[Fetomaternal haemorrhage in delivery by cesarean section]. / Fetomaternální hemoragie pri porodu císarským rezem.

OBJECTIVE: To determine the incidence and volume of fetomaternal haemorrhage (FMH) in normal vaginal delivery and in delivery by cesarean section. Determination of these parameters would enable optimalization of guidelines for RhD alloimmunization prophylaxis. DESIGN: A prospective cohort study. SETTING: Palacky University Hospital, Olomouc, Czech Republic; University Hospital, Ostrava, Czech Rebublic. METHODS: A total of 4862 examinations were performed. The volume of fetal red blood cell (RBC) entering maternal circulation in normal vaginal delivery (control group, n = 3295) and in delivery by cesarean section (risk group, n = 1567) was assessed by flow cytometry. FMH = fetal RBC volume; fetal blood volume si double (expected fetal hematocrit is 50%). RESULTS: The fetal RBC volume diagnosed in maternal circulation after delivery ranged from insignificant FMH < or = 0.1 ml to excessive FMH = 65.9 ml (median 0.7; mean 0.79; SD 1.38). High values of FMH > 1.7 ml were observed in 5.8% cases (280/4862), FMH > 2.0 ml in 3.2% (157/4862), FMH > 2.0 ml in 1.4% (69/4862) and excessive FMH > 5ml (IgG anti-D insufficient dose 100 microg) in 0.25% (15/4862). Delivery by cesarean section presented a higher risk of incidence of high values of FMH > 1.7 ml (OR 1.6; p 0.0002), FMH > 2.0 ml (OR 2.2; p <0.0001) and FMH > 2.5 ml (OR 2.2; p 0.002) when compared with normal vaginal delivery. It did not, however, present a statistically significant risk factor for the incidence of excessive FMH > 5ml. CONCLUSION: In normal vaginal delivery as well as in delivery by cesarean section, FMH less than 5 ml (10 ml of whole blood) occurs in the great majority of cases, and thus for the prevention of RhD alloimmunization, an IgG anti-D dose of 100 microg should be sufficient. Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present a risk factor.

[The influence of maternal age, parity, gestational age and birth weight on fetomaternal haemorrhage during spontaneous delivery]. / Vliv veku rodicky, parity, délky trvání tehotenství a hmotnosti plodu na fetomaternální hemoragii pri spontánním porodu.

OBJECTIVE: Determine the influence of maternal age, parity, gestational age and birth weight on the volume of fetal erythrocytes which enter the maternal circulation during spontaneous delivery. Determining these parameters would enable improving the guidelines for RhD alloimmunization prophylaxis. DESIGN: Prospective clinical study. SETTING: Department of Obstetrics and Gynecology, University Hospital, Olomouc. METHODS: A total of 2413 examinations were performed. The amount of fetal erythrocytes entering maternal circulation during uncomplicated spontaneous delivery of one fetus was determined by flow cytometry using the BDFACSCanto cytometer (Becton Dickonson International). Laboratory processing: Fetal Cell Count kit (Diagnosis of Feto-maternal transfusion by flow cytometry), IQ Products, IQP-379. Calculation of total volume of fetal erythrocytes entering maternal circulation: Scientific Subcommittee of the Australian and New Zealand Society of Blood Transfusion. Guidelines for laboratory assessment of fetomaternal haemorrhage. 1st ed. Sydney: ANZSBT, 2002: 3-12. RESULTS: The average maternal age when FMH 1.8 ml (95 perc) was 29.4 years vs. 29.1 years when FMH > 1.8 ml, median 30 years in both groups, the difference was not statistically significant (p = 0.501). The average gestational age when FMH 1.8 ml (95 perc) was 275.3 days vs. 276.9 days when FMH > 1.8 ml, median 278 days (39 weeks +5 days) vs. 276 days (39 weeks + 3 days), the difference was not statistically significant (p = 0.849). The average birth weight when FMH 1.8 ml (95 perc) was 3312 g vs. 3353 g when FMH > 1.8 ml, median 3340 g vs. 3330 g, the difference was not statistically significant (p = 0.743). FMH > 1.8 ml (5 perc) was present in 4.1% of primiparas (42/1023), in 4.2% of secundiparas (44/1050) and in 5.3% of multiparas (18/340), the difference was not statistically significant (p = 0.607). The difference in maternal age, parity, gestational age and birth weight were also not statistically significant for fetomaternal hemorrhage FMH > 2.1 ml (2.5 perc), FMH > 2.5 ml (n = 25), FMH > 5 ml (n = 5). CONCLUSION: Maternal age, parity, gestational age and birth weight does not present a risk factor for excessive fetomaternal hemorrhage during spontaneous delivery.

