472 TOLUENE DIISOCYANATE
SIR,- The four I.e.L scientists attempted to highlight agreements and differences concerning the toxicity of toluene diisocyanate (T.D.I.) from studies conducted by three groups.2-4 It is easy to understand I.C.I.’s interest in T.D.I. Chemical companies want their products to be safe. It appeared to us that an effort was made to minimise important health effects Of T.D.I. in an unbalanced critique. The major conclusion of our paper3was not that there is a significant association between acute and chronic decrement in F.E.V., (as Adams et al. stated), but that there is a significant relationship between level of chronic exposure to T.D.I. and loss of F.E.V’l over a two-year period of time which is dose-related. Further, this relationship cannot be explained by lung size as they imply. In our view it is not reasonable for any group (no matter what their lung size) to lose over 100 ml Of F.E.V., per year as a result of occupational exposure. All working populations, whether or not they are exposed to respiratory irritants, contain persons with respiratory symptoms. To remove these persons artificially "improves" the health of the remaining cohort. It is not surprising then to see little effect Of T.D.I. in the Adams study.2 Another important factor is the nature of the exposure. Our studies have all involved the production of polyurethane products on a continuous or semi-continuous basis. Exposures to T.D.I. are rather consistent with small excursions. Producing T.D.I., on the other hand, results in exposures which vary from very low to quite high depending on the situation (leaks, spills, etc.). It is therefore not surprising to find different results on that basis. We used Monday morning for baseline measurements of pulmonary function to allow for recovery from acute effects. We have repeatedly observed acute symptom-free falls in F.E.V., over a workshift,5 which are clearly different from the "sensitisation" referred to in the I.C.I. letter. In reviewing the Tulane study, the most surprising finding in our view is the increase in pulmonary function over a 3 2 year period. This would appear to be physiologically impossible and suggests difficulties in making accurate measurements rather than lack of T.D.I. effect. It continues to be our view that T.D.I. is a highly toxic chemical which has serious respiratory effects including accelerated loss of lung function at levels of 0.003 p.p.m. and above. It is also our view that workers should be protected from these effects. Health Program, Harvard School of Public Health, Boston, Massachusetts 02115, U.S.A.
Occupational
JOHN M. PETERS DAVID H. WEGMAN
ELEVATED METABOLIC RATES IN OBESITY
SIR,-Dr Rucker (July 8, p. 106) finds that the resting metabolic rates (R.M.R.) of our obese patients conform with animal nutritionists’ long-standing recognition of the relation between basal metabolic rates and an index of metabolic size. This was precisely our point but instead of expressing the data in the standard way we emphasised the rise in R.M.R. in the obese state, noting that this increase had been neglected by human nutritionists when they considered energy balance in obesity. We maintain that a major conceptual error can be made by not comparing the R.M.R. of an obese individual with that of a "normal" individual of the same height. These conceptual disagreements reflect two of the different approaches to metabolism. Animal nutritionists have related R.M.R. to a unit Adams, W. G. F., Carney, I. F., Chamberlain, V. D., Paddle, G. M. Lancet, 1978, i, 1308. 2. Adams, W. G. F., Br. J. ind. Med. 1975, 32, 72. 3. Wegman, D. H., Peters, J. M., Pagnotto, L. J. ibid. 1977, 34, 196. 4. Butcher, B. T. and others. Am. Rev. resp. Dis. 1977, 116, 411. 5. Peters, J. M., Murphy, R. L. H., Pagnotto, L. Van Ganse, W. F. Archs environ. Hth, 1968, 16, 642. 1.
