Circulating endothelial cells in essential thrombocythemia and polycythemia vera: correlation with JAK2-V617F mutational status,angiogenic factors and coagulation activation markers

Angiogenesis plays an important role in the biology of hematological malignancies, including essential thrombocythemia (ET) and polycythemia vera (PV). Some data suggests that it has a role in the pathogenesis of thrombosis, the major clinical problem in ET and PV. The number of different subpopulations of circulating endothelial cells (CECs), plasma levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 1 and 2 (sVEGFR-1,2) and placenta growth factor (PlGF) were determined in 30 patients with ET and 16 patients with PV. Correlations between angiogenesis and JAK2-V617F mutational status, risk factors for thrombosis and coagulation activation markers were also assessed. The number of CEC subpopulations, were markedly higher in ET and PV patients, irrespective of JAK2-V617F status, when compared to the control group. The median values of activated CECs were markedly higher in PV patients with WBC >8.7 (×10⁹/l). Significantly higher VEGF plasma levels were found in ET patients and a similar trend was seen in PV patients in relation to healthy volunteers. The plasma levels of sVEGFR-1 were significantly higher, and PlGF levels markedly lower, in the ET and PV group than in controls. Our study also demonstrated markedly increased levels of D-dimer and TAT complexes in the patient groups. In conclusion, we found that angiogenesis, as measured by CEC numbers, is increased in ET and PV patients regardless of JAK2-V617F mutational status. Our results demonstrated that angiogenic cytokines interact with known thrombotic risk factors. We confirmed the coagulation activation in ET and PV patients but found no differences in levels of coagulation activation markers in relation to JAK2-V617F mutational status.     

Epistatic relationship between the cancer susceptibility genes CHEK2 and p27.

We studied the effects of p27 and CHEK2 variants on prostate and colon cancer risk in a case-control study. Modest effects on prostate cancer risk were observed for both CHEK2 missense and truncating variants. However, the excess cancer risk was restricted to the subgroup of men who were homozygous for the VV genotype in codon 109 of the p27 gene. Among men with the VV p27 genotype, the odds ratios associated with truncating and missense CHEK2 mutations were 3.1 (P < 0.0001) and 1.9 (P < 0.0001), respectively. Among men with other p27 genotypes (GG and VG), the odds ratios were 1.5 and 1.2 for truncating and missense CHEK2 mutations, respectively, and were not statistically significant. The interaction between CHEK2 and p27 was confirmed in a group of patients with colon cancer. Thus, it seems that the clinical expression of CHEK2 variant alleles on prostate and colon cancer risk may be restricted to individuals with a specific genotype (VV) of the p27 gene. Two-gene models provide numerous challenges for gene identification and cancer risk assessment.     

The effect of monocytes on early activation of lymphocytes T among children with idiopathic uveitis

PURPOSE: We have investigated T Lymphocytes ability for CD69 molecule induction in presence and absence of monocytes in idiopathic uveitis. MATERIAL AND METHODS: Twenty-five children with idiopathic uveitis were studied. The control group consisted of 12 healthy children. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinised venous blood, by density gradient centrifugation. CD69 expression was cytometrically assessed on freshly isolated and cultured T lymphocytes. RESULTS: CD69 expression on freshly isolated peripheral blood T lymphocytes was low in both studied groups. LPS-stimulated monocytes added to cultures of T lymphocytes induced increase in CD69 expression but significantly lower in children with idiopathic uveitis compare to healthy children.     

Evolution of relation P1(P2) describing saturation decompressions after air hyperbaric expositions

The basic problem in decompression is the limit of maximum tolerable change of pressure after diving. Due to the number of parameters involved in decompression models (bottom time, ambient pressure, exposition profile, content of breathing mixtures, properties of inert gases) the number of possible solutions is theoretically unlimited. Since the beginning of modern decompression models the starting point has been direct saturation decompression using air. The generally accepted form of solution is the linear relation between tolerable pressure P2 after saturation exposition to pressure P1 described by the equation in the form P1 = P2 x A + B, where A and B are parameters obtained by experiments. Since the introduction of this equation values of parameters have been changing in order to decrease the rate of decompression illness. The aim of this study was to analyse and interpret the trend of those changes. Sixteen published models, including the one developed in our center, were compared and gradual change of parameters was identified. This trend should result in safer decompression systems.     

