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MEGALOBLASTIC ANÆMIA AND FOLATE LEVELS
1103 blood-levels returned to optimal values. In only 1 further patient did we notice unusual resistance to heparin, and it was necessary to increase the 24 hours’ dosage to 60,000 units to obtain a blood-level of about 0-3 units per ml. Neither hxmorrhagic complications nor recurrent thromboembolic episodes occurred in the
perfusion-rate, heparin
controlled patients. This procedure seems to us the safest yet described, if the of infusion can be controlled by qualified day or night nurses, or if a constant-dose infusion apparatus is employed. (We have been using such an apparatus [’ Unita-Braun ’ constant-rate automatic pump], mainly for hasmodialysis, and have found it satisfactory.) With both techniques the heparinblood levels are constant, and only in the one case mentioned above was dose adjustment required because of unusual resistance. In our medical wards continuous intravenous heparinisation is reserved for the acute period in myocardial infarction, and dicoumarin therapy is, as a rule, started after 48-96 hours. In patients with severe thrombophlebitis and/or pulmonary embolism, intravenous heparin may be maintained for several days. Recently we have introduced subcutaneous heparinisation, instead of dicoumarol therapy, using a calcium heparinate of high efficiency in a 12-hourly administration schedule, and have obtained very steady blood-levels (0-1-0-3 units per ml.) with 24-hour doses ranging from 25,000 to 40,000 units. With this substance as well as with continuous venous perfusion, laboratory control in the course of the treatment is a prerequisite for proper dose-adjustment. We decidedly agree with Dr. White, and feel like him that uncontrolled intravenous administration of heparin in as high a 6-hourly dosage as 15,000 units is a great risk to the patient. Laboratoire d’Hémostase, C. A. BOUVIER University Hospital, S. BERTHOUD. Geneva, Switzerland. rate
THE YY SYNDROME SiR,—The account by Dr. Richards and Mr. Stewart (April 30) of a patient with YY chromosome constitution and a varicose ulcers, prompts me to report -two patients, one with XXYY constitutionand one in a 72-year-old man with XXXY/I XXXXY mosaicism, both with severe leg ulceration. A skin biopsy (initiated by Dr. N. Mishra) revealed that both patients had scleroderma, and that this was a causative factor in the
production of the leg ulcers. Llanfrechfa Grange Hospital, Cwmbran, Monmouthshire.
T. S. DAVIES.
GENETIC THERAPEUTIC ABORTION
SIR,-Dr. Gordon writes (March 5) about the " heartening of stopping malformations by genetic therapeutic abortion ". This idea of genetic therapeutic abortion " is incorrect and dangerous. The passage in Professor Scott’s letter (Jan. 22) which Dr. Gordon quotes approvingly differs little from the euthanasia programme practised in Germany "
thought "
"
in Hitler’s time. It was such thoughts as this that discredited German genetics at that time. If deliberate termination of life at birth is euthanasia, an abortion when a chromosomal defect is detected must cause hesitation. What right has a doctor to decide, for instance, about the survival of a child with Down’s syndrome, if he knows how happy these children are in their limited intellectual horizon ? Would he let a child of his own with Down’s syndrome die ? The problem with rubella in pregnancy is similar. An abortion is therapeutic " only if the life of the mother is directly endangered. Abortion on any other indication is intentional killing. If we did not acknowledge this, we should not differ from the Spartans who threw their diseased children into the sea. U. LANGENBECK. "
1.
Laurence, K. M., Ishmael, J., Davies, T. S. Cytogenetics, 1963, 2, 50.
,
MEGALOBLASTIC ANÆMIA AND FOLATE LEVELS SIR,-Dr. Strelling and his colleagues (April 23) have made a useful contribution by giving values of blood-folate in babies and showing the frequency of folic-acid deficiency in premature infants. They note the usefulness of buffy-coat smears for premature infants with progressive anasmia, but occasionally these may yield equivocal results and bone-marrow examination should then be done (a Gimsonneedle is a great help with very small babies). They found megaloblasts in the peripheral blood from the 5th to the llth weeks. Megaloblastic anxmia can occur earlier than this, however, and our youngest case was 21 days old.2 The diagnosis should be suspected in any premature infant who develops progressive ansmia, especially after an infection or other illness. In the 2 years since routine folic-acid supplements have been given to all special-care babies, there has been no further case of megaloblastic anxmia. The routine is to start the folic acid at the end of the lst week along with the other supplements. This is inexpensive (a penny a week), and I suggest that Dr. Strelling and his colleagues have provided sufficient evidence to make this practice more widespread. Special Care Unit, Maternity Hospital, Glossop Terrace,
The
Cardiff.
