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OZONETHERAPY
HEALTH TECHNOLOGY ASSESSMENT UNITMEDICAL DEVELOPMENT DIVISION
MINISTRY OF HEALTHMOH/P/PAK/110.06 (TR)he
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BERSATU•BERUSAHA•BERBAKTI•
Ozone TherapyCompleted December 2005
Head, Health Technology Assessment UnitMedical Development DivisionMinistry of Health MalaysiaLevel 4, Block E1, Parcel E,Government’s Office Complex,62590 Putrajaya,Malaysia
Tel: 603 – 8883 1228Fax: 603 – 8883 1230
Available on the following website : http://www.moh.gov.my
Disclaimer
This health technology assessment has been developed from analysis, interpretation and synthesisof scientific research and/or technology assessment conducted by other organizations. It alsoincorporates, where available, Malaysian data, and information provided by experts and applicantto the Ministry of Health Malaysia. While every effort has been made to do so, this documentmay not fully reflect all scientific research available. Additionally, other relevant scientific findingmay have been reported since completion of the review.
MEMBERS OF EXPERT COMMITTEE
Dr Gun Suk ChynConsultant PhysicianMedical DepartmentHospital Seremban
Dr Ngau Yen YauConsultant PhysicianMedical DepartmentHospital Kuala Lumpur
Dr Safari bin ElisClinical SpecialistDepartment of CardiologyHospital Pulau Pinang
Dr Abraham GeorgeClinical SpecialistMedical DepartmentHospital Selayang
Puan Fudziah ArrifinHead of New Drug Unit,Center for Product RegistrationNational Pharmaceutical Control Bureau
PROJECT COORDINATORS
Dr S SivalalDeputy DirectorMedical Development DivisionMinistry of Health Malaysia
Dr Sheamini SivasampuPrincipal Assistant DirectorHealth Technology Assessment UnitMinistry of Health Malaysia
Puan Nik Jah Nik MatScientific OfficerMedical Development DivisionMinistry of Health Malaysia
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EXECUTIVE SUMMARY OZONE THERAPY
INTRODUCTIONOzone (O3) is a controversial gas because, owing to its potent oxidant properities, it exerts damaging effectson the respiratory tract and yet it has been used for decades as a therapy. The disinfectant activity of O3 iswidely been used however the use of ozone in medical therapy is still controversial.
Presently there are nine methods of ozone therapy in medical practice namely direct intra-arterial andintravenous application, rectal insufflations, intramuscular injections, major and minor autohemotherapy,ozonated water, intra-articular injection, ozone bagging, ozonated oil and inhalation of ozone.
OBJECTIVESTo assess the safety and effectiveness of ozone therapy in clinical care.
RESULTSSafetyThere are some case reports of the use of ozone resulting in air embolism, blood borne infections and bilateralvisual field loss after receiving ozone therapy.
Effectiveness(i) HIV and other infectious diseases
There is only anedocatal evidence to support the effectiveness of ozone therapy in the treatmentof HIV or other blood borne infectious diseases. The current evidence is insufficient to recommendthe use of ozone in the treatment of HIV infected patients.
(ii) IschemiaThere is insufficient evidence showing the benefits of ozone in the treatment of limb ischemia,stroke and ischemic heart disease.
(iii) OphthalmologyThere was temporary improvement in three studies that patients had retinitis pigmentosa whowere treated with ozone therapy.
(iv) OrtholaryngologyThere is insufficient evidence to recommend ozone therapy in the treatment of ENT conditions.
(v) Obstetric and GynaecologyThe evidence showing the effectiveness of ozone therapy treatment in reducing the infectionrate in caesarian section are observational studies only.
Similarly, there is insufficient evidence to recommend the use of ozone in the treatment ofpuerperal diseases.
The evidence is only anecdotal in nature as with regards to the use of ozone in the treatment ofprimary infertility.
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(vi) Orthopedic DisordersThere are only three relevant clinical trials on these subjects, thus making it difficult to drawconclusive results.
(vii) CancerThere is insufficient evidence with regards to the effectiveness and safety of ozone therapy incancer patients.
(viii) Skin disordersThe evidence is only anecdotal in nature as with regards to the use of ozone in the treatmentof skin conditions.
CONCLUSIONSCurrent data on the usage of ozone therapy as therapeutic options for various health conditions lacks sufficientsafety and therapeutic advantage over available conventional therapeutic modalities.
RECOMMENDATIONSThere is insufficient evidence to recommend the use of ozone therapy as a form of alternative treatment inpatients with haemotological disorders, autoimmune diseases, ischaemia, eye conditions, ENT, obstetric andgynaecology, orthopaedic conditions, cancer and skin disorders.
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TABLE OF CONTENTS
EXPERT COMMITTEE i
EXECUTIVE SUMMARY iii
TABLE OF CONTENTS v
1 INTRODUCTION 1
2 BACKGROUND 1
3 TECHNICAL FEATURES 3
4 POLICY QUESTION 3
5 OBJECTIVES 3
6 METHODOLOGY 3
7 RESULTS
7.1 SAFETY 4
7.2 EFFECTIVENESS 47.2.1 HIV AND INFECTIOUS DISEASES 47.2.2 ISCHEMIA
Limb IschemiaCNS IschemiaIschemic Heart Disease
7.2.3 ASTHMA 57.2.4 OPHTHALMOLOGY 57.2.5 ORTHOLARYNGOLOGY 57.2.6 OBSTETRICS & GYNAECOLOGY 57.2.7 ORTHOPAEDIC DISORDERS 67.2.8 CANCER 67.2.9 SKIN DISORDERS 6
8 CONCLUSIONS 6
9 RECOMMENDATIONS 6
10 REFERENCES 7
11 EVIDENCE TABLE 13
12 STUDY PROTOCOL 33
OZONE THERAPY
1. INTRODUCTIONOzone is an elemental form of oxygen occurring naturally in the Earth’s atmosphere. It surrounds the earth atan altitude of 50 000 to 100 000 feet. Ozone, in its gaseous state, is toxic to the human tissues. In aqueousform, however, it may have therapeutic effects.
Ozone was first discovered by the German chemist Christian Frederick Schonbein in the year 1840 in theUniversity of Basel in Switzerland. Ozone was used for the first time to disinfect operating rooms in 1856and subsequently for water treatment in 1860 (Foundation for alternative science & Technology). The GermanArmy used ozone to treat battle wounds and other infections during World War I.
According to the Europe based Medical Society for Ozone and the National Centre for Scientific Researchin Cuba, physicians are currently treating the following diseases with different forms of ozone: abscesses,acne, AIDS, allergies, anal fissures, arthritis, asthma, cancerous tumors, cerebral sclerosis, circulatorydisturbances, cirrhosis of liver, constipation, corneal ulcers, cystitis, decubitus ulcers (bedsores), diarrhea,fungal diseases, gangrene, gastroduodenal ulcers, glaucoma, hepatitis, herpes simplex and zoster,hypercholesterolemia, osteomyelitis, Parkinson’s disease, Raynaud’s disease, rheumatoid arthritis, seniledementia, sepsis, sinusitis, spondylitis, thrombophlebitis, wound healing and others. This list is not exhaustive.(Ref: Proceedings of the first Ibero Latin American Congress on Ozone Application 1990)
Ozone therapy is still a controversial form of alternative therapy. Young children and adults with lung problemsare told to stay indoors, because ozone can aggravate allergies, bronchitis, asthma and other health problems.On the other hands, many believe that ozone will help heal them of cancer, heart disease, candida, HIV-related problems and a host of other diseases including autoimmune disease, rheumatoid arthritis and lowback pain. There are few elements that have been as controversial as ozone, and none that have created sucha medical paradox: how can a gas be both dangerous to health as a pollutant, yet can also be used to effectivelytreat some of humanity’s most threatening diseases?
Many physicians and clinics offering this form of therapy in Canada and the United States have been forcedout of practice by various government agencies. Yet, in the past decade this therapy has gained more prominenceand credibility in other apart of the world. For the most part, ozone therapy is only available in Mexico, someCaribbean countries like the Bahamas, Cuba and the Dominican Republic as well as in Europe, especiallyGermany and eastern Europe.
2. BACKGROUNDMedical OzoneAfter the turn of the century, interest began to focus on the uses of ozone in medical therapy. However, it wasnot until 1932 that ozone was seriously studied by the scientific community, when ozonated water was usedas a disinfectant by Dr. E.A. Fisch, a German dentist. One of his patients was the surgeon Erwin Payr, whoimmediately saw the therapeutic possibilities of ozone in medical therapy. Dr. Payr, along with the Frenchphysician P. Aubourg, was the first medical doctor to apply ozone gas through rectal insufflations to treatmucous colitis and Fistulae.
At the present time, there are eight simple methods and one highly complex method of ozone therapy that areused in medical practice.
1. Direct intra-arterial and intravenous applicationAn ozone/oxygen mixture is slowly injected into an artery or vein with a hypodermic syringe. This method is usedprimarily for arterial circulatory disorders. According to Gerard V. Sunnen, M.D., “Due to accidents produced bytoo rapid introduction of the gas mixture into the circulation, this technique is now rarely used” (1988).
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2. Rectal insufflationsFirst pioneered by Payr and Aubourg in the 1930’s, a mixture of ozone and oxygen is introduced through therectum and absorbed into the body through the intestine. Used for a wide variety of health problems, thismethod is considered one of the safest. In a typical treatment for ulcerative colitis, for example, 75 microgramsof ozone per milliliter of oxygen are used (treatment begins with 50ml of oxygen which can be increasedslowly to 500 ml per treatment) 16 While administered under medical supervision in Germany, Russia andCuba, a growing number of private individuals in the United States use this method for self-treatment forcancer, HIV-related problems and other diseases.
3. Intramuscular injectionA small amount of an ozone and oxygen mixture (up to 10 ml) are injected into the patient (usually in thebuttocks) like a normal injection would be. This method is commonly used to treat allergies and inflammatorydiseases. Intramuscular injections are sometimes utilized as an adjunct to cancer therapies in Europe.
4. Major and minor autohaemotherapyUsed since the 1960’s, minor autohaemotherapy involves removing a small amount (usually 10 ml) of thepatient’s blood from a vein with a hypodermic syringe. The blood is then treated with ozone and oxygen, andgiven back to the patient with an intramuscular injection. Thus the blood and ozone becomes a type of auto-vaccine given to the patient that is derived from their own cells, thus forming a unique vaccine that can bevery specific and effective in treating the patient’s health problem. Major autohaemotherapy calls for theremoval of between 50-100 ml of the patient’s blood. Ozone and oxygen are then bubbled into the blood forseveral minutes, and then the ozonated blood is re-introduced into a vein. These methods have been used totreat a wide variety of health problems, including herpes, arthritis, cancer, heart disease and HIV-infection.It is probably the most commonly used type of ozone therapy today.
5. Ozonated waterThis method calls for ozone gas to be bubbled through water, and the water is used externally to bathewounds, burns and slow-healing skin infections. It is also used as a disinfectant by dentists who performdental surgery. In Russia, physicians are using ozonated water to irrigate body cavities during surgery. Inboth Russia and Cuba, ozonated water is used to treat a wide variety of intestinal and gynecological problems,including ulcerative colitis, duodenal ulcers, gastritis, diarrhea and vulvovaginitis (Proceedings of the FirstIberolatinamerican Congress on Ozone Applications, 1990).
6. Intra-articular injectionIn this method, ozone gas is bubbled through water and the mixture is injected directly between the joints. Itis used primarily by physicians in Germany, Russia and Cuba to treat arthritis, rheumatism and other jointdiseases.
7. Ozone baggingThis non-invasive method uses a specially made plastic bag that is placed around the area to be treated. Anozone/oxygen mixture is pumped into the bag and the mixture is absorbed into the body through the skin.Ozone bagging is primarily recommended for treating leg ulcers, gangrene, fungal infections, burns andslow-healing wounds.
8. Ozonated oilUsed primarily to treat skin problems, ozone gas is added to olive oil and applied as a balm or salve for long-term, low-dose exposure.
9. Inhalation of ozoneThe lungs are the organs most sensitive to ozone. Physicians who use medical ozone warn that inhalingozone into the lungs can bring about alterations in the density of the lung tissue, can damage delicate lungmembranes, irritate the epithelium [the surface layer of mucus] in the trachea and bronchi, and can lead to
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emphysema. They caution users that no ozone should escape into the room in which it is being used. Modernmedical ozone generators are specially designed so that the accidental escape of ozone gas cannot take place.Dr. Stephen A. Levine, the co-author of Antioxidant Adaptation, cautions people against using commercialair purifiers which generate small amounts of ozone to clean the air, since ozone should not be inhaled.
The therapeutic concentrations of ozone vary with the mode of administration, the lowest concentrationbeing in major autohaemotherapy.
Various private medical practitioners located mainly in the Klang Valley currently offer ozone therapy forvarious indications like cancer treatment, rheumatism, chronic viral infections and maintaining youthfullooks. In addition, ozonated water is commercially available
3. TECHNICAL FEATURESOzone is an inactivated, trivalent (O
3) form of oxygen (O
2). Ozone breaks down into two atoms of regular
oxygen by giving up an atom of singlet oxygen over a period of 20 to 30 minutes. Ozone is considered one ofthe most potent oxidants in nature, but the mechanism of its therapeutic action is unclear. Some of thepossible explanations for this include the generation of peroxides by ozonolysis with unsaturated fatty acidsin cell membranes, activation or generation of reactive oxygen species which function as physiologicalenhancers of various biological processes (including increased production of ATP), and increased expressionof intracellular enzymes with antioxidant activity. It has been reported that exposure to ozone results in achange in the level of a variety of biological factors, e.g. cytokines [IFNc, TNFa, TGFb and IL-8], acutephase reactants and adhesion molecules from the integrin family such as CD11b. Other reports suggestincreased motility and adhesion of peripheral blood polymorphonuclear cells to epithelial cell lines afterexposure to ozone. Similarly, major autohaemotherapy-induced leucocytosis and enhanced phagocytic activityof polymorphonuclear cells have been reported.
4. POLICY QUESTIONShould ozone therapy be offered as standard therapy for specific indications?
5. OBJECTIVETo assess the safety and effectiveness of ozone therapy in treatment of medical conditions. This assessmentdoesn’t look at the effects of ozone in the atmosphere onto the health of the individual or patient.
6. METHODOLOGYThe databases searched were Pubmed, Cochrane Library, E-medicine, International Ozone Associationdatabase, Foundation for Alternative Science & Technology, general databases like Google as well as webpages,and many other collections of articles downloaded from internet. The key words used for search includedozone, ozone therapy, medical ozone, oxygen-ozone therapy, ozone therapy and autoimmune diseases, ozonetherapy and RA OR rheumatoid arthritis, ozone therapy AND low back pain, ozone AND haematolog*,ozone AND obstetric, ozone AND gynaecology, ozone AND orthopaedic, ozone AND ischaemia, ozoneAND cancer and ozone AND skin.
There were no limits in search; papers of any language were included. Problems encountered in the literaturesearch were related to the paucity of randomised control clinical trials in the area of ozone therapy in allfields of medicine.
A critical appraisal of all relevant literature was carried out and the evidence graded according to the modifiedCatalonian Agency of Health Technology Assessment (CAHTA) scale.
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7. RESULTSOzone’s use in medicine has been debated for decades, but references to its use were sporadic in the majormedical journals. Most of the claims of its efficacy were anecdotal. Ozone had been claimed to be able to killviruses, bacteria, parasites, fungi and be useful for cancers (Bocci, 1992). The treatment may activate thehost’s immune system by inducing the production of immunoactive cytokines. It is also suggested that sinceviruses, bacteria and other organisms need an anaerobic environment, exposure to ozone should kill theseharmful organisms.
7.1. SAFETY
There has been a reported case of death due to air embolism during the use of ozone in the treatment ofpsoriasis (Marchetti & Monaca, 2000).
Hepatitis C and HIV infections have also been reported following ozone autohaemotherapy (Daschner, 1997).A more recent cross sectional study demonstrated that transmission of HCV infection due to crosscontamination occurred amongst 6 out of 31 patients who were exposed to autohaemotherapy or intramuscularinjection in a outpatient department of a hospital in Italy (Faustini et al 2005).
Apart from this, it has been reported that a 45-year-old woman complained of acute bilateral visual loss afterintra-discal and peri-ganglionic injection of ozone-oxygen gas mixture for lumbar disk herniation (Lo Giudice,2004). Corea (2004) also reported a case of vertebrobasilar stroke after treatement with ozone-oxygen forlumbar disc herniation.
