L carnitine is needed for the transport of long-chain fatty acids
across the mitochondrial membrane for oxidation into acetyl coenzyme A and
entry into the Krebs cycle. Long-chain fatty acids nay also increase
temperature, and hence metabolic rate, oxygen consumption [Q10 effect]
and net ATP yield by uncoupling oxidative phosphorylation. If excessive
the uncoupling might have the reverse effect....
L carnitine is needed for the transport of long-chain fatty acids
across the mitochondrial membrane for oxidation into acetyl coenzyme A and
entry into the Krebs cycle. Long-chain fatty acids nay also increase
temperature, and hence metabolic rate, oxygen consumption [Q10 effect]
and net ATP yield by uncoupling oxidative phosphorylation. If excessive
the uncoupling might have the reverse effect.
That L carnitine supplements were successful in these case reports of
the cyclical vomiting syndrome raises the possibility that the vomiting
might have been a product of a decline in Daniel Atkinson energy charge
[1] and accompanying gut motor dysfunction [2].
If so the energy charge needs to be measured, probably best done
with its clinically validated stochiometric surrogate the gastric
intramucosal pH [3]. If found to be deficient the cause, such as an
inherited disorder of metabolism, hypothyroidism or a pharmacological
agent, needs to be identified and removed. Supplements alone are unlikely
to have long term benefits in any of these metabolic circumstances.
References
1. Hardie DG, Hawley SA. AMP-activated protein kinase: the energy
charge hypothesis revisited.
Bioessays. 2001 Dec;23(12):1112-9.
2. Iatrogenic diseases with a common cause?
Richard G Fiddian-Green (25 October 2002) eLetter re: Edward H Wagner
and Trish Groves
Care for chronic diseases
BMJ 2002; 325: 913-914
Barker et al. recently reported a relationship between short length
at age 1 year and lower incomes in adulthood [1]. Citing results from an
early report from the Newcastle Thousand Families Study showing a
relationship between height at age 3 years and intelligence at age 11 [2].
Barker et al. interpreted this as evidence that slow infant growth may
lead to a lifelong impairment of cognitive functio...
Barker et al. recently reported a relationship between short length
at age 1 year and lower incomes in adulthood [1]. Citing results from an
early report from the Newcastle Thousand Families Study showing a
relationship between height at age 3 years and intelligence at age 11 [2].
Barker et al. interpreted this as evidence that slow infant growth may
lead to a lifelong impairment of cognitive function, which may explain the
relationship between infant growth and income 50 years later, assuming
that childhood IQ is related to income 50 years later.
We tested this assumption in the Thousand Families Study using data
on growth and IQ collected during childhood and total household income
collected at age 50 [3]. Information on both IQ at age 11 and income at
age 50 was available for 430 participants.
A recent multivariable analysis of the Thousand Families data
suggests that there is a continuing relation between post-natal growth and
childhood cognition beyond the age of 9 years [4]. There was a highly
significant correlation between childhood IQ and household income at age
50 (p<_0.0001 predicting="predicting" an="an" increase="increase" of="of" around="around" _300="_300" per="per" annum="annum" for="for" every="every" point="point" in="in" iq="iq" at="at" age="age" _11="_11" after="after" adjusting="adjusting" social="social" class="class" birth.="birth." results="results" were="were" similar="similar" boys="boys" and="and" girls.="girls." while="while" our="our" previous="previous" analysis="analysis" showed="showed" that="that" height="height" _9="_9" was="was" significantly="significantly" associated="associated" with="with" p0.0001="p0.0001" birth="birth" we="we" found="found" there="there" no="no" such="such" relationship="relationship" between="between" later="later" income="income" p="p" suggest="suggest" childhood="childhood" does="does" predict="predict" this="this" is="is" mainly="mainly" due="due" to="to" postnatal="postnatal" growth="growth" effect="effect" which="which" may="may" continue="continue" throughout="throughout" childhood.="childhood." promotion="promotion" infancy="infancy" important="important" be="be" more="more" beneficial="beneficial" maximizing="maximizing" cognitive="cognitive" function.="function."/>References
1. Barker DJP, Eriksson JG, Forsén T, et al. Infant growth and income
50 years later. Arch Dis Child 2005;90:272-273.
2. Miller FJW, Court SDM, Knox EG, et al. The school years in
Newcastle upon tyne, 1952-62. London: Oxford University Press, 1974.
3. Lamont DW, Parker L, Cohen MA, et al. Early life and later
determinants of adult disease: a 50 year follow-up study of the Newcastle
Thousand Families cohort. Public Health 1998;112:85-93.