Thalidomide and bortezomib overcome the prognostic significance of proliferative index in multiple myeloma.

UNLABELLED: We analyzed proliferative index of myeloma plasmocytes (PC-PI) in acohort of 217 patients with multiple myeloma (MM) treated with conventional chemotherapy and biological agents, thalidomide and bortezomib. In the whole group was adifference between overall survival (OS) favoring patients with PC-PI ven after 40 months (median overall survival 25 vs 10months, p= 0.015), whereas in the group treated with thalidomide and bortezomib was no difference, with medians over 39 months. Even patients with low PC-PI profited from the treatment with novel drugs. Presented results suggest that the treatment of MM with novel agents overcomes the prognostic significance of PC-PI and should be used in all MM patients. KEYWORDS: myeloma -prognostication -proliferative index -biological therapy.

[Possibility to identify fetomaternal haemorrhage]. / Moznosti stanovení fetomaternální hemoragie.

UNLABELLED: Fetomaternal haemorrhage (FMH) is a status characterised by penetration of fetal blood into the maternal circulation which happens mostly at delivery. FMH may cause erythrocytal alloimmunisation of woman. That is why anti-D immunoglobulin (IgG anti-D) is being administered to RhD negative women after delivery of RhD positive fetus. IgG anti-D is administered to RhD negative women standardly and in much greater quantities than is actually necessary. However, on the other hand, it is not possible to diagnose cases where a greater dose is required. To optimalise prevention of RhD alloimmunization in RhD negative women, it is important to diagnose conditions where fetomaternal haemorrhage (FMH) occurs, precisely define its volume and consequently administer the required dose of IgG anti-D. The ability to reliably detect fetomaternal haemorrhage (FMH) and precisely define its volume would allow better and less expensive prevention of RhD alloimmunization in RhD negative women. IgG anti-D could thus be administered only in cases that are actually indicated and only in doses necessary for preventing RhD alloimmunization. Accurate quantification of FMH is determined by flow cytometry. DESIGN: Review. SETTING: Department of Obstetrics and Gynecology, Department of Alergology and Clinical Immunology, University Hospital Olomouc.

[Assessment of plasmatic cell proliferation and apoptosis indexes in the course of multiple myeloma]. / Hodnocení proliferacního a apoptotického indexu plazmatických bunek v prubehu mnohocetného myelomu.

INTRODUCTION: The proliferation and apoptosis indexes are a significant prognostic factor in multiple myeloma (MM). The objective of the study was to assess the indexes in the course of MM from the point of view of the disease activity and potential clinical use. METHOD: A sample of 120 patients was studies, of which 49 at diagnosis, 36 in progression and 35 in remission. The proliferation and apoptosis indexes were assessed according to the achieved treatment response and were compared with subsequent progression in patients in remission. The proliferation potential was measured with the propidium-iodide index (PC-PI/CD138), apoptosis was measured with annexine-V (PC-AI/CD138), assessed by the method of flow cytometry. RESULTS: The sample of49 newly diagnosed patients recorded a decrease in PC-PI (M 2.9-2.1, p < 0.0001) and an increase in PC-AI (M 4.7-8.6, p < 0.0001) at remission. Patients without treatment response showed no difference in PC-PI (p = NS), while PC-AI decreased (M 6.2-3.9, p = 0.004). The sample of36 patients in MM progression with treatment response recorded a decrease in PC-PI (M 2.9-2.2, p < 0.0001) and an increase in PC-AI (M 4.6-8.8, p < 0.019). There was no difference in any of the indicators (p = NS) in cases with zero treatment response. 35 patients in remission with developing progression recorded an increase in PC-PI (M 2.3-2.7, p < 0.0001) and a decrease in PC-AI (M 8.3-4.2, p < 0.0001). CONCLUSION: The study has shown that monitoring PC-PI and PC-AI in the course of different phases of MM is beneficial from the point of view of the assessment of changes in the proliferation activity and the degree of apoptosis of myeloma cells. Monitoring the two parametres allows for timely prediction of disease progression.

