[Importance of determining the propidium-iodide index of plasmacytes in multiple myeloma. I. Relation to selected laboratory indicators of the disease]. / Význam vysetrení propidium-jodidového indexu plazmocytu u mnohocetného myelomu. I. Vztah k vybraným laboratorním ukazatelum nemoci.

In a group of 85 patients with multiple myeloma (MM) incl. 50 patients examined at the time when the diagnosis was established the relationship of the values of the propidium-iodide index (PI index) of myeloma plasmocytes of the patients were examined by flow cytometry using the double staining method, and selected laboratory parameters of the disease were analyzed. It was revealed that the values of the PI index examined with the aid of different "identification" monoclonal antibodies did not differ significantly. The median and average value of the PI index was in the whole group for PI/CD38 2.3 and 2.3%, for PI "UHKT" 1.8 and 1.8% and for PI/B-B4(CD138) 2.2 and 2.4%. In the group of patients examined at the time when the diagnosis of MM was established before chemotherapy the median and average value of the PI/CD38 index was 2.0 and 2.2%, PI/"UHKT" was 1.5 and 1.6%, PI/B-B4 (CD138) 2.6 and 2.5%. In the two analyzed groups no statistically significant correlations of PI/CD38,/"UHKT" and B-B4(CD138) index were found with the number of granulocytes, thrombocytes, immunochemical type and the value of the serum M-component, and levels of S-beta 2 microglobulin, S-urea, S-creatinine, S-calcium, and S-lactic dehydrogenase. A significant positive correlation was found in both groups with the level of S-thymidine kinase, in the whole group of indexes PI/CD38 and PI/B-B4(CD138) with the severity of anaemia, index PI/CD38 correlated with S-albumin and index PI/B-B4(CD138) with the percentage ratio of plasmocytes in bone marrow. It was revealed that examination of the propidium-iodide index is a suitable and prompt method for evaluation of proliferative properties of the myeloma population.

[Importance of determining the propidium-iodide index of plasmacytes in multiple myeloma. II. Relation to disease extent and activity]. / Význam vysetrení propidium-jodidového indexu plazmocytu u mnohocetného myelomu. II. Vztah k rozsahu a aktivite nemoci.

The authors evaluated in a group of 50 patients with multiple myeloma (MM), examined when the diagnosis was established before onset of treatment, and in a group of 85 patients examined in different stages of MM the relationship of proliferative characteristics of myeloma plasmocytes assessed by means of the propidium-iodide index PI/CD38, PI/"UHKT" and PI/B-B4(CD138) with the progression, "performance status" and the activity of the disease. With the exception of a different value of the PI/CD38 index between stages 1 and 3 evaluated according to Durie-Salmon, in the whole group of patients no relationship was found with the progress of the disease. When evaluating the whole group the authors observed a difference between sub-stages A and B (i.e. between patients without and with a serious impairment of renal function) when using indexes PI/CD38 and PI/B-B4(CD138). Only in the whole group of 85 patients the authors found a significant relationship of all proliferation indexes (PI/CD38PI/"UHKT" and PI/B-B4) with the "performance status" according to ECOG score to or > or = 3 vs. < 3. In both groups there was a very close statistically significant relationship without the activity of the disease whichever of the three proliferation indexes was used. It was revealed that patients with the active but stable form of the disease have different PI/CD38 and PI/B-B4(CD138) indexes within the framework of the same stage of MM (stages 1 + 2 vs. 3). From the investigation ensues that examination of the PI proliferation index, in particular PI/B-B4(CD138) or possibly PI/CD38 using multiparametric flow cytometry is a valuable method extending hitherto used examination procedures in MM, and that it replaces adequately former autoradiographic and microscopic immunofluorescent techniques.

[Determination of the bromodeoxyuridine index in multiple myeloma. II. Relation to level of advancement and disease activity]. / Vysetrení bromodeoxyuridinového indexu u mnohocetného myelomu. II. Vztah ke stupni pokrocilosti a aktivite nemoci.

