799 has to pay for an anticholinergic compound not penetratthe ing blood-brain barrier. We have reviewed ten papers on the effect of emepronium bromide, mostly on bladder function in geriatric patients, 182 altogether. The studies were usually double-blind and crossover in design. Doses of 150-200 mg before bedtime or 3-4 times daily significantly reduced frequency and number of involuntary micturitions, and also relieved distress in patients with detrusor hyperreflexia. Two studies34 indicated better effect in "rehabilitation" or "short-stay" geriatric patients than in long-stay geriatric patients. In patients with multiple sclerosis and detrusor hyperreflexia, 100 mg t.i.d. and 200 mg t.i.d. were equally effective in increasing volume at first bladder spasm and functional bladder capacity (difference between first bladder spasm volume and residual volume). However, only 200 mg t.i.d. significantly reduced the number of voidings over 24 h periods, and subjective evaluation by the patients in a double-blind crossover study definitely favoured the 200 mg dose.’ Favourable effects occurred at plasma-levels of emepronium above 20-30 .g/1, concentrations far below those causing dry mouth, tachycardia, and disturbed visual accommodation. Clinically, emepronium bromide given orally, 200 mg three times daily, has proved to be valuable in the treatment of urinary incontinence.
ISOQUINOLINE ALKALOIDS AS POSSIBLE
one
Clinical Research Division, AB Kabi, 112 87 Stockholm, Sweden
FREDRIK BERGLUND PER-OLOV GLENNE
* * This letter has been shown
to
Dr Ritch and his
colleagues,
whose reply follows.-ED.L.
StR,—If oral emepronium bromide has no urodynamic effect, clinical improvement in incontinence is unlikely. Furthermore clinical assessment relies principally on incontinence charts which are inherently inaccurate and unreliable on busy wards. Urodynamic studies provide objective measurements which are easily interpreted. If the results of the bladder capacity after intramuscular administration are misleading because of increased residual volume this would not be true for the four other variables which also improved significantly (r001) after intramuscular injection but did not change after oral therapy. Dr Berglund and Dr Glenne claim that ten studies show clinical improvement in bladder capacity in the elderly after emepronium bromide but of the three references chosen, two are unpublished. In the other, Brocklehurst et al.’ found a small reduction in incontinence "from about 50 to about 45 per cent" and although some results were statistically significant at the 5% level there was no consistent pattern of improvement.
Syversen et all have shown that in post-prostatectomy paa change in dose of emepronium bromide from 50 mg intramuscularly to 600 mg orally results in a ten-fold decrease in plasma concentration and a loss of effect on bladder capacity. Thus we are surprised by Berglund and Glenne’s claim that plasma concentrations of around 30 .g/1 had a beneficial effect on the bladder; however, no data are given or have been
tients
published elsewhere on the
extent
of the increase in functional
REGULATORS OF ALCOHOL ADDICTION
S!R,—A possible biochemical explanation for a link between opiates and ethanol was provided in 1970, when two groups reported the formation of tetrahydroisoquinoline (T.i.Q.) alkaas a consequence of ethanol metabolism. 1 This discovery was significant because it was the first demonstration that mammalian tissues could "synthesise" alkaloids and
loids
because benzylisoquinoline alkaloids (e.g., tetrahydropapaveroline), are intermediates in the biosynthesis of morphine in the poppy. We can only speculate how these alkaloids might link the biochemical and behavioural actions of ethanol and opiates, but enough is known of their pharmacology for some mechanisms to be suggested. The chronic administration of ethanol and opiates produces an increase in central noradrenaline (norepinephrine) (N.A.). We do not know how this happens, but the formation of T.I.Q. alkaloids may explain the increase after ethanol. The formation of dopamine-derived T.i.Q.s would decrease the synthesis ofN.A. by removing the substrate for dopamine-p-hydroxylase. This decrease of N.A. would remove end-product inhibition and stimulate synthesis. Furthermore, salsolinol releases N.A. from nerve endings and inhibits its uptake.3 This would further decrease end-product inhibition of tyrosine hydroxylase and promote N.A. turnover.
