Endogenous p63 acts as a survival factor for tumour cells of SCCHN origin

The human p63 gene encodes a series of proteins that differ in their N- and/or C-terminal sequences and have widely differing properties in promoting or repressing p53-related functions such as growth arrest and apoptosis. In addition, p63 has important roles in the maintenance and differentiation of epithelial cell populations. Squamous cell carcinomas of the head and neck (SCCHN) express high levels of DeltaNp63 and p63beta isoforms compared to normal tissue from the same patients, suggesting a role for these isoforms in the pathogenesis of this common human malignancy. Here, we explore the function of p63 in SCCHN cells by using small interfering RNA (siRNA) to silence the expression of different isoforms in two SCCHN cell lines, FaDu and SCC-25. Silencing results in statistically significant decreased survival for tumour cells when all p63 isoforms, the N-terminal truncated or the alpha isoforms are inhibited. No effect was observed on cell proliferation or on the expression of epithelial differentiation markers. We also demonstrate that inhibition of endogenous p63 expression sensitises cells to the effects of ionizing radiation and cisplatin, common treatments for SCCHN patients. The data indicate that p63 has oncogenic properties in SCCHN and is predominantly involved in maintaining cell survival, rather than acting as a directly proliferative factor or as an inhibitor of terminal differentiation. Moreover, targeted inhibition of p63 expression in SCCHN could be a useful adjunct for conventional treatments of this disease.     

The influence of a false-positive mammogram on a woman's subsequent behaviour for detecting breast cancer

The aim was to investigate the influence of undergoing further examinations due to a false-positive mammogram on women's re-attendance at the next scheduled screening and their frequency of breast self-examination (BSE). Study participants included 517 women (62% response) recalled due to findings on screening mammograms indicating possible malignancies, and a matched control group of 285 women (68% response) with normal mammograms. Participants completed five and three questionnaires, respectively, during the 2 years following screening participation. While the groups did not differ significantly in screening re-attendance, women recalled due to false-positive mammograms reported significantly higher levels of anxiety related to the next screening than did women with normal mammograms. At the 1-year assessment, women with false-positive mammograms reported a significantly higher frequency of BSE than did women with normal mammograms. The present results indicate that being recalled due to a false-positive mammogram does not seem to negatively affect screening re-attendance, and may have a positive impact on BSE.     

Mapping pathological (99m)Tc-d,l-hexamethylpropylene amine oxime uptake in Alzheimer's disease and frontal lobe dementia with SPECT

Seventeen patients with probable Alzheimer's disease (AD), 7 patients with frontal lobe dementia (FLD) and 19 control subjects (NOR) were examined by (99m)Tc-d,l- hexamethylpropylene amine oxime ((99m)Tc-HMPAO) SPECT. Images were standardised in the same 3D space and averaged within each group. After normalisation, the three sets of images were analysed in all cerebral lobes, hippocampus, thalamus and basal ganglia. In AD, the (99m)Tc-HMPAO uptake values were significantly reduced, as compared to NOR, in the parietal, temporal and insular lobes. In patients with FLD, the uptake was altered in all lobes with the exception of the parietal lobe. The uptake in the nucleus caudatus decreased significantly in both AD and FLD as compared to NOR. The uptake in the anterior cingulate cortex was significantly reduced in FLD. Subtraction images highlighted all significantly decreased areas. In conclusion, standardising SPECT in a common space and subtracting data from a control group improves the visual interpretation of images. In this study, the typical temporo-parietal and fronto-parietal (99m)Tc-HMPAO uptake reductions were found in AD and FLD, respectively. The uptake in the nucleus caudatus was found to decrease significantly in AD and FLD and the one in the anterior cingulate cortex was reduced in FLD.     

Behavioural Effects of the Methanolic Root Bark Extract of Securinega Virosa in Rodents

Securinega virosa is used traditionally as sedative in children and in mental illnesses. In this study, the behavioral effects of methanolic root bark extract of S. virosa were investigated in mice. The results revealed that the extract significantly (P<0.05) and dose-dependently reduced the onset and prolonged the duration of sleep. The extract significantly (P<0.05) decreased exploratory activity and reduced the rate of apomorphine-induced stereotyped climbing at the doses tested (6.25–25mg/kg). It also produced a significant and dose-dependent motor coordination deficit in mice at the doses tested (P<0.01). The intraperitoneal median lethal dose in mice was 774.6mg/kg while the preliminary phytochemical screening revealed the presence of alkaloids, tannins, saponins and flavonoids. These results suggest that methanolic root bark extract of S. virosa contains biologically active principles that are sedative in nature and lend pharmacological credence to the ethnomedical use of the plant.     

