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MAGNESIUM AND SUDDEN UNEXPECTED INFANT DEATH
871 From my studies of this methodIcame to the conclu-
Letters
to
the Editor
sion that the widely held belief that the results in the normal are too variable to establish confidence in its trustworthiness can be traced to uncontrolled variables rather than to the method itself. The most important error-inducing factors are drugs and the temperature of the tested tissues. In my study of aspirin,3 I established that this drug in some people, even in apparently normal subjects, can significantly increase the bleeding-time in 2 hours. This effect is not produced with unacetylated salicylic acid. On this basis the aspirin-tolerance test was developed. Even more unexpected were the results of chilling the ear lobe on the bleeding-time. Whereas the bleeding-time is normal when the ear is warm, cooling the lobe with ice often triples the bleeding-time. This seems paradoxical, since cold is generally applied to control bleeding because it contracts blood-vessels. Nevertheless, the surgeon achieves hsemostasis in the operating field by the application of hot saline sponges. One important caution should be emphasised. The aspirin-tolerance test by the Ivy technique can be hazardous in haemophiliacs. For example, Kaneshiro and his associates4 have reported that 7 hxmophiliacs out of a group of 19 required transfusions to control post-test bleeding. Hemostasis Research Laboratory,
subject MAGNESIUM AND SUDDEN UNEXPECTED INFANT DEATH
SIR,-Joan Caddell’s hypothesis (Aug. 5, p. 258) attempts explain all cot deaths " and to produce the cause of the condition. Many of us dealing with these cases suspect that there is no single cause but a variety of causes, and we "
to
hypernatrxmic dehydration, or even simple hypoglycsemia, may be as important as magnesium deficiency. The only common symptomatology of cot death is a completely negative one-i.e., unexpected death-and there are almost certainly a number of pathways to this situation, of which magnesium deficiency related to protein load (as suggested by Dr. Caddell) may be one. Dr. Caddell’s suggestion that cot deaths are due to an suggest that
induced state of histamine release is not unlike that of Coombs et al. in relation to cow’s milk allergy. If indeed death in these children is due to a pulmonary anaphylactic state, we would expect this, as she indicates, to be associated with a degranulation of the mast cells in the lung. We are attempting to quantitate these cells in the lungs of children who have been found unexpectedly dead. In most cases there is no evidence of degranulation; whether the low levels found in some children are significant or not awaits full assessment. What evidence we have at the moment is somewhat against the pulmonary anaphylactic hypothesis as a
Medical College of Wisconsin
(Marquette),
Milwaukee, Wisconsin 53233.
QUICK.
general one.
points out, the assessment of magnesium is not easy. We have attempted to do this using the vitreous humour, where haemolysis is not present and fluid turnover relatively slow-in such tissue fluids postmortem changes are likely to show least. In a survey of twelve recent child deaths the magnesium levels of this fluid varied from 5-3 to 2-2 mg. per 100 ml. The magnesium levels in four cases were completely within the range found in children whose deaths had been expected. Companies producing dried milks have informed us that the magnesium level in milk is variable and also related to the differing magnesium levels in waters in different parts of the country. Perhaps the best way to test Caddell’s hypothesis would be to attempt a correlation of the incidence of unexpected death to areas where there is a deprivation of magnesium in the water-supply and where animal-foodstuff producers feel the need to add magnesium to animal diets. We must not abandon the investigation of many hypotheses in the study of unexpected child deaths. Department of Pathology, P. G. F. SWIFT
MEDICAL INFORMATION SYSTEMS
As Dr. Caddell
state at necropsy
Children’s Hospital, Sheffield.
JOHN L. EMERY.
BLEEDING-TIME
SiR,—The opening question, " What is the bleedingtime ? ", in your editorial (Sept. 16, p. 579) could be answered in part by saying that it is perhaps one of the most important hxmostatic tests ever devised. Morawitz, one of the most astute authorities on hxmostasis, many years ago said that " If the bleeding-time is normal, one may dispense with further investigation ". Unfortunately, this test came into the clinical laboratory before it was properly standardised or critically studied clinically. Duke1 merely reported that the bleeding-time was normal in haemophilia and prolonged in thrombocytopenia. As a result, the test gave rise to discordant results, thereby undermining the confidence in Duke’s procedure. 1.
