Professor Salazar-De-Sousa,[1] commenting on the recent paper by Høst et al,[2] maintains that recent prospective and randomised clinical studies have shown that
soy protein (SP) is as allergenic as cow's milk (CM) protein citing a review paper[3]; however, the author failed to detail which are these studies.
In 1990 we demonstrated[4] that Eastham et al[5] have shown an antibody response to SPs in...
Professor Salazar-De-Sousa,[1] commenting on the recent paper by Høst et al,[2] maintains that recent prospective and randomised clinical studies have shown that
soy protein (SP) is as allergenic as cow's milk (CM) protein citing a review paper[3]; however, the author failed to detail which are these studies.
In 1990 we demonstrated[4] that Eastham et al[5] have shown an antibody response to SPs in all SP-fed infants that was comparable to that found to CM in CM-fed infants. However, only soy antigenicity was studied,[4] since the authors measured not IgE antibodies but hemagglutinins to soy and to CM, which mainly belong to IgG antibodies.[5] As the
matter remained controversial, I have published a paper with 142 references and 7 tables, encompassing all diverse aspects of SPs.[6]
If Professor Salazar-De-Sousa reads attentively the data shown in the tables of the paper, he shall convince himself that SFs are recommended for the treatment and/or
prevention of food allergy, also following a recent document of the American Academy of Pediatrics.[7] However, we were distressed about the news "against soy formulas" that we read on the literature, such as "soy formulas should not
prescribed to allergic infants, due to the high incidence of
crossreactions with cow milk proteins".[8]
Professor Salazar, however, appears to be really interested in hydrolysate formulas (HFs). We have documented 202 reactions to HFs in a paper, and 41 case-reports in
another. In total 17 cases of shock-anaphylaxis (one every 3.3 years) versus one/22.3 years provoked by SPFs, with a difference of 676%.
ARNALDO CANTANI
University Professor of Pediatrics Professor of Pediatric Allergy and Immunology University of Roma "La Sapienza"
MONICA MICERA University of Roma "La Sapienza"
References
(1) Salazar-De-Sousa J. Dietary products used in infants for treatment and prevention of food allergy [letter]. Arch Dis Child 2000;83:88.
(2) Høst A, Koletzko B, Dreborg S, et al Dietary products used in infants for treatment and prevention of food allergy. Joint Statement of the European Society for Paediatric Allergology and Clinical Immunology Committee on Hypoallergenic Formulas and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
Committee on Nutrition. Arch Dis Child 1999;81:80-4.
(3) Kerner JA. Use of infant formulas in preventing or postponing atopic manifestations. J Pediatr Gastroenterol Nutr 1997;24:442-6.
(4) Cantani A, Ferrara M, Ragno W, Businco L. Efficacy and safety of a soy-protein-formula for feeding
babies with atopic dermatitis and cow's milk hypersensitivity. Eur Rev Med Pharmacol Sci 1990;12:311-18.
(5) Eastham EJ, Lichauco T, Grady MI, Walker WA. Antigenicity of infant formulas: role of immature intestine on protein permeability. J Pediatr 1978;93:561-4.
(6) Cantani A, Lucenti P. Natural history of soy allergy and/or intolerance in children, and clinical use of soy-protein formulas. Pediatr Allergy Immunol 1997;8:59-74.
(7) American Academy of Pediatrics. Committee on Nutrition. Soy protein-based formulas: recommendations for use in infant feeding. Pediatrics 1998;101:148-53.
(8) Guarino A. Commento ai testi. In La allergia alimentare. Milano: Plada, 2000.
We thank Dr Grigg for his interest in our work.[1] We agree that the asthma attacks may have resolved spontaneously in some cases, which was
precisely why we stated that the markers fell in association with steroid
therapy, and nowhere implied causality. Nevertheless, the statistical
analysis suggests that the chances this occurred at random are extremely
low.
We thank Dr Grigg for his interest in our work.[1] We agree that the asthma attacks may have resolved spontaneously in some cases, which was
precisely why we stated that the markers fell in association with steroid
therapy, and nowhere implied causality. Nevertheless, the statistical
analysis suggests that the chances this occurred at random are extremely
low.
We agree that corticosteroids do not inhibit, except at very high
concentrations, degranulation of the eosinophils induced by incubation
with opsonised particles, such as Sepharose beads in vitro.[2] However,
there is overwhelming evidence that cytokines such as IL-5 prime
eosinophils for increased release of granule proteins in this situation,[3,4] and that they inhibit cytokine-mediated prolongation of eosinophil
survival.[5] These observations, coupled with the abundant evidence that
corticosteroids reduce the expression of eosinophil-active cytokines, such
as IL-5, provide a convincing chain of evidence linking the clinical use
of corticosteroids with reduced release of eosinophil granule proteins in
vivo.
With regard to the controls in this study the ratio of atopic to non-
atopic asthmatics was 4:1 and of atopic to non-atopic controls was 3:1.
These differences are not significant by chi-squared testing. Whilst we
agree that more controls might have strengthened our conclusions,
nonetheless the evidence of unresolved inflammation after an apparently
clinically adequate course of prednisolone, as shown by the elevated
levels of IL-5 and sCD25, remains strong.
