Impact of breast cancer neoadjuvant chemotherapy on plasma and urine amino acid profile, plasma proteins and nitrogen metabolism.

Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0-6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.

Unique wood ash Co-coloured glass tessera from mediaeval Madonna: Raman spectroscopic study of production technology.

While the natron and plant ash glass tesserae may be found on places of importance across the former Roman and Byzantine empires, wood ash glass tesserae are scarce. This is the first time a wood ash glass tessera is studied in detail. It was part of a magnificent 8-metres tall statue of Madonna in Malbork, Poland, created at the end of the 14th century and destroyed at the end of World War Two. It was found to be coloured by cobalt with possible impact of copper, and opacified by Ca-phosphate. Processes previously described in sodium-rich glasses were observed also in the studied potassium-rich wood ash glass tessera, such as diffusion of the respective alkali metal into the Ca-phosphate grains. The elemental composition of the tessera indicates that it is original - mediaeval, from the area north of Alps. Two phases were identified for the first time, to authors' best knowledge, in any glass tessera - leucite (tetragonal KAlSi2O6) and pseudowollastonite (monoclinic CaSiO3). As pseudowollastonite is a high-temperature phase, it may serve as an indicator of production temperature, which was further supported by the study of polymerisation index of model glasses. This study contributes to the knowledge of old technologies and showed that the know-how for opacification was imported from the Mediterranean, while the raw materials employed for the base glass preparation were from the area north of Alps.

The effectiveness of three mobile-based psychological interventions in reducing psychological distress and preventing stress-related changes in the psycho-neuro-endocrine-immune network in breast cancer survivors: Study protocol for a randomised controlled trial.

Background: A growing body of literature shows that psychological distress is not only a major threat to psychological well-being but can also have a significant impact on physical health. In cancer patients, it can negatively affect prognosis and posttreatment recovery processes. Since face-to-face psychological interventions are often inaccessible to cancer patients, researchers have recently been focusing on the effectiveness of eHealth adaptations of well-established approaches. In this context, there has been a call for high-quality randomised controlled trials that would allow for a direct comparison of different approaches, potentially addressing different needs and preferences of patients, and also for more systematic research focusing on how psychological interventions affect not only psychological but also biological markers of stress. Both of these questions are addressed in the present study. Methods: A randomised controlled trial will be carried out to test and compare the effectiveness of three eight-week eHealth programmes for the mental health support of cancer patients. All programmes will be delivered through the same application for mobile devices MOU MindCare. N = 440 of breast cancer survivors will be recruited at the end of their adjuvant treatment (chemotherapy, radiotherapy, or both) and randomly assigned to one of the three interventions - Mindfulness-Based Cognitive Therapy for Cancer (MBCT-Ca), Positive Psychology (PP), or Autogenic Training (AT) - or the treatment-as-usual (TAU) control group. Psychological and biological markers of stress and adaptive functioning will be assessed at baseline (T0), post-treatment (T1), three-month follow-up (T2), and nine-month follow-up (T3). Primary outcomes will include heart-rate variability and self-report measures of depression, anxiety, perceived stress, general quality of life, and positive mental health. Secondary outcomes will include the levels of serum cortisol and immunomarkers, sleep quality, fatigue, common health symptoms, and several transdiagnostic psychological variables that are expected to be specifically affected by the MBCT-Ca and PP interventions, including dispositional mindfulness, emotion regulation, self-compassion, perceived hope, and gratitude. The data will be analysed using the mixed model repeated measures (MMRM) approach. Discussion: This trial is unique in comparing three different eHealth interventions for cancer patients based on three well-established approaches to mental health support delivered on the same platform. The study will allow us to examine whether different types of interventions affect different indicators of mental health. In addition, it will provide valuable data regarding the effects of stress-reducing psychological interventions on the biomarkers of stress playing an essential role in cancer recovery processes and general health.

The Clinical Significance of DJ1 and L1CAM Serum Level Monitoring in Patients with Endometrial Cancer.

Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC patients. Serial serum levels of DJ1, L1CAM, CA125 and HE4 were collected in 65 enrolled patients. Serum DJ1, L1CAM, CA125 and HE4 levels were significantly higher at the time of diagnosis compared to those measured during follow-up (FU). In patients with recurrent disease, serum DJ1, CA125 and HE4 levels were significantly higher at the time of recurrence compared to levels in disease-free patients. Serum L1CAM levels were also higher in patients with recurrence but without reaching statistical significance. While DJ1 levels were not affected by any of the observed patient-related characteristics, L1CAM levels were significantly higher in patients with age ≥60 years who were overweight. At the time of EC diagnosis, DJ1 and L1CAM serum levels did not correlate with stage, histological type or risk of recurrence. This is a preliminary description of the potential of serial DJ1 and L1CAM serum level measurement for monitoring the effects of treatment in EC patients.

Interpretive discrepancies caused by target values inter-batch variations in chemiluminescence immunoassay for SARS-CoV-2 IgM/IgG by MAGLUMI.

Plasma specimens from coronavirus disease 2019 patients were double-tested for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies by two different batches of MAGLUMI 2019-nCov immunoglobulin M/immunoglobulin G (IgM/IgG) assays to evaluate IgM/IgG levels, qualitative interpretation, antibody kinetics, and linearity of diluted specimen. Here we show that (i) high-level IgM specimens need to be diluted with negative human plasma but not kit diluents and (ii) measured anti-SARS-CoV-2 IgM/IgG concentrations are substantially higher with later marketed immunoassay batch leading to (iii) the change of qualitative interpretation (positive vs. negative) in 12.3% of specimens measured for IgM, (iv) the informative time-course pattern of antibody production only when data from different immunoassay batches are not combined.

Systemic inflammatory response with high CRP values as the dominant symptom of multiple myeloma.

A man aged 60 years was examined for intense inflammatory response, night sweats, subfebrile and later febrile temperatures and a weight loss of 18 kg in 7 months. CRP was 270 mg / l, i.e. more than 20 times the upper limit of the physiological range. Reactive leukocytosis (10 × 109/l), thrombocytosis (530 × 109/l), increased fibrinogen (greater than 7 g/l), and anemia with hemoglobin of 80 g/l were present. No infection or systemic autoimmune disease has been proven. The patient had normal renal function and had no osteolytic deposits detectable by FDG-PET/CT. The procalcitonin level was not elevated. The bone marrow examination revealed a 30-40% infiltration of proplasmacyte type with admixture of plasmablasts, expressing light chains λ. Monoclonal immunoglobulin IgA λ was at a low concentration of about 8 g/l and the ratio of free light chains κ/λ was 0.13. The extent of bone marrow infiltration and anemia met the criteria for the diagnosis of symptomatic multiple myeloma. Following initiation of the combination therapy using thalidomide, bortezomib and dexamethasone, the maximum decrease in the concentrations of monoclonal immunoglobulin, free light chains and CRP was observed already after the first 2 cycles of treatment. Later, during the following two 2 cycles, the disease began to progress again. The patient underwent successful stem cell collection after the application of cyclophosphamide 2.5 g/m 2 and leukocyte growth factor (G-CSF), and high-dose chemotherapy (melphalan 200 mg/m 2) with the support of stem cell transplantation. At 2 months following high-dose chemotherapy, CRP levels of the physiological range decreased, the blood count was normalized, and monoclonal immunoglobulin was not detectable. Conclusion: The chronic inflammatory response may be due to plasmocytary bone marrow infiltration even if there are no other symptoms of multiple myel-oma present, except for anemia which, however, also involves the inflammatory reaction. In this case, the systemic inflammatory reaction with high CRP levels signalled aggressive behaviour of the disease. Key words: CRP - multiple myeloma - procalcitonin - systemic inflammatory response.

[Heart transplantation and follow-up treatment with AL-amyloidosis in 5 patients]. / Transplantace srdce a následující lécba AL-amyloidózy u 5 pacientu.

