1172 Case 15.-Mild
hsemophilia (vn!:c 11%); clinical signs of a hsematoma. Pain and thigh flexion
postraumatic iliopsoas
the administration of vn!:c from 11 to 43%. The increase was much lower after three successive doses which were given after 10, 20, and 44 h. There was, however, a rapid regression of clinical symptoms without major changes of plasma osmolality or sodium or body-weight.
greatly improved a few hours after D.D.A.V.P. (0-4 {ig/kg) which increased
Case 16.-Mild haemophilia (VIIl:C 10%); surgical removal of a plate which had been inserted 2 years before for a fractured right radius. The operation had been accompanied by severe bleeding. After two 12-hourly doses of D.D.A.V.P. (0-4 jjtg/kg) vm:c rose from 11 to 98% and from 36 to 104%: two subsequent infusions given 24 and 48 h after surgery were followed by a lower response. Haemostasis was satisfactory, and there was no major change in plasma osmolality and sodium or
body weight. Case 17.--Classical
von,
Willebrand’s disease
(VIII:C 27%;
factor-vnwelated antigen 40%, factor-vm-related ristocetin cofactor 7%); hysterectomy for fibromatosis. She was treated with D.D.A.V.P. (0.4 µg/kg) before surgery, then with the same dose 12, 24, and 48 h postoperatively. After each infusion, there was a 2-3 fold increase of factor-vm-retated properties, and the early postoperative course was uneventful despite the lack of a shortening of bleeding-time. On the 10th postoperative day, removal of the sutures was followed by persistent oozing, which was stopped by an additional dose of D.D.A.v.P.
Although
the dosage of D.D.A.V.P. used in this series of smaller than that previously used, factor vm increased and closed and surgical bleeding were successfully controlled. There was no sign of water overload. Our experience suggests that the higher D.D.A.v.p. dosage (0-5 p.g/kg) used by Lowe and his colleagues is unlikely to account for the problems encountered with their patient, who was probably unduly sensitive to the drug. Water retention seems to be a rare complication of D.D.A.V.P. treatment and can probably be avoided by monitoring the patients and adopting the simple precautions suggested by Professor Ingram (Oct. 1, p.721). We suggest that D.D.A.v.p. can be used until compounds devoid of antidiuretic action become available. Dr F. E. Preston has told us of prominent cardiovascular reactions (tachycardia and hypotension) ina patient treated with 0.5µg/kg infused over 5 min. Although such severe symptoms were not observed in our series, a 20-40% increase in heart-rate and mild facial flushing without changes in blood-pressure were often seen. These side-effects, possibly related to the peptide structure of the drug, were not disturbing and can probably be avoided by extending the infusion-time to 13-20 min.
patients
was
As in our first series some patients became progressively less responsive to D.D.A.v.p. This "resistance", which seems to develop earlier in patients treated frequently, limits a prolonged use of the drug after surgery, though responsiveness is re-established in subsequent treatments. If D.D.A.V.P. treatment is restricted to patients having vm:c of 10% or higher, the basal levels of D.D.A.V.P. and the non-specific increase induced by surgery are likely to be sufficient to maintain haemostasis
this has been well established in the first 24 h after surgery. In patients with lower vui:c levels, D.D.A.V.P. could be adopted to reduce the amounts of antihaemophilic globulin concentrates. The development of hepatitis in the patient treated with prothrombin-complex concentrate by Lowe and his colleagues emphasises once again the risk of hepatitis run by mild haemophiliacs and the importance of evaluating means of avoiding such concentrates. once
International Training Centre Angelo Bianch: Bonomi of the World Federation of Hæmophilia, University of Milan, 120122 Milan, Italy
P. M. MANNUCCI Z. M. RUGGERI F.I.PARETI A. CAPITANIO
MORTALITY ASSOCIATED WITH THE PILL
SIR,—The report of the Royal College of General Practitioners (R.C.G.P.) Oral Contraceptive Study (Oct. 8) describes a 40% increase in the total mortality-rate for women who had ever used oral contraceptives. As a summary statistic, this estimate is severely flawed as a result of imprecise definitions, technical ambiguities, and lack of an orientation toward the prevention of avoidable mortality. The rates are not total mortality-rates because 17 deaths attributed to conditions which had been diagnosed before recruitment into the study were excluded. It would be more accurate, perhaps, to describe these rates as "total mortality from previously undiagnosed conditions", although such an unusual measure is difficult to
