[Bilateral simultaneous central retinal vein occlusion in protein S deficiency]. / Bilateraler simultaner retinaler Zentralvenenverschluss bei Protein-S-Mangel.

CASE REPORT: This article reports a case of bilateral simultaneous central retinal vein occlusion (CRVO) and protein S deficiency. The 27-year-old male patient presented with a sudden decrease in vision in both eyes. The patient's medical history documented the death of his father at the age of 33 years due to pulmonary embolism. Thrombophilia screening revealed protein S deficiency. OBJECTIVES: We report this case to emphasize that in any case of young onset retinal vein occlusion, protein S deficiency should be suspected. CONCLUSIONS: Thrombophilia assays and taking a thorough medical history should be performed.

Complement activation in thrombotic thrombocytopenic purpura.

BACKGROUND: Ultra-large von Willebrand factor and deficiency of its cleaving protease are important factors in the events leading to thrombotic microangiopathy; however, the mechanisms involved are only partly understood. Whereas pathological activation of the alternative complement pathway is linked to atypical hemolytic uremic syndrome, the role of complement activation in thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was to investigate whether signs of complement activation are characteristic of TTP. PATIENTS AND METHODS: Twenty-three patients with TTP (18 women, median age 38 years) and 17 healthy controls (13 women, median age 38 years) were included. Complement parameters (C3, Factors H, I, B and total alternative pathway activity) together with complement activation fragments (C3a) or complexes (C1rs-INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti-ADAMTS13 inhibitory antibodies were measured by the VWF-FRET73 assay. RESULTS: Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as compared with healthy controls. Decreased complement C3 levels indicative of complement consumption occurred in 15% of acute TTP patients. Significant decrease of complement activation products C3a and SC5b9 was observed during plasma exchange (PEX). The sustained presence of anti-ADAMTS13 inhibitory antibodies in complete remission was associated with increased complement activation. CONCLUSION: These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance.

Application of flow cytometry immunophenotyping and multidrug resistance assay in B-cell acute lymphoid leukemia and multiple myeloma.

Multidrug resistance is one of the mechanisms how to explain failure of chemotherapy in patients with different hematological malignancies. In this study we aimed to evaluate and compare the drug resistance in B-cell acute lymphoid leukemia (B-ALL) and multiple myeloma (MM) in association with their immunophenotypes and genotypes. Eleven patients with B-ALL and 14 patients with MM were classified according to prognostic factors. Standard MoAb panel for ALL and triple labeled antibodies (CD38/CD56/CD19) and detection of intracellular light chains for MM were used. Flow cytometric calcein assay was performed for measure of P- glycoprotein (MDR-1) and multidrug resistance associated protein (MRP-1) activity. Markers CD19, CD20 and HLA-DR proved to be useful in identifying cells of B-lymphoid lineage. CD34 progenitor cell antigen was present in high proportion of ALL blasts. Both the abnormal plasmacell populations and their monoclonality in MM were confirmed by immunophenotyping, too. The mean MDR activity factor (MAF) values were not different in patients with MM and B- ALL. However, the mean MRP-1 values in MM were significantly lower than MAF-MDR-1 (1.85+/-3.8 versus 5.92+/-7.45, p=0.05), but we have found lower values in refractory conditions as expected from previous studies of acute myeloid leukemia. The immunophenotyping was helpful in detection of abnormal populations showing no correlation with the MDR. However, in this study we could not confirm high MDR activity despite of the failure of chemotherapy. The calcein assay seems to be useful for quantitative and sensitive measurement of the MDR proteins. The low activity of MDR- 1 and MRP-1 in MM need further clarification, indicating the involvement of different transport in the resistance mechanism.

Evidence of prolactin immunoreactivity in the bone marrow of untreated multiple myeloma patients.

