1. Radonbalneology Prof. Dr.med. habil. Dr.rer.nat. Helmut G. Pratzel President of the International Society of Medical Hydrology and Climatology (I.S.M.H.) Prof. Dr.med. habil. Dr.rer.nat. Helmut G. Pratzel President of the International Society of Medical Hydrology and Climatology (I.S.M.H.)

2. Quality limits for medical bath waters Chemical effects can be used in bath tubs if –no disinfection –Concentration in tub is H 2 S > 10 mg/l Radon > 1 kBq/l CO 2 > 1 g/l Brine 10-150 g/l Physical effects can be used in pools if –water is disinfected –temperature >30 °C Which elements in spring waters are effective in bath therapy?

3. Radon Units 1 Mache Unit = 3,64 x 10 -10 Ci/l 1 Ci = 3,7 x 10 10 Bq 1 Mache Unit = 13,468 Bq/l

4. Spas using Radonwater

5. Russian Radon Spas Belochurika (Altai) 4-16 nCi/l Dzchey-Ogus, Issyk-Kul (Kirgisia) 30- 125 nCi/l Nowosibirsk (Sibiria) 4-670 nCi/l Pjatigorsk (North Kaukasus) 18-330 nCi/l Chmelnik (Ukraine) 2-97 nCi/l Zhal-Tubo (Georgia) 2,5-33 nCi/l 250 Sanatoria with artificial Radon

6. Indications Radon-Water in bath tubs and Radon-Gas-baths or Radon-mines Ankylosing spondylitis Degenerative joint disease Spondylarthrosis Myofascial soft tissue syndrome Ovarian hypofunction Allergic bronchial Asthma

7. Clinical Trial Protocol by the Guidelines for Good Clinical Practice (GCP) of the European Community  Trial objectives and purpose  Trial design  Randomisation, Blinding  Selection and withdrawal of subjects  inclusion and exclusion criteria  Treatment of subjects and control medication  Assessment of efficacy  Assessment of safety  Control of side effects and interactions  Control of Compliance  Statistics  Direct Access to Source Data/Documents  Quality control and Quality Assurance Procedures  Ethics

8. Primary Efficacy Variable Only validated parameters should be used. Only one efficacy parameter is to defined. Endpoints used to determine efficacy should be clearly specified. Multiple parameters should be assembled to one score parameter. An efficacy threshold is to defined.

9. Controlled Double-Blind Trials on Radon  Pratzel, Legler, Aurand, Baumann, Franke: Phys Rehab Kur Med 3 (1993) 76-82  Lind-Albrecht 1994  Heisig, Klein, Pratzel 1997  Reiner, Vulpe, Pratzel 1998  Skorepa, Klein, Pratzel 1999  Keil, Klein, Pratzel (not finished)  Pratzel, Legler, Aurand, Baumann, Franke: Phys Rehab Kur Med 3 (1993) 76-82  Lind-Albrecht 1994  Heisig, Klein, Pratzel 1997  Reiner, Vulpe, Pratzel 1998  Skorepa, Klein, Pratzel 1999  Keil, Klein, Pratzel (not finished)

10. Pressure Pain Threshold Test areas 1. M. levator scapulae 2. M. supraspinatus 3. M. teres minor 4. M. deltoideus 5. M. glutaeus maximus 6. M. glutaeus medius 7. M. bizeps femoris 8. M. semimembranosus

11. Double-blind-control equipment Electronic control with bar-code- reader Technical roomBathroom Tap-water line Radon-water line Bath-tub Magnetic valves Bar-code- reader

12. The Barcode-Reader

13. Pratzel, Legler, Baumann: Analgesic Efficacy of Radon baths in case of spondylosis with cervical pain Subject: 23 + 23 patients 45-65 y Verum: Radon baths 3000 Bq/l Control: Water baths Treatment: 9 baths 36 °C during 3 weeks Design: ambulant, massage and gymnastics Follow-up: 2 and 4 months Result: difference in follow-up period p<0,001 Subject: 23 + 23 patients 45-65 y Verum: Radon baths 3000 Bq/l Control: Water baths Treatment: 9 baths 36 °C during 3 weeks Design: ambulant, massage and gymnastics Follow-up: 2 and 4 months Result: difference in follow-up period p<0,001

