I was pleased to read the letter from Richards et al proposing a
collaberative study to validate the ILL criteria. Firstly, I support this
proposal fully.
I was interested in their statement regarding the ILL criteria in
those suspected of having meningococcaemia suggesting that the ILL
criteria are of limited use. The abstract they refer to presented at the
RCPCH meeting last year[1] state...
I was pleased to read the letter from Richards et al proposing a
collaberative study to validate the ILL criteria. Firstly, I support this
proposal fully.
I was interested in their statement regarding the ILL criteria in
those suspected of having meningococcaemia suggesting that the ILL
criteria are of limited use. The abstract they refer to presented at the
RCPCH meeting last year[1] states that the presence of poor capillary
refill, meningism, altered concious level, or tachypnoea identified 28 of
32 children with culture proven meningococcal disease. 3 of the 4 children
not identified had a maculopapular rash (ie not petechial?). Moreover, 12
of 32 children with meningococcal disease had total WCC greater than 15,
but we are not told if any of the "missed" cases had abnormal total white
cell count, or elevation of serum C reactive protein.
It must be emphasised that the full "ILL criteria" included 5
components, (irritability, low capillary refill, lethargy, abnormal total
white cell count, and abnormal C reactive protein), although Richards et
al have only concentrated on the first 3 risk factors. Furthermore, they
may have applied the criteria to children who did not have petechial rash
(the 3 "missed" children with meningococcal disease with maculopapular
rash).[1]
In order not to miss any cases of invasive bacteraemia, a screening
test with high sensitivity at the expense of specificity is desirable. We
proposed that the ILL criteria, in its full form, when applied to children
with fever and petechiae, operate as a "SnNOUT" test (if a test is highly
sensitive, if that test is negative the diagnosis can be ruled out)for
invasive bacteraemia. We cannot draw the same conclusions if only part of
the risk assessment analysis is applied, or the risk factors are applied
to children who do not have fever and petechiae.
Following my study of publication of work presented to the Paediatric
Research Society {PRS} and the British Paediatric Association {BPA}
Plenary sessions,[1] I sought further factors, which may affect
subsequent publication.
Using the same method of searching Medline, I
identified which of the 225 studies presented to sub-speciality groups of
the BPA in 1996 were published by October 2000.
I found 1...
Following my study of publication of work presented to the Paediatric
Research Society {PRS} and the British Paediatric Association {BPA}
Plenary sessions,[1] I sought further factors, which may affect
subsequent publication.
Using the same method of searching Medline, I
identified which of the 225 studies presented to sub-speciality groups of
the BPA in 1996 were published by October 2000.
I found 111 (49%) were published. This meant 143 (54%) of plenary and sub-
speciality studies presented to the BPA in 1996 were published within 4
years.
Sub-speciality studies were published in 61 different journals; 19
paediatric. 77 articles (54%) were in paediatric journals, 46 in Archives
of Disease in Childhood.
Publication rates varied with specialty group, type of study and the place
where the study was done. Publication rates in sub-specialty groups varied
from 100% (4/4) to 0% (0/12). Sixteen studies were randomized controlled
trials, 13 of which were published. Only 1 of 17 (6%) studies from
District General Hospitals was published, compared with 118/218 (54%) from
University departments or teaching hospitals.
Submission for publication strongly influences publication rate. However,
study design and place where the study was done also affect publication of
studies presented to scientific meetings.
F Andrew I Riordan
Birmingham Heartlands Hospital
Birmingham, UK
(1) Riordan FAI. Do presenters to paediatric meetings get their work
published? Arch Dis Child 2000;83:524-6.
As Jaster mentioned in his letter,[1] some cases of sudden unexpected
death in children and adolescents associated with tumors of the brainstem
have been reported. Most of these tumors sized more than 2 cm.[2][3]
Sudden unexplained death (similar to sudden infant death syndrome (SIDS))
is diagnosed when no cause of death is found after an exhaustive
postmortem investigation including a complete auto...
As Jaster mentioned in his letter,[1] some cases of sudden unexpected
death in children and adolescents associated with tumors of the brainstem
have been reported. Most of these tumors sized more than 2 cm.[2][3]
Sudden unexplained death (similar to sudden infant death syndrome (SIDS))
is diagnosed when no cause of death is found after an exhaustive
postmortem investigation including a complete autopsy, toxicological
analysis and review of the medical history.
