Impact of smoking on imiquimod response in patients with vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a precancerous condition that may progress to invasive malignancy. VIN is associated with human papillomavirus (HPV) infection in most cases, and with inflammatory skin disorders in a smaller proportion of patients. Treatment of VIN has traditionally been surgical excision; however, topical treatments, including imiquimod cream, are becoming increasingly used. Patient factors influencing response to imiquimod therapy, in particular smoking, have not yet been published. AIM: To assess the impact of smoking and other patient characteristics that may influence the treatment response to topical imiquimod for VIN. METHODS: This was a retrospective cohort study of 46 women treated with topical imiquimod for VIN in a single centre dermatology unit from January 2011 to July 2017. RESULTS: Complete clinical resolution of VIN was observed in 28 of 46 patients (61%), but was significantly reduced in the smoking cohort. CONCLUSIONS: Smoking may impair response to imiquimod for VIN, and should be considered when discussing VIN treatment options with patients.

[Organization and perception of low threshold services for older migrants in communities. Chances for social participation in the context of voluntary engagement]. / Gestaltung und Wahrnehmung niedrigschwelliger Angebote für ältere Migranten im Stadtteil. Chancen für eine soziale Teilhabe im Kontext des freiwilligen Engagements.

BACKGROUND: There is still a problematic situation in Germany for older migrants, who can be characterized by poverty, lack of knowledge of the healthcare system, generation conflicts and social exclusion. AIM: The objective of this article is the analysis of the chances for social participation of older migrants from two perspectives. MATERIAL AND METHODS: This qualitative study is based on an interdisciplinary research project sponsored by the German Federal Ministry of Education and Research entitled "Cultures of social participation in local communities" (KUSTIS) from the promotion program "Social innovations for quality of life in old age " (SILQUA) and presents selected results from two subprojects. The investigation explored the possibilities for social participation by older migrants in two suburbs of Bremen in Germany, Gröpelingen and Vahr, which have higher than average migrant Turkish and Russian populations. The results of the 3-year study are presented. The first subproject looked at how 40 migrants aged 60 years and over perceived the support from migrant low threshold services and focused on their wishes and needs using a qualitative content analysis. The second subproject investigated the voluntary engagement for older migrants in an intercultural context through considering the views of volunteers who worked with older migrants (28 interviews and 4 focus groups). RESULTS AND CONCLUSION: Both subprojects complement each other to provide an integrated view of low threshold services for older migrants. The analysis shows the significance of migrant organizations for social participation, the heterogeneity of life circumstances, the motivation of engagement and the need for social acknowledgement.

Utility of Preoperative CA125 Assay in the Management Planning of Women Diagnosed with Uterine Cancer.

