Association of the Brain-derived Neurotrophic Factor Val66Met Polymorphism with Body Mass Index, Fasting Glucose Levels and Lipid Status in Adolescents.

Brain-derived neurotrophic factor (BDNF) has an important role in energy balance. It suppresses food intake, reduces hepatic glucose production and converts white fat into brown fat in adipose tissue, leading to energy dissipation, lowered blood glucose and a lean phenotype. Studies have shown that the single nucleotide polymorphism (SNP) Val66Met within BDNF may be associated with obesity, insulin sensitivity, type 2 diabetes mellitus (T2DM) and dyslipidemia. The objective of the study was to investigate the association of the Val66Met polymorphism with body mass index (BMI), fasting glucose levels and lipid profile in Serbian adolescents. The study included 308 randomly selected healthy adolescents, 153 (49.68%) boys and 155 girls (50.32%), 15 years of age. Data including age, gender, height, weight, lipid profile and fasting glucose were recorded. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No association of this polymorphism was found with BMI and lipid profile. However, significant association was observed between this polymorphism and fasting blood glucose (FBG). Carriers of a Val/Val genotype had significantly higher mean values of fasting glucose level compared to carriers of Val/ Met and Met/Met genotypes (p = 0.01). To confirm these results multiple linear regression analysis was performed. Body mass index and gender were taken as covariates. Carriers of the Val/Val genotype had significantly higher levels of FBG (ß = -0.152, p = 0.02). A statistically significant association between BMI and glucose level was also observed (ß = 0.124,p = 0.033). This polymorphism could be associated with fasting glucose level in Serbian adolescents, thus further research would be of great interest to validate these results.

Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients.

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616-0.837 and AUC 0.824, p˂0.001, 95 % CI 0.690-0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.

EFFICACY OF METAMITRON IN APPLE THINNING IN SERBIA.

The thinning of fruits is a required pomotechnical measure in intensive fruit production which ensures the production of good quality fruits and high yields. Metamitron, known as inhibitor of photosynthesis, has been successfully used in the thinning of apple fruits. This study had the aim to determine the efficacy of metamitron on the thinning of apple fruits in the agroecological conditions of Serbia and to evaluate the possibility of its practical application. Two varieties of apples that are widely grown in Serbia, dared and Golden Delicious, have been chosen for this research. The experiments were carried out during 2011 and 2012 according to the EPPO PP 1/158 (3) method. Metamitron has shown a good efficacy in the thinning of apple fruits. The effect of metamitron on the thinning of apple fruits depends on multiple factors, pri- marily the application dose, time of application, apple variety, but also on the number of fruits developed. The best efficacy on the Idared variety was in plots where metamitron was applied at a dose of 1.1 kg ha⁻¹, once (in the growth stage when the fruits were 8 mm in diameter) or twice (in the growth stages when the fruits were 8 mm and 12 mm in diameter), when the number of developed fruits per tree is smaller, or 1.65 kg ha⁻¹ applied once when the fruits are 12 mm in size when a larger number of fruits per tree is developed. On the Golden Delicious variety, the best efficacy was in treatments when metamitron was applied twice (in the growth stages when the fruits were 8 mm and 12 mm in diameter) in quantities of 1.1 kg ha⁻¹, when less fruits per tree were formed or 1.65 kg ha⁻¹, applied once or twice when a larger number of fruits per tree were formed.

Only particular cytogenetic events are related to disease progression in sequential cytogenetic studies in myelodysplastic syndromes.

We performed prospective sequential cytogenetic studies in 76 patients with myelodysplastic syndromes (MDS) followed up to 82 months. Their karyotypes were followed routinely, regardless of clinical status. The incidence of evolutive karyotypes was similar in patients with a normal karyotype at referral and in patients with clonal abnormalities at diagnosis (24.5 and 26.1%, respectively). We did not find association between karyotype evolution and leukemic transformation or reduced survival, since the majority of secondary cytogenetic changes in evolutive karyotypes of our patients were aberrations with good or intermediate prognosis. Therefore, we concluded that only particular cytogenetic events are related to disease progression, while others represent secondary changes of little biologic and prognostic significance.

The impact of mesotrione on several microbiological activity of chernozem soil.

