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SERUM-TRANSAMINASE LEVELS IN PATIENTS TREATED WITH PROPRANOLOL
1338
Letters to the Editor
3. Would it be wise for the State itself
undertake
to
or
participate in the manufacture of drugs ? 4. Should the Government acquire share holdings in a number of major firms ? 5. Should the Ministry of Health be given power to obtain information aboutcosts and profits, and sales-promotion costs, and to secure pricing policies in keeping with national ’
WOMEN IN MEDICINE
SIR,-Your annotation (Nov. 14) refers
to the " lost women". As potential among medically qualified and we like should to consultants, registrars, lecturers,, draw attention to one aspect of this problem which you did not touch upon.
It was for many years possible to obtain consultant work for a varying number of weekly sessions-anything from four to seven being common. This was particularly so in ancillary specialties such as anaesthetics, physical medicine, and radiology, but it was hoped that similar opportunities might be available in medicine, obstetrics, pathology, and other specialties. ’In recent months, however, there appears to have been a complete change in policy and the available consultant sessions are advertised, almost without exception, as full-time or maximum part-time appointments. Frequently, this has been achieved by an amalgamation of posts from three or four hospitals, each requiring two or three sessions only. However, in a number of recent cases such posts have not been filled because of the lack of suitably qualified candidates. There are many women who, realising the problem inherent in having both a family and a career, chose specialties in which they were led to believe that part-time consultant work would be available. Some of these, highly qualified after years of specialist training, now find the prospect of full-time work more than they may reasonably wish to undertake. However, they are offered no alternative, ’while at the same time posts remain unfilled or-what is surely undesirable-staffed permanently by locums. We feel that the present state of affairs, if it continues, will discourage many of those women who qualify from attempting to continue with a medical career. We wish to suggest that consultant work in all branches of medicine
should be available to those seeking part-time employment as well as to those who wish to work full time. MORAG BASTAPLE ANN BEARDWELL ELEANOR BESTERMAN MARGARET CASH EVELYN COATES JEAN COLSTON MARY CORBETT PRETIFAR CRACROFT CELIA DAVIES ULUNED DAVIES RUTH EDELSTON PAULINE EMERSON
PATRICIA EDWARDS CHARLOTTE FELDMAN BERYL GOETZEE HELENE GOODMAN SYLVIA HEPTON SHIRLEY JONES PATRICIA LAST LEILA LESSOF URSULA HAMILTON PATERSON JEAN PRITCHARD KATRINA RHODES MURIEL SIDAWAY.
NO CHARGE
SIR,-Before joining issue on the prescription charge (Nov. 21) may I mention a few facts and ask some questions ? In 1961, 60% of prescriptions were for proprietary preparations and they accounted for about 80% of the In the financial year 1962-63, cost of prescriptions. E82 million was spent on drugs under the N.H.S. This is’ about 10% of total cost of the N.H.S. and about 3/5 of total home sales of the pharmaceutical industry. The development of the industry obviously depends on the Government’s policy and the industry’s preoccupation with its return on invested capital. excessive charging and wasteful sales expenditure promotion of proprietary products ? 2. Is there need to review the Voluntary Price Regulation Scheme between Government and the industry, and insist that prices be related to unbranded standard equivalents instead of to export prices ? 1. Is there evidence of on
needs ? 6. Should the Ministry expand its present system (Prescribers’ Notes) of supplying information on drugs direct to doctors ? 7. Should the Ministry establish a publicly owned testing laboratory to deal with the important subjects of drug toxicity, side-effects of drugs, and contraindications ?
Incidentally,
we are not
it is bad for a pre-
discussing " whether
for the average citizen to pay two bob or not scription ". This is a matter of principle. As you say in your leader, " citizens maintain the National Health Service according to their means, through taxation... ". H. N. LEVITT. London, N.W.I. ALMONERS VERSUS MEDICAL SOCIAL WORKERS SIR,-Is it too late to protest about the proposed
of almoners as medical social workers ? The former title was time-honoured and short; the latter, as I see it, has no particular virtue, and replaces one word with three. Are all rat-catchers rodent operatives now ?
re-naming
Edgware General Hospital,
Edgware, Middlesex.
