- Email: [email protected]
BOTULISM AND SUDDEN INFANT DEATH
147 of oxygen at the tissues. Under these conditions, more glucose, sorbitol, or fructose will be metabolised anaerobically to lactate, which would appear to encourage the incidence of lacticacidosis. Since the blood-flow (and therefore the oxygen supply) to the peripheral tissues cannot be increased by exercise in the immobile patient the potential of unit volume of blood to oxygenate the tissues must not be allowed to fall (as it seems may
happen
in
hypophosphataemia). Perhaps, therefore,
the
incidence of lacticacidosis could be lessened by careful attention to phosphate supplementation in the patient whose pH appears on the low side if parenteral nutrition is being applied to that patient. 21 Walliscote Road, Weston-super-Mare,
MICHAEL J. SPURR
Avon
BOTULISM AND SUDDEN INFANT DEATH
SiR,--Midura and Arnon’ ask if infant botulism might of sudden-infant-death syndrome (S.I.D.S.). suggestion, but would indict an exogenous source of botulin toxin, probably the infant’s food. An infant with botulism could die suddenly and unexpectedly without any pathological evidence to account for the cause of death; this is one criterion for S.I.D.S.2 The clinical appearance of S.LD.S. is obscure. The same is often true of botulism. Botulism may vary from a mild illness to a fulminant disease which ends in death within 24 h, in which neurological symptoms may occur with startling swiftness. Yet on examination patients are usually alert and afebrile even with severe disease.3 Although unexplained postural hypotension, dilated unreactive pupils, ptosis of eye, extremely dry mucous
explain
some cases
We agree with this
MORTALITY FROM PNEUMOCOCCAL MENINGITIS
S)R,—The report of Baird et al.on mortality patterns from pneumococcal meningitis was of great interest to us. They refer to various series, including one from Harlem Hospital in New York where the mortality-rate was 47% in 62 cases reported over a five-year period. Later, they state that "in Eurnow static with an overall around 20%." We have reviewed the records of all culture-confirmed cases of meningitis due to Streptococcus pnellmoniae reported to and investigated by the Bureau of Preventable Diseases over the five years 1972-76. Our analysis of mortality-rates for the whole of New York City over a five-year period, while differing from previous estimates of mortality-rates cited, supports the contention of Baird et al.I and Fraser et al. that Blacks are predisposed to this disease. In our series of 293 culture-confirmed cases of Strep. pneumonice meningitis the mortality-rate was 63.8% (Whites 62.4%, Blacks 65.6%). Mean age at onset of disease did not significantly differ among Whites and Blacks, nor did the male/female ratio. However; the race-adjusted incidence (based on 1970 census) demonstrates a 2.54/1 Black/White ratio, which is highly significant (/=84; P«0-0005). The disproportionate attack-rate in Blacks cannot be ascribed to lack of access to care, diagnosis, or treatment since case-fatality rates did not differ significantly among the two groups. Our survey supports the view of Baird ei al. that some genetic factor may predispose Blacks to pneumococcal meningitis. We are reviewing our cases of other bacterial meningitides to see whether this predisposition is unique to Strep.
ope and the U.S.A. the situation is
mortality persisting
at
pneumonice. Beureau of Preventable
Diseases,
Department of Health, City of New York, New York, N.Y. 10013, U.S.A.
JOHN S. MARR EDWARD I. GALAID
SIR,-The paper by Baird et al.--especially their remarks about serum treatment-reminded of a patient admitted by my "chief’in 1936. The patient was a strong young man who was deeply comatose, and the consultant bacteriologist identified pneumococci in the cerebrospinal fluid. I remember the patient’s mother being told that there was no hope. Treated with Felton’s serum intravenously he remained unconscious for several days. Thereafter he was violently delirious and was given intravenous hexobarbitone sodium followed by rectal paraldehyde, a cocktail usually reserved for alcoholics. The recovery was apparently complete, but unfortunately he lived only a few years. In 1940 while working on mine disposal with the Royal Navy he was killed by an explosion. Greater Glasgow Health Board, GlasgowG23HT
J. CLARK
1 Baird,D.R.,Whittle,H.C.,Greenwood, B. M.Lancet, 1976, ii, 1344. 2 Fraser, D. W., Darby, C. P., Koehler, R. E., Jacobs, C F, Feldman, R. J infect.Dis. 1973, 127, 271.
