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BLOOD LIPIDS AND VITAMIN-C STATUS
1055 fluid containing 10 or 11 mmol/1 (180 or 200 mg/dl) glucose. 6 of the women and all of the men had previously been treated with steroids at some time. Growth-hormone and insulin levels
TABLE I-LEUCOCYTE ASCORBATE AND SERUM CHOLESTEROL
a
were
estimated
ma-glucose
was
AND TRIGLYCERIDE LEVELS IN BLOOD-DONORS
double antibody radioimmunoassays; plasmeasured by automated ferricyanide reduc-
by
tion.
Plasma-growth-hormone was <2µU/l in 4 female patients at the start of dialysis but in the other patients it ranged from 3 to 117 (mean 20). Plasma-growth-hormone fell during dialysis by 33-98% of the predialysis level to µU/l in 13 patients (P<0.05, Wilcoxon paired test); in 2 female patients it rose from 4 to 42 and 6 to 29 p.U/1, respectively; and in 4 patients it remained at the predialysis level of <2µU/l. The response was unrelated to previous steroid therapy and we could find no factor which accounted for the two atypical cases in which plas-
ma-growth-hormone rose. Plasma-glucose rose by 0-98 mmol/1 (17 mg/dl) during the dialysis. Corresponding rises in plasma-insulin (average 2.0 mU/1) were correlated with the glucose increases (r=0.65; P<0.05). There was no correlation between the magnitude of the growth-hormone changes and either the glucose or insulin responses. The fall in plasma-growth-hormone was not accompanied by changes in plasma levels of luteinising hormone or follicle-stimulating hormone during the dialysis. That a rise in plasma-glucose inhibits growth-hormone secretion is well known. Such inhibition seems likely in the patients whose plasma-glucose was raised by use of a dialysis fluid containing a high concentration of glucose. Growth hormone has a molecular weight of 19 500 and is unlikely to be removed from the plasma by heemodialysis. The drop in growth hormone could possibly be a stress response but there were no consistent changes in plasma-cortisol. It will be of interest to determine the nature and cause of the growth-hormone response and its duration in children on dialysis who have growth failure. In one child we have studied, plasma-growth-hormone took several hours to return to the pre-dialysis level after a 4 h dialysis against 11 mmol/1 glucose. We thank Prof. R. Shackman and Dr J. F. Moorhead who allowed us access to their patients and Prof. T. Chard and Prof. 1. D. P. Wooton for the hormone and glucose assays, respectively. Institute of Obstetrics and Gynæcology, Hammersmith Hospital, London W12 0HS
* Means ±S.E.M.
(mg/dl)
were:
low 167±02, moderate 24.9±02,
high 36.4±0.6. t Significantly lower than for low-ascorbate group (P<0.05
or
better).
TABLE II—PREVALENCE OF HYPERCHOLESTEROLAMIA AND
HYPERTRIGLYCERIDÆMIA IN BLOOD-DONORS GROUPED ACCORDING TO LEUCOCYTE ASCORBATE LEVEL
Figures in parentheses give the numbers of blood-donors in the subgroup. * Prevalence significantly lower than for low-ascorbate group (P<0.05 or
better).