G. S. C. SOWRY.
SERUM-TRANSAMINASE LEVELS IN PATIENTS TREATED WITH PROPRANOLOL
SIR,-Eight patients (seven men and one woman) with intractable angina were treated with propranolol (’Inderal’) in a double-blind trial. Patients received the drug (30 mg. thrice daily) and the placebo consecutively for a 4-week period, the order of administration being made at random. Three of the patients (cases 1, 3, and 5) received the placebo during the first 4 weeks of the trial and propranolol during the second 4 weeks. One patient (case 2) received propranolol during the first 4 weeks and the placebo during the second 4 weeks. ’
Serum-transaminase and blood-urea
were
estimated bi-
weekly. One patient had severe vomiting while taking the placebo, and we decided not to continue with the trial of propranolol. Of the seven remaining patients the serum-glutamic-oxaloacetic-transaminase level rose (S.G.O.T.) in four, and the serumglutamic-pyruvic-transaminase level rose (S.G.P.T.) in three, at some time during the 8-week period (see accompanying table). In case 1 S.G.O.T. rose slightly at the end of 2 weeks on placebo treatment; this returned to normal at the end of a further 2 weeks and remained normal for the remainder of the trial. No significant changes were found in the s.G.P.T. In case 2 the S.G.O.T. rose slightly after 4 weeks of propranolol. This persisted for a further 2 weeks on the placebo and was associated with a slight rise in the s.G.P.T.; both enzymes returned to normal within a further 2 weeks. In case 3 both S.G.O.T. and S.G.P.T. were raised during the first 4 weeks on the placebo, returning to normal during the 4-week period of treatment with the drug. In case 5 both S.G.O.T. and S.G.P.T. rose during the first 4 weeks of placebo treatment, falling to normal during the first 2 weeks of treatment with propranolol, only to rise SERUM-TRANSAMINASE LEVELS IN PATIENTS RECEIVING PROPRANOLOL
1339
again during the second period. The blood-urea showed no rise during the 8-week period in any of the patients. Thus, in the four patients a slight rise of similar magnitude in the s.G.o.T. and S.G.P.T. occurred irregularly during the control period and the period of treatment with propranolol. In view of these findings, possible hepatotoxicity of the drug in these cases cannot be determined and we suggest that in future trials further attention should be given to this point. R. J. KERNOHAN Waveney Hospital, Ballymena, R. A. NEELY. Northern Ireland.
GUANOXAN IN HYPERTENSION
SIR,-During the past year we have used guanoxan (’ Envacar ’, Pfizer) in the treatment of hypertension. 48 patients (18 male, 30 female) have been seen regularly in the hypertension clinic for between four and fifty-two weeks: of these, 6 were first treated as inpatients (table I). TABLE I-PATIENTS IN TRIAL
INTRAVENOUS PLASTIC CATHETERS
SIR,-We have been instructed by our respective Councils to draw the attention of the profession to the dangers that are attendant upon the use of intravenous plastic catheters inserted through a needle. During the past few months the three defence societies have been made aware of several cases in which a piece of plastic catheter has been lost in the venous system during intravenous therapy. If an attempt is made to withdraw the plastic catheter through the needle there is a real danger that the bevel of the needle will cut through the catheter, thus leaving a part of the catheter inside the lumen of the vein. If any difficulty is encountered when the plastic tube is inserted into the vein through a needle, it is most important that both the catheter and the needle should be removed at the
came
*
Diastolic pressure >
Diastolic Diastolic § Diastolic
140 mm. Hg. pressure 125-139 mm. Hg. mm. Hg. 110-124 pressure pressure < 109 mm. Hg.