O. P. GRAY.
PHYTOHÆMAGGLUTININ IN LEUKÆMIA SIR,-We have reportedthat lymphocytes from healthy persons, cultured in a medium containing phytohaemagglutinin (P.H.A.) and 20% of plasma from patients with chronic lymphocytic leukxmia (C.L.L.), developed blast-like cells to the same low proportion as did lymphocytes from c.L.L. patients. We therefore suggested that c.L.L. plasma contains a factor that inhibits the blastic development of lymphocytes from healthy people. In a new series of experiments, however, lymphocytes from healthy persons reacted very actively to P.H.A. stimulation when they were cultured either in autologous or heterologous normal plasma, or in C.L.L. plasma. In our first experiments, by an error of our technician, the addition of C.L.L. plasma to the cultures of lymphocytes from healthy persons had not been preceded by sufficient high-speed centrifugation of the plasma. In this way numerous c.L.L. lymphocytes were added together with plasma, thus changing enormously the proportion in the cultures of P.H.A.-responsive and P.H.A.-non-responsive lymphocytes. This explanation is also in agreement with the observation, made at that time, that there was no inhibition when c.L.L. serum, instead of plasma, was added to the cultures of lymphocytes from healthy persons, since the serum was cell-free. We have now carried out a third series of experiments. C.L.L. blood-lymphocytes were washed with pure culture medium 0, 1, 2, 3, and 4 times, and then cultured with P.H.A. in a medium with 20% of plasma from healthy persons. As control, lymphocytes from the same C.L.L. patients were cultured in the same medium, but with 20% of autologous (leukxmic) plasma. The results showed that: (1) C.L.L. lymphocytes cultured either in autologous (leukaemic) or normal plasma give low proportions of blast-like cells; and (2) previous washing does not modify the usual P.H.A.-hyporesponsiveness of C.L.L. lymphocytes. This suggests that in patients with C.L.L. most lymphocytes are themselves defective in reacting to P.H.A. We apologise for our original mistake, which has certainly brought some confusion into the subject. On the evidence of the above results, and now in full agreement with Openheim et al.,4 we admit that the P.H.A.-hyporesponsiveness of C.L.L. lymphocytes is primarily due to a cellular defect, and not to environmental inhibiting factors. The Blood Research G. ASTALDI Foundation Centre, R. AIRÒ. Tortona Hospital, Italy. 1. 2. 3. 4.
Gimson, J. D. Br. med. J. 1944, i, 748. Gray, O. P., Butler, B. Archs Dis. Childh. 1965, 40, 53. Astaldi, G., Cósta, G., Airò, R. Lancet, 1965, i, 1394. Openheim, J. J., Whang, J., Frei E., III Blood 1965, 26,
121.
perfusion-rate, heparin
controlled patients. This procedure seems to us the safest yet described, if the of infusion can be controlled by qualified day or night nurses, or if a constant-dose infusion apparatus is employed. (We have been using such an apparatus [’ Unita-Braun ’ constant-rate automatic pump], mainly for hasmodialysis, and have found it satisfactory.) With both techniques the heparinblood levels are constant, and only in the one case mentioned above was dose adjustment required because of unusual resistance. In our medical wards continuous intravenous heparinisation is reserved for the acute period in myocardial infarction, and dicoumarin therapy is, as a rule, started after 48-96 hours. In patients with severe thrombophlebitis and/or pulmonary embolism, intravenous heparin may be maintained for several days. Recently we have introduced subcutaneous heparinisation, instead of dicoumarol therapy, using a calcium heparinate of high efficiency in a 12-hourly administration schedule, and have obtained very steady blood-levels (0-1-0-3 units per ml.) with 24-hour doses ranging from 25,000 to 40,000 units. With this substance as well as with continuous venous perfusion, laboratory control in the course of the treatment is a prerequisite for proper dose-adjustment. We decidedly agree with Dr. White, and feel like him that uncontrolled intravenous administration of heparin in as high a 6-hourly dosage as 15,000 units is a great risk to the patient. Laboratoire d’Hémostase, C. A. BOUVIER University Hospital, S. BERTHOUD. Geneva, Switzerland. rate
THE YY SYNDROME SiR,—The account by Dr. Richards and Mr. Stewart (April 30) of a patient with YY chromosome constitution and a varicose ulcers, prompts me to report -two patients, one with XXYY constitutionand one in a 72-year-old man with XXXY/I XXXXY mosaicism, both with severe leg ulceration. A skin biopsy (initiated by Dr. N. Mishra) revealed that both patients had scleroderma, and that this was a causative factor in the
production of the leg ulcers. Llanfrechfa Grange Hospital, Cwmbran, Monmouthshire.