[Study of the eosinophilic inflammation activity in bronchial asthma]. / Moznosti sledování aktivity eozinofilního zánetu u asthma bronchiale.

BACKGROUND: Bronchial asthma is a chronic inflammatory disease of the respiratory tract where variety of cells plays a role, particularly mast cells, eosinophils (Eo), and T lymphocytes. At present, there is no clear-cut clinical or laboratory parameter to monitor the activity of this disease. Our study was designed to examine and compare serum eosinophilic cationic protein (S-ECP) levels, plasma ET-1 (P-ET) levels and percentage of eosinophils with CD44 (EoCD44) in paediatric asthmatic patients. METHODS AND RESULTS: In our study, a group of 97 atopic children with persisting mild asthma, had a detailed analysis of their personal history. In addition, S-ECP, P-ET, EoCD44, eosinophil blood count (Eo) and serum levels of IgE(S-IgE) in peripheral blood were determined. Subsequently, children were treated with montelukast (singular), a leukotriene receptor antagonist for a period of three weeks (montelukast tablets in a dose of 5 mg once a day). A second S-ECP, P-ET, EoCD44 were determined in the interval of 3 months from the first collection. In 97 asthmatic children a correlation between P-ET and EoCD44 (p=0.002; r= -0.5) were found. CONCLUSIONS: Our follow-up study surprisingly confirmed a correlation between P-ET and EoCD44. The lower percentage of EoCD44 in peripheral blood in asthmatic children is due to Eo inflammation activity and attests the massive Eo invasion into the airways. The determination of combination - S-ECP, P-ET, EoCD44 - provides an indirect evidence of the multiple features of Eo inflammation.

Prognostic significance of plasma cell propidium iodide and annexin-V indices and their mutual ratio in multiple myeloma.

The aim of this study was a contemporaneous measurement of plasma cells proliferative and apoptotic activity in patients examined at the time of multiple myeloma (MM) diagnosis before initiation of chemotherapy, focussed on the following aspects: determination of prognostic significance of plasma cell propidium iodide (PC-PI) and annexin-V FITC (PC-AI) indices; optimal cut off of PC-PI and PC-AI with regard to overall survival; calculation of summary kinetic index of plasma cells (PC-PI/AI ratio) for evaluation of its prognostic importance; determination of an index (out of PC-PI, PC-AI and PC-PI/AI) showing the closest relation to prognosis of multiple myeloma. The analyzed 122 patients fulfilling SWOG multiple myeloma criteria were treated by conventional chemotherapy. Plasma cell proliferative activity was measured by means of PC-PI examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI), flow-cytometry method with annexin-V FITC and MoAb CD138 was used. The PC-PI median in 122 patients was 2.6(0.4-4.8)%. The sequence prognostic analysis showed that the optimal PC-PI cut off was 2.9% and displayed a significant relationship with overall survival (OS) (p=0.031). The group of 94 patients had PC-AI median of 5.0(1.4-24.5)%. The best statistical significance of the rate of apoptosis related to overall survival was found at cut off value of 4.4% (p=0.022). The median of overall kinetic index of plasma cells (PC-PI/AI) examined in 94 MM patients was 0.5(0.05-2.60) and the overall kinetic index was found to display a very good relationship to OS at the cut off value of 0.71 (p=0.032). All the three indices expressing various aspects of kinetics of plasma cells allow the stratification of patients into two prognostically different groups with statistically significantly different medians of overall survival: good risk - OS still undeterminable at the time of analysis; bad risk - M: OS was for PC-PI 17 months, for PC-AI 23 months and for PC-PI/AI 16 months. The ratio of both indices, i.e. PC- PI/AI, however did not bring any further contribution to overall survival/prognosis evaluation, when compared with single PC-PI and PC-AI. Results of present study indicates that the evaluation of both proliferation and apoptotic activities of plasma cells is important for prognosis thus extending possibilities of initial stratification of MMpatients into groups with different prognostic risk.

International prognostic index (IPI)--a critical comparison with five multiple myeloma staging systems in the group of 270 patients treated by conventional chemotherapy.

