1052
pranolol treated patients, when osteodystrophic repair would be expected to be most active. Follow-up of these patients from four months onwards showed normal S.A.P. levels, irrespective of preoperative preparation.
thyrocalcitonin release may indeed play some part in explaining transient falls in serum-calcium after thyroid operations, we feel that proponents of this idea should back it by using highly sensitive immunoassays of calcitonin now available. We cannot agree, however, that hypocalczmia lasting longer than a day can be so explained, and we believe that the avidity of thyrotoxic osteodystrophic bone for calcium is then the best explanation. Furthermore the thyroids of pigs pretreated with methylthiouracil had an impaired ability to secrete calcitonin.5 This might help to explain why the fall in While
serum-calcium in the series of Wilkin et al. was of greater statistical significance in the patients with functionally normal non-toxic goitre. W. MICHIE Departments of Surgery, Medicine, and J. M. STOWERS Chemical Pathology, S. C. FRAZER of Aberdeen University
mean
investigation which is not for their benefit where the studies are sound, promise important new knowledge and there is no discernible risk", adding the necessity for informed parental consent.
Campbe1l6 states "the only real protection for the individual scrupulousness, conscience and personal integrity of the investigator." But individual conscience varies too, and who then decides what is negligible risk, discomfort, and "inlies in the
formed" consent? Ethical committees are admirable in concept but "they vary in their membership, their influence and in There is no consistent their interpretation of their role ...
policy."6 Perhaps any further guidelines have to wait until, as Sir Cyril Clarkes suggests, someone makes a test case with the backing of a medical defence body: but, should such support be wanting, what individual doctor, acting against legal and protessional advice, is going to risk his head on the chopping block and rely on an ethical committee’s decision to stop it tumbling off. "Tar-baby, she ain’t saying nothing-and Brer Fox, he still lay low!"’ Town Farm, West Street,
RESEARCH ON INFANTS
SIR,-I am grateful to Dr Gairdner for the references in his letter (April 16, p. 852) concerning blood-sampling in infants but I cannot agree with his suggestion that I "need not have left the matter there". I did not. The Medical Defence Union confirmed the advice of the paediatrician on the local ethical research committee (i.e., that blood-sampling for research in infants was not legally permissible), and cautioned me against proceeding with this. I then referred, at the suggestion of the British Medical Association, to Professor Oppe, professor of paediatrics, London University, who, informed of the circumstances, supported this view. Both knew that my research programme (to determine whether the type of early feeding is related to the incidence of asthma in children) involved following up babies at home in preference to hospital outpatients, and that this included regular bloodsampling for assessment of immunoglobulins and milk antibodies. As Dr Dodge and Dr Evans point out in their letter (April 16, p. 852) there are risks in blood-sampling, however slight, and, in view of the advice I had been given, it did not seem justifiable to me (a mother, a doctor, and a magistrate) to proceed with this, when, although immunoglobulin studies are relevant, they are not essential to what I am trying to establish. This was a "value judgement",’ as it happens by a woman. (I note that all the writings I have seen in support of blood-
sampling are by men!) research blood-sampling in general which letter. prompted my The views of authoritative bodies vary from the Department of Health view expressed by Sir George Godber2 that it is not legitimate to do experiments in children which are not in the interests of that particular child, to the Royal College of Physicians recommendation3 that "clinical research investigation of children ... which is not of direct benefit to the patient should be conducted, but only when the procedures entail negligible risk or discomfort and subject to the provisions of any common and statute law prevailing at the time. The parent or guardian should be consulted and his agreement recorded." The Medical Research Council statement4 questions the legal competence of parents to give such consent. The 1973 editorial in the Archives of Diseases in Childhood concurs with Curran and Beecher5 that "children under 14 may participate in clinical But it
Marlow, Bucks SL7
HELENOR PRATT
2BP
WHOOPING-COUGH VACCINATION
SiR,-The heated debate in Britain for or against whooping-cough vaccination seems puzzling on this side of the Atlantic. In the United States the incidence of pertussis has fallen in the past thirty years from some 120 000 cases per year to 1000-2000. And, while serious adverse reactions are known, I have yet to see one, although, as a public-health physician, I have over the years given or been responsible for at least 100 000 of these inoculations. There is little of the anxiety here, so prevalent in Britain about the whooping-cough vaccine, and in American medical j< ’rnals opposition to this immunisation is virtually non-existent. Are we overlooking veiled adverse effects? Are we dealing with a different product? Our combined diphtheria-pertussis-tetanus vaccine is certainly effective. In New Haven, a city of 140 000, we have had an average of 1 case of whooping-cough per year reported in the past ten years, and well over 85% of all children have received the vaccine, apparently without injury. I assume that the mode of administration is similar in Britain-i.e., it is given mainly in infancy and only up to the age of five. New Haven Health Department, New Haven, Connecticut 06511, U.S.A.