Septic shock is characterised by a hyperdynamic, vasodilated
circulation associated with cytolin release and its inhibitory effect upon
oxygen uptake and utilisation. Most deaths are late and occur after
patients have developed multiple organ dysfunctions. In these cases
cardiac arrest is preceded by a declining cardiac output the invariable
cause of death. Haemorrhagic shock differs only in that i...
Septic shock is characterised by a hyperdynamic, vasodilated
circulation associated with cytolin release and its inhibitory effect upon
oxygen uptake and utilisation. Most deaths are late and occur after
patients have developed multiple organ dysfunctions. In these cases
cardiac arrest is preceded by a declining cardiac output the invariable
cause of death. Haemorrhagic shock differs only in that it may become
irreversible when the volume of unreplaced blood loss has exceeded some 50%
of the blood volume. It is irreversible because the heart fails just as it
does in those adults who develop the low-cardiac-output syndrome after
coming off bypass following cardiac surgery [1]. Late deaths after
hamorrhagic shock and indeed cardiac surgery also occur after organ
dysfunctions have developed and occur from cardiac arrest preceded by a
decline in cardiac output.
The therapeutic challenge in sepsis would seem, therefore, to be the
prevention and reversal of a progressive decline in cardiac output and
cardiac arrest. Forty eight years ago Lillehei recognised that maintaining
splancchnic tissue oxygenation during haemorrhage could prevent
irreversible shock [2]. His observations have been conformed by a series
of later investigators and ascribed to a variety of factors, notably the
elusive gut factor [3]. This factor may be no more than the ability of
the liver to metabolise anaerobic products washed out of ischaemic
tissues beds during resuscitation for reasons most recently considered in
the context of acute liver failure [4].
The essence of the thesis is that a shift in the dependence of ATP
resynthesis occurs from aerobic to anaerobic glycolysis and imposes an
escalating and ultimately overwhelming workload upon the heart. This is
because it takes 20 times as much nutrient to be delivered to tissues to
generate one mole ATP by anaerobic glycolysis as compared with aerobic
glycolysis and accompanying oxidative phosporylation. Indeed when reducing
oxygen dispatch progressively in anasthetised and ventilated dogs by
reducing FiO2 this was in retrospect the probably cause of their cardiac
arrests [5]. Indeed when repeating the experiments in pigs we were able
to prevent the compensatory increase in cardiac output, and hence the
increase in myocardial workload imposed by the acute reductive stress, we
had induced with an FiO2 of 0.15 by delivering oxygen to the lumen of the
gut [6].
The therapeutic challenge in sepsis accompanied by a fall in gastric
intramucosal pH and associated with a poor prognosis would seem,
therefore, to be to prevent the heart from being subjected to an
overwhelming workload by an unfulfilled demand for glucose dispatch to
support ATP resynthesis by anaerobic glycolysis. In so doing it would need
to be appreciated that the Daniel Atkinson energy charge, upon which
myocardial and indeed all organ function ultimately depends, may decline
either because ATP production is inhibited (e.g., ischaemia) or because
ATP consumption is accelerated (e.g., exercise in skeletal muscle or
increased myocardial workload) beyond the capacity for ATP resynthesis.
The energy charge is derived from the formula, [ATP] + 1/2
[ADP]/[ATP] + [ADP] + [AMP]. As one mole [H+] is released with every mole
ATP hydrolysed into ADP and every mole ADP hydrolysed into AMPthe
following reactions occur in acute reductive stress.
ATP = ADP + H+
ADP + ADP = ATP + AMP
ATP = ADP + H+
ADP = AMP + H+
As pH 7.40 is equivalent to 40 nMol/L H+ the degree of dysoxia
increases as [H+] increases above this level and as the pH falls below
7.40, as considered in my review of gastric intramucal pH [7]. The degree
of dysoxia present is, therefore, a function of the energy charge. Both
may be inferred from the intramucosal pH or intramucosal [H+].
The one variable that has not been clearly defined in this regard is
the rise in pH above normality that may occur [5], presumably from proton
consumption in the reductive biosynthesis of fatty acids and other
products that is able to occur only when the energy charge is normal.
Perhaps a rise in pH above normality is a function of the degree to which
the ATP pool has been increased above normoxic levels at pH 7.40 to
support reductive biosynthesis especially in wound healing wounds and
organ repair. Certainly sepsis is well known to impair wound healing and
to cause organ dysfunctions. Perhaps it does so by preventing the energy
charge from returning to normoxic levels and the rate of ATP resynthesis
rising to levels able to support these important functions.
References:
1. Fiddian-Green RG. Gut mucosal ischemia during cardiac surgery.
Semin Thorac Cardiovasc Surg. 1990 Oct;2(4):389-99.
2. LILLEHEI RC. The prevention of irreversible hemorrhagic shock in
dogs by controlled cross perfusion of the superior mesenteric artery.
Surg Forum. 1957;7:6-11.
