BACKGROUND: Fabry disease is an X-linked recessive disorder caused by deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A). Previous studies identified many cases of Fabry disease among men with left ventricular hypertrophy (LVH). The purpose of this study was to define the frequency of Fabry disease among Korean men with LVH. METHODS: In this national prospective multicenter study, we screened Fabry disease in men with LVH on echocardiography. The criterion for LVH diagnosis was a maximum LV wall thickness 13 mm or greater. We screened 988 men with LVH for plasma α-Gal A activity. In patients with low α-Gal A activity (< 3 nmol/hr/mL), we searched for mutations in the α-galactosidase gene. RESULTS: In seven men, α-Gal A activity was low. Three had previously identified mutations; Gly328Arg, Arg301Gln, and His46Arg. Two unrelated men had the E66Q variant associated with functional polymorphism. In two patients, we did not detect GLA mutations, although α-Gal A activity was low on repeated assessment. CONCLUSION: We identified three patients (0.3%) with Fabry disease among unselected Korean men with LVH. Although the prevalence of Fabry disease was low in our study, early treatment of Fabry disease can result in a good prognosis. Therefore, in men with unexplained LVH, differential diagnosis of Fabry disease should be considered.
Diagnosis ; Diagnosis, Differential ; Echocardiography ; Fabry Disease ; Humans ; Hypertrophy, Left Ventricular ; Male ; Plasma ; Prevalence ; Prognosis ; Prospective Studies

Background: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue. We examined the applicability of Waon therapy as a new method of fatigue treatment in patients with ME/CFS. Methods: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Canadian clinical case definition of ME/CFS participated in this study. Patients received 30 sessions of modified Waon therapy, infrared-ray dry sauna maintained at an even temperature of 40°C or 45°C for 15 minutes twice a day for 3 weeks in a hospital, or once a day for five weeks at an outpatient clinic. Their functional health and well-being scores were determined using SF-36 and compared with those of six ME/CFS patients who did not undergo Waon therapy. Results: Seven of nine Waon therapy patients experienced a significant improvement in physical and mental condition, and the effect continued throughout the observation period. Waon therapy brought improvements in the scores of: Role physical (p<0.05); Bodily pain (p<0.05); General health perceptions (p<0.05); and Role emotional (p<0.05) of SF-36 in those who responded well (good responders) to the therapy. In two patients who responded poorly (poor responders) to Waon therapy, and in the non-Waon therapy patients, no significant improvement in the scores was observed. Conclusions: Waon therapy is effective for the treatment of ME/CFS.

  In 1989, we developed a form of thermal therapy for heart failure. In 2007, I changed the name to Waon therapy: “Wa” means soothing, and “On” means warmth, hence Waon infers soothing warmth that comfortably refreshes the mind and body.   “Waon therapy” is defined as “therapy in which the entire body is warmed in an evenly maintained in a far infrared dry sauna at a temperature of 60°C for 15 min, and then rest supine on a bed outside the sauna where they are covered with blankets for an additional 30 min, with fluids corresponding to perspiration being supplied at the end.”   Waon therapy has several characteristic features, that is, safe and no toxicity, gentle and cost effective. It is just a holistic medical care and gives a global optimization to the patients with refractory diseases.   There are various clinical applications of “Waon therapy and the effects are often dramatic. In particular, a drastic recovery is often seen in severe congestive heart failure (CHF) as well as peripheral artery disease (PAD) with intractable ulcer, chronic fatigue syndrome, fibromyalgia syndrome and salivary secretion failure caused by Sjögren’s syndrome etc. In this presentation, I would like to focus the effects and mechanisms of Waon therapy on refractory CHF and PAD.   We demonstrated that Waon therapy improved the hemodynamics, cardiac function, ventricular arrhythmias, vascular endothelial function, neurohumoral factors, sympathetic and para-sympathetic nervous system function, and also found that 2 - 4 weeks of Waon therapy (once a day, 5 days a week) significantly improved clinical symptoms, and deceased BNP and cardiac size in patients with CHF. Waon therapy improved the prognosis of CHF patients as well as CHF models of hamster and mouse. It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and expression of endothelial nitric oxide synthase (eNOS) and capillary density.   Moreover, repeated Waon therapy is effective for patients with severe PAD, as evidenced by substantial decrease in pain scores, increases in both ankle-brachial pressure index and blood flow assessed by laser Doppler perfusion imaging, and by formation of new collateral vessels on angiography. Waon therapy often heals ischemic ulcers markedly. Waon therapy upregulates heat shock protein 90 (Hsp90) and leads to angiogenesis through the akt-eNOs pathway in mouse hindlimb ischemia.   In conclusion, Waon therapy is an innovative and highly promising strategy for cardiovascular diseases, especially treating refractory CHF and PAD.