ANDREW BUSH
Reader and Honorary Consultant Royal Brompton Hospital
Sydney Street, London SW3 6NP, UK
Email: a.bush@rbh.nthames.nhs.uk
CLAIRE HOGG
Specialist Registrar, Paediatrics Royal Brompton Hospital
Email: c.hogg@rbh.nthames.nhs.uk
CHRIS J CORRIGAN
Senior Lecturer, Dept Resp Med & Allergy
Thomas Guy House, Guy’s Hospital, London SE1 9RT, UK
Email: chris.corrigan@kcl.ac.uk
References
(1) Grigg J. Oral steroids and inflammatory markers in asthma. Arch Dis Child [Rapid Response] 16 August 2000.
(2) Kita H, Abu-Ghazaleh R, Sanderson CJ, et al. Effect of steroids
on immunoglobulin-induced eosinophil degranulation. J Allergy Clin Immunol
1991;87:70-7.
(3) Kita H, Weiler DA, Abu-Ghazaleh RI, et al. Release of granule
proteins from eosinophils cultured with IL-5. J Immunol 1992;149:629-35
(4) Fujisawa T, Abu-Ghazaleh RI, Kita M, Sanderson CJ, Gleich GJ.
Regulatory effect of cytokines on eosinophil degranulation. J Immunol
1990;144:642-6.
(5) Wallen N, Kita H, Weiler D, Gleich GJ. Glucocorticoids inhibit
cytokine-mediated eosinophil survival. J Immunol 1991;147:3490-5.
Partsch and colleagues speculate that a rise in
testicular temperature in infants and young children
consequent to the wearing of modern plastic lined disposable
nappies [diapers] may have contributed to both the fall in sperm
counts and the increase in testicular cancer which have been
reported in some countries.[1] In support of this hypothesis
Partsche et al refer to reports of rising incidence ra...
Partsch and colleagues speculate that a rise in
testicular temperature in infants and young children
consequent to the wearing of modern plastic lined disposable
nappies [diapers] may have contributed to both the fall in sperm
counts and the increase in testicular cancer which have been
reported in some countries.[1] In support of this hypothesis
Partsche et al refer to reports of rising incidence rates in
testicular cancer.[2-6] These studies report increased
cancer risk in men born from before 1900 to 1988 diagnosed
up to 1988, from 1916 to 1978, before 1970, from 1907 to 1981,
and from 1865 to 1975, respectively. None reports incidence
of testicular cancer in men who have had the opportunity to
wear modern disposable nappies which have only been widely
available since the late 1970s. There is some suggestion
that the rise in testicular cancer may not be continuing.[7]
There are no data on testicular cancer incidence in men who
are likely to have worn modern disposable nappies as the
peak age for this disease is the late 20s and the men are
simply too young. Similarly, the reports of a declining
sperm count do not include any men born after 1975,[8-11] and even the most recent study from Denmark
includes men born only before 1978.[12]
There is no way that
modern disposable nappies could have contributed to the
changes in male gonadal health reported in men observed to
date since all studies are of men who were born before they
were available.
Partsch et al[1] claim that the scrotal cooling mechanism
was often completely abolished in boys wearing modern
disposable nappies. This would appear to be
over-interpretation of the data they had available, for two
reasons. Firstly, they compared 24-hour mean scrotal
temperature with spot rectal temperature and were unable to
take into account the considerable circadian variation in
core temperature in infants.[13] Secondly, they used
measurement techniques validated in adults but not in
nappy-wearing infants. They have not demonstrated that their
methods, which included covering a considerable portion of
the scrotal surface with adhesive tape, did not interfere
with two aspects of scrotal cooling, ie, evaporation from the
skin surface and contraction and relaxation of the scrotal
sac. There is the very real possibility that the measurement
process itself increased scrotal temperatures in all
children.
There are several inconsistencies in the results table (table 1 in the paper by Partsch et al)[1]; for example, the
mean temperatures and the calculated difference between
temperatures measured with modern plastic lined disposable
nappies and cotton nappies can not be reconciled, which the
authors may wish to clarify.[1]
Further scientific research is clearly needed to establish
the normal range of temperatures in infant testes and
the extent to which they may be affected by different types
of nappies and also the extent to which any changes may
affect testicular health. However, it is clear that modern
plastic lined disposable nappies can have played no role in
the changes in male gonadal health reported worldwide to
date.
References
1. Partsch C-J, Aukamp M and Sippell WG. Scrotal
temperature is increased in disposable plastic lined
nappies. Arch Dis Child 2000;83:364-8.
2. Adami H, Bergström R, Möhner M, et al. Testicular cancer
in nine northern European countries. Int J Cancer
1994;59:33-8.
3. Forman D, Möller H. Testicular cancer. Cancer Surv
1994;19-20:323-41.
4. Hoff Wanderas E, Tretli S, Fossa SD. Trends in incidence
of testicular cancer in Norway 1955-1992. Eur J Cancer
1995;31A:2044-8.