interpret. Two of the standardisation procedures used in the analysis also raised questions in my mind. Every reference to age standardisation refers to age at entry. If women who switched from one group to another continued to be labelled with their age at entry into the study, both the taker and ex-taker groups would have subpopulations of women older than the corresponding control groups. The 1974 R.C.G.P. interim report’ indicates that these shifts between groups are sizeable, and the potential effect of this age drift can be seen in table v, which shows a strong correlation between age and death from cardiovascular diseases. Similarly, the standardisation for smoking, with all smokers grouped together, obscures an important difference between the oral-contraceptive-taker group and the control group. Mann et al. found that women who smoked more than 25 cigarettes per day had a relative risk of myocardial infarction 4.3times greater than women who smoked 15-24 cigarettes per day, and 10.2times greater than women who smoked 1-15 cigarettes per day. A similar tendency is seen for subarachnoid hæmorrhage.3 It is of interest, therefore, that the 1974 R.C.G.P. report (p. 10) indicates that heavy smokers are more heavily concentrated in the oral-contraceptive takers than are light smokers:
Daily cigarette consumption
Taker-control
Controls
Takers
ratio
0.88 51.9% 58-4% 1.08 36.1% 33.3% 1.45 12.0% 8.3% 1.16 48.1% 41.6% Unless heavy smokers are considered separately, the taker and control groups are not comparable, despite standardisation for smoking. This is particularly important, since nearly 80% of the observed deaths from cardiovascular diseases occurred in smokers. By citing total mortality-rates and overall excess mortalityrates the R.C.G.P. report risks distracting its readers from the very strong suggestion in the data that the risk of death associated with oral contraceptives seems to be highly concentrated in a subpopulation that can be identified. Analysis of the heavy-smoker group could facilitate the identification of this 0 1-20 20+ All smokers
high risk subpopulation. The report also seems to have underestimated the degree to which mortality is concentrated in older women who have taken oral contraceptives for more than 60 months. The mortality-rates by age and duration of oral-contraceptive use listed in table VI apparently include total woman-years of observation in the denominator. Since a woman is not at risk of death associated with more than 60 months of contraceptive use until she has taken contraceptives for 60 months, she should make no contribution to the denominator before she reaches that point. Since the average taker had approximately 2 years of use before recruitment into the study (1974 R.C.G.P. report, p. 13) then to correct the denominator one should 1.
Royal College of General Practitioners.
Oral
Contraceptives
and Health. Pit-
London, 1974. 2. Mann, J. I., Doll, R., Thorogood, M., Vessey, M. P., Waters, W. E. Br. J. prev. soc. Med. 1976, 30, 94. man:
Group for Ass. 1975, 231, 718.
3. Collaborative
the
Study
of Stroke in
Young Women J. Am. med.
1173 remove three woman-years for each original taker and 5 woman-years for each newly recruited taker. On this basis, I estimate that the corrected denominator for women aged 35-49 with a duration of oral contraceptive use of 60 months or more is of the order of 1500 woman-years rather than 7900. Thus, approximately 2.5% of the total woman-years of observation for the taker group accounts for 9/16 (56%) of the deaths caused by cardiovascular disease for that group, corresponding to a mortality-rate for cardiovascular diseases of 600 per 100 000 woman-years, or 1 death per 167 woman-years. From a public health perspective, this concentration of risk in an easily identifiable subpopulation, which could be further enhanced by reanalysis of smoking as a risk factor, provides the basis for screening high-risk candidates for oral contracep-
tion and for reducing the risk a very low level.
