Biomedical subjects
Publications and source records attributed to M Rosen.
Premedication with nalbuphine and morphine delayed gastric emptying in the period after operation, but oral diazepam did not. All three drugs delayed co-ordinated intestinal motility, although nalbuphine did so for less than half as long as morphine. This property of nalbuphine, if confirmed, could make it a valuable analgesic drug in the period after operation.
An animal preparation has been developed to test therapeutic agents in the extradural and intradural spaces. Under anaesthesia a hole was drilled in the penultimate lumbar vertebra of male Wistar rats and the appropriate space cannulated. The catheter was tunnelled subcutaneously to emerge at the neck. There was no spinal cord or meningeal reaction after 1 month. Catheters remained patent for 3 months. The method of cannulation allowed free rostral spread of drugs. Using plain 2% lignocaine, paralysis and anesthesia of the hind limbs required an intradural volume of 32 +/- 3 mulitre: the required volume on extradural injection was 46 +/- 2 mulitre (P less than 0.01). Paralysis of all limbs required an intradural volume of 115 +/- 12 mulitre. Respiratory arrest and death required a mean intradural volume of 179 +/- 15 mulitre.
In a randomized study of patients undergoing Caesarean section, either enflurane (mean 0.24 MAC-h) or halothane (mean 0.23 MAC-h) and 50% nitrous oxide in oxygen were administered to women (n = 12) with severe pre-eclampsia-eclampsia and to 16 healthy pregnant patients with normal renal and hepatic function. No evidence of nephrotoxicity was found in any pre-eclamptic or normal patient. Metabolism of enflurane resulted in plasma inorganic fluoride concentrations (max 15 mumol litre -1) which were well below the toxic value. Postoperative liver function tests showed no important changes from preoperative values, although reductive metabolites of halothane were not measured. In patients with severe pre-eclampsia there appears no contraindication to enflurane or, probably, halothane as volatile supplements during general anaesthesia.
This study examines the changing pattern of maternal analgesia administration during the decade 1970-1979. In addition, the relationship between analgesia, anaesthesia and the infant's Apgar score was documented. Approximately 40000 deliveries to South Glamorgan residents were included in the study. Over the two quinquennia 1970-1974 and 1975-1979 the administration of epidural block increased from 5.6% to 17.5%. The Apgar score of babies in the epidural block group was significantly better in the latter period. Respiratory depression following Caesarean section remains a problem. The group delivered by elective Caesarean section contained a substantial proportion of infants with a low Apgar score; 30% had an Apgar score less than 8 and 10% had a score of less than 4. Likely causative factors include undue sensitivity of the infants' respiratory centre and aortocaval compression during surgery.
A comparison of the analgesic efficacy of enflurane 1% in air with Entonox (50% nitrous oxide in oxygen) was performed in 20 consenting women during the first stage of labour. The two drugs were given in a random sequence to each woman, who also acted as her own control. Pain scores were significantly lower with enflurane than Entonox, although drowsiness scores were higher. No untoward effects were reported with either agent. The use of enflurane as an analgesic in the first stage of labour warrants further investigation.
A field trial is reported of the use of a fixed concentration of 25% nitrous oxide to produce sedation in anxious dental patients. Three hundred and ninety-four patients were treated on 1005 occasions. Ninety-nine per cent of patients were treated successfully without any incidence of loss of consciousness, including 47 children who were treated on 88 occasions.
Litters of 12 pups produced the optimum results for survival (P less than 0.005) and for weaning weights (P less than 0.05) when compared with litters of 8 and 10 pups. This number is similar to the normal litter size and normal number of teats in rats. In our study, the normal litter size was means = 12.5. Our results were obtained under favourable conditions without disturbing the animals and facilitating access to food and water for the mothers and pups.