of metabolic size or to surface area when presenting information on small and large adult animals of equivalent body composition. Since metabolic data are always expressed in this way it is natural to expect that an obese person will conform with this general rule. In practice we do find that an obese woman 1.5m tall, weighing 65 kg instead of 48 kg, has an R.M.R. approximately equivalent to that of a subject of 59 kg with a normal body composition. Yet obesity is considered traditionally to involve only an increase in total triglyceride and this should not in itself increase metabolic activity. In man obesity does lead to an increase in B.M.R., whereas in the genetically obese ob/ob mouse this is not so. The mouse has a low fat-free mass whereas our patients had a marked increase in fat-free mass and a corresponding rise in R.M.R. The observed decrease in R.M.R. on slimming exceeds that expected from the relation between R.M.R. and metabolic size because there are changes in the efficiency of energy use in addition to the metabolic consequences of a reduction in fatfree mass. An alteration in efficiency on semistarvation was recognised in the classical Minnesota experiments--changes occurred in both metabolic efficiency and in lean body mass.’ M.R.C. Dunn Nutrition Centre, Old Addenbrookes Hospital,
Cambridge CB2 1QE
W. P. T. JAMES M. J. DAUNCEY H. L. DAVIES
UNEXPLAINED EPISODES OF COMA IN A TWO-YEAR-OLD
SIR,-Iwish to report a very exceptional case of neurological disorder in a child, the like of which I have never seen. Intensive inquiries among colleagues have failed to elicit a positive reply and no such case has yet been reported to the National Childhood Encephalopathy Study. I am writing not just to draw attention to the rarity and interest of the case but principally in the hope that some readers may have seen similar cases and could help us in the diagnosis and management. A two-year-old boy was noted by his parents to be a little less easy wake than usual for a week or so. He was admitted to an orthopaedic hospital with a trivial foot complaint, having been treated by his family doctor with cephalexin. There was no evidence of infection in his foot, but while in hospital he unexpectedly became totally unconscious. He had no preceding fit or fever. He may have had a trivial head injury when he fell. For this reason he was transferred to the department of neurosurgery in Sheffield. He was totally unconscious on arrival, but there were no abnormal neurological signs and normal fundi. Blood-pressure, blood-sugar, and lumbar c.s.F. were all normal, as was an EMI scan. Next morning he was fully conscious and, according to the parents, back to his normal self.He was returned to the referring hospital, where his excellent condition was noted, but by the time the resident doctor finished writing up his case notes he became totally unconscious. again. He was returned to the neurosurgical department in Sheffield where he arrived totally unconscious without additional features. He was transferred under my care early next morning when he was again totally unconscious and grossly hypotonic. One could put his limbs and body in any position and he behaved like a rubber toy. His pupils were small and equal. His fundi were normal and, apart from inconsistent upgoing plantar responses with areflexia, he presented no focal or general abnormal signs. There was no difficulty with breathing. The heart-rate, blood-pressure, blood sugar, urea, and electrolytes, E.E.G., and many other investigations were normal. The possibility of poisoning was entertained but he had no access to drugs. He was not given any anticonvulsant or sedative by doctors, and blood screening detected no poisoning. By now, he was on dexamethasone (1 mg three times a day), which neither helped nor caused trouble. He may have eaten some fungi which grew in the parents’ garden, but we obtained samples of the fungi and our professor of botany-has pronounced them non-poisonous. He has been on my ward for the past four days (that is up to Aug. 15), during which time he regained full consciousness to the degree of to
1.
Keys, A., Brozek, J., Henschel, A., Mickelsen, O., Taylor, H. L. The Biology of Human Starvation; vol. I, p. 329. Minneapolis, 1950.
473 playing with his parents, only six subsequent occasions. The coma may last up to ten hours and so may his normal consciousness. He remained afebrile throughout. Monitored continually over several hours, the E.E.G. showed no abnormality while he was conscious, nor while he was unconscious, except that, when he was unconscious, the voltage was appropriately low. There were no focal signs. I have not indicated all the negative results; and viral studies have not yet been completed and may not be helpful. There is one additional positive feature. It was noted by the parents and confirmed by us that at the very beginning of an unconscious episode, and usually preceding it by a few minutes, a papular rash developed over the bridge of his nose, his face, and his neck above the scapula. Invariably this rash faded within half an hour, but almost always recurred at the beginning of the unconscious episode. talking normally, eating normally, to relapse into the deepest coma
.
