Olivera Markovic

Anxiety, personality traits and quality of life in functional dyspepsia‐suffering patients

BACKGROUND Psychosocial stressors either acute or more sustained frequently precede the onset and exacerbation of the symptoms of the functional dyspepsia (FD). Depressive mood and quality of life have been already reported for interference in functional dyspepsia suffering patients. METHODS The examination were performed on 60 FD patients (30 females and 30 males), aged 20-79 years, 60 peptic ulcer subjects and 60 healthy volunteers in which we have investigate levels of anxiety and depression, personality traits and quality of life. RESULT According to the Hamilton Depression and Anxiety Rating Scales, the population with FD had the average score which classified them into the group of patients with the moderate depression (20.57 ± 4.45). Personality traits estimation based on data obtained by the Eysenck personality questionnaire revealed higher neuroticism scores in the group with functional dyspepsia. Both parameters, level of the neuroticism and anxiety level, expressed highly significant level of mutual concordance. Patients with functional dyspepsia reported a greater adverse impact of symptoms of emotional distress and food and drink problems. CONCLUSION Results are indicating that the depression and anxiety level is the highest in patients with functional dyspepsia and that anxiety level corroborates with the neuroticism level from the Eysenck scale. Psychological disturbances are influencing the quality of life mostly in patients with dyspepsia in the form of emotional distress and the problem with the food and beverage intake.

Clinical and prognostic significance of apoptotic profile in patients with newly diagnosed nodal diffuse large B-cell lymphoma (DLBCL)

Background:  Apoptosis‐related proteins might play an important role in the pathogenesis of lymphoma and sensibility to chemotherapy (CH) in patients with non‐Hodgkin’s lymphoma. We have analyzed the relationship between expression of two proapoptotic (CD95, caspase‐3) and four antiapoptotic proteins (c‐FLIP, bcl‐2, survivin, and XIAP) and clinical outcome of patients with nodal diffuse large B‐cell lymphoma (DLBCL).

Potentiation of metaphit-induced audiogenic seizures by REM sleep deprivation in rats.

The possibility that REM sleep deprivation (REMD) induced increased susceptibility of rats to the convulsive effects of metaphit was investigated. Metaphit-induced audiogenic seizures were studied in three groups of animals: 1) caged controls; 2) large platform animals; and 3) small platform, REMD animals. After 48 h of confinement to their environments the rats from all three groups were injected with metaphit (10 mg kg-1, IP) and the procedures continued for the next 24 h. Immediately after removal from platforms and at 3-h intervals thereafter all rats were individually subjected to intense sound stimulation. Convulsive responses were recorded and analyzed with respect to incidence, intensity, and duration. The REMD rats were found to be more sensitive to the convulsive effects of metaphit compared to nondeprived rats. This was manifested in significantly shorter latencies to seizures, and significantly higher incidence, severity, and duration of seizures, especially of the most severe seizure component-tonic extensor convulsion. Inducing rats to convulse while they were being REM sleep deprived eliminated the REM sleep rebound observed in REMD rats that did not convulse. The occurrence of spontaneous EEG seizures during the undisturbed recovery period reduced REM sleep rebound. The results demonstrate a reciprocal relation between seizure behavior and REM sleep.

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 imunohistochemical 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.

Diffuse cavernous hemangioma of the left leg, vulva, uterus, and placenta of a pregnant woman

analysis of pelvic arteries following bilateral internal iliac artery ligation for severe postpartum hemorrhage. Int J Gynecol Obstet 2009;104(1):22–4. [3] Papathanasiou K, Tolikas A, Dovas D, Fragkedakis N, Koutsos J, Giannoylis C, et al. Ligation of internal iliac artery for severe obstetric and pelvic haemorrhage: 10 year experience with 11 cases in a university hospital. J Obstet Gynaecol 2008;28(2): 183–4. [4] Polner K, Gosi G, Vas SI, Kalina I, Acsády G. Management of abdominal aortic and iliac artery aneurysms by stent-graft implantation in a patient on CAPD. Clin Nephrol 2009;71(3):359–62.