7.2. EFFECTIVENESS
7.2.1. HIV AND INFECTIOUS DISEASESAn anonymous report (1994) claimed that ozone together with oxygen can inactivate the HIV virus. Carpendaleet al (1993) reported the efficacy of ozone in the treatment of AIDS related diarrhoea. In this paper, three ofthe four patients with diarrhoea of unknown etiology treated with daily insufflations of medical ozone,experienced complete resolution, while the other patient had marked improvement.
A review by Wells et al (1991) reported that ozone inactivates HIV-1 virions in a dose dependant manner.
Two studies reported that ozone being a strong oxidizer, can stimulate the increase of cellular anti-oxidantenzymes, eventually inhibiting the oxidative stress, and these may have implications in the treatment ofmany diseases including HIV (Rodder et al 1991, Bocci 1996).
A non randomized controlled study in patients suffering from Hepatitis A, B or C demonstrated that all 40patients who received ozone were totally cured of hepatitis, and the rate of healing was faster in this group,but there was no mention of the breakdown of patients infected with hepatitis in the respective groups(Betancourt et al)
7.2.2. ISCHAEMIALimb ischaemiaWhile there have been a number of reports on the effectiveness of ozone in the treatment of limb ischemia(Sroczynski et al, 1992; Turczynski et al, 1991; Maslennikov et al, 1997; Tylicki et al, 2001; Tylicki et al,2003; Biedunkiewicz et al, 2004), these were small non-randomized clinical trials, from a few centers mainlyin Poland and Russia. Tafil-Klawe et al (2002) study involving 62 patients with lower limb ischaemia, ofwhom 32 patients were treated with ozone whereas the remainder were treated with traditional balneology,found better results with ozone.
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CNS Ischaemia
A study of 85 patients with ischaemic insult by Kotov et al treated with ozone demonstrated a decrease in theintra-cerebral blood circulation asymmetry, increased cerebral circulation reactivity and a functional restorationin the circle of Willis.
Ischaemic Heart DiseaseAnother cross sectional study of ozone therapy in patients with progressive angina pectoris resulted inelimination of non-stable conditions with significant reduction of coronary insufficiency symptoms (Shaarovet al).
7.2.3. OPHTHALMOLOGYA double blind RCT involving 123 subjects suffering from retinitis pigmentosa demonstrated that ozonetreatment was effective, although its action is temporary (Moreno et al). A cross sectional study by Mapolonet al reported remission of photophobia and phototopsia in all 50 patients with retinitis pigmentosa treatedwith ozone.
Similarly, another study by Diaz et al comprising of 180 patients with different ophthalmologic diseases likeretinitis pigmentosa, myopia, chronic open angle glaucoma, optic atrophy and diabetic retinopathy weretreated with daily rectal ozone therapy, demonstrated improvement ranging from 23%- 63% at follow-upover one year.
Satiesteban et al in a cross sectional study of 60 patients suffering from optic nerve dysfunction treated withozone demonstrated 86% and 83% improvement in Pelli Robson Contrast Sensitivity Test (PRCST) andvisual field (VF) by Goldmann Perimetry.
7.2.4. ORTHOLARYNGOLOGYIn a small randomized controlled trial by Basabe it was demonstrated that there was improvement inaudiometry, electrophysiological threshold and the latency of the wave V to 90 DB for the same ear, in agreat percentage of children that received ozone therapy.
A cross sectional study of patients with chronic purulent mesotympanitis treated with ozone in Russia,observed inflammation control of mucous membrane, discharge reduction and restoration of auditory tubefunction that (Shakov & Edeleva 1996)
7.2.5. OBSTETRICS & GYNAECOLOGYTwo unpublished non randomized controlled trials demonstrated that the patients with caesarian sectionstreated with ozone had less infectious complications compared to controls (Kovalev & Clemente-Apumayta,Kovalev). An unpublished cross sectional study by Kachlina reported that the maximum positive effect ofozone was seen in those patients with intrauterine infections without signs of inflammation compared tothose with signs of inflammatory process.
Similarly, another non randomized controlled trial noted benefits in patients with various puerperal diseasesin postnatal period treated with ozone compared with the control group (Kachalina et al - unpublished article)
Two cross sectional studies using ozone therapy in the treatment of female infertility and for endometritisshowed improvement. However, these studies had small sample sizes (Mello & ‘Mello;, Gretchkanev et al -unpublished article)
7.2.6. ORTHOPAEDIC DISORDERS
There were only 3 relevant clinical trials available on these subjects, thus making it difficult to draw conclusiveresults (D’Erme M et al 1998; Andreula CF et al 2003; Alex B)
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7.2.7. CANCERA review by Ernst (2001) concluded that knowledge regarding the potential benefit and harm of ozone incancer patients is insufficient. Therefore such therapy can’t be recommended as an alternative form of treatmentfor cancer patient.
Similarly the American Cancer Society has recommended in two review articles that that there is little or noevidence that ozone is effective for the treatment of cancer (Cancer Journal for Clinicians 1993, CancerJournal for Clinicians 1994).
7.2.8. SKIN CONDITIONSThe evidence is only anecdotal in nature as with regards to the use of ozone in the treatment of skin conditions(Jordan et al 2002; Panminerva et al 1995).
8. CONCLUSIONSCurrent data on the usage of ozone therapy as therapeutic options for various health conditions lacks sufficientsafety and therapeutic advantage over available conventional therapeutic modalities.
9. RECOMMENDATIONSThere is insufficient clinical evidence to recommend ozone therapy as a form of alternative treatment inpatients with HIV AND infectious diseases, autoimmune diseases, ischaemia, eye conditions, ENT, obstetricsand gynecology, orthopedic disorders, cancer and skin conditions.
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49. Homutinnikova NE, Durnovo EA. The effect of ozone on the lipid peroxidation processes in caseof mandible fractures. Nizhny Novgorod State Medical Academy, Department of Surgical Dentistryand Maxillofacial Surgery. Russia. Available at: www.oxyplus.net
50. Indications for ozone therapy. In: Viebahn R. The use of ozone in medicine. 4th English edition.Germany; 2002:69-71.
51. Is Medical Ozone Therapy Legal? Available at:www.terra.es
52. Kachalina T. S, Katkova N. Yu, Grechkanev G. O. The use of ozone therapy in the treatment andprophylaxis of intrauterine fetus infection. Department of Obstetrics and Gynecology, NizhnyNovgorod, Russia.Available at: www.oxyplus.net
53. Kachalina T. S, Peretyagina N. S, Antonova N. S. Possibility for parenteral application of ozone inearly postnatal period in case of infectious complications. (Unpublished full article)
54. Kotov S, Gustov A, Mochalov A, Novgorod N. Ozone therapy influence on hemodynamics in patientswith ischemic insult. (Abstract from 3rd International Symposia on Ozone Applications, Cuba)
55. Kovalev M.I. Clemente-Apumayta I.M. Immune status during ozone therapy for the prophylaxisof infections after caesarian. (Unpublished full article)
56. Kovalev. Ozone treated women after caesarean and interferon profile. (Unpublished full article)
57. Kramer, Fritz, “Ozone in the Dental Practice”, Medical Applications of Ozone (Norwalk, CT:International Ozone Association, Pan American Committee, 1983) pp. 258-65
58. Lipatov KV, Sopromadze MA, Shekhter AB,Rudenko TG, Emel’ianov AIu. Ozone-ultrasonic therapyin the treatment of purulent wounds. Khirurgiia (Mosk). 2002;(1):36-9.[abstract] [Article in Russian]
59. Lo Giudice G, Valdi F, Gismondi M, Prosdocimo G, de Belvis V (2004). Acute bilateral vitreo-retinal hemorrhages following oxygen-ozone therapy for lumbar disk herniation. Am J Ophthalmol.Jul; 138(1):175-7.
60. Lower limb ulcers: ozone oil therapy. Performed in: Louis Pasteur Policlinic & National Center forScientific Research www.o3zone.com
61. Lynch E, Johnson N, Johnson J. Clinical reversal of root caries using ozone. Queen’s University ofBelfast, United Kingdom.Available at:www.dentalozone.co.uk
9
62. Malanchuk VA, Kopchak AV. Ozone-oxygen therapy in maxillo-facial bone surgery. Departmentof Oral and Maxillo-facial Surgery, National Medical University. Ukraine.Available at: www.oxyplus.net.
63. Marchetti D, La Monaca G (2000). An unexpected death during oxygen-ozone therapy. Am J ForensicMed Pathol. Jun; 21(2):144-7
64. Maslennikov OV, Sharov IG, Potekhina IP, Dushkina NG, Kryzhanovskaia NA, Maslennikova NO,Bolgov VF, Pavlovskaia EE, Zheglova LV, Chalkina SN (1997). Effect of ozone therapy onhemostatic changes in patients with vascular atherosclerosis. [Article in Russian]; 75(10):35-7.
65. Matsumoto A, Sakurai S, Shinriki N, Suzuki S, Miura T. Therapeutic effects of ozonized olive oilin the treatment of intractable fistula and wound after surgical operation.Available at: www.oxyplus.com.
66. Menendez, Silvia, Ozomed/Ozone Therapy (Havana: National Center for Scientific
67. Mochalov A. Kotov. S. Ozone Therapy and the Neurologic Behaviour Of A BackboneOstechondrosis. (Abstract from 3rd International Symposia on Ozone Applications, Cuba)
68. Moreno N, Peláez O, Alemán T, Barceló C. Controlled clinical trial on the use of ozonated bloodas a treatment for retinitis pigmentosa. (Abstract from 2nd International Symposia on OzoneApplications, Cuba)
69. Naba’a AL, Shorman HAI, Lynch E. Ozone management of Occlusal Pit and Fissure caries (PFC):12 months review. Oral Health Research Centre, School of Dentistry, Queen’s University Belfast,Northern Ireland, UK.Available at: www.dentalozone.co.uk
70. No authors listed (1993). Questionable methods of cancer management: hydrogen peroxide andother “hyperoxygenation” therapies. CA Cancer J Clin. Jan- Feb; 43 (1); 47-56
71. No authors listed (1994). Questionable methods of cancer management; electronic devices. CACancer J Clin; 44; 115-127
72. Othmer, Kirk, Encyclopedia of Chemical Technology, Vol. 16, 3rd ed. (New York: John Wiley &Sons, 1981) p. 705
73. Ozone: ‘The silent healer’ Available at: www.stanfordcenter.com.
74. Ozone therapy and viscosity of blood and plasma distance of intermittent claudication and certainbiochemical components in patients with diabetes type II and ischemia of the lower extremities.Pol Tyg Lek. Sep 9-30; 46(37-39): 708-10.
75. Ozone Therapy. In: Complementary & Alternative Medicine by Natural Standard and the Facultyof the Harvard Medical School.Available at: www.intelihealth.com
76. Ozone Therapy-The Healing Power of Ozone.Available at: www.caringmedical.com/therapies/ozonetherapy.asp
77. Ozone. Documentation for immediately dangerous to life or health concentrations. Available at:www.cdc.gov/niosh/idlh/10028156.html
78. Peralta C, Leon OS, Xaus C, Prats N, Jalil EC, Planell ES, Puig-Parellada P, Gelpi E, Rosello-Catafau J. Protective effect of ozone treatment on the injury associated with hepatic ischemia-reperfusion: antioxidant-prooxidant balance. Department of Medical Bioanalysis, Instituto deInvestigaciones Biomedicas de Barcelona, CSIC-IDIBAPS, Spain
79. Peretyagin SP, Kostina OV, Strutchkov AA,Vilkov SA, Borisevitch AL, Dmitriev DG, SchichragimovVA. Methodology of using ozone in the early complex treatment of burn disease at early stage.Available at:www.oxyplus.net
80. Proceedings of the First Iberolatinamerican Congress on Ozone Application (Havana: NationalCenter for Scientific Research, 1990)
10
81. Questionable methods of cancer management: hydrogen peroxide and other ‘hyperoxygenation’therapies. CA Cancer J Clin. 1993 Jan-Feb; 43(1):47-56.
82. R Chandra-D’Mello, R ‘Mello. Ozone therapy in female infertility. (Unpublished full article )
83. Santiesteban R, Menéndez1 S, Francisco M, Luis S. Ozone therapy in patients suffering fromoptic nerve dysfunction. (Abstract from 2nd International Symposia on Ozone Applications, Cuba)
84. Rasterayeva M, Struchkov S, Belova A,Peretaygin S, Khroulev S. Ozone therapy in complextreatment of neuropathy in burn patients.Available at: www.oxyplus.net
85. Recommended dosages and treatment frequencies depending on indication and application method.In: Viebahn R. The use of ozone in medicine. 4th English edition. Germany; 2002:143
86. Rilling, S. and Viebahn, R., The Use of Ozone in Medicine (Heidelberg: Haug Publishers, 1987) p. 17
87. Roder W, Muller WE, Merz H (1991). Is ozone suitable for sterilization of HIV infected bones?Unfallchirurg. Jan; 94(1): 50- Article in German
88. Salem A, Marashdeh MM, Lynch E. Ozone efficacy in treatment of occlusal caries in primaryteeth. Oral Health Care Research Centre, School of Dentistry, Queen’s University Belfast, NorthernIreland, UK.Available at: www.dentalozone.co.uk.
89. Schierhorn K, Zhang M, Matthias C, Kunkel G. Influence of ozone and nitrogen dioxide on histamineand interleukin formation in human nasal mucosa culture system. Department of ClinicalImmunology and Asthma-OPD and Department of Otorhinolaryngology, Virchow-Klinikum,Humboldt-University, Berlin, Germany. Am J Respir Cell Mol Biol 1999;20:1013-9
90. Shaarov Y, Maslennikova N, Dushkina N, Maslennikov O. Ozone therapy in ischemic heart disease(IHD). (Abstract from 2nd International Symposia on Ozone Applications, Cuba)
91. Shakhov V, Edeleva A. The Use of Ozone Therapy In Chronic Purulent Mesotympanitis. (Abstractfrom 2nd International Symposia on Ozone Applications, Cuba)
92. Sorokina S, Lukinych L. Ozone therapy as a part of complex treatment of a paradontium disease.2nd International Symposium on Ozone Applications, Cuba, 24-26 Maret 1997. “Ozone inMedicine”. [abstract]
93. Sroczynski J, Antoszewski Z, Matyszczyk B, Krupa G, Rudzki H, Zbronska H, Skowron J (1992).Clinical assessment of treatment results for atherosclerotic ischemia of the lower extremities withintraarterial ozone injections. [Article in Polish] Pol Tyg Lek. Oct 19-26; 47(42-43):964-6.
94. Sunnen GV. Ozone in medicine: Overview and future direction.Available at: www.triroc.com/sunnen/topics/ozonemed.htm
95. Sunnen GV. The utilization of ozone for external medical applications. 1998.Available at: www.triroc.com/sunnen/topics/utilization.htm
96. Sunnen, Gerard, “Ozone in Medicine: Overview and Future Direction”, Journal of Advancementin Medicine, Vol. 1, No. 3, Fall 1988.
97. Turcic J, Hancevic J, Antoljak T, Zic R, Alfirevic I. Effects of ozone on how well split-thicknessskin grafts according to Thiersch take in war wounds. Results of prospective study. Clinical HospitalCenter Rebro, Croatia [abstract]
98. Turczynski B, Sroczynski J, Antoszewski Z, Matyszczyk B, Krupa G, Mlynarski J, Strugala M(1991) Ozone therapy and viscosity of blood and plasma, distance of intermittent claudication andcertain biochemical components in patients with diabetes type II and ischemia of the lowerextremities. [Article in Polish] Pol Tyg Lek. Sep 9-30;46(37-39):708-10
99. Tylicki L, Biedunkiewicz B, Nieweglowski T, Chamienia A, Slizien AD, Luty J, Lysiak-SzydlowskaW, Rutkowski B (2004). Ozonated autohemotherapy in patients on maintenance hemodialysis:influence on lipid profile and endothelium. Artif OrgansFeb;28(2):234-7
11
100. Tylicki L, Niew Glowski T, Biedunkiewicz B, Burakowski S, Rutkowski B (2001).Beneficial clinicaleffects of ozonated autohemotherapy in chronically dialysed patients with atherosclerotic ischemiaof the lower limbs—pilot study. Int J Artif Organs. Feb;24(2):79-82.
