- Email: [email protected]
SOYBEAN-PROTEIN DIET AND PLASMA-CHOLESTEROL
905
type-1 agranulocytosis. Although the bone-marrow may temporarily lack promyelocytes, granulocytes are apparently selectively destroyed without bone-marrow toxicity." 12 Antibodies which agglutinate granulocytes in the presence of of
levamisole have been found in the serum of a few patients with levamisole-induced agranulocytosis.’ 8 Levamisole thus seems
hapten on the leucocyte membrane. The condition is spontaneously reversible upon discontinuation of treatment. Reversible agranulocytosis has also been described with pyrazolone derivatives (such as phenylbutazone) and other commonly used drugs such as gold salts, sulphonamides, and phenothiazines.lO As with these other drugs, the frequency of levamisoleinduced agranulocytosis is much higher in rheumatoid arthritis than in other diseases. Our best estimate at present is that the frequency is approximately 3% in patients with severe rheumatic diseases, whereas this complication is rare in other conditions. The figure in rheumatoid arthritis is based on data obtained from pilot studies in as yet small numbers of severely affected patients. Only as their number increases and those treated become representative of the total population of rheumatoid subjects will the true frequency become known. The patient’s disease, his immunological profile, drug interaction, and/or previous sensitisation to other drugs may all be predis-
to act as a
memorandum on the Treatment and Supervision of Heroin Addiction. Paragraph 8, on outpatient services, stated: "Some addicts will not accept withdrawal treatment, at any rate to start with, and complete refusal of supplies will not cure their addiction-it will merely throw them on the black market and encourage the development of an organized illicit traffic on a scale hitherto unknown in this country." I agree with you that "it would be oversanguine to suppose that the system of treatment and control conceived 10 years ago did not, in the light of experience and changing circumstances, require critical review and probably some revision." At the same time, it would be a sad day if one were to see a rising tide of crime on the streets of London to support a 10-year heroin habit because of a change of policy at the national level. I trust that your plea, that the report of the special committee of the Advisory Council on the Misuse of Drugs be published, is successful. Division of Resource National Institute on
Rockville, Maryland 20852, U.S.A.
be harmful. M. ROSENTHAL A. ST J. DIXON Y. BREYSSE P. FRANCHIMONT E. C. HUSKISSON K. L. SCHMIDT Y. SCHUERMANS E. VEYS T. L. VISCHER Consultant rheumatologists to the steering committee of the E.U.L.A.R. Multicentre Study on Levamisole in Rheumatoid Arthritis
Janssen Pharmaceutica, B-2340 Beerse, Belgium Janssen Pharmaceutical Ltd,
Marlow, Bucks SL7
1ET
W. K. AMERY P. A. J. JANSSEN J. DE CREPE J. BRUGMANS SYMOENS J.
A. L. MACNAIR
DRUG-DEPENDENCE CLINICS
SIR,—I read with much interest and some dismay your edi(Feb 19, p. 405) in which you suggest that tighter pre-
torial
scribing and the general switch from heroin to methadone may have made the clinics less attractive to potential patients, so that addicts will see little gain in registration and will prefer continue on the black market. I also believe that a recent tendency for many clinics to refuse to continue to supply addicts (some of whom have been on continuous treatment since 1968) with methadone and/or heroin for self-injection is causing many of them to drop out of treatment and return to the street and to criminal activities to support their habit. On March 7, 1967, the Minister of Health issued a hospital
RICHARD V. PHILLIPSON
SOYBEAN-PROTEIN DIET AND PLASMA-CHOLESTEROL
13
posing factors.5 Agranulocytosis may happen at any time, and it has developed as long as two years after the start of treatment. It is often accompanied by sudden illness. In patients with rheumatic diseases, regular blood examinations are recommended, but a clear warning to the patient that he must return to his doctor as soon as he experiences suggestive symptoms is still the most efficient measure to detect this adverse reaction early. Sudden fever, shivering, and infection (sore throat, ulceration) clearly call for an immediate blood examination. Rapid and spontaneous recovery is the rule when the drug is withdrawn. Infection should be treated appropriately. Corticosteroids and blood transfusions should be avoided and might
Development, Drug Abuse,
SIR,-Although the hypocholesterolaemic effect of soybeanprotein reported by Dr Sirtori and his colleagues (Feb. 5, p. 275) in patients with type-n hyperlipoproteinamua is remarkable, their report does not disprove the value of a low-lipid/ low-cholesterol diet. They did not state how strictly the patients adhered to the low-lipid diet, and whether plasma-cholesterol concentrations altered during the three months the patients were on this diet. Levy et al. reported a fall from 440 to 330 mg/dl using the same diet. Furthermore, the downward trend of plasma-cholesterol in the cross-over trial, which compared the effect of a soybean-protein diet with that of a low-lipid diet, might be due to the high P/S ratio (polyunsaturated/saturated fat) in both diets. The addition of cholesterol to the diet did not modify the hypocholesterolsemic effect of soybean protein. This lack of effect of cholesterol could be caused by the very low dietary lipid content and the high P/S ratio. There is evidence of an inter-action between the effect of dietary cholesterol, fat level,23 and degree of saturation of dietary fat, although there are conflicting reports.’ 5 Unfortunately, Sirtori et al. did not state whether dietary cholesterol affected plasma-lipids in patients on the control low-lipid diet. Extrapolation of the effect of soybean protein to other vegetable proteins is not warranted. Our experiments6 with rabbits do not support the suggestion that animal proteins as such induce higher plasma-cholesterol levels than vegetable proteins. We demonstrated that hypercholesterolaemia in casein-fed rabbits could be largely prevented by replacing part of the casein by other animal proteins, such as gelatin and fish protein. We suggest that this is due to differences in aminoacid composition between the proteins. It would be interesting to investigate whether the observed effect is a general one or confined to the type-n patient. If its effect can be confirmed in controlled long-term studies, soybean protein might be a very useful adjunct to treatment.