T. S. DAVIES.
GENETIC THERAPEUTIC ABORTION
SIR,-Dr. Gordon writes (March 5) about the " heartening of stopping malformations by genetic therapeutic abortion ". This idea of genetic therapeutic abortion " is incorrect and dangerous. The passage in Professor Scott’s letter (Jan. 22) which Dr. Gordon quotes approvingly differs little from the euthanasia programme practised in Germany "
thought "
"
in Hitler’s time. It was such thoughts as this that discredited German genetics at that time. If deliberate termination of life at birth is euthanasia, an abortion when a chromosomal defect is detected must cause hesitation. What right has a doctor to decide, for instance, about the survival of a child with Down’s syndrome, if he knows how happy these children are in their limited intellectual horizon ? Would he let a child of his own with Down’s syndrome die ? The problem with rubella in pregnancy is similar. An abortion is therapeutic " only if the life of the mother is directly endangered. Abortion on any other indication is intentional killing. If we did not acknowledge this, we should not differ from the Spartans who threw their diseased children into the sea. U. LANGENBECK. "
1.
Laurence, K. M., Ishmael, J., Davies, T. S. Cytogenetics, 1963, 2, 50.
,
MEGALOBLASTIC ANÆMIA AND FOLATE LEVELS SIR,-Dr. Strelling and his colleagues (April 23) have made a useful contribution by giving values of blood-folate in babies and showing the frequency of folic-acid deficiency in premature infants. They note the usefulness of buffy-coat smears for premature infants with progressive anasmia, but occasionally these may yield equivocal results and bone-marrow examination should then be done (a Gimsonneedle is a great help with very small babies). They found megaloblasts in the peripheral blood from the 5th to the llth weeks. Megaloblastic anxmia can occur earlier than this, however, and our youngest case was 21 days old.2 The diagnosis should be suspected in any premature infant who develops progressive ansmia, especially after an infection or other illness. In the 2 years since routine folic-acid supplements have been given to all special-care babies, there has been no further case of megaloblastic anxmia. The routine is to start the folic acid at the end of the lst week along with the other supplements. This is inexpensive (a penny a week), and I suggest that Dr. Strelling and his colleagues have provided sufficient evidence to make this practice more widespread. Special Care Unit, Maternity Hospital, Glossop Terrace,
The
Cardiff.
O. P. GRAY.
PHYTOHÆMAGGLUTININ IN LEUKÆMIA SIR,-We have reportedthat lymphocytes from healthy persons, cultured in a medium containing phytohaemagglutinin (P.H.A.) and 20% of plasma from patients with chronic lymphocytic leukxmia (C.L.L.), developed blast-like cells to the same low proportion as did lymphocytes from c.L.L. patients. We therefore suggested that c.L.L. plasma contains a factor that inhibits the blastic development of lymphocytes from healthy people. In a new series of experiments, however, lymphocytes from healthy persons reacted very actively to P.H.A. stimulation when they were cultured either in autologous or heterologous normal plasma, or in C.L.L. plasma. In our first experiments, by an error of our technician, the addition of C.L.L. plasma to the cultures of lymphocytes from healthy persons had not been preceded by sufficient high-speed centrifugation of the plasma. In this way numerous c.L.L. lymphocytes were added together with plasma, thus changing enormously the proportion in the cultures of P.H.A.-responsive and P.H.A.-non-responsive lymphocytes. This explanation is also in agreement with the observation, made at that time, that there was no inhibition when c.L.L. serum, instead of plasma, was added to the cultures of lymphocytes from healthy persons, since the serum was cell-free. We have now carried out a third series of experiments. C.L.L. blood-lymphocytes were washed with pure culture medium 0, 1, 2, 3, and 4 times, and then cultured with P.H.A. in a medium with 20% of plasma from healthy persons. As control, lymphocytes from the same C.L.L. patients were cultured in the same medium, but with 20% of autologous (leukxmic) plasma. The results showed that: (1) C.L.L. lymphocytes cultured either in autologous (leukaemic) or normal plasma give low proportions of blast-like cells; and (2) previous washing does not modify the usual P.H.A.-hyporesponsiveness of C.L.L. lymphocytes. This suggests that in patients with C.L.L. most lymphocytes are themselves defective in reacting to P.H.A. We apologise for our original mistake, which has certainly brought some confusion into the subject. On the evidence of the above results, and now in full agreement with Openheim et al.,4 we admit that the P.H.A.-hyporesponsiveness of C.L.L. lymphocytes is primarily due to a cellular defect, and not to environmental inhibiting factors. The Blood Research G. ASTALDI Foundation Centre, R. AIRÒ. Tortona Hospital, Italy. 1. 2. 3. 4.
Gimson, J. D. Br. med. J. 1944, i, 748. Gray, O. P., Butler, B. Archs Dis. Childh. 1965, 40, 53. Astaldi, G., Cósta, G., Airò, R. Lancet, 1965, i, 1394. Openheim, J. J., Whang, J., Frei E., III Blood 1965, 26,
121.