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PARTICLE COUNTS IN AMINOACID SOLUTIONS
540
Quinine is rapidly absorbed after oral administration and serum concentrations reach a peak in 1-3 h; quinine’s half-life is 10 h.’ An oral dose of 500 mg quinine leads to serum concentrations of about 4 mg/1.2 Although a daily oral dose of 25 mg quinine is well below the therapeutic dosage, it may have had a suppressive effect on parasitaemia. In the old days tonic water was used in the tropics to avoid malaria. Our patient’s mild clinical picture, the prolonged negative blood smear, and the low number of parasites in the blood may be explained by the bitter lemon she had drunk. Tetracycline, sulphonamides, and even clindamycin may render blood smears negative in patients with malaria, thus delaying diagnosis.3 A patient suspected of having malaria but who has negative blood smears should be asked not just about the use of these drugs but also about consumption of drinks or medications containing quinine or its derivatives. D. OVERBOSCH
Department of Infectious Diseases, University Hospital,
J. W. M. VAN
2333 AA
H. MATTIE
Leiden, Netherlands
Laboratory of Parasitology, State University of Leiden
H. J.
DER MEER
VAN DER
KAAIJ
We do
not
yet know the
nature
of these
particles and there is no
harmful, although when Garvan and Gunner3 examined the lungs of rabbits who had received intravenous fluids,
proof that they
are
they found multiple granulomas which contained cellulose. In the absence of such knowledge, we feel that clearer guidelines are required. The phrase "practically free from particles" lacks precision, so that, despite a large difference in particle counts, both solutions could be considered to meet B.P. standards. The U.S. Pharmacopeia44 has precisely defined limits of acceptable contamination by particles, and we ask those involved with parenteral nutrition to consider whether precise limits of contamination by visible particles as well as compliance with the limit test should be applied to all large volume intravenous infusions in the U.K. Further studies may tell us whether particulate contamination is important. P. J. FABRICIUS ANNE COPE R. PURKISS A. K. DAVIS General Hospital, P. W. DYKES Birmingham B4 6NH NOVEL IRON METABOLISM ABNORMALITY
PARTICLE COUNTS IN AMINOACID SOLUTIONS
SIR,-The British Pharmacopoeia requires all solutions for or intravenous infusion to be "clear and practically free from particles",1 and most large-volume infusions for which there are B.P. monographs must comply with the limit test for particulate matter. Aminoacid solutions, which may be used for long periods of time in intravenous feeding, require special vigilance, although, having no B.P. monograph, they need not comply with the limit
injection
test.
We have viewed under polarised light 120 bottles from a single batch of each of two brands of aminoacid solution. Both solutions are widely available, their manufacturers share about 65% of the U.K. market for intravenous aminoacids, and both preparations are marketed by companies with a good record of quality control and concern for the safety of their products. The table shows the number of visible particles in the two solutions. 80% of the particles in solution A were seen within 30 s, the remainder taking up to 2 min to see. No bottle was free of particles and 40% of the bottles had more than 10 particles per bottle. No bottle of solution B was seen to contain more than one particle and these were all seen within 60 s. Subsequently, Coulter counting was done under the conditions of the limit test on 8 bottles of each solution selected randomly. The B.P. limits for 2 m and 5 /-1m particles are 1000/ml and 100/ml, respectively, for those fluids to which the test applies. Solution A contained a mean of 2096/ml (SD 933) and 120/ml (SD 58) respectively, whereas in solution B there were 557/ml (SD 207) and 48/ml (SD 34). 1. Peters W. Chemotherapy of malaria. In: Kreier JP, ed. Malaria: Vol. I. New York: Academic Press, 1980: 145. 2. Hall AP, Czerwinsk AW, Madonia EC, Evenson KL. Human plasma and urine quinine levels, following tablets, capsules and intravenous infusion. Clin Pharmacol Ther 1973; 14: 580. 3. Schreiber W. An Malaria denken! Fortschr Med 1981; 99: 81. 1. British 2. British
pharmacopoeia. London H.M. Stationery Office, 1980: 578. pharmacopoeia. London H.M. Stationery Office, 1980: A120. NUMBER OF PARTICLES IDENTIFIED IN EACH BOTTLE