101. Tylicki L, Nieweglowski T, Biedunkiewicz B, Chamienia A, Debska-Slizien A, Aleksandrowicz E,Lysiak-Szydlowska W, Rutkowski B (2003). The influence of ozonated autohemotherapy onoxidative stress in hemodialyzed patients with atherosclerotic ischemia of lower limbs. Int J ArtifOrgans. Apr;26(4):297-303
102. Using Ozone in General Dental Practice. Available at: www.uksmile.co.uk.
103. V. M. Zuev; N. M. Pobedynsky; D. G. Krasnicov; T. A. Djibladze; L. S. Alexandrov y M. I. Kovalev.Ozone effectiveness in the treatment of chronic fetal hypoxia. (Abstract from 3rd InternationalSymposia on Ozone Applications, Cuba)
104. Vaiano F, Franzini M. O2-O3-therapy of non healing foot and leg ulcers in diabetic patients. ESCI2003: 37th Annual Scientific Meeting of the European Society for Clinical Investigation Verona,Italy, 2-5 April 2003 “The Pathophysiology of Diseases: from bench to bedside”.
105. Van der zee H, De Monte A. Ozone autohemotherapy in lower limb ulcerations.Available at: www.oxyplus.com
106. Verazzo G, Coppola L, Luongo C, Sammartino A, Giunta R, Grassia A, et al. Hyperbaric oxygen,oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusivearterial disease. Undersea Hyperb Med 1995;22:17-22 [abstract].
107. Vulvovaginitis. Ozonised ovules application. C.G. Central clinic and National Centre for ScientificResearch.Available at: www.naturozone.com/ingles/clitesti.htm
108. Watson DE. Lawrence Radiation Laboratory University of California Livermore. The risk ofcarcinogenesis from long-termlow-dose exposure to pollution emitted by fossilfueled power plants.Available at: www.enformy.com/!lrl1.html
109. Wells KH, Latino J, Gavalchin J, Poiesz BJ (1991). Inactivation of human immunodeficiency virustype 1 by ozone in vitro. Blood. Oct 1; 78(7): 1882-90
110. Williams LK, Langley R, Howell RJ (2000). Ozone. The good, the bad and the ugly. NC Med J;Mac-Apr: 61(2); 84-9.
111. Wozniak A, Klawe MT, Drewa T, Ponikowska I,Drewa J, Drewa G, et al. Ozone therapy and theactivity of selected lysosomal enzymes in blood serum of patients with lower limb ischaemiaassociated with obliterative atheromatosis. Med Sci Monit 2002;8:CR520-5.
112. Xie W, Zhang L, Yang R. Peran larutan ozon pada debridement dan sterilisasi luka bakar. ZhonghuaShao Shang Za Zhi. 2000;16:163-5. China. [abstract] [Article in Chinese]
113. Y. Betancourt Y., J.M. Toledo, E. Recio1, A. Gómez, M. Rodríguez1, C. Harrys1, J.P. Pina2. Ozonetherapy: an useful alternative on virulent hepatitis treatment. (Abstract from 2nd InternationalSymposia on Ozone Applications, Cuba)
114. Y. Mapolon, M. Palma1, E. Resio, M. Rodríguez, E. Dyce1, C. Harrys, J. C. Pina1 Effects of ozonein patients with retinitis pigmentosa. (Abstract from 2nd International Symposia on OzoneApplications, Cuba
12
EV
IDE
NC
E T
AB
LE
: OZ
ON
E T
HE
RA
PY
ASP
EC
T:
H
IV/ H
BV
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Gar
ber
GE
, Cam
eron
DW
, Haw
ley-
Fos
sN
, Gre
enw
ay D
, Sha
nnon
ME
(19
91)
The
use
of
ozon
e-tr
eate
d bl
ood
in th
eth
erap
y of
HIV
infe
ctio
n an
d im
mun
edi
seas
e: a
pil
ot s
tudy
of
safe
ty a
ndef
fica
cy.
AID
S.
Aug
; 5(8
): 9
81-4
.
Wel
ls K
H, L
atin
o J,
Gav
alch
in J
, Poi
esz
BJ
(199
1).
Inac
tiva
tion
of
hum
anim
mun
odef
icie
ncy
viru
s ty
pe 1
by
ozon
ein
vit
ro.
Blo
od.
Oct
1; 7
8(7)
: 188
2-90
Rod
er W
, Mul
ler
WE
, Mer
z H
(19
91).
Is o
zone
sui
tabl
e fo
r st
eril
izat
ion
of H
IVin
fect
ed b
ones
?
Unf
allc
hiru
rg.
Jan;
94(
1):5
0[A
rtic
le in
Ger
man
]
RC
T
Rev
iew
A p
hase
I st
udy
of o
zone
blo
od tr
eatm
ents
in 1
0 pa
tien
ts w
ith
HIV
.N
o si
gnif
ican
t tox
icity
was
obs
erve
d. T
hree
pat
ient
s w
ith m
oder
ate
imm
unod
efic
ienc
y sh
owed
im
prov
emen
t in
sur
roga
te m
arke
rs o
fH
IV-a
ssoc
iate
d im
mun
e di
seas
e.
A p
hase
II
cont
rolle
d an
d ra
ndom
ized
dou
ble-
blin
ded
stud
y w
asin
itiat
ed c
ompa
ring
rein
ject
ion
of o
zone
-tre
ated
blo
od, a
nd re
inje
ctio
nof
unp
roce
ssed
blo
od fo
r 8 w
eeks
, fol
low
ed b
y a
4-w
eek
obse
rvat
ion
peri
od. O
zone
had
no
sign
ific
ant e
ffec
t on
hem
atol
ogic
, bio
chem
ical
or c
linic
al t
oxic
ity w
hen
com
pare
d w
ith p
lace
bo.
CD
4 ce
ll co
unt,
inte
rleu
kin-
2, g
amm
a-in
terf
eron
, bet
a 2-
mic
rogl
obul
in, n
eopt
erin
and
p24
antig
en w
ere
also
una
ffec
ted
by b
oth
trea
tmen
t arm
s.
In c
oncl
usio
n, o
zone
the
rapy
doe
s no
t en
hanc
e pa
ram
eter
s of
imm
une
acti
vati
on n
or d
oes
it d
imin
ish
mea
sure
able
p24
ant
igen
in H
IV-i
nfec
ted
indi
vidu
als.
Thi
s st
udy
sugg
est
that
ozo
ne v
ia a
spe
cial
ly d
esig
ned
devi
cead
min
iste
red
to b
ody
fluid
s off
ers p
rom
ise a
s a m
eans
to in
activ
ate h
uman
retro
viru
ses
in h
uman
bod
y flu
ids
and
bloo
d pr
oduc
t pre
para
tions
.
Ozo
ne w
as f
ound
to
inac
tivat
e H
IV-1
vir
ions
in
a do
se-d
epen
dent
man
ner.
The
dat
a in
dica
te th
at th
e an
tivir
al e
ffec
ts o
f ozo
ne in
clud
evi
ral p
artic
le d
isru
ptio
n, re
vers
e tr
ansc
ript
ase
inac
tivat
ion,
and
/or a
pertu
rbat
ion
of th
e ab
ility
of t
he v
irus t
o bi
nd to
its r
ecep
tor o
n ta
rget
cel
ls.
Thi
s ex
peri
men
tal
in v
itro
stu
dy s
how
ed t
hat
ozon
e tr
eatm
ent
cann
ot in
acti
vate
HIV
in b
one
for
tran
spla
ntat
ion
HIV
inf
ecti
on c
an b
e tr
ansf
erre
d by
blo
od,
bloo
d pr
oduc
ts a
ndor
gan
tran
spla
ntat
ion.
In
trau
mat
ic s
urge
ry a
llog
enei
c bo
netr
ansp
lant
atio
n is
com
mon
ly u
sed
for r
econ
stru
ctio
n in
sev
ere
bone
inju
ries
. Thi
s te
chni
que
has
been
aba
ndon
ed s
ince
the
appe
aran
ceof
rep
orts
of
infe
ctio
ns w
ith
HIV
.
Thi
s st
udy
clai
med
the
met
hodo
logy
used
was
RC
T.H
owev
er, t
hede
scri
ptio
ngi
ven
does
not
refl
ect
this
.
Sm
all s
ampl
esi
ze
1. 2. 3.
13
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Car
pend
ale
MT,
Fre
eber
g J,
Gri
ffis
s JM
(199
3).
Doe
s oz
one
alle
viat
e A
IDS
dia
rrhe
a?
J C
lin
Gas
troe
nter
ol.
Sep
; 17(
2): 1
42-5
.
Boc
ci V
(19
99).
Bio
logi
cal a
nd c
lini
cal e
ffec
ts o
f oz
one.
Has
ozo
ne th
erap
y a
futu
re in
med
icin
e?
Br
J B
iom
ed S
ci 5
6(4)
:270
-9.
Boc
ci V
(19
92).
Ozo
niza
tion
of
bloo
d fo
r th
e th
erap
y of
vira
l dis
ease
s an
d im
mun
odef
icie
ncie
s.A
hyp
othe
sis.
Med
Hyp
othe
ses.
Sep
; 39(
1):3
0-4.
Cro
ss s
ecti
onal
Rev
iew
art
icle
Rev
iew
Fiv
e pa
tien
ts w
ith
acqu
ired
imm
une
defi
cien
cy s
yndr
ome
(AID
S)
or A
IDS
-rel
ated
com
plex
(A
RC
) an
d in
trac
tabl
e di
arrh
ea w
ere
trea
ted
wit
h da
ily
colo
nic
insu
ffla
tion
s of
med
ical
ozo
ne (o
xyge
n/oz
one
mix
ture
) fo
r 21
-28
days
.
Thr
ee o
f the
four
pat
ient
s w
hose
dia
rrhe
a w
as o
f unk
now
n et
iolo
gyex
peri
ence
d co
mpl
ete
reso
luti
on,
and
one
pati
ent
had
mar
ked
impr
ovem
ent.
The
fif
th p
atie
nt,
who
se d
iarr
hea
was
due
to
Cry
ptos
pori
dium
, exp
erie
nced
no
chan
ge. N
o co
nsis
tent
cha
nge
in t
he a
bsol
ute
num
ber
of h
elpe
r (C
D4)
or
supp
ress
or (
CD
8)ly
mph
ocyt
es w
as d
etec
ted,
and
no
obvi
ous
chan
ges
wer
e se
en in
the
PO2
or th
e re
sults
of r
outin
e he
mat
olog
ic a
nd b
lood
che
mis
try
stud
ies.
The
resu
lts
of th
is s
erie
s su
gges
t tha
t med
ical
ozo
ne a
dmin
iste
red
by r
ecta
l ins
uffl
atio
n is
sim
ple,
saf
e, a
nd e
ffec
tive
.
Thi
s pa
per
sum
mar
ises
stu
dies
aim
ed a
t cl
arif
ying
bio
logi
cal
effe
cts,
def
inin
g an
y po
ssib
le d
amag
e, t
he t
hera
peut
ic w
indo
w,
and
suit
able
dos
es o
f oz
one
that
was
abl
e to
exp
ress
the
rape
utic
acti
vity
. T
his
pape
r st
ates
tha
t oz
one
ther
apy,
alt
houg
hun
fash
iona
ble
and
unpo
pula
r ne
eds
to b
e cr
itic
ally
ass
esse
d by
the
orth
odox
med
icin
e
In th
e la
st 3
dec
ades
maj
or a
utoh
emot
hera
py a
fter
exp
osur
e to
ozo
neha
s be
en u
sed
in E
urop
e in
unc
ontr
olle
d tr
ials
car
ried
out
in p
atie
nts
with
man
y ill
ness
es, p
artic
ular
ly c
hron
ic v
iral
dis
ease
s and
neo
plas
ms.
It a
ppea
rs th
at th
e tr
eatm
ent m
ay a
ctiv
ate
the
host
’s im
mun
e sy
stem
by in
duci
ng th
e pr
oduc
tion
of i
mm
unoa
ctiv
e cy
toki
nes
and
it m
ayno
w b
e po
ssib
le to
rati
onal
ize
the
proc
edur
e, im
prov
e th
e re
gim
enan
d as
sess
the
out
com
e. I
t is
app
aren
t, h
owev
er,
that
suc
h a
ther
apeu
tic
appr
oach
, in
ord
er t
o be
acc
epta
ble,
req
uire
s an
inve
stig
ativ
e ef
fort
of
biol
ogis
ts a
nd c
lini
cian
s.
Onc
e th
is is
don
e, o
win
g to
the
larg
e ra
nge
of m
edic
al a
pplic
atio
nsan
d th
e si
mpl
icit
y of
the
pro
cedu
re,
auto
hem
othe
rapy
cou
ldbe
com
e ve
ry v
alua
ble
part
icul
arly
in u
nder
deve
lope
d co
untr
ies.
4. 5. 6.
14
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Y. B
etan
cour
t, J.
M. T
oled
o, E
. Rec
io1,
A. G
ómez
, M. R
odrí
guez
1, C
. Har
rys1
,J.
P. P
ina2
.
Ozo
ne th
erap
y: a
use
ful a
lter
nati
ve o
nvi
rule
nt h
epat
itis
trea
tmen
t.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Mar
chet
ti D
, La
Mon
aca
G. (
2000
)
An
unex
pect
ed d
eath
dur
ing
oxyg
en-
ozon
e th
erap
y.
Am
J F
oren
sic
Med
Pat
hol.
2000
Jun;
21(2
):14
4-7
Non
-ran
dom
ised
con
trol
led
tria
l
80 s
ubje
cts,
Pat
ient
s, b
etw
een
17 a
nd 4
5ye
ars
old,
A s
tudy
wit
h 80
pat
ient
ssu
ffer
ing
from
A, B
, Che
pati
tis,
sin
ce A
ugus
t 199
6, in
Cub
a w
as p
erfo
rmed
Cas
e R
epor
t
Con
vent
iona
l tr
eatm
ent
(res
pons
e an
d di
et p
resc
ript
ed)
plus
ozon
e th
erap
y w
as a
ppli
ed to
40
pati
ent,
the
othe
r 40
pat
ient
son
ly r
ecei
ved
conv
enti
onal
trea
tmen
t.
Dur
ing
the
firs
t w
eek
of t
reat
men
t, r
emis
sion
of
all
the
sym
ptom
s to
ok p
lace
as
wel
l as
the
enl
arge
men
t of
the
liv
er,
impr
ovin
g th
eir c
ondi
tions
and
thei
r app
etite
. All
patie
nts
wer
eto
tally
cur
ed a
t the
end
of t
he tr
eatm
ent.
Und
er th
e co
nven
tiona
ltr
eatm
ent t
hese
sym
ptom
s re
mai
n fo
r m
ore
than
10
days
and
the
tota
lly
cure
was
ach
ieve
d ap
prox
imat
ely
6 m
oths
lat
er.
Com
pari
ng t
hese
res
ults
we
can
say
that
ozo
ne t
hera
py i
s a
suit
able
tre
atm
ent
agai
nst
hepa
titi
s, i
mpr
ovin
g th
e pa
tien
t’s
heal
th a
nd th
e he
alin
g ti
me
of th
e di
seas
e.
An
unex
pect
ed d
eath
is
desc
ribe
d th
at w
as c
ause
d by
gas
embo
lism
that
occ
urre
d du
ring
oxy
gen-
ozon
e (O
2/O
3) th
erap
yad
min
iste
red
by a
utoh
emot
rans
fusi
on f
or p
sori
asis
. T
his
unus
ual
com
plic
atio
n su
gges
ts t
he n
eces
sity
of
inve
stig
atin
gbe
nefi
ts a
nd a
dver
se e
ffec
ts o
f m
edic
al o
zone
app
lica
tion
.
Fai
r
Smal
l sam
ple
size
.N
ot a
ran
dom
ized
cont
rol s
tudy
-E
lem
ent o
f bi
as.
The
pap
er d
oesn
’tin
form
us
on th
ebr
eakd
own
of h
owm
any
pati
ents
infe
cted
wit
hhe
pati
tis
in b
oth
grou
ps i.
e. o
zone
or c
onve
ntio
nal
trea
tmen
t.T
here
fore
the
reco
uld
be m
ore
pati
ents
wit
hhe
pati
tis
A in
thos
e re
ceiv
ing
ozon
e
7. 1.SAF
ET
Y
15
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
[No
auth
ors
list
ed]
Que
stio
nabl
e m
etho
ds o
f ca
ncer
man
agem
ent:
hyd
roge
n pe
roxi
de a
ndot
her
‘hyp
erox
ygen
atio
n’ th
erap
ies.
CA
Can
cer
J C
lin.
199
3 Ja
n-F
eb;
43(1
):47
-56.
Bos
son
J, S
tenf
ors
N, B
ucht
A, H
elle
day
R, P
oura
zar
J, H
olga
te S
T, K
elly
FJ,
San
dstr
om T
, Wil
son
S, F
rew
AJ,
Blo
mbe
rg A
. (20
03)
Ozo
ne-i
nduc
ed b
ronc
hial
epi
thel
ial
cyto
kine
exp
ress
ion
diff
ers
betw
een
heal
thy
and
asth
mat
ic s
ubje
cts.