H. H. NEUMANN
was
7. Duncan, T., Care, A. D. Br. J. Surg. 1967, 54, 196. 1. Archs. Dis. Childh. 1973, 48, 751. 2. Constraints on the Advance of Medicine. Proc. R. Soc. Med. 1974, 67, 1311. 3. Royal College of Physicians Report on Ethics; p. 2. See Proc. R. Soc. Med.
1974, 67, 1308. 4. M.R.C. Statement on Medical Ethics Br. med. J. 1964, ii, 178. 5. Curran, W. J., Beecher, H. K. J. Am. med. Ass. 1969, 210, 77.
SALMONELLA MENINGITIS IN INFANTS
SIR,-In response to the report by Professor Denis and his colleagues (April 23, p. 910) of their experience in Senegal we would like to describe our experience of Salmonella meningitis in African children admitted to King Edward VIII Hospital during the period 1960-75. Among 3395 patients infected with various Salmonella enteritidis serotypes, 51 (1.5%) had Salmonella meningitis, including 6 caused by S. typhi. The
S. enteritidis serotype isolated from was typhimurium (see table). In 90% of cases meningitis was encountered in children less than a year old (median age three months), and the mortality-rate in the whole series was high (59%); most patients had other debilitating conditions such as malnutrition and bronchopneumonia. Treatment was with chloramphenicol, alone or in combination with gentamicin and/or sulphonamide; all drugs were most common
cerebrospinal
fluid
(c.s.F.)
Campbell, A. G. M. Br. med. J. 1974, iii, 334. 7. Harris, J. C. (retold by Jane Shaw). Uncle Remus Stories: Brer Rabbit and
6.
the Tar Baby.
1053 SEROTYPES, MORTALITY,
PHOSPHOLIPID COMPOSITION OF TRACHEAL ASPIRATES OF INFANTS WITH EARLY-ONSET GROUP-B STREPTOCOCCAL
AND AGE DISTRIBUTION IN SALMONELLA
MENINGITIS CASES
SEPSIS
*Results as % of
cal
phospholipid phosphorus.
picture resembling
R.D.S.
if infected with
group-B strepto-
cocci, but that the respiratory distress is not due to a deficiency or to an
alteration in surfactant
Rather, the respiratory distress
phospholipid composition.
to interference with surfactant function by bacterial products or tissue exudate, or to mechanical obstruction of alveoli with exudate.
*Available antisera insufficient for accurate identification.
given parenterally.
Salmonellee were isolated from C.S.F. alone and blood in 9, C.S.F. and stool in 5, and c.s.F., blood, and stool in 8. Organisms probably gained entry into the c.s.F. by haematogenous spread from primary infection in the gastrointestinal tract. in 29 cases,
c.s.F.
Departments of Microbiology and Pædiatrics, University of Natal Medical School, Durban, South Africa
La Jolla, California 92093, U.S.A.