leucocyte ascorbate concentration" in 600 fasting blood(300 males and 300 females aged 25-55). Most of the samples were taken between November, 1976, and March, donors
D. F. HAWKINS FIONA STRANG
BLOOD LIPIDS AND VITAMIN-C STATUS
SIR,-In guineapigs with chronic ascorbate deficiency cholesterol transformation to bile acids is reduced/-3 since vita-’ min C is needed for 7&agr;-hydroxylation.4,5Data in man are conflicting, however. Some workers find a negative correlation between vitamin-C status and serum-cholesterol,6.7 while others refute such a relationship. Bates et al. S noted an association between vitamin-C status and high-density lipoprotein cholesterol but not between vitamin C and total cholesterol. We have looked for a correlation between vitamin-C status and the blood lipids in a large series of healthy people, and we measured leucocyte ascorbate concentration, which is the best indicator of tissue vitamin C. We measured serum total cholesterol and triglyceride9,10 and 1. Ginter, E. Science, 1973, 179, 702. 2. Hornig, D., Weiser, H. Experientia, 1976, 32, 687. 3. Harris, W. S., Kottke, B. A. Fed Proc. 1977, 36, 1177. 4. Ginter, E. Ann. N.Y. Acad. Sci. 1975, 258, 410. 5. Björkhem, I., Kallner, A.J. Lipid Res. 1976, 17, 360. 6. Masek, J. Nutr. Dieta. 1960, 2, 193. 7. Cheraskin, E., Ringsdorf, W. M. Int.J. Vit. Res. 1968, 38, 415. 8. Bates, C. J., Mandal, A. R., Cole, T. J. Lancet, 1977, ii, 611. 9. Watson, D. Clin. chim. Acta. 1960, 5, 637. 10. Grafnetter, D. Vnitr. lek. 1973, 19, 808.
1977, but there results.
was no
evidence for
a
seasonal influence on the
A significant negative linear correlation was found between the leucocyte-ascorbate concentration and serum-cholesterol in both males and females. For both sexes the correlation was significant (P<0.001), although the coefficient was low A similar (r=-0.18). negative correlation was found for serum-triglyceride (P<0.001, r=—0.15). When the blood-donors were divided into groups with low, medium, or high leucocyte ascorbate concentration, cholesterol and triglyceride values fell as ascorbate concentrations rose (table i). Statistical significance does not necessarily mean clinical significance, so we next divided blood-donors into four groups on the basis of their cholesterol and triglyceride levels. For serumcholesterol we used Grundy’s12 criteria: normal (<225 mg/dl) or hypercholesterolæmia (mild 225-275, moderate 276-350, or severe >350 mg/dl). Our criteria for serum-triglyceride were: normal (<170 mg/dl) or hypertriglyceridaemia (mild 170-250, moderate 251-500, or severe >500 mg/dl). For statistical evaluation we pooled moderate and severe hypercholesterolaemia (and hypertriglyceridæmia). Table n shows that normal cholesterol and triglyceride levels were most common in the group with a high ascorbate concentration. The probability of high lipid values in the presence of high leucocyte (and hence tissue13,14) ascorbate is two to three times smaller than in individuals with low ascorbate levels. The ascorbate concen11. Bessey, A. A., Lowry, O. H., Brock, M. J. J. biol. Chem. 1947, 168, 197. 12. Grundy, S. M.Am.J. clin. Nutr. 1977, 30, 985. 13. Beattie, A. D., Sherlock, S. Gut, 1976, 17, 571.
14. Gerson, C. D. Ann. N.Y. Acad. Sci. 1975, 258, 483.
1056 tration in the leucocytes of people with a daily intake of 30 mg vitamin C (recommended dietary intakes in the U.K.) is below 30 mg/dl, and a large proportion of these subjects probably have leucocyte ascorbate levels below 20 mg/dI. 11 ,
Institute of Human Nutrition, 880 30 Bratislava, Czechoslovakia
O. ČERNÁ E. GINTER
15. Sauberlich, H.E. ibid. 1975, 258, 438.
Commentary from
Westminster
reward for basic commitment to be on-call for patients. One aspect of the new contract which would be beneficial for consultants is the proposal that fees be paid for emergency recalls to hospital at night and weekends. A maximum of 200 recalls a year has been set, which on the face of it and subject to pricing, could mean much more money for many consultants. In addition, a fee would be provided for consultants with heavy on-call responsibilities, according to the extent of their commitment.