3. Haglund U. Therapeutic potential of intraluminal oxygenation.
Crit Care Med. 1993 Feb;21(2 Suppl):S69-71
4. Anaerobic glycolysis in acute liver failure
Richard G Fiddian-Green (9 March 2005) eLetter re: J G O’Grady
Acute liver failure
Postgrad Med J 2005; 81: 148-154
5. Grum CM, Fiddian-Green RG, Pittenger GL, Grant BJ, Rothman ED,
Dantzker DR. Adequacy of tissue oxygenation in intact dog intestine.
J Appl Physiol. 1984 Apr;56(4):1065-9.
6. Gross BD, Sacristan E, Peura RA, Shahnarian A, Devereaux D, Wang
HL, Fiddian-Green R. Supplemental systemic oxygen support using an
intestinal intraluminal membrane oxygenator.
Artif Organs. 2000 Nov;24(11):864-9.
The authors are to be congratulated for the systematic review 'Are
there patterns of bruising in childhood which are diagnostic or suggestive
of abuse?' It is an extremely valuable piece of work, providing data for
paediatricians working in the field of child protection.
Results show that non-abusive bruises are generally small, sustained
over bony prominences and found on the front of the...
The authors are to be congratulated for the systematic review 'Are
there patterns of bruising in childhood which are diagnostic or suggestive
of abuse?' It is an extremely valuable piece of work, providing data for
paediatricians working in the field of child protection.
Results show that non-abusive bruises are generally small, sustained
over bony prominences and found on the front of the body. Abusive bruises
are away from bony prominences, and the commonest site is the head and
neck (particularly face), followed by buttocks, trunk and arms.
The paper highlights that children with significant motor delay would
not be expected to have the same bruising pattern as their peers but
points out that most studies in the literature exclude children with neuro-disability or diseases that predispose to bruising, to a varying degree.
Locally a small pilot study examining the bruising pattern in 14
children with a variety of disabilities aged 15 months – 4 years who
attend two pre-school special needs opportunity groups has shown
interesting results. 13 of the 14 children (where there were no concerns
about abuse) had bruises, the child with no bruises being the only child
in the study who was unable to crawl. The other children were all cruising
or walking, although one wore piedro boots, another had splints and some
had an unsteady gait. The average number of bruises was 5.7 (range 0 – 20)
and size varied between 0.5 cm and 2.0 cm in diameter. Five children
(35.7%), had bruising on their buttocks/bottom, four (28.6%) had bruising
on their arms and two (14.3%) had bruises on their face or neck – all
areas usually associated with abusive bruising.
Bruising patterns in children with disabilities or special needs may
be very different to bruising patterns in their peer group. Further
research is needed.
Charlotte Barton
Fiona Finlay
Child Health Department
Bath NHS House
Newbridge Hill
Bath BA1 3QE
We were interested in the article by Konig, Benger and Goldsworthy [1]
describing the use of an Automated External Defibrillator (AED) in a 6-
year-old child and would like to congratulate them and the paramedic team
on saving this girl’s life.
As the authors point out in their discussion, data on the use of AEDs
in children is scant and any publication in this area is encouraged. In
the ab...
We were interested in the article by Konig, Benger and Goldsworthy [1]
describing the use of an Automated External Defibrillator (AED) in a 6-
year-old child and would like to congratulate them and the paramedic team
on saving this girl’s life.
As the authors point out in their discussion, data on the use of AEDs
in children is scant and any publication in this area is encouraged. In
the absence of good quality information, the International Liaison
Committee on Resuscitation (ILCOR) did not feel able to recommend their
use in children less than 8 years old in its International Guidelines 2000
for CPR and ECC. A major concern was that an AED may not have adequate
specificity for analysis of paediatric arrhythmias and consequently
recommend a potentially damaging shock inappropriately. Clearly, if a
child is certainly in ventricular fibrillation (VF), the risk of an adult
energy level shock is less than no shock at all.
Since the 2000 consensus process, further evidence on the specificity
of rhythm analysis in children [2] and the safety of shocks of greater than
4J/kg [3] have, together with the increasing distribution of AEDs in both
hospital and community, prompted an update and revision of the original
statement. This was published in Circulation [4] Resuscitation [5] and
Pediatrics [6] in 2003. Information on this subject is also on the
Resuscitation Council (UK) website [7].
The current recommendation is: “Standard Automated External
Defibrillators (AEDs) may be used in children over 1 year of age who have
no signs of circulation. Ideally, the device should deliver a paediatric
dose. The arrhythmia detection algorithm used in the device should
demonstrate high specificity for paediatric shockable rhythms, i.e. it
will not recommend delivery of a shock for nonshockable rhythms”.