Poor outcome in patients with diffuse large B-cell lymphoma is associated with high percentage of bcl-2 and Ki 67-positive tumor cells.

BACKGROUND/AIM Newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) tretaed with immunochemotherapy have durable remission and improved overall survival. It is important to identify high risk patients who may benefit from even more effective therapies. METHODS In a group of 50 newly diagnosed patients with DLBCL, treated with CHOP/R-CHOP (cyclophosphemide doxorubicine, vincristine, prednisone with or without rituximab) regimen, we analyzed the prognostic value of the expression of Ki67 and bcl-2 at diagnosis as well as other standard clinical parameters: International Prognostic Index (IPI), bulky disease, extranodal distribution and lactat dehydrogenase (LDH). Significance was tested according to response rate and overall survival. RESULTS Univariate survival analysis showed that high IPI had a statistically significant negative influence on overall and event free survival time (log rank, p < 0.01). The log rank test analysis signified that patients with a high proliferative fraction (Ki-67 > 60%) had a worse overall survival rate (OS5y) of 40% compared to those with low proliferation (Ki-67 < 60%) with OS5y of 80% (p < 0.01). There was a clear difference between bcl-2 positivity (treshold 50%) and the achievement of complete remission (66% vs 86% in patients with bcl-2 high and low levels respectively, p < 0.05). In survival analysis, patients with low bcl-2 expression had significantly higher OS5y - 68% compared to those with high bcl-2+ with OS5y 37% (p < 0.05). Multivariate analysis performed by Cox model revealed that IPI > 3, high Ki-67+, bcl-2 positivity had a significant independent prognostic value concerning overall survival (p < 0.05). CONCLUSION An initial high IPI score associated with high Ki-67+ and bcl2+ could represent possible predictive factors of poor prognosis, which would help to identify a high risk subgroup of newly diagnosed DLBCL.

An unusual case of smoldering AML with prolonged indolent clinical course and spontaneous remission in the terminal phase

An unusual case of acute myeloblastic leukemia (AML) with indolent clinical course and spontaneous remission in the terminal phase is described. A 63-year-old male has been diagnosed to suffer from AML, subtype M2. Chromosomal analysis showed 46,XY,del(6)(q21). Clinical course was slowly progressive (“smoldering” AML). The patient did not require cytoreductive drugs, and occasional supportive therapy was his only treatment. Five years from diagnosis patient exhibited spontaneous remission of the disease, accompanied with disappearance of del(6q) clone. Six months after, relapse occured and patient died from CNS bleeding. Additional curiosity in this case is the fact that patients older brother died of acute lymphoblastic leukemia at the age of 71 years. Possible mechanisms of spontaneous remission of AML and genetic predisposition for human leukemia are discussed with a review of the literature.

The proto-oncogene expression varies over the course of chronic myeloid leukemia

Abstract The chronic phase (CP) of chronic myeloid leukemia (CML) is characterized by the expression of chimeric BCR/ABL gene, extended survival, and profligate growth of maturing granulocyte stemline. The accelerated phase (AP) and blast crisis (BC) of CML are usually manifested by additionally acquired oncogene aberrations, resistance to therapy, advancing anaplasia, progressive organomegaly, and increased blast count. Abnormal expression of some proto-oncogenes may accompany or even precede AP or BC of CML. Our objective was to follow-up oncogene expression over time covering different clinical phases of CML. A total of 85 patients [44 females and 41 males; median age 51 years; range 16–75 years] were studied. At the start of the study, 29 patients were in CP, 25 in an AP, and 31 in BC. Temporal variation in expression (percentage positivity per 1000 analyzed cells) of c-kit, c-myc, H-Ras, cyclin A1, p53, bcl-2 and VEGF oncogenic proteins in CP, AP, and BC of CML was studied by immunohistochemical procedures. This was then correlated with parameters of clinical disease (organomegaly, duration of CP, AP, and BC) and laboratory (Hb, WBC and platelet counts, and the percentage of blasts) data. The level of c-kit expression differed significantly over the course of disease (x2, p = 0·025). Antiapoptotic bcl-2 protein increased significantly with the progression of CML (x2, p = 0·005). The expression of c-myc was most pronounced in the AP (Anova, p = 0·033) and then tended to decline. There was no significant difference in the level of expression of H-Ras, cyclin A1 and p53 over the course of disease. The expression of VEGF protein was most pronounced in the AP (Anova, p = 0·033) and it was inversely correlated with degree of splenomegaly (Pearson, r = −0·400, p = 0·011) and overall survival (log rank, p = 0,042). Conclusion: The changes in oncogene expression, assessed by immunohistochemical approach over the course of CML may have clinical relevance in deciding on and timing of therapy. Temporal distribution of changes in oncoprotein expression in CML requires further study at the molecular level.