Secretary, Medical Defence Union
The degree of control was assessed by the arbitrary criteria adopted by Peart and MacMahon.1 " Good " meant a diastolic pressure in the standing position of less than 101 mm. Hg and a diastolic pressure below 111 mm. Hg lying down. " Poor " meant a diastolic pressure in the standing position of over 120 mm. Hg, and " moderate " meant a fall in diastolic pressure greater than 20 mm. Hg and intermediate between " good " and " poor ". Moderate control may, in fact, be clinically the best for some patients, and arbitrary definitions cannot cover these particular cases (table 11).
HERBERT CONSTABLE
TABLE II-RESPONSE TO TREATMENT
time.
"
PHILIP H. ADDISON
"
Secretary, Medical Protection Society
C. C. MILLAR Secretary, Medical and Dental Defence Union of Scotland.
SYMPTOMLESS CANCER IN WOMEN
SIR,-In your leading article (Dec. 5) you stress the need for a comprehensive programme to screen symptomfree women for carcinoma of the cervix uteri. Part of such a programme is the investigation of possible alternatives to
cytology.
Bonham and Gibbsreported excellent results in the biochemical estimation of 6-phosphoglucoriate-dehydrogenase activity in vaginal fluid as a screening test. Comparing this enzyme assay with cytology in an extensive trial, we, too, have been impressed by the consistently raised 6-phosphogluconatedehydrogenase activity in early invasive carcinoma of both cervix and corpus uteri. There are several serious limitations, however, to this technique as a screening test at present. The first is that only half the patients with carcinoma-in-situ have raised 6-phosphogluconate-dehydrogenase activity. The second is the frequency of false-positive reactors-women with raised enzyme activity but no clinical or cytological evidence of malignancy-particularly in the postmenopausal group. Thirdly, no way has yet been found to preserve the activity of the enzyme long enough for the convenient centralisation of samples for analysis.
If these limitations can be overcome (and we believe there is a reasonable chance that they can be), a biochemical assay such as this would be very welcome, since it lends itself readily to automation. We envisage its place as that of a first screening test. Samples would be taken concurrently for both enzyme analysis and cytology; but only in cases with a positive enzyme test would the smears need to be examined cytologically. Royal Marsden Hospital and the Institute of Cancer Research, London, S.W.3. 1.
Bonham,
D.
G., Gibbs,
C. B. CAMERON P. E. THOMPSON HANCOCK. D. F. Brit.
med. J. 1962, ii,
823.
Of the 3 patients whose response was " poor ", 1 failed to attend, and the other 2 stopped taking the drug before a therapeutic level was reached. No other patient failed to respond, and our trial included 17 patients who were poorly controlled by other hypotensive drugs. 6 of the 17 patients whose response was " moderate " had troublesome postural or exertional hypotension, and we did not therefore try to lower their blood-pressure further. Tolerance has not so far been encountered. The most common side-effects were nausea (11patients), vomiting (13), diarrhoea and urgency of defecation (11), and lassitude (7). Some patients had more than one side-effect. If these could not be controlled with simple measures (e.g., promethazine, chlorotheophyllidinate [’ Avomine ’], codeine phosphate) we usually halved the dose of guanoxan and added the diuretic polythiazide (’Nephril’) in a daily dose of 1 mg. In 5 patients, a coated guanoxan tablet was effective, both to control the blood-pressure and to overcome side-effects. Out of 33 patients who at some time had side-effects, 20 are now free of them, 8 still have them, and 5 are on other drugs because the side-effects were not tolerable. Routine blood-counts and liver-function tests were carried out on all patients before admission to the trial, and regularly during its course. 1 patient was withdrawn from the trial because the serum-bilirubin rose from 02 mg. per 100 ml. to 2-8 mg. per 100 ml. after six weeks of guanoxan therapy. He remained symptom-free, and no other clinical or biochemical abnormality was found. The bilirubin has remained normal during subsequent treatment with guanethidine. The cause of this transient rise in bilirubin remains unexplained. 1 patient became jaundiced after fourteen weeks on guanoxan. 1.
