The induction of epidermal ornithine decarboxylase following tape stripping is inhibited by a topical vitamin D3 analogue (MC903)

The efficacy of MC903, a vitamin D3 analogue, in reducing hyperproliferation as determined by levels of ornithine decarboxylase (ODC) was investigated in a double-blind study of 15 patients with chronic plaque psoriasis. The lesions of psoriasis were treated for 8 weeks with MC903 in one of two different cream bases or with a placebo cream. Biopsies were taken before and after treatment. In addition an uninvolved area of skin was treated during the last 3 weeks and this as well as control areas were then sellotape stripped and biopsied after 8 h. Clinical improvement was seen in eight out of 11 patients treated with MC903 but there was no reduction in the level of ODC in psoriatic lesions after 8 weeks of treatment. The levels of ODC in the tape-stripped uninvolved skin after 3 weeks of treatment with MC903 averaged 22.5 +/- 4.2 pmol/min/mg protein as compared to 58.6 +/- 12.6 pmol/min/mg protein (P = 0.004). The trauma-induced induction of ODC activity was markedly inhibited by the application of MC903.     

Adrenocortical responsiveness in neonates weaned from the ventilator with dexamethasone

Adrenocortical responsiveness was assessed in eight very low birthweight neonates who had bronchopulmonary dysplasia and had been weaned from mechanical ventilation using dexamethasone. Three of the eight infants did not respond to ACTH stimulation during the first week after cessation of dexamethasone, but all three responded normally when retested at least 1 month later. The present authors have thus demonstrated that some infants have at least temporary adrenocortical unresponsiveness after prolonged courses of glucocorticoid therapy, and suggest that adrenocortical function should be assessed in all infants who are weaned from mechanical ventilation using dexamethasone.     

Radiofrequency Current Ablation of Porcine Right Atrium: Increased Lesion Size with Bipolar Two Catheter Technique Compared to Unipolar Application In Vitro and In Vivo

Interruption of atrial flutter and fibrillation by RF catheter ablation may be favored by large, elongated lesions. We administered RF current in unipolar and bipolar mode in porcine right atrium. Bipolar ablation was performed between the tip electrodes of two serially coupled catheters. With 4-mm tip electrodes in vitro, lesion length increased from a mean (SD) of 7.9 (1.2) mm at 3 mm-interelectrode distance (IED) to 13.3 (3.3) mm at 9-mm IED, but decreased at 12-mm IED due to nonconfluent lesions (P < 0.0001), With 4 mm distal electrodes and 8 mm IED, bipolar lesions were 65% longer than corresponding unipolar ablations. Switching to bipolar mode increased the lesion length more than increasing electrode tip length to 6 mm in unipolar mode. Power and temperature controlled ablation created equally sized lesions. Twelve anesthetized pigs were randomized to unipolar or two catheter bipolar temperature controlled ablation of the right atrial free wall. Bipolar ablation created confluent lesions with endocardial length × width of 13.5 (5.8) × 7.3 (3.7) mm, unipolar ablation 6.4 (2.8) × 4.6 (1.4) mm (P < 0.001 when comparing length and P = 0.013 for lesion width). The atrial lesions in both groups were transmural and extended into hilar lung lesions with maximal depth of 3.0 (1.1) and 2.6 (1.0) mm, respectively (P = 0.44). Five bipolarly and four unipolarly ablated pigs developed right diaphragmal paresis. We conclude that bipolar ablation may be preferable in situations where large, elongated lesions are favorable. The two catheter technique is feasible in porcine right atrium. Both bipolar and unipolar ablation of the porcine right atrial free wall may frequently be complicated by injury to the phrenic nerve and adjacent lung tissue.     