Biochemical estimations: A.S.T., A.L.T., L.D.H., C.P.K., aldolase, glucose, magnesium, calcium, urea, phosphate, albumen, total protein, sodium, electrophosesis, T3, T4, free thyropac index. Immunoglobulins: IgA 9 i.u./ml, IgG 105 i.u./ml, IgM 28 i.u./ml. Bacteriology.-Nose, throat, and rectal swabs sterile, meconium
and
on
I have never seen a case of encephalitis lethargica (von Economo’s disease). Could this be one? I would be grateful for help from any reader by telephone (Sheffield [0742] 71111), telegram, or any other means. The Children’s Hospital, Western Bank, Sheffield S10 2TH
J. LORBER
sterile. Cord-blood serology.-Toxoplasma antibody 1/10 (postnatally, mother’s serum 1/64); rubella H.A.I. 1/320, C.F.T. 1/10; adenovirus
1/20; cytomegalovirus < 1/10. Urine.-No aminoaciduria, cells, or organisms. X-rays.-No abnormal calcifications or other lesions in skull, heart, or lungs.
In the absence of any clinical abnormality and the presence of normal total and differential white counts, and normal plasma viscosity and immunoglobulins, it was felt that the rubella antibody was almost certainly maternal, but this will be pursued. Cord-blood toxoplasma antibody was 1/10, mother’s antenatally was 1/32 and on the fifth postnatal day 1/64, and the infant’s was less than 1/32. Thus, by all tests we failed to demonstrate that the infant had infection, major congenital anomaly, or toxic damage from the Steptoe-Edwards
technique. We greatly appreciate the help from our laboratory colleagues in many centres and the normality of care provided by the midwifery c;;:tff nncipr thi- c-irciimztnnri-q
SUCCESSFUL PREGNANCY FOLLOWING IN-VITRO FERTILISATION
SIR,-It seems prudent to publish the details of the first infant successfully delivered after A.I.H. in vitro by Steptoe and Edwards.’ The findings should allay fears that their technique is necessarily fraught with dangers to the fetus. The apparent normality of the infant should avert controversy that might have arisen had there been a major anomaly, or should there be subsequent illness that might affect her development. Many investigations were performed on the mother and on the cord blood to seek evidence of congenital abnormalities or of infection transmitted in the laboratory. Investigations on the infant were thus minimised. Relevant antepartum maternal features.-Apart from those in your columns’, the maternal thyroid function factors were normal and the toxoplasma antibody dye test was positive, 1/32. The infant.-A 38-week infant was deiivered by elective lower-segment csesarian section by Mr Steptoe. Her airways were drained and cleared and she cried within 20 seconds, before the cord was clamped. The Apgar at 1 minute was 10. She was a normal female weighing 2608 g (5 Ib 12 oz), crying well and maintaining a good colour. Placenta.-Healthy, 18 cm diameter, 450 g (1 lb). Normal umbilical cord, length 60 cm, three blood-vessels. 40 ml cord blood was taken
reported
for to
laboratory investigation of fetal state. The infant was transferred special-care baby unit for further examination and observation.
the
She was fed 20 ml sterile water and 30 ml 5% dextrose at 3 h and 30 ml of dextrose at 5 h; she sucked vigorously and slept between feeds. At 10 h she was put to the breast and fed 3-hourly thereafter, complementing feeds with Cow and Gate Premium milk as demanded. Retinoscopy with 1% homatropine eye-drops was normal. Progress was satisfactory until discharge on the 12th day, when she weighed 2693 g (6 Ib 1 oz), on breast and complementary feeding. Measurements and Investigations Gestational age: 10 -5=approximately 270 days’ gestation.2 The following reflexes were present and normal: Moro; asymmetric tonic neck; hand and foot grasp; stepping, walking, rooting.
