Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes.

Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus 'not reached' for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.

Heparin induced thrombocytopenia. Contemporary therapeutic approaches in light of the new oral anticoagulants.

Heparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

Expression of three ß-type carbonic anhydrases in tomato fruits.

Carbonic anhydrase (CA) and phosphoenolpyruvate carboxylase (PEPC) activity were found in different Solanum lycopersicum fruit tissues, predominantly in the locular parenchyma and pericarp. The distribution of the CA and PEPC proteins in the tomato fruit tissues was examined by immunohistolocalization. CA and PEPC proteins were found in all fruit tissues examined as well as in the seeds. Three full length cDNA clones designated SlCA1, SlCA2 and SlCA3 coding for ß-carbonic anhydrases (CA; EC 4.2.1.1) were identified and characterized from tomato fruit. SlCA1 and SlCA3 encode two putative cytosolic isoforms whereas SlCA2 encodes a putative plastidial isoform. Quantitative real time RT-PCR analysis revealed that accumulation of SlCA1 mRNA transcripts was detected in all examined tomato fruit tissues or organs, whereas SlCA2 gene transcripts were found in abundance in leaves. Stems also had SlCA2 transcripts, with transcript levels being higher in flowers than in stems. The SlCA3 gene transcripts were found only in the flowers and the roots. The SlPEPC1 and SlPEPC2 gene transcript levels in different fruit tissues of the tomato were also examined. Τhe possible role of CA isoforms in relation to PEPC in tomato fruit is discussed.

Lymphoepithelioma-like carcinoma of the breast: cytological and histological features and review of the literature.

OBJECTIVE: We present, for the first time, the cytological features of lymphoepithelioma-like carcinoma (LELC) of the breast in preoperative fine-needle aspiration (FNA) and touch imprints from secondary deposits in the sentinel lymph node (SLN). STUDY DESIGN: We report a case of a 53-year-old woman who was diagnosed with breast carcinoma on preoperative FNA and was subjected to SLN biopsy, partial mastectomy and axillary lymph node dissection. The final diagnosis was LELC of the breast. Cytological and histological features were analyzed. RESULTS: The smears from preoperative FNA contained cohesive clusters and isolated tumour cells in a haemorrhagic background with scattered lymphocytes. Some of the clusters were infiltrated by the inflammatory cells. The cells had large, pleomorphic nuclei and scanty, ill-defined cytoplasm. The intraoperative touch imprints from the SLN were highly cellular, comprising abundant scattered lymphoid cells, among which were tight clusters of indistinct cells, about 3 times larger than the lymphocyte population. CONCLUSION: In our case, LELC shares many cytological features with LELC described in other organs. Immunostains with epithelial markers play an important role in establishing the epithelial nature of the neoplastic cells. LELC should be borne in mind in the evaluation of breast lesions with prominent lymphoid cell infiltration. Its cytological features, as presented, could contribute to its preoperative evaluation on cytological grounds.

Anterior mandible canal communications: a potential portal of entry for tumour spread.

OBJECTIVES: CT is often used to assess the fine anatomy of the anterior mandible. The objectives of this study were to (1) investigate the presence of communications between the inner and outer bone plates in this area, (2) localize these communications in relation to surgical-anatomical landmarks and (3) review the literature related to mandibular cancer invasion. METHODS: CT images of 50 patients were used for the identification of the intrabony canals and for the localization of canalicular communications connecting the labial and lingual mandibular plates, in relation to the mental foramen. RESULTS: Communications between the labial and lingual mandibular plates were found in 14 (28%) of 50 patients. These communications mainly appeared as a crossing of the lateral lingual with the incisive canal, but also as an extension of the median lingual canal to the labial plate. CONCLUSION: There is radiological evidence for the presence of a canalicular network bringing into communication the inner and outer bone plates in the anterior mandible. There are also indications that such a finding could assist in the better understanding of bone tumour invasion and spread. Further studies are required to verify and evaluate these findings.

Electromagnetic modelling of current flow in the heart from TASER devices and the risk of cardiac dysrhythmias.