Cli
n E
xp A
ller
gy.
Jun;
33(
6):7
77-8
2.(A
bstr
act o
nly
)
Rev
iew
Cli
nica
l tr
ial w
itho
ut c
ontr
olgr
oup
Sam
ple
size
not
men
tion
ed
Hyp
erox
ygen
atio
n” th
erap
y—al
so c
alle
d “o
xym
edic
ine,
” “b
io-
oxid
ativ
e th
erap
y,”
“oxi
dati
ve t
hera
py,”
and
“ox
idol
ogy”
-is
am
etho
d of
can
cer
man
agem
ent b
ased
on
the
erro
neou
s co
ncep
tth
at c
ance
r is
cau
sed
by o
xyge
n de
fici
ency
and
can
be
cure
d by
expo
sing
can
cer
cell
s to
mor
e ox
ygen
tha
n th
ey c
an t
oler
ate.
The
mos
t hi
ghly
tou
ted
“hyp
erox
ygen
atin
g” a
gent
s ar
e hy
dro-
gen
pero
xide
, ge
rman
ium
ses
quio
xide
, an
d oz
one.
Alt
houg
hth
ese
com
poun
ds h
ave
been
the
subj
ect o
f le
giti
mat
e re
sear
ch,
ther
e is
litt
le o
r no
evi
denc
e th
at th
ey a
re e
ffec
tive
for
the
trea
t-m
ent o
f an
y se
riou
s di
seas
e, a
nd e
ach
has
dem
onst
rate
d po
ten-
tial
for
har
m. T
here
fore
, the
Am
eric
an C
ance
r S
ocie
ty r
ecom
-m
ends
that
indi
vidu
als
wit
h ca
ncer
not
see
k tr
eatm
ent f
rom
in-
divi
dual
s pr
omot
ing
any
form
of
hype
roxy
gena
tion
the
rapy
as
an “
alte
rnat
ive”
to p
rove
n m
edic
al m
odal
itie
s.
Hea
lthy
and
mild
alle
rgic
ast
hmat
ic s
ubje
cts
(usi
ng o
nly
inha
led
beta
2-ag
onis
ts p
rn) w
ere
expo
sed
for 2
h in
blin
ded
and
rand
omiz
edse
quen
ce t
o 0.
2 pp
m o
f O
3 an
d fi
ltere
d ai
r. B
ronc
hosc
opy
with
bron
chia
l muc
osal
bio
psie
s w
as p
erfo
rmed
6 h
aft
er e
xpos
ure.
Whe
n co
mpa
ring
the
tw
o gr
oups
at
base
line
, th
e as
thm
atic
subj
ects
sho
wed
a s
igni
fica
ntly
hig
her
expr
essi
on o
f IL
-4 a
ndIL
-5. A
fter
O3
expo
sure
the
epit
heli
al e
xpre
ssio
n of
IL
-5, G
M-
CS
F, E
NA
-78
and
IL-8
incr
ease
d si
gnif
ican
tly
in a
sthm
atic
s, a
sco
mpa
red
to h
ealt
hy s
ubje
cts.
The
pre
sent
stu
dy c
onfi
rms
a di
ffer
ence
in
epit
heli
al c
ytok
ine
expr
essi
on b
etw
een
mild
ato
pic
asth
mat
ics
and
heal
thy
cont
rols
,as
wel
l as
a di
ffer
enti
al e
pith
elia
l cyt
okin
e re
spon
se to
O3.
Thi
sO
3-in
duce
d up
regu
lati
on o
f T
hel
per
type
2 (
Th2
)-re
late
dcy
toki
nes
and
neut
roph
il c
hem
oatt
ract
ants
sho
wn
in t
heas
thm
atic
gro
up m
ay c
ontr
ibut
e to
a s
ubse
quen
t w
orse
ning
of
the
airw
ay i
nfla
mm
atio
n, a
nd h
elp
to e
xpla
in t
heir
dif
fere
ntia
lse
nsit
ivit
y to
O3
poll
utio
n ep
isod
es.
1. 1.CA
NC
ER
AST
HM
A
16
LIM
B I
SHA
EM
IA
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Tyli
cki L
, Nie
w g
low
ski T
,B
iedu
nkie
wic
z B
, Bur
akow
ski S
,R
utko
wsk
i B (
2001
)
Ben
efic
ial c
lini
cal e
ffec
ts o
f oz
onat
edau
tohe
mot
hera
py in
chr
onic
ally
dia
lyse
dpa
tien
ts w
ith
athe
rosc
lero
tic
isch
emia
of
the
low
er li
mbs
—pi
lot s
tudy
.
Int J
Art
if O
rgan
s.
Feb
; 24(
2):7
9-82
.
Tyli
cki L
, Nie
weg
low
ski T
,B
iedu
nkie
wic
z B
, Cha
mie
nia
A,
Deb
ska-
Sli
zien
A, A
leks
andr
owic
z E
,L
ysia
k-S
zydl
owsk
a W
, Rut
kow
ski B
(200
3).
The
infl
uenc
e of
ozo
nate
dau
tohe
mot
hera
py o
n ox
idat
ive
stre
ss in
hem
odia
lyze
d pa
tien
ts w
ith
athe
rosc
lero
tic
isch
emia
of
low
er li
mbs
.
Int J
Art
if O
rgan
s.
Apr
; 26(
4):2
97-3
03.
(Abs
trac
t onl
y)
Cro
ss s
ecti
onal
stu
dy
12 p
atie
nts
5 he
mod
ialy
zed
pati
ents
and
7pa
tien
ts tr
eate
d w
ith
peri
tone
aldi
alys
is w
ere
exam
ined
imm
edia
tely
bef
ore
and
afte
r 14
sess
ions
of
ozon
ated
auto
haem
othe
rapy
Non
ran
dom
ized
con
trol
tria
l
12 s
ubje
cts
Thi
s is
a p
reli
min
ary
stud
y on
the
infl
uenc
e of
blo
od o
zona
tion
on
the
inte
nsit
y of
sym
ptom
s of
isc
hem
ia o
f th
e lo
wer
ext
rem
itie
sam
ong
dial
ysed
pat
ient
s w
ith
chro
nic
rena
l fai
lure
.
Ele
ven
patie
nts
(91.
6%) r
epor
ted
a su
bjec
tive
decr
ease
in p
erce
ived
inte
nsity
of i
sche
mic
pai
ns, o
r obs
erve
d pr
olon
gatio
n of
inte
rmitt
ent
clau
dica
tion
dist
ance
. Dur
ing
mar
ch te
sts
perf
orm
ed o
n a
trea
dmill
,th
ere
was
a s
igni
fica
nt p
rolo
ngat
ion
of i
nter
mit
tent
cla
udic
atio
ndi
stan
ce i
n al
l ex
amin
ed p
atie
nts
- 65
.6%
(m
ean
valu
e, p
(<
or
=0.
01).
Pat
ient
s tr
eate
d w
ith
peri
tone
al d
ialy
sis
achi
eved
muc
hgr
eate
r im
prov
emen
t tha
n di
d he
mod
ialy
zed
patie
nts (
165%
vs.
42%
).
It w
as c
oncl
uded
tha
t au
tohe
mot
hera
py w
ith
ozon
e, i
n a
conc
entr
atio
n of
34.
4 m
cg/m
l of
bloo
d, is
saf
e, e
asil
y ap
plie
d an
dm
ay b
e us
eful
In
the
ther
apy
of a
ther
oscl
erot
ic is
chem
ia o
f lo
wer
extr
emit
ies
amon
g di
alyz
ed p
atie
nts.
The
aim
of
the
stud
y w
as to
inve
stig
ate
the
infl
uenc
e of
ozo
nate
dau
tohe
mot
hera
py o
n th
e ox
idat
ive
stre
ss e
xten
t in
hem
odia
lyze
dpa
tien
ts,
know
n to
be
part
icul
arly
exp
osed
to
gene
rati
on a
ndde
lete
riou
s ef
fect
s of
fre
e ra
dica
ls.
Twel
ve c
onti
nuou
sly
hem
odia
lyze
d su
bjec
ts w
ith
athe
rosc
lero
tic
isch
emia
of
the
low
er l
imbs
wer
e ex
amin
ed i
n a
pros
pect
ive,
cont
roll
ed,
sing
le b
lind
stu
dy.
Aut
ohem
othe
rapy
wit
h bl
ood
expo
sure
to
oxyg
en s
erve
d as
a c
ontr
ol.
The
pro
tein
and
lip
idpe
roxi
dati
on p
rodu
cts,
the
redu
ced
glut
athi
one
leve
l in
red
bloo
dce
lls
and
free
hem
oglo
bin
plas
ma
conc
entr
atio
n w
as m
easu
red.
The
stu
dy s
how
ed t
hat
ozon
ated
aut
ohem
othe
rapy
wit
h oz
one
conc
entr
atio
n 50
mic
rog/
ml p
er g
ram
of b
lood
indu
ced
a si
gnif
ican
tde
crea
se i
n gl
utat
hion
e le
vel
afte
r 9
sess
ions
of
this
pro
cedu
re.
The
rapy
did
not
cau
se e
ithe
r th
e en
hanc
emen
t of
prot
ein
and
lipi
dpe
roxi
dati
on, o
r er
ythr
ocyt
es d
amag
e.
Poo
r
Fai
r
1. 2.
17
Tylic
ki L
, Bie
dunk
iew
icz
B, N
iew
eglo
wsk
iT,
Cha
mie
nia
A, S
lizi
en A
D, L
uty
J,Ly
siak
-Szy
dlow
ska
W, R
utko
wsk
i B (2
004)
.
Ozo
nate
d au
tohe
mot
hera
py in
pat
ient
son
mai
nten
ance
hem
odia
lysi
s: in
flue
nce
on li
pid
prof
ile
and
endo
thel
ium
.
lesz
ek.ty
lick
i@w
p.pl
Art
if O
rgan
s F
eb; 2
8(2)
:234
-7.
(Abs
trac
t on
ly )
Bie
dunk
iew
icz
B, T
ylic
ki L
,N
iew
eglo
wsk
i T, B
urak
owsk
i S,
Rut
kow
ski B
(20
04).
Cli
nica
l eff
icac
y of
ozo
nate
dau
tohe
mot
hera
py in
hem
odia
lyze
dpa
tien
ts w
ith
inte
rmit
tent
cla
udic
atio
n:an
oxy
gen-
cont
roll
ed s
tudy
.
Int J
Art
if O
rgan
s. J
an; 2
7(1)
:29-
34.
(Abs
trac
t onl
y)
Sro
czyn
ski J
, Ant
osze
wsk
i Z,
Mat
yszc
zyk
B, K
rupa
G, R
udzk
i H,
Zbr
onsk
a H
, Sko
wro
n J
(199
2).
Clin
ical
ass
essm
ent o
f tre
atm
ent r
esul
ts fo
rat
hero
scle
rotic
isch
emia
of t
he lo
wer
extre
miti
es w
ith in
traar
teria
l ozo
ne in
ject
ions
[Art
icle
in P
olis
h] P
ol T
yg L
ek.
Oct
19-
26; 4
7(42
-43)
:964
-6.
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Con
trol
led
tria
l
Twel
ve h
emod
ialy
zed
subj
ects
wit
h at
hero
scle
roti
c is
chem
ia o
flo
wer
lim
bs (
AIL
L)
rece
ived
auto
hem
othe
rapy
wit
h ox
ygen
as a
con
trol
fol
low
ed b
y O
3-A
HT
wit
h oz
one
conc
entr
atio
nof
50
mic
ro g
/ml.
Cro
ss o
ver
sing
le b
lind
ed
10 s
ubje
cts
Cli
nica
l tr
ial
Ten
inje
ctio
ns o
f O
3 in
tofe
mor
al a
rter
ies
wer
ead
min
iste
red
50 p
atie
nts
wit
h at
hero
scle
roti
cis
chem
ia o
f the
low
er e
xtre
miti
esan
d to
49
diab
etic
pat
ient
s
Seru
m li
pids
and
pla
sma
activ
ity o
f von
Will
ebra
nd fa
ctor
(vW
F)w
ere
mea
sure
d. A
fter
O3-
AH
T, t
otal
cho
lest
erol
sig
nifi
cant
lyde
crea
sed
com
pare
d to
the
bas
elin
e (-
8.34
%)
[P <
0.0
1]. L
DL
chol
este
rol w
as a
lso
sign
ific
antl
y lo
wer
than
the
init
ial v
alue
(-
17.7
1%)
[P <
0.0
01].
No
sign
ific
ant
chan
ges
in t
he a
ctiv
ity
ofvW
F w
ere
foun
d af
ter
the
firs
t ses
sion
of
O3-
AH
T a
nd a
fter
all
nine
ses
sion
s of
O3-
AH
T. T
he s
tudy
sho
wed
that
O3-
AH
T d
idno
t aff
ect d
elet
erio
usly
the
endo
thel
ium
in p
atie
nts
wit
h ch
roni
cre
nal
fail
ure
on m
aint
enan
ce h
emod
ialy
sis.
It
may
sti
mul
ate
bene
fici
al c
hang
es i
n se
rum
lip
id p
rofi
le m
anif
esti
ng a
s a
decr
ease
in th
e to
tal-
and
LD
L-c
hole
ster
ol le
vels
.
Ten
subj
ects
wit
h in
term
itte
nt c
laud
icat
ion
(Fon
tain
II
stag
e)re
ceiv
ed t
he c
ycle
of
ozon
ated
aut
ohem
othe
rapy
wit
h oz
one
conc
entr
atio
n of
50
mic
rog/
ml
and
the
cycl
e of
oxy
gen
auto
hem
othe
rapy
as
a co
ntro
l in
a cr
osso
ver,
sing
le-b
lind
man
ner.
Pain
-fre
e di
stan
ce a
nd m
axim
al w
alki
ng d
ista
nce
wer
e m
easu
red.
Pat
ient
s as
sess
ed th
e ef
fica
cy o
f th
erap
y su
bjec
tive
ly.
The
resu
lts
show
ed s
igni
fica
nt p
rolo
ngat
ion
of m
axim
al w
akin
gdi
stan
ce a
fter
ozo
nate
d au
tohe
mot
hera
py c
ompa
red
to.
The
re w
as a
lso
sign
ific
ant
incr
ease
in
pain
-fre
e di
stan
ce a
fter
ozon
ated
aut
ohem
othe
rapy
, com
pare
d to
bas
elin
e (b
y 71
.7%
) and
to th
e ox
ygen
con
trol
(by
62.8
%) 9
0% o
f pat
ient
s rep
orte
d cl
inic
alim
prov
emen
t rel
ativ
e to
bas
elin
e af
ter o
zona
ted
auto
hem
othe
rapy
,co
mpa
red
to o
nly
40%
aft
er th
e ox
ygen
-con
trol
trea
tmen
t.
All
pat
ient
s w
ere
asse
ssed
cli
nica
lly
wit
h th
e an
kle-
arm
inde
x,m
easu
rem
ent o
f in
term
itte
nt c
laud
icat
ion
dist
ance
pri
or to
and
afte
r th
e tr
eatm
ent.
The
trea
tmen
t sho
wed
a s
igni
fica
nt im
prov
emen
t in
both
gro
ups
man
ifes
ted
by a
n in
crea
se in
ank
le-a
rm in
dex,
and
pro
long
atio
nof
the
int
erm
itte
nt c
laud
icat
ion
dist
ance
by
mor
e th
an t
wic
e.T
he t
reat
men
t of
ath
eros
cler
otic
isc
hem
ia o
f th
e lo
wer
extr
emit
ies
wit
h O
3 is
bot
h va
luab
le a
nd s
afe.
Fai
r
The
sam
esu
bjec
ts s
erve
das
con
trol
s.H
ence
com
pari
son
mor
e va
lid.
Poo
r
Sub
ject
ive
eval
uati
on
Tim
e fr
ame
not
men
tion
ed. N
om
enti
on o
fw
asho
ut p
erio
dbe
twee
n th
ecr
oss
over
3. 4. 5.
18
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Mas
lenn
ikov
OV
, Sha
rov
IG, P
otek
hina
IP, D
ushk
ina
NG
, Kry
zhan
ovsk
aia
NA
,M
asle
nnik
ova
NO
, Bol
gov
VF,
Pav
lovs
kaia
EE
, Zhe
glov
a LV
, Cha
lkin
a S
N (
1997
).
Eff
ect o
f oz
one
ther
apy
on h
emos
tati
cch
ange
s in
pat
ient
s w
ith
vasc
ular
athe
rosc
lero
sis
Kli
n M
ed (
Mos
k). 7
5(10
):35
-7.
