Pharmacokinetics of aditoprim and trimethoprim in buffalo calves

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.     

Nitric oxide synthase inhibitor,nitro-iminoethyl-L-ornithine,reduces ischemia-reperfusion injury in rabbit skeletal muscle

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 μM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 μM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. © 1994 Wiley-Liss, Inc.     

Using psychometric ability to improve education in ultrasound-guided regional anaesthesia: a multicentre randomised controlled trial

The learning curve for novices developing regional anaesthesia skills, such as real-time ultrasound-guided needle manipulation, may be affected by innate visuospatial ability, as this influences spatial cognition and motor co-ordination. We conducted a multinational randomised controlled trial to test if novices with low visuospatial ability would perform better at an ultrasound-guided needling task with deliberate practice training than with discovery learning. Visuospatial ability was evaluated using the mental rotations test-A. We recruited 140 medical students and randomly allocated them into low-ability control (discovery learning), low-ability intervention (received deliberate practice), high-ability control, and high-ability intervention groups. Primary outcome was the time taken to complete the needling task, and there was no significant difference between groups: median (IQR [range]) low-ability control 125 s (69–237 [43–600 s]); low-ability intervention 163 s (116–276 [44–600 s]); high-ability control 130 s (80–210 [41–384 s]); and high-ability intervention 177 s (113–285 [43–547 s]), p = 0.06. No difference was found using the global rating scale: mean (95%CI) low-ability control 53% (95%CI 46–60%); low-ability intervention 61% (95%CI 53–68%); high-ability control 63% (95%CI 56–70%); and high-ability intervention 66% (95%CI 60–72%), p = 0.05. For overall procedure pass/fail, the low-ability control group pass rate of 42% (14/33) was significantly less than the other three groups: low-ability intervention 69% (25/36); high-ability control 68% (25/37); and high-ability intervention 85% (29/34) p = 0.003. Further research is required to determine the role of visuospatial ability screening in training for ultrasound-guided needle skills.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.