The prognosis for patients with cardiac impairment due to AL-amyloid deposition and severe cardiac insufficiency is poor, with a survival median in the order of months. The classical treatment of AL-amyloidosis in combination with cardiac insufficiency is very poorly tolerated and the treatment of such patients is associated with considerably higher mortality than among other patients with AL-amyloidosis. If, however, patients with an isolated or another dominating cardiac impairment, without severe damage to other organs and tissues, have a heart transplant performed, their cardiovascular condition will significantly improve as a result, along with their ability to tolerate any kind of treatment for AL-amyloidosis including that using high-dose chemotherapy with a transplant of autologous hematopoietic stem cells. The achievement of complete remission of AL-amyloidosis is a precondition for long-term survival, since when not achieved, amyloid deposition also arises in the transplanted heart. At the Centre for Cardiovascular and Transplantation Surgery, Brno, the first heart transplant due to its impairment by AL-amyloidosis was performed in 2010. By the year 2017 the number of patients with AL-amyloidosis, who had first undergone a heart transplant with subsequent treatment for AL-amyloidosis, increased to 5. The median age at which a heart transplant was performed is 60 (48-65) years. Four patients were men, one was a woman. The median monitoring equals 65 (88-15) months. Complete remission of AL-amyloidosis was achieved in all the patients. There were 5 lines of treatment needed for the first patient to attain it, of that twice high-dose melphalan with autologous stem cell transplantation, for the second patient a second-line treatment, high-dose melphalan and bortezomib-based therapy. No specific therapy was needed for the third patient, as immunosuppressive therapy following the heart transplant containing prednison led to complete remission of AL-amyloidosis. In the fourth case, sustainable complete remission was reached by high-dose melphalan and in the fifth case by one line of bortezomib-based therapy. The aforementioned data illustrate that a heart transplant is the first step which makes the patients with a severe heart failure, not tolerating any efficient therapy of AL-amyloidosis, capable of undergoing intense treatment of AL-amyloidosis. Sometimes one high-dose chemotherapy is sufficient, while at other times multiple treatment lines are needed to reach complete remission of AL-amyloidosis.Key words: AL-amyloidosis - autologous hematopoietic stem cells transplantation - bortezomib - cardiomyopathy - lenalidomide - thalidomide - heart transplantation.

The New Possibilities in Early Diagnosis of Preeclampsia by Soluble fms-Like Tyrosine Kinase-1 and Placental Growth Factor in 16-20 Weeks Gestation.

BACKGROUND: Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are used in diagnosing preeclampsia (PE), but their potential in early prediction in pregnant women at 16 to 20 weeks gestation (WG) has remained unexplored. METHODS: We retrospectively measured serum levels of sFlt-1 and PlGF in 120 pregnant women at 16 to 20 WG. Among these women, 16 had early-onset PE and 23 had late-onset PE. RESULTS: Compared with normal pregnancy values, in the serum of women in whom PE later developed, sFlt-1 values increased (P <.001), values of PlGF decreased (P = .001), and the sFlt-1/PlGF ratio increased (P <.001) as early as 16 to 20 WG. Receiver operating characteristic (ROC) curve analysis for the sFlt-1/PlGF ratio at 16 to 20 WG showed an area under the curve (AUC) value of 0.863 (95% confidence interval [CI], 0.788-0.918), P <.001, sensitivity of 74.4%, and specificity of 86.6% for PE in general; and AUC of 0.970 (95% CI, 0.913-0.994), P <.001, sensitivity of 100%, and specificity of 81.5% for early-onset PE only. Also, we determined the 5th and 95th percentiles for sFlt-1, PlGF, and sFlt-1/PlGF ratio values of healthy pregnant women. CONCLUSION: sFlt-1 and PlGF and, in particular, the sFlt-1/PlGF ratio can detect PE as early as 16 to 20 WG-as long as 10 to 15 weeks before PE onset.

Comparison of the Copenhagen Index versus ROMA for the preoperative assessment of women with ovarian tumors.

