Therapeutics

THERAPEUTICS (from¹ Greek therapeia-treatment), in the literal sense, treatment. The term "therapeutics" is conventionally used to denote the branch of medicine known as private pathology and therapy of internal diseases. Until the mid-19th century, therapeutics covered the majority of clinical forms, except for those requiring special methods of treatment, such as surgery, obstetrics, etc. With the growth and development of medical science, a number of disciplines gradually separated from therapeutics—neurology, laryngology, and in more recent times, endocrinology and physiotherapy. This separation is to some extent artificial, as in a number of countries to this day, nervous and endocrine diseases are studied and taught in so-called medical, i.e., therapeutic, clinics. Despite the separation of daughter specialties, therapeutics remains the broadest field of medical knowledge, constitutes the foundation of clinical medicine, and is the leading discipline among other clinical specialties. The scientific organization of internists in our country began about 40 years ago with the establishment of therapeutic societies in Moscow (by Pavlinov), in Leningrad, Kharkiv in the form of sections of the Pirogov and medical societies. Subsequently, congresses of Russian therapists began to be convened (starting from 1907), of which only six were held before the October Revolution. The true unification of therapists and the large-scale development of therapeutic research work began only in the last 12 years in the USSR, where six all-Union and two all-Ukrainian (of all-Union significance) therapeutic congresses have already been held, republican societies and the All-Union Association of Therapeutic Physicians have been organized. Many regional societies have also been created in the largest centers of the Union (Sverdlovsk, Ivanovo, Voronezh, Saratov, Rostov-on-Don, etc.). In addition, scientific congresses and conferences were convened, in which therapeutics played the main role (conferences on tuberculosis, rheumatism, cardiovascular diseases, etc.). Finally, since 1920, a special "Therapeutic Archive" began to be published. On the scope of questions covered by therapeutics and the history of their development—see Internal Diseases, Treatment, Medicine. Lysate therapy (from Greek lysis-dissolution, breakdown), treatment with lysates, i.e., products of tissue and organ breakdown. The use of breakdown products of endocrine and other organs and tissues for therapeutic purposes was introduced into medical practice in 1922 by Abderhalden, who proposed special preparations made by him using enzymatic hydrolysis and representing mainly high-molecular breakdown products of proteins from various organs, which he named optopes. Among the scientists who developed the issues of lysate therapy, the Japanese Miyagawa and Russian authors should be named: Tushnov, Kazakov, Steppun with their colleagues. Lysates are complex complex preparations containing in their composition breakdown products of proteins (polypeptides and amino acids), hormones, inorganic substances (compounds of phosphorus, sulfur, iodine, bromine, etc.), lipoids, extractive substances, histidine, choline, etc. A number of researchers identify the action of lysates with protein therapy, others explain the effectiveness of lysate therapy by the presence of hormones and so-called autogormones-local tissue exciters in lysates. When using lysates, the action of intermediate breakdown products of proteins, which due to the peculiarities of their physicochemical structure and high specific-dynamic action have both specifically irritating and sensitizing properties, undoubtedly has great importance. It has also been proven that in some lysates there are hormone-like acting substances. While lysates of the pancreas, ovario- and testolysates do not give biological reactions specific to their hormones, thyreolysate gives a biological effect on mice similar to thyreoidin, and lysates from the adrenal glands when tested on blood pressure give a picture similar to the action of adrenaline. On the basis of existing data, one has to come to the conclusion that when explaining the mechanism of action of lysates, the action of the entire lysate as a complex preparation affecting both the breakdown products of protein and hormone-like substances and a number of other substances (lipoids, inorganic and extractive substances, derivatives of choline and histidine, etc.) should be taken into account. There are a number of methods for preparing lysates, the main purpose of which is to obtain a complex of deep breakdown products of proteins and other substances contained in tissues and organs. The most accepted method for obtaining lysates is enzymatic breakdown of tissue. Two methods are used to obtain lysates enzymatically: autolysis-breakdown occurring directly under the influence of the tissue's own enzymes, and heterolysis-breakdown occurring under the influence of added enzymes, mainly digestive juices (treatment of tissue with pepsin and trypsin or gastric and pancreatic juice). Along with enzymatic breakdown, acid hydrolysis (breakdown of macerated tissues in the presence of highly dissociated mineral acids) and autoclaving-action of high pressure and high temperatures are also used. In autoclaving, there is deep breakdown of protein and the possibility of the formation of artificial substances under the influence of high temperatures and pressure that do not normally form in metabolism. Close to enzymatic methods of breakdown is the biological