Southwest Neonatal Center, Sunrise Hospital, Las Vegas, Nevada
BRIAN S. SAUNDERS T. ALLEN MERRITT
ELSA KIRKPATRICK LOUIS GLUCK
BERNARD H. FELDMAN
NECROTISING ENTEROCOLITIS P. C. APPELBAUM
J. SCRAGG
GROUP-B STREPTOCOCCI IN THE NEWBORN
SIR,-You refer (March 5, p. 520) to the striking clinical resemblance of early-onset group-B streptococcal infection in the newborn to the respiratory-distress syndrome (R.D.S.). Hyaline membranes are a prominent finding at necropsy in both conditions, and in cases of group-B sepsis streptococci have been demonstrated in the membranes.1 Although similar clinically and radiographically, the two syndromes show marked differences when pulmonary surfactant is examined. R.D.S. is the clinical expression of surfactant deficiency, and infants with R.D.S. have a deficiency of surfactant and an immature phospholipid pattern in tracheal effluent.2,3 In R.D.S. lecithin has less palmitic acid esterified to the beta carbon and phosphatidyl glycerol is absent.2 Three full-term infants with clinical symptoms similar to R.D.S. and culture-confirmed group-B sepsis were studied in our laboratory. Phospholipid composition of tracheal aspirates shows a mature pattern when separated by two-dimensional
thin-layer chromatography (table). Gas-liquid chromatography on the acetone-precipitable lecithin demonstrated that 69% of the beta carbon fatty acids were palmitic acid (mature pattern). The results suggest that early-onset group-B streptococcal sepsis does not alter the phospholipid pattern of pulmonary surfactant in full-term infants. The clinical counterpart of this is the finding by Ablow et al. that, for mechanical ventilations of patients with group-B streptococcal pneumonia, lower distending pressures are needed than in infants with R.D.S.4 We conclude that a full-term infant can present with a clini1. 2.
Department of Pediatrics, University of California, San Diego
may be due
Katzenstein, A. L., Davis, C., Braude, A. J. infect. Dis. 1976, 133, 430. Hallman, M., Feldman, B. H., Kirkpatrick, E., Gluck, L. Pediat. Res. (in the press). 3. Obladen, M., Merritt, T. A., Gluck, L. ibid. (in the press). 4. Ablow, R. C. and others New Engl J. Med. 1976, 294, 65.
SIR,-In your editorial (Feb. 26, p. 459) the most significant part for us was towards the end where you discuss the evidence that a major xtiological factor in necrotising enterocolitis (N.E.C.) is infection of the bowel wall with gram-negative organisms such as Klebsiella. This is important because these organisms are not available to produce infection in the gut of the breast-fed baby. The bacterial population is almost exclusively made up of bifidobacteria under these circumstances. It would thus be expected that, as has been proven in rats, breast milk would protect against N.E.C. More evidence of a direct type is needed. Breast milk has been used exclusively for lowbirthweight babies in the Children’s Hospital in Helsinki since the 1920s, and Dr N. Hallman tells us that N.E.C. is very rare there. There are some parallels between N.E.c. and the "pig-bel" of the New Guinea highlands. Both seen to be related to the bacterial flora in the intestinal canal-in N.E.C. with a dominance of gram-negative organisms and in pig-bel with clostridia. Division of Population, Family and International Health School of Public Health,
University of California, Los Angeles, California, 90024, USA
DERRICK B. JELLIFFE E. F. PATRICE JELLIFFE
BLOOD-LEAD AND MENTAL RETARDATION
SIR,-While prospective studies relating lead concentrations in blood obtained by heelprick to subsequent mental performance’ would seem a form of investigation free from bias, we will shortly2 be reporting on a very strong association between placental lead level and fetal and neonatal death; this leads us to believe that the concentration of lead in the placenta may often be secondary to disturbances in placental function associated with lethal fetal disease. 1. Moore, M. R., Meredith, P. A., Goldberg, A. Lancet, 1977, i, 717. 2. Wibberley, D. G., Khera, A. K., Edwards, J. H., Rushton, D. I. J. med. Genet. (in the press).
