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BLOOD DONATION AND RISK OF CARDIOVASCULAR DISEASE
1424
Teniposide immunisation has since been sought in cancer patients under teniposide therapy but no further example has been found among the nineteen patients tested so far. This case suggests that anti-teniposide antibody should be sought in all patients who had received large cumulative doses and in those exhibiting adverse reactions to the drug. National Blood Transfusion 53 Boulevard Diderot, 75012 Paris, France
Centre,
Groupe Hospitalier Pitié-Salpétrière, Paris
B. HABIBI A. BAUMELOU M. SERDARU
COMFREY TOXICITY IN PERSPECTIVE
SIR,-Lancet correspondence on the potential hepatotoxicity of the herb comfrey has referred to a study in Afghanistan where wheat was contaminated with seeds of Heliotropium, which contain pyrrolizidine alkaloids, and where liver disease resulted. In referring to this work, others 2,3 have quoted only one of the analyses-that of total alkaloids in the Heliotropium seeds themselves. However, samples of contaminated wheat flour were also analysed and total alkaloid content varied around O’ 186%, representing a daily intake of approximately 1300 mg alkaloids in 700 g flour. This is in marked contrast to the estimated intake of 2 mg alkaloids daily, extrapolated from the other analysis based on seeds. It is clear that there are wide differences between concentrations of alkaloids in young and older comfrey leaves.4In addition, cooking will ensure some of the soluble alkaloids are lost in the vegetable water. However, little is known of the cumulative effects of a regular dietary intake of comfrey on man and, at this stage, the comments of Mattocks4 should at least be noted: "People who consider the benefit of comfrey to outweigh the (perhaps slight) risk involved may like to know that large, mature leaves carry the lowest concentration of toxic alkaloids." "The external use of comfrey preparations should not be hazardous since the alkaloids are converted to toxic metabolites by liver enzymes only after being ingested." Laboratory of Pharmacokinetics and Toxicology, Department of Clinical Pharmacology, School of Medicine, University College London, London WC1E 6JJ
CLARE ANDERSON
PARAQUAT POISONING AND KIDNEY FUNCTION TESTS
SIR,—Publications on paraquat poisoning are now emphasising the renal handling of this compound. Paraquat is renally excreted and renal failure will promote sustained tissue levels and thus encourage pulmonary uptake. Paraquat is an organic base and the existence of active secretion by organic base transport is supported by infusion studies with other organic bases which inhibit paraquat secretion. The degree to which paraquat clearance will exceed ,glomerular filtration rate expressed as creatinine clearance must be interpreted with caution, however (see figure). The Jaffe reaction is poorly understood but forms the basis of most creatinine determinations. The nature of the interference shown is not known but is significant in experimental and clinical studies. A recent case gave a urine concentration of paraquat of 570 µg/ml for the period 3-4 -5h after ingestion. The urinary creatinine of4’3mmol/l should be corrected to 3 -6mmol/l. We would suggest that studies of paraquat nephrotoxicity must include controls to allow for this interference and, because of the
1. Mohabbat
O, Srivastava RN, Younos MS, Sediq GC, Merzad AA,
outbreak
Aram GA. An
of hepatic veno-occlusive disease in North-Western Afghanistan. Lancet
1976; 11 269-71.
CCJ, Clarke M, Edgar JA, Frahn JL, Jago MV, Peterson JE, Smith LW. Structure and toxicity of the alkaloids of Russian comfrey (Symphytum x uplandicum Nyman), a medicinal herb and item of human diet. Experientia 1980; 36: 377-79. 3. Roitman JW. Comfrey and liver damage Lancet 1981; i. 944. 4. Mattocks AR Toxic pyrrolozidine alkaloids in comfrey. Lancet 1980; 11: 1136-37.
