1414 The factors implicated in the aetiology of those three cancers complex and are related to sociological, environmental, and geographic variations. However, I consider that a low intake of dietary iodine is not correlated with increased incidence of these cancers in tropical Africa-indeed it could be postulated that the reverse obtains. are
triglycerides were on the upper limit of normal: 150, 158, 165, 171, 178 and 182 mg/dl (normal range 74-172). The increased levels of urinary D-glucaric acid and serum-G.G.T. activity suggest the presence of hepatic microsomal enzyme induction in our patients,t-4 and we conclude, in agreement with Martin et al. 56 that the tendency to hypertriglyceridsemia could be related
Department of Pathology, Ahmadu Bello University,
G. M. EDINGTON
Zaria, Nigeria
to
enzyme induction.
Institute of Clinical Medicine University of Milan, 20122 Milan, Italy
III,
G. ANNONI G. L. BARBI
G. IDEO
ENZYME INDUCTION AND ALCOHOLISM
SIR,-We were interested to read the suggestion by Dr Martin and his colleagues (May 22, p. 1107) that the hyperlipideemia associated with the use of oral contraceptives might be produced by hepatic enzyme induction. Hyperlipida’mia also occurs in alcoholic patients, and in an epidemiological survey2 serum-triglyceride concentrations correlated with alcohol consumption in healthy individuals. Raised gamma-glutamyl transpeptidase (G.G.T.) activity is also seen in alcoholics, even in the absence of liver damageand probably reflects hepatic enzyme induction. We have attempted to assess the degree to which enzyme induction contributes to the hyperlipidaemia seen in alcoholic patients. Fasting serum from 51 alcoholics was assayed for triglyceride concentration and G.G.T. activity. All the patients had been drinking more than ten pints (about 6 litres) of beer or its equivalent daily for at least two years and had been abstinent for less than two weeks at the time of study. Liver biopsy showed cirrhosis in 18 patients, moderate to severe fatty change with or without increased periportal fibrosis in 20, and minimal or absent fatty change or portal infiltration in 13. Fasting serum-triglyceride concentrations ranged from 0-44 to 4.36 mmol/1, and were above normal in 8 patients. G.G.T. activity ranged from 25 to 970 i.u./l. There was no correlation between serum-triglyceride and G.G.T. activity either in the whole group or in any histological subgroup. 21 patients had raised serum-alkaline-phosphatases so increased G.G.T. activity may have reflected liver damage rather than enzyme induction. However, when these 21 patients were excluded from analysis no correlation was found. Alcoholic hyperlipidwmia is not secondary to reduced clearance of triglyceride from the bloodnor is it due to the calorie content of alcohol.’ Oxidation of alcohol in the liver increases the hepatocyte reduced N.A.D./N.A.D. ratio which in turn increases the supply of fatty acids for triglyceride synthesis.5 Our data suggest that there is no further significant contribution from enzyme induction. We thank Dr A. Paton and Dr M. I. Akhter for
permission to inves-
tigate patients under their care. Clinical Investigation Unit, Dudley Road Hospital, Birmingham B18 7QH
GEOFFREY NICHOLSON K. O. LEWIS
ENZYME INDUCTION AND INCREASED SERUM-TRIGLYCERIDE
SIR,-In six epileptic patients during phenobarbitone and
hydantoin therapy serum-7-glutamyl-transpeptidase (G.G.T.) activity, triglyceride concentration, and urinary D-glucaricacid excretion have been investigated. All the patients showed an increased urinary D-glucaric-acid excretion; serum-G.G.T. activity
was
increased in five
out
THE RADIOALLERGOSORBENT TEST
SIR,--Your editorial (May 15, p. 1061) on this test (R.A.S.T.) may underestimate its potential usefulness to the clinician divorced from central laboratory facilities. R.A.S.T. diagnosis may be carried out with blood dried on filter-paper or cloth.’ Filter-paper techniques have many advantages in collection, shipment, and storage over conventional methods which use liquid blood. The sensitivity of the R.A.S.T. may be improved further by the incubation of two or more non-cross-reacting allergen discs in a single stain extract. In this way Werrett and King’ measured IgE antibody activity levels against Dermatophagoides glomerata, D. pteronyssinus, and cat epithelium by using a single extract from 50 µl (0.050 ml) of dried blood. Central Research Establishment,
Aldermaston, Reading, Berkshire RG7 4PN
SIR,—Iread, with interest, your editorial of May 15. Certainly, this test has great theoretical advantages; however, in practice, as done by the commercial laboratories there are certain drawbacks.