Bidirectional transvenous/subcutaneous defibrillation of ventricular fibrillation in dogs: success rates, energy requirements, currents, voltages and impedance

Four hundred and thirteen defibrillations of alternating current-inducedventricular fibrillation were performed in 10 halothane-anaesthetizeddogs (body weight: 24.5–30.5 kg). Success rates, energydemands, currents, peak voltages and impedance were determined.A transvenous catheter electrode system (Medtronic 6880, rightventricular apex and superior vena cava, distance 100 or 150mm) and subcutaneous patch electrodes (Intec 67 L, 2nd/3rd and/or3rd/4th left intercostal space) were used for bidirectionaldefibrillation. Loading voltages ranged from 600 to 850 V. Withan electrode distance of 100 mm and a pulse duration of 2 msseparated by 1 ms, success rates were 100%, 40% and 0% for 850,650 and 600 V, respectively. With a 3-ms pulse duration, thecorresponding rates were 100%, 60% and 50%. With a 2-ms pulseduration, successful defibrillation was achieved with energieslower than 15 J in 27%, with energies between 15 and 20 J in77%, and 100% with energies higher than 20 J. Defibrillationcurrents were 4.4–9.3 A for pulse 1 (superior vena cava/ventricularapex) and 6.3–13.4 A for pulse 2 (patch/ventricular apex),respectively. Effective peak voltages ranged from 510 to 787V and from 514 to 777 V and averaged 89.6% of the loading voltages.Impedance values (peak voltage/current) were 75.5–117.7(pulse 1) and 51.7–94.9 Ohms (pulse 2). Fifty consecutivedefibrillations in one animal resulted in a decrease of impedance(114.6 to 84.9 Ohms, pulse 1; 75.4 to 53.0 Ohms, pulse 2). Defibrillationof ventricular fibrillation can be achieved with acceptablylow energies using a bidirectional transvenous/subcutaneoussystem, avoiding thoracotomy and general anaesthesia for implantationof the defibrillation system.     

Utilization of oxygen by the contractile apparatus is disturbed during reperfusion of post-ischaemic myocardium

Post-ischaemic ventricular function remains depressed ( = myocardialstunning) despite nearly normal coronary blood flow during reperfusion.In order to illuminate the causes of this phenomenon, we studiedthe relationship between ventricular function and myocardialoxygen consumption (MVO_2tot) in experiments on 15 isolated rabbithearts perfused with erythrocyte suspension (hct=30%). Leftventricular systolic function was assessed by measuring aorticflow (ml. min ^–1), peak systolic pressure (L VP_max), dPldt_max,and early relaxation in terms of dPldt_min during control and30 min after the onset of reperfusion, following 20 min globalno-flow ischaemia. The pressure-volume area was calculated asa measure of total mechanical energy. The external mechanicalefficiency (E_ext) was assessed from stroke work and MVO_2torBothcontractile efficiency (E_con= inverse slope of the MVO₂-PVArelationship) and MVO₂ of the unloaded contracting heart (MVO_2unl=basal MVO₂ + MVO₂ for excitation-contraction coupling) werecalculated using pressure-volume area and MVO_2tot Results: At matched heart rate (149 ± 30 vs 147 ±31 min ^–1; mean ± SD) and end-diastolic volume(1.3 ± 0.2 ml), the systolic variables were significantlydecreased in the stunned myocardium: aortic flow: 38 ±13 vs9 ± 11 ml. min ^–1, LVP_max: 112 ±19vs 74±18mmHg, and dP/dt_max: 1475 ±400 vs 1075±275 mmHg. s^–1. Likewise, dP/dt_min was significantlyimpaired (– 1275 ±250 vs – 975 ±250).The decrease in pressure-volume area (570 ±280 vs 270±200mmHg.ml. 100g^–1) was not statistically significant. In contrast,both E_ext (0.75±0.29 vs 0.18±0.26 arbitrary units)and E_con (31 ± 18 vs 14± 7%) were significantlydecreased, whereas MVO_2tot (40±9 vs 34±8µl.beat^–1. 100g^–1) and MVO_2unl (26±9 vs22±6µl.beat^–1. 100g^–1) were not. Summary: Ventricular function after brief episodes of ischaemiais decreased whereas MVO_2tot is maintained, i.e. external efficiencyis decreased. MVO₂ for the unloaded contraction remained unchanged,indicating that MVO₂for excitation-contraction coupling is inappropriatelyhigh for the depressed contractile state. The decreased contractileefficiency indicates further that O₂ utilization of the contractileapparatus is disturbed during reperfusion.