In the group of 270 patients with multiple myeloma (MM) treated during 1991-2004 by conventional chemotherapy, the prognostic value and practical utility of IPI (International Prognostic Index) was assessed and compared with five other actual staging systems. Prognostic significance was assessed using the curves of overall survival (OS) according to Kaplan-Meier and log rank test (p<0.05). Good practical utility and prognostic significance of Durie-Salmon (D-S) system was confirmed (p<0.001). Good overall prognostic significance was observed in simple staging systems based on the measurement of beta2-microglobulin and albumin serum levels according to Bataille (p<0.001), SWOG (South West Oncology Group, p<0.001) and IPI (p<0.001). Regardless of a short 5-year duration of the study, the scoring system according to San Miguel enclosing apart from other parameters also propidium iodide proliferation index (PC-PI) of myeloma plasmocytes seems to be promising with very different characteristics of curves of overall survival (p<0.001). Very good prognostic value and easy practical utility were examined in Olomouc staging system (OSS) based on the measurement of beta2-microglobulin and thymidinekinase serum levels (p<0.001). With regard to detection of patients of stage 1, i. e. "low risk", not requiring an immediate initiation of conventional chemotherapy ("wait and see" approach), the most suitable was the system according to D-S, SWOG and IPI (median OS 77, 76 and 77 months). To select a cohort of "high risk" patients, i.e. stage 3, with very unfavourable disease prognosis, the most advantageous was the system OSS and San Miguel (median OS was 5 and 6 months) and/or SWOG system selecting patients of stage 4, i.e. "worst prognosis", with median OS 8 months. It was found that IPI did not meet expectations for effective identification of "high risk" patients (median OS of stage 3 was 20 months) nor for the distinction of different prognosis of patients during initial 25 months of MM course at stage 2 vs. 3. The study indicates that under conditions of common clinical practice and conventional chemotherapy, the staging system according to D-S is still useful, while practical application of SWOG and IPI as simpler alternative to the assessment of clinical stage should be verified by further comparative studies. In harmony with the progress in cytogenetics and molecular biology as well as a prospective requirement of individual target therapy, a future suitable stratification system should be based on parameters of internal biological properties of myeloma tissue and microenvironment of bone marrow, allowing in addition a continuous evaluation of the disease course and the effect of therapy.

C1q complement component and -antibodies reflect SLE activity and kidney involvement.

The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM

Immunological profiles of patients with chronic myeloid leukaemia. I. State before the start of treatment.

In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broaden the present knowledge on the immune reactivity of CML patients. A group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papillomaviruses. To clearly discriminate between changes associated with the disease and those induced by the therapy, all patients were enrolled prior to the start of any anti-leukaemic therapy. Statistically significant differences between patients and controls were found in the levels of IgA, C4 component of complement, CRP and IL-6, the production of Th1 cytokines in stimulated CD3 cells and the E. coli stimulatory index. The analysis of the interrelationship between the results obtained in the individual patients presented some unexpected findings, such as the lack of correlation between the CRP and IL-6 levels. It will be the purpose of a follow-up to determine whether and how the immune status of the patients prior to the treatment correlates with their response to therapy and how the individual immunological profiles change in the course of the disease. These observations will be utilized in the future immunotherapeutic studies to constitute the vaccine- and placebo-treated groups.

[Contribution to the evaluation of the relationship between angiogenic cytokines, selected biological parameters and prognostic factors in multiple myeloma]. / Príspevek k hodnocení vztahu angiogenních cytokinu a vybraných biologických ukazatelu k prognostickým faktorum mnohc'etného myelomu.