The role of prolactin (PRL) in the physiological regulation of the immune system and in hematopoiesis is well known. There is also evidence of the significance of PRL in several pathological conditions such as autoimmune diseases and some malignancies, e.g. colon and breast carcinomas and also B cell malignancies. Multiple myeloma is known as a B cell malignancy. It is the result of malignant transformation of a single clone of neoplastic plasma cells that synthesize abnormal amounts of monoclonal immunoglobulins or immunoglobulin fragments. In our present studies, the possible expression of PRL in bone marrow cells obtained from diagnosed multiple myeloma (17 cases) or nonmyeloma (5 cases) patients was examined by the method of immunocytochemistry. Samples obtained from those multiple myeloma patients (13 cases) who had not received chemotherapy for 6 months prior to these studies showed a positive immunocytochemical reaction for PRL. Bone marrow smears of patients diagnosed with multiple myeloma who had received chemotherapy within 6 months of the study and also the smears of patients without diagnosed multiple myeloma failed to show a positive immune reaction for PRL. In the case of a patient who was examined prior to and also after a period of 3 months of chemotherapy, the PRL-immunopositive bone marrow cells had disappeared due to the treatment. According to the light microscopic analysis of the cell morphology, PRL-immunopositive cells in the bone marrow were mainly, but not exclusively, plasma cells. There was no correlation between the positive PRL staining of cells and the type of monoclonal immunoglobulin or the ratio of plasma cells detected in the bone marrow. Taken together, our results indicate a possible role of PRL in multiple myeloma. Further experiments are necessary to identify the prognostic value of PRL in multiple myeloma.

Mouse plasmacytoma: an experimental model of human multiple myeloma.

BACKGROUND AND OBJECTIVES: There is no ideal animal model for human multiple myeloma (MM). All the models resemble the human disease in some respect, but none of them fulfils all the criteria of a perfect animal model. EVIDENCE AND INFORMATION SOURCES: The pristane oil (2,6,10,12-tetramethylpentadecane)-induced mouse plasmacytoma (MPC) model is the most widely used and accepted model and has provided the most data on plasmacytomagenesis so far. This model gives the opportunity to study the role of c-myc dysregulations, the mechanisms leading to cytogenetic changes involving Ig genes, the role of chronic inflammatory factors, the role of interleukin-6 (IL-6), insulin-like growth factor-I, prostaglandins, as well as signal transduction pathways in the neoplastic process. Therapeutic agents have been successfully tested. Although MPC growth is usually restricted to the peritoneal environment, intraperitoneal injection of MPC cell suspensions can reproduce the disseminated characteristics of the human disease in recipients. The IL-6 transgene and knockout models are important tools for clarifying the role of IL-6 in the pathogenesis of MM. Transgenic mice and retroviral gene transfer facilitate the study of oncogenes in neoplastic transformation. Spontaneous development of plasmacytomas in C57BL/ KaLwRij aging mice has several advantages, mainly because the disseminated growth, the typical bone lesions and renal involvement resemble, in part, the human disease. Furthermore, this model has already proved useful in studies on the effect of bisphosphonate in the treatment of bone disease in MM. The severe combined immunodeficiency (SCID) mouse model is also very attractive. A disseminated-like disease can be reproduced in this model. Multiple osteolytic bone lesions and bone marrow involvement are generated, and conventional drugs applied in the treatment of human multiple myeloma have proven to be effective. Nevertheless, the immune system of SCID mice basically differs from that of a MM patient. PERSPECTIVES: Taken together, all these models have contributed to our understanding of MM, but demonstrate the opportuness of developing a more appropriate model of the human disease.

Elevated levels of serum prolactin in patients with advanced multiple myeloma.

BACKGROUND AND OBJECTIVE: The role of prolactin in immunoregulation and normal hemopoiesis is well known. However, prolactin also seems to be involved in the pathomechanism of malignancies and autoimmune diseases. Elevated serum prolactin levels were reported in patients with malignant lymphoma, colon and breast carcinoma, systemic lupus erythematosus and rheumatoid arthritis. Recently we demonstrated prolactin immunostaining in bone marrow cells of patients with multiple myeloma. DESIGN AND METHODS: Serum prolactin levels of 56 patients with multiple myeloma, as well as serum beta(2)-microglobulin, and interleukin-6 concentrations were determined in this study. RESULTS: Patients with advanced disease showed a significant increase in serum prolactin concentration, while patients with a clinical stage of I and II, and also control patients had normal values. The concentration of serum beta(2)-microglobulin and interleukin-6 changed in parallel with that of serum prolactin in patients with multiple myeloma. Determining serum prolactin levels several times during the disease process in a given patient clearly showed that the prolactin concentration was increasing during the disease progression. INTERPRETATION AND CONCLUSIONS: Our results indicate a role of prolactin in disease progression in multiple myeloma.

