The soluble tumor necrosis factor receptor I is an early predictor of local infective complications after colorectal surgery

The clinical implications of increased cytokine levels after major surgery remain unclear. In this study, systemic concentration of a spectrum of cytokines, including interleukins IL-6, IL-8, IL-10, IL-1ra, and soluble tumor necrosis factor receptor-I (sTNF-RI) was examined in patients with and without postoperative septic complications following colorectal surgery. Although there were no significant changes in IL-1, TNF-, and IL-8 serum levels during the observation period, there was a significant rise in IL-6, IL-1ra, and sTNF-RI concentrations in the entire group of patients between postoperative day 1 and 14. There were no differences between the group without and with local complications when IL-6, IL-1ra, and IL-10 were examined. The serum levels of sTNF-RI, IL-1ra, and IL-6 were found to be sensitive indicators of the pro- and anti-inflammatory response to the surgical trauma, but only sTNF-RI turned out to be a sensitive early marker of local septic postoperative complications in patients with colorectal carcinoma.     

The kinetics of mast cells in lymph nodes of immunized mice

Normal mouse peritoneal exudate cells (PEC), consisting of 90–95 per cent macrophages, were used to augment haemagglutination in microtrays. Antibody titres were augmented 1000-fold when 10⁶ PEC/ml were mixed with sheep erythrocytes (SRBC) and added to serial dilutions of mouse anti-SRBC sera. This method has certain advantages over conventional antiglobulin augmented haemagglutination. It is thought that augmented haemagglutination by PEC is mediated by macrophage receptors for cytophilic antibodies or by a non-specific surface mechanism.     

Arrhythmogenic right ventricular cardiomyopathy in two pairs of monozygotic twins

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritant disease with an autosomal dominant mode of transmission with incomplete penetrance and variable expression. Linkage analysis in affected families succeeds in identifying 9 loci determining 9 subtypes of the disease. Genotype phenotype correlation is unclear and the influence of various environmental factors is discussed. OBJECTIVES: Genotype phenotype correlation in 2 pairs of monozygotic twins with ARVC and the role of environmental factors are analyzed. PATIENTS AND METHODS: Among 40 pts with ARVC and their 195 relatives there were 2 pairs of monozygotic twins: brothers, age 47 y; and sisters, age 48 y. History, ECG, Holter monitoring, 2D and Doppler Echo, and MRI were analyzed. RESULTS: Twin brothers: ARVC was diagnosed in the proband after the episode of VT with LBBB morphology (enlarged right ventricle, focal hypokinesia of apex, MR evidence of adipose tissue in RV wall). Identical morphology of RV was seen in asymptomatic twin brother. The patient presenting arrhythmia has been rowing for 4 years. Twin sisters: diagnosis was done during family screening. Both were asymptomatic. RV morphology typical for ARVC was found discrete in one of them (bulges adipose tissue in the RV apex); the latter showed changes suggesting RV abnormality (mild segmental dilatation of infundibulum, adipose tissue in a free wall of the RV). No differences in previous viral infections and sports involvement were observed. CONCLUSIONS: 1. Clinical picture of ARVC in monozygotic twins is not identical. 2. Strenuous effort may be a factor triggering the arrhythmia in pts with ARVC.     

Uniformity of Thermoluminescence and Optically Stimulated Luminescence Signals Over the Length of Doped LiMgPO4 Crystal Rods Grown by Micro-Pulling-Down Method

The purpose of this work was to systematically assess the distribution of thermoluminescence (TL) and optically stimulated luminescence (OSL) properties along the length of crystals grown by the micro-pulling-down method, in relation to the microstructure and distribution of activators. We analyzed lithium magnesium phosphate (LiMgPO₄; LMP) crystals doped with terbium (Tb; 0.8 mol%) or with a combination of thulium (Tm; 0.8 mol% or 1.2 mol%) and boron (B; 10 mol%). Crystals of several centimeters in length and 3 mm in diameter were cut into 20–40 slices, depending on length. For each sample, TL glow curves and OSL decay curves were examined. Optical microscopy and scanning electron microscopy were used to assess the microstructure and elemental composition of several selected samples. Two-dimensional TL readouts were performed to identify the areas with higher and lower signal emission. Our study showed that there may be significant differences not only in LMP sensitivity along the crystal’s axis but also on the surface of the slice. The distribution of activators varies depending on the type of crystals and strongly affects luminescence properties.     