A.
Age
distribution of
cases
of S.I.D.S. and introduction of foods. et al4 (0),
Age distribution of cases of s.t.D.s. reported by Froggat Adelson and Kinney’ (e), and Bergman et al.6 (x). I.
membranes, and progressive muscle paresis
in
a
previously
individual should suggest botulism, there are exceptions.3The child brought to a clinic for a routine checkup, who died in the physician’s arms, going from seemingly full health to death in a matter of minutes,4 may very well have been a case of infant botulism. We have correlated published data on the age distribution of s. L D. S. 4-6 with the usual age of introduction of cereals, prepared foods, and junior foods to infants not being breast fed. S.LD.S. age data and prepared-food consumption seem to be well correlated (see figure). In the United States mothers serve prepared foods after gently warming them to temperatures far below that required for denaturation of botulin (10 min of boiling). Table foods, on the other hand, are generally well cooked, and S.I.D.S. is much less common in babies of an age who have progressed to table foods. Breast-fed babies are not introduced to solid foods until 3 or 4 months of age, and we would expect S.I.D.S. to be much less common in this group. Botulin paralyses cholinergic nerve endings. Acetylcholine release and neurotransmission are blocked, and bulbar paresis of the hypoglossal and glossopharyngeal nerves leads to respir8 atory arrest.’ This mode of action correlates well with indica-
healthy
1. Midura, T. F., Arnon, S. S. Lancet, 1976, n, 934 2. Valdes-Dapenia, M. A. Pediatrics, 1967, 39, 123. 3. Doenig, M. G., Rogers, D. H. in Harrison’s Principles of Internal Medicine; p. 858. New York, 1970. 4. Froggat, P., Lynas, M. A., Marshall, T. K. Am. J. Cardiol. 1968, 22, 457. 5. Adelson, L., Kinney, E. R. Pediatrics, 1956, 17, 663. 6. Bergman, A. B., Ray, C. G., Pomeroy, M. A., Wahl, P. W., Beckwith, J. B. ibid. 1972, 49, 860. 7. Thienes, C. H., Haley, T. J. Clinical Toxicology; p. 149 Philadelphia, 1964. 8. Goodman, L. S., Gilman, A. The Pharmacological Basis of Therapeutics; p. 430. New York, 1965.
148 tive
epidemiological factors in s.t.D.s. (i.e., respiratory dysfunction or infant apncea).9-11 1 mg of pure botulin may contain 20 000 fatal doses and the lethal dose can be as low as 50 ng. For infants the lethal dose may be so low that fatal contamination of infant foods may not be detectable. C. botulinum contaminated food is sometimes only sour and not disagreeable in taste, 12 and food tainted with type-E toxin may look and taste normal.3 Lack of gas formation 13 in the product is no guarantee of sterilisation of C. botulinum. Fatal botulism in a child less than 9 years old has not been recorded although ten cases of botulism in children up to 9 years old were tabulated by the National Communicable Disease Center between 1962 and 1967.14 Of eighty-eight patients aged 10-60, about a quarter died. Since it is likely that only small amounts of ingested toxin are needed to be lethal in children, this difference is odd. ’ We feel there is presumptive evidence that s.i.D.s. and infant botulism may be correlated in a cause-and-effect relationship. As Midura and Amon’ and Pickett et al." have stated, additional studies are warranted. ‘
Department of Pathology, South Hills Health System, Pittsburgh, Pennsylvania 15203, U.S.A.