Various concentrations of local anaesthetic agents have been injected into the rat and marmoset via a chronically implanted cannula in the subarachnoid space. In the rat, cocaine at a concentration of 0.125% produced analgesia without motor blockade whereas higher concentrations produced motor blockade in some animals. No clear differentiation could be shown with any concentrations of lignocaine or bupivacaine. In the marmoset, 0.125% cocaine resulted in sensory block in four out of five marmosets without motor blockade, whereas 0.25% cocaine produced motor block in two out of four marmosets. It would appear that differential blockade of sensory function without motor loss can be achieved by cocaine. New local anaesthetics based on cocaine or similar chemical structures would seem potentially valuable.
Repeated intrathecal injections were given through catheters which had been chronically implanted in the subarachnoid space of rats. Injections were made of cocaine 0.25%, 0.125% and 0.0625%; bupivacaine 0.5%; lignocaine 2% and 0.5%; adrenaline 0.01% (1 in 10 000) and 0.002% (1 in 200 000); and sodium chloride 0.9%. Five injections of 35 microliter of each concentration of each drug were given hourly each day for two days to three rats. No clinical nerve damage was detectable in any rat. The only pathological change found in any rat was the development of cytoplasmic vacuolation in the neurones of the anterior and posterior horns. The changes were most prominent after injection of 0.9% sodium chloride and bupivacaine, whilst lignocaine (0.5 and 2%) showed the least number of vacuoles, which were also the smallest in size. Adrenaline and cocaine were intermediate in effect. There was no evidence of cell death. These changes were not seen in control animals in which catheters had been implanted but no injections had been given. The changes were mild and it is concluded that the agents tested caused no significant damage.
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An on demand intramuscular analgesic system using the Cardiff Palliator was tested. Forty consenting patients were studied after cholecystectomy in a double blind trial using increments of buprenorphine (0.15 mg), meptazinol (50 mg), morphine (5 mg), and pethidine (50 mg). Most patients attained good levels of pain relief (mean analogue pain score 36.5), comparable to intravenous on demand analgesia. There were no technical complications. Significant differences were found between drugs in dizziness (pethidine produced the worst score) but not with other side effects. Buprenorphine produced longer lasting analgesia than meptazinol or pethidine and also gave the lowest pain scores. Patterns of analgesic consumption were the same as with intravenous on demand systems, but larger amounts of drug were generally used. Relative analgesic potencies derived from drug consumption rates were also consistent with those from intravenous on demand studies. An on demand intramuscular analgesic system offers a simple but effective means of relieving severe postoperative pain.
A double-blind comparison between buprenorphine and pentazocine was performed in 20 patients using an on demand analgesic system to provide analgesia after operation. The quality of analgesia, assessed subjectively, was good with both drugs and drug consumptions were compatible with previous potency estimates. The mean doses demanded in 24 h of buprenorphine (1.68 mg) and of pentazocine (382 mg) are consistent with those found in other trials although the between-patient variation was five- or six-fold. There was no significant difference in side-effects between the two groups. Buprenorphine and pentazocine may be used successfully in an on demand system to provide relief of severe pain after operation.
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Following intravenous injection of labeled choline or phosphorylcholine in rats and mice, the brain uptake as percent injected dose was less than 0.2% with 6-12% going to kidney and 3-6% to liver. A study of [14C]choline autoradiography in a stump-tailed macaque demonstrated a five- to sixfold greater uptake in gray matter than in white matter. Dynamic positron imaging of [11C]choline in a rhesus monkey demonstrated rapid brain uptake followed by rapid washout, with heavy late uptake in muscle. The use of labeled choline and choline analogs as imaging agents in human studies is constrained by the low brain uptake relative to extracerebral tissues.
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Patients receiving staff-administered analgesics after upper abdominal surgery had higher pain scores than similar patients having self-administered analgesics, but this was associated with a considerably smaller average amount of analgesic given. This survey was subject to observer and patient bias and it was necessary to use 'pethidine equivalents' to enable comparisons to be made between drugs with effects of different duration; thus the striking differences in pain scores and grades can be considered indicative only. They nevertheless support the continued investigation of on-demand systems and make a strong case for a double-blind controlled trial.