The B.M.A. and others putting on the pressure have succeeded in abolishing differentials between those N.H.S. consultants who do private practice and those who do not. But, they believe, they are winning the contest. Hence the Central Committee for Hospital Medical Services was last week overwhelmingly in favour of accepting the new contract. The belief, it seems, is that the contract will be flexible enough to lead to a large increase in pay and to some growth in private practice. The offered contract is now to be put to ballot among the nation’s 13 000 consultants and senior registrars in June; and, if it is accepted, it will be priced by the independent Review Body on Doctors’ and Dentists’ Remuneration. The ultimate attitude of the profession to the package will be determined by its pricing. A favourable vote in the ballot does not commit the profession to accept the pricing. not
From Our Parliamentary
Correspondent The Contract Acclaimed-But What of the Pricing? SATISFACTION all round seemed to be the immediate new contract offered to National Health Service consultants by the Government last week. Mr David Ennals, Secretary of State for Social Services, was satisfied that he had protected the interests of the N.H.S; the British Medical Association negotiators were well pleased; and, surprisingly perhaps, Labour r.t.P.s were content that an acceptable compromise had been reached. Yet so worried was Mr Ennals about the reaction of his backbenchers that he saw them a week before his announcement so that he could explain the new contract to them. As Mr Ennals said in his statement on May 3, the Government was anxious throughout the protracted negotiations to achieve three objectives: to preserve the primacy of whole-time commitment to the N.H.S.; to establish provisions which would stimulate recruitment to specialties and posts where there had been difficulties in keeping up with needs; and to introduce reforms in the distinction-awards system whereby confidentiality might be modified and a more equitable distribution might be secured between regions and response to the
specialties. Mr Ennals has plainly achieved the last two objectives. Under the proposed new arrangements health authorities would be able to appoint consultants directly on to the present maximum salary scale of ,10 897 in specialties and areas of the country which have hitherto proved unpopular and unattractive. The modified awards system would be based on the understanding that distinguished service to the N.H.S., as well as clinical or academic excellence, would be a measure of qualification for more money. The aim is to achieve more awards in the regions, as well as to open up the system, so that other consultants, members of employing authorities, and M.P.S would be able to secure information about the awards made. There may well be less agreement about whether or not Mr Ennals has achieved his first (and his most important) objective of preserving the "primacy of wholetime commitment to the N.H.S.". The new contract would replace the present open-ended commitment with an industrial-type contract in which extra sessions of work attract extra pay. There would be a standard contract of ten sessions a week; and the possibility of extra regular sessions would be limited to five for whole-timers and to three for part-timers. At the moment the number of N.H.S. whole-timers, 5102, represents just over 42% of all consultants in England and Wales. Of the basic ten sessions, one would be in recognition of regular administrative and management work and a second would be a
Payments to the Vaccine-damaged Tax-free lump-sum payments of £ 10 000 are to be paid to children or adults severely damaged by vaccines recommended since July 1948 for the benefit of the community. Announcing this in the Commons on May 9, Mr Ennals insisted that it should not be seen as a compensation scheme. It was a system of lump-sum payments, which, because of the need for speed, would be fixed amounts rather than graduated payments. The initial test of eligibility will be whether a person is in receipt of an attendance or mobility allowance for conditions which could be attributed to vaccine damage. Decisions as to whether the damage was due to vaccination will be made on the balance of probabilities and there will be a right of appeal to an independent panel of two medical specialists and a legal chairman. Mr Ennals estimated that on the basis of some 700 cases of severe damage the cost of the scheme would be around C7 million. The first payments are expected to begin before the end of the year. He said the scheme would in no way preempt the Government’s decisions on the Pearson report on civil liability and compensation for personal injury. This recommended that there should be strict liability in tort for severe damage suffered by anyone as a result of recommended vaccination and that a new weekly benefit of ,4 should be paid to all seriously disabled children whatever the source of their handicap. But this was bound to take time and the lump-sum payments would not prejudice the rights of those who had suffered damage to take action in the future. Reaction in the Commons to the Government’s announcement was on the whole favourable. But several M.P.s made it quite clear that they saw this as an interim measure and that they would expect further Government help in the future.