pranolol treated patients, when osteodystrophic repair would be expected to be most active. Follow-up of these patients from four months onwards showed normal S.A.P. levels, irrespective of preoperative preparation.
thyrocalcitonin release may indeed play some part in explaining transient falls in serum-calcium after thyroid operations, we feel that proponents of this idea should back it by using highly sensitive immunoassays of calcitonin now available. We cannot agree, however, that hypocalczmia lasting longer than a day can be so explained, and we believe that the avidity of thyrotoxic osteodystrophic bone for calcium is then the best explanation. Furthermore the thyroids of pigs pretreated with methylthiouracil had an impaired ability to secrete calcitonin.5 This might help to explain why the fall in While
serum-calcium in the series of Wilkin et al. was of greater statistical significance in the patients with functionally normal non-toxic goitre. W. MICHIE Departments of Surgery, Medicine, and J. M. STOWERS Chemical Pathology, S. C. FRAZER of Aberdeen University
mean
investigation which is not for their benefit where the studies are sound, promise important new knowledge and there is no discernible risk", adding the necessity for informed parental consent.
Campbe1l6 states "the only real protection for the individual scrupulousness, conscience and personal integrity of the investigator." But individual conscience varies too, and who then decides what is negligible risk, discomfort, and "inlies in the
formed" consent? Ethical committees are admirable in concept but "they vary in their membership, their influence and in There is no consistent their interpretation of their role ...
policy."6 Perhaps any further guidelines have to wait until, as Sir Cyril Clarkes suggests, someone makes a test case with the backing of a medical defence body: but, should such support be wanting, what individual doctor, acting against legal and protessional advice, is going to risk his head on the chopping block and rely on an ethical committee’s decision to stop it tumbling off. "Tar-baby, she ain’t saying nothing-and Brer Fox, he still lay low!"’ Town Farm, West Street,
RESEARCH ON INFANTS
SIR,-I am grateful to Dr Gairdner for the references in his letter (April 16, p. 852) concerning blood-sampling in infants but I cannot agree with his suggestion that I "need not have left the matter there". I did not. The Medical Defence Union confirmed the advice of the paediatrician on the local ethical research committee (i.e., that blood-sampling for research in infants was not legally permissible), and cautioned me against proceeding with this. I then referred, at the suggestion of the British Medical Association, to Professor Oppe, professor of paediatrics, London University, who, informed of the circumstances, supported this view. Both knew that my research programme (to determine whether the type of early feeding is related to the incidence of asthma in children) involved following up babies at home in preference to hospital outpatients, and that this included regular bloodsampling for assessment of immunoglobulins and milk antibodies. As Dr Dodge and Dr Evans point out in their letter (April 16, p. 852) there are risks in blood-sampling, however slight, and, in view of the advice I had been given, it did not seem justifiable to me (a mother, a doctor, and a magistrate) to proceed with this, when, although immunoglobulin studies are relevant, they are not essential to what I am trying to establish. This was a "value judgement",’ as it happens by a woman. (I note that all the writings I have seen in support of blood-
sampling are by men!) research blood-sampling in general which letter. prompted my The views of authoritative bodies vary from the Department of Health view expressed by Sir George Godber2 that it is not legitimate to do experiments in children which are not in the interests of that particular child, to the Royal College of Physicians recommendation3 that "clinical research investigation of children ... which is not of direct benefit to the patient should be conducted, but only when the procedures entail negligible risk or discomfort and subject to the provisions of any common and statute law prevailing at the time. The parent or guardian should be consulted and his agreement recorded." The Medical Research Council statement4 questions the legal competence of parents to give such consent. The 1973 editorial in the Archives of Diseases in Childhood concurs with Curran and Beecher5 that "children under 14 may participate in clinical But it
Marlow, Bucks SL7
HELENOR PRATT
2BP
WHOOPING-COUGH VACCINATION
SiR,-The heated debate in Britain for or against whooping-cough vaccination seems puzzling on this side of the Atlantic. In the United States the incidence of pertussis has fallen in the past thirty years from some 120 000 cases per year to 1000-2000. And, while serious adverse reactions are known, I have yet to see one, although, as a public-health physician, I have over the years given or been responsible for at least 100 000 of these inoculations. There is little of the anxiety here, so prevalent in Britain about the whooping-cough vaccine, and in American medical j< ’rnals opposition to this immunisation is virtually non-existent. Are we overlooking veiled adverse effects? Are we dealing with a different product? Our combined diphtheria-pertussis-tetanus vaccine is certainly effective. In New Haven, a city of 140 000, we have had an average of 1 case of whooping-cough per year reported in the past ten years, and well over 85% of all children have received the vaccine, apparently without injury. I assume that the mode of administration is similar in Britain-i.e., it is given mainly in infancy and only up to the age of five. New Haven Health Department, New Haven, Connecticut 06511, U.S.A.