We found that intracerebral administration of salsolinol to mice undergoing withdrawal from ethanol vapour either ameliorated (10 .g/animal) or exacerbated (100 p.g/animal) ethanol-induced withdrawal symptoms (unpublished). Salsolinol releases neural stores of catecholamines, so the exacerbation could be the result of N.A. release and activation of central N.A.-ot-receptors. Implicit in this argument is the fact that N.A.-cx-activation takes preference over dopamine (D.A.) activation because these alkaloids release both D.A. and N.A. from neural stores.3 The biphasic action of salsolinol, though seeming contradictory, may be explained by the fact that salsolinol can block ex-receptors4 and is an agonist at D.A. receptors.’ Thus, large exogenous doses of salsolinol probably exert their effect through a catecholamine release, while the smaller amount acts through direct receptor antagonism (ex) and/or activation (D.A.). Support for this explanation is derived from the findings of Blum et al.6 showing that N.A. exacerbates the withdrawal convulsions induced by ethanol, whereas D.A. ameliorates this condition.7 A lot of evidence indicates voluntary alcohol opiates and ethanol. Morphine suppresses voluntary alcohol consumption in hamsters8 and a single injection of an opiate agonist significantly suppresses voluntary alcohol consumption in both mice and rats.9 Ross et al. 10 have reported the same effects in hamsters and have also shown that dextrorphan did not affect alcohol consumption, indicating the necessity for an active opiate enantiomer. We have found that naloxone or naltrexone at 5 mg/kg can inhibit ethanol narcosis in mice, while higher doses (10 mglkg) potentiate the narcosis (unpublished). Concurrent administration of ethanol can affect morphine withdrawal in rats," and withdrawal of ethanol after chronic administration
bladder capacity. We agree that there is need for a safe drug which can act the bladder, but we feel that the published evidence suggests that emepronium bromide does not meet this require-
on
ment.
A. E. S. RITCH C. M. CASTLEDEN C. F. GEORGE M. R. P. HALL
Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO9 4XY 3 Brocklehurst, J. C., Armitage, P., Jouhar, 4. Pathy, H. S., Jouhar, A. J. Unpublished. 5 Hebjørn, S. Unpublished.
A. J.
Age Ageing, 1972, 1, 152.
1. Brocklehurst, J. C., Armitage, P., Jouhar, A. J. Age Ageing, 1972, 1, 152. J. H. N., and others Scand. J. Urol. Nephrol. 1976, 10, 201.
2. Syversen,
1. Cohen, G., Collins, M. Science, 1970, 167, 1749. 2. Davis, V. E., Walsh, M. D. ibid. p. 1005. 3. Cohen, G., Mytillineou, C., Barrett, R. E. ibid. 1972, 175, 1269. 4. Hamilton, M. G., Hirst, M. Eur. J. Pharmac. 1976, 39, 237. 5. Dougan, D., Wade, D., Mearrick, P. Nature, 1975, 254, 70. 6. Blum, K., Meyer, E., Futterman, S., Wallace, J. E., Schwertner, H. A. Pharmacologist, 1976, 18, 681. 7. Blum, K., Eubanks, J. D., Wallace, J. E., Schwertner, H. A. Experientia,
1976, 32, 493. Sinclair, J. D., Atkins, J., Walker, S. Nature, 1973, 246, 425. Ho., A. K. S., Chen, R. A. C., Morrison, M. J. in Alcohol and Opiates: Neurochemical and Behavioral Mechanisms (edited by K. Blum); p. 189. New York, 1977. 10. Ross, D. H., Geller, I., Hartmann, R. J. Proc. west. Pharmac. Soc. 1976, 19, 8. 9.
326. 11.
Jones, M. A., Spratto, G. R. Unpublished.