Peart, W. S., MacMahon, M. Brit. med. J. 1964, i, 398.
Letters to the Editor
3. Would it be wise for the State itself
undertake
to
or
participate in the manufacture of drugs ? 4. Should the Government acquire share holdings in a number of major firms ? 5. Should the Ministry of Health be given power to obtain information aboutcosts and profits, and sales-promotion costs, and to secure pricing policies in keeping with national ’
WOMEN IN MEDICINE
SIR,-Your annotation (Nov. 14) refers
to the " lost women". As potential among medically qualified and we like should to consultants, registrars, lecturers,, draw attention to one aspect of this problem which you did not touch upon.
It was for many years possible to obtain consultant work for a varying number of weekly sessions-anything from four to seven being common. This was particularly so in ancillary specialties such as anaesthetics, physical medicine, and radiology, but it was hoped that similar opportunities might be available in medicine, obstetrics, pathology, and other specialties. ’In recent months, however, there appears to have been a complete change in policy and the available consultant sessions are advertised, almost without exception, as full-time or maximum part-time appointments. Frequently, this has been achieved by an amalgamation of posts from three or four hospitals, each requiring two or three sessions only. However, in a number of recent cases such posts have not been filled because of the lack of suitably qualified candidates. There are many women who, realising the problem inherent in having both a family and a career, chose specialties in which they were led to believe that part-time consultant work would be available. Some of these, highly qualified after years of specialist training, now find the prospect of full-time work more than they may reasonably wish to undertake. However, they are offered no alternative, ’while at the same time posts remain unfilled or-what is surely undesirable-staffed permanently by locums. We feel that the present state of affairs, if it continues, will discourage many of those women who qualify from attempting to continue with a medical career. We wish to suggest that consultant work in all branches of medicine
should be available to those seeking part-time employment as well as to those who wish to work full time. MORAG BASTAPLE ANN BEARDWELL ELEANOR BESTERMAN MARGARET CASH EVELYN COATES JEAN COLSTON MARY CORBETT PRETIFAR CRACROFT CELIA DAVIES ULUNED DAVIES RUTH EDELSTON PAULINE EMERSON
PATRICIA EDWARDS CHARLOTTE FELDMAN BERYL GOETZEE HELENE GOODMAN SYLVIA HEPTON SHIRLEY JONES PATRICIA LAST LEILA LESSOF URSULA HAMILTON PATERSON JEAN PRITCHARD KATRINA RHODES MURIEL SIDAWAY.
NO CHARGE
SIR,-Before joining issue on the prescription charge (Nov. 21) may I mention a few facts and ask some questions ? In 1961, 60% of prescriptions were for proprietary preparations and they accounted for about 80% of the In the financial year 1962-63, cost of prescriptions. E82 million was spent on drugs under the N.H.S. This is’ about 10% of total cost of the N.H.S. and about 3/5 of total home sales of the pharmaceutical industry. The development of the industry obviously depends on the Government’s policy and the industry’s preoccupation with its return on invested capital. excessive charging and wasteful sales expenditure promotion of proprietary products ? 2. Is there need to review the Voluntary Price Regulation Scheme between Government and the industry, and insist that prices be related to unbranded standard equivalents instead of to export prices ? 1. Is there evidence of on
needs ? 6. Should the Ministry expand its present system (Prescribers’ Notes) of supplying information on drugs direct to doctors ? 7. Should the Ministry establish a publicly owned testing laboratory to deal with the important subjects of drug toxicity, side-effects of drugs, and contraindications ?
Incidentally,
we are not
it is bad for a pre-
discussing " whether
for the average citizen to pay two bob or not scription ". This is a matter of principle. As you say in your leader, " citizens maintain the National Health Service according to their means, through taxation... ". H. N. LEVITT. London, N.W.I. ALMONERS VERSUS MEDICAL SOCIAL WORKERS SIR,-Is it too late to protest about the proposed
of almoners as medical social workers ? The former title was time-honoured and short; the latter, as I see it, has no particular virtue, and replaces one word with three. Are all rat-catchers rodent operatives now ?
re-naming
Edgware General Hospital,
Edgware, Middlesex.
