By reactivating natural defence mechanisms, the use of oxygen-ozone surprisingly solves a painful problem. On a conceptual basis, this result was not expected mostly because we know that ozone is a very reactive and potentially offensive gas. PARADOXICALLY, it can elicit beneficial effects. We still have to go a long way before fully understanding its versatility and capacity, when properly used, to display useful biological effects. These results shouldstimulate an intelligent reflection of the most stubborn opponents of the use of ozone in medicine. It would be wrong and simplistic to believe that ozone has definitively solved the problem of back-ache and in fact new approaches, even less invasive and risky, are continuously proposed.

Because ozone cannot be always available, I prepared a protocol proposing to evaluate the local effect (into paravertebral muscles) of a solution of hydrogen peroxide diluted in a 5% glucose solution. We may be able to ascertain if this basic compound, an ozone messenger, acts on nociceptors and evokes the analgesic response. Samanta and Beardsley (1999) wondered what was the best way to treat low back pain, but they did not not mention ozone therapy. If orthopaedic surgeons read this book and try this approach, they may produce new and interesting results, useful for science and above all for patients

Orthodox medical care (antidepressants, corticosteroids, immunotherapy and metabolic drugs) is scarcely beneficial and with some side effects in CFS patients. Although GET and CBT appear to represent an effective intervention for CFS, they do not entirely solve the problem. We have been stimulated in evaluating ozonetherapy because, in other pathologies, most of the patients have reported a feeling of well-being and euphoria. This result is interesting and we can only speculate that the reasons for these positive effects are, at least in part, due to a functional restoration of hormonal and neurotransmitter functions. Moreover, ozonetherapy may interrupt the vicious circle due to a chronic oxidative stress and deranged muscle metabolism. The clinical results so far obtained appear to justify the use of ozone because it is able to activate simultaneously several metabolic pathways gone astray in these frustrating pathologies. This also explains why CBT, that certainly involves the psycho- neurohumoral system, is somehow more effective than using conventional drugs. Our data need to be expanded and compared with a group of patients treated with CBT. The use of a placebo (simple autotransfusion or only oxygenated blood) would be interesting, but these patients are severely distressed and randomisation appears unethical.

A few observations ought to be kept in mind for the future. Our schedule and the volume of blood exposed to O2-O3 may not have been optimal because the clinical improvement has progressed slowly. Whilewe are insisting on the validity of the strategy "start low, go slow", we may have been too cautious. The schedule of two treatments per week appears valid and well accepted by patients but, while we should start with a 225 ml volume of blood and an ozone concentration of 20 mcg/ml, during a four week period, we should escalate the blood volume to the maximum of 270 ml and an ozone concentration of 40 mcg/ml. It also appeared clear that a priori we cannot fix a