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NAMES OF PROGESTATIONAL COMPOUNDS
113 a variable amount of hyperof epithelial type: in two, there was local cellularity mainly with adhesions. One other glomerulus showed reaction capsular scattered local areas of hypercellularity. The remaining glomeruli were within normal limits. There were one or two small foci of tubular atrophy with thickening of the basement membrane. There was no vascular abnormality. At subsequent reviews the patient has been well, with a blood-pressure of 140/80, no proteinuria, and only scanty red blood-cells in his urine.
solid with hyalinisation, with
This illness suggests that this was a case of " lung purpura with nephritis " as described by Rusby and Wilson2 in that he fell into the right age-group, had hxmoptysis followed by focal glomerulonephritis and anaemia out of proportion to the blood-loss. The chief interest lies in the patient’s recovery without corticosteroids unlike their patient, and it seems likely there is a wider spectrum of the disease than is accepted at present, extending perhaps from idiopathic pulmonary haemosiderosis to hxmoptysis with fatal nephritis. I am grateful to the Director General, R.A.F. Medical Services, for permission to report this case. R.A.F.
Hospital, Wroughton, Swindon, Wilts.
D. J. STOKER.
NAMES OF PROGESTATIONAL COMPOUNDS SiR,-Among the new synthetic progestational compounds now available in Great Britain are two preparations ’Metrulen-M’ andOvulen ’, marketed by Messrs. Searle. They consist of the same compounds in exactly the same quantities-i.e., 1 mg. ethynodiol diacetate and 0-1 mg. mestranol. A third preparationMetrulen’ contains twice as much ethynodiol diacetate. This is an unfortunate proliferation of names for the same preparation, and has occurred despite the protest which appeared in your columns3 whenConovid ’ andEnavid ’ were promoted in a similar manner. Metrulen-M is recommended for use in gynaecological disorders and ovulen as a contraceptive. The justification given for the different names is " for the convenience of physician and patient" and has little basis in reality. Duplication of names for the same drug because of a variation in therapeutic application is quite unacceptable and does a disservice to relations between the medical profession and the pharmaceutical industry. If every company used the same promotional technique the result would be chaos. The advertising of progestational compounds in the medical Press gives cause for concern in another respect. For instance, the product’Volidan ’ is promoted as an orally active form of progesterone-" the body’s natural hormone ". It does in fact contain megestrol, a derivative of 17K-hydroxyprogesterone which is physiologically quite different from progesterone, and this compound is no more natural or related to progesterone than is medroxyprogesterone (’ Provera ’). No true progesterone derivatives are available on the British market. It is often possible to apply quite truthfully several different chemical descriptions to the same compound; a fact which has been used by certain companies. The product allyloestrenol (’ Gestanin ’) is referred to as "a pure oral gestagen" (our italics), the reference being in terms of the oestrogen nucleus. It is in fact a nor-testosterone derivative, 17 allyl-3 desoxy-19 nortestosterone, and was described as such by the earlier clinical investigators. ’4 In view of the proven inability of nortestosterone derivatives, such as norethynodrel (the progestagen in enavid) and norethisterone (’ Norlutin-A ’, ’Primolut-N’) to mimic the activity of progesterone in maintaining pregnancy in spayed animals, it is surprising that it is advertised for pregnancy maintenance. 2. 3. 4.
Rusby, N. L., Wilson, C. Quart. J. Med. 1960, 29, 501. Macgregor, A. G. Lancet, 1961, i, 399. Willemsen, H. M.D. Thesis, University of Groningen, 1960.
The research departments within the pharmaceutical industry make real contributions to human knowledge. It
is unfortunate therefore that commercial motives may determine a less creditable marketing policy. Departments of Materia Medica and Therapeutics, and Obstetrics and Gynæcology, University of Aberdeen.
J. CROOKS A. I. KLOPPER.
HYPOTENSIVE THERAPY IN CEREBROVASCULAR DISEASE SIR,-While welcoming an attempt to evaluate the use of hypotensive drugs in cerebrovascular disease, I think it unwise for Dr. Marshall (Jan. 4) to make such a sweeping statement as " Our results should remove any fears that long-term hypotensive therapy might be hazardous in patients with cerebrovascular disease ", even though he
qualifies this later. All experienced physicians will know that complications do occur. I had under my own observation a patient with progressive visual deterioration who became demented every time we tried to reduce his blood-pressure. The risk from uncontrolled hypertension may be greater than with therapy, and Dr. Marshall’s paper certainly gives support to the policy adopted by many clinicians-namely, a partial reduction of the blood-pressure to an arbitrary level. West End Hospital for Neurology and Neurosurgery, 91, Dean Street, London, W.1.