The effect of mesotrione on microbiological activity in soil was investigated. Trials were set up in laboratory on chernozem soil (pH 7.0, organic matter 3.5%, sand 26%, silt 45%, clay 29%) at Surcin, Serbia. Mesotrione was added at rates 0.5 (field rate), 5, 25 i 50 mg/kg soil. Untreated soil served as control. Samples were collected for analysis 5, 20, 40 and 60 days after mesotrione application. The effects were assessed on bacteria abundance, fungi abundance, and dehydrogenase activity. Mesotrione was found to cause different effects on the soil microbial activity in soil and its influence depended on the rate of application and duration of activity. Mesotrione applied at 0.5 and 5 mg/kg soil did not have any effect on microbial activity. The higher herbicide doses (25 and 50 mg/kg) induced increasing activity from the 5th to 60th day. These experimental data indicated that mesotrione affected soil microbial activity, but the effects were only detected at higher doses far exceeding the recommended field rate.

Survivin expression in patients with newly diagnosed nodal diffuse large B cell lymphoma (DLBCL).

Survivin is one of the inhibitors of apoptosis proteins (IAP) that might play an important role in the pathogenesis of diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the clinical and prognostic significance of survivin expression in nodal DLBCL. We analyzed lymph node biopsy specimens obtained from 56 patients with newly diagnosed nodal DLBCL, treated with immunochemotherapy (R-CHOP). The expression of survivin was analyzed using the standard immunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semiquantitatively as a percentage of tumor cells. Survivin immunoexpression (>45 % positive tumor cells) was found in 22 (39.28 %) and observed as cytoplasmic staining in 15 patients, or mixed (cytoplasmic and nuclear) staining in 7 patients. A significant difference in survivin immunoexpression was noticed between the GCB and the non-GCB subtypes of DLBCL (p = 0.031). However, survivin immunoexpression had no significant association with IPI, "bulky" disease, extranodal localization, hemoglobin, Ki-67 immunoexpression or other clinicopathological parameters. A univariate analysis showed that survivin positivity was an unfavorable factor for therapy response and a predictor of shorter survival in patients with DLBCL (p = 0.048 and p = 0.034, respectively). Patients with survivin overexpression experienced a relapse more often than patients without expression of this apoptotic protein (27.3 vs. 11.8 %), but this difference did not reach statistical significance (p = 0.131). The results of this study showed that disregulation of survivin expression had an important role in the determination of the course of the disease in patients with nodal DLBCL treated with R-CHOP. Therefore, survivin represents a potential target for therapeutic intervention in DLBCL.

Pulmonary events in antiphospholipid syndrome: influence of antiphospholipid antibody type and levels.

OBJECTIVE: This prospective clinical study examined the association between subclasses of antiphospholipid antibodies (aPL) and pulmonary manifestations in antiphospholipid syndrome (APS). METHODS: The cohort involved 329 patients: 214 patients with primary APS (PAPS) and 115 patients with secondary APS (SAPS). aPL analysis included detection of serum anticardiolipin antibodies [aCL (IgG/IgM)], ß2 glycoprotein I [ß2GPI (IgG/IgM)], and lupus anticoagulant (LA). RESULTS: In SAPS, high aCL IgG levels (> 100 PLU/mL) were more common in major pulmonary arterial thrombosis (p = 0.006) and medium aCL IgG levels (41-99 PLU/mL) in adult respiratory distress syndrome (ARDS; p = 0.047) and fibrosing alveolitis (p = 0.002). aCL IgG antibodies were more common in SAPS (p = 0.037). In PAPS, fibrosing alveolitis was more common in patients with medium ß2GPI IgM levels (p = 0.0001). LA correlated with pulmonary embolism (p = 0.03) and microthrombosis (p = 0.03) in SAPS, and with pulmonary microthrombosis (p = 0.03) in PAPS. Males were more likely to develop secondary pulmonary hypertension when diagnosed with PAPS (p = 0.019). CONCLUSION: Certain classes of aPL are associated with distinct pulmonary manifestation, indicating their predictive role and importance in diagnosis and treatment of APS.

Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study.

Repeated thromboses are the most frequent clinical manifestation of antiphospholipid syndrome (APS) in the presence of antiphospholipid antibodies (aPL). The objective of this study was to observe the prevalence and localization of thrombosis, and to investigate the importance of aPL type and level for thrombosis-related events in patients diagnosed with APS. These are the first results of patients enrolled in Serbian National Cohort Study which comprises 256 patients: 162 with primary antiphospholipid syndrome (PAPS) and 94 with APS associated with systemic lupus erythematosus (SLE). aPL analysis included detection of aCL (IgG/IgM), ß(2)GPI, and lupus anticoagulant. Thrombosis was diagnosed in 119 (46.5%) patients, with higher prevalence in PAPS compared with SLE patients (51.2% and 38.3%, respectively, p = 0.045). There was similar prevalence of arterial thrombosis in PAPS and SLE groups (34.6% and 34%, respectively, p = 0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p = 0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibody (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p = 0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p = 0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis.

