Boletín Médico del - Hospital Infantil de México Federico Gómez
Boletín Médico del - Hospital Infantil de México Federico Gómez
Boletín Médico del - Hospital Infantil de México Federico Gómez
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<strong>Boletín</strong> <strong>Médico</strong> <strong><strong>de</strong>l</strong><br />
ISSN-1665-1146
EDITORIAL<br />
249 Thoracoscopy using ultrasonic scalpel: importance in the etiologic study of interstitial lung disease in children<br />
Luis Jasso Gutiérrez<br />
REVIEW ARTICLE<br />
251 Efficacy and safety of omega 3 and omega 6 fatty acid supplementation in <strong>de</strong>velopmental neurological<br />
disor<strong>de</strong>rs: systematic review<br />
Antonio Cal<strong>de</strong>rón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba<br />
RESEARCH ARTICLES<br />
257 Use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in pediatric patients with interstitial lung<br />
disease<br />
Ricardo Villalpando Canchola, Esmeralda Piedra Buena Muñoz, Isis Beatriz Me<strong><strong>de</strong>l</strong> Morales, Edgar Morales Juvera, Gabriel Reyes<br />
García, Fortino Solórzano Santos<br />
262 Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital<br />
Yolanda Vázquez Lara, Juan Carlos Bravo Ortiz, Claudia Hernán<strong>de</strong>z Galván, Narlly <strong><strong>de</strong>l</strong> Carmen Ruíz Quintero, Carlos Augusto<br />
Soriano Beltrán<br />
268 Association of steroid use with weight gain in pediatric patients with rheumatic disease<br />
Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasís-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez,<br />
Patricia Yañez-Sánchez<br />
275 Analysis of socio<strong>de</strong>mographic features of patients with end-stage chronic renal disease: differences in a 6-year<br />
period<br />
Guillermo Cantú, Graciela Rodríguez, Merce<strong>de</strong>s Luque-Coqui, Benjamín Romero, Saúl Valver<strong>de</strong>, Silvia Vargas, Alfonso Reyes-<br />
López, Mara Me<strong>de</strong>iros<br />
CASE REPORTS<br />
280 Bronchial mucoepi<strong>de</strong>rmoid carcinoma: a rare tumor in children<br />
Luis Hernán<strong>de</strong>z-Motiño, Yarisa Brizuela, Verónica Vizcarra, Rubén Cruz, Lour<strong>de</strong>s Jamaica, José Karam<br />
284 Hermansky-Pudlak syndrome: variable clinical expression in two cases<br />
Rogelio Pare<strong>de</strong>s Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón<br />
CLINICOPATHOLOGICAL CASE<br />
<strong>Boletín</strong> <strong>Médico</strong> <strong><strong>de</strong>l</strong><br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong><br />
BIMONTHLY PUBLICATION<br />
Vol. 69 July-August, 2012 No.4<br />
CONTENTS<br />
291 Newborn with hypoplastic left heart syndrome<br />
Luis Alexis Arévalo-Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Perezpeña<br />
Diazconti
TOPICS IN PEDIATRICS<br />
298 Shaping a new strategy against B. pertussis: a public health problem in Mexico<br />
Lorena Suárez Idueta, Ilse Herbas-Rocha, César Misael <strong>Gómez</strong> Altamirano, Vesta Richardson López-Collada<br />
VITAL STATISTICS<br />
305 Mortality due to drowning in children less than 15 years of age in Mexico, 1998-2010<br />
Sonia B. Fernán<strong>de</strong>z-Cantón, Ana María Hernán<strong>de</strong>z Martínez, Ricardo Viguri Uribe<br />
<strong>Boletín</strong> <strong>Médico</strong> <strong><strong>de</strong>l</strong> <strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong><br />
In<strong>de</strong>xed in<br />
Scopus, Elsevier<br />
Embase/Excerpta Medica<br />
Current Awareness in Biological Sciences (CABS)<br />
In<strong>de</strong>x Medicus Latinoamericano (IMLA)<br />
Literatura Latinoamericana en Ciencias <strong>de</strong> la Salud (LILACS)<br />
Scientific Electronic Library Online (SciELO)<br />
Biblioteca Virtual en Salud (BVS)Periódica-Índice <strong>de</strong> Revistas Latinoamericanas en Ciencias, UNAM<br />
Latin<strong>de</strong>x<br />
EBSCO/MedicLatina<br />
Artemisa<br />
Complete electronic version<br />
www.himfg.edu.mx<br />
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Chief: Dr. Gonzalo Gutiérrez. Title reserved according to the Dirección General <strong><strong>de</strong>l</strong> <strong>de</strong>recho <strong>de</strong> Autor (SEP): 04-1985-000000000361-102.<br />
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<strong>Boletín</strong> <strong>Médico</strong> <strong><strong>de</strong>l</strong><br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong><br />
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editorial<br />
Thoracoscopy using ultrasonic scalpel: importance in the etiologic<br />
study of interstitial lung disease in children<br />
Dr. Luis Jasso Gutiérrez<br />
Interstitial lung disease (ILD) may present itself in<br />
children of any age. However, it is most frequent<br />
during the first 2 years of life and has a mortality<br />
rate of ∼30%. The principal causes are lung injuries or<br />
problems in lung <strong>de</strong>velopment which, in good measure,<br />
explains its frequency at this age and does not occur<br />
in children of other ages. In past years, i<strong>de</strong>ntifying a<br />
patient and establishing a specific diagnosis has been a<br />
challenge for pulmonologists, radiologists and pediatric<br />
pathologists as well as for neonatologists and internists. 1<br />
Among the principal and most frequent causes are diffuse<br />
<strong>de</strong>velopmental anomalies such as the case of congenital<br />
alveolar dysplasia, disor<strong>de</strong>rs of lung growth as well as<br />
chronic pulmonary disease of prematurity, pulmonary<br />
interstitial glycogenosis, hyperplasia of neuroendocrine<br />
cells of infancy, dysfunction of the alveolar surfactant T<br />
and E, host disor<strong>de</strong>rs (such as infections, hypersensitivity<br />
or aspiration), systemic diseases such as metabolic<br />
disor<strong>de</strong>rs, and collagen or autoimmune disor<strong>de</strong>rs, among<br />
others. In<strong>de</strong>pen<strong>de</strong>nt of the causes, ILD can affect, in ad-<br />
Departamento <strong>de</strong> Evaluación y Análisis <strong>de</strong> Medicamentos, <strong>Hospital</strong><br />
<strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong>, <strong>México</strong>, D.F., <strong>México</strong><br />
Correspon<strong>de</strong>nce to:<br />
Dr. Luis Jasso Gutiérrez<br />
Jefe <strong><strong>de</strong>l</strong> Departamento <strong>de</strong> Evaluación y Análisis <strong>de</strong> Medicamentos<br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong><br />
<strong>México</strong>, D.F., <strong>México</strong><br />
E-mail: ljasso@himfg.edu.mx<br />
Received for publication: 8-27-12<br />
Accepted for publication: 8-28-12<br />
Vol. 69, July-August 2012<br />
Bol Med Hosp Infant Mex 2012;69(4):249-250<br />
dition to the interstitium, different compartments of the<br />
lung such as airways, alveolar space, lymphatic channels<br />
and pleura. For this reason, the term diffuse parenchymal<br />
lung disease was coined. 2<br />
From the clinical viewpoint, its common manifestations<br />
are tachypnea, exercise intolerance, growth <strong><strong>de</strong>l</strong>ay,<br />
cyanosis, resting dyspnea and, <strong>de</strong>pen<strong>de</strong>nt on the time of<br />
evolution, Hippocratic fingers. After clinical suspicion and<br />
according to each case, it is necessary to perform chest xray,<br />
high-resolution computed tomography, bronchoscopy<br />
(that may inclu<strong>de</strong> bronchial washings for investigation<br />
of microorganisms or for genetic analysis of its content),<br />
pulmonary function tests and, when required, lung biopsy.<br />
With respect to lung biopsy, in the article published in<br />
the present number of Boletin Medico <strong><strong>de</strong>l</strong> <strong>Hospital</strong> <strong>Infantil</strong><br />
<strong>de</strong> Mexico (BMHIM) by Villalpando et al., five cases are<br />
<strong>de</strong>scribed in a retrospective series of children subjected<br />
to lung biopsies using thoracoscopy with three working<br />
ports and ultrasonic scalpel during a 12-month period. 3<br />
According to the authors' <strong>de</strong>scription, at least in these five<br />
cases the result was satisfactory. For this reason we believe<br />
that this innovation with respect to other techniques used<br />
in thoracoscopy is the safest due to scant bleeding and to<br />
the effect of aerostasia (absence of air leak). Although<br />
the results were satisfactory, it would be appropriate to<br />
increase the size of the sample to verify the findings. Also,<br />
the results could be compared with experiences of thoracoscopies<br />
performed in children using other methods. 4<br />
It should be mentioned that, for the general pediatrician,<br />
minimally invasive thoracoscopy is not only useful for<br />
lung biopsies but also for aortopexies, repair of congenital<br />
diaphragmatic hernias, excision of bronchogenic cysts,<br />
249
Luis Jasso Gutiérrez<br />
and exploratory thoracotomy or ligatures of the ductus<br />
arteriosus, among other important procedures. 5,6<br />
REFERENCES<br />
1. Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean<br />
JA, et al. Diffuse lung disease in young children: application<br />
of a novel classification scheme. Am J Respir Crit Care Med<br />
2007;176:1120-1128.<br />
2. Deterding RR. Infants and young children with children’s<br />
interstitial lung disease. Pediatr Allergy Immunol Pulmonol<br />
2010;23:25-31.<br />
3. Villalpando CR, Piedra BME, Me<strong><strong>de</strong>l</strong> MIB, Morales JE, Reyes<br />
GG, Solórzano SF. Uso <strong><strong>de</strong>l</strong> bisturí ultrasónico para la toma <strong>de</strong><br />
biopsias pulmonares por toracoscopia en pacientes pediátricos<br />
con enfermedad pulmonar intersticial. Bol Med Hosp Infant<br />
Mex 2012;69:257-261<br />
4. Ponsky TA, Rothenberg SS. Thoracoscopic lung biopsy in<br />
infants and children with endoloops allows smaller trocar<br />
sites and discreet biopsies. J Laparoendosc Adv Surg Tech<br />
A 2008;18:120-122.<br />
5. Ponsky TD, Rothenberg S, Tsao KJ, Ostlie DJ, St Peter SD,<br />
Holcomb GW. Thoracoscopy in children: is a chest tube<br />
necessary? J Laparoendosc Adv Surg Tech A 2009;19(suppl<br />
1):S23-S25.<br />
6. Glüer S, Schwerk N, Reismann M, Metzel<strong>de</strong>r ML, Nuste<strong>de</strong> R,<br />
Ure BM, et al. Thoracoscopic biopsy in children with diffuse<br />
parenchymal lung disease. Pediatr Pulmonol 2008;43:992-996.<br />
doi: 10.1002/ppul.20896.<br />
250 Bol Med Hosp Infant Mex
eview article<br />
Efficacy and safety of omega 3 and omega 6 fatty acid supplementation<br />
in <strong>de</strong>velopmental neurological disor<strong>de</strong>rs: systematic review<br />
Antonio Cal<strong>de</strong>rón-Moore 1 , Mariel Pizarro-Castellanos 2 , Antonio Rizzoli-Córdoba 3<br />
AbSTRACT<br />
Vol. 69, July-August 2012<br />
Bol Med Hosp Infant Mex 2012;69(4):251-256<br />
background. Available information on clinical gui<strong><strong>de</strong>l</strong>ines and review articles is controversial and is insufficient to <strong>de</strong>termine the clinical<br />
efficacy of supplementation with omega 3 and omega 6 fatty acids in neuro<strong>de</strong>velopmental disor<strong>de</strong>rs. Additional treatment may be effective<br />
for treatment of these disor<strong>de</strong>rs.<br />
methods. We conducted a systematic review based on the gui<strong><strong>de</strong>l</strong>ines of the Cochrane group by searching for clinical trials in MEDLINE,<br />
COCHRANE DATABASE in the time interval 1990 to 2011, in English and Spanish, and in pediatric patients that comply with the information<br />
required by the CONSORT group. One hundred and two articles were obtained; 97 articles were exclu<strong>de</strong>d choosing five randomized,<br />
double-blind, placebo-controlled trials to perform the review.<br />
Results. In the trials analyzed we found no significant difference in the improvement of ADHD symptoms between placebo group and the<br />
intervention, but there was clear clinical improvement. No serious adverse events were reported. There are no similar characteristics in<br />
the reviewed articles to carry out a meta-analysis and accurate assessment of the effectiveness of supplementation.<br />
Conclusions. With the results of this systematic review, we cannot state categorically that the use of this supplementation is significantly<br />
effective due to the different characteristics of the studies <strong>de</strong>scribed above. However, due to clinical improvement and a<strong>de</strong>quate safety<br />
profile, it may be useful without replacing pharmacological treatment.<br />
Key words: essential fatty acids, omega 3, omega 6, attention <strong>de</strong>ficit disor<strong>de</strong>r.<br />
INTRODuCTION<br />
According to the Diagnostic and Statistical Manual<br />
of Mental Disor<strong>de</strong>rs (DSM-IV), neuro<strong>de</strong>velopmental<br />
disor<strong>de</strong>rs are classified in Axis I, which are the clinical<br />
disor<strong>de</strong>rs that do not involve a syndrome. Among<br />
these are the Attention Deficit Hyperactivity Disor<strong>de</strong>r<br />
(ADHD) and Developmental Coordination Disor<strong>de</strong>r<br />
(DCD). 1 Characteristics of attention <strong>de</strong>ficit disor<strong>de</strong>rs are<br />
mismatching, inattention and impulsivity–hyperactivity.<br />
1 Departamento <strong>de</strong> Pediatría,<br />
2 Departamento <strong>de</strong> Neurología Pediátrica,<br />
3 Dirección <strong>de</strong> Investigación, <strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico<br />
<strong>Gómez</strong>, <strong>México</strong>, D.F., <strong>México</strong><br />
Correspon<strong>de</strong>nce: Dr. Antonio Rizzoli-Córdoba<br />
Dirección <strong>de</strong> Investigación<br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong><br />
<strong>México</strong>, D.F., <strong>México</strong><br />
E-mail: antoniorizzoli@hotmail.com<br />
Received for publication: 2-2-12<br />
Accepted for publication: 4-17-12<br />
The recommen<strong>de</strong>d treatment options for ADHD inclu<strong>de</strong><br />
pharmacological therapy with and without stimulant<br />
medications, and nonpharmacological treatment, mainly<br />
behavioral therapy. 2 The base treatment for DCD consists<br />
of the acquisition of skills and problem solving, although<br />
there is no established pharmacological treatment for this<br />
disor<strong>de</strong>r. Essential long-chain fatty acids are those that<br />
the body cannot synthesize or are synthesized in small<br />
amounts, so there is a need for dietary supplementation<br />
to meet the metabolic functions that they perform such as<br />
forming an important part of the cell membrane.<br />
At present, according to the French Agency for Food<br />
Sanitary Safety (AFSSA), the diet in <strong>de</strong>veloped countries<br />
provi<strong>de</strong>s sufficient concentrations of omega 6 and very low<br />
omega 3, with an omega 6/omega 3 ratio insufficient for<br />
the proper functioning of neuroconduction. 3<br />
Long-chain polyunsatured fatty acids (LC-PUFAs)<br />
are metabolically very active. The highest concentrations<br />
of these are found in the central nervous system (CNS),<br />
predominantly in the neuronal membranes. The most<br />
abundant is docosahexaenoic acid (DHA), which mainly<br />
participates in neuronal synapses where it intervenes in<br />
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Antonio Cal<strong>de</strong>rón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba<br />
neuronal signaling and formation of neurotransmitters,<br />
increasing neuronal permeability through the activation of<br />
sodium channels, and eicosapentaenoic acid (EPA), which<br />
is the precursor of DHA and an important activator of metabolism<br />
in the CNS. In addition, it favors the generation<br />
of eicosanoids and cytokines. 4 The relationship between<br />
LC-PUFA <strong>de</strong>ficiency and hyperactivity was initially proposed<br />
by Colquhoun and Bunday. 5 In 1995, Stevens et al.<br />
suggested a link between the <strong>de</strong>ficiency of omega 3 and<br />
omega 6 and ADHD, learning disabilities, reading disor<strong>de</strong>rs,<br />
dyspraxia and ADHD-related symptoms. 6,7<br />
In most neuro<strong>de</strong>velopmental disor<strong>de</strong>rs, first-line treatment<br />
is pharmacological. However, up to 20% of the<br />
patients with ADHD with pharmacological therapy have<br />
si<strong>de</strong> effects that hin<strong>de</strong>r its effects, causing distrust in<br />
parents over their use and resulting in treatment discontinuation.<br />
As mentioned previously, DCD patients have<br />
no established drug treatment.<br />
It has been suggested that supplementation with omega<br />
3 and omega 6 can function as an additional treatment to<br />
those treatments already established, for improvement of<br />
the clinical status of patients with ADHD and DCD.<br />
Some authors have suggested that children with ADHD,<br />
with and without a learning problem, respond differently<br />
to fatty acid supplementation. A higher response was observed<br />
in those children with learning disabilities. 8 It has<br />
even been suggested that some combinations of omega 3,<br />
omega 6, zinc and magnesium may be beneficial for these<br />
patients. Huss et al. suggested that these combinations<br />
have beneficial effects on attention and on behavioral and<br />
emotional problems in children and adolescents with this<br />
type of disor<strong>de</strong>r. 9 There are research groups who have<br />
reported that there is no hard evi<strong>de</strong>nce to justify this type<br />
of supplement; therefore, they do not recommend omega<br />
3 and omega 6 as adjuvant treatment options for ADHD. 10<br />
Information available in clinical gui<strong><strong>de</strong>l</strong>ines and review<br />
articles are controversial and insufficient. Therefore, the<br />
objective of this review was to assess the available information<br />
on the efficacy and safety of supplementation with<br />
omega 3 and omega 6 for neuro<strong>de</strong>velopmental disor<strong>de</strong>rs<br />
using a systematic review of the literature.<br />
mATERIALS AND mETHODS<br />
A systematic review was conducted based on the gui<strong><strong>de</strong>l</strong>ines<br />
of the Cochrane systematic reviews, 11 in Medline/<br />
PubMed database, Cochrane Database and Artemis, and<br />
references of retrieved articles published between 1990<br />
and 2011. The search was limited to clinical trials conducted<br />
in English and Spanish by a pediatric group. Studies<br />
were randomized and double-blind comparison was ma<strong>de</strong><br />
between administration of essential fatty acids and placebo<br />
administration, which evaluate the clinical efficacy as well<br />
as safety of the intervention <strong>de</strong>scribed. We sought clinical<br />
trials that complied with the required information in the<br />
articles of clinical trials, <strong>de</strong>veloped by the CONSORT<br />
Group (Consolidated Standards of Reporting Trials) in<br />
2010. 12 From the research done by two reviewers, 102<br />
articles were obtained. Of these, we selected five clinical<br />
trials that met the requirements established initially to<br />
perform the review.<br />
RESuLTS<br />
The <strong>de</strong>sign of the five articles analyzed was randomized,<br />
double-blind, placebo-controlled clinical trials (Table<br />
1). 3,7,13-15 In four of the five articles, the effect of fatty acid<br />
supplementation in children with ADHD and symptoms<br />
related to it was analyzed, whereas one study examined<br />
the effect on children diagnosed with DCD. Interventions<br />
performed, supplement given, doses and time of administration<br />
were different in all studies, ranging from 2–6<br />
months (Table 1).<br />
To evaluate the effectiveness of the supplement, the<br />
methods and scales used in the articles were diverse. No<br />
significant difference was found in improving ADHD<br />
symptoms between the placebo group and interventional<br />
group (Table 2). However, when assessing the clinical<br />
response in the intervention group, significant clinical<br />
improvement was found. Because this improvement was<br />
so significant, parents <strong>de</strong>ci<strong>de</strong>d to continue with the PU-<br />
EFAs supplement after study completion.<br />
In the study conducted by Sinn et al. where a combination<br />
of EPA, DHA, γ-linolenic acid and vitamin E<br />
(558 mg of EPA + 174 mg of DHA + 60 mg γ-LA + 10.8<br />
mg of vitamin E daily, for 15 weeks) was administered,<br />
a statistically significant difference was <strong>de</strong>monstrated<br />
between groups (supplement and placebo) in the Conners<br />
test for parents, with improvement of more than one<br />
standard <strong>de</strong>viation (SD) in 30 to 40% of children. In the<br />
second phase, the same intervention was performed in both<br />
groups and clinical improvement was found in Conners<br />
252 Bol Med Hosp Infant Mex
Efficacy and safety of omega 3 and omega 6 fatty acid supplementation in <strong>de</strong>velopmental neurological disor<strong>de</strong>rs: systematic review<br />
Table 1. Differences between type of supplement, dose and time of administration<br />
Author (year) Intervention Dose (per day) Time of administration<br />
Sinn, et al (2007) 7 EPA + DHA + GLA + Vit E 558 mg EPA + 174 mg DHA + Two periods, one of 15 and another of<br />
60 mg GLA + 10.8mg Vit E 30 weeks<br />
Jonhson, et al (2008) 13 EPA + DHA + GLA + Vit E 558 mg EPA + 174 mg DHA +<br />
60 mg GLA + 10.8 mg Vit E<br />
Two periods, each of 3 months<br />
Hirayama, et al (2004) 14 DHA + EPA 100 mg EPA<br />
+ 514 mg DHA<br />
One period of 2 months<br />
Voigt, et al (2001) 15 DHA 345 mg DHA One period of 4 months<br />
Richardson, et al (2005) 3 EPA + DHA + GLA + Vit E 558 mg EPA + 174 mg DHA + Two periods, each of 3 months<br />
(en DCD)<br />
60 mg GLA + 9.6 mg Vit E<br />
EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; GLA, gamma-linoleic acid; Vit E, vitamin E; DCD, <strong>de</strong>velopmental coordination<br />
disor<strong>de</strong>r.<br />
test in all groups with supplement, with a <strong>de</strong>crease of >1<br />
SD in 40 to 50% of the children. However, no significant<br />
difference was observed in the Conners test given to the<br />
teachers. 7 Likewise, Johnson et al. found a favorable<br />
clinical response (not statistically significant) in the subgroup<br />
of patients with predominantly inattentive ADHD<br />
(26%). This group showed a reduction in symptoms of<br />
50% in their<br />
symptoms. 13 Upon analyzing the safety of administration<br />
of the supplementation, no adverse effects were reported.<br />
Adverse effects were observed only in the gastrointestinal<br />
system (diarrhea and dyspepsia) in three patients, with no<br />
clinical compromise.<br />
DISCuSSION<br />
As discussed above, there are no similar features in the analyzed<br />
studies to perform a meta-analysis and an accurate<br />
assessment of the effectiveness of supplementation with<br />
LC-EPAs, omega 3 and omega 6 in neuro<strong>de</strong>velopmental<br />
disor<strong>de</strong>rs.<br />
The articles reviewed showed a wi<strong>de</strong> age range (6–18<br />
years). The supplement with which the intervention was<br />
ma<strong>de</strong>, its dose and time of administration ranged from 2<br />
to 6 months. Methods of evaluation of the efficacy were<br />
diverse. This does not allow us to compare results between<br />
studies or to measure the effectiveness of the supplement<br />
used.<br />
Vol. 69, July-August 2012<br />
Although no statistically significant differences were<br />
found in the articles that evaluated the effectiveness of the<br />
supplement in ADHD patients, between the intervention<br />
group and the placebo group, there was obvious clinical<br />
improvement, mainly in the areas of hyperactivity/impulsivity,<br />
inattention and coordination disor<strong>de</strong>rs.<br />
The combination most used and recommen<strong>de</strong>d for<br />
improvement of symptoms of ADHD is essential polyunsaturated<br />
fatty acids omega 3 (EPA, DHA) and omega 6<br />
(arachidonic acid and γ-LA). The most commonly used<br />
dose is 558 mg of EPA + 174 mg of DHA + 60 mg γ-LA<br />
+ 10.8 mg vitamin E/day.<br />
Clinical improvement observed in the areas of hyperactivity/impulsivity,<br />
inattention and coordination disor<strong>de</strong>rs,<br />
although not statistically significant, was sufficient to<br />
