Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas.

BACKGROUND: As a step towards clinical use of AAV-mediated gene therapy, brains of large animals are used to settle delivery parameters as most brain connections, and relative sizes in large animals and primates, are reasonably common. Prior to application in the clinic, approaches that have shown to be successful in rodent models are tested in larger animal species, such as dogs, non-human primates, and in this case, minipigs. NEW METHOD: We evaluated alternate delivery routes to target the basal ganglia by injections into the more superficial corona radiata, and, deeper into the brain, the thalamus. Anatomically known connections can be used to predict the expression of the transgene following infusion of AAV5. For optimal control over delivery of the vector with regards to anatomical location in the brain and spread in the tissue, we have used magnetic resonance image-guided convection-enhanced diffusion delivery. RESULTS: While the transduction of the cortex was observed, only partial transduction of the basal ganglia was achieved via the corona radiata. Thalamic administration, on the other hand, resulted in widespread transduction from the midbrain to the frontal cortex COMPARISON WITH EXISTING METHODS: Compared to other methods, such as delivery directly to the striatum, thalamic injection may provide an alternative when for instance, injection into the basal ganglia directly is not feasible. CONCLUSIONS: The study results suggest that thalamic administration of AAV5 has significant potential for indications where the transduction of specific areas of the brain is required.

[Can we cure atrial flutter with radiofrequency ablation in an hour?]. / Je mozné vylécit typický flutter síní radiofrekvencní ablací do jedné hodiny?

BACKGROUND: Radiofrequency ablation of common atrial flutter requires the creation of a complete transmural ablation line across cavotricuspid region to achieve bidirectional conduction block. Irrigated tip catheters facilitate rapid achievement of this block by creation larger and deeper lesions. The EASTHER registry was organized to collect data about the efficacy of the procedure in small and middle volume centres in Central and Eastern Europe, all using THERMOCOOL catheter technology. METHODS: Easther is a prospective registry (April 2002-February 2003). 133 consecutive patients (81.1% male, age 59.0 +/- 10.4 years, range 30-81 years) with common atrial flutter were enrolled. Coincidence with atypical flutter was observed in 2.7%. Patients had a history of flutter of 31.0 +/- 53.6 month (range 1-403) and concomitant atrial fibrillation was observed in 42.9%. Structural heart disease was present in 38.9%. Amount of re-ablated cases was 14%. RF energy was applied during 60 sec in power-controlled mode at a setting between 40 to 50 W with an average flow rate of 19.0 ml/min. RESULTS: Acute success rate defined as bi-directional block was achieved in 93.1%, although 94.7% of cases were assessed successful by the treating electrophysiologist. Average number of RF applications was 12.0 +/- 7.0 (range 2-40) per procedure. Average delivered power varied between a minimum of 36.1 +/- 15.1 W till a maximum of 45.3 +/- 13.0 W, while the average maximum temperature observed at the same time was varied between 39.0 +/- 3.4 degrees C and 45.4 +/- 4.0 degrees C. Total procedure time was 100.1 +/- 42.7 min (range 20-280 min) and fluoroscopy time was 15.8 +/- 9.6 min (range 4-45 min). In comparable French TC registry Average total and fluoroscopy time were 46.4 +/- 33.6 min, and 10.0 +/- 6.8 min resp. In the Middle European centres total and fluoroscopy time was 96.1 +/- 40.9 min, and 15.0 +/- 8.9 min resp. In centres from Eastern Europe it was 120.3 +/- 51.2 min, and 20.4 +/- 11.9 min resp. Two adverse events were reported. Both patients had strong chest pain during ablation. These results are comparable with the literature data published. CONCLUSIONS: Irrigated tip catheters are effective and safe in ablation of common atrial flutter. This technology helps to accelerate and facilitate achievement of bi-directional isthmus block. Most of procedures were terminated to one hour in experienced centers in France as early as 2002. Procedures not exceeding one hour are feasible in case of spreading this method as method of first choice with gaining of experiences in centres of Middle and Eastern Europe.

[The ergometry stress test in patients with stenosis of the left main coronary artery]. / Ergometrický zátezový test u nemocných se stenózou kmene levé vencité tepny.

In 168 patients with ischaemic heart disease an ergometric loading test on a bicycle ergometer was made before coronarography. A total of 19 patients had on coronarography a finding of significant stenosis of the lumen of the trunk of the left coronary artery--group A. These patients were compared with a control group of 20 patients with confirmed coronary heart disease (narrowing of the diameter of the lumen by 50 or more percent) without affection of the trunk of the left coronary artery-group B. As to the investigated parameters of the ergometric test the two groups differed significantly in the total time of the load (group A: 6.21 minutes, group B: 7.94 minutes, p < 0.05), while in all other parameters--total amount of performed work, sum of depressions of the ST segments during a maximum load, time of onset of stenocardias, time since development of 1 mm depressions of the ST segment, maximal depression of the ST segment in lead V5 and number of leads with ST depressions above 1 mm--no significant difference was found. From the work ensues that from the ergometric loading test the finding of stenosis of the left coronary artery on coronarography cannot be predicted.