Value of the intraoperative assessment of the depth of myometrial invasion in endometrial carcinoma

OBJECTIVES: The aim of the study was to evaluate the value of intraoperative assessment of depth of myometrial invasion in patients with FIGO stage I of the endometrial carcinoma. MATERIAL AND METHODS: A total number of 112 patients with FIGO stage I of the endometrial carcinoma undergoing surgery were enrolled in the study. All patients had undergone intraoperative assessment of the depth of myometrial invasion performed by a surgeon. The depth was determined as more or less than 50% of myometrial thickness according to FIGO classification. Gross visual estimation of the depth of myometrial invasion at the time of the operation was compared with the final histopathological report. Sensitivity, specificity and positive and negative predictive values of the method were determined by means of statistical analyses. RESULTS: The depth of the myometrial invasion was accurately determined by the surgeon in 82.1% of cases. Sensitivity and specificity were 68% and 82.1%, respectively. The accurate prediction rate of the myometrial invasion in the group of patients with well differentiated (G1) endometrial carcinoma was higher (88.4%) than in group with moderately and low differentiated tumour (78.3%). CONCLUSIONS: The accuracy of macroscopic evaluation of myometrial invasion is high and reaches up to 82.1%. The accurate determination rate increases if the differentiation of tumour is higher.     

Differences in simulated liver concentrations of toxic coumarin metabolites in rats and different human populations evaluated through physiologically based biokinetic (PBBK) modeling

Coumarin is bioactivated via 3,4-epoxidation resulting in formation of the hepatotoxic o-hydroxyphenylacetaldehyde (oHPA) and detoxified by cytochrome P450 2A6 (CYP2A6) hydroxylation leading to 7-hydroxycoumarin. The present study defines physiologically based biokinetic (PBBK) models to predict liver levels of the toxic oHPA metabolite of coumarin in rats and in human subjects with normal or deficient CYP2A6 catalyzed coumarin 7-hydroxylation. The results reveal that the predicted maximum tissue concentration (C(max)) of oHPA in the liver of wild type human subjects and of subjects deficient in CYP2A6 catalyzed 7-hydroxylation are, respectively, three and one order of magnitude lower than the values predicted for rat liver. Another difference between CYP2A6 deficient and wild type human subjects is a 500-fold difference in the area under the curve 0-24h (AUC(0-24h)) for the time-dependent oHPA liver concentration pointing at a relative higher percentage of the original dose converted in time through this pathway when CYP2A6 is deficient. For wild type human subjects and the subjects with completely deficient coumarin 7-hydroxylation the AUC(0-24h) values for oHPA in the liver are, respectively, three and one order of magnitude lower than that for rat liver. Even when 7-hydroxylation is deficient, the chances on formation of the hepatotoxic oHPA metabolite will be significantly lower in the liver of humans than those expected in the liver of rats when exposed to a similar dose on a body-weight basis. This conclusion should be taken into account when extrapolating data from experimental studies in sensitive animals, i.e., rats, to the general human population.     

Inflammatory prostate cancer: an underestimated paraneoplastic clinical manifestation

PURPOSE: To identify the incidence of prostate cancer associated-systemic inflammatory syndrome (SIS), and to characterize further this entity, we searched our database as well as the medical literature. METHODS: We retrospectively analyzed all patients with prostate cancer admitted to the Department of Medical Oncology of the Ioannina University Hospital during the last 3 years. Systematic review of peer-reviewed medical literature was further performed at 3 major libraries (i.e., MEDLINE, ISI Web of Science, and Cochrane Central Register of Controlled Trials). No publication year or language restriction was set in the literature search. RESULTS: Retrospective analysis of our patient population identified 4 patients with a SIS (of 63 patients who were metastatic hormone resistant), in whom fever was a sign of disease progression. Inversely, only 4 cases of prostate cancer-related fever were found in the literature, in all of them at disease presentation. Consequently, the incidence of inflammatory syndrome in metastatic prostate cancer seems to be strongly underestimated. A SIS can be an early or late event during the course of the disease, and is generally associated with rapid progression and bad prognosis. Back pain, fatigue, night sweats, anemia, bone metastases, and bone marrow infiltration are the most commonly associated signs and symptoms. Because of occasional responses to hormonal or chemotherapeutic treatment, prompt differential diagnosis and therapy are required. CONCLUSIONS: The role of proinflammatory cytokines in biochemical pathways of neoplastic growth has been established in prostate cancer, along with evidence for high levels of interleukin (IL)-6 among patients with hormone refractory disease. However, little is known about the frequency of a SIS in patients with prostatic carcinoma.