800 increases morphine self-administration in
monkeys.12 Furtherin mice is suppressed syndrome by a single injection of morphine.’3I The findings that morphine attenuates the ethanol-withdrawal syndrome," that naloxone inhibits the development of dependence to ethanol," that biochemical cross-tolerance exists between morphine and ethanol,15 and that naloxone blocks T.i.Q.-induced convulsions in mice,16 suggests that ethanol, or some metabolite, affects the opiate receptor. Hamilton et al." found that salsolinol behaves as a weak opiate agonistantagonist in the guineapig ileum. Salsolinol depletes regional brain calcium as does morphine, when administered peripherally.I8 Both effects are inhibited by naloxone, suggesting that the site of action is the opiate receptor. Furthermore, salsolinol was found to stereospecifically bind to the opiate receptor in guineapig brain. 19 Marshall et al. 20 found that 3-carboxysalsolinol produces analgesia by itself and potentiates morphine analgesia. Intracerebral administration of salsolinol has also been found to affect morphine analgesia in mice.21These results support a weak agonist-antagonist role for salsolinol with regard to opiate-receptor interaction. The findings that salsolinol and 3-carboxysalsolinol prolong ethanol-induced narcosis,22 but have no effect on barbiturate-induced hypnosis, more, the ethanol-withdrawal
supports a role for T.i.Q.s in ethanol actions. We need now to find out ifT.i.Q. alkaloids are formed in vivo during ethanol intoxication and in sufficient amounts to produce physical dependence. However, it could be that these compounds are formed in synaptic nerve endings at concentrations which are active physiologically but which cannot be detected by current techniques. M.G.H. Texas.
is an
exchange
student from Canada to the
University
of
Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78284, U.S.A.
KENNETH BLUM MURRAY G. HAMILTON ELEANOR K. MEYER
Department of Pharmacology, University of Western Ontario, London, Ontario, Canada
MAURICE HIRST ALICE MARSHALL
QUALITY-CONTROL SCHEMES IN PATHOLOGY SIR,-Iwas astonished to read the letter from Dr Jacobs and his colleagues (March 19, p. 652) in which they criticised the organisers of the National Quality Control Scheme for Clinical Chemistry for their plan to offer advice and assistance to those laboratories shown to provide a poor analytical service over a long period. No doubt there will be differing views as to how this can best be done, but few would disagree that consistently inadequate performance by a participating laboratory serious attention. Unfortunately there are still biochemists who are unable or even unwilling to take action even when confronted by appalling results on external quality-control schemes. Patients have a right to be protected from such laboratories, and the very tentative steps planned by the N.Q.C.S. panel go a little way towards achieving this objective. To some extent I support the view that consultants should warrants
12. Uyeno, E. Personal communication. 13. Blum, K., Wallace, J. E., Schwertner, H. A., Eubank, J. D. Experientia, 1976, 32, 79. 14. Blum, K., Wallace, J. E., Futterman, S. L. Nature, 1976, 265, 49. 15. Ross, D. H. in Work in Progress on Alcoholism (edited by F. A. Seixas and S. Eggleston) Ann. N.Y. Acad. Sci. 1975, 273, 280. 16. Blum, K., Eubanks, J. D., Wallace, J. E. Proc. 37th Meeting Comm. Prob.
Drug Dependence, 1975, p. 551. Hamilton, M. G., Marshall, A. M., Blum, K., Hirst, M. Pharmacologist, 1976, 18, 102. 18. Ross, D. H., Medina, M. A., Cardenas, H. L. Science, 1974, 186, 63. 19. Goldstein, A. Personal communication. 20. Marshall, A., Hirst, M., Blum, K. Experientia (in the press). 21. Blum, K., Meyer, E., Wallace, J. E., Schwertner, H. A., Futterman, S., Hirst, M., Marshall, A., Hamilton, M. G. Neuroscience, 1976, 2, 1241. 22. Marshall, A., Hirst, M. Experientia 1976, 32, 201. 17.