Two points in this statement deserve clarification:
Delivery of a paediatric dose from an AED may be achieved by the use
of a manually adjustable model or by the use of paediatric pads, which
attenuate the output to (typically) 50-80J.
Not all manufacturers have tested their machines against paediatric
arrhythmias and this should be considered when evaluating machines for
purchase if there is any possibility they might need to be used in
paediatric patients.
The incidence of VF in children requiring resuscitation is
traditionally thought to be 7-10% although the true incidence may be
higher, particularly if early rhythm analysis is performed [8]. It is
extremely important to identify this group as the outcome from this form
of cardiac arrest is likely to be good with prompt defibrillation. The
appropriate use of AEDs in children should be encouraged.
References
1. Konig B, Benger J and Goldsworthy L. Automatic external
defibrillation in a 6 year old. Arch Dis Child. 2005;90:310-311
2. Cecchin F, Jorgenson DB, Berul CI, Perry JC, Zimmerman AA, Duncan
BW, Lupinetti FM, Snyder D, Lyster TD, Rosenthal GL, Cross B, Atkins DL.Is
arrhythmia detection by automatic external defibrillator accurate for
children?: sensitivity and specificity of an automatic external
defibrillator algorithm in 696 pediatric arrhythmias. Circulation.
2001;103:2483-2488.
3. Gurnett CA, Atkins DL. Successful use of a biphasic waveform
automated external defibrillator in a high-risk child. Am J Cardiol.
2000;86:1051-1053.
4. Samson RA. Berg RA. Bingham R et al. Use of automated external
defibrillators for children: an update: an advisory statement from the
Pediatric Advanced Life Support Task Force, International Liaison
Committee on Resuscitation. Circulation. 2003;107(25):3250-5.
8. Mogayzel C, Quan L, Graves JR. Our-of-hospital ventricular
fibrillation in children and adolescents: Causes and outcomes. Ann Emerg
Med. 1995;25:484-491.
Since 1991 there has been talk of abolishing community paediatrics as
a specialty [1]. At that time, a group of related specialties was
proposed: a specialty of child development and rehabilitation
(neurodisability); child protection would be subsumed into general
paediatrics and there would be child public health doctors. Since then
there has been a view amongst some paediatricians that community...
Since 1991 there has been talk of abolishing community paediatrics as
a specialty [1]. At that time, a group of related specialties was
proposed: a specialty of child development and rehabilitation
(neurodisability); child protection would be subsumed into general
paediatrics and there would be child public health doctors. Since then
there has been a view amongst some paediatricians that community
paediatricians should become the general paediatricians of the future
[2,3]. Dr Chambers’ recent article proposes a narrow view of community
paediatrics, concentrating on chronic illness and confining its role to
diagnosis and medical management [4]. He rather misses the point.
The challenge of community paediatrics
Children do not come in neat packages, with diagnostic labels. They
and their families need all their needs met. Hospital practice
traditionally concentrates on the illness, not the patient, although this
is becoming less with time and paediatricians have always been more
holistic than adult counterparts. Hospital practice often deals with
complex problems by having specialists for each problem. Our adult
physician colleagues are beginning to realise that doesn’t work and are re
-inventing the general physician.
It has been shown that community paediatric patients have
significantly more complex problems than those presenting to general
paediatricians [5]. Many of the conditions we diagnose and treat have no
diagnostic tests. Community paediatricians need excellent clinical
skills, must be able to manage complexity and uncertainty, and must have
the ability to communicate across disciplines and across agencies,
creating understanding in those who come from different backgrounds and
with different agendas. It is not an easy job.
The National Service Framework
The NSF was constructed by multidisciplinary groups including
parents. It is therefore no accident that child health, not illness, is
emphasised. Hospital practice has rather less emphasis than crosscutting
‘out of hospital’ issues. Communication, coordination and early
intervention are all key themes. Parents and our sister agencies value
medical input that is holistic, available where it is needed (not just in
the clinic) and attuned to the needs of the child and family in the
community. They demand more of it than we can currently give.
Nevertheless, child health outside hospital has moved up the agenda and it
will be hard for Local Authorities to deliver Every Child Matters without
focused child health support to education, social and voluntary services,
as well as child health per se. This new agenda requires exactly the
skills community paediatricians have. If community paediatricians did not
exist, it would be necessary to invent them to deliver the NSF. The
challenge is how we tackle it.
Competing interests: Dr Ni Bhrolchain in a Specialty Training Advisor
in Community Child Health. These views are her own.
References
1. Hall DMB. Do we really need community paediatricians? A summary
of the lecture given to the Triennial Meeting of the Scottish Paediatric
Society. European Journal of Pediatrics 1991; 150 (7): 530 - 531.
2. Chambers TL. Death of the general paediatrician? Arch Dis Child
1997; 77: 364 – 367.
