- Email: [email protected]
HANDLING SERA FOR TUMOUR MARKER STUDIES
877 HANDLING SERA FOR TUMOUR MARKER STUDIES
SIR,-Our laboratory offers a national tumour marker service for of a-fetoprotein (AFP), human chorionic gonadotropin (hCG), and carcinoembryonic antigen (CEA). Many of our patients are followed up so that rising values can be acted the measurement
swiftly. We occasionally see inconsistent results such as a sudden sharp increase followed by an immediate fall to the original baseline. On tracing back to the source laboratory we find this to be due to the practice of using the same pipette for more than one sample. Whilst this may be acceptable for analytes in which the variation between samples is low, for the analytes we measure it is upon
totally unacceptable. hCG in non-pregnant individuals is generally unmeasurable, although we give normal ranges up to 5 IU/1. By the twelfth week of gestation, this figure can be 100 000 IU/1, although a typical midterm result would be around 20 000 IU/1. In hydatidiform mole, this value can be in excess of 2 000 000 IU/1. We have seen similar levels for AFP and CEA. One pipetteful of serum will leave behind, if the pipette is plastic (which is less wettable), an average of 75 iii adhering to the inside surface. With glass pipettes, the volume may be up to 200 1. Thus a glass pipette could transfer 4 IU from a midterm pregnancy serum (not unlikely in a typical chemical pathology laboratory) which, in 2 ml of normal serum, would be equivalent to 2000 IU/1, all due to carry-over. We have found this shared use of pipettes in ten major hospitals. In all cases the practice was adopted to save money. We believe it to be a false economy. Supraregional Assay Service Laboratory, Department of Medical Oncology, Charing Cross Hospital, London W6 8RF
HUGH MITCHELL
SALT
SIR,-Dr Brown and colleagues’ letter (Aug 25, p 456) is utterly compare the implementation at the population level of a reduction of salt intake with the introduction of a drug. Whereas controlled clinical trials are essential before a new drug can be introduced, the situation with salt is totally different. Naturally available foods worldwide contain little sodium. Salt is a food additive, added to preserve food not to improve its taste. No other mammal regularly adds salt to its food. Your correspondents are laboratory scientists. May we propose that they stop their experiments in rats because, if they are willing to negate the importance of epidemiological findings in different populations, how can they extrapolate their findings in rats to the human
misleading. They
population? The relation between salt intake and blood pressure is very may be confounded by other factors such as other cations (K’, Ca’’"*’, Mg’ ’), saturated and/or polyunsaturated fat intake, alcohol consumption, obesity, and genetic predisposition. We are well aware that, at least in Western populations, it is nearly impossible nowadays to find any positive correlation between sodium intake and blood pressure, nor a negative one between Reasons for this have been potassium intake and blood pressure. thoroughly discussed elsewhere.’I The rewarding Belgian experience with a reduction of salt intake at the population level has been mentioned by Professor de Wardener (Sept 22, p 688) and resulted in a substantial decrease in deaths from stroke and stomach cancer between 1968 and 1978. However, salt intake in Belgium fell only slightly if at all in later years and since 1979 there has been no further decrease in deaths from stroke, stomach cancer, and all causes in Belgium-indeed 1983 data may even indicate an upward trend. In Korea salt intake is very high and stroke is very common.22 Korean intensive care units are full of comatose or hemiplegic patients, as one of us (H. K.) has seen. A positive correlation between blood pressure and urinary sodium excretion, and a negative one with potassium was found in both Korean males and
complex and
females.2 Evidence is
up linking salt intake to the aetiology of This could explain why stroke mortality is so closely related to stomach cancer, both between and within countries.3-5 It is also possible to estimate 24 h salt excretion in different populations and in different time periods starting from
stomach
building
cancer.