be free
to choose methods thought to be most suited to their particular environment, but if it can be shown conclusively that results are analytically unsatisfactory or even clinically
dangerous then the situation must be rectified. Some departments achieve poor results because of insufficient staffing or equipment, and where this is so better provision should be made by the authorities. However, if unsatisfactory analyses are due to deficiencies in senior staff then more extreme measures must eventually be taken. Department of Chemical Pathology, St James’s University Hospital, Leeds LS9 7TF
R. T. EVANS
SIR,-Some of your readers may have been mystified by the reference to the National Quality Control Scheme (N.Q.C.S.) in the letter by Dr Jacobs and his colleagues. This scheme, whereby portions of the same blood serum (usually human) are distributed for analysis by laboratories throughout the country and the results compared, began in 1969 for clinical biochemistry.’ Comparable schemes have since been introduced for haematology and microbiology laboratories. The scheme has always been voluntary and laboratories were anonymous, referred to by a code number. The scheme is operated by laboratory workers for laboratory workers; the D.H.S.S. has supported the scheme financially, but its officials have scrupu-. lously avoided interfering in any way. The scheme has revealed what was always suspected-that results from a small minority of laboratories consistently (i.e., over many months) diverge markedly and erratically from those obtained in most laboratories using similar analytical methods. Some discrepancies are large enough to be clinically misleading.’ Schemes such as the N.Q.C.S. can lead to improved laboratory performnance.33 Many laboratory consultants feel that it is a corporate professional responsibility to assist such laboratories. New proposals for the N.Q.C.S., whereby the identity of laboratories persistently shown to have serious problems would be revealed to a small panel of advisers, were discussed recently at a national meeting in Birmingham, attended by clinical biochemists from all over the country. The proposals were endorsed almost unanimously. Any pathologist who disapproves may simply opt out. This is a far cry from "a Central Administration is appropriating a right to interfere with a consultant’s management of his department". As I see it, the intention is to enable selected clinical biochemists to assist colleagues and thus forestall the type of State interference and licensing operating in some countries. In several regions, schemes have been working for some time whereby local laboratories voluntarily reveal their code number to a regional adviser, with considerable benefit and no obvious problems. The quality of laboratory performance is an emotive subject which must be faced realistically, without unsubstantiated alarmist reactions. Poor laboratory performance is a difficult problem, particularly when funds for staff and equipment are scarce. The offer of assistance from independent professional laboratory workers is constructive, and has the support of all the professional bodies involved, from which representatives will be drawn to form the advisory panels. It could be argued that it is more ethical to offer advice to a colleague in serious difficulties than to wait until help is specifically requested. Indeed I suspect such help would usually be welcomed by those who might feel inhibited from seeking assistance. There is already too much secrecy about laboratory performance, and I believe that, although not strictly relevant to quality control schemes, laboratory directors should be much more open in in-
1. Whitehead, T. P., Browning, D. M., Gregory, A. J. clin. Path. 1973, 26, 435. 2. Bold, A. M., Browning, D. M. ibid. 1975, 28, 234. 3. Whitehead, T. P., Browning, D. M., Gregory, A. m Quality Control in Clinical Chemistry (edited by de Gruyter). Berlin, 1976.
ISOQUINOLINE ALKALOIDS AS POSSIBLE
one
Clinical Research Division, AB Kabi, 112 87 Stockholm, Sweden
FREDRIK BERGLUND PER-OLOV GLENNE
* * This letter has been shown
to
Dr Ritch and his
colleagues,
whose reply follows.-ED.L.
StR,—If oral emepronium bromide has no urodynamic effect, clinical improvement in incontinence is unlikely. Furthermore clinical assessment relies principally on incontinence charts which are inherently inaccurate and unreliable on busy wards. Urodynamic studies provide objective measurements which are easily interpreted. If the results of the bladder capacity after intramuscular administration are misleading because of increased residual volume this would not be true for the four other variables which also improved significantly (r001) after intramuscular injection but did not change after oral therapy. Dr Berglund and Dr Glenne claim that ten studies show clinical improvement in bladder capacity in the elderly after emepronium bromide but of the three references chosen, two are unpublished. In the other, Brocklehurst et al.’ found a small reduction in incontinence "from about 50 to about 45 per cent" and although some results were statistically significant at the 5% level there was no consistent pattern of improvement.