3. Royal College of Paediatrics and Child Health. The Next Ten
Years. Educating paediatricians for the new roles in the 21st century.
London 2002.
4. Chambers TL. An open letter to Doctors Mather and Bannon. Arch
Dis Child 2005; 90: 236 – 237.
5. Holmes N, Ni Bhrolchain CM. Case mix presenting to paediatricians
in a UK district (1998). Public Health 2002; 116: 179-183.
We read the article of McLoughlin et al. [1], reporting a 7 year old boy
with cyclic vomiting syndrome (CVS), whose episodes were controlled by L-
carnitine, with great interest. Here we present a 10 year-old girl with
CVS, whose episodes were also controlled by L-carnitine, but restarted
after an eight-month period.
The first episode of our patient was at 1 year of age, which was
characteri...
We read the article of McLoughlin et al. [1], reporting a 7 year old boy
with cyclic vomiting syndrome (CVS), whose episodes were controlled by L-
carnitine, with great interest. Here we present a 10 year-old girl with
CVS, whose episodes were also controlled by L-carnitine, but restarted
after an eight-month period.
The first episode of our patient was at 1 year of age, which was
characterized with antecedent anorexia lasting a few days followed by
vomiting approximately 20 per day and abdominal pain lasting one week. The
frequency of these episodes was reported as every three weeks. We have
established the diagnosis as cyclic vomiting syndrome at age 9 years, in
her first admission to our hospital, with negative blood investigations,
radiological studies, and 24-hour pH monitoring and with her
characteristic clinical presentation. The current episode was successfully
subsided with one dose chlorpromazine 0.5 mg/kg IV. For prophylactic
treatment, amitriptyline was started. Because the frequency and the
severity of the episodes did not change, carnitine at a dose of 50 mg/kg
(1.5 g/d) was started in addition to amitriptyline four months after the
diagnosis. Pretreatment free and total carnitine level was found as 20.7
µmol/ (normal range: 22-66 µmol/) and 38.8 µmol/ (normal range: 28-83
µmol/), respectively. For subsequent eight months, no episode was
observed. At 12th month, since measured serum total carnitine level was
higher than reference levels (93.7 µmol/l); carnitine dose was decreased
to 30 mg/kg (1 g/d). Unfortunately, episodes were restarted and got more
severe. Carnitine dose was re-increased to its original dose, but it did
not work. While she was still on carnitine treatment, erythromycin and
cyproheptadine was subsequently introduced instead of amitriptyline. Despite carnitine and cyproheptadine treatment, she experienced severe
episodes which could not be subsided with three doses of chlorpromazine,
therefore carnitine dose was increased to 3 g/d (100 mg/kg) after
determination of free and total carnitine levels (71.5 µmol/l, 46.8
µmol/l, respectively). Two episodes observed after this dose adjustment
were milder but episodes did not disappear.
We first decided to use carnitine for episode prophylaxis when we
read the article of Calcar et al. [2], who were successful in reducing the
cyclic vomiting episodes of six children with carnitine supplementation.
How carnitine works in CVS is unknown. It is believed that some probable
noxious compound is being bound by carnitine as a carnitine ester, thus
reducing its toxicity [2].
In our patient serum carnitine level was low as was in two of five
children in the mentioned study [2]. However, it was also shown that
carnitine supplementation works despite normal serum values [1,2].
McLoughlin et al. [1] explains this situation with carnitine dependence due
to a high metabolic turnover in those patients. Interestingly, decreasing
carnitine dose or stopping medication caused new episodes in two cases and
returning the carnitine dose to its original level decreased the frequency
of vomiting episodes in both of them [2]. In our case returning to original
dose did not work, only a partially response was provided with even
maximum dose of carnitine.
None of the treatment modalities for CVS used so far is a hundred
percent effective. CVS presents many similarities with the migraine so its
treatment is similar with anti-migraine treatment [3]. Recently, two
adolescent girls with migraine, whose carnitine levels were low, responded
to carnitine supplementation in respect with the frequency of episodes as
well as associated symptoms and other complaints [4].
Even though the long-term effectiveness of carnitine in preventing
episodes is not clear, we think that introduction of carnitine into the
treatment of CVS is a great contribution. On the behalf of patients with
CVS and physicians who deal with them, many thanks to Calcar et al. [2].
References
1. McLoughlin LM, Trimble ER, Jackson P, Chong SKF. L-carnitine in
cyclical vomiting syndrome. Arch Dis Child 2004;89:1180.
2. Calcar SC, Harding CO, Wolff JA. L-Carnitine administration
reduces number of episodes in cyclic vomiting syndrome. Clin Paediatr
2002;41:171-4.
3. Faucher S, Le Heuzey MF, Rouyer V, Mouren-Simeoni MC. On the
subject of the cyclic vomiting syndrome. Arch Pediatr 2003;10:385-91.
