THE METHOD OF THERAPEUTIC INTERVENTION ON PATHOLOGICAL PROCESSES IN ORGANISM

The problem of creation of the method of therapeutic intervention on pathological processes in organism is put at the bottom. This method would be effective for therapy of a wide range of different diseases.

It is possible to succeed while curing oncologic patient only applying multiple stage therapy. At the heart of realization of this conception lies combined parallel and/or consecutive usage of local, local-regional and systemic methods of antitumorial influence. The methods can be basic and auxiliary. Surgery, radial and medicinal therapy are referred to the basic. Different types of correcting therapy like immunomodulators are referred to auxiliary. Last years some types of non-traditional physical methods of treatment have been successfully developed. They confidently turn into basic category from auxiliary: laser radiation, photo-dynamic influence, etc.

It is necessary to concentrate on terms which are obligatory for planning of oncological patient treatment before coming to analysis of basic methods of treatment.

1.   Clinical diagnosis must be confirmed morphologically. If all the attempts turn out to be unsuccessful (punctures, trepanobiopsy, knife biopsy), operation serves as final stage of the diagnosis.

The only one urgent clinical situation is the exception: affection of mediastinum with crush syndrome of upper cava or trachea. In these cases provisional diagnosis is made on the basis of roentgenologic examination including as far as possible computerized axial tomography and ultrasonic examination. After that expanded council of specialists solve the question of urgent medical benefit. These are exactly such patients who can be cured by ex juvantibus (medical therapy, radiation therapy). As soon as status of a patient improves specialists resort to the specifying diagnostics including invasive methods as tracheobronchoscopy with biopsy of trancetracheal or trancebronchial puncture, trancethoracal puncture, parasternal mediastinotomy. Corrections are made in the treatment plan if histogenesis of tumor is qualified.

2.   After completion of initial and specifying diagnostics the treatment plan is not obligatory made by the only specialist but a council which include at the least a surgeon, a radial therapeutist and a chemotherapeutist. Complex of medical influences and sequence of their realization can be rightly diagnosed only by such membership of consultants.

The presence on the council of diagnosticians, therapeutist and anaesthetist is also quiet desirable.

3.   While curing oncological patients as a rule the matter is about necessity of usage of enough loading methods of treatment. At the same time tumors themselves often condition not only sharp lowering of compensatory capabilities of organism in the whole but also fraught with progressing of hard local aftereffects as parancrose inflammatory infiltrate, fistulas, perichondritis, arrosion of vessels. That’s why after detection of therapeutic approach it is necessary to weigh what prevails: benefit from antitumoral treatment or risk from hard aftereffects and worsening of patients’ quality of life. It is especially urgent by giving palliative help.

However described procedures have essential defects:

1.     Therapy requires complex equipment, availability of highly skilled specialists and enough expensive.

2.     A patient feels considerable discomfort from the process of therapy which in the whole is ineffective.

3.     Dynamic change of the patient’s state is not taken into account.

The goal of the given technology is therapy of a wide sphere of diseases among which oncological are in the first place. It doesn’t require complex equipment and highly skilled specialists that allows to carry out such procedures mass and without harm to a patient. It consists in transfusion of free from plasma neutrophils or lymphocytes suspension in certain day time in accordance with self-oscillation phase of neutrophils or lymphocytes concentrations.

Transfusion is required to be made periodically till the necessary clinical result is achieved.

The proposed method is based on principle new idea to consider human organism and his circulatory system as dynamically changing feedback system and to diagnose and cure different diseases including oncological diseases and leukemia on basis of simple blood tests, which were taken from patients in multiple time intervals.

The before proposed by the authors method of diagnostics of a patient based on periodic blood tests, which were taken from him in multiple time intervals, consists in the following: The number of blood cells including leukocytes, lymphocytes and segmented neutrophils is registered after the test intake. Afterwards parameters and oscillation mode which describe changes of number of blood cells in accordance with the taken tests are calculated and studied. And in case of abnormality of staging of oscillations, which describe changes of blood cells’ number, the disease described by type and combination of phase changes is diagnosed.

The application for patent ―Method of diagnostics on periodic blood tests‖ which is the most similar to this technology of treatment was sent on the technology. The given application is also the method of diagnostics and preparatory step for implementation of therapy.

Let’s consider functions of blood cells used in this invention for diagnostics. These blood cells are white blood cells or leukocytes. Leukocyte is quiet a big group of different cells. Primary function of them consists in protection of organism from infections, toxins and foreign bodies. These cells have a nucleus, they can change theirs delineation and pass through tissues. Leukocytes are generated in bone marrow. They are accepted to be divided on several separate kinds.