Correction of creatinine values for paraquat concentrations Pooled plasma was dialysed for 24 h to reduce creatinine to approximate to the lowest physiological levels. Creatinine was added to give the true creatinine concentrations as shown and then assayed using the Jaffe reaction on a creatinine analyser (Beckman R11C) at doubling concentrations of paraquat dichloride. Because there is no difference in creatinine in association with paraquat at 1 or 5 j-tg/ml the point of intersection with the ordinate gives the true creatinine.
obscure nature of the mechanism, correction curves similar to those above will be necessary for each individual assay system. Department of Renal Medicine, K.R.U.F. Institute,
D. B. WEBB C. G. DAVIES
Royal Infirmary, Cardiff CF2 ISZ
BLOOD DONATION AND RISK OF CARDIOVASCULAR DISEASE SIR,-Dr Sullivan’s hypothesis (June 13, p. 1293) that stored iron levels influence the development of cardiovascular disease is particularly attractive in that it can be readily tested. A trial of phlebotomy would be invaluable in supporting or refuting his hypothesis, but such a trial would be lengthy. As a preliminary to such a study it might be rewarding to examine the effect of regular blood donation on the incidence of cardiovascular disease. An estimated 2 million people give blood in this country each year
(Ibbotson RN, personal communication). Titmussi concluded from the Blood Transfusion Service Donor Survey (1967) that the donor sample closely resembled the structure of the general population in terms of age, sex, income, and social class. This survey also found that 61% of male donors and 56% of female donors had given more than fifteen units of blood. Therefore, it should be possible to find a sample of regular blood donors who could be matched with nondonors in terms of age, sex, social class, and known cardiovascular disease risk factors and thus establish the effect of regular for artifacts owing phlebotomy on cardiovascular disease. A to differences in volunteering behaviour2 between donors and nondonors could be obtained by including a group of potential donors who had been rejected for reasons such as being HBsAg carriers. It has been noted that no such study seems to have been done3 From a Med-line current literature search and a check through Index Medicus for the last 10 years I can find no reports of such a
control
study. I would like to thank Dr R. N. Ibbotson Director, Transfusion Centre, for his helpful discussion.
Junior Common Room, Birmingham University Medical School, Birmingham B15 2TJ
DIANA N.
Regional
Blood
J. LOCKWOOD
2. Culvenor
1. Titmuss RM. The gift relationship. London: Allen and Unwin, 1970. 2. Rosenthal R, Rosnow RL. The volunteer subject. New York- Wiley, 1975. 3. Seely S. blood donors and coronary disease. Am Heart J 1978; 95: 675.
Teniposide immunisation has since been sought in cancer patients under teniposide therapy but no further example has been found among the nineteen patients tested so far. This case suggests that anti-teniposide antibody should be sought in all patients who had received large cumulative doses and in those exhibiting adverse reactions to the drug. National Blood Transfusion 53 Boulevard Diderot, 75012 Paris, France
Centre,
Groupe Hospitalier Pitié-Salpétrière, Paris
B. HABIBI A. BAUMELOU M. SERDARU
COMFREY TOXICITY IN PERSPECTIVE
SIR,-Lancet correspondence on the potential hepatotoxicity of the herb comfrey has referred to a study in Afghanistan where wheat was contaminated with seeds of Heliotropium, which contain pyrrolizidine alkaloids, and where liver disease resulted. In referring to this work, others 2,3 have quoted only one of the analyses-that of total alkaloids in the Heliotropium seeds themselves. However, samples of contaminated wheat flour were also analysed and total alkaloid content varied around O’ 186%, representing a daily intake of approximately 1300 mg alkaloids in 700 g flour. This is in marked contrast to the estimated intake of 2 mg alkaloids daily, extrapolated from the other analysis based on seeds. It is clear that there are wide differences between concentrations of alkaloids in young and older comfrey leaves.4In addition, cooking will ensure some of the soluble alkaloids are lost in the vegetable water. However, little is known of the cumulative effects of a regular dietary intake of comfrey on man and, at this stage, the comments of Mattocks4 should at least be noted: "People who consider the benefit of comfrey to outweigh the (perhaps slight) risk involved may like to know that large, mature leaves carry the lowest concentration of toxic alkaloids." "The external use of comfrey preparations should not be hazardous since the alkaloids are converted to toxic metabolites by liver enzymes only after being ingested." Laboratory of Pharmacokinetics and Toxicology, Department of Clinical Pharmacology, School of Medicine, University College London, London WC1E 6JJ
CLARE ANDERSON
PARAQUAT POISONING AND KIDNEY FUNCTION TESTS
SIR,—Publications on paraquat poisoning are now emphasising the renal handling of this compound. Paraquat is renally excreted and renal failure will promote sustained tissue levels and thus encourage pulmonary uptake. Paraquat is an organic base and the existence of active secretion by organic base transport is supported by infusion studies with other organic bases which inhibit paraquat secretion. The degree to which paraquat clearance will exceed ,glomerular filtration rate expressed as creatinine clearance must be interpreted with caution, however (see figure). The Jaffe reaction is poorly understood but forms the basis of most creatinine determinations. The nature of the interference shown is not known but is significant in experimental and clinical studies. A recent case gave a urine concentration of paraquat of 570 µg/ml for the period 3-4 -5h after ingestion. The urinary creatinine of4’3mmol/l should be corrected to 3 -6mmol/l. We would suggest that studies of paraquat nephrotoxicity must include controls to allow for this interference and, because of the
1. Mohabbat
O, Srivastava RN, Younos MS, Sediq GC, Merzad AA,
outbreak
Aram GA. An
of hepatic veno-occlusive disease in North-Western Afghanistan. Lancet
1976; 11 269-71.
