Eudokia Mandala

Non-thromboembolic pulmonary hypertension in multiple myeloma, after thalidomide treatment: A pilot study

BACKGROUND Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects and endothelial damage. Thalidomide has been associated with an increased risk of thromboembolic pulmonary hypertension (PH). PH in the absence of venous thromboembolism has also been described in MM patients during thalidomide treatment. AIM Detection of clinical and subclinical nonthromboembolic PH in MM patients after thalidomide treatment. PATIENTS AND METHODS Eighty-two patients, 46-82 years (median age 61 years), 42 males, were studied. They underwent echocardiographic study at baseline, 1 month thereafter, 6 months later and whenever symptoms indicating deterioration of cardiac function appeared. Echocardiographic signs of PH were especially identified. RESULTS Clinical and echocardiographic evaluation revealed four patients (out of 82 patients, 4.87%) with PH. Nonimaging and imaging diagnostic methods excluded thromboembolic PH. Statistical analysis demonstrated significant correlation between structural heart disease and PH (r = 14.078; P = 0.008). No significant correlation between age (r = 0.770; P = 0.724), gender (r = 1.157; P = 0.285), International Staging System (ISS) (r = 0.316; P = 0.716) and PH was found. CONCLUSIONS Preexisted endothelial dysfunction due to structural cardiac disease enhances the vasoactive substances release causing increased pulmonary vascular resistance. Thalidomide possibly causes a vasodilator and vasoconstriction imbalance, which may cause abnormal pulmonary vascular response interfering to a vicious circle perpetuating PH.

High Prevalence of Helicobacter pylori Infection in Greek Patients with Myelodysplastic Syndromes

Background/Aims/Methods: To determine the frequency of Helicobacter pylori infection (Hp-I) in 73 patients with myelodysplastic syndromes (MDS) and 40 controls, serologic analyses of Hp and 13C-urease breath tests (INFAI) were performed. Gastric mucosal biopsy specimens were obtained to determine the presence of Hp-I using a rapid urease test, i.e. the Campylobacter-like organism (CLO) test, and cresyl violet staining. Peripheral blood (PB) flow cytometry for CD3, CD4, CD8, CD14, CD19 and CD34 was conducted in 35 patients and in controls. Results:Hp-I was detected by: (a) serology in 75.34% of patients (p = 0.000), (b) INFAI in 57.69% of patients, (c) CLO in 60.71% of patients and (d) histological confirmation in 80.36% of patients (p = 0.001). No correlation between Hp-I and CD3, CD4, CD8, CD14, CD19 expression, leukemic transformation or death was observed. However, in 20 cases, significant variation in the PB lymphocytic proportion possibly attributable to Hp-I was ascertained, in contrast to the expected MDS ratio. Conclusion: Although there is no evidence for a causal relationship between Hp-I and MDS, the increased prevalence of Hp-I among the MDS patients is an interesting finding that deserves further investigation as it may indicate a common factor causing susceptibilities to both MDS and Hp-I or that Hp might influence the pathophysiology of MDS.

Methylation status of RASSF1A in patients with chronic myeloid leukemia

RASSF1A, a key cell cycle related gene, is expressed in all hematopoietic cells, it is implicated in ras signaling pathway and its promoter hypermethylation is observed in a wide variety of solid tumors. Till now, RASSF1A methylation status has not been investigated in patients with chronic myeloid leukemia (CML). In this study, we analyzed 41 patients carrying the BCR-ABL rearrangement, in different stages of the disease. No patient displayed RASSF1A promoter methylation, although the K562 erythroleukemia cell line, bearing the BCR-ABL rearrangement, was found methylated. Thus, our findings indicate that RASSF1A methylation does not appear to represent a critical step in the pathogenesis and/or the progression of CML.

Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses

Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment. We demonstrated that (i) patients at advanced-stage displayed an increased expression of the standard-survivin form along with a significant decrease of survivin-2B and -ΔEx3 levels, (ii) patients in chronic phase with higher expression of the standard-survivin exhibited a 3.5-fold increased probability not to achieve an optimal response to imatinib (p=0.048), (iii) responders displayed a significant up-regulation of all survivin isoforms in bone marrow, and (iv) anti-survivin CD8(+) T cells were undetectable both at diagnosis and during treatment. Accordingly, our results question the validity of immunotherapeutic approaches targeting survivin in CML.

Primary non-Hodgkin's lymphoma arising in an intramammary lymph node

Non-Hodgkins lymphoma (NHL) of the breast may be primary or secondary. Both are rare and there are no morphological criteria to make the differential diagnosis. Benign intramammary lymph nodes are often encountered, but the development of either primary or secondary lymphoma within an intramammary lymph node is extremely rare. We report the case of a 72-year-old woman who presented with a palpable mass in her right breast. A mammography showed a large intramammary lymph node from which a biopsy was taken. On morphological and immunohistochemical examination the tumor fulfilled the criteria of NHL originating in an intramammary lymph node. The patient received chemotherapy which led to the disappearance of the mass. A review of the literature revealed that this is the third reported case of primary NHL originating in an intramammary lymph node.

Helicobacter pylori infection might protect from the leukaemic transformation of myelodysplastic syndromes.

MDD. Another recent study analyzed data from about 7000 members of the Vietnam Era Twin Registry [4]. This study is the first to use a twin design to quantify the degree to which a common genetic vulnerability explains the etiology of the association between PTSD and MDD. The authors found substantial genetic overlap between PTSD and MDD and suggested that genes implicated in the etiology of MDD are strong candidates for PTSD and vice versa. This observation supports the idea that comorbid PTSD and MDD may be a distinct neurobiological condition that can be named ‘‘post-traumatic mood disorder.’’ Post-traumatic mood disorder is associated with greater symptom severity and higher risk for suicidal behavior compared to PTSD [1,2]. Traumatic experiences are common, if we consider the preponderance of individuals exposed to sexual or non-sexual assault, natural disasters (e.g. flooding), accidents (e.g. work, motor vehicle), and war [5]. Many individuals exposed to traumas may have post-traumatic mood disorder. Studies of PTSD and PTSD with symptoms of major depression are merited. References

Postpartum mesenteric, splenic and portal vein thrombosis

platelets (Solanki et al. 1986). The widespread splenic infarction was secondary to the increased intrasplenic pressure preventing adequate arterial perfusion. Venous thrombosis formation is a multi-hit phenomenon, with often several risk factors combining together to bring about a clinical event. In our case, acquired risk factors included the postpartum period, caesarean section, immobilisation and dehydration from postoperative vomiting. Thrombophilia tests performed postnatally were negative Laboratory investigation in superior mesenteric vein thrombosis is non-specific and radiological examination is the key to the diagnosis. Plain X-ray films can rule out perforated viscus and may reveal small bowel obstruction. CT angiogram is the preferred modality, revealing thrombosis with a sensitivity of 90%. Management is usually conservative, aimed at adequate hydration, analgesia, blood transfusion and anticoagulation with therapeutic doses of unfractionated or low molecular weight heparin. Laparotomy may be indicated if there are signs of peritonitis. The role of exchange transfusion remains unclear but in this patient, there was little evidence of active sickling, with a normal lactate dehydrogenase and no increase in reticulocyte count above baseline. Microvascular occlusion and resulting tissue ischaemia is a hallmark of sickle cell disease. The significance of large vessel thrombosis has only recently been mentioned in the literature and the involvement of large veins has seldom been stressed. Yet thrombosis of the cerebral venous sinuses and in particular that of the superior sagittal sinus are known complications (Sarnaik et al. 1979; Ross et al. 1974). Superior mesenteric vein thrombosis has been described in two patients but not in pregnancy on the post natal period (Warshauer et al. 2001; Arnold et al. 1993). The sickled erythrocyte–endothelial adhesions could be occurring in large vessels and could contribute to endothelial injury, vascular intimal hyperplasia and thrombosis (Francis and Johnson 1991; Francis 1991). It has been suggested that the vulnerability of the splenic and cerebral circulation may be related to the large proportion of cardiac output they receive (Powars 1990). Acute splenic sequestration is a rare finding in adults and this may, in part, be due to under diagnosis. This case demonstrates the difficulty in diagnosing such cases. Abdominal CT aids early detection and prompt treatment that should involve a multidisciplinary team approach. Underlying venous thrombosis should be considered, as anticoagulation may be an important addition to the treatment. This case highlights the risk of splenic sequestration in adult patients with sickle cell variants and emphasises the possibility of venous thrombosis as an underlying mechanism in this disorder. It also raises awareness of the increased thrombotic risk of patients with sickle cell disease undergoing delivery, even when on thromboprophylaxis.