OBJECTIVE: To compare the Copenhagen Index (CPH-I) and the Risk of Ovarian Malignancy Algorithm (ROMA) in the differential diagnosis of ovarian tumors. METHODS: In a retrospective study, data were reviewed from women with ovarian tumors who attended University Hospital Brno, Czech Republic, between July 2011 and June 2015. The women were classified into the benign tumor group or malignant tumor group (borderline and malignant tumors). Serum levels of CA125 and HE4 were extracted from medical records. The two tumor indices were calculated using relevant clinical data. RESULTS: Among 267 included women, 110 had benign tumors, 42 had borderline ovarian tumors, and 115 had malignant tumors. The two indices showed similar discriminatory performance with no significant differences (P>0.05). In the differentiation of benign tumors from all stages of borderline tumor and ovarian cancer, ROMA showed a sensitivity of 71% at a specificity of 88%, whereas CPH-I showed a sensitivity of 69% at a specificity of 85%. CONCLUSION: CPH-I is a potential tumor index that is independent of menopausal status. It might be applied as a simple alternative to ROMA in settings of basic medical care.

[Schnitzlers SyndromeDifferential diagnostics, an overview of therapeutic options and description of 5 cases treated with anakinra]. / Schnitzlerové syndromDiferenciální diagnostika, prehled lécebných mozností a popis 5 prípadu lécených anakinrou.

Schnitzlers syndrome is an acquired auto-inflammatory disease of still unclear origin. The Strasbourg criteria were adopted (non-infectious fever, chronic urticaria, changes in the bone structure, leukocytosis and higher values of inflammatory markers - CRP and presence of monoclonal immunoglobulin mostly of type IgM, very rarely of IgG) to establish this diagnosis. The first-choice therapy for this disease is the blocking of interleukin-1 effects. In practice, the interleukin-1 receptor antagonist, anakinra, is the most commonly used. Currently reports also appear of the use of other medicines blocking the effect of interleukin-1, namely canakinumab and rilonacept. We have been treating 5 patients with anakinra (108, 72, 33, 32 and 1 months) on a long-term basis. In all the patients, we commenced administration of anakinra in a dose of 100 mg once a day. As a result of 100 mg being administered once a day, all symptoms went away completely in 4 patients, while they receded by about 75 % in 1 patient, without disappearing completely. This patient needs an increased dose of 2 ampoules per day on the days of spontaneously intensified medical ailments. After one year of treatment it turned out for one of the four patients whose symptoms had completely disappeared when administered the 100mg daily dose, that he only needed the respective dose of anakinra at 48-hour intervals. However this patient does not tolerate further extension of the intervals between dose administrations. We have not recorded any adverse effects of anakinra in the course of the treatment, and no decline in the efficiency of anakinra has been observed: it acts as effectively now as it did at the beginning of the treatment. The text discusses the differential diagnostics of the Schnitzler syndrome.Key words: anakinra - auto-inflammatory diseases - canakinumab - fever of unknown origin - FUO - interleukin 1 - cryopyrin-associated autoinflammatory syndrome (CAPS) - monoclonal gammopathy - rilonacept - Schnitzlers Syndrome - Adult Stills disease.

[Hypercalcemia, symptoms, differential diagnostics and treatment, or importance of calcium investigation]. / Hyperkalcemie, príznaky, diferenciální diagnostika a lécba aneb dulezitost vysetrování kalcia.

