The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?

Tissue factor, a 47 kDa membrane glycoprotein, lies at the basis of the extrinsic pathway of the coagulation cascade. Interaction of TF with factor VIIa results in the formation of fibrin from fibrinogen, thereby inducing the formation of a blood clot. In addition to this well-established role in blood coagulation, TF is associated with various other physiological processes such as sepsis, inflammation, angiogenesis, metastasis and atherosclerosis. The molecular basis of the latter events is slowly emerging. It has become clear that TF-FVIIa interaction elicits a variety of intracellular signalling events that may be implicated in these actions. These events include the sequential activation of Src-like kinases, MAP kinases, small GTPases and calcium signalling. How this progress in the understanding of TF associated signal transduction may generate answers as to the mechanism through which TF exerts it pleiotropic effects will be focus of this review.     

Postoperative treatment and prognosis of patients with resected single brain metastasis: how useful are established prognostic scores?

Objective

To evaluate postoperative prognosis and the performance of known prognostic scores in patients treated with surgical resection for single brain metastasis.

Methods

We evaluated prognostic factors and five previously published prognostic scores in a group of 74 patients with single brain metastasis treated with surgery with or without immediate whole-brain radiotherapy (WBRT).

Results

In multivariate analysis, good performance status, absence of extracranial metastases and primary tumor control were significantly associated with improved overall survival. Survival (median 10.8 months) was not significantly prolonged by immediate WBRT. Salvage treatment was necessary in 87% of patients without immediate WBRT. All five scores identified groups of patients with superior prognosis. The recursive partitioning analysis (RPA) classes, the graded prognostic assessment (GPA) score and the score developed by Rades et al. identified a poor prognosis group, but the numbers of poor prognosis patients were very small.

Conclusions

RPA and GPA appear to have the most utility in delineating exceptionally good or poor prognosis patients after resection of single brain metastasis, but this finding remains to be validated in a larger study population. Identification and validation of suitable prognostic scores hopefully will guide decision making regarding local treatment of solitary brain metastasis.     

What's in a smile?: Quantification of the vertical smile of patients with myasthenia gravis

Many patients with myasthenia gravis who experience bulbar symptoms show a vertical smile, which may have a considerable, and often underestimated, impact on social life. Peri-oral muscle function can be quantified by calculating lip-length and snout indices, which indicate the degree to which a person is capable of smiling and of pursing the lips, respectively. In the present study patients with bulbar myasthenia gravis were compared to patients with ocular myasthenia gravis, patients now in remission (but previously suffering from bulbar myasthenia gravis), and healthy subjects. The lip-length and snout indices of patients with bulbar myasthenia gravis were significantly lower than those of the other groups. The facial impairments were no longer detectable in patients with bulbar myasthenia gravis in remission and no subclinical impairments in lip-length and snout indices were found in the ocular myasthenia gravis group. These findings were consistent with the patients' reports of impairment of smiling and other oral functions. The patients suffering from a vertical smile or other oral impairments were well aware of their condition, most probably because of the social consequences of being unable to smile. The indices could be of importance in the longitudinal evaluation of therapy in individual patients and in pharmacotherapeutical research. We found a low correlation between the lip-length and snout indices, which reflects the capricious pattern of involvement of separate muscles in myasthenia gravis. Therefore both indices deserve special attention if they are used for monitoring myasthenic symptoms.     

The Internet: home to a severe population of individuals with social anxiety disorder?

The current study sought to understand better the psychological characteristics of socially anxious individuals who seek information on the internet about social anxiety disorder and its treatment. Participants were 434 individuals who responded to an internet-based survey linked to the website of an anxiety specialty clinic. Using established cut-off scores, 92% of the sample met criteria for social anxiety disorder. Internet survey respondents who met these criteria reported greater severity of and impairment due to social anxiety than a treatment-seeking sample of persons with social anxiety disorder. Nevertheless, only about one-third of these internet respondents reported having received psychotherapy, and a similar percentage reported having received pharmacotherapy. Those with the most severe social interaction anxiety and who spent the most time interacting on the internet endorsed positive effects of internet use. However, a significant number of negative effects also were endorsed.     

Intensive case management for severe psychotic illness: is there a general benefit for patients with complex needs?

The UK700 trial failed to demonstrate an overall benefit of intensive case management (ICM) in patients with severe psychotic illness. This does not discount a benefit for particular subgroups, and evidence of a benefit of ICM for patients of borderline intelligence has been presented. The aim of this study is to investigate whether this effect is part of a general benefit for patients with severe psychosis complicated by additional needs. In the UK700 trial patients with severe psychosis were randomly allocated to ICM or standard case management. For each patient group with complex needs the effect of ICM is compared with that in the rest of the study cohort. Outcome measures are days spent in psychiatric hospital and the admission and discharge rates. ICM may be of benefit to patients with severe psychosis complicated by borderline intelligence or depression, but may cause patients using illicit drugs to spend more time in hospital. There was no convincing evidence of an effect of ICM in a further seven patient groups. ICM is not of general benefit to patients with severe psychosis complicated by additional needs. The benefit of ICM for patients with borderline intelligence is an isolated effect which should be interpreted cautiously until further data are available.     