encourage parents to continue with the treatment of<br />
supplemental essential long-chain fatty acids, omega-3<br />
and omega 6, even after completion of studies. This is<br />
coupled with its safety and no significant adverse effects.<br />
Based on the results of this systematic review, we cannot<br />
categorically state that supplementation with essential<br />
long-chain fatty acids of omega 3 and omega 6 in neuro<strong>de</strong>velopmental<br />
disor<strong>de</strong>rs present significant efficacy due<br />
to the different characteristics of the previously <strong>de</strong>scribed<br />
studies. Although only statistically significant differences<br />
were shown in reading and spelling skills in the placebo<br />
group and the supplement group, it is suggested, for clinical<br />
improvement in other aspects such as hyperactivity/<br />
impulsivity and inattention, the possibility of supplementing<br />
with omega 3 essential fatty acids and omega 6<br />
when these symptoms predominate in the patient. For this<br />
reason, and an appropriate safety profile, the treatment<br />
may be useful in children with ADHD and DCD with the<br />
253
Antonio Cal<strong>de</strong>rón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba<br />
Table 2. Description of analyzed studies<br />
Author (year) Population Groups Intervention Evaluation Results<br />
Sinn (2007) 7<br />
ADHD<br />
Voigt (2001) 15<br />
ADHD<br />
n=104<br />
n=87<br />
n= 54<br />
Hirayama (2004) 14<br />
ADHD n=40<br />
Johnson (2008) 13<br />
ADHD<br />
n=75<br />
PUFA +<br />
MVM n=41<br />
PUFA<br />
n=36<br />
Placebo<br />
n=27<br />
PUFA +<br />
MVM<br />
DHA<br />
n=27<br />
Placebo<br />
n=27<br />
DHA<br />
n=20<br />
Placebo<br />
n=20<br />
PUFA<br />
n=37<br />
Placebo<br />
n=38<br />
n=59 AGPI<br />
558 mg EPA + 174<br />
mg DHA + 60 mg<br />
GLA + 10.8 mg vit E/<br />
day + MVM<br />
558 mg EPA + 174<br />
mg DHA + 60 mg<br />
GLA + 10.8 mg vit<br />
E/day<br />
First stage (15 weeks)<br />
Improvement in inattention, impulsivity,<br />
Conners scale, parents and hyperactivity in >1 SD in 30-40% of<br />
children<br />
Conners scale, teachers Without significant improvement<br />
Improvement in inattention, impulsivity<br />
Conners scale, parents and hyperactivity in >1 SD in 30-40% of<br />
children<br />
Conners scale, teachers Without significant improvement<br />
Placebo Conners scale Without significant improvement<br />
Second stage (30 weeks)<br />
558 mg EPA + 174<br />
mg DHA + 60 mg<br />
Conners scale, parents<br />
GLA + 10.8 mg vit E/<br />
day +MVM<br />
345 mg/day DHA for<br />
4 months<br />
Placebo<br />
3,600 mg DHA+700<br />
mg EPA/week for 2<br />
months<br />
Olive oil<br />
558 mg EPA + 174<br />
mg DHA/day, 60 mg<br />
GLA, 10.8 mg Vit E<br />
Olive oil<br />
558 mg EPA + 174<br />
mg DHA/day, 60 mg<br />
GLA, 10.8 mg Vit E<br />
TOVA (omission/<br />
commission)<br />
Improvement of 40-50% of patients in<br />
regard to symptoms of inattention and<br />
hyperactivity/impulsivity<br />
Increase of 3 SD in errors of omission,<br />
<strong>de</strong>crease of 1 SD in errors of commission,<br />
time of response with increase of 2<br />
SD (NS)<br />
254 Bol Med Hosp Infant Mex<br />
CCTT<br />
Decrease of time of carrying out test 1 of<br />
2 SD and of 3 SD in test 2 (NS)<br />
Decrease in internalization of 2 SD,<br />
outsi<strong>de</strong> behavior of 2 SD, socialization<br />
CBCL<br />
of 3 SD, thought processes of 2 SD,<br />
inattention 1.5 SD (NS)<br />
Conners No results shown (NS)<br />
Attention No results shown (NS)<br />
Auditory and visual<br />
memory<br />
Without increase in number of remembered<br />
objects<br />
Visuomotor integration Increase of 9 points in regard to normal age<br />
Continuity<br />
Without changes in errors of omission or<br />
commission<br />
Impatient Decrease of number of errors in 1<br />
First stage (3 months)<br />
26% presented >25% reduction in score<br />
ADHD-RS-IV<br />
and 12% presented >50% reduction in<br />
score<br />
ADHD-RS-IV 7% presented >25% improvement in<br />
score<br />
Second stage (3 months)<br />
TDAH-RS-IV 47% improved their score and of these,<br />
12% improved in >50% of symptoms
Efficacy and safety of omega 3 and omega 6 fatty acid supplementation in <strong>de</strong>velopmental neurological disor<strong>de</strong>rs: systematic review<br />
Table 2. Description of analyzed studies<br />
Author (year) Population Groups Intervention Evaluation Results<br />
Richardson (2005) 3<br />
DCD<br />
n= 117<br />
Vol. 69, July-August 2012<br />
PUFA<br />
n=60<br />
Placebo<br />
n=57<br />
n=100<br />
558 mg EPA + 174<br />
mg DHA + 60 mg<br />
GLA + 9.6 mg Vit E<br />
Olive oil<br />
558 mg EPA + 174<br />
mg DHA + 60 mg<br />
GLA + 9.6 mg Vit E<br />
First stage (3 months)<br />
Motor function (MABC)<br />
Reading and spelling<br />
(WORD)<br />
ADH symptoms<br />
teachers<br />
CTRS-L<br />
Increase of score from 6th to 12th percentile<br />
(NS)<br />
Increase in 1 SD in writing (z = 2.87, p<br />
Antonio Cal<strong>de</strong>rón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba<br />
10. Aben A, Danckaerts M. Omega-3 and omega-6 fatty acids in<br />
the treatment of children and adolescents with ADHD. Tijdschr<br />
Psychiatr 2010;52:89-97.<br />
11. Davey J, Turner RM, Clarke MJ, Higgins JP. Characteristics<br />
of meta-analyses and their component studies in the Cochrane<br />
Database of Systematic Reviews: a cross-sectional,<br />
<strong>de</strong>scriptive analysis. BMC Med Res Methodol 2011;11:160.<br />
doi:10.1186/1471-2288-11-160.<br />
12. Schulz K, Altman DG, Moher D, for the CONSORT Group.<br />
CONSORT 2010 Statement: updated gui<strong><strong>de</strong>l</strong>ines for reporting<br />
parallel group randomised trials. PLoS Med 2010;7:e1000251.<br />
doi:10.1371/journal.pmed.1000251.<br />
13. Johnson M, Ostlund S, Fransson G, Ka<strong>de</strong>sjo B, Gillberg C.<br />
Omega-3/omega-6 fatty acids for attention <strong>de</strong>ficit hyperactivity<br />
disor<strong>de</strong>r: a randomized placebo-controlled trial in children and<br />
adolescents. J Atten Disord 2009;12:394-401.<br />
14. Hirayama S, Hamazaki T, Terasawa K. Effect of docosahexaenoic<br />
acid-containing food administration on symptoms of<br />
attention-<strong>de</strong>ficit/hyperactivity-disor<strong>de</strong>r—a placebo-controlled<br />
double-blind study. Eur J Clin Nutr 2004;58:467-473.<br />
15. Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berreta MC,<br />
Heird WC. A randomized, double-blind, placebo-controlled trial<br />
of docosahexanoic acid supplementation in children with attention-<strong>de</strong>ficit/hyperactivity<br />
disor<strong>de</strong>r. J Pediatr 2001;139:189-196.<br />
256 Bol Med Hosp Infant Mex
esearch article<br />
use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in<br />
pediatric patients with interstitial lung disease<br />
Vol. 69, July-August 2012<br />
Bol Med Hosp Infant Mex 2012;69(4):257-261<br />
Ricardo Villalpando Canchola, 1 Esmeralda Piedra Buena Muñoz, 2 Isis Beatriz Me<strong><strong>de</strong>l</strong> Morales, 2<br />
Edgar Morales Juvera, 3 Gabriel Reyes García, 4 Fortino Solórzano Santos 5<br />
AbSTRACT<br />
background. Diagnosis of interstitial lung disease (ILD) in children is challenging. Open lung biopsy was long consi<strong>de</strong>red to be the best<br />
procedure to obtain lung tissue in children. Thoracoscopic biopsy may be equally effective and less aggressive. In this report we analyze<br />
the results of the use of ultrasonic scalpel with the placement of three 5-mm trocars (one for thoracoscope and two working ports) for lung<br />
biopsy through thoracoscopy.<br />
methods. We present a retrospective case series of children un<strong>de</strong>rgoing lung biopsy through thoracoscopy using three working ports and<br />
ultrasonic scalpel. The study was carried out from January 2011 to January 2012 in a third-level pediatric hospital.<br />
Results. A total of five patients aged 1 to 13 years were inclu<strong>de</strong>d. There were no complications in the five cases analyzed. The sample obtained<br />
was sufficient in all cases for histopathological study. During surgery, bleeding was reported on average of 4.3 ml (range: 0.5–10 ml).<br />
Operative time ranged from 2 to 3 h. Two cases required chest tube placement. These were removed 2 to 3 days after the surgical event,<br />
and patients were discharged without complications.<br />
Conclusions. Feasibility is confirmed of a technique for lung biopsy using an ultrasonic scalpel, which is easily reproducible in any hospital<br />
with the necessary resources to perform thoracoscopy. In this series there were no complications, bleeding was low and there was<br />
opportune placement of transpleural chest tube.<br />
Key words: lung biopsy, ultrasonic scalpel, interstitial lung disease.<br />
INTRODuCTION<br />
Diagnosis of interstitial lung disease (ILD) in infancy<br />
constitutes a real challenge for the pediatrician.1 Within<br />
the term ILD, a very heterogeneous group of subacute and<br />
chronic lung diseases are grouped that share in common the<br />
production of chronic inflammatory process with a diffuse<br />
1 Cirugía <strong>de</strong> Tórax,<br />
2 Resi<strong>de</strong>nte <strong>de</strong> Cirugía Pediátrica,<br />
3 Servicio <strong>de</strong> Urología,<br />
4 Servicio <strong>de</strong> Gastrocirugía,<br />
5 Pediatría Médica, Unidad Médica <strong>de</strong> Alta Especialidad <strong>Hospital</strong><br />
<strong>de</strong> Pediatría, Centro <strong>Médico</strong> Nacional Siglo XXI, Instituto Mexicano<br />
<strong><strong>de</strong>l</strong> Seguro Social, <strong>México</strong> D.F., <strong>México</strong><br />
Correspon<strong>de</strong>nce: Dr. Ricardo Villalpando Canchola<br />
Cirugía <strong>de</strong> Tórax, Unidad Médica <strong>de</strong> Alta Especialidad<br />
<strong>Hospital</strong> <strong>de</strong> Pediatría, Centro <strong>Médico</strong> Nacional Siglo XXI<br />
Instituto Mexicano <strong><strong>de</strong>l</strong> Seguro Social<br />
<strong>México</strong> D.F., <strong>México</strong><br />
E-mail: drricvillalpando@me.com<br />
Received for publication: 5-24-12<br />
Accepted for publication: 6-12-12<br />
lesion of the lung parenchyma, affecting the interstitium,<br />
epithelium, alveolar spaces and capillary endothelium.<br />
Because the interstitium is not affected alone, and the term<br />
pulmonary interstitial disease can cause some confusion,<br />
some authors prefer to refer to these groups as diffuse<br />
parenchymatous lung disease. 2 The clinical picture is<br />
predominantly characterized by tachypnea, hypoxia and<br />
diffuse pulmonary infiltrates. Other pathologies also are<br />
taken into consi<strong>de</strong>ration for the differential diagnosis such<br />
as some infections, chronic aspiration, some cardiac diseases<br />
and pulmonary vascular disease. 3 ILD is less frequent<br />
in children than in adults, but with higher comorbidities<br />
and mortality.4,5 By the time of <strong>de</strong>velopment, it can be<br />
<strong>de</strong>fined as either acute or chronic (lasting >6 months), and<br />
of known cause, unknown (idiopathic) or associated with<br />
other processes.<br />
From the histopathological point of view, the most<br />
wi<strong><strong>de</strong>l</strong>y used classification is based on the predominant cell<br />
type involved in thickening of the alveolar wall, so it can<br />
be usual interstitial pneumonia, <strong>de</strong>squamative interstitial<br />
pneumonia, giant cell interstitial pneumonia, plasma cell<br />
interstitial pneumonia, interstitial lymphoid pneumonia or<br />
257
Ricardo Villalpando Canchola, Esmeralda Piedra Buena Muñoz, Isis Beatriz Me<strong><strong>de</strong>l</strong> Morales, Edgar Morales Juvera, Gabriel Reyes García,<br />
Fortino Solórzano Santos<br />
bronchiolitis obliterans with interstitial pneumonia. The<br />
histological appearance of usual interstitial pneumonia is<br />
large heterogeneous lesions from alveolar inflammation<br />
to diffuse interstitial fibrosis. During lung biopsy (LB),<br />
lesions may be seen in various stages of <strong>de</strong>velopment<br />
with other areas of apparently healthy lung. It is very<br />
rare in children; therefore, many of the cases would be<br />
7, 8<br />
diagnosed today as nonspecific interstitial pneumonitis.<br />
Desquamative interstitial pneumonitis is characterized<br />
by an inflammatory process, initially homogeneous, and<br />
with abundant intraalveolar macrophage. This disease,<br />
although rare, is well characterized in children. Most<br />
cases have been reported in children
Vol. 69, July-August 2012<br />
Use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in pediatric patients with interstitial lung disease<br />
Figure 1. Tissue obtained with thorascopic grasper.<br />
Figure 2. Cut with ultrasonic scalpel.<br />
RESuLTS<br />
Inclu<strong>de</strong>d in the analysis were five patients with a median<br />
age of 9 years (1–13 years). No cases presented intra- or<br />
postoperative complications. The material obtained from<br />
the biopsy was consi<strong>de</strong>red sufficient in all cases by the<br />
pathology <strong>de</strong>partment (Figure 3). Perioperative bleeding<br />
was at minimum 0.5 ml and at maximum 10 ml. Median<br />
operative time was 2 h 15 min (range: 2–3 h). In two of<br />
the cases, placement of a chest tube was required, which<br />
was removed after 2 days in one patient and 3 days after<br />
surgery in the other patient. In all cases, therapeutic behavior<br />
was modified in accordance with the histopathological<br />
report of the LB (Table 1). One case presented neoplastic<br />
disease. The remaining four were of infectious etiology.<br />
Figure 3. Final sampling of the biopsied pulmonary tissue without<br />
evi<strong>de</strong>nce of residual bleeding.<br />
DISCuSSION<br />
Obtaining an LB was a procedure that was consi<strong>de</strong>red to<br />
be invasive for many years and remained as a last resort.<br />
However, it is recognized that with LB the etiology, extent,<br />
severity and aggressiveness of disease can be verified. 24<br />
LB is carried out at the end of a sequence of <strong>de</strong>cisions and<br />
diagnostic procedures, not as the first choice. However,<br />
in many instances, this has as a consequence a <strong><strong>de</strong>l</strong>ayed<br />
diagnosis and treatment, which may further <strong>de</strong>teriorate<br />
the patient’s prognosis. 25<br />
It is believed that in or<strong>de</strong>r to have a useful biopsy, the<br />
tissue must be representative of the problem it seeks to<br />
explore. The i<strong>de</strong>al situation is a biopsy performed by an<br />
experienced thoracic surgeon who is familiar with the<br />
patient and is aware of the diagnostic possibilities. Hence,<br />
the surgeon’s experience during intraoperative lung evaluation<br />
and of the possible pathological processes involved<br />
will permit the surgeon to obtain tissue representative in<br />
quality and quantity, without incipient or advanced alterations<br />
that result in being nonspecific. This will allow<br />
for an appropriate diagnosis to be ma<strong>de</strong> from the tissue<br />
obtained. Also, it will be able to be <strong>de</strong>termined at which<br />
time tissue can be provi<strong>de</strong>d for cultures or special studies.<br />
LB does not tend to be a procedure that allows for repetitions.<br />
Therefore, perhaps more than other tissues obtained<br />
for biopsy, it is of particular importance that the tissues<br />
be managed carefully and appropriate measures used to<br />
optimize their informative value. 26<br />
For a long time, open LB was consi<strong>de</strong>red to be a major<br />
procedure to obtain lung tissue in children. Contraindica-<br />
259
Ricardo Villalpando Canchola, Esmeralda Piedra Buena Muñoz, Isis Beatriz Me<strong><strong>de</strong>l</strong> Morales, Edgar Morales Juvera, Gabriel Reyes García,<br />
Fortino Solórzano Santos<br />
Table 1. General characteristics of pediatric patients subjected to pulmonary biopsy with thorascopy using ultrasonic scalpel<br />
Case Age<br />
(years)<br />
Complications Sufficient<br />
sample<br />
Bleeding<br />
(ml)<br />
tions for open LB via thoracotomy are essentially surgical.<br />
The patient must be in optimal clinical and laboratory<br />
condition to be able to cope with the surgical procedure<br />
with the least possible risk. 20 Transbronchial LB is a<br />
procedure that, up to a certain point, is consi<strong>de</strong>red blind<br />
and with a greater risk of complications. Indication for a<br />
transbronchial biopsy is geared for the most part towards<br />
infectious and acute processes and is contraindicated in<br />
chronic interstitial diseases as its discriminatory value<br />
in these situations is limited. The usefulness of a transbronchial<br />
biopsy in young children is <strong>de</strong>batable due to<br />
the reduced size of the sample obtained because, in most<br />
cases, it is insufficient to establish a diagnosis. In a study<br />
in which percutaneous needle biopsies with an 18-gauge<br />
needle gui<strong>de</strong>d by high-resolution CT were used, histological<br />
diagnosis was achieved in only 58% of the cases. 23,27<br />
In pediatrics, LB is a standard diagnostic method for<br />
ILD. At present there is the possibility of offering the<br />
patient the thoracoscopic procedure, which carries the<br />
basic principles and benefits that endoscopic surgery<br />
has <strong>de</strong>monstrated during the last <strong>de</strong>ca<strong>de</strong>s. With respect<br />
to surgical technique, the current reports encourage the<br />
practice of obtaining biopsies by means of pre-knotted<br />
loops (Endoloop) or mechanical sutures (stapler) with the<br />
disadvantage of displacement of the pre-knotted loop when<br />
the lung is re-expan<strong>de</strong>d or the size of the stapler, which<br />
makes it ina<strong>de</strong>quate for pediatric patients. 28<br />
Based on the results of the five cases reported, it is<br />
consi<strong>de</strong>red that the technique <strong>de</strong>scribed in this study is<br />
the safest because of the small amount of bleeding and<br />
the effect of the aerostasia (no air leak) with the use of the<br />
<strong>de</strong>scribed instrument. In these cases, placement of chest<br />
tube is optional. If placed, it should always be removed<br />
within
Vol. 69, July-August 2012<br />
Use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in pediatric patients with interstitial lung disease<br />
10. Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis<br />
and the pathogenesis of pulmonary disease. Annu Rev<br />
Med 2010;61:105-119.<br />
11. Katzenstein AL, Gordon LP, Oliphant M, Swen<strong>de</strong>r PT.<br />
Chronic pneumonitis of infancy. A unique form of interstitial<br />
lung disease occurring in early childhood. Am J Surg Pathol<br />
1995;19:439-447.<br />
12. Copley SJ, Coren M, Nicholson AG, Rubens MB, Bush A,<br />
Hansell DM. Diagnostic accuracy of thin-section CT and chest<br />
radiography of pediatric interstitial lung disease. AJR Am J<br />
Roentgenol 2000;174:549-554.<br />
13. Koh DM, Hansell DM. Computed tomography of diffuse interstitial<br />
lung disease in children. Clin Radiol 2000;55:659-667.<br />
14. Bokulic RE, Hilman BC. Interstitial lung disease in children.<br />
Pediatr Clin North Am 1994;41:543-567.<br />
15. Redding GJ, Fan LL. Idiopathic pulmonary fibrosis and lymphocytic<br />
interstitial pneumonia. In: Taussig LM, Landau LI,<br />
eds. Pediatric Respiratory Medicine. St. Louis: Mosby; 1999.<br />
pp. 794-804.<br />
16. Chollet S, Soler P, Dournovo P, Richard MS, Ferrans VJ, Basset<br />
F. Diagnosis of pulmonary histiocytosis X by immuno<strong>de</strong>tection<br />
of Langerhans cells in bronchoalveolar lavage fluid. Am J<br />
Pathol 1984;115:225-232.<br />
17. Martin RJ, Coalson JJ, Rogers RM, Horton FO, Manous LE.<br />
Pulmonary alveolar proteinosis: the diagnosis by segmental<br />
lavage. Am Rev Respir Dis 1980;121:819-825.<br />
18. Fan LL, Lung MC, Wagener JS. The diagnostic value of<br />
bronchoalveolar lavage in immunocompetent children with<br />
chronic diffuse pulmonary infiltrates. Pediatr Pulmonol<br />
1997;23:8-13.<br />
19. Fan LL, Kozinetz CA, Deterding RR, Brugman SM. Evaluation<br />
of a diagnostic approach to pediatric interstitial lung disease.<br />
Pediatrics 1998;101:82-85.<br />
20. Coren ME, Nicholson AG, Goldstraw P, Rosenthal M, Bush A.<br />
Open lung biopsy for diffuse interstitial lung disease in children.<br />
Eur Respir J 1999;14:817-821.<br />
21. Hilman BC, Amaro-Galvez R. Diagnosis of interstitial lung<br />
disease in children. Paediatr Respir Rev 2004;5:101-107.<br />
22. Rothenberg SS, Wagner JS, Chang JH, Fan LL. The safety<br />
and efficacy of thoracoscopic lung biopsy for diagnosis and<br />
treatment in infants and children. J Pediatr Surg 1996;31:100-<br />
103; discussion: 103-104.<br />
23. Spencer DA, Alton HM, Raafat F, Weller PH. Combined percutaneous<br />
lung biopsy and high-resolution computed tomography<br />
in the diagnosis and management of lung disease in children.<br />
Pediatr Pulmonol 1996;22:111-116.<br />
24. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/<br />
fibrosis. Histologic features and clinical significance. Am J Surg<br />
Pathol 1994;18:136-147.<br />
25. Dishop MK, Askin FB, Galambos C, White FV, Deterding RR,<br />
Young LR, et al, for the chILD Network. Classification of diffuse<br />
lung disease in ol<strong>de</strong>r children and adolescents: a multiinstitutional<br />
study of the Children’s Interstitial Lung Disease<br />
(chILD) pathology working group. Mod Pathol 2007;2:2878.<br />
26. Leslie KO, Viggiano RW, Trastek VF. Optimal processing of<br />
diagnostic lung specimens. In: Leslie KO, Wick MR, eds. Practical<br />
Pulmonary Pathology. A Diagnostic Approach. Phila<strong><strong>de</strong>l</strong>phia:<br />
Churchill Livingstone; 2005. pp. 19-32.<br />
27. Langston D, Patterson K, Dishop MK, chILD Pathology Co-operative<br />
Group. A protocol for the handling of tissue obtained by<br />
operative lung biopsy: recommendations of the chILD pathology<br />
co-operative group. Pediatr Dev Pathol 2006;9:173-180.<br />
28. Ponsky TA, Rothenberg SS. Thoracoscopic lung biopsy in<br />
infants and children with endoloops allows smaller trocar<br />
sites and discreet biopsies. J Laparoendosc Adv Surg Tech<br />
A 2008;18:120-122.<br />
261
esearch article<br />
Bol Med Hosp Infant Mex 2012;69(4):262-267<br />
Risk factors associated with retinopathy of prematurity in preterm<br />
infants treated at a tertiary level hospital<br />
Yolanda Vázquez Lara, 1 Juan Carlos Bravo Ortiz, 1 Claudia Hernán<strong>de</strong>z Galván, 1 Narlly <strong><strong>de</strong>l</strong> Carmen Ruíz<br />
Quintero, 2 Carlos Augusto Soriano Beltrán 1<br />
AbSTRACT<br />
background. Retinopathy of prematurity (ROP) is <strong>de</strong>fined as a peripheral proliferative vitreoretinopathy in which immaturity (<strong>de</strong>termined<br />
by gestational age and birth weight) and oxygen are more <strong>de</strong>cisive factors. We un<strong>de</strong>rtook this study to analyze the relative risk for <strong>de</strong>velopment<br />
of ROP in relation to gestational age and birth weight in infants.<br />
methods. We carried out a retrospective, analytical, cross-sectional, single center trial in preterm infants with a gestational age
PATIENTS AND mETHODS<br />
Vol. 69, July-August 2012<br />
Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital<br />
We conducted a retrospective, observational, <strong>de</strong>scriptive,<br />
cross-sectional, unicentric and open study of premature<br />
newborns with a gestational age
Yolanda Vázquez Lara, Juan Carlos Bravo Ortiz, Claudia Hernán<strong>de</strong>z Galván, Narlly <strong><strong>de</strong>l</strong> Carmen Ruíz Quintero, Carlos Augusto Soriano<br />
Beltrán<br />
Table 1. International classification of PROP<br />
Stage<br />
• Stage 1. Line of <strong>de</strong>marcation: a fine white line that separates the vascular from the avascular retina<br />
• Stage 2. Elevated ridge: line of <strong>de</strong>marcation that appears in stage I increases in volume and extends outsi<strong>de</strong> the plane of<br />
the retina<br />
• Stage 3.Increase in vascular tissue towards the vitreous space<br />
• Stage 4. Subtotal retinal <strong>de</strong>tachment—subdivi<strong>de</strong>d into 4A if the macula is attached and 4B if the macula is <strong>de</strong>tached<br />
• Stage 5. Total retinal <strong>de</strong>tachment<br />