UNLABELLED: The concentration of calcium is carefully maintained under physiological conditions with parathormone, calcitonin and 1,25-dihydroxyvitamin D at appropriate levels. There are multiple causes that may bring about increased concentrations of calcium which exceed physiological values. Increased production of parathormone in parathyroid glands is only one of the possible causes. Malignant diseases are a very frequent cause of hypercalcemia, due to their creating mediators which stimulate osteoclasts and thereby osteolysis. A less frequent cause is represented by granulomatous processes, a typical example of which is sarcoidosis, whose cells increasingly (independently of parathormone) hydroxylate 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. However there are also hereditary forms of hypercalcemia. One of the causes of the hereditary form of hypercalcemia is mutations of the calcium sensing receptor. In order to locate the adenoma of parathyroid glands, essential apart from sonographic imaging is scintigraphy 99mTc-methoxyisobutylisonitrile (MIBI) and even more exact is PET-CT examination with a radio-pharmaceutical 18F-fluorocholine. PET-CT examinations are beneficial with regard to detecting a malignant cause of hypercalcemia in until then undetected malignancy or an undetected granulomatous process. The essential treatment procedures for malignant hypercalcemia include appropriate hydratation of ionic solutions without calcium, administering of bisphosphonates or denosumab. The text describes in detail the symptoms of hypercalcemia and diagnostics of causes of hypercalcemia. KEY WORDS: bisphosphonates - cinacalcet - denosumab - granulomatous diseases - hereditary hypercalcemia - hypercalcemia - hypercalciuria - hyperparathyreosis - calcimimetics - calcitonin - multiple myeloma - malignant hypercalcemia - parathormone - sarcoidosis - 1,25-dihydroxyvitamin D.

[Treatment of 14 cases of Castlemans disease: the experience of one centre and an overview of literature]. / Lécba 14 prípadu Castlemanovy nemoci: zkusenosti jednoho centra a prehled literatury.

Castlemans disease is the term for reactive lymphocytary and plasmocytary proliferation which occurs in the unicentric (localized) form, usually without systemic symptoms, or in the generalized/multicentric form, typically with systemic symptoms (www.vzacne-diagnozy.cz). Over the past 25 years we diagnosed, treated and followed 14 histologically proven cases of Castlemans diseases. Seven patients had the localised form of the disease. In 5 of 7 cases the pathological lesion was located intrathoracically or intraabdominally and in only 2 cases it was on the surface of the body. No clinical symptoms were present in any of the patients with the unicentric form of the disease and surgical treatment led to the total removing of the disease in all of them. As opposed to that, all 7 patients with the multicentric form of Castlemans disease experienced febrile or subfebrile temperatures. Three of the 7 patients complained of severe troubling night sweats. Clinical expressions of vasculitis which was the cause of stroke, were present in 1 of 7 patients. Osteosclerotic changes on the skeleton were detected in 1 patient, who also suffered from fluid retention likely associated with this disease. Polyclonal propagation of immunoglobulins, predominantly immunoglobulin IgG type, was present in 5 of 7 patients with the multicentric form. In one case there was one complete molecule of monoclonal imunoglobuline present and in one case loose light chains κ were increased More than 1 sampling of material for histological examination of enlarged lymph nodes were needed in 6 of 7 patients for diagnosing the multicentric form of the disease. It has turned out beneficial with respect to diagnosing the disease to carry out surgical removal and histological examination of the nodes which accumulated the most fluorodeoxyglucose within PET-CT examination. The text describes experience of the treatment. In recent years the basis for the treatment has been the monoclonal antibody antiCD20 rituximab, or thalidomide and lenalidomide, or possibly their combination. The new medicine for these patients is interleukin-6 antibody called siltuximab (Sylvant), of which we have no own experience so far. Five of our seven patients with the multicentric form received treatment, 1 patient refused treatment and in one patient the signs of the disease activity are not expressed to such extent that would require treatment. The therapy containing rituximab reached complete remission in 2 patients and the therapy containing thalidomide and lenalidomide achieved the complete remission of the disease in 3 patients. In one of the above described cases the disease did not respond to the initial treatment with rituximab and remission was reached by thalidomide and lenalidomide and in one case the disease did not respond to the initial treatment with thalidomide and complete remission was reached with rituximab. Following the treatment, no patient with the multicentric form of Castlemans disease has had a relapse until now.

[Pomalidomide in the treatment of multiple myeloma - own experience and overview of literature]. / Pomalidomid v lécbe mnohocetného myelomu - vlastní zkusenosti a prehled literatury.