ARMAND J.
Duke, W. W. J. Am. med.
Ass.
1910, 55, 1185.
SiR,—The masterly article by Professor Knox and his colleagues (Sept. 30, p. 696) contains a statement that would benefit from qualification. Although data processing for clinical records may need different equipment from that for laboratory records, the long-term data-processing requirements of clinical-chemistry departments may not be dissimilar to those of other pathology departments. When computer equipment is purchased the probable development of computer-assisted reporting in microbiology and haematology should influence the decisions. In microbiology a batch-processing mode is adequate, using a remote job-entry terminal with regular access to a central processor large enough to manipulate the specific dictionary and with an adequate backing store for previous results. Even the largest clinical-chemistry department could be served by a small front-end computer also linked to a large computer.6 Cost-effectiveness is emphasised by Professor Knox, and thus it will be hard to justify real-time systems. In microbiology a visual display unit (V.D.U.) for recall of previous results could, with its software, cost at least E20,000 in addition to a batch-mode system, and it would require a doubling of the systems-analysis effort; whereas an interrogation facility once an hour, generating a print-out of previous results, would provide the same information and is perfectly acceptable within the normal work-flow of a microbiology department. Many doctors imagine that a computer system must include v.D.u.s. In Stockholm I have visited a microbiology department with 2 v.D.u.s which was able to process via the computer only 60 out of the 250 daily results. Repeated informal contact between medical and computer personnel allows wild ideas and misconceptions to be rejected quickly. For this reason, and for many other reasons, strong support should be maintained for the conclusion of Professor Knox and his Quick, A. J. Am. J. clin. Path. 1967, 47, 459. Quick, A. J. Am. J. med. Sci. 1966, 252, 265. Kaneshiro, M. M., Mielke, C. H., Kasper, C. K., Rapaport, S. I. New Engl. J. Med. 1969, 281, 1039. 5. Flynn, F. V. J. clin. Path. 1969, 22, suppl. p. 62.
2.
3. 4.
Letters
to
the Editor
sion that the widely held belief that the results in the normal are too variable to establish confidence in its trustworthiness can be traced to uncontrolled variables rather than to the method itself. The most important error-inducing factors are drugs and the temperature of the tested tissues. In my study of aspirin,3 I established that this drug in some people, even in apparently normal subjects, can significantly increase the bleeding-time in 2 hours. This effect is not produced with unacetylated salicylic acid. On this basis the aspirin-tolerance test was developed. Even more unexpected were the results of chilling the ear lobe on the bleeding-time. Whereas the bleeding-time is normal when the ear is warm, cooling the lobe with ice often triples the bleeding-time. This seems paradoxical, since cold is generally applied to control bleeding because it contracts blood-vessels. Nevertheless, the surgeon achieves hsemostasis in the operating field by the application of hot saline sponges. One important caution should be emphasised. The aspirin-tolerance test by the Ivy technique can be hazardous in haemophiliacs. For example, Kaneshiro and his associates4 have reported that 7 hxmophiliacs out of a group of 19 required transfusions to control post-test bleeding. Hemostasis Research Laboratory,
subject MAGNESIUM AND SUDDEN UNEXPECTED INFANT DEATH
SIR,-Joan Caddell’s hypothesis (Aug. 5, p. 258) attempts explain all cot deaths " and to produce the cause of the condition. Many of us dealing with these cases suspect that there is no single cause but a variety of causes, and we "
to
hypernatrxmic dehydration, or even simple hypoglycsemia, may be as important as magnesium deficiency. The only common symptomatology of cot death is a completely negative one-i.e., unexpected death-and there are almost certainly a number of pathways to this situation, of which magnesium deficiency related to protein load (as suggested by Dr. Caddell) may be one. Dr. Caddell’s suggestion that cot deaths are due to an suggest that
induced state of histamine release is not unlike that of Coombs et al. in relation to cow’s milk allergy. If indeed death in these children is due to a pulmonary anaphylactic state, we would expect this, as she indicates, to be associated with a degranulation of the mast cells in the lung. We are attempting to quantitate these cells in the lungs of children who have been found unexpectedly dead. In most cases there is no evidence of degranulation; whether the low levels found in some children are significant or not awaits full assessment. What evidence we have at the moment is somewhat against the pulmonary anaphylactic hypothesis as a
Medical College of Wisconsin
(Marquette),
Milwaukee, Wisconsin 53233.