Neutrophil is numerous group of leukocytes which are capable of phagocytosis. Its cytoplasm contains great number of granules filled with ferments and biologically active substances. If bacteria or virus penetrates into organism then neutrophil moves to the foreign cell, captures it and destroys. Eosinophils are blood cells which perform protective function by destroying pathogenic organisms by means of phagocytosis. They function in mucous membrane of respiratory tracts, bowels and in urinary excretion system. Basocyte is not numerous group of small oval cells which take part in development of inflammatory process and anaphylactic shock. Macrophages are the cells which actively destroy virus particles and bacterial cells but have granules gathering in cytoplasm. Monocytes are characterized by specific function as they can develop or on the contrary slow down an inflammatory process. Lymphocytes are leukocytes which are responsible for immune reaction. Their peculiarity consists in possibility to form steadiness to microorganisms which have already penetrated into human’s blood.

Abnormality of cell differentiation process is observed during diseases of tumourous nature, first of all acute leukemia, lymphosarcoma and solid tumors of different locating and also diabetes. Besides, the abnormality of cell differentiation is observed in progressing of such diseases as AIDS, liver  cirrhosis, hepatitis C and also inherent congenital anomaly.

In order to explain effectiveness of the proposed method let’s consider a physico-mathematical approach to modelling of the abnormality of blood cells differentiation during leukemia, which is the most glaring model of tumorous diseases.

Majority of modern authors support an opinion that human’s leukemia is a disease of tumourous nature. General regularities of leukemia and tumors progressing or their combination sometimes, similar abnormalities of metabolic processes, uniformity of hormonal abnormalities and inherited influences all of them points to the preference of pathogenetic community of leukemia and malignant tumor.

Theory of leukemia genesis as a systemic disease considers leukemia as a disease which begins simultaneously in the whole hematopoietic system of normal cells as a result of abnormality of process of their differentiation. Exogenous and endogenic factors are considered to be the reason of these abnormalities. Specific viruses, penetrating radiation and blastomogenic substances are referred to exogenous factors. Malfunction of endocrine system of organism, products of disturbed metabolism are referred to endogenic factors. Endogenous connections referred to class of steroids (gonadal hormones, bile acids, etc.) can possess blastomogenic (leukogenic) action.

Chromosome mutation in any one hemopoietic cell with its subsequent unrestrained reproduction in quantity and formation of pathologic cells clone underlies the clonal theory of leukemia genesis. Different factors such as viruses, radiation, different physical and chemical agents can be the cause of mutations. With the help of clone theory it turns out possible to explain presence of chromosome abnormalities during leukemia, predisposition of people with chromosome aberration (for example, a mongoloid person or person with anomaly of gender chromosomes) to morbidity of acute leukemia, progress of congenital leukemia and also family leukemia, at the root of which different endogenic and exogenous factors can lie, promoting progressing of mutations with appearance of new inherited characteristics.

For the purpose of modelling of the physical mechanism of leukemia genesis as a model of many diseases, arising as a result of abnormality of process of blood cells differentiation, a fundamental physical model of the process of differentiation out of strong blood cells into leukemic have been developed on the base of connected chains of Ginsborg- Landau and return phenomena of Fermi-Pasta-Ulama (FPU). Two cycles of blood cells differentiation were interpreted in the form of two chains of interconnected attractors within the dynamics’ frameworks of two parametrically coupled discrete chains of Ginsborg-Landau. Presence of oscillations of concentration of blood cells in vitro was interpreted as a result of beats in solutions of connected equalization chains, describing dynamics of passages between the attractors, modelling different conditions of cells differentiation. Initiation of leukemia, tumor disease or diabetes within the bounds of the model is described in vitro as dimension reduction of the attractor in the model of blood cells differentiation, which   can be described with the help of Ginsburg-Landau’s chain and transition from cycle of complicated attractors in chains of basic conditions of cells differentiation into cycle of simple attractors of leukemic, tumor or altered, for example, during diabetes of cells. It was found that change of oscillating parameters of a DNA molecule as a result of violation of its structure or fragmentation of the molecule itself (virus introduction, radiation injury, incorporation into molecule of blastomogenic substances) is the reason of the attractor’s dimension reduction. As a result of modelling there was also found that Furie spectrum of mechanical oscillations in a model of the DNA molecule in case of availability of changes in it, typical for acute leukemia, sharply widens as compared with spectrum of ―healthy‖ DNA. This widening connected with rearrangement of the DNA molecule, for example, its fragmentation and beginning of FPU local returns in its oscillating dynamics. At the same time continuity of transition between different pictures of spectrum of basic FPU return, typical for FPU spectrums of the ―healthy‖ DNA molecule and the dynamics of basic return is replaced by the dynamics of local returns. This result tells in favor of revision necessity of different schemes of chemotherapy of malignant diseases because of all the cytostatics are inductors of cells differentiation. If patient is diabetes diseased he constantly used to take insulin, which wouldn’t allow to ―redifferentiate‖ altered cells of pancreas. According to results of the model research every new cycle of chemotherapy inevitably brings to changing of progress of a disease scenario. Notably, the recovery scenario from the disease as a result of using medicine can be changed by the scenario of a disease relapse during its application in ―unsuccessful‖ period of time. Therefore it is necessary to carry out modelling of influence of every medicinal drug on an organism in the whole chain of disease progress scenario.