Firstly, at approximately$5 per test it is more expensive than skin testing and history taking. Secondly, the time from when the blood is drawn until the laboratory sends the results back to the doctor has been between 2 and 4 weeks. The selection of tests has been limited. Many obvious antigens are not obtainable while the laboratories are doing other antigens of no or limited importance. Also, as you pointed out, its correlation with provocation depends on the purity of the antigen. This is no different from skin testing. Certainly, excellent correlation with pollens is obtained by both R.A.S.T. and skin testing; while poor correlation with both tests is often found with animal danders and house dust. For inhalants, there are many false positives with skin testing, while with R.A.S.T.S, there are false negatives. This discordance, between provocation and testing, is reversed in the case of foods, with R.A.S.T. having false positives. There is a pardiatrician at the College of Medicine and Dentistry of New Jersey who has obvious ragweed allergies. She gets a constitutional reaction to skin testing with as little as 1 P.N.U. of ragweed, but extensive R.A.S.T.s have been completely negative. Some of these false-negative R.A.S.T.S may theoretically be due to skin-fixing antibodies not of the IgE class and, therefore, not picked up by R.A.S.T. as ;t is done commercially. Because of these limitations, 1 would suggest that for the vast majority of patients, history, physical examination, and selective skin tests are preferable. R.A.S.T.S should be reserved
of the six patients. Serum 1.
1. 2.
3. 4. 5.
P. H. WHITEHEAD
Losowsky, M. S., Jones, D. P., Davidson, C. S., Lieber, C. S. Am. J. Med. 1963, 35, 794. Ostrander, L. D., Lamphier, D. E., Block, W. D., Johnson, B. C., Ravenscroft, C., Epstein, F. H. Archs intern. Med. 1974, 134, 451. Rosalki, S. B., Rau, D. Clin. Chim. Acta, 1972, 39, 41. Chait, A., Mancini, M., February, A. W., Lewis, B. Lancet, 1972, ii, 62. Lieber, C. S., Rubin, E., De Carli, L. M. in The Biology of Alcoholism (edited by B. Kissin and H. Begleiter); vol. I, p. 263. New York, 1974.
Hunter, J., Maxwell, J. D., Carrella, M., Stewart, D. A., Williams, R. Lancet, 1971, i, 572. 2. Rosalki, S. B., Tarlow, D. ibid. 1971, ii, 376. 3. Ideo, G., de Franchis, R., Del Ninno, E., Dioguardi, N. ibid. 1971, u, 825. 4. Whitfield, J. B., Moss, D. W., Neale, G., Orme, M., Breckenridge, A., Br. med. J. 1973, i, 316. 5. Martin, P. J., Martin, J. V., Goldberg, D. M. ibid. 1975, i, 17. 6. Martin, J. V., Martin, P. J., Goldberg, D. M. Lancet, 1975, i, 1107. 7. Werrett, D. J., King, L. A. Clin. Allergy, 1976, 6, 75.
triglycerides were on the upper limit of normal: 150, 158, 165, 171, 178 and 182 mg/dl (normal range 74-172). The increased levels of urinary D-glucaric acid and serum-G.G.T. activity suggest the presence of hepatic microsomal enzyme induction in our patients,t-4 and we conclude, in agreement with Martin et al. 56 that the tendency to hypertriglyceridsemia could be related
Department of Pathology, Ahmadu Bello University,
G. M. EDINGTON
Zaria, Nigeria
to
enzyme induction.
Institute of Clinical Medicine University of Milan, 20122 Milan, Italy
III,
G. ANNONI G. L. BARBI
G. IDEO
ENZYME INDUCTION AND ALCOHOLISM
SIR,-We were interested to read the suggestion by Dr Martin and his colleagues (May 22, p. 1107) that the hyperlipideemia associated with the use of oral contraceptives might be produced by hepatic enzyme induction. Hyperlipida’mia also occurs in alcoholic patients, and in an epidemiological survey2 serum-triglyceride concentrations correlated with alcohol consumption in healthy individuals. Raised gamma-glutamyl transpeptidase (G.G.T.) activity is also seen in alcoholics, even in the absence of liver damageand probably reflects hepatic enzyme induction. We have attempted to assess the degree to which enzyme induction contributes to the hyperlipidaemia seen in alcoholic patients. Fasting serum from 51 alcoholics was assayed for triglyceride concentration and G.G.T. activity. All the patients had been drinking more than ten pints (about 6 litres) of beer or its equivalent daily for at least two years and had been abstinent for less than two weeks at the time of study. Liver biopsy showed cirrhosis in 18 patients, moderate to severe fatty change with or without increased periportal fibrosis in 20, and minimal or absent fatty change or portal infiltration in 13. Fasting serum-triglyceride concentrations ranged from 0-44 to 4.36 mmol/1, and were above normal in 8 patients. G.G.T. activity ranged from 25 to 970 i.u./l. There was no correlation between serum-triglyceride and G.G.T. activity either in the whole group or in any histological subgroup. 21 patients had raised serum-alkaline-phosphatases so increased G.G.T. activity may have reflected liver damage rather than enzyme induction. However, when these 21 patients were excluded from analysis no correlation was found. Alcoholic hyperlipidwmia is not secondary to reduced clearance of triglyceride from the bloodnor is it due to the calorie content of alcohol.’ Oxidation of alcohol in the liver increases the hepatocyte reduced N.A.D./N.A.D. ratio which in turn increases the supply of fatty acids for triglyceride synthesis.5 Our data suggest that there is no further significant contribution from enzyme induction. We thank Dr A. Paton and Dr M. I. Akhter for