method of obtaining lysates with the help of bacteriolysis. Combined methods of obtaining lysates are also possible, for example, enzymatic breakdown followed by hydrochloric acid hydrolysis or autoclaving. Lysates are prepared from organs of young, completely healthy and non-exhausted animals. Theory of action of lysates. Miyagawa and Tushnov consider the action of lysates as the influence on the body of products of normal cellular or tissue metabolism (natural cellular poisons of Tushnov or physiological irritants of Miyagawa), qualifying their action as organ-specific. According to Tushnov's hypothesis, the introduction into the body of natural or artificial breakdown products of highly differentiated tissues and organs, in particular endocrine glands, causes functional irritation of homologous tissue, and this irritation, depending on the dose and reactivity of the tissue, can manifest either in an increase in the functional activity of organs or in its suppression until complete cessation of activity. According to Tushnov, the mechanism of action of lysates reduces to the specific irritating effect on certain organs and tissues of high-molecular breakdown products of specific protein. Along with this, there is also a non-specific action of lysates on the body, which is explained by the presence of urea-like breakdown products of amino acids and biogenic amines. Miyagawa, based on a number of experimental observations showing that breakdown products of erythrocytes, renal epithelium, liver cells and other tissues in small doses affect the corresponding tissue, stimulating it to regeneration and increased function, and in large doses lead to degeneration and necrosis, believes that the constituent parts of cells of tissues or organs dying in the body are physiological irritants of the corresponding living cells. According to Kazakov's hypothesis, the essence of pathological conditions of the body, despite their external diversity, lies in the violation of the dynamics of intermediate exchange processes: lysate therapy, which is therapy with products of deep breakdown of tissue protein, acts on the assimilation-dissimilation processes in the body, and with the resumption of the normal course of intermediate exchange processes in the body, pathological symptoms should disappear. Lysates obviously sensitize the body to the influence of protein breakdown products, increasing its sensitivity to various hormonal and pharmacological factors (Pavlenko). This may explain the therapeutic activity of those lysates that do not contain hormones, as they, by sensitizing the patient's body, make it receptive to the insufficient amount of hormonal substances that are produced in the body itself by pathologically changed endocrine glands. The question of the organ-specific action of lysates, closely related to the question of the organotropism of protein breakdown products and their role as autogormones, has not yet been finally resolved, although "the available factual material to a large extent speaks in favor of recognizing relative specificity for lysates, i.e., in most cases, the predominant influence on homologous tissue, along with the influence on other organs and tissues" (Genes). Thus, for example, according to the observations of Tushnov and his students, therapeutic doses of various lysates never cause the appearance of protein in the urine and only lysate from the kidneys causes phenomena indicating kidney damage. Injection into the thickness of the skin of dermolysate together with Trypan blue dye gives a long-lasting coloring of the underlying area of skin, which is not obtained with other lysates. Ovariolysate causes an increase in bone mass in chickens, while testolysate does not have such an effect. Mammolysate increases milk secretion in goats, which is not caused by other lysates.

Hemolysates obtained from blood sharply change the composition of blood, while other preparations, in particular testolysate, act many times more weakly. Myolysate will give an increase in the weight of animals, while a similar action cannot be achieved by other preparations. Lienolysate causes a pronounced resistance to infectious diseases by irritating the reticulo-endothelial apparatus. A favorable influence of thyroid gland lysates has been established in cases of insufficient function of gl. thyreoideae. The principle of T. lysates is based on a different principle than ordinary hormone therapy. While in hormone therapy the therapeutic effect in most cases occurs relatively quickly after the administration of hormone preparations, in lysatotherapy, which is designed to revive and increase the functioning capacity of one gland or another under the influence of introducing into the body specific products of decomposition that have an irritating effect on tissues, the effect, gradually increasing, occurs relatively slowly. When applying lysatotherapy, it is necessary to remember the Arndt-Schulz law: "weak irritations enhance the vital activity of cells, medium ones maintain it, strong ones inhibit it, and very strong ones stop it". Experiments show that large doses of lysates introduced into the bodies of experimental animals, being already toxic doses, cause degeneration of a number of organs. Thus, when strong solutions of testolysate are introduced into the sex gland of a guinea pig, necrosis of the entire gland occurs, and when a concentrated solution of testolysate is administered to roosters, they die, and on autopsy degenerative processes are found in the sex glands and parenchymatous