Electrophysiologic actions of clofilium and lidocaine in ischemically injured canine epicardium.

The electrophysiologic actions of the Class III antiarrhythmic drug, clofilium, and the Class IB antiarrhythmic drug, lidocaine, were examined in ischemically injured canine epicardium, 4 days after coronary artery occlusion. Experiments were performed utilizing 1) composite electrode recordings from the intact heart in the anesthetized dog and 2) intracellular and extracellular recordings from superfused canine epicardium. In intact hearts, both clofilium (2 mg/kg i.v.) and lidocaine (6 mg/kg i.v.) increased refractoriness (188 +/- 16 to 331 +/- 39 and 288 +/- 18 msec, respectively, P less than .01), and produced tachycardia-dependent conduction disorders in ischemically injured epicardium. For both drugs, slowing the sinus heart rate with vagus nerve stimulation (32 +/- 6/min) returned activation delays to predrug values. Unlike lidocaine, clofilium failed to increase maximal activation delays in ischemically injured epicardium preceding conduction block (116 +/- 14 msec vs. 71 +/- 7 msec and 147 +/- 16 msec for clofilium and lidocaine, respectively, P less than .01 for both drugs). In superfused epicardium, both clofilium (3 x 10(-7) M) and lidocaine (4 mg/l) prolonged refractoriness in ischemically injured epicardium (175 +/- 16 predrug vs. 273 +/- 33 msec, P less than .01) and (181 +/- 3 predrug vs. 216 +/- 10 msec, P less than .01), respectively, whereas only lidocaine reduced Vmax and prolonged local conduction times in the same tissue. The results demonstrate that 1) lidocaine increases refractoriness in ischemically injured tissue via a decrease in Vmax and conduction velocity and 2) clofilium increases refractoriness in ischemically injured tissue without altering action potential duration, Vmax or conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissociation of the Medial Prefrontal, Posterior Parietal, and Posterior Temporal Cortex for Spatial Navigation and Recognition Memory in the Rat

Rats with lesions of the medial prefrontal, posterior parietal,or posterior temporal cortex were tested in five spatial navigationtasks, which varied in egocentric or allocentric demands, avisual discrimination task, and two delayed nonmatching-to-sampletasks. Rats with prefrontal lesions were impaired at every spatialnavigation task, whereas rats with posterior parietal lesionshad selective spatial navigation impairments. Rats with prefrontallesions were also impaired at a visual delayed nonmatching-to-sampletask, as they were unable to learn the task, even with no delay.The results are consistent with the idea that the basic planof mammalian cortex includes prefrontal, posterior parietal,and posterior temporal regions, each of which have generallysimilar functions across mammalian taxa. There are, however,species-typical differences that reflect specific ecologicalpressures on the development of the different regions.     

Frame-based immobilization and targeting for stereotactic body radiation therapy.

Frame-based stereotactic body radiation therapy (SBRT), such as that conducted with Elekta's Stereotactic Body Frame, can provide an extra measure of precision in the delivery of radiation to extracranial targets, and facilitates secure patient immobilization. In this paper, we review the steps involved in optimal use of an extra-cranial immobilization device for SBRT treatments. Our approach to using frame-based SBRT consists of 4 steps: patient immobilization, tumor and organ motion control, treatment/planning correlation, and daily targeting with pretreatment quality assurance. Patient immobilization was achieved with the Vac-Loc bag, which uses styrofoam beads to conform to the patient's shape comfortably within the body frame. Organ and motion control was assessed under fluoroscopy and controlled via a frame-mounted abdominal pressure plate. The compression screw was tightened until the diaphragmatic excursion range was < 1 cm. Treatment planning was performed using the Philips Pinnacle 6.2b system. In this treatment process, a 20 to 30 noncoplanar beam arrangement was initially selected and an inverse beam weight optimization algorithm was applied. Those beams with low beam weights were removed, leaving a manageable number of beams for treatment delivery. After planning, daily targeting using computed tomography (CT) to verify x-, y-, and z-coordinates of the treatment isocenter were used as a measure of quality assurance. We found our daily setup variation typically averaged < 5 mm in all directions, which is comparable to other published studies on Stereotactic Body Frame. Treatment time ranged from 30 to 45 minutes. Results demonstrate that patients have experienced high rates of local control with acceptable rates of severe side effects - by virtue of the tightly constrained treatment fields. The body frame facilitated comfortable patient positioning and quality assurance checks of the tumor, in relation to another set of independent set of coordinates defined by the body frame fiducials. The ability to impose abdominal compression proved to be a simple way to reduce target and tissue motion. SBRT with Stereotactic Body Frame enables comfortable patient immobilization and facilitates repeated registering and re-registering of the patient to the frame. With the body frame, large-dose-per fraction treatment is possible for localized tumor deposits with the aim of attaining a more therapeutic result.     

Mechanism of Pseudomonas aeruginosa persistence during treatment with broad-spectrum cephalosporins of lung infections in patients with cystic fibrosis.

Beta-lactam resistance in Pseudomonas aeruginosa detected only during ceftazidime therapy of cystic fibrosis patients was studied. Evaluation of resistant and susceptible isolates from one patient and resistant laboratory derivatives indicated that elevated beta-lactamase levels were the primary determinant of resistance. Susceptible isolates outgrew resistant isolates on antibiotic-free medium.     

Biphasic Shocks Compared with Monophasic Damped Sine Wave Shocks for Direct Ventricular Defibrillation during Open Heart Surgery

Background: Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves.

Methods: Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used.

Results: Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated;P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J;P = 0.003), less cumulative energy (12.6 vs. 23.4 J;P = 0.002), and fewer shocks (2.5 vs. 3.5;P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested.     

Partial k-space reconstruction in single-shot diffusion-weighted echo-planar imaging.

Partial k-space sampling is frequently used in single-shot diffusion-weighted echo-planar imaging (DW-EPI) to reduce the TE and thereby improve the SNR. However, it increases the sensitivity of the technique to bulk rotational motion, which introduces a phase gradient across the tissue that shifts the echo in k-space. If the echo is displaced into the high spatial frequencies, conventional homodyne reconstruction fails, causing intensity oscillations across the image. Zero-padding, on the other hand, compromises the image resolution and may cause truncation artifacts. We present an adaptive version of the homodyne algorithm that detects the location of the echo in k-space and adjusts the center and width of the homodyne filters accordingly. The adaptive algorithm produces artifact-free images when the echo is shifted into the high positive k-space range, and reduces to the standard homodyne algorithm in the absence of bulk motion.     

Physico-chemical characterisation of rinderpest virus

Rinderpest virus grown in Vero cells was purified by equilibrium sedimentation in potassium tartrate gradients. The characteristics of the virus and its RNA dependend on the passage history of the virus. Undiluted passage virus had a density ofc 1.21 g/ml in potassium tartrate and contained RNA sedimenting atc. 20S and 5S. Virus obtained by dilute passage had a density ofc. 1.24 g/ml and contained 50S in addition to 20S and 5S RNA. Both diluted passage and undiluted passage viruses contained polypeptides with molecular weights of 98, 79, 75, 66, 48, 43 and 37×10³. Trace amounts of polypeptides with molecular weights of 29 and 20×10³ were also detected. The molecular weights of the major polypeptides are similar to those of the polypeptides present in measles and canine distemper viruses.     

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology,progression, and patient outcome

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.