Concerning our report,[4] in all cases a complete gross and
histological examination was performed and in none of the 11 unexplained
deaths any brainstem or other neuropathological lesion was observed.
Benito Morentin
Instituto Vasco de Medicina Legal
Buenos Aires, 4-6.
Bilbao (Basque Country). E- 48001.
Fax: + 94 401 66 27
References
(1) J Howard Jaster. Some cases of unexpected sudden death are
associated with tumors [eLetter]. Arch Dis Child 29 November 2000.
(2) Opeskin K, Ruszkiewicz A, Anderson R McD. Sudden death due to
undiagnosed medullary-pontine astrocytoma. Am J Forensic Med Pathol
1995;16:168-71.
(3) Gleckman AM, Smith TW. Sudden unexpected death from primary
posterior fossa tumors. Am J Forensic Med Pathol 1998;19:303-8.
(4) Morentin B, Garamendi PM, Aguilera B, Suarez-Mier MP. Sudden
unexpected non-violent death between 1 and 19 years in north Spain. Arch
Dis Child 2000;82:456-61.
We were interested to read Brogan and Raffles audit of the management
of fever and petechiae.[1] This is an important audit for many general
paediatricians in the UK. In Newcastle 36% of children with petechiae were
treated with antibiotics, only 10% had meningococcal disease (MCD). Brogan
and Raffles correctly state that more studies are required to validate
their proposed guideline. We offer two such studie...
We were interested to read Brogan and Raffles audit of the management
of fever and petechiae.[1] This is an important audit for many general
paediatricians in the UK. In Newcastle 36% of children with petechiae were
treated with antibiotics, only 10% had meningococcal disease (MCD). Brogan
and Raffles correctly state that more studies are required to validate
their proposed guideline. We offer two such studies:
(1) The ILL criteria (irritability, lethargy, low capillary refill) were applied retrospectively to a cohort of
children presenting with petechiae who were part of a multi-centre
prospective study of MCD from Merseyside, UK.[2] The ILL criteria would have
identified all except two of 66 children with MCD and petechiae. Both
those not identified presented with seizures, one had meningism, the other
a maculopapular rash. However, the ILL criteria were also present in 62 of
65 children with petechiae initially thought to have MCD, whose final
diagnosis was a viral illness. In this cohort the features that suggested
MCD were tachypnoea or signs of meningitis or septicaemia.[3] The ILL
criteria are therefore of limited use in children already suspected of
having MCD.
Local paediatricians-in-training asked for an algorithm to help
assess children with fever and petechiae. We therefore designed an
algorithm which includes risk factors from previous studies (recently
reviewed[4]), the ILL criteria, the criteria from the above Merseyside
study and a period of observation (a copy of this algorithm is available on request from the author - unfortunately eLetters do not support illustrations). We introduced this
algorithm into routine use in our hospitals this year. We are
prospectively validating its use.
(2) During the first three months 49 children presented with
petechiae. Only one child had meningococcal disease. The algorithm was
correctly followed in 34 (68%) children; this included prompt treatment
for the child with MCD. For 15 children the algorithm was not followed; 7
were given antibiotics when not indicated, 8 were not treated when the
algorithm suggested they should be.
It is obviously vitally important that antibiotics are not withheld
from children with possible MCD. When paediatricians suspects MCD they
should give prompt antibiotic treatment and then seek to confirm the
diagnosis.
Any algorithm for the management of children with fever and petechiae
must be shown to be clinically valid.[5] A large number of cases will be
needed to show our algorithm is safe and effective. This requires
collaboration between a number of centres. Any centre wishing to help
validate our algorithm would be welcome to do so: please contact one of
the authors.
Chris Richards
Ansgar Thimm
Royal Victoria Infirmary
Newcastle, UK
Julia Clark
Newcastle General Hospital
Newcastle, UK
Alistair PJ Thomson
Leighton Hospital
Crewe, UK
Tina Newton
F Andrew I Riordan
Birmingham Heartlands Hospital
Birmingham, UK
References
(1) Brogan PA, Raffles A. The management of fever and petechiae: Making sense of rash decisions. Arch Dis Child 2000;83:506-7.
(2) Riordan FAI, Thomson APJ, Sills JA, Hart CA. Who spots the spots?
The diagnosis and treatment of early meningococcal disease in children.
BMJ 1996;313:1255-6.
