The mode of action of sumatriptan is vascular? A debate

Two mechanisms have been proposed to explain the primary mode of action of sumatriptan: vasoconstriction, and trigeminal nerve terminal inhibition. Sumatriptan is a potent vasoconstrictor of intracranial arteries. It has been shown to increase blood flow velocity in large intracranial arteries in man in a dose-dependent fashion both during and between migraine attacks. Since the vasoconstrictor response of sumatriptan is reproducible outside the migraine attack, this action appears to be a direct vascular effect and not indirectly mediated via neural mechanisms. Sumatriptan also causes rapid constriction of dural and meningeal vessels in vivo. It does not modify cerebral blood flow but does constrict arteriovenous anastamoses that may be dilated during a migraine attack. This evidence suggests that sumatriptan has a direct, dose-related, vasoconstrictor action on certain intracranial blood vessels that correlates with its antimigraine activity. Alternatively, sumatriptan may act directly on the trigeminal sensory nerve terminals within the cranial blood vessel, inhibiting the release of sensory neuropeptides. Experimental data from animal studies have shown that following electrical stimulation of the trigeminal ganglion there is a neurogenic inflammatory response with plasma protein extravasation from dural blood vessels. This response can be significantly reduced by sumatriptan at a dose level similar to that used in clinical treatment. This finding is further supported by the clinical observation that sumatriptan reduces the plasma levels of calcitonin gene-related peptide which are raised during a migraine attack.     

Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice

Introduction  

Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which frequently develops in models of VILI, should be prevented. To study VILI in healthy mice, the authors used a MV model with clinically relevant ventilator settings, avoiding massive damage of lung structures and shock, and preventing metabolic acidosis.     

Young children's use of a visual aid: an experimental study of the effectiveness of training

We report an experiment concerning the use of a stand magnifier by young children with visual impairments (21 males, 12 females; mean age 4y 8mo [SD 11mo]). Children had a normative developmental level and a visual acuity of 0.4 or less (≤20/50 in Snellen's notation). To measure magnifier use objectively, we developed a task that closely resembled the dynamics of its real-life (pre-reading) use. Children had to follow trails visually, from a start location to an unseen end location. This could only be done successfully and reliably by proper use of the magnifier. In addition to this, we analyzed the effect of specific training with the magnifier by using a repeated-measures (before and after training) matched-groups (with respect to age and near-visual acuity) design. Results established both the task's efficacy as an instrument for measuring magnifier use in young children and the effectiveness of the training. Improvement in task performance after training was found in both groups, except for the youngest children (<3y 6mo). On average, 1.8 times as many paths were followed in both groups after training ( p =0.001). The without-magnifier training group became 2.5 times as good at finding the correct end location, whereas the with-magnifier training group became 4.3 times as good ( p =0.05).     

Correction: Ethnic differences in BMI among Dutch adolescents: what is the role of screen viewing, active commuting to school, and consumption of soft drinks and high-caloric snacks?

Background  

The threats posed by the rising prevalence of overweight and obesity on public health have been widely acknowledged. Several population groups, which deserve special attention because of their higher prevalence rates, have been identified. These include adolescents and ethnic sub-groups. The aim of the present study was twofold: (1) to assess ethnic differences in body mass index (BMI) and in behaviours that are related to both energy intake and energy expenditure, and (2) to examine whether these behaviours explain the relationship between ethnicity and BMI.     

Molecular markers for detection, surveillance and prognostication of bladder cancer

Many markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular markers for detection, prognostication and surveillance. The purpose of this review is to highlight the most important urinary molecular biomarker developments that have been studied and reported recently. In the current review we have summarized the most recent and relevant published reports on molecular urinary markers. The results of this review show that the first generation of urinary markers did not add much to urinary cytology. The current generation of markers is better, but additional clinical trials are needed. Our knowledge of molecular pathways in bladder cancer is growing and new methods of marker development emerge, but the perfect marker is still to be found. Currently, there are not clinically usable molecular markers that can guide us in diagnosis or surveillance, nor guide us in lowering the frequency of urethrocystoscopy in bladder cancer.     

二甲双胍在癌症治疗中的益处

双胍类降糖药物的历史 二甲双胍、苯乙双胍和丁双胍是植物山羊豆提取物(又叫法国紫丁花、山羊豆),起初用于治疗高血糖和2型糖尿病.将法国紫丁花当茶饮可追溯到古埃及和中世纪的欧洲,可起到缓解多尿和口臭(呼气中有甜味)的作用,而多尿和口臭均是现在大家熟悉的糖尿病症状.20世纪20年代的研究发现,双胍类是法国紫丁花中的活性物质,并进而在20世纪50年代开发用于治疗糖尿病.     

The dimensional structure of the functional abilities in cases of long-term sickness absence

Background  

The health problems that working people suffer can affect their functional abilities and, consequently, can cause a mismatch between those abilities and the demands of the work, leading to sickness absence. A lasting decrease in functional abilities can lead to long-term sickness absence and work disability, with negative consequences for both the worker and the larger society. The objective of this study was to identify common disability characteristics among large groups of long-term sick-listed and disabled employees.     

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests

Background

We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer.

Methods

545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing.

Results

The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%.

Conclusion

No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.