J. N. MILNES.
MULTIPLE CONGENITAL ABNORMALITIES SIR,-Since the publication of our note,1 12 more sibships have been found with at least one example of
multiple congenital malformations characterised by lack of bone elements. Joint analysis of our total sample of 25 sibships shows: All the parents are normal except one. In 2 families only, the propositi have sibs with a similar defect. In 1 case only, members of the family other than sibs show an abnormality similar to that found in the propositus, though different types of peromelia were verified in other relatives of 3 sibships. Thus we have 5 cases where sibs or other relatives of the propositi show a similar or related abnormality. 1 example only of cousin marriage has been verified among the parents from a highly inbred Brazilian region. This incidence of cousin marriages (1/25) is of the same order of magnitude as would be expected in a random sample.2 No birth-order effect has been found (X2=13.11, df=8, P>0-10), though our ascertainment method (through questionnaires) is not ideal for this kind of analysis. The pooled findings reveal that among 73 liveborn males, 17 are affected (23%), and that among 66 liveborn females, 14 are affected (21%, X2=0.09). Sex does not, therefore, influence the occurrence of abnormalities. The great majority of the affected subjects are now adults. The pregnancies leading to the 5 youngest propositi started between December, 1957, and March, 1960. The 3rd of these 5 children (August, 1959) is from Portugal, and we are told that no drug had been used by the mother during pregnancy; the other 4 cases are from Brazil.
Thalidomide was first sold in Brazil in March, 1959, and therefore the deformities in the last 2 cases only could have been produced by thalidomide. The mother who became pregnant in January, 1960, took thalidomide for a month between the second and the third months of pregnancy, and the mother who became pregnant in March, 1960, took about 20 tablets between the fortyfifth and sixtieth days of pregnancy. The 2nd affected 1. 2.
Freire-Maia, N., Freire-Maia, A. Lancet, 1961, ii, 1363. Freire-Maia, N. Amer. J. hum. Genet. 1957, 9, 284.
solid with hyalinisation, with
This illness suggests that this was a case of " lung purpura with nephritis " as described by Rusby and Wilson2 in that he fell into the right age-group, had hxmoptysis followed by focal glomerulonephritis and anaemia out of proportion to the blood-loss. The chief interest lies in the patient’s recovery without corticosteroids unlike their patient, and it seems likely there is a wider spectrum of the disease than is accepted at present, extending perhaps from idiopathic pulmonary haemosiderosis to hxmoptysis with fatal nephritis. I am grateful to the Director General, R.A.F. Medical Services, for permission to report this case. R.A.F.
Hospital, Wroughton, Swindon, Wilts.
D. J. STOKER.
NAMES OF PROGESTATIONAL COMPOUNDS SiR,-Among the new synthetic progestational compounds now available in Great Britain are two preparations ’Metrulen-M’ andOvulen ’, marketed by Messrs. Searle. They consist of the same compounds in exactly the same quantities-i.e., 1 mg. ethynodiol diacetate and 0-1 mg. mestranol. A third preparationMetrulen’ contains twice as much ethynodiol diacetate. This is an unfortunate proliferation of names for the same preparation, and has occurred despite the protest which appeared in your columns3 whenConovid ’ andEnavid ’ were promoted in a similar manner. Metrulen-M is recommended for use in gynaecological disorders and ovulen as a contraceptive. The justification given for the different names is " for the convenience of physician and patient" and has little basis in reality. Duplication of names for the same drug because of a variation in therapeutic application is quite unacceptable and does a disservice to relations between the medical profession and the pharmaceutical industry. If every company used the same promotional technique the result would be chaos. The advertising of progestational compounds in the medical Press gives cause for concern in another respect. For instance, the product’Volidan ’ is promoted as an orally active form of progesterone-" the body’s natural hormone ". It does in fact contain megestrol, a derivative of 17K-hydroxyprogesterone which is physiologically quite different from progesterone, and this compound is no more natural or related to progesterone than is medroxyprogesterone (’ Provera ’). No true progesterone derivatives are available on the British market. It is often possible to apply quite truthfully several different chemical descriptions to the same compound; a fact which has been used by certain companies. The product allyloestrenol (’ Gestanin ’) is referred to as "a pure oral gestagen" (our italics), the reference being in terms of the oestrogen nucleus. It is in fact a nor-testosterone derivative, 17 allyl-3 desoxy-19 nortestosterone, and was described as such by the earlier clinical investigators. ’4 In view of the proven inability of nortestosterone derivatives, such as norethynodrel (the progestagen in enavid) and norethisterone (’ Norlutin-A ’, ’Primolut-N’) to mimic the activity of progesterone in maintaining pregnancy in spayed animals, it is surprising that it is advertised for pregnancy maintenance. 2. 3. 4.