• Disease “plus”. Refers to dilatation and tortuosity of the vessels of the posterior pole and indicates that there is activity—can<br />
present in any stage of retinopathy<br />
• Baseline retinopathy. Five continuous or 8 total clock hours of disease with a stage 3 “plus” in zone 1 or 2<br />
Localization<br />
• Zone 1. Circle whose radius is two times the distance between the papila and the fovea<br />
• Zone 2. Comprises a band of retina from the limits of zone 1 up to the ora serrate nasally in the horizontal meridian<br />
• Zone 3. The remaining semilunar space, outsi<strong>de</strong> zone 2<br />
Extension<br />
Extension of the retinopathy is <strong>de</strong>scribed in clock sectors<br />
ROP, retinopathy of prematurity.<br />
Figure 1. Representation of the retina in hourly sectors and divi<strong>de</strong>d<br />
according to zones.<br />
In our population, 59.09% of all premature NB weighing<br />
from 751-1,000 g <strong>de</strong>veloped ROP. The rest of the<br />
sample population, <strong>de</strong>pending on weight, had a relatively<br />
lower risk of <strong>de</strong>veloping ROP as birth weight increased.<br />
The factors that were related with a greater risk of <strong>de</strong>veloping<br />
ROP were oxygen with a 1.30 times greater risk of<br />
<strong>de</strong>veloping ROP, mechanical ventilation with 1.65 times<br />
greater risk, pulmonary bronchodysplasia with a 1.60<br />
times greater risk and sepsis with 1.27 times greater risk<br />
of <strong>de</strong>veloping ROP. All these values were statistically<br />
significant. The remaining factors analyzed did not present<br />
a significant risk but should be followed up.<br />
DISCuSSION<br />
ROP is a peripheral proliferative vitreoretinopathy that<br />
<strong>de</strong>velops in premature children and in its most serious<br />
forms can cause blindness. Survival of premature infants<br />
has increased in the last <strong>de</strong>ca<strong>de</strong>; however, <strong>de</strong>spite this it<br />
appears that the prevalence of ROP has <strong>de</strong>creased. 17,18 It is<br />
essential to use screening systems to <strong>de</strong>tect all of cases of<br />
severe newborn ROP and adapt them to the changes that<br />
are present in the epi<strong>de</strong>miology of the disease.<br />
It is difficult to try to unify the criteria regarding the<br />
inci<strong>de</strong>nce of ROP among different populations because<br />
different variables can influence the results such as immaturity<br />
and the survival rate as well as the race of the<br />
patients studied. 17,19,20<br />
The inci<strong>de</strong>nce of ROP in this study was 36.9%, similar<br />
to that observed by Bossi and Koerner 21 and Pallás et<br />
al. 22 who found an inci<strong>de</strong>nce between 25 and 35%. In a<br />
comparative study, Blair et al. 23 reported an inci<strong>de</strong>nce of<br />
36.1% and in the UK an inci<strong>de</strong>nce of ROP was reported<br />
in general as 31.2%. 12<br />
However, our study showed an inci<strong>de</strong>nce less than<br />
that found in the studies by Holmström et al., Palmer et<br />
al. and Párraga et al. who reported inci<strong>de</strong>nces of between<br />
40 and 60%. 24-26<br />
In the study performed between 2000 and 2002 by the<br />
Early Treatment for Retinopathy of Prematurity Coopera-<br />
264 Bol Med Hosp Infant Mex
Vol. 69, July-August 2012<br />
Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital<br />
Table 2. Evaluation of risk of ROP in accordance with gestational age<br />
Gestational<br />
age (weeks)<br />
Without<br />
ROP<br />
With ROP Total RR (p) Inci<strong>de</strong>nce<br />
(%)<br />
24-25 2 0 2 — —<br />
26-27 10 14 24 1.65<br />
(0.008)*<br />
58.33<br />
28-29 33 59 92 2.37<br />
(0.0005)*<br />
64.13<br />
30-31 71 29 100 0.72<br />
(0.063)<br />
29.00<br />
32-33 75 23 98 0.55<br />
(0.003)*<br />
23.46<br />
34-35 24 2 26 0.196<br />
(0.017)*<br />
7.6<br />
≥36 2 0 2 — —<br />
Total 217 127 344 — —<br />
ROP: retinopathy of prematurity; RR: risk factor.<br />
*p value statistically significant<br />
Table 3. Evaluation of ROP risk with regard to weight<br />
Weight (g) Without<br />
ROP<br />
With ROP RR Inci<strong>de</strong>nce (%)<br />
501-750 4 6 1.65<br />
(0.0600)<br />
60<br />
751-1,000 27 39 1.86<br />
(0.0005)*<br />
59.09<br />
1,001-1,250 57 55 1.58<br />
(0.001)*<br />
49.10<br />
1,251-1,500 87 25 0.508<br />
(0.0005)*<br />
22.32<br />
1,501-1,750 40 2 0.115<br />
(0.002)*<br />
4.76<br />
1,751-2,000 0 0 — —<br />
>2,000 2 0 — —<br />
Total 217 127 — —<br />
ROP, retinopathy of prematurity; RR, relative risk.<br />
*p value statistically significant.<br />
tive Group (ETROP), an inci<strong>de</strong>nce of 68% was reported,<br />
which was similar to that reported by the CRYO-ROP<br />
group in 1986 and 1987. 25,27 The number of patients studied<br />
and the screening parameters are different between the different<br />
studies analyzed, which make comparisons difficult.<br />
Screening for ROP should not only take into account<br />
gestational age and weight at birth, but should be enlarged<br />
to inclu<strong>de</strong> other patients whose perinatal disease predisposes<br />
them to an elevated risk for <strong>de</strong>veloping ROP. Efficient<br />
care now requires that children at high risk receive retinal<br />
exams carefully synchronized by an experienced ophthalmologist<br />
with experience in examinations of premature<br />
NB with risk of retinopathy, and that all pediatricians who<br />
care for these patients in risk situations be aware of the<br />
need for early examination. 28<br />
In <strong>de</strong>veloped countries such as the U.S. and UK, gui<strong><strong>de</strong>l</strong>ines<br />
for screening of these children have been established.<br />
However, it must be kept in mind that each region could<br />
have different parameters for screening due to the characteristics<br />
of the patients and that management is different<br />
in each region. These gui<strong><strong>de</strong>l</strong>ines recommend screening<br />
for children born 1500 g was only 4.76%, although it resulted<br />
to be statistically significant even when compared with<br />
22.32% corresponding to those patients who weighed<br />
Yolanda Vázquez Lara, Juan Carlos Bravo Ortiz, Claudia Hernán<strong>de</strong>z Galván, Narlly <strong><strong>de</strong>l</strong> Carmen Ruíz Quintero, Carlos Augusto Soriano<br />
Beltrán<br />
ROP continues to be a leading cause of blindness in<br />
children worldwi<strong>de</strong>. A significant number of children who<br />
<strong>de</strong>velop ROP will have serious visual problems (14.5%)<br />
and unfavorable structural problems (9.1%) <strong>de</strong>spite ablative<br />
treatment with laser or cryotherapy. 30,31<br />
It is important to emphasize that ophthalmological<br />
control of these patients should not be limited to the<br />
diagnosis and management of retinopathy until it progresses<br />
or until treatment is indicated. We must control<br />
these children in the early years due to the greater inci<strong>de</strong>nce<br />
of late refractive errors, strabismus and retinal<br />
<strong>de</strong>tachments. 32-35 Based on the results, we can conclu<strong>de</strong><br />
that preterm infants with gestational age between 28 and<br />
29 weeks have a risk of up to 2.37 greater of <strong>de</strong>veloping<br />
ROP. In infants with birth weights of 751 to 1,000 g, the<br />
risk is up to 1.6 times of <strong>de</strong>veloping ROP. Supplemental<br />
oxygen, mechanical ventilation and sepsis are risk factors<br />
of up to 1.6 times for the <strong>de</strong>velopment of ROP in<br />
premature NB.<br />
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Cooperative Group. The Early Treatment for Retinopathy of<br />
Prematurity Study: structural findings at age 2 years. Br J<br />
Ophthalmol 2006;90:1378-1382.<br />
35. Larsson EK, Holmström GE. Development of astigmatism<br />
and anisometropia in preterm children during the first 10<br />
years of life: a population based study. Arch Ophthalmol<br />
2006;124:1608-1614.<br />
267
esearch article<br />
Bol Med Hosp Infant Mex 2012;69(4):268-274<br />
Association of steroid use with weight gain in pediatric patients with<br />
rheumatic disease<br />
Sonia González-Muñiz, 1 Donají Miranda-González, 2 Miguel Ángel Villasis-Keever, 3 Vicente Baca-Ruíz, 4<br />
Teresa Catalán-Sánchez, 4 Patricia Yañez-Sánchez 4<br />
AbSTRACT<br />
background: Prevalence of obesity in pediatric patients with rheumatic disease (RD) receiving steroids can be as high as 43%. The aim<br />
of this study was to <strong>de</strong>termine the association between low dose of prednisone and weight gain among children with RD.<br />
methods: We carried out a prospective cohort study. One cohort was comprised of patients exposed to steroids (group B) and the other<br />
group was comprised of patients not exposed to steroids (group A). After standardization, all patients were followed for 24 weeks and<br />
weight, height, waist circumference, arm circumference and body fat percentage were assessed.<br />
Results: There were 20 patients in group A and 32 in group B. In the first group, juvenile rheumatoid arthritis was the main diagnosis (40%)<br />
and systemic lupus erythematosus (56%) in the second group. Between groups, from the beginning and during the entire study period<br />
there was no difference in the averages of each anthropometric variable, but there were four (12.5%) new cases of obesity in group B and<br />
none in group A. Eleven (55%) patients in group A and 18 (56%) patients of group B showed an increase in fat percentage. Of these, only<br />
in group B patients was there was a statistically significant gain (p 60 days with prednisone. It was conclu<strong>de</strong>d that the risk<br />
of obesity was low among children who were at their<br />
normal weight at baseline as a result of continuous use of<br />
steroids. 2 In 1988, a study in Kuwait evaluated the effects<br />
of chronic therapy with low-doses of prednisone on stature<br />
and obesity of 37 patients aged 2–15 years with nephrotic<br />
syndrome who had frequent relapses. Serial measurements<br />
of height and weight showed the persistence of obesity<br />
in only 2/13 of the children who were initially obese. 3 In<br />
2006, a Canadian study reported in a group of patients<br />
with nephrotic syndrome that the inci<strong>de</strong>nce of obesity was<br />
35 to 43% during GC treatment and found that the weight<br />
<strong>de</strong>creased when the GC dose was reduced or suspen<strong>de</strong>d. 4<br />
Obesity is <strong>de</strong>fined as a chronic metabolic disor<strong>de</strong>r<br />
characterized by excessive body fat. A child is consi<strong>de</strong>red<br />
obese when his/her weight is >20% of the i<strong>de</strong>al. 5<br />
According to the growth charts published in 2000 by the<br />
Centers for Disease Control and Prevention (CDC) in the<br />
268 Bol Med Hosp Infant Mex
U.S., obesity is <strong>de</strong>fined as body mass in<strong>de</strong>x (BMI) ≥95th<br />
percentile for age and gen<strong>de</strong>r and overweight is <strong>de</strong>fined<br />
when the percentile is ≥85 and ≤94. 6-8 Worldwi<strong>de</strong>, obesity<br />
and overweight are consi<strong>de</strong>red a public health problem.<br />
In Mexico, beginning with the National Health Survey<br />
in 2000, it was <strong>de</strong>termined that this was a problem that<br />
also occurs in the pediatric population. Prevalence of<br />
overweight was documented in children between 10 and<br />
17 years of age: 10.8–16.1% in males and 14.3–19.1% in<br />
females. Prevalence of obesity was 9.2–14.7% in males<br />
and 6.8–10.6 % in females. 9-11<br />
In clinical practice, the most frequently used indicator<br />
for diagnosis of obesity is the BMI. However, when the<br />
BMI is high, it is not distinguished whether the increase<br />
in weight with respect to height is a function of fat mass<br />
or fat-free mass. 8 Therefore, other measurement methods<br />
should be used to assess the total body composition such<br />
as biompedance. 4,12<br />
The aim of this study was to <strong>de</strong>termine whether there is<br />
a relationship between low-dose steroid use and changes<br />
in nutritional status in children with RD during the first<br />
months after establishing the diagnosis.<br />
PATIENTS AND mETHODS<br />
We conducted an observational, longitudinal, prospective<br />
and analytical cohort study with patients between 2<br />
and 16 years of age who were recruited in the Service of<br />
Rheumatology of the Pediatric <strong>Hospital</strong>, Centro Medico<br />
Nacional Siglo XXI. Patients who were inclu<strong>de</strong>d had to<br />
have a certain initial diagnosis of RD. Patients were divi<strong>de</strong>d<br />
into two groups: group A patients who did not require<br />
steroids for a minimum of 24 weeks and group B inclu<strong>de</strong>d<br />
patients with RD who initiated treatment with steroids<br />
(prednisone) and in whom it was necessary to continue<br />
treatment for at least 24 weeks. The <strong>de</strong>cision of whether or<br />
not to administer prednisone was ma<strong>de</strong> by the physician in<br />
charge of each patient. We exclu<strong>de</strong>d patients who received<br />
additional doses of steroids (such as methylprednisolone)<br />
as a result of complications of the disease itself during<br />
the monitoring period. The protocol was approved by the<br />
Local Committee for Health Research of the hospital. For<br />
admission to the study, parents signed an informed consent<br />
and patients >8 years provi<strong>de</strong>d informed assent.<br />
Prior to the initiation of the study, one of the investigators<br />
(SGM) conducted a standardization process for<br />
Vol. 69, July-August 2012<br />
Association of steroid use with weight gain in pediatric patients with rheumatic disease<br />
assessment of weight, height, waist circumference (WC),<br />
arm circumference and electrical bioimpedance to <strong>de</strong>termine<br />
total body composition, in particular the percentage<br />
of fat mass. Weight was <strong>de</strong>termined using a mechanical<br />
scale (BAME, Puebla, Mexico) with 140-kg maximum<br />
range and minimum weight of 1 kg. Height was measured<br />
using a stadiometer and a maximum range of 194 cm. Waist<br />
circumference (WC) and mid-upper arm circumference<br />
(MUAC) were measured with a fiberglass tape measure<br />
with a maximum length of 150 cm. Electrical bioimpedance<br />
was assessed with a four <strong>de</strong>rivation mo<strong><strong>de</strong>l</strong> (325F,<br />
Omron Healthcare, Bannockburn, IL). All measurements<br />
were performed at the time of confirmation of diagnosis<br />
and were repeated four times every 6 weeks during the 24<br />
weeks of surveillance. We <strong>de</strong>fined overweight when BMI<br />
was between the 85 th and 94 th percentile and as obese when<br />
it was ≥95 th percentile.<br />
Statistical Analysis<br />
Information was captured in a database. Subsequently,<br />
statistical analysis was performed using SPSS v.13.<br />
For <strong>de</strong>scriptive analysis, we used measures of central<br />
ten<strong>de</strong>ncy according to the scale of measurement variables.<br />
Qualitative variables were presented as mo<strong>de</strong>s and<br />
simple frequencies, whereas quantitative variables such<br />
as average and standard <strong>de</strong>viation (SD) showed a normal<br />
distribution after making a logarithmic conversion. For<br />
inferential analysis, we used the χ 2 test. For in<strong>de</strong>pen<strong>de</strong>nt<br />
and <strong>de</strong>pen<strong>de</strong>nt samples, t test was performed as well as<br />
one- and two-way analyses of variance (ANOVA). Furthermore,<br />
Pearson r correlation test was conducted; p
Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasis-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez, Patricia Yañez-<br />
Sánchez<br />
Table 1. Comparison of the characteristics of patient with rheumatic<br />
disease with or without steroid exposure<br />
Characteristics Group A<br />
(without steroids)<br />
n = 20<br />
Group B<br />
(with steroids)<br />
n = 32<br />
Age (years) Average ± SD 11.6 (± 3.3) 12.0 (± 3.2) 0.7<br />
Pediatric stage (n)<br />
• Preschool 1 1<br />
• School age 4 5<br />
• Adolescents 15 26<br />
Gen<strong>de</strong>r n (%)<br />
• Female<br />
• Male<br />
Type of RD n (%)<br />
14 (70)<br />
6 (30)<br />
22 (68.8)<br />
10 (31.2)<br />
• SLE 4 (20) 18 (56.2)<br />
• JIA 8 (40) 4 (12.5)<br />
• Vasculitis 1 (5) 4 (12.5)<br />
• Dermatomyositis 2 (10) 2 (6.2)<br />
• DEL 3 (15) —<br />
• APS 1 (5) 1 (3.1)<br />
• Progressive systemic<br />
sclerosis<br />
— 1 (3.1)<br />
• Overlap syndrome — 1 (3.1)<br />
• Sclero<strong>de</strong>rma 1 (5) —<br />
With respect to the amount of steroid prescribed in<br />
group B, there was little difference observed during the<br />
study period. The average dose at baseline was 0.32 mg/<br />
kg/day (range: 0.05–1.4 mg/kg/day), whereas for the fourth<br />
measurement, the average was 0.25 mg/kg/day (variation<br />
of 0.05–1.2 mg/kg/day).<br />
Table 2 compares the anthropometric measurements in<br />
the two groups: at baseline and at the end of the 24-week<br />
monitoring period. As noted, there were no differences<br />
between groups with respect to baseline and final measurements.<br />
However, it is worth noting that in both groups<br />
there was a slight increase in weight, WC, MUAC and fat<br />
percentage, which was a little higher in the steroid group.<br />
Figure 1 shows the behavior of the latter four variables.<br />
The remaining did not show changes of the four measurements<br />
at any given time. In terms of weight, compared<br />
with group A (which remained unchanged), group B had<br />
progressive increases. This was also observed in the WC<br />
and MUAC. Regarding the percentage of fat, group B<br />
p<br />
0.9<br />
0.03<br />
SD, standard <strong>de</strong>viation; SLE, systemic lupus erythematosus;<br />
JIA, juvenile idiopathic arthritis; APS, antiphospholipid syndrome;<br />
DLE, discoid lupus erythematosus; RD, rheumatic disease.<br />
had a lower percentage at the beginning, but in the end<br />
it nearly equaled the other group. According to ANOVA,<br />
the behavior of these variables between groups over time<br />
was not statistically significant (p >0.05).<br />
The average weight gain was higher in group B (0.3 kg<br />
vs. 1.3 kg) but was not statistically significant (p = 0.2);<br />
however, during the observation period, one patient from<br />
group A (5%) and five patients from group B (15%) showed<br />
an increase in weight much more than the average for the<br />
rest of the group (Figure 2). In the latter group, two patients<br />
increased their weight almost 15 kg as compared with the<br />
patient in group A who only showed an increase of 4.1 kg.<br />
Furthermore, according to the BMI, group A had four<br />
overweight patients (20%) and three obese patients (15%)<br />
from the first evaluation and who did not change their<br />
status during the study. In contrast, at baseline, group B<br />
had four overweight patients (12.5%) and seven obese<br />
patients (21.8%), but at the end there were six (18.7%) and<br />
eight (25%) patients, respectively. It should be noted that<br />
in these eight children with obesity, one patient had BMI<br />
within normal limits at the beginning of the surveillance<br />
period and another child was overweight, so the change<br />
in BMI percentile occurred during the steroid treatment<br />
period. Likewise, of the six patients who were <strong>de</strong>tected<br />
with overweight at the end of the study, their BMI (in three<br />
cases) was normal at initiation of the monitoring period. At<br />
the beginning and at the end of the study, the prevalence<br />
of overweight and obesity increased from 34 to 43%, and<br />
the inci<strong>de</strong>nce was 20%. In other words, there were five<br />
new cases of overweight or obesity. In contrast, it was<br />
also observed that the BMI improved in two patients: a<br />
patient with obesity changed to overweight and another<br />
overweight patient lowered to normal status.<br />
By analyzing the variation in fat percentage, we i<strong>de</strong>ntified<br />
11 patients in group A (55%) and 18 in group B (56%)<br />
with some increase in the percentage of fat during the 24week<br />
follow-up. Of these patients, only those from group<br />
B showed a statistically significant gain (p
Vol. 69, July-August 2012<br />
Association of steroid use with weight gain in pediatric patients with rheumatic disease<br />
Table 2. Basal and final measurements of patients with generalized rheumatic disease according to steroid exposure<br />
Variable No steroids<br />
n=20<br />
Basal Final*<br />
With steroids<br />
n=32<br />
No steroids<br />
n=20<br />
With steroids<br />
n=32<br />
Average ± SD Average ± SD Average ± SD Average ± SD<br />
Weght (kg) 45.4 (17.0) 46.8 (16.7) 45.7 (16.5) 48.1 (17.1)<br />
Length (cm) 145.4 (18) 145.4 (16.8) 145.7 (17.7) 145.9 (16.5)<br />
BMI 20.5 (3.1) 21.4 (3.2) 20.6 (2.3) 21.8 (0.6)<br />
WC (cm) 72.6 (14.0) 74.2 (13.8) 72.7 (13.3) 75.6 (14.2)<br />
Arm circumference (cm) 23.6 (4.7) 23.9 (4.9) 23.7 (4.4) 24.7 (5.2)<br />
Fat (%) 31.7 (10.0) 30.0 (10.0) 32.3 (9.3) 30.8 (8.2)<br />
*No statistical difference between groups or before or after in the same group.<br />
Figure 1. Comparison of four variables during the study period according to each group. BPI, brachial perimeter in<strong>de</strong>x.<br />
271
Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasis-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez, Patricia Yañez-<br />
Sánchez<br />
Figure 2. Comparison of the weight increment between groups.<br />
performing the correlation between cumulative steroid dose<br />
and weight change, fat, WC and arm circumference, we only<br />
obtained a low correlation between steroid dose with the<br />
fat percentage (r = 0.31, p = 0.08); the other three variables<br />
did not show any correlation.<br />
DISCuSSION<br />
With the results of this investigation we observed that there<br />
is a relationship between administration of steroids and<br />
weight gain in pediatric patients with RD receiving low<br />
doses of steroids. This observation was seen particularly<br />
in five patients (15.6%) because their weight increase<br />
was significant (5 kg–13 kg during a 6-month period).<br />
These findings were in spite of the fact that in the group<br />
exposed to steroid use since the beginning of the surveillance<br />
period, 11 patients were already overweight or<br />
obese (34%), whereas at the end of the study there were<br />
14 patients (43%). The weight gain in these five patients<br />
was as significant from the clinical point of view. In four<br />
of these patients who initially had normal BMI, at the end<br />
of the follow-up period three were overweight and one<br />
was obese, whereas the fifth patient changed from being<br />
overweight to obesity.<br />
The results of this study are similar to other studies such<br />
as the one by Merrit et al. where there was an increased<br />
inci<strong>de</strong>nce of obesity over a period of about 2 years, but in<br />
children with nephrotic syndrome; nevertheless, the steroid<br />
dose administered was not clearly specified. 2 Likewise, it<br />
has also been <strong>de</strong>scribed that upon discontinuation of steroids,<br />
the opposite effect was observed. In other words, it<br />
<strong>de</strong>creases the frequency of overweight or obese patients. 3<br />
In particular, in the case of patients with RD information<br />
on the modification of nutritional status has not been<br />
previously published. The only related studies refer to the<br />
possible impact of steroids in terms of stature. 13,14 However,<br />
the results of this study cannot be compared because<br />
the patients inclu<strong>de</strong>d in this study had a minimal change<br />
in their height, which is related to the monitoring time of<br />
our study (6 months) compared to previous studies with<br />
a much longer surveillance period.<br />
Another aspect used in this study that has not been<br />
<strong>de</strong>scribed previously was the analysis of body composition<br />
by measurement of the percentage of body fat using<br />
impedance. As <strong>de</strong>scribed, averages obtained between<br />
groups did not differ because during the study week there<br />
were patients who increased and others who <strong>de</strong>creased<br />
the amount of fat. Therefore, we procee<strong>de</strong>d to analyze the<br />
