Volume 24 (2016): Issue 3 (September 2016)

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is characterized by the presence of an absolute monocytosis (1 × 10^ 9/l) in the peripheral blood, the overlap of myelodisplastic aspects and myeloproliferative aspects in the bone marrow and tendency to transform into acute myeloid leukemia. CMML is considered to be the most aggressive chronic myeloid leukemia. We present the case of a 48 years old woman who was hospitalized in March 2013 in the Center of Hematology and Bone Marrow Transplantation for anemia related symptoms. Initial investigations showed anemia, relative monocytosis (10% monocytes of the WBC differential) with an increasing absolute number of monocytes (> 1,000/μl) in the following months. Initial exploration of the bone marrow (aspirate and bone marrow biopsy and immunohistochemistry IHC tests) revealed elements of trilinear dysplasia and an increased percentage of myeloblasts (11-14%). In the next four months myeloblasts percentage remained below 20% (8-14%) and it has been observed a gradually increasing of monocytoid elements (> 20%). Immunophenotyping in the bone marrow aspirate identified a monocytic proliferation with high percentage (8%) of immature cells. The karyotype reported the presence of clones with t (1;3). Initially diagnosed as RAEB-2 (WHO) the case was recomitted in CMML-type 2 with a progression to acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been performed after getting the best possible therapeutic response with AML chemotherapy type (complete remission). Allo-HSCT was performed using myeloablative conditioning, 12 months after diagnosis. The patient is now in complete remission, 24 months after allo-HSCT.

Introduction: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN), polycytemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), are prone to develop thrombotic events. We aimed to investigate the coagulation status in their plasma using thrombin generation assay (TGA), a functional global assay, on Ceveron® Alpha.

Materials and methods: The samples were collected from 89 consecutive Ph-negative MPN patients and from 78 controls into K2EDTA and CTAD tubes for blood cell counts, TGA and coagulation screening tests. Thrombin generation was analysed in platelet-poor plasma using Technothrombin® TGA assay kit.

Results: We found a significantly increased peak thrombin generation (p=0.049) and velocity index (VI) (p=0.012) in patients in comparison with controls, especially in ET patients, and a significantly higher values for peak thrombin (p=0.043) and VI (p=0.042) in patients receiving anagrelide in comparison with those treated with hydroxyurea. We also noticed an inverse correlation between the length of cytoreductive therapy and TGA parameters, (peak thrombin R=-0.25, p=0.018, AUC R=-0.257, p=0.015, and VI R=-0.21, p=0.048).

Conclusion: Our results suggest that Ph-MPN patients, and especially those with ET, are predisposed to thrombotic events due to their higher peak thrombin and VI values and their risk may decreases as treatment is longer. Patients treated with hydroxyurea generate less thrombin and could be less prone to develop thrombotic events in comparison with those treated with anagrelide.

Objective: The present case-control study aimed at evaluating the contribution of thrombophilic polymorphisms to acute venous (VTE) as well as arterial thrombotic events (ATE) in a population of young women with few traditional thrombotic factors (CVRF).

Methods: We consecutively enrolled patients under 45 years of age, with less than 3 CVRF, evaluated for VTE or ATE, women and men as a comparator. The control group consisted of healthy young women. A thrombophilia panel and genetic testing for Factor V Leiden (FVL), G20210A Prothrombin and MTHFR polimorphisms were done.

Results: A total of 323 persons were enrolled: 71 women and 121 men with thromboembolic events, and 131 healthy female as controls. Hyperhomocysteinemia was more frequent in ATE (30.4%) than VTE female patients (6.25%), p<0.01. Genetic testing was available in 45 women and 84 men with acute thrombotic events and in all controls. Homozygous FVL was associated with VTE in young women (10.3% vs 0% controls, p<0.01). Prothrombin G20210A polymorphism had the lowest prevalence – 5.4% and only heterozygosity was found. MTHFR C677T heterozygosity showed no significant difference between women patients and controls (62.2 % vs 43.5% respectively, p=0.1). The homozygous status, less frequent (6.6%), was not associated with ATE or VTE. Homozygous MTHFR A1298C was associated with VTE in women (17.2% patients vs 4.5% controls, OR 4.34, p 0.02, CI 1.22-15.3).

Conclusion: In young women with few CVRF, mild hyperhomocysteinemia, homozygosity for FVL and for MTHFR A1298C polymorphisms increase the risk for VTE but not ATE. MTHFR polymorphisms are found with increased frequency in both healthy persons and patients therefore, their significance as an important thrombotic risk modifier remains unclear.

Background: Thioredoxin reductase (TrxR), epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains.