5. Weir HK, Marrett LD, Moravan V. Trends in the incidence
of testicular germ cell cancer in Ontario by histologic
subgroup, 1964-1996. CMAJ 1999;160:201-5.
6. Zheng T, Holford TR, Ma Z, Ward BA, Flannery J, Boyle P.
Continuing increase in incidence of germ-cell testis cancer
in young adults: experience from Connecticut, USA,
1035-1992. Int J Cancer 1996;65:723-9.
7. Andersen AG, Jensen TK, Carlsen E, et al. High frequency of sub-optimal semen quality in an unselected
population of young men Hum Reprod 2000;15:366-72.
8. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in
semen quality among fertile men in Paris during the past 20
years. N Engl J Med 1995;332:281-5.
9. Benshushan A, Shoshani O, Paltiel O, Schenker JG, Lewin
A. Is there really a decrease in sperm parameters among
healthy young men? A survey of sperm donations during 15
years. J Assist Reprod Genet 1997;14:347-53.
10. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE.
Evidence for decreasing quality of semen during past 50
years. BMJ 1992;305:609-13.
11. Irvine S, Cawood E, Richardson D, MacDonald E, Aitken J.
Evidence of deteriorating semen quality in the United
Kingdom: birth cohort study in 577 men in Scotland over 11
years. BMJ 1996;312:467-71.
12. Pharris-Ciurej ND. Cook LS. Weiss NS. Incidence of
testicular cancer in the United States: has the epidemic
begun to abate?. Am J Epidemiol 1999;150:45-6.
13. Wailoo MP. Petersen SA. Whittaker H. Goodenough P.
Sleeping body temperatures in 3-4 month old infants.
Arch Dis Child 1989;64:596-9.
Conflict of Interest
I have provided advice on scientific and epidemiological aspects of this
study to 2 trade associations which act on behalf of modern plastic lined
disposable nappy manufacturers EDANA and AHPMA.
The development of visceral leishmaniasis after travel to
endemic countries is not a new facet to this problem. At the time of
writing, a Medline search using the key words visceral leishmaniasis and Malta yielded 16
papers. Of these, almost a third (n=5) deal with patients who visited
Malta and contracted visceral leishmaniasis.[1-5]
The development of visceral leishmaniasis after travel to
endemic countries is not a new facet to this problem. At the time of
writing, a Medline search using the key words visceral leishmaniasis and Malta yielded 16
papers. Of these, almost a third (n=5) deal with patients who visited
Malta and contracted visceral leishmaniasis.[1-5]
References
(1) Wheatley T, Sacks S, Flemans RJ, Rubenstein D.
Visceral leishmaniasis: a rare imported disease. J
Infect 1983;7:166-7.
(2) Ornvold K, Carstensen H, Magnussen P, Nielsen MH,
Pedersen FK. Kala-azar in a four-year-old child 18
months after brief exposure in Malta. Acta Paediatr
Scand 1989;78:650-2.
(3) Rudi J, Racz P, Horner M, Kommerell B. Visceral
leishmaniasis (kala-azar) after a visit to the
Mediterranean region. Clin Investig 1993;71:616-19.
(4) Schou P, Husted H, Mejer J. Visceral leishmaniasis
after a holiday in Malta. Ugeskr Laeger 1993;155:3133-
4.
(5) Meinecke CK, Schottelius J, Oskam L, Fleischer B.
Congenital transmission of visceral leishmaniasis
(Kala Azar) from an asymptomatic mother to her child.
Pediatrics 1999;104:e65.
We read with interest this report by Grech et al.[1] It
appears from their population-based study that as a result of the
eradication of stray dogs, the annual incidence of visceral leishmaniasis
(VL) declined considerably in Malta. VL is still endemic around the
Mediterranean sea and sporadic cases are reported in children living in
Northern Europe. It seems likely that with increasing tourism the...
We read with interest this report by Grech et al.[1] It
appears from their population-based study that as a result of the
eradication of stray dogs, the annual incidence of visceral leishmaniasis
(VL) declined considerably in Malta. VL is still endemic around the
Mediterranean sea and sporadic cases are reported in children living in
Northern Europe. It seems likely that with increasing tourism the
incidence of VL will also increase in areas where until recently this
condition would not even be thought of. During the last 18 months, we
diagnosed three children with VL. As the presentation features can be
fairly dramatic and physicians in Northern Europe are not always alert to
the possibility of this condition, we would like to call attention again
to the possibility of VL in non-endemic countries.
The main clinical features of the patients are shown in the table.
