臨床上使用 wIRA 的基本建議

Fundamental recommendations for the clinical use of wIRA

The following fundamental recommendations can be given for clinical use of wIRA:
• Typically wIRA acts only on bare skin, i.e. wIRA does not penetrate clothes or most kinds of bandages or wound dressings.
• If possible, irradiation should be vertical to the skin; irradiation distance should be at least as indicated by the distance rod of the radiator (depends on the type of radiator, e.g. 25 cm) [1].
• Irradiation time should be at least 20 minutes (better 30 minutes) [1].
• If the patient gets too warm, at full term the irradiation distance should be extended (and by this the irradiance decreased); if possible, the irradiation should not be stopped [1].
• In routine clinical practice often markedly larger irradi- ation distances than the minimum distance are used. Then the typical total irradiances (wIRA and visible light) are approximately 80-160 mW/cm² (depending on size of the irradiated area, on tissue temperature and amount of subcutaneous soft tissues, e.g. lower used irradiances at the tibial border compared to the anterior part of the thigh), corresponding to wIRA irra- diances of only 60-120 mW/cm² [13].
• Special caution, i.e. a larger irradiation distance, should be taken in patients with an impaired sensation (e.g. diabetic polyneuropathy) or a deteriorated ability to express themselves, and when irradiating cold tissue or tissue badly supplied with blood or an area with low subcutaneous tissue (e.g. tibial border) [1].

wIRA for the improvement of wound healing in dermatology and surgery

Acute wounds and especially chronic wounds, intractable wounds or infected problem wounds should be irradiated with wIRA ideally once or twice per day for (20-)30 minutes each (longer irradiation times per day are pos- sible and often helpful), at least three times per week for (20-)30 minutes [1]. wIRA does not replace other sen- sible/necessary therapeutic procedures (such as the important compression garment therapy of chronic venous stasis ulcers of the lower legs [62], [63], [64]) but complements them. Correspondingly the therapy with wIRA has to be embedded in an overall therapeutic concept. wIRA can be used independently from therapy preferences concerning wound management (e.g. moist wound management). Typically for wIRA irradiation the wound has to be uncovered, see Figure 6, as most bandages or wound dressings (with the exception of e.g. some tested transparent foils) are not adequately per- meable for wIRA (as demonstrated by spectral transmis- sion measurements) [1].

Figure 6: Example for an irradiation of a wound with a water-filtered infrared-A radiator
(published with kind approval of Prof. James Mercer, Tromsø/Norway) [27]
According to modern concepts [65] for the assessment of wound healing also other end-points and variables of interest aside from a complete wound closure have to be used like reduction of pain, improvement of quality of life, improvement of the cosmetic result, reduction of scars, clinically relevant shortening of the time of wound healing and improved quality of healing [1]. Nowadays great im- portance is placed on the reduction or avoidance of pain in order to improve the wound healing and to avoid the formation of a pain memory with chronification of the pain [66], [67] associated with the application of manage- ment strategies of common acute and chronic wounds.