TABLE I-LEUCOCYTE ASCORBATE AND SERUM CHOLESTEROL
a
were
estimated
ma-glucose
was
AND TRIGLYCERIDE LEVELS IN BLOOD-DONORS
double antibody radioimmunoassays; plasmeasured by automated ferricyanide reduc-
by
tion.
Plasma-growth-hormone was <2µU/l in 4 female patients at the start of dialysis but in the other patients it ranged from 3 to 117 (mean 20). Plasma-growth-hormone fell during dialysis by 33-98% of the predialysis level to µU/l in 13 patients (P<0.05, Wilcoxon paired test); in 2 female patients it rose from 4 to 42 and 6 to 29 p.U/1, respectively; and in 4 patients it remained at the predialysis level of <2µU/l. The response was unrelated to previous steroid therapy and we could find no factor which accounted for the two atypical cases in which plas-
ma-growth-hormone rose. Plasma-glucose rose by 0-98 mmol/1 (17 mg/dl) during the dialysis. Corresponding rises in plasma-insulin (average 2.0 mU/1) were correlated with the glucose increases (r=0.65; P<0.05). There was no correlation between the magnitude of the growth-hormone changes and either the glucose or insulin responses. The fall in plasma-growth-hormone was not accompanied by changes in plasma levels of luteinising hormone or follicle-stimulating hormone during the dialysis. That a rise in plasma-glucose inhibits growth-hormone secretion is well known. Such inhibition seems likely in the patients whose plasma-glucose was raised by use of a dialysis fluid containing a high concentration of glucose. Growth hormone has a molecular weight of 19 500 and is unlikely to be removed from the plasma by heemodialysis. The drop in growth hormone could possibly be a stress response but there were no consistent changes in plasma-cortisol. It will be of interest to determine the nature and cause of the growth-hormone response and its duration in children on dialysis who have growth failure. In one child we have studied, plasma-growth-hormone took several hours to return to the pre-dialysis level after a 4 h dialysis against 11 mmol/1 glucose. We thank Prof. R. Shackman and Dr J. F. Moorhead who allowed us access to their patients and Prof. T. Chard and Prof. 1. D. P. Wooton for the hormone and glucose assays, respectively. Institute of Obstetrics and Gynæcology, Hammersmith Hospital, London W12 0HS
* Means ±S.E.M.
(mg/dl)
were:
low 167±02, moderate 24.9±02,
high 36.4±0.6. t Significantly lower than for low-ascorbate group (P<0.05
or
better).
TABLE II—PREVALENCE OF HYPERCHOLESTEROLAMIA AND
HYPERTRIGLYCERIDÆMIA IN BLOOD-DONORS GROUPED ACCORDING TO LEUCOCYTE ASCORBATE LEVEL
Figures in parentheses give the numbers of blood-donors in the subgroup. * Prevalence significantly lower than for low-ascorbate group (P<0.05 or
better).