(Abs
trac
t onl
y )
Tur
czyn
ski B
, Sro
czyn
ski J
,A
ntos
zew
ski Z
, Mat
yszc
zyk
B, K
rupa
G,
Mly
nars
ki J
, Str
ugal
a M
(19
91).
Ozo
ne th
erap
y an
d vi
scos
ity
of b
lood
and
plas
ma
dist
ance
of
inte
rmit
tent
clau
dica
tion
and
cer
tain
bio
chem
ical
com
pone
nts
in p
atie
nts
wit
h di
abet
esty
pe II
and
isch
emia
of t
he lo
wer
ext
rem
ities
Pol T
yg L
ek. S
ep 9
-30;
46(
37-3
9):7
08-1
0[A
rtic
le in
Pol
ish]
Per
alta
C, L
eon
OS
, Xau
s C
, Pra
ts N
,Ja
lil E
C, P
lane
ll E
S, P
uig-
Par
ella
da P
,G
elpi
E, R
osel
lo-C
ataf
au J
.
Pro
tect
ive
effe
ct o
f oz
one
trea
tmen
t on
the
inju
ry a
ssoc
iate
d w
ith
hepa
tic
isch
emia
-rep
erfu
sion
: ant
ioxi
dant
-pr
ooxi
dant
bal
ance
.
Dep
artm
ent o
f M
edic
al B
ioan
alys
is,
Inst
itut
o de
Inv
esti
gaci
ones
Bio
med
icas
de B
arce
lona
, CS
IC-I
DIB
AP
S, S
pain
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
81 s
ubje
cts
[Art
icle
in R
ussi
an]
It w
as f
ound
tha
t us
e of
ozo
ne-o
xyge
n m
ixtu
res
lead
s to
hypo
coag
ulat
ory
chan
ges
(dim
inut
ion
of p
late
let
aggr
egat
ion,
low
erin
g of
fibr
inog
en c
once
ntra
tion
, pro
long
atio
n of
act
ivat
edpa
rtia
l thr
ombo
plas
tin ti
me,
enh
ance
d fi
brin
olyt
ic a
ctiv
ity) w
hich
cont
ribu
te to
cli
nica
l res
pons
e
A s
igni
fica
nt i
mpr
ovem
ent
in i
nter
mit
tent
cla
udic
atio
n an
dre
duct
ion
in b
lood
and
pla
sma
visc
osit
y oc
curr
ed a
fter
ozo
neth
erap
y.
The
eff
ect o
f ozo
ne tr
eatm
ent o
n th
e in
jury
ass
ocia
ted
to h
epat
icis
chem
ia-r
eper
fusi
on (
I/R
) w
as e
valu
ated
. O
zone
tre
atm
ent
(1m
g/kg
dai
ly d
urin
g 10
day
s by
rec
tal
insu
ffla
tion
) is
sho
wn
tobe
pro
tect
ive
as it
atte
nuat
ed th
e in
crea
ses
in tr
ansa
min
ases
(AST
,A
LT) a
nd la
ctat
e le
vels
obs
erve
d af
ter I
/R. I
/R le
ad to
a d
ecre
ase
in e
ndog
enou
s ant
ioxi
dant
(SO
D a
nd g
luta
thio
ne) a
nd a
n in
crea
sein
rea
ctiv
e ox
ygen
spe
cies
(H
2O2)
wit
h re
spec
t to
the
con
trol
grou
p. T
he p
rese
nt s
tudy
rep
orts
a p
rote
ctiv
e ef
fect
of
ozon
etr
eatm
ent
on t
he i
njur
y as
soci
ated
to
hepa
tic
I/R
. T
heef
fect
iven
ess
of o
zone
cou
ld b
e re
late
d to
its
act
ion
onen
doge
nous
ant
ioxi
dant
s an
d pr
ooxi
dant
s ba
lanc
e in
fav
our
ofan
tiox
idan
ts, t
hus
atte
nuat
ing
oxid
ativ
e st
ress
Poo
r6. 7. 8.
19
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
S. K
otov
; A. G
usto
v an
dA
.Moc
halo
v.N
izhn
i Nov
goro
d
Ozo
ne th
erap
y in
flue
nce
onhe
mod
ynam
ics
in p
atie
nts
wit
h is
chem
icin
sult
.
(Abs
trac
t fro
m 3
rd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Y. S
haar
ov, N
. Mas
lenn
ikov
a, N
.D
ushk
ina,
O. M
asle
nnik
ov.
Ozo
ne th
erap
y in
isch
emic
hea
rt d
isea
se(i
hd).
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
85 s
ubje
cts
trea
ted
wit
hin
trav
enou
s oz
oniz
ed n
orm
alsa
line
sol
utio
n (O
NS
) w
ith
anoz
one
conc
entr
atio
n of
300
ug/l
.
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
85 s
ubje
cts,
80
havi
ng s
tabl
e II
-II
I st
enoc
ardi
a, 5
pat
ient
s ha
dpr
ogre
ssiv
e an
gina
pec
tori
s.
The
trea
tmen
t cou
rse
was
don
ein
3-4
wee
ks. O
zone
/oxy
gen
mix
ture
s w
ere
adm
inis
tere
d in
intr
aveo
us d
rops
infu
sion
s an
dre
ctal
insu
ffla
tion
s. T
he p
atie
nts
cond
itio
n w
as c
heck
ed b
ycl
inic
al s
igns
(nu
mbe
r of
sten
ocad
ial a
ttac
ks a
ndni
trog
lyce
rine
use
), to
lera
nce
toph
ysic
al lo
ads
data
, EK
Gre
adin
gs, e
choc
ardi
osco
py.
In 8
5 pa
tien
ts w
ith
isch
emic
ins
ult
are
show
n th
at p
osit
ive
ultr
ason
ic d
oppl
erog
raph
y dy
nam
ics
was
mar
ked
in 7
9 %
of
case
s, in
the
acut
e pe
riod
, and
in 6
3 %
of c
ases
in th
e re
stor
atio
npe
riod
of
isch
emic
insu
lt.
It w
as s
how
n a
decr
ease
in
the
inte
rcer
ebra
l bl
ood
circ
ulat
ion
asym
met
ry a
nd i
n th
e ci
rcul
ator
y re
sist
ance
, as
wel
l as
an
incr
ease
of
the
cere
bral
cir
cula
tion
rea
ctiv
ity
and
a fu
ncti
onal
rest
orat
ion
of f
orw
ard
and
back
war
d co
nnec
ting
art
erie
s in
the
Wil
lis
circ
le. I
n th
is c
ase
line
ar b
lood
vel
ocit
y di
d no
t var
y.
The
ON
S in
fusi
ons
also
pro
mot
ed m
aint
enan
ce o
f th
e ef
fect
ive
hear
t wor
k. T
he s
trok
e vo
lum
e by
the
end
of th
e tr
eatm
ent c
ours
eha
s gr
own
on 2
9 %
, and
the
min
ute
volu
me
on 2
4 %
. The
gen
eral
peri
pher
al c
ircu
lato
ry r
esis
tanc
e ha
s de
crea
sed
on 3
1 %
. As
aw
hole
, eu
kine
tic
type
of
circ
ulat
ion
is 1
, 5
tim
es m
ore
ofte
naf
ter
ozon
ethe
rapy
.
Pos
itiv
e re
sult
s w
ere
rece
ived
in 7
6 pa
tien
ts (o
f 80
pati
ents
wit
hst
able
ste
noca
rdia
-95%
) tha
t wer
e on
ozo
ne th
erap
y. A
ttac
ks o
fst
enoc
ardi
al p
ains
wer
e co
mpl
etel
y co
ntro
lled
in
46 o
ut o
f 80
pati
ents
(58
%)
wit
h st
able
ste
noca
rdia
. T
he a
mou
nt o
f pa
inat
tack
s w
as d
imin
ishe
d in
50%
in
30 p
atie
nts
(37.
5%).
Thi
sen
able
d th
e pa
tien
ts to
low
the
dose
of
nitr
ates
and
in a
num
ber
of c
ases
to
disc
onti
nue
thei
r us
e. 4
pat
ient
s (5
%)
did
not
have
any
impr
ovem
ent i
n th
eir
cond
itio
n.
Ozo
ne t
hera
py p
rove
d to
be
high
ly e
ffec
tive
in
pati
ents
wit
hpr
ogre
ssiv
e an
gina
pec
tori
s an
d re
sult
ed in
eli
min
atio
n of
non
-st
able
con
diti
on w
ith
sign
ific
ant
redu
ctio
n of
cor
onar
yin
suff
icie
ncy
sym
ptom
s.
All
the
pat
ient
s sh
owed
the
inc
reas
e to
dom
esti
c an
d do
sed
phys
ical
loa
ds.
Inst
rum
enta
l re
adin
gs h
ad p
osit
ive
dyna
mic
s.H
ence
, oz
one
ther
apy
can
be r
egar
ded
as a
hig
hly
effi
cien
tm
etho
d of
IHD
trea
tmen
t. Po
sitiv
e re
sults
are
pro
vide
d by
ozo
nein
flue
nce
on a
ntio
xida
nt, c
oagu
lati
on a
nd o
xyge
n-tr
ansp
ort
Poo
r
Poo
r
9. 10.
20
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
N. M
oren
o, O
. Pel
áez,
T. A
lem
án, C
.B
arce
ló.
Con
trol
led
clin
ical
tria
l on
the
use
ofoz
onat
ed b
lood
as
a tr
eatm
ent f
orre
tini
tis
pigm
ento
sa.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
E. C
. Día
z, L
.Bor
rego
1, S
. Men
énde
z2,
L. R
. Bor
rego
3, R
. A. B
orre
go3.
I.
Ozo
ne th
erap
y in
dif
fere
ntop
htha
lmol
ogic
dis
ease
s.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
A d
oubl
e bl
ind
RC
T, 1
23su
bjec
ts, 1
5 to
65
year
s, a
ndsu
ffer
ing
from
typi
cal f
orm
s of
reti
niti
s pi
gmen
tosa
part
icip
ated
62 p
atie
nts
assi
gned
to th
etr
eatm
ent a
nd 6
1 to
con
trol
grou
p (p
lace
bo)
Cli
nica
l tri
al w
itho
ut g
roup
180
subj
ects
1-ye
ar f
ollo
w-u
p
Patie
nts
wer
e tr
eate
d w
ith d
aily
rect
al o
zone
ther
apy,
dur
ing
20da
ys, r
epre
sent
ing
80 w
ithR
etin
itis
Pigm
ento
sa (
nosy
stem
ic, s
tage
I a
nd I
I), 4
5 w
ithpr
ogre
ssiv
e m
yopi
a, 2
5 w
ithch
roni
c gl
auco
ma
of o
pen
angl
e(t
onom
etri
cally
com
pens
ated
),20
with
opt
ic a
trop
hy (
less
than
one
year
of
evol
utio
n an
d no
the
redi
tary
), 1
0 w
ith d
iabe
ticre
tinop
athy
(no
pro
lifer
ativ
e).
A c
ompl
ete
gene
ral
and
opht
halm
olog
ic e
xam
inat
ion
was
perf
orm
ed a
fter
sign
ing
an in
form
ed c
onse
nt S
nelle
n vi
sual
acu
ityw
as m
easu
red
(les
s th
an 2
.5 l
ines
con
side
red
non
sign
ific
ant
chan
ges)
and
Gol
dman
n ki
neti
c vi
sual
fie
ld w
ith
31.5
asb
.B
ackg
roun
d an
d V
-4e
targ
et. V
isua
l fie
ld a
reas
wer
e di
gitiz
ed a
ndm
easu
red
with
a c
ompu
ter
prog
ram
(V
ISU
AL
). O
zona
ted
bloo
dw
as a
dmin
iste
red
to p
atie
nts
in t
he t
reat
men
t gr
oup,
in
a da
ilyfa
shio
n fo
r 15
day
s, w
hile
pat
ient
s in
the
cont
rol g
roup
rec
eive
don
ly b
lood
. Par
ticip
ants
wer
e bl
ind
with
rega
rds t
o th
is, t
hrou
ghou
tth
e du
ratio
n of
the
stu
dy.
Vis
ual
acui
ty r
emai
ned
the
sam
e, 6
mon
ths
afte
r th
e tr
eatm
ent,
in 7
4.2%
of
the
patie
nts,
impr
ove
in21
% a
nd w
orse
n in
4.8
%. V
isua
l fie
ld a
rea
rem
aine
d th
e sa
me,
6m
onth
s af
ter
the
trea
tmen
t, in
41.
9% o
f th
e pa
tient
s, im
prov
e in
46.7
% a
nd w
orse
n in
11.
35%
. S
igni
fica
nt d
iffe
renc
es w
ere
obse
rved
bet
wee
n gr
oups
with
low
er fr
eque
ncie
s of i
mpr
ovem
ents
in c
ontr
ols
are
larg
er p
ropo
rtio
ns o
f w
orse
ning
. Im
prov
emen
tsw
ere
not o
bser
ved
in 9
1.9%
of p
atie
nts o
ne y
ear a
fter
the
trea
tmen
t.T
his
tend
ency
was
fir
st n
oted
aft
er 6
mon
ths
from
the
trea
tmen
t.O
zone
trea
tmen
t is
prov
ed o
f ben
efit
in p
atie
nts
with
RP,
alth
ough
its a
ctio
n is
tem
pora
ry.
Cli
nica
l ev
alua
tion
was
mad
e ea
ch 3
mon
ths,
up
to 1
yea
r. In
pati
ents
wit
h R
etin
itis
Pig
men
tosa
, 75
% im
prov
ed th
eir
visu
alac
uity
(po
st-t
reat
men
t and
6 m
onth
s la
ter)
.
Aft
er 1
yea
r, 23
% o
f im
prov
emen
t st
ill r
emai
ned.
Acc
ordi
ng t
ovi
sual
fiel
d, 7
6% o
f pat
ient
s im
prov
ed it
aft
er tr
eatm
ent a
nd u
p to
9m
onth
s, b
ut a
fter
1 y
ear,
16%
lost
thei
r im
prov
emen
t. R
espe
ct to
prog
ress
ive
myo
pia,
the
vis
ual
acui
ty i
ncre
ased
in
78%
(po
st-
trea
tmen
t and
9 m
onth
s la
ter)
and
rem
aine
d 58
% a
fter
1 y
ear.
Ingl
auco
ma,
65%
incr
ease
d th
e vi
sual
acu
ity (
post
-tre
atm
ent a
nd 9
mon
ths l
ater
), m
aint
aini
ng 5
3% o
f im
prov
emen
t aft
er 1
yea
r. V
isua
lfi
eld
incr
ease
d in
76%
of p
atie
nts,
pos
t-tr
eatm
ent a
nd a
fter
1 y
ear.
In d
iabe
tic r
etin
opat
hy,
60%
im
prov
ed t
heir
vis
ual
acui
ty (
post
-tr
eatm
ent)
, dim
inis
hing
to
40%
, 6 m
onth
s la
ter
and
20%
, aft
er 1
year
. Res
pect
to o
ptic
atr
ophy
, 45%
of i
mpr
ovem
ent i
n vi
sual
fiel
dw
as a
chie
ved
(pos
t-tr
eatm
ent)
mai
ntai
ning
its
figu
re a
fter
1 y
ear.
Goo
d
Poo
rSm
all s
ubse
t sam
ple
size
. Tho
se w
hopa
rtic
ipat
ed in
this
stud
y w
ith th
eop
htha
lmol
ogic
dise
ases
wer
e w
ithm
ild
or n
oco
mpl
icat
ions
. Thi
sst
udy
has
a sh
ort
foll
ow-u
p. T
here
is a
nee
d fo
r a
rand
omiz
ed cl
inic
altr
ial l
ooki
ng a
tva
rious
seve
ritie
s of
each
oph
thal
mol
ogic
alco
ndit
ion.
1. 2.EY
E
21
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Y. M
apol
on, M
. Pal
ma1
, E. R
esio
, M.
Rod
rígu
ez, E
. Dyc
e1, C
. Har
rys,
J. C
.P
ina1
.
Eff
ects
of
ozon
e in
pat
ient
s w
ith
reti
niti
spi
gmen
tosa
.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
R. S
anti
este
ban,
S. M
enén
dez1
, M.
Fra
ncis
co, S
. Lui
s.
Ozo
ne th
erap
y in
pat
ient
s su
ffer
ing
from
opti
c ne
rve
dysf
unct
ion.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Des
crip
tive
rep
ort
50 s
ubje
cts
The
eff
ect o
f oz
one
in 5
0pa
tien
ts w
ith
reti
niti
spi
gmen
tosa
was
eva
luat
ed in
the
Ret
init
is P
igm
ento
sa C
ente
r,C
amag
üey,
Cub
a.