BACKGROUND: Multiple myeloma is an unusually heterogeneous disease with individually different clinical course, sensitivity to therapy and prognosis. The undoubted limitation of contemporary diagnostic stratification systems is the insufficient credit of those parameters that express the intrinsic biological properties of myeloma cells and the microenvironment of the bone marrow. The aim of this study was to evaluate the relationship of 10 biological parameters to 6 fundamental prognostic factors of multiple myeloma. METHODS AND RESULTS: The analysed group consisted of 66 individuals examined at the time of diagnosis before the start of therapy. For the estimation of serum levels of investigated molecules there were used following methods: REA RIA, ELISA and the technique of quantitative sandwich enzyme immunoassay. For the analysis of proliferative and apoptotic properties of myeloma cells we used propidium iodide (PC-PI) and annexin-V (PC-AI) indices. The statistical estimation was carried out with the help of Pearson and Spearman test, eventually with the help of U-test according to Mann-Whitney. Increased incidence of abnormal serum levels of examined parameter was registered in the case of S-beta2-microglobulin (95.5%), S-thymidinekinase (57.5%), S-sVCAM-1 (78.5%), S-ICTP (87.0%), S-solubile osteoprotegerin (sOPG 76.5%), S-sSyndecan-1 (56.5%) and low index of plasma cell apoptosis (PC-AI, 78.0%). The statistical analysis (Pearson's test) revealed the mutual relationship of serum levels of: S-beta2-microglobulin to sVCAM-1, (r = 0.39, p = 0.002), sICAM-1 (r = 0.33, p = 0.011), sOPG (r = 0.53, p = 0.001), sHGF (r = 0.34, p = 0.006), sSyndecan-1 (r = 0.38, p = 0.003) and sFas (r = 0.42, p = 0.001); S-albumin to sVCAM-1 (r = -0.29, p = 0.036), ICTP (r = -0.33, p = 0.016), sOPG (r = -0.63, p = 0.000), sHGF (r = -0.39, p = 0.003), sSyndecan-1 (r = -0.29, p = 0.042); S-thymidinekinase to sSyndecan-1 (r = 0.46, p = 0.000) and sFas (r=0.29, p = 0.019). There was no relationship of PINP and VEGF to any of the evaluated prognostic factors. There was no relationship found between either of the analysed parameters to PC-PI and PC-AI. With the help of U-test there was found the relationship of sIL-6R to S-beta2-microglobulin (p = 0.001), albumin (p = 0.002) and PC-PI (p = 0.046). CONCLUSIONS: The presented study implies that the traditional algorithm of parameters used in clinical practice for individual characteristics of MM should be enriched with sOPG, sHGF, sSyndecan-1 and sFas.

A contribution to examination of propidium iodide and annexin V plasma cells indices in multiple myeloma.

The aim of this study was a contemporaneous measurement and a mutual comparison of plasma cells proliferative activity and grade of apoptosis in patients with monoclonal gammopathy of undetermined significance (MGUS) and various phases of MM i.e. smoldering (SMM), stable/plateau and active (progression/relapse) forms of this disease. The analyzed group of 197 patients consisted of 30 MGUS, 21 SMM, 82 patients examined at the time of MM diagnosis and 64 patients analyzed during various phases of the disease after previous chemotherapy. Plasma cell proliferative activity was measured by means of a propidium iodide index (PC-PI) examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI) flow cytometry method with annexin V FITC and MoAb CD138 was used. The individuals with MGUS, SMM and stable/plateau form of MM had overall low levels of PC-PI (M-1.8, 1.7% and 2.1%) and relatively high levels of PC-AI (M-9.1, 10.8 and 9.0%). The correlation between PC-PI and PC-AI was in all the groups mutually highly statistically significant (p=0.000). Analysis of plasma cells proliferative activity (PC-PI) was statistically significant in comparison of MGUS or SMM and versus: patients examined at the time of MM diagnosis (p=0.018 or 0.016); patients evaluated during various phases of MM after previous chemotherapy (p=0.021 or 0.019); stable/plateau MM phase in the cohort of all patients (p=0.017 or 0.040); in the plateau phase after chemotherapy (p=0.008 or 0.024) but insignificant in comparison of MGUS and SMM and with the stable group examined at the time of MM diagnosis. Analysis of the apoptotic process revealed significant differences when comparing PC-AI of SMM but not MGUS group versus all cohort of stable/plateau MM patients (p=0.045); there were also insignificant differences in comparison of MGUS and SMM groupsand versus the stable form of MM measured at the time of MM diagnosis or plateau phase after chemotherapy. There was observed a statistically significant difference in the PC-AI in comparison of SMM group versus group of all patients examined at the time of MM diagnosis (p=0.001) or in various phases of this disease (p=0.015) and the group of MGUS patients compared with patients evaluated at the time of MM diagnosis (p=0.03). Very significant statistical differences of plasma cell proliferative (PC-PI) and apoptotic (PC-AI) activity were found when comparing the levels of both the indices of MGUS, SMM and stable/plateau MM group versus the active (progression/relapse) form of MM marked by a higher level of PC-PI (3.2%, p=0.000) and PC-AI (4.8%, p=0.000) in the whole cohort of MM patients, but also in comparison with both the active forms at the time of MM diagnosis or active forms evaluated during various phases of the disease after chemotherapy. Highly significant inverse relationship between PC-PI versus PC-AI was also revealed in the group of patients in the active (progression/relapse) phase of MM (p=0.000). These results revealed importance of measurement not only of proliferative but also of apoptotic plasma cells indices for a complex evaluation of the cells kinetics of plasma cells compartments in patients with MGUS or MM. This study confirmed the initial hypothesis of a common 'inverse relationship between the proliferative (PC-PI) and the apoptosis activity (PC-AI) in plasma cells compartments in patients with MGUS, smoldering, stable/plateau and active (progression/ relapse) forms of MM'.