Increasing use by law enforcement agencies of the M26 and X26 TASER electrical incapacitation devices has raised concerns about the arrhythmogenic potential of these weapons. Using a numerical phantom constructed from medical images of the human body in which the material properties of the tissues are represented, computational electromagnetic modelling has been used to predict the currents arising at the heart following injection of M26 and X26 waveforms at the anterior surface of the chest (with one TASER 'barb' directly overlying the ventricles). The modelling indicated that the peak absolute current densities at the ventricles were 0.66 and 0.11 mA mm(-2) for the M26 and X26 waveforms, respectively. When applied during the vulnerable period to the ventricular epicardial surface of guinea-pig isolated hearts, the M26 and X26 waveforms induced ectopic beats, but only at current densities greater than 60-fold those predicted by the modelling. When applied to the ventricles in trains designed to mimic the discharge patterns of the TASER devices, neither waveform induced ventricular fibrillation at peak currents >70-fold (for the M26 waveform) and >240-fold (for the X26) higher than the modelled current densities. This study provides evidence for a lack of arrhythmogenic action of the M26 and X26 TASER devices.

Effect of humidity on cuticular water permeability of isolated cuticular membranes and leaf disks.

The effects of humidity on water permeability of astomatous, isolated cuticular membranes and leaf disks of Citrus aurantium L., Vinca major L., Prunus laurocerasus L., Hedera helix L. and Forsythia intermedia (Thunb.) Vahl. were investigated by a new method using 3H2O. With isolated cuticular membranes of P. laurocerasus the isotope method resulted in values similar to those obtained by a well-established gravimetric method. Cuticular water permeability significantly increased by factors of 2 to 3 when air humidities increased from 2 to 100%. Plots of permeances vs. air humidity were non-linear and the slope increased with increasing air humidity. Permeances of intact leaf disks showed a response to increasing humidity similar to those of isolated cuticular membranes. When cuticular water permeability was measured using wax-free, isolated polymer matrix membranes that had been methylated, the effect of air humidity was significantly suppressed compared to non-methylated polymer matrix membranes. From this observation it is concluded that non-esterified, free carboxyl groups present in the cutin polymer matrix significantly contribute to the effect of humidity on cuticular water permeability. These and other polar groups sorb water, which in turn increases the water permeability of polar domains of the cuticle. This humidity-sensitive, polar path of cuticular water permeability is arranged in parallel with the major, dominating and humidity-independent, non-polar path of cuticular water permeability formed by the lipophilic wax components of the cuticle. This conclusion is supported by the fact that cuticular transpiration can be increased by orders of magnitude upon (i) wax extraction, (ii) increase in temperature or (iii) the action of plasticizers, none of which influenced or only marginally influenced the permeability of inorganic ions penetrating plant cuticles across humidity-sensitive polar pores.

Fetal magnetoencephalographic mapping in normal and pre-eclamptic pregnancies.

This study investigates the fetal brain activity in normal and pre-eclamptic pregnancies. Measurements were performed by means of a superconducting quantum interference device (SQUID) in an electrically shielded room of low magnetic noise. The study was prospective. Ten pregnant women with pre-eclampsia and 11 healthy gravidae were included. All were preterm at 28 to 37 weeks' gestation. Biomagnetic signals (waveforms), recorded from the fetal brains in the frequencies 2-7 Hz, were expressed in terms of magnetic power spectral amplitudes: these were low in almost all normal pregnancies, and high in most pregnancies complicated with pre-eclampsia. The pictorial representation of the results in the form of iso-spectral amplitude (ISO-SA) mapping showed two different patterns: (a) iso-contour lines 'organised' in dense concentration zones (pre-eclamptic pattern), (b) iso-contour lines at random distribution without dense concentration zones (normal pattern). Biomagnetic measurements of fetal brain activity is a promising screening procedure for assessing the cerebral function, especially at high risk pregnancies.

The prognostic significance of AgNOR counts in lymph node deposits of breast carcinomas.

Low AgNOR counts in metastatic lymph node deposits confer a longer 5-year survival rate in patients with breast carcinoma compared with those having high AgNOR counts. This was demonstrated in a series of 30 axillary lymph nodes from an equal number of patients with malignant breast disease. The beneficial effect of the low AgNOR status was independent of tumour differentiation, tumour size and the patients' age using univariate analysis, but it was related to the number of lymph nodes with metastatic disease. It is thought that AgNOR counts in axillary lymph node metastases may be an additional prognostic variable in assessing breast tumour behaviour.