PAUL POTTGEN LEONARD M. HILLEGASS
POSTURE, WATER CONTENT, AND SERUM CHEMISTRY
SiR,-While measuring the concentrations of elements in normal serum we found that the values of serum samples from persons in a recumbent position were significantly different from values in samples taken from the same people in an upright position or immediately after lying down. One reason for this difference is the change in the water content of the serum in relation to posture. When a person lies down, water flows into the blood-vessels while the total amount of protein remains constant !6 Because of this dilution the concentration of a protein-bound element decreases when calculated for the wet weight or for the volume of the sample, but remains unchanged when related to the amount of protein or, since dried serum is mostly protein, to the dry weight of the sample (see Se in the figure). Elements which are not bound to proteins show an increase in dry-weight content as a result of the decrease in the protein/water ratio (see Br and Na in the figure). Change in posture can also be responsible for a genuine alteration in the concentration of an element. The drop in zinc content, for example, though much reduced by calculation on a dry-weight basis, was still significant which shows that the serum-zinc falls when a person passes from an upright to a recumbent position. We conclude that effects of posture on serum-element levels should be prevented by means of standardised sampling procedures. The concentrations of protein-bound elements should be related to the dry weight of the sample and not, as has been common practice until now, to the wet weight or to the volume. Otherwise changes in the protein/water ratio which are due to different factors (e.g., posture, stress, food, hor’mones, pregnancy, or age) may lead to apparently significant changes in element levels or may simulate correlations between protein-bound elements. The dilution effect offers the oppor9.
10.
11. 12. 13. 14. 15. 16.
A. B., Beckwith, J. B., Ray, C. G. in Proceedings of the Second International Conference on Causes of Sudden Death in Infants. Seattle, 1970. Boushey, H. A., Richardson, P. S., Widdicombe, J. G. J. Physiol., Lond. 1972, 224, 501. Steinchneider, A. Pediatrics, 1972, 50, 646. Dack, G. M. Food Poisoning; p. 42, Chicago, 1949. Schoenholz, P., Esty, J. R., Meyer, K. F. J. infect. Dis. 1923, 33, 289. Gangarosa, E. J. ibid. 1968, 119, 307. Pickett, J., Berg, B., Caplin, E., Brunstetter-Shafer, M. New Engl. J. Med. 1976, 295, 770. Lange, H. F. Acta med. scand. 1946, suppl. 176.
Bergman,
Bromine (Br), sodium (Na), selenium (Se), and zinc (Zn) concentrations measured by neutron-activation analysis in serum samples taken from 18 people at different times after moving from an upright to a recumbent position. The element levels (calculated for each person as a percentage of the mean of the last four values) are related to the wet weight and to the dry weight of the samples.
tunity of finding out in a relatively simple way whether or not an element is present in serum in a protein-bound form by determining the element level in relation to changes in the serum water content.
Hahn-Meitner-Institut für
Kernforschung Berlin, D-1000 Berlin 39, Federal Republic of Germany
D. BEHNE H. JÜRGENSEN
ARM COMPRESSION AND DEEP-VENOUS
THROMBOSIS
SIR,-Having heard about the work of Mr Knight and Mr Dawson, I was most interested to read their paper’ showing a lower incidence of deep-venous thrombosis in the legs of patients after intermittent compression of the arms was used during and after surgery. Work done at the Queen Victoria Hospital, East Grinstead, on the incidence of deep-venous thrombosis in patients after hypotensive anæsthesia2suggested that these patients, despite being tilted foot down, had a lower incidence than normotensive patients so tilted, although the number of patients in the series was not sufficient for rigorous statistical comparison. We felt that a lower incidence in hypotensive patients could be due to arm compression because the blood-pressure of this group of patients was monitored almost continuously using a repeatedly inflated cuff on the arm. Middlesbrough General Hospital, Middlesbrough, Cleveland TS5 5AZ 1. Knight, M. T. N., Dawson, R. Lancet, 1976, ii, 1265. 2. Hale Enderby, G. E., Patel, H., Hackett, M., Poole, Anœsthesia, 1976, 31, 1273.