Rusby, N. L., Wilson, C. Quart. J. Med. 1960, 29, 501. Macgregor, A. G. Lancet, 1961, i, 399. Willemsen, H. M.D. Thesis, University of Groningen, 1960.
The research departments within the pharmaceutical industry make real contributions to human knowledge. It
is unfortunate therefore that commercial motives may determine a less creditable marketing policy. Departments of Materia Medica and Therapeutics, and Obstetrics and Gynæcology, University of Aberdeen.
J. CROOKS A. I. KLOPPER.
HYPOTENSIVE THERAPY IN CEREBROVASCULAR DISEASE SIR,-While welcoming an attempt to evaluate the use of hypotensive drugs in cerebrovascular disease, I think it unwise for Dr. Marshall (Jan. 4) to make such a sweeping statement as " Our results should remove any fears that long-term hypotensive therapy might be hazardous in patients with cerebrovascular disease ", even though he
qualifies this later. All experienced physicians will know that complications do occur. I had under my own observation a patient with progressive visual deterioration who became demented every time we tried to reduce his blood-pressure. The risk from uncontrolled hypertension may be greater than with therapy, and Dr. Marshall’s paper certainly gives support to the policy adopted by many clinicians-namely, a partial reduction of the blood-pressure to an arbitrary level. West End Hospital for Neurology and Neurosurgery, 91, Dean Street, London, W.1.
J. N. MILNES.
MULTIPLE CONGENITAL ABNORMALITIES SIR,-Since the publication of our note,1 12 more sibships have been found with at least one example of
multiple congenital malformations characterised by lack of bone elements. Joint analysis of our total sample of 25 sibships shows: All the parents are normal except one. In 2 families only, the propositi have sibs with a similar defect. In 1 case only, members of the family other than sibs show an abnormality similar to that found in the propositus, though different types of peromelia were verified in other relatives of 3 sibships. Thus we have 5 cases where sibs or other relatives of the propositi show a similar or related abnormality. 1 example only of cousin marriage has been verified among the parents from a highly inbred Brazilian region. This incidence of cousin marriages (1/25) is of the same order of magnitude as would be expected in a random sample.2 No birth-order effect has been found (X2=13.11, df=8, P>0-10), though our ascertainment method (through questionnaires) is not ideal for this kind of analysis. The pooled findings reveal that among 73 liveborn males, 17 are affected (23%), and that among 66 liveborn females, 14 are affected (21%, X2=0.09). Sex does not, therefore, influence the occurrence of abnormalities. The great majority of the affected subjects are now adults. The pregnancies leading to the 5 youngest propositi started between December, 1957, and March, 1960. The 3rd of these 5 children (August, 1959) is from Portugal, and we are told that no drug had been used by the mother during pregnancy; the other 4 cases are from Brazil.
Thalidomide was first sold in Brazil in March, 1959, and therefore the deformities in the last 2 cases only could have been produced by thalidomide. The mother who became pregnant in January, 1960, took thalidomide for a month between the second and the third months of pregnancy, and the mother who became pregnant in March, 1960, took about 20 tablets between the fortyfifth and sixtieth days of pregnancy. The 2nd affected 1. 2.
Freire-Maia, N., Freire-Maia, A. Lancet, 1961, ii, 1363. Freire-Maia, N. Amer. J. hum. Genet. 1957, 9, 284.