to
the
remaining population
to
Program Evaluation Branch, Family Planning Evaluation Division, Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
JAMES R. HEIBY
DIETARY FAT AND HEART-DISEASE
SIR,—Our concepts of how diet and plasma lipids relate to the development of coronary heart-disease (C.H.D.) are indeed in the melting-pot, but your editorial (Nov. 19, p. 1061) has not stirred deeply enough for my taste. It is surprising to find you still harping on the lack of correlation between dietary fat and plasma-cholesterol in single measurements within a group living in the same environment and culture. This has been explained. 1,2 Why not agonise about the similar lack of correlation in Framingham between iron intake and haemoglobin?3 Does this undermine our confidence in the dietary-iron hypothesis of hæmopoiesis? And the frequently rediscovered lack of correlation between energy (calorie) intake and adiposity underlies a report on diet and C.H.D. published on the same date as your editorial: Professor Morris and his colleagues4 find that people with low energy intake were more likely to get C.H.D. but this does not mean that obesity is not a risk factor (though a relatively weak one). Fat intake is one of the most unreliable dietary constituents to estimate and in homogenous communities the variation of fat intake with repeat measurements within single individuals is as great as it is between individuals at one time.6 Different constituents of dietary fat do not all have the same effect on plasma-cholesterol. There are at present no food tables in which one can look up saturated and polyunsaturated fats, cholesterol, and phytosterols in British foods. The next surprise is that you refer only to "dietary fat". The days of relating dietary total fat to plasma-cholesterol or C.H.D. passed in 1956 when you published the first article reporting that saturated fats raise and polyunsaturated fats lower plasma-cholesterol. The picture has been modified for chain length since then and is described in standard textbooks.8 You ask whether fats (plural) are related to low-density lipoprotein (L.D.L.) and high-density lipoprotein (H.D.L.) cholesterol in different ways. This too is clear in the article you published in 1956:7 x-lipoprotein cholesterol was not affected, only -lipoprotein cholesterol went up or down on saturated or 1. Fidanza, F. Proc. Nutr. Soc. 1972, 31, 317. 2. Truswell, A. S. Postgrad. med. J. 1976, 52, 424. 3. Kannel, W. B., Gordon, T. The Framingham Study: section 24 the Framington Diet Study: diet and the regulation of serum cholesterol. U.S. Government Printing Office, Washington, D.C. 4. Morris, J. N., Marr, J. W., Clayton, D. G. Br. med. J. 1977, ii, 1307. 5. Balogh, M., Khan, H. A., Madalie, J. H. Amer. J. Clin. Nutrition, 1971, 24, 304. 6. Keys, A. (editor) Circulation, 1970, 41, suppl. no. 1. 7. Bronte-Stewart, B., Antonis, A., Eales, L., Brock, J. F. Lancet, 1956, i, 521. 8. Davidson, S., Passmore, R., Brock, J. F., Truswell, A. S. Human Nutrition
and Dietetics; p. 388. Edinburgh,
1975.
polyunsaturated fats. There are, however,. dietary as well as other environmental influences on H.D.L. which are now being discovered. Obesity depresses H.D.L. but alcohol9 increases this lipoprotein class. You even published a letter reporting that plasma-vitamin-C is correlated with H.D.L. in men.1o If confirmed in human feeding experiments this would be a more important reason for self-medication with ascorbic acid than the dubious possibility of slightly reducing the risk of coryza. We should no longer be arguing for or against the dietaryfat hypothesis. It has served its purpose and, if expressed as saturated and polyunsaturated fats, remains valid as far as it goes but it does not explain all the thousands of research observations that have accumulated in the past 25 years since the hypothesis was developed. The present position is that we have to consider how to modify in the right direction the dietary factors that affect first plasma-L.D.L. (saturated fats, dietary cholesterol, polyunsaturated fats, some types of dietary fibre"), secondly plasma-H.D.L. (obesity, alcohol, others still ’to be found), and thirdly those altering the tendency to thrombosis (polyunsaturated fats,12 onions,13 and so on), and also environmental factors other than diet in every case. Regular exercise, for example, is associated with high (i.e., favourable) H.D.L. concentrations. Plasma triglycerides or very-low-density lipoproteins no longer seems to be independent risk factors for the development of C.H.D. I have developed many of these points in more detail in my Gunnar Levin memorial lecture in Stockholm (Nov. 30,1977). Nutrition Department, Queen Elizabeth College, London W8
A. S. TRUSWELL
HOW MUCH INTRAVENOUS FLUID DOES THE PATIENT GET?