H. H. NEUMANN
was
7. Duncan, T., Care, A. D. Br. J. Surg. 1967, 54, 196. 1. Archs. Dis. Childh. 1973, 48, 751. 2. Constraints on the Advance of Medicine. Proc. R. Soc. Med. 1974, 67, 1311. 3. Royal College of Physicians Report on Ethics; p. 2. See Proc. R. Soc. Med.
1974, 67, 1308. 4. M.R.C. Statement on Medical Ethics Br. med. J. 1964, ii, 178. 5. Curran, W. J., Beecher, H. K. J. Am. med. Ass. 1969, 210, 77.
SALMONELLA MENINGITIS IN INFANTS
SIR,-In response to the report by Professor Denis and his colleagues (April 23, p. 910) of their experience in Senegal we would like to describe our experience of Salmonella meningitis in African children admitted to King Edward VIII Hospital during the period 1960-75. Among 3395 patients infected with various Salmonella enteritidis serotypes, 51 (1.5%) had Salmonella meningitis, including 6 caused by S. typhi. The
S. enteritidis serotype isolated from was typhimurium (see table). In 90% of cases meningitis was encountered in children less than a year old (median age three months), and the mortality-rate in the whole series was high (59%); most patients had other debilitating conditions such as malnutrition and bronchopneumonia. Treatment was with chloramphenicol, alone or in combination with gentamicin and/or sulphonamide; all drugs were most common
cerebrospinal
fluid
(c.s.F.)
Campbell, A. G. M. Br. med. J. 1974, iii, 334. 7. Harris, J. C. (retold by Jane Shaw). Uncle Remus Stories: Brer Rabbit and
6.
the Tar Baby.
1053 SEROTYPES, MORTALITY,
PHOSPHOLIPID COMPOSITION OF TRACHEAL ASPIRATES OF INFANTS WITH EARLY-ONSET GROUP-B STREPTOCOCCAL
AND AGE DISTRIBUTION IN SALMONELLA
MENINGITIS CASES
SEPSIS
*Results as % of
cal
phospholipid phosphorus.
picture resembling
R.D.S.
if infected with
group-B strepto-
cocci, but that the respiratory distress is not due to a deficiency or to an
alteration in surfactant
Rather, the respiratory distress
phospholipid composition.
to interference with surfactant function by bacterial products or tissue exudate, or to mechanical obstruction of alveoli with exudate.
*Available antisera insufficient for accurate identification.
given parenterally.
Salmonellee were isolated from C.S.F. alone and blood in 9, C.S.F. and stool in 5, and c.s.F., blood, and stool in 8. Organisms probably gained entry into the c.s.F. by haematogenous spread from primary infection in the gastrointestinal tract. in 29 cases,
c.s.F.
Departments of Microbiology and Pædiatrics, University of Natal Medical School, Durban, South Africa
La Jolla, California 92093, U.S.A.