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
60 p
atie
nts
suff
erin
g fr
om O
ND
of d
iffe
rent
eti
olog
ies
and
tim
eof
evo
luti
on w
ere
give
n m
ixtu
reof
ozo
ne/o
xyge
n en
dove
nous
lyby
aut
ohem
othe
rapy
, dur
ing
15se
ssio
ns.
The
pat
ient
s su
ffer
of p
hoto
phob
ia, p
hoto
psia
and
redu
ce v
isio
non
dar
k pl
aces
.
Con
side
ring
tha
t th
e pa
tien
ts w
ith
rem
issi
on o
f tw
o sy
mpt
oms
of t
he d
isea
se a
fter
the
ozo
ne t
reat
men
t is
con
side
red
as s
igns
impr
ovem
ent,
in th
is c
ase
all o
f the
m a
fter
the
7th
and
8th
ozon
eap
plic
atio
n di
dn’t
pre
sent
pho
toph
obia
and
pho
toto
psia
,in
crea
sing
als
o th
e qu
alit
y of
the
ir v
isio
n (b
y m
eans
of
impr
ovem
ent
in t
he v
isua
l ac
uity
and
vis
ual
fiel
d). I
n sp
ite
of,
afte
r 6
mon
th th
e ap
pear
ance
of
sign
s an
d sy
mpt
oms
in a
ll th
epa
tien
ts to
ok p
lace
.
The
mai
n ob
ject
of
this
stu
dy w
as to
eva
luat
e th
e fe
asib
ilit
y of
impr
ovin
g th
e vi
sual
fun
ctio
n of
a g
roup
of
pati
ents
, w
ith
diff
eren
t de
gree
s of
ON
D w
ith
redu
ced
poss
ibil
itie
s of
vis
ion
impr
ovem
ent,
by m
eans
of
ozon
e th
erap
y.
Ozo
ne c
once
ntra
tion
and
dos
es a
re u
sed
acco
rdin
g to
the
bioc
hem
ical
sta
tus
of e
ach
pati
ent.
An
opht
halm
olog
ical
exam
inat
ion
and
a se
t of t
ests
con
form
ed b
y vi
sual
acu
ity
(VA
),vi
sual
fie
ld b
y G
oldm
ann
Per
imet
ry (
VF
), v
isua
l ev
oked
pote
ntia
ls (
VE
P),
Pel
li R
obso
n C
ontr
ast
Sen
siti
vity
Tes
t(P
RC
ST
) was
app
lied
to p
atie
nts
befo
re a
nd a
fter
ozo
ne th
erap
ytr
eatm
ent.
PRC
ST a
nd V
F w
ere
the
para
met
ers
mos
tly im
prov
ed in
pat
ient
sw
ith 8
6% a
nd 8
3% re
spec
tivel
y, fo
llow
ed b
y V
A (5
5%) a
nd V
EP
(37%
). G
ood
resu
lts
wer
e ac
hiev
ed i
n al
l et
iolo
gies
stu
died
,ex
cept
Leb
er o
ptic
atr
ophy
, w
here
no
impr
ovem
ent
was
obse
rved
, nei
ther
obj
ecti
ve n
or s
ubje
ctiv
e.
Poo
r
A lo
ng te
rmfo
llow
-up
or a
coho
rt s
tudy
isre
quir
ed to
dete
rmin
ew
heth
er th
ese
find
ings
are
on
shor
t ter
m o
rlo
ng te
rm b
asis
.
Poo
r
3. 4.
22
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
E. B
asab
e.
Ana
lysi
s of
the
elec
trop
hysi
olog
ical
thre
shol
d, e
udio
met
ry a
nd la
tenc
y of
the
wav
e v
in c
hild
ren
wit
h he
arin
g lo
sssu
bmit
ted
to o
zone
ther
apy.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
V. S
hakh
ov, A
. Ede
leva
.
The
Use
Of
Ozo
ne T
hera
py I
n C
hron
icP
urul
ent M
esot
ympa
niti
s
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
V. M
. Zue
v; N
. M. P
obed
ynsk
y; D
. G.
Kra
snic
ov; T
. A. D
jibl
adze
; L. S
.A
lexa
ndro
v y
M. I
. Kov
alev
.
Ozo
ne e
ffec
tive
ness
in th
e tr
eatm
ent o
fch
roni
c fe
tal h
ypox
ia.
(Abs
trac
t fro
m 3
rd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
RC
T, d
oubl
e bl
ind
stud
y
34 c
hild
ren
wer
e se
lect
ed w
ith
the
sam
e ed
ucat
iona
l pro
file
and
divi
ded
at r
ando
m in
2 g
roup
s:17
rec
eive
d re
ctal
oxy
gen
and
the
othe
rs 1
7 re
ceiv
ed r
ecta
loz
one
Non
ran
dom
ized
con
trol
led
tria
l
50 s
ubje
cts.
40
pati
ents
unde
rwen
t a c
ours
e of
trea
tmen
tth
at c
onsi
sted
of
7-10
dai
lypr
oced
ures
. Con
trol
gro
up o
f 10
pati
ents
was
on
a co
nven
tion
alth
erap
y.
Non
ran
dom
ized
con
trol
led
tria
l
166
subj
ects
Tre
atm
ent
grou
p 13
2 an
dco
ntro
l- 3
4
Com
pari
ng t
he r
esul
ts,
audi
omet
ry,
elec
trop
hysi
olog
ical
thre
shol
d an
d th
e la
tenc
y of
the
wav
e V
to 9
0 D
B, f
or th
e sa
me
ear,
impr
oved
in
a gr
eat
perc
enta
ge o
f ch
ildr
en t
hat
rece
ived
ozon
e th
erap
y.
Dif
fere
nt b
ehav
ior a
mon
g su
bjec
ts tr
eate
d w
ith o
zone
com
pare
dto
chi
ldre
n th
at r
ecei
ved
oxyg
en, w
as o
bser
ved.
The
res
ults
dem
onst
rate
d th
at o
zone
the
rapy
hav
e no
neg
ativ
eef
fect
on
inte
rnal
ear
or
laby
rint
h fu
ncti
on,
even
in
prol
onge
dap
plic
atio
ns o
f hi
gh o
zone
con
cent
rati
ons
effe
ctin
g m
ucou
sm
embr
ane
of m
edia
l wal
l.
Cli
nica
l eff
ect w
as o
bser
ved
in in
flam
mat
ion
cont
rol o
f muc
ous
mem
bran
e, d
isch
arge
redu
ctio
n an
d re
stor
atio
n of
aud
itor
y tu
befu
ncti
on.
Mon
itor
ing
by u
ltra
soun
d, D
oppl
er, s
tero
id, c
ardi
otoc
hogr
aphy
,m
orfo
logi
cal i
nves
tiga
tion
of
plac
enta
.
Ozo
ne t
hera
py w
as a
ppli
ed b
y in
trav
enou
s ad
min
istr
atio
n of
ozon
ized
sol
utio
n of
sod
ium
chl
orid
e.
In t
he o
zone
gro
up,
norm
al s
tate
of
fetu
s w
as o
btai
ned
muc
hea
rlie
r an
d w
as s
uppo
rted
wit
h hi
gh in
tens
ific
atio
n of
ada
ptiv
em
echa
nism
, sho
wed
in p
lace
nta
bloo
d ci
rcul
atio
n.
Goo
d
Fai
r
Fai
r
1. 2. 1.EN
T
OB
STR
ET
IC &
GY
NA
EC
OL
OG
Y
23
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Cle
men
te-A
pum
ayta
.J. M
, Zue
v V
. M,
Lja
shko
E. S
. Vol
osch
uk I
. N, K
ovga
nko
P. A
. S
eche
nov
M.
Ozo
ne th
erap
y in
chr
onic
pla
cent
alin
suff
icie
ncy
Sou
rce:
Abs
trac
ts f
rom
3rd I
nter
nati
onal
Sym
posi
um o
n O
zone
App
lica
tion
, Cub
a
M.I
.Kov
alev
y I.
M.C
lem
ente
-Apu
may
ta.
Imm
une
stat
us d
urin
g oz
one
ther
apy
for
the
prop
hyla
xis
of in
fect
ions
aft
erce
asar
ean.
(Unp
ubli
shed
ful
l art
icle
)
I.K
oval
ev.
Ozo
ne tr
eate
d w
omen
aft
er c
aesa
rean
and
inte
rfer
on p
rofi
le.
(Unp
ubli
shed
ful
l art
icle
)
Non
ran
dom
ized
con
trol
led
tria
l
48 p
regn
ant w
omen
wit
h at
the
begi
nnin
g an
d at
the
end
of th
ege
stat
ion
ages
fro
m 2
6 to
37
wee
ks w
ere
exam
ined
. Con
trol
grou
p w
as r
epre
sent
ed b
y 20
preg
nant
wom
en th
at w
ere
trea
ted
by m
eans
of
com
mon
ther
apeu
tic
met
hods
Non
ran
dom
ized
con
trol
led
tria
l
80 s
ubje
cts
in th
e tr
eatm
ent
grou
p
Num
ber
of s
ubje
cts
in th
eco
ntro
l gro
up n
ot m
enti
oned
.T
he c
ontr
ol g
roup
did
not
rece
ived
ozo
ne th
erap
y, o
nly
trad
itio
nal m
etho
ds.
Non
ran
dom
ized
con
trol
led
tria
l
78 s
ubje
cts
Num
ber
of s
ubje
cts
in th
eco
ntro
l gro
up n
ot m
enti
oned
.
Dop
pler
exa
min
atio
n (S
/D ra
tio,
PI a
nd R
I) w
as c
arri
ed o
ut o
ne,
two
and
thre
e w
eeks
pos
t tr
eatm
ent
in t
he u
teri
ne,
spir
al a
ndum
bili
cal (
incl
udin
g th
e en
d-br
anch
es)
arte
ries
.
Mor
phol
ogic
al e
xam
inat
ion
of p
lace
nta
from
the
wom
enun
derw
ent
ozon
e ap
plic
atio
n re
veal
ed a
ctiv
atio
n of
the
com
pens
ator
y pr
oces
ses,
i.e
., th
e in
crea
sed
num
ber
of v
esse
ls,
thei
r re
mar
ked
plet
hora
; in
som
e ca
ses
the
deve
lopm
ent o
f th
evi
lli a
ngeo
mat
osis
foc
i was
det
ecte
d.
The
impr
ovem
ent o
f the
PL
O in
dice
s an
d di
sapp
eara
nce
of h
yper
coag
ulat
ion
wer
e al
so s
how
n.
80 w
omen
, who
had
del
iver
y by
ces
area
n, w
ere
trea
ted
on th
e 1s
t,2n
d, 3
rd a
nd 4
th p
osto
pera
tive
day
by in
trav
enou
s ozo
ne so
lutio
n.
All
the
patie
nts
have
got
bef
ore
and
afte
r the
trea
tmen
t a c
ompl
ete
bloo
d co
unt a
nd T
and
B c
ell d
iffe
rent
iati
on. I
mm
unog
lobu
lins
leve
ls, p
hago
cyte
act
ivit
y w
ere
also
stu
died
.
The
ozo
ne t
reat
ed g
roup
had
sig
nifi
cant
ly l
ess
infe
ctio
usco
mpl
icat
ions
aft
er th
e ce
sare
an c
ompa
red
to th
e co
ntro
l gro
up. A
nim
mun
e m
odul
atin
g ac
tion
of th
e oz
one
ther
apy
coul
d be
sho
wn
inth
e tr
eate
d gr
oup,
the
mea
n qu
antit
y C
D4+
cell
and
phag
ocyt
eac
tivity
was
hig
her i
n co
mpa
riso
n w
ith th
e co
ntro
l gro
up.
78 c
onse
cuti
ve w
omen
, w
ho h
ad d
eliv
ery
by c
esar
ean,
wer
etr
eate
d on
the
1st
, 2n
d, 3
rd a
nd 4
th p
osto
pera
tive
day
by
I.V
.oz
one.
Int
erfe
ron
was
mea
sure
d in
all
pat
ient
s be
fore
and
aft
erth
e oz
one
trea
tmen
t. C
ontr
ol g
roup
had
got
no
ozon
e th
erap
y.
The
lev
els
of a
lfa-
and
gam
ma-
inte
rfer
on i
n th
e oz
one
trea
ted
grou
p w
ere
high
er th
an in
the
cont
rol g
roup
. The
ozo
ne tr
eate
dgr
oup
had
sign
ific
antl
y le
ss i
nfec
tiou
s co
mpl
icat
ions
aft
er t
hece
sare
an c
ompa
red
wit
h th
e tr
adit
iona
lly
trea
ted
grou
p.
Fai
r
Poo
r
Poo
r
2. 3. 4.OB
STR
ET
IC &
GY
NA
EC
OL
OG
Y
24
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Gre
tchk
anev
GO
, Kat
chal
ina
TS
,K
atch
alin
a O
V
The
new
met
hod
of tr
eatm
ent o
fin
flam
mat
ory
dise
ases
of
low
er f
emal
ege
nita
l org
ans.
(Unp
ubli
shed
ful
l art
icle
)
Kac
hali
na T
. S, P
eret
yagi
na N
. S,
Ant
onov
a N
. S.
Pos
sibi
lity
for
par
ente
ral a
ppli
cati
on o
foz
one
in e
arly
pos
tnat
al p
erio
d in
cas
e of
infe
ctio
us c
ompl
icat
ions
.
(Unp
ubli
shed
ful
l art
icle
)
Kac
hali
na T
. S, K
atko
va N
. Yu,
Gre
chka
nev
G. O
.
The
use
of
ozon
e th
erap
y in
the
trea
tmen
tan
d pr
ophy
laxi
s of
intr
aute
rine
fet
usin
fect
ion.
(Unp
ubli
shed
ful
l art
icle
)
Non
ran
dom
ized
con
trol
led
tria
l
60 p
atie
nts
wit
h no
n-sp
ecif
icco
lpit
is w
ere
divi
ded
into
2gr
oups
. 40
in te
st g
roup
and
20
cont
rols
Non
ran
dom
ized
con
trol
led
tria
l
The
sam
ple
cons
iste
d of
34
pati
ents
in e
arly
pos
tnat
al p
erio
d(7
- 1
0 da
ys)
wit
h va
riou
spu
erpe
ral d
isea
ses.
(N=
19)
rece
ived
trad
itio
nal
trea
tmen
t in
com
bina
tion
wit
hda
ily
intr
aven
ous
ozon
ated
sal
ine
infu
sion
s. C
ontr
ol g
roup
(n=1
5) w
aspe
rfor
med
ant
ibac
teria
l, de
toxi
ficat
ion
and
dese
nsib
iliz
atio
n th
erap
y, a
sw
ell a
s th
e us
ed o
f ph
ysic
al f
acto
rs.
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
102
preg
nant
wom
en w
ith
a ri
skgr
oup
of in
trau
teri
ne in
fect
ion
offe
tus
and
new
born
chi
ld w
ere
exam
ined
.
The
pat
ient
s w
ere
divi
ded
into
2gr
oups
, the
1st
gro
up c
ompr
isin
g60
pat
ient
s w
ith
intr
aute
rine
infe
ctio
n ca
rrie
rs w
itho
utin
flam
mat
ion
sign
s, a
nd th
e 2n
don
e in
clud
ing
45 p
atie
nts
show
ing
the
sign
s of
an
infl
amm
ator
ypr
oces
s.
The
test
gro
up re
ceiv
ed v
agin
al c
ircu
lato
ry in
suff
latio
ns o
f an
ozon
e-ox
ygen
mix
ture
, whi
le c
ontr
ols
rece
ived
ant
isep
tics
solu
tions
. T
his
was
rep
eate
d da
ily
wit
hin
7-10
day
s.
All
und
erw
ent b
acte
rios
copi
c an
d ba
cter
iolo
gica
l inv
esti
gati
on p
rean
d po
st-t
reat
men
t. A
fter
trea
tmen
t, 76
% in
the
trea
ted
grou
p di
dn’t
show
any
opp
ortu
nist
ic in
fect
ion,
whi
le in
the
cont
rol g
roup
, 50%
retu
rned
to n
orm
al a
nd 2
5% g
ot w
orse
.
Res
ults
- e
ffic
ienc
y of
the
ozo
ne t
hera
py,
in c
ombi
nati
on w
ith
trad
itio
nal
trea
tmen
t in
pat
ient
s w
ith
infe
ctio
us p
ostp
artu
mco
mpl
icat
ions
. In
this
gro
up, t
he v
alue
s of
end
ogen
ic in
toxi
cati
onw
ere
decr
ease
d m
uch
fast
er, a
s w
ell a
s er
ythr
ocyt
e se
dim
enta
tion
rate
, le
ukoc
ytos
is,
inde
x of
leu
kocy
te i
ntox
icat
ion
and
leve
l of
mid
dle
mol
ecul
e pe
ptid
es.
