Concomitant vinorelbine and radiation in head and neck squamous cell carcinoma in vitro

Concomitant chemoradiotherapy has been used for locally advanced head and neck squamous cell carcinoma (HNSCC) particularily with cisplatin, 5-FU, methotrexate, bleomycin and taxanes. Vinorelbine is a semisynthetic vinca alcaloid, which causes a block in the G2/M phase of the cell cycle. HNSCC cell lines have previously been reported to be sensitive to vinorelbine in nanomolar concentrations. In the current study the effect of vinorelbine as a radiosensitizer in vitro was studied and eight recently established head and neck SCC cell lines of the UT-SCC-series were tested. Vinorelbine concentrations of 0.4-1.6 nM were used, corresponding to the IC70, IC50 and IC30 values of each cell line, resulting in 30%, 50% and 70% inhibition in clonogenic survival. The desired concentrations of vinorelbine were added to the medium and the cells were plated in 96-well culture plates in this solution. The plated cells were irradiated 24 h later with 4MeV photons generated by a linear accelerator and incubated at 37 degrees C with 5% CO2 for 4 weeks. Thereafter, the number of wells containing coherent, living colonies, consisting of 32 cells or more, was counted. The plating efficiency was calculated and the fraction survival data were fitted to the linear quadratic model [F = exp[-(alphaD + betaD2)]]. An additive effect of combining vinorelbine and irradiation could be demonstrated. The dose-dependent decrease in survival was seen at vinorelbine doses of 0.4-1.6 nM in all cell lines tested.     

Frequent chromosome Y loss in primary, second primary and metastatic squamous cell carcinomas of the head and neck region

The loss of chromosome Y has often been observed in human solid tumors. This chromosome aberration has been proposed as one of genetic changes predisposing men to squamous cell carcinoma of the head and neck (SCCHN). In this study, using cytogenetic analysis and fluorescence in situ hybridization we analyzed: 16 cell lines derived from primary and recurrent SCCHN, a group of 22 samples derived from of previously analyzed primary larynx tumors and their corresponding metastases and a group of eight multiple primary tumors received from two different locations within the head and neck region of the same patients. In the majority of analyzed cell lines we found both loss of chromosome Y and SRY-probe signals (68.7% of samples) and these were nearly always found in the analyzed metaphases. The whole chromosome Y was usually lost, but in two cases we observed translocation of this chromosome to chromosomes 1, 3 and 17. Among all primary tumors, 14 (63.6%) and 15 of their metastases (68.2%) showed a loss of chromosome Y in a prevailing number of analyzed nuclei. Also, in the group of primary tumors and second primary tumors, all samples had a loss of the chromosome Y in the majority of analyzed nuclei.     

Help-seeking for mental health problems among young physicians: is it the most ill that seeks help?

Abstract Objectives The aims of this study were to assess the prevalence of self-reported mental health problems and help-seeking among young physicians, and identify predictors of seeking help. Methods A prospective cohort sample of Norwegian medical students (N=631) were assessed in their final semester (T1), and in the first (T2) and fourth (T3) postgraduate year. The average observation period was 3.6 years. Results The prevalence of mental health problems that needed treatment over the preceding year was observed to have increased from 11% at T2 to 17% at T3. There was no increase in help-seeking. Longitudinally, 34% reported that they needed treatment on one or several occasions. Adjusted predictors of help-seeking were perceived level of mental health problems and a reality weakness personality trait. Conclusion Those who sought help had higher levels of emotional distress than those who did not. However, higher reality weakness scores predicted lower help-seeking and, therefore, may be a risk factor for avoiding necessary care.     

ADAM12: a novel first-trimester maternal serum marker for Down syndrome

OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration. RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers. CONCLUSION: ADAM12 is a promising marker for Down syndrome.     