29 patients separately (n = 11, without steroids; n = 18,<br />
with steroids) in whom the amount of body fat increased.<br />
Although there was no difference in the rate of increase<br />
of fat between groups (55% vs. 56.2%), interestingly, it<br />
was <strong>de</strong>termined that in this subgroup the patients who<br />
received steroids gained more weight and had a greater<br />
increase in WC and arm circumference compared to the<br />
group without steroid use (Table 3). This would support<br />
the fact that the weight gain in patients who use prednisone<br />
would be related to the higher fat <strong>de</strong>position. Furthermore,<br />
it is worth mentioning the manner in which fat accumulates<br />
with steroid use. Based on data from this study, it is<br />
possible to assume that there is no preference for either<br />
central or peripheral fat accumulation when it is expected<br />
that the accumulation of fat would be predominantly<br />
central, as occurs in Cushing’s syndrome. However, it<br />
must be noted that this syndrome is associated with high<br />
doses of steroids. The findings on how fat accumulates in<br />
patients using steroids, which is <strong>de</strong>scribed in this study,<br />
is consistent with those reported by other authors using<br />
other assessment tools such as DEXA. 15-17<br />
Although in this study we consi<strong>de</strong>red important aspects,<br />
it is appropriate to mention that the study had some weaknesses.<br />
For example, although SLE patients who require<br />
high doses of steroids are not inclu<strong>de</strong>d, monitoring of<br />
patients who participated in this study took about 3 to 6<br />
months to be initiated after the conclusive diagnosis. The<br />
272 Bol Med Hosp Infant Mex
greater proportion of patients with SLE required high doses<br />
of steroids at the beginning of treatment for disease control.<br />
Thereafter, the dose is progressively reduced. Thus, it is<br />
possible that, in some patients, the cause of overweight<br />
or obesity prior to the study was due to the use of high<br />
doses of steroids. Another important point is that during<br />
the time the study was conducted, there was no control of<br />
food intake or physical activity of the patients. Of these<br />
two confounding variables, physical activity is probably<br />
the most important according to the type of disease<br />
because it is possible that the weight gain is due to lack<br />
of activities commonly carried out by children. In these<br />
patients, clinical manifestations can cause a <strong>de</strong>crease in<br />
physical activity due to pain or musculoskeletal disability<br />
or articulation. It is also possible that during the different<br />
phases of treatment, family members do not allow the<br />
child to perform physical activities, work, or go to school<br />
without specific medical advice. In this regard, it should<br />
be noted that there are studies in pediatric patients with<br />
chronic diseases that note that it is common for the patients<br />
to frequently miss school, which is not necessarily related<br />
to functional or organic problems. 18 Finally, this study<br />
did not consi<strong>de</strong>r adherence to the treatment as a possible<br />
confounding variable, although it could support the findings.<br />
In view of the above, and in or<strong>de</strong>r to explore and<br />
<strong>de</strong>termine the most clear relationship between low doses of<br />
steroids and weight gain, further studies are necessary that<br />
would take into account the nutritional status of children<br />
prior to the initiation of steroids, their growth rate, time<br />
of exposure to steroids, and therapeutic adherence as well<br />
as dietary habits and physical activity.<br />
Vol. 69, July-August 2012<br />
Association of steroid use with weight gain in pediatric patients with rheumatic disease<br />
Table 3. Baseline and final anthropometric evaluation of patients with increase in the percentage of fat in accordance with steroid exposure<br />
Variable Without steroids<br />
n = 11<br />
Basal Final*<br />
With steroids<br />
n = 18<br />
In conclusion, according to the results obtained in this<br />
study, it appears that there is a greater likelihood that children<br />
with RD receiving low dose steroids are exposed to a<br />
significant increase in weight. These findings should be an<br />
alert to healthcare workers caring for these patients in or<strong>de</strong>r<br />
to offer precautionary measures to prevent overweight and<br />
obesity as well as dietary gui<strong><strong>de</strong>l</strong>ines.<br />
REFERENCIAS<br />
Without steroids<br />
n = 11<br />
With steroids**<br />
n = 18<br />
Average ± SD Average ± SD Average ± SD Average ± SD<br />
Weight (kg) 39.9 (14.9) 45.7 (16.9) 41.23 (15.3) 48.7 (17.9)<br />
WC (cm) 65.5 (9.2) 71.3 (13.4) 67.8 (9.6) 75.3 (14.8)<br />
Arm circumference (cm) 23.8 (4.2) 23.6 (4.3) 23.7 (3.8) 25.4 (5.1)<br />
Fat (%) 28.9 (9.4) 23.8 (8.4) 31.3 (9.1) 29.6 (7.1)<br />
*No statistically significant differences between groups (p >0.05).<br />
**p
Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasis-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez, Patricia Yañez-<br />
Sánchez<br />
in<strong>de</strong>x cut offs to <strong>de</strong>fine thinness in children and adolescents:<br />
international survey. BMJ 2007;335:194.<br />
9. Rudolf MC. The obese child. Arch Dis Child Educ Pract Ed<br />
2004;89:ep57-ep62.<br />
10. <strong><strong>de</strong>l</strong> Río-Navarro BE, Velázquez-Monroy O, Sánchez-Castillo<br />
P, Lara-Esqueda A, Berber A, Fanghänel G, et al. The high<br />
prevalence of overweight and obesity in Mexican children.<br />
Obes Res 2004;2:217-223.<br />
11. Centers for Disease Control and Prevention. About BMI for children<br />
and teens. Disponible en: http://www.cdc.gov/healthyweight/<br />
assessing/bmi/childrens_bmi/about_childrens_bmi.html<br />
12. Pi-Sunyer FX. Obesity: criteria and classification. Proc Nutr<br />
Soc 2000;59:505-509.<br />
13. Simon D, Lucidarme N, Prieur AM, Ruiz JC, Czemichow P.<br />
Linear growth in children suffering from juvenile idiopathic<br />
arthritis requiring steroid therapy: natural history and effects<br />
of growth hormone treatment on linear growth. J Pediatr Endrocrinol<br />
Metab 2001;14(suppl 6):1483-1486.<br />
14. Simon D, Fernando C, Czernichow P, Prieur AM. Linear growth<br />
and final height in patients with systemic juvenile idiopathic<br />
arthritis treated with longterm glucocorticoids. J Rheumatol<br />
2002;29:1296-1300.<br />
15. Foster BJ, Shults J, Zemel BS, Leonard MB. Interactions<br />
between growth and body composition in children treated<br />
with high-dose chronic glucocorticoids. Am J Clin Nutr<br />
2004;80:1334–1341.<br />
16. Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ,<br />
Stallings VA. Long-term, high-dose glucocorticoids and bone<br />
mineral content in childhood glucocorticoid-sensitive nephrotic<br />
syndrome. N Engl J Med 2004;351:868-875.<br />
17. Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics<br />
and pharmacodynamics of systemically administered glucocorticoids.<br />
Clin Pharmacokinet 2005;44:61-98.<br />
18. Lollar DJ, Hartzell MS, Evans MA. Functional difficulties and<br />
health conditions among children with special needs. Pediatrics<br />
2012; 129: e714-e722.<br />
274 Bol Med Hosp Infant Mex
esearch article<br />
Analysis of socio<strong>de</strong>mographic features of patients with end-stage chronic<br />
renal disease: differences in a 6-year period<br />
Vol. 69, July-August 2012<br />
Bol Med Hosp Infant Mex 2012;69(4):275-279<br />
Guillermo Cantú, 1 Graciela Rodríguez, 2 Merce<strong>de</strong>s Luque-Coqui, 3 Benjamín Romero, 3 Saúl Valver<strong>de</strong>, 3 Silvia<br />
Vargas, 4 Alfonso Reyes-López, 4 Mara Me<strong>de</strong>iros 3<br />
AbSTRACT<br />
background. Chronic renal disease (CRD) has a strong impact on the Mexican childhood population with short-range limiting and serious<br />
consequences. Poverty and a social environment <strong>de</strong>void of social justice hin<strong>de</strong>r timely medical attention and long-range rehabilitation. The<br />
aim of this study was to <strong>de</strong>termine the differences regarding socio<strong>de</strong>mographic features in patients un<strong>de</strong>r treatment at <strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong><br />
<strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong>, with a 6-year difference: patients diagnosed in 2003 as compared to those diagnosed in 2009.<br />
methods. A retrospective comparative study was carried out with end-stage chronic renal disease (ESRD) patients with information obtained<br />
from the clinical files. Data were obtained on age, gen<strong>de</strong>r, renal insufficiency etiology, socioeconomic level, type of financing, place<br />
of origin, and whether patient entered a rehabilitation program (dialysis or transplant).<br />
Results. In 2003, 69 patients with ESRD were treated, whereas 50 patients were treated in 2009. There were no differences in age or<br />
gen<strong>de</strong>r between dates. Etiology of uremia was <strong>de</strong>termined in 40% of the children in 2003 and 50% in 2009. Most patients in the assessed<br />
years belong to the lowest socioeconomic levels, coming from the State of Mexico and metropolitan Mexico City. There was a <strong>de</strong>creasing<br />
trend in the number of patients coming from other states of the country: 30% in 2003 and 16% in 2009. Twenty-three patients (33%)<br />
entered the rehabilitation program in 2003 and 29 patients (58%) in 2009 (p = 0.007).<br />
Conclusions. There was a 28% <strong>de</strong>crease between 2003 and 2009 in the number of cases being managed. Attention has been focused on<br />
the State of Mexico and metropolitan Mexico City area. In spite of socioeconomic level being apparently similar in the studied years, there<br />
was a significant increase in the proportion of children entering a long-range rehabilitation program (from 33% in 2003 to 58% in 2009).<br />
Key words: renal insufficiency, pediatrics, distributive justice, bioethics.<br />
INTRODuCTION<br />
Chronic renal disease (CRD) is consi<strong>de</strong>red to be a public<br />
health problem in our country, in children as well as in<br />
adults. 1,2 At a worldwi<strong>de</strong> level it tends to increase. According<br />
to international gui<strong><strong>de</strong>l</strong>ines, CRD in pediatrics is<br />
<strong>de</strong>fined as structural or functional damage to the kidneys<br />
1 Escuela <strong>de</strong> Medicina, Universidad Panamericana, Mexico, D.F.,<br />
Mexico<br />
2 Facultad <strong>de</strong> Psicología, Universidad Nacional Autónoma <strong>de</strong><br />
<strong>México</strong>, Mexico, D.F., Mexico<br />
3 4 Departamento <strong>de</strong> Nefrología, Subdirección <strong>de</strong> Investigación,<br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong>,<br />
<strong>México</strong> D.F., <strong>México</strong><br />
Correspon<strong>de</strong>nce: Dra. Mara Me<strong>de</strong>iros Domingo<br />
Departamento <strong>de</strong> Nefrología<br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong><br />
<strong>México</strong>, D.F., <strong>México</strong><br />
E-mail: me<strong>de</strong>iro.mara@gmail.com<br />
Received for publication: 5-31-12<br />
Accepted for publication: 8-21-12<br />
for a period of 3 months or more, which may <strong>de</strong>crease<br />
the glomerular filtration rate, and the presence of any of<br />
the following findings: 1) alteration in the composition<br />
of the blood or urine, 2) alteration in imaging studies and<br />
3) impaired renal biopsy, or those patients who have a<br />
glomerular filtration rate
Guillermo Cantú, Graciela Rodríguez, Merce<strong>de</strong>s Luque-Coqui, Benjamín Romero, Saúl Valver<strong>de</strong>, Silvia Vargas, Alfonso Reyes-López,<br />
Mara Me<strong>de</strong>iros<br />
are reported and in Japan 16.6% of its population of
Vol. 69, July-August 2012<br />
Analysis of socio<strong>de</strong>mographic features of patients with end-stage chronic renal disease: differences in a 6-year period<br />
an unspecified level (42%), probably because they were not<br />
treated in the emergency <strong>de</strong>partment and were not admitted<br />
into a rehabilitation program. In 2009 there were 32 level 1<br />
patients (64%), nine patients from level 2 (18%) and only<br />
one patient (2%) at an unspecified level (Table 2).<br />
With regard to type of financial support, in 2003 (as<br />
well as in 2009) the father was the main provi<strong>de</strong>r. The<br />
most frequent tra<strong>de</strong>s were tra<strong>de</strong>sman, businessman, driver<br />
and bricklayer. In regard to maternal financial support,<br />
the most frequently reported type of work was that of<br />
housekeeper (Table 2).<br />
In the years evaluated, most patients came from the<br />
State of Mexico and from the Fe<strong>de</strong>ral District. There was<br />
a downward trend in the number of patients from other<br />
states, with 30% in 2003 and 16% in 2009 (p = 0.06) (Table<br />
2). In 2003, in addition to the 48 patients from the Fe<strong>de</strong>ral<br />
District and State of Mexico, there were six patients<br />
from the state of Guanajuato (7%), three from the state<br />
of Guerrero (4%) and 12 patients representing more than<br />
nine different states. Moreover, in 2009 there were only<br />
eight patients from seven different states.<br />
Table 2. Socioeconomic level, type of financing, place of resi<strong>de</strong>nce<br />
and admission to long-term rehabilitation program for children with<br />
CRI atten<strong>de</strong>d in 2003 and 2009<br />
2003<br />
(n=69)<br />
2009<br />
(n=50)<br />
Socioeconomic level (n,%) 0.01<br />
• 1 31 (45%) 32 (64%)<br />
• 2 8 (12%) 9 (18%)<br />
• Other 0 8 (16%)<br />
• Not specified 29 (42%) 1 (2%)<br />
Type of financing (n,%) 0.28<br />
• Paternal 56 (81.2%) 34 (68%)<br />
• Maternal 10 (14.5%) 12 (24%)<br />
• Not specified 3 (4.3%) 1 (2%)<br />
Place of resi<strong>de</strong>nce (n,%) 0.06<br />
• State of <strong>México</strong> 44 (64%) 34 (68%)<br />
• Fe<strong>de</strong>ral District 4 (6%) 8 (16%)<br />
• 34 Other states 21 (30%) 8 (16%)<br />
Admission to long-term<br />
rehabilitation program (n,%)<br />
23 (33%) 29 (58%) 0.007<br />
*p value obtained using c 2 .<br />
CRD, chronic renal disease.<br />
p*<br />
In 2003, only 33% of patients were able to enter a longterm<br />
rehabilitation program. This means that 46 patients<br />
returned home with ESRD due to lack of socioeconomic<br />
resources. Of the 23 patients who managed to enter the<br />
rehabilitation program, 16 were transplanted within 12<br />
months. Admission into the rehabilitation program increased<br />
significantly in 2009 with 29 patients (58%). Of<br />
these, 13 patients were transplanted during a 12-month<br />
span (Table 2).<br />
DISCuSSION<br />
In accordance with theories of distributive justice in health<br />
care such as that provi<strong>de</strong>d in the HIMFG, one can conclu<strong>de</strong><br />
that liberal theory seeks to give every person according<br />
to his right and property. The criticism of this approach<br />
is that it benefits only patients whose families have the<br />
financial resources to receive medical care, which does not<br />
correspond to the reality of our environment. 17,18<br />
This report documents that the number of patients<br />
who presented to the HIMFG for ESRD was lower, with<br />
a <strong>de</strong>crease of 28% between 2003 and 2009. This may<br />
be because other highly specialized hospitals have been<br />
created in several states, along with the phenomenon of<br />
epi<strong>de</strong>miological inversion by reducing the number of<br />
births. Although most patients came from the State of<br />
Mexico, the percentage of patients from other states <strong>de</strong>creased<br />
significantly (from 30% in 2003 to 16% in 2009).<br />
There were no differences in age at diagnosis. The average<br />
age was 11 years. This may indicate that there has<br />
been progress in the early diagnosis of the disease. There<br />
were no differences regarding gen<strong>de</strong>r.<br />
Regarding the etiology of renal failure, in 2009 the<br />
primary cause in 54% of children was able to be achieved,<br />
whereas in 2003 it was only 40%. This is important<br />
because some conditions may recur in the transplanted<br />
kidney, and knowing the epi<strong>de</strong>miology of renal failure<br />
can allow for <strong>de</strong>veloping strategies for timely <strong>de</strong>tection<br />
and treatment. 6,19,20<br />
In adults, early <strong>de</strong>tection of risk groups (diabetic patients,<br />
obese patients, hypertensive patients or relatives<br />
with kidney disease) has been implemented by the National<br />
Kidney Foundation program called KEEP (Kidney Early<br />
Evaluation Program). To date the program is the most effective<br />
community screening to i<strong>de</strong>ntify individuals >18<br />
years of age with risk of renal disease. 20, 21 In Mexico, us-<br />
277
Guillermo Cantú, Graciela Rodríguez, Merce<strong>de</strong>s Luque-Coqui, Benjamín Romero, Saúl Valver<strong>de</strong>, Silvia Vargas, Alfonso Reyes-López,<br />
Mara Me<strong>de</strong>iros<br />
ing this program we have <strong>de</strong>tected a prevalence of chronic<br />
kidney disease of 22% in the Fe<strong>de</strong>ral District and of 33%<br />
in the state of Jalisco. The high prevalence is highlighted,<br />
little known even in subjects with high risk factors. 8 A<br />
similar program for the pediatric population does not<br />
exist, and given that the causes of uremia are different in<br />
children, one would have to select the specific risk factors<br />
for screening in this population. History of prematurity,<br />
acute renal insufficiency, urinary tract infections, congenital<br />
malformations, type I diabetes mellitus, obesity, and<br />
hypertension, among others, are suggested. 1<br />
Regarding socioeconomic status, there was an increase<br />
in the level of poverty (socioeconomic levels 1 and 2) from<br />
57 to 84% in patients who were treated at the hospital. It<br />
is noteworthy that in 2003 there was a high percentage of<br />
patients at an unspecified level, so the data are now more<br />
representative.<br />
Although a greater number of patients with low socioeconomic<br />
status are seen, the number of patients who<br />
entered a long-term rehabilitation program (dialysis or<br />
transplantation) increased from 33% in 2003 to 58% in<br />
2009.<br />
It is gratifying to report that more than half of the<br />
children entering rehabilitation programs are transplanted<br />
during the 12 months following diagnosis. Kidney transplantation<br />
is the optimal treatment for these patients<br />
because it allows better growth and <strong>de</strong>velopment and<br />
impacts on the quality of life. 9 It is also noted as the best<br />
method for low-income countries because the cost of<br />
maintaining an immunosuppressed patient is less than<br />
maintaining them un<strong>de</strong>r dialysis. 22<br />
We hope that the Seguro Popular program in Mexico<br />
will soon inclu<strong>de</strong> renal transplantation as the universal<br />
treatment for children with renal insufficiency as in other<br />
countries in Latin America and the Caribbean. 17<br />
REFERENCES<br />
1. Me<strong>de</strong>iros M, Muñoz-Arizpe R. Enfermedad renal en niños.<br />
Un problema <strong>de</strong> salud pública. Bol Med Hosp Infant Mex<br />
2011;68:259-261.<br />
2. López-Cervantes M, Rojas-Russell M, Tirado-<strong>Gómez</strong> LL,<br />
Durán-Arenas L, Pacheco-Domínguez RL, Venado-Estrada<br />
AA, et al. Enfermedad renal crónica y su atención mediante<br />
tratamiento sustitutivo en <strong>México</strong>. Facultad <strong>de</strong> Medicina, Universidad<br />
Nacional Autónoma <strong>de</strong> <strong>México</strong>, <strong>México</strong> D.F. <strong>México</strong>;<br />
2009.<br />
3. Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ,<br />
Coresh J, et al. National Kidney Foundation's Kidney Disease<br />
Outcomes Quality Initiative clinical practice gui<strong><strong>de</strong>l</strong>ines for<br />
chronic kidney disease in children and adolescents: evaluation,<br />
classification, and stratification. Pediatrics 2003;111:1416-<br />
1421.<br />
4. Klarenbach S, Manns B. Economic evaluation of dialysis<br />
therapies. Semin Nephrol 2009;29:524-532.<br />
5. Harambat J, van Stralen KJ, Kim JJ, Tizard EJ. Epi<strong>de</strong>miology<br />
of chronic kidney disease in children. Pediatr Nephrol<br />
2012;27:363-373.<br />
6. Warady BA, Chadha V. Chronic kidney disease in children:<br />
the global perspective. Pediatr Nephrol 2007;22:1999-2009.<br />
7. Ardissino G, Dacco V, Testa S, Bonaudo R, Claris-Appiani A,<br />
Taioli E, et al. Epi<strong>de</strong>miology of chronic renal failure in children:<br />
data from the ItalKid project. Pediatrics 2003;111:e382-e387.<br />
8. Obrador GT, García-García G, Villa AR, Rubilar X, Olvera N,<br />
Ferreira E, et al. Prevalence of chronic kidney disease in the<br />
Kidney Early Evaluation Program (KEEP) <strong>México</strong> and comparison<br />
with KEEP US. Kidney Int Suppl 2010:S2-S8.<br />
9. Me<strong>de</strong>iros-Domingo M, Romero-Navarro B, Valver<strong>de</strong>-Rosas<br />
S, Delgadillo R, Varela-Fascinetto G, Muñoz-Arizpe R. [Renal<br />
transplantation in children]. Rev Invest Clin 2005;57:230-236.<br />
10. Beauchamp TL. Methods and principles in biomedical ethics.<br />
J Med Ethics 2003;29:269-274.<br />
11. Buchanan A. A health-care <strong><strong>de</strong>l</strong>ivery and resource allocation.<br />
In: Veatch RM, ed. Medical Ethics. Boston: Jones and Bartlett<br />
Publishers; 1997. pp. 321-358.<br />
12. Sakhuja V, Sud K. End-stage renal disease in India and Pakistan:<br />
bur<strong>de</strong>n of disease and management issues. Kidney Int<br />
Suppl 2003:S115-S118.<br />
13. Yeates K. Health disparities in renal disease in Canada. Semin<br />
Nephrol 2010;30:12-18.<br />
14. Xue JL, Eggers PW, Agodoa LY, Foley RN, Collins AJ. Longitudinal<br />
study of racial and ethnic differences in <strong>de</strong>veloping<br />
end-stage renal disease among aged medicare beneficiaries.<br />
J Am Soc Nephrol 2007;18:1299-1306.<br />
15. Franco-Marina F, Tirado-<strong>Gómez</strong> LL, Venado-Estrada A,<br />
Moreno-López JA, Pacheco-Domínguez RL, Durán-Arenas L,<br />
et al. Una estimación indirecta <strong>de</strong> las <strong>de</strong>sigualda<strong>de</strong>s actuales y<br />
futuras <strong>de</strong> la frecuencia <strong>de</strong> enfermedad renal crónica terminal<br />
en <strong>México</strong>. Salud Publica Mex 2011;53(suppl 4):506-515.<br />
16. García-García G, Renoirte-López K, Márquez-Magaña I.<br />
Disparities in renal care in Jalisco, Mexico. Semin Nephrol<br />
2010;30:3-7.<br />
17. Cantú-Quintanilla G, Orta-Sibú N, Romero-Navarro B, Luque-<br />
Coqui M, Me<strong>de</strong>iros-Domingo M, Grimoldi I, et al. Patrones <strong>de</strong><br />
suficiencia y prioridad <strong>de</strong> la justicia distributiva en atención<br />
<strong>de</strong> los pacientes pediátricos con enfermedad renal crónica<br />
terminal en América Latina y el Caribe. Arch Latin Nefr Ped<br />
2010;10:25-33.<br />
18. Cantú-Quintanilla G, Orta-Sibu N, Romero-Navarro B, Luque-<br />
Coqui M, Rodríguez-Ortega EG, Reyes-López A, et al. Acceso<br />
a trasplante renal <strong>de</strong> donante fallecido en pacientes pediátricos<br />
<strong>de</strong> América Latina y el Caribe. Pers Bioét 2010;14:151-162.<br />
19. Staples A, Wong C. Risk factors for progression of chronic<br />
kidney disease. Curr Opin Pediatr 2010;22:161-169.<br />
20. Whaley-Connell AT, Vassalotti JA, Collins AJ, Chen SC,<br />
McCullough PA. National Kidney Foundation's Kidney Early<br />
278 Bol Med Hosp Infant Mex
Vol. 69, July-August 2012<br />
Analysis of socio<strong>de</strong>mographic features of patients with end-stage chronic renal disease: differences in a 6-year period<br />
Evaluation Program (KEEP) annual data report 2011: executive<br />
summary. Am J Kidney Dis 2012;59(suppl 2):S1-S4.<br />
21. Obrador GT, Mahdavi-Maz<strong>de</strong>h M, Collins AJ; Global Kidney<br />
Disease Prevention Network. Establishing the Global Kidney<br />
Disease Prevention Network (KDPN): a position statement<br />
from the National Kidney Foundation. Am J Kidney Dis<br />
2011;57:361-370.<br />
22. Garcia GG, Har<strong>de</strong>n P, Chapman J; for the World Kidney Day<br />