In the Czech Republic, pomalidomide is covered for patients with multiple myeloma (in combination with dexamethasone), in the treatment of patients with relapsed and refractory multiple myeloma, who underwent at least 2 previous treatment schedules including both lenalidomide and bortezomibe, with disease progression despite the last therapy (i.e. during the therapy or within 60 days of its end), for whom the only remaining alternative of treatment (apart from pomalidomide) is that using high-dose dexamethasone, and who are not indicated for myeloablative treatment followed by a transplant of stem cells. At our centre pomalidomide was used in 53 patients at a median age of 66 years based on this indication. Pomalidomide was administered in 1 daily dose over 21 days in 28-day cycles. Considering the risk of thromboembolism occurring in this therapy, all patients were administered a prophylactic dose of low-molecular-weight heparin. No patient achieved complete remission (Czech Republic), 5 patients (9.4 %) achieved very good partial remission (VGPR), partial remission (PR) was achieved by 16 (30.2 %) patients, a minimum therapeutic response (MR) was recorded for 6 (11.3 %) patients. The median number of administered cycles was 4.4 (1-22). 16 (28.5 %) patients received treatment for more than 6 months. The overall survival median cannot be evaluated so far due to a short follow-up period. Nonetheless it was possible to evaluate a median time interval to progression (TTP) for the patients, which amounted to 7.0 (3.8-8.2) months. These results are consistent with large registration studies where therapeutic response (at least PR) is reached by 1/3 of the patients and medians of therapeutic response range between 7-10 months. Pomalidomide is a medicine with very good tolerance which is efficient in patients with a progressing multiple myeloma.Key words: lenalidomide - multiple myeloma - pomalidomide - thalidomide.

The efficiency of micro-Raman spectroscopy in the analysis of complicated mixtures in modern paints: Munch's and Kupka's paintings under study.

Twenty one mock-up samples containing inorganic pigments primarily used at the turn of the 19th and 20th century were selected for comparative study and measured by micro-Raman and portable Raman spectrometers. They included pure grounds (chalk-based, earth-based and lithopone-based), grounds covered by resin-based varnish, and different paint layers containing mixtures of white, yellow, orange, red, green, blue and black pigments, usually in combination with white pigments (titanium, zinc and barium whites or chalk). In addition, ten micro-samples obtained from seven paintings of two world-famous modern painters Edvard Munch and Frantisek Kupka have been investigated. Infrared reflection spectroscopy (FTIR), portable X-ray fluorescence (XRF) and scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) were used as supplementary methods. The measurements showed that blue pigments (ultramarine, Prussian blue and azurite), vermilion and ivory black in mixture with whites provided characteristic Raman spectra, while Co-, Cd- and Cr- pigments' bands were suppressed by fluorescence. The best success rate of micro-Raman spectroscopy has been achieved using the 780 nm excitation, however, the sensitivity of this excitation laser in a portable Raman instrument significantly decreased. The analyses of micro-samples of paintings by E. Munch and F. Kupka showed that micro-Raman spectroscopy identified pigments which would remain unidentified if analyzed only by SEM-EDS (zinc yellow, Prussian blue). On the other hand, chromium oxide green and ultramarine were not detected together in a sample due to overlap of their main bands. In those cases, it is always necessary to complement Raman analysis with other analytical methods.

[Myopathy in patients with Waldenströms macroglobulinemia. A case study and an overview of autoimmune expressions of type IgM monoclonal immunoglobulins]. / Myopatie pri Waldenströmove makroglobulinemii. Popis prípadu a prehled autoimunitních projevu monoklonálních imunoglobulinu typu IgM.

Waldenströms macroglobulinemia which was manifested by muscle pain and anemia. The female patient had suffered from back pain for about 3 years before she came to our clinic. In the last year pain in the muscles of the upper and lower extremities developed in addition to back pain. This led to the suspicion of polymyositis. However this was not confirmed by a special examination. The patient was diagnosed with clearly established infiltration of lympho-plasmacytic lymphoma and 10.8 g/l of type IgM monoclonal immunoglobulin in the bone marrow. Serum myoglobin levels and serum CK activity were repeatedly significantly increased. Therefore the treatment with anti-CD20 monoclonal antibody (Mabthera) 375 mg/m2 i. v. was started, administered once a month, with cyclophosphamide 500 mg/m2 i. v. on days 1 and 15 of a 28-day cycle, and dexamethasone 20 mg from 1st through to 4th days and 15th through to 18th days of the treatment cycle. There were 8 cycles planned. Already after a 5th cycle, the disappearance of monoclonal immunoglobulin (negative immunofixation), normalisation of myoglobin and CK values and significant relief from muscle pain were achieved. The hemoglobin concentrations before treatment were significantly reduced, while they were normalised after treatment. After 5 cycles, the complete remission of Waldenströms disease was reached according to biochemical parameters, and normalisation of the serum myoglobin and creatine kinase levels was achieved.