leucocyte ascorbate concentration" in 600 fasting blood(300 males and 300 females aged 25-55). Most of the samples were taken between November, 1976, and March, donors
D. F. HAWKINS FIONA STRANG
BLOOD LIPIDS AND VITAMIN-C STATUS
SIR,-In guineapigs with chronic ascorbate deficiency cholesterol transformation to bile acids is reduced/-3 since vita-’ min C is needed for 7&agr;-hydroxylation.4,5Data in man are conflicting, however. Some workers find a negative correlation between vitamin-C status and serum-cholesterol,6.7 while others refute such a relationship. Bates et al. S noted an association between vitamin-C status and high-density lipoprotein cholesterol but not between vitamin C and total cholesterol. We have looked for a correlation between vitamin-C status and the blood lipids in a large series of healthy people, and we measured leucocyte ascorbate concentration, which is the best indicator of tissue vitamin C. We measured serum total cholesterol and triglyceride9,10 and 1. Ginter, E. Science, 1973, 179, 702. 2. Hornig, D., Weiser, H. Experientia, 1976, 32, 687. 3. Harris, W. S., Kottke, B. A. Fed Proc. 1977, 36, 1177. 4. Ginter, E. Ann. N.Y. Acad. Sci. 1975, 258, 410. 5. Björkhem, I., Kallner, A.J. Lipid Res. 1976, 17, 360. 6. Masek, J. Nutr. Dieta. 1960, 2, 193. 7. Cheraskin, E., Ringsdorf, W. M. Int.J. Vit. Res. 1968, 38, 415. 8. Bates, C. J., Mandal, A. R., Cole, T. J. Lancet, 1977, ii, 611. 9. Watson, D. Clin. chim. Acta. 1960, 5, 637. 10. Grafnetter, D. Vnitr. lek. 1973, 19, 808.
1977, but there results.
was no
evidence for
a
seasonal influence on the
A significant negative linear correlation was found between the leucocyte-ascorbate concentration and serum-cholesterol in both males and females. For both sexes the correlation was significant (P<0.001), although the coefficient was low A similar (r=-0.18). negative correlation was found for serum-triglyceride (P<0.001, r=—0.15). When the blood-donors were divided into groups with low, medium, or high leucocyte ascorbate concentration, cholesterol and triglyceride values fell as ascorbate concentrations rose (table i). Statistical significance does not necessarily mean clinical significance, so we next divided blood-donors into four groups on the basis of their cholesterol and triglyceride levels. For serumcholesterol we used Grundy’s12 criteria: normal (<225 mg/dl) or hypercholesterolæmia (mild 225-275, moderate 276-350, or severe >350 mg/dl). Our criteria for serum-triglyceride were: normal (<170 mg/dl) or hypertriglyceridaemia (mild 170-250, moderate 251-500, or severe >500 mg/dl). For statistical evaluation we pooled moderate and severe hypercholesterolaemia (and hypertriglyceridæmia). Table n shows that normal cholesterol and triglyceride levels were most common in the group with a high ascorbate concentration. The probability of high lipid values in the presence of high leucocyte (and hence tissue13,14) ascorbate is two to three times smaller than in individuals with low ascorbate levels. The ascorbate concen11. Bessey, A. A., Lowry, O. H., Brock, M. J. J. biol. Chem. 1947, 168, 197. 12. Grundy, S. M.Am.J. clin. Nutr. 1977, 30, 985. 13. Beattie, A. D., Sherlock, S. Gut, 1976, 17, 571.
14. Gerson, C. D. Ann. N.Y. Acad. Sci. 1975, 258, 483.
1056 tration in the leucocytes of people with a daily intake of 30 mg vitamin C (recommended dietary intakes in the U.K.) is below 30 mg/dl, and a large proportion of these subjects probably have leucocyte ascorbate levels below 20 mg/dI. 11 ,
Institute of Human Nutrition, 880 30 Bratislava, Czechoslovakia
O. ČERNÁ E. GINTER
15. Sauberlich, H.E. ibid. 1975, 258, 438.
Commentary from
Westminster
reward for basic commitment to be on-call for patients. One aspect of the new contract which would be beneficial for consultants is the proposal that fees be paid for emergency recalls to hospital at night and weekends. A maximum of 200 recalls a year has been set, which on the face of it and subject to pricing, could mean much more money for many consultants. In addition, a fee would be provided for consultants with heavy on-call responsibilities, according to the extent of their commitment.
