Distinction awards.
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Biomedical subjects
Publications and source records attributed to M Rosen.
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A specific and quantitative GLC method for warfarin in human plasma is described. The procedure uses papaverine as the internal standard and involves a dichloroethane extraction of the acidified specimen. The organic extract is evaporated, and the evaporated extract is dissolved in 50 microliter of chloroform. Aliquots of 2-3 microliter are injected into a gas chromatograph equipped with a flame-ionization detector. The sensitivity of the method is such that 0.3 microgram of intact warfarin can be detected in 1 ml of plasma. Statistical analyses indicate a recovery of 97.26 +/- 1.89% SD. The procedure was successfully applied to plasma drug level studies in humans.
In a pilot study in six mothers using 50% nitrous oxide and 50% oxygen (Entonox) as an intermittent self-administered analgesic during labour, a significant reduction in the mean times to attain specified end-tidal nitrous oxide concentrations was obtained by a continuous nasal supplement of Entonox. The method proved acceptable in this small number of patients and there were no demonstrable effects upon fetal heart rate.
Pregnant rats, treated with high doses of propranolol, gave birth to small for dates neonates. Litter size was affected in daily doses of 100 and 150 mg/kg/day. Propranolol markedly influenced the gain in weight normally observed in pregnant rats. The placentas of the rats which received the higher doses of propranolol weighed about 30% less than normal placentas. Pregnant rats, treated with propranolol, gave birth to small for dates neonates. This effect is possibly the result of a drug-induced reduction in transport across cellular membranes, resulting in malnutrition. Since similar effects were reported in humans, treatment with propranolol during pregnancy should be further reevaluated in laboratory animals.
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A simple occluding device of the urethra has been described and the rationale for its configuration given. Twenty-three patients have been operated on and 18 have been cured. The main complications are device failure and sepsis. The results so far justify a limited optimism that the device has a significant role to play in the management of male urinary incontinence.
Infants whose mothers had had pethidine during labour were given either naloxone 40 microgram or isotonic saline administered intravenously double-blind within one minute of birth. Peak alveolar carbon dioxide tension, carbon dioxide excretion, alveolar ventilation, feeding behaviour, and habituation to a specific sound stimulus were measured regularly up to 48 hours after birth. Alveolar carbon dioxide tension was significantly lower and alveolar ventilation significantly higher half an hour after birth in the naloxone-treated group than in the saline-treated group, but these differences between the groups were not significant at any other time, and there were no significant differences in sucking frequency or pressure, milk consumption, or habituation to the auditory stimulus.
Thirty full-term infants whose mothers had had pethidine during labour were given either naloxone 200 microgram or normal saline intramuscularly. The drugs were chosen blindly and administered within one minute of birth. Naloxone produced a significant reduction in mean alveolar carbon dioxide tension and an increase in carbon dioxide excretion and mean alveolar ventilation at all times up to 48 hours after birth. The mean rate of habituation to a repeated auditory stimulus, the mean sucking frequency, the sucking pressure, and the mean consumption of milk were all significantly higher in the naloxone-treated group than in the placebo-treated group up to 48 hours after birth. Intramuscular naxolone therefore seemed to reverse the undesirable effects of pethidine.
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A stability-indicating method of analysis of homatropine methylbromide in pharmaceutical formulations was developed. This method is based on the formation of a picric acid-quaternary ammonium complex, which is adsorbed on acid-washed diatomaceous earth in alkaline media followed by on-column chloroform extraction. The picrate complex is measured spectrophotometrically at 365 nm. The method was selective for homatropine methylbromide in that there was no interference from its major hydrolytic decomposition products, tropinium methylbromide and mandelic acid.
With improving standards of antenatal care, severe pre-eclampsia dn eclampsia are becoming less common and experience in the management of these conditions is lessening. Co-ordinated plans for the care of patients should be established by obstetricians and anaesthetists working as a team. A suitable regime for drug therapy in severe pre-eclampsia or eclampsia is the following: Initial management Diazepam 10 mg slowly i.v. Pethidine 100-150 mg i.m. or i.v. in incremental dosage, or extradural blocks, if analgesia is also required. Hydrallazine 20 mg i.v. initially, followed by 5 mg at intervals of 20 min until the diastolic pressure is less than 110 mm Hg. Then, preferably by syringe pump in a concentration of 2 mg/ml, at a rate of 2-20 mg/h. If vomiting occurs this can be controlled by administration of atropine. Subsequent management Sedation and anticonvulsant therapy. Continue diazepam and, in severe cases, institute chlormethiazole infusion. Continue analgesia with pethidine or extradural block. Control of hypertension by adjusting the dose of hydrallazine. If tachycardia exceeds 120 beat/min give propanolol 2-4 mg i.v. Plasma protein depletion with groww oedema is treated by administration of salt-free albumin or plasma protein fraction. Diuretic therapy is indicated if there is gross oedema or signs suggestive of acute renal failure. Oliguria associated with increased blood urea may be a result of renal failure or dehydration. The latter should be evident from the patient's condition and central venous pressure, but i.v. fluids and frusemide 20-40 mg can be used as a therapeutic test. Mannitol reduces cerebral oedema and may be given if diuresis has been first produced with frusemide. Potassium chloride is given if the plasma potassium decreases to less than 3 mmol/litre. Heparin therapy is considered if there is clinical evidence of disseminated intravascular coagulation.