or stomach cancer mortality data. There is evidence showing that salt enhances the influence of experimental known stomach carcinogensband that hypertonic salt, like glandular stomach carcinogens, induces DNA synthesis and produces a 200-fold increase in ornithine decarboxylase activity in
either stroke
rats.7 We believe that it would be ill-advised to reduce the efforts directed towards a decrease in salt intake in the general population. What should be done is a careful and gradual lowering of salt intake over the next few years combined with intensive and standardised monitoring of salt intake, blood pressure, and cerebrovascular and stomach cancer mortality. We predict that further lowering of salt intake will be accompanied by reductions in mortality rates from both stroke and stomach cancer. H. KESTELOOT
Division
of Epidemiology, University of Leuven, B-3000 Leuven, Belgium
J. GEBOERS J. V. JOOSSENS
1. Kesteloot
H, Joossens JV, eds. The epidemiology of arterial blood pressure. The Hague: Martinus Nijhoff, 1980. 2 Kesteloot H, Park BC, Lee CS, Brems-Heyns E, Claessens J, Joossens JV. A comparative study of blood pressure and sodium intake in Belgium and in Korea. Eur J Cardiol 1980; 11: 169-82 3. Joossens JV, Geboers J Nutrition and gastric cancer. Nutr Cancer 1981; 2: 250-61 4. Joossens JV, Geboers J. The epidemiology of gastric cancer: a clue to etiology. In: Sherlock P, Morson BC, Barbara L, Veronesi U, eds. Precancerous lesions of the gastrointestinal tract New York Raven Press, 1983: 97-113 5. Joossens JV, Geboers J. Diet and environment in the etiology of gastric cancer. In: Riddell RH, Levin B, eds Frontiers of gastrointestinal cancer. New York: Elsevier Science Publishing, 1984: 167-83 6. Takahashi M, Kokubo T, Furukawa F, Kurokawa Y, Hayashi Y Effects of sodium chloride, saccharine, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with NMNG. Gann 1984; 75: 494-501. 7. Furihata C, Sato Y, Hosaka M, Matsushima T, Furukawa F, Takahashi M. NaCl induced ornithine decarboxylase and DNA synthesis Biochem Biophys Res Commun 1984; 121: 1027-32.
in
rat
stomach
mucosa.
SIR,-If, as Dr MacGregor claims (Sept 22, p 688) sodium restriction to 60-80 mmol daily is easily achieved, why can the studies reporting such intakes in free-living subjects over the past ten years be counted in single figures? At the recent conference on Diet and Primary Prevention of High Blood Pressure in Kuopio, Dr T. C. Beard also claimed that intakes in this range were readily achieved, but admitted that his observation was based on "young, white, intelligent, middle class, health-conscious, future-orientated, Australian civil servants". At the same meeting Finnish workers reported that 40% of adult hypertensives found a reduction in sodium intake from 200 to 80 mmol difficult, compared with only 1407o for a reduction in fat intake from 39% to 25% of total energy. The Finns also reported their failure to make any impression on the mean sodium intake of the male population of North Karelia, despite a three year campaign. In our experience in South Wales with normotensive young adults, who had shown their willingness by complying with a study requiring seven consecutive 24 h urine collections, most found it difficult to reduce their intake below 80 mmol for eight weeks, despite intensive support and the provision of 12 worth of foodstuffs per person per week. The official reports which recommend reductions in sodium intake are based on a balance of evidence, but do not take into I account the substantial recent negative findings from Finland, South Wales.5 While we do not and Belgium,2Chicago,3,4 disagree that sodium intakes in Western populations are probably unnecessarily high, it seems to us that these reports underestimate the practical difficulty and exaggerate the likely benefits of a sodium restriction campaign. MacGregor also continues his attempt to discredit our work on moderate sodium restriction in mild hypertension,including a bizarre reanalysis of our results without the original data. Contrary to his suggestion, there is no reason, other than to bias the results, why patients whose blood pressures rose during sodium restriction should be excluded from analysis, but even if this is done, there is only a statistically and clinically insignificant fall of 1 mm Hg, despite an 80 mmol reduction in sodium intake. MacGregor’s own observation of a 7 mm Hg fall in pressure in patients with initial standing pressures of 155/108 mm Hg (after two months’ observation) is the best evidence of an effect of sodium restriction on blood pressure, but it does not alter the critical point. Published
