Giant atypical carcinoid of the liver with vascular metastases and local sinusoidal invasion: a case report

We present the case of a 46 year old woman with a giant, 23-centimeter, atypical carcinoid of the liver. A primary site for this neoplasm could not be identified despite multiple radiographic imaging studies, including a somatostatin scan, and a thorough inspection of the bowel during surgical resection of the lesion. Histologically, the tumor displayed mild cytologic atypia, abundant necrosis, and intravascular metastases, the last feature of which was identified by immunohistochemical markers for chromogranin and synaptophysin. Also described is the unusual sinusoidal infiltration, or "spillage," of tumor cells into the surrounding liver parenchyma, a feature that has not been described as far as we are aware but may suggest an aggressive clinical course. Even though an exact definition of atypia for these lesions apparently does not exist at this point, the multiple atypical features in this case strongly suggest the diagnosis of atypical carcinoid of the liver, thus far an altogether rare and vaguely reported entity. As more cases arise in the medical literature, it may be worthwhile to establish a set of guidelines to define atypical hepatic carcinoids and other gastrointestinal carcinoids, although survivorship data thus far indicates no significant difference in the prognosis between typical versus atypical variants

The effectiveness of a preferred intensity exercise programme on the mental health outcomes of young people with depression: a sequential mixed methods evaluation

<p>Abstract</p> <p>Background</p> <p>People with mental illness are more likely to suffer physical health problems than comparable populations who do not have mental illness. There is evidence to suggest that exercise, as well has having obvious physical benefits, also has positive effects on mental health. There is a distinct paucity of research testing its effects on young people seeking help for mental health issues. Additionally, it is generally found that compliance with prescribed exercise programmes is low. As such, encouraging young people to exercise at levels recommended by national guidelines may be unrealistic considering their struggle with mental health difficulties. It is proposed that an exercise intervention tailored to young people's preferred intensity may improve mental health outcomes, overall quality of life, and reduce exercise attrition rates.</p> <p>Methods/Design</p> <p>A sequential mixed methods design will be utilised to assess the effectiveness of an individually tailored exercise programme on the mental health outcomes of young people with depression. The mixed methods design incorporates a Randomised Controlled Trial (RCT), focus groups and interviews and an economic evaluation. <it>Participants: </it>158 young people (14-17 years) recruited from primary care and voluntary services randomly allocated to either the intervention group or control group. <it>Intervention group</it>: Participants will undertake a 12 week exercise programme of 12 × 60 minutes of preferred intensity aerobic exercise receiving motivational coaching and support throughout. Participants will also be invited to attend focus groups and 1-1 interviews following completion of the exercise programme to illicit potential barriers facilitators to participation. <it>Control group</it>: Participants will receive treatment as usual. <it>Primary Outcome measure</it>: Depression using the Children's Depression Inventory 2 (CDI-2). <it>Secondary Outcome measures</it>: Quality of Life (EQ-5D), physical fitness (Borg RPE scale, heart rate), incidents of self-harm, treatment received and compliance with treatment, and the cost effectiveness of the intervention. Outcome measures will be taken at baseline, post intervention and 6 month follow up.</p> <p>Discussion</p> <p>The results of this study will inform policy makers of the effectiveness of preferred intensity exercise on the mental health outcomes of young people with depression, the acceptability of such an intervention to this population and its cost effectiveness.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01474837">NCT01474837</a></p

JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats

BACKGROUND: Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model. METHODS: A suspension of 5 × 10(6 )RCN-9 (rat colon cancer cells) was injected into the tail vein of 24 anesthetized male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day) was administered from the day before RCN-9 injection until the end of the study. Twenty-four days later, the lungs were removed from sacrificed rats and weighed. Pulmonary metastatic tumors were microscopically evaluated in the largest cross sections. We also performed immunohistochemical staining for both COX-2 and VEGF. RESULTS: JTE-522 dose-dependently decreased lung weight (p = 0.001) and the size of pulmonary metastatic tumors (p = 0.0002). However, the differences in the number of metastatic tumors among 4 groups were insignificant. Significant adverse effects of JTE-522 were undetectable. Immunohistochemical staining showed high levels of both COX-2 and VEGF in pulmonary metastatic tumors. CONCLUSION: JTE-522 dose-dependently decreased the size, but not the number of pulmonary metastases. COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis. Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