14. Pressure pain threshold by Radon baths series Ende der Behandlung Period of inspection kg/cm 2 After 1 week After 2 weeks After 3 weeks After 2 month After 4 month 2,0 2,2 2,4 2,6 2,8 3,0 RADON WATER TAP WATER End of Treatment

15. Pressure Pain Threshold 3000 Bq/L Rn Schlema 1993 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 kg/qcm Control Radon p=0,0007p=0,028 Period of evaluation after 1st week after 2nd week after 3rd week Follow up after 2 months Follow up after 4 months

16. Pressure Pain Threshold and subjective feeling of pain 0.5 1 1.5 20 10 20 30 40 50 60 70 80 90 VAS before after 1 week after 2 weeks after 3 weeks after 4 months PPT general pressure pain threshold VAS subjective pain feeling 3 baths 3 kBq/L Follow-up period after 2 months PPT

17. Subjective feeling of pain WaterRadon

18. Pain on movement Water Radon

19. Pain at rest WaterRadon

20. Heisig: Analgetic effect of Radon baths in degenerative joint disease and spondylarthrosis Subject: 25 + 27 patients 28-74 y Verum: Radon baths 800 Bq/l Control: Water baths Treatment: 8 baths 36 °C during 3 weeks Design: ambulant, mono-therapy Follow-up: 2 and 4 months Result: difference in follow-up period p<0,05 Subject: 25 + 27 patients 28-74 y Verum: Radon baths 800 Bq/l Control: Water baths Treatment: 8 baths 36 °C during 3 weeks Design: ambulant, mono-therapy Follow-up: 2 and 4 months Result: difference in follow-up period p<0,05

21. Change of Pressure Pain Threshold Bad Steben 1995 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 kg/qcm p=0,0141 Control Radon Period of evaluation after 1st week after 2nd week after 3rd week Follow up after 2 months Follow up after 4 months

22. 1 1.5 2 2.5 1 1.5 2 Pressure Pain Threshold (mean and max) MAX beforeafter 1 weekafter 2 weeksafter 3 weeksafter 2 months after 4 months PPT general pressure pain threshold MAX maximum pressure pain threshold 3 baths 0,8 kBq/L PPT Follow-up period

23. 1 1.5 2 2.5 0 10 20 30 40 50 60 70 Pressure Pain Threshold and Subjective feeling of pain VAS before after 1 week after 2 weeks after 3 weeks after 2 months after 4 months PPT PPT general pressure pain threshold VAS subjective pain feeling 3 baths 0,8 kBq/L Follow-up period PPT

24. Skorepa: Effect of CO 2 in Radon baths treatment in degenerative joint disease and spondylarthrosis Subject: 35 + 33 patients 22-73 y Verum: Radon 400 Bq/l and CO 2 1 kg/l Control: Radon baths 800 Bq/l Treatment: 8 baths 36 °C during 3 weeks Design: ambulant, mono-therapy Result: no difference: CO 2 increase radon effect

25. Pressure Pain Threshold Bad Steben 1997 before after 1 week after 2 weeks after 3 weeks after 4 months Follow-up period after 2 months

26. Subjective Feeling of Pain Bad Steben 1997 before after 1 week after 2 weeks after 3 weeks after 4 months Follow-up period after 2 months

27. Maximum Pressure Pain Threshold Bad Steben 1997 before after 1 week after 2 weeks after 3 weeks after 4 months Follow-up period after 2 months

28. Franke, Reiner, Pratzel, Franke, Resch: Long-term efficacy of radon spa therapy in rheumatoid arthritis – a randomized, sham- controlled study and follow-up. Rheumatology 2000:39:894-902 Subject: 30 + 30 RA patients <75 y Verum: natural radon 1,3 kBq/l and CO 2 1,6 kg/l Control: artificial CO 2 1,6 kg/l Application: 15 baths 35 °C during 4 weeks Follow up: 3 and 6 month after end of treatment Result: relevant difference in follow-up period

29. Subjective pain feeling Rheumatoide Arthritis (Radon trial Bad Brambach 1997) 1st value CO 2 Radon + CO 2 mm VAS N = 30N = 30/27N = 28/30 Differences to 1st value and 95%-Confidence interval Improvement