Als
o th
e pH
-val
ue h
ad a
tend
ency
to b
alan
ce. T
he li
pid
pero
xida
tion
valu
es c
onfi
rmed
the
im
port
ant
acti
on o
f oz
one,
inc
reas
ing
the
anti
oxid
ant d
efen
ce s
yste
m. T
he e
ffic
ienc
y of
ozo
ne th
erap
y us
edin
com
bina
tion
wit
h tr
adit
iona
l tr
eatm
ent
was
dem
onst
rate
d by
redu
cing
hos
pita
l car
e ti
me
by 5
day
s.
Eac
h gr
oup
was
tre
ated
wit
h th
e tr
adit
iona
l m
etho
ds (
incl
udin
gan
tibi
otic
s an
d im
mun
omod
ulat
ors)
.
All
the
wom
en re
ceiv
ed a
n oz
onat
ed p
hysi
olog
ical
sal
ine
solu
tion
,in
trav
enou
sly,
dai
ly f
or 3
- 5
day
s.
Thi
s st
udy
reve
aled
the
max
imum
pos
itiv
e th
erap
euti
c ef
fect
in
patie
nts
of th
e 1s
t gro
up. T
he n
orm
aliz
atio
n of
the
lipid
per
oxyd
atio
nan
d th
e an
tioxi
dativ
e sy
stem
inde
x w
ere
obse
rved
in 7
2 %
of w
omen
of th
is g
roup
. The
nor
mal
izat
ion
of th
e im
mun
e sy
stem
inde
x w
asob
tain
ed in
42
%.
Pat
ient
s w
ith
uter
opla
cent
al b
lood
flo
w d
istu
rban
ces
show
ed a
tend
ency
to
impr
ove
the
dopp
ler
inde
x (7
8 %
). B
esid
es,
no o
neca
se o
f inf
ecti
ous
agen
t tra
nsm
itte
d to
fetu
s w
as re
veal
ed in
the
1st
grou
p. T
he d
escr
ibed
eff
ects
wer
e no
t re
veal
ed i
n th
e 2n
d gr
oup.
Thu
s, a
ppli
cati
on o
f oz
one
has
max
imum
eff
ect
whe
n a
mot
her
show
s th
e pr
esen
ce o
f T
OR
CH
-inf
ecti
on a
gent
s w
itho
ut th
e si
gns
of in
flam
mat
ory
proc
ess
acti
vati
on.
Poo
r
No
stat
itis
ical
test
ava
ilab
le
Fair
Det
ails
of
the
stud
y ar
e no
tgi
ven
Poo
r
5. 6. 7.
25
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
R C
hand
ra-D
’Mel
lo, R
‘M
ello
Ozo
ne th
erap
y in
fem
ale
infe
rtil
ity
(Unp
ubli
shed
ful
l art
icle
)
Gre
tchk
anev
GO
, Kat
chal
ina
TS
,K
atch
alin
a O
V
The
trea
tmen
t of
endo
met
riti
s in
com
bina
tion
wit
h oz
onet
hera
py(U
npub
lish
ed f
ull a
rtic
le)
A. M
ocha
lov
and
S. K
otov
.
Ozo
ne T
hera
py A
nd T
he N
euro
logi
cB
ehav
iour
Of A
Bac
kbon
eO
stec
hond
rosi
s.
(Abs
trac
t fro
m 3
rd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
D’E
rme
M e
t al (
1998
)
Ozo
ne th
erap
y in
lum
bar
scia
tic
pain
Rad
iol M
ed (T
orin
a) J
an-F
eb; 9
5(1-
2): 2
1-4
Cli
nica
l tr
ial w
itho
ut c
ontr
olgr
oup
56 s
ubje
cts
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
15 s
ubje
cts
Non
ran
dom
ized
con
trol
led
tria
l
107
pati
ents
wit
h m
uscu
loto
nic,
neur
odys
trop
hic
and
radi
cula
rsy
ndro
mes
of
back
bone
oste
ocho
ndro
sis
(cer
vica
l and
lum
bar
loca
liza
tion
) w
ere
inve
stig
ated
.
Non
-ran
dom
ised
con
trol
led
pros
pect
ive
tria
l N=
50
Fol
low
-up
for
6 m
onth
s
56 p
atie
nts
wit
h in
fert
ilit
y of
infl
amm
ator
y et
iolo
gy w
ere
give
nco
mpl
ete
ozon
ethe
rapy
cou
rse
for 1
2 da
ys.
The
n af
ter 4
4 pa
tient
sw
ere
pres
crib
ed r
ecta
l in
suff
lati
ons
and
vagi
nal
appl
icat
ions
dail
y fo
r 3
days
wit
h an
inte
rval
of
15 d
ays.
12 p
atie
nts
wer
e gi
ven
a ga
p of
25
to 3
0 da
ys. L
ab in
vest
igat
ions
wer
e do
ne p
re a
nd p
ost t
reat
men
t.O
zone
ther
apy
has
a go
od p
osit
ive
effe
ct in
.
15 p
atie
nts
wit
h ac
ute
form
of
post
abor
tive
and
pos
tnat
alen
dom
etri
tis re
ceiv
ed in
trau
teri
ne ir
riga
tion
with
ozo
nise
d-di
still
edw
ater
. T
he tr
eatm
ent w
as c
arri
ed o
ut o
nce
a da
y w
ithin
1-3
day
sw
itho
ut i
nter
vals
, w
ith
com
bina
tion
of
gent
amic
in.
Pat
ient
ssh
owed
im
prov
emen
ts i
n ge
nera
l st
ate,
dec
reas
ed s
ympt
oms
ofin
toxi
catio
n, b
ette
r sl
eep
and
appe
tite
and
fast
er p
ain
relie
f.
The
ave
rage
age
of
pati
ents
was
43.
8 ye
ars;
mea
n du
rati
on o
fth
e di
seas
e w
as a
bout
6.5
yea
rs.
In t
he t
reat
men
t of
the
bas
icgr
oup
(81
pati
ents
, al
l m
en)
was
use
d oz
one
ther
apy
byin
trod
ucti
on o
f oz
one-
oxyg
en m
ixtu
re (
OO
M)
in p
arav
erte
bral
zone
s an
d in
bio
logi
call
y ac
tive
poi
nts,
and
als
o lo
cal
auto
hem
othe
rapy
(L
AH
T).
Con
trol
gro
up in
clud
ed 2
6 a
patie
nt (a
ll m
en) a
t whi
ch in
trod
uctio
nof
oxy
gen
(as
a pl
aceb
o) w
as c
ombi
ned
with
LA
HT
with
not
ozon
ized
blo
od. A
t the
end
of
the
trea
tmen
t, th
e pa
tient
s m
arke
des
sent
ial
impr
ovem
ent
of h
ealth
sta
te e
xpre
ssed
in
decr
ease
of
pain
, di
sapp
eara
nce
of h
yper
path
ic c
ompo
nent
, tim
e in
terv
als
with
out p
ain,
nar
row
ing
of ir
radi
atio
n zo
ne. S
imul
tane
ousl
y, th
eba
ckbo
nes m
obili
ty w
as e
nlar
ged,
the
nigh
t a d
ream
was
impr
oved
.
At 3
mon
ths
post
trea
tmen
t, 68
% h
ad p
osit
ive
resu
lts
and
32%
nega
tive
res
ults
Poo
r
Poo
r
Fai
r
Fai
r
8. 9. 1. 2.OR
TH
OPA
ED
ICS
26
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
And
reul
a C
F e
t al (
2003
)
Min
imal
ly in
vasi
ve o
xyge
n-oz
one
ther
apy
for
lum
bar
disk
her
niat
ion
AJN
R A
m J
Neo
rora
diol
May
; 24(
5): 9
96-1
000
Ale
x B
Ozo
neth
erap
y in
com
plex
sur
gica
ltr
eatm
ent o
f pa
tien
ts w
ith
infe
cted
tibi
alfr
actu
res
and
soft
tiss
ue d
efec
ts
(Abs
trac
t fro
m 3
rd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Ale
x B
.
Oss
eous
res
idua
l tre
atm
ent i
n pa
tien
tsw
ith
chro
nic
oste
omye
liti
s of
long
tubu
lar
bone
s us
ing
ozon
e
(Abs
trac
t fro
m 3
rd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Dou
ble
blin
d pr
ospe
ctiv
e tr
ial
N=
600
Fol
low
-up
6 m
onth
s
Non
ran
dom
ized
cot
roll
ed tr
ial
25 s
ubje
cts
Inst
itut
e of
Tra
umat
olog
y an
dO
rtho
pedi
cs, N
.Nov
goro
d,R
ussi
a.
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
63 p
atie
nts
wit
h ch
roni
cos
teom
yeli
tis
of lo
ng tu
bula
rbo
nes
wer
e st
udie
d.
Gro
up A
(pat
ient
who
m re
ceiv
ed s
ingl
e se
ssio
n of
oxy
gen-
ozo
nein
trad
isca
l and
per
igan
glio
nic)
.
Gro
up B
(pat
ient
who
m re
ceiv
ed tr
eatm
ent a
s gr
oup
A in
add
ition
a pe
riga
nglio
nic
inje
ctio
n of
cor
ticos
tero
id a
nd a
nest
hetic
. Gro
upA
-suc
cess
in 7
0.3%
, poo
r ou
tcom
e in
29.
7% G
roup
B-S
ucce
ssin
78.
3% a
nd f
ailu
re i
n 21
.7%
. T
he d
iffe
rent
in
outc
ome
was
Stat
isti
call
y si
gnif
ican
t (P
<. 0
5)
Bet
wee
n 19
97 a
nd 1
999,
18
patie
nts
with
infe
cted
tibi
al fr
actu
res
(14
pati
ents
wit
h so
ft ti
ssue
def
ects
) re
ceiv
ed c
ompl
ex s
urgi
cal
trea
tmen
t com
bine
d w
ith
ozon
e th
erap
y.
Infe
ctio
us c
ompl
icat
ions
wer
e no
t fo
und
in t
he s
ampl
e. I
n th
eco
ntro
l gr
oup
mad
e up
of
11 p
atie
nts,
ozo
ne t
hera
py w
as n
otca
rrie
d ou
t, on
ly th
e co
nven
tion
al tr
eatm
ent w
as u
sed.
In tw
o of
them
dee
p w
ound
infe
ctio
n w
as d
evel
oped
with
an
oste
omye
litis
outc
ome.
The
sur
gica
l in
terv
enti
on c
onsi
sts
of s
eque
stra
and
im
plan
tsre
mov
al, o
steo
necr
osis
rese
ctio
n, ir
riga
tion
and
exte
rnal
fixa
tion
by I
liza
rov
devi
ce o
r pl
aste
r ba
ndag
e. I
mm
edia
tely
aft
er t
hepa
tien
t aw
aken
ed, s
ucti
on d
rain
age
of re
sidu
al o
sseo
us a
nd s
oft
tissu
es c
avity
by
salin
e so
lutio
n w
ith o
zone
con
cent
ratio
n w
as st
arte
d.
On
the
2nd–
3rd
day
the
perf
usat
e w
as c
lear
ed o
f bl
ood,
on
the
7th
day
fibr
in w
as n
ot s
een.
By
the
end
of th
e se
cond
wee
k th
eso
luti
on a
nd th
e pe
rfus
ate
did
not d
iffe
r vis
uall
y. A
vera
ge te
rms
of d
rain
age
tube
rem
oval
in
cont
rol
grou
p (3
9 pa
tien
ts),
wer
e24
day
s, in
the
sam
ple
- 17
day
s.
Thi
s pr
oced
ure,
in p
atie
nts
with
pur
ulen
t com
plic
atio
ns o
f low
erli
mbs
can
red
uce
the
tim
e of
pos
tope
rati
ve w
ound
lav
age
and
com
plet
e de
brid
emen
t by
putt
ing
a su
ture
. Loc
al in
flam
mat
ory
reac
tion
to d
rain
age
tube
long
-ter
m s
tay
in s
oft t
issu
es w
as n
ever
foun
d.
Goo
d
Fai
r
Poo
r
3. 4. 5.
27
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Esc
arpa
nter
J.C
.
Ozo
ne th
erap
y in
the
trea
tmen
t of
bone
infe
ctio
ns.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Con
de B
, Cas
as M
, Del
gado
M.,
Ram
osF. O
zone
ther
apy
in th
e tr
eatm
ent o
fos
teoa
rthr
itis
.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
Sam
ple
size
not
men
tion
ed.
Des
crip
tive
stu
dy
200
subj
ects
Gen
eral
trea
tmen
t was
per
form
ed u
sing
ozo
ne re
ctal
app
licat
ion
and
loca
l ozo
ne tr
eatm
ent a
nd o
zoni
zed
oil (
OL
EO
ZO
N).
Ozo
neth
erap
y di
rect
ly i
nto
the
sept
ic b
one
was
app
lied
as
a un
ique
trea
tmen
t or
com
bine
d w
ith
anti
biot
ic t
hera
py,
surg
ery
ofle
sion
s, e
tc.
Goo
d re
sult
s w
ere
obta
ined
in
a gr
eat
perc
ent
of p
atie
nts,
but
an o
utst
andi
ng im
prov
emen
t was
see
n in
pat
ient
s tr
eate
d w
ith
ozon
e as
the
only
ther
apeu
tic
met
hod.
It w
as w
ell
acce
pted
by
pati
ents
and
no
side
eff
ects
wer
eob
serv
ed.
It w
as c
oncl
uded
rec
omm
endi
ng i
ts a
ppli
cati
on i
nth
e tr
eatm
ent o
f chr
onic
infe
ctio
ns o
f the
ost
eoar
ticu
lar s
yste
m.
We
have
bee
n us
ing
ozon
e th
erap
y, d
urin
g 5
year
s, i
n 20
0pa
tien
ts w
ith
diff
eren
t ty
pes
of a
rthr
itis
, fo
r ex
ampl
e: l
umba
rar
thri
tis,
gen
eral
ized
art
hros
is,
hipo
steo
arth
riti
s an
d kn
eear
thro
sis.
In
our
grou
p of
pat
ient
s, 6
0% f
emal
e an
d 40
% o
fm
ale
wer
e pr
esen
t (8
0% w
ith
mor
e th
an 4
0 ye
ars
old)
. Thr
eegr
oups
of
trea
tmen
t w
ere
cons
ider
ed:
grou
p I,
usi
ng o
zone
ther
apy
alon
e; g
roup
II,
ozo
ne t
hera
py p
lus
med
icat
ion
(ant
infl
amat
ory
and/
or a
nalg
esic
s dr
ugs)
and
gro
up I
II, o
zone
ther
apy
plus
med
icat
ion
and
phys
ioth
erap
y. In
gen
eral
. 85%
of
impr
ovem
ent w
as o
btai
ned.
Poo
r
Poo
r
6. 7.
28
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Gor
buno
v S
, Gor
buno
va L
., R
omas
hov
Ph,
V. D
mit
riev
V.
Tota
l ozo
ne th
erap
y of
trop
hic
ulce
rs o
flo
wer
ext
rem
itie
s in
eld
erly
pat
ient
s.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Con
de B
., C
asas
M, M
artí
nez,
C. R
amos
F. Ozo
ne th
erap
y in
rea
ctiv
e ar
thri
tis.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Cas
e se
ries
42 s
ubje
cts
Ozo
ne h
as b
een
used
in th
eco
mpl
ex tr
eatm
ent o
f 42
pat
ient
sw
ith
long
-ter
m tr
ophi
c ul
cers
of
foot
and
cru
s (a
ge r
ange
61-
84ye
ars)
.
Des
crip
tive
rep
ort
30 s
ubje
cts
We
have
use
d oz
one
ther
apy,
like
par
t of
the
trea
tmen
t, of
30
pati
ents
suf
feri
ng f
rom
rea
ctiv
ear
thri
tis,
in th
e la
st th
ree
year
s.
Com
plex
ozo
ne th
erap
y in
clud
ed lo
cal e
ffec
t of
gase
ous
ozon
ein
pla
stic
sac
. B
esid
es,
for
the
firs
t 8-
10 d
ays
the
ulce
r w
asco
vere
d w
ith
ozon
e sa
tura
ted
anti
sept
ic d
ress
ing.
Wit
h th
e si
gns
of m
arke
d ep
ithe
liza
tion
, ant
isep
tic
dres
sing
s w
ere
subs
titu
ted
by th
e on
es w
ith
ozon
ated
oli
ve o
il.
