A 'silent' cholinesterase gene detected by western blotting

A 38 year old Asian Indian female with a history of prolonged succinylcholine-induced apnoea was shown to have negligible levels of serum cholinesterase as determined by the dibucaine number test and quantitative enzyme estimation by the modified Ellman method. Electrophoresis of the patients's serum on a 5-20 percent gradient gel stained with Fast Red TR and O-naphthyl acetate detected no cholinesterase inesterase gene in this individual. A family study was initiated to include 19 other members; a similar pattern of cholinesterase activity could be demonstrated in a sister of proband. Western blotting was performed on the sera of the two sisters and selected family members. The cholinesterase antigenic banding pattern of the sisters' sera expressing the 'silent' gene was similar to controls, with additional bands. The cholinesterase gene segregating in this family correspond to the Type II 'silent' gene was similar to controls, with additional bands. The cholinesterse gene segregating in this family correspond to the Type II 'silent' gene variant which has about 3 percent of usual enzyme activity (AU)

Atypical cholinesterase gene Ea: rarity in the Jamaican population - abstract

This paper reports on the rarity of the atypical cholinesterase gene Ea in the Jamaican population, via experimentally observed specific activities and percentage inhibition by dibucaine.. Homozygotes for the abnormal enzyme may develop prolonged apnoea when the muscle relaxant suxamethonium is administered prior to surgery. A total of 499 subjects were studied; of these 240 had normal serum cholinesterase activity (2669 ñ 514 mU/ml of serum) and normal dibucaine number 88. The remaining 259 subjects had lower than normal activity (1422 ñ 259 mU/ml) but normal dibucaine number 87. Homozygous carriage of the atypical gene is associated with dibucaine numbers below 20. Based upon these findings, the ensuing apnoea often caused by the abnormal enzyme (Ea) is therefore expected to be very rare among Jamaicans: 25 percent of our 17 subjects who underwent suxamenthonium administration had low cholinesterase activity (1479 ñ 210 mU/ml) but had normal dibucaine number 89 and suffered prolonged apnoea, lasting from 30 to 78 minutes. These preliminary results suggest that the determination of cholinesterase activity and dibucaine numbers may not always be the most reliable criteria to differentiate the suxamenthonium-sensitive and -insensitive subjects (AU)

Slient cholinesterase gene in an East Indian family in Trinidad - abstract

During a study to determine the frequency distribution of the enzyme pseudocholinesterase (Cholinesterase) in the population of Trinidad, an East Indian individual developed prolonged respiratory apnoea on administration of a routine dose of suxamethonium. This paper reports the results of analyses of the frequency distribution of pseudocholinesterase in the sera from the index case and 19 family members. Cholinesterase was detected qualitatively in the serum, using the Dibucaine Number (DN) and Fluoride Number (FN) tests (normal values: 78.8 per cent and 61.4 per cent, respectively), and quantitatively, using the modified Ellman method (normal plasma levels: 8:44 ñ 1.78 u/ml). Patients with low activity of the enzyme (inhibited < 20 per cent by dibucaine) are "suxamethonium-sensitive". DN and FN values in the serum of the index case could not be determined because of the negligible enzyme activity (0.17 u/ml). Of the 6 of 7 siblings available for testing, 1 was found with undeterminable DN and FN values and even lower enzyme activity (0.09 u/ml). The proband's marital partner, 2 children and father had normal enzyme patterns. This condition of `trace' enzyme activity is controlled by a `silent gene' (AU)

The incidence and important of post-suxamethonium pain in Barbadian patients

A survey of the incidence of post-suxamethonium muscle pain and/or stiffness (PSPS) following its administration for muscle relaxation during anaesthesia was carried out at the Queen Elizabeth Hospital in Barbados. It revealed a much lower overall incidence of PSPS (10.9 per cent) than usually reported. The incidence of severe PSPS of 2.52 per cent was also lower than in other reports. This may suggest a geographical or population difference. The relationship of PSPS to such factors as the degree of fasciculation, postoperative activity, type of operation, dose of suxamethonium, serum cholinesterase levels and dibucaine numbers and the use of the thiopentone and non--depolarising relaxants was also investigated. No relationship could be found. The predominance of PSPS in women between 21 and 30 years of age and those over 71 years of age found in Barbados merits further study. (AU)

A study of the incidence and importance of post suxamethonium pains following anaesthesia - abstract

A two part questionnaire was filled out for Barbadian patients undergoing anaesthesia at the Queen Elizabeth Hospital. Members of the Department of Anaesthesia filled out part I on clinical details, anaesthetic technique, surgical procedure and types of fasciculation. A trained interviewer who was unaware of the aims of the project completed part II with the patient within 10 days of the operation. Questions were directed to the time of ambulation, degree of exercise, and the amount of pain or stiffness. The results show a low incidence of post suxamethonium pains (4.46 percent). Pain and or stiffness is most likely to occur after suxamethonium in patients undergoing major operations, performing mild exercise in the postoperative period, in the 21-30 year age group and in females. Ambulation appears to be a factor in the production of pain. The dose of suxamethonium given on a body weight basis is unimportant in the production of pain and no protection is apparent in the use of thiopentone during induction, or of halothane, omnopon, valium or pethidine as supplements to anaesthesia. Severe fasciculations were not particularly common and did not necessarily produce post suxamethonium pains (AU)

The antagonism of the neuromuscular blocking action of D-Tubocurarome, chloride, succinylcholine chloride and pancuronium bromide by anacardium occidentale

The cardiovascular and antiarrhythmic effects of purified extract of the inner bark of Anacardium Occidentale (cashew tree) have been documented. The antiarrhythmic effect was shown to be due to myoinositol of which the bark contains 25 percent w/w. With the exception of succinylcholine chloride, both d-tubocurarine chloride and pancuronium bromide are potent non-depolarising neuromuscular blocking agents. It is an accepted fact that there is no satisfactory antagonist for the depolarising blocking drugs such as succinycholine chloride. It was interesting to note that anacardium occidentale (AO) blocked the action of all 3 drugs on the rat phrenic-nerve-diaphragm neuromuscular preparation. A total dose of 1mg in a 50ml organ bath blocks the action of 100ug of d-tubocurarine 200ug of succinylcholine chloride and 200ug of pancuronium bromide. Pancuronium bromide is about 5 times as potent as d-tubocurarine chloride. These results indicate that AO is more effective against pancuronium. A graphical representation of the result showed that the antagonism against these 3 drugs is competitive. The onset of action of AO is slow and each dose was allowed to act for 5 minutes before the additioin of the agonist. The non-depolarising drugs are antagonised by acetylcholine and the anti-cholinesterases, but preliminary experiments showed that AO had no acetylcholine nor anticholinesterase properties. The findings indicate that there may be some other mechanism of action of non-depolarising blocking drugs than occupation of the nicotinic receptors on the motor and plate (AU)