DON HILSON R. L. BRUCE D. G. SIMS
Paediatric Department, Oldham and District General Hospital, Rochdale Road, Oldham OL1 2JH
SEASONAL VARIATION IN SUDDEN-INFANT-DEATH SYNDROME
SIR,-Beal’ and Professor Goldberg and
Dr Stein (July 8, 107) have shown that deaths due to sudden-infant-death syndrome (S.LD.S.) are more frequent in the winter months in South Australia and Chicago, at least for children dying at
p.
four months of age or older. Beal found no seasonal variation for those dying under three months of age. We believe that there is an important factor that they both failed to consider. In the United States, the National Center for Health Statistics2 reports that the occurrence of births is not uniform throughout the year and that the major peak occurs in September, with fewest births occurring in April and
May.
reported the number of s.i.D.s. deaths which is dependent on the seasonal variation in the number of births, a reanalysis of their data using life-table survivorship curves for monthly birth cohorts would be a more appropriate means of determining if there is a seasonality in s.i.D.s. deaths, and if this seasonality is ageSince both authors
occurring per month,
dependent. Epidemiology Program, School of Public Health,
University ofIllinois Medical Center, Chicago, Illinois 60680, U.S.A.
MARILYN D. FARBER VIJAY CHANDRA
MEASUREMENT OF THEOPHYLLINE
SIR,-Dr Kelly and Dr O’Malley (July 8, p. 98) criticise the validity of the Schack and Waxler method3for the measurement of theophylline in plasma. There exists a modification4 of this method which is not influenced by theophylline metabolites, caffeine, or barbiturates. This modification offers a simple and satisfactory means of monitoring theophylline levels in blood or plasma. Umbilical cord blood.-The normal laboratory range:
following
factors
were
all within the
Leucocyte count was 12.6x 109/1 (neutrophils 58%, lymphocytes 40, monocytes 2%), plasma viscosity 1-31. 1. 2.
Steptoe, P. C., Edwards, R. G. Lancet, Aug. 12, 1978, p. 366. Parkin, J. M., et al. Archs Dis. Childh 1976, 51, 259.
Biochemistry Department, Infirmary,
Western
Glasgow
G11 6NT
1. Beal, S. Lancer, 1978, i, 1257. 2. National Center for Health Statistics,
D. B.
1970, Series 21, No. 19,18. 3. Schack, J. A., Waxler, S. H.J. Pharmacol. exp. Ther. 1949, 97, 283 4. Jatlow, P. Clin. Chem. 1975, 21, 1518.
JACK
SIR,- The four I.e.L scientists attempted to highlight agreements and differences concerning the toxicity of toluene diisocyanate (T.D.I.) from studies conducted by three groups.2-4 It is easy to understand I.C.I.’s interest in T.D.I. Chemical companies want their products to be safe. It appeared to us that an effort was made to minimise important health effects Of T.D.I. in an unbalanced critique. The major conclusion of our paper3was not that there is a significant association between acute and chronic decrement in F.E.V., (as Adams et al. stated), but that there is a significant relationship between level of chronic exposure to T.D.I. and loss of F.E.V’l over a two-year period of time which is dose-related. Further, this relationship cannot be explained by lung size as they imply. In our view it is not reasonable for any group (no matter what their lung size) to lose over 100 ml Of F.E.V., per year as a result of occupational exposure. All working populations, whether or not they are exposed to respiratory irritants, contain persons with respiratory symptoms. To remove these persons artificially "improves" the health of the remaining cohort. It is not surprising then to see little effect Of T.D.I. in the Adams study.2 Another important factor is the nature of the exposure. Our studies have all involved the production of polyurethane products on a continuous or semi-continuous basis. Exposures to T.D.I. are rather consistent with small excursions. Producing T.D.I., on the other hand, results in exposures which vary from very low to quite high depending on the situation (leaks, spills, etc.). It is therefore not surprising to find different results on that basis. We used Monday morning for baseline measurements of pulmonary function to allow for recovery from acute effects. We have repeatedly observed acute symptom-free falls in F.E.V., over a workshift,5 which are clearly different from the "sensitisation" referred to in the I.C.I. letter. In reviewing the Tulane study, the most surprising finding in our view is the increase in pulmonary function over a 3 2 year period. This would appear to be physiologically impossible and suggests difficulties in making accurate measurements rather than lack of T.D.I. effect. It continues to be our view that T.D.I. is a highly toxic chemical which has serious respiratory effects including accelerated loss of lung function at levels of 0.003 p.p.m. and above. It is also our view that workers should be protected from these effects. Health Program, Harvard School of Public Health, Boston, Massachusetts 02115, U.S.A.