SIR,—Our experience differs from that of Mr Millard (Sept. 24, p. 665). A closed (non-vented) infusion system offers potential advantages: the risk of microbiological contamination or air embolism is reduced and the possibility of sudden and significant increases in flow-rate should an airway filter become wet and dry out during an infusion is eliminated.’ The choice of commercially available solutions is between the semirigid ‘Polyfusor’ or ‘Bottle-Pak’ or the non-rigid ’Viaflex’ or ’Steriflex’. In our experience the filled volume of a nominal 500 ml container varies from 520 to 550 ml, but the volume delivered by gravity through a Travenol administration set varies significantly between brands. In vitro the polyfusor delivers 440-480 ml, whilst the bottle-pak delivers only 330-380 ml. The viaflex and vented polyfusor or bottle-pak deliver close to the filled volume, and the excess over the nominal 500 ml allows priming of the administration set. Similar performance would be expected from the steriflex or a vented glass bottle. Just as important as the delivered volume is the rate of flow. With vented containers and non-rigid units, the flow-rate falls steadily with the reduction in hydrostatic head. With a nonvented polyfusor, however, the flow-rate falls more quickly. By the time that half the nominal volume has been delivered, the flow-rate has reduced to 75% of the original, and 50% of the original flow rate is reached when less than 400 ml have been delivered. The bottle-pak exhibits interesting characteristics, with a rapid initial fall in flow-rate, followed by a recovery or levelling of the rate until a fall over the final 50 ml of the infusion. Where a constant flow-rate is important, the flow from all commercially available containers requires constant manual or automatic monitoring and adjustment. Where an accurately 9. Castelh, W. P., and others Lancet, 1977, ii, 153. 10. Bates, C. J., Mandal, A. R., Cole, T. J. ibid. p. 611. 11. Truswell, A. S., Kay, R. M. ibid. 1975, i, 922. 12. O’Brien, J. R., Etherington, M., Jamieson, S., Vergroesoen, A. F. ibid. 1976, ii, 995 13. Baghurst, K. I., Raj, M. J., Truswell, A. S. ibid. 1977, i, 101. 1. D.H.S.S. Health Equipment Information no. 64 21/76(1976).
J., Ten Hoov,
hsemophilia (vn!:c 11%); clinical signs of a hsematoma. Pain and thigh flexion
postraumatic iliopsoas
the administration of vn!:c from 11 to 43%. The increase was much lower after three successive doses which were given after 10, 20, and 44 h. There was, however, a rapid regression of clinical symptoms without major changes of plasma osmolality or sodium or body-weight.
greatly improved a few hours after D.D.A.V.P. (0-4 {ig/kg) which increased
Case 16.-Mild haemophilia (VIIl:C 10%); surgical removal of a plate which had been inserted 2 years before for a fractured right radius. The operation had been accompanied by severe bleeding. After two 12-hourly doses of D.D.A.V.P. (0-4 jjtg/kg) vm:c rose from 11 to 98% and from 36 to 104%: two subsequent infusions given 24 and 48 h after surgery were followed by a lower response. Haemostasis was satisfactory, and there was no major change in plasma osmolality and sodium or
body weight. Case 17.--Classical
von,
Willebrand’s disease
(VIII:C 27%;
factor-vnwelated antigen 40%, factor-vm-related ristocetin cofactor 7%); hysterectomy for fibromatosis. She was treated with D.D.A.V.P. (0.4 µg/kg) before surgery, then with the same dose 12, 24, and 48 h postoperatively. After each infusion, there was a 2-3 fold increase of factor-vm-retated properties, and the early postoperative course was uneventful despite the lack of a shortening of bleeding-time. On the 10th postoperative day, removal of the sutures was followed by persistent oozing, which was stopped by an additional dose of D.D.A.v.P.