SiR,—Dr Hyman has described an apparently novel abnormality in iron metabolism (Jan. 15, p. 91).His patient had a severe anaemia associated with a raised serum iron concentration, transferrin saturation, and serum ferritin concentration. The iron kinetic data are less clear-cut because the methods used do not give a specific transferrin label, do not distinguish between erythroid and nonerythroid iron turnover, do not allow a quantitation of ineffective erythropoiesis, and are highly dependent upon the serum iron concentration.’ What the iron kinetics studies do show is that iron flow through the plasma was well above normal. In our experience it would seem likely that this was accounted for by erythroid iron turnover. The inference must be that the marrow was quite capable of taking up iron. The conclusion that there was an impairment of iron transport in this woman cannot be drawn from this evidence. An alternative explanation is that the anaemia was caused not by failure of iron supply but by massive intramedullary ineffective erythropoiesis. This would have led to the raised serum iron and the low percentage of 59Fe in mature red cells. The rapid turnover of 59Fe through the marrow would also have resulted in a very short 59Fe residence time which would have registered as an apparent low marrow iron uptake by surface counting. The patient’s response to steroid therapy is similar to that which we saw in a woman who also had a refractory anaemia with ineffective erythropoiesis whose remission was the result of an attenuation of that ineffectiveness.2 Department of Haematology, University Hospital of Wales,
I. CAVILL
Cardiff CF4 4XN
PATHOGENESIS OF NEONATAL NECROTISING ENTEROCOLITIS
hypothesisof ours on this subject mentioned work we doing on an animal model for necrotising enterocolitis in neonatal germ-free rats. Since publication we have run into difficulty with the experimental work and our model no longer works. Despite great efforts we have been unable to understand the reasons for the change. We thought that others, who might be working on similar lines, should know of the failure of our model. The hypothesis itself may still explain cases of necrotising enterocolitis. SIR,-A
were
Queensland Institute of Medical Research, Herston, Brisbane,
G. W. LAWRENCE
Australia 4006
J. BATES
JM, Gunner BW. Med J Aust 1964; ii: 1-6. 4. United States pharmacopeia XX. Rockville, Maryland: U.S. Pharmacopeial Convention, 1980: 863. 1 Cavill I, Ricketts C, Jacobs A. Radioiron and erythropoiesis. Clins Haematol 1977, 6: 583-99. 2 Napier JAF, Cavill I, Dunn CDR, et al Oxymethalone in the treatment of aplastic anaemia. Br Med J1976, ii: 1426. 3. Lawrence G, Bates J, Gaul A. Pathogenesis of neonatal necrotising enterocolitis. Lancet 1982; i: 137-39.
3. Garvan
Quinine is rapidly absorbed after oral administration and serum concentrations reach a peak in 1-3 h; quinine’s half-life is 10 h.’ An oral dose of 500 mg quinine leads to serum concentrations of about 4 mg/1.2 Although a daily oral dose of 25 mg quinine is well below the therapeutic dosage, it may have had a suppressive effect on parasitaemia. In the old days tonic water was used in the tropics to avoid malaria. Our patient’s mild clinical picture, the prolonged negative blood smear, and the low number of parasites in the blood may be explained by the bitter lemon she had drunk. Tetracycline, sulphonamides, and even clindamycin may render blood smears negative in patients with malaria, thus delaying diagnosis.3 A patient suspected of having malaria but who has negative blood smears should be asked not just about the use of these drugs but also about consumption of drinks or medications containing quinine or its derivatives. D. OVERBOSCH
Department of Infectious Diseases, University Hospital,
J. W. M. VAN
2333 AA
H. MATTIE
Leiden, Netherlands
Laboratory of Parasitology, State University of Leiden
H. J.
DER MEER
VAN DER
KAAIJ
We do
not
yet know the
nature
of these
particles and there is no
harmful, although when Garvan and Gunner3 examined the lungs of rabbits who had received intravenous fluids,
proof that they
are
they found multiple granulomas which contained cellulose. In the absence of such knowledge, we feel that clearer guidelines are required. The phrase "practically free from particles" lacks precision, so that, despite a large difference in particle counts, both solutions could be considered to meet B.P. standards. The U.S. Pharmacopeia44 has precisely defined limits of acceptable contamination by particles, and we ask those involved with parenteral nutrition to consider whether precise limits of contamination by visible particles as well as compliance with the limit test should be applied to all large volume intravenous infusions in the U.K. Further studies may tell us whether particulate contamination is important. P. J. FABRICIUS ANNE COPE R. PURKISS A. K. DAVIS General Hospital, P. W. DYKES Birmingham B4 6NH NOVEL IRON METABOLISM ABNORMALITY
PARTICLE COUNTS IN AMINOACID SOLUTIONS
SIR,-The British Pharmacopoeia requires all solutions for or intravenous infusion to be "clear and practically free from particles",1 and most large-volume infusions for which there are B.P. monographs must comply with the limit test for particulate matter. Aminoacid solutions, which may be used for long periods of time in intravenous feeding, require special vigilance, although, having no B.P. monograph, they need not comply with the limit
injection
test.