TACI Expression and Signaling in Chronic Lymphocytic Leukemia

TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL), including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches.

Evaluation of Treatment with Bosentan in Patients with Carcinoid Heart Disease: Single Center Study

Background: The primary aim of this study was to evaluate a combined therapeutic intervention, including the dual endothelin receptor antagonist bosentan, in patients with carcinoid heart disease (CaHD). The efficacy of the treatment protocol was investigated using serological, echocardiographic, and clinical markers. Patients and Methods: Since 2003, 40 patients with neuroendocrine tumours were identified; 14 had echocardiographic findings consistent with CaHD. Six of the 14 patients with CaHD and a New York Heart Association (NYHA) functional class ≥ III received bosentan and were eligible for inclusion in this study. Results: N-terminal pro-brain natriuretic peptide (NT-pro-BNP) had decreased 6 months after treatment with bosentan (median: 646 pg/ml vs. 400.5 pg/ml; p = 0.02); the right ventricular systolic pressure had decreased after 3 and 6 months (median: 69 mmHg vs. 61 mmHg, p = 0.02; median: 69 mmHg vs. 48.5 mmHg, p = 0.02); the 6-minute walk distance (6MWD) had significantly improved after 3 and 6 months of treatment (median: 293.5 vs. 406.5 m; p = 0.02; median: 293.5 vs. 578.5 m; p = 0.02). The NYHA functional class improved in 5/6 patients receiving bosentan. Conclusions: Combined treatment with bosentan is effective in patients with CaHD, based on functional class, 6MWD, and NT-pro-BNP. Further clarification of the CaHD fibrosis pathogenesis is needed to facilitate development of targeted antifibrotic therapeutic agents.

Pro-Brain Natriuretic Peptide is a Sensitive Marker for Detecting Cardiac Metastases in Patients with Non-Small Cell Lung Cancer

Background: B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) are important diagnostic tools for patients with suspected cardiac disorders. The aim of this study was to evaluate the predictive value of plasma NT-pro-BNP in identifying cardiac metastases in patients with non-small cell lung cancer (NSCLC) and dyspnoea. Patients and Methods: A total of 120 patients, median age 62 years (range 46–83), with NSCLC and dyspnoea were studied. Patients with heart failure or documented coronary artery disease were excluded. Echocardiographic imaging was used to detect cardiac metastases and estimate global left ventricular function. Ejection fraction and E/A ratio from transmitral inflow pattern were calculated. Plasma NT-pro-BNP was also measured. 72 patients (72/120, 60%) with cardiac metastases were identified. Results: NT-pro-BNP was significantly higher in patients with metastases (1347.5 ± 1004.30 pg/ml vs. 159.02 ± 93.29 pg/ml; p = 0.001). No differences between groups, regarding s-creatinine (p = 0.45), haemoglobin (p = 0.71), left ventricular hypertrophy (p = 0.91), and diastolic dysfunction (p = 0.79), were observed. Conclusion: Plasma NT-pro-BNP is remarkably elevated in patients with NSCLC and myocardial/pericardial infiltrations and may be used as a sensitive marker for detecting cardiac metastases in these patients.