Changes in intensive care from 1987 to 1997 - has outcome improved? A single centre study

OBJECTIVES: To study changes in a single intensive care unit (ICU) over a 10 year period and to investigate possible concomitant changes in outcome. SETTING: The ICU populations in 1987 and 1997 in a university hospital. DESIGN AND METHODS: Prospective and retrospective cohort study. The ICU database was used for comparison of the ICU populations, and SAPS II-estimated hospital survival was compared with observed survival. Three year follow-up survival (the Peoples Registry) was compared with population survival (Statistics Norway). In the year 2000 the Short Form 36 (SF 36) questionnaire was used for quality of life (QOL) measurement. Results were compared with a reference population. INTERVENTIONS: None. RESULTS: From 1987 to 1997 the numbers of patients and stays increased from 219 and 236 to 338 and 370. ICU activity per stay increased considerably, but length of stay remained unchanged (6.0 versus 5.9 days). The 1997 ICU patients were, on average, older (50.3 versus 46.0 years) and more severely ill (SAPS II 42.7 versus 34.7). They had a higher crude mortality, but the time from admission to when the observed mortality reached the predicted mortality was longer, indicating an increased survival length. Two years after intensive care, there was no excess mortality compared with population survival in either cohort. QOL was significantly reduced in both cohorts compared to population scores. CONCLUSIONS: This study indicates that the increased intensive care activity over the 10 year period was associated with a prolonged severity-adjusted survival. QOL was still reduced 3 and 13 years after ICU, compared to population scores.     

Heparin-coated circuits (Duraflo II) with reduced versus full anticoagulation during coronary artery bypass surgery

BACKGROUND: Introduction of completely heparin-coated cardiopulmonary bypass (CPB) circuits combined with reduced systemic anticoagulation has been shown to reduce postoperative bleeding and requirements for allogeneic transfusions after cardiac surgery. However, some uncertainty exists whether this effect is due to the reduced amount of heparin or to the heparinized surface itself. Therefore, a retrospective study was undertaken, comparing two different anticoagulation protocols applied to coronary artery bypass patients treated with identical heparin-coated CPB equipment. METHOD: Over a 12 month period all coronary artery bypass patients operated with extracorporeal circulation were subjected to a Duraflo II heparin-coated circuit (Baxter Healthcare Corp, Bentley Laboratories Division, Irvine, Calif) and full heparin dose (activated clotting time [ACT] > 480 seconds; Group F, n = 651). Over the next 24 months, all coronary patients who were treated with an identical circuit combined with reduced systemic heparinization (ACT > 250 seconds) were included in Group R (n = 675). Except for the different anticoagulation protocols, all treatment regimens before, during, and after the operation remained unchanged throughout the study period. RESULTS: There were no statistically significant differences in any major demographic or operative parameters. In Group R, the postoperative bleeding was mean 665 +/- 257 ml versus 757 +/- 367 ml in Group F (p < 0.0001), and the perioperative decrease in hemoglobin concentration was significantly lower in Group R (22 +/- 1.2 gm/L versus 25 +/- 1.3 gm/L, p < 0.0001). The time for postoperative ventilatory support was shorter in Group R (1.7 +/- 1.3 hours versus 1.9 +/- 1.1 hours in Group F, p = 0.0006), and the incidence of new episodes of atrial fibrillation after the operation was lower (26.4% in Group R versus 32.8% in Group F, p = 0.01). There were no significant differences in the incidences of perioperative myocardial infarction, stroke, transient neurological disturbances, physical rehabilitation, or mortality. No technical or coagulation problems were recorded in either group. CONCLUSION: The use of Duraflo II coated circuits for CPB combined with reduced anticoagulation decrease postoperative bleeding and hemoglobin loss compared with full heparin dose treatment. In addition, the intubation time was shorter and the incidence of postoperative atrial fibrillation was lower in the patients treated with low heparin doses.     

