Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH) is the most important prognostic factor for the decompensation of liver cirrhosis and death, therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH) and severe PH(SPH). As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG), the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study. Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero, dretro, d RMS) and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm. Average endogenous strain μ and standard deviation σ of strain were assessed in the regions of interest(ROI)(1 cm × 1 cm and 2 cm × 2 cm in size) and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P 0.05) correlation with HVPG measurement. The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm × 2 cm ROI size). Three parameters showed statistically significant differences between patient groups with CSPH, but only dretro showed significant results in SPH analysis. According to ROC analysis area under the curve(AUC) of the σROI[0…10 Hz, 2 cm × 2 cm] parameter reached 0.71(P = 0.036) for the diagnosis of CSPH; with a cut-off value of 1.28 μm/cm providing 73% sensitivity and 70% specificity. AUC for the diagnosis of CSPH for μROI[0…10 Hz, 1 cm × 1 cm] was 0.78(P = 0.0024); with a cut-off value of 3.92 μm/cm providing 73% sensitivity and 80% specificity. Dretro parameter had an AUC of 0.86(P = 0.0001) for the diagnosis of CSPH and 0.84(P = 0.0001) for the diagnosis of SPH. A cut-off value of-132.34 μm yielded 100% sensitivity for both conditions, whereas specificity was 80% and 72% for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.     

Surfactant-induced cell toxicity and cell lysis. A study using B16 melanoma cells

The effects of a variety of detergents (non-ionic, ionic and bile derivatives) on B16 melanoma cells have been examined. Two main effects can be clearly differentiated: loss of cell viability and cell lysis. Under our conditions, cell-surfactant interaction is highly dependent on the nature of the amphiphile (more specifically, on its critical micellar concentration). Loss of cell viability occurs at surfactant concentrations below the critical micellar concentration, i.e. the incorporation of detergent monomers into the cell membranes is enough to impair their barrier function, so that Trypan Blue is no longer actively secreted outside the cell. On the other hand, cell lysis only occurs at or near the critical micellar concentration of the detergent, i.e. when the bilayer-micelle transition may take place. Comparative studies using B16 cells and phospholipid vesicles indicate that the amount of detergent required to induce cell lysis is the same that produces disruption of the lipid bilayer. Thus, our results suggest that membranes are the primary target for the toxicologic effects of surfactants on cells. Moreover, they provide a rationale for the interpretation of other studies in this field: previous results from different laboratories are shown to fit very well our data.     

Effects of Lentinan on Cytotoxic Functions of Human Lymphocytes

The in vitro effects of lentinan on natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), lectin-dependent cell-mediated cytotoxicity (LDCC) and mitogen-induced blast transformation were studied in patients with solid tumors and chroyic lymphocytic leukemia (CLL). NK activity was measured against Cr-labelled K-562 targets, ADCC against antibody-coated chicken red cells. LDCC and natural cell-mediated cytotoxicity (NCMC) was assessed using ³H-thymidine prelabelled HEp-2 targets. Mitogen (PHA-and Con A-) induced blast transformation was measured by thymidine incorporation.

Blastogenesis and LDCC was not influenced by lentinan. 1 μg/ml lentinan increased NCMC of tumor-bearing subjects. The most prominent enhancement of NK and ADCC activity was seen in CLL patients, where a dose-related increase was seen (from 0.01 to 1 μg/ml).     

Differential sensitivity to Arg side chain modification of IL-1β binding to type I and type II receptors

The central role of interleukin-1 (IL-1) in several disease processes, including fever and inflammation, makes the characterization of ligand-receptor interaction of prime importance.The role of arginine (Arg) side chains of hr-IL-1 in receptor recognition was studied by the modification of Arg residues with the specific reagent 1,2-cyclohexanedione. It was found that chemical modification of Arg residues decreased the binding potential of IL-1 to type I receptor dramatically (by 230-fold) while the affinity to type II receptor was reduced only moderately (by 10-fold), with an insignificant reduction of the dissociation rate.These studies suggest that intact Arg side chains of IL-1 may be necessary for high affinity binding to type I IL-1 receptor, but have less importance for the interaction of IL-1 with type II IL-1 receptor.This observation may be useful in the study of type II IL-1 receptor-mediated biological responses and design of receptor-subtype specific ligands as well.     

Automatic analysis of immunocytochemically stained tissue samples

An automatic colour image segmentation and cell counting software system has been developed for immunocytochemical analysis of stained tissue samples. The system was designed to count the total number of positive and negative cells in tissue samples treated with cytokine DNA probes from pigs naturally parasitised with Taenia solium metacestodes, using in situ hybridisation. A reaction index was calculated as the ratio of the number of cells with a positive reaction to the total number of cells (positives plus negatives) for each of five different probes. The objectives of automatic counting were to improve the reproducibility of the analysis and reduce the processing time of large image batches. A fast KNN classifier was used for colour segmentation. Watershed segmentation combined with edge detection was used to isolate individual cells that were then automatically labelled, using the results of the corresponding colour segmented image. Validation was performed on 122 non-training digital images with a total of 1069 positive cells and 1459 negative cells, with the following results: a mean true positive rate of 90.2% for positive cells and a mean true positive rate of 85.4% for negative cells. The corresponding mean false positive rates were 9.6% and 6.6%. The mean reaction index error of the automatic analysis was 5.35%. The processing of each digital image took 10 s on a Pentium IV PC.     

Deficient IFNα production in hairy cell leukemia

Summary Since the application of low doses of IFN-alpha is necessary to maintain remissions in Hairy Cell Leukemia (HCL) it is of interest whether peripheral blood mononuclear cells (MNC) of HCL patients can be induced in vitro to produce IFN-alpha. 9 patients suffering from advanced HCL were included in the study. The diagnoses were confirmed by characteristic findings in peripheral blood and bone marrow biopsies. For IFN treatment we initially used natural IFN-alpha (Bioferon) and switched later to recombinant IFN-alpha₂ (Boehringer). MNC of 5 patients before IFN therapy and of 6 patients during IFN therapy (2–47 weeks) were induced by phythemagglutinin (PHA), Corynebacterium parvum (C.p.), and sendai virus (SV). PHA is known to induce IFN-gamma. Both, C.p. and SV induced IFN-alpha but no IFN-gamma in MNC of healthy controls and of IFN treated breast cancer patients. In HCL patients normal antiviral activities could be induced by PHA. Zero or only low antiviral activities could be induced in MNC from 9 patients tested on 22 occasions. It is concluded that MNC from patients with advanced HCL can be induced to produce IFN-gamma but no IFN-alpha. Since IFN-alpha but not IFN-gamma is produced by monocytes it is likely that reduced numbers of monocytes which were found in our HCL patients before and during IFN treatment account for the described deficiency of IFN-alpha production.     

Kidney biopsy in the elderly: diagnostic adequacy and yield

International Urology and Nephrology - The number of kidney biopsies (KB) performed in elderly patients has been increasing. Safety and usefulness of elderly KB have been well established, whereas...