Patient 1
Patient 2
Patient 3
Age at diagnosis (years)
1
1.5
2
Holiday destination where infected
South of France
Elba
South of Spain
Interval from exposure to appearance of symptoms (months)
7
12
6-18
Interval between appearance of symptoms and diagnosis (weeks)
6
3
12
Hepatomegaly (cm)
6
1
5
Splenomegaly (cm)
10
3
15
Haemoglobin (mmol/dl)
2.9
3.0
4.1
White blood cell count (x 109/l)
4.5
3.5
1.5
Platelets ( x 109/l)
47
107
10
Ferritin (µg/l)
10813
260
4612
Lactate dehydrogenase (U/l)
4779
911
1761
Triglycerides (mmol/l)
3.64
6.9
3.9
Serum IgG (g/l)
13.9
15.6
36
All
three children presented with spiking high fevers, anorexia, hepato-
splenomegaly and pancytopenia. The onset of the symptoms was insidious and
it took 3-12 weeks to establish the diagnosis. In all three patients this
was achieved through bone marrow aspiration and the demonstration of the
typical amastigotes in macrophages. The diagnosis was further confirmed
through the demonstration of antibodies to the leishmania parasite. All
three patients needed erythrocyte transfusions and patient 3 also platelet
transfusions. A 5-10 day course of liposomal amphotericin-B was given to
all three children. The treatment was well tolerated, and they all became
afebrile within a week. Pancytopenia subsided over the ensuing 2-3 weeks
and the children gradually returned to normal activity in a few months.
Naturally, we cannot draw epidemiological conclusions from such a
small number of patients. Nevertheless, it is rather intriguing to find
three unrelated cases within a relatively short time. While the
eradication of stray dogs may go a long way to reduce the incidence of VL,
vaccination would be more desirable.[2] Although resistance and immunity
against the leishmania parasites is not well understood, the seemingly
increasing incidence of VL in children travelling from Northern Europe
might be due to the fact, that they have no transplacental immunity
against the parasite and are therefore more prone to develop VL than local
children. There is much in common between the presentation features of the
haemophagocytic syndromes and VL. It is noteworthy that all three of our
patients showed signs of macrophage activation and haemophagocytosis was
observed in their bone marrow smears. With increased awareness over this
condition by physicians in non-endemic countries, the time required to
reach the correct diagnosis and institute therapy should be reduced.
TOM RÉVÉSZ
TOM F W WOLFS GABRIELLA KARDOS
MARCELLINE A VAN FURTH
University Medical Centre Utrecht, The Netherlands
Free University Amsterdam Amsterdam, The Netherlands
References
(1) Grech V, Mizzi J, Mangion M, Vella C. Visceral leishmaniasis in Malta - an 18 year paediatric, population based study. Arch Dis Child 2000;82:381-5.
(2) Herwaldt B. Leishmaniasis. Lancet 1999;354:1191-9.
We read with interest Professor Gill’s[1] concerns about complete
avoidance of lumbar puncture (LP) in the emergency management of
meningococcal disease according to the algorithm suggested by Pollard and
colleagues.[2] However, from public health perspective, we agree with Professor Gill's remarks that the correct diagnosis and identification of strains
would help in prophylaxis of contacts and prev...
We read with interest Professor Gill’s[1] concerns about complete
avoidance of lumbar puncture (LP) in the emergency management of
meningococcal disease according to the algorithm suggested by Pollard and
colleagues.[2] However, from public health perspective, we agree with Professor Gill's remarks that the correct diagnosis and identification of strains
would help in prophylaxis of contacts and prevention of clusters.[3]
However we feel that there are two other potential reasons why LP would
help in the management of the child with acute meningococcal disease.
There is a valuable diagnostic opportunity offered by cerebrospinal
fluid (CSF) analysis, especially that by polymerase chain reaction (PCR).
Meningococcal DNA detection in CSF by PCR assay is a sensitive test giving
positive results even on samples taken up to 72 hours after antibiotics
are initiated.[3] The ability to confirm the diagnosis on a “late” CSF
sample provides an opportunity for clinicians to perform LP once a
critically ill patient
is stable. A study from the meningococcal reference laboratory reports
that confirmation of the diagnosis has improved in Ireland after
introduction of CSF PCR assay and has helped with long-term management of
patients.[3]
We accept the fact that PCR is not of much use in the initial
management of a suspected case, however it is of immense benefit to public
health staff for management of contacts. This issue is going to be
important following the recent introduction of meningococcal C
vaccine. PCR assays based on sialyltrasferase (SiaD) gene sequence are
able to identify and discriminate between serogroup B and C infections,
allowing monitoring the effectiveness of vaccination.[4] Laboratory
confirmation of clinical suspicion is an important part of management in
the community. Late CSF specimen analysis can make a clear diagnosis
instead of clinical description of “definite”, “probable” or “possible”
cases.
We would like to mention another potential advantage of LP in cases
of meningococcal septicaemia associated with signs of meningeal irritation
in a clinically stable child seen in District General Hospitals. The
absence of meningitis is a bad prognostic sign[5] and might lower the
threshold to transfer the child to a Paediatric Intensive Care Unit. The
presence of pleocytosis in the CSF might encourage medical staff to manage
the child locally thereby avoiding unnecessary distress to the child and
inconvenience to the family at the same time sparing an intensive care bed
for another child.
We strongly agree that LP should be avoided in a seriously ill
child.
R Chodhari, N Sharief
References
(1) Gill D. Emergency management of meningococcal disease. Arch Dis Child 2000;82:266-73.