30. Moving test by Keitel To bend the fingers Motility of hand joins and arms Stand up from lying Active straddle of legs from lying Stand up from a stool Standing on toes and heel Knee-crooking Standing on one foot Outside Rotation of the hit join Mobility of legs and feet Walking Climbing stairs

31. Moving Test by Keitel Rheumatoide Arthritis (Radon trial Bad Brambach 1997) Radon+CO 2 N = 30N = 28/30N = 30/29 Skt Differenzen zum Ausgangswert und 95%-Konfidenzintervall Improvement 1st value CO 2

32. Measurement of Patient Outcome – MOPO (AIMS –questionaire) Physical handicap and psychosocial Consequences by Rheumatoid Arthritis Mobility Physical activity Skill Activities at home Activities in daily life Social activities Pain Depression Anxiety Assessment included:

33. Measurement of Patient Outcome (MOPO) Rheumatoide Arthritis (Radon trial Bad Brambach 1997) Radon+CO 2 Differenzen zum Ausgangswert und 95%-Konfidenzintervall Skt N = 29/30 Improvement 1st value CO 2

34. Lind-Albrecht: Treatment of ankylosing spondylitis in radon mine Bad Kreuznach Subject: 144 + 118 SA patients, randomized Verum: 10 x 1 hour radon mine Control: no mine Application: 4 weeks Follow up: 3, 6, 9, 12 month after end of treatment Result: relevant difference in follow-up period

35. Relat. Pain after Radon mine treatment Bad Kreuznach Spondylitis Ankylosans (Studie Lind-Albrecht)

36. Relat. NSAIDS-use after Radon mine treatment Bad Kreuznach Spondylitis Ankylosans (Studie Lind-Albrecht)

37. Meta- Analyse Forest-Plot treatmentcontrol

38. Die Permeabilität der Haut Resorption für Gase und Flüssigkeiten durch 2 m 2 Haut L/h 10 1 0,1 0,01 N2N2 He Ar H 2 H2SH2S O2O2 CO 2 Rn mL/h 100 10 1 n-Pentanol n-Butanol Wasser iso-Butanol Ethanol DMSO

39. 0,0001 0,001 0,01 0,1 1 10 100 1000 µl Lösung/cm 2 /h Cortison Corticosteron Indomethacine Salicylic acid Hydrocortison Heparin Acetylsalicylic acid DMSO Progesteron Testosteron Estron Methylsalicylat Jodide Sulfate Strontium Cobalt Silver Pertechnetate Arsenic Bromide Ferrum II Selenite Chromium III Ferrum III Cadmium Caesium Calcium Chloride Potassium Sodium Phenylmercuryborate Methanol Water H2SH2S Radon CO 2 Permeability of skin Skin clearance for solutions in water Water Ethanol Propanol Campher Camphen Heptanol Octanol

40. How Dosis can be calculated by Skin-Clearance? Dosis = Skin-Clearance x Area x Concentration x Time Dosis limit is the amount on the Skin Skin-Clearance is realized by optimal Penetration situation ( Bath, wet Skin, Okklusion Effect of temperature (Q 10. = 1,1-1,4) but skin temperature only low variable

41. Blood level and time of bathing Badedauer Fließgleichgewicht erreicht nicht erreicht

42. Calculation about Radon-kinetic Skin-Clearance = 200 µl/cm 2 h -1 Concentration in bath = 3 kBq/l Area of skin = 2 m 2 Absorption rate = 200 x 3 x 2/100 = 12 kBq/h Skin-Clearance = 200 µl/cm 2 h -1 Concentration in bath = 3 kBq/l Area of skin = 2 m 2 Absorption rate = 200 x 3 x 2/100 = 12 kBq/h Distribution volum = 20 l bei 80 kg KG Elimination constant = 20 h -1 Blood level in steady state= 12 kBq/h / (20 l x 20 h -1 ) = 0,030 kBq/l Blood level after 10 min-bath = 0,030 x (1-e -20 h-1 x 10 min ) = 0,029 kBq/l Concentration in bath water : Blood level = 100 : 1 Distribution volum = 20 l bei 80 kg KG Elimination constant = 20 h -1 Blood level in steady state= 12 kBq/h / (20 l x 20 h -1 ) = 0,030 kBq/l Blood level after 10 min-bath = 0,030 x (1-e -20 h-1 x 10 min ) = 0,029 kBq/l Concentration in bath water : Blood level = 100 : 1

43. Radon-222 Dissolution Polonium Bismutum Plumbum

44. The main effect of radon Radon and the dissolution products penetrate into the horny layer. Alpha-radiation from the horny layer is effective in the stratum spinosum. Dissolution products cannnot penetrate into the living tissue. Radon and the dissolution products penetrate into the horny layer. Alpha-radiation from the horny layer is effective in the stratum spinosum. Dissolution products cannnot penetrate into the living tissue.

