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PENICILLAMINE AND DIMERCAPROL
963 the present anti-larval and hygienic measures widely applied, aided by the much of drug prophylaxis and treatment, improved methods has been created where the malarial that a state of affairs I anxmia, with which used to be so familiar, exists no more. I remember in particular a group of Arabs from the Hedjaz in hospital in Cairo in 1916. They were one and all suffering from such a severe form of anaemia of the pernicious type that they became the subject of hxmatological studies by the contemporary blood experts. In some few the spleen was palpable. However, after careful scrutiny of their blood by the thick-film method, scanty crescents of the subtertian parasite were found in all and they recovered after
As
regards malaria, have been
so
long-continued quinine therapy. PHILIP MANSON-BAHR.
London, W. 1.
ABSENCE FROM WORK ON A MEDICAL CERTIFICATE to write SIR,-I support the statement of Dr. Gough He asks (April 19). employers to accept a written statement from employees concerning their sick absences rather than demanding a doctor’s certificate. This company pays all clerical and factory employees for absence due to sickness. Twelve months ago we dispensed with doctors’ certificates for any absence of less than four days. On return to work after illness employees now report to the nurse in the works surgery and sign a declaration that their absence was due to genuine sickness. This scheme, which is greatly appreciated by the employees as well as by the local doctors, has in no way been abused and the absence due to sickness has not
increased. Wm. R Warner & Co. Ltd., Eastleigh, Hants.
H. WOODHOUSE Personnel Manager.
PENICILLAMINE AND DIMERCAPROL SIR,-Ihave read with interest of Dr. Aposhian’s studies (April 19) on the relative efficacy of BAL and penicillamine in protecting rats against mercuric-chloride poisoning. He criticises my work on the relative activity of these two compounds in mobilising copper from patients with Wilson’s disease1 on the grounds that the two drugs were not
given in equimolar amounts or by the
same route.
May I suggest to Dr. Aposhian, first that penicillamine and BAL should not be compared on a molar basis but in terms of available sulphydryl groups-i.e., one molecule of BAL (M.w. 124) to two molecules of penicillamine hydrochloride (M.w. 205 x 2), approximately 1 unit of BAL to 3-3 of penicillamine HCI. On this basis he will find, if he reads my paper again and carefully, that cases 3, 4, and 6 were given approximately comparable doses of these two compounds. In each case the response, in terms of increased copper excretion in the urine, showed that the penicillamine was a very much more powerful cupruretic agent than BAL. Second, in clinical practice, as opposed to animal experiment, it is ridiculous to limit the usefulness of a new treatment by scaling it down to the limitations of the old. To compare the activity of BAL and penicillamine in man why reduce the dose of the latter and give it parenterally, why not raise the dose of BAL so that it is comparable to the maximum tolerated dose of penicillamine (around 4 g.) and give both by mouth ? The procedure would be just as logical.
Finally I suggest that Dr. Aposhian has tumbled into pitfall of trying to argue direct from the experi-
the old
1.
Walshe, J. M. Amer. J. Med. 1956, 21, 487.
mental animal to man. From his results with mercuricchloride poisoning in rats he is attempting to draw valid conclusions about copper intoxication in man, a hazardous procedure. From the patient’s point of view the usefulness of a drug can be decided only in terms of the response obtained to the maximum tolerated dose. Department of Experimental Medicine, Tennis Court Road, Cambridge.
J. M. WALSHE.
PLASTIC BAGS FOR STORING AND TRANSFUSING BLOOD
SIR,-The article by Dr. Dudley and his colleagues those of us in the United States who have been concerned with the development of improved blood-transfusion equipment. The studies reported undoubtedly represent a sincere effort to compare plastic and glass containers, and at first glance the conclusion that red cells are no better preserved in plastic than in glass seems to be supported by the experimental data. I feel it my duty, however, to point out that the experiments reported did not truly compare the preservation, during refrigerated storage, of red cells collected in plastic bags and glass bottles.