(3) Ragunathan L, Ramsay M, Borrow R Guiver M, Gray S, Kaczmarski EB. Clinical features, laboratory findings and management of meningococcal meningitis in England and Wales: report of a 1997 survey. J Infect 2000;40:74-9.
(4) Borrow R, Claus H, Guiver M, et al. Non-culture diagnosis and serogroup determination of meningococcal B and C infection by a sialyltransferase (siaD) PCR ELISA. Epidemiol Infect 1997;118:111-17.
(5) Niklasson PM, Lundbergh P, Strandell T. Prognostic factors in
meningococcal disease. Scand J Infect Dis 1971;3:17-25.
We noted with interest the recent study reported by Murray
et al[1] in which the characteristics of a cohort of 46 children with
reflex sympathetic dystrophy (RSD) were reported. In a similar fashion in
our paediatric rheumatology unit, chronic idiopathic musculoskeletal pain
syndromes including RSD form a significant proportion of referrals. A
retrospective review of 23 children referred to us in...
We noted with interest the recent study reported by Murray
et al[1] in which the characteristics of a cohort of 46 children with
reflex sympathetic dystrophy (RSD) were reported. In a similar fashion in
our paediatric rheumatology unit, chronic idiopathic musculoskeletal pain
syndromes including RSD form a significant proportion of referrals. A
retrospective review of 23 children referred to us in whom a diagnosis of
RSD was made between April 1993 and November, revealed many similarities
with the population described by Murray et al. This is illustrated in the table below:
Clinical characterisitics
of 23 children with RSD compared with 46 described by Murray et al
In a similar manner many of our patients had seen multiple medical
and health practitioners prior to referral and diagnosis. Five patients
had pre-existing medical conditions (2 inactive juvenile idiopathic
arthritis, 2 recurrent transient synovitis of the hip, one mild cerebral
palsy,and one patient with asthma). A high level of pre-exisiting
conditions with psychological components was seen in our cohort with 4
patients reporting a history of chronic recurrent headaches, 1 of chronic
abdominal pain, 5 of sleep disorders, 2 of anxiety and 2 of depression.
Three patients had a history of conversion disorders: and one recurrent
hyperventilation. In addition 11 (48%) had one or more close relatives
with a chronic or debilitating illness, and in seven of these it was of
musculoskleletal origin. Five patients had a total of 7 first degree
relatives with a diagnosed psychiatric condition.
Presenting symptoms were similar to the reported study with all
patients reporting severe pain in the affected limb(s) in addition to
restriction of joint range of motion (91%); sensory symptoms (55%);
swelling (50%); colour change (55%), and abnormal sweating (14%).
Seventeen patients (77%) had used crutches at some point during their
illness and 7 (32%) had used a wheelchair.
Investigation prior to diagnosis was similar to the reported study.
Eighteen patients (82%) had had plain radiographs of which 4 showed
osteopenia. Eight patients (36%) underwent a bone scan of which 3
demonstrated reduced uptake in the affected limb. No other investigations,
which included MRI, EMG, thermography and nerve conduction studies were
felt to be contributory to diagnosis or management.
Six of 19 patients were admitted to another hospital prior to
referral to our unit of which only 2 of these were reported to have
received in-patient physiotherapy. Ten patients (53%) had outpatient
physiotherapy in some form. In contrast 10 patients (53%), were treated
with a period of limb immobilisation.
Examination findings on presentation to our unit included tenderness
in 100%, hyperalgesia 76%, reduced temperature 71%; discolouration 67%;
muscle wasting 48%; swelling 38%; abnormal sweating 24%, hair loss14%,
and skin atrophy in 9%. Fifteen patients required admission to hospital,
and all received physiotherapy, in addition to simple analgesics and non
steroidal anti-inflammatory drugs as required. All patients had a
pscyhological assessment by the paediatric team, received specific
education and were taught self-management strategies. All were given a
tailored home-exercise programme on discharge.
5 patients in whom adverse psychological factors were felt to be severe
were referred for formal clinical psychology assessment and intervention.
Intervention included patient and family counselling, behavioural and pain
management interventions. Of the patients not admitted, information about
RSD was given in the outpatient department, referral made to local
physiotherapy services and specific medical follow-up arranged.
Average follow-up time from diagnosis was 26 months in our group
(range 5 months to 7 years). Current status was determined from the time
of last clinic visit or by telephone interview (if this was more than 6
months previously). Full outcome information is currently available for 19
patients, 11 of whom were completely well (58%), 5 were clinically
improved but still symptomatic (26%), and 3 patients had not improved
since diagnosis (15%). Of those who had recovered fully the median time to
definite improvement was 4 weeks (range 2-10 weeks) and the mean time to
full recovery 25 weeks (range 4 weeks to 15 months). As with the reported
study by Murray et al, a high rate of reccurence or relapse in our
patient group was seen with 11/19 (58%) having further episodes, of which
4 patients relapsed more than once, and in 2 patients the recurrence
developed in different limb.