CCJ, Clarke M, Edgar JA, Frahn JL, Jago MV, Peterson JE, Smith LW. Structure and toxicity of the alkaloids of Russian comfrey (Symphytum x uplandicum Nyman), a medicinal herb and item of human diet. Experientia 1980; 36: 377-79. 3. Roitman JW. Comfrey and liver damage Lancet 1981; i. 944. 4. Mattocks AR Toxic pyrrolozidine alkaloids in comfrey. Lancet 1980; 11: 1136-37.
Correction of creatinine values for paraquat concentrations Pooled plasma was dialysed for 24 h to reduce creatinine to approximate to the lowest physiological levels. Creatinine was added to give the true creatinine concentrations as shown and then assayed using the Jaffe reaction on a creatinine analyser (Beckman R11C) at doubling concentrations of paraquat dichloride. Because there is no difference in creatinine in association with paraquat at 1 or 5 j-tg/ml the point of intersection with the ordinate gives the true creatinine.
obscure nature of the mechanism, correction curves similar to those above will be necessary for each individual assay system. Department of Renal Medicine, K.R.U.F. Institute,
D. B. WEBB C. G. DAVIES
Royal Infirmary, Cardiff CF2 ISZ
BLOOD DONATION AND RISK OF CARDIOVASCULAR DISEASE SIR,-Dr Sullivan’s hypothesis (June 13, p. 1293) that stored iron levels influence the development of cardiovascular disease is particularly attractive in that it can be readily tested. A trial of phlebotomy would be invaluable in supporting or refuting his hypothesis, but such a trial would be lengthy. As a preliminary to such a study it might be rewarding to examine the effect of regular blood donation on the incidence of cardiovascular disease. An estimated 2 million people give blood in this country each year
(Ibbotson RN, personal communication). Titmussi concluded from the Blood Transfusion Service Donor Survey (1967) that the donor sample closely resembled the structure of the general population in terms of age, sex, income, and social class. This survey also found that 61% of male donors and 56% of female donors had given more than fifteen units of blood. Therefore, it should be possible to find a sample of regular blood donors who could be matched with nondonors in terms of age, sex, social class, and known cardiovascular disease risk factors and thus establish the effect of regular for artifacts owing phlebotomy on cardiovascular disease. A to differences in volunteering behaviour2 between donors and nondonors could be obtained by including a group of potential donors who had been rejected for reasons such as being HBsAg carriers. It has been noted that no such study seems to have been done3 From a Med-line current literature search and a check through Index Medicus for the last 10 years I can find no reports of such a
control
study. I would like to thank Dr R. N. Ibbotson Director, Transfusion Centre, for his helpful discussion.
Junior Common Room, Birmingham University Medical School, Birmingham B15 2TJ
DIANA N.
Regional
Blood
J. LOCKWOOD
2. Culvenor
1. Titmuss RM. The gift relationship. London: Allen and Unwin, 1970. 2. Rosenthal R, Rosnow RL. The volunteer subject. New York- Wiley, 1975. 3. Seely S. blood donors and coronary disease. Am Heart J 1978; 95: 675.