Pulmonary lymphangitic spread of carcinoma: appearance on CT scans

Chest computed tomography (CT), including high-resolution CT with thin (1.5-mm) sections was used to evaluate proved (pathologically or clinically) lymphangitic spread (LS) of tumor in 12 patients. These appearances were compared with thin-section scans obtained in 11 healthy subjects. Thin-section CT demonstrated findings consistent with thickening of the normal lung interstitium. In all patients, thin sections showed an increase in the number of peripheral lines (1-2 cm in length) that were diffuse in generalized disease and localized in focal disease. Normal peripheral arcades were not increased in number, but the limbs forming the arcades were thickened in all patients. A diffuse increase in linear and curvilinear structures (reticular pattern) was seen toward the center of the lung. Polygonal structures 1-2 cm in diameter were seen in seven patients with LS but not in healthy subjects. Fissures were thickened in nine patients. Selected 1.5-mm-thick CT sections are recommended through abnormal areas (seen at CT or on chest radiographs) or if these are normal at three levels (midapex, hilus, and 3 cm above the diaphragm) when scanning patients with tumors known to cause LS.     

Obstetric and nonmalignant gynecologic bleeding: treatment with angiographic embolization

Eight patients (seven post partum, one post abortion) with massive pelvic hemorrhage related to pregnancy and one patient with uncontrollable bleeding following a cervical biopsy underwent angiography to facilitate the identification and treatment of bleeding sites. In all nine patients pelvic hemorrhage was successfully controlled with embolization under angiographic guidance. Angiographic embolization allowed preservation of the uterus in six patients referred prior to hysterectomy, and one patient subsequently became pregnant. When conservative measures and minor surgical repairs have failed, embolization should be the next step in the treatment of postpartum hemorrhage to avoid major surgery in an unstable patient and to maintain reproductive function.     

Chronic daily headache with medication overuse: a randomized follow-up by neurologist or PCP

Several studies have shown the benefit of withdrawal therapy when medication overuse headache (MOH) is suspected. Our aim was to compare the effect of withdrawal therapy in patients followed by a neurologist (group A, n  = 42) and a primary care physician (PCP) (group B, n  = 38). Patients were randomized to A or B, and follow-up was at 3, 6 and 12 months. Calculated mean headache (MH at 6 months + MH at 12 months)/2 (primary end-point) was similar; A 1.04 (0.87, 1.21) and B 1.02 (0.82, 1.21) ( P  = 0.87). The number of patients with 50% improvement of headache days was also similar; 14/42 in group A vs. 12/34 in B ( P  = 0.86) at 3 months, 15/42 vs. 11/33 ( P  = 0.83) at 6 months and 15/42 vs. 14/38 ( P  = 0.92) at 12 months. Days without headache during the last 9 months of follow-up were 123 (96, 150) in group A and 137 (112, 161) in B ( P  = 0.62). After 3 months one-third were classified as MOH. Patients with MOH improved similarly in group A and B, and so did patients without MOH. Within 1 year 7/42 in A and 9/38 in B had recurrent medication overuse ( P  = 0.43). In summary, there were no significant differences in follow-up results between the two groups.     

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large- pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.     

An evaluation of a strategy to improve the support of orthopaedic nurses through a team preceptorship programme

Transition to a new work area is often stressful for both experienced and new graduate nurses. It is essential that the new graduate be supported through this transition period to enable them to adjust to the environment itself, refine knowledge, and develop skills specific to their chosen clinical stream. In past years, several strategies have been designed with varying levels of success.This study evaluates an Australian transition support model, where the fundamental difference is that the management of the program is facilitated by a nurse possessing refined leadership, communication, clinical and organisational skills.The model has been evaluated on its effectiveness in meeting specific outcomes. The findings revealed that this coordinated team approach provided increased support for the new graduate, reduced the stress and workloads on the preceptors, whilst promoting confidence in the new starters and preventing conflict between preceptors and preceptees. The Coordinator’s role was shown to be an effective and crucial component in the Coordinated Team Preceptorship Model (CTPM) and findings illustrated that a team preceptorship model is not sustainable without a Coordinator.