Ulc
ers
wit
h py
o-ne
crot
ic d
epos
it w
ere
cove
red
wit
h oz
onat
eden
tero
sorb
ents
for
the
fir
st 3
-5 d
ays.
Alo
ng w
ith
exte
rnal
trea
tmen
t in
pla
stic
sac
s, t
he s
urro
undi
ng s
urfa
ce o
f ul
cer
was
subc
utan
eous
ly i
njec
ted
wit
h oz
one/
oxyg
en m
ixtu
re. W
ith
the
aim
of
deto
xica
tion
, as
wel
l as
nor
mal
izat
ion
of o
xyge
n-de
pend
ent
proc
esse
s an
d im
prov
emen
t of
mic
roci
rcul
atio
n, a
llth
e pa
tien
ts r
ecei
ved
intr
aven
ous
inje
ctio
ns o
f oz
onat
edrh
eopo
lygl
ukin
e, d
aily
. T
he m
ost
effi
cien
t w
as f
ound
to
be a
com
plex
tre
atm
ent
of v
ulne
roso
rbti
on w
ith
pres
s-va
cuum
exte
rnal
ozo
ne th
erap
y in
har
d-fr
ame
cham
ber.
By
the
10 -
12 d
ay o
f tre
atm
ent t
he u
lcer
sur
face
bec
ame
ster
ile,
epit
heli
zati
on r
ate
bein
g no
t m
ore
than
4-5
% a
day
, st
arti
ngfr
om th
e th
ird
wee
k it
reac
hed
11-1
2 %
a d
ay. O
nly
one
pati
ent,
out o
f 42
, did
not
hav
e a
com
plet
e co
ver
of u
lcer
ativ
e de
fect
insk
in s
urfa
ce.
No
sign
ific
ant d
iffe
renc
es in
sex
dis
trib
utio
n w
ere
pres
ent,
wit
hpr
edom
inan
ce in
age
s le
ss th
an 4
5 ye
ars.
Pat
ient
s w
ith
reac
tive
pol
yart
hrit
is a
nd R
eite
r S
yndr
ome
wer
ein
clud
ed in
our
stu
dy. I
n 55
% o
f pa
tien
ts, r
eact
ive
arth
riti
s w
asco
nseq
uenc
e of
upp
er re
spir
ator
y se
psis
. The
cli
nica
l eva
luat
ion
was
sat
isfa
ctor
y, w
ith
a fa
st i
mpr
ovem
ent
and
wit
hout
sid
e-ef
fect
s.
Poo
r
Sub
ject
to b
ias
Poo
r
8. 9.
29
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Cur
sio
L,.M
enal
do G
.
Oxy
gen
ozon
e an
d co
locy
nthi
s-ci
mif
uga
trea
tmen
t in
slip
ped
disc
.
(Abs
trac
t fro
m 2
nd I
nter
nati
onal
Sym
posi
a on
Ozo
ne A
ppli
cati
ons,
Cub
a)
Ern
st E
(20
01).
A p
rim
er o
f co
mpl
emen
tary
and
alte
rnat
ive
med
icin
e co
mm
only
use
d by
canc
er p
atie
nts.
Med
J A
ust.
Jan
15;1
74(2
):88
-92
No
auth
ors
list
ed (
1994
)
Que
stio
nabl
e m
etho
ds o
f ca
ncer
man
agem
ent;
ele
ctro
nic
devi
ces.
Thi
s in
form
atio
n is
cur
rent
as
ofN
ovem
ber
10, 2
005C
A C
ance
r J
Cli
n;44
; 115
-127
Cli
nica
l tri
al w
itho
ut c
ontr
olgr
oup
73 s
ubje
cts
Rev
iew
Rev
iew
Thi
s st
udy
look
ed a
t her
nia
of th
e sp
inal
col
umn
loca
ted
in L
4-L
5, L
5-S1
, as
thes
e si
tes
repr
esen
t 90
% o
f all
back
bon
e he
rnia
s.
In 7
3 pa
tien
ts,
mix
ture
of
oxyg
en-o
zone
and
col
ocyn
this
-ci
mic
ifug
a w
ere
inje
cted
int
ram
uscu
larl
y ar
ound
the
ver
tebr
a.T
he m
ixtu
re o
f 20
mL
of
oxyg
en-o
zone
was
inj
ecte
d in
to f
our
site
s w
ith
4 m
L (
tota
l) o
f co
locy
nthi
s-ci
mic
ifug
a ne
ar v
erte
bra
l4-l
5 an
d l5
-s1,
bil
ater
ally
.
The
pai
n fe
lt a
fter
the
inj
ecti
on, l
aste
d on
ly a
few
min
utes
, no
side
eff
ect
or c
ompl
icat
ion
was
ref
erre
d. I
n 57
pat
ient
s pa
into
tall
y di
sapp
eare
d an
d al
l sym
ptom
s an
d m
uscl
es to
ne re
turn
edto
nor
mal
. In
16 p
atie
nts
the
pain
impr
oved
and
sym
ptom
s w
ere
redu
ced,
but
non
e co
mpl
etel
y su
ppre
ssed
.
Com
plem
enta
ry a
nd a
lter
nati
ve m
edic
ine
incl
udin
g oz
one
ther
apy
is fr
eque
ntly
use
d by
can
cer p
atie
nts.
Seve
ral t
echn
ique
sof
adm
inis
teri
ng o
zone
are
bei
ng p
rom
oted
as
trea
tmen
t fo
rca
ncer
.How
ever
, fe
w v
igor
ous
clin
ical
tri
als
of t
he t
reat
men
tex
ist.
Tho
se p
ubli
shed
hav
e de
mon
stra
ted
no e
vide
nce
ofef
fect
.Num
erou
s re
port
s of
ser
ious
com
plic
atio
ns,
incl
udin
ghe
pati
tis,
and
at
leas
t fi
ve f
atal
itie
s ha
ve b
een
repo
rted
. U
ntil
mor
e po
siti
ve e
vide
nce
emer
ges,
ozo
ne t
hera
py s
houl
d be
avoi
ded.
Am
eric
an C
ance
r so
ciet
y ha
s st
ated
tha
t th
ere
is n
o ev
iden
ceth
at th
e oz
one
gene
rato
rs a
re s
afe
and
effe
ctiv
e fo
r the
trea
tmen
tof
can
cer.
Lac
king
suc
h ev
iden
ce, t
he A
mer
ican
Can
cer S
ocie
tyst
rong
ly u
rges
indi
vidu
als
with
can
cer n
ot to
see
k tr
eatm
ent w
ithsu
ch d
evic
es.
Poo
r
76
10.
1. 2.Can
cer
30
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
No
auth
ors
list
ed (
1993
)
Que
stio
nabl
e m
etho
ds o
f ca
ncer
man
agem
ent:
hyd
roge
n pe
roxi
de a
ndot
her
“hyp
erox
ygen
atio
n” th
erap
ies.
CA
Can
cer
J C
lin.
Jan
- F
eb; 4
3 (1
); 4
7-56 Jo
rdan
Liz
, Bea
ver
K, F
oy S
(20
02)
Ozo
ne tr
eatm
ent f
or r
adio
ther
apy
skin
reac
tion
s; is
ther
e an
evi
denc
e ba
se f
orpr
acti
ce?
Eur
opea
n Jo
urna
l of
Onc
olog
y N
ursi
ng.
6(4)
; Dec
embe
r, 22
0-22
7
Rev
iew
Rev
iew
‘hyp
erox
ygen
atio
n” t
hera
py a
lso
calle
d;’
oxym
edic
ine”
,“b
ioox
idat
ive
ther
apy”
, “
oxid
ativ
e th
erap
y” a
nd ‘
oxid
olog
y” is
a m
etho
d of
can
cer
man
agem
ent b
ased
on
the
erro
neou
s co
ncep
t th
at c
aner
is
caus
ed b
y ox
ygen
defi
cien
cy a
nd c
an b
e cu
red
by e
xpos
ing
canc
er c
ells
to
mor
e ox
ygen
tha
t th
ey c
an t
oler
ate.
Alth
ough
ozo
ne h
asbe
en s
ubje
ct t
o le
gitim
ate
rese
arch
, th
ere
is l
ittle
or
noev
iden
ce th
at th
ey a
re e
ffec
tive
for t
he tr
eatm
ent o
f ser
ious
dise
ase,
and
eac
h ha
s de
mon
stra
ted
pote
ntia
ls f
or h
arm
.
The
refo
re th
e A
mer
ican
Can
cer
soci
ety
reco
mm
ends
that
indi
vidu
als w
ith c
ance
r not
seek
trea
tmen
t fro
m in
divi
dual
spr
omot
ing
any
form
of
hype
roxy
gent
ion
ther
apy
as a
nal
tern
ativ
e to
pro
ven
med
ical
ther
apie
s.
Thi
s pa
per
repo
rts
the
prac
tice
of
trea
ting
sev
ere
radi
othe
rapy
ski
n re
acti
ons
wit
h oz
one
ther
apy.
Am
ulti
disc
ipli
nary
tea
m o
f cl
inic
al s
taff
and
res
earc
hers
ques
tion
ed t
he e
vide
nce
base
for
thi
s pr
acti
ce a
nd a
liter
atur
e se
arch
reve
aled
littl
e su
ppor
t for
the
effe
ctiv
enes
sof
this
trea
tmen
t for
the
part
icul
ar c
onte
xt.
Whi
le p
atie
nts
perc
eive
d th
e oz
one
trea
tmen
t to
be
bene
fici
al in
term
s of p
ain
relie
f, it
was
impo
ssib
le to
isol
ate
the
impa
ct o
f ozo
ne a
lone
as
othe
r tre
atm
ents
wer
e gi
ven.
A m
ore
form
al e
valu
atio
n of
this
trea
tmen
t is b
eing
pla
nned
with
reg
ards
tot h
is is
sue.
3. 1.SKIN
DIS
OR
DE
RS
31
Aut
hor,
Tit
le, J
ourn
al, Y
ear,
Vol
ume,
Pag
e N
umbe
rSt
udy
Des
ign,
Sam
ple
Size
Fol
low
-up
Out
com
es a
nd C
hara
cter
isti
csG
rade
&C
omm
ent
No
Lo
Giu
dice
G, V
aldi
F, G
ism
ondi
M,
Pro
sdoc
imo
G, d
e B
elvi
s V
(20
04).
Acu
te b
ilat
eral
vit
reo-
reti
nal
hem
orrh
ages
fol
low
ing
oxyg
en-o
zone
ther
apy
for
lum
bar
disk
her
niat
ion.
Am
J O
phth
alm
ol.
Jul
; 138
(1):
175
-7.
(Abs
trac
t onl
y)
Cor
ea F
, Am
ici S
, Mur
gia
N, T
amba
sco
N (
2004
)
A c
ase
of v
erte
brob
asil
ar s
trok
e du
ring
oxyg
en –
ozon
e th
erap
y
Jour
nal o
f St
roke
and
Cer
ebro
vasc
ular
Dis
ease
; 13(
6), N
ovem
ber-
Dec
embe
r20
04, p
ages
259
-261
A C
ase
Rep
ort
Cas
e R
epor
t
Thi
s is
a c
ase-
repo
rt o
f a
45-y
ear-
old
wom
an w
ho c
ompl
aine
dof
acu
te b
ilate
ral v
isua
l los
s af
ter i
ntra
disc
al a
nd p
erig
angl
ioni
cin
ject
ion
of o
zone
-oxy
gen
gas
mix
ture
for
lum
bar
disk
hern
iati
on.
Oph
thal
mos
copy
reve
aled
a p
rem
acul
ar h
emor
rhag
e in
volv
ing
the
left
mac
ula.
In th
e ri
ght e
ye, m
ulti
ple,
fla
t, re
tina
l hem
orrh
ages
aro
und
the
opti
c di
sk a
nd th
e po
ster
ior
pole
wer
e ob
serv
ed. H
owev
er, t
heM
RI
scan
for
intr
acra
nial
hem
orrh
age
was
unr
emar
kabl
e.
A p
atie
nt w
ith
lum
bar
disc
her
niat
ion
fail
ed t
o re
spon
d to
cons
erva
tive
man
agem
ent
and
was
giv
en c
ombi
ned
ther
apy
intr
adis
cal a
nd p
erig
angl
ioni
c in
ject
ion
of m
edic
al o
zone
and
peri
gang
ioni
c in
ject
ion
of s
tero
ids.
How
ever
the
pat
ient
deve
lope
d a
vert
ebro
basi
lar s
trok
e as
a re
sult
of t
he p
roce
dure
.
1. 2.SAF
ET
Y
Poo
r
32
OZONE THERAPY STUDY PROTOCOL
Research question1. Should ozone therapy be used for treatment of specific condition?
Requested byMedical Department, Hospital Sultanah Aminah, Johor Bharu.
Background
Ozone therapy is a term that describes a number of different practices in which oxygen, ozone, or hydrogenperoxide are administered via gas or water to kill disease microorganisms, improve cellular function andpromote the healing of damaged tissues. The rationale behind bio-oxidative therapies (as ozone is a powerfuloxidizing agent), is that as long as the body’s needs for antioxidants are met, the use of certain oxidativesubstance will stimulate the movement of oxygen atoms from the bloodstream to the cells. With higherlevels of oxygen in the tissues, bacteria and viruses are killed along with defective tissue cells. The healthycells will survive and multiply more rapidly. The result is a stronger immune system.
I. ObjectivesTo assess the safety, effectiveness and cost implications of ozone therapy.
II. Scope
1. The technologyOzone is an activated, trivalent (three atoms) form of oxygen. Oxygen is O2 whereas ozone is O3. Over aperiod of 20 to 30 minutes, ozone breaks down into two atoms of regular oxygen by giving up one atom ofsinglet oxygen. Medical ozone is made of electrically activated medical grade Oxygen (using ozone generator),made from air or oxygen by ozone discharge or by ionizing radiation. Ozone is germicidal, bactericidal andfungicidal.
Inclusion criteria:
Exclusion criteria:Oxygen therapy –use of hydrogen peroxide, hyperbaric oxygen, stabilized oxygen, ionization.
1. Scope
♦ IV/Intramuscular/intraarticular injections♦ Rectal insufflation (1.5 litres)♦ Vagina insufflation (5 minutes)♦ Autohemotherapy (withdrawing blood and reinfusing after putting ozone in)♦ Air purification – low levels of O3 in room air♦ Ozonated drinking water♦ Ozonated oil♦ Sauna/Ozone bagging –body excluding head in bag full of O3 for up to 2 hours♦ Ear insufflation (5 minutes)
33
34
2. Medical problems
i) Arteriosclerosis obliteransii) Skin disease - Indurative hypodermatitis and localised lipodystrophies, skin cancer, psoriasis,iii) Cancer – cervical, prostate,iv) Ischaemic, strokev) Pulmonary diseasesvi) Immune system disordersvii) Degenerative diseasesviii) Peripheral nervous system diseasesix) Aging processx) Arthritisxi) Bruises, burns, fistula, decubitus, gangrene, infections, muscle pains, radiation damage, and
used to promote the healing of wounds.xii) Parkinson’s and Alzheimer’s diseasesxiii) Opthalmology
III. Aspects to be considered
1. Safety- patient side effects- death due to gas embolism- Operator - poisoning/others (FDA- ozone is toxic gas with no medical uses)- US Environmental Protection Agency- ozone level in air ‘unhealthy’ if>0.015ppm, lung and
eye irritant
2. Cost- Direct cost such as the cost of the technology, and the equipment, disposables
3. Effectiveness
4. Training
STRATEGY
1. New Health Technology Assessment.
35
METHODOLOGY
1. Systematic review
a) Gathering of all available evidence- Health Technology Assessment reports- Literature (Published/unpublished)
b) Analysis of evidence drawing up Evidence Table(Under various aspects identified)c) Synthesis of evidence
2. Collection of information on local situation- survey on different tests planning to be carried out/ has been carried out, equipment models,
costs implications involved, safety, improve quality of service
3. Report writing- Report writing for individual section- Suggested headings of the report- Background- Introduction- Objective- Methodology- Results-synthesis of evidence (evidence tables)- Conclusions- Recommendations
4. Merging of individual reports and preparation of draft reports
5. Feedback on Draft report and preparation of final report
6. Presentation of report to Technical Advisory Committee
7. Presentation of report to HTA Council
8. Approved policy sent to implementing agency
9. Translation into CPG and clinical pathway
10. Monitoring of feedback
Websites searched1. MSN2. Alta Vista3. Ovid- Cancerlit4. MEDline5. Cochrane database6. www.geocities.com/ojoronen/oz.HTM