Syversen et all have shown that in post-prostatectomy paa change in dose of emepronium bromide from 50 mg intramuscularly to 600 mg orally results in a ten-fold decrease in plasma concentration and a loss of effect on bladder capacity. Thus we are surprised by Berglund and Glenne’s claim that plasma concentrations of around 30 .g/1 had a beneficial effect on the bladder; however, no data are given or have been
tients
published elsewhere on the
extent
of the increase in functional
REGULATORS OF ALCOHOL ADDICTION
S!R,—A possible biochemical explanation for a link between opiates and ethanol was provided in 1970, when two groups reported the formation of tetrahydroisoquinoline (T.i.Q.) alkaas a consequence of ethanol metabolism. 1 This discovery was significant because it was the first demonstration that mammalian tissues could "synthesise" alkaloids and
loids
because benzylisoquinoline alkaloids (e.g., tetrahydropapaveroline), are intermediates in the biosynthesis of morphine in the poppy. We can only speculate how these alkaloids might link the biochemical and behavioural actions of ethanol and opiates, but enough is known of their pharmacology for some mechanisms to be suggested. The chronic administration of ethanol and opiates produces an increase in central noradrenaline (norepinephrine) (N.A.). We do not know how this happens, but the formation of T.I.Q. alkaloids may explain the increase after ethanol. The formation of dopamine-derived T.i.Q.s would decrease the synthesis ofN.A. by removing the substrate for dopamine-p-hydroxylase. This decrease of N.A. would remove end-product inhibition and stimulate synthesis. Furthermore, salsolinol releases N.A. from nerve endings and inhibits its uptake.3 This would further decrease end-product inhibition of tyrosine hydroxylase and promote N.A. turnover.
We found that intracerebral administration of salsolinol to mice undergoing withdrawal from ethanol vapour either ameliorated (10 .g/animal) or exacerbated (100 p.g/animal) ethanol-induced withdrawal symptoms (unpublished). Salsolinol releases neural stores of catecholamines, so the exacerbation could be the result of N.A. release and activation of central N.A.-ot-receptors. Implicit in this argument is the fact that N.A.-cx-activation takes preference over dopamine (D.A.) activation because these alkaloids release both D.A. and N.A. from neural stores.3 The biphasic action of salsolinol, though seeming contradictory, may be explained by the fact that salsolinol can block ex-receptors4 and is an agonist at D.A. receptors.’ Thus, large exogenous doses of salsolinol probably exert their effect through a catecholamine release, while the smaller amount acts through direct receptor antagonism (ex) and/or activation (D.A.). Support for this explanation is derived from the findings of Blum et al.6 showing that N.A. exacerbates the withdrawal convulsions induced by ethanol, whereas D.A. ameliorates this condition.7 A lot of evidence indicates voluntary alcohol opiates and ethanol. Morphine suppresses voluntary alcohol consumption in hamsters8 and a single injection of an opiate agonist significantly suppresses voluntary alcohol consumption in both mice and rats.9 Ross et al. 10 have reported the same effects in hamsters and have also shown that dextrorphan did not affect alcohol consumption, indicating the necessity for an active opiate enantiomer. We have found that naloxone or naltrexone at 5 mg/kg can inhibit ethanol narcosis in mice, while higher doses (10 mglkg) potentiate the narcosis (unpublished). Concurrent administration of ethanol can affect morphine withdrawal in rats," and withdrawal of ethanol after chronic administration
bladder capacity. We agree that there is need for a safe drug which can act the bladder, but we feel that the published evidence suggests that emepronium bromide does not meet this require-
on
ment.
A. E. S. RITCH C. M. CASTLEDEN C. F. GEORGE M. R. P. HALL
Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO9 4XY 3 Brocklehurst, J. C., Armitage, P., Jouhar, 4. Pathy, H. S., Jouhar, A. J. Unpublished. 5 Hebjørn, S. Unpublished.
A. J.
Age Ageing, 1972, 1, 152.
1. Brocklehurst, J. C., Armitage, P., Jouhar, A. J. Age Ageing, 1972, 1, 152. J. H. N., and others Scand. J. Urol. Nephrol. 1976, 10, 201.