<p>Abstract</p> <p>Background</p> <p>The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Methods</p> <p>The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from <it>Spodoptera frugiperda</it>. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo.</p> <p>Results</p> <p>An <it>in vitro </it>isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An <it>in vitro </it>glass vial efficacy and mortality study against various life stages of the ticks <it>Ixodes ricinus, Rhipicephalus sanguineus </it>and <it>Dermacentor reticulatus </it>and against the flea (<it>Ctenocephalides felis</it>) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of these actives from a neck collar (compounded with 10% imidacloprid and 4.5% flumethrin) was extensively studied in dogs and cats under laboratory and field conditions. Acaricidal concentrations of the actives were found to be consistently released from the collar matrix for 8 months. None of the collar studies in dogs or cats were associated with any significant collar related adverse event.</p> <p>Conclusion</p> <p>Here we demonstrated the synergism between the pyrethroid flumethrin and the neonicotinoid imidacloprid, both provided in therapeutically relevant doses by a slow release collar matrix system over 8 months. This collar is therefore a convenient and safe tool for a long-term protection against ectoparasites.</p

Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomized trial

<p>Abstract</p> <p>Background</p> <p>Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only.</p> <p>Design</p> <p>Patients are randomly assigned to ‘nurse-led self-help treatment plus usual care’ (134 participants) or ‘usual care’ (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year).</p> <p>Discussion</p> <p>The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self-help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients.</p> <p>Trial registration</p> <p>NTR3001 (<url>http://www.trialregister.nl</url>)</p

Profiles of Small Non-Coding RNAs in Schistosoma japonicum during Development

Schistosomiasis, a debilitating disease, caused by agents of the genus Schistosoma afflicts more than 200 million people worldwide. Schistosomes could serve as an interesting model to explore gene regulation due to its evolutional position, complex life cycle and sexual dimorphism. We previously indicated that sncRNA profile in the parasite S. japonicum was developmentally regulated in hepatic and adult stages. In this study, we systematically investigated mircoRNA (miRNA) and endogenous siRNA (endo-siRNA) profile in this parasite in more detailed developmental stages (cercariae, lung-stage schistosomula, separated adult worms, and liver tissue-trapped eggs) using high-throughput RNA sequencing technology. We observed that the ratio of miRNAs to endo-siRNAs was dynamically changed throughout different developmental stages of the parasite. MiRNAs were expressed dominantly in cercariae, while endo-siRNAs accumulated in adult female worms and hepatic eggs. We demonstrated that miRNAs were mostly derived from intergenic regions whereas siRNAs were mostly derived from transposable elements. We also annotated miRNAs and siRNAs with stage- and gender- biased expression. Our findings would facilitate to understand the gene regulation mechanism of this parasite and discover novel targets for anti-parasite drugs

Advances in intensity-modulated radiotherapy delivery.

Fixed-field intensity-modulated treatments, delivered by conventional linac-plus-multileaf systems, have rapidly become the most common form of IMRT. Several innovative alternative IMRT options are also now available, including tomotherapy, CyberKnife and jaws-only linacs. These innovative approaches have divergent rationales. Jaws-only IMRT is being developed because it allows treatments to be delivered using conventional linacs without expensive multileaf collimators and not because it improves dose distributions. On the other hand, tomotherapy and CyberKnife systems have different geometric degrees of freedom, beam sizes and modulation techniques than those of conventional linacs, which may enable these innovative systems to deliver superior dose distributions to some treatment sites. Because conventional linacs are themselves finely honed machines, enhancement of one aspect of machine performance is sometimes accompanied by diminution of another. For example, tomotherapy systems possess an enhanced rotational IMRT capability but currently can only deliver coplanar radiation beams. Thus the various delivery systems may prove optimal for different types of treatments, specific machine designs excelling for specific disease sites. In practice, of course, IMRT delivery systems will be distinguished not just by the quality of the dose distributions they deliver but also by factors not discussed in this chapter, such as the efficiency of their treatment process, the integration of on-board imaging into that process, and their ability to measure, minimise and compensate for the effects of respiratory motion, a major detriment to accurate IMRT delivery