Although
the dosage of D.D.A.V.P. used in this series of smaller than that previously used, factor vm increased and closed and surgical bleeding were successfully controlled. There was no sign of water overload. Our experience suggests that the higher D.D.A.v.p. dosage (0-5 p.g/kg) used by Lowe and his colleagues is unlikely to account for the problems encountered with their patient, who was probably unduly sensitive to the drug. Water retention seems to be a rare complication of D.D.A.V.P. treatment and can probably be avoided by monitoring the patients and adopting the simple precautions suggested by Professor Ingram (Oct. 1, p.721). We suggest that D.D.A.v.p. can be used until compounds devoid of antidiuretic action become available. Dr F. E. Preston has told us of prominent cardiovascular reactions (tachycardia and hypotension) ina patient treated with 0.5µg/kg infused over 5 min. Although such severe symptoms were not observed in our series, a 20-40% increase in heart-rate and mild facial flushing without changes in blood-pressure were often seen. These side-effects, possibly related to the peptide structure of the drug, were not disturbing and can probably be avoided by extending the infusion-time to 13-20 min.
patients
was
As in our first series some patients became progressively less responsive to D.D.A.v.p. This "resistance", which seems to develop earlier in patients treated frequently, limits a prolonged use of the drug after surgery, though responsiveness is re-established in subsequent treatments. If D.D.A.V.P. treatment is restricted to patients having vm:c of 10% or higher, the basal levels of D.D.A.V.P. and the non-specific increase induced by surgery are likely to be sufficient to maintain haemostasis
this has been well established in the first 24 h after surgery. In patients with lower vui:c levels, D.D.A.V.P. could be adopted to reduce the amounts of antihaemophilic globulin concentrates. The development of hepatitis in the patient treated with prothrombin-complex concentrate by Lowe and his colleagues emphasises once again the risk of hepatitis run by mild haemophiliacs and the importance of evaluating means of avoiding such concentrates. once
International Training Centre Angelo Bianch: Bonomi of the World Federation of Hæmophilia, University of Milan, 120122 Milan, Italy
P. M. MANNUCCI Z. M. RUGGERI F.I.PARETI A. CAPITANIO
MORTALITY ASSOCIATED WITH THE PILL
SIR,—The report of the Royal College of General Practitioners (R.C.G.P.) Oral Contraceptive Study (Oct. 8) describes a 40% increase in the total mortality-rate for women who had ever used oral contraceptives. As a summary statistic, this estimate is severely flawed as a result of imprecise definitions, technical ambiguities, and lack of an orientation toward the prevention of avoidable mortality. The rates are not total mortality-rates because 17 deaths attributed to conditions which had been diagnosed before recruitment into the study were excluded. It would be more accurate, perhaps, to describe these rates as "total mortality from previously undiagnosed conditions", although such an unusual measure is difficult to
interpret. Two of the standardisation procedures used in the analysis also raised questions in my mind. Every reference to age standardisation refers to age at entry. If women who switched from one group to another continued to be labelled with their age at entry into the study, both the taker and ex-taker groups would have subpopulations of women older than the corresponding control groups. The 1974 R.C.G.P. interim report’ indicates that these shifts between groups are sizeable, and the potential effect of this age drift can be seen in table v, which shows a strong correlation between age and death from cardiovascular diseases. Similarly, the standardisation for smoking, with all smokers grouped together, obscures an important difference between the oral-contraceptive-taker group and the control group. Mann et al. found that women who smoked more than 25 cigarettes per day had a relative risk of myocardial infarction 4.3times greater than women who smoked 15-24 cigarettes per day, and 10.2times greater than women who smoked 1-15 cigarettes per day. A similar tendency is seen for subarachnoid hæmorrhage.3 It is of interest, therefore, that the 1974 R.C.G.P. report (p. 10) indicates that heavy smokers are more heavily concentrated in the oral-contraceptive takers than are light smokers:
Daily cigarette consumption
Taker-control
Controls
Takers
ratio
0.88 51.9% 58-4% 1.08 36.1% 33.3% 1.45 12.0% 8.3% 1.16 48.1% 41.6% Unless heavy smokers are considered separately, the taker and control groups are not comparable, despite standardisation for smoking. This is particularly important, since nearly 80% of the observed deaths from cardiovascular diseases occurred in smokers. By citing total mortality-rates and overall excess mortalityrates the R.C.G.P. report risks distracting its readers from the very strong suggestion in the data that the risk of death associated with oral contraceptives seems to be highly concentrated in a subpopulation that can be identified. Analysis of the heavy-smoker group could facilitate the identification of this 0 1-20 20+ All smokers
high risk subpopulation. The report also seems to have underestimated the degree to which mortality is concentrated in older women who have taken oral contraceptives for more than 60 months. The mortality-rates by age and duration of oral-contraceptive use listed in table VI apparently include total woman-years of observation in the denominator. Since a woman is not at risk of death associated with more than 60 months of contraceptive use until she has taken contraceptives for 60 months, she should make no contribution to the denominator before she reaches that point. Since the average taker had approximately 2 years of use before recruitment into the study (1974 R.C.G.P. report, p. 13) then to correct the denominator one should 1.
