The significance of beta-catenin, E-cadherin, and P-cadherin expressions in neoplastic progression of colorectal mucosa: an immunohistochemical study

BACKGROUND AND STUDY AIMS: The purpose of the current study was to investigate the role of beta-catenin, E-cadherin and P-cadherin in colorectal carcinogenesis using tissue array method. PATIENTS AND METHODS: Core tissue biopsies were taken from paraffin-embedded tissue blocks of 167 cases including 26 normal mucosae (NM), 99 colorectal polyps (10 hyperplastic polyps (HP), 8 traditional serrated (TSA), 17 tubular (TA), 37 tubulovillous (TVA), and 27 villous adenomas (VA)), 14 adenomas with intramucosal carcinoma (ACA), and 28 colorectal cancers (CCA). Immunohistochemistry was performed using antibodies to beta-catenin, E-cadherin, and P-cadherin. Distribution of positivity was assessed using percentage expression while an arbitrary grading scale was used for staining intensity. RESULTS: beta-catenin expression was cytoplasmic, membranous, and nuclear. Both E-cadherin and P-cadherin expressions were confined to cytoplasmic-membranous compartments. Membranous expression of beta-catenin significantly decreased in CCA (p < 0.01). Nuclear beta-catenin expression significantly increased in close correlation with neoplastic sequence reaching its highest expression in ACA and CCA (p < 0.001). Polyps with intraepithelial neoplasia (IEN) showed significantly higher nuclear beta-catenin expression in parallel with increasing grades of IEN (p < 0.001). E-cadherin and P-cadherin expression increased in polyps, whereas a significant decrease in their expression was observed in CCA (p < 0.001) while E-cadherin expression significantly increased in CCA compared to NM (p < 0.001), no such difference was observed in P-cadherin expression. CONCLUSIONS: Nuclear beta-catenin expression correlating with the grade of IEN in polyps and carcinomas supports its role in colorectal carcinogenesis. E-cadherin and P-cadherin expressions in adenomas suggest that these molecules might have role in adenoma formation though not necessarily be involved in neoplastic progression.     

The effects of chronic L-name and L-arginine administration on beta-adrenergic responsiveness of STZ-diabetic rat atria.

Recent studies have shown that NO acts as a negative inotrope and chronotrop in cardiac muscle. In the present study, we investigated the effects of the chronic administration of L-NAME and L -arginine on 14-week streptozotocin (STZ)-diabetic rat atria. To study these effects, we compared the alterations of inotropic and chronotropic responses to isoprenaline (ISO) on electrically-driven left atria and spontaneously beating right atria. In addition, we compared the blood pressures of rats in all groups. The chronic administration of L-arginine resulted in a significant reduction in blood pressure of the diabetic rats. On the other hand, the chronic nitric oxide synthase inhibition resulted in a significant increase in blood pressure of diabetic animals. To our findings, maximum positive inotropic responses of ISO diminished in STZ-diabetic, L-arginine and L-NAME treated diabetic groups relative to controls but neither the basal contractility of the left atria nor the pD(2)values were altered significantly in all groups. The basal atrial rate and maximum positive chronotropic responses to ISO were found to be significantly lower in treated and untreated diabetic groups, no significant changes were observed in pD(2)values. Our results demonstrate that the changes in inotropic and chronotropic responses in diabetic rat atria were not influenced by the chronic administration of L-arginine and L-NAME treatments.     