Occupational
JOHN M. PETERS DAVID H. WEGMAN
ELEVATED METABOLIC RATES IN OBESITY
SIR,-Dr Rucker (July 8, p. 106) finds that the resting metabolic rates (R.M.R.) of our obese patients conform with animal nutritionists’ long-standing recognition of the relation between basal metabolic rates and an index of metabolic size. This was precisely our point but instead of expressing the data in the standard way we emphasised the rise in R.M.R. in the obese state, noting that this increase had been neglected by human nutritionists when they considered energy balance in obesity. We maintain that a major conceptual error can be made by not comparing the R.M.R. of an obese individual with that of a "normal" individual of the same height. These conceptual disagreements reflect two of the different approaches to metabolism. Animal nutritionists have related R.M.R. to a unit Adams, W. G. F., Carney, I. F., Chamberlain, V. D., Paddle, G. M. Lancet, 1978, i, 1308. 2. Adams, W. G. F., Br. J. ind. Med. 1975, 32, 72. 3. Wegman, D. H., Peters, J. M., Pagnotto, L. J. ibid. 1977, 34, 196. 4. Butcher, B. T. and others. Am. Rev. resp. Dis. 1977, 116, 411. 5. Peters, J. M., Murphy, R. L. H., Pagnotto, L. Van Ganse, W. F. Archs environ. Hth, 1968, 16, 642. 1.
of metabolic size or to surface area when presenting information on small and large adult animals of equivalent body composition. Since metabolic data are always expressed in this way it is natural to expect that an obese person will conform with this general rule. In practice we do find that an obese woman 1.5m tall, weighing 65 kg instead of 48 kg, has an R.M.R. approximately equivalent to that of a subject of 59 kg with a normal body composition. Yet obesity is considered traditionally to involve only an increase in total triglyceride and this should not in itself increase metabolic activity. In man obesity does lead to an increase in B.M.R., whereas in the genetically obese ob/ob mouse this is not so. The mouse has a low fat-free mass whereas our patients had a marked increase in fat-free mass and a corresponding rise in R.M.R. The observed decrease in R.M.R. on slimming exceeds that expected from the relation between R.M.R. and metabolic size because there are changes in the efficiency of energy use in addition to the metabolic consequences of a reduction in fatfree mass. An alteration in efficiency on semistarvation was recognised in the classical Minnesota experiments--changes occurred in both metabolic efficiency and in lean body mass.’ M.R.C. Dunn Nutrition Centre, Old Addenbrookes Hospital,
Cambridge CB2 1QE
W. P. T. JAMES M. J. DAUNCEY H. L. DAVIES
UNEXPLAINED EPISODES OF COMA IN A TWO-YEAR-OLD
SIR,-Iwish to report a very exceptional case of neurological disorder in a child, the like of which I have never seen. Intensive inquiries among colleagues have failed to elicit a positive reply and no such case has yet been reported to the National Childhood Encephalopathy Study. I am writing not just to draw attention to the rarity and interest of the case but principally in the hope that some readers may have seen similar cases and could help us in the diagnosis and management. A two-year-old boy was noted by his parents to be a little less easy wake than usual for a week or so. He was admitted to an orthopaedic hospital with a trivial foot complaint, having been treated by his family doctor with cephalexin. There was no evidence of infection in his foot, but while in hospital he unexpectedly became totally unconscious. He had no preceding fit or fever. He may have had a trivial head injury when he fell. For this reason he was transferred to the department of neurosurgery in Sheffield. He was totally unconscious on arrival, but there were no abnormal neurological signs and normal fundi. Blood-pressure, blood-sugar, and lumbar c.s.F. were all normal, as was an EMI scan. Next morning he was fully conscious and, according to the parents, back to his normal self.He was returned to the referring hospital, where his excellent condition was noted, but by the time the resident doctor finished writing up his case notes he became totally unconscious. again. He was returned to the neurosurgical department in Sheffield where he arrived totally unconscious without additional features. He was transferred under my care early next morning when he was again totally unconscious and grossly hypotonic. One could put his limbs and body in any position and he behaved like a rubber toy. His pupils were small and equal. His fundi were normal and, apart from inconsistent upgoing plantar responses with areflexia, he presented no focal or general abnormal signs. There was no difficulty with breathing. The heart-rate, blood-pressure, blood sugar, urea, and electrolytes, E.E.G., and many other investigations were normal. The possibility of poisoning was entertained but he had no access to drugs. He was not given any anticonvulsant or sedative by doctors, and blood screening detected no poisoning. By now, he was on dexamethasone (1 mg three times a day), which neither helped nor caused trouble. He may have eaten some fungi which grew in the parents’ garden, but we obtained samples of the fungi and our professor of botany-has pronounced them non-poisonous. He has been on my ward for the past four days (that is up to Aug. 15), during which time he regained full consciousness to the degree of to
1.
