1293 that T3 radioimmunoassay is index of
not
the ultimate
laboratory
Christchurch Hospital,
Christchurch, New Zealand.
J. G. TURNER B. E. W. BROWNLIE W. A. SADLER C. A. JENSEN.
PLASMA IRON AND IRON-BINDING CAPACITY SIR,-Of course it all depends on what you mean by the anaemia of chronic disorders. If, like me, you mean the anaemia found in inflammatory and malignant conditions and characterised by reduced numbers of sideroblasts in the marrow and increased haemosiderin within macrophages, and exclude that found in myxoedema, uraemia, and liver disorders, then I stick to my assertion (May 10, p. 1090) that these ;are " likely to have hypochromic, microcytic red cells ". If I may quote a more comprehensive and up-to-date textbook than that cited by Dr Zilva (May 24, p. 1191),"... hypochromia has been observed in 23 to 50% of patients with chronic infection, 50 to 100% of patients with rheumatoid arthritis, and 44 to 64% of patients with cancer."1 I agree that many cases of iron deficiency can be distinguished from this condition on hasmatological grounds alone, but as Dr Turnbull has indicated (May 24, p. 1191), many cannot. I also agree with your correspondents who complain that serum-irons are over-requested, and what a wonderful world it would be if pathologists alone could make requests of the laboratory. But in the real world are they more abused than Bl2s and folates, or even haemoglobins and plasma-electrolytes ? By all means, let us encourage a greater dialogue with clinicians, but, please, biochemists, don’t stop doing the test. If haematologists have to set it up themselves, what will the coefficient of variation be then ? Royal Victoria Hospital, Boscombe, Bournemouth BH1 4JG.
the
was
thyrotoxicosis.
Nuclear Medicine Department,
In the 3 remaining patients the cholesterol altered constituent, but in none did it exceed 300 mg. per 100 ml. Basal immunoreactive insulin levels and blood-glucose were normal in all the patients.
lipolytic activity). most
Our study does not confirm Casaretto’s reported results but agrees with Beaumont’s experience. However, we cannot support Beaumont’s hypothesis that normal bloodlipids could be due to the alternate-day corticosteroid therapy, since we have observed normal lipid levels with daily corticosteroid treatment.
J. MASRAMON A. CARALPS M. LLORACH R. COMPANYS A. BRULLES J. LLOVERAS J. ANDREU.
Unidad de Trasplante Renal, Catedra de Urologia (Facultad de Medicina),
Hospital Clínico y Provincial, Barcelona, Spain.
TOXICITY OF ASPARAGINASES are being used in the is obtained from Escherichia coli (Escherichia asparaginase), the other from the plant pathogen, Erwinia carotovora (Erwinia asparaginase). Although they appear to be equally effective as antileuksemic agents.l some reports suggest that they differ in toxicity.2.3 To clarify this I examined the records of patients with acute leukasmia who have been treated with asparaginase at three London hospitals. The doses used were similar at each hospital, either 200 i.u. per kg. body-weight or 6000 i.u. per sq.m. bodysurface area of reconstituted freeze-dried asparaginase. There were no deaths attributable to enzyme therapy but toxicity interrupted 12 of the 31 (39%) courses of Escherichia
SiR,—Two bacterial asparaginases
treatment
of acute leukaemia:
one
FREQUENCY OF SERIOUS TOXICITY
*
TERRY HAMBLIN. * Serious toxicity asparaginase changed or discontinued. t Course=at least 3 full doses given without toxicity or one =
HYPERLIPIDÆMIA AFTER RENAL
SiR,-Casaretto et awl. reported a significant rise in basal plasma-levels of triglyceride, cholesterol, and immunoreactive insulin after successful renal transplantation in 37 patients receiving an average dose of 17 mg. of prednisolone per day. They found that hyperlipoproteinxmia was a general feature in these patients. In contrast, Beaumont et al. (March 15, p. 599) find normal serum-lipid profiles in 78% of 42 successfully
transplanted patients receiving an average dose of 22 mg. of prednisone every other day. The remaining 22% show hyperlipidaemia, but they are significantly more obese and older. Both the normal subjects and the hyperlipidaemic patients show normal basal immunoreactive insulin levels. Beaumont and his colleagues postulate that this high percentage of patients with normal blood-lipid levels cquld be due to the alternate-day corticosteroid therapy. In 19 an
patients with successful renal transplantation treated with prednisone per day for at least
average dose of 12 mg. of
3 months and with serum-creatinine levels below 20 mg. per 100 ml., we found 16 (84%) with no change in any of the lipid parameters studied (overnight-fasting cholesterol, triglycerides, free fatty acids, free glycerol, lipidogram in cellulose acetate, thin-layer chromatography of neutral lipids, and post-heparin 1. Wintrobe, M. M. Clinical Hæmatology; p. 673. Philadelphia,1974. 2. Casaretto, A., Marchioro, T. L., Goldsmith, R., Bagdade, J. D. Lancet, 1974, i, 481.
