Bioavailability and dose-dependent anti-tumour effects of 9-cis retinoic acid on human neuroblastoma xenografts in rat

Neuroblastoma, the most common extracranial solid tumour in children, may undergo spontaneous differentiation or regression, but the majority of metastatic neuroblastomas have poor prognosis despite intensive treatment. Retinoic acid regulates growth and differentiation of neuroblastoma cells in vitro, and has shown activity against human neuroblastomas in vivo. The retinoid 9-cis RA has been reported to induce apoptosis in vitro, and to inhibit the growth of human neuroblastoma xenografts in vivo. However, at given dosage, the treatment with 9-cis RA caused significant toxic side effects. In the present study we investigated the bioavailability of 9-cis RA in rat. In addition, we compared two different dose schedules using 9-cis RA. We found that a lower dose of 9-cis RA (2 mg day−1) was non-toxic, but showed no significant effect on tumour growth. The bioavailability of 9-cis RA in rat was 11% and the elimination half-life (t1/2) was 35 min. Considering the short t1/2, we divided the toxic, but tumour growth effective dose 5 mg dayminus;1 into 2.5 mg p.o. twice daily. This treatment regimen showed no toxicity but only limited effect on tumour growth. Our results suggest that 9-cis RA may only have limited clinical significance for treatment of children with poor prognosis neuroblastoma. © 2001 Cancer Research Campaign http://www.bjcancer.co

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

<p>Abstract</p> <p>Background</p> <p>The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression.</p> <p>Methods/Design</p> <p>The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm²or >10 cm². Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process.</p> <p>Discussion</p> <p>The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes.</p> <p>Trial Registration</p> <p>ACTRN12608000599370</p

Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status

Neuroblastoma and its benign differentiated counterpart, ganglioneuroma, are paediatric neuroblastic tumours arising in the sympathetic nervous system. Their broad spectrum of clinical virulence is mainly related to heterogeneous biologic background and tumour differentiation. Neuroblastic tumours synthesize various neuropeptides acting as neuromodulators. Previous studies suggested that galanin plays a role in sympathetic tissue where it could be involved in differentiation and development. We investigated the expression and distribution of galanin and its three known receptors (Gal-R1, Gal-R2, Gal-R3) in 19 samples of neuroblastic tumours tissue by immunohistochemistry, in situ hybridization and fluorescent-ligand binding. This study provides clear evidence for galanin and galanin receptor expression in human neuroblastic tumours. The messengers coding for galanin, Gal-R1 and -R3 were highly expressed in neuroblastoma and their amount dramatically decreased in ganglioneuroma. In contrast, Gal-R2 levels remained unchanged. Double labelling studies showed that galanin was mainly co-expressed with its receptors whatever the differentiation stage. In neuroblastic tumours, galanin might promote cell-survival or counteract neuronal differentiation through the different signalling pathways mediated by galanin receptors. Finally, our results suggest that galanin influences neuroblastoma growth and development as an autocrine/paracrine modulator. These findings suggest potential critical implications for galanin in neuroblastic tumours development

Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability

A simple multivariate test for asymmetry

Since many macroeconomic models are linear, it is not desirable to use them with an asymmetric dependent variable. In this article, we formulate a univariate test for symmetry, based on the third central moment and extend it to a multivariate test; the test does not require modelling and it is robust against serial correlation, Autoregressive Conditional Heteroscedasticity (ARCH) and nonnormality. In the empirical application of the test it is found that orthodox theory seem to be supported; consumption expenditure on durable goods is found to be symmetric while consumption expenditure on nondurable goods is asymmetric for the USA and the UK, with peaks being higher than troughs are deep. Also, the empirical importance of the choice between the univariate and the multivariate test for possibly correlated series is underscored; the results from the two approaches clearly differ. Given the widespread practice of using consumption expenditure on nondurable goods as the dependent variable in linear models for the USA and the UK, our results might be noteworthy.

Pinch grafting of chronic leg ulcers in primary care: Fourteen years' experience

Pinch grafting for treatment of chronic leg ulcers has been evaluated mainly in hospitalized and immobilized patients. This study describes the results of 199 pinch graft operations of 126 chronic leg and foot ulcers in 85 patients in primary care between 1987 and 2001. The aetiology of the ulcers was venous insufficiency in 43% and multi-factorial in 25% (77% with venous insufficiency as the main determinant). The mean ulcer size was 13.5 cm(2) and the mean ulcer duration was 15.9 months. The overall healing rate within 3 months was 33%, ranging from 19% for multi-factorial or combined venous and arterial ulcers to 48% for venous ulcers. Within 12 months the overall healing rate was 60%, with 67% healed venous ulcers. The results from our study suggest that pinch grafting is suitable for treating chronic leg ulcers, especially venous ulcers, in primary care

Preoperative prediction of histopathologic outcome in basal cell carcinoma - flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types

Background: Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC). Objectives: To assess the accuracy of the preoperative prediction of subtypes of BCC in clinical practice, to evaluate whether dermoscopic examination enhances accuracy and to find dermoscopic criteria for discriminating sBCC from other subtypes. Materials and methods: The main presurgical diagnosis was compared with the histopathological, postoperative diagnosis of routinely excised skin tumours in a predominantly fair-skinned patient cohort of northern Europe during a study period of 3 years (2011\u201313). The study period was split in two: during period 1, dermoscopy was optional (850 cases with a pre- or postoperative diagnosis of BCC), while during period 2 (after an educational dermoscopic update) dermoscopy was mandatory (651 cases). A classification tree based on clinical and dermoscopic features for prediction of sBCC was applied. Results: For a total of 3544 excised skin tumours, the sensitivity for the diagnosis of BCC (any subtype) was 93\ub73%, specificity 91\ub78%, and the positive predictive value (PPV) 89\ub70%. The diagnostic accuracy as well as the PPV and the positive likelihood ratio for sBCC were significantly higher when dermoscopy was mandatory. A flat surface and multiple small erosions predicted sBCC. Conclusions: The study shows a high accuracy for an overall diagnosis of BCC and increased accuracy in prediction of sBCC for the period when dermoscopy was applied in all cases. The most discriminating findings for sBCC, based on clinical and dermoscopic features in this fair-skinned population, were a flat surface and multiple small erosions