Objective. This study assesses the role of preoperative serum CA125 levels in the planning treatment options for women diagnosed with uterine cancer. Material and Method. Ninety five consecutive patients diagnosed with uterine cancer during a four-year period were identified. Age ranged from 35 to 89 years with a mean age of 69 years. The preoperative CA125 levels were dichotomised at 28 U/mL (using ROC analysis to identify the best discriminating threshold for 5-year survival). This level was then correlated with preoperative prognostic indicators: patient age, tumour grade, and histopathological tumour cell type. Survival data was plotted using Kaplan-Meier curves and analysed using the log-rank test. Univariate and multivariate analysis were performed to identify the predictors of overall survival. Results. The mean age of patients was 69 years (range: 35-89). On univariate analysis, the use of preoperative CA125 levels of greater or less than 28 U/mL correlated significantly with age (P = 0.01), the grade of disease (P = 0.02) and unfavourable tissue type (P = 0.03). This threshold CA125 level had a sensitivity of 75%, specificity of 76%, positive predictive value of 35% and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for predicting nodal disease. Using a threshold of preoperative CA125 level of 28 U/mL (area under curve: 0.60) was also a significant predictor of 5-year survival (log-rank test, P = 0.01). Using Cox multivariate survival analysis to identify predictive preoperative factors overall, unfavourable cell type was the strongest predictor of survival (Chi square = 36.5, df = 4, and P = 0.001), followed by preoperative CA125 level (CA125 > 28 U/mL, P = 0.011) and unfavourable preoperative grade (P = 0.017). Amongst patients with a favourable histological tissue type (endometrioid), preoperative CA125 levels predicted overall survival (Chi square = 6.039, df = 2, P = 0.02); however unfavourable preoperative grade did not (P = 0.5). Overall, at five-year follow-up, while there were no deaths among the women with preoperative serum CA125 less than 12 U/mL, eleven of the twenty-three deaths (47.82%) in the study occurred in women with a preoperative CA125 more than 28 U/mL. Conclusions. A preoperative CA125 assay for women with uterine cancer is a relatively inexpensive, reproducible, and objective test which provides valuable information regarding the risk of metastatic disease and overall likelihood of long term survival. Patients with a low likelihood of metastatic/nodal disease (favourable tissue type and CA125 level < 28 U/mL) and significant comorbidities may benefit from avoiding an extended complete staging procedure. Alternatively, a high level of CA125 may prompt further imaging and multidisciplinary discussions to plan for individualised management and consideration for recruitment to clinical trials.

Risk of significant gynaecological pathology in women with glandular neoplasia on cervical cytology.

OBJECTIVE: To review the risk of pre-invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. METHODS: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary's Hospital Sidcup. The category of 'borderline nuclear change in endocervical cells', result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. RESULTS: A total of 200 women were identified using the hospitals' pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre-invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty-four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. CONCLUSION: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.

The impact of temporal inaccuracies on 4DCT image quality.

Accurate delineation of target volumes is one of the critical components contributing to the success of image-guided radiotherapy treatments and several imaging modalities are employed to increase the accuracy in target identification. Four-dimensional (4D) techniques are incorporated into existing radiation imaging techniques like computed tomography (CT) to account for the mobility of the target volumes. However, these methods in some cases introduce further inaccuracies in the target delineation when further quality assurance measures are not implemented. A source of commonly observed inaccuracy is the misidentification of the respiration cycles and resulting respiration phase assignments used in the construction of the 4D patient model. The aim of this work is to emphasize the importance of optimal respiration phase assignment during the 4DCT image acquisition process and to perform a quantitative assessment of the effect of inaccurate phase assignments on the overall image quality. The accuracy of the phase assignment was assessed by comparison with an independent calculation of the respiration phases. Misplaced phase assignments manifest themselves as deformations and artifacts in reconstructed images. These effects are quantified as volumetric discrepancies in the localization of target objects represented by spherical phantoms. Measurements are performed using a fully programmable motion phantom designed and built at Mayo Clinic (Rochester, MN). Implementation of a case based independent check and correction procedure is also demonstrated with emphasis on the use of this procedure in the clinical environment. Review of clinical 4D scans performed in this institution showed discrepancies in the phase assignments in about 40% of the cases when compared to our independent calculations. It is concluded that for improved image reconstruction, an independent check of the sorting procedure should be performed for each clinical 4DCT case.

Charge degree of freedom and the single-spin fluid model in YBa2Cu4O8

We present a 17O nuclear magnetic resonance study in the stoichiometric superconductor YBa2Cu4O8. A double irradiation method enables us to show that, below around 200 K, the spin-lattice relaxation rate of plane oxygen is not only driven by magnetic fluctuations, but also significantly by quadrupolar fluctuations, i. e., low-frequency charge fluctuations. In the superconducting state, on lowering the temperature, the quadrupolar relaxation diminishes faster than the magnetic one. These findings show that, with the opening of the spin pseudogap, a charge degree of freedom of mainly oxygen character is present in the electronic low-energy excitation spectrum.