Keys, A., Brozek, J., Henschel, A., Mickelsen, O., Taylor, H. L. The Biology of Human Starvation; vol. I, p. 329. Minneapolis, 1950.
473 playing with his parents, only six subsequent occasions. The coma may last up to ten hours and so may his normal consciousness. He remained afebrile throughout. Monitored continually over several hours, the E.E.G. showed no abnormality while he was conscious, nor while he was unconscious, except that, when he was unconscious, the voltage was appropriately low. There were no focal signs. I have not indicated all the negative results; and viral studies have not yet been completed and may not be helpful. There is one additional positive feature. It was noted by the parents and confirmed by us that at the very beginning of an unconscious episode, and usually preceding it by a few minutes, a papular rash developed over the bridge of his nose, his face, and his neck above the scapula. Invariably this rash faded within half an hour, but almost always recurred at the beginning of the unconscious episode. talking normally, eating normally, to relapse into the deepest coma
.
Biochemical estimations: A.S.T., A.L.T., L.D.H., C.P.K., aldolase, glucose, magnesium, calcium, urea, phosphate, albumen, total protein, sodium, electrophosesis, T3, T4, free thyropac index. Immunoglobulins: IgA 9 i.u./ml, IgG 105 i.u./ml, IgM 28 i.u./ml. Bacteriology.-Nose, throat, and rectal swabs sterile, meconium
and
on
I have never seen a case of encephalitis lethargica (von Economo’s disease). Could this be one? I would be grateful for help from any reader by telephone (Sheffield [0742] 71111), telegram, or any other means. The Children’s Hospital, Western Bank, Sheffield S10 2TH
J. LORBER
sterile. Cord-blood serology.-Toxoplasma antibody 1/10 (postnatally, mother’s serum 1/64); rubella H.A.I. 1/320, C.F.T. 1/10; adenovirus
1/20; cytomegalovirus < 1/10. Urine.-No aminoaciduria, cells, or organisms. X-rays.-No abnormal calcifications or other lesions in skull, heart, or lungs.
In the absence of any clinical abnormality and the presence of normal total and differential white counts, and normal plasma viscosity and immunoglobulins, it was felt that the rubella antibody was almost certainly maternal, but this will be pursued. Cord-blood toxoplasma antibody was 1/10, mother’s antenatally was 1/32 and on the fifth postnatal day 1/64, and the infant’s was less than 1/32. Thus, by all tests we failed to demonstrate that the infant had infection, major congenital anomaly, or toxic damage from the Steptoe-Edwards
technique. We greatly appreciate the help from our laboratory colleagues in many centres and the normality of care provided by the midwifery c;;:tff nncipr thi- c-irciimztnnri-q
SUCCESSFUL PREGNANCY FOLLOWING IN-VITRO FERTILISATION
SIR,-It seems prudent to publish the details of the first infant successfully delivered after A.I.H. in vitro by Steptoe and Edwards.’ The findings should allay fears that their technique is necessarily fraught with dangers to the fetus. The apparent normality of the infant should avert controversy that might have arisen had there been a major anomaly, or should there be subsequent illness that might affect her development. Many investigations were performed on the mother and on the cord blood to seek evidence of congenital abnormalities or of infection transmitted in the laboratory. Investigations on the infant were thus minimised. Relevant antepartum maternal features.-Apart from those in your columns’, the maternal thyroid function factors were normal and the toxoplasma antibody dye test was positive, 1/32. The infant.-A 38-week infant was deiivered by elective lower-segment csesarian section by Mr Steptoe. Her airways were drained and cleared and she cried within 20 seconds, before the cord was clamped. The Apgar at 1 minute was 10. She was a normal female weighing 2608 g (5 Ib 12 oz), crying well and maintaining a good colour. Placenta.-Healthy, 18 cm diameter, 450 g (1 lb). Normal umbilical cord, length 60 cm, three blood-vessels. 40 ml cord blood was taken
reported
for to
laboratory investigation of fetal state. The infant was transferred special-care baby unit for further examination and observation.