QUICK.
general one.
points out, the assessment of magnesium is not easy. We have attempted to do this using the vitreous humour, where haemolysis is not present and fluid turnover relatively slow-in such tissue fluids postmortem changes are likely to show least. In a survey of twelve recent child deaths the magnesium levels of this fluid varied from 5-3 to 2-2 mg. per 100 ml. The magnesium levels in four cases were completely within the range found in children whose deaths had been expected. Companies producing dried milks have informed us that the magnesium level in milk is variable and also related to the differing magnesium levels in waters in different parts of the country. Perhaps the best way to test Caddell’s hypothesis would be to attempt a correlation of the incidence of unexpected death to areas where there is a deprivation of magnesium in the water-supply and where animal-foodstuff producers feel the need to add magnesium to animal diets. We must not abandon the investigation of many hypotheses in the study of unexpected child deaths. Department of Pathology, P. G. F. SWIFT
MEDICAL INFORMATION SYSTEMS
As Dr. Caddell
state at necropsy
Children’s Hospital, Sheffield.
JOHN L. EMERY.
BLEEDING-TIME
SiR,—The opening question, " What is the bleedingtime ? ", in your editorial (Sept. 16, p. 579) could be answered in part by saying that it is perhaps one of the most important hxmostatic tests ever devised. Morawitz, one of the most astute authorities on hxmostasis, many years ago said that " If the bleeding-time is normal, one may dispense with further investigation ". Unfortunately, this test came into the clinical laboratory before it was properly standardised or critically studied clinically. Duke1 merely reported that the bleeding-time was normal in haemophilia and prolonged in thrombocytopenia. As a result, the test gave rise to discordant results, thereby undermining the confidence in Duke’s procedure. 1.
ARMAND J.
Duke, W. W. J. Am. med.
Ass.
1910, 55, 1185.
SiR,—The masterly article by Professor Knox and his colleagues (Sept. 30, p. 696) contains a statement that would benefit from qualification. Although data processing for clinical records may need different equipment from that for laboratory records, the long-term data-processing requirements of clinical-chemistry departments may not be dissimilar to those of other pathology departments. When computer equipment is purchased the probable development of computer-assisted reporting in microbiology and haematology should influence the decisions. In microbiology a batch-processing mode is adequate, using a remote job-entry terminal with regular access to a central processor large enough to manipulate the specific dictionary and with an adequate backing store for previous results. Even the largest clinical-chemistry department could be served by a small front-end computer also linked to a large computer.6 Cost-effectiveness is emphasised by Professor Knox, and thus it will be hard to justify real-time systems. In microbiology a visual display unit (V.D.U.) for recall of previous results could, with its software, cost at least E20,000 in addition to a batch-mode system, and it would require a doubling of the systems-analysis effort; whereas an interrogation facility once an hour, generating a print-out of previous results, would provide the same information and is perfectly acceptable within the normal work-flow of a microbiology department. Many doctors imagine that a computer system must include v.D.u.s. In Stockholm I have visited a microbiology department with 2 v.D.u.s which was able to process via the computer only 60 out of the 250 daily results. Repeated informal contact between medical and computer personnel allows wild ideas and misconceptions to be rejected quickly. For this reason, and for many other reasons, strong support should be maintained for the conclusion of Professor Knox and his Quick, A. J. Am. J. clin. Path. 1967, 47, 459. Quick, A. J. Am. J. med. Sci. 1966, 252, 265. Kaneshiro, M. M., Mielke, C. H., Kasper, C. K., Rapaport, S. I. New Engl. J. Med. 1969, 281, 1039. 5. Flynn, F. V. J. clin. Path. 1969, 22, suppl. p. 62.
2.
3. 4.