In a group of 70 subjects with multiple myeloma (MM) formed by 25 patients examined before establishment of the diagnosis and 45 patients evaluated in different developmental stages of the disease, the authors evaluated the relationship between the value of the bromodeoxyuridine "labelling index" (BrdUrd-LI) and the clinical activity, stage and course of the disease. The authors revealed statistically significantly higher values of BrdUrd-LI in the group of patients in the "active" phase of the disease than in the "stable-plateau" phase of the disease. This applies also to findings within different clinical stages of the disease. The authors did not reveal any relationship of BrdUrd-LI values and the stage of progress of the disease evaluated by means of staging systems according to Durie-Salmon, the British Medical Research Council and Bataille. Patients in the "stationary-plateau" phase with a longer than five-year duration of the disease (61-211 months) had all low BrdUrd-LI values (median 1.4%), while subjects in the "late-preterminal" stage of MM with possible extramedullary spread and leukaemization of the process had in all instances higher values (3.2%). Evidence was provided that examination of the proliferating characteristics of myeloma plasmocytes by means of BrdUrd-LI contributes to a better evaluation of the severity, development and prognosis of the disease.

[The bromodeoxyuridine index in multiple myeloma. I. Relation with selected laboratory indicators of the disease]. / Vysetrení bromodeoxyuridinového indexu u mnohocetného myelomu. I. Vztah k vybraným laboratorním ukazatelum nemoci.

In a group of 70 patients with multiple myeloma (MM), formed by 25 patients examined while establishing the diagnosis and 45 patients examined in different stages of the disease, the authors evaluated the relationship of the bromodeoxyuridine "labelling index" (BrdUrd-LI) of myeloma plasma cells assessed by the method of double immunofluorescence (using antibody BU-1) and selected laboratory indicators of the disease. In the whole group the median and mean values of BrdUrd-LI of myeloma plasma cells were 2.0 (0.6-4.4%) and 2.1 +/- 0.9%, in the group of 25 patients examined during diagnosis it was 1.8 (0.6-4.1%) and 1.9 +/- 0.9%, in the group of 45 patients examined during different stages of MM it was 2.4 (0.6-4.4%) and 2.4 +/- 0.8%. Neither in the whole group nor in the sub-groups any statistically significant correlations were found between BrdUrd-LI values and the degree of anaemia, values of S-creatinine, S-MIG, S-albumin, S-B2M, S-ferritin, S-thymidine kinase, S-IL-6, S-IL-2, S-kIL-2R, the percentage ratio of myeloma plasma cells in bone marrow and the synthetic index of myeloma plasma cells paraprotein.

Lymphocyte proliferation and T-lymphocyte subsets during experimental immunomodulation of Balb/C mice by Olimunostim.

To objectivize possible immunomodulatory effects of polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus), splenic lymphocyte proliferation and T-lymphocyte subsets were followed-up in Balb/c mice administered perorally the lysate or saline (controls). The enhanced spontaneous lymphocyte proliferation observed at the beginning of Olimunostim application preceded a gradual increase of lymphocyte reactivity to T-mitogens reaching the maximum five days after the administration of the last dose and returning back to the control levels ten days afterwards. This stimulation of lymphocyte proliferation was accompanied by Olimunostim induced increase of CD4+ splenic lymphocytes being most pronounced five days after the end of immunomodulation and later returning to the initial values. The last experiment revealed an enhanced response of the in vivo primed lymphocytes after the re-exposure to Olimunostim in vitro. It is concluded that mostly nonspecific activation mechanisms, plausibly also parallelly induced specific immunity, are involved in Olimunostim modulatory effects on the cellular immune response.

Study of modulatory effects of Olimunostim on cellular immunity in healthy humans.

To objectivize potential modulatory effects of polybacterial lysate Olimunostim on cellular immunity, the T-lymphocyte subpopulations and lymphocyte reactivity to mitogens were followed up in 10 healthy volunteers subjected to Olimunostim application and parallelly in 6 healthy individuals receiving placebo. The preparation, which was applied perorally in seven consecutive daily doses, had no effects on T-lymphocytes and their subpopulations and exerted only a limited influence on lymphocyte reactivity to mitogens. Both the moderate suppression of proliferative response to Con A and PWM, observed after the application of the three doses of Olimunostim, and the insignificantly enhanced response to PHA and Con A, revealed shortly after the last dose was given, were only of transient character and in comparison with the control group were not proved to be statistically significant. To explain the discordance of these results with the recently reported modulatory effects of Olimunostim on murine lymphocytes it is suggested, that the performed tests using the peripheral blood lymphocytes cannot mirror the processes developing in the diseased tissues. With respect to this presumption and also to the observations of enhanced immunomodulatory effect of Olimunostim on terrain altered by infection, it is proposed to investigate cellular immune parameters in specific disease sites of Olimunostim treated patients suffering from recurrent infections.