Biological and clinical features of non-Hodgkin's lymphoma in the elderly.

PURPOSE: The incidence of non-Hodgkin's lymphomas (NHLs) in elderly people has increased in recent years because the world population is getting older. The aim of this study was to compare the biological and clinical features in patients diagnosed with NHLs younger and older than 65 years, and the possible influence of age on the choice of optimal therapeutic approach. METHODS: We retrospectively evaluated 193 patients with NHLs: 111 (68%) were <65 years and 82 (42%) ≥65 years. The following parameters were analysed: age, gender, clinical stage, International Prognostic Index (IPI), histological type, presence of B symptoms, disease localization, presence of bulky mass, Karnofsky performance status (PS), comorbidities, blood counts, liver and renal function and serum LDH. RESULTS: Elderly patients had statistically more frequent indolent NHLs (p=0.036), IPI 3 and 4 (p<0.0001), presence of comorbidities (p<0.001), and less frequent presence of bulky disease (p7equals;0.043). Response to therapy was different in the 2 age groups: 29% of patients ≥65 years achieved complete remission (CR) in contrast to 71% of patients <65 years (p<0.001). The most frequent cause of death was disease progression (PD) (86% of younger patients and 71% of elderly patients (p7equals;0.150). Older patients died more frequently because of comorbidities compared younger ones (21 and 107percnt;, respectively; p=0.250), and had more complications of therapy (8.1 and 47percnt;, respectively (p=0.320). Overall survival (OS) was shorter in older patients in all lymphoma types: indolent lymphoma (36 vs. 17 months), aggressive (22 vs. 20 months) and very aggressive (14 vs. 1 months). Multivariate analysis showed that parameters for shorter survival in the elderly were Karnofsky PS <60, increased serum LDH and treatment toxicity. CONCLUSION: In elderly NHLs patients, treatment response and survival are significantly poorer. Since older patients mostly died of PD, they should be treated with standard regimens and best supportive measures.

Clinical and histopathological study of angiogenesis in multiple myeloma.

PURPOSE: Angiogenesis is an essential component in the growth and progression of multiple myeloma (MM). We studied the clinical significance of angiogenesis in patients with MM estimated by precise counting of the number of vessels (i.e. microvessel density, MVD) and compared these results with the results obtained using semi-quantitative grading of angiogenesis. METHODS: Fifty-nine newly diagnosed cases of MM were analyzed with respect to clinical features, laboratory findings, histological features, angiogenesis parameters, and response to treatment. Bone marrow microvessels were examined using immunohistochemical staining for CD34. Bone marrow angiogenesis was estimated by two different methods. The mean number of vessels per area in each sample was characterized as the MVD. Microvessels were counted manually on light microscopy in 3 hot spots at ×400 magnification. Semiquantitative estimation of angiogenesis was based on visual assessment of slides at ×100 magnification. Each slide was assigned as low, intermediate or high intensity of angiogenesis. RESULTS: The median MVD was 15 vessels per 3 hot spots (range 1-89). Intensity of angiogenesis was assigned as low in 24 (40.7%) patients, intermediate in 17 (28.8%) and high in 18 (30.5%). Significant correlation between intensity of angiogenesis (estimated using both methods) and histological grade, extent of bone marrow infiltration, proliferative activity of myeloma cells and poor survival was found. Semiquantitatively assessed intensity of angiogenesis additionally correlated with clinical stage. There was a statistically highly significant correlation between MVD and semi-quantitatively estimated intensity of angiogenesis (p <0.001). CONCLUSION: Tumor-associated angiogenesis is an important prognostic feature in MM and should be routinely done on bone marrow biopsies of these patients. Simple semiquantitative grading of angiogenesis can be recommended for daily practice, as an alternative method for complicated and time-consuming estimation of MVD.

Using herbicides in spring rapeseed and effect on quantity and quality parameters of yeald.