[PET-CT documented remission of multicentric Castleman disease after treatment with rituximab: case report and review]. / PET-CT dokumentovaná remise multicentrické formy Castlemanovy choroby po lécbe rituximabem Popis prípadu a prehled literatury.

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

Temperature-related degradation and colour changes of historic paintings containing vivianite.

Temperature-related degradation of pure synthetic as well as partly oxidised natural vivianite has been studied by high-temperature X-ray diffraction (HT-XRD) covering the whole extent of the temperature-related stability of its structure. While temperatures around 70°C are already damaging to vivianite, exposition to 160°C results in complete amorphisation of both the vivianite and its oxidation products. As indicated by Mössbauer spectroscopy, temperature-induced oxidation of vivianite starts at 90°C. To study the occurring structural as well as accompanying colour changes in more detail, model vivianite paint layer samples with different historic binders were prepared and subjected to increased temperatures. Exposition to 80°C caused pronounced colour changes of all the samples: ground natural blue vivianite became grey--a colour change which has been described in actual works of art. Regarding the binders, the oil seemed to facilitate the transfer of heat to vivianite's grains. To simulate conditions of conservation treatment under which the painting is exposed to increased temperatures, oil-on-canvas mock-ups with vivianite were prepared and relined in a traditional way using iron. The treatment affected preferentially larger grains of vivianite; the micro-samples documented their change to grey, and their Raman spectra showed the change from vivianite to metavivianite.

[Monoclonal immunoglobulin (M-Ig) and skin diseases from the group of mucinoses--scleredema adultorum Buschke and scleromyxedema. Description of four cases and an overview of therapies]. / Monoklonální imunoglobulin a kozní nemoci ze skupiny mucinóz--scleredema adultorum Buschke a scleromyxedema: popis 4 prípadu a prehled lécebných mozností.

INTRODUCTION: The mucinoses of the type of scleredema and scleromyxedema are diseases marked by excessive production of mucin deposits in the skin and subcutaneous tissue, which causes skin hardening. The skin and subcutaneous deposits hamper the movement of limbs, the thorax as well as mouth. The same mechanism also damages other organs (the heart, lungs, oesophagus). It is probably caused by the stimulation of mucin production in fibroblasts by immunoglobulins, frequently monoclonal immunoglobulin. Therefore these diseases are typically associated with monoclonal gammopathy. CASE REPORTS: We describe a cohort of 4 patients, skin manifestations were twice identified as scleredema and twice as scleromyxedema. All the four patients had type IgG monoclonal immunoglobulin and had clonal plasma cells in the bone marrow proven by histologic examination and flow cytometry. Therefore we commenced chemotherapy in all of them. In one case this chemotherapy was ended by a high-dose chemotherapy with transplanting of autologous red blood cells. This therapy attained the complete disappearance of monoclonal immunoglobulin as well as cutaneous and extracutaneous manifestations of scleredema (obstipation). In one case chemotherapy led to partial hematologic remission and partial improvement of skin manifestations. The other two patients did not respond to standard chemotherapy. The condition of one of them resulted in dermato-neuro syndrome (confusion, somnolence passing into coma and grand mal seizure) and improved following an intensive treatment including also intravenous application of immunoglobulins in a dose of 2 g/per 1 kg weight. This patient has now been under long-term treatment with these immunoglobulins, during which the skin symptoms have significantly diminished, but the concentration of monoclonal immunoglobulin has not changed. The fourth patient not responding to standard chemotherapy was treated with intravenous immunoglobulins also in a dose of 2 g/per 1 kg of weight 1× in a month. After 4 applications the thickening of skin and subcutaneous tissue moderately diminished, so the range of possible movement of the upper limbs and neck became larger and the itchy skin morphs which accompanied the disease disappeared completely. CONCLUSION: It is possible to use chemotherapy and high-dose chemotherapy in the treatment of mucinosis associated with monoclonal gammopathy, as in the treatment of multiple myeloma. If such treatment is not possible or it has not attained disappearance of monoclonal immunoglobulin, improvement can be achieved through repeated application of intravenous immunoglobulins. The treatment with intravenous immunoglobulins in an immunomodulation dose of 2 g/per 1 kg of weight effects the moderation of skin manifestations, but it does not lead to the decrease in monoclonal immunoglobulin.

