Advanced age

The first description of the disease, which is, apparently, multiple myeloma, belongs to Henry Bence Jones and William McIntyre. These two London physician reported medical history of Thomas McBean, who died in 1846 from an illness manifested bone pain and swelling. Bence-Jones and McIntyre noted the presence in urine of a particular protein, which when heated first precipitated and then dissolved. Bone marrow registers John Dalrymple - a surgeon who conducted the autopsy of the deceased. The term "multiple myeloma" was proposed in 1873 Rustitskim and only in 1900, Wright drew attention to the relationship of the disease with involvement of plasma cells.

Use after 1940 electrophoretic methods revealed a correlation between brand name viagra serum monoclonal protein and a malignant tumor composed of plasma cells. The study of monoclonal myeloma immunoglobulin played an important role in the development of common understanding about the molecular structure and function of immunoglobulins. These studies and related research using tissue culture techniques and cell labeling in vivo contributed to a better understanding of the origin and kinetics of myeloma cells.

Although chemotherapy and radiotherapy contribute to the increase in the duration and quality of life of myeloma patients, successful treatment of this disease lags behind the level achieved in relation to other malignant tumors of the hematopoietic system. Treatment of multiple myeloma and its many complications is still a difficult task for the physician.

This disease affects mainly the elderly. The possibility of family members of patient care at home is often limited, so it is very important aid society. In such circumstances it is difficult to overestimate the role of qualified geriatrics in long-term care for the patient.

INCIDENCE

Multiple myeloma - a disease of advanced age. Of all tumors, except for chronic lymphocytic leukemia, myeloma is most clearly associated with age. The average age of patients at the time of diagnosis is 62 years, the frequency of the disease increased steadily in the older age groups [Blattner, 1980], the share of persons under 40 years accounted for only 2% of all cases, and 80-year-olds suffer 10 times more in 1950 year-olds. In the general population incidence is 3 per 100 000, and among 80-year-olds - 37 per 100 000. A slight predominance of men. (61%) among patients. Among U.S. blacks disease occurs in 2 times more likely than whites [McPhedran et al., 1972]. Blacks have multiple myeloma is the most common malignant lesion of the hematopoietic system (33%) and whites, it ranks third (14%). It is assumed that in recent years, the frequency of the disease actually increased [Osserman, 1982].

Etiology and Pathogenesis

Myeloma arises from a malignant proliferation of plasma cells, which occurs mainly in the bone marrow, but occasionally in extramedullary foci. On models with the use of experimental animals have shown that the development of malignant plasma cells are involved both genetic and environmental factors. However, in humans the role of any of these factors has not yet been proved. In mice Compare Viagra and injections susceptible lines BALB / c and NZB plasmacytoma can induce by exposure to certain chemicals [Potter, 1973]. In mice of other lines such exposure does not cause the development of plasmacytoma.

There are anecdotal reports of familial cases with multiple myeloma (a disease, but reliable evidence of genetic susceptibility in humans do not. The hypothesis of "two strikes» [Salmon, Seligmann, 1974] postulates the role of two environmental factors in the etiology of myeloma. Benign monoclonal gammopathy is quite common among the elderly . It is the result of monoclonal proliferation of plasma cells that secrete immunoglobulin of the same idiotype. The number of cells (probably less than 1011) is quite stable and only a small number of cases there is a malignant tumor. In some patients with multiple myeloma paraprotein has a specificity to certain antigens (eg, streptolysin or g-globulin). Salmon, Seligmann (1974), based on the results of experiments in mice suggested that the myeloma begins with education, in response to antigenic stimulus, a clone of malignant B-cells (benign gammopathy ). Later, in response to an oncogenic stimulus may have a viral nature, this clone can undergo malignant transformation, and when the number of cells reaches 1011-1012 (myeloma), there is a clinical picture.

Scheme of maturation of B lymphocytes and the alleged target cells during the development of lymphoproliferative diseases of B-cell origin. CLL - chronic lymphocytic leukemia; HDLL - well-differentiated lymphocytic lymphoma; PDLL - poorly differentiated lymphocytic lymphoma; BTts - heavy chain disease; MB - Waldenstrom macroglobulinemia; MB - myeloma.

The cause of myeloma is largely unclear, but now a lot is known about the cellular substrate and the growth kinetics of this tumor. Maturation of normal B-lymphocytes and their evolution up to the antibody plasma cells can now be traced back to using antibodies to the light or heavy chains of immunoglobulin molecules (Fig. 21). Using immunofluorescent and immunoperoxidase techniques allows the identification of early pre-B cells, in the cytoplasm, which contained IgM. As the maturation of these cells lose their cytoplasmic immunoglobulin, but immunoglobulin (IgM and IgD) appears on their surface membrane. These "virgin" B cells are able to respond to specific antigens. Contact with antigen leads to maturation to the stage of lymphoblasts, which is accompanied by increased synthesis of surface immunoglobulin, and then to stage plazmatizirovannogo lymphocytes capable of synthesizing cytoplasmic immunoglobulins. Ultimately, these cells become fully mature plasma cells, which eventually lose their surface immunoglobulins, but are capable of secreting immunoglobulins of the respective division in the extracellular media.

Using the mentioned methods to identify cell markers, we can assume that many types of malignant tumors of lymphoid tissue are B-cell origin. For example, chronic lymphocytic leukemia (B-CLL) is caused by proliferation of cells at the stage of "virgin" B lymphocytes, whereas most non-Hodgkin's lymphomas originate from cells of the same stage of differentiation that B-CLL (well-differentiated lymphoma, HDLL), or lymphoblasts (poorly differentiated lymphoma, PDLL). When macroglobulinemia dominated plazmatizirovannye lymphocytes (along with plasmocytes), and clonal expansion of cells of this stage of differentiation leads to the secretion of IgM, which can be easily identified in the serum. When multiple myeloma in the process involved only the plasma cells, and clonal nature of their proliferation leads to the fact that both serum paraprotein and cytoplasmic immunoglobulin have the same heavy (g or a) and light chains.

Ability to identify the cellular phenotype has important diagnostic value. Cells in tissue sections can be painted using antibody-conjugated peroxidase. These dyes with the specificity of immunoperoxidase to heavy or light chains to help determine whether the plasma cell infiltrate reactive (polyclonal) or malignant (monoclonal).

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