Possibility to chemically control weeds in spring rapeseed has been tested in two locations ( Novi Sad and Kragujevac) and following herbicides (a.i.) : trifluralin, clomazone, quizalofop-p-ethyl and clopyralid. We tested the effect of the herbicides on yield and hectoliter weight of seed and oil and protein contents in seed. In the trial in Kragujevac, a large number of weed species were present, with somewhat increased density and uneven distribution of weed plants. This was particularly evident with grassy weeds and with the species Rubus caesius in several plots. Rapeseed yield and quality were determined by measuring and analyzing the following parameters: grain yield (kg/plot (30 m2), hectoliter weight, oil content (%) and protein content (%) in seed.Basic statistical calculations of rapessed yield and quality were done by the t-test. The tested herbicides showed no adverse effect on the yield and hectoliter weight of seed in either location, with the exception of quizalofop-p-ethyl in Kragujevac, which affected the control variants. Oil content was negatively affected by the combination, trifluralin + clopyralid in the location of Novi Sad and by quizalofop-p-ethyl in the other location. Trifluralin and quizalofop-p-ethyl exhibited a negative effect on protein content in the location of Novi Sad, while there were no statistically significant negative effects in the other location.

Weight and body composition changes during R-CHOP chemotherapy in patients with non-Hodgkin's lymphoma and their impact on dose intensity and toxicity.

PURPOSE: To estimate weight and body composition changes during R-CHOP combination therapy in patients with non-Hodgkin's lymphoma (NHL) and their impact on dose intensity (DI) and toxicity. METHODS: We prospectively evaluated body composition in patients with NHL before starting chemotherapy (visit 1), before the 3rd cycle (visit 2) and before the 6th cycle (visit 3). Body composition was assessed by bioelectrical impedance analysis (BIA) and confirmed by anthropometric measurements. RESULTS: Thirty patients with NHL were studied. There was no weight change from visit 1-2, but weight increased from visit 2-3 (-1.36 - or + 1.89 kg) and from visit 1-3 (-1.93 + or - 3.21 kg). Patients with weight gain had significantly better overall response rate (p=0.013) and 5-year survival rate (p <0.01). Fat mass increased from visit 1-2 (-1.068 + or - 1.72 kg; p=0.002), from visit 2-3 (-1.32 + or - 1.89 kg; p=0.001) and from visit 1-3 (-2.502 + or - 3.23 kg; p=0.001). There was no statistically significant change in lean body mass (LBM) during chemotherapy. Total body water changed significantly from visit 1-2 (-0.08 + or -2.55l kg; p=0.097), from visit 2-3 (-1.036 + or - 1.10 kg; p=0.001) and from visit 1-3 (-1.89 + or - 3.2l kg; p=0.004). The average relative DI (ARDI) of the R-CHOP regimen was 90% and the rate of complete remission was 63.3%. Overall hematologic toxicity was evident in 14 (46.7%) patients. There was statistical significance between concentrations of cyclophosphamide and doxorubicin (mg/kg fat and mg/kg LBM) whether overall hematologic toxicity was present or not. CONCLUSION: Patients in the study gained weight during chemotherapy with unfavorable changes in body composition. Attempt has been made to identify clinical variables to predict patients at risk for hematologic toxicity, but an approach for individualizing drug dosing should be continued.

Clinical implications of immunophenotypic abnormalities of bone marrow myeloid cell compartment in myelodysplastic syndromes.

PURPOSE: to evaluate the biological and clinical implications of immunophenotypic abnormalities of bone marrow myeloid cell compartment in patients with primary myelodysplastic syndromes (MDS). METHODS: analysis of cell surface antigen profiles was performed by flow cytometric immunophenotyping on bone marrow mononuclear cell (BMMNCs) specimens from 39 adult MDS patients and 5 healthy individuals. Expression of cell surface antigen profiles was correlated with FAB subtype, cytogenetics, CFU-GM colony growth, overall survival (OS) and leukemic transformation (LT). RESULTS: expression levels of early differentiation and myelo-monocytic antigens (CD38, CD13, CD33, CD14 and CD15) on myeloid cell compartment of BMMCs were significantly higher in MDS patients in comparison to healthy control group, suggesting maturational left shift of bone marrow myeloid cell compartment in MDS. CD34 antigen expression was in a positive linear correlation with HLA-DR antigen expression (r=0.652; p=0.0004), and in negative correlation with the expression of CD11b and CD15 antigens (r=-0.48; p=0.014 and r=-0.564; p=0.0033, respectively). Myeloid antigen ratio (HLA-DR/CD11b) was 2.5 fold higher in patients with MDS in comparison to control group. Patients with advanced disease had significantly higher myeloid antigen ratio than patients with low risk MDS (p<0.05). The type of CFU-GM colony growth and the presence of chromosomal aberrations were unrelated to the proportion of CD34(+) cells and elevated myeloid ratio. Patients with elevated proportion of CD34(+) BMMNCs or elevated myeloid ratio had significantly shorter OS and higher LT rate in comparison to patients whose proportion of CD34(+) BMMNCs and myeloid ratio were within normal range. CONCLUSION: the presence of abnormalities in antigen expression profiles of bone marrow myeloid cell compartment has clinical implication in MDS, with particular contribution in predicting the patient outcome. Elevated proportion of CD34(+) BMMNCs and elevated myeloid ratio of bone marrow myeloid compartment are useful immunophenotypic tools for estimation of prognosis in this very heterogeneous disorder group.