or more
full doses if toxicity developed.
TRANSPLANTATION
asparaginase and 9 of the 46 (20%) Erwinia courses (see accompanying table). Allergic reactions were the commonest side-effects, and their occurrence always led to a change or discontinuance of asparaginase. They did not appear until at least ten days after the start of enzyme treatment unless the patient had been treated previously with the same type of enzyme. 11 patients were re-exposed to the same asparaginase;
1 of the 5 Escherichia-treated and 1 of the 6 Erwinia-treated had an anaphylactic reaction; the former required intravenous hydrocortisone, the latter recovered without treatment.
10
patients were given the alternative enzyme because of hypersensitivity-3 sensitive to Erwinia, 7 to Escherichia asparaginase. In all of these, enzyme therapy was continued satisfactorily without cross-toxicity. In 2 cases asparaginases were substituted because of vomiting, but without benefit. One child was given Erwinia asparaginase intravenously twice weekly for fifty-four weeks, except for gaps of one week every 8 weeks when prednisone and arabinosyl cytosine were given. No toxicity occurred during this 1. 2. 3.
Kay, H. E. M., Fairley, G. H., Knapton, P. J. Colloques int. C.N.R.S., 1971, no. 197 : l’asparaginase, p. 295. Ohnuma, T., Holland, J. F., Meyer, P. Cancer, N.Y. 1972, 30, 376. Ohnuma, T., Holland, J. F., Meyer, P. Proc. Am. Ass. Cancer Res. 1972, 13, 117 (abstr. 465).
not
the ultimate
laboratory
Christchurch Hospital,
Christchurch, New Zealand.
J. G. TURNER B. E. W. BROWNLIE W. A. SADLER C. A. JENSEN.
PLASMA IRON AND IRON-BINDING CAPACITY SIR,-Of course it all depends on what you mean by the anaemia of chronic disorders. If, like me, you mean the anaemia found in inflammatory and malignant conditions and characterised by reduced numbers of sideroblasts in the marrow and increased haemosiderin within macrophages, and exclude that found in myxoedema, uraemia, and liver disorders, then I stick to my assertion (May 10, p. 1090) that these ;are " likely to have hypochromic, microcytic red cells ". If I may quote a more comprehensive and up-to-date textbook than that cited by Dr Zilva (May 24, p. 1191),"... hypochromia has been observed in 23 to 50% of patients with chronic infection, 50 to 100% of patients with rheumatoid arthritis, and 44 to 64% of patients with cancer."1 I agree that many cases of iron deficiency can be distinguished from this condition on hasmatological grounds alone, but as Dr Turnbull has indicated (May 24, p. 1191), many cannot. I also agree with your correspondents who complain that serum-irons are over-requested, and what a wonderful world it would be if pathologists alone could make requests of the laboratory. But in the real world are they more abused than Bl2s and folates, or even haemoglobins and plasma-electrolytes ? By all means, let us encourage a greater dialogue with clinicians, but, please, biochemists, don’t stop doing the test. If haematologists have to set it up themselves, what will the coefficient of variation be then ? Royal Victoria Hospital, Boscombe, Bournemouth BH1 4JG.
the
was
thyrotoxicosis.
Nuclear Medicine Department,
In the 3 remaining patients the cholesterol altered constituent, but in none did it exceed 300 mg. per 100 ml. Basal immunoreactive insulin levels and blood-glucose were normal in all the patients.
lipolytic activity). most
Our study does not confirm Casaretto’s reported results but agrees with Beaumont’s experience. However, we cannot support Beaumont’s hypothesis that normal bloodlipids could be due to the alternate-day corticosteroid therapy, since we have observed normal lipid levels with daily corticosteroid treatment.
