1026
bit, which is associated with delayed growth and embryo
mor-
These results suggest that intrafollicular overripeness of the ovum can be the source, not only of reproductive wastage in man,’ but also of a trouble in the programming of fetal growth.
tality in blastocysts or post-implantation.
I.N.S.E.R.M. Unit for Statistical 94800 Villejuif, France
Research,
E. PAPIERNIK A. SPIRA O. BOMSEL-HELMRICH S. LEBEL
CONGENITAL HYPOTHYROIDISM
SiR,-Your editorial of Sept. 29 (p. 678) describes clearly persuasive arguments in favour of neonatal screening for congenital hypothyroidism; if serious impairment of develop-
the
is to be avoided treatment should be started before the age of 3 months, but diagnosis is difficult in young babies and in all published series many patients remain unrecognised until
ment
0.2
0.4
0.6
Total
0.8
Doctor
10
1.2
1.4
16
delay (years)
later.
comparison with the development of children recognised screening, we are carrying out a retrospective by regional study of the development of children with hypothy-
Delays in diagnosis.
For
neonatal
roidism. The first part has involved 30 children under the age of 10 years with severe congenital hypothyroidism, having clinical, biochemical, and radiological evidence of onset before the age of 3 months. The mean of the intelligence quotient (Griffiths or WISC) of the group was one standard deviation below that of a normal population. However, of children whose treatment was started before the age of 3 months 75% had IQ scores greater than 95; of those treated between 3 months and 1 year 50% had IQs greater than 95; while only 23% in the group treated after 1 year had IQs greater than 95. Scores of all subtests were significantly better when a child was treated early, though like McFaul et a1.1 we found that neurological abnormalities were less directly related to age of diagnosis, abnormal signs being found commonly even in patients who had been diagnosed
there are significant doctor delays, frequent and important maternal delays also occur. These are unlikely ever to be prevented by medical education. One-third of the children had been admitted to a special-care baby unit during the newborn period and even amongst this group half were not diagnosed until after the age of 3 months. These findings confirm the difficulties in making an early diagnosis and support the plea for neonatal screening. G. J. FROST Department of Child Health, J. M. PARKIN University of Newcastle upon Tyne, D. ROWLEY Newcastle upon Tyne NE1 4LP
TEACHING ABOUT SEXUALLY TRANSMITTED DISEASES
early. As the home environment has an important influence upon the development of young children we attempted to make allowance for this by comparing the patient’s IQ with that of a sibling. The findings in 10 sibling pairs are shown in the table. These results confirm the importance of treatment being started before the age of 3 months. The median age of diagnosis of the patients in this study was 6 months, the range being from 10 days to 3tyears; only 30% were diagnosed before the age of 3 months. We were interested in the reasons for the delay in the diagnosis. In the figure, the age at which each child was taken to the doctor (maternal delay) is plotted against the time from presentation to the doctor to diagnosis (doctor delay). Although in many patients
Hertig AT. The overall problem in man. In: Benirschke K, ed. Comparative aspects of reproductive failure. Berlin: Springer-Verlag, 1967: 11-41. 1. MacFaul R, Dorner S, Brett EM, Grant DB. Neurological abnormalities in patients treated for hypothyroidism in early life. Arch Dis Childh 1978;
4.
53:611-19.
IQ
SIR,-We read with interest
Dr Robertson’s letter (Oct. 20, 856). The teaching on sexually transmissible diseases (STD) in England shows much variation and this is being studied by the British Co-operative Clinical Group. Leeds is perhaps fortunate in that undergraduates are taught in small groups of 20-30 throughout the year, each student receiving 5 hours of p.
lectures/tutorials and 8-12 hours of clinical instruction, 2 or 3 students sitting in on a consultation. This continuity places great demands on a specialty where there are few teachers. No doubt the proposed expansion of the medical school from 160 will exacerbate this continued demand on teachers. We agree with Robertson that if doctors are to become more aware about the proper management of STD undergraduates must be taught well. The extent of STD is such that the workload in Leeds, in number of patients seen per annum, exceeds that of any other specialty, and this is probably true of most other provincial cities. We agree that only good teaching will attract high calibre individuals into this often neglected shortage specialty. Some of our best supporters are our patients,
OF PATIENTS WITH CONGENITAL HYPOTHYROIDISM COMPARED WITH
IQ OF SIBLINGS
1027 who one
come
despite quite inadequate premises. Unfortunately
of our greatest
be to sweep away the apabout STD in some sectors of the medical
problems
palling ignorance nursing professions.