Safety aspects of the clinical use of wIRA

wIRA in clinical use at appropriate irradiances has been described since more than 15 years as helpful and safe [1], [2], [23], [24], [26], [27], [34], [44], [45], [46], [47], [48], [49], [55], [57], [58], [59], [61], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81].
In accordance with previous investigations [19], [20], [21] water-filtered infrared-A (wIRA) at appropriate irradi- ances is unlike ultraviolet-A especially not implicated in photoaging of the skin, mediated by the collagenase matrix metalloproteinase 1 (MMP-1) [13], [23], [24]. wIRA can even be implicated in a protective manner [13], [19], [20], [22], [23], [24].
Investigations of human skin fibroblasts after single ex- posures between 15 minutes and 8 hours to wIRA or 15-45 minutes to ultraviolet-A (UV-A) radiation at two physiologic temperatures as well as after repeated exposures with wIRA are presented in [13]: Single expo- sure of cultured human dermal fibroblasts to UV-A radi- ation yielded a very high increase in MMP-1 mRNA expression (11-fold expression for conventional Reverse Tran- scriptase Polymerase Chain Reaction (RT-PCR) and 76- fold expression for quantitative real-time RT-PCR) and a dose-dependent decrease in cell survival. In contrast, even at an investigated disproportionally high irradiance wIRA did not produce cell death and did not induce an increase in MMP-1 mRNA expression. Additionally, re- peated exposure to wIRA did not induce MMP-1 mRNA expression.
The results of the recent publication [13], in which par- ticularly a great effort to avoid any temperature alteration of the cells was undertaken, are consistent with publica- tions of several study groups [13], [19], [20], [21], [22], [23], [24], [82] and contradict publications primarily of one study group [83], [84], [85], [86], which described undesired effects of infrared-A and wIRA radiation in cell cultures.
Reasons for the different results are presented in detail in [13]: so [13] used normal skin fibroblasts and not foreskin fibroblasts of the newborn or young child which are well known to behave differently and are not repre- sentative of human skin. Effects on cells depend not only on the irradiation dose but also on the irradiance. In some other publications it was not taken into account that cell cultures, which represent a monolayer of cells and which have in contrast to human skin no horny layer and no heat distribution by blood circulation, cannot be irradiated with the same irradiance as a living skin (the remarkable difference between irradiating a material without circula- tion and a living patient is described and documented, for example, in two infrared thermography video se- quences in [27]): corresponding to this partly the three- to tenfold (e.g. 333 mW/cm² [83]) of a physiologic irradi- ance was used in cell cultures [83], [84], [85], [86]. In [13] with careful and effortful temperature fixing of the cells, which prevented an overheating of the cells, no undesired thermic effects were seen even at the investi- gated disproportionally high irradiance. Such a tempera- ture fixing is important to avoid misinterpretations, as MMP-1 mRNA, whose increase is interpreted partly as an indication for skin aging, shows an increased expression already by temperature increase about a threshold – a pure thermic effect independent from the cause of the temperature increase and thus also independent from specific properties of infrared-A or wIRA radiation. Inter- estingly a current publication with emphasis to avoid any overheating [82] from the same institute as the publica- tions [83], [84], [85], [86] showed no damaging effect of water-filtered infrared-A radiation (0, 100, 250, 500, 1000 J/cm²) to a glyceraldehyde-3-phosphate dehydro- genase (GAPDH) solution as a model enzyme for environ- mentally induced protein damage, while irradiation with UV-A (0, 100, 250, 500, 1000 J/cm²), UV-B (0, 250, 500, 1000, 2000 mJ/cm²), and gamma-irradiation (0, 50, 100, 250, 500 Gy) caused a dose-dependent increase in pro- tein modification (fragmentation and aggregation) and loss of enzyme activity with complete loss of enzyme activity at the highest doses. The striking difference between appropriate and inappropriate irradiances can be illustrated by the maximum skin temperature: Mercer [47] showed that a clinically typical irradiation with wIRA increased skin surface temperature (starting from 32.5°C) by nearly 6°C to a mean of 38.2°C (maximum value was 39.1°C). In accordance with that skin surface temperature (starting with approximately 32°C) reaches approximately only 38°C even under Mediterranean conditions in the summer at noon after 30 minutes stay in the sun [13]. These approximately 38(-39)°C are de- cisively lower than the induced “43°C for 90 minutes” with inappropriately high irradiance [87]: above 39.5- 40°C heat-shock proteins can be induced [13] (the heat- shock-induced matrix metalloproteinase-1 expression in human epidermal keratinocytes is mediated by the tran- sient receptor potential vanilloid-1 kation channel [88]), and this is a thermal effect and especially a thermic effect (temperature limits are exceeded), independent from the cause of exceeding temperature limits, and not a direct radiation effect. Some more examples of inappropriate irradiances in vivo and in vitro are presented in [13]. Appropriate therapeutic irradiances of wIRA – typically within the range 60-120 mW/cm² – are clearly lower than the above described investigated disproportionally high irradiance (333 mW/cm² [83]), particularly if the diffe- rence between living skin and cell culture is taken into account. The infrared-A irradiance by the sun at the sur- face of the earth on sea-level during the summer at noontime in moderate climatic zones is once more con- siderably lower (maximum approximately 20 mW/cm²) – and even under extreme atmospheric conditions at the equator only approximately 34 mW/cm². Therefore related to infrared-A irradiances and doses no indications for a necessary or sensible protection of the skin against in- frared-A or wIRA radiation of an appropriate therapeutic use or of the sun can be seen [13] in contrast to the un- disputedly sensible and necessary protection against an excessive UV irradiation.
As explained in the section about thermal and thermic effects of wIRA, wIRA with its special properties allows a high energy transfer into tissue (with relevant desired thermal effects, like increase of tissue temperature, tissue oxygen partial pressure, and tissue perfusion) combined with a limited temperature increase in the tissue (with limited thermic effects, omitting undesired effects) and with ideal dosing properties.