J. MASRAMON A. CARALPS M. LLORACH R. COMPANYS A. BRULLES J. LLOVERAS J. ANDREU.
Unidad de Trasplante Renal, Catedra de Urologia (Facultad de Medicina),
Hospital Clínico y Provincial, Barcelona, Spain.
TOXICITY OF ASPARAGINASES are being used in the is obtained from Escherichia coli (Escherichia asparaginase), the other from the plant pathogen, Erwinia carotovora (Erwinia asparaginase). Although they appear to be equally effective as antileuksemic agents.l some reports suggest that they differ in toxicity.2.3 To clarify this I examined the records of patients with acute leukasmia who have been treated with asparaginase at three London hospitals. The doses used were similar at each hospital, either 200 i.u. per kg. body-weight or 6000 i.u. per sq.m. bodysurface area of reconstituted freeze-dried asparaginase. There were no deaths attributable to enzyme therapy but toxicity interrupted 12 of the 31 (39%) courses of Escherichia
SiR,—Two bacterial asparaginases
treatment
of acute leukaemia:
one
FREQUENCY OF SERIOUS TOXICITY
*
TERRY HAMBLIN. * Serious toxicity asparaginase changed or discontinued. t Course=at least 3 full doses given without toxicity or one =
HYPERLIPIDÆMIA AFTER RENAL
SiR,-Casaretto et awl. reported a significant rise in basal plasma-levels of triglyceride, cholesterol, and immunoreactive insulin after successful renal transplantation in 37 patients receiving an average dose of 17 mg. of prednisolone per day. They found that hyperlipoproteinxmia was a general feature in these patients. In contrast, Beaumont et al. (March 15, p. 599) find normal serum-lipid profiles in 78% of 42 successfully
transplanted patients receiving an average dose of 22 mg. of prednisone every other day. The remaining 22% show hyperlipidaemia, but they are significantly more obese and older. Both the normal subjects and the hyperlipidaemic patients show normal basal immunoreactive insulin levels. Beaumont and his colleagues postulate that this high percentage of patients with normal blood-lipid levels cquld be due to the alternate-day corticosteroid therapy. In 19 an
patients with successful renal transplantation treated with prednisone per day for at least
average dose of 12 mg. of
3 months and with serum-creatinine levels below 20 mg. per 100 ml., we found 16 (84%) with no change in any of the lipid parameters studied (overnight-fasting cholesterol, triglycerides, free fatty acids, free glycerol, lipidogram in cellulose acetate, thin-layer chromatography of neutral lipids, and post-heparin 1. Wintrobe, M. M. Clinical Hæmatology; p. 673. Philadelphia,1974. 2. Casaretto, A., Marchioro, T. L., Goldsmith, R., Bagdade, J. D. Lancet, 1974, i, 481.
or more
full doses if toxicity developed.
TRANSPLANTATION
asparaginase and 9 of the 46 (20%) Erwinia courses (see accompanying table). Allergic reactions were the commonest side-effects, and their occurrence always led to a change or discontinuance of asparaginase. They did not appear until at least ten days after the start of enzyme treatment unless the patient had been treated previously with the same type of enzyme. 11 patients were re-exposed to the same asparaginase;
1 of the 5 Escherichia-treated and 1 of the 6 Erwinia-treated had an anaphylactic reaction; the former required intravenous hydrocortisone, the latter recovered without treatment.
10
patients were given the alternative enzyme because of hypersensitivity-3 sensitive to Erwinia, 7 to Escherichia asparaginase. In all of these, enzyme therapy was continued satisfactorily without cross-toxicity. In 2 cases asparaginases were substituted because of vomiting, but without benefit. One child was given Erwinia asparaginase intravenously twice weekly for fifty-four weeks, except for gaps of one week every 8 weeks when prednisone and arabinosyl cytosine were given. No toxicity occurred during this 1. 2. 3.
Kay, H. E. M., Fairley, G. H., Knapton, P. J. Colloques int. C.N.R.S., 1971, no. 197 : l’asparaginase, p. 295. Ohnuma, T., Holland, J. F., Meyer, P. Cancer, N.Y. 1972, 30, 376. Ohnuma, T., Holland, J. F., Meyer, P. Proc. Am. Ass. Cancer Res. 1972, 13, 117 (abstr. 465).