Department of Genito-Urinary Medicine, General Infirmary at Leeds, Leeds LS1 3EX
M. A. WAUGH G. R. KINGHORN
BALLOT IN SCOTLAND ON PROPOSED CONSULTANT CONTRACT
SiR,-After the collapse of negotiations on the N.H.S. consultants’ contract very few consultants were aware of the fact that fresh discussions were taking place with Mr Patrick Jenkin or were aware of their nature until a letter appeared in The Scotsman on Aug. 24 by a member of the N.H.S. Consultants Association giving some details of proposals which appeared greatly to favour part-time consultants. The letter prompted a rebuff from Mr David Bolt, which ended "I am sure that Scottish consultants will wish to be fully informed of the details of the offer before making up their minds about the new situation". Elsewhere’ Mr Bolt stated: "it is essential, however, that the profession give very careful thought to the offer now before it and that the regional representatives on CCHMS are fully briefed on the views ’of their colleagues when the final decision has to be taken". However, nothing further was heard until there was a rush to push a decision through the Scottish Committee for Hospital Medical Services on Sept. 25. Very few regional representatives had been given information in time to arrange the meetings which Mr Bolt considered essential. The S.C.H.M.S. meeting, under pressure from the C.C.H.M.S., accepted the new proposals, though some representatives did so against the expressed wishes of those whom they represented. The voting was 27 to 13 in favour. There was an immediate wave of protest from all parts of Scotland. Mr James Kyle, chairman of the S.C.H.M.S, was asked to arrange an official ballot, but he declined on the grounds that this would require a special meeting, it would be too expensive, and a complete list of Scottish consultants was not available. Those difficulties have now been overcome by a small group of full-time consultants. 2164 ballot papers were sent out and 1205 (55-7%) were returned (the Electoral Reform Society states that an unofficial ballot with unstamped envelopes does not normally result in a poll of more than 30%). The first question asked whether the four main proposals were acceptable: the result was 44% in favour and 56%’against. The second question was of much less general importance but was included to assess the overall wish to preserve the present situation in which the vast majority of Scottish consultants are whole-time. The result was an almost equal split, 51% being in favour and 49% not having strong convictions at this point. The ballot was held to determine if the S.C.H.M.S. vote did indeed represent the views of the majority of Scottish consultants. It was not held to try to destroy the proposed contract changes. Senior registrars were not called because it was impossible in the time available to compile an up-to-date list of their whereabouts. The ballot was not held in an attempt to obtain a separate contract for Scottish consultants.
Aberdeen
J. D. BROWN W. GIBSON D. HAMILTON A. A. MARR J. MCCORMICK C. V. RUCKLEY W. WALKER
The Borders
J. WARD
Ayr Dundee
Glasgow Kirkcaldy Dumfries
Edinburgh
PURE ANTI-HEPARIN COMPONENT OF
PROTAMINE
seems to
SIR,-A tiresome feature of the reversal of heparin therapy by protamine is the necessity to titrate the amount of protamine given against clotting tests.’ This is because of the anticoagulant effect of protamine alone, if given in excess. However, at alkaline pH, protamine dissociates into two components. One of these possesses an anti-heparin activity, whilst the other has some anticoagulant effect. This was noticed by chance. I was separating protamine from other materials on a ’Sephadex’ (Pharmacia) column. Protamine (Evans) 50 mg in
v
D
v 1.
Anticoagulant (or anti-heparin) activity
ii: 748.
V 2.u
4.
of
protamine
com-
ponents.
5 ml diluted in 10 ml of bicarbonate buffer 0.5mol/1 pH 9 was eluted from a 100 ml column of G25 sephadex beads with isotonic phosphate-buffered saline as eluant at a working pressure of 100 cm water. The first protein-bearing fractions (A and B) to appear exhibited antiheparin activity only, whilst the subsequent fraction (C) showed an anticoagulant effect (see figure). The fractions were tested against various dilutions of. mucous heparin from 0.0 to 0.25 units/ml using a standard thrombin clotting test in 0.025 mol/1 calcium chloride. The results suggest the existence of a low-molecular-weight companent of protamine possessed of heparin-neutralising activity alone. The use of this substance to reverse heparin therapy would presumably obviate the need precisely to titrate the amount
required.
Department of Surgery, Guy’s Hospital,
T. K. DAY
London SE1 9RT
1. Wade A, ed. Martindale: The
1. Br med J 1979;
1.0
Heparin (IJ. Iml)
Press, 1977: 340.
extra
pharmacopoeia. London: Pharmaceutical
bit, which is associated with delayed growth and embryo
mor-
These results suggest that intrafollicular overripeness of the ovum can be the source, not only of reproductive wastage in man,’ but also of a trouble in the programming of fetal growth.
tality in blastocysts or post-implantation.