The polybacterial lysate Olimunostim modulates lymphocyte function in vitro and restores depressed cellular immunity in vivo.

Immunobiological activity of the polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus) was examined by investigating its effects on murine lymphocytes. When added to in vitro lymphocyte cultures, Olimunostim induced interleukin-2 (IL-2) biological activity (in a 2-d culture) and subsequently potentiated lymphocyte proliferation (on day 3); the latter effect was dependent on the presence of adherent cells. In vivo, significant enhancement of lymphocyte reactivity to T-mitogens and increase of CD4+ helper-inducer T lymphocytes were observed 3 d after a subcutaneous application of Olimunostim to mice with cellular immune deficiency. These results confirm the modulatory properties of Olimunostim towards lymphocytes both in vitro and in vivo, which may form a basis for its clinical application.

[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.

[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.

[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.

[Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected clinical and laboratory indicators in multiple myeloma]. / Vztah hladin solubilních cytoadhezivních molekul VCAM-1 a ICAM-1 k vybraným klinickým a laboratorním ukazatelum mnohocetného myelomu.

Hitherto conducted studies concerned with the problem of cytoadhesive molecules (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM). The subject of the submitted paper was evaluation of the relationship of soluble forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and serum from a bone marrow aspirate (BMA) with selected clinical and laboratory indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of plasmocytes in bone marrow, age, performance status, stage and substage of MM and activity of disease) and proliferation characteristics of myeloma plasmocytes. The authors analyzed two groups of patients with MM, a group of 64 examined in different stages of MM and a group of 39 examined when the diagnosis of MM was established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180 and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and 33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518 vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann-Whitney's test, p0.05) revealed in both groups a significant relationship of both CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p-0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64 patients a relationship was found between sVCAM-1 in PBS and values of S-creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2-microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64 patients there was no relationship between s-ICAM levels in PBS with any of the examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038) and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the total group of 64 a relationship was found between sVCAM-1 in PBS with the patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39 patients a relationship between sVCAM on PBS and the substage of MM (p -0.031). On analysis of sICAM-1 a relationship was found between levels in BMA only with the patient's age (p -0.015). From the investigation ensued that despite evidence of a number of correlations between sVCAM and sICAM-1 levels and clinical and laboratory indicators of MM no relationship was found which could be applied under conditions of clinical practice. Assessment of levels of different indicators in serum of bone marrow aspirate did not reveal any advantages over examination in peripheral blood serum.

[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.

Expression of CCX CKR in pulmonary sarcoidosis.

OBJECTIVE: CCX CKR is a decoy chemokine receptor that specifically binds the chemokines CCL19, CCL25 and CCL21. CCL19 was previously found to be upregulated in pulmonary sarcoidosis. We have, therefore, investigated CCX CKR expression in this inflammatory disease. METHODS AND RESULTS: CCX CKR mRNA was semiquantitated using RT-PCR in unseparated bronchoalveolar (BAL) cells from sarcoidosis patients (S, n = 29) and healthy control subjects (C, n = 9). CCX CKR transcripts were upregulated in patients (mean +/- SEM); S, 0.82 +/- 0.10; C, 0.44 +/- 0.04; p = 0.01; this upregulation paralleled the disease course as assessed by the chest radiographic stage (p < 0.02). Immunocytochemistry localised the CCX CKR protein to ciliated bronchial cells. Flow cytometric fluorescent ligand uptake assay showed that these cells are able to internalize its ligand. CONCLUSION: These observations implicate CCX CKR in the modulation of the inflammatory response in sarcoidosis.