Biological implications of circulating CD34(+) cells in myelodysplastic syndromes.

PURPOSE: to evaluate the biological and clinical significance of circulating CD34(+) cells in patients with myelodysplastic syndromes (MDS). METHODS: the relative count of CD34(+) cells in peripheral blood was evaluated by flow cytometry and the results were recorded on the total number of mononuclear cells (MNCs). CD34(+) status was correlated with the percentage of circulating and bone marrow blasts, cytogenetic studies, CFU-GM colony growth, overall survival and transformation to acute myeloid leukemia (AML). RESULTS: the number of MNC positive for anti-CD34 monoclonal antibody in the healthy control group ranged from 0.00% to 0.73%. Therefore, the cutoff value for overexpression of CD34 antigen on peripheral blood MNC of MDS patients was ≥ 1% (CD34(+) cases). The mean number of circulating CD34(+) MNCs in 30 MDS patients was significantly higher than in the control group (p=0.009). The proportion of circulating CD34(+) MNCs did not correlate with the blast count in the peripheral blood (r=0.282, p=0.131), neither with the blast count in the bone marrow. In contrast, the proportion of circulating CD34(+) cells in MDS patients was significantly correlated with the proportion of bone marrow CD34(+) cells (r=0.461, p=0.035). The proportion of circulating CD34(+) cells did not correspond to the percentage of blast count in the bone marrow, neither with the presence of cytogenetic abnormalities or abnormal growth of GM-progenitors. The median actuarial survival of 19 patients with elevated proportion of circulating CD34(+) cells was 16 months, as compared to >57 months in 11 patients with CD34(+) cells within normal range (p=0.16). Five patients with elevated proportion of circulating CD34(+) cells progressed to AML, as compared to only one of CD34(-)negative (CD34(-)) cases. CONCLUSION: the presence of circulating CD34(+) cells is a common finding in MDS, but no significant correlations with clinical and/or biological features of the disease have been found.

Expression of VEGF and microvessel density in patients with multiple myeloma: clinical and prognostic significance.

The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was estimated by counting the number of microvessels in three "hot spots" at 400x magnification. VEGF immunoreactivity was estimated on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity). No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29 vs. 34 months, P = 0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three "hot spots". There was significant correlation between MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (> or = 15) (46 vs. 22 months, P = 0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone and a predictor of poor survival in newly diagnosed myeloma.

[The role of wireless capsule endoscopy in the evaluation of patients with suspected small bowel bleeding: a single center experience].

BACKGROUND: Capsule endoscopy (CE) is a new diagnostic tool for the study of patients with suspected small bowel pathology. The aim of the study was to clarify the usefulness of CE in the group of patients with obscure (overt / occult) gastrointestinal (GI) bleeding. PATIENTS AND METHODS: Thirty patients (14 men, 16 women, mean age 50 years, range 9 -79 years) were enrolled in the study. All of them undergone non-diagnostic esophagogastroduodenoscopy, colonoscopy and barium follow-through of the small bowel. All patients underwent capsule endoscopy. Fourteen patients had overt and sixteen occult bleeding. The single senior endoscopist interpreted CE findings in an unblinded manner. RESULTS: CE identified a source of bleeding in 14/30 patients (46.6%). Lesions identified were: tumors in five pts, vascular lesions, Crohnzs disease and Meckelzs diverticulum in two pts and fresh bleeding, segmental celiac disease and colonic diverticulosis in one patient each. CE identified a source of bleeding in 9/14 (64.3%) of patients with ongoing overt bleeding and in only 5/16 (31.3%) of patients with occult bleeding. The positive suspicious findings were seen in 6/30 (20%) of patients (2/14 with overt bleeding and 4/16 with occult bleeding. In 3/14 (21.4%) with overt and 7/16 (43.7%) with occult bleeding findings on CE were negative. All patients with negative findings on follow-up remained asymptomatic for one year. Capsule retention because of unsuspected stenosis occurred in a single patient and required surgery, which resolved the problem. CONCLUSION: CE is an effective diagnostic tool for patients with obscure GI bleeding. It is safe and painless technique which can diagnose the bleeding site beyond the reach of conventional endoscopy. The best candidates for the procedure are those with ongoing and overt bleeding.