permission to inves-
tigate patients under their care. Clinical Investigation Unit, Dudley Road Hospital, Birmingham B18 7QH
GEOFFREY NICHOLSON K. O. LEWIS
ENZYME INDUCTION AND INCREASED SERUM-TRIGLYCERIDE
SIR,-In six epileptic patients during phenobarbitone and
hydantoin therapy serum-7-glutamyl-transpeptidase (G.G.T.) activity, triglyceride concentration, and urinary D-glucaricacid excretion have been investigated. All the patients showed an increased urinary D-glucaric-acid excretion; serum-G.G.T. activity
was
increased in five
out
THE RADIOALLERGOSORBENT TEST
SIR,--Your editorial (May 15, p. 1061) on this test (R.A.S.T.) may underestimate its potential usefulness to the clinician divorced from central laboratory facilities. R.A.S.T. diagnosis may be carried out with blood dried on filter-paper or cloth.’ Filter-paper techniques have many advantages in collection, shipment, and storage over conventional methods which use liquid blood. The sensitivity of the R.A.S.T. may be improved further by the incubation of two or more non-cross-reacting allergen discs in a single stain extract. In this way Werrett and King’ measured IgE antibody activity levels against Dermatophagoides glomerata, D. pteronyssinus, and cat epithelium by using a single extract from 50 µl (0.050 ml) of dried blood. Central Research Establishment,
Aldermaston, Reading, Berkshire RG7 4PN
SIR,—Iread, with interest, your editorial of May 15. Certainly, this test has great theoretical advantages; however, in practice, as done by the commercial laboratories there are certain drawbacks.
Firstly, at approximately$5 per test it is more expensive than skin testing and history taking. Secondly, the time from when the blood is drawn until the laboratory sends the results back to the doctor has been between 2 and 4 weeks. The selection of tests has been limited. Many obvious antigens are not obtainable while the laboratories are doing other antigens of no or limited importance. Also, as you pointed out, its correlation with provocation depends on the purity of the antigen. This is no different from skin testing. Certainly, excellent correlation with pollens is obtained by both R.A.S.T. and skin testing; while poor correlation with both tests is often found with animal danders and house dust. For inhalants, there are many false positives with skin testing, while with R.A.S.T.S, there are false negatives. This discordance, between provocation and testing, is reversed in the case of foods, with R.A.S.T. having false positives. There is a pardiatrician at the College of Medicine and Dentistry of New Jersey who has obvious ragweed allergies. She gets a constitutional reaction to skin testing with as little as 1 P.N.U. of ragweed, but extensive R.A.S.T.s have been completely negative. Some of these false-negative R.A.S.T.S may theoretically be due to skin-fixing antibodies not of the IgE class and, therefore, not picked up by R.A.S.T. as ;t is done commercially. Because of these limitations, 1 would suggest that for the vast majority of patients, history, physical examination, and selective skin tests are preferable. R.A.S.T.S should be reserved
of the six patients. Serum 1.
1. 2.
3. 4. 5.
P. H. WHITEHEAD
Losowsky, M. S., Jones, D. P., Davidson, C. S., Lieber, C. S. Am. J. Med. 1963, 35, 794. Ostrander, L. D., Lamphier, D. E., Block, W. D., Johnson, B. C., Ravenscroft, C., Epstein, F. H. Archs intern. Med. 1974, 134, 451. Rosalki, S. B., Rau, D. Clin. Chim. Acta, 1972, 39, 41. Chait, A., Mancini, M., February, A. W., Lewis, B. Lancet, 1972, ii, 62. Lieber, C. S., Rubin, E., De Carli, L. M. in The Biology of Alcoholism (edited by B. Kissin and H. Begleiter); vol. I, p. 263. New York, 1974.
Hunter, J., Maxwell, J. D., Carrella, M., Stewart, D. A., Williams, R. Lancet, 1971, i, 572. 2. Rosalki, S. B., Tarlow, D. ibid. 1971, ii, 376. 3. Ideo, G., de Franchis, R., Del Ninno, E., Dioguardi, N. ibid. 1971, u, 825. 4. Whitfield, J. B., Moss, D. W., Neale, G., Orme, M., Breckenridge, A., Br. med. J. 1973, i, 316. 5. Martin, P. J., Martin, J. V., Goldberg, D. M. ibid. 1975, i, 17. 6. Martin, J. V., Martin, P. J., Goldberg, D. M. Lancet, 1975, i, 1107. 7. Werrett, D. J., King, L. A. Clin. Allergy, 1976, 6, 75.
