Why study transport of peptides and proteins at the neurovascular interface

The blood–brain barrier (BBB) is an immense neurovascular interface. In neurodegenerative, ischemic, and traumatic disorders of the central nervous system (CNS), the BBB may hinder the delivery of many therapeutic peptides and proteins to the brain and spinal cord. Fortunately, the mistaken dogma that peptides and proteins do not cross the BBB has been corrected during the past two decades by the accumulating evidence that peptides and proteins in the periphery exert potent effects in the CNS. Not only can peptides and proteins serve as carriers for selective therapeutic agents, but they themselves may directly cross the BBB after delivery into the bloodstream. Their passage may be mediated by simple diffusion or specific transport, both of which can be affected by interactions in the blood compartment (outside the BBB) and within the endothelial cells (at the BBB level). Although the majority of current delivery strategies focuses on modification of the molecule to be delivered, understanding the mechanisms of transport will eventually facilitate regulation of the BBB directly. We review the different aspects of interactions and discuss recent advances in the cell biology of peptide/protein transport across the BBB. Better understanding of the nature and regulation of the transport systems at the BBB will provide a new direction to enhance the interactions of peripheral peptides and proteins with the CNS.     

Safe anesthesia for endoscopic laryngeal laser surgery

Anesthesia safety for endoscopic laryngeal laser surgery has been a major limiting factor for laser applications in the larynx and the hypopharynx. Several anesthesia techniques have been proposed and each technique appears to have its own limitations. This paper will deal with the distinct advantages offered by the malleable copper tube which is used for delivery of the open Venturi system anesthesia for endoscopic laser surgery. A retrospective study of 100 patients who have undergone this modality of anesthesia at our institution will be presented. Our conclusion from this study shows clearly the superiority of the copper tube over the conventional aluminium-foil-wrapped endotracheal tube in safety and the exposure of the larynx during surgery.     

Postgraduate qualifications of British doctors

Among British-qualified doctors of 1974 and 1977, about 80% held postgraduate qualifications of some kind. The commonest qualifications were DRCOG, MRCP and MRCOG. There were considerable differences between medical schools in the numbers of qualifiers taking various examinations. Apart from the MRC Psych, DRCOG and Family Planning Certificate, qualifications were more commonly held by men than women. Tables show the type of work being done 9-13 years after leaving medical school by holders of various postgraduate qualifications; e.g. 60% of MRCP holders were working in medicine or a medical specialty and 84% of FRCS holders in general surgery or a surgical specialty. Discussion deals with the plurality, specificity, variability, perceived necessity, sufficiency, international utility and career significance of British postgraduate qualifications.     

MANAGEMENT OF UNCONTROLLED GLAUCOMA WITH THE MOLTENO SYSTEM

In glaucomatous eyes refractory to medication, laser techniques and conventional drainage surgery, intraocular pressure is often high, and visual loss rapid. In this situation a reliable, robust artificial outflow system is required. Molteno has evolved a plastic tube and plate device combined with a fibrosis suppression medication regimen. Thirty-eight eyes of 32 patients with uncontrolled glaucoma were treated with the Molteno system. Six months after operation mean intraocular pressure had been reduced from 41.0 ± 13.6 to 16.2 ± 5.6 mmHg. Eighteen eyes had pressures of 20 mmHg or less on no hypotensive therapy, 17 on reduced treatment. Three eyes had a pressure of 21 to 35 mmHg on treatment at six months. The 13 aphakic eyes responded as well as 25 phakic eyes. Five eyes with rubeotic glaucoma demonstrated pressures of less than 20 mmHg without therapy, four eyes with traumatic glaucoma required continuing medication with three having pressures below 22 mmHg. Of the seven eyes with uveitic glaucoma, one was lost, two required maintenance therapy; five of six surviving eyes had pressures below 20 mmHg. Fifteen eyes with congenital or juvenile glaucoma achieved pressures below 20 mmHg, three of these with timolol drops, three with timolol and acetazolamide, and nine with no treatment. While seven of seven eyes with refractory primary open-angle glaucoma attained pressures below 20 mmHg. all seven needed continuing mild hypotensive therapy. Eleven eyes underwent a one-stage procedure, while 27 eyes required a two-stage operation. Twenty-eight eyes received fibrosis suppression medication after the second stage, and 24 maintained or improved their preoperative visual acuity. Results have been encouraging: in general the Molteno system is recommended as the second drainage operation in all glaucomatous eyes in which conventional therapy has failed, and as the primary surgical procedure (after laser techniques) in eyes with rubeotic and uveitic glaucoma. Ciliary body destructive procedures should be restricted to control of symptoms in blind eyes.     