Separation of quadrupolar and magnetic contributions to spin-lattice relaxation in the case of a single isotope

We present a NMR pulse double-irradiation method which allows one to separate magnetic from quadrupolar contributions in the spin-lattice relaxation. The pulse sequence fully saturates one transition while another is observed. In the presence of a ||Deltam || = 2 quadrupolar contribution, the intensity of the observed line is altered compared to a standard spin-echo experiment. We calculated analytically this intensity change for spins I = 1, 32, 52, thus providing a quantitative analysis of the experimental results. Since the pulse sequence we used takes care of the absorbed radiofrequency power, no problems due to heating arise. The method is especially suited when only one NMR sensitive isotope is available. Different cross-checks were performed to prove the reliability of the results obtained. The applicability of this method is demonstrated by a study of the plane oxygen (17)O (I = 52) in the high-temperature superconductor YBa(2)Cu(4)O(8): the (17)O spin-lattice relaxation rate consists of magnetic as well as quadrupolar contributions. Copyright 2000 Academic Press.

Automated seed localization from CT datasets of the prostate.

With the increasing utilization of permanent brachytherapy implants for treating carcinoma of the prostate, the importance of accurate post-treatment dose calculation also increases for assessing patient outcome and planning future treatments. An automatic method for seed localization of permanent brachytherapy implants, using CT datasets of the prostate, has been developed and tested on a phantom using an actual patient planned seed distribution. This method was also compared to results with the three-film technique for three patient datasets. The automatic method is as accurate or more accurate than the three film technique for 1 mm, 3 mm, and 5 mm contiguous CT slices, and eliminates the inter- and intra-observer variability of the manual methods. The automated method improves the localization of brachytherapy seeds while reducing the time required for the user to input information, and is demonstrated to be less operator dependent, less time consuming, and potentially more accurate than the three-film technique.

Wide frequency range 31P relaxation in the ion conducting glass LiPO3.

Spin-lattice relaxation studies on the stationary 31P nucleus have been performed in order to investigate to which extent the dynamics of the mobile lithium ions are reflected in the behavior of the glassy network. The temperature dependence of the 31P relaxation, which is governed by the heteronuclear dipole-dipole interaction between lithium and phosphorus, can be described in terms of a Gaussian distribution of activation energies and that over a wide frequency range from about 34 kHz to 81 MHz. A relaxation rate maximum, which provides useful information about correlation times and activation energies of the lithium-ion diffusion process, could only be observed in the rotating frame relaxation measurements.

The human synapsin II gene promoter. Possible role for the transcription factor zif268/egr-1, polyoma enhancer activator 3, and AP2.

Synapsin II is a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Here we report the cloning and sequencing of the 5'-flanking region of the human synapsin II gene. This sequence is very GC-rich and lacks a TATA or CAAT box. Two major transcriptional start sites were mapped. A hybrid gene consisting of the Escherichia coli chloramphenicol acetyltransferase gene under the control of 837 base pairs of the synapsin II 5'-upstream region was transfected into neuronal and nonneuronal cells. While reporter gene expression was low in neuroblastoma and non-neuronal cells, high chloramphenicol acetyltransferase activities were monitored in PC12 pheochromocytoma cells. However, there was no correlation between reporter gene expression in the transfected cells and endogenous synapsin II immunoreactivity. Using DNA-protein binding assays we showed that the transcription factors zif268/egr-1, polyoma enhancer activator 3 (PEA3), and AP2 specifically contact the synapsin II promoter DNA in vitro. Moreover, the zif268/egr-1 protein as well as PEA3 were shown to stimulate transcription of a reporter gene containing synapsin II promoter sequences. In the nervous system, zif268/egr-1 functions as a "third messenger" with a potential role in synaptic plasticity. PEA3 is expressed in the brain and its activity is regulated by proteins encoded from non-nuclear oncogenes. We postulate that zif268/egr-1 and PEA3 couple extracellular signals to long-term responses by regulating synapsin II gene expression.