Quantitative determination of coumarins,flavonoids and chlorogenic acid in the leaves and underground parts of some species of genus Scopolia Jacq

The quantitative determination of coumarins, flavonoids and chlorogenic acid in the leaves and underground parts of Scopolia carniolica Jacq., S. lurida Dun. and S. sinensis Hemsl. using the RP-HPLC method has been described.     

Assessment of long-term effects of exposure to toluene based on the analysis of selected behavioral responses with particular reference to the ability to trigger behavioral hypersensitivity in rats

Toluene is a major component of numerous commercial organic solvent formulations. It is often listed among the chemicals capable of producing the organic solvent syndrome and a neurobehavioral hypersensitivity condition. The hypersensitivity condition (continued long-term intensification of some behavioral reactions in response to pharmacological or environmental stressors) is usually associated with the increased tonus of the functional dopaminergic system. The aim of our current research was to determine whether, under conditions of inhalation exposure, toluene can produce long-term behavioral changes or modify the intensity of the behavioral response to apomorphine, a dopaminergic receptor agonist. In our experiment, male rats were exposed to 25, 100 and 250 ppm toluene for 4 weeks (5 days/week, 6h/day). The following behaviors were tested: finding water in a radial maze; open field motor activity, acquiring the conditional response of passive avoidance; sensitivity to a thermal pain stimulus (hot plate test) and changes in this sensitivity caused by stress; and acquiring the conditional response of two-directional active avoidance. The behavioral response to apomorphine, i.e. the increased spontaneous locomotor activity, was assessed on day 10 after the termination of the exposure in the rotary drum test. In the behavioral experiment, significant differences between groups were recorded only for the hot plate test; in the 100 and 250 ppm rats, electric-shock-related anxiety response was stronger than in the control group. In the experiment using pharmacological provocation, the behavioral response to apomorphine in the rats exposed to 100 ppm or 250 ppm toluene was significantly lower. Our results indicate that low concentrations of toluene may produce long-term behavioral changes in rats. However, these changes seem to be linked with reduced rather than increased functional tonus of the dopaminergic system.     

Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.     

Retrospective assessment of the antidepressants tolerance in the group of patients with diagnosis of depression and different CYP2D6 genotype

The majority of antidepressants undergo the oxidative biotransformation catalysed by cytochrome P-450, particularly by izoenzyme CYP2D6, whose activity is genetically determined. In many cases poor tolerance of antidepressants depends on CYP2D6 activity. The aim of the study was the evaluation of the relationship between the CYP2Dg genotype and the occurrence of side effects during antidepressive pharmacotherapy.     

The search for optimal treatment in relapsed and refractory acute myeloid leukemia

Despite the significant progress in the treatment of AML during the last 5-10 years, 20-40% of patients still do not achieve remission with standard induction therapy. In addition, 50-70% of patients in CR are likely to relapse. A major limitation of successful AML therapy is intrinsic or acquired drug resistance. Several pharmacological inhibitors of mechanisms inducing chemoresistance in leukemic cells have been investigated. New cytotoxic drugs, agents with novel mechanisms of action, and new treatment strategies are currently being investigated. The management of refractory or relapsed AML patients is reviewed in this study.     

Prognostic factors in the acute phase of haemorrhagic stroke

The aim of the study was establishing which parameters play a significant prognostic role in acute haemorrhagic stroke in its acute phases (during 30 days from stroke onset). The material included 110 patients with haemorrhagic stroke (HS) treated in the years 1997-1999 at the II Neurology Department, Institute of Psychiatry and Neurology in Warsaw or at the Neurology Department, Hospital in Pi?a. The analysis of risk factors, fitness before stroke and on the first day of the disease was based on history data. On the first day of the disease the assessment included state of consciousness, brain stem signs, vomiting, stroke type on the basis of clinical condition (according to Oxford classification, OCSP), blood pressure, body temperature measurements, intensity of neurological signs according to Scandinavian scale (SSS). In the blood glucose level, fibrinogen, leucocyte count and ESR were determined. In the first week consciousness state, blood pressure and miction were checked repeatedly. It was found that serious consciousness disturbances, stroke type TACS, POCS and severe not classified stroke, presence of brain stem involvement, low SSS score, high body temperature, high leucocyte count and glucose level were more frequent in patients who died within 30 days after stroke onset. Prognostically important were also instability of blood pressure and urinary incontinence in the first week. All clinical observation and laboratory analyses of prognostic importance in the acute phase of HS can be done in typical hospital settings.