Estimates of the net excitatory currents evoked by visual stimulation of identified neurons in cat visual cortex

The action potential discharge response of single neurons to both visual stimulation and injections of current were obtained during intracellular recordings in cat visual cortex in order to estimate the net excitatory current arriving at the soma during visual stimulation. Of 45 neurons recorded intracellularly, 19 pyramidal neurons and one basket cell were labelled with horseradish peroxidase. The discharge of all neurons adapted to constant current. For 40 neurons, a single exponential provided a good fit to the adapting discharge (r2 = 0.73 +/- 0.03) for all current intensities. Superficial layer neurons were significantly faster adapting [P < 0.001, mean (+/- SEM) time constant of adaptation = 11.5 +/- 1.3 ms; n = 20] than deep layer neurons (mean time constant of adaptation = 51.4 +/- 6.4 ms; n = 10). The percentage adaptation of the spike frequency, %(peak - adapted rate)/peak, was determined from the fitted exponential. Superficial layer neurons adapted significantly more strongly (P < 0.01, mean = 67 +/- 3%) than deep layer neurons (mean = 51 +/- 5%). The mean firing frequency in response to a current step of 320 ms duration had a linear relationship to the amplitude of the injected current (slope 66 spikes/s/nA; origin zero, mean r2 = 0.94; n = 33). This relationship provided a means of estimating the net peak excitatory current generated by visual stimuli. The estimated mean peak somatic current during the passage of a bar across the receptive field was 1.1 nA and the average current for the duration of the visually evoked discharge was 0.64 nA (n = 17). The transfer response of real and model neurons was obtained by differentiating the discharge response to a step input current and was then used to predict the output of the neuron following an arbitrary input. When these transfer responses were convolved with known input signals in model neurons, the predicted output was close to the simulated response of the model neuron to the same input waveforms. The transfer response was calculated for eight real neurons. Estimates of the net excitatory current arriving at the soma during visual stimulation was obtained by deconvolution. The mean peak somatic current for these neurons was 0.62 nA.      

Feasibility and cost of treatment with drug eluting stents of surgical candidates with multi-vessel coronary disease.

OBJECTIVE: To determine the feasibility and cost of treatment with drug eluting stents in patients with multi-vessel coronary disease referred currently for surgical revascularisation. METHODS: Two experienced interventional cardiologists reviewed retrospectively the clinical records and pre-operative coronary angiograms of 209 patients who underwent their first coronary bypass operation for multi-vessel disease without other adjunctive surgical procedures at the Royal Brompton Hospital in 2002. They were classified according to the technical feasibility and completeness of percutaneous revascularisation. A cost decision-analysis model with a cost of drug eluting stents of euro 2,100 and simulated 1-year costs was constructed. RESULTS: Mean age was 64.6+/-8.9 years with 54 diabetics (25.8%). Each patient received at least 1 arterial graft and a mean of 3.0+/-0.8 distal anastomoses. Mean post-operative stay was 8.9+/-7.2 days and total cost euro 19,821+/-1,964. Percutaneous revascularisation was judged to be feasible in 158 (76%) cases. The contraindications were at least 1 unfavourable total occlusion subtending viable myocardium in 48 patients (23%) and extreme tortuosity or calcification in 4 patients (2%). Percutaneous revascularisation of grafted major epicardial vessels was anticipated to be complete in 138 (66%) patients and partial but acceptable in 19 (9.1%) patients. Stenting of the left main, of a 'favourable' total occlusion, of bifurcations or in an ostial location would have been required in 32 (20.4%), 60 (38.2%), 77 (49.0%) and 74 (47.1%), respectively, of cases treated. 3.6+/-1.4 drug eluting stents of total length 72.6+/-37.3 mm were required to treat 3.3+/-1.2 lesions per patient at an estimated cost of euro 17,266+/-2,850. When one year repeat revascularisation was modelled at a rate of 15% in the stent group there was no significant cost saving from stenting. CONCLUSIONS: Although percutaneous revascularisation is feasible in 76% of patients currently undergoing coronary artery bypass grafting for multi-vessel disease, such an approach will involve frequent treatment of complex lesions for which no long term results are available and is unlikely to provide appreciable economic savings.     