Clinical researches were held after numerical investigation of the model. They were directed at reorganization of energy of cells cycles with the help of segmented neutrophils suspension, prepared from donor blood and also traditional cytostatics.

Preliminary scenario of medical treatment has been perfected on a computer model with the help of which the most optimal time of influence on the system of blood was defined.

In spite of difficulty of this method connected with necessity of intake of 8 blood tests per day there were observed

cases of full elimination of leukemic process.

The biggest difficulty was ―successful‖ coincidence of the model dynamics and dynamics of oscillating processes in blood of patient diseased with acute leukemia.

Besides, it was found that during carrying out of therapeutic interventions by means of intravenous induction of neutrophils suspension, patient’s symptoms of allergic diseases existed before for a long time disappeared.

Given approach allows proceeding with developing models of treatment of other diseases, connected with violation of cells differentiation mechanism, in particular AIDS, hepatitis C and also autoimmune diseases as asthma. Preliminary clinical investigations of using the foregoing method show its evident perspective for treatment of these diseases.

Treatment success is also confirmed by 12 experiments which allow considering that highly wide range of diseases answers to the medical treatment.

1.     The Patient H. Aged 5. Acute lymphoblastic leukemia. 50% of lymphoblasts are in peripheral blood. Neck lymph nodes are enlarged.

Because of parents’ refusal of a course of chemotherapy, it was decided to hold a course of treatment by neutrophils. Neutrophils suspension, obtained from donor blood, was injected to the patient once in amount of 50 ml. Blood and marrow value completely normalized during two weeks. Sizes of lymph nodes reduced to standard.

2.   The Patient X. Aged 44. Melanoma. State after surgery on excision of a shin top’s tissues part. Presurgical enlargement of inguinal lymph nodes. Lungs – without peculiarities. Refusal of a course of chemotherapy.

Twofold transfusion of neutrophils suspension out of donor blood was implemented during three weeks in amount of 50 ml each. Sizes of lymph nodes reduced to standard. The patient was back to work.

3. The Patient K. Aged 53. Inoperable stomach cancer. Neutrophils suspension therapy was carried out.

Ten transfusions were implemented during four months in amount of 50 ml each. Half a year later a tumor wasn’t displayed roentgenologically. The patient was back to work.

4.    The Patient C. Aged 36. Forth stage of ovarian carcinoma. Neutrophils suspension therapy was carried out.

Twelve transfusions were implemented during 6 months in amount of 50 ml each. Half a year later a tumor wasn’t displayed roentgenologically. The patient was back to work.

5. The Patient K. Aged 42. Seminomas relapse. Refusal of a course of chemotherapy.

Twofold transfusion of neutrophils suspension was implemented during a month in amount of 50 ml each. Two months later a tumor deposit wasn’t displayed roentgenologically. The patient was back to work.

6. The Patient B. Aged 68. Total transitional-cellular urinary bladder cancer. Refusal of a radiation therapy.

Fourfold transfusion of neutrophils suspension was implemented during a month in amount of 50 ml each. Two months later after therapy a tumor wasn’t displayed roentgenologically. The patient was back to work.

7. The Patient G. Aged 25. Hepatitis B. Persistent form. Refusal of a therapy.

Transfusion of neutrophils suspension was implemented once in amount of 50 ml. Transaminas indicators was back to standard during two weeks. Disease relapses no more appeared.

8.   The Patient T. Aged 71. Lymphosarcoma affirmed by histological analysis of a punctate from a submaxillary lymph node. Refusal of a course of chemotherapy.

Three transfusions of neutrophils suspension were implemented during a month in amount of 50 ml each. Blood value and sizes of lymph nodes recovered to standard.