M. D. POOLE
M., Roberts, V. C.
happen
in
hypophosphataemia). Perhaps, therefore,
the
incidence of lacticacidosis could be lessened by careful attention to phosphate supplementation in the patient whose pH appears on the low side if parenteral nutrition is being applied to that patient. 21 Walliscote Road, Weston-super-Mare,
MICHAEL J. SPURR
Avon
BOTULISM AND SUDDEN INFANT DEATH
SiR,--Midura and Arnon’ ask if infant botulism might of sudden-infant-death syndrome (S.I.D.S.). suggestion, but would indict an exogenous source of botulin toxin, probably the infant’s food. An infant with botulism could die suddenly and unexpectedly without any pathological evidence to account for the cause of death; this is one criterion for S.I.D.S.2 The clinical appearance of S.LD.S. is obscure. The same is often true of botulism. Botulism may vary from a mild illness to a fulminant disease which ends in death within 24 h, in which neurological symptoms may occur with startling swiftness. Yet on examination patients are usually alert and afebrile even with severe disease.3 Although unexplained postural hypotension, dilated unreactive pupils, ptosis of eye, extremely dry mucous
explain
some cases
We agree with this
MORTALITY FROM PNEUMOCOCCAL MENINGITIS
S)R,—The report of Baird et al.on mortality patterns from pneumococcal meningitis was of great interest to us. They refer to various series, including one from Harlem Hospital in New York where the mortality-rate was 47% in 62 cases reported over a five-year period. Later, they state that "in Eurnow static with an overall around 20%." We have reviewed the records of all culture-confirmed cases of meningitis due to Streptococcus pnellmoniae reported to and investigated by the Bureau of Preventable Diseases over the five years 1972-76. Our analysis of mortality-rates for the whole of New York City over a five-year period, while differing from previous estimates of mortality-rates cited, supports the contention of Baird et al.I and Fraser et al. that Blacks are predisposed to this disease. In our series of 293 culture-confirmed cases of Strep. pneumonice meningitis the mortality-rate was 63.8% (Whites 62.4%, Blacks 65.6%). Mean age at onset of disease did not significantly differ among Whites and Blacks, nor did the male/female ratio. However; the race-adjusted incidence (based on 1970 census) demonstrates a 2.54/1 Black/White ratio, which is highly significant (/=84; P«0-0005). The disproportionate attack-rate in Blacks cannot be ascribed to lack of access to care, diagnosis, or treatment since case-fatality rates did not differ significantly among the two groups. Our survey supports the view of Baird ei al. that some genetic factor may predispose Blacks to pneumococcal meningitis. We are reviewing our cases of other bacterial meningitides to see whether this predisposition is unique to Strep.
ope and the U.S.A. the situation is
mortality persisting
at
pneumonice. Beureau of Preventable
Diseases,
Department of Health, City of New York, New York, N.Y. 10013, U.S.A.
JOHN S. MARR EDWARD I. GALAID
SIR,-The paper by Baird et al.--especially their remarks about serum treatment-reminded of a patient admitted by my "chief’in 1936. The patient was a strong young man who was deeply comatose, and the consultant bacteriologist identified pneumococci in the cerebrospinal fluid. I remember the patient’s mother being told that there was no hope. Treated with Felton’s serum intravenously he remained unconscious for several days. Thereafter he was violently delirious and was given intravenous hexobarbitone sodium followed by rectal paraldehyde, a cocktail usually reserved for alcoholics. The recovery was apparently complete, but unfortunately he lived only a few years. In 1940 while working on mine disposal with the Royal Navy he was killed by an explosion. Greater Glasgow Health Board, GlasgowG23HT
J. CLARK
1 Baird,D.R.,Whittle,H.C.,Greenwood, B. M.Lancet, 1976, ii, 1344. 2 Fraser, D. W., Darby, C. P., Koehler, R. E., Jacobs, C F, Feldman, R. J infect.Dis. 1973, 127, 271.