4. Kabbouche MA, Powers SW, Vockell AB, LeCates SL, Hershey AD.
Carnitine palmityltransferase II (CPT2) deficiency and migraine headache:
two case reports. Headache 2003;43:490-5.
It is interesting to note that now birth size is shown to be related
to income in later life! However, I wonder whether a correlation of 0.04 or 0.1
can be considered substantial. Although the P values are impressive
(<_0 it="it" is="is" due="due" to="to" the="the" relative="relative" large="large" sample="sample" size="size" in="in" their="their" study="" p="p"> Another interesting po...
It is interesting to note that now birth size is shown to be related
to income in later life! However, I wonder whether a correlation of 0.04 or 0.1
can be considered substantial. Although the P values are impressive
(<_0.0001 it="it" is="is" due="due" to="to" the="the" relative="relative" large="large" sample="sample" size="size" in="in" their="their" study.="study." p="p"/> Another interesting point is that in this study Professor Barker and
his co-authors used birth height rather than their favourite birth weight.
I guess it might be because they want to compare their results to a
previous study, but, however, it would be interesting to know if they can
find similar correlations between birth weight/BMI/Ponderal index and
income in later life.
Another point I would like to make is that in their conclusions
they said "Protection of infant growth will not only reduce infant
mortality and childhood morbidity, but will improve cognitive function,
and reduce morbidity from coronary heart disease and type 2 diabetes in
adult life". Notwithstanding the questionable statistical analyses in most
studies on fetal origins of adult diseases hypothesis, [1] two studies found
high birth weight increases the risk of breast cancer in women [2,3]. So
does this mean that we should only protect the growth of male babies?
References
1. Tu Y-K, West R, Ellison GTH, Gilthorpe MS. Why evidence of fetal
origins of adult diseases can be statistical artifact: the reversal
paradox examined for hypertension. American Journal of Epidemiology
2005;161:27-32.
2. Ahlgren M, Melbye M, Wohlfahrt J, Sorensen TA. Growth patterns and
the risk of breast cancer in women. New England Journal of Medicine
2004;351:1619-1626.
3. Michels KB et al. Birthweight as a risk factor for breast cancer.
Lancet 1996;348:1542-1546.
The meta-analysis of adenotonsillectomy trial results reported by van
Staaij and colleagues[1], from which they concluded that the operation
confers “an additional, but small, reduction of sore throat episodes . . .
compared to watchful waiting,” falls short on numerous counts and misleads
the unwary reader.
Their analysis of the trials conducted between the 1920s and 1960s
not only overlooks prev...
The meta-analysis of adenotonsillectomy trial results reported by van
Staaij and colleagues[1], from which they concluded that the operation
confers “an additional, but small, reduction of sore throat episodes . . .
compared to watchful waiting,” falls short on numerous counts and misleads
the unwary reader.
Their analysis of the trials conducted between the 1920s and 1960s
not only overlooks previously published critiques of those trials[2-4] but
fails to incorporate the sense of those critiques’ most telling
criticisms, namely, the exclusion from most of the trials, on ethical
grounds, of children thought to be severely affected; the inclusion of
children who were only mildly affected and in whom, therefore, the
benefits of surgery could at best be modest; and the limited nature of
follow-up procedures and, accordingly, of ascertainment of the numbers and
types of succeeding episodes of throat infection. Relatedly, their
analysis of trials conducted since the 1960s[5,6] (each of which I led)
omits mention of key elements and, most importantly, misconstrues the
trials’ results and consequently their clinical implications.
The main single shortcoming of the meta-analysis is its failure, by
considering only pooled risk differences across studies, to relate the
outcomes of individual randomized trials to the stringency of the
indications used in determining trial eligibility. Although the authors
note that “the inclusion citeria of the trials varied from mild and
nonspecific to severe and very strict,” they pursue this issue no further
and appear not to recognize its importance in determining outcomes. Thus,
for example, the results of tonsillectomy in children meeting the
stringent eligibility criteria of our first trial[5] were more distinctly
favorable than the results of either tonsillectomy or adenotonsillectomy
in children who met the somewhat less stringent criteria of our second
trial[6], even though the latter criteria were considerably more stringent
than those used in the studies conducted before 1970.