In the management of idiopathic thrombocytopenic purpura
(ITP) Bolton-Maggs[1] stated that "when treatment is required, options
include oral steroids, intravenous immunoglobulin (IVIG) and lately, anti-D for patients who are rhesus D positive", without taking into
consideration our mega dose methylprednisolone (MDMP) administration.[2]
In
our study the patients with acute ITP were divided into three gr...
In the management of idiopathic thrombocytopenic purpura
(ITP) Bolton-Maggs[1] stated that "when treatment is required, options
include oral steroids, intravenous immunoglobulin (IVIG) and lately, anti-D for patients who are rhesus D positive", without taking into
consideration our mega dose methylprednisolone (MDMP) administration.[2]
In
our study the patients with acute ITP were divided into three groups:
no
treatment
oral steroid (2 mg/kg for 2 weeks)
MDMP (30 mg/kg
initially intravenously, orally 30 mg/kg for 3 days, and 20 mg/kg for 4
days lately[3]).
The results of our original study which includes
corresponding antiplatelet determinations, indicated that oral (2 mg/kg)
steroid in raising platelet count was not more effective than no treatment, it may actually delay the spontaneous improvement.[2] But MDMP was
very effective in 3 days which is supported by the others.[4][5] Therefore,
if treatment is required MDMP, iv or orally which is more convenient,
should not be ignored, since it is cheaper, effective and more easily
applied.
However, if parents are convinced, children with ITP could be followed
without treatment. About 20-30% chronicity in childhood ITP seems to be
higher according to our findings. Relapses occur about 5% and chronicity
in 11.4% of children respectively with conventional (2 mg/kg) steroid
which is more close to of Dickerhoff and von ruecker recent finding.[6] MDMP chronicity was observed in 4 of 59 (6.8%) children with acute ITP.
If this effect of MDMP is supported by other reserchers, it could be more
advised for the treatment of patients with acute ITP.
Þinasi Özsoylu MD
Prof of Pediatrics and Hematology
Fatih University Medical Faculty
Alparslan Türkeþ cad. No.57, 06510 Emek-ANKARA, Turkey
(2) Özsoylu Þ, Ýrken G, Karabent A. High dose intravenous methyprednisolone
for acute childhood thrombocytopenic purpura. Eur J Haematol 1989;42:431-5.
(3) Özsoylu Þ, Þaylý RT, Öztürk G. Oral megadose methylprednisolone versus
intravenous immunglobulin for acute childhood idiopathic thrombocytopenic
purpura. Pediatr Hematol Oncol 1993;10:317-21.
(4) van Hoff J, Ritchey AK. Pulse methylprednisolone therapy for acute
childhood idiopathic thrombocytopenic purpura. J Pediatr 1988;113:563-6.
(5) Del Principe D, Menichelli A. Methylprednisolone in childhood
idiopathic thrombocytopenic purpura. Acta Haematol 1988;79:224-6.
(6) Dickerhoff R, von Ruecker A. The clinical course of immune
thrombocytopenic purpura in children who did not receive intravenous
immunoglobulins or sustained prednisone treatment. Pediatrics 2000;137:629-2.
I read with interest the comments by Leslie and Gibson concerning my
reference[1] to their study.[2] They describe their study as the first
on ICSI conceived children with controls but make no reference to the
study by Bonduelle et al[3] in the same edition of the Lancet, which had
contradictory findings. I previously corresponded[4] at the time their
study was published concerning their findings a...
I read with interest the comments by Leslie and Gibson concerning my
reference[1] to their study.[2] They describe their study as the first
on ICSI conceived children with controls but make no reference to the
study by Bonduelle et al[3] in the same edition of the Lancet, which had
contradictory findings. I previously corresponded[4] at the time their
study was published concerning their findings and wish to respond to their
points.
Power In their small single-centre study, a difference of 6.6 was found
between the mean mental development index (MDI) of the ICSI group and that
of a normally conceived control group (95.9 vs 102.5). However, a power
calculation based on this difference and the test intrinsic SD of 15
showed that to achieve 95% CI, at least 135 children would be needed in
each group. A control group of 80 children would achieve power of
only 79.4%.
It is unfortunate that Leslie and Gibson chose to refer only to the
interim findings of the UK population study of ICSI conceived children
rather than the final findings for comparisons of power. These findings
were presented at ESHRE meeting in Tours, France, 1999[5] at which Gibson
was present. These findings are presently being considered by a major
international journal but suffice it to say that the 208 ICSI conceived
toddlers and 221 normally conceived well matched controls were strikingly
similar in their neurodevelopmental abilities (5) at mean age 18 months. In this study there was a power of greater than 99% to detect a 5 point
difference in the newly standardised Griffiths scales of mental
development between study and control groups.