A.
Age
distribution of
cases
of S.I.D.S. and introduction of foods. et al4 (0),
Age distribution of cases of s.t.D.s. reported by Froggat Adelson and Kinney’ (e), and Bergman et al.6 (x). I.
membranes, and progressive muscle paresis
in
a
previously
individual should suggest botulism, there are exceptions.3The child brought to a clinic for a routine checkup, who died in the physician’s arms, going from seemingly full health to death in a matter of minutes,4 may very well have been a case of infant botulism. We have correlated published data on the age distribution of s. L D. S. 4-6 with the usual age of introduction of cereals, prepared foods, and junior foods to infants not being breast fed. S.LD.S. age data and prepared-food consumption seem to be well correlated (see figure). In the United States mothers serve prepared foods after gently warming them to temperatures far below that required for denaturation of botulin (10 min of boiling). Table foods, on the other hand, are generally well cooked, and S.I.D.S. is much less common in babies of an age who have progressed to table foods. Breast-fed babies are not introduced to solid foods until 3 or 4 months of age, and we would expect S.I.D.S. to be much less common in this group. Botulin paralyses cholinergic nerve endings. Acetylcholine release and neurotransmission are blocked, and bulbar paresis of the hypoglossal and glossopharyngeal nerves leads to respir8 atory arrest.’ This mode of action correlates well with indica-
healthy
1. Midura, T. F., Arnon, S. S. Lancet, 1976, n, 934 2. Valdes-Dapenia, M. A. Pediatrics, 1967, 39, 123. 3. Doenig, M. G., Rogers, D. H. in Harrison’s Principles of Internal Medicine; p. 858. New York, 1970. 4. Froggat, P., Lynas, M. A., Marshall, T. K. Am. J. Cardiol. 1968, 22, 457. 5. Adelson, L., Kinney, E. R. Pediatrics, 1956, 17, 663. 6. Bergman, A. B., Ray, C. G., Pomeroy, M. A., Wahl, P. W., Beckwith, J. B. ibid. 1972, 49, 860. 7. Thienes, C. H., Haley, T. J. Clinical Toxicology; p. 149 Philadelphia, 1964. 8. Goodman, L. S., Gilman, A. The Pharmacological Basis of Therapeutics; p. 430. New York, 1965.
148 tive
epidemiological factors in s.t.D.s. (i.e., respiratory dysfunction or infant apncea).9-11 1 mg of pure botulin may contain 20 000 fatal doses and the lethal dose can be as low as 50 ng. For infants the lethal dose may be so low that fatal contamination of infant foods may not be detectable. C. botulinum contaminated food is sometimes only sour and not disagreeable in taste, 12 and food tainted with type-E toxin may look and taste normal.3 Lack of gas formation 13 in the product is no guarantee of sterilisation of C. botulinum. Fatal botulism in a child less than 9 years old has not been recorded although ten cases of botulism in children up to 9 years old were tabulated by the National Communicable Disease Center between 1962 and 1967.14 Of eighty-eight patients aged 10-60, about a quarter died. Since it is likely that only small amounts of ingested toxin are needed to be lethal in children, this difference is odd. ’ We feel there is presumptive evidence that s.i.D.s. and infant botulism may be correlated in a cause-and-effect relationship. As Midura and Amon’ and Pickett et al." have stated, additional studies are warranted. ‘
Department of Pathology, South Hills Health System, Pittsburgh, Pennsylvania 15203, U.S.A.