Another important shortcoming of the meta-analysis is its failure to
consider, in addition to the mean numbers of episodes overall occurring
after randomization, the nature and severity of the episodes that occurred
and how they were distributed among the trial participants. Thus, in our
first randomized trial in the first year after randomization, there was a
2.5-fold reduction among surgical subjects in the mean number of throat
infection episodes overall (47 episodes in 38 surgical subjects vs 108
episodes in 35 control subjects), but a 4-fold reduction in the proportion
of surgical subjects who had three or more episodes of any type (13% [5 of
38] vs 54% [19 of 35]) and a 14-fold reduction in the mean number of
episodes rated clinically as moderate or severe (3 episodes in 38 surgical
subjects vs 41 episodes in 35 control subjects).[5]
It is certainly the case that, overall, children severely affected
with recurrent episodes of throat infection who do not undergo
tonsillectomy will likely have fewer episodes during succeeding years, but
it is also the case that the risk of frequent and/or severe episodes
continuing to occur in such children is sharply reduced by tonsillectomy.
Physicians and parents considering the advisability of tonsillectomy must
be cognizant of this balance of probabilities. Finally, it is important
to emphasize that, in children meeting throat infection criteria less
stringent than those of our first trial, the likelihood of substantial
benefit from tonsillectomy is indeed small.[6] However, to generalize
from results obtained in children most of whom were not severely affected
to children who are, and who might benefit substantially from surgery, is
unjustified, and tantamount to throwing out the baby with the bathwater.
References
1. van Staaij BK, van den Akker EH, van der Heijden GJMG, Schilder
AG, Hoes AW. Adenotonsillectomy for upper respiratory infections;
evidence based? Arch Dis Child 2005;90:19-25.
2. Feinstein AR, Levitt M. The role of tonsils in predisposing to
streptococcal infections and recurrences of rheumatic fever. N Engl J Med
1970;282:285-91.
4. Paradise JL. Clinical trials of tonsillectomy and adenoidectomy:
limitations of existing studies and a current effort to evaluate efficacy.
South Med J 1976;69:1049-53.
5. Paradise JL, Bluestone CD, Bachman RZ, et al. Efficacy of
tonsillectomy for recurrent throat infection in severely affected
children: Results of parallel randomized and nonrandomized clinical
trials. N Engl J Med 1984;310:674-83.
6. Paradise JL, Bluestone CD, Colborn DK, et al. Tonsillectomy and
adenotonsillectomy for recurrent throat infection in moderately affected
children. Pediatrics 2002;110:7-15.
We read with interest the recent article by Aggarwal et al evaluating the haematological effect of iron supplementation in breast fed term low birth weight (LBW) infants. [1]
Low birth weight infants are more susceptible to iron deficiency owing to their proportionately smaller iron store at birth and their relative higher growth rate in the first months of life. Erythropoiesis at all ages...
We read with interest the recent article by Aggarwal et al evaluating the haematological effect of iron supplementation in breast fed term low birth weight (LBW) infants. [1]
Low birth weight infants are more susceptible to iron deficiency owing to their proportionately smaller iron store at birth and their relative higher growth rate in the first months of life. Erythropoiesis at all ages is dependent upon adequate nutrition, and particularly on protein and iron intake. However, there is still confusion about the optimal time and dose for iron supplementation for LBW infants. We investigated the effects of early enteral iron supplementation on erythrocyte and iron status parameters in very low birth weight infants. Thirty healthy preterm infants (gestational age between 26-32 weeks) with birth weights 920-1500 g included in the study at a mean age of 16 days. Seventeen infants were randomized to receive 2-4 mg/kg/day enteral iron and 13 infants served as controls. Hemoglobin concentrations, mean corpuscular volume, reticulocyte count, serum iron, transferrin, transferrin saturation, and ferritin levels were studied on three consecutive venous blood samples taken at the beginning, 7th and 28th days of the study. Laboratory values of these parameters were shown in Table 1.
Study Entry
28th Day
EI
Control
EI
Control
Hemoglobin (g/dL)
12.6+-2.3
(12.6)
9.1-17.5
12.1+-2.3
(12.6)
7.6-15.6
10.2+-2.3
(9.6)
7.5-14.6
9.5+-1.7
(9.6)
7-11.5
MCV (fL)
99.4+-6.03
(100.0)
89.6-111.0
96.9+-5.4
(98.0)
88.9-107.4
92.9+-4.8
(93.2)
83.0-99.3
89.2+-4.5
(89.0)
81.0-98.1
Reticulocyte (%)
1.9+-0.9
(1.8)
0.6-4.1
2.7+-1.5
(2.3)
0.9-6.4
4.3+-2.6
(3.9)
1.2-8.3
4.6+-1.6
(4.8)
1.8-6.7
Serum iron (ug/dL)
74.9+-26.6**
(70)
27-130
87.0+-28.5
(86)
41-142
98.5+-34.0**
(86)
68-181
75.5+-16.8
(74.5)
54-102
Ferritin (ng/mL)
334.8+-215.6
(262)
78-985
412.2+-185.8
(383)
175-796.9
346.3+-250.8
(271.5)
142-894
347.4+-151.7
(308.5)
124-614
Transferrin (mg/dL)
146.1+-34.6
(135.5)
88-207
162.8+-27.9
(157)
114-213
141.1+-22.8
(137)
117-195
151.3+-33.8
(158)
89-196
Transferrin saturation (%)
38.2+-17.0**
(34.6)
10.3-70.5
37.5+-10.6
(36.1)
18.0-55.3
50.4+-20.1**
(45.9)
25.85-71.3
36.6+-12.2
(33.6)
24.8-60.5
Table: Erythrocyte and iron status
parameters of the two study groups*
EI: early iron; MCV: mean corpuscular
volume
* The results were shown as mean +-
standard deviation (median), minimum-maximum
** p<0.05
Hemoglobin concentration declined throughout the study in both groups. We did not observe any significant improvement in serum ferritin levels in early enteral iron group. Serum iron levels and transferrin saturation increased significantly during the study period in iron supplemented infants (p = 0.014 and p = 0.026 respectively). We concluded that early enteral iron supplementation in very low birth weight infants seems beneficial by maintaining adequate iron levels.