[Regression of gastric MALT lymphoma after eradication of Helicobacter pylori infection followed by endoscopic ultrasound]. / Endoszkópos ultrahanggal követett primer gyomor MALT lymphoma visszafejlódése Helicobacter pylori-eradikáció után.

The authors report a case of a 42 year-old female patient, who was admitted with epigastric pain and weight loss to our department. Upper gastrointestinal endoscopy two ulcerated lesions revealed in the stomach at the corpus-antrum border. Histologically the lesion proved to be a low grade, malignant B cell MALT lymphoma. Coexistent Helicobacter pylori infection was detected with modified Giemsa staining. Endoscopic ultrasonography was performed to determine the depth of tumorous infiltration of the gastric wall: the tumor was confined to the mucosa and submucosa. No regional lymph node was observed. As a result of successful Helicobacter pylori eradication the regression of MALT lymphoma occurred. The follow-up examinations showed the regression of the tumour and the patient became asymptomatic. A control ultrasonographic examinations demonstrated the normal five layers structure of the gastric wall without any alteration. In our patient Helicobacter pylori eradication was an effective therapy for gastric MALT lymphoma as well. Our results similar as are published in the literature. Endoscopic ultrasonography is very useful in the assessment of the tumours involvement of the gastric wall. In the proper follow-up examinations of the patient endoscopy, histology and endoscopic ultrasound together are the methods to apply including Helicobacter pylori control.

Role of INTERLEUKIN-6 in the pathogenesis of multiple myeloma.

Multiple myeloma (MM) is a currently incurable disease caused by the proliferation of malignant plasma cells. Although the pathogenesis of the disease still remains unclear, recent research in the biology of MM has produced new insights into the factors that control the growth and survival of myeloma cells. Among the growth factors, interleukin-6 (IL-6) has an essential role. Evidence suggests that IL-6 is not only a growth factor, but also a survival factor in MM, inhibiting apoptosis in myeloma cells. IL-6 interacts with several factors which are involved in the pathogenesis of MM, such as adhesion molecules, tumour suppressor genes and oncogenes. Considering the essential role of IL-6, it could serve as a target for new therapeutic interventions. Neutralizing the effect of IL-6 may result in a regression of tumour progression.

[Three unusual cases of mastocytosis]. / A mastocytosis három különbözö esete.

A unique opportunity arose to introduce the rare disease called mastocytosis as we had three patients with radically different clinical signs and disease progression. The authors would like to draw attention to the diagnostic problems that may emerge with this disease, as well as the diagnostic procedures are detailed. These problems, however, are dwarfed by the therapeutic difficulties faced by the clinicians. Complete remission with the present treatment opportunities may not be achieved, nevertheless, there are options to improve quality of life and to alleviate the symptoms that cause suffering to patients.

Human herpesvirus 8 in hematologic diseases.

Human herpesvirus type 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a new member of the g-herpesvirus family. It is an unusual herpesvirus in that it carries a large number of genes that encode oncoproteins or cell signaling proteins. In addition to being the causative agent of both HIV-associated and non-HIV-associated Kaposi's sarcoma this DNA tumor virus has been implicated in the pathogenesis of several diseases. These include multiple myeloma (MM), Waldenstöm's macroglobulinemia (WM), multicentric Castleman's disease (MCD), body cavity-based lymphoma (BCBL), and various other conditions such as sarcoidosis and pemphigus. While the causative role of the viral infection is fairly certain in the development of BCBL and multicentric Castleman's disease, HHV-8 may act through a different mechanism to induce plasma cell malignancies. It has been suggested though the finding is still controversial - that infection of bone marrow stromal dendritic cells by HHV-8 might be a key factor in the etiology and pathogenesis of monoclonal gammopathies. The aim of this review is to provide a short introduction into the tumorigenic potential of HHV-8 as well as to detail the available data and possible mechanisms on the involvement of this virus in different hematologic diseases.