(Feb. 8) is of great interest
to
The solution used in the bottles
(A.C.D.
formula
A, U.S.P.)
transferred from the plastic bags to the bottles, presumably shortly before collection of blood. This solution was auto-
was
claved in the plastic bags and had been exposed to the plastic up to the time of use. It was not autoclaved or stored in the bottles in which the blood was collected. Thus the survival experiments of the bloods collected in the bottles cannot reflect deleterious effects on red cells of changes taking place in’the solution on long exposure to glass. There is increasing evidence that an interaction between contained solutions and glass surfaces does take place under such conditions. On Oct. 12, 1957, a conference on the Deterioration of Parenteral Solutions was called by the National Research Council in Washington, D.C. At that conference a report on particulate matter in intravenous fluids was presented from the Walter Reed Army Institute of Research. Using an instrument primarily designed for red-cell counting, it was found that solutions of saline, dextrose, and dextrose plus saline, dextran, and A.C.D., which had been stored for varying periods of time, registered particle-counts up to a million per 100 ml. These particles were found to be silica. Precipitation of fibrin from whole blood by means of finely divided glass is often used. Such a reaction may well account for the frequent finding of " sludging " of red cells in blood collected in bottles. This is destructive to red cells of stored blood, as shown by the elevation of the haemoglobin content of plasma. In contrast, the A.c.D. solutions processed in plastic bags had particle counts of less than 10,000 per 100 ml. Widespread experience has shown haemoglobin levels of plasma of blood collected in plastic bags to be consistently lower than that of blood collected in glass.
It may therefore be truthfully said that the experiments reported merely demonstrate the excellent stability of A.C.D. solution autoclaved and stored in plastic containers. No claim has
ever
been made that
A.c.D.
blood collected in
plastic bags could be used routinely beyond the 21-day limit prescribed by the Minimum Requirements for Human Blood (Citrated)1 of the National Institutes of Health. In the article by Walter2 referred to by Dudley et al. in eleven experiments the post-infusion survival of the red cells of blood stored 21 days at 4OC ranged from 66 to 93%, averaging 84%, certainly a very safe and satisfactory level, even for multiple transfusions. 1. Federal Register. Department of Health, Education and Welfare, Public Health Service (42 CFR, part 73, 1) Biologic Products, Whole Blood (Human) p. 6840. 2. Walter, C. W., Button, L. N., Ritts, R. E., Jr. Surg. Gynec. Obstet. 1957, 105, 315.
As
regards malaria, have been
so
long-continued quinine therapy. PHILIP MANSON-BAHR.
London, W. 1.
ABSENCE FROM WORK ON A MEDICAL CERTIFICATE to write SIR,-I support the statement of Dr. Gough He asks (April 19). employers to accept a written statement from employees concerning their sick absences rather than demanding a doctor’s certificate. This company pays all clerical and factory employees for absence due to sickness. Twelve months ago we dispensed with doctors’ certificates for any absence of less than four days. On return to work after illness employees now report to the nurse in the works surgery and sign a declaration that their absence was due to genuine sickness. This scheme, which is greatly appreciated by the employees as well as by the local doctors, has in no way been abused and the absence due to sickness has not
increased. Wm. R Warner & Co. Ltd., Eastleigh, Hants.
H. WOODHOUSE Personnel Manager.
PENICILLAMINE AND DIMERCAPROL SIR,-Ihave read with interest of Dr. Aposhian’s studies (April 19) on the relative efficacy of BAL and penicillamine in protecting rats against mercuric-chloride poisoning. He criticises my work on the relative activity of these two compounds in mobilising copper from patients with Wilson’s disease1 on the grounds that the two drugs were not
given in equimolar amounts or by the
same route.
