Rumen fistulation of sheep by the Schalk and Amadon method, as described here, is a comparatively simple, safe and ethical procedure, with minimal effect on or complications for the animal.
As a consequence of delayed treatment of intraarterial flucloxacillin, distal gangrene has occurred, I although flucloxacillin is the least 'membrane detrimental' of the antibiotics to arteries according to Knil!. 2 A ten-year-old achondroplastic boy weighing 30 kg presented for a five-level lumbar laminectomy for the treatment of spinal canal stenosis. He was anaesthetised in the routine manner and positioned prone on the operating table. An intraarterial line (20 gauge Jelco) was inserted into the right radial artery to facilitate monitoring. An intravenous line had been placed in the left hand. As surgery commenced, the surgeon requested the IV administration of flucloxacillin 750 mg. A new staff member, who was not familiar with the method of identification of lines used in this hospital, drew up and injected the drug into a threeway tap in the arterial line. Three millilitres of the flucloxacillin solution (750 mg in 10 ml water) was given before the mistake was recognised. Soon after injection, swelling and erythema developed the dorsal aspect of the wrist in an area of about 0.5 cm. The fingers appeared to be spared. The serious nature of the incident was appreciated, and residual drug in the line removed. However, further treatment was a problem. A stellate ganglion block was impossible because the patient was prone and now well into an operation which was expected to take a total of six hours. Heparinisation was not feasible because of the nature of the operation, and ceasing the operation to perform these manoeuvres was not considered practicable. One possible option was to initiate sympathetic blockade using intra-arterial guanethidine. Guanethidine, as a solution of 5 mg in 5 ml normal
The physicochemical properties of benzodiazepines are suitable for studying dose-effect relationships and examining variations caused by pharmacokinetic and pharmacodynamic effects. In particular, benzodiazepines with appropriate pKa values and lipid solubilities can penetrate rapidly into the central nervous system (CNS) and reach a rapid equilibrium between blood and all regions of the CNS. The normal protein level in cerebrospinal fluid (CSF) is only about 0.010 g.IOOml-' i.e. about 1000 times less than in blood, so CSF matches closely the unbound plasma level. Animal studies with diazepam [4] and clonazepam [5] have shown that CSF and blood can reach a rapid equilibrium and give a close correlation between free (unbound) drug concentrations in blood and the CSF level. We have recently shown a good correlation (r = 0.81) between the measured fraction of unbound temazepam in plasma and the level of temazepam in C S F in 13 human subjects administered temazepam 20 mg, 75 to 240 min before venous blood and lumbar CSF sampling [6]. Therefore, the concentration of benzodiazepines in the CSF should be a good measure of the concentration to which the neurones within the CNS are exposed, and measurement of the CSF drug concentration should give a n estimate of the concentrationleffect relationship.To explore this relationship, we have studied patients undergoing a lumbar puncture for spinal anaesthesia. The lumbar CSF temazepam levels after oral dosing have been taken to represent the 'biophase' drug concentrations to which the CNS benzodiazepine receptors are exposed, and used to evaluate the drug concentration-effect relationship, independent of pharmacokinetic variation.Temazepam (3-Hydroxydiazepam) is a commonly pre-G
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