SIR,-Our laboratory offers a national tumour marker service for of a-fetoprotein (AFP), human chorionic gonadotropin (hCG), and carcinoembryonic antigen (CEA). Many of our patients are followed up so that rising values can be acted the measurement
swiftly. We occasionally see inconsistent results such as a sudden sharp increase followed by an immediate fall to the original baseline. On tracing back to the source laboratory we find this to be due to the practice of using the same pipette for more than one sample. Whilst this may be acceptable for analytes in which the variation between samples is low, for the analytes we measure it is upon
totally unacceptable. hCG in non-pregnant individuals is generally unmeasurable, although we give normal ranges up to 5 IU/1. By the twelfth week of gestation, this figure can be 100 000 IU/1, although a typical midterm result would be around 20 000 IU/1. In hydatidiform mole, this value can be in excess of 2 000 000 IU/1. We have seen similar levels for AFP and CEA. One pipetteful of serum will leave behind, if the pipette is plastic (which is less wettable), an average of 75 iii adhering to the inside surface. With glass pipettes, the volume may be up to 200 1. Thus a glass pipette could transfer 4 IU from a midterm pregnancy serum (not unlikely in a typical chemical pathology laboratory) which, in 2 ml of normal serum, would be equivalent to 2000 IU/1, all due to carry-over. We have found this shared use of pipettes in ten major hospitals. In all cases the practice was adopted to save money. We believe it to be a false economy. Supraregional Assay Service Laboratory, Department of Medical Oncology, Charing Cross Hospital, London W6 8RF
HUGH MITCHELL
SALT
SIR,-Dr Brown and colleagues’ letter (Aug 25, p 456) is utterly compare the implementation at the population level of a reduction of salt intake with the introduction of a drug. Whereas controlled clinical trials are essential before a new drug can be introduced, the situation with salt is totally different. Naturally available foods worldwide contain little sodium. Salt is a food additive, added to preserve food not to improve its taste. No other mammal regularly adds salt to its food. Your correspondents are laboratory scientists. May we propose that they stop their experiments in rats because, if they are willing to negate the importance of epidemiological findings in different populations, how can they extrapolate their findings in rats to the human
misleading. They
population? The relation between salt intake and blood pressure is very may be confounded by other factors such as other cations (K’, Ca’’"*’, Mg’ ’), saturated and/or polyunsaturated fat intake, alcohol consumption, obesity, and genetic predisposition. We are well aware that, at least in Western populations, it is nearly impossible nowadays to find any positive correlation between sodium intake and blood pressure, nor a negative one between Reasons for this have been potassium intake and blood pressure. thoroughly discussed elsewhere.’I The rewarding Belgian experience with a reduction of salt intake at the population level has been mentioned by Professor de Wardener (Sept 22, p 688) and resulted in a substantial decrease in deaths from stroke and stomach cancer between 1968 and 1978. However, salt intake in Belgium fell only slightly if at all in later years and since 1979 there has been no further decrease in deaths from stroke, stomach cancer, and all causes in Belgium-indeed 1983 data may even indicate an upward trend. In Korea salt intake is very high and stroke is very common.22 Korean intensive care units are full of comatose or hemiplegic patients, as one of us (H. K.) has seen. A positive correlation between blood pressure and urinary sodium excretion, and a negative one with potassium was found in both Korean males and
complex and
females.2 Evidence is
up linking salt intake to the aetiology of This could explain why stroke mortality is so closely related to stomach cancer, both between and within countries.3-5 It is also possible to estimate 24 h salt excretion in different populations and in different time periods starting from
stomach
building
cancer.