Plasmacytoma of the lung: an indolent disease resistant to conventional myeloma treatment: report of a case.

Solitary lung plasmacytoma is a rare form of plasma cell tumors. The case of a 56-yr-old man is presented, who had a massive tumor of the right pulmonary apex. Percutaneous transthoracic lung biopsy demonstrated a tumor-cell population consisting of mature plasma cells, proplasmacytes, and rare plasmablasts. Immunohistochemically, the cells were CD79a+, kappa+, cyclin D1-, p53-, MDR-. Proliferative index was low (number of Ki-67+ tumor cells was 8%). Serum and urine immunoelectrophoresis did not show the presence of paraprotein. Screening for multiple myeloma with skeletal X-ray survey and bone marrow biopsy were negative. Radiotherapy and chemotherapy with alkylating agents were ineffective. However, the course of the disease is indolent and the patient is well, alive, and with no signs of multiple myeloma >5 yr after the diagnosis was established. Some pathogenetic aspects of tumor resistance to conventional myeloma treatment in this case are discussed.

Myelofibrosis in primary myelodysplastic syndromes: clinical and biological significance.

In a retrospective study of 236 patients with primary myelodysplastic syndromes (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was observed that fibrosis mostly occurs focally or patchy, and collagen deposits were found very rarely (only four patients). The histopathology of bone marrow biopsies revealed several differences between fibrotic and non-fibrotic MDS: cellularity is significantly higher, dysmegakaryopoiesis is more pronounced, plasmocytes and mast cells are more often increased, and disturbance of marrow topography (particularly of the MK- and G-line) can be found more frequently in MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelomonocytic leukemia. The frequency of abnormal growth of GM-progenitors was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly higher WBC, more frequent presence of immature granulocytes, and higher percentage of myeloblasts in peripheral blood and bone marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis, compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore seems to herald a poor prognosis.

Acute panmyelosis with myelofibrosis: clinical, immunophenotypic and cytogenetic study of twelve cases.

The clinical, cytogenetic, and immunophenotypic features in 12 adult patients with acute panmyelosis with myelofibrosis (APMF; ICD-0-3: 9931/3; C42.1) are reported (median age: 57 years; f/m = 1.4). The white cell count (WBC) was normal in 3 patients; 9 had leucopenia. The median hemoglobin value was 64.5 g/l, and median platelet count 12 x 10(9)/l. Bone marrow biopsy showed a hypercellular marrow in 10/12 patients with a significant infiltration of pathological blasts (range: 30 - 60%). All the cases had marked reticulin fibrosis. Immunophenotyping of bone marrow blast cells showed the expression of early (CD34) and lineage-unspecified antigens (HLA-DR) in 6/7, and 7/7 patients, respectively. "Early" myeloid antigens (CD13, CD33) were seen in 6/7 and 4/6 patients respectively. Monocyte antigen (CD14) was expressed in 3/7 patients. Megakaryocyte antigen (CD61) and erythroid cell antigen (GpA) were each expressed in only 1 patient. Two patients had expression of CD34, HLA-DR and "early" myeloid antigens by their bone marrow blast cells and 1 of these also had a co-expression of the antigens from a differentiated monocytic cell proliferation (lysozyme+, CD68+). Nonspecific chromosomal aberrations were recorded in 8/10 patients. The median survival was 2 months. These findings suggest an immature myeloid phenotype of blast cells in APMF. In 6/9 patients a leukemic cell differentiation into monocytic, megakaryocytic or erythroid lineage was also demonstrated.

Immunohistochemical analysis of cyclin D1 and p53 in multiple myeloma: relationship to proliferative activity and prognostic significance.

Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.