The B.M.A. and others putting on the pressure have succeeded in abolishing differentials between those N.H.S. consultants who do private practice and those who do not. But, they believe, they are winning the contest. Hence the Central Committee for Hospital Medical Services was last week overwhelmingly in favour of accepting the new contract. The belief, it seems, is that the contract will be flexible enough to lead to a large increase in pay and to some growth in private practice. The offered contract is now to be put to ballot among the nation’s 13 000 consultants and senior registrars in June; and, if it is accepted, it will be priced by the independent Review Body on Doctors’ and Dentists’ Remuneration. The ultimate attitude of the profession to the package will be determined by its pricing. A favourable vote in the ballot does not commit the profession to accept the pricing. not
From Our Parliamentary
Correspondent The Contract Acclaimed-But What of the Pricing? SATISFACTION all round seemed to be the immediate new contract offered to National Health Service consultants by the Government last week. Mr David Ennals, Secretary of State for Social Services, was satisfied that he had protected the interests of the N.H.S; the British Medical Association negotiators were well pleased; and, surprisingly perhaps, Labour r.t.P.s were content that an acceptable compromise had been reached. Yet so worried was Mr Ennals about the reaction of his backbenchers that he saw them a week before his announcement so that he could explain the new contract to them. As Mr Ennals said in his statement on May 3, the Government was anxious throughout the protracted negotiations to achieve three objectives: to preserve the primacy of whole-time commitment to the N.H.S.; to establish provisions which would stimulate recruitment to specialties and posts where there had been difficulties in keeping up with needs; and to introduce reforms in the distinction-awards system whereby confidentiality might be modified and a more equitable distribution might be secured between regions and response to the
specialties. Mr Ennals has plainly achieved the last two objectives. Under the proposed new arrangements health authorities would be able to appoint consultants directly on to the present maximum salary scale of ,10 897 in specialties and areas of the country which have hitherto proved unpopular and unattractive. The modified awards system would be based on the understanding that distinguished service to the N.H.S., as well as clinical or academic excellence, would be a measure of qualification for more money. The aim is to achieve more awards in the regions, as well as to open up the system, so that other consultants, members of employing authorities, and M.P.S would be able to secure information about the awards made. There may well be less agreement about whether or not Mr Ennals has achieved his first (and his most important) objective of preserving the "primacy of wholetime commitment to the N.H.S.". The new contract would replace the present open-ended commitment with an industrial-type contract in which extra sessions of work attract extra pay. There would be a standard contract of ten sessions a week; and the possibility of extra regular sessions would be limited to five for whole-timers and to three for part-timers. At the moment the number of N.H.S. whole-timers, 5102, represents just over 42% of all consultants in England and Wales. Of the basic ten sessions, one would be in recognition of regular administrative and management work and a second would be a
Payments to the Vaccine-damaged Tax-free lump-sum payments of £ 10 000 are to be paid to children or adults severely damaged by vaccines recommended since July 1948 for the benefit of the community. Announcing this in the Commons on May 9, Mr Ennals insisted that it should not be seen as a compensation scheme. It was a system of lump-sum payments, which, because of the need for speed, would be fixed amounts rather than graduated payments. The initial test of eligibility will be whether a person is in receipt of an attendance or mobility allowance for conditions which could be attributed to vaccine damage. Decisions as to whether the damage was due to vaccination will be made on the balance of probabilities and there will be a right of appeal to an independent panel of two medical specialists and a legal chairman. Mr Ennals estimated that on the basis of some 700 cases of severe damage the cost of the scheme would be around C7 million. The first payments are expected to begin before the end of the year. He said the scheme would in no way preempt the Government’s decisions on the Pearson report on civil liability and compensation for personal injury. This recommended that there should be strict liability in tort for severe damage suffered by anyone as a result of recommended vaccination and that a new weekly benefit of ,4 should be paid to all seriously disabled children whatever the source of their handicap. But this was bound to take time and the lump-sum payments would not prejudice the rights of those who had suffered damage to take action in the future. Reaction in the Commons to the Government’s announcement was on the whole favourable. But several M.P.s made it quite clear that they saw this as an interim measure and that they would expect further Government help in the future.