to
11. Pisciotta, A. V. Sem. Hemat. 1973,10, 279. 12 Lobuglio, A. New Engl. J. Med. 1976, 295, 1533. 13 Hennemann, H. H., Schief, A. Dt. med. Wschr. 1975, 100, 519.
Department of Human Nutrition, Agricultural University, Wageningen, Netherlands
R. J. J. HERMUS M. STASSE-WOLTHUIS J. G. A. J. HAUTVAST
R. I., Bonnell, M., Ernst, N. D. J. Am. diet. Ass. 1971, 58, 406. Grande, F., Anderson, J. T., Chlouverakis, C., Proja, M., Keys, A. J. Nutr. 1965, 87, 52. 3. Keys, A., Grande, F., Anderson, J. T. Am. J. clin. Nutr. 1974, 27, 188. 4. Brown, H. B. Proc. 2nd int. Symp. Atherosclerosis. 1969, p. 426. 5. Anderson, J. F., Grande, F., Keys, A. Am. J. clin. Nutr. 1976, 29, 1184. 6. Hermus, R. J. J. PH.D. thesis. (Agric. Res. Rep. 838, Pudoc, Wageningen). 7. Hamilton, R. M. G., Carroll, K. K. Atherosclerosis, 1976, 24, 47. 1. 2.
Levy,
type-1 agranulocytosis. Although the bone-marrow may temporarily lack promyelocytes, granulocytes are apparently selectively destroyed without bone-marrow toxicity." 12 Antibodies which agglutinate granulocytes in the presence of of
levamisole have been found in the serum of a few patients with levamisole-induced agranulocytosis.’ 8 Levamisole thus seems
hapten on the leucocyte membrane. The condition is spontaneously reversible upon discontinuation of treatment. Reversible agranulocytosis has also been described with pyrazolone derivatives (such as phenylbutazone) and other commonly used drugs such as gold salts, sulphonamides, and phenothiazines.lO As with these other drugs, the frequency of levamisoleinduced agranulocytosis is much higher in rheumatoid arthritis than in other diseases. Our best estimate at present is that the frequency is approximately 3% in patients with severe rheumatic diseases, whereas this complication is rare in other conditions. The figure in rheumatoid arthritis is based on data obtained from pilot studies in as yet small numbers of severely affected patients. Only as their number increases and those treated become representative of the total population of rheumatoid subjects will the true frequency become known. The patient’s disease, his immunological profile, drug interaction, and/or previous sensitisation to other drugs may all be predis-
to act as a
memorandum on the Treatment and Supervision of Heroin Addiction. Paragraph 8, on outpatient services, stated: "Some addicts will not accept withdrawal treatment, at any rate to start with, and complete refusal of supplies will not cure their addiction-it will merely throw them on the black market and encourage the development of an organized illicit traffic on a scale hitherto unknown in this country." I agree with you that "it would be oversanguine to suppose that the system of treatment and control conceived 10 years ago did not, in the light of experience and changing circumstances, require critical review and probably some revision." At the same time, it would be a sad day if one were to see a rising tide of crime on the streets of London to support a 10-year heroin habit because of a change of policy at the national level. I trust that your plea, that the report of the special committee of the Advisory Council on the Misuse of Drugs be published, is successful. Division of Resource National Institute on
Rockville, Maryland 20852, U.S.A.