A full recovery from the original episode was achieved in 80% of
patients. We found that although there was no reduction in the time
reported to definite improvement in symptoms, patients admitted had a
significantly reduced time interval between diagnosis and full recovery
being 3.25 months, (range 1-7 months) compared with 6 months, (range 2-12)
months in those not admitted. In our cohort a higher proportion of
patients in whom the diagnosis was made within 4 months of onset of RSD
made a full recovery (88% compared to 67%).
We agree with Murray et al[1] that RSD in children is an important cause
of morbidity and suggest that earlier recognition and treatment is likely
to result in improved outcome. It is clear that psychological issues are
common and perhaps under recognised, and we believe it is mandatory that
these be actively sought and addressed in all patients, as has been
suggested by previous authors.[2,3] Although formal psychological
intervention or psychiatric referral may only be required in some
patients, we believe psychological assessment and teaching of coping
skills and pain management strategies is essential in the management of
all patients with chronic pain syndromes including RSD. If intensive
outpatient physiotherapy support is not available, admission for a period
of intensive physiotherapy should always be considered. We also strongly
agree that there is a very limited role for sympathetic nerve blocks, or
narcotic analgesia in the management of RSD in children, and that limb
immobilisation in this condition is inappropriate and contraindicated.
Karen Davies
Specialist Registrar in Paediatric Rheumatology
R Khubchandani
Consultant Paediatrician
Kevin J Murray
Consultant Paediatric Rheumatologist
Institute of child Health Great Ormond Street Hospital
London WC1N 3JH, UK
Kevin.Murray@gos-tr.nthames.nhs.uk
References
(1) Murray CS, Cohen A, Perkins T, Davidson JE, Sills JA. Morbidity
in reflex sympathetic dystrophy. Arch Dis child 2000;82:231-3.
(2) Sherry DD, McGuire T, Mellins E, Salmonson K, Wallace CA, Nepom
B. Psychomatic musculoskeletal pain in childhood: clinical and
psychological analysis of 100 children. Pediatrics 1991;88:1093-9.
(3) Sherry DD, Wallace CA, Kelley C, Kidder M, Sapp L. Short- and
long-term outcomes of children with complex regional pain syndrome type I
treated with exercise therapy. Clin J Pain 1999;15:218-23.
We thank Dr Briars for his comments and are aware of his opinions
regarding the potential source of the intestinal cytokines which we have
discussed in the paper including reference to his previous paper.[1] We do not agree that our data is dependant upon IL-8 alone. We have
shown statistically significant differences for a whole range of proteins
and types of assays.
We thank Dr Briars for his comments and are aware of his opinions
regarding the potential source of the intestinal cytokines which we have
discussed in the paper including reference to his previous paper.[1] We do not agree that our data is dependant upon IL-8 alone. We have
shown statistically significant differences for a whole range of proteins
and types of assays.
Due to the large number of proteins and types of assays that we have
performed we have not the performed the extensive experiments as reported
by Dr Briars for IL-8. We do know that the polyethylene glycol, a key
constituent of the lavage fluid, does not affect the IL-8 assay. There
are two reasons why variable recovery is unlikely to be a major factor in
our results. First by collecting whole gut lavage (WGL) any intestinal
secretions present, including bile, are extremely dilute. Substances found
in faeces such as stercobilin are effectively absent. Secondly WGL is a
perfusion system found to be equivalent to balloon perfusion systems.[2,3]
Thus the dilution of any interfering factors would be very similar between
the subjects and controls. Using WGL minimises any interference from
intestinal material as much as feasible in vivo.
Assuming the worst case scenario from Dr Briars' data (i.e. a two fold
overestimate of IL-8 in the cystic fibrosis (CF) patients which is not
found in the controls) still shows very significantly increased IL-8
output in the CF patients (p<_0.0001 and="and" unfeasible="unfeasible" volumes="volumes" of="of" sputum="sputum" would="would" still="still" be="be" required.="required." p="p"/> For these and reasons detailed in our paper and previous
correspondence[4] we do not believe that sputum is the primary cause of the
abnormalities found. Our observations concerning the increase in
intestinal inflammatory markers in the WGL of CF patients have now been
supported by a study which investigates intestinal inflammation within
mucosal biopsy samples.[5] This provides additional support to the
hypothesis that the basic defect of CFTR can be proinflammatory.
Dr Eisenberg correctly points out the potential influence of
pancreatic enzymes and degradation. The results we found for alpha-1-
antitrypsin were unexpected given differences for albumin and IgG. Some
discordance in data has been found previously in WGL from subjects with
active inflammatory bowel disease[6] who are pancreatic sufficient and also
can have raised intestinal permeability.[7]
However our data demonstrating raised albumin and IgG are consistent
with well established data showing raised intestinal permeability in
children with CF.[8] As we discussed, it has been found that protein outputs
from balloon perfusion experiments (which exclude upper intestinal
secretions) are similar to those found in whole gut lavage suggesting that
any potential effect of degradation from pancreatic enzymes is minimal.[2,3] We also showed ECP to be raised in CF children. Like alpha-1-
antitrypsin this is relatively stable in faeces at room temperature
(approx 21%
loss over 24 hours).[10] This loss would be considerably lower during WGL.