Remifentanil/midazolam versus tramadol/midazolam use for colonoscopy

One of the most commonly performed outpatient procedure is colonoscopy. The pain and anxiety is frequently associated with colonoscopy. The aim of this study was to compare the effectiveness of remifentanil/midazolam, and tramadol/midazolam for iv sedation and analgesia during colonoscopy. Twentysix patients (age range 18-65 years) scheduled for ambulatory colonoscopy were included to study. All patients received midazolam 1 mg intravenous. After two minutes in Group R (remifentanil/midazolam, n=18) remifentanil bolus (10 microg) and infusion 0.03 microg kg(-1) min(-1) were administered until adequate sedation level was achieved. In Group T (tramadol/midazolam, n=18) iv tramadol 50 mg was given concurrently. During procedure 2 L/min oxygen was supplemented via face mask to all patients. Haemodynamic variables, respiratory depression, level of sedation, postoperative recovery, patient and gastroenterologist satisfaction were surveyed. Patients were asked to verbally rate their level of pain, on an 10-point numerical rating scale (1=no pain, 10=severe pain). Chi-square, student t test, and mann whitney U test were used for statistical analysis. Colonoscopy was carried out successfully in all patients. There were no episodes of desaturation or airway compromise. Haemodynamic parameters were similar in both groups. Sistolic arterial and diastolic arterial pressures were increased at 10 and 15 minutes in all patients (P<0.05). There were no significant changes in heart rate in both groups. The level of sedation in group R was higher than group T during colonoscopy. The patients in group T had higher pain scores. Gastroenterologist satisfaction and patient satisfaction were similar in both groups. Our results suggests that, sedoanalgesia with midazolam/remifentanil may be an alternative to sedoanalgesia with midazolam/tramadol for colonoscopy.     

Mobilization of peripheral blood stem cells with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation of different doses of rhG-CSF

To date, no randomized study has compared different doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34+ peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25) versus 16 microg/kg/d (n = 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34+ cells collected after 8 microg/kg/d of rhG-CSF was 2.36 x 10(6)/kg (range, 0.21-7.80), compared with 7.99 (2.76-14.89) after 16 microg/kg/d (P < 0.001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 microg/kg and 16 microg/kg of rhG-CSF were 12 (10-20) and 9 (8-11) respectively (P < 0.001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P = 0.10), number of red blood cell (P = 0.56) and platelet transfusions (P = 0.22), days of total parenteral nutrition requirement (P = 0.84), fever (P = 0.93) and antibiotics (P = 0.77), and number of different antibiotics used (P = 0.58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose-response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 microg/kg/d was as effective as 16 microg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era.     

Second recurrence of familial cardiac myxomas in atypical locations

Recurrence rates reported for cardiac myxomas are 4% to 7% for sporadic cases and 10% to 21% for familial cases. Although recurrence rates are high, second recurrences are rare. Familial cardiac myxomas in a mother and daughter are reported, both of whom had their second recurrences within six years. Both had recurrences in uncommon places, such as the left atrial posterior wall, between the left atrial appendage and the pulmonary vein, and the anterior mitral leaflet.     

Effects of radiofrequency catheter ablation on myocardial performance index and plasma NT-Pro-BNP levels in patients with Wolff-Parkinson-White syndrome

Background: The myocardial performance index (Tei index) is an echocardiographic index of combined systolic and diastolic functions. Brain natriuretic peptide (BNP) and its biologically inactive fragment N-terminal pro-BNP (NT-pro-BNP) are secreted by the heart in response to myocardial stretch. In this study, we investigated Tei index and NT-pro-BNP levels in patients with Wolff-Parkinson-White (WPW) syndrome before and after radiofrequency catheter ablation therapy (RFCA).
Methods: Thirty patients (19 males, 11 females, aged 35.5 ± 14.4 years) with WPW syndrome were enrolled in this study. Echocardiographic examination was performed before and 24 hours after RFCA. Tei index was calculated using Doppler echocardiography. Blood samples were taken before and 24 hours after RFCA to detect levels of NT-pro-BNP. Results: Although isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) did not change, aortic ejection time (ET) was decreased after RFCA (276 ± 22 ms vs 254 ± 30 ms, P < 0.01). So Tei index was significantly higher in postablation period (0.36 ± 0.11 vs 0.42 ± 0.21, P < 0.05). NT-pro-BNP levels did not change significantly after RFCA. Conclusions: We demonstrated that restoration of normal atrioventricular conduction by RFCA, leads to increase in Tei index but does not effect plasma NT-pro-BNP levels .