or stomach cancer mortality data. There is evidence showing that salt enhances the influence of experimental known stomach carcinogensband that hypertonic salt, like glandular stomach carcinogens, induces DNA synthesis and produces a 200-fold increase in ornithine decarboxylase activity in
either stroke
rats.7 We believe that it would be ill-advised to reduce the efforts directed towards a decrease in salt intake in the general population. What should be done is a careful and gradual lowering of salt intake over the next few years combined with intensive and standardised monitoring of salt intake, blood pressure, and cerebrovascular and stomach cancer mortality. We predict that further lowering of salt intake will be accompanied by reductions in mortality rates from both stroke and stomach cancer. H. KESTELOOT
Division
of Epidemiology, University of Leuven, B-3000 Leuven, Belgium
J. GEBOERS J. V. JOOSSENS
1. Kesteloot
H, Joossens JV, eds. The epidemiology of arterial blood pressure. The Hague: Martinus Nijhoff, 1980. 2 Kesteloot H, Park BC, Lee CS, Brems-Heyns E, Claessens J, Joossens JV. A comparative study of blood pressure and sodium intake in Belgium and in Korea. Eur J Cardiol 1980; 11: 169-82 3. Joossens JV, Geboers J Nutrition and gastric cancer. Nutr Cancer 1981; 2: 250-61 4. Joossens JV, Geboers J. The epidemiology of gastric cancer: a clue to etiology. In: Sherlock P, Morson BC, Barbara L, Veronesi U, eds. Precancerous lesions of the gastrointestinal tract New York Raven Press, 1983: 97-113 5. Joossens JV, Geboers J. Diet and environment in the etiology of gastric cancer. In: Riddell RH, Levin B, eds Frontiers of gastrointestinal cancer. New York: Elsevier Science Publishing, 1984: 167-83 6. Takahashi M, Kokubo T, Furukawa F, Kurokawa Y, Hayashi Y Effects of sodium chloride, saccharine, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with NMNG. Gann 1984; 75: 494-501. 7. Furihata C, Sato Y, Hosaka M, Matsushima T, Furukawa F, Takahashi M. NaCl induced ornithine decarboxylase and DNA synthesis Biochem Biophys Res Commun 1984; 121: 1027-32.
in
rat
stomach
mucosa.
SIR,-If, as Dr MacGregor claims (Sept 22, p 688) sodium restriction to 60-80 mmol daily is easily achieved, why can the studies reporting such intakes in free-living subjects over the past ten years be counted in single figures? At the recent conference on Diet and Primary Prevention of High Blood Pressure in Kuopio, Dr T. C. Beard also claimed that intakes in this range were readily achieved, but admitted that his observation was based on "young, white, intelligent, middle class, health-conscious, future-orientated, Australian civil servants". At the same meeting Finnish workers reported that 40% of adult hypertensives found a reduction in sodium intake from 200 to 80 mmol difficult, compared with only 1407o for a reduction in fat intake from 39% to 25% of total energy. The Finns also reported their failure to make any impression on the mean sodium intake of the male population of North Karelia, despite a three year campaign. In our experience in South Wales with normotensive young adults, who had shown their willingness by complying with a study requiring seven consecutive 24 h urine collections, most found it difficult to reduce their intake below 80 mmol for eight weeks, despite intensive support and the provision of 12 worth of foodstuffs per person per week. The official reports which recommend reductions in sodium intake are based on a balance of evidence, but do not take into I account the substantial recent negative findings from Finland, South Wales.5 While we do not and Belgium,2Chicago,3,4 disagree that sodium intakes in Western populations are probably unnecessarily high, it seems to us that these reports underestimate the practical difficulty and exaggerate the likely benefits of a sodium restriction campaign. MacGregor also continues his attempt to discredit our work on moderate sodium restriction in mild hypertension,including a bizarre reanalysis of our results without the original data. Contrary to his suggestion, there is no reason, other than to bias the results, why patients whose blood pressures rose during sodium restriction should be excluded from analysis, but even if this is done, there is only a statistically and clinically insignificant fall of 1 mm Hg, despite an 80 mmol reduction in sodium intake. MacGregor’s own observation of a 7 mm Hg fall in pressure in patients with initial standing pressures of 155/108 mm Hg (after two months’ observation) is the best evidence of an effect of sodium restriction on blood pressure, but it does not alter the critical point. Published