Steering Committee. The global role of kidney transplantation.<br />
Transplantation 2012;93:337-341.<br />
279
clinical case<br />
Bol Med Hosp Infant Mex 2012;69(4):280-283<br />
bronchial mucoepi<strong>de</strong>rmoid carcinoma: a rare tumor in children<br />
Luis Hernán<strong>de</strong>z-Motiño, Yarisa Brizuela, Verónica Vizcarra, Rubén Cruz, Lour<strong>de</strong>s Jamaica, José Karam<br />
AbSTRACT<br />
background. Lung neoplasms are rare in children. Mucous and serous glands from trachea and upper airway contain cells similar to those<br />
of the major salivary glands. Of these glands there is a group of very rare tumors including a<strong>de</strong>noid cystic carcinoma, mucoepi<strong>de</strong>rmoid<br />
carcinoma, pleomorphic a<strong>de</strong>noma, acinic cell carcinoma and oncocytoma. Mucoepi<strong>de</strong>rmoid carcinomas (MEC) represent 0.2% of cases<br />
of lung cancer at any age, and slightly more than 100 children have been reported with this entity in the international literature. Formerly<br />
classified as bronchial a<strong>de</strong>noma, this term is inappropriate for a slow-growing neoplasm and may be locally invasive. These tumors present<br />
a relatively benign course when they correspond to tumors of low-gra<strong>de</strong> malignancy and may be manifested as recurrent pneumonia or<br />
slow resolution. Children with these clinical manifestations should be thoroughly evaluated including endoscopic and tomographic studies.<br />
Surgical resection of the affected lung lobe with the respective lobar hilar lymph no<strong>de</strong>s is the most accepted treatment.<br />
Case Report. We report the case of a 10-year-old female with a history of recurrent airway infection and two left lung pneumonias. Chest<br />
tomography showed a left bronchus stenosis confirmed by endoscopy. Following pneumonectomy, histopathological and immunohistochemical<br />
findings reported a low-gra<strong>de</strong> MEC.<br />
Conclusions. MEC of low-gra<strong>de</strong> malignancy has a good prognosis with complete tumor excision that requires a comprehensive approach<br />
that inclu<strong>de</strong>s bronchoscopy.<br />
Key words: mucoepi<strong>de</strong>rmoid carcinoma, cancer, lung.<br />
INTRODuCTION<br />
Primary pulmonary neoplasms are rare in children. 1<br />
Because symptoms are nonspecific, diagnosis and<br />
management may be <strong><strong>de</strong>l</strong>ayed, thus worsening the prognosis.<br />
These tumors should be suspected when there are<br />
persistent or recurrent respiratory symptoms. Initially,<br />
common causes should be ruled out such as infectious,<br />
immuno<strong>de</strong>ficiencies, and cystic fibrosis, among others.<br />
Diagnostic approach should inclu<strong>de</strong> imaging studies such<br />
as plain chest x-rays and, if necessary, other studies such<br />
as chest computed tomography (CT) or bronchoscopy,<br />
which <strong>de</strong>termine the nature of the process. 2 Among the<br />
bronchial tumors, the most frequent are carcinoid tumors<br />
Servicio <strong>de</strong> Neumología Pediátrica, <strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong><br />
Fe<strong>de</strong>rico <strong>Gómez</strong>, <strong>México</strong> D.F., <strong>México</strong><br />
Correspon<strong>de</strong>nce: Dr. Luis Carlos Hernán<strong>de</strong>z Motiño<br />
Servicio <strong>de</strong> Neumología Pediátrica<br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong><br />
<strong>México</strong> D.F., <strong>México</strong><br />
E-mail: luismotino@yahoo.com; luischmotino@hotmail.com<br />
Received for publication: 1-9-12<br />
Accepted for publication: 6-8-12<br />
(in 80–90% of the cases). The remaining tumors (10–20%)<br />
are those <strong>de</strong>scribed as carcinomas of the salivary glands<br />
(a<strong>de</strong>nocystic and mucoepi<strong>de</strong>rmal carcinomas). 3 Pulmonary<br />
mucoepi<strong>de</strong>rmoid carcinoma (MEC) is a rare malignant<br />
tumor (0.2%). It may originate in the trachea, main bronchus,<br />
or in the lobes or segmental bronchi. Despite its low<br />
malignant potential, it has a benign behavior. Therefore, in<br />
the majority of the cases conservative pulmonary resection<br />
is an a<strong>de</strong>quate and sufficient treatment with an eventual<br />
good prognosis. 1,3-5<br />
CLINICAL CASE<br />
We present the case of a 10-year-old previously healthy<br />
female stu<strong>de</strong>nt who from 2008 presented with recurrent<br />
airway infections (RAI) and was hospitalized twice for<br />
left lung pneumonia. She has been treated at our service<br />
since June 2011. She was referred due to RAI with occasional<br />
episo<strong>de</strong>s of hemoptysis. An approach to rule<br />
out common causes of RAI was begun, e.g., sinusitis,<br />
immuno<strong>de</strong>ficiencies, cystic fibrosis, among others. Chest<br />
x-ray was done and <strong>de</strong>monstrated total left atelectasis with<br />
an area of consolidation at the left base (Figure 1). The<br />
patient was initially managed with antibiotics, steroids and<br />
280 Bol Med Hosp Infant Mex
Figure 1. Posteroanterior chest x-ray where atelectasis of the left<br />
lower lobe is seen with overdistention of the right lung.<br />
bronchodilators with no improvement and with persistence<br />
of total atelectasis. High-resolution chest CT reported left<br />
bronchial stenosis, left pulmonary necrosis, areas of bronchiectasis<br />
and fibrosis (Figure 2). The diagnostic approach<br />
was later complemented with bronchoscopy. The findings<br />
in the left bronchus were as follows: ill-<strong>de</strong>fined reddishcolored,<br />
solid granulomatous mass completely occluding<br />
the lumen of the left bronchus without allowing passage of<br />
the bronchoscope (Figure 3). Biopsy of the lesion reported<br />
left bronchial granuloma. A ventilation/perfusion scan of<br />
the lung was done that showed functional absence of the<br />
left lung and the right lung with normal perfusion and<br />
ventilation. Total pneumonectomy was performed. The<br />
pathology report was as follows:<br />
1. Left bronchial tumor. Low-gra<strong>de</strong> MEC with vascular<br />
permeation and lesion on the surgical margins<br />
(pancytokeratin, EMA, CD 31, CD 34, FACTOR<br />
VIII positive, a<strong>de</strong>quate controls).<br />
2. Hypoplastic left lung.<br />
It was later <strong>de</strong>ci<strong>de</strong>d, in conjunction with the Oncology<br />
Service, to keep the patient un<strong>de</strong>r observation because of<br />
the low gra<strong>de</strong> of malignancy of the tumor. During outpatient<br />
pulmonary follow-up there have been no episo<strong>de</strong>s of<br />
pneumonia or RAI.<br />
Vol. 69, July-August 2012<br />
A<br />
b<br />
Bronchial mucoepi<strong>de</strong>rmoid carcinoma: a rare tumor in children<br />
Figure 2. Axial cut (A) and coronal cut (B) chest computed tomography<br />
(CT). Total obstruction of the left bronchus with total left<br />
atelectasis is seen (black arrow) and areas of necrosis within the<br />
interior (arrowhead).<br />
DISCuSSION<br />
Primary lung tumors are rare in the pediatric population.<br />
The majority correspond to carcinoid tumors, a<strong>de</strong>nocystic<br />
carcinoma and MEC. 6,7 Of these, mucoepi<strong>de</strong>rmoid tumors<br />
are the least frequent. It has been proposed that the MEC<br />
originates in the mucosal and serosal glands of the central<br />
tracheobronchial tree. Other structures can <strong>de</strong>velop<br />
MEC such as the salivary, mammary, thyroid gland or<br />
skin. 2,3 Histologically, two types of MEC are characterized<br />
according to the <strong>de</strong>gree of malignancy as proposed<br />
by Heitmiller et al. 8<br />
281
Luis Hernán<strong>de</strong>z-Motiño, Yarisa Brizuela, Verónica Vizcarra, Rubén Cruz, Lour<strong>de</strong>s Jamaica, José Karam<br />
Figure 3. Fiberoptic bronchoscopy where tumor is observed occluding<br />
the left main bronchus (arrow).<br />
1) Low gra<strong>de</strong>⎯present macroscopically as well-<strong><strong>de</strong>l</strong>ineated<br />
endobronchial polypoid tumors covered with a thin<br />
mucosa. Microscopically they are heterogeneous with predominance<br />
of glandular elements with muocoid content.<br />
Benign tumors represent the majority of pediatric cases.<br />
In the international literature only one case that <strong>de</strong>veloped<br />
metastasis to peribronchial no<strong>de</strong>s has been reported.<br />
2) High-gra<strong>de</strong> macroscopically infiltrating. Microscopic<br />
study reveals a predominance of epi<strong>de</strong>rmoid<br />
elements, atypias, hyperchromatism and elevated mitotic<br />
activity. This type of MEC is less common and with a poor<br />
prognosis and almost always presents in adults. Only two<br />
cases of this type have been reported in the pediatric age.<br />
Symptoms produced by endobronchial tumors are<br />
irritation (cough and hemoptysis) or bronchial obstruction.<br />
9,10 The insidious evolution with nonspecific clinical<br />
manifestations are generally suggestive of other diagnoses<br />
such as asthma, obstructive pneumonia or foreign body. 11<br />
They can present as pulmonary phenomena in the zones<br />
distal to the bronchial obstruction, as recurrent pneumonia,<br />
bronchiectasis, pulmonary hyperinsufflation (in case of<br />
partial obstruction) and atelectasis (if there is total bronchial<br />
obstruction). 11,12 Prolonged evolution of the patient<br />
resulted in total obstruction of the bronchus and total col-<br />
lapse of the left lung. This prolonged evolution of almost 2<br />
years was due to lack of an a<strong>de</strong>quate diagnostic approach<br />
before arrival at our hospital and <strong><strong>de</strong>l</strong>ayed the diagnosis 18<br />
months, resulting in pneumonectomy.<br />
The most common radiological manifestation is the<br />
presence of an intraluminal mass in the tracheobronchial<br />
tree, although it is difficult to predict its endobronchial<br />
situation when it is found in the segmental bronchus.<br />
Pulmonary lesion secondary to obstruction such as the<br />
atelectasis presented by our patient is found in one third<br />
of the cases. 13,14 On chest CT it may appear as an oval or<br />
lobulated mass with well-<strong>de</strong>fined bor<strong>de</strong>rs with puntiform<br />
calcifications in half of the cases, and slight reinforcement<br />
with contrast media. The greatest diameter of the<br />
tumor is parallel to the direction of the branches of the<br />
airway in which it is found. 1,2 In this case, no well-<strong>de</strong>fined<br />
mass was seen, only stenosis of the left main bronchus,<br />
total left atelectasis and left pulmonary necrosis secondary<br />
to the prior events of pneumonia. For this reason,<br />
it was <strong>de</strong>ci<strong>de</strong>d to do an exploratory endoscopy, which<br />
corroborated the presence of a mass that occlu<strong>de</strong>d the<br />
entire left bronchus.<br />
A biopsy was carried out followed by scheduling of<br />
pneumonectomy. This reinforces the importance of carrying<br />
out endoscopic study for the diagnostic approach of<br />
these patients. 4,11 For a low-gra<strong>de</strong> malignant pulmonary<br />
MEC, lobectomy or segmentectomy is sufficient for cure.<br />
Bronchoscopic laser resection may be indicated in the case<br />
of small tumors where there is no question of compromise<br />
of the parenchyma. 7,15-18 The prognosis for mucoepi<strong>de</strong>rmoid<br />
bronchial tumors is closely related with tumor gra<strong>de</strong><br />
and extension at the time of diagnosis. Unlike high-gra<strong>de</strong><br />
MECs, progression of low-gra<strong>de</strong> MECs predominantly<br />
in children is slow, which allows for a good prognosis<br />
at the time of diagnosis (if established at the beginning<br />
of the diagnostic process). Diagnosis can be ma<strong>de</strong> more<br />
rapidly with the early search of these tumors in patients<br />
with chronic cough or RAI, improving the prognosis. 5,7,14<br />
In conclusion, primary lung neoplasms, although rare in<br />
children, should be inclu<strong>de</strong>d in the differential diagnosis of<br />
patients with chronic lung disease. With the presentation<br />
of persistent respiratory symptoms, chest x-ray should be<br />
done. Diagnosis of lung atelectasis that does not improve<br />
with conservative treatment warrants diagnostic bronchoscopy.<br />
Among the list of endobronchial lesions, one must<br />
consi<strong>de</strong>r MEC and confirm its diagnosis with endoscopic<br />
282 Bol Med Hosp Infant Mex
iopsy. During pediatric age, with complete excision, MEC<br />
has a good prognosis.<br />
REFERENCES<br />
1. Alves dos Santos JW, Licks da Silveira M, Tonello C, Dubermann<br />
M. Carcinoma mucoepi<strong>de</strong>rmoi<strong>de</strong> <strong>de</strong> bajo grado:<br />
una causa rara <strong>de</strong> neumonía recurrente. Rev Am Med Resp<br />
2005;1:52-54.<br />
2. Sánchez RI, Arce QM. Carcinoma mucoepi<strong>de</strong>rmoi<strong>de</strong> bronquial.<br />
Diagnóstico diferencial <strong>de</strong> neumonía recurrente. Rev Med<br />
Costa Rica Centroamérica 2007;64:113-117.<br />
3. Reyes-Kattar J, <strong>Gómez</strong> M, <strong>Gómez</strong> L, Mota D, Giménez C,<br />
Arcamone G, et al. Carcinoma mucoepi<strong>de</strong>rmoi<strong>de</strong> <strong>de</strong> pulmón<br />
en la infancia. Reporte <strong>de</strong> caso, revisión <strong>de</strong> la literatura. Rev<br />
Venez Oncol 2007;19:344-348.<br />
4. Oura H, Ishida I, Niikawa H, Mori Y, Ube K, Sasajima T, et<br />
al. Sleeve resection of the left main bronchus for bronchogenic<br />
carcinoid for preserving lung parenchyma. Kyobu Geka<br />
2010;63:795-799.<br />
5. El Mezni F, Ben Salha I, Ismaïl O, Braham E, Zeddini A, Ayadi-<br />
Kaddour A, et al. Mucoepi<strong>de</strong>rmoid carcinoma of the lung. A<br />
series of 10 cases. Rev Pneumol Clin 2005;61:78-82.<br />
6. Fujita K. Mucoepi<strong>de</strong>rmoid carcinoma in a 13-year-old girl;<br />
report of a case. Kyobu Geka 2009;62:423-426.<br />
7. Ghraïri H, Kartas S, Ammar J, Abid H, Ayadi A, Kilani T, et al.<br />
Prognosis of mucoepi<strong>de</strong>rmoid carcinoma of the bronchi. Rev<br />
Pneumol Clin 2007;63:29-34.<br />
8. Heitmiller RF, Mathisen DJ, Ferry JA, Mark EJ, Grillo HC.<br />
Mucoepi<strong>de</strong>rmoid lung tumors. Ann Thorac Surg 1989;47:394-<br />
399.<br />
Vol. 69, July-August 2012<br />
Bronchial mucoepi<strong>de</strong>rmoid carcinoma: a rare tumor in children<br />
9. Wu M, Wang Q, Xu XF, Xiang JJ. Bronchial mucoepi<strong>de</strong>rmoid<br />
carcinoma in children. Thorac Cardiovasc Surg 2011;59:443-<br />
445.<br />
10. Vogelberg C, Mohr B, Fitze G, Friedrich K, Hahn G, Roesner<br />
D, et al. Mucoepi<strong>de</strong>rmoid carcinoma as an unusual cause for<br />
recurrent respiratory infections in a child. J Pediatr Hematol<br />
Oncol 2005;27:162-165.<br />
11. An<strong>de</strong>rsen JB, Mortensen J, Damgaard K, Skov M, Sparup J,<br />
Petersen BL, et al. Fourteen-year-old girl with endobronchial<br />
carcinoid tumour presenting with asthma and lobar emphysema.<br />
Clin Respir J 2010;4:120-124.<br />
12. Yu CH, Li J, Yu JQ, Wang B, Wang T, Wang DJ. Clinicopathological<br />
features and prognosis of bronchial mucoepi<strong>de</strong>rmoid<br />
carcinoma: analysis of 21 cases. Zhonghua Yi Xue Za Zhi<br />
2007;87:41-43.<br />
13. Firinci F, Ates O, Karaman O, Tekin A, Ozer E, Cakmakci H, et<br />
al. A 7-year-old girl with cough, fever, pneumonia. Diagnosis:<br />
mucoepi<strong>de</strong>rmoid carcinoma (MEC). Pediatr Ann 2011;40:124-<br />
127.<br />
14. Sogut A, Yilmaz O, Yuksel H. A rare cause of persistent atelectasis<br />
in childhood: mucoepi<strong>de</strong>rmoid carcinoma. Tuberk Toraks<br />
2008;56:325-328.<br />
15. Lei J. Successful treatment of bronchial mucoepi<strong>de</strong>rmoid<br />
carcinoma in a longstanding collapsed lung. Ann Thorac Surg<br />
2010;90:655-657.<br />
16. Fauroux B, Aynie V, Larroquet M, Boccon-Gibod L, Ducau le<br />
Pointe H, Tamalet A, et al. Carcinoid and mucoepi<strong>de</strong>rmoid<br />
bronchial tumours in children. Eur J Pediatr 2005;164:748-752.<br />
17. Roby BB, Drehner D, Sidman JD. Pediatric tracheal and endobronchial<br />
tumors: an institutional experience. Arch Otolaryngol<br />
Head Neck Surg 2011;137:925-929.<br />
18. Al-Qahtani AR, Di Lorenzo M, Yazbeck S. Endobronchial tumors<br />
in children: institutional experience and literature review.<br />
J Pediatr Surg 2003;38:733-736.<br />
283
clinical case<br />
Bol Med Hosp Infant Mex 2012;69(4):284-290<br />
Hermansky-Pudlak syndrome: variable clinical expression in two cases<br />
Rogelio Pare<strong>de</strong>s Aguilera, 1 Norma López Santiago, 1 Angélica Monsiváis Orozco, 2 Daniel Carrasco Daza, 2<br />
José Luis Salazar-Bailón 1<br />
AbSTRACT<br />
background. Hermansky-Pudlak syndrome is a genetic disor<strong>de</strong>r characterized by albinism and bleeding of varying <strong>de</strong>grees due to alteration<br />
in the structure of the platelets. The disor<strong>de</strong>r may be accompanied by pulmonary, intestinal or kidney involvement. I<strong>de</strong>ntification of<br />
several genetic alterations in this syndrome has been reported.<br />
Case reports. We present two cases: the first of an adolescent male with mucocutaneous albinism and renal involvement. Bleeding episo<strong>de</strong>s<br />
started after being subjected to invasive studies and venipunctures, <strong>de</strong>veloping a perinephric hematoma. After severe sepsis, the<br />
patient <strong>de</strong>veloped hemoperitoneum and pulmonary hemorrhage, which precipitated the patient’s <strong>de</strong>ath. Diagnosis was ma<strong>de</strong> postmortem.<br />
In the second case, a female patient was diagnosed during infancy due to albinism and bleeding episo<strong>de</strong>s, with progressive pulmonary<br />
fibrosis that to date has limited her vital lung capacity.<br />
Conclusions. Early diagnosis of the syndrome as well as the correct approach may prevent the <strong>de</strong>velopment of complications or limit<br />
the evolution. It is still un<strong>de</strong>r <strong>de</strong>bate whether the genetic alterations <strong>de</strong>scribed are associated with the expression of any particular clinical<br />
manifestation.<br />
Key words: Hermansky-Pudlak syndrome, albinism, hemorrhage, pulmonary fibrosis, renal failure.<br />
INTRODuCTION<br />
Hermansky-Pudlak Syndrome (HPS) is a multisystemic<br />
disor<strong>de</strong>r characterized by the presence of tyrosinase-positive<br />
oculocutaneous albinism, hemorrhagic disease with<br />
impaired platelet structure and, in some cases, pulmonary<br />
fibrosis, colitis granulomatous or enteropathic granulomatous<br />
renal disease secondary to disease due to lysosomal<br />
storage of ceroid lipofuscin. HPS was first <strong>de</strong>scribed in<br />
1959. Initially, it was believed to be a single disease;<br />
however, it is now consi<strong>de</strong>red to be a heterogeneous group<br />
of at least eight autosomal recessive linked disor<strong>de</strong>rs that<br />
share a common genetic pathway.<br />
A diverse number of experimental studies have recognized<br />
the association of HPS1, AP3B1, HPS3, HPS4,<br />
1 Servicio <strong>de</strong> Hematología Pediátrica, 2 Servicio <strong>de</strong> Patología<br />
Clínica, Instituto Nacional <strong>de</strong> Pediatría, <strong>México</strong>, D.F., <strong>México</strong><br />
Correspon<strong>de</strong>ncia: Dr. José Luis Salazar Bailón<br />
Servicio <strong>de</strong> Hematología Pediátrica, Instituto Nacional <strong>de</strong> Pediatría<br />
<strong>México</strong>, D.F., <strong>México</strong><br />
E-mail: drluissalazar@gmail.com<br />
Received for publication: 7-6-11<br />
Accepted for publication: 4-12-12<br />
HPS5, HPS6, DTNBP1 and BLOC1S3 genes with HPS.<br />
However, to date there is a <strong>de</strong>bate about whether any<br />
particular expression is directly related to a <strong>de</strong>termined<br />
clinical picture. We are presenting two clinical cases of<br />
patients with this syndrome in which classic clinical signs<br />
were observed, but seriously affected two different organs.<br />
CLINICAL CASES<br />
Case 1<br />
We present the case of a 13-year-old male who was the<br />
second child in his family and a <strong>de</strong>scendant of Mexican<br />
origin. His parents are healthy and a natural birth was<br />
recor<strong>de</strong>d with weight and height in the 50th percentile for<br />
age. The patient experienced normal growth and <strong>de</strong>velopment<br />
with an albino phenotype, for which no specific<br />
diagnosis was ma<strong>de</strong>. His clinical condition initiated with<br />
a high fever without predominance of occurrence, general<br />
malaise, fatigue, weakness, nonproductive cough, sore<br />
throat and ascending and rapidly progressive lower limb<br />
e<strong>de</strong>ma. He was prescribed intramuscular gentamicin treatment<br />
for 4 consecutive days, furosemi<strong>de</strong> (20 mg/12 h for<br />
8 days), trimethoprim with sulfamethoxazole (unspecified<br />
dose for 5 days) and prednisone (10 mg/24 h for 8 days).<br />
284 Bol Med Hosp Infant Mex
The patient experienced a torpid evolution that progressed<br />
insidiously. One month after the onset of fever, the parents<br />
brought the patient to the emergency room of the National<br />
Institute of Pediatrics in Mexico City (INP) because of<br />
shortness of breath and orthopnea. Physical examination<br />
documented wi<strong>de</strong>spread lack of skin pigment, wi<strong>de</strong>spread<br />
poliosis, high-speed horizontal nystagmus, iris atrophy<br />
with gray/blue coloring, positive transillumination, and<br />
retina with macular bilateral hypoplasia without pigment<br />
in the right eye. They also corroborated further clinical data<br />
such as acute renal illness, anasarca, nephritis, congestive<br />
heart failure due to hypervolemia, arterial hypertension,<br />
pulmonary e<strong>de</strong>ma, and ascites.<br />
Laboratory analysis showed the following results: 7.0<br />
Hg, Hct 21%, MCV 90, MCH 28, 11,700 leukocytes, neutrophils<br />
83%, bands 2%, lymphocytes 15%, and platelets<br />
265,000. Blood chemistry results were as follows: serum<br />
creatinine 9.96, BUN 190, glucose 153, sodium 131,<br />
potassium 6.1, and chlori<strong>de</strong> 106. Urinalysis was cloudy<br />
yellow, urine specific gravity 1.020, pH 5, protein 75,<br />
blood 250, leukocytes 5, erythrocytes 75. Venous blood<br />
gases were pH 7.26, pCO 2 20.0, pO 2 39, HCO 3 8.9, base<br />
excess -16.9, lactate 6.<br />
With the above, the following diagnoses were integrated:<br />
normochromic normocytic anemia, uremia, proteinuria,<br />
hematuria, compensated metabolic acidosis and symptomatic<br />
hyperkalaemia. The patient received medical treatment<br />
based on loop diuretics, acute peritoneal dialysis, and prazosin<br />
for arterial tension management. The patient exhibited<br />
a successful evolution over a 3-week period.<br />
To achieve stabilization of the patient, ultrasoundgui<strong>de</strong>d<br />
percutaneous renal biopsy was performed. During<br />
the immediate postoperative period, the patient <strong>de</strong>veloped<br />
a left perirenal hematoma of 5 x 4 x 2 cm with 38 mL fluid.<br />
This was corroborated with an ultrasound and involved the<br />
renal capsule, fascia and adjacent muscle (Figure 1). It was<br />
reabsorbed after 15 days of conservative treatment. The<br />
biopsy material obtained was insufficient or inconclusive<br />
to establish a diagnosis.<br />
Based on the suspicion of a multisystemic disease<br />
(kidney, lung, hematologic) with <strong>de</strong>creased C4 and normal<br />
C3, the patient was initially treated for systemic lupus<br />
erythematosus (SLE) and consisted of boluses of methylprednisolone<br />
at 30 mg/kg of weight for 7 consecutive days.<br />
When the patient was discharged due to improvement,<br />
primary and secondary outpatient coagulation tests were<br />
Vol. 69, July-August 2012<br />
Hermansky-Pudlak syndrome: variable clinical expression in two cases<br />
conducted and normal clot retraction was found, positive<br />
tourniquet, normal bleeding time and aggregometry with<br />
a slight <strong>de</strong>crease in the ADP (a<strong>de</strong>nosine diphosphate)<br />
curve and epinephrine. From the time of symptom onset,<br />
the patient showed normochromic normocytic anemia<br />
(chronic disease). Total neutrophils ranged from 1,800 to<br />
2,600 and platelets between 146,000 and 334,000. Clotting<br />