Thus degradation would be unlikely to explain this difference.
Nicholas M Croft
Department of Paediatric Gastroenterology
St Bartholomew’s and the Royal London School
of Medicine and Dentistry,
Queen Mary and Westfield College
London, UK
Rosalind L Smyth
Una O’Hea
University Institute of Child Health
Royal Liverpool Children’s Hospital
Liverpool, UK
Tom G Marshall
Royal Hospital for Sick Children
Edinburgh UK
References
(1) Briars GL, Dean TP, Murphy JL, Rolles CJ, Warner JO. Faecal
interleukin-8 and tumour necrosis factor-alpha concentrations in cystic
fibrosis. Arch Dis Child 1995;73:74-6.
(2) Ferguson A, Sallam J, McLintock L, Croft NM, Poxton I. The gut as an
immune organ: intestinal antiendotoxin antibodies. In: Kinney JM, Tucker
HN, eds. Organ Metabolism and Nutrition: Ides for Future Critical Care. New York: Raven Press, Ltd, 1994:231-44.
(3) Croft NM, Ferguson A. High intraluminal fluid flow increases
intestinal IgA output. Scand J Gastroenterol 2000;35:726-31.
(4) Croft NM, Marshall TG, Ferguson A. Gut inflammation in children
with cystic fibrosis on high dose enzyme supplements [letter]. Lancet 1996;347:327.
(5) Raia V, Maiuri L, de Ritis G, et al. Evidence of chronic
inflammation in morphologically normal small intestine of cystic fibrosis
patients. Pediatr Res 2000;47:344-50.
6) Choudari CP, O’Mahony S, Brydon G, Mwantembe O, Ferguson A. Gut
lavage fluid protein concentrations; objective measures of disease
activity in inflammatory bowel disease. Gastroenterology 1993;104:1064-71.
(7) Tibble JA, Sigthorssen G, Bridger S, Fagerhol MK, Bjarnason I.
Surrogate markers of intestinal inflammation are predictive of relapse in
patients with inflammatory bowel disease. Gastroenterology 2000;119:15-22.
(8) Flick JA, Perman JA. Increased intestinal permeability in cystic
fibrosis correlates with the degree of pancreatic exocrine dysfunction.
Pediatr Pulmonol 1990;(suppl):97-8.
(9) Berstad A, Borkje B, Riedel B, Elsayed S. Increased fecal
eosinophilic cationic protein in inflammatory bowel disease. Hepatol Gastroenterol 1993;40:276-8.
I was interested by the report of Smyth et al regarding the
finding of markers of intestinal inflammation in whole gut
lavage in patients with cystic fibrosis.[1] As the alpha 1
antitrypsin levels were not increased compared to
controls, perhaps another hypothesis needs to be considered.
Conceivably the inflammatory markers are not actually
increased within the bowel, but rather, they are...
I was interested by the report of Smyth et al regarding the
finding of markers of intestinal inflammation in whole gut
lavage in patients with cystic fibrosis.[1] As the alpha 1
antitrypsin levels were not increased compared to
controls, perhaps another hypothesis needs to be considered.
Conceivably the inflammatory markers are not actually
increased within the bowel, but rather, they are not
degraded due to the lack of intestinal enzymes. Alpha 1
antitrypsin, which is resistent to proteolytic enzyme
activity, would not be affected by such a phenomenon and
therefore, would be the same in patients with cystic
fibrosis and controls. Perhaps the authors would need to
resort to the somewhat dated technique of radiolabeled
albumin to definitively answer this question.
Larry Eisenberg
Reference
(1) Smyth RL, Croft NM, O'Hea U, Marshall TG, Ferguson A. Intestinal inflammation in cystic fibrosis. Arch Dis Child 2000;82:394-9.
Our study[1] was done on a selected group of children who were at an
increased risk of having urinary tract infection (UTI). The inclusion
criteria were the presence of any of the following
1. Clinical suspicion of UTI
2. History of previous UTI or renal anomalies
3. Children requiring antibiotics (urine culture was send prior to
starting antibiotics)...
Our study[1] was done on a selected group of children who were at an
increased risk of having urinary tract infection (UTI). The inclusion
criteria were the presence of any of the following
1. Clinical suspicion of UTI
2. History of previous UTI or renal anomalies
3. Children requiring antibiotics (urine culture was send prior to
starting antibiotics)
4. Any of the dipstick tests (nitrites, protein, leukocyte esterase or
blood) being abnormal.
Out of the 500 children admitted to the hospital during the study period,
only 312 who met above criteria were included in the study and
urine culture was done on all them. This reflected the local practice at
our hospital of sending urine for culture. We wanted to see if a change in
practice where urine culture is undertaken only if nitrites or leukocyte
esterase was positive would be effective in reducing the number of urine
cultures. The inclusion criteria for Sherif et al's study[2] was a clinical
suspicion of UTI, when urine cultures were send and dipstick testing was
done.