Methods: Sprague-Dawley rats divided into three groups. Rats in control group were not subjected to any of treatments and their brains were removed under anesthesia. Middle cerebral arters were exposed but not occluded for the sham-operated rats. Animals were subjected to permanent middle cerebral arter occlusion (MCAO) in MCAO-operated group. The rats were decapitated at 16 hours (h), 48 h and 96 h after sham operation and focal cerebral ischemia. TrxR activities, EGF and TNF-α levels were measured in ischemic and non-ischemic hemispheres for all groups.

Results: In group MCAO, TrxR activities were significantly low at 48 h in ischemic hemisphere in comparison to control. After the 48 h, a remarkable increase was observed at 96 h. EGF and TNF-α levels were substantially high at 96 h in group MCAO of ischemic brain.

Conclusion: TrxR activity was reduced by oxidative stress which was formed by ischemia. EGF levels increased to exhibit neurotrophic and neuroprotective effects. After ischemia, TNF-α levels increased as a response to the tissue damage. Further studies with a higher number of experimental subjects and shorter or longer periods such as from first 30 minutes up to 3 months may be more informative to show the time-dependent variations in TrxR, EGF and TNF-α in cerebral ischemic injury.

Oxidative stress appears when the amount of free radicals that are formed in a living organism exceed its spin-trapping ability. One of the most dangerous free radicals that are formed in the human body is the hydroxyl radical. It can alter several biomolecules, including the unsaturated fatty acids; this process is known as lipid peroxidation and can lead to cell necrosis and generation of several harmful byproducts including malondialdehyde, which serves also as a biomarker of oxidative stress. A new HPLC method with visible detection was developed for the detection of malondialdehyde in human serum and saliva samples. The method was verified in terms of specificity, linearity, limits of detection (0.35 ng/ml), limit of quantification (1.19 ng/ml), recovery (90.13±10.25 – 107.29±14.33) and precision (3.84±1.49% – 6.66±1.76%). An analysis time of only 1 minute was obtained and no interferences from the matrices were observed. Statistical analysis (Pearson correlation test) showed a moderate correlation (R = 0.5061, p = 0.0099) between serum and saliva concentrations (N = 25). The possibility of measuring salivary concentrations of malondialdehyde extents the applications of oxidative stress/lipid peroxidation estimations to categories of population unreachable before (pregnant women, small children, etc); repeated sample studies are also easier to make.

Objective: The aim of our research was to identify physiological and biochemical changes induced by training at medium altitude.

Methods: Ten biathlon athletes underwent 28-day training camp at medium altitude in order to improve their aerobic effort, following the living high-base train high-interval train low (Hi-Hi-Lo) protocol. There were investigated three categories of functional and biochemical parameters, targeting the hematological changes (RBC, HCT, HGB), the oxidative (lipoperoxid, free malondialdehyde and total malondialdehyde) and antioxidative balance (the hydrogen donor capacity, ceruloplasmin and uric acid) and the capacity of effort (the maximum aerobic power, the cardiovascular economy in effort, the maximum O2 consumption).

Results: All the biochemical and functional evaluated parameters showed significant increases between the pre-training testing and post-training testing (5.13 ± 0.11 vs. 6.50 ± 0.09, p < 0.0001 for RBC; 44.80 ± 1.22 vs. 51.31 ± 2.31, p < 0.0001 for HCT; 15.06 ± 0.33 vs. 17.14 ± 0.25, p < 0.0001 for HGB; 1.32 ± 0.04 vs.1.62 ± 0.01, p < 0.0001 for LPx; 1.61 ± 0.01 vs. 1.73 ± 0.01, p < 0.0001 for free MDA; 2.98 ± 0.08 vs. 3.37 ± 0.03, p < 0.0001 for total MDA; 45.92 ± 0.13 vs. 57.98 ± 0.12, p < 0.0001 for HD; 25.95 ± 0.13 vs. 31.04 ± 0.06, p < 0.0001 for Crp; 3.47 ± 0.03 vs.7.69 ± 0.02, p < 0.0001 for UA; 63.91 ± 1.00 vs. 81.53 ± 1.97, p < 0.0001 for MAP; 33.13 ± 0.57 vs. 57.41 ± 0.63, p < 0.0001 for CVEE; 4190 ± 50.45 vs. 5945 ± 46.48, p < 0.0001 for VO2max).

Conclusions: Aerobic effort capacity of biathlon athletes has increased in the post-training period, using Hi-Hi-Lo protocol.

Hereby, we report a case of severe multi-lobular pneumococcal pneumonia with gangrene requiring pneumonectomy and accompanying septic shock that developed 1 day after a live-attenuated measles-mumps-rubella vaccination in a 58-year old kindergarten teacher.