Southwest Neonatal Center, Sunrise Hospital, Las Vegas, Nevada
BRIAN S. SAUNDERS T. ALLEN MERRITT
ELSA KIRKPATRICK LOUIS GLUCK
BERNARD H. FELDMAN
NECROTISING ENTEROCOLITIS P. C. APPELBAUM
J. SCRAGG
GROUP-B STREPTOCOCCI IN THE NEWBORN
SIR,-You refer (March 5, p. 520) to the striking clinical resemblance of early-onset group-B streptococcal infection in the newborn to the respiratory-distress syndrome (R.D.S.). Hyaline membranes are a prominent finding at necropsy in both conditions, and in cases of group-B sepsis streptococci have been demonstrated in the membranes.1 Although similar clinically and radiographically, the two syndromes show marked differences when pulmonary surfactant is examined. R.D.S. is the clinical expression of surfactant deficiency, and infants with R.D.S. have a deficiency of surfactant and an immature phospholipid pattern in tracheal effluent.2,3 In R.D.S. lecithin has less palmitic acid esterified to the beta carbon and phosphatidyl glycerol is absent.2 Three full-term infants with clinical symptoms similar to R.D.S. and culture-confirmed group-B sepsis were studied in our laboratory. Phospholipid composition of tracheal aspirates shows a mature pattern when separated by two-dimensional
thin-layer chromatography (table). Gas-liquid chromatography on the acetone-precipitable lecithin demonstrated that 69% of the beta carbon fatty acids were palmitic acid (mature pattern). The results suggest that early-onset group-B streptococcal sepsis does not alter the phospholipid pattern of pulmonary surfactant in full-term infants. The clinical counterpart of this is the finding by Ablow et al. that, for mechanical ventilations of patients with group-B streptococcal pneumonia, lower distending pressures are needed than in infants with R.D.S.4 We conclude that a full-term infant can present with a clini1. 2.
Department of Pediatrics, University of California, San Diego
may be due
Katzenstein, A. L., Davis, C., Braude, A. J. infect. Dis. 1976, 133, 430. Hallman, M., Feldman, B. H., Kirkpatrick, E., Gluck, L. Pediat. Res. (in the press). 3. Obladen, M., Merritt, T. A., Gluck, L. ibid. (in the press). 4. Ablow, R. C. and others New Engl J. Med. 1976, 294, 65.
SIR,-In your editorial (Feb. 26, p. 459) the most significant part for us was towards the end where you discuss the evidence that a major xtiological factor in necrotising enterocolitis (N.E.C.) is infection of the bowel wall with gram-negative organisms such as Klebsiella. This is important because these organisms are not available to produce infection in the gut of the breast-fed baby. The bacterial population is almost exclusively made up of bifidobacteria under these circumstances. It would thus be expected that, as has been proven in rats, breast milk would protect against N.E.C. More evidence of a direct type is needed. Breast milk has been used exclusively for lowbirthweight babies in the Children’s Hospital in Helsinki since the 1920s, and Dr N. Hallman tells us that N.E.C. is very rare there. There are some parallels between N.E.c. and the "pig-bel" of the New Guinea highlands. Both seen to be related to the bacterial flora in the intestinal canal-in N.E.C. with a dominance of gram-negative organisms and in pig-bel with clostridia. Division of Population, Family and International Health School of Public Health,
University of California, Los Angeles, California, 90024, USA
DERRICK B. JELLIFFE E. F. PATRICE JELLIFFE
BLOOD-LEAD AND MENTAL RETARDATION
SIR,-While prospective studies relating lead concentrations in blood obtained by heelprick to subsequent mental performance’ would seem a form of investigation free from bias, we will shortly2 be reporting on a very strong association between placental lead level and fetal and neonatal death; this leads us to believe that the concentration of lead in the placenta may often be secondary to disturbances in placental function associated with lethal fetal disease. 1. Moore, M. R., Meredith, P. A., Goldberg, A. Lancet, 1977, i, 717. 2. Wibberley, D. G., Khera, A. K., Edwards, J. H., Rushton, D. I. J. med. Genet. (in the press).