G. S. C. SOWRY.
SERUM-TRANSAMINASE LEVELS IN PATIENTS TREATED WITH PROPRANOLOL
SIR,-Eight patients (seven men and one woman) with intractable angina were treated with propranolol (’Inderal’) in a double-blind trial. Patients received the drug (30 mg. thrice daily) and the placebo consecutively for a 4-week period, the order of administration being made at random. Three of the patients (cases 1, 3, and 5) received the placebo during the first 4 weeks of the trial and propranolol during the second 4 weeks. One patient (case 2) received propranolol during the first 4 weeks and the placebo during the second 4 weeks. ’
Serum-transaminase and blood-urea
were
estimated bi-
weekly. One patient had severe vomiting while taking the placebo, and we decided not to continue with the trial of propranolol. Of the seven remaining patients the serum-glutamic-oxaloacetic-transaminase level rose (S.G.O.T.) in four, and the serumglutamic-pyruvic-transaminase level rose (S.G.P.T.) in three, at some time during the 8-week period (see accompanying table). In case 1 S.G.O.T. rose slightly at the end of 2 weeks on placebo treatment; this returned to normal at the end of a further 2 weeks and remained normal for the remainder of the trial. No significant changes were found in the s.G.P.T. In case 2 the S.G.O.T. rose slightly after 4 weeks of propranolol. This persisted for a further 2 weeks on the placebo and was associated with a slight rise in the s.G.P.T.; both enzymes returned to normal within a further 2 weeks. In case 3 both S.G.O.T. and S.G.P.T. were raised during the first 4 weeks on the placebo, returning to normal during the 4-week period of treatment with the drug. In case 5 both S.G.O.T. and S.G.P.T. rose during the first 4 weeks of placebo treatment, falling to normal during the first 2 weeks of treatment with propranolol, only to rise SERUM-TRANSAMINASE LEVELS IN PATIENTS RECEIVING PROPRANOLOL
1339
again during the second period. The blood-urea showed no rise during the 8-week period in any of the patients. Thus, in the four patients a slight rise of similar magnitude in the s.G.o.T. and S.G.P.T. occurred irregularly during the control period and the period of treatment with propranolol. In view of these findings, possible hepatotoxicity of the drug in these cases cannot be determined and we suggest that in future trials further attention should be given to this point. R. J. KERNOHAN Waveney Hospital, Ballymena, R. A. NEELY. Northern Ireland.
GUANOXAN IN HYPERTENSION
SIR,-During the past year we have used guanoxan (’ Envacar ’, Pfizer) in the treatment of hypertension. 48 patients (18 male, 30 female) have been seen regularly in the hypertension clinic for between four and fifty-two weeks: of these, 6 were first treated as inpatients (table I). TABLE I-PATIENTS IN TRIAL
INTRAVENOUS PLASTIC CATHETERS
SIR,-We have been instructed by our respective Councils to draw the attention of the profession to the dangers that are attendant upon the use of intravenous plastic catheters inserted through a needle. During the past few months the three defence societies have been made aware of several cases in which a piece of plastic catheter has been lost in the venous system during intravenous therapy. If an attempt is made to withdraw the plastic catheter through the needle there is a real danger that the bevel of the needle will cut through the catheter, thus leaving a part of the catheter inside the lumen of the vein. If any difficulty is encountered when the plastic tube is inserted into the vein through a needle, it is most important that both the catheter and the needle should be removed at the
came
*
Diastolic pressure >
Diastolic Diastolic § Diastolic
140 mm. Hg. pressure 125-139 mm. Hg. mm. Hg. 110-124 pressure pressure < 109 mm. Hg.