I.N.S.E.R.M. Unit for Statistical 94800 Villejuif, France
Research,
E. PAPIERNIK A. SPIRA O. BOMSEL-HELMRICH S. LEBEL
CONGENITAL HYPOTHYROIDISM
SiR,-Your editorial of Sept. 29 (p. 678) describes clearly persuasive arguments in favour of neonatal screening for congenital hypothyroidism; if serious impairment of develop-
the
is to be avoided treatment should be started before the age of 3 months, but diagnosis is difficult in young babies and in all published series many patients remain unrecognised until
ment
0.2
0.4
0.6
Total
0.8
Doctor
10
1.2
1.4
16
delay (years)
later.
comparison with the development of children recognised screening, we are carrying out a retrospective by regional study of the development of children with hypothy-
Delays in diagnosis.
For
neonatal
roidism. The first part has involved 30 children under the age of 10 years with severe congenital hypothyroidism, having clinical, biochemical, and radiological evidence of onset before the age of 3 months. The mean of the intelligence quotient (Griffiths or WISC) of the group was one standard deviation below that of a normal population. However, of children whose treatment was started before the age of 3 months 75% had IQ scores greater than 95; of those treated between 3 months and 1 year 50% had IQs greater than 95; while only 23% in the group treated after 1 year had IQs greater than 95. Scores of all subtests were significantly better when a child was treated early, though like McFaul et a1.1 we found that neurological abnormalities were less directly related to age of diagnosis, abnormal signs being found commonly even in patients who had been diagnosed
there are significant doctor delays, frequent and important maternal delays also occur. These are unlikely ever to be prevented by medical education. One-third of the children had been admitted to a special-care baby unit during the newborn period and even amongst this group half were not diagnosed until after the age of 3 months. These findings confirm the difficulties in making an early diagnosis and support the plea for neonatal screening. G. J. FROST Department of Child Health, J. M. PARKIN University of Newcastle upon Tyne, D. ROWLEY Newcastle upon Tyne NE1 4LP
TEACHING ABOUT SEXUALLY TRANSMITTED DISEASES
early. As the home environment has an important influence upon the development of young children we attempted to make allowance for this by comparing the patient’s IQ with that of a sibling. The findings in 10 sibling pairs are shown in the table. These results confirm the importance of treatment being started before the age of 3 months. The median age of diagnosis of the patients in this study was 6 months, the range being from 10 days to 3tyears; only 30% were diagnosed before the age of 3 months. We were interested in the reasons for the delay in the diagnosis. In the figure, the age at which each child was taken to the doctor (maternal delay) is plotted against the time from presentation to the doctor to diagnosis (doctor delay). Although in many patients
Hertig AT. The overall problem in man. In: Benirschke K, ed. Comparative aspects of reproductive failure. Berlin: Springer-Verlag, 1967: 11-41. 1. MacFaul R, Dorner S, Brett EM, Grant DB. Neurological abnormalities in patients treated for hypothyroidism in early life. Arch Dis Childh 1978;
4.
53:611-19.
IQ
SIR,-We read with interest
Dr Robertson’s letter (Oct. 20, 856). The teaching on sexually transmissible diseases (STD) in England shows much variation and this is being studied by the British Co-operative Clinical Group. Leeds is perhaps fortunate in that undergraduates are taught in small groups of 20-30 throughout the year, each student receiving 5 hours of p.
lectures/tutorials and 8-12 hours of clinical instruction, 2 or 3 students sitting in on a consultation. This continuity places great demands on a specialty where there are few teachers. No doubt the proposed expansion of the medical school from 160 will exacerbate this continued demand on teachers. We agree with Robertson that if doctors are to become more aware about the proper management of STD undergraduates must be taught well. The extent of STD is such that the workload in Leeds, in number of patients seen per annum, exceeds that of any other specialty, and this is probably true of most other provincial cities. We agree that only good teaching will attract high calibre individuals into this often neglected shortage specialty. Some of our best supporters are our patients,
OF PATIENTS WITH CONGENITAL HYPOTHYROIDISM COMPARED WITH
IQ OF SIBLINGS
1027 who one
come
despite quite inadequate premises. Unfortunately
of our greatest
be to sweep away the apabout STD in some sectors of the medical
problems
palling ignorance nursing professions.