2. Syversen,
1. Cohen, G., Collins, M. Science, 1970, 167, 1749. 2. Davis, V. E., Walsh, M. D. ibid. p. 1005. 3. Cohen, G., Mytillineou, C., Barrett, R. E. ibid. 1972, 175, 1269. 4. Hamilton, M. G., Hirst, M. Eur. J. Pharmac. 1976, 39, 237. 5. Dougan, D., Wade, D., Mearrick, P. Nature, 1975, 254, 70. 6. Blum, K., Meyer, E., Futterman, S., Wallace, J. E., Schwertner, H. A. Pharmacologist, 1976, 18, 681. 7. Blum, K., Eubanks, J. D., Wallace, J. E., Schwertner, H. A. Experientia,
1976, 32, 493. Sinclair, J. D., Atkins, J., Walker, S. Nature, 1973, 246, 425. Ho., A. K. S., Chen, R. A. C., Morrison, M. J. in Alcohol and Opiates: Neurochemical and Behavioral Mechanisms (edited by K. Blum); p. 189. New York, 1977. 10. Ross, D. H., Geller, I., Hartmann, R. J. Proc. west. Pharmac. Soc. 1976, 19, 8. 9.
326. 11.
Jones, M. A., Spratto, G. R. Unpublished.
800 increases morphine self-administration in
monkeys.12 Furtherin mice is suppressed syndrome by a single injection of morphine.’3I The findings that morphine attenuates the ethanol-withdrawal syndrome," that naloxone inhibits the development of dependence to ethanol," that biochemical cross-tolerance exists between morphine and ethanol,15 and that naloxone blocks T.i.Q.-induced convulsions in mice,16 suggests that ethanol, or some metabolite, affects the opiate receptor. Hamilton et al." found that salsolinol behaves as a weak opiate agonistantagonist in the guineapig ileum. Salsolinol depletes regional brain calcium as does morphine, when administered peripherally.I8 Both effects are inhibited by naloxone, suggesting that the site of action is the opiate receptor. Furthermore, salsolinol was found to stereospecifically bind to the opiate receptor in guineapig brain. 19 Marshall et al. 20 found that 3-carboxysalsolinol produces analgesia by itself and potentiates morphine analgesia. Intracerebral administration of salsolinol has also been found to affect morphine analgesia in mice.21These results support a weak agonist-antagonist role for salsolinol with regard to opiate-receptor interaction. The findings that salsolinol and 3-carboxysalsolinol prolong ethanol-induced narcosis,22 but have no effect on barbiturate-induced hypnosis, more, the ethanol-withdrawal
supports a role for T.i.Q.s in ethanol actions. We need now to find out ifT.i.Q. alkaloids are formed in vivo during ethanol intoxication and in sufficient amounts to produce physical dependence. However, it could be that these compounds are formed in synaptic nerve endings at concentrations which are active physiologically but which cannot be detected by current techniques. M.G.H. Texas.
is an
exchange
student from Canada to the
University
of
Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78284, U.S.A.
KENNETH BLUM MURRAY G. HAMILTON ELEANOR K. MEYER
Department of Pharmacology, University of Western Ontario, London, Ontario, Canada
MAURICE HIRST ALICE MARSHALL
QUALITY-CONTROL SCHEMES IN PATHOLOGY SIR,-Iwas astonished to read the letter from Dr Jacobs and his colleagues (March 19, p. 652) in which they criticised the organisers of the National Quality Control Scheme for Clinical Chemistry for their plan to offer advice and assistance to those laboratories shown to provide a poor analytical service over a long period. No doubt there will be differing views as to how this can best be done, but few would disagree that consistently inadequate performance by a participating laboratory serious attention. Unfortunately there are still biochemists who are unable or even unwilling to take action even when confronted by appalling results on external quality-control schemes. Patients have a right to be protected from such laboratories, and the very tentative steps planned by the N.Q.C.S. panel go a little way towards achieving this objective. To some extent I support the view that consultants should warrants
12. Uyeno, E. Personal communication. 13. Blum, K., Wallace, J. E., Schwertner, H. A., Eubank, J. D. Experientia, 1976, 32, 79. 14. Blum, K., Wallace, J. E., Futterman, S. L. Nature, 1976, 265, 49. 15. Ross, D. H. in Work in Progress on Alcoholism (edited by F. A. Seixas and S. Eggleston) Ann. N.Y. Acad. Sci. 1975, 273, 280. 16. Blum, K., Eubanks, J. D., Wallace, J. E. Proc. 37th Meeting Comm. Prob.