times were always normal. Bone marrow presented data of<br />
red cell hyperplasia without evi<strong>de</strong>nce of blue histiocytes<br />
or alterations in megakaryocytes (Table 1).<br />
One month after discharge, the patient was readmitted<br />
to the emergency room with symptoms of acute hypertension<br />
secondary to renal failure. The event was controlled<br />
with prazosin and diuretics for 3 days, for which the patient<br />
had a favorable outcome.<br />
As a consequence to the progressive <strong>de</strong>cline in renal<br />
function, it was necessary to place a permanent catheter<br />
for dialysis. This became infected three times with<br />
Staphylococcus epi<strong>de</strong>rmidis, thus requiring treatment with<br />
vancomycin i.v. and i.p. for 10 days without complications.<br />
Figure 1. Renal ultrasound showing the size and the relationship<br />
between the cortex and normal marrow.<br />
Table 1. Results of patient aggregometry<br />
Patient (%) Control (%)<br />
ADP 62 84<br />
Collagen 64 78<br />
Epinephrine 60 86<br />
Ristocetin 78 70<br />
AA 70 70<br />
ADP, a<strong>de</strong>nosine diphosphate; AA, arachidonic acid.<br />
285
Rogelio Pare<strong>de</strong>s Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón<br />
During the third colonization, the patient <strong>de</strong>veloped<br />
bacterial peritonitis complicated with bilateral pneumonia.<br />
Despite treatment with specific antibiotics according to the<br />
culture and sensitivity, the patient experienced <strong>de</strong>terioration<br />
in his condition and eventually led to septic shock.<br />
Deterioration of the patient’s general condition persisted<br />
<strong>de</strong>spite supportive treatment. Disseminated intravascular<br />
coagulation (DIC) was presented with organ dysfunction<br />
involving the heart, lung and liver. Peritonitis was<br />
documented due to Candida albicans and Enterococcus<br />
faecium, as well as a right lung abscess with empyema.<br />
Treatment inclu<strong>de</strong>d broad spectrum antibiotics (meropenem<br />
and vancomycin) for 21 days, with doses adjusted for<br />
renal function. The patient <strong>de</strong>monstrated whitish, hyperemic<br />
lesions on gums and cheeks, with a necrotic aspect on<br />
the nose, which led to suspicion of fungal infection. Nasal<br />
and oral aspergillosis secondary to DIC was confirmed<br />
by culture, and bleeding <strong>de</strong>veloped in venipuncture sites<br />
along with malignant hemoperitoneum.<br />
The patient died as a result of massive pulmonary<br />
hemorrhage and cardiac arrest <strong>de</strong>spite the treatment he<br />
received.<br />
During postmortem study and conducting an intentional<br />
search, bone marrow and patient’s blood were analyzed by<br />
electronic microscopy. Platelets showed an irregular discoid<br />
shape, granulations, canalicular system, mitochondria<br />
and normal structure microtubules (Figure 2). Absence of<br />
<strong>de</strong>nse granules in the platelet structure was noted as well<br />
as replacement by collagen fragments (Figure 3). These<br />
data, together with the clinical course of the patient, allowed<br />
us to establish the diagnosis of HPS in this patient.<br />
Case 2<br />
We present the case of a 5-year-old female who was admitted<br />
without relevant perinatal history. The patient was<br />
of Mexican origin and <strong>de</strong>scent. Her father had sequelae<br />
of neurocysticercosis and a paternal aunt was reported to<br />
have lupus erythematosus. The patient’s two brothers are<br />
apparently healthy.<br />
Among her important clinical events, the patient presented<br />
a Henoch-Schönlein blister at the age of 1 year<br />
and 3 months, for which she received unspecified hospital<br />
treatment. She was discharged at 2 weeks without apparent<br />
sequelae.<br />
During her follow-up and while performing serial blood<br />
counts, mild transient neutropenic events were docu-<br />
Figure 2. Electron microscopy showing granulations (1), canalicular<br />
system (2), mitochondria (3) and microtubules (4). Irregular collagen<br />
fragments replacing <strong>de</strong>nse granules are also seen.<br />
mented without cyclical pattern and with total neutrophil<br />
nadir between 1,500 and 1,800. For this reason, the patient<br />
was referred to the pediatric hematologist who initiated<br />
treatment with granulocyte-stimulating colony factor<br />
(GSCF) at a dose of 5 µg/kg/weight during alternating<br />
periods. With this treatment, the numbers of neutrophils<br />
rose to normal levels. No specific alterations were seen in<br />
the platelet counts. There was an intentionally search of<br />
structural alterations in the platelet number. Using electron<br />
microscopy, 32 platelets were studied of which 27 lacked<br />
<strong>de</strong>nse granules, i.e., an average of 0.27 <strong>de</strong>nse bodies per<br />
platelet, which is well below the normal values (Figure 4).<br />
Again, during routine examination, hepatomegaly was<br />
found. An ultrasound <strong>de</strong>termined the presence of a 3 x 4<br />
x 3 cm liver mass. Liver biopsy was performed at the age<br />
of 2 years and 3 months. It was conclu<strong>de</strong>d that the mass<br />
was secondary to infection caused by Epstein-Barr virus.<br />
To date the patient receives monthly treatment with i.v.<br />
doses of immuomodulatory gammaglobulin.<br />
At 3 years of age the patient <strong>de</strong>monstrated severe<br />
mucositis with sloughing of both cheeks and mucosal<br />
286 Bol Med Hosp Infant Mex
Figure 3. Replacement of missing collagen-<strong>de</strong>nse granules is<br />
clearly shown.<br />
<strong>de</strong>tachment, compromising gums and tongue. She was<br />
treated with clindamycin and fluconazole for 10 days with<br />
favorable results.<br />
The patient has presented multiple cases of lower<br />
respiratory tract infection with varying severity. The<br />
first event was pneumonia was at 11 months of age with<br />
unspecified treatment. At 2 years of age, pneumonia was<br />
complicated by pleural effusion, which required hospital<br />
treatment for 6 weeks. The third case of pneumonia was<br />
2 months after discharge from the hospital and required<br />
treatment with mechanical ventilation and 15 days of<br />
treatment with unspecified broad-spectrum antibiotics.<br />
The fourth event of pneumonia was presented at 2 years<br />
and 8 months of age, with a torpid evolution <strong>de</strong>spite<br />
management with broad-spectrum antibiotics. Bronchoscopy<br />
was performed with bronchoalveolar lavage, and<br />
pulmonary candidiasis was reported. On this ocassion,<br />
the patient was treated with itraconazole (50 mg/kg of<br />
weight for 21 days) and subsequently with continuous<br />
prophylaxis. She persisted with a sporadic, productive<br />
Vol. 69, July-August 2012<br />
Hermansky-Pudlak syndrome: variable clinical expression in two cases<br />
Figure 4. Electron microscopy performed in blood. Normal platelet<br />
structures are observed as well as the absence of <strong>de</strong>nse granules.<br />
cough for >2 years, progressive wheezing with medium<br />
efforts and later with lower efforts. At 3 years of age the<br />
patient already showed signs of chronic hypoxia with<br />
clubbing fingers and pectus carinatum. She also had<br />
recurrent cases of bronchospasm necessitating hospital<br />
treatment with supplemental oxygen, bronchodilators<br />
and antibiotics. For this reason she was referred to the<br />
National Pediatric Institute (INP).<br />
Physical examination of the patient revealed light tan<br />
skin color, silver-colored hair with dark brown eyebrows<br />
and eyelashes, coarse facies with bulbous nose, prominent<br />
forehead at the level of the metopic suture, bilateral epicanthus,<br />
eyes with isochoric pupils and normal reflexes,<br />
fundus of the eye with 30 to 40% excavation of the papilla,<br />
macula with no foveolar brightness, gingival hyperplasia,<br />
no cardiovascular compromise, hepatomegaly of 4-4-1 cm<br />
below the costal margin and generalized hypotonia, pectus<br />
carinatum, normal inspiration and expiration, bilateral<br />
crepitant rales with “sail sign” and bilateral reticulonodular<br />
infiltrates on chest x-ray (Figure 5). At 5 years of age the<br />
287
Rogelio Pare<strong>de</strong>s Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón<br />
Figure 5. AP chest x-ray showing bilateral reticulonodular infiltration<br />
and prominent pulmonary artery is <strong>de</strong>monstrated.<br />
patient presented with a new case of pneumonia, which<br />
was treated with meropenem for 14 days.<br />
Bilateral micronodular infiltrate was observed with<br />
chest CAT (with no apparent subpleural affection) and leftsi<strong>de</strong>d<br />
roun<strong>de</strong>d pulmonary nodule (with well-<strong>de</strong>fined edges)<br />
(Figure 6). Bronchoscopy was performed, <strong>de</strong>monstrating<br />
normal results. Bronchoalveolar lavage reported the presence<br />
of abundant hemosi<strong>de</strong>rophages and compatible data<br />
with lymphocytic interstitial pneumonia. Angioresonance<br />
reported vasculitis data with posterior bilateral basal consolidation,<br />
suggestive of bronchiectasis.<br />
Lung biopsy was performed where data were consistent<br />
with pulmonary fibrosis. To complement the data,<br />
echocardiogram was performed, which showed evi<strong>de</strong>nce<br />
of pulmonary hypertension with pulmonary artery pressure<br />
of 87 mmHg. The patient was was treated with<br />
sil<strong>de</strong>nafil.<br />
Respiratory function showed progressive <strong>de</strong>terioration,<br />
increasing dyspnea with less stress, persistent rales,<br />
acrocyanosis, and clubbing. Treatment was initiated with<br />
supplemental oxygen when necessary, methotrexate 500<br />
mg/kg monthly and 18 mg of <strong>de</strong>flazacort daily, nebulization<br />
with bu<strong>de</strong>soni<strong>de</strong> and salbutamol with ipratropium<br />
bromi<strong>de</strong> as nee<strong>de</strong>d and i.v. gammaglobulin to 500 mg<br />
monthly. With this treatment, respiratory symptoms have<br />
<strong>de</strong>creased and the breathlessness improved as well as<br />
the overall status of the patient. In addition, the patient<br />
changed her resi<strong>de</strong>nce to a location at sea level. Her<br />
other laboratory studies were normal except for mild<br />
persistent neutropenia and discreetly <strong>de</strong>creased NK cell<br />
cytotoxicity.<br />
Figure 6. Lateral chest x-ray confirming the presence of reticulonodular<br />
infiltrate.<br />
DISCuSSION<br />
The classic form and <strong>de</strong>scription of diagnostic criteria<br />
of HPS are the presence of mucocutaneous albinism and<br />
bleeding diathesis of variable severity. 1,2 It is of high diagnostic<br />
value to document the <strong>de</strong>creased in<strong>de</strong>x of <strong>de</strong>nse<br />
granular bodies in platelets using electron microscopy.<br />
This was carried out in both patients. In an optional and<br />
complementary form we can <strong>de</strong>termine the presence of a<br />
complex amorphous lipid protein and ceroid-lipofuscin<br />
autofluorescence in urinary sediment and in parenchymal<br />
cells. However, this is not essential for diagnosis. 1,3-9<br />
Albinism in this syndrome is characterized with the<br />
skin having a white to olive color, but always in a lighter<br />
sha<strong>de</strong> than the rest of the family. In addition, hair color is<br />
usually between white and light brown, with a ten<strong>de</strong>ncy to<br />
become darker over the years. 1,4-6 A constant is the presence<br />
of nystagmus from birth that, generally, is <strong>de</strong>creased alternating<br />
with visual acuity. It is fast moving with a ten<strong>de</strong>ncy<br />
to <strong>de</strong>crease with age, and it is usually most severe when the<br />
patient is tired or un<strong>de</strong>r stress. The iris color is bluish and<br />
288 Bol Med Hosp Infant Mex
arely does it turn blue or brown. Visual acuity is found<br />
between 20/50 and 20/400, but it is typically 20/200 and<br />
usually remains constant after early childhood. 1<br />
From the hematological viewpoint, bleeding is secondary<br />
to the lack of <strong>de</strong>nse granules in the platelets. In the<br />
normal structure, these granules contain calcium, serotonin,<br />
ADP, ATP, pyrophosphate and lysosomal membrane<br />
proteins. Once the platelets are activated, the granules fuse<br />
with the plasma membrane via the soluble receptor of the<br />
protein factor of the fixative sensitive to N-ethylmaleimi<strong>de</strong><br />
and un<strong>de</strong>rgo exocytosis, resulting in platelet recruitment.<br />
In the absence of this mechanism (secondary aggregation<br />
response), patients have prolonged bleeding time, absence<br />
of secondary wave in the ADP test and epinephrine in aggregometry<br />
results, as well as absence of ATP secretion<br />
in lumi-aggregometry. These studies are not suitable for<br />
diagnosis because they present a high rate of variation.<br />
However, <strong>de</strong>monstration of platelet hypogranulation in<br />
electron microscopy is consi<strong>de</strong>red, along with the clinical<br />
features, in the <strong>de</strong>finitive diagnosis of HPS. 1,3,8,9<br />
Pulmonary fibrosis consists of a progressive lung disease<br />
with a highly variable course, although symptoms<br />
generally worsen during the fourth <strong>de</strong>ca<strong>de</strong> of life due to the<br />
<strong>de</strong>position of ceroid lipofuscin. 1,10 Granulomatous colitis<br />
presents with clinical resemblance to Crohn’s disease due<br />
to wi<strong>de</strong>spread inflammation and is not infrequent to be seen<br />
in the entire digestive tract. Renal failure has been reported<br />
in cases with an isolated syndrome or even associated with<br />
lupus nephritis. However, renal dysfunction, colitis and<br />
pulmonary fibrosis have been associated with infiltration<br />
by lysosomal <strong>de</strong>posits of ceroid lipofuscin. 1,11,12 Through<br />
genetic analysis we can sequence the genes involved in the<br />
origin of the syndrome, although it is still <strong>de</strong>bated whether<br />
there is direct correlation with the clinical scenario of<br />
each patient. Therefore, it is only applied in experimental<br />
studies and not in daily clinical practice. 1,3-9<br />
HPS1-mutation is common among homozygous patients<br />
from Puerto Rico. It is associated with pulmonary<br />
fibrosis; likewise, the HPS4 in European individuals<br />
confers a similar predisposition so it is suggested that the<br />
mutation of these genes may cause lung and hemorrhagic<br />
disease. The AP3B1 mutation is associated with persistent<br />
neutropenia and recurrent infectious conditions in the<br />
patient. Congenital neutropenia tends to be less severe<br />
than in patients with severe or cyclic chronic neutropenia<br />
and presents a ten<strong>de</strong>ncy to <strong>de</strong>velop syndromes of activa-<br />
Vol. 69, July-August 2012<br />
Hermansky-Pudlak syndrome: variable clinical expression in two cases<br />
tion of macrophages and NK cell function. Patients with<br />
HPS3 usually have slightly marked symptoms. Albinism<br />
is characterized by minimal cutaneous hypopigmentation<br />
and even the only condition becomes ocular. Mutations<br />
of HP5, HP6, HPS7 and HPS8 have been sporadically<br />
reported. 1,11-23<br />
The patients <strong>de</strong>scribed in this study met the diagnostic<br />
criteria of HPS and illustrated the heterogeneity of possible<br />
manifestations. Our data are consistent with those reported<br />
by Gamboa et al. which, due to the prominence of hematologic<br />
and pulmonary manifestations, can be consi<strong>de</strong>red<br />
as type 1. However, lack of purposeful approach causes<br />
a subdiagnosis and lacks most representative cases. We<br />
must always consi<strong>de</strong>r HPS in the differential diagnosis<br />
of newborns with oculocutaneous albinism so as to not<br />
overlook the <strong>de</strong>termination of a <strong>de</strong>ficiency in clotting that<br />
could lead to serious complications in the patient.<br />
REFERENCES<br />
1. Gahl WA. Hermansky Pudlak Syndrome. Gene Reviews.<br />
Available at: http://www.ncbi.nlm.nih.gov/books/NBK1287<br />
2. Gamboa-Marrufo JD, Loperena-Anzaldúa L, Bello-González<br />
A. Albinismo y enfermedad hemorrágica. Síndrome <strong>de</strong> Hermansky<br />
y Pudlak. Presentación <strong>de</strong> un caso. Bol Med Hosp Inf<br />
Mex 1984;41:53-55.<br />
3. Boztug K, Welte K, Zeidler C, Klein C. Congenital neutropenia<br />
syndromes. Immunol Allergy Clin North Am 2008;28:259-275.<br />
4. Bomalaski JS, Greene D, Carone F. Oculocutaneous albinism,<br />
platelet storage pool disease, and progressive lupus nephritis.<br />
Arch Intern Med 1983;143:809-811.<br />
5. Schachne JP, Glaser N, Lee SH, Kress Y, Fisher M. Hermansky-Pudlak<br />
syndrome: case report and clinicopathologic<br />
review. J Am Acad Dermatol 1990;22:926-932.<br />
6. Sánchez MR. Cutaneous diseases in Latinos. Dermatol Clin<br />
2003;21:689-697.<br />
7. El-Molfy MA, Esmat SM, Ab<strong><strong>de</strong>l</strong>-Halim MR. Pigmentary disor<strong>de</strong>rs<br />
in the Mediterranean area. Dermatol Clin 2007;25:401-<br />
417.<br />
8. Neunert CE, Journeycake JM. Congenital platelet disor<strong>de</strong>rs.<br />
Hematol Oncol Clin North Am 2007;21:663-684.<br />
9. Córdova A, Barrios NJ, Ortiz I, Rivera E, Cadilla C, Santiago-<br />
Borrero PJ. Poor response to <strong>de</strong>smopressin acetate (DDAVP)<br />
in children with Hermansky-Pudlak syndrome. Pediatr Blood<br />
Cancer 2005;44:51-54.<br />
10. Brantly M, Avila NA, Shotelersuk V, Lucero C, Huizing M,<br />
Gahl WA. Pulmonary function and high-resolution CT findings<br />
in patients with an inherited form of pulmonary fibrosis,<br />
Hermansky-Pudlak syndrome, due to mutations in HPS-1.<br />
Chest 2000;117:129-136.<br />
11. Sandrok K, Bartsch I, Rombach N, Schmidt K, Nakamura<br />
L, Hainmann I, et al. Compound heterozygous mutations in<br />
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siblings with Hermansky-Pudlak syndrome type 1 (HPS1). Klin<br />
Padriatr 2010;3:168-174.<br />
12. Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T,<br />
Curtis J, et al. Genetic diagnosis of primary immune <strong>de</strong>ficiencies.<br />
Immunol Allergy Clin North Am 2008;28:387-412.<br />
13. Dessinioti C, Stratigos AJ, Rigopoulus D, Katsambas AD. A review<br />
of genetic disor<strong>de</strong>rs of hypopigmentation: lessons learned<br />
from the biology of melanocytes. Exp Dermatol 2009;18:741-<br />
749.<br />
14. Ciciotte S, Gwynn B, Moriyama K, Huizing M, Gahl WA, Bonifacino<br />
JS, et al. Cappuccino, a mouse mo<strong><strong>de</strong>l</strong> of Hermansky-<br />
Pudlak syndrome, enco<strong>de</strong>s a novel protein that is part of the<br />
pallidin-muted complex (BLOC-1). Blood 2003;101:4402-4407.<br />
15. Huizing M, Anikster Y, Gahl WA. Hermansky-Pudlak syndrome<br />
and related disor<strong>de</strong>rs of organelle formation. Traffic<br />
2000;1:823-835.<br />
16. Jung J, Bohn G, Allroth A, Boztug K, Bran<strong>de</strong>s G, Sandrock<br />
I, et al. I<strong>de</strong>ntification of a homozygous <strong><strong>de</strong>l</strong>etion in the AP3B1<br />
gene causing Hermansky-Pudlak syndrome, type 2. Blood<br />
2006;108:362-369.<br />
17. Gerrard JM, Lint, D, Sims PJ, Wiedmer T, Fugate RD, McMillan<br />
E, et al. I<strong>de</strong>ntification of a platelet <strong>de</strong>nse granule membrane<br />
protein that is <strong>de</strong>ficient in a patient with the Hermansky Pudlak<br />
syndrome. Blood 1991;1:101-112.<br />
18. Fontana S, Parolini S, Vermi W, Booth S, Gallo F, Donini M,<br />
et al. Innate immunity <strong>de</strong>fects in Hermansky Pudlak type 2<br />
syndrome. Blood 2006;107:4857-4864.<br />
19. En<strong>de</strong>rs A, Zieger B, Schwarz K, Yoshimi A, Speckmann<br />
C, Knoepfle EM, et al. Lethal hemophagocytic lymphohistiocytosis<br />
in Hermansky-Pudlak syndrome type II. Blood<br />
2006;108:81-87.<br />
20. Gunay-Aygun M, Huizing M, Gahl WA. Molecular <strong>de</strong>fects<br />
that affect platelet <strong>de</strong>nse granules. Semin Thromb Hemost<br />
2004;30:537-547.<br />
21. White JG, Edson JR, Desnick SJ, Witkop CJ Jr. Studies of<br />
platelets in a variant of the Hermansky-Pudlak syndrome. Am<br />
J Pathol 1971;63:319-332.<br />
22. Feng L, Novak EK, Hartnell LM, Bonifacino JS, Collinson<br />
LM, Swank RT. The Hermansky Pudlak syndrome 1 (HPS1)<br />
and HPS2 genes in<strong>de</strong>pen<strong>de</strong>ntly contribute to the production<br />
and function of platelet <strong>de</strong>nse granules, melanosomes, and<br />
lysosomes. Blood 2002;99:1651-1658.<br />
23. Carmona-Rivera C, Golas G, Hess R, Cardillo ND, Martin<br />
EH, O’Brien K, et al. Clinical, molecular, and cellular features<br />
of non-Puerto Rican Hermansky-Pudlak syndrome patients<br />
of Hispanic <strong>de</strong>scent. J Invest Dermatol 2011;131:2394-2400.<br />
doi: 10.1038/jid.2011.228.<br />
290 Bol Med Hosp Infant Mex
clinicopathological case<br />
Newborn with hypoplastic left heart syndrome<br />
Vol. 69, July-August 2012<br />
Bol Med Hosp Infant Mex 2012;69(4):291-297<br />
Luis Alexis Arévalo Salas, 1 Sandrino José Fuentes Alfaro, 1 Jorge Omar Osorio Díaz, 1 Begoña Segura<br />
Stanford, 1 Mario Pérezpeña Díazconti 2<br />
Summary of the Clinical History<br />
We present the case of a male newborn (NB) 4 days of age<br />
who was referred to a tertiary hospital due to polypnea and<br />
cyanosis. The infant was the product of a first pregnancy<br />
of a 17-year-old mother who reported prenatal care from<br />
the second month of pregnancy. At 20 weeks an obstetric<br />
ultrasound noted a cardiac alteration. For this reason the<br />
mother was sent to a high specialty hospital where the<br />
condition was confirmed. Treatment based on folic acid<br />
and ferrous sulfate and two doses of anti-tetanus vaccine<br />
was provi<strong>de</strong>d. At 38.6 weeks of gestation there was<br />
spontaneous rupture of membranes with onset of labor.<br />
The NB was born via eutocic labor with spontaneous cry<br />
and respiration: Apgar 9/9, weight 2515 g, height 47.5 cm.<br />
Cyanosis was noted and the newborn was transferred to<br />
the neonatal intensive care unit (NICU) where treatment<br />
with prostaglandin E1 (PGE1) was begun at an initial dose<br />
of 0.05 μg/kg/min until a maintenance dose of 0.01 μg/kg/<br />
min was reached. On the fourth day of life, the NB was<br />
transferred to the <strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> Mexico Fe<strong>de</strong>rico<br />
Gomez (HIMFG) for cardiac management.<br />
On admission the NB was found to be active and<br />
reactive, without characteristic facies, perioral and nail<br />
cyanosis I/IV, and <strong>de</strong>creased pulses in all four extremities.<br />
1 Departamento <strong>de</strong> Cardiología,<br />
2 Departamento <strong>de</strong> Patología Clínica y Experimental, <strong>Hospital</strong><br />
<strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong>, <strong>México</strong>, D.F., <strong>México</strong><br />
Correspon<strong>de</strong>nce: Dr. Luis Alexis Arévalo Salas<br />
Departamento <strong>de</strong> Cardiología<br />
<strong>Hospital</strong> <strong>Infantil</strong> <strong>de</strong> <strong>México</strong> Fe<strong>de</strong>rico <strong>Gómez</strong><br />
<strong>México</strong>, D.F., <strong>México</strong><br />
E-mail: luisalas17@hotmail.com<br />
Received for publication: 2-9-12<br />
Accepted for publication: 3-22-12<br />
Blood pressure on the right arm was 72/36/48 and oxygen<br />
saturation was 85%. The infant was normocephalic,<br />
anterior fontanelle 2 x 2 cm, and normotensive. There<br />
was polypnea at rest, xiphoid retraction and intercostal<br />
retraction, intense left parasternal precordial hyperactivity<br />
and palpable S2. On auscultation there were rhythmic<br />
heart sounds, intense and single second sound, and a 2/6<br />
systolic murmur in the 4th left intercostal parasternal<br />
space. Pulmonary fields were clear. Abdomen was soft<br />
with mummified umbilical stump without evi<strong>de</strong>nce of<br />
infection. Liver was 3 cm below the right costal margin<br />
and of firm consistency. Spleen was nonpalpable. Normal<br />
male genitalia were reported.<br />
X-ray on admission showed situs solitus, levocardia<br />
and gra<strong>de</strong> III cardiomegaly with evi<strong>de</strong>nce of venocapillary<br />