Squamous cell carcinoma secondary to recessive dystrophic epidermolysis bullosa: report of eight tumours in four patients

BACKGROUND: The development of squamous cell carcinomas is the main cause of death of patients with Dystrophic epidermolysis bullosa. We think it is of interest to know their clinical characteristics and the treatment difficulties they cause. METHODS: We followed the clinical evolutions and carried out histopathological studies of eight primary cutaneous squamous cell carcinomas on three males and one female with recessive dystrophic epidermolysis bullosa. Patient ages ranged from 16 to 34 years (mean 27). RESULTS: Two patients had two tumours and one three, all were in characteristically scarred skin; four on upper limbs; four on lower. Maximum tumour dimensions ranged from 2 to 28 cm (mean 13), and represented 6 or more months of evolution. In three cases the affected limb must be amputated. Five tumours were well differentiated, three were moderately differentiated. CONCLUSIONS: The patients consulted too late and their large lesions needed aggressive treatment. Appropriate information and regular examination of patients with RDEB helps early diagnosis of tumours and may avoid disabling operations.     

Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in female rats and their pups at dietary doses

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary carcinogen in female rats and is present in a wide variety of cooked meats. We address here the excretion of PhIP and its metabolites into the breast-milk of lactating rats and the ability of chlorophyllin, a food product derivative with chemopreventive properties, to affect these levels at low PhIP doses. Lactating female F344 rats with suckling pups were orally administered 50, 500 and 1000 ng [14C]PhIP/kg body weight. The excretion of the [14C]PhIP into milk and its distribution among the mammary tissue, liver and blood of the dam, as well as among stomach contents and liver of their suckling pups was measured using accelerator mass spectrometry (AMS). PhIP, PhIP-4'- sulfate, 4'-hydroxy-PhIP, and N2-hydroxy-PhIP-N3-glucuronide were found in the milk at all doses. The chlorophyllin (500 microg/kg) co- administration with PhIP (500 ng/kg) caused increased levels of [14C]PhIP in the milk (32%) and stomach contents (35%) of the pups relative to the animals not receiving chlorophyllin at these low PhIP doses. In contrast, lower [14C]PhIP levels in the chlorophyllin treated animals were observed in the blood (47%) and mammary tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared to the animals receiving only PhIP. Chlorophyllin co-administration resulted in an increased amount of N2-hydroxy-PhIP-N3-glucuronide (42%), increased PhIP (79%) and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not receiving chlorophyllin. These results suggest that PhIP and PhIP metabolites are present in the breast-milk of lactating rats at human dietary PhIP exposures and that PhIP is absorbed by the newborn. Furthermore, these results suggest that other dietary components can affect the dosimetry of PhIP in breast-feeding offspring.      

Incidental finding of meningioma on bone scintigraphy

An incidental finding of an intracranial posterior fossa meningioma detected by bone scintigraphy is presented. Most of the published literature on the diagnosis of meningioma is on the use of CT and MRI. There is limited published literature on the detection of meningioma with bone scintigraphy.     

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Symptomatic calcific stenosis of a Toronto stentless porcine valve

We describe the calcific structural failure of a Toronto stentless porcine valve (TSPV) which had been used to replace a calcified bicuspid aortic valve in a 46-year-old man. Against expectations, left ventricular hypertrophy persisted and the transvalvular pressure gradient rose to 125 mmHg by 6 years with the patient becoming symptomatic and requiring redo surgery. On removal the TSPV showed atypical calcification of the leaflet hinges and wall. To our knowledge this is the first case reported and it may have implications for long term durability and future surgery using this prosthesis.     

Objective assessment of technical skills in cardiac surgery.

OBJECTIVE: Reduced training time combined with no rigorous assessment for technical skills makes it difficult for trainees to monitor their competence. We have developed an objective bench-top assessment of technical skills at a level commensurate with a junior registrar in cardiac surgery. METHODS: Forty cardiothoracic surgeons were recruited for the study, consisting of 12 junior trainees (year 1-3), 15 senior trainees (year 4-6) and 13 consultants. The assessment consisted of four key tasks on standardised bench-top models: aortic root cannulation, vein-graft to aorta anastomosis, vein-graft to Left Anterior Descending (LAD) anastomosis and femoral triangle dissection. An expert surgeon was present at each station to provide passive assistance and rate performance on a validated global rating scale giving rise to a total possible score of 40. Three expert surgeons repeated the ratings retrospectively, using blinded video recordings. Data analysis employed non-parametric tests. RESULTS: Both live and video scores differentiated significantly between performances of all groups of surgeons for all four stations (P < 0.01) (median live and video score for LAD; Junior 19,17; Senior 29,22; Consultant 36,28). Correlations between live and blinded rating were high (r = 0.67-0.84; P < 0.001) as was inter-rater reliability between the three expert video raters (alpha = 0.81). CONCLUSIONS: The use of bench-top tasks to differentiate between cardiac surgeons of differing technical abilities has been validated for the first time. Furthermore, it is unnecessary to perform post-hoc video rating to obtain objective data. These measures can provide formative feedback for surgeons-in-training and lead to the development of a competency-based technical skills curriculum.