Multiple observers In their study there were two observers. In the UK population study
only one. Unfortunately a common reason for invalid results in such
studies is interobserver error, since 100% agreement between observers
seldom occurs.
Unstandardised testing systems Leslie and Gibson defend their use of the Bayley scales but do not
acknowledge that these scales had not been standardised in Australia. The
reassuring report from Bonduelle et al referred to above[3] also used the
Bayley scales but their translated version had been standardised against
the indigent population of Dutch speaking children.
To put the significance of non-standardisation into a more general
context, during the restandardisation of the Griffiths scales of mental
development (1996) the scales were compared to scales standardised in the
early 70s. It was noted a toddler of average ability when tested in 1996
(mean score 100) would get a mean score of 107.8 on the old scales. Leslie
and Gibson refer to testing children close to twenty-four months and
possible pitfalls of this in the application of the scales. Allowance was
made in the design of the new Griffiths scales for children of above
average ability but I acknowledge that 2 children in each group (2 out of
208 study and 2 out of 221 controls) may have been theoretically affected
by this.
Failure to allow for confounders Unfortunately the Sydney study chose to use control children
recruited from an earlier study (ie, retrospective controls). This may
have made the study results available quicker but is scientifically
unwise. Colleagues in Sydney have also questioned the different
socioeconomic features of the neighborhoods from whence the control and
study children were recruited.
Of the original 108 pregnancies, I note 38 were from embryos replaced
after cryopreservation. Minor developmental deficits have already been
noted in children born after replacement of cryopreserved embryos before
the introduction of ICSI.[6] Although in the UK study there were a few
minor confounders for neurodevelopmental outcome this was allowed for in
the analysis.
There is an ongoing European 5 nation study of ICSI conceived
children at aged 5 years (ICSI-CFO; International Collaborative Study of ICSI - Child and Family Outcomes).
Involving 650 ICSI conceived children, 650 normally conceived control
children and a 650 IVF comparison group this should give further
information about longer term outcome.[7]
The paper by Bowen, Lesley, Gibson et al[2] has increased awareness
of the necessity to enquire about outcome after ICSI. It also had many
good points such as the inclusion of multiple births and the blinding of
the two observers involved to outcome. However the anxiety the paper
caused to the families who have benefited from this treatment and their
associated fertility treatment teams worldwide was probably not warranted
in view of my comments above.
Alastair G. Sutcliffe MD, MRCP, MRCPCH
Lecturer in Child Health
Centre for Community Child Health Studies
Department of Paediatrics
Royal Free Campus
Royal Free and University College Medical School
University College London, Rowland Hill Street
Hampstead, London NW3 2PF, UK
References
(1) Sutcliffe A G. Intracytoplasmic sperm injection and other aspects
of new reproductive technologies. Arch Dis Child 2000;83:98-100.
(2) Bowen JR, Gibson FL, Leslie GI, Saunders DM. Medical and
developmental outcome at 1 year for children conceived by intracytoplasmic
sperm injection. Lancet 1998;351:1529-31.
(3) Bonduelle M, Joris H, Hofmans K, Liebaers I, Van Steirteghem.
Mental development of 201 ICSI children at 2 years of age Lancet
1998;351:1553.
(4) Sutcliffe A G, Taylor B, Li J, Grudzinskas G, Thornton S, Lieberman B, Children conceived by intracytoplasmic sperm injection.
Lancet 1998;352:578-9.
(5) Sutcliffe A G, Taylor B, Li J, Grudzinskas G, Thornton S, Lieberman B,
UK study of children born after Intracytoplasmic sperm injection [abstract 0-018]. Human Reproduction 1999;14:13.
(6) Sutcliffe AG, DeSouza SW, Cadman J, Richards B, McKinlay IA,
Lieberman B. Outcome in children from cryopreserved embryos. Arch Dis Child 1995;72:290-3.
(7) Sutcliffe AG, Bonduelle M, Tarlatzis V, Loft A, Wennerholm U-B. ICSI-CFO an International collaborative study of ICSI - child and family
outcomes: European Commission research contract No: QLG4 - 2000 - 00545.
l'Hoir et al suggest that the male excess in SIDS is created by more
infant males sleeping or turning prone than females. This does not appear
to be the case because the male fraction in SIDS remained constant after
the campaign to reduce prone sleeping in the USA.
