Hyperthermia is becoming more accepted clinically, due to the substantial technical improvements made in achieving selected increase of temperatures in superficial and deep-seated tumours. At present, the combination of hyperthermia and chemotherapy or radiochemotherapy is further tested within clinical protocols (phase II/III) in order to improve local tumour control and relapse-free survival in patients with high-risk or advanced tumours of different entities. 30. Am J Chin Med. 2002;30(4):495-505. Effects of hydroxyapatite in combination with far-infrared rays on spontaneous mammary tumorigenesis in SHN mice. Udagawa Y, Ishigame H, Nagasawa H. Experimental Animal Research Laboratory, Meiji University, Kawasaki, Japan. Abstract We have found that the administration of a diet containing 5% hydroxyapatite (HAP) derived from pig and cattle bones, and exposure to far-infrared rays (FIR) markedly inhibited spontaneous mammary tumorigenesis in SHN mice. Thus, the effect of combined treatment with HAP and FIR on mammary tumorigenesis was examined. The significant inhibition of tumor development by individual treatment with HAP or FIR was not enhanced by combined treatment; instead, the decrease in the inhibitory effect of HAP with age was ameliorated. Associated with this, life span was elongated and a decline in ovarian function was prevented by HAP plus FIR. Normal and preneoplastic growth of mammary glands and plasma component levels were not significantly affected by any treatment. The findings indicate that HAP and FIR have characteristics common to most natural products; in combination with other agents, they have little additive effect, when each is highly active. 31. In Vivo. 2000 May-Jun;14(3):431-5. Effects of combined treatment with coffee cherry and whole-body hyperthermia on the growth of spontaneous mammary tumours in SHN mice. Udagawa Y, Nagasawa H. Experimental Animal Research Laboratory, Meiji University, Kawasaki, Japan. Abstract Based on findings that free access in drinking water of the extract of coffee cherry (CC), the residue left after the removal of coffee beans, and whole-body hyperthermia (WBH) induced by far-infrared ray (FIR) can markedly inhibit the growth of spontaneous mammary tumours of SHN mice, the effects of the combined treatment with these agents were examined in this study. The significant inhibition of tumour growth by single treatment with either CC or WBH was not enhanced by their combination. Meanwhile, the body weight loss during WBH was significantly decreased by CC. Normal and preneoplastic growth of mammary glands and plasma component levels were affected little by either treatment. The findings confirmed the “normalization effects” of CC usually obtained with natural products and stress the need for prudence in the choice of any agent, natural or synthetic, to be applied simultaneously to increase the efficacy of WBH. Chronic Fatigue Syndrome 32. Nippon Rinsho. 2007 Jun;65(6):1093-8. A new treatment: thermal therapy for chronic fatigue syndrome [Article in Japanese] Masuda A, Munemoto T, Tei C. Masuda Clinic. Abstract Thermal therapy using far-infrared ray dry sauna was performed for patients with chronic fatigue syndrome (CFS). Symptoms such as fatigue, pain, and low-grade fever were dramatically improved on two patients. And prednisolone administration was discontinued and became socially rehabilitated 6 months after discharge. On other 11 patients with CFS, physical symptoms such as fatigue and pain improved, too. Furthermore, we reported that repeated thermal therapy had relaxation effect and diminishes appetite loss and subjective complaints in mildly depressed patients. These results suggest that repeated thermal therapy may be a promising method for the treatment of CFS. 33. J Psychosom Res. 2005 Apr;58(4):383-7. The effects of repeated thermal therapy for two patients with chronic fatigue syndrome. Masuda A, Kihara T, Fukudome T, Shinsato T, Minagoe S, Tei C. Respiratory and Stress Care Center, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Abstract OBJECTIVE: This paper describes the successful treatment of two patients with chronic fatigue syndrome (CFS) using repeated thermal therapy. METHODS: Two patients with CFS underwent treatment with prednisolone (PSL), with no satisfactory effect. They were subjected to thermal therapy that consisted of a far-infrared ray dry sauna at 60 degrees C and postsauna warming. The therapy was performed once a day, for a total of 35 sessions. After discharge, these subjects continued the therapy once or twice a week on an outpatient basis for 1 year. RESULTS: Symptoms such as fatigue, pain, sleep disturbance, and low-grade fever were dramatically improved after 15 to 25 sessions of thermal therapy. Although PSL administration was discontinued, the subjects showed no relapse or exacerbation of symptoms during the first year after discharge. The patients became socially rehabilitated 6 months after discharge. CONCLUSIONS: These results suggest that repeated thermal therapy might be a promising method for the treatment of CFS. Chronic Pain 34. Psychother Psychosom. 2005;74(5):288-94. The effects of repeated thermal therapy for patients with chronic pain. Masuda A, Koga Y, Hattanmaru M, Minagoe S, Tei C. Nishi Kyusyu University, Saga, Japan. Abstract BACKGROUND: It has been reported that local thermal therapy with a hot pack or paraffin relieves pain. We hypothesized that systemic warming may decrease pain and improve the outcomes in patients with chronic pain. The purpose of this study was to clarify the effects of systemic thermal therapy in patients with chronic pain. METHODS: Group A (n = 24) patients with chronic pain were treated by a multidisciplinary treatment including cognitive behavioral therapy, rehabilitation, and exercise therapy, whereas group B (n = 22) patients were treated by a combination of multidisciplinary treatment and repeated thermal therapy. A far-infrared ray dry sauna therapy and post-sauna warming were performed once a day for 4 weeks during hospitalization. We investigated the improvements in subjective symptoms, the number of pain behavior after treatment and outcomes 2 years after discharge. RESULTS: The visual analog pain score, number of pain behavior, self-rating depression scale, and anger score significantly decreased after treatment in both groups. After treatment, the number of pain behavior was slightly smaller (p = 0.07) and anger score was significantly lower in group B than those in group A (p = 0.05). Two years after treatment, 17 patients (77%) in group B returned to work compared with 12 patients (50%) in group A (p < 0.05). CONCLUSION: These results suggest that a combination of multidisciplinary treatment and repeated thermal therapy may be a promising method for treatment of chronic pain. Copyright 2005 S. Karger AG, Basel. Wound Healing 35. Exp Biol Med (Maywood). 2003 Jun;228(6):724-9. Promotive effects of far-infrared ray on full-thickness skin wound healing in rats. Toyokawa H, Matsui Y, Uhara J, Tsuchiya H, Teshima S, Nakanishi H, Kwon AH, Azuma Y, Nagaoka T, Ogawa T, Kamiyama Y. First Department of Surgery and Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi City, Osaka, 570-8507, Japan. Abstract The biological effects of far-infrared ray (FIR) on whole organisms remain poorly understood. The aim of our study was to investigate not only the hyperthermic effect of the FIR irradiation, but also the biological effects of FIR on wound healing. To evaluate the effect of FIR on a skin wound site, the speed of full-thickness skin wound healing was compared among groups with and without FIR using a rat model. We measured the skin wound area, skin blood flow, and skin temperature before and during FIR irradiation, and we performed histological inspection. Wound healing was significantly more rapid with than without FIR. Skin blood flow and skin temperature did not change significantly before or during FIR irradiation. Histological findings revealed greater collagen regeneration and infiltration of fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in wounds in the FIR group than in the group without FIR. Stimulation of the secretion of TGF-beta1 or the activation of fibroblasts may be considered as a possible mechanisms for the promotive effect of FIR on wound healing independent of skin blood flow and skin temperature.