Royal College of General Practitioners.
Oral
Contraceptives
and Health. Pit-
London, 1974. 2. Mann, J. I., Doll, R., Thorogood, M., Vessey, M. P., Waters, W. E. Br. J. prev. soc. Med. 1976, 30, 94. man:
Group for Ass. 1975, 231, 718.
3. Collaborative
the
Study
of Stroke in
Young Women J. Am. med.
1173 remove three woman-years for each original taker and 5 woman-years for each newly recruited taker. On this basis, I estimate that the corrected denominator for women aged 35-49 with a duration of oral contraceptive use of 60 months or more is of the order of 1500 woman-years rather than 7900. Thus, approximately 2.5% of the total woman-years of observation for the taker group accounts for 9/16 (56%) of the deaths caused by cardiovascular disease for that group, corresponding to a mortality-rate for cardiovascular diseases of 600 per 100 000 woman-years, or 1 death per 167 woman-years. From a public health perspective, this concentration of risk in an easily identifiable subpopulation, which could be further enhanced by reanalysis of smoking as a risk factor, provides the basis for screening high-risk candidates for oral contracep-
tion and for reducing the risk a very low level.
to
the
remaining population
to
Program Evaluation Branch, Family Planning Evaluation Division, Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
JAMES R. HEIBY
DIETARY FAT AND HEART-DISEASE
SIR,—Our concepts of how diet and plasma lipids relate to the development of coronary heart-disease (C.H.D.) are indeed in the melting-pot, but your editorial (Nov. 19, p. 1061) has not stirred deeply enough for my taste. It is surprising to find you still harping on the lack of correlation between dietary fat and plasma-cholesterol in single measurements within a group living in the same environment and culture. This has been explained. 1,2 Why not agonise about the similar lack of correlation in Framingham between iron intake and haemoglobin?3 Does this undermine our confidence in the dietary-iron hypothesis of hæmopoiesis? And the frequently rediscovered lack of correlation between energy (calorie) intake and adiposity underlies a report on diet and C.H.D. published on the same date as your editorial: Professor Morris and his colleagues4 find that people with low energy intake were more likely to get C.H.D. but this does not mean that obesity is not a risk factor (though a relatively weak one). Fat intake is one of the most unreliable dietary constituents to estimate and in homogenous communities the variation of fat intake with repeat measurements within single individuals is as great as it is between individuals at one time.6 Different constituents of dietary fat do not all have the same effect on plasma-cholesterol. There are at present no food tables in which one can look up saturated and polyunsaturated fats, cholesterol, and phytosterols in British foods. The next surprise is that you refer only to "dietary fat". The days of relating dietary total fat to plasma-cholesterol or C.H.D. passed in 1956 when you published the first article reporting that saturated fats raise and polyunsaturated fats lower plasma-cholesterol. The picture has been modified for chain length since then and is described in standard textbooks.8 You ask whether fats (plural) are related to low-density lipoprotein (L.D.L.) and high-density lipoprotein (H.D.L.) cholesterol in different ways. This too is clear in the article you published in 1956:7 x-lipoprotein cholesterol was not affected, only -lipoprotein cholesterol went up or down on saturated or 1. Fidanza, F. Proc. Nutr. Soc. 1972, 31, 317. 2. Truswell, A. S. Postgrad. med. J. 1976, 52, 424. 3. Kannel, W. B., Gordon, T. The Framingham Study: section 24 the Framington Diet Study: diet and the regulation of serum cholesterol. U.S. Government Printing Office, Washington, D.C. 4. Morris, J. N., Marr, J. W., Clayton, D. G. Br. med. J. 1977, ii, 1307. 5. Balogh, M., Khan, H. A., Madalie, J. H. Amer. J. Clin. Nutrition, 1971, 24, 304. 6. Keys, A. (editor) Circulation, 1970, 41, suppl. no. 1. 7. Bronte-Stewart, B., Antonis, A., Eales, L., Brock, J. F. Lancet, 1956, i, 521. 8. Davidson, S., Passmore, R., Brock, J. F., Truswell, A. S. Human Nutrition
and Dietetics; p. 388. Edinburgh,
1975.