Using US SIDS data
obtained at the CDC WONDER web site, wonder.cdc.gov, I tested the male
SIDS rates for all races in the age group 28 t...
l'Hoir et al suggest that the male excess in SIDS is created by more
infant males sleeping or turning prone than females. This does not appear
to be the case because the male fraction in SIDS remained constant after
the campaign to reduce prone sleeping in the USA.
Using US SIDS data
obtained at the CDC WONDER web site, wonder.cdc.gov, I tested the male
SIDS rates for all races in the age group 28 to 364 days as neonatal
infants cannot turn themselves. In the period 1979-91 before the
back-to-sleep campaign there were 39,252 male SIDS and 25,430 female SIDS cases,
for a male fraction of 0.605. In the period 1992-98 when the back-to-sleep campaign caused an average SIDS rate decline by 35%,the male SIDS
were 14,705 and the female SIDS were 9,543 for a male fraction 0.606.
Therefore, the excess male fraction in SIDS appears to be constant,
independent of the change in fractions of prone sleep of the male and
female infants, so the mechanism for creating the constant male excess in
infant mortality must be found elsewhere.
I read with interest the report of Morentin et al[1] describing
unexpected sudden death occurring between the ages of 1 and 19 years. Of
the 34 cases described eleven remained unexplained. The authors failed to
mention whether neuropathologic examination was performed in the eleven
unexplained cases, and why such examination is essential.
Tumors and infarctions of the brainstem, especially the me...
I read with interest the report of Morentin et al[1] describing
unexpected sudden death occurring between the ages of 1 and 19 years. Of
the 34 cases described eleven remained unexplained. The authors failed to
mention whether neuropathologic examination was performed in the eleven
unexplained cases, and why such examination is essential.
Tumors and infarctions of the brainstem, especially the medulla
oblongata, have been discovered at postmortem examination in some cases of
unexpected sudden death where death could not otherwise be explained. In
the age group studied by the authors most reported cases have involved
tumors[2][3] as is also true for infants[4] and young adults .[3][5] In
the elderly most reported cases have described infarctions.[6-12]
The mechanism of unexpected sudden death associated with brainstem
tumors and infarctions is unknown,[9][11-13] as is the manner in which
the mechanism may vary with age of the patient, type of pathology, or
specific location within the brainstem.
References
(1) Morentin B, Garamendi PM, Aguilera B, Suarez-Mier MP. Sudden
unexpected non-violent death between 1 and 19 years in north Spain. Arch
Dis Child 2000;82:456-61.
(2) Nelson J, Frost JL, Schochet SS. Sudden, unexpected death in a 5-
year-old boy with an unusual primary intracranial neoplasm: ganglioglioma
of the medulla. Am J Forensic Med Pathol 1987;8:148-52.
(3) Gleckman AM, Smith TW. Sudden unexpected death from primary
posterior fossa tumors. Am J Forensic Med Pathol 1998;19:303-8.
(4) Matturri L, Ottaviani G, Rossi L. Sudden and unexpected infant
death due to an hemangioendothelioma located in the medulla oblongata. Adv Clin Path 1999;3:29-33.
(5) Opeskin K, Ruszkiewicz A, Anderson R McD. Sudden death due to
undiagnosed medullary-pontine astrocytoma. Am J Forensic Med Pathol
1995;16:168-71.
(6) Jaster JH, Porterfield LM, Bertorini TE, Dohan FC Jr, Becske T.
Cardiac arrest following vertebrobasilar stroke. J Tenn Med Assoc
1995;88:309.
(7) Jaster JH, Porterfield LM, Bertorini TE, Dohan FC Jr, Becske T.
Stroke and cardiac arrest [letter]. Neurology 1996;47:1357.
(8) Jaster JH, Smith TW. Arrhythmia mechanism of unexpected sudden
death following lateral medullary infarction. Tenn Med 1998;91:284.
(9) Jaster JH, Smith TW, Gleckman AM. A medullary syndrome
characterized by wild arm ataxia [letter]. Neurology 2000;55:321.
(10) Jaster JH. Unexpected sudden death after lateral medullary
infarction.
J Neurol Neurosurg Psychiatry [letter]. [In press]
(11) Carod Artal FJ, Cuadrado Perez ML, Gonzalez Gutierrez JL, Egido
Herrero JA.