Changes in health-related quality of life from 6 months to 2 years after discharge from intensive care

Background  

Intensive care patients have, both before and after the ICU stay, a health-related quality of life (HRQOL) that differs from that of the normal population. Studies have described changes in HRQOL in the period from before the ICU stay and up to 12 months after. The aim of this study was to investigate possible longitudinal changes in HRQOL in adult patients (>18 years) from 6 months to 2 years after discharge from a general, mixed intensive care unit (ICU) in a university hospital.     

Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines

J Oral Pathol Med (2011) 40 : 739–746 Background: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines. Methods: The expression of epidermal growth factor receptor, survivin, Bax, Bcl‐2, Bcl‐X_L, cyclooxygenase‐2 (COX‐2), and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse. Results: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (IR; r = 0.36, P = 0.02). The combination of survivin, Bax, Bcl‐2, Bcl‐X_L, COX‐2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r = 0.553, P < 0.001). Conclusion: These data indicate that the IR of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.     

Multichannel data acquisition system for mapping the electrical activity of the heart

BACKGROUND: Details of the electrical conduction pattern of the heart are revealed to the electrophysiologist when multichannel data are used for activation mapping. Commercial electronic systems are available for simultaneous acquisition of many surface electrograms; however, the cost of these systems may be prohibitive and they can be mostly inflexible for adaptation to other research projects. Furthermore, the hardware and software design is often proprietary. In this article we describe the in-house design and implementation of a 320-multichannel acquisition system for animal electrophysiologic research. METHOD AND RESULTS: Several modules comprise this system. The multichannel data are first preprocessed by amplification, filtering, and analog multiplexing. An algorithm for automatic adjustment of signal gains is implemented to maximize the voltage resolution and minimize noise pickup. Signals are then digitized, and sequenced to order the multichannel data and to add markers required for analysis. The digital data are streamed to archival storage media. Additionally, the electrocardiogram (ECG), blood pressure, and stimulus channel signals are stored simultaneously. Selected signals are then displayed in real-time for measurement and analysis and as a check of the system integrity. Examples of multielectrode arrays and surface recordings are provided. Costs for building such a system are estimated. CONCLUSIONS: Multichannel data acquisition systems that are designed and constructed in-house have several advantages over turnkey commercial systems, including the potential for considerable cost savings, flexibility in acquiring data, and the ability to subsequently add additional components.     

Left ventricular volumes assessed by different new three-dimensional echocardiographic methods and ordinary biplane technique

Three-dimensional (3D) echocardiography may overcome the problems with inadequate accuracy and reproducibility of 2D volume measurements of the left ventricle. Aims: To establish the in vitro accuracy and reproducibility of two new methods for 3D echocardiographic volume determination as compared to biplane measurements. Methods: Validation of volume measurements by a multiplane 3D method was performed on asymmetric latex phantoms (n=8, true volumes 45-304 ml) using rotational acquisition of 90 image planes. Porcine agarose-filled asymmetrical left ventricles (n=7, true volumes 34 – 280 ml) were measured by the same multiplane 3D method based on images acquired by probe rotation axis perpendicular (A) and parallel (B) to the ventricular long axis. Ventricular volumes were also obtained by a simplified 3D system using only the three standard apical views (C) and by the ordinary biplane Simpson’s method (D). Results: On latex phantoms systematic deviation from true volumes by multiplane 3D was less than 2%, and 95% variability of individual measurements from this mean was ± 4,9%. For accuracy on left ventricles, systematic bias was small with all the methods (<5%), but 95% variability of individual measurements was ±9,0%, 15.4%, 18.8% and 41.3% of true volumes for methods A-D respectively. Corresponding results in the same range were obtained for inter- and intraobserver variability. Conclusion: Individual in vitro volume estimates of left ventricles are of similar quality using apical multiplane or apical triplane 3D echocardiography. Both methods were superior to the ordinary apical biplane method, but inferior to multiplane 3D method with the probe directed perpendicular to the ventricular long axis.