Background: Transient severe myocardial ischemia in patients with coronary vasospasm impairs regional left ventricular (LV) relaxation which persists for several weeks. Methods: We studied 40 consecutive patients (17 women, 52±8) with vasospastic angina (VA) who had recurrent angina despite treatment with the conventional calcium channel blockers (CCBs) during the follow-up period. These 40 patients were registered and randomly assigned to either Waon therapy group or the high dose of CCBs therapy. In Waon therapy, the patients were treated with a far infrared-ray dry sauna at 60 degrees centigrade for 15 minutes and then kept on bed rest with a blanket for 30 minutes for 2 weeks. Strain imaging (SI) was acquired in the LV mid-papillary short-axis view and radial strain was measured using 2D speckle tracking echocardiography. The peak values of stain at the closure of aortic valve (A) and at the one third diastole duration (B) were measured. The SI-diastolic index (SI-DI) was determined as (A-B)/A 100%. The repeated SI study was conducted 1 weeks and 2 weeks in Waon therapy. Chest pain was scored by a numeric pain intensity rating scale. Results: The mean SI-DIs was 20±17% in the 45 territories perfused by the coronary arteries with spasm at baseline. The SI-DI significantly improved at 1 weeks (50±14%, p<0.001), and further improved after 2 weeks (77±10%, p<0.001). In contrast, the index did not improve in the high-dose CCBs therapy group. The pain score significantly decreased after 2 weeks of Waon therapy. Conclusion: The repeated Waon therapy improved the LV postischemic diastolic dysfunction and chest pain in patients with VA.

Objectives: Many patients with chronic pain and fibromyalgia (FM) consult health care clinics continually, and move from hospital to hospital without gaining pain relief. In some patients, prolonged refractory pain affects their daily life and social function despite various treatments. The purpose of this study was to clarify the effects of Waon therapy in patients with chronic pain and FM. Patients and Methods: Study A: 46 patients with chronic pain were assigned to Waon therapy group (n = 22) or non-Waon therapy group (n = 24). All patients were admitted to our hospital for 5 weeks. In non-Waon therapy group, cognitive behavior therapy (CBT), rehabilitation, and exercise therapy were performed during hospitalization. Waon therapy was started 2 weeks after admission in addition to CBT, rehabilitation, and exercise therapy. And the therapy was performed for 4 weeks. Pain was evaluated by the visual analog scale (VAS). Pain behavior was assessed based on the 11 items and the number per day was counted. Anger score was evaluated using the mentral complaints in the Cornell Medical Index. The degree of satisfaction with treatment was evaluated at discharge. Study B: 12 patients who fulfilled the FM criteria of the American College of Rheumatology. All patients received 20 sessions of Waon Therapy at our outpatients clinic. The VAS pain scale and the Fibromyalgia Impact Questionnaire (FIQ), Profile of Mood State (POMS) were evaluated before and after 10 and 20 sessions of Waon Therapy. Results: Study A: The differences in number of pain behavior and anger scores before and after treatment were significantly larger in Waon therapy group than those in non-Waon therapy group. The treatment was rated as ‘satisfactory’ or ‘very satisfactory’ by 55% in non-Waon-therapy group and 82% in Waon Therapy group. Study B: The VAS pain scores and FIQ scores were improved after the 10 and 20 sessions of Waon therapy. In the POMS, depression and anger, anxiety, confusion scales were sigificantly decresed and vigor score was elevated. Conclusion: Waon therapy may be a promising method for treatment of chronic pain and fibromyalgia.

 Waon therapy uses a far infrared-ray dry sauna, which is evenly maintained at 60°C and differs from the traditional sauna. The patients were placed in a 60°C sauna system for 15 minutes, in which the deep-body temperature has increased by 1.0 to 1.2°C. Then, after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 minutes. All patients were weighed before and after the therapy, and they drank some water at the end of Waon therapy to compensate for weight lost due to perspiration and prevent the dehydration.  We have previously reported that Waon therapy improves the cardiac and vascular endothelial function in patients with chronic heart failure (CHF) and the limb ischemia and symptoms in patients with arteriosclerosis obliterans (ASO). As underlying molecular mechanisms, we demonstrated that Waon therapy upregulates nitric oxide (NO) and endothelial NO synthase (eNOS), which would improve vascular endothelial and cardiac function in TO-2 cardiomyopathic hamsters and augment ischemia-induced angiogenesis. In order to investigate the mechanism of Waon therapy, we examined the effect of Waon therapy on heat shock proteins (Hsp) in failed myocardium and ischemic limb. Hsp are stress response proteins that can be induced by stress signals, including thermal stimulation. Hsp function as chaperones to assist with protein folding in order to protect cells from protein denaturation or cell death under stress conditions.  In TO-2 cardiomyopathic hamsters, the cardiac expression of 4-hydroxy-2-nonenal (4HNE), a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. Also, the cardiac expressions of Hsp 27, Hsp 32 and manganese superoxide dismutase (Mn-SOD), which reduce oxidative stress, were significantly upregulated by the 4-week Waon therapy compared to untreated hamsters. In addition, Waon therapy upregulated Hsp90, which contributes to the activation of the AkteNOSNO pathway, and induced angiogenesis in mice with hindlimb ischemia. However, Waon therapy did not increase the expression of Hsp70, Hsp60, Hsp32 and Hsp27 in the same model mice. The thermal stimulation with Waon therapy upregulated specific Hsp isoforms depending on different organs and diseases. The specific function of Hsp induced by Waon therapy is suggested to play an important role in improving cardiovascular diseases.