[Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes]. / Neopterin a solubilní receptor interleukinu-2 u nemocných se systémovým lupus erythematodes.

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.

[Therapeutic results and changes in prognosis in patients with multiple myeloma in central and northern Moravia over the past 40 years]. / Výsledky lécby a zmena prognózy nemocných s mnohocetným myelomem v období predchozích 40 let v oblasti strední a severní Moravy--rozbor souboru 562 nemocných.

OBJECTIVE: The objective of the investigation is evaluation of therapeutic results and the development of the prognosis of patients with multiple myeloma (MM) as a result of consecutive changes of therapeutic procedures in patients of central and northern Moravia in the course of the last 40 years. METHODS AND RESULTS: The analyzed group of 562 patients with MM was concentrated at the Ist and IIIrd Medical Clinic of the Faculty Hospital Olomouc in 1959 - 2000, median age 63 (28-91) male/female ratio 1.1: 1.0. From analysis of Kaplan-Meier survival curves and the results of statistical analysis (log rank test p = 0.0000) ensued that during the evaulated period a very substantial change of prognosis occurred with improvement of theraupeutic results and a significant prolongation of survival in general. The first " turning point" was the introduction of chemotheraphy with alkylating substances with Prednisone (1963-1975), leading as compared with the period of symptomatic treatment alone (1959-1063) to a significant prolongation of the media value of general survival (M) from 8 to 19 months (p = 0.0031) and 3-year survival from 4 to 23 % patients, whereby 10-year survival was only 0 % and 1 %. The second "turning point" was the period from 1976 - 1980 with introduction of systematic chemotherapy using conventional doses of polychemotherapeutic (CP) regimes with better opportunities of supporting treatment (M = 40 months, p = 0.0000; 3-year and 10-year survival 55% and 5.5% patients). The therapeutic results acheived during the subsequent 15 years were however an unsatisfactory advance. During the interval between 1976-1995 in a group of 295 patients divided into 5-year sub-periods remission was acheived (R = < 25 % of the baseline value of M-protein) in 10-24 % patients, an inadequate response (NR) = persistence in > 50 % M-protein) in 55-28 %, prolongation of the median of total survival in 232 of the accessble patients for 44 months and long-term survival of 5 - 10 years after establisment of the diagnosis increased from 25 to 36 % and from 5.5 to 16.5 % patients. The third "turning point" was 1996 characterized by the introduction of high-dosage chemotheraphy with transplantation of autologuos peripheral haematopoietic cells ("HD" therapy with ASCT) leading ina group of so far only 33, assessable patients under 65 years to acheived remission in 71 %, to decline of NR in 10 % only and 5 -year suvival so far in 91 % patients ( p = 0.0037). Improvement of therapeutic results and prognosis of the disease as compared with 1976 - 1995 occurred in the whole group of patients also in 1996 - 2000 (CP and "HD"-therapy with ASCT) characterized by remission in 36 %, NR IN 33 % and 5 -year survival in 57 % (p = 0.030). It was reveled that the application of "HD" theraphy with ASCT led in 1995-2000 to the acheivement of more favorable therapeutic results (R - 71 % NR - 10 %. 5-year survival after the interval which elapsed so far 91 %), as compared with 2 similar groups of subjects under 65 years meeting the criteria of "HD" theraphy with ASCT, but treated only by conventional polychemotheraphy (1991 - 1995 and 1996 - 2000: R - 24 and 32 %, NR - 42 and 23 %, 5-year survival 46 and 68 % of the patients). In the group of 148 patients from the period of 1991-2000 the patients had as regards remission (R) more favourable results as compared with patients with NR concerning the prognosis [M 63 vs.22 months, 5-year and 10-year survival 53 vs. 17 % and 17 vs. 0 % of patients (p = 0.0000)]. CONCLUSION: From the submitted analysis ensured that during the period form 1959 - 2000 in patients with mutiple myeloma in central and northern Moravia as a result of the application of modern methods of chemotheraphy and supporting treatment a significant improvements of results of conventional treatment occurred with a more than 5 fold prolongation of so far assessable median values of survival (8 - 44 months) and long-term 10-year survival of almost one sixth of the patients. The real asset of "HD" theraphy with transplantation of ASCT will be revealed by analyses made after a longer time interval.

[Magnetic resonance in examination of the spine in patients with multiple myeloma]. / Význam magnetické rezonance pri vysetrení pátere u nemocných s mnohocetným myelomem.

Multiple myeloma (MM) is a malignant disease of the haematopoietic system characterized by the formation of osteolytic foci of the skeleton with predilection of the thoracolumbar portion of the spine. The submitted investigation evaluates the importance of examination of the spine by magnetic resonance (MR), as compared with results of conventional radiology (CR). The analyzed group of 75 patients with multiple myeloma was assembled in the course of the previous four years. All patients were examined by conventional radiology and magnetic resonance and the assembled results were mutually compared. On examination by MR a pathological finding was recorded in 68/75 (91%) patients, when using CR in 41/75 (55%) patients. Compression of the vertebral bodies was assessed by means of magnetic resonance in 42/75 (56%) patients, when using CR in 37/75 (49%) patients. Secondary stenosis of the spinal canal was detected by MR in 23/75 (30%), extramedullary spread of myelomatous masses was found in 15/75 (20%) patients whereby radiographic examination was negative in these patients. Osteolytic foci in the area of the spine were recorded in 62/75 (83%) patients examined by MR, while by using CR only in 3/75 (4%). From the presented results ensues that nuclear magnetic resonance is for evaluation of spinal lesions in MM much more sensitive than conventional radiography, mainly due to the possibility of direct visualization of soft tissue tumourous masses and evaluation of their relationship to the spinal canal. The contribution of MR examination is invaluable in particular in patients with obscure back pain and a negative finding on radiographic examination of the skeleton where X-ray examination does not explain adequately the patient's complaints, as well as in patients with suspected compression of the spinal cord. In some liminal situations it contributes to more accurate assessment of the clinical stage and thus to selection of adequate treatment.

