Efficacy of cross-sectional imaging guided sympathetic neurolysis in abdoiniuopelvic tumors

Aim of work

To study the efficacy of visceral neurolytic blocks in the abdominopelvic cancer when guided by ultrasound/CT.

Role of multi-detector computerized tomography in diagnosis of traumatic urinary bladder injuries

Background

Urinary tract injuries occur in 3–10% of abdominal trauma. Early recognition and diagnosis of ruptured bladder is essential to lower this mortality rate. CT is the method of choice for the evaluation of patients with blunt or penetrating abdominal and/or pelvic trauma. Imaging in patients with suspected bladder injury with CT cystography may be performed using either an intravenous or retrograde technique.

Tailoring therapy for locally advanced breast cancer using molecular profiles: are we there yet?

The term 'locally advanced breast cancer' covers a range of clinical scenarios, and has the implications that surgical clearance and local control will be difficult or impossible, and long-term survival rates will be poor. Treatment selection is particularly important in this group of patients to try to obtain maximum control of disease, and potentially improve surgical options and cure rates. Currently, assessment of estrogen receptor, progesterone receptor and human epidermal receptor 2 status in tumour samples remains the gold standard for prediction of response to endocrine therapy, chemotherapy or targeted agents such as trastuzumab. Progress has been made in identifying markers that can help select treatments likely to be associated with response and avoid those associated with resistance. These potential markers include Ki67 proliferation rate, cytochrome P450 (CYP) 2D6 expression, BRCA1/2 gene status and others.     

Identification of μ‐ and κ‐opioid receptors as potential targets to regulate parasympathetic,sympathetic, and sensory neurons within rat intracardiac ganglia

Recent interest has been focused on the opioid regulation of heart performance; however, specific allocation of opioid receptors to the parasympathetic, sympathetic, and sensory innervations of the heart is scarce. Therefore, the present study aimed to characterize such specific target sites for opioids in intracardiac ganglia, which act as a complex network for the integration of the heart's neuronal in‐ and output. Tissue samples from rat heart atria were subjected to RT‐PCR, Western blot, radioligand‐binding, and double immunofluorescence confocal analysis of μ (M)‐ and κ (K)‐opioid receptors (ORs) with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene‐related peptide (CGRP), and substance P (SP). Our results demonstrated MOR‐ and KOR‐specific mRNA, receptor protein, and selective membrane ligand binding. By using immunofluorescence confocal microscopy, MOR and KOR immunoreactivity were colocalized with VAChT in large‐diameter parasympathetic principal neurons, with TH‐immunoreactive small intensely fluorescent (SIF) cells, and on nearby TH‐IR varicose terminals. In addition, MOR and KOR immunoreactivity were identified on CGRP‐ and SP‐IR sensory neurons throughout intracardiac ganglia and atrial myocardium. Our findings show that MOR and KOR are expressed as mRNA and translated into specific receptor proteins on cardiac parasympathetic, sympathetic, and sensory neurons as potential binding sites for opioids. Thus, they may well play a role within the complex network for the integration of the heart's neuronal in‐ and output. J. Comp. Neurol. 518:3836–3847, 2010. © 2010 Wiley‐Liss, Inc.     

Which medical error to disclose to patients and by whom? Public preference and perceptions of norm and current practice

Background

HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania.

Methods

A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits.

Results

99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy.

Conclusions

Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings.

Trial registration

Current Controlled Trials ISRCTN64716212     

A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences

Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERα, ERβ1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phenotype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERβ1/2 clusters. A striking feature was the occurrence of ERα on distinct clusters between genders. In female breast cancer, ERα clustered with PR and its isoforms; in male breast cancer, ERα clustered with ERβ isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.     

Effect of surfactant on surface hardness of dental stone and investment casts produced from polyvinyl siloxane duplicating materials

Polyvinylsiloxane duplicating materials are typically treated with a topical surfactant before pouring dental models, but the use of topical surfactants in the dental laboratory may affect the surface hardness of the resultant models. The effect of two different topical surfactants on surface hardness of two dental stones (FujiRock and Dentstone) and one phosphate bonded investment material (Croform WB) produced from polyvinyl siloxane (PVS) dental laboratory duplicating moulds was investigated. Topical surfactants affected the surface hardness of FujiRock, Dentstone and Croform WB investment material. Surface hardness of FujiRock increased with Wax-Mate surfactant. However, surface hardness of Croform WB investment material decreased with both topical surfactants.     

Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma

CUB and SUSHI multiple domain protein 1 (CSMD1) is a candidate tumour suppressor gene that maps to chromosome 8p23, a region deleted in many tumour types including 50% of breast cancers. CSMD1 has homologies to proteins implicated in carcinogenesis. We aimed to study the expression pattern of the CSMD1 protein and evaluate its prognostic importance in invasive ductal carcinoma (IDC). An anti-CSMD1 antibody was developed and validated. The expression pattern of CSMD1 in normal breast and IDC samples was investigated by immunohistochemistry in 275 patients. Univariate and multivariate Cox regression analyses were performed. In normal breast duct epithelial cells, luminal, membranous and cytoplasmic CSMD1 staining was identified. Reduced expression of CSMD1 was detected in 79/275 (28.7%) of IDC cases. Low CSMD1 expression was significantly associated with high tumour grade (P = 0.003). CSMD1 expression was associated with overall survival (OS; HR = 0.607, 95%CI: 0.4–0.91, P = 0.018) but not with disease-free survival (DFS; HR = 0.81, 95%CI: 0.46–1.43, P = 0.48). Multivariate analysis showed that CSMD1, together with Nottingham Prognostic Index, was considered an independent predictor of OS (HR = 0.607, 95%CI: 0.4–0.91, P = 0.018) but not DFS (HR = 0.84, 95%CI: 0.46–1.5, P = 0.573). Reduction of CSMD1 expression was significantly associated with high tumour grade and decreased OS. Therefore, our results support the idea that CSMD1 is a tumour suppressor gene and suggest its possible use as a new prognostic biomarker. The membrane expression pattern of CSMD1 suggests that it may be a receptor or co-receptor involved in the process of signal transduction.