[Evaluation of prognostic factors for colon cancer]. / Evaluarea factorilor de prognostic în cancerul de colon.

INTRODUCTION: Colon cancer represents a major health problem in the world. The outcome of newly diagnosed cases predominantly relies on stage as defined by the UICC-TNM and American Joint Committee on Cancer classifications. AIMS: The aim of this retrospective study was to identify the additional prognostic factors for patients with colon cancer. PATIENTS AND METHODS: We retrospectively analyzed the incidence and significance of 8 clinical and pathological factors in 225 patients treated over a 2-year period in Surgery Clinic No. III, Cluj-Napoca. In order to avoid selection bias, all cases with a prior diagnostic of colon cancer and intervention for recurrence or metastasis, as well as cases lacking more than 20% of necessary datawere excluded. The candidate variables were analyzed using the Cox Proportional Hazards Model in order to select those who influence the outcome. RESULTS: The overall 5-year survival rate was 42%. Patients treated with resection of the primary tumor had a survival rate of 50%, ranging from 82% in patients with stage I malignancy to 11% in the presence of metastatic disease. 21% of all patients underwent emergency operation for obstruction or perforation but this did not significantly influence survival (p = 0.1). TheTNM stage of the tumor (HR = 1.2-8.4), grade of tumor differentiation (HR = 2.1) and perineural invasion (HR = 1.8) were independent negative prognostic factors. Venous invasion and status of resection margins were found to influence the outcome on univariate analysis, but were discarded when integrated in the multivariate model. The number of lymph nodes analyzed (p = 0.9) and the tumor location (p = 0.3) did not significantly affect the outcome of patients. CONCLUSION: These results suggest that the prognosis of newly diagnosed cases of colon cancer is influenced by the TNM stage, the degree of tumor differentiation and the presence of perineural invasion.

(17) O NMR study of the intrinsic magnetic susceptibility and spin dynamics of the quantum kagome antiferromagnet ZnCu3(OH)(6)Cl(2).

We report, through 17O NMR, an unambiguous local determination of the intrinsic kagome lattice spin susceptibility as well as that created around nonmagnetic defects arising from natural Zn/Cu exchange in the S=1/2 (Cu2+) herbertsmithite ZnCu3(OH)6Cl2 compound. The issue of a singlet-triplet gap is addressed. The magnetic response around a defect is found to markedly differ from that observed in nonfrustrated antiferromagnets. Finally, we discuss our relaxation measurements in the light of Cu and Cl NMR data and suggest a flat q dependence of the excitations.

Quantum magnetism in the paratacamite family: towards an ideal kagomé lattice.

We report muon spin rotation measurements on the S=1/2 (Cu2+) paratacamite ZnxCu4-x(OH)6Cl2 family. Despite a Weiss temperature of approximately -300 K, the x=1 compound is found to have no transition to a magnetic frozen state down to 50 mK as theoretically expected for the kagomé Heisenberg antiferromagnet. We find that the limit between a dynamical and a partly frozen ground state occurs around x=0.5. For x=1, we discuss the relevance to a singlet picture.

Unconventional dynamics in triangular Heisenberg antiferromagnet NaCrO2.

We report magnetization, specific heat, muon spin rotation, and Na NMR measurements on the S=3/2 rhombohedrally stacked Heisenberg antiferromagnet NaCrO2. This compound appears to be a good candidate for the study of isotropic triangular Heisenberg antiferromagnets with very weak interlayer coupling. While specific heat and magnetization measurements indicate the onset of a transition in the range Tc approximately 40-50 K, both muon spin rotation and NMR reveal a fluctuating crossover regime extending well below Tc, with a peak of relaxation rate T1(-1) around T approximately 25 K. This novel finding is discussed within the context of excitations in the triangular Heisenberg antiferromagnets.

Direct evidence for a dynamical ground state in the highly frustrated Tb(2)Sn(2)O(7) pyrochlore.

mSR experiments have been performed on a powder sample of the "ordered spin ice" Tb(2)Sn(2)O(7) pyrochlore. At base temperature (T=35 mK), the muon relaxation is found to be of dynamical nature, which demonstrates that strong fluctuations persist below the ferromagnetic transition (T(C)=0.87 K). Hints of long-range ordering appear as oscillations of the muon polarization when an external field is applied and also as a hysteretic behavior below T(C). We propose that dynamics results from fluctuations of clusters of correlated spins with the ordered spin ice structure.

WITHDRAWN: Non-invasive Estimation of Left Ventricular End-diastolic Pressure by Pulmonary Venous Flow Deceleration Time.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 162-168, . The duplicate article has therefore been withdrawn.

Non-invasive estimation of left ventricular end-diastolic pressure by pulmonary venous flow deceleration time.