May I suggest to Dr. Aposhian, first that penicillamine and BAL should not be compared on a molar basis but in terms of available sulphydryl groups-i.e., one molecule of BAL (M.w. 124) to two molecules of penicillamine hydrochloride (M.w. 205 x 2), approximately 1 unit of BAL to 3-3 of penicillamine HCI. On this basis he will find, if he reads my paper again and carefully, that cases 3, 4, and 6 were given approximately comparable doses of these two compounds. In each case the response, in terms of increased copper excretion in the urine, showed that the penicillamine was a very much more powerful cupruretic agent than BAL. Second, in clinical practice, as opposed to animal experiment, it is ridiculous to limit the usefulness of a new treatment by scaling it down to the limitations of the old. To compare the activity of BAL and penicillamine in man why reduce the dose of the latter and give it parenterally, why not raise the dose of BAL so that it is comparable to the maximum tolerated dose of penicillamine (around 4 g.) and give both by mouth ? The procedure would be just as logical.
Finally I suggest that Dr. Aposhian has tumbled into pitfall of trying to argue direct from the experi-
the old
1.
Walshe, J. M. Amer. J. Med. 1956, 21, 487.
mental animal to man. From his results with mercuricchloride poisoning in rats he is attempting to draw valid conclusions about copper intoxication in man, a hazardous procedure. From the patient’s point of view the usefulness of a drug can be decided only in terms of the response obtained to the maximum tolerated dose. Department of Experimental Medicine, Tennis Court Road, Cambridge.
J. M. WALSHE.
PLASTIC BAGS FOR STORING AND TRANSFUSING BLOOD
SIR,-The article by Dr. Dudley and his colleagues those of us in the United States who have been concerned with the development of improved blood-transfusion equipment. The studies reported undoubtedly represent a sincere effort to compare plastic and glass containers, and at first glance the conclusion that red cells are no better preserved in plastic than in glass seems to be supported by the experimental data. I feel it my duty, however, to point out that the experiments reported did not truly compare the preservation, during refrigerated storage, of red cells collected in plastic bags and glass bottles.
(Feb. 8) is of great interest
to
The solution used in the bottles
(A.C.D.
formula
A, U.S.P.)
transferred from the plastic bags to the bottles, presumably shortly before collection of blood. This solution was auto-
was
claved in the plastic bags and had been exposed to the plastic up to the time of use. It was not autoclaved or stored in the bottles in which the blood was collected. Thus the survival experiments of the bloods collected in the bottles cannot reflect deleterious effects on red cells of changes taking place in’the solution on long exposure to glass. There is increasing evidence that an interaction between contained solutions and glass surfaces does take place under such conditions. On Oct. 12, 1957, a conference on the Deterioration of Parenteral Solutions was called by the National Research Council in Washington, D.C. At that conference a report on particulate matter in intravenous fluids was presented from the Walter Reed Army Institute of Research. Using an instrument primarily designed for red-cell counting, it was found that solutions of saline, dextrose, and dextrose plus saline, dextran, and A.C.D., which had been stored for varying periods of time, registered particle-counts up to a million per 100 ml. These particles were found to be silica. Precipitation of fibrin from whole blood by means of finely divided glass is often used. Such a reaction may well account for the frequent finding of " sludging " of red cells in blood collected in bottles. This is destructive to red cells of stored blood, as shown by the elevation of the haemoglobin content of plasma. In contrast, the A.c.D. solutions processed in plastic bags had particle counts of less than 10,000 per 100 ml. Widespread experience has shown haemoglobin levels of plasma of blood collected in plastic bags to be consistently lower than that of blood collected in glass.
It may therefore be truthfully said that the experiments reported merely demonstrate the excellent stability of A.C.D. solution autoclaved and stored in plastic containers. No claim has
ever
been made that
A.c.D.
blood collected in
plastic bags could be used routinely beyond the 21-day limit prescribed by the Minimum Requirements for Human Blood (Citrated)1 of the National Institutes of Health. In the article by Walter2 referred to by Dudley et al. in eleven experiments the post-infusion survival of the red cells of blood stored 21 days at 4OC ranged from 66 to 93%, averaging 84%, certainly a very safe and satisfactory level, even for multiple transfusions. 1. Federal Register. Department of Health, Education and Welfare, Public Health Service (42 CFR, part 73, 1) Biologic Products, Whole Blood (Human) p. 6840. 2. Walter, C. W., Button, L. N., Ritts, R. E., Jr. Surg. Gynec. Obstet. 1957, 105, 315.