We have viewed under polarised light 120 bottles from a single batch of each of two brands of aminoacid solution. Both solutions are widely available, their manufacturers share about 65% of the U.K. market for intravenous aminoacids, and both preparations are marketed by companies with a good record of quality control and concern for the safety of their products. The table shows the number of visible particles in the two solutions. 80% of the particles in solution A were seen within 30 s, the remainder taking up to 2 min to see. No bottle was free of particles and 40% of the bottles had more than 10 particles per bottle. No bottle of solution B was seen to contain more than one particle and these were all seen within 60 s. Subsequently, Coulter counting was done under the conditions of the limit test on 8 bottles of each solution selected randomly. The B.P. limits for 2 m and 5 /-1m particles are 1000/ml and 100/ml, respectively, for those fluids to which the test applies. Solution A contained a mean of 2096/ml (SD 933) and 120/ml (SD 58) respectively, whereas in solution B there were 557/ml (SD 207) and 48/ml (SD 34). 1. Peters W. Chemotherapy of malaria. In: Kreier JP, ed. Malaria: Vol. I. New York: Academic Press, 1980: 145. 2. Hall AP, Czerwinsk AW, Madonia EC, Evenson KL. Human plasma and urine quinine levels, following tablets, capsules and intravenous infusion. Clin Pharmacol Ther 1973; 14: 580. 3. Schreiber W. An Malaria denken! Fortschr Med 1981; 99: 81. 1. British 2. British
pharmacopoeia. London H.M. Stationery Office, 1980: 578. pharmacopoeia. London H.M. Stationery Office, 1980: A120. NUMBER OF PARTICLES IDENTIFIED IN EACH BOTTLE
SiR,—Dr Hyman has described an apparently novel abnormality in iron metabolism (Jan. 15, p. 91).His patient had a severe anaemia associated with a raised serum iron concentration, transferrin saturation, and serum ferritin concentration. The iron kinetic data are less clear-cut because the methods used do not give a specific transferrin label, do not distinguish between erythroid and nonerythroid iron turnover, do not allow a quantitation of ineffective erythropoiesis, and are highly dependent upon the serum iron concentration.’ What the iron kinetics studies do show is that iron flow through the plasma was well above normal. In our experience it would seem likely that this was accounted for by erythroid iron turnover. The inference must be that the marrow was quite capable of taking up iron. The conclusion that there was an impairment of iron transport in this woman cannot be drawn from this evidence. An alternative explanation is that the anaemia was caused not by failure of iron supply but by massive intramedullary ineffective erythropoiesis. This would have led to the raised serum iron and the low percentage of 59Fe in mature red cells. The rapid turnover of 59Fe through the marrow would also have resulted in a very short 59Fe residence time which would have registered as an apparent low marrow iron uptake by surface counting. The patient’s response to steroid therapy is similar to that which we saw in a woman who also had a refractory anaemia with ineffective erythropoiesis whose remission was the result of an attenuation of that ineffectiveness.2 Department of Haematology, University Hospital of Wales,
I. CAVILL
Cardiff CF4 4XN
PATHOGENESIS OF NEONATAL NECROTISING ENTEROCOLITIS
hypothesisof ours on this subject mentioned work we doing on an animal model for necrotising enterocolitis in neonatal germ-free rats. Since publication we have run into difficulty with the experimental work and our model no longer works. Despite great efforts we have been unable to understand the reasons for the change. We thought that others, who might be working on similar lines, should know of the failure of our model. The hypothesis itself may still explain cases of necrotising enterocolitis. SIR,-A
were
Queensland Institute of Medical Research, Herston, Brisbane,
G. W. LAWRENCE
Australia 4006
J. BATES
JM, Gunner BW. Med J Aust 1964; ii: 1-6. 4. United States pharmacopeia XX. Rockville, Maryland: U.S. Pharmacopeial Convention, 1980: 863. 1 Cavill I, Ricketts C, Jacobs A. Radioiron and erythropoiesis. Clins Haematol 1977, 6: 583-99. 2 Napier JAF, Cavill I, Dunn CDR, et al Oxymethalone in the treatment of aplastic anaemia. Br Med J1976, ii: 1426. 3. Lawrence G, Bates J, Gaul A. Pathogenesis of neonatal necrotising enterocolitis. Lancet 1982; i: 137-39.
3. Garvan