9. The Patient P. Aged 49. Breast cancer with metastases in axillary lymph nodes. Refusal of an operation.

Five transfusions of neutrophils suspension were implemented during four months in amount of 50 ml each. A tumor and metastases wasn’t detected. The patient was back to work.

10.   The Patient B. Aged 51. Lymphogranulomatosis. State after excision of mediastinum lymph nodes. Relapse.

Three transfusions of neutrophils suspension were implemented during four months in amount of 50 ml each. As a result lymph nodes sizes and blood tests normalized.

11.   The Patient C. Aged 25. HIV infection and hepatitis C. An infiltrate in the liver of 2 cm in diameter.

Transfusion of neutrophils suspension was implemented once in amount of 50 ml. A month later the infiltrate was not detected, HIV and hepatitis C stopped to reveal themselves serologically. The patient was back to work and got married.

12.   The Patient B. Aged 27. Hay fever arisen at pubertal period.

Transfusion of neutrophils suspension out of donor blood was refused. In connection with it, neutrophils suspension was isolated out of own blood and transfused him once. Hay fever symptoms disappeared.

This method doesn’t require complicated equipment or presence of highly qualified specialists in comparison with other methods of therapy by famous doctors. The patient doesn’t feel discomfort or harm from the therapy process. Dynamic change of patient’s condition is taken into consideration.

List of references

1.     Mahonova L.A., Peterson I.S., Mayakova S.A., Berezin A.A., Gubarev K.M. Investigation of circadian rhythms of peripheral blood in children with acute leukemia.//Pediatry, 1979, №8, p. 16-21.

2.     Mahonova L.A., Buachidze LN, Mayakova S.A., Peterson I.S., Berezin A.A., Gubarev K.M. Infiltration of

neutrophils suspension in order to correct circadian rhythms of peripheral blood in children with acute leukemia and lymphosarcoma.//Pediatry, 1979, №12, p.5-10.

3.     Mahonova L.A., Mayakova S.A., Berezin A.A., Gubarev K.M. Circadian rhythms of peripheral blood in children with acute leukemia and lymphosarcoma and their correction by means of different methods.//Writings of 9th international symposium on comparative study of leukemia and coexisting illnesses. Sukhumi, 1979, p. 48-52.

4.     Berezin A.A., Mayakova S.A. Biophysical model of acute leukemia.// Writings of 2d All-Union conference: scientific problems of student’s health protection. Moscow, 1979, p. 219-225.

5.     Berezin A.A. et al. In vitro oscillations of absolute concentrations of leukemic and normal cells.//Writings of the first Ukrainian conference of hematologists and transfusiologists. Kiev, 1980, p. 92-93.

6.     Pavlova L.A., Kharkovskaya N.A., Khrustalev S.A., Berezin A.A. Changing of circadian biorhythms of blood in

case of experimental leukemia.//Hematology and transfusiology, 1982, №2, p. 23-28.

7.     Makhonova L.A., Berezin A.A., Bomshtain A.K., Gavrilova I.I., Peterson I.S. Comparative study of circadian rhythms of peripheral blood in patients with malignant neoplasms and other diseases.//Topical matter of pediatric oncology. 1984, №3 , p. 36-42.

8.     Makhonova L.A., Khrustalev S.A., Kharkovskaya N.A., Belyakova S.A., Berezin A.A. Usage of parameters of circadian biorhythms of peripheral blood for optimization of acute leukemia treatment.//Writings of symposium. Topical matter of diagnostics and lymphoproliferative diseases treatment in children. Moscow, 1983, p.51-60.

9.     Berezin A.A., Scheglov V.A. Physical approach to oscillations modeling of blood cells concentrations of healthy and diseased with leukemia organism in vitro conditions. – Short review on physics. Institute of Physics of Science Academy, issue 6, 2002, p. 22-32.

10. Berezin A.A., Scheglov V.A. Physical approach to oscillations modeling of blood cells concentrations of healthy and diseased with leukemia organism in vivo conditions. – Short review on physics. Institute of Physics of Science Academy, issue 8, 2002, p. 34-44.

11. Berezin A.A. Frelich approach in modeling of dynamics of mechanical oscillations in the DNA molecule and its changes typical for acute leukemia. – Short review on physics. Institute of Physics of Science Academy, issue 12, 2002, p. 27-36.

12. Berezin A.A. Oscillations modeling of different blood cells concentrations of healthy and diseased with acute leukemia donors in vitro conditions by means of connected retarded Van der Pol equations and connection of parameters of concentrations oscillation of specified types of cells with oscillations of DNA molecules. – Short review on physics. Institute of Physics of Science Academy, issue 7, 2003, p. 42.