Cytokine regulation of the acute-phase protein levels in multiple myeloma.

BACKGROUND: Interleukin (IL) 6 has an important role in the regulation of acute-phase proteins (APPs) during an acute-phase response. We studied IL-6 and other cytokines to determine if they regulate serum APP levels in the same way under the condition of the aberrant, long-lasting 'acute-phase response' that occurs in patients with chronic inflammation and cancer. METHODS: Serum levels of nine positive APPs [CRP, SAA, C1-INH, Bf, C5, C8, C9, alpha 1-acidic glycoprotein (AGP) and haptoglobin] and two negative APPs [transferrin and alpha 2-HS glycoprotein (AHSG)] were measured using immunochemical methods in 59 multiple myeloma patients and in 72 healthy control subjects. Serum IL-6 and tumour necrosis factor (TNF) alpha levels were determined by bioassays. RESULTS: IL-6 was negatively correlated with five out of nine (C1-INH, C8, C9, AGP and haptoglobin) positive APPs but positively correlated with C-reactive protein (CRP). When patients with high and low IL-6 serum concentration were compared, CRP levels were higher, AGP and haptoglobin levels were lower in the high- than in the low-L-6 group, whereas no significant difference between the two groups was found in levels of the other positive and negative APPs. TNF-alpha levels were negatively correlated with transferrin and AHSG levels. No difference in the levels of positive APPs was observed between patients with low and high TNF-alpha serum concentration. By contrast, levels of both transferrin and AHSG were significantly lower in the high- than in the low-TNF-alpha group. CONCLUSIONS: These findings indicate that, except for regulation of the negative APPs by TNF-alpha, the mechanism of APP regulation is different under the conditions of the short-term and the chronic, long-lasting 'acute-phase reaction'.

Application of near infrared spectroscopy to the determination of haemoglobin.

Seventy-two whole blood samples were investigated to determine the relationship between their spectral data measured in the near infrared (NIR) wavelength region and haemoglobin content based on laboratory data determined by a routine standard method as reference. Blood samples were obtained from the 1st Department of Medicine, Imre Haynal University of Health Sciences. Donors were selected randomly without respect to age, sex, state of health or medical treatment, from apparently healthy volunteers as well as from ambulatory and hospitalized patients. NIR spectra were measured with a SPECTRALYZER 1025 (PMC) computerized spectrophotometer in the 1000-2500 nm wavelength region. The relationship between laboratory data and values of the second derivative (i.e. second order finite difference) of the log(1/TF) spectra measured at different wavelengths was determined by multiple linear regression (MLR) using three- and four-term linear summation equations. The cross-validated standard error of performance (SEP) for haemoglobin was 1.348 g dL-1 with a three term model and 1.251 g dL-1 with a four term model over the range from 5.9 to 20 g dL-1. This preliminary study indicates that NIR measurements can be directly related to haemoglobin content and can be used to determine haemoglobin content in human whole blood.

Theoretic opinion and future treatment of amyloidosis.

Amyloidosis is still enigmatic. The etiology and mechanism of storage and organ impairment are still unknown. Not all amyloidogen molecules are definitely pathogenic; some precursors of tissue amyloid are structurally analogous to normal substances produced in the organism. This paper reviews the currently accepted categories, aspects of etiology and pathogenesis, and therapeutic trends of amyloidosis with a special emphasis on plasmapheresis.

[Childhood acute lymphoid leukemia relapsing in adult age?]. / Gyermekkori akut lymphoid leukaemia felnöttkori relapsusa?

