Evaluation of oestrogen and progesterone receptor status in HER-2 positive breast carcinomas and correlation with outcome

Aim: HER-2/neu amplification occurs in 15-25% of breast carcinomas. This oncogene, also referred to as c-erbB-2, encodes a transmembrane tyrosine kinase receptor belonging to the epidermal growth factor receptor family. HER-2 over-expression is reported to be associated with a poor prognosis in breast carcinoma patients and in some studies is associated with a poorer response to anti-oestrogen therapy. These patients are less likely to benefit from CMF (cyclophosphamide, methotrexate, fluorouracil)-based chemotherapy compared with anthracycline-based chemotherapy. The aim of this study was to evaluate breast carcinomas to determine hormone receptor status and if there is a difference in breast cancer specific survival for HER-2 positive patients. Methods: A total of 591 breast carcinomas were evaluated using immunohistochemistry (IHC) for oestrogen receptor (ERp), progesterone receptor (PRp) and three different HER2 antibodies (CB11, A0485 and TAB250). Percentage of tumour cells and intensity of staining for ERp were evaluated using a semiquantitative method. Results: Of the 591 tumours, 91 (15.4%) showed 3+ membrane staining for HER-2 with one or more antibodies. Of these 91 tumours, 41 (45.1%) were ERp+/ PRp+, seven (7.7%) were ERp+/PR-, six (6.6%) were ERp-/PRp+ and 37 (40.7%) were ERp-/PR-. Of HER-2 positive tumours, 5.5% showed > 80% 3+ staining for ERp compared with 31.8% of 0-2+ HER-2 tumours; 24.2% of HER-2-positive tumours showed 60% or more cells with 2+ or 3+ staining for ERp. Treatment data were available for 209 patients and no difference was observed in breast cancer specific survival (BCSS) with HER-2 status and tamoxifen. Conclusion: Oestrogen receptor status cannot be used to select tumours for evaluation of HER-2 status, and oestrogen and progesterone receptor positivity does not preclude a positive HER-2 status. There is a higher proportion of ERp negative tumours associated with HER-2 positivity, however, more than 20% of HER-2 positive tumours show moderate or strong staining for ERp. HER-2 positive patients in this study did not show an adverse BCSS with tamoxifen treatment unlike some previous studies.

Evaluation of resynchronization of contractile function following biventricular pacing using colour tissue Doppler imaging

Biventdcular (BV) pacing is evaluated as an alternative treatment for patients with dilated cardiomyppathy (both ischemic and non-ischemic) and end-stage heart failure. Colour tissue Doppler imaging using echocardiography allows noninvasive, quantitative assessment of radial motion in the long-axis with measurement of peak systolic velocity timing. The aim of the present study was to evaluate quantitatively, the systolic performance of the left ventricle and the resynchrenization of contraction (before vs after implantation). Patients and methods: 25 patients with dilated cardiomyopathy (11 ischemic), NYHA class III or IV, QRS duration >120 ms received a biventricular pacemaker. Routine 2D echo and colour tissue Doppler imaging were performed before and within 1 week following implantation. LVEF was assessed using the biplane Sampson's method.Peak systolic velocity (PSV) and time to PSV (TPV) were assessed in 4 regions (basal anterior, inferior, lateral and septal). By averaging the TPV from all 4 regions, a synchronization index was dedved from these measurements. Reaults: LVEF improved by 9±9% following pacing; 17 patients improved LVEF 5% or more. The change in PSV in the septal and lateral regions related significantly to the change in LVEF (r=0.74, r=0.62).The change in synchronization index before vs after pacing (as a measurement of REsynchronization) was related to the change in LVEF (y=120x+5.6, r=0.79, P

Drug utilization evaluation of parenteral proton pump inhibitors

Current evidence supports parenteral infusion of proton pump inhibitors (PPI) after endoscopic treatment of bleeding peptic ulcers and such treatment seems reasonable where there is active bleeding or visible vessel on endoscopy. Parenteral boluses of PPI can be used in patients nil by mouth who cannot tolerate oral therapy. We sought to examine the appropriateness of parenteral PPI use. Drug utilisation evaluation was performed on 94 patients admitted to a 500 bed metropolitan hospital. 39 patients received continuous parenteral infusion of omeprazole (8 mg/ h) over a mean of 60 ± 29 h. 55 patients had parenteral boluses (40 mg bd) of omeprazole over a mean of 5 ± 4 days. Indications for PPI infusion (n = 39) were: major haemorrhage requiring transfusion (23), minor haemorrhage (8), dyspepsia (4) and others (4). 31 of the 39 patients on PPI infusion had upper gastrointestinal (GI) endoscopy. PPI infusion was commenced prior to endoscopy in 26 (84%) patients. 13 patients (33%) had active bleeding or visible non bleeding vessels at endoscopy. Only 11 patients (28%) had endoscopically treated peptic ulcers. Indications for parenteral PPI boluses (n = 55) included patients nil by mouth unable to take maintenance PPI orally (21), minor haemorrhage (8), peptic ulcer prophylaxis in seriously unwell (6), major haemorrhage (4), dyspepsia (2), postoprative period following peptic ulcer surgery (2) and others (12). Endoscopy was performed in 10 patients (18%) with only 1 endoscopically treated peptic ulcer. Our data suggest significant inappropriate use of parenteral PPI, which may be used for minor GI bleeding and dyspepsia and are typically commenced prior to endoscopy. These findings can explain the costly hospital expenditure on PPI.

Statistical racing techniques for improved empirical evaluation of evolutionary algorithms

In empirical studies of Evolutionary Algorithms, it is usually desirable to evaluate and compare algorithms using as many different parameter settings and test problems as possible, in border to have a clear and detailed picture of their performance. Unfortunately, the total number of experiments required may be very large, which often makes such research work computationally prohibitive. In this paper, the application of a statistical method called racing is proposed as a general-purpose tool to reduce the computational requirements of large-scale experimental studies in evolutionary algorithms. Experimental results are presented that show that racing typically requires only a small fraction of the cost of an exhaustive experimental study.

Numerical evaluation of e-fields induced by body motion near high-field MRI scanner

In modern magnetic resonance imaging (MRI), both patients and radiologists are exposed to strong, nonuniform static magnetic fields inside or outside of the scanner, in which the body movement may be able to induce electric currents in tissues which could be possibly harmful. This paper presents theoretical investigations into the spatial distribution of induced E-fields in the human model when moving at various positions around the magnet. The numerical calculations are based on an efficient, quasistatic, finite-difference scheme and an anatomically realistic, full-body, male model. 3D field profiles from an actively-shielded 4 T magnet system are used and the body model projected through the field profile with normalized velocity. The simulation shows that it is possible to induce E-fields/currents near the level of physiological significance under some circumstances and provides insight into the spatial characteristics of the induced fields. The results are easy to extrapolate to very high field strengths for the safety evaluation at a variety of field strengths and motion velocities.