be harmful. M. ROSENTHAL A. ST J. DIXON Y. BREYSSE P. FRANCHIMONT E. C. HUSKISSON K. L. SCHMIDT Y. SCHUERMANS E. VEYS T. L. VISCHER Consultant rheumatologists to the steering committee of the E.U.L.A.R. Multicentre Study on Levamisole in Rheumatoid Arthritis
Janssen Pharmaceutica, B-2340 Beerse, Belgium Janssen Pharmaceutical Ltd,
Marlow, Bucks SL7
1ET
W. K. AMERY P. A. J. JANSSEN J. DE CREPE J. BRUGMANS SYMOENS J.
A. L. MACNAIR
DRUG-DEPENDENCE CLINICS
SIR,—I read with much interest and some dismay your edi(Feb 19, p. 405) in which you suggest that tighter pre-
torial
scribing and the general switch from heroin to methadone may have made the clinics less attractive to potential patients, so that addicts will see little gain in registration and will prefer continue on the black market. I also believe that a recent tendency for many clinics to refuse to continue to supply addicts (some of whom have been on continuous treatment since 1968) with methadone and/or heroin for self-injection is causing many of them to drop out of treatment and return to the street and to criminal activities to support their habit. On March 7, 1967, the Minister of Health issued a hospital
RICHARD V. PHILLIPSON
SOYBEAN-PROTEIN DIET AND PLASMA-CHOLESTEROL
13
posing factors.5 Agranulocytosis may happen at any time, and it has developed as long as two years after the start of treatment. It is often accompanied by sudden illness. In patients with rheumatic diseases, regular blood examinations are recommended, but a clear warning to the patient that he must return to his doctor as soon as he experiences suggestive symptoms is still the most efficient measure to detect this adverse reaction early. Sudden fever, shivering, and infection (sore throat, ulceration) clearly call for an immediate blood examination. Rapid and spontaneous recovery is the rule when the drug is withdrawn. Infection should be treated appropriately. Corticosteroids and blood transfusions should be avoided and might
Development, Drug Abuse,
SIR,-Although the hypocholesterolaemic effect of soybeanprotein reported by Dr Sirtori and his colleagues (Feb. 5, p. 275) in patients with type-n hyperlipoproteinamua is remarkable, their report does not disprove the value of a low-lipid/ low-cholesterol diet. They did not state how strictly the patients adhered to the low-lipid diet, and whether plasma-cholesterol concentrations altered during the three months the patients were on this diet. Levy et al. reported a fall from 440 to 330 mg/dl using the same diet. Furthermore, the downward trend of plasma-cholesterol in the cross-over trial, which compared the effect of a soybean-protein diet with that of a low-lipid diet, might be due to the high P/S ratio (polyunsaturated/saturated fat) in both diets. The addition of cholesterol to the diet did not modify the hypocholesterolsemic effect of soybean protein. This lack of effect of cholesterol could be caused by the very low dietary lipid content and the high P/S ratio. There is evidence of an inter-action between the effect of dietary cholesterol, fat level,23 and degree of saturation of dietary fat, although there are conflicting reports.’ 5 Unfortunately, Sirtori et al. did not state whether dietary cholesterol affected plasma-lipids in patients on the control low-lipid diet. Extrapolation of the effect of soybean protein to other vegetable proteins is not warranted. Our experiments6 with rabbits do not support the suggestion that animal proteins as such induce higher plasma-cholesterol levels than vegetable proteins. We demonstrated that hypercholesterolaemia in casein-fed rabbits could be largely prevented by replacing part of the casein by other animal proteins, such as gelatin and fish protein. We suggest that this is due to differences in aminoacid composition between the proteins. It would be interesting to investigate whether the observed effect is a general one or confined to the type-n patient. If its effect can be confirmed in controlled long-term studies, soybean protein might be a very useful adjunct to treatment.
to
11. Pisciotta, A. V. Sem. Hemat. 1973,10, 279. 12 Lobuglio, A. New Engl. J. Med. 1976, 295, 1533. 13 Hennemann, H. H., Schief, A. Dt. med. Wschr. 1975, 100, 519.
Department of Human Nutrition, Agricultural University, Wageningen, Netherlands
R. J. J. HERMUS M. STASSE-WOLTHUIS J. G. A. J. HAUTVAST
R. I., Bonnell, M., Ernst, N. D. J. Am. diet. Ass. 1971, 58, 406. Grande, F., Anderson, J. T., Chlouverakis, C., Proja, M., Keys, A. J. Nutr. 1965, 87, 52. 3. Keys, A., Grande, F., Anderson, J. T. Am. J. clin. Nutr. 1974, 27, 188. 4. Brown, H. B. Proc. 2nd int. Symp. Atherosclerosis. 1969, p. 426. 5. Anderson, J. F., Grande, F., Keys, A. Am. J. clin. Nutr. 1976, 29, 1184. 6. Hermus, R. J. J. PH.D. thesis. (Agric. Res. Rep. 838, Pudoc, Wageningen). 7. Hamilton, R. M. G., Carroll, K. K. Atherosclerosis, 1976, 24, 47. 1. 2.
Levy,