[Soluble interleukin-6 receptors in the serum in multiple myeloma]. / Príspevek k vysetrení solubilního receptoru interleukinu-6 v séru u mnohocetného myelomu.

BACKGROUND: Infrequent studies, having been published so far, have brought few, partly contradictory, results on the importance of soluble receptor of Interleukin-6 (sIL-6R) in serum in patients with multiple myeloma (MM). The aim of the study was to find out, if there are applicable relations between the levels of sIL-6R and the values of selected clinical and biochemical indices and the levels of some cytokines in serum. METHODS AND RESULTS: The authors analyzed a cohort of 50 patients suffering from MM (age median 64 years, range 34-83 years, ratio of men versus women 1.2:1.0). The soluble IL-6R and other cytokines were examined by ELISA assay, clinical stages of the disease were evaluated according to Durie-Salmon and Bataille. Increased values of sIL-6R (> 90 ng/ml) were in 28 (56%) of patients, median value was 87.4 (range 28.3-220 ng/l). Correlation analysis (Pearson test, p < 0.05) proved a statistically significant relation between the levels of sIL-6R and the values of beta 2-microglobulin (S-B2M) and thymidine kinase (S-TK) in serum. There was no relation to the erythrocyte sedimentation velocity, haemoglobin levels, calcium, urea, creatinine, lactate dehydrogenase, albumin, monoclonal immunoglobulin, C-reactive protein, ferritin, IL-1, IL-2, sIL-2R, IL-6, TNF-alfa, and the occurrence of myeloma plasmocytes in bone marrow. No differences were found between the patients with normal values of S-B2M (< 3 ng/ml) and plasmocytes in bone marrow (< 5%) in comparison with the groups of patients with increased values (3-6, > 6 ng/ml and > 20%, respectively). There was no statistically significant relation of the levels of sIL-6R to clinical stages of MM (1-3) and the degree of activity of the disease. CONCLUSIONS: Increased values of sIL-6R, detected in more than a half of the cohort, were, with the exception of S-B2M, S-TK and massive infiltration of bone marrow by myeloma plasmocytes, in no applicable relation to selected biochemical indices, to the level of some cytokines and to the degree of advancement and activity of the disease.

[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.

[Serum beta 2-microglobulin in multiple myeloma. II. Its significance in monitoring the disease]. / Beta 2-mikroglobulin séra u mnohotného myelomu. II. Význam pro sledování prubehu nemoci.

In a group of 71 patients with multiple myeloma the importance of beta 2-microglobulin (S-B2M) serum levels was evaluated with regard to their importance for monitoring of the disease. No significant relationship was found between B2M levels and monoclonal serum immunoglobulin, only in one third of the patients parallel changes of the two proteins were observed. One third of the patients had permanently normal S-B2M values and thus could not be evaluated with regard to the therapeutic results, 9% of the patients had very low S-B2M values throughout the disease regardless of the high activity of the latter and the marked increase of myeloma mass (stage III A). "Non-corrected" values of S-B2M proved useful in the evaluation of therapeutic results in patients with primarily elevated S-B2M values and satisfactory renal function but not in patients with elevated serum creatinine values. Normal or only slightly variable S-B2M values were part of the plateau phase of the disease, while during the relapse a rise of varying speed and extent occurred. S-B2M appears a suitable, though in some patients only supplementary, indicator for the long-term follow-up of the course of multiple myeloma.

[Serum beta 2-microglobulin in multiple myeloma. I. Relation to selected indicators, clinical stage and disease prognosis]. / Beta 2-mikroglobulin séra u mnohotného myelomu. I. Vztah k vybraným ukazatelum, klinickému stadiu a prognóze choroby.

The authors evaluated in a group of 89 patients with monoclonal gammapathy (18 patients with monoclonal gammapathy of undermined significance, 34 patients examined at the time of diagnosis of multiple myeloma (MM) and in a group of 71 patients with MM examined in different stages of the disease) the serum beta 2-microglobulin. It was revealed that the mentioned indicator is of no differential diagnostic value, it is not related to sex nor to the immunochemical type of monoclonal immunoglobulin. A relationship of serum beta 2-microglobulin to age, serum urea and serum creatinine, to the severity of anaemia, serum albumin, sedimentation rate of red cells, degree of infiltration of bone marrow by myeloma plasmocytes and the stage of the disease, evaluated by the systems of Durie-Salmon and Medical Research Council, was found. The authors tested the importance of serum levels of this indicator for the prognosis of the disease.

Clinical significance of correction of serum beta 2-microglobulin levels for serum creatinine in multiple myeloma.

In the group of 78 patients with multiple myeloma a comparison of the clinical significance of measured and corrected serum beta 2-microglobulin levels was carried out. There was confirmed a significant relationship between serum beta 2-microglobulin and serum creatinine levels. Pretreatment and follow-up of uncorrected serum beta 2-microglobulin levels were useful in confirming tumor mass grade (assessed according to Durie and Salmon or the British Medical Research Council) and survival prediction. No gain was evident from correcting the serum beta 2-microglobulin for the level of serum creatinine (according to Cassuto et al or Garewal et al).