Trastorno autonomico y muerte subita en un caso de sindrome de Wallenberg.
Neurologia 1997;12:46-7.
(12) Andres del Barrio MT, De las Heras Revilla V, Martin Estefania C,
Gonzalez, Gutierrez JL. Fallo respiratorio secundario a disautonomia en el
infarto bulbar lateral. Neurologia 1998;13:312-13.
(13) Perez de Llano LA, Pego Reigosa R, Branas Fernandez F. Comentario a
Fallo respiratorio secundario a disautonomia en el infarto bulbar lateral.
Neurologia 1999;14:94-5.
Following the publication of our paper,[1] we would like to thank the
authors for their comments and respond to them to clarify our study
methodology, interpretation of the data, the impact of the media and on
the directions of future work in this area.
The possibility of PCR contamination has been suggested by Franciosi
an...
Following the publication of our paper,[1] we would like to thank the
authors for their comments and respond to them to clarify our study
methodology, interpretation of the data, the impact of the media and on
the directions of future work in this area.
The possibility of PCR contamination has been suggested by Franciosi
and Koletzko and we agree that this is a potential problem in studies of
this type. We guarded against this by utilisation of separate laboratory
areas and pipettes for pre-PCR, PCR and post-PCR stages of the procedure,
use of sterile bunged pipette tips and inoculation of the positive control
as a last step in the pre-PCR preparation. In each run, we used sterile
distilled water and DNA extract from human ureter as negative controls,
and we examined samples in duplicate. Throughout our study, duplicated
samples consistently gave concordant results, and negative controls were
consistently negative.[1]
Dr Koletzko suggests that the two separate nested PCR-ELISAs utilised
in our study may have doubtful specificity as we did not sequence the
products. We agree that amplicon sequencing is desirable not only to
ensure specificity but in the present context would also provide
additional data on the molecular epidemiology of the cagA gene which was
detected in these cases. We believe our assays to be specific. For
example, the binding of oligonucleotides of 20 or more bases to template
DNA at 55ºC has been shown to be 100% specific. And in one of our PCR-
ELISAs, there were five such interactions.[1] We agree with Dr Koletzko and
other workers that it would be valuable to test other tissues from the
same patients by the same method.
Regarding our controls, use of these cases is quite appropriate and
to illustrate this we include additional relevant data in the Table. Dr
Vieth says our controls have had no normal environmental contact, however,
five of these eight had spent time in the home environment since birth
(Table). Regarding antibiotic treatment, only one control had received
antibiotics for more than one day prior to death, and this is the case in
which H pylori was detected (Table).
Information on antibiotic exposure, environmental exposure and PCR-ELISA
testing for H pylori ureC and cagA genes in the stomach, trachea and lung
of control cases used in the study: An association between sudden infant
death syndrome (SIDS) and Helicobacter pylori infection.[1] Results of
PCR-ELISA testing is expressed as optical density. Those specimens with
a cut-off value greater than or equal to the mean plus two times the standard
deviation of these controls (designated negative) are marked with an asterisk.
Case No.
Age at death (weeks)
Cause of death
Time of diagnosis
Antibiotic exposure
Exposure to the home
environment >1 month
H pylori ureC
gene
H pylori cagA
gene
Stomach
Trachea
Lung
Stomach
Trachea
Lung
C1
3
Prematurity
AM
-
-
0.100
0.150
0.180
0.120
0.130
0.090
C2
4
Prematurity
AM
-
-
NT
0.200
0.090
NT
0.120
0.100
C3
7
Ileal perforation
AM
+
-
0.265
* 0.298
0.283
* 0.414
* 0.303
0.317
C4
7
Necrotising enterocolitis
AM
1 day only
+
0.200
0.150
0.180
0.120
0.200
0.150
C5
20
E coli septicaemia
PM
-
+
0.170
0.160
0.177
0.150
0.120
0.160
C6
24
Suffocation
PM
-
+
0.210
0.080
NT
0.150
0.090
NT
C7
32
Pneumonia
PM
-
+
NT
0.130
0.180
NT
0.150
0.180
C8
44
Pneumococcal septicaemia
PM
-
+
0.100
0.140
NT
0.120
0.090
NT
Mean
0.174
0.163
0.181
0.179
0.150
0.166
±SD
±0.065
±0.063
±0.060
±0.116
±0.071
±0.080
C1, control case number 1;
AM, ante-mortem; PM, post-mortem; NT, not tested
Dr Koletzko states that "the fact that H pylori was not demonstrated
in the stomach, trachea or lung by histology in any of the children must
raise major concerns that the applied methods were not specific." However,
as pointed out by Dr Vieth, haematoxylin and eosin staining, although a
routinely used stain in histopathology practice, may not be optimal for
microscopic visualisation of H pylori.
