The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

The application of ozone in dentistry: a systematic review of literature.

After five decades characterized by empiricism and several pitfalls, some of the basic mechanisms of action of ozone in pulmonary toxicology and in medicine have been clarified. The present knowledge allows to understand the prolonged inhalation of ozone can be very deleterious first for the lungs and successively for the whole organism. On the other hand, a small ozone dose well calibrated against the potent antioxidant capacity of blood can trigger several useful biochemical mechanisms and reactivate the antioxidant system. In detail, firstly ex vivo and second during the infusion of ozonated blood into the donor, the ozone therapy approach involves blood cells and the endothelium, which by transferring the ozone messengers to billions of cells will generate a therapeutic effect. Thus, in spite of a common prejudice, single ozone doses can be therapeutically used in selected human diseases without any toxicity or side effects. Moreover, the versatility and amplitude of beneficial effect of ozone applications have become evident in orthopedics, cutaneous, and mucosal infections as well as in dentistry.

/pdf/the-ozone-paradox-ozone-is-a-strong-oxidant-as-well-as-a-2tkhc5as10.pdf

The ozone paradox: ozone is a strong oxidant as well as a medical drug.

Introduction -- Chapter 1 Physical-chemical properties of ozone. natural production of ozone. the toxicology of ozone -- Chapter 2 How ozone is generated and its concentrations measured? -- Chapter 3 Preparation of ozonated water and oil for the topical therapy. ozone as a drinking water disinfectant. ozone disinfection to prevent nosocomial infections.-Chapter 4 How does ozone act? how and why can we avoid ozone toxicity? -- Chapter 5 How is ozone administered? -- Chapter 6 The actual six therapeutic modalities -- Chapter 7 The potential toxicity of ozone. side effects and contraindications of ozone therapy -- Chapter 8 Is ozone really a “wonder drug”? -- Chapter 9 The clinical application of ozone therapy -- Chapter 10 The dilemma between hyperbaric oxygen therapy (hot) and ozone therapy -- Chapter 11 The promising future of ozone therapy in medicine.

OZONE A New Medical Drug

Ozone is an intrinsically toxic gas and its hazardous employment has led to a poor consideration of ozone therapy. The aim of this review is to indicate that a wrong dogma and several misconceptions thwart progress: in reality, properly performed ozone therapy, carried out by expert physicians, can be very useful when orthodox medicine appears inadequate. The unbelievable versatility of ozone therapy is due to the cascade of ozone-derived compounds able to act on several targets leading to a multifactorial correction of a pathological state. During the past decade, contrary to all expectations, it has been demonstrated that the judicious application of ozone in chronic infectious diseases, vasculopathies, orthopedics and even dentistry has yielded such striking results that it is deplorable that the medical establishment continues to ignore ozone therapy.

/pdf/ozone-as-janus-this-controversial-gas-can-be-either-toxic-or-5391gzgu0b.pdf

Ozone as Janus: this controversial gas can be either toxic or medically useful.

Twenty-seven subjects suffering from peripheral occlusive arterial disease (POAD, clinical stage II–III according to Fontaine) were enrolled in this study to evaluate the effect of oxygen-ozone therapy upon hemorheological parameters and hemoglobin-oxygen affinity in patients with POAD. All patients underwent a major ozonized autohemotransfusion consisting of the slow reinfusion of 100 ml of autologous blood, previously exposed to a O2-O3 mixture in a glass box for 10 min. Whole blood viscosity, erythrocyte filterability, hematocrit, and fibrinogen levels were assessed at the basal time and 30 min after the reinfusion of ozonized blood. At the same time p50 standard (p50std) values (an indicator of hemoglobin-oxygen affinity) and plasma values of malonyl dialdehyde (MDA, an indicator of lipid peroxidation) were evaluated. At the baseline, patients had significantly higher (p<0.05–p<0.001) whole blood viscosity, MDA, and p50std values and significantly lower blood filterability (p<0.01) as compared with 20 matched healthy volunteers (controls). Thirty minutes after the end of a major autohemotransfusion, whole blood viscosity significantly decreased (p<0.01). This was accompanied by a significant fall in plasma fibrinogen level (p<0.01) with no change in hematocrit. Blood filterability, MDA plasma level, and p50std values increased significantly at the same time (p<0.01–p<0.005). The 2,3–DPG value did not change significantly. No significant changes occurred when the same patients received a non-ozonized autohemotransfusion (control test). In conclusion, ozonized autohemotransfusion may be useful to improve both the poor rheological properties of the blood and the oxygen delivery to tissues in patients suffering from POAD.

Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease.

For many years, clinical practice has consolidated the use of both hyperbaric oxygen and oxygen-ozone therapy in the treatment of peripheral occlusive arterial disease (POAD). We investigated the influence of these treatments on hemorrheologic parameters that play an important role in the pathogenesis and the clinical course of arteriosclerosis. Two groups of 15 patients suffering from POAD, assigned at random either to a cycle of HBO therapy or O2-O3 therapy, were evaluated for blood viscosity, erythrocyte filterability, hematocrit value, fibrinogen concentration, and thrombin time. The O2-O3 therapy caused a significant increase of erythrocyte filterability and a significant decrease of blood viscosity. By contrast, HBO therapy did not produce any significant change. The increase of lipid peri-oxidation, proved by raised malonyldialdehyde plasma levels, seems a likely mechanism involved in the hemorrheologic effects of O2-O3 therapy.

Hyperbaric oxygen, oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusive arterial disease.

The use of ozone in the treatment of peripheral vascular disease (PVD) is increasing. The purpose of this study was to evaluate the effect of ozone on haemoglobin oxygen affinity in Type-2 diabetic patients with PVD. Twenty diabetic patients presenting with PVD (Clinical stage II-IV according to Fontaine) and 20 non-diabetic healthy matched subjects were studied. In both groups, aliquots of blood were ozonised with mixtures of oxygen-ozone (O2-O3) to reach end-concentrations of 6.5, 13, 26 and 78 micrograms O3 per ml of substrate. At baseline, diabetic patients presented significantly lower haemoglobin oxygen affinity values but higher plasma levels of free haemoglobin and malonyldialdehyde (MDA) than controls. In both diabetic patients and controls, exposure of blood to ozone reduced haemoglobin oxygen affinity in an "all-or-none" fashion, without changing 2-3, diphosphoglycerate concentrations in erythrocytes. Both free haemoglobin and MDA concentrations showed significant, dose-dependent increases after blood ozonisation. Thus, ozone caused a significant increase in oxygen unloading of haemoglobin in both normal subjects and Type-2 diabetic patients with PVD.

Influence of ozone on haemoglobin oxygen affinity in type-2 diabetic patients with peripheral vascular disease: in vitro studies

The acute effects of a major ozonized autohaemotransfusion on blood fibrinolytic capacity were evaluated in 20 subjects affected by peripheral arterial occlusive disease (PAOD). The parameters examined were tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). In subjects not previously submitted to autohaemotransfusion ('unaccustomed' subjects), whether they were PAOD patients or healthy volunteers, the PAI-1/t-PA ratio in the blood samples taken 15 min before the autohaemotransfusion was higher (P < or = 0.05) than at baseline. These changes were independent of the presence of ozone in the autohaemotransfusion blood. Values in both healthy and PAOD-affected individuals were again at baseline 120 min after the end of autohaemotransfusion. In PAOD patients and in healthy subjects previously submitted to several autohaemotransfusions ('accustomed' subjects), the PAI-1/t-PA ratio did not significantly change before, during and after an additional autohaemotransfusion. The results (the increased heart rate and epinephrine and norepinephrine urinary excretion only in non-accustomed subjects) suggest that the acute fibrinolytic imbalance is caused by the apprehensive state produced by the procedure in unaccustomed subjects. Autohaemotransfusion with ozonized blood per se does not significantly influence the fibrinolytic balance.

A Sammartino

Papers

Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease.

Hyperbaric oxygen, oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusive arterial disease.

Influence of ozone on haemoglobin oxygen affinity in type-2 diabetic patients with peripheral vascular disease: in vitro studies

Ozonized autohaemotransfusion and fibrinolytic balance in peripheral arterial occlusive disease.