A 30-years-old woman developed an acute lymphoblastic leukemia 16 years after a successfully treated childhood acute lymphoblastic leukemia. The developed second malignancy unexpectedly seemed identical to her previous malignant disease. That's why and because of the literature doesn't mention acute lymphoblastic leukemia as a second neoplasm after an acute lymphoblastic leukemia we considered the disease unusual late relaps of the original childhood malignancy.

Cytokines in the treatment of malignancies.

Cytokines are pleiotropic peptides produced by lymphoid cells that play important roles in cellular proliferation and multiplication. Diminished or enhanced production or constitutive secretion of cytokines contributes to the aetiology and pathogenesis of several diseases. They are soluble mediators eliciting specific responses of different target cells of paracrine, autocrine and cascade systems of the organism. Their secretion is regulated at the molecular genetic level. Gene rearrangements of cytokines and their receptors have been demonstrated in several diseases. As means of specific or supportive therapy, cytokine treatment has been used both in neoplastic and other proliferative diseases. Lymphokines and interferons comprise the first, whereas colony stimulating factors and growth factors yield the second group of cytokines. Most scientific experience is with interferon-alpha. Its anti-viral mechanism of action has been extensively studied and clarified, whereas its antitumour effect is more obscure and is a result of many simultaneous biologic events.

[Complex evaluation of risk factors in patients after myocardial infarction]]. / Rizikótényezök komplex vizsgálata szívinfarktuson átesett betegeken.

In this work the authors have constructed a clinical epidemiological score system for characterizing the severity of the diseased state of our 85 patients got over myocardial infarction. The important role is commonly known which is played by the free radical processes in the pathogenesis of the heart infarct. From these free radical reactions the authors have focused their attention to studying the lipid peroxides. Beside the determinations of the malondialdehyde content of native serums they have measured the intensity of the malondialdehyde development in the free radical system generated by hydrogen-peroxide in vitro treatment of serums. With the help of the newly elaborated and applied method they have obtained a 67.11% average increase of the amount of malondialdehyde developed in vitro in comparison with the mean malondialdehyde value measured in the same analytical conditions with 154 healthy controls. They have made a statistical calculation for studying the question if there is any relationship between the scores of the age of patients and the malondialdehyde values of hydrogen-peroxide treated serums. On the basis of results of biochemical measurements and statistical analyses it seems very important to pay more attention both to the intensity of free radical reactions and the patients age in the severity's relations of the diseased state at heart infarct patients.

[Distribution of the causes of congenital thrombophilia]. / A veleszületett thrombosis-hajlam (thrombophilia) okainak megoszlása.

In recent years there have been discovered more and more such connatal mostly hereditary coagulopathies, which can explain the thrombosis susceptibility of the given individual or/and the family. The International Thrombosis and Haemostasis Society made a survey to estimate the frequency of those defects causing thrombophilias. In this survey the authors analysed the cases of their patients according to the given points of view. In their work they discuss some theoretical and practical problems of the theme, which can have an importance in respect to the everyday medical practice.

Studies on the antimutagenic activities of garlic extract.

Experiments with Salmonella tester strains indicated that aqueous garlic extract possesses antimutagenic properties toward ionizing radiation, peroxides, adriamycin, and N-methyl-N'-nitro-nitrosoguanidine. The assumption that radical scavenging garlic constituents, i.e., molecules with sulfur moieties, might be responsible for the inhibitory effect of aqueous extract toward mutagenesis induced by radiation and radiomimetic compounds was confirmed by the results of subsequent experiments; 1) garlic extract attenuated the lethal effects of gamma-rays on repair-deficient E. coli strains; 2) the garlic constituent allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is partly responsible for the reduced radiation-induced mutagenesis in Salmonella typhimurium TA 102. No such inhibitory effects were detected with alliin (S-allyl-L-cysteine sulfoxide) or cysteine; 3) aqueous garlic extract inhibited hydrogen-peroxide-induced lipid peroxidation. Results obtained in preliminary experiments with Chinese hamster ovary cells suggest that the antimutagenic properties of garlic extract are not restricted to procaryotic cells.