Effects of self-management training in Type 2 diabetes: a randomized, prospective trial.

AIMS: The efficacy of three education programmes for Type 2 diabetic patients was tested in a randomized trial. A didactic-oriented training programme (treatment A) was compared with a self-management-oriented programme delivered in group sessions (treatment B). The latter programme was compared with a more individualized approach (treatment C). METHODS: One hundred and eighty-one Type 2 diabetic patients (age 55.6 +/- 6.3 years, diabetes duration 6.6 +/- 6.2 years, HbA(1c) 7.8 +/- 1.6%, female 49.7%) took part. Efficacy was assessed 3 months (t1) after baseline (t0) and at a follow-up 15 months (t2) after baseline. RESULTS: The fall in HbA(1c) in treatment B at t1 was sustained at t2 (t0 8.1 +/- 1.8%, t1 7.3 +/- 1.7%, t2 7.4 +/- 1.9%). In treatment A, HbA(1c) was unchanged throughout (t0 7.6 +/- 1.5%, t1 7.5 +/- 1.3%, t2 7.7 +/- 1.7%; treatment A vs. treatment B; P < 0.05). With the more individualized approach of treatment C, there was a fall in HbA(1c) at t1, but this was not sustained at t2 (t0 7.8 +/- 1.6%, t1 7.1 +/- 1.3%, t2 7.6 +/- 1.6%; treatment B vs. treatment C; P = 0.73). There were also significant benefits in treatment B subjects compared with treatment A in further medical (body mass index and fasting blood glucose), psychological (control, irritability and hunger dependency of eating behaviour, and trait anxiety) and behavioural (exercise) variables. There were no significant benefits of the more individualized treatment C compared with group treatment B. No significant differences were found regarding triglyceride levels, high-density lipoprotein, diabetes-related knowledge, negative well-being, urine or blood glucose levels or foot care. CONCLUSION: Self-management training had a significantly higher medium-term efficacy than didactic diabetes education. The group sessions were more effective than a more individualized approach.     

Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.     

The outcome of ganglion clipping in hyperhidrosis and blushing

A total of 114 patients with various sympathetic disorders underwent endoscopic sympathetic block over different thoracic ganglions by the clipping method. The advantages of this method include the recognition of the clipped level, changeability, and reversibility. However, 4.4% of patients were unilaterally clipped at the wrong level.     

TUVP手术时间对血红蛋白及电解质的影响

目的 了解经尿道前列腺汽化电切手术时间对血红蛋白及血清电解质的影响。方法 对64例经尿道前列腺汽化电切术患按手术时间分组，观察手术前后血红蛋白及血清电解质的变化。结果 手术时间对血清电解质的降低有的影响，对血红蛋白降低的影响不显。结论 减少TUR综合征的关键是要操作熟练，缩短手术时间及手术中注意止血。     

Family Stress and Functioning in Children: the Moderating Effects of Children''s Beliefs About Their Control Over Parental Conflict

While factors such as gender and SES have been studied as moderators of stress for children, their perceptions of control have received little attention. In the current study, children's domain-specific perceptions of their control during marital conflict were investigated as potential moderators of the impact of family stress on children's behavior problems, and perceptions of competence. Ninety-four children aged 6-12 years and mothers from families ranging in level of parental conflict from nondiscordant to discordant to physically violent were interviewed. Multiple regression analyses revealed that higher levels of conflict control beliefs acted as compensatory moderators of stress, being associated with lower levels of problem behaviors across stress levels. However, higher conflict control beliefs acted as vulnerability moderators with regard to children's perceptions of competence.