AIMS: The scope of this study was to assess the potential value of pulmonary venous flow diastolic deceleration time to predict end-diastolic pressure and stratify patients with regard to elevation of left ventricular end-diastolic pressures. METHODS AND RESULTS: In 174 consecutive patients, pulmonary venous flow diastolic deceleration time was determined and compared with left ventricular end-diastolic pressures measured invasively. The sample was randomly divided into two subgroups of equal size for modelling of prediction and independent testing of the model. Predicted left ventricular end-diastolic pressures calculated from pulmonary venous flow diastolic deceleration time (left ventricular end-diastolic pressures=-10.87 + 5261/pulmonary venous flow diastolic deceleration time) agreed well with measured left ventricular end-diastolic pressures (mean difference: -1.3 +/- 3.4 mmHg). The correlation of left ventricular end-diastolic pressures with pulmonary venous flow diastolic deceleration time is fair (r=0.73989). A value of pulmonary venous flow diastolic deceleration time <220 ms is suggestive of elevated left ventricular end-diastolic pressures and should be monitored. A value of pulmonary venous flow diastolic deceleration time <190 ms predicts elevated left ventricular end-diastolic pressures. A value of pulmonary venous flow diastolic deceleration time <165 ms predicts severely elevated left ventricular end-diastolic pressures. With 190 ms as a cut-off value for elevated and 165 ms for severely elevated left ventricular end-diastolic pressures, cross-table analysis classifies all patients with normal left ventricular end-diastolic pressures correctly. No patient with severe elevation (<18 mmHg) of left ventricular end-diastolic pressures is classified as normal (chi2=102, P<0.0001). CONCLUSION: Pulmonary venous flow diastolic deceleration time is an appropriate non-invasive measurement to stratify patients with respect to elevation of left ventricular end-diastolic pressures.

Immunocytochemical evidence that amyloid beta (1-42) impairs endogenous antioxidant systems in vivo.

Amyloid beta, the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. We have previously demonstrated that potent antioxidants idebenone and alpha-tocopherol prevent learning and memory impairment in rats which received a continuous intracerebroventricular infusion of amyloid beta, suggesting a role for oxidative stress in amyloid beta-induced learning and memory impairment. To test the hypothesis, in the present study, we investigated alterations in the immunoreactivity of endogenous antioxidant systems such as mitochondrial Mn-superoxide dismutase, glutathione, glutathione peroxidase and glutathione-S-transferase following the continuous intracerebroventricular infusion of amyloid beta for 2 weeks. The infusion of amyloid beta (1-42) resulted in a significant reduction of the immunoreactivity of these antioxidant substances in such brain areas as the hippocampus, parietal cortex, piriform cortex, substantia nigra and thalamus although the same treatment with amyloid beta (40-1) had little effect. The alterations induced by amyloid beta (1-42) were not uniform, but rather specific for each immunoreactive substance in a brain region-dependent manner. These results demonstrate a cytological effect of oxidative stress induced by amyloid beta (1-42) infusion. Furthermore, our findings may indicate a heterogeneous susceptibility to the oxidative stress produced by amyloid beta.

Memory deficits and increased emotionality induced by beta-amyloid (25-35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus.

In the present study we found that chronic infusion of beta-amyloid fragment (25-35) at nanomolar concentration into rat cerebral ventricle impairs learning and memory. At a concentration of 3 nmol/day but not 0.3 nmol/day, beta-amyloid significantly reduced the spontaneous alternation behavior and the memory performance in the water maze and multiple passive avoidance tests. A significant increase in anxiety was also found in the animals infused with 3 nmol/day beta-amyloid fragment. Memory deficits and the increased emotionality were correlated with a decreased nicotine-evoked acetylcholine release from the frontal cortex/hippocampus, as assessed by microdialysis, in freely moving rats. The amyloid fragment infused either at pico- or nanomolar concentrations reduced the affinity of [3H] phorbol dibutyrate binding, an index of activated protein kinase C (PKC), and increased the total number of binding sites in the hippocampal particulate fraction. Our results suggest that the amnesic and anxiogenic effects of chronic infusion of beta-amyloid (25-35) are related to the decreased acetylcholine release and reduced PKC activation.

Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats.

Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These results suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

Impairments of long-term potentiation in hippocampal slices of beta-amyloid-infused rats.

In this study, we investigated the neuronal activity of hippocampal slices from the beta-amyloid protein-infused (300 pmol/day for 10-11 days) rats using the extracellular recording technique. Perfusion of nicotine (50 microM) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the vehicle control rats, but not in those of the beta-amyloid protein-infused rats, suggesting the impairment of nicotinic signaling in the beta-amyloid protein-infused rats. Long-term potentiation induced by tetanic stimulations in CA1 pyramidal cells, which was readily observed in the vehicle control rats, was also impaired in the beta-amyloid protein-infused rats. Nicotinic blockade by adding hexamethonium into the perfused solution inhibited long-term potentiation induction. Taken together, our previous and present results suggest that beta-amyloid protein infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of long-term potentiation induction and may lead to learning deficits.

The ways through which the hypothalamic paraventricular nucleus (PVH) and the medial hypothalamus affect the organism's defence function.

In the rats, mechanical lesion or isolation of the PVH either alone or together with the medial hypothalamic sympathetic area, which includes hypophyseotropic area, too, induces a long lasting decrease of the total number of leukocytes and of the most components of the leukocytary formula, which are attributed mainly to the decreased sympathetic tonus, induced by medial hypothalamus disconnection.

The role of the hypothalamic paraventricular nucleus upon the activity of thyroid and adrenal glands and their relation with body defense function.

Lesion of the PVH or its isolation--either alone or together with the medial hypothalamus, at fronto-lateral or complete level, induces a significant decrease in plasma thyroxine and a negligible modification of triiodothyronine. Variations recorded with various groups, having the medial hypothalamus deconnected, suggest that the main thyroliberin secreting (TRH) region is located at the level of PVH. Immunization of animals restores the thyroid function in the animals with damaged PVH, under the action of thyrotropin (TSH) of lymphocyte origin. Although the main CRH source occurs at the level of PVH, the results obtained after lesions or isolations of the hypophysotropic region demonstrate the extended distribution of CRH within various nervous areas, and its possible involvement in maintaining the adrenal gland function.