the
She was fed 20 ml sterile water and 30 ml 5% dextrose at 3 h and 30 ml of dextrose at 5 h; she sucked vigorously and slept between feeds. At 10 h she was put to the breast and fed 3-hourly thereafter, complementing feeds with Cow and Gate Premium milk as demanded. Retinoscopy with 1% homatropine eye-drops was normal. Progress was satisfactory until discharge on the 12th day, when she weighed 2693 g (6 Ib 1 oz), on breast and complementary feeding. Measurements and Investigations Gestational age: 10 -5=approximately 270 days’ gestation.2 The following reflexes were present and normal: Moro; asymmetric tonic neck; hand and foot grasp; stepping, walking, rooting.
DON HILSON R. L. BRUCE D. G. SIMS
Paediatric Department, Oldham and District General Hospital, Rochdale Road, Oldham OL1 2JH
SEASONAL VARIATION IN SUDDEN-INFANT-DEATH SYNDROME
SIR,-Beal’ and Professor Goldberg and
Dr Stein (July 8, 107) have shown that deaths due to sudden-infant-death syndrome (S.LD.S.) are more frequent in the winter months in South Australia and Chicago, at least for children dying at
p.
four months of age or older. Beal found no seasonal variation for those dying under three months of age. We believe that there is an important factor that they both failed to consider. In the United States, the National Center for Health Statistics2 reports that the occurrence of births is not uniform throughout the year and that the major peak occurs in September, with fewest births occurring in April and
May.
reported the number of s.i.D.s. deaths which is dependent on the seasonal variation in the number of births, a reanalysis of their data using life-table survivorship curves for monthly birth cohorts would be a more appropriate means of determining if there is a seasonality in s.i.D.s. deaths, and if this seasonality is ageSince both authors
occurring per month,
dependent. Epidemiology Program, School of Public Health,
University ofIllinois Medical Center, Chicago, Illinois 60680, U.S.A.
MARILYN D. FARBER VIJAY CHANDRA
MEASUREMENT OF THEOPHYLLINE
SIR,-Dr Kelly and Dr O’Malley (July 8, p. 98) criticise the validity of the Schack and Waxler method3for the measurement of theophylline in plasma. There exists a modification4 of this method which is not influenced by theophylline metabolites, caffeine, or barbiturates. This modification offers a simple and satisfactory means of monitoring theophylline levels in blood or plasma. Umbilical cord blood.-The normal laboratory range:
following
factors
were
all within the
Leucocyte count was 12.6x 109/1 (neutrophils 58%, lymphocytes 40, monocytes 2%), plasma viscosity 1-31. 1. 2.
Steptoe, P. C., Edwards, R. G. Lancet, Aug. 12, 1978, p. 366. Parkin, J. M., et al. Archs Dis. Childh 1976, 51, 259.
Biochemistry Department, Infirmary,
Western
Glasgow
G11 6NT
1. Beal, S. Lancer, 1978, i, 1257. 2. National Center for Health Statistics,
D. B.
1970, Series 21, No. 19,18. 3. Schack, J. A., Waxler, S. H.J. Pharmacol. exp. Ther. 1949, 97, 283 4. Jatlow, P. Clin. Chem. 1975, 21, 1518.
JACK
