Impaired motor imagery in patients with essential tremor: a case control study.

Motor imagery (MI), which refers to the process of mental representation of movements, has not been studied in patients with essential tremor (ET). We investigated the presence of impaired MI in ET patients compared with healthy controls. A group of drug-naive and nondemented ET patients and age-matched controls were studied using transcranial magnetic stimulation, while they were specifically instructed to try and imagine themselves performing two motor tasks. The various clinical and electrophysiological variables were evaluated and compared. Repeated measures ANOVA demonstrated a significant difference between ET patients and controls with respect to mean motor-evoked potential (MEP) amplitudes (F(1,38) = 31.92, P < 0.005) during MI. The process of MI effectively facilitated MEP amplitude in controls but not in ET patients, regardless of side of stimulation or motor tasks. We provide evidence to demonstrate impairment of MI in a group of ET patients compared with healthy controls. The basis for this novel finding is unclear, and further studies are warranted to determine whether it is related to cerebellar or motor cortical dysfunction.     

CD44v6和组织蛋白酶D表达与食管癌预后的关系

目的　研究CD4 4v6和组织蛋白酶D(cathepsinD ,CD)表达与食管癌生物学行为的关系。方法　应用免疫组化法 ,检测 6 5例食管鳞状细胞癌组织中CD4 4v6和CD表达水平。结果　在食管癌中CD4 4v6和CD表达阳性率分别为 5 8.5 %和 6 4 .6 %。CD4 4v6和CD表达均与肿瘤分级、浸润、淋巴结转移和预后相关。结论　CD4 4v6和CD异常表达与食管癌的病理生物学行为密切相关 ,可作为是预测食管癌转移潜能和评估食管癌预后的客观指标     

Hippocampal EEG responses induced by carbachol and atropine infusions into the septum and the hippocampus in the urethane-anaesthetized rat

Infusion of 1 μg of carbachol, a potent cholinergic agonist, into the lateral septum of the urethane-anaesthetized rat systematically caused the induction of clear-cut hippocampal theta (θ). However, infusion of an equivalent amount of the drug into the hippocampus, close to the recording electrode, failed to induce θ in 50% of the animals and produced a mixture of θ waves and desynchronized activity, resulting in atypical EEG patterns, in the remaining subjects. Both carbachol EEG effects were blocked by intraseptal infusion of the antimuscarinic agent, atropine. Our data demontrate that muscarinic receptors in the septum are predominent sites for cholinergic agonist-antagonist action capable of generating or suppressing hippocampal θ in the rat. They also indicate that intraseptal cholinergic mechanisms play an important role in the initiation and generation of this rhythm.     

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.     

Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

1 Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia.
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30  mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL C _max 59  nmol l⁻¹ and AUC (0, t h) 144  nmol l⁻¹h, mean MDL C _max 183  nmol l⁻¹ and AUC 2627  nmol l⁻¹h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL C _max 356  nmol l⁻¹ and AUC 10512  nmol l⁻¹h, MDL concentrations below limit of quantitation).
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.     

Increase in levels of total free fatty acids in rat brain regions following 3-nitropropionic acid administration

Acute exposure to a neurotoxin, 3-nitropropionic acid (3-NPA), in rats results in an increase in total free fatty acid (FFA) concentration in selective brain regions. We investigated the effect of 3-NPA administration on the cerebral concentrations of FFA used as a marker of oxidative stress. Rats (n=3/group) were dosed subcutaneously (s.c.) either with a vehicle (phosphate buffer) or 3-NPA in phosphate buffer at 30 mg/kg body weight. Animals were sacrificed after 1, 2, 3, and 6 h of injection. Brains were then dissected into frontal cortex (FC), caudate nucleus (CN), and hippocampus (HIP). The concentration of total FFA increased from 130 to 300% within 1–2 h after 3-NPA injection in all brain regions when compared with the baseline level obtained from the control rats and taken as 100%. In CN, FFA returned to the baseline level within 3 h of treatment. However, in FC and HIP the concentration of FFA remained significantly elevated above the baseline until 6 h. The released FFA provide a substrate for free radicals formation. The results of this study suggest a role of oxidative stress in the mechanism of 3-NPA toxicity.     

To market! To market! A new dawn for community care?

The public sector in Britain has been subjected to over a decade of major reform aimed at breaking up public service monopolies, at containing costs while at the same time opening services up to greater consumer choice. Health and social services have not been exempt from this revolution in the organization and management of public sector services. The long-standing policy of care in the community is being subjected to market principles and the introduction of a ‘contract culture’ very similar to the NHS reforms introduced in 1991. This paper reviews the origins of these developments in the doctrines of ‘new public management’, a movement which has proved attractive to policy-makers in many countries. Local authority social services departments have been identified as the lead agency for the development of a mixed economy of care following a review of community care policy by the government's health adviser, Sir Roy Griffiths, and a subsequent white paper. This paper examines the limited empirical evidence available on how managers and providers are meeting the challenge bestowed upon them, and concludes that most authorities are moving ahead cautiously if at all. Only a handful of authorities studied have embraced the reforms with any degree of enthusiasm. The paper concludes with an assessment of the reforms from two perspectives: a pessimistic one and an optimistic one. There are many worrying features of the reforms, not least among these being a lack of clarity over their intended purpose. Tensions and contradictions are plentiful, which places in jeopardy the certainty of the reforms in becoming user led rather than provider driven. A more optimistic scenario is that the changes are leading to a loosening up of services and practices which have often suffered from sclerotic tendencies, paternalism and sometimes complacency. If the reform process is skilfully handled and not rushed and if the ends are clearly established and communicated then users and carers could prove to be the principal beneficiaries.     

Health policy, epidemiology and power: the interest web

The relation between epidemiological research results and policy-making is reviewed. Apparently, traditional models of policy-making(incrementalism, mixed scanning synoptic planning) do not explainwhy research findings are hardly used in policy-making procedures. It is suggested that this phenomenon is related to three determinantsof policy-making: (i) a bias stemming from sets of causal, finaland normative assumptions and presuppositions; (ii) interestwebs of groups in certain domains; and (iii) the power of organizationsto monitor and communicate. The conclusion is that epidemiologistsshould engage in the policy-making process more consciouslyand conscientiously.     

固体硅胶隆鼻术后感染排异的原因与预防探讨

感染及排异是固体硅胶隆鼻术较为严重的并发症。其发生原因主要在于手术适应证掌握不当；硅胶假体的质量不过关，假体的修雕成形不佳，假体消毒处理不严；手术操作及术后处理欠妥等。提出了加强术前体检及适应证的掌握，选择质量过关的硅胶假体，努力提高术者的审美及专业技术水平，设计修雕成形出恰当的假体，并注意规范假体的消毒处理，这都可有效减少感染及排异并发症的发生。强调手术操作时尽量减少局部组织的损伤，勿剥破鼻部的皮肤及粘膜，并做好术后的处理及护理，这同样也是减少感染排异并发症的关键。