45. Langerhans Cells of the skin

46. Effect of Alpha-Radiation on Langerhans Cells

47. Dosis by use of Radon-baths (Radon concentration 1,5 kBq/L; 37 °C) Dosis of skin Dosis of kidneys Dosis of other organs natürliche Dosisleistung Maximum Zeit in Stunden Bath period 20 minutes Risk by radon skin-dosis of ca. 1 mSv per cure treatment is lesser than risk by long use of medicaments..

48. Trial in radon treatment should be used in future research by the following disease assessments Rheumatoide A.HAQ BechterewBASFI Narrow spinal channelLSS-Inst. OsteoarthrosisWOMAC German translation by Sangha O et.al. Rheumatol 56:322-333, 1997

49. BASFI for Ankylosing Spondylitis Ohne Hilfe und Hilfsmittel Socken und Strümpfe anziehen Ohne Hilfe von der Hüfte aus nach vorn beugen um einen Kugelschreiber vom Boden aufzuheben Ohne Hilfe etwas von einem Regal nehmen Von einem Wohnzimmerstuhl ohne Armlehne aufstehen ohne dabei die Hände oder eine andere Hilfe zu benutzen Ohne Hilfe vom Boden aufstehen, wenn Sie auf dem Rücken liegen German translation by Sangha O et.al. Rheumatol 56:322-333, 1997

50. BASFI for Ankylosing Spondylitis Ohne Schmerzen 10 Minuten stehen ohne sich anzulehnen Ohne Benutzung eines Geländers oder Gehhilfen 12-15 Treppenstufen steigen. 1 Fuß pro Stufe Über die Schulter schauen ohne dabei den Körper abzudrehen. Körperlich anstrengende Tätigkeiten verrichten (z.B. krankengymnastische Übungen, Gartenarbeit oder Sport) Zu Hause oder bei der Arbeit den ganzen Tag aktiv sein. German translation by Sangha O et.al. Rheumatol 56:322-333, 1997

51. Literature of Radonbalneology Pratzel, Deetjen: Radon in der Kurortmedizin, I.S.M.H. Verlag 1997, ISBN 3-9804437-2-8 Pratzel: Application of Pressure Algometry in Balneology for Evaluation of Physical Therapeutic Modalities and Drug Effects. Journal of Musculoskeletal Pain:1998:6:111-137 Deetjen, Falkenbach: Radon und Gesundheit, Peter Lang Verlag 1999, ISBN 3-631-35532-7 Franke, Reiner, Pratzel, Franke, Resch: Long-term efficacy of radon spa therapy in rheumatoid arthritis – a randomized, sham- controlled study and follow-up. Rheumatology 2000:39:894-902 Pratzel, Deetjen: Radon in der Kurortmedizin, I.S.M.H. Verlag 1997, ISBN 3-9804437-2-8 Pratzel: Application of Pressure Algometry in Balneology for Evaluation of Physical Therapeutic Modalities and Drug Effects. Journal of Musculoskeletal Pain:1998:6:111-137 Deetjen, Falkenbach: Radon und Gesundheit, Peter Lang Verlag 1999, ISBN 3-631-35532-7 Franke, Reiner, Pratzel, Franke, Resch: Long-term efficacy of radon spa therapy in rheumatoid arthritis – a randomized, sham- controlled study and follow-up. Rheumatology 2000:39:894-902

52. The following power point-files Perkutane Resorption und Balneologie (German) Kneipp-Therapie (German) Radonbalneology (English) Health Tourism and Medical Treatment - two parts in Health Resorts (English) Las nuevas investigaciones en termalismo y los nuevos retos medicos (Spanish) can be downloaded from the web side of the International Society of Medical Hydrology and Climatology: http://www.med.uni-muenchen.de/ismh

53. End of Slides