Reference
(1). Aggarwal D, Sachdev HPS, Nagpal J, Singh T, Mallika V. Haematological effect of iron supplementation in breast fed term low birth weight infants. Arch Dis Child 2005;90:26-29.
Dear Editor,
L carnitine is needed for the transport of long-chain fatty acids across the mitochondrial membrane for oxidation into acetyl coenzyme A and entry into the Krebs cycle. Long-chain fatty acids nay also increase temperature, and hence metabolic rate, oxygen consumption [Q10 effect] and net ATP yield by uncoupling oxidative phosphorylation. If excessive the uncoupling might have the reverse effect....
Dear Editor,
Barker et al. recently reported a relationship between short length at age 1 year and lower incomes in adulthood [1]. Citing results from an early report from the Newcastle Thousand Families Study showing a relationship between height at age 3 years and intelligence at age 11 [2]. Barker et al. interpreted this as evidence that slow infant growth may lead to a lifelong impairment of cognitive functio...
Dear Editor,
Septic shock is characterised by a hyperdynamic, vasodilated circulation associated with cytolin release and its inhibitory effect upon oxygen uptake and utilisation. Most deaths are late and occur after patients have developed multiple organ dysfunctions. In these cases cardiac arrest is preceded by a declining cardiac output the invariable cause of death. Haemorrhagic shock differs only in that i...
Dear Editor,
The authors are to be congratulated for the systematic review 'Are there patterns of bruising in childhood which are diagnostic or suggestive of abuse?' It is an extremely valuable piece of work, providing data for paediatricians working in the field of child protection.
Results show that non-abusive bruises are generally small, sustained over bony prominences and found on the front of the...
Dear Editor,
We were interested in the article by Konig, Benger and Goldsworthy [1] describing the use of an Automated External Defibrillator (AED) in a 6- year-old child and would like to congratulate them and the paramedic team on saving this girl’s life.
As the authors point out in their discussion, data on the use of AEDs in children is scant and any publication in this area is encouraged. In the ab...
Dear Editor,
Since 1991 there has been talk of abolishing community paediatrics as a specialty [1]. At that time, a group of related specialties was proposed: a specialty of child development and rehabilitation (neurodisability); child protection would be subsumed into general paediatrics and there would be child public health doctors. Since then there has been a view amongst some paediatricians that community...
Dear Editor,
We read the article of McLoughlin et al. [1], reporting a 7 year old boy with cyclic vomiting syndrome (CVS), whose episodes were controlled by L- carnitine, with great interest. Here we present a 10 year-old girl with CVS, whose episodes were also controlled by L-carnitine, but restarted after an eight-month period.
The first episode of our patient was at 1 year of age, which was characteri...
Dear Editor,
It is interesting to note that now birth size is shown to be related to income in later life! However, I wonder whether a correlation of 0.04 or 0.1 can be considered substantial. Although the P values are impressive (<_0 it="it" is="is" due="due" to="to" the="the" relative="relative" large="large" sample="sample" size="size" in="in" their="their" study="" p="p"> Another interesting po...
The meta-analysis of adenotonsillectomy trial results reported by van Staaij and colleagues[1], from which they concluded that the operation confers “an additional, but small, reduction of sore throat episodes . . . compared to watchful waiting,” falls short on numerous counts and misleads the unwary reader.
Their analysis of the trials conducted between the 1920s and 1960s not only overlooks prev...
Dear Editor,
We read with interest the recent article by Aggarwal et al evaluating the haematological effect of iron supplementation in breast fed term low birth weight (LBW) infants. [1]
Low birth weight infants are more susceptible to iron deficiency owing to their proportionately smaller iron store at birth and their relative higher growth rate in the first months of life. Erythropoiesis at all ages...
Pages