In response to Dr Vieth's claim that our suggested role for
interleukin-1beta (IL-1beta) in H pylori infection is "totally speculative", we
would like to point out that these mechanisms have been demonstrated in an
animal model.[2][3] Also, proteins of H pylori are known to activate
macrophages leading to production of IL-1beta[4-6] which is known to inhibit
acid secretion by parietal cells and may actually be the most potent
inhibitor of acid secretion discovered to date.[7] IL-1beta gene
polymorphisms associated with increased IL-1beta production have recently
been associated with an increased risk of gastric cancer.[8] In addition,
systemic and mucosal humoral recognition of the cagA protein has been
linked with peptic ulceration,[9][10] duodenal ulcer patients may more
frequently harbour cagA+ H pylori strains,[6][10] and it has been
demonstrated that infection with cagA+ as compared with cagA- strains is
associated with increased transcription of IL-1beta.[6] It is therefore
interesting that 25 of 28 cases of H pylori-associated SIDS in our study
had a detectable cagA gene in their tissues,[1] which may provide further
support for the proposed pathogenesis of H pylori in SIDS and a
contributory role for IL-1beta.[11]
Dr Paul Beggs from Macquarie University in Australia points out the
link between dwelling crowding and H pylori infection,[12][13] which has
been shown to be independent of socioeconomic status,[14] and the need for
research on the possible link between dwelling crowding and SIDS. We agree
that "given the importance of SIDS and the growing body of evidence
suggesting H pylori as a cause of SIDS, it would be pertinent for future
studies to consider dwelling crowding in more detail."
We feel that Wiklund and colleagues and MacKay and colleagues have
misunderstood the proposed hypothesis. Wiklund states that total breakdown
of ingested urea occurs in all normal infants without ammonia intoxication
and that SIDS victims have undigested urea in their faeces. MacKay states
that "it is difficult to imagine that an organism specifically adapted to
the microaerophilic and acidic conditions of the gastric mucosa thriving
well enough in the lung to produce toxic amounts of ammonia in infants
that presumably had normal livers." To reiterate, there are two parts to
the hypothesis. First, interleukin-1b production in the H pylori-infected
stomach, and second, supply of ammonia to the systemic circulation11 (and
not the hepatic circulation as MacKay implies). Therefore, faecal urea
content is irrelevant and so is ammonia produced in the stomach as this
will be detoxified by the liver.
Regarding comments in the media, these are clearly not under our
control and we have always stated that our findings are preliminary and
require confirmation.
In conclusion, we would encourage researchers to repeat our studies
and those of Pattison and colleagues[15-17] in order to clarify the
proposed role of H pylori in SIDS. In the meantime, we re-emphasise
accepted measures to reduce mortality from SIDS and suggest the following
additional precautions, all of which constitute good personal hygiene and
are therefore advisable even in the absence of such a link. First, to
prevent the transfer of saliva from the mouths of carers to babies.
Second, prompt disposal of vomitus, decontamination of soiled surfaces,
and washing of soiled clothes/bedclothes, followed by hand washing, in
order to minimise transmission to the baby via the gastro-oral route.
Third, good general hand and personal hygiene. In addition, parents should
be reassured that they do not need to do anything more than the above at
present.
JR Kerr
JP Burnie
Infectious Diseases Research Group
The University of Manchester
AJ Barson
Department of Paediatric Pathology
The University of Manchester
Clinical Sciences Building
Manchester Royal Infirmary
Oxford Road, Manchester M13 9WL, UK
References
(1) Kerr JR, Al-Khattaf A, Barson AJ, Burnie JP. An association
between sudden infant death syndrome (SIDS) and Helicobacter pylori
infection. Arch Dis Child 2000;83:429-34.
(2) Pattison CP, Marshall BJ, Scott LW, Herndon B, Willsie SK.
Proposed link between Helicobacter pylori and sudden infant death syndrome
(SIDS): possible pathogenic mechanisms in an animal model. I. Effects of
intratracheal urease. Gastroenterology 1998;114:G3689.