Clinical indications for wIRA

A review concerning clinical indications for wIRA in acute wounds including prospective, randomized, controlled, double-blind studies is presented in [89].
A review concerning clinical indications for wIRA in chronic wounds including prospective, randomized, con- trolled, double-blind studies is presented in [14]. Clinical indications for wIRA outside wound healing are [1]:

In dermatology: wIRA alone (which means without simul- taneously topically administered substance and without the subject of photodynamic therapy PDT) can be used for therapeutic purposes in recalcitrant common hand and foot warts (one therapy cycle with continous kerato- lysis with salicylic acid plaster, bloodless curettage, one wIRA irradiation of 30 minutes per week for 6-9 weeks [2], [55]), in herpes labialis, herpes zoster (fast decrease of pain in the acute phase as observed in casuistics), condylomata acuminata, scleroderma [60], [72], morphea [55], [56], acne papulopustulosa [90], [91], and possibly in alopezia areata.
wIRA can be used to improve the penetration of topically applied substances [69], [70], [71] (like cortisone or local anaesthetics) as an alternative to an occlusive dressing. This can be considered (indications under investigation) in neurodermitis, psoriasis, herpes zoster (with acyclovir topically), acne papulopustulosa (with topical acne therapeutic [91]), alopezia areata (with topical cortisone). wIRA can be used within a photodynamic therapy PDT (and a photodynamic diagnosis PDD = fluorescence dia- gnosis FD) – if clinically an indication for a PDT or a PDD with PDT is given – together with one or several absorp- tion bands in the visible range in actinic keratosis [73], [74] and in (superficial) basal cell carcinomas (BBC) [74], [92]. Perspectives for a use of PDT (with wIRA) in wound healing are presented in [14].
In physiotherapy, sports medicine, and orthopedics: the clinical application of wIRA can be in preventive, thera- peutic, regenerative, or rehabilitative intention. Muscular hardenings, myogeloses [66], lumbago, diseases of the rheumatic disorders circle [76], M. Bechterew [77], ar- throses, arthritises, contusions; fibromyalgia (preferably wIRA in combination with motion, i.e. wIRA with a small amount of ergometer work) [93], regeneration after sports [78] (wIRA alone or wIRA in combination with motion), postoperative rehabilitation [89], [94], improvement of lipolysis (wIRA in combination with motion) [61].
In neonatology: keeping or rising of the body temperature, generating a “heat depot” ahead of a necessary transport of a neonate [79].
In oncology: (local or systemic) hyperthermia in combina- tion with radiotherapy (e.g. in metastatic breast cancer [95]), hyperthermia in combination with chemotherapy [96].

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Corresponding author:
Prof. Dr. med. Gerd Hoffmann
Johann Wolfgang Goethe University Frankfurt/Main, Institute of Sports Sciences, Ginnheimer Landstrasse 39, D-60487 Frankfurt/Main, Germany, Tel+Fax+Q:
0049-6181-62287
Hoffmann@em.uni-frankfurt.de

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