congestion. Electrocardiogram (EKG) showed right atrial<br />
enlargement and right ventricular hypertrophy. Transfontanelle<br />
and renal ultrasound were done with normal results.<br />
Laboratory tests were consi<strong>de</strong>red within normal limits.<br />
Two-dimensional Echocardiography with Doppler Color<br />
Flow (Eco-bi)<br />
In the subcostal axis there was situs solitus, levocardia,<br />
and normal systemic and pulmonary venous return.<br />
Atresia of the left A-V valve was documented as well as<br />
an interatrial septal <strong>de</strong>fect of 4.8 mm in diameter with left<br />
to right shunt without gradient.<br />
In the apical four-chamber cut a dominant right ventricular<br />
cavity was <strong>de</strong>monstrated with mo<strong>de</strong>rate tricuspid<br />
valve insufficiency with hypoplastic left ventricular cavity<br />
(Figure 1).<br />
In the parasternal long axis, a hypoplastic left ventricular<br />
cavity is seen from which emerges the aorta with severe<br />
hypoplasia with a 2-mm diameter (Z = -9.6). On color<br />
flow Doppler, no flow was observed through the aortic and<br />
291
Luis Alexis Arévalo Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Pérezpeña Díazconti<br />
A b<br />
Figure 1. (A) Four-chamber apical view where a dominant right<br />
ventricular cavity and a hypoplastic left ventricle chamber are seen.<br />
(B) Schematically, right atrium (RA), left atrium (LA), right ventricle<br />
(RV) and hypoplastic left ventricle (LV) are seen.<br />
mitral valves. In the parasternal short axis the diameter of<br />
the aortic ring was observed to be 2.8 mm (Z = -8.47) and<br />
pulmonary ring 12.3 mm (Z = +3.34) in anterior and left<br />
position. The ratio of the rings was 4.3:1 in favor of the<br />
pulmonary ring. The pulmonary branches were confluent.<br />
On color flow Doppler, systolic flow from a large patent<br />
ductus arteriosus (PDA) was observed. In the suprasternal<br />
axis was appreciated a suprasternal narrowing at the level<br />
of the aortic isthmus (Figure 2) suggesting juxtaductal<br />
aortic coarctation. There is a large PDA that showed a short<br />
circuit from right to left into the aorta, with retrogra<strong>de</strong> flow<br />
to the aortic arch and ascending aorta.<br />
On admission, management was begun by restricting<br />
parenteral fluids to 80 ml/kg/day, glucose 6 g/kg/min,<br />
sodium 3 mEq/kg day, 4% potassium, calcium 100 mEq/<br />
kg/ day, PGE1 0.01 μg/kg/min, furosemi<strong>de</strong> 1 mg/kg/dose<br />
every 12 h, and captopril 0.2 mg/kg/dose every 8 h. During<br />
the second day of hospital stay, jaundice was <strong>de</strong>tected with<br />
indirect bilirubin 12.68 mg dL, direct bilirubin 0.67 mg<br />
dL, albumin 3.2 g/dL, and globulin 2.6 g dL. Phototherapy<br />
was begun and was maintained for 3 days.<br />
A b<br />
Figure 2. (A) Suprasternal projection with color Doppler where the<br />
anatomy of the aortic arch is observed as well as retrogra<strong>de</strong> filling<br />
(red) of the isthmus, transverse portion and ascending portion of<br />
the aortic arch. (B) In the same suprasternal projection the position<br />
of the ascending aorta (AoA), the transverse portion and the<br />
isthmus of the aortic arch (Ao Arco), the relationship of the trunk<br />
of the pulmonary artery (TAP) with patent ductus arteriosus (PDA)<br />
and the <strong>de</strong>scending aorta (AoD) are diagrammed. The area of aortic<br />
coarctation (CoA) is noted (arrow).<br />
The case was discussed in a joint session with the Cardiovascular<br />
Surgery Service concluding that the patient<br />
was a candidate for total correction using the Norwood<br />
technique, which was done 10 days after admission.<br />
Operative report notes a perfusion of 1 h 55 min with a<br />
minimum temperature of 16-18°C. Surgery was without<br />
complications or inci<strong>de</strong>nts. However, on attempting to<br />
wean from the cardiopulmonary bypass pump, the patient<br />
showed persistent hypotension, bradycardia and <strong>de</strong>saturation<br />
without recovery and died in the operating room.<br />
During the surgical waiting period, the NB remained in<br />
good general condition without signs of acute heart failure<br />
and was un<strong>de</strong>r oral feeding until the surgical event.<br />
Case Discussion<br />
This was a NB who was the product of a first pregnancy<br />
of a healthy young mother who had satisfactory prenatal<br />
care. At 20 weeks of gestation (WG), congenital heart<br />
disease was <strong>de</strong>tected by fetal echocardiography. For this<br />
reason the patient was sent to a tertiary level institution for<br />
management where the impression of cardiac dysfunction<br />
was confirmed. At 38 weeks there was spontaneous rupture<br />
of membranes and the NB was vaginally <strong><strong>de</strong>l</strong>ivered with<br />
Apgar scores of 9/9.<br />
The reason for admission to our service was the presence<br />
of generalized cyanosis and resting polypnea with<br />
intercostal retractions, along with findings of intense precordial<br />
hyperactivity and a second palpable tone, which are<br />
significant conditions for diagnosis of severe congenital<br />
heart disease. These alterations during the neonatal stage<br />
are characterized by the condition of relying on a PDA<br />
for survival because, upon closure, signs and symptoms<br />
that tend to be lethal appear. At this point three physiopathological<br />
conditions should be mentioned in which this<br />
may occur: a) pulmonary flow is <strong>de</strong>pen<strong>de</strong>nt on the PDA<br />
whose clinical manifestation is hypoxia, b) with an inappropriate<br />
mixture of blood, a state of metabolic acidosis<br />
will <strong>de</strong>velop when there is closure of the PDA and c) when<br />
the systemic flow <strong>de</strong>pends on a PDA and when it closes<br />
there is cardiogenic shock.<br />
In the condition mentioned, congenital heart disease<br />
is characterized by an obstruction present at the outflow<br />
tract of the right ventricle (stenosis or atresia) and a <strong>de</strong>fect<br />
that allows mixing of intracardiac blood (ventricular<br />
septal <strong>de</strong>fect, atrioseptal <strong>de</strong>fect) or extracardiac (PDA).<br />
This group is characterized by reduced pulmonary flow,<br />
292 Bol Med Hosp Infant Mex
and clinical data in addition to cyanosis are tachypnea at<br />
rest and a second pulmonary sound that is inaudible or<br />
difficult to <strong>de</strong>tect, which is occasionally associated with<br />
an ejection murmur specifically in the tetralogy of Fallot.<br />
Other abnormalities in this group such as pulmonary<br />
atresia or Ebstein’s disease may present without murmurs.<br />
This group can be ruled out by the respiratory pattern,<br />
auscultation and cardiomegaly, in addition to the fact that<br />
the clinical manifestation is the hypoxic crisis.<br />
The second group mentioned are heart diseases in which<br />
there may be no intracardiac <strong>de</strong>fects, but there is a ventricular<br />
arterial discordance in the case of D-transposition of<br />
the great vessels or double outlet of the right ventricle with<br />
subpulmonary interventricular communication (Taussig-<br />
Bing disease) in which the circulation is parallel. By force,<br />
a <strong>de</strong>fect is nee<strong>de</strong>d so that the mixture can “oxygenate” the<br />
blood in the aorta. Symptoms are cyanosis and metabolic<br />
acidosis but usually the cardiomegaly is small or nonexistent<br />
and associated with a narrow vascular pedicle, for<br />
which this group of symptoms can also be ruled out.<br />
The third group inclu<strong>de</strong>s those heart diseases in which<br />
some type of left obstruction predominates and is manifested<br />
by cardiac insufficiency, pulmonary e<strong>de</strong>ma and,<br />
un<strong>de</strong>r extreme conditions, by cardiogenic shock. In this<br />
group, the PDA allows a right to left shunt that retains<br />
systemic output to the extent possible with possible cardiac<br />
diseases such as critical aortic stenosis of the NB, Shone<br />
Syndrome, hypoplastic left heart syndrome (HLHS),<br />
and total anomalous connection of infradiaphragmatic<br />
pulmonary veins. 1<br />
Physical examination is a crucial weapon to establish<br />
the diagnosis of cardiac disor<strong>de</strong>rs. In the case in question,<br />
pulses were <strong>de</strong>creased in all four extremities; therefore,<br />
aortic coarctation can be ruled out because one would<br />
find intense pulses in the arms and neck and absent or<br />
diminished in the lower extremities with a pressure gradient<br />
between arm and leg. However, coarctation of the<br />
aorta may accompany other left-si<strong>de</strong>d obstructions and<br />
the classic clinical picture may be modified, particularly<br />
in the presence of a PDA that allows improvement of<br />
cardiac systemic pulses, which may be felt even in the<br />
legs. Furthermore, in the case of critical aortic stenosis,<br />
whereas the pulses may be filiform in all four extremities<br />
and be accompanied by variable cardiomegaly, there is<br />
often an ejection murmur in the second right intercostal<br />
space, sometimes accompanied by an opening snap. This<br />
Vol. 69, July-August 2012<br />
Newborn with hypoplastic left heart syndrome<br />
is different from what was <strong>de</strong>scribed for this patient<br />
whose auscultatory focus was the fourth left intercostal<br />
parasternal space (tricuspid), very possibly related to<br />
tricuspid regurgitation. Therefore, diagnosis of critical<br />
aortic stenosis can be eliminated.<br />
In 1963 an anomaly called Shone syndrome 2 was<br />
<strong>de</strong>scribed and characterized by serial left obstructions<br />
(aortic coarctation, subaortic stenosis, parachute mitral<br />
valve and mitral supraventricular ring) that could imply<br />
a diagnostic complexity similar to that shown in extreme<br />
cases of left-si<strong>de</strong> obstruction such as HLHS. Clinical data<br />
may be similar with regard to the magnitu<strong>de</strong> of cardiac<br />
insufficiency, pulmonary e<strong>de</strong>ma or shock un<strong>de</strong>r great<br />
precordial hyperactivity and pulmonary hypertension,<br />
which is manifested by an intense second pulmonary<br />
sound. However, in Shone syndrome it is possible to <strong>de</strong>tect<br />
murmurs due to aortic obstruction. In HLHS the clinical<br />
severity will be related to the size of the foramen ovale.<br />
If it is restricted or absent, symptoms will begin minutes<br />
after birth. 3 In this case there was an interatrial communication<br />
of 4.8 mm in diameter that allowed early treatment of<br />
PGE1 as well as <strong>de</strong>monstrating clinical stability for some<br />
days. Closure of PDA is crucial to the survival of these<br />
patients because it allows <strong>de</strong>congestion of the pulmonary<br />
vasculature by <strong>de</strong>creasing pulmonary e<strong>de</strong>ma. If the patient<br />
becomes lethargic, more dyspneic, with <strong>de</strong>saturation and<br />
increased heart failure, then the PDA has certainly started<br />
to close. 4 In or<strong>de</strong>r to be able to establish the differential<br />
diagnosis between these conditions, imaging studies are<br />
mandatory. X-rays as well as EKG are nonspecific in<br />
both conditions because they show diverse <strong>de</strong>grees of<br />
cardiomegaly as well as right ventricular hypertrophy.<br />
Undoubtedly, accurate diagnosis is provi<strong>de</strong>d by an Eco-Bi<br />
because it reports extreme hypoplasia of the left ventricle<br />
associated with aortic and mitral atresia and it is the one<br />
examination that <strong>de</strong>termines an ascending aorta of 2 mm<br />
in diameter, which is a relevant prognostic factor for postoperative<br />
survival. 5 Interatrial communication of 4.8 mm<br />
in diameter possibly provi<strong>de</strong>d hemodynamic stability by<br />
allowing a free short circuit from left to right. In this way,<br />
there was <strong>de</strong>congestion of the lungs and tricuspid evi<strong>de</strong>nce<br />
that could eventually contraindicate a Fontan circulation.<br />
It is relevant to mention that this case had a prenatal<br />
diagnosis and that from birth the patient received optimal<br />
treatment due to the infusion of PGE1, 6 which allowed<br />
for transfer without inci<strong>de</strong>nce, maintaining hemodynamic<br />
293
Luis Alexis Arévalo Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Pérezpeña Díazconti<br />
stability and acid-base equilibrium during the patient’s<br />
admission. It also allowed the surgical team, together<br />
with the family, to <strong>de</strong>ci<strong>de</strong> on the type of correction that<br />
was finally provi<strong>de</strong>d. When the available treatment options<br />
were evaluated, hybrid palliation was ruled out<br />
because of the echographically <strong>de</strong>monstrated association<br />
with aortic coarctation which, at the same time, could<br />
impe<strong>de</strong> a waiting period for heart transplant so that the<br />
only option was to perform a Norwood-type correction.<br />
This option had a poor prognosis due to the weight limits<br />
for this procedure (2515 g) and an ascending aorta of 2<br />
mm in diameter, which are factors associated with a rate<br />
of mortality. 5<br />
At 16 days of life, a stage I Norwood procedure was<br />
performed that consisted of reconstructing the ascending<br />
aorta, creating an anastomosis with the trunk of the pulmonary<br />
artery including release of the coarctation, placing<br />
a bandage in each pulmonary branch with the goal of<br />
regulating pulmonary flow and placing a tube un<strong>de</strong>r Sano<br />
technique between the right ventricle and the pulmonary<br />
artery to provi<strong>de</strong> pulmonary flow. At this time, a perfusion<br />
time of 1 h 55 min was reported with hypothermia of 16 to<br />
18°. This is relevant because the complications related to<br />
circulatory failure are greater after 40 min and are inherent<br />
to a greater metabolic suppression. Although this scenario<br />
was predictable because of the anatomic characteristics<br />
of the case, this was possibly the reason why the patient<br />
could not be weaned from the pump. The final diagnoses<br />
were as follows:<br />
1. Term NB with weight appropriate for gestational<br />
age<br />
2. HLHS associated with mitral-aortic atresia and<br />
aortic coarctation<br />
3. Norwood type surgery with Sano tube<br />
4. Cardiogenic shock as cause of <strong>de</strong>ath.<br />
Histopathological Description<br />
Autopsy was performed on the NB in the Pathology Department<br />
with an incision over the sternal line of 10 cm in<br />
length. On opening the chest and abdominal cavity, there<br />
was 13 mL of bloody material coming from the left pleural<br />
cavity and 15 mL in the abdominal cavity. The heart was<br />
in levocardia with situs solitu, the cardiopulmonary block<br />
weighed 99 g (for an expected 66 g). This increase was<br />
at the expense of the heart that showed dilatation of the<br />
right ventricle as well as right atrium and vena cavas. The<br />
external surface of the right ventricle showed hemorrhagic<br />
zones and a sutured surgical wound.<br />
On atrial dissection there was atrioventricular concordance<br />
observed and a surgically wi<strong>de</strong>ned foramen ovale<br />
of 1 cm in its greatest axis. When the right ventricle<br />
was opened, the right morphology in a very dilated and<br />
hypertrophic cavity was documented with a thickness of<br />
0.6 mm as well as zones of different colors throughout the<br />
length of the myocardium in this ventricle. The tricuspid<br />
valve was redundant and its output had a pulmonary valve<br />
with a 1-cm diameter ring with normal-appearing valves.<br />
The trunk of the pulmonary artery was anastomosed to<br />
the aorta up to the level of the arch. There was no ductus<br />
arteriosus seen and the supraaortic trunk arose normally.<br />
There was a wi<strong>de</strong>ned aortic arch and <strong>de</strong>scending aorta<br />
seen. At the level of the infundibulum the exit of the<br />
polytetrafluoroethylene (Gore-Tex) tube was found, which<br />
connected with the proximal third of the left pulmonary<br />
branch without obstructions. Five right pulmonary veins<br />
were discovered: three right and two left, which connect<br />
to the left atrium. The mitral valve was atresic and communicated<br />
with a small cavity that correspon<strong>de</strong>d to the<br />
left ventricle without <strong>de</strong>monstrating permeability towards<br />
the aorta (Figure 3). The histological sections carried out<br />
in the right ventricular myocardium showed multiple<br />
areas of infarction of ∼4 h of evolution in which areas of<br />
hemorrhage, e<strong>de</strong>ma, erythrocytes between myofibrils and<br />
disruption of the fibers was seen, which correlate with<br />
findings of color changes <strong>de</strong>scribed macroscopically. In<br />
addition to the above, there were myocytolysis cellular<br />
changes that translate into cardiogenic shock (Figure 4).<br />
In the lungs there was emphysema with rupture of<br />
alveolar walls and enlargement of the air spaces. No inflammation,<br />
e<strong>de</strong>ma or hemorrhage was noted; however,<br />
small- and medium-caliber vessels showed changes in<br />
the arterial media by muscularization secondary to pulmonary<br />
hypertension. When these cells were stained with<br />
Masson trichrome, there was fibrosis around the vessel<br />
and <strong>de</strong>creased lumen. Elastic fiber disorganization and<br />
rupture of the muscle were <strong>de</strong>monstrated by staining that<br />
correspon<strong>de</strong>d to changes due to gra<strong>de</strong> A pulmonary arterial<br />
hypertension according to the Rabinovitch classification<br />
(Figure 5). 7<br />
The enlarged liver was congested microscopically, with<br />
extramedullary hematopoiesis and steatosis. Portal spaces<br />
were normal and liver and kidneys showed an increase<br />
294 Bol Med Hosp Infant Mex
A b<br />
C D<br />
Figure 3. (A) Cardiopulmonary block weighing 99 g (expected<br />
weight 66 g) due to the increased size and weight of the heart.<br />
Changes in the color of the cardiac surface are observed, which<br />
correlate with histological changes of extensive infarction. (B)<br />
Pulmonary veins, three right and two left, show no alterations.<br />
(C) Gore-Tex tube extends from the middle third ventricle into the<br />
pulmonary artery on the left si<strong>de</strong>. (D) At the opening of the heart<br />
chambers, the atrium and right ventricle are of right morphology.<br />
The first is very dilated, and there is ventricular wall hypertrophy.<br />
There is interatrial communication (blue arrow) that is enlarged<br />
during surgery and measures 1 cm on the long axis. Wall thickness<br />
<strong>de</strong>monstrates changes in coloration.<br />
A b<br />
Figure 4. (A) Histological sections of the left ventricular wall show<br />
changes of acute infarction of ∼4 h. Changes are extensive and are<br />
observed in all studied sections. There is disorganization of the myofibrils,<br />
recent hemorrhage, e<strong>de</strong>ma and shock changes represented<br />
by myocytolysis. (B) Intense e<strong>de</strong>ma is shown in this field (arrows).<br />
in size and weight due to intense congestion. All these<br />
changes were secondary to cardiac insufficiency. The brain<br />
showed a normal weight and <strong>de</strong>velopment with congestion<br />
of the blood vessels. Two zones of hemorrhage were<br />
<strong>de</strong>tected in the brain, possibly secondary to congestion.<br />
The digestive tract showed bands of contraction caused<br />
by the shock status (Table 1).<br />
Vol. 69, July-August 2012<br />
A b<br />
Newborn with hypoplastic left heart syndrome<br />
Figure 5. (A) Pulmonary parenchyma cuts show rupture of alveolar<br />
walls forming large air spaces, which represent areas of<br />
emphysema. (B) In this Masson trichrome stain, small and mid-size<br />
vessels <strong>de</strong>monstrate perivascular fibrosis and muscularization of<br />
the median.<br />
Table 1. Final anatomic diagnoses<br />
PRINCIPAL DISEASE<br />
HLHS<br />
CONCOmITANT ALTERATIONS<br />
Status postsurgery of Norwood/Sano<br />
Mitral atresia<br />
Aortic atresia<br />
Wi<strong>de</strong>ned foramen ovale 1 cm<br />
Left hemithorax 15 ml<br />
Recent hemorrhage in visceral and parietal pericardium<br />
RVH<br />
Recent hemorrhage in myocardium of right atrium and<br />
ventricle<br />
Pulmonary arterial hypertension (gra<strong>de</strong> A Rabinovitch)<br />
Acute extensive infarct to myocardium<br />
(~4 h of evolution)<br />
Serosanguineous ascitic fluid 13 ml<br />
Recent sutured surgical wound in the anterior chest of 10 cm<br />
in length<br />
Partial surgical absence of the thymus<br />
Hemorrhagic areas in the brain<br />
Panlobular steatosis affecting 30% of the hepatic parenchyma<br />
Anatomic data of shock<br />
Ischemic visceral hypoxic myopathy affecting the esophagus,<br />
stomach, colon and blad<strong>de</strong>r<br />
Decrease in the lymphoid tissue of the thymus<br />
Recent subarachnoid cerebellar hematoma<br />
HLHS, hypoplastic left heart syndrome: RVH, right ventricular<br />
hypertrophy.<br />
Comment<br />
This case reported here is of particular interest according to<br />
two aspects. The first, because the diagnosis of congenital<br />
heart disease was ma<strong>de</strong> at 20 weeks of gestation with fetal<br />
echocardiography, and second because the patient was<br />
treated immediately with PGE1 from the time of birth. Referring<br />
to the echocardiography, it is important to note that<br />
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Luis Alexis Arévalo Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Pérezpeña Díazconti<br />
from 2002 8 there have been high percentages reported of<br />
high diagnostic accuracy in fetal echocardiography. It has<br />
been mentioned that among the most frequently diagnosed<br />
heart diseases, HLHS is the most notable. 9 However, there<br />
are diagnostic failures related to the skill and experience<br />
of the radiologist and even to the quality of the equipment.<br />
In the second aspect, it is of utmost importance to provi<strong>de</strong><br />
a<strong>de</strong>quate treatment from the time of birth that leads to<br />
maintaining stable conditions in these children, <strong>de</strong>creasing<br />
as much as possible <strong>de</strong>velopment of cardiac insufficiency.<br />
For this reason, we must emphasize that multidisciplinary<br />
management is required that involves obstetricians, neonatologists,<br />
nurses, cardiologists, surgeons and intensivists<br />
trained in severe congenital heart disease.<br />
The priority is the PGE1 infusion at doses of 0.01 to 0.05<br />
μg/kg/min. This is used to maintain PDA with the intention<br />
of allowing a proper systemic output and to reduce, as far<br />
as possible, heart failure and un<strong>de</strong>rlying pulmonary e<strong>de</strong>ma.<br />
On occasions, orotracheal intubation is necessary in which<br />
case it is fundamental to keep these patients in hypercarbia<br />
trying to maintain a pCO 2 between 35 and 45 mmHg and<br />
a PaO 2 between 30 and 40 mmHg in or<strong>de</strong>r to safeguard<br />
the high pulmonary vascular resistance and prevent the<br />
pulmonary vasodilator effect of oxygen. As secondary<br />
effects, an improved cerebral perfusion is obtained (beneficial)<br />
and the possibility of <strong>de</strong>veloping metabolic acidosis<br />
that can be treated by administering sodium bicarbonate at<br />
conventional doses of 1 to 2 mEq/kg/dose. It is noteworthy<br />
that parenteral fluids should be restricted and rapid boluses<br />
avoi<strong>de</strong>d. When there is need of providing inotropic support,<br />
it is recommen<strong>de</strong>d that it be a combination of dobutamine<br />
and dopamine, with the latter a dopaminergic dose with the<br />
goal of favoring renal circulation. On the other hand, higher<br />
doses of these inotropes (>5 μg/kg/min) tend to increase the<br />
systemic vascular resistence with <strong><strong>de</strong>l</strong>eterious effects on the<br />
systemic flow and tissue perfusion. 3<br />
In this case, once the fetal diagnosis was ma<strong>de</strong>, therapeutic<br />
options can be presented to the parents: interruption<br />
of pregnancy, carry pregnancy to term and offer only compassionate<br />