polyunsaturated fats. There are, however,. dietary as well as other environmental influences on H.D.L. which are now being discovered. Obesity depresses H.D.L. but alcohol9 increases this lipoprotein class. You even published a letter reporting that plasma-vitamin-C is correlated with H.D.L. in men.1o If confirmed in human feeding experiments this would be a more important reason for self-medication with ascorbic acid than the dubious possibility of slightly reducing the risk of coryza. We should no longer be arguing for or against the dietaryfat hypothesis. It has served its purpose and, if expressed as saturated and polyunsaturated fats, remains valid as far as it goes but it does not explain all the thousands of research observations that have accumulated in the past 25 years since the hypothesis was developed. The present position is that we have to consider how to modify in the right direction the dietary factors that affect first plasma-L.D.L. (saturated fats, dietary cholesterol, polyunsaturated fats, some types of dietary fibre"), secondly plasma-H.D.L. (obesity, alcohol, others still ’to be found), and thirdly those altering the tendency to thrombosis (polyunsaturated fats,12 onions,13 and so on), and also environmental factors other than diet in every case. Regular exercise, for example, is associated with high (i.e., favourable) H.D.L. concentrations. Plasma triglycerides or very-low-density lipoproteins no longer seems to be independent risk factors for the development of C.H.D. I have developed many of these points in more detail in my Gunnar Levin memorial lecture in Stockholm (Nov. 30,1977). Nutrition Department, Queen Elizabeth College, London W8
A. S. TRUSWELL
HOW MUCH INTRAVENOUS FLUID DOES THE PATIENT GET?
SIR,—Our experience differs from that of Mr Millard (Sept. 24, p. 665). A closed (non-vented) infusion system offers potential advantages: the risk of microbiological contamination or air embolism is reduced and the possibility of sudden and significant increases in flow-rate should an airway filter become wet and dry out during an infusion is eliminated.’ The choice of commercially available solutions is between the semirigid ‘Polyfusor’ or ‘Bottle-Pak’ or the non-rigid ’Viaflex’ or ’Steriflex’. In our experience the filled volume of a nominal 500 ml container varies from 520 to 550 ml, but the volume delivered by gravity through a Travenol administration set varies significantly between brands. In vitro the polyfusor delivers 440-480 ml, whilst the bottle-pak delivers only 330-380 ml. The viaflex and vented polyfusor or bottle-pak deliver close to the filled volume, and the excess over the nominal 500 ml allows priming of the administration set. Similar performance would be expected from the steriflex or a vented glass bottle. Just as important as the delivered volume is the rate of flow. With vented containers and non-rigid units, the flow-rate falls steadily with the reduction in hydrostatic head. With a nonvented polyfusor, however, the flow-rate falls more quickly. By the time that half the nominal volume has been delivered, the flow-rate has reduced to 75% of the original, and 50% of the original flow rate is reached when less than 400 ml have been delivered. The bottle-pak exhibits interesting characteristics, with a rapid initial fall in flow-rate, followed by a recovery or levelling of the rate until a fall over the final 50 ml of the infusion. Where a constant flow-rate is important, the flow from all commercially available containers requires constant manual or automatic monitoring and adjustment. Where an accurately 9. Castelh, W. P., and others Lancet, 1977, ii, 153. 10. Bates, C. J., Mandal, A. R., Cole, T. J. ibid. p. 611. 11. Truswell, A. S., Kay, R. M. ibid. 1975, i, 922. 12. O’Brien, J. R., Etherington, M., Jamieson, S., Vergroesoen, A. F. ibid. 1976, ii, 995 13. Baghurst, K. I., Raj, M. J., Truswell, A. S. ibid. 1977, i, 101. 1. D.H.S.S. Health Equipment Information no. 64 21/76(1976).
J., Ten Hoov,