Health-related quality of life in adult patients with chronic immune thrombocytopenia in Serbia

Chronic immune thrombocytopenia (CIT) in adults is a chronic acquired autoimmune disorder characterized by accelerated platelet destruction, predominantly antibody-mediated, and decreased platelet production [1]. Many patients with CIT present with either no symptoms or minimal bruising, but some experience serious bleeding. The severity of thrombocytopenia correlates to some extent but not entirely with the bleeding risk [2] and is highly variable from one patient to another. These signs and symptoms of the disease and treatment side effects can then affect various domains of health-related quality of life (HRQOL), including emotional and functional health, work life, social and leisure activities, as well as reproductive health. All of these can affect many areas of patient everyday life and overall wellbeing [3–9]. However, the majority of individuals with CIT have a good prognosis, so the most beneficial treatment should not only focus on the platelet count but also on improving their HRQoL. The aim of this study was to analyze associations between demographic and clinical characteristics including type of therapy and HRQOL in patients with CIT. A total of 111 patients with primary CIT attending the Clinic of Hematology, Clinical Center of Serbia and the ‘‘Bezanijska Kosa’’ Clinical Hospital either as in-patients or out-patients from 2007 to 2008 were assessed. To be eligible, subjects were required to have active disease and be 18 years of age. Exclusion criteria included the presence of cognitive disorders and psychiatric diseases. The study received the approval of the Institutional Review Board and each patient provided written informed consent before enrolling. The demographic data and clinical characteristics were gathered from medical records and presented in Table I. Regarding the effects of the disease on the patients’ life style we evaluated absence from work/school and what bothered patients the most: reduced work ability, fear, fatigue, bleeding, infections or corticosteroid side effects. Their subjective fear of bleeding was recorded on a 4-point scale: (1) no fear at all; (2) a little fear; (3) fear; and (4) extreme fear. SF-36 (Serbian translation) [10] is a self-administered measure of generic health status and was used to assess HRQoL. Anxiety was assessed by the Hamilton anxiety rating scale (HARS); scores were as follows 518 points no anxiety, 19–25 points – moderate anxiety, and425 points severe anxiety [11]. Depression was assessed by the Hamilton depression rating scale (HDRS); scoring was as follows: 58 points – no depression, 8–13 points – mild depression, 14–18 points – moderate, 19–22 points – severe and 422 points – very severe depression [12]. Non-parametric measures of correlation were evaluated using Spearman’s rank correlation coefficient. Differences between subgroups were analyzed by 2 test and ANOVA. The predictive value of variables was assessed by multiple linear regression analysis. Regarding the effects of the disease and/or its treatment on the patients’ life style 90% reported absence from work/school. The patients were mostly bothered with reduced work ability (26.1%), fear (25.2%), bleeding (19.8%) and fatigue (19.8%). Among them 11 (9.9%) had severe fear of bleeding, 28 (25.2%) moderate fear and 47 (42.3%) a little fear. Over 72.1% of the patients expressed some degree of depression: mild in 63 (35.2%), moderate in 19 (18.9%), severe in 8 (5.4%) and very severe in 14 (12.6%). About a fifth (21%) of the patients was anxious. The impact of CIT and its treatment on patients’ daily functions and HRQoL were studied using SF-36 as shown in Table II. We also investigated the impact of demographic characteristics on HRQoL. Women had lower scores in domains of physical functioning (p1⁄4 0.045) and bodily pain (p1⁄4 0.042), while men were more anxious and more depressed (p50.05). Older patients had worse physical functioning, general health, vitality, emotional functioning, mental health as well as composite scores of physical and mental health. A higher educational level significantly improved HRQoL in all domains. Moreover, married patients exhibited better HRQoL in domains of physical functioning, bodily pain, general health and composite score of physical health compared to the unmarried. Duration of CIT correlated significantly with body pain, while transfusions of both red blood cells and platelets had no impact on HRQoL. Splenectomy did not influence HRQoL, but successful splenectomy markedly (p50.001) improved general health (patients considered cured by splenectomy) and also significantly Keywords