Calprotectin and lactoferrin in the cerebrospinal fluid; biomarkers utilisable for differential diagnostics of bacterial and aseptic meningitis?

BACKGROUND: The aim of our work was to assess the diagnostic contribution of calprotectin and lactoferrin determinations in the cerebrospinal fluid when distinguishing between bacterial and aseptic meningitides. METHODS: In 23 patients with bacterial meningitis (BM) and in 50 patients with aseptic meningitis (AM), we determined the concentrations of calprotectin, lactoferrin and the conventional biomarkers like glucose, total protein, lactate and polynuclear count in the cerebrospinal fluid (CSF). The discriminative power of the various parameters studied was determined by means of receiver operating characteristic (ROC) curves: the area under the curve (AUC), sensitivity, specificity, the positive likelihood ratio (+LR), and the negative likelihood ratio (-LR). RESULTS: The diagnostic efficiency of calprotectin, lactoferrin, lactate, and polynuclear count when distinguishing between bacterial and aseptic meningitides, expressed by ROC curve parameters, was as follows: AUC (0.736, 0.946, 0.932, 0.932), sensitivity (86.2, 96.6, 90.0, 89.7), specificity (58.5, 92.4, 87.0, 90.6), +LR (2.08, 12.8, 6.9, 9.50), -LR (0.24, 0.04, 0.11, 0.11), respectively. The optimal cut point for calprotectin and lactoferrin was 191 ng/mL and 17.8 ng/mL, respectively. CONCLUSIONS: Our findings show, that the determination of lactoferrin in the CSF was diagnostically the most efficient marker in distinguishing between bacterial and viral meningitides. Calprotectin was far less efficient diagnostic marker. The polynuclear count and lactate concentration showed a very good diagnostic efficiency as well. The determination of protein and glucose was diagnostically less beneficial.

Unstable angina pectoris prior to ST elevation myocardial infarction in patients treated with primary percutaneous coronary intervention has no influence on prognosis.

BACKGROUND: Pre-infarction unstable angina pectoris (UAP) can be considered ischemic preconditioning. The aim of this study was to compare short and long term outcomes in patients with or without pre-infarction UAP and ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS: 593 patients with STEMI (388 without and 205 with UAP) were evaluated. Levels of biomarkers (troponin I, BNP, NT-ProBNP, neopterin, endoglin and pentraxin-3) at hospital admission and 24 h after STEMI onset were assessed. Echocardiography was undertaken on the fourth day after MI and after 12 months. The median follow-up was 37 months. RESULTS: We found no significant differences in sex, age or risk factors for atherosclerosis between the UAP and non-UAP group. As the median time from the onset of chest pain to admission was significantly longer in the UAP group (228 min vs 258 min; P=0.009), we used a propensity score to obtain comparable matched groups for use in further analyses. The levels of NT-proBNP were significantly higher on admission and after 24 hours in the UAP group. Left ventricular functions according to invasive and echocardiographic parameters were entirely comparable at hospitalization and after 12 months. No differences were found in severity index of acute heart failure during hospitalization. The incidence of major acute coronary events during follow-up was comparable for the groups. CONCLUSIONS: In patients with STEMI treated with primary PCI, pre-infarction UAP has no beneficial clinical effect during hospitalization or during long-term follow-up.