Secretary, Medical Defence Union
The degree of control was assessed by the arbitrary criteria adopted by Peart and MacMahon.1 " Good " meant a diastolic pressure in the standing position of less than 101 mm. Hg and a diastolic pressure below 111 mm. Hg lying down. " Poor " meant a diastolic pressure in the standing position of over 120 mm. Hg, and " moderate " meant a fall in diastolic pressure greater than 20 mm. Hg and intermediate between " good " and " poor ". Moderate control may, in fact, be clinically the best for some patients, and arbitrary definitions cannot cover these particular cases (table 11).
HERBERT CONSTABLE
TABLE II-RESPONSE TO TREATMENT
time.
"
PHILIP H. ADDISON
"
Secretary, Medical Protection Society
C. C. MILLAR Secretary, Medical and Dental Defence Union of Scotland.
SYMPTOMLESS CANCER IN WOMEN
SIR,-In your leading article (Dec. 5) you stress the need for a comprehensive programme to screen symptomfree women for carcinoma of the cervix uteri. Part of such a programme is the investigation of possible alternatives to
cytology.
Bonham and Gibbsreported excellent results in the biochemical estimation of 6-phosphoglucoriate-dehydrogenase activity in vaginal fluid as a screening test. Comparing this enzyme assay with cytology in an extensive trial, we, too, have been impressed by the consistently raised 6-phosphogluconatedehydrogenase activity in early invasive carcinoma of both cervix and corpus uteri. There are several serious limitations, however, to this technique as a screening test at present. The first is that only half the patients with carcinoma-in-situ have raised 6-phosphogluconate-dehydrogenase activity. The second is the frequency of false-positive reactors-women with raised enzyme activity but no clinical or cytological evidence of malignancy-particularly in the postmenopausal group. Thirdly, no way has yet been found to preserve the activity of the enzyme long enough for the convenient centralisation of samples for analysis.
If these limitations can be overcome (and we believe there is a reasonable chance that they can be), a biochemical assay such as this would be very welcome, since it lends itself readily to automation. We envisage its place as that of a first screening test. Samples would be taken concurrently for both enzyme analysis and cytology; but only in cases with a positive enzyme test would the smears need to be examined cytologically. Royal Marsden Hospital and the Institute of Cancer Research, London, S.W.3. 1.
Bonham,
D.
G., Gibbs,
C. B. CAMERON P. E. THOMPSON HANCOCK. D. F. Brit.
med. J. 1962, ii,
823.
Of the 3 patients whose response was " poor ", 1 failed to attend, and the other 2 stopped taking the drug before a therapeutic level was reached. No other patient failed to respond, and our trial included 17 patients who were poorly controlled by other hypotensive drugs. 6 of the 17 patients whose response was " moderate " had troublesome postural or exertional hypotension, and we did not therefore try to lower their blood-pressure further. Tolerance has not so far been encountered. The most common side-effects were nausea (11patients), vomiting (13), diarrhoea and urgency of defecation (11), and lassitude (7). Some patients had more than one side-effect. If these could not be controlled with simple measures (e.g., promethazine, chlorotheophyllidinate [’ Avomine ’], codeine phosphate) we usually halved the dose of guanoxan and added the diuretic polythiazide (’Nephril’) in a daily dose of 1 mg. In 5 patients, a coated guanoxan tablet was effective, both to control the blood-pressure and to overcome side-effects. Out of 33 patients who at some time had side-effects, 20 are now free of them, 8 still have them, and 5 are on other drugs because the side-effects were not tolerable. Routine blood-counts and liver-function tests were carried out on all patients before admission to the trial, and regularly during its course. 1 patient was withdrawn from the trial because the serum-bilirubin rose from 02 mg. per 100 ml. to 2-8 mg. per 100 ml. after six weeks of guanoxan therapy. He remained symptom-free, and no other clinical or biochemical abnormality was found. The bilirubin has remained normal during subsequent treatment with guanethidine. The cause of this transient rise in bilirubin remains unexplained. 1 patient became jaundiced after fourteen weeks on guanoxan. 1.
Peart, W. S., MacMahon, M. Brit. med. J. 1964, i, 398.