Influence of rituximab–CHOP therapy on clinical course and autoimmune parameters in rheumatoid arthritis associated with diffuse large B cell non-Hodgkin lymphoma

Dear Editor, Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphomas, in particular nonHodgkin lymphoma (NHL) [12]. The addition of rituximab (R), an anti-CD20 antibody, was shown to increase the effectiveness of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with diffuse large B cell non-Hodgkin lymphoma (DLBCL) [13]. Rituximab is a newly approved therapeutic agent for patients with active RA [11] because the potential decrease or elimination of autoreactive B lymphocytes could improve autoimmune condition. As patients with NHL and concurrent autoimmune disease offer the unique opportunity of monitoring the effects of administered immunochemotherapy on rheumatologic parameters, we have evaluated serologic autoimmune markers and the clinical outcome of a patient with RA who developed DLBCL and received treatment with R-CHOP during the course of her disease. In June 2003, a 51-year-old Caucasian female was referred with 2 months history of tender and swollen joints of the hands and feet, wrists, ankles, and right knee with early morning stiffness of 1-h duration. Physical exam revealed symmetric arthritis affecting wrists; second proximal interphalangeal, fifth proximal interphalangeal, and third metacarpophalangeal joints; and right knee effusion. Her erythrocyte sedimentation rate (ESR) was 83 mm in 1 h and rheumatoid factor (RF) was found positive: Rose– Waaler test 1/80, latex RF 1/640. X-rays of the hands and feet showed narrow radiocarpal articular space (Fig. 1a) and symmetrical subcortical cystic lesions in the fifth metatarsophalangeal joint (MTP5) (Fig. 1b). She fulfilled the American College of Rheumatology (ACR 1987) criteria for diagnosis of RA [1], and therapy with diclofenac started. In February 2004, symptoms of RA worsened and she received additional therapy with chloroquine (250 mg/day) which led to clinical improvement of her RA, while increase of inflammatory and autoimmune markers (ESR 58 mm in 1 h, latex RF 1/320) persisted. In July 2006, 3 years from the diagnosis of RA, she presented with right cervical and axillary lymphadenopathy without B symptoms. Performance status was zero. Laboratory findings showed normal blood cell count, serum LDH level a 1.3 times normal value (597 U/l, referent range <460 U/l) and β2-microglobulin level on the upper limit of the referent range (3.01 mg/l, referent range <3 mg/l). A CT scan and ultrasonography revealed right supraclavicular (20 mm), bilateral axillary (25 mm), retroperitoneal (16 mm), parailiacal, and mediastinal (16 mm) lymphadenopathy and a large focal lesion (43×37 mm) in the spleen. The bone marrow biopsy was unremarkable for a lymphomatous involvement. Morphological and immunohistochemical analysis of the lymph node tissue sections revealed lymphoid proliferation consistent with DLBCL. Namely, Ann Hematol (2008) 87:767–769 DOI 10.1007/s00277-008-0475-y