(3) Pattison CP, Scott LW, Herndon B, Willsie SK. Proposed link
between Helicobacter pylori and SIDS: possible pathogenic mechanisms in an
animal model. II. Effects of intratracheal urease after pretreatment with
intravenous IL-1 beta. Gastroenterology 1998;114:G3690.
(4) Noach LA, Bosma B, Jansen J, Hoek FJ, vanDeventer SJ, Tytgat GN.
Mucosal tumour necrosis factor-a, interleukin-1b, and interleukin-8
production in patients with Helicobacter pylori infection. Scand J
Gastroenterol 1994;29:425-9.
(5) Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, Imanishi J.
Expression of cytokine mRNA in gastric mucosa with Helicobacter pylori
infection. Scand J Gastroenterology 1995;30:1153-9.
(6) Peek RM, Miller GG, Tham KT, et al. Heightened inflammatory
response and cytokine expression in vivo to cagA+ Helicobacter pylori
strains. Lab Invest 1995;73:742-5.
(7) Wallace JL, Cucala M, Mugridge, Parente L, Secretagogue-specific
effects of interleukin-1 on gastric acid secretion. Am J Physiol
1991;261:G559-64.
(8) El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1
polymorphisms associated with increased risk of gastric cancer. Nature
2000;404:398-402.
(9) Crabtree JE, Taylor JD, Wyatt JI, et al. Mucosal IgA recognition
of Helicobacter pylori 120 kDa protein, peptic ulceration and gastric
pathology. Lancet 1991;338:332-5.
(10) Cover TL, Glupczynski Y, Lage AP, et al. Serologic detection of
infection with cagA+ Helicobacter pylori infections. J Clin Microbiol
1995;33:1496-500.
(11) Pattison CP, Marshall BJ. Proposed link between Helicobacter
pylori and sudden infant death syndrome. Med Hypotheses 1997:49:365-9.
(12) Fall CHD, Goggin PM, Hawtin P, Fine D, Duggleby S. Growth in
infancy, infant feeding, childhood living conditions, and Helicobacter
pylori infection at age 70. Arch Dis Child 1997;77:310-14.
(13) Webb PM, Knoght T, Greaves S, et al. Relation between infection
with Helicobacter pylori and living conditions in childhood: evidence for
person to person transmission in early life. BMJ 1994;308:750-4.
(14) Elitsur Y, Short JP, Neace C. Prevalence of Helicobacter pylori
infection in children from urban and rural West Virginia. Dig Dis Sci
1998;43:773-8.
(15) Pattison CP, Marshall BJ, Young TW, Vergara GG. Is Helicobacter
pylori the missing link for sudden infant death syndrome? Gastroenterology
1997;112(4SS):A254.
(16) Pattison CP, Vergara GG, Young TW, Smith GP. Prevalence of
Helicobacter pylori in sudden infant death syndrome. Gastroenterology
1998;114:G3688.
(17) Pattison CP, Smoot DT, Ashtorab H, Vergara GG, Young TW, Smith
GP. Confirmation of Helicobacter pylori by PCR in sudden infant death
syndrome. Gastroenterology 1998;114:G3686.
Dear Editor:
I was pleased to read the letter from Richards et al proposing a collaberative study to validate the ILL criteria. Firstly, I support this proposal fully.
I was interested in their statement regarding the ILL criteria in those suspected of having meningococcaemia suggesting that the ILL criteria are of limited use. The abstract they refer to presented at the RCPCH meeting last year[1] state...
Following my study of publication of work presented to the Paediatric Research Society {PRS} and the British Paediatric Association {BPA} Plenary sessions,[1] I sought further factors, which may affect subsequent publication.
Using the same method of searching Medline, I identified which of the 225 studies presented to sub-speciality groups of the BPA in 1996 were published by October 2000. I found 1...
Dear Editor:
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In our study the patients with acute ITP were divided into three gr...
Dear Editor,
I read with interest the comments by Leslie and Gibson concerning my reference[1] to their study.[2] They describe their study as the first on ICSI conceived children with controls but make no reference to the study by Bonduelle et al[3] in the same edition of the Lancet, which had contradictory findings. I previously corresponded[4] at the time their study was published concerning their findings a...
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Dear Editor,
Following the publication of our paper,[1] we would like to thank the authors for their comments and respond to them to clarify our study methodology, interpretation of the data, the impact of the media and on the directions of future work in this area.
The possibility of PCR contamination has been suggested by Franciosi an...
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