PAUL POTTGEN LEONARD M. HILLEGASS
POSTURE, WATER CONTENT, AND SERUM CHEMISTRY
SiR,-While measuring the concentrations of elements in normal serum we found that the values of serum samples from persons in a recumbent position were significantly different from values in samples taken from the same people in an upright position or immediately after lying down. One reason for this difference is the change in the water content of the serum in relation to posture. When a person lies down, water flows into the blood-vessels while the total amount of protein remains constant !6 Because of this dilution the concentration of a protein-bound element decreases when calculated for the wet weight or for the volume of the sample, but remains unchanged when related to the amount of protein or, since dried serum is mostly protein, to the dry weight of the sample (see Se in the figure). Elements which are not bound to proteins show an increase in dry-weight content as a result of the decrease in the protein/water ratio (see Br and Na in the figure). Change in posture can also be responsible for a genuine alteration in the concentration of an element. The drop in zinc content, for example, though much reduced by calculation on a dry-weight basis, was still significant which shows that the serum-zinc falls when a person passes from an upright to a recumbent position. We conclude that effects of posture on serum-element levels should be prevented by means of standardised sampling procedures. The concentrations of protein-bound elements should be related to the dry weight of the sample and not, as has been common practice until now, to the wet weight or to the volume. Otherwise changes in the protein/water ratio which are due to different factors (e.g., posture, stress, food, hor’mones, pregnancy, or age) may lead to apparently significant changes in element levels or may simulate correlations between protein-bound elements. The dilution effect offers the oppor9.
10.
11. 12. 13. 14. 15. 16.
A. B., Beckwith, J. B., Ray, C. G. in Proceedings of the Second International Conference on Causes of Sudden Death in Infants. Seattle, 1970. Boushey, H. A., Richardson, P. S., Widdicombe, J. G. J. Physiol., Lond. 1972, 224, 501. Steinchneider, A. Pediatrics, 1972, 50, 646. Dack, G. M. Food Poisoning; p. 42, Chicago, 1949. Schoenholz, P., Esty, J. R., Meyer, K. F. J. infect. Dis. 1923, 33, 289. Gangarosa, E. J. ibid. 1968, 119, 307. Pickett, J., Berg, B., Caplin, E., Brunstetter-Shafer, M. New Engl. J. Med. 1976, 295, 770. Lange, H. F. Acta med. scand. 1946, suppl. 176.
Bergman,
Bromine (Br), sodium (Na), selenium (Se), and zinc (Zn) concentrations measured by neutron-activation analysis in serum samples taken from 18 people at different times after moving from an upright to a recumbent position. The element levels (calculated for each person as a percentage of the mean of the last four values) are related to the wet weight and to the dry weight of the samples.
tunity of finding out in a relatively simple way whether or not an element is present in serum in a protein-bound form by determining the element level in relation to changes in the serum water content.
Hahn-Meitner-Institut für
Kernforschung Berlin, D-1000 Berlin 39, Federal Republic of Germany
D. BEHNE H. JÜRGENSEN
ARM COMPRESSION AND DEEP-VENOUS
THROMBOSIS
SIR,-Having heard about the work of Mr Knight and Mr Dawson, I was most interested to read their paper’ showing a lower incidence of deep-venous thrombosis in the legs of patients after intermittent compression of the arms was used during and after surgery. Work done at the Queen Victoria Hospital, East Grinstead, on the incidence of deep-venous thrombosis in patients after hypotensive anæsthesia2suggested that these patients, despite being tilted foot down, had a lower incidence than normotensive patients so tilted, although the number of patients in the series was not sufficient for rigorous statistical comparison. We felt that a lower incidence in hypotensive patients could be due to arm compression because the blood-pressure of this group of patients was monitored almost continuously using a repeatedly inflated cuff on the arm. Middlesbrough General Hospital, Middlesbrough, Cleveland TS5 5AZ 1. Knight, M. T. N., Dawson, R. Lancet, 1976, ii, 1265. 2. Hale Enderby, G. E., Patel, H., Hackett, M., Poole, Anœsthesia, 1976, 31, 1273.
M. D. POOLE
M., Roberts, V. C.