Glyphosate-based herbicide: a risk factor for demyelinating conditions of the peripheral nervous system?

<正>Glyphosateisabroad-spectrumherbicideoriginallyintroducedto themarketin1974bytheagrochemicalcompanyMonsanto.More than 40 years down the line, glyphosate has become one of the most economically meaningful herbicides, with a global use of more than1.8 million pounds in 2014 (Benbrook, 2016). In non resistant plants,     

Neuronal mdr-1 gene expression after experimental focal hypoxia: a new obstacle for neuroprotection?

Neuronal damage after stroke-associated brain hypoxia is a leading cause of long-term disability and death. The refractoriness to therapeutic strategies for neuroprotection after 3 h post brain ischemia is poorly understood. P-glycoprotein (P-gp), the multidrug resistance gene (MDR-1) product is normally expressed at blood-brain-barrier. P-gp neuronal expression has been demonstrated in refractory epilepsy and after brain ischemia. In this report we investigated the hypoxia-induced neuronal P-gp expression after local injection of CoCl(2) (1-200 mM) in the fronto-parietal cortex of male adult rats (Bregma -1.30 mm) by stereotaxic surgery. P-gp immunostaining of brain slides was analyzed using specific monoclonal antibodies and double immunolabeling was done with specific astrocytic and neuronal markers. Five days after injection of 1 mM CoCl(2), P-gp expression surrounding the lesion site was observed in neurons, astrocytic end-foot on capillary blood vessels and endothelial cells on blood vessels. Higher CoCl(2) doses (200 mM) resulted in additional P-gp immunostaining of the entire astrocytic and neuronal cytoplasm. Electron microscopy (EM) studies showed alterations in neurons as early as 6 h after the CoCl(2) injection. P-gp expression in hypoxic neurons and astrocytic end-foot could potentially impair of drugs access to the brain parenchyma thus suggesting the presence of two P-gp-based pumping systems (one in astrocytes and other in the hypoxic neurons) that are able to behave as a previously unnoticed obstacle for pharmacological strategies of neuroprotection.     

Schizophrenic psychosis: a contraindication for treatment of hepatitis C with interferon alpha?

Depressive or psychotic symptoms are a well known side-effect of interferon alpha (INF-alpha). Therefore, the questions arises whether a chronic psychosis should be considered a contraindication for the treatment of active hepatitis C with INF-alpha. We report on a 38-year-old woman with a chronic schizophrenic psychosis, who acquired chronic aggressive hepatitis C. Considering the young age of the woman, the potential risk of developing a hepatocellular carcinoma and the result of the liver biopsy, treatment with interferon alpha 2 b (3x5 million IU/week) was started. The patient was seen three times a week, her psychiatric condition was monitored using the positive and negative symptoms score (PANSS). No signs of psychotic or depressive symptoms appeared during INF-alpha therapy. During the first 6 months the liver enzymes dropped slowly but the virus load was increasing. After adding ribavirin to the therapy, the liver enzymes dropped again, and the PCR carried out 9 months after initiation and 6 months after the end of the 12 months INF-alpha treatment did not detect any virus RNA. This positive result should encourage prospective studies including patients with these two diagnoses on whether patients benefit from INF-alpha.     

Reasons for adolescent deliberate self-harm: a cry of pain and/or a cry for help?

The present study examines reasons for adolescent deliberate self-harm. A cross-sectional survey using an anonymous self-report questionnaire was carried out in seven countries (Australia, Belgium, England, Hungary, Ireland, the Netherlands and Norway). Data on 30,477 school pupils between the ages of 14–17 were analysed. Past year and lifetime deliberate self-harm were assessed, along with the self-reported reasons for deliberate self-harm. The results showed that ‘wanted to get relief from a terrible state of mind’ and ‘wanted to die’ were most commonly reported. Principal component analysis indicated two underlying dimensions in the reasons for deliberate self-harm, i.e. a cry of pain motive and/or a cry for help motive. The majority of self-harmers reported at least one cry of pain motive (‘to die’, ‘to punish myself’, and ‘to get relief from a terrible state of mind’) and an additional cry for help motive (‘to show how desperate I was feeling’, to frighten someone’, ‘to get my own back on someone’, ‘to find out whether someone really loved me’, and ‘to get some attention’). Females reported more reasons than males. Only females showed an age difference, with girls aged 16–17 more frequently reporting a cry for help motive. There was considerable consistency in choice of motives across countries and genders. Systematic assessment of the reasons for deliberate self-harm can help clinicians to better understand the meaning of self harming behaviour, select appropriate treatment, suggest alternative coping strategies, and hopefully prevent future suicidal behaviour.