We found that UTI could be easily missed if urine culture is
undertaken only if nitrites or leukocyte esterase is positive. Quite
surprisingly the results of our study and Sherif et al's study seems to be
similar. Sensitivity was 34.4% vs 20.0% and specificity was 90.7% vs 99.2%
in our study and Sherif et al's study respectively. Negative predictive value was
92.4% in our study and 96.7% in Sherif et al's study. Only the interpretation of
these results seems to be different.
A test with such a low sensitivity reported in both these studies
cannot be recommended as screening test to exclude UTI. Urinary tract
infection is supposed to produce maximum damage in infants and therefore
one would not like to miss any UTI in this age group. Unfortunately this
is the age group where sensitivity of dipstick testing is the least (20%).
I agree with Sherif et al[3] that because of its high negative predictive
value, it may have some role as a screening test for UTI in situations
where the incidence of UTI is very low.
Positive nitrites had a very high specificity for UTI, which was the basis
of my suggestion that if nitrites are positive, especially in a febrile
infant, empirical treatment with antibiotics may be considered till the
result of urine culture is obtained. But it should not be the whole
criterion for diagnosing UTI.
Dr Sudhin Thayyil-Sudhan
Dr Santosh Gupta
University Hospital of Leicester
55 Hospital Close
Leicester LE5 4WQ, UK
References
(1) Thayyil-Sudhan S, Gupta S. Dipstick examination for urinary tract infections [letter]. Arch Dis Child 2000;82:271.
(2) Sharief N, Hameed M, Petts D. Use of rapid dipstick tests to exlude urinary tract
infection in children. Br J Biomed Sci 1998;55:242-6.
(3) Sharief N, Petts D. Dipstick testing of urine [rapid response]. Arch Dis Child 10th August 2000.
Dear Sir
Professor Salazar-De-Sousa,[1] commenting on the recent paper by Høst et al,[2] maintains that recent prospective and randomised clinical studies have shown that soy protein (SP) is as allergenic as cow's milk (CM) protein citing a review paper[3]; however, the author failed to detail which are these studies.
In 1990 we demonstrated[4] that Eastham et al[5] have shown an antibody response to SPs in...
Dear Editor,
We thank Dr Grigg for his interest in our work.[1] We agree that the asthma attacks may have resolved spontaneously in some cases, which was precisely why we stated that the markers fell in association with steroid therapy, and nowhere implied causality. Nevertheless, the statistical analysis suggests that the chances this occurred at random are extremely low.
We agree that corticosteroid...
Dear Editor:
Partsch and colleagues speculate that a rise in testicular temperature in infants and young children consequent to the wearing of modern plastic lined disposable nappies [diapers] may have contributed to both the fall in sperm counts and the increase in testicular cancer which have been reported in some countries.[1] In support of this hypothesis Partsche et al refer to reports of rising incidence ra...
The development of visceral leishmaniasis after travel to endemic countries is not a new facet to this problem. At the time of writing, a Medline search using the key words visceral leishmaniasis and Malta yielded 16 papers. Of these, almost a third (n=5) deal with patients who visited Malta and contracted visceral leishmaniasis.[1-5]
References
(1) Wheatley T, Sacks S, Flemans RJ, Rubenste...
Dear Editor
We read with interest this report by Grech et al.[1] It appears from their population-based study that as a result of the eradication of stray dogs, the annual incidence of visceral leishmaniasis (VL) declined considerably in Malta. VL is still endemic around the Mediterranean sea and sporadic cases are reported in children living in Northern Europe. It seems likely that with increasing tourism the...
Dear Editor
We read with interest Professor Gill’s[1] concerns about complete avoidance of lumbar puncture (LP) in the emergency management of meningococcal disease according to the algorithm suggested by Pollard and colleagues.[2] However, from public health perspective, we agree with Professor Gill's remarks that the correct diagnosis and identification of strains would help in prophylaxis of contacts and prev...
Dear Editor:
We noted with interest the recent study reported by Murray et al[1] in which the characteristics of a cohort of 46 children with reflex sympathetic dystrophy (RSD) were reported. In a similar fashion in our paediatric rheumatology unit, chronic idiopathic musculoskeletal pain syndromes including RSD form a significant proportion of referrals. A retrospective review of 23 children referred to us in...
We thank Dr Briars for his comments and are aware of his opinions regarding the potential source of the intestinal cytokines which we have discussed in the paper including reference to his previous paper.[1] We do not agree that our data is dependant upon IL-8 alone. We have shown statistically significant differences for a whole range of proteins and types of assays.
Due to the large number of pr...
Dear Editor:
I was interested by the report of Smyth et al regarding the finding of markers of intestinal inflammation in whole gut lavage in patients with cystic fibrosis.[1] As the alpha 1 antitrypsin levels were not increased compared to controls, perhaps another hypothesis needs to be considered.
Conceivably the inflammatory markers are not actually increased within the bowel, but rather, they are...
Dear Editor,
Our study[1] was done on a selected group of children who were at an increased risk of having urinary tract infection (UTI). The inclusion criteria were the presence of any of the following
1. Clinical suspicion of UTI
2. History of previous UTI or renal anomalies
3. Children requiring antibiotics (urine culture was send prior to starting antibiotics)...
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