Drug Dependence, 1975, p. 551. Hamilton, M. G., Marshall, A. M., Blum, K., Hirst, M. Pharmacologist, 1976, 18, 102. 18. Ross, D. H., Medina, M. A., Cardenas, H. L. Science, 1974, 186, 63. 19. Goldstein, A. Personal communication. 20. Marshall, A., Hirst, M., Blum, K. Experientia (in the press). 21. Blum, K., Meyer, E., Wallace, J. E., Schwertner, H. A., Futterman, S., Hirst, M., Marshall, A., Hamilton, M. G. Neuroscience, 1976, 2, 1241. 22. Marshall, A., Hirst, M. Experientia 1976, 32, 201. 17.
be free
to choose methods thought to be most suited to their particular environment, but if it can be shown conclusively that results are analytically unsatisfactory or even clinically
dangerous then the situation must be rectified. Some departments achieve poor results because of insufficient staffing or equipment, and where this is so better provision should be made by the authorities. However, if unsatisfactory analyses are due to deficiencies in senior staff then more extreme measures must eventually be taken. Department of Chemical Pathology, St James’s University Hospital, Leeds LS9 7TF
R. T. EVANS
SIR,-Some of your readers may have been mystified by the reference to the National Quality Control Scheme (N.Q.C.S.) in the letter by Dr Jacobs and his colleagues. This scheme, whereby portions of the same blood serum (usually human) are distributed for analysis by laboratories throughout the country and the results compared, began in 1969 for clinical biochemistry.’ Comparable schemes have since been introduced for haematology and microbiology laboratories. The scheme has always been voluntary and laboratories were anonymous, referred to by a code number. The scheme is operated by laboratory workers for laboratory workers; the D.H.S.S. has supported the scheme financially, but its officials have scrupu-. lously avoided interfering in any way. The scheme has revealed what was always suspected-that results from a small minority of laboratories consistently (i.e., over many months) diverge markedly and erratically from those obtained in most laboratories using similar analytical methods. Some discrepancies are large enough to be clinically misleading.’ Schemes such as the N.Q.C.S. can lead to improved laboratory performnance.33 Many laboratory consultants feel that it is a corporate professional responsibility to assist such laboratories. New proposals for the N.Q.C.S., whereby the identity of laboratories persistently shown to have serious problems would be revealed to a small panel of advisers, were discussed recently at a national meeting in Birmingham, attended by clinical biochemists from all over the country. The proposals were endorsed almost unanimously. Any pathologist who disapproves may simply opt out. This is a far cry from "a Central Administration is appropriating a right to interfere with a consultant’s management of his department". As I see it, the intention is to enable selected clinical biochemists to assist colleagues and thus forestall the type of State interference and licensing operating in some countries. In several regions, schemes have been working for some time whereby local laboratories voluntarily reveal their code number to a regional adviser, with considerable benefit and no obvious problems. The quality of laboratory performance is an emotive subject which must be faced realistically, without unsubstantiated alarmist reactions. Poor laboratory performance is a difficult problem, particularly when funds for staff and equipment are scarce. The offer of assistance from independent professional laboratory workers is constructive, and has the support of all the professional bodies involved, from which representatives will be drawn to form the advisory panels. It could be argued that it is more ethical to offer advice to a colleague in serious difficulties than to wait until help is specifically requested. Indeed I suspect such help would usually be welcomed by those who might feel inhibited from seeking assistance. There is already too much secrecy about laboratory performance, and I believe that, although not strictly relevant to quality control schemes, laboratory directors should be much more open in in-
1. Whitehead, T. P., Browning, D. M., Gregory, A. J. clin. Path. 1973, 26, 435. 2. Bold, A. M., Browning, D. M. ibid. 1975, 28, 234. 3. Whitehead, T. P., Browning, D. M., Gregory, A. m Quality Control in Clinical Chemistry (edited by de Gruyter). Berlin, 1976.