organs. Clinical observations show that most lysates, especially lysates from male and female sex glands, have a tonifying effect on the body - they enhance the vital activity of the body, cause an increase in working capacity, increase appetite, improve sleep, enhance metabolism and increase sexual function, having a beneficial effect in general weakness, neurasthenia, asthenia, decreased sexual function, climacteric phenomena and diseases associated with decreased activity of the sex glands. Lysates are prepared from all glands, organs and tissues (Testolysat, Ovariolysat, Thyreolysat, Hypophysolysat, Pancreolysat, Mammolysat, Hepatolysat, Lienolysat, Renolysat, Myolysat, Cutolysat, etc.). Both monolysate (one lysate) and polylisate (a combination of two, three or more lysates) therapy are used. Monolysate T. is used mainly as a tonic and as replacement therapy, primarily in a number of endocrine diseases in which decreased activity of one gland or another is observed. When applying polylisate therapy, an attempt is made in each specific case to be guided by the data of the study of metabolism and hormonal schemes of the interrelationships of glands with internal secretion. - The method of applying lysates consists both in subcutaneous and intramuscular administration, and in their use orally in the form of drops. For intramuscular and subcutaneous injections, 25-50-100% solutions of lysates are usually used in doses from 0.25 to 2.0 every other day or 2 times in 5 days or daily, according to each specific case. The course of injections consists of 15-30 injections. The dosage and duration of the injection course are determined by the effectiveness of their action. The basic (100%) preparation of Tushnov for injections is a solution of one part of dry substance in 50 parts of water. In other words, 1 cm³ contains 0.02 of dry substance (a 1% solution contains 1 part of dry substance to 5,000 parts of water, a 5% solution contains 1 part of dry substance to 1,000 parts of water). Intravenous injections of lysates are not given out of fear of the so-called pepton shock. Ordinary injections are intramuscular, less often subcutaneous. No significant difference in therapeutic action has been found between them. Intramuscular injections apparently act faster (absorption by blood and lymphatic pathways), are less painful and do not give complications. Subcutaneous injections sometimes give infiltrates in some individuals. Doses for various lysates, in the absence of precise criteria, are determined proportionally to the weight of the organs (approximately). For example, if testolysate is 1.0, then thyreolysate is 0.1, and hypophysolysate is 0.01. Injections should be started with small doses: 0.5-1.0 (50-100%) for such preparations as testolysate, ovariolysate, myolysate, 0.2-0.5 (15-25%) for thyreolysate, suprarenolysate, and 0.1-0.3 (5-10%) for hypophysolysate, parathyreolysate, etc. The use of the same dose (without increase) gives a smaller effect than the use of gradually increasing doses. The larger the dose administered, the longer the interval required between injections. Thus, after an injection, for example, of testolysate in a dose of 0.5, the second injection can be performed after 1-2 days, but after a dose of 2.0, the second injection should not be performed earlier than 5-10 days. Long-term continuous administration of lysates can gradually lead to proteinogenic cachexia. The use of lysates in the form of drops, although it is a less reliable form of administration of lysates, also often gives a pronounced result. For oral administration, testolysate, ovariolysate, mammolysat, lienolysat, myolysat are mainly used. The other lysates are administered parenterally. When using lysates orally, a dose of 200.0 per course is usually prescribed, and starting from 30 drops, gradually increasing to 90 drops per day. No diet is required, but the consumption of egg yolks and sugar is desirable. The primary contraindication to the use of lysates is active tbc. In case of gastrointestinal disorders, the oral administration of lysates should be avoided. In kidney diseases, constant observation of the urine (protein), edema, etc., is necessary. In latent chronic diseases, the possibility of provocation should be kept in mind. When repeating a course of injections, if this should be necessary, there should be an interval of at least two months. - Lysates can be stored for a long time (several months) without visible changes. They should be stored in a cool and dark place. Before use, shake well, as after long standing a light albumose precipitate may form. This is especially noticeable in preparations for internal use due to the presence of alcohol in the latter. - Lysatotherapy is a new therapeutic method, undoubtedly needing further development. At the same time, lysatotherapy should not be considered as a remedy that cures all diseases, and it should be regarded only as an addition to the numerous arsenal of therapeutic means at the disposal of modern therapy. Lit.: Dombé I., Borodulin F. and Eruzalimchik D., Materials on histolysates by Prof. M. Tushnov, M., 1933; Lysates and lysatotherapy, ed. by S. Genes, Kharkov, 1936; Pavlenko S. and Kiselev V., On the problem of lysates, Klin. med., No. 11-12, 1933; Collection of works on the study of histolysates, issues 1-2, Kazan, 1931; Theory and practice of lysatotherapy according to the method of I. Kazakov, Works of the Institute of Metabolism, M.-L., 1934; Tushnov M., Theory and mechanism of action of histolysates, Klin. med., No. 11-12, 1933.