Department of Genito-Urinary Medicine, General Infirmary at Leeds, Leeds LS1 3EX
M. A. WAUGH G. R. KINGHORN
BALLOT IN SCOTLAND ON PROPOSED CONSULTANT CONTRACT
SiR,-After the collapse of negotiations on the N.H.S. consultants’ contract very few consultants were aware of the fact that fresh discussions were taking place with Mr Patrick Jenkin or were aware of their nature until a letter appeared in The Scotsman on Aug. 24 by a member of the N.H.S. Consultants Association giving some details of proposals which appeared greatly to favour part-time consultants. The letter prompted a rebuff from Mr David Bolt, which ended "I am sure that Scottish consultants will wish to be fully informed of the details of the offer before making up their minds about the new situation". Elsewhere’ Mr Bolt stated: "it is essential, however, that the profession give very careful thought to the offer now before it and that the regional representatives on CCHMS are fully briefed on the views ’of their colleagues when the final decision has to be taken". However, nothing further was heard until there was a rush to push a decision through the Scottish Committee for Hospital Medical Services on Sept. 25. Very few regional representatives had been given information in time to arrange the meetings which Mr Bolt considered essential. The S.C.H.M.S. meeting, under pressure from the C.C.H.M.S., accepted the new proposals, though some representatives did so against the expressed wishes of those whom they represented. The voting was 27 to 13 in favour. There was an immediate wave of protest from all parts of Scotland. Mr James Kyle, chairman of the S.C.H.M.S, was asked to arrange an official ballot, but he declined on the grounds that this would require a special meeting, it would be too expensive, and a complete list of Scottish consultants was not available. Those difficulties have now been overcome by a small group of full-time consultants. 2164 ballot papers were sent out and 1205 (55-7%) were returned (the Electoral Reform Society states that an unofficial ballot with unstamped envelopes does not normally result in a poll of more than 30%). The first question asked whether the four main proposals were acceptable: the result was 44% in favour and 56%’against. The second question was of much less general importance but was included to assess the overall wish to preserve the present situation in which the vast majority of Scottish consultants are whole-time. The result was an almost equal split, 51% being in favour and 49% not having strong convictions at this point. The ballot was held to determine if the S.C.H.M.S. vote did indeed represent the views of the majority of Scottish consultants. It was not held to try to destroy the proposed contract changes. Senior registrars were not called because it was impossible in the time available to compile an up-to-date list of their whereabouts. The ballot was not held in an attempt to obtain a separate contract for Scottish consultants.
Aberdeen
J. D. BROWN W. GIBSON D. HAMILTON A. A. MARR J. MCCORMICK C. V. RUCKLEY W. WALKER
The Borders
J. WARD
Ayr Dundee
Glasgow Kirkcaldy Dumfries
Edinburgh
PURE ANTI-HEPARIN COMPONENT OF
PROTAMINE
seems to
SIR,-A tiresome feature of the reversal of heparin therapy by protamine is the necessity to titrate the amount of protamine given against clotting tests.’ This is because of the anticoagulant effect of protamine alone, if given in excess. However, at alkaline pH, protamine dissociates into two components. One of these possesses an anti-heparin activity, whilst the other has some anticoagulant effect. This was noticed by chance. I was separating protamine from other materials on a ’Sephadex’ (Pharmacia) column. Protamine (Evans) 50 mg in
v
D
v 1.
Anticoagulant (or anti-heparin) activity
ii: 748.
V 2.u
4.
of
protamine
com-
ponents.
5 ml diluted in 10 ml of bicarbonate buffer 0.5mol/1 pH 9 was eluted from a 100 ml column of G25 sephadex beads with isotonic phosphate-buffered saline as eluant at a working pressure of 100 cm water. The first protein-bearing fractions (A and B) to appear exhibited antiheparin activity only, whilst the subsequent fraction (C) showed an anticoagulant effect (see figure). The fractions were tested against various dilutions of. mucous heparin from 0.0 to 0.25 units/ml using a standard thrombin clotting test in 0.025 mol/1 calcium chloride. The results suggest the existence of a low-molecular-weight companent of protamine possessed of heparin-neutralising activity alone. The use of this substance to reverse heparin therapy would presumably obviate the need precisely to titrate the amount
required.
Department of Surgery, Guy’s Hospital,
T. K. DAY
London SE1 9RT
1. Wade A, ed. Martindale: The
1. Br med J 1979;
1.0
Heparin (IJ. Iml)
Press, 1977: 340.
extra
pharmacopoeia. London: Pharmaceutical