support, plan a surgical intervention (Norwood)<br />
or the possibility of heart transplantation. It is essential<br />
to clearly explain the options to parents, emphasizing the<br />
high mortality rate of the Norwood procedure, the shortage<br />
of donor hearts and the high possibility of neurological<br />
sequelae, even if patient survival is achieved. With this<br />
information a joint <strong>de</strong>cision can be ma<strong>de</strong>.<br />
Upon acceptance to a particular therapeutic program,<br />
the best option then needs to be consi<strong>de</strong>red according to<br />
the anatomy of the lesion. In the present case, mo<strong>de</strong>rate<br />
tricuspid regurgitation, ascending aortic diameter of 2 mm<br />
and juxtaductal aortic coarctation are <strong>de</strong>scribed. There<br />
are elements to consi<strong>de</strong>r when <strong>de</strong>termining a therapeutic<br />
approach. To plan a corrective Norwood-type surgery<br />
has the disadvantage that when tricuspid regurgitation<br />
is severe, it practically contraindicates the second stage<br />
(cavopulmonary connection).<br />
The hybrid treatment option (surgical/interventional)<br />
aims to first control pulmonary flow by performing a cerclage<br />
of each pulmonary branch, ensuring systemic flow<br />
by means of stent implantation in the ductus arteriosus and<br />
freeing the obstruction of pulmonary flow by performing<br />
a medical or surgical atrial septostomy. This option was<br />
consi<strong>de</strong>red to be contraindicated due to the fact of having<br />
an ascending aorta of 2 mm in diameter as well as an aortic<br />
coarctation because these inhibit retrogra<strong>de</strong> circulation<br />
towards the ascending and coronary aorta, thereby ruling<br />
out this procedure. 10.11<br />
When discussing the anatomic conditions of this case<br />
that has several adverse factors for success in any type of<br />
surgery, the obligation to treat or not treat these patients<br />
should be consi<strong>de</strong>red. This discussion is not new and<br />
there are literature reports that support or do not support<br />
intervention 12 with the conclusion that it is not necessarily<br />
the disease that leads to <strong>de</strong>ath and that the options <strong>de</strong>pend<br />
on the experience of the responsible physicians 13 to the<br />
point that extreme cases are offered only palliative care.<br />
It is without a doubt an obligation to clearly inform<br />
parents of the surgical and medical possibilities of longterm<br />
results that may inclu<strong>de</strong> psychomotor retardation,<br />
high mortality in each of the three surgeries that make<br />
up the Norwood program and the almost nil donation of<br />
neonatal heart, so jointly parents as well as the physicians,<br />
social worker and psychologists make a consensus <strong>de</strong>cision<br />
to accept or reject the therapeutic option. It is a medical<br />
obligation to act with a <strong>de</strong>ep sense of ethics to address<br />
cases such as the one presented to offer the best action in<br />
the face of conflicting <strong>de</strong>cisions. Ethical principles should<br />
not be ignored, such as autonomy as well as the right to<br />
self-<strong>de</strong>termination and the benefit to provi<strong>de</strong> truthful<br />
information of the medical group’s surgical experience. 14<br />
Finally, from the medical point of view, it is extremely<br />
important to formalize the treatment of these cases by<br />
296 Bol Med Hosp Infant Mex
taking into consi<strong>de</strong>ration the best possibilities. We must<br />
remember that this particular surgery has a long learning<br />
curve. Diagnosis should be ma<strong>de</strong> as early as possible, and<br />
a transfer system should be established to ensure the use<br />
of PGE1 and to maintain metabolic constants in or<strong>de</strong>r to<br />
achieve a better prognosis.<br />
REFERENCES<br />
1. Lees MH. Cyanosis of the newborn infant. Recognition and<br />
clinical evaluation. J Pediatr 1970;77:484-498.<br />
2. Shone JD, Sellers RD, An<strong>de</strong>rson RC, Adams P, Lillehei C,<br />
Edwards JE. The <strong>de</strong>velopmental complex of “parachute mitral<br />
valve”, supravalvular ring of left atrium, subaortic stenosis, and<br />
coarctation of the aorta. Am J Cardiol 1963;11:714-725.<br />
3. Rudolph A. Aortic atresia, mitral atresia, and hypoplastic left<br />
ventricle. In: Rudolph A, ed. Congenital Diseases of the Heart.<br />
Clinical-Physiological Consi<strong>de</strong>rations. West Sussex: Wiley-<br />
Blackwell; 2009. pp. 257-288.<br />
4. Marino BS, Bird GL, Wernovsky G. Diagnosis and management<br />
of the newborn with suspected congenital heart disease. Clin<br />
Perinatol 2001;28:91-136.<br />
5. Jenkins KJ. Risk adjustment for congenital heart surgery: the<br />
RACHS-1 method. Semin Thorac Cardiovasc Surg Pediatr<br />
Card Surg Annu 2004;7:180-184.<br />
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6. Browning Carmo KJ, Barr P, West M, Hopper NW, White JP,<br />
Badawi N. Transporting newborn infants with suspected duct<br />
<strong>de</strong>pen<strong>de</strong>nt congenital heart disease on low-dose prostaglandin<br />
E1 without routine mechanical ventilation. Arch Dis Child Fetal<br />
Neonatal Ed 2007;92:F117-F119.<br />
7. Rabinovitch M. Pathobiology of pulmonary hypertension:<br />
impact on clinical management. Semin Thorac Cardiovasc<br />
Surg Pediatr Card Surg Annu 2000;3:63-81.<br />
8. Haak MC, Twisk JW, Van Vugt JM. How successful is fetal<br />
echocardiographic examination in the first trimester of pregnancy?<br />
Ultrasound Obstet Gynecol 2002;20:9-13.<br />
9. Marantz P, García-Guevara C. Ecocardiografía fetal. Rev<br />
Argent Cardiol 2008;76:392-398.<br />
10. Bacha E. Hybrid therapy for hypoplastic left heart syndrome:<br />
system-wi<strong>de</strong> approach is vital. Pediatr Cardiol 2008;29:479-<br />
480.<br />
11. Hoffman J. Hypoplastic left heart syndrome. In: Hoffman J,<br />
ed. The Natural and Unnatural History of Congenital Heart<br />
Disease. West Sussex: Wiley-Blackwell; 2009. pp. 531-545.<br />
12. Osiovich H, Phillipos E, Byrne P, Robertson M. Hypoplastic<br />
left heart syndrome: “to treat or not to treat”. J Perinatol<br />
2000;20:363-365.<br />
13. Feinstein JA, Benson DW, Dubin AM, Cohen MS, Maxey DM,<br />
Mahle WT, et al. Hypoplastic left heart syndrome: current consi<strong>de</strong>rations<br />
and expectations. J Am Coll Cardiol 2012;59(suppl<br />
1):S1-S42.<br />
14. Zeigler VL. Ethical principles and parental choice: treatment<br />
options for neonates with hypoplastic left heart syndrome.<br />
Pediatr Nurs 2003;29:65-69.<br />
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pediatric theMe<br />
Bol Med Hosp Infant Mex 2012;69(4):298-304<br />
Shaping a new strategy against B. pertussis: a public health problem in<br />
mexico<br />
Lorena Suárez-Idueta, 1 Ilse Herbas-Rocha, 2 César Misael <strong>Gómez</strong>-Altamirano, 3 Vesta Richardson-López<br />
Collada 4<br />
AbSTRACT<br />
Despite vaccination against pertussis, there are still a large number of pertussis <strong>de</strong>aths worldwi<strong>de</strong>. Waning vaccine-induced immunity and<br />
the gradual increase in reported inci<strong>de</strong>nce among adolescents and adults have supported the role of these age groups in the transmission.<br />
Several countries have implemented a booster vaccination in or<strong>de</strong>r to reduce transmission and clinical significance. Pertussis is a current<br />
public health problem in Mexico. The clinical suspicion in toddlers, adolescents and adults, <strong><strong>de</strong>l</strong>ayed or incomplete vaccination series and<br />
diagnostic confirmation are the most important challenges for pertussis control. The introduction of new vaccination strategies in adults<br />
and adolescents as well as pregnant women should improve disease control.<br />
Key words: Pertussis, whooping cough, B. pertussis, immunization, vaccines.<br />
INTRODuCTION<br />
Pertussis is a disease of worldwi<strong>de</strong> distribution 1 that<br />
continues to cause a large number of <strong>de</strong>aths <strong>de</strong>spite the<br />
existence of a vaccination against Bor<strong>de</strong>tella pertussis<br />
that has been in existence for >50 years. In 2008, the<br />
World Health Organization (WHO) estimated 195,000<br />
annual <strong>de</strong>aths attributed to the disease. In relation to other<br />
vaccine-preventable diseases, it ranks as the fifth leading<br />
cause of <strong>de</strong>ath in children
Table 1. Operational <strong>de</strong>finitions, coqueluchoi<strong>de</strong> syndrome and pertussis 12<br />
inhabitants) and the year 2009 (five cases/million population)<br />
(Figure 1). 14 The most affected region during the last<br />
epi<strong>de</strong>mic year (2009) was the northern bor<strong>de</strong>r. During that<br />
year, 1,959 suspected cases or coqueluchoi<strong>de</strong> syndrome<br />
were documented, confirming 579 cases of pertussis. The<br />
states of Nuevo Leon, Sonora and Tamaulipas had the highest<br />
inci<strong>de</strong>nce rates: 44.5, 42.6 and 16.6/million inhabitants,<br />
respectively, corresponding to 62% of all confirmed cases<br />
during that year for the country. 14<br />
The real bur<strong>de</strong>n of disease is un<strong>de</strong>restimated both by<br />
the low diagnostic suspicion as well as the low percentage<br />
of confirmation. In Mexico, we diagnosed two cases of<br />
pertussis per every 10 cases of coqueluchoi<strong>de</strong> syndrome<br />
that are studied. In the last 10 years, the percentage of<br />
confirmation was maintained uniform (~20%) (Figure 1).<br />
Difficulties of laboratory diagnosis through culture inclu<strong>de</strong><br />
ina<strong>de</strong>quate sample collection, collection of the sample<br />
after starting antibiotics and late sample collection (third<br />
week after the onset of cough). Despite the heterogeneity<br />
in epi<strong>de</strong>miological surveillance of pertussis worldwi<strong>de</strong>,<br />
different operational <strong>de</strong>finitions and diagnostic methods<br />
used, 15 the percentages of confirmation from countries<br />
like Australia, 16 U.S., 6 Canada, 17 Spain 18 and Switzerland 19<br />
are reported in 90%, 55%, 25.6%, 57.6% and 24.3%,<br />
respectively.<br />
The age group most affected was that of
Lorena Suárez-Idueta, Ilse Herbas-Rocha, César Misael <strong>Gómez</strong>-Altamirano, Vesta Richardson-López Collada<br />
Figure 1. Probable and confirmed cases and inci<strong>de</strong>nce of pertussis (<strong>México</strong>, 1995-2011). 14<br />
Since 1991, national coverage with these immunogens<br />
has remained close to 90% at 1 year of age; 24,25 nevertheless,<br />
the main difficulty was the late implementation of<br />
the series of immunogens. According to the National<br />
Immunization Coverage Survey (ENCOVA) carried out<br />
between April and June, 2010 by the National Public<br />
Health Institute, among children
Figure 2. Age distribution of confirmed cases of pertussis (<strong>México</strong>, 2000-2010). 14<br />
pediatric DTaP vaccine, but with a lower concentration of<br />
antigen. 43 Ward et al. <strong>de</strong>scribed it as a safe vaccine with<br />
an efficacy of 92% (95% CI 32-99%). 44 A 5-year followup<br />
of post-adolescents after a Tdap reinforcement has<br />
shown an a<strong>de</strong>quate response in both humoral as well as<br />
cell-mediated immunity. 45<br />
Both the Global Pertussis Initiative 15,46 as well as the<br />
Advisory Committee on Immunization of the United<br />
States of America (ACIP) 47 have recommen<strong>de</strong>d a booster<br />
of Tdap in adolescents and adults, as well as a vaccination<br />
of healthcare staff and pregnant women, based on the loss<br />
of acquired immunity through vaccination in these specific<br />
Vol. 69, July-August 2012<br />
Shaping a new strategy against B. pertussis: a public health problem in Mexico<br />
Figure 3. Vaccination coverage with pentavalent acellular vaccine in Mexico and vaccine effectivity. 26,27<br />
age groups, the increase in inci<strong>de</strong>nce, 10,12,31 their role in the<br />
transmission of the disease 37,38 and as a potential measure<br />
to reduce morbidity and mortality, especially in infants. 48<br />
Countries like the U.S., Canada, Australia, France, Costa<br />
Rica, and Argentina have recognized and implemented<br />
these new vaccination strategies into their schemes. 8,49<br />
The introduction of Tdap as a booster in the adolescent<br />
population has proven effective in reducing the<br />
inci<strong>de</strong>nce of pertussis in this age group. Kandola et al.<br />
evaluated the impact of the introduction of Tdap in adolescents<br />
of 14–16 years of age and found an inci<strong>de</strong>nce<br />
of pertussis before the introduction of the vaccine in<br />
301
Lorena Suárez-Idueta, Ilse Herbas-Rocha, César Misael <strong>Gómez</strong>-Altamirano, Vesta Richardson-López Collada<br />
18/100,000 of the population compared to 0.2/100,000<br />
of the population after its introduction. 50 Quinn et al.<br />
<strong>de</strong>monstrated the impact of vaccination with Tdap in<br />
the adolescent population in the reduction of reported<br />
cases of pertussis in the group of adolescents and in<br />
children 95% coverage with pentavalent acellular vaccine<br />
is recognized, as well as to ensure timely vaccination of<br />
the first dose of biological to the population 36 million diapers with the logo of<br />
"vaccinate on time," and they produced 1 million collars to<br />
adhere to baby products. They trained over 400 hospitals<br />
with a range of >7,000 nurses as well as dissemination<br />
through leaflets and posters in the hospital. However, it is<br />
clear that effective vaccination for infants and toddlers will<br />
not be a sufficient measure to control the disease. There is<br />
a need to implement new strategies for vaccination in the<br />
adolescent and adult population, such as a strategy to reduce<br />
transmission to the group of infants
2008;9:201-211; quiz 211-212. Available at: http://www.sepeap.<br />
org/archivos/pdf/10885.pdf<br />
6. Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, Murphy<br />
TV. Trends in pertussis among infants in the United States,<br />
1980-1999. JAMA 2003;290:2968-2975.<br />
7. Mooi FR, van Loo IH, King AJ. Adaptation of Bor<strong>de</strong>tella pertussis<br />
to vaccination: a cause for its reemergence? Emerg Infect<br />
Dis 2001;7(3 suppl):526-528.<br />
8. Tan T, Trinda<strong>de</strong> E, Skowronski D. Epi<strong>de</strong>miology of pertussis.<br />
Pediatr Infect Dis J 2005;24(suppl 5):S10-S18.<br />
9. Singh M, Lingappan K. Whooping cough: the current scene.<br />
Chest 2006;130:1547-1553.<br />
10. Halperin SA. Pertussis immunization for adolescents: what<br />
are we waiting for? Can J Infect Dis 2001;12:74-76.<br />
11. Edwards KM. Overview of pertussis: focus on epi<strong>de</strong>miology,<br />
sources of infection, and long term protection after infant vaccination.<br />
Pediatr Infect Dis J 2005;24(suppl 6):S104-S108.<br />
12. Dirección General <strong>de</strong> Epi<strong>de</strong>miología. Manuales Simplificados<br />
Enfermeda<strong>de</strong>s Prevenibles por Vacunación. Secretaría <strong>de</strong><br />
Salud. <strong>México</strong>; 2005.<br />
13. Dirección General <strong>de</strong> Epi<strong>de</strong>miología. Programa <strong>de</strong> Acción<br />
Sistema Nacional <strong>de</strong> Vigilancia Epi<strong>de</strong>miológica SINAVE.<br />
Secretaría <strong>de</strong> Salud. <strong>México</strong>; 2001.<br />
14. Anuarios <strong>de</strong> morbilidad. Dirección General <strong>de</strong> Epi<strong>de</strong>miología.<br />
Secretaría <strong>de</strong> Salud.<br />
15. Guiso N, Wirsing von König CH, Forsyth K, Tan T, Plotkin<br />
SA. The Global Pertussis Initiative: report from a round<br />
table meeting to discuss the epi<strong>de</strong>miology and <strong>de</strong>tection<br />
of pertussis, Paris, France, 11-12 January 2010. Vaccine<br />
2011;29:1115-1121.<br />
16. Quinn HE, McIntyre PB. The impact of adolescent pertussis<br />
immunization, 2004-2009: lessons from Australia. Bull World<br />
Health Organ 2011;89:666-674.<br />
17. Rivest P, Richer F, Bédard L. Difficulties associated with pertussis<br />
surveillance. Can Commun Dis Rep 2004;30:29-33,36.<br />
18. Crespo I, Car<strong>de</strong>ñosa N, Godoy P, Carmona G, Sala MR, et al.<br />
Epi<strong>de</strong>miology of pertussis in a country with high vaccination<br />
coverage. Vaccine 2011;29:4244-4248.<br />
19. Wymann MN, Richard JL, Vidondo B, Heininger U. Prospective<br />
pertussis surveillance in Switzerland, 1991-2006. Vaccine<br />
2011;29:2058-2065.<br />
20. Sapián-López LA, Val<strong>de</strong>spino JL, Salvatierra B, Tapia-Conyer<br />
R, Gutiérrez G, Macedo J, et al. Seroepi<strong>de</strong>miology of whooping<br />
cough in Mexico. Salud Publica Mex1992;34:177-185.<br />
21. Sandoval PT, Arreola L <strong><strong>de</strong>l</strong> P, Quechol GR, Gallardo HG.<br />
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Rev Sau<strong>de</strong> Publica 2008;42:679-683.<br />
22. Ruiz Palacios, et al. A prospective cohort study of pertussis in<br />
adolescents attending middle school in Mexico City (ICAAC<br />
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23. Centro Nacional para la Salud <strong>de</strong> la Infancia y la Adolescencia.<br />
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<strong>México</strong>; 2008.<br />
24. Organización Mundial <strong>de</strong> la Salud. Estadísticas Sanitarias<br />
Mundiales; 2010. Available at: http://www.who.int/whosis/<br />
whostat/ES_WHS10_Full.pdf<br />
25. WHO/UNICEF. Regional Global Coverage; 2010. Available<br />
at: http://www.who.int/immunization_monitoring/routine/immunization_coverage/en/in<strong>de</strong>x4.html<br />
Vol. 69, July-August 2012<br />
Shaping a new strategy against B. pertussis: a public health problem in Mexico<br />
26. Instituto Nacional <strong>de</strong> Salud Pública. Encuesta Nacional <strong>de</strong><br />
Cobertura <strong>de</strong> Vacunación. Informe Final <strong>de</strong> Resultados.<br />
<strong>México</strong>; 2010.<br />
27. Bisgard KM, Rho<strong>de</strong>s P, Connelly BL, Bi D, Hahn C, Patrick<br />
S, et al. Pertussis vaccine effectiveness among children 6 to<br />
59 months of age in the United States, 1998-2001. Pediatrics<br />
2005;116:e285-e294.<br />
28. Juretzko P, von Kries R, Hermann M, Wirsing von König CH,<br />
Weil J, Giani G. Effectiveness of acellular pertussis vaccine<br />
assessed by hospital-based active surveillance in Germany.<br />
Clin Infect Dis 2002;35:162-167.<br />
29. Salmaso S, Mastrantonio P, Tozzi AE, Stefanelli P, Anemona<br />
A, Ciofi<strong>de</strong>gliatti ML, et al. Sustained efficacy during the first<br />
6 years of life of 3-component acellular pertussis vaccines<br />
administered in infancy: the Italian experience. Pediatrics<br />
2001;108:e81.<br />
30. Gustafsson L, Hessel L, Storsaeter J, Olin P. Long-term followup<br />
of Swedish children vaccinated with acellular pertussis<br />
vaccines at 3, 5, and 12 months of age indicates the need for<br />
a booster dose at 5 to 7 years of age. Pediatrics 2006;118:978-<br />
984.<br />
31. Wen<strong><strong>de</strong>l</strong>boe AM, Van Rie A, Salmaso S, Englund JA. Duration<br />
of immunity against pertussis after natural infection or vaccination.<br />
Pediatr Infect Dis J 2005;24(suppl 5):S58-S61.<br />
32. Jenkinson D. Duration of effectiveness of pertussis vaccine:<br />
evi<strong>de</strong>nce from a 10 year community study. Br Med J (Clin Res<br />
Ed) 1988;296:612-614.<br />
33. Ramsay ME, Farrington CP, Miller E. Age-specific efficacy of<br />
pertussis vaccine during epi<strong>de</strong>mic and non-epi<strong>de</strong>mic periods.<br />
Epi<strong>de</strong>miol Infect 1993;111:41-48.<br />
34. Van Buyn<strong>de</strong>r PG, Owen D, Vurdien JE, Andrews NJ, Matthews<br />
RC, Miller E. Bor<strong>de</strong>tella pertussis surveillance in England and<br />
Wales: 1995-7. Epi<strong>de</strong>miol Infect 1999;123:403-411.<br />
35. Tindberg Y, Blennow M, Granström M. A ten year follow-up<br />
after immunization with a two component acellular pertussis<br />
vaccine. Pediatr Infect Dis J 1999;18:361-365.<br />
36. Lugauer S, Heininger U, Cherry JD, Stehr K. Long-term clinical<br />
effectiveness of an acellular pertussis component vaccine<br />
and a whole cell pertussis component vaccine. Eur J Pediatr<br />
2002;161:142-146.<br />
37. Kowalzik F, Barbosa AP, Fernan<strong>de</strong>s VR, Carvalho PR, Avila-<br />
Aguero ML, et al. Prospective multinational study of pertussis<br />
infection in hospitalized infants and their household contacts.<br />
Pediatr Infect Dis J 2007;26:238-242.<br />
38. Wen<strong><strong>de</strong>l</strong>boe AM, Njamkepo E, Bourillon A, Floret DD, Gau<strong><strong>de</strong>l</strong>us<br />
J, Gerber M, et al. Transmission of Bor<strong>de</strong>tella pertussis to<br />
young infants. Pediatr Infect Dis J 2007;26:293-299.<br />
39. Bisgard KM, Pascual FB, Ehresmann KR, Miller CA, Cianfrini<br />
C, Jennings CE, et al. Infant pertussis: who was the source?<br />
Pediatr Infect Dis J 2004;23:985-989.<br />
40. Deen JL, Mink CA, Cherry JD, Christenson PD, Pineda EF,<br />
Lewis K, et al. Household contact study of Bor<strong>de</strong>tella pertussis<br />
infections. Clin Infect Dis 1995;21:1211-1219.<br />
41. Elliott E, McIntyre P, Ridley G, Morris A, Massie J, McEniery<br />
J, et al. National study of infants hospitalized with pertussis in<br />
the acellular vaccine era. Pediatr Infect Dis J 2004;23:246-252.<br />
42. Perret C, Viviani T, Peña A, Abarca K, Ferrés M. Source of<br />
infection in young infants hospitalized with Bor<strong>de</strong>tella pertussis.<br />
Rev Med Chil 2011;139:448-454.<br />
303
Lorena Suárez-Idueta, Ilse Herbas-Rocha, César Misael <strong>Gómez</strong>-Altamirano, Vesta Richardson-López Collada<br />
43. Bro<strong>de</strong>r KR, Cortese MM, Iskan<strong>de</strong>r JK, Kretsinger K, Sla<strong>de</strong> BA,<br />
Brown KH, et al. Preventing tetanus, diphtheria, and pertussis<br />
among adolescents: use of tetanus toxoid, reduced diphtheria<br />
toxoid and acellular pertussis vaccines recommendations of<br />
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MMWR Recomm Rep 2006;55(RR-3):1-34.<br />
44. Ward JI, Cherry JD, Chang SJ, Partridge S, Lee H, Treanor<br />
J, et al. Efficacy of an acellular pertussis vaccine among adolescents<br />
and adults. N Engl J Med 2005;353:1555-1563.<br />
45. E<strong><strong>de</strong>l</strong>man K, He Q, Mäkinen J, Sahlberg A, Haanperä M,<br />
Schuerman L, et al. Immunity to pertussis 5 years after<br />
booster immunization during adolescence. Clin Infect Dis<br />
2007;44:1271-1277.<br />
46. Ulloa-Gutierrez R, Hozbor D, Avila-Aguero ML, Caro J, Wirsing<br />
von König CH, Tan T, et al. The global pertussis initiative:<br />
meeting report from the Regional Latin America Meeting,<br />
Costa Rica, 5-6 December, 2008. Hum Vaccin 2010;6:876-<br />
880.<br />
47. Updated recommendations for use of tetanus toxoid, reduced<br />
diphtheria toxoid and acellular pertussis vaccine (Tdap)<br />
in pregnant women and persons who have or anticipate<br />
having close contact with an infant aged
vital statistics<br />
mortality due to drowning in children less than 15 years of age in<br />
mexico, 1998-2010<br />
Sonia Fernán<strong>de</strong>z Cantón, 1 Ana María Hernán<strong>de</strong>z Martínez, 1 Ricardo Viguri Uribe 2<br />
Nationally in Mexico, acci<strong>de</strong>nts are the fourth<br />
leading cause of <strong>de</strong>ath for the general population.<br />
When we refer to children
Sonia Fernán<strong>de</strong>z Cantón, Ana María Hernán<strong>de</strong>z Martínez, Ricardo Viguri Uribe<br />
Table 1. Deaths caused by drowning and acci<strong>de</strong>ntal submersion in the population
Vol. 69, July-August 2012<br />
Mortality due to drowning in children less than 15 years of age in Mexico, 1998-2010<br />
Figure 1. Relative weight of <strong>de</strong>aths by drowning and acci<strong>de</strong>ntal submersion in regard to the total <strong>de</strong>aths due to acci<strong>de</strong>nts in children
Sonia Fernán<strong>de</strong>z Cantón, Ana María Hernán<strong>de</strong>z Martínez, Ricardo Viguri Uribe